caek literatur 10 2010 by HC12080706230

VIEWS: 7 PAGES: 63

									                  EUROPEAN SOCIETY OF ENDOCRINE SURGEONS



  ESES Review of Recently Published Literature

                                            1                                    2
                  Collection: T. Clerici , T. Defechereux, F. Triponez
                                                                        1
                           Compilation and design: U. Beutner
            1: Department of Surgery, Cantonal Hospital St. Gallen, St Gallen, Switzerland
 2: Department of Thoracic and Endocrine Surgery, University Hospital of Geneva, Geneva, Switzerland

                                      Ulrich.beutner@kssg.ch



                               May - Aug 2010
                  Data retrival from Pubmed: 25. Oct 2010


Contents
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                                                                                             Page
Thyroid ......................................................................................... 2

Parathyroid ................................................................................ 38

Adrenals ..................................................................................... 50

NET ............................................................................................. 57

GI and General ........................................................................... 62

Pubmed-ID: PubMed-Identifier (unique number for each Pubmed entry
blue underline:   Hyperlink to PubMed entry or web site of publisher. Clicking on hyperlink
                  opens the corresponding web site in browser (in Vista: CTRL-click).
Thyroid

Meta-Analyses
Use of Tissue Glue for Surgical Incision Closure: a Systematic Review and Meta-Analysis of Randomized
Controlled Trials.
J Am Coll Surg, 211(1):114-25.
Chow A, Marshall H, Zacharakis E, Paraskeva P, Purkayastha S. 2010.
PubMed-ID: 20610257
http://dx.doi.org/10.1016/j.jamcollsurg.2010.03.013

Hemostasis in Thyroid Surgery: Harmonic Scalpel Versus Other Techniques--a Meta-Analysis.
Otolaryngol Head Neck Surg, 143(1):17-25.
Ecker T, Carvalho AL, Choe JH, Walosek G, Preuss KJ. 2010.
OBJECTIVE: The objective is to systematically review the literature studying the harmonic scalpel versus other
hemostatic techniques in thyroid surgical patients. Although thyroidectomy is one of the most common surgical
procedures, the safest, most efficient, and cost-effective way to achieve hemostasis is hotly debated. DATA
SOURCES: We searched the electronic databases Medline and the Cochrane Library using relevant search
strategies. REVIEW METHODS: Two reviewers (G.W., T.E.) independently assessed titles and abstracts of 72
identified studies. Twelve prospective randomized controlled studies were considered relevant and included in
this meta-analysis (1153 patients). RESULTS: In all studies, operating time was reduced by using the harmonic
scalpel. Compared with surgical hemostasis by suture ligation or suture/clip ligation combined with
electrocauterization or electrothermal bipolar vessel sealer (n = 602), the mean operating time reduction for the
harmonic scalpel was equivalent to 22.67 minutes (95% CI, -27.98; -17.37, P < 0.00001) or nearly 25 percent of
the total operating room time. When harmonic scalpel was used, blood loss was reduced significantly by 20.03
mL (95% CI, -27.83; -12.22, P < 0.00001), and a mean reduction in postoperative pain (0.86 points [95% CI, -
1.60; -0.13, P = 0.02]) was measured. Length of stay was reduced by 0.12 days (95% CI, -0.25; 0.00, P = 0.05).
Differences regarding volume of drainage fluid were in favor of harmonic scalpel but not statistically significant;
complications were similar in both groups. CONCLUSION: There is clear evidence that using the harmonic
scalpel for hemostasis in thyroid surgery significantly reduces operating time and blood loss and that it is not
associated with an increase in volume of drainage fluid, complication rate, or hospital stay.
PubMed-ID: 20620614
http://dx.doi.org/10.1016/j.otohns.2010.03.018


Randomized controlled trials
Five-Year Follow-Up of a Randomized Clinical Trial of Total Thyroidectomy Versus Dunhill Operation
Versus Bilateral Subtotal Thyroidectomy for Multinodular Nontoxic Goiter.
World J Surg, 34(6):1203-13.
Barczynski M, Konturek A, Hubalewska-Dydejczyk A, Golkowski F, Cichon S, Nowak W. 2010.
BACKGROUND: The extent of thyroid resection in multinodular nontoxic goiter (MNG) is controversial. The aim
of the present study was to evaluate results of various thyroid resection modes, with special emphasis put on the
recurrence rate and morbidity rate, in a 5-year follow-up. MATERIALS AND METHODS: From 01/2000 through
12/2003, 600 consenting patients with MNG qualified for thyroidectomy at our institution were randomized to
three groups equal in size, n = 200 in each. Patients in group A underwent total thyroidectomy (TT); patients in
group B underwent Dunhill operation (DO), whereas patients in group C underwent bilateral subtotal
thyroidectomy (BST). All patients were subjected to ultrasonographic, cytological, and biochemical follow-up at
least for 60 months postoperatively. The primary outcome measure was prevalence of recurrent goiter and need
for redo surgery. The secondary outcome measure was the postoperative morbidity rate (hypoparathyroidism
and recurrent laryngeal nerve injury). RESULTS: Recurrent goiter was found in 0.52% TT versus 4.71% DO
versus 11.58% BST (p = 0.01 for TT versus DO, p = 0.02 for DO versus BST, p < 0.001 for TT versus BST), and
completion thyroidectomy was necessary in 0.52% TT versus 1.57% DO versus 3.68% BST (p = 0.03 for TT
versus BST). Transient postoperative hypoparathyroidism was present in 10.99% versus 4.23% versus 2.1% (p
= 0.007 for TT versus DO, p < 0.001 for TT versus BST), whereas the recurrent laryngeal nerve injury rate was
5.49% and 1.05% TT versus 4.23% and 0.79% DO versus 2.1% and 0.53% BST (transient and permanent,
respectively; p = 0.007 for transient events TT versus BST). CONCLUSIONS: Total thyroidectomy can be


ESES Review of Recently Published Literature 2010-2                                                   Page 2 of 63
regarded as the procedure of choice for patients with MNG. It is associated with a significantly lower incidence of
goiter recurrence and less frequent need for completion thyroidectomy than other more limited thyroid
resections. However, TT involves a significantly higher risk of postoperative transient but not permanent
hypoparathyroidism and recurrent laryngeal nerve paresis.
PubMed-ID: 20174803
http://dx.doi.org/10.1007/s00268-010-0491-7

Vandetanib (100 Mg) in Patients With Locally Advanced or Metastatic Hereditary Medullary Thyroid
Cancer.
J Clin Endocrinol Metab, 95(6):2664-71.
Robinson BG, Paz-Ares L, Krebs A, Vasselli J, Haddad R. 2010.
PURPOSE: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and
epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity.
Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary
medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in
patients with advanced hereditary MTC. PATIENTS AND METHODS: Eligible patients with unresectable,
measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease
progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal
criterion was met. The primary objective was to assess the objective response rate by response evaluation
criteria in solid tumors. RESULTS: The study comprised 19 patients (13 males, six females; mean age 45 yr).
Confirmed objective partial responses were observed in three patients, yielding an objective response rate of
16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10
patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of
calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16%
(three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and
consistent with previous vandetanib monotherapy studies. CONCLUSIONS: Vandetanib at a once-daily dose of
100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC
and an overall acceptable safety profile.
PubMed-ID: 20371662
http://dx.doi.org/10.1210/jc.2009-2461

Evaluation of a New Ultrasonic Device in Thyroid Surgery: Comparative Randomized Study.
Am J Surg, 199(6):736-40.
Miccoli P, Materazzi G, Miccoli M, Frustaci G, Fosso A, Berti P. 2010.
BACKGROUND: Conventional techniques for hemostasis during thyroidectomy rely on knot tying, clips, and
electrocoagulation. Recently, the Harmonic FOCUS Shear (Ethicon Endo-Surgery, Inc, Cincinnati, OH) was
developed for thyroidectomy. METHODS: Between December 2007 and March 2008, 62 consecutive patients
(45 women, 17 men; mean age 50.9 years) undergoing thyroidectomy were randomized into 2 groups: group A,
where the FOCUS was used, and group B, where electrocoagulation and clamp-and-tie technique were used.
RESULTS: The 2 groups were similar in terms of age, sex ratio, indication for surgery, and thyroid volume.
Operative time was significantly shorter in group A. Significantly fewer clips and ties were used, and
postoperative pain and suction balloon amount were also significantly lower in the FOCUS group. The only
postoperative complication was a patient with transient hypocalcemia in group B. CONCLUSIONS: FOCUS is a
reliable and safe tool for thyroidectomy. Its utilization is associated with a shorter operative time, less blood loss,
and less postoperative pain.
PubMed-ID: 20609718
http://dx.doi.org/10.1016/j.amjsurg.2009.04.003

Randomized Controlled Trial of Bilateral Superficial Cervical Plexus Block Versus Placebo in Thyroid
Surgery.
Br J Surg, 97(7):1000-6.
Steffen T, Warschkow R, Brandle M, Tarantino I, Clerici T. 2010.
BACKGROUND: Bilateral superficial cervical block during thyroid surgery can reduce postoperative pain but its
value is unclear. This randomized clinical trial assessed the efficacy of such regional anaesthesia on
postoperative pain after thyroid surgery performed under general anaesthesia. METHODS: Patients undergoing
thyroid surgery were randomized to one of four groups in a double-blind fashion. Patients received a cervical
block with placebo or bupivacaine at the start or end of surgery. Postoperative pain, analgesic use and length of
hospital stay were assessed. RESULTS: There were 159 patients eligible for analysis. The bupivacaine group
had significantly less pain than the placebo group (P = 0.016). The timing of bupivacaine administration did not

ESES Review of Recently Published Literature 2010-2                                                      Page 3 of 63
significantly influence pain (preoperative versus postoperative, P = 0.723). There was no difference between
groups in the amount of analgesic used. Length of hospital stay was the same in the bupivacaine and placebo
groups (P = 0.925) and when bupivacaine was administered at the beginning or end of surgery (P = 0.087).
CONCLUSION: Bilateral superficial cervical block with bupivacaine combined with general anaesthesia
significantly reduced postoperative pain after thyroid surgery. Registration number: NCT00472446
(http://www.clinicaltrials.gov).
PubMed-ID: 20632263
http://dx.doi.org/10.1002/bjs.7077


Other Articles
Cervical Lymph Node Dissection in Papillary Thyroid Cancer: Current Trends, Persisting Controversies,
and Unclarified Uncertainties.
Surg Oncol, 19(2):e57-e70.
Sakorafas GH, Sampanis D, Safioleas M. 2010.
Cervical lymph node metastases are very common in patients with papillary thyroid cancer (PTC). Despite that
PTC has an excellent prognosis, lymphatic spread is associated with increased risk of loco-regional recurrence,
which significantly impairs quality-of-life and can alter prognosis of the patient. Therefore, the identification of
lymph node metastases preoperatively is very important for the surgeon to plan the optimal surgical therapy for
the individual patient. In most western countries, cervical lymph node dissection (CLND) is performed in the
presence of cervical lymphadenopathy (therapeutic CLND). In contrast, in eastern countries (mainly in Japan,
where the use of postoperative radioiodine adjuvant therapy is restricted by law), most surgeons perform
prophylactic CLND (i.e., CLND in the absence of cervical lymphadenopathy). CLND is performed on a
compartment-oriented basis. Currently, given the very high incidence of cervical lymph node metastases in PTC,
there is a clear trend -even in western countries- in favor of central (level IV) node dissection, even in patients
without clinically or ultrasonographically evident node disease. This surgical strategy will prevent disease
recurrence, which may require an additional and more morbid surgery. Experience is therefore required from the
part of the operating surgeon, who should be able to perform safely CLND at the time of initial surgery
(thyroidectomy), to minimize surgical morbidity.
PubMed-ID: 19447608
http://dx.doi.org/10.1016/j.suronc.2009.04.002

[Primary Hyperparathyroidism. Postoperative Normocalcemic Hyperparathyrinemia After Curative
Parathyroidectomy]
Primarer Hyperparathyreoidismus. Postoperative Normokalzamische Hyperparathyrinamie Nach
Kurativer Parathyreoidektomie.
Chirurg, 81(5):447-53.
Hermann M. 2010.
INTRODUCTION: Normocalcemic hyperparathyrinemia, i.e. elevated parathyroid hormone (PTH) levels after
parathyroidectomy in patients with primary hyperparathyroidism (pHPT) may occur in the course of postoperative
recovery without the development of persistence or relapse. MATERIALS, METHODS AND RESULTS:
Intraoperative and long-term (7 year) postoperative PTH and calcium levels after curative parathyroidectomy are
demonstrated on the basis of a case report of a 62-year-old female patient with severe pHPT and pronounced
osseous and renal manifestations. The intraoperative PTH gradient displayed a decrease from 1072 pg/ml to 13
pg/ml (normal range 11-67 pg/ml) followed by an increase of up to 287 pg/ml. The hyperparathyoid values
decline to subnormal levels on administration of calcium and vitamin D and increase again after tapering these
medications. The inverse calcium/PTH correlation in the course of the 7-year observation period suggests an
intact feed-back mechanism. Preoperative PTH screening was performed in 316 consecutive normocalcemic
thyroid patients to evaluate the rate of incidental hyperparathyroidism in patients with normal serum calcium
levels. Of these patients 31 (9.8%) with normocalcemia (average 2.28 mmol/l, normal range 2.1-2.7 mmol/l)
exhibited increased PTH levels averaging 84.2 pg/ml. A parathyroid adenoma was found intraoperatively as the
cause for normocalcemic pHPT in only 1 of these 31 patients. DISCUSSION AND CONCLUSIONS: A review of
the literature revealed that late postoperative elevated parathyroid hormone levels after successful pHPT surgery
occur in 21.5%. Multiple causes are discussed, e.g. reactive hyperparathyroidism in cases of relative
hypocalcemia, hungry bone syndrome, vitamin D deficiency, renal dysfunction and ethnic or lifestyle differences.
In mild cases of postoperative hyperparathyrinemia observation of the patient may be sufficient. In cases of
reactive hyperparathyroidism due to hypocalcemia, administration of calcium is indicated, in symptomatic
patients, additional administration of vitamin D or calcitriol is necessary. Vitamin D deficiency per se needs


ESES Review of Recently Published Literature 2010-2                                                   Page 4 of 63
adequate substitution. In cases of ongoing hyperparathyrinemia an interdisciplinary diagnostic and therapeutic
approach is required.
PubMed-ID: 19468699
http://dx.doi.org/10.1007/s00104-009-1717-9

Thyroid Ultrasonography.
World J Surg, 34(6):1171-80.
Ito Y, Amino N, Miyauchi A. 2010.
BACKGROUND: The recent prevalence of ultrasonography (US) has facilitated the early detection and
qualitative evaluation of thyroid nodules. Furthermore, novel technical developments are extending the
application range of US for other thyroid diseases. METHODS: The use of US to differentiate between thyroid
carcinoma and benign nodule, between a metastatic lymph node and a reactive node, between thyroid
lymphoma and chronic thyroiditis, and between destruction-induced thyrotoxicosis and Graves' disease is
introduced. RESULTS: Classification systems for thyroid nodule have shown high diagnostic accuracy for thyroid
carcinomas except follicular carcinoma. US diagnosis of lymph node metastasis showed high specificity but low
sensitivity. Patients who were suspected of thyroid lymphoma based on US findings should undergo incisional
biopsy or thyroidectomy for diagnosis of the histologic type if fine-needle aspiration biopsy findings suggest
lymphoma. Patients should be carefully followed even if they were diagnosed as negative based on cytologic
findings. Measurement of thyroid blood flow is helpful for diagnosing destruction-induced thyrotoxicosis, such as
painless thyroiditis, by distinguishing the lesion from Graves' disease. CONCLUSIONS: Ultrasonography is
useful for diagnosing various thyroid diseases, including thyroid carcinoma. The remaining issue to be resolved
is the diagnosis of follicular carcinoma. Trials using novel techniques to differentiate these lesions are expected.
PubMed-ID: 19823911
http://dx.doi.org/10.1007/s00268-009-0211-3

Re-Evaluation of Histopathological Factors Affecting Prognosis of Differentiated Thyroid Carcinoma in
an Iodine-Sufficient Country.
World J Surg, 34(6):1265-73.
Sugitani I, Toda K, Yamamoto N, Sakamoto A, Fujimoto Y. 2010.
BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) was recognized as an independent
clinicohistological entity of thyroid cancer in the 2004 World Health Organization (WHO) classifications,
separated from papillary (PTC) and follicular carcinoma (FTC). The Turin proposal provides more specific criteria
for the diagnosis of PDTC. However, in an iodine-sufficient country such as Japan, PDTC comprises <1% of all
thyroid cancers. In 1983, Sakamoto analyzed pathological characteristics of PTC and FTC that recurred within 5
years after initial surgery and identified solid, trabecular, insular (STI) and scirrhous growth patterns as important
predictors of poor prognosis. We re-evaluated the impact of histopathological findings on the clinical course of
PTC and FTC. MATERIALS AND METHODS: Specimens from 376 consecutive cases diagnosed as PTC (n =
351) or FTC (n = 25) between 1994 and 2001 were reviewed. RESULTS: Nine (2%) patients were diagnosed
with PDTC according to WHO criteria. Only 1 case (0.3%) met the Turin criteria. In addition, STI components
were seen in various specimens as follows: >or=50%, >or=10% but <50%, >0% but <10%, and 0% of
specimens for 9 (2%), 31 (8%), 19 (5%), and 317 cases (85%), respectively. As for cause-specific survival, a
significant difference was apparent between the >or=50% and >or=10% but <50% groups. Disease-free survival
was identical between these groups and was significantly worse than in the >0% but <10% and 0% groups.
According to multivariate analysis, histological features of STI >or=10% and squamous metaplasia were
significantly related to cause-specific survival, but scirrhous infiltration, necrosis, nuclear atypia, and vascular
invasion were not. The presence of STI at a level >or=10% was also a significant risk factor, together with
clinical risk factors including large tumor size, large nodal metastasis, and distant metastasis. According to
AMES risk-group definition, clinically high-risk patients with STI >or=10% showed the worst 10-year cause-
specific survival, at 57%, irrespective of total thyroidectomy with radioactive iodine (RAI) treatment. Ten of 25
PTC patients (40%) with STI >or=10% developed cervical recurrence, whereas 9 of 15 FTC patients (60%) with
STI >or=10% showed distant metastasis. CONCLUSIONS: The measurement of STI >or=10% represents a
distinctly important risk factor for patient survival. In particular, clinically high-risk patients with STI >or=10%
need further therapy beyond RAI. Original histological pattern, as papillary or follicular, affects the site of
recurrence.
PubMed-ID: 19953247
http://dx.doi.org/10.1007/s00268-009-0305-y

A Tale of Two Celts.
World J Surg, 34(6):1151-6.

ESES Review of Recently Published Literature 2010-2                                                    Page 5 of 63
Wheeler MH. 2010.
The eponym "Graves' disease" is usually applied to the condition of immunogenic hyperthyroidism, in no small
part due to the promotion and influence of the French physician Armand Trousseau who wrote in 1862, "Du
Goitre Exophthalmique, ou Maladie de Graves." However, the distinguished Bath physician Caleb Hillier Parry, a
friend of both Edward Jenner and John Hunter, first described the clinical picture of thyrotoxicosis associated
with exophthalmos and cardiac dysfunction in a paper published posthumously in 1825, some 10 years before
Robert Graves' initial report. Graves was unaware of Parry's earlier description and considered that the thyroid
condition in the four female cases that he studied might be secondary to functional cardiac disorders and
palpitations. The many outstanding contributions to medicine and science of Parry and Graves, two truly
remarkable nineteenth century Celtic physicians, are compared and discussed. A case is made for considering
the renaming of immunogenic hyperthyroidism as Parry's disease, a proposal made by Sir William Osler, who
was the first to recognise Parry's claim for priority for the recognition of exophthalmic goitre.
PubMed-ID: 19953250
http://dx.doi.org/10.1007/s00268-009-0297-7

Primary Hyperparathyroidism.
Cancer Treat Res, 153:87-103.
Kelly KJ, Chen H, Sippel RS. 2010.
PubMed-ID: 19957221
http://dx.doi.org/10.1007/978-1-4419-0857-5_6

Risks and Adequacy of an Optimized Surgical Approach to the Primary Surgical Management of
Papillary Thyroid Carcinoma Treated During 1999-2006.
World J Surg, 34(6):1239-46.
Grant CS, Stulak JM, Thompson GB, Richards ML, Reading CC, Hay ID. 2010.
BACKGROUND: Intense disease surveillance and frequent lymph node metastases (LNMs) in papillary thyroid
cancer (PTC) have resulted in increased locoregional recurrences. We examined the safety and efficacy of an
optimized surgical approach including preoperative ultrasonography (US), bilateral thyroidectomy, routine
compartment VI dissection, and lateral neck dissection for LNM. METHODS: During 1999-2006, a total of 420
patients underwent optimized primary surgery; 291(69%) females, median age 46 years; follow-up 98%, median
4.4 years. Patients were reviewed for tumor characteristics, pattern of LNM, staging, and outcomes. RESULTS:
Total or near-total thyroidectomy was performed in 212 (51%) and 208 (49%) patients, respectively. Tumors
were multicentric, 40% (average 1.7 cm); were bilateral, 30%; and showed extrathyroidal extension, 17%.
Overall, 223 (53%) patients had LNMs: 213 (51%) were central and 85 (20%) were lateral jugular. pTNM
staging: I, 258 (61%); II, 35 (8%); III, 88 (21%); IV, 39 (9%). AGES (age, grade, extension, and size-thyroid
tumor; and MACIS (metastasis, age, completeness of resection, invasion, and size) prognostic scores were low
risk in 362 (86%) and 352 (84%), respectively. Relapse developed in 57 (14%) patients: LNM in 44, soft tissue
local recurrence (LR) in 5, distant metastases (DM) in 8. Hypoparathyroidism occurred in 5 (1.2%) patients and 1
had unintentional laryngeal nerve damage. Relapse with LNM occurred in previously operated fields in 19 (5%)
patients, 11(3%) from disease virulence (LR or DM), preoperative false-negative (FN) US in 12 (3%), and
combination of FN-US and recurrence in the operated field in 5 (1%) patients. CONCLUSIONS: Recurrence was
limited to 5% of patients when the extent of disease was accurately defined and potentially curable. This
optimized surgical strategy is relatively safe.
PubMed-ID: 20012290
http://dx.doi.org/10.1007/s00268-009-0307-9

Comparison of Consumer Information on the Internet to the Current Evidence Base for Minimally
Invasive Parathyroidectomy.
World J Surg, 34(6):1304-11.
McLean T, Delbridge L. 2010.
BACKGROUND: The Internet is increasingly used as a source of health information by patients. Under these
circumstances, the opportunity exists for Internet sites ostensibly providing patient information to act to promote
surgical referrals based on exaggerated claims. This study aims to assess quantitatively and qualitatively the
Internet-based consumer health information for minimally invasive parathyroidectomy (MIP) techniques.
METHODS: This is a prospective analysis of Internet web sites. Descriptive information about specific published
claims on each of the web sites was documented and compared to the published evidence base. Web sites
were then rated using a validated composite score (CS) tool and an MIP score tool developed specifically for the
study. RESULTS: The search yielded 308 web sites, which, after assessment by the inclusion criteria left 44
unique web sites suitable for analysis. "Exaggerated," "misleading," or "false" claims were present in 27.3% of

ESES Review of Recently Published Literature 2010-2                                                  Page 6 of 63
the web sites analyzed. The false claims category had a high negative item-total correlation with the overall
score, and accuracy was found to have a statistically significant (p < 0.05) negative correlation with quality.
However, analysis performed for country of origin and the organization responsible for the web site found no
significant difference. CONCLUSIONS: Web sites offering information in relation to MIP have a surprisingly high
rate of claims that are not in accord with the evidence. Such claims may be posted to attract surgical referrals. It
is difficult for consumers to differentiate quality consumer health web sites from poor ones as there are no hard
and fast rules to differentiate them.
PubMed-ID: 20012291
http://dx.doi.org/10.1007/s00268-009-0306-x

Total Thyroidectomy Is Superior to Subtotal Thyroidectomy for Management of Graves' Disease in the
United States.
World J Surg, 34(6):1261-4.
Wilhelm SM, McHenry CR. 2010.
BACKGROUND: In the United States, Graves' disease is most commonly treated with radioiodine, yet
thyroidectomy remains an important option for correcting hyperthyroidism. In many countries, limited access to
thyroid hormone makes subtotal thyroidectomy the procedure of choice. In the United States, where
levothyroxine is widely available, we hypothesized that total (TT) or near-total thyroidectomy (NT) is superior to
subtotal thyroidectomy (ST) for long-term control of Graves' disease. METHODS: A retrospective review of
patients who underwent ST, NT, or TT for Graves' disease between 1990 and 2008 was conducted. Differences
in rates of disease recurrence were assessed by analysis of variance (ANOVA). Rates of parathyroid
autotransplantation, complications, gland weight, and final pathology were determined. RESULTS: A total of 136
patients with Graves' disease were treated with thyroidectomy. Average age was 36.4 +/- 11.3 years (range: 16-
81 years) and 88% were female. From 1990 to 1994, 10 patients underwent ST and 6 had NT. Since then, all
patients have undergone TT (n = 120). There was a significantly higher rate of recurrence for ST (30%)
compared to NT (0%; P = 0.15) and TT (0%; P < 0.0001). Parathyroid autotransplantation was performed in 36
(26.5%) patients, only 2 of whom underwent ST or NT. Transient postoperative hypocalcemia was more
common after TT (P = 0.04). No patient in any group had permanent hypoparathyroidism. Two TT pts had
transient recurrent laryngeal nerve palsy. CONCLUSIONS: Subtotal thyroidectomy resulted in 30% long-term
failure to correct Graves' hyperthyroidism. We saw no recurrences and no increase in postoperative
complications in the TT group. We feel that TT is safe and superior to ST for management of Graves' disease in
the United States.
PubMed-ID: 20033406
http://dx.doi.org/10.1007/s00268-009-0337-3

Transoral Thyroid and Parathyroid Surgery.
Surg Endosc, 24(6):1261-7.
Karakas E, Steinfeldt T, Gockel A, Westermann R, Kiefer A, Bartsch DK. 2010.
BACKGROUND: Translumenal endoscopic interventions via so-called natural orifices are gaining increasing
interest because they allow surgical treatment without any incision of the skin. Moreover, minimally invasive
procedures have found their way into thyroid and parathyroid surgery. Our goal was to develop a new access for
thyroid and parathyroid resection via an entirely transoral approach. METHODS: We managed to find an entirely
transoral sublingual access to the thyroid region in pigs and human cadavers. Using a modified rigid rectoscope
(oraloscope) hemithyroidectomies as well as resection of parathyroid glands were performed via this new
approach. Preparation and resection was performed using conventional laparoscopic instruments. In living pigs,
integrity of the recurrent laryngeal nerve after resection could be documented by neuromonitoring. An
absorbable suture was used to seal the mucosal incision. RESULTS: First, hemithyroidectomy was performed
via the transoral access in 10 porcine cadavers, then in 10 living and orally intubated pigs, and finally in five
human corpses. In humans, resection of parathyroid glands also was performed. We gained access to the
thyroid region by blunt dissection of the layer behind the hyoid bone and the strap muscles of the neck. We did
not observe any complication during the insertion, resection, and removal part of the new procedure.
CONCLUSIONS: Entirely transoral thyroid and parathyroid surgery via sublingual access seems to be feasible.
However, further investigations are needed to evaluate the safety of the new technique, especially potential and
clinically relevant contamination of the access route has to be excluded.
PubMed-ID: 20033730
http://dx.doi.org/10.1007/s00464-009-0757-z

Comparison of Video-Assisted Thyroidectomy and Traditional Thyroidectomy for the Treatment of
Papillary Thyroid Carcinoma.

ESES Review of Recently Published Literature 2010-2                                                    Page 7 of 63
Surg Endosc, 24(7):1658-62.
Wu CT, Yang LH, Kuo SJ. 2010.
BACKGROUND: There is concern regarding the oncological effectiveness of minimally invasive video-assisted
thyroidectomy (VAT) for thyroid carcinoma. This study compared the surgical results of VAT and traditional
thyroidectomy in patients with small papillary thyroid carcinomas (PTC). METHODS: Of 44 patients with PTC
offered the choice between VAT and traditional thyroidectomy, 21 underwent VAT and 23 underwent traditional
thyroidectomy. Residual thyroid tissue and function were assessed postoperatively by measuring thyroid-
stimulating hormone (TSH), T4, thyroglobulin, and anti-thyroglobulin antibody levels and with sonographic
examination. RESULTS: Operative time, maximum tumor size, number of positive lymph nodes, and TSH and
T4 levels 4 weeks postoperatively were similar in the two groups (all p > 0.05). Patients in the traditional
thyroidectomy group had significantly higher postoperative serum thyroglobulin levels 4 weeks after surgery than
did patients in the VAT group (5.4 versus 0.5 ng/ml, respectively; p = 0.007). Postoperative ultrasonography
showed no residual thyroid tissue or evidence of recurrence in any of the patients. The median follow-up period
was 60 months (range 31-77 month) for the VAT group and 53 months (range 31-80 months) for the traditional
thyroidectomy group. Thyroglobulin levels of all patients in both groups decreased to <0.2 ng/ml at last follow-up.
CONCLUSIONS: VAT is safe and effective for the treatment of small papillary thyroid carcinomas, and has
similar oncological effectiveness to traditional thyroidectomy.
PubMed-ID: 20035348
http://dx.doi.org/10.1007/s00464-009-0826-3

Excellent Prognosis of Patients With Solitary T1N0M0 Papillary Thyroid Carcinoma Who Underwent
Thyroidectomy and Elective Lymph Node Dissection Without Radioiodine Therapy.
World J Surg, 34(6):1285-90.
Ito Y, Masuoka H, Fukushima M, Inoue H, Kihara M, Tomoda C, Higashiyama T, Takamura Y, Kobayashi K,
Miya A, Miyauchi A. 2010.
BACKGROUND: The extent of surgery for papillary carcinoma significantly differs between western countries
and Japan. Almost routine total thyroidectomy with radioiodine ablation therapy has been performed in western
countries, whereas limited thyroidectomy has been adopted in Japan, especially for low-risk cases. In this study,
the prognosis of patients with solitary papillary carcinoma measuring 2 cm or less without massive extrathyroid
extension, clinically apparent lymph node metastasis or distant metastasis at diagnosis (T1N0M0 in the UICC
TNM classification) was investigated to elucidate the appropriate extent of surgery for these patients.
METHODS: We investigated the prognosis of 2,638 patients with solitary T1N0M0 papillary carcinoma who
underwent initial surgery between 1987 and 2004. Total or near total thyroidectomy was performed for 1,037
patients and the remaining 1,601 patients underwent more limited thyroidectomy. Elective central node
dissection was performed for 2,511 patients, accounting for 96%, and 1,545 (59%) also underwent prophylactic
lateral node dissection. Radioiodine ablation therapy was performed only for three patients. RESULTS: The 10-
year disease-free survival (DFS) rate of our series was 97%. To date, recurrence was observed in 62 patients
(2%) and 41 showed recurrence to the regional lymph nodes. Seventeen of 1,601 patients who received limited
thyroidectomy (1%) showed recurrence to the remnant thyroid. Pathological nodal-positive patients showed a
worse DFS, but the 10-year DFS rate was still high at 96%. Patients with total or near total thyroidectomy had a
better DFS, but the difference disappeared if recurrence to the remnant thyroid was excluded. A number needed
to treat (NNT) for total or near total thyroidectomy over hemithyroidectomy was 83 to prevent 1 recurrence.
CONCLUSIONS: These findings suggest that solitary T1N0M0 patients have an excellent prognosis when they
undergo thyroidectomy and elective lymph node dissection without radioiodine therapy. Regarding the extent of
thyroidectomy, hemithyroidectomy is adequate for these patients, if a 1% risk of recurrence to the remnant
thyroid is accepted.
PubMed-ID: 20041244
http://dx.doi.org/10.1007/s00268-009-0356-0

Papillary Thyroid Microcarcinoma: Extrathyroidal Extension, Lymph Node Metastases, and Risk Factors
for Recurrence in a High Prevalence of Goiter Area.
World J Surg, 34(6):1214-21.
Lombardi CP, Bellantone R, De CC, Paladino NC, Fadda G, Salvatori M, Raffaelli M. 2010.
BACKGROUND: Although papillary thyroid microcarcinoma (PTMC) is diagnosed with increasing frequency, the
best therapeutic option and follow-up protocol have not been established yet, especially in the case of incidental
diagnosis. We reviewed our series of patients with PTMC to determine risk factors for recurrence in an area
where there is a high prevalence of goiter. METHODS: The medical records of all patients who underwent
thyroidectomy with a final pathology report of PTMC between October 2002 and June 2007 were reviewed.
PTMC was defined as a papillary thyroid carcinoma 10 mm or less in diameter. Follow-up evaluation was


ESES Review of Recently Published Literature 2010-2                                                  Page 8 of 63
obtained by outpatient consultation and/or telephone interview. RESULTS: In a series of 2,220 patients who
underwent thyroidectomy for a thyroid carcinoma, 933 had a PTMC. Diagnosis was incidental in 704 patients
(75.5%). Upon multivariate analysis, tumor size, nonincidental diagnosis, and neck node metastases at
diagnosis were independent risk factors for extracapsular spread (ECS), while ECS, multifocal disease, and
number of removed lymph nodes were independent risk factors for lymph node metastases at diagnosis. Follow-
up evaluation was completed in 287 patients, 9 (3.1%) of whom experienced recurrence. The number of
removed and metastasized nodes at first operation and the length of the follow-up were independent risk factors
for recurrent disease. CONCLUSIONS: Incidental diagnosis of PTMC is frequent in a high prevalence of goiter
area. PTMC shows a variable degree of aggressiveness. Management protocols should be based on patient-
and tumor-related prognostic factors, as for larger tumors.
PubMed-ID: 20052467
http://dx.doi.org/10.1007/s00268-009-0375-x

Vitamin D3 Deficiency Is Associated With Late-Onset Hypocalcemia After Minimally Invasive
Parathyroidectomy in a Vitamin D Borderline Area.
World J Surg, 34(6):1350-5.
Lang BH, Lo CY. 2010.
BACKGROUND: Concurrent vitamin D(3) deficiency is common in primary hyperparathyroidism (pHPT). We
aimed to examine the clinicopathologic features and short-term outcomes of vitamin D(3)-deficient patients after
minimally invasive parathyroidectomy (MIP). METHODS: Over 2-year period, 80 consecutive MIP patients had
preoperative-fasting 25-hydroxyvitamin D(3) (25OHD(3)) checked. Forty-five patients had a 25OHD(3) level <20
ng/ml and were defined as deficient. Intraoperative parathyroid hormone (IOPTH) assay was used for all MIP.
Postoperative adjusted calcium (Ca) was checked at 6, 16 (with intact PTH), and 24 h. Oral calcium and vitamin
D supplements were given if hypocalcemic symptoms developed or Ca < 2.00 mmol/l. Late-onset hypocalcemia
(LOH) was defined as symptoms developed after 24 h. RESULTS: Both deficient and nondeficient groups had
similar demographic data and bone density scores. The deficient group had significantly higher PTH (190 vs.
121 pg/ml, p = 0.015). Although IOPTH in the deficient group were higher at induction and 0 min after excision,
the percentage drop from induction to 10 min after excision was similar. Ca was similar at 6 and 16 h in the two
groups but was significantly lower in the deficient group at 24 h (2.10 vs. 2.45 mmol/l, p = 0.033). At 1 week, the
proportion of LOH was significantly higher in the deficient group (12/42 vs. 3/34, p = 0.043) and in those with
preoperative PTH > 100 pg/ml (15/57 vs. 0/19, p = 0.013). CONCLUSIONS: Vitamin D(3) deficiency was
associated with a higher preoperative PTH level and a greater risk of LOH after MIP. However, the likely cause
of LOH remains unclear as both low preoperative vitamin D(3) and high PTH levels could be responsible.
PubMed-ID: 20054540
http://dx.doi.org/10.1007/s00268-009-0377-8

Should Routine Analysis of the MEN1 Gene Be Performed in All Patients With Primary
Hyperparathyroidism Under 40 Years of Age?
World J Surg, 34(6):1294-8.
Skandarajah A, Barlier A, Morlet-Barlat N, Sebag F, Enjalbert A, Conte-Devolx B, Henry JF. 2010.
BACKGROUND: Familial hyperparathyroidism, especially Multiple Endocrine Neoplasia Type 1, is more likely to
present with primary hyperparathyroidism (1 degrees HPT) at a young age, mandating bilateral exploration of the
parathyroid glands. However, the majority of young patients will not be gene carriers or have a family history.
Recent evidence suggests that young adults under 40, in whom there is no suspicion of family history, can be
managed with the same pre- and perioperative strategy as used for sporadic primary HPT of any age. Our aim
was to evaluate the prevalence of mutations in the MEN1 gene in young adults under 40 who present with
apparent sporadic 1 degrees HPT. METHODS: A retrospective review was undertaken of all patients who
underwent surgery for 1 degrees HPT between 1993 and 2004. From a total of 1253 patients, 87 (6.2%) were
under the age of 40. Thirty-three patients provided informed consent to a detailed personal and family history,
physical examination, and genetic analysis of the MEN1 gene. Twelve patients were subsequently excluded as
they were known gene carriers prior to surgery (10 MEN1 and 2 MEN2A patients). Twenty-one patients
underwent genetic analysis. RESULTS: Of the 21 patients who consented to genetic analysis, the mean age
was 30.8 years (range = 18-39 years with 43% younger than 30). These patients had no suspicious family or
personal histories suggestive of a MEN phenotype. Fifteen patients presented with symptomatic hypercalcemia.
All 21 patients underwent parathyroid surgery by conventional cervicotomy (12) or endoscopic
parathyroidectomy in cases (9) where the parathyroid gland was localized preoperatively. Nineteen patients
(91%) had uniglandular disease. Surgical cure was achieved in all patients. Of the 21 patients, only one patient
(4.7%) was found to have a MEN1 gene mutation (exon 3, at codon 190, c;680_681delGGinsC). This patient
was found to have double adenomas at surgery with subsequent histological confirmation. The overall


ESES Review of Recently Published Literature 2010-2                                                   Page 9 of 63
prevalence of MEN1 mutation in all patients under 40 was 13%. CONCLUSION: Although young age is often the
only criterion to suspect MEN1, our results do not support routine MEN1 analysis in patients under 40. We
propose that these patients be managed with the same preoperative and surgical approach as those presenting
with sporadic 1 degrees HPT of any age.
PubMed-ID: 20058152
http://dx.doi.org/10.1007/s00268-009-0388-5

Vandetanib for the Treatment of Patients With Locally Advanced or Metastatic Hereditary Medullary
Thyroid Cancer.
J Clin Oncol, 28(5):767-72.
Wells SA, Jr., Gosnell JE, Gagel RF, Moley J, Pfister D, Sosa JA, Skinner M, Krebs A, Vasselli J, Schlumberger
M. 2010.
PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma
(MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong
therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of
vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth
factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable
locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg.
The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression
or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST
[Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib
300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a
confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of
patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate
of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from
baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum
carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue
(63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial
responses and disease control with a manageable adverse event profile. These results demonstrate that
vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease
for which there has been no effective therapy.
PubMed-ID: 20065189
http://dx.doi.org/10.1200/JCO.2009.23.6604

Three Distinctly Different Kinds of Papillary Thyroid Microcarcinoma Should Be Recognized: Our
Treatment Strategies and Outcomes.
World J Surg, 34(6):1222-31.
Sugitani I, Toda K, Yamada K, Yamamoto N, Ikenaga M, Fujimoto Y. 2010.
BACKGROUND: Papillary microcarcinoma (PMC) of the thyroid generally follows a benign clinical course.
However, treatment strategies remain controversial. According to our previous retrospective review of 178
patients with PMC who underwent surgery between 1976 and 1993, the most significant risk factors affecting
cancer-specific survival were clinical symptoms at presentation due to invasion or metastasis. Distant metastasis
and cancer-specific death were never seen postoperatively for 148 cases (83%) of asymptomatic PMC without
clinically apparent (>or=1 cm) lymph node metastasis or recurrent nerve palsy. Based on these results, we
identified three biologically different types of PMC that should be treated differently. Type I comprises incidentally
detected PMC without any symptoms, which is harmless and the lowest-risk cancer. Conservative follow-up with
ultrasonography every 6 or 12 months is feasible. Type II involves the early stage of the usual low-risk papillary
carcinoma. This can be treated by lobectomy when increasing size is noted during conservative follow-up. Type
III comprises clinically symptomatic PMC, representing a high-risk cancer. Immediate wider resection followed by
radioiodine treatment and suppression of thyroid-stimulating hormone is recommended. METHODS: Since 1995,
we have been conducting a prospective clinical trial of nonsurgical observation for asymptomatic PMC. As of
2008, 230 of 244 candidates (94%) have decided to accept this policy, whereas 56 patients underwent surgery
for symptomatic PMC between 1976 and 2006. RESULTS: Nonsurgical observation for a mean of 5 (range, 1-
17) years for 300 lesions of asymptomatic PMC revealed that 22 (7%) had increased in size, 269 (90%) were
unchanged, and 9 (3%) had decreased. No patients developed extrathyroidal invasion or distant metastasis.
Three patients (1%) who developed apparent lymph node metastasis and nine patients (4%) in whom tumor
increased in size eventually received surgery after 1-12 years of follow-up. No recurrences have been identified
postoperatively. Conversely, 10-year cause-specific survival for symptomatic PMC was 80%. Multivariate
analysis identified extrathyroidal invasion, large lymph node metastasis (>or=2 cm), and poorly differentiated


ESES Review of Recently Published Literature 2010-2                                                   Page 10 of 63
component as significantly related to adverse outcomes. CONCLUSIONS: Nonsurgical observation seems to
represent an attractive alternative to surgery for asymptomatic PMC. Almost 95% of asymptomatic PMC patients
are type I, and another 5% are type II and can be treated with conservative surgery. A small number of PMCs
with bulky lymph node metastasis or extrathyroidal invasion are high-risk type III and require aggressive
treatment.
PubMed-ID: 20066418
http://dx.doi.org/10.1007/s00268-009-0359-x

Long-Term Outcome in 215 Children and Adolescents With Papillary Thyroid Cancer Treated During
1940 Through 2008.
World J Surg, 34(6):1192-202.
Hay ID, Gonzalez-Losada T, Reinalda MS, Honetschlager JA, Richards ML, Thompson GB. 2010.
BACKGROUND: Controversy exists regarding the aggressiveness of initial therapy in childhood papillary thyroid
cancer (PTC). Few studies with long-term outcome exist and second primary malignancies have rarely been
analyzed. METHODS: We studied 215 PTC patients younger than 21 years old managed during 1940 through
2008. The patients were aged 3-20 year old (median age = 16 years); the median follow-up was 29 years.
Recurrence and mortality details were taken from a computerized database. RESULTS: Median primary tumor
size was 2.2 cm. Six percent had distant metastases at presentation, 5% had incomplete tumor resection, 86%
had nodes removed at initial surgery, and 78% had nodal metastases. After complete surgical resection, PTC
recurred in 32% by 40 years. At 20 years, the recurrence rates at local, regional, and distant sites were 7, 21,
and 5%, respectively. During 1940-1969, local and regional recurrence rates after unilateral lobectomy (UL) were
significantly (P < 0.001) higher than after bilateral lobar resection (BLR). During 1950-2008 radioiodine remnant
ablation (RRA) was administered within 18 months to 32%; it did not diminish the 25-year regional recurrence
rate of 16% seen after BLR alone (P = 0.86). Only two fatal events from PTC occurred at 28 and 30 years, for a
cause-specific mortality at 40 years of only 2%. All-causes mortality rates did not exceed expectation through 20
years, but from 30 through 50 years, the number of deaths was significantly (P < 0.001) higher than predicted.
Fifteen of 22 deaths (68%) resulted from nonthyroid malignancy. CONCLUSION: Survival from childhood PTC
should be expected, but later death from nonthyroid malignancy is disconcerting. Seventy-three percent of those
who died from nonthyroid malignancy had received postoperative therapeutic irradiation.
PubMed-ID: 20087589
http://dx.doi.org/10.1007/s00268-009-0364-0

Diagnostic Utility of Fine-Needle Aspiration Cytology in Pediatric Differentiated Thyroid Cancer.
World J Surg, 34(6):1254-60.
Bargren AE, Meyer-Rochow GY, Sywak MS, Delbridge LW, Chen H, Sidhu SB. 2010.
BACKGROUND: Pediatric patients present with thyroid nodules less often than adults, but the rate of
malignancy is much higher. This study was designed to determine the ability of fine-needle aspiration cytology
(FNA) to diagnose accurately and facilitate management of thyroid neoplasms in pediatric patients. METHODS:
A retrospective study revealed 110 patients <19 years old who had undergone thyroid surgery and FNA biopsy
at two academic institutions over the last 28 years. FNA sensitivity for diagnosing papillary thyroid cancer (PC)
and follicular neoplasm (FN) was investigated. RESULTS: Of 110 patients who presented for surgery, 27 had PC
and 33 had a FN: 4 follicular carcinomas (FCs) and 29 follicular adenomas (FAs). Among the PCs patients, the
FNA results were as follows: 1 (4%) nondiagnostic, 6 (22%) atypical, 2 (7%) benign, and 18 (67%) malignant
lesions. The sensitivity of a malignant FNA was 90% for diagnosing a PC. Sensitivity of an atypical FNA was
75% for FCs and 69% for FAs, giving an overall FN sensitivity of 70%. Of the atypical FNA readings, 60% had
confirmed histological atypical features, and 19% were malignant. In 95% of the malignant FNA reports, final
histology confirmed PC, resulting in a positive predictive value of 95%. CONCLUSIONS: FNA biopsy can reliably
diagnose malignancy in pediatric thyroid patients and should be used as a standard technique to indicate
surgical treatment. Atypical or suspicious FNA results do not predict cancer effectively, confirming the current
accepted practice for adults that diagnostic excision is required to exclude malignancy in pediatric patients.
PubMed-ID: 20091309
http://dx.doi.org/10.1007/s00268-010-0391-x

Is Thymectomy Worthwhile in Central Lymph Node Dissection for Differentiated Thyroid Cancer?
World J Surg, 34(6):1181-6.
El KZ, Lamblin J, Aubert S, Arnalsteen L, Leteurtre E, Caiazzo R, Pattou F, Carnaille B. 2010.
BACKGROUND: Clinical guidelines edited in 2006 by the American Thyroid Association (ATA) and stated in the
European Thyroid Association Consensus (ETA) recommend routine central lymph node dissection (level VI
neck dissection) in addition to thyroidectomy for the surgical treatment of differentiated thyroid cancer. This

ESES Review of Recently Published Literature 2010-2                                               Page 11 of 63
central dissection increases the incidence of postoperative hypocalcemia, which is related to the resection or
devascularization of the inferior parathyroids together with bilateral thymectomy. Some authors perform
unilateral thymectomy in order to minimize this complication. Our aim was to study the benefit/risk (incidence of
thymic lymph node metastases versus postoperative hypocalcemia) of both procedures. METHODS: We
retrospectively reviewed the records of 138 patients who underwent total thyroidectomy with central neck lymph
node dissection for differentiated thyroid cancer between 2004 and 2007. Bilateral thymectomy was performed in
45 patients (group 1, 15 males and 30 females) and unilateral thymectomy was performed in 93 patients (group
2, 27 males and 66 females). Forty-two papillary and 3 medullary cancers were found in group 1, and 75
papillary, 2 follicular, and 17 medullary cancers were found in group 2. The presence of thymic metastases at
pathology and the occurrence of postoperative hypocalcemia were reviewed. RESULTS: Two cases of papillary
thymic metastases were found in group 1. These were lymph node micrometastases localized in the ipsilateral
side of the primary tumor in both cases. Transient hypocalcemia was significantly more frequent (P < 0.001) in
group 1 than in group 2: 16 patients (35.5%) versus 10 (10.7%). There was one case of permanent
hypocalcemia in group 1 after the follow-up period. CONCLUSIONS: Bilateral thymectomy risk outweighs any
likely carcinologic benefit. We do not recommend routine bilateral thymectomy during central neck dissection for
differentiated thyroid cancer.
PubMed-ID: 20094884
http://dx.doi.org/10.1007/s00268-009-0363-1

Weight Difference Between Double Parathyroid Adenomas Is the Cause of False-Positive IOPTH Test
After Resection of the First Lesion.
World J Surg, 34(6):1337-42.
Sitges-Serra A, az-Aguirregoitia FJ, de la QA, Gil-Sanchez J, Jimeno J, Prieto R, Sancho JJ. 2010.
BACKGROUND: Some patients with double parathyroid adenoma show a greater than 50% decline in
intraoperative parathyroid hormone (IOPTH) after resection of the first lesion. The present study was designed to
test the hypothesis that significant adenoma weight differences may explain this inappropriate decline of IOPTH.
METHODS: We reviewed prospective database records at two tertiary institutions. Patients with a
histopathologic diagnosis of double adenoma and no familial history of hyperparathyroidism were included.
Diagnosis of double adenoma was confirmed either preoperatively (double uptake), intraoperatively (bilateral
exploration), or at reintervention. IOPTH was determined following the Miami protocol. The 10-min postexcision
sample was considered as the 0-min sample for IOPTH determinations at the time of resection of the second
lesion. RESULTS: Thirteen patients met the inclusion criteria. After resection of the first lesion, IOPTH failed to
decline in four patients and a second adenoma was removed. They had similar weight (404 vs. 598 mg). In nine
patients IOPTH showed a false greater than 50% decline. These patients had the largest adenoma removed first
(846 +/- 226 mg), and only two had normal PTH serum concentrations 10 min after resection. The second
adenoma was always smaller (284 +/- 177 mg; P = 0.02) and its resection either during the same operation (7
cases) or at reoperation (2 cases) led to normalization of IOPTH at 10 min in all cases. CONCLUSIONS: Two-
thirds of patients with double parathyroid adenoma show a false-positive decline of IOPTH after resection of the
first adenoma. This appears to be due to the initial removal of the larger lesion.
PubMed-ID: 20107797
http://dx.doi.org/10.1007/s00268-010-0413-8

Course of Ionized Calcium After Thyroidectomy.
World J Surg, 34(5):987-92.
de Andrade SA, Salles JM, Soares JM, de Moraes GM, Carvalho JR, Rocha PR. 2010.
BACKGROUND: The goal of the present study was to investigate the course of ionized calcium after
thyroidectomy and to define a cut-off value that indicates symptoms of hypocalcemia. METHODS: The sample
included 333 patients undergoing thyroidectomy at the University Hospital of UFMG between September 2000
and December 2005. Ionized calcium was determined before and after surgery (days 1, 2, and 30) in all patients
and on postoperative days 90 and 180 in those with hypocalcemia. Asymptomatic patients received no calcium
replacement therapy, irrespective of calcium concentration. Patients with clinical manifestation of hypocalcemia
were treated after laboratory confirmation. The presence or absence of postoperative hypocalcemia was
associated with ionized calcium concentration measured on the reported days. RESULTS: Ionized calcium
declined on the first two days after surgery in all patients when compared to preoperative levels (P = 0.000).
Forty-seven (34.6%) of the 136 (40.8%) patients with postoperative hypocalcemia had symptoms. Patients with
symptomatic hypocalcemia had significantly lower ionized calcium levels than those with asymptomatic
hypocalcemia (P = 0.001). Fourteen (4.2%) patients progressed to definitive hypoparathyroidism by the end of 6
months. CONCLUSIONS: Measurement of ionized calcium on postoperative days 1 and 2 is sufficient for the
evaluation of post-thyroidectomy hypocalcemia. Ionized calcium concentrations <1.03 mmol/l on postoperative


ESES Review of Recently Published Literature 2010-2                                                 Page 12 of 63
day 1 are indicative of the presence of symptoms and the need for treatment.
PubMed-ID: 20127243
http://dx.doi.org/10.1007/s00268-010-0415-6

Impact of Prophylactic Central Neck Lymph Node Dissection on Early Recurrence in Papillary Thyroid
Carcinoma.
World J Surg, 34(6):1187-91.
Moo TA, McGill J, Allendorf J, Lee J, Fahey T, III, Zarnegar R. 2010.
BACKGROUND: Although the role of prophylactic central neck lymph node dissection (CNLD) in the treatment of
papillary thyroid carcinoma (PTC) is controversial, many surgeons perform routine prophylactic CNLD. The
present study compares local recurrence rates in PTC patients undergoing total thyroidectomy with and without
prophylactic CNLD. MATERIALS AND METHODS: A retrospective review of 206 patients undergoing
thyroidectomy for PTC was conducted at two tertiary referral centers. Of these, 81 patients had total
thyroidectomy for PTC and a follow-up between 2 and 9 years with a mean of 3.1 years. Of these 81 patients, 45
underwent routine prophylactic CNLD and 36 did not. For those two groups, demographics, clinical and
pathologic findings, radioactive iodine (RAI) treatment, and the incidence of recurrence were compared.
Univariate statistical analysis was performed. RESULTS: There was no significant difference in age, gender,
multifocality, or extrathyroidal extension for the two groups. Patients with CNLD had an average tumor size of
1.4 cm versus 2 cm in the group without CNLD (p < 0.05). Patients who underwent CNLD had an average of 8
nodes removed, and positive nodes were found in 33%. Patients with CNLD received a higher dose of RAI,
102.7 mCi versus 66.3 mCi (p < 0.05). The incidence of positive nodes correlated with an increased RAI dose (r
= 0.55). Rates of parathyroid removal and autotransplantation were higher in the CNLD group, 36 and 16% in
the CNLD group versus 22 and 3% in the group without CNLD (p = 0.4 and p = 0.07). Rates of temporary
hypocalcemia were higher in the CNLD group (31 versus 5%; p = 0.001), however rates of permanent
hypocalcemia were similar, 1/35 in the no CNLD group versus 0/45 in the CNLD group (p = 0.4). There was a
higher recurrence rate among patients without CNLD 6/36 (16.7%) versus 2/45 (4.4%), although this difference
was not statistically significant (p = 0.13). CONCLUSIONS: Routine CNLD as an adjunct to total thyroidectomy
identifies positive nodes in over 30% of patients with PTC. The discovery of positive nodes is associated with
higher doses of RAI for postoperative ablation, and there is a trend toward decreased recurrence in patients
undergoing CNLD.
PubMed-ID: 20130868
http://dx.doi.org/10.1007/s00268-010-0418-3

Removal of Autografted Parathyroid Tissue for Recurrent Renal Hyperparathyroidism in Hemodialysis
Patients.
World J Surg, 34(6):1312-7.
Tominaga Y, Matsuoka S, Uno N, Tsuzuki T, Hiramitsu T, Goto N, Nagasaka T, Watarai Y, Uchida K. 2010.
BACKGROUND: Recurrent renal hyperparathyroidism (HPT) is a serious problem after parathyroidectomy
(PTx). We evaluated the frequency of graft-dependent recurrent HPT and the clinical outcomes after removal of
the autograft. METHODS: Between March 1980 and January 2009, 2660 patients underwent total PTx with
forearm autograft. After resection of all parathyroid glands, 30 pieces of 1 x 1 x 3 mm parathyroid tissue from
diffuse hyperplasia, if possible, were autografted into brachioradial muscle. Graft-dependent recurrence of HPT
was diagnosed by a high PTH gradient and detection of swollen autografts by palpation and/or MRI or US.
RESULTS: In 248/2660 (9.3%) patients, removal of the graft was required a total of 327 times (53 patients
required removal of the autograft several times). The cumulative frequency of graft-dependent recurrent HPT
was 17.4% ten years after the initial PTx. Thirty-two patients underwent both resection of missed glands located
in the neck or mediastinum and removal of the graft. En-bloc resection of autograft with surrounding muscle was
required to avoid reoperation. When the intact PTH level dropped under 300 pg/ml, in the majority of patients
renal HPT could be medically managed after the operation. The mean weight of the resected parathyroid tissue
was 1583.7 mg. No specimen had histopathologically malignant features. Three patients suffered from
hematoma in the wound. CONCLUSIONS: Graft-dependent recurrent renal HPT is not negligible. However, in
the majority of patients, renal HPT can be controlled by removal of the autograft noninvasively. Total PTx with
forearm autograft is preferable for hemodialysis patients, especially when long-term survival is expected.
PubMed-ID: 20130870
http://dx.doi.org/10.1007/s00268-010-0412-9

Surgeon-Performed Ultrasound in Patients Referred for Thyroid Disease Improves Patient Care by
Minimizing Performance of Unnecessary Procedures and Optimizing Surgical Treatment.
World J Surg, 34(6):1164-70.

ESES Review of Recently Published Literature 2010-2                                              Page 13 of 63
Mazzaglia PJ. 2010.
BACKGROUND: Ultrasonography has become an indispensable tool in the evaluation of thyroid nodular
disease, and most patients will have had a thyroid ultrasound prior to initial surgical evaluation. This study
examines the added benefit of office-based, surgeon-performed ultrasonography in patients referred for thyroid
disease. METHODS: All patients referred to a single endocrine surgeon for evaluation of thyroid disease over a
2-year period were reviewed. Outside ultrasonographic findings were compared to the surgeon-performed
ultrasound that was used to formulate treatment decisions. RESULTS: Of 286 consecutive patients referred for
surgical evaluation of thyroid disease, 261 had an outside ultrasound available for comparison. There were 239
women and 47 men. Mean age was 54.7 +/- 16.6. In 46 patients (17.6%), differences between the two
ultrasounds were significant enough to alter treatment plans. For 18 patients no distinct nodule was identified
and biopsy was avoided. Nine of these patients had ultrasound characteristics of Hashimoto's disease. In five
patients the nodule was significantly smaller than reported and biopsy was not warranted. Twelve patients had
nonpalpable, enlarged lymph nodes not previously identified; these were biopsied. Three were positive for
metastatic thyroid cancer, which prompted the addition of neck dissection to the operative procedure. In 8 of 132
patients undergoing thyroidectomy, the surgical procedure was significantly altered by the ultrasound findings.
CONCLUSIONS: This study demonstrates a clear advantage for patients who undergo a surgeon-performed
ultrasound. For many, unnecessary procedures were prevented. For others, substantial modifications to the
extent of surgery were made when new ultrasonographic findings were identified during the preoperative
investigation.
PubMed-ID: 20135315
http://dx.doi.org/10.1007/s00268-010-0402-y

Exclusion of Malignancy in Thyroid Nodules With Indeterminate Fine-Needle Aspiration Cytology After
Negative 18F-Fluorodeoxyglucose Positron Emission Tomography: Interim Analysis.
World J Surg, 34(6):1247-53.
Traugott AL, Dehdashti F, Trinkaus K, Cohen M, Fialkowski E, Quayle F, Hussain H, Davila R, Ylagan L, Moley
JF. 2010.
BACKGROUND: In all, 20% of fine-needle aspiration (FNA) biopsies of thyroid nodules have an indeterminate
diagnosis; of these, 80% are found to be benign after thyroidectomy. Some previous reports indicate that
positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) imaging may predict malignancy
status. We now report results on the first 51 patients in the largest prospective study of FDG-PET in patients with
an indeterminate thyroid nodule FNA. METHODS: Eligible patients had a dominant thyroid nodule that was
palpable or >or=1 cm in greatest dimension as seen by ultrasonography, and indeterminate histology of the FNA
biopsy specimen. Participants underwent preoperative neck FDG-PET alone or FDG-PET with computed
tomography (FDG-PET/CT). Images were evaluated qualitatively and semiquantitatively using the maximum
standardized uptake value (SUV(max)). Final diagnosis was determined by histopathologic analysis after
thyroidectomy. Descriptive statistical analysis was performed. RESULTS: A total of 51 patients underwent
preoperative FDG-PET or FDG-PET/CT. Studies without focally increased uptake localized to the lesion were
considered negative. For all lesions (10 malignant, 41 benign), the sensitivity, specificity, positive-predictive
value (PPV), and negative-predictive value (NPV) were 80%, 61%, 33%, and 93%, respectively. Postoperatively,
two malignant and six benign lesions were found to be <1 cm by pathology examination; one lesion was not
measured. When these lesions were excluded, the sensitivity, specificity, PPV, and NPV were 100%, 59%, 36%,
and 100%, respectively. CONCLUSIONS: Based on these preliminary data, FDG-PET may have a role in
excluding malignancy in thyroid nodules with an indeterminate FNA biopsy. This finding justifies ongoing accrual
to our target population of 125 participants.
PubMed-ID: 20140435
http://dx.doi.org/10.1007/s00268-010-0398-3

The Impact of Intraoperative Neuromonitoring (IONM) on Surgical Strategy in Bilateral Thyroid Diseases:
Is It Worth the Effort?
World J Surg, 34(6):1274-84.
Goretzki PE, Schwarz K, Brinkmann J, Wirowski D, Lammers BJ. 2010.
BACKGROUND: Intraoperative nerve monitoring (IONM) of the recurrent laryngeal nerve and the vagal nerve
can detect nonfunctioning nerves (recurrent laryngeal nerve palsy, RLNP) that are visibly intact. The use of
IONM is questionable, however, as we still lack evidence that it reduces the rate of postoperative nerve injuries.
Since negative IONM results after thyroid dissection of the first side could change our surgical strategy and thus
could prevent patients from bilateral RLNP, we questioned whether IONM results are reliable enough to base
changes in surgical strategy and whether this has any effect on surgical outcome. METHODS: We
retrospectively analyzed the data of 1333 consecutive patients with suggested benign bilateral thyroid disease


ESES Review of Recently Published Literature 2010-2                                                Page 14 of 63
who had been operated on under a defined protocol, including the use of a specific IONM technique (tube
electrodes and stimulation of the vagal nerve and the inferior recurrent nerve before and after thyroid resection),
between January 1, 2006 and December 31, 2008. RESULTS: In four patients the IONM system did not work,
two nerves had not been found, and in eight patients the tube had to be readjusted. Of five permanent nerve
injuries, four were visible during surgery and one was suspected. Sensitivity of IONM in detecting temporary
nerve injuries of macroscopically normal-appearing nerves was 93%. Specificity was 75-83% at first side of
dissection and 55-67% at the second side, with an overall specificity of 77%. In 11 of 13 patients (85%) with
known nerve injury (preexisting or visible) and in 20 of 36 patients (56%) with negative IONM stimulation at the
first side of dissection, the surgical strategy was changed (specific surgeon or restricted resection) with no
postoperative bilateral RLNP. This was in contrast to 3 of 18 (17%) bilateral RLNP (p < 0.05), when surgeons
were not aware of a preexisting or highly likely nerve injury at the first side of thyroid dissection.
CONCLUSIONS: Failed IONM stimulation of the vagal or recurrent laryngeal nerve after resection of the first
thyroid lobe is specific enough to reconsider the surgical strategy in patients with bilateral thyroid disease to
surely prevent bilateral RLNP.
PubMed-ID: 20143072
http://dx.doi.org/10.1007/s00268-009-0353-3

New Operative Surgical Concept of Two Fascial Layers Enveloping the Recurrent Laryngeal Nerve.
Ann Surg Oncol , 17(6):1628-36.
Serpell JW. 2010.
BACKGROUND: Avoiding recurrent laryngeal nerve (RLN) injury is aided by a precise anatomical understanding
of the RLN before entry into the larynx where it is at greatest risk. METHODS: A literature review and study of
977 RLNs at operation have been used to describe the last 2 cm of the anatomical course of the extralaryngeal
RLN. RESULTS: The tertiary branches of the inferior thyroid artery pass in a superficial vascular fascial layer
anterolateral to the RLN. The tubercle of Zuckerkandl and the superior parathyroid glands lie within this
superficial vascular fascial covering layer. The RLN lies on a deeper layer of more fibrous tissue, the ligament of
Berry. In all 977 RLNs, the RLN was sandwiched between an anterolateral vascular layer and a medial layer, the
ligament of Berry. CONCLUSIONS: The site of greatest risk during thyroidectomy to the RLN is in the 2-cm
course of the extralaryngeal nerve above the trunk of the inferior thyroid artery where tension forms an artificial
genu of the nerve. Once the superficial vascular fascial and Berry's ligament layers are released, the nerve falls
back into the tracheoesophageal groove and adopts a serpiginous appearance, indicating completeness of the
dissection of the lobe from the lateral trachea and division of the ligament of Berry.
PubMed-ID: 20143268
http://dx.doi.org/10.1245/s10434-010-0928-0

Outcome of Total Parathyroidectomy and Autotransplantation As Treatment of Secondary and Tertiary
Hyperparathyroidism in Children and Adults.
World J Surg, 34(5):993-1000.
Kievit AJ, Tinnemans JG, Idu MM, Groothoff JW, Surachno S, Aronson DC. 2010.
BACKGROUND: Treatment safety and effectiveness of total parathyroidectomy and autotransplantation for
secondary and tertiary hyperparathyroidism have been extensively proven in adults; the evidence for children,
however, is scarce. Children and adolescents cannot simply be seen as young adults in the case of chronic
kidney disease and hyperparathyroidism. The aim of this retrospective study was therefore, to evaluate whether
parathyroidectomy with forearm autograft is as effective and safe in children and adolescents as in adults.
METHODS: A group of 64 adults and 8 children and adolescents treated for secondary or tertiary
hyperparathyroidism were retrieved from our database. The outcomes were compared on patient demographics,
operation results, and blood parameters consisting of parathyroid hormone (PTH) and calcium levels. Our results
were compared with all currently available articles on parathyroidectomy in children with secondary or tertiary
hyperparathyroidism (n = 11). RESULTS: For adults, preoperative mean serum calcium was 2.67 +/- 0.29 mmol/l
and mean parathyroid hormone (PTH) level was 120 +/- 86 pmol/l. For children, preoperative mean serum
calcium was 2.62 +/- 0.20 mmol/l and mean parathyroid hormone (PTH) level was 80 +/- 38 pmol/l.
Postoperative calcium and parathyroid hormone levels for adults dropped to 2.39 +/- 0.23 mmol/l and 30 +/- 53
pmol/l, respectively. Postoperative calcium and parathyroid hormone levels for children dropped to 2.41 +/- 0.16
mmol/l and 26 +/- 33 pmol/l, respectively. The effectiveness of parathyroidectomy with autotransplantation was
75% in children and 72% in adults. Thus, effectiveness did not differ significantly between children and adults.
CONCLUSIONS: Combining the results of our own study with a literature review on pediatric parathyroidectomy,
we conclude that parathyroidectomy and forearm autograft is as effective a treatment for secondary and tertiary
hyperparathyroidism in children and adolescents as it is in adults.



ESES Review of Recently Published Literature 2010-2                                                 Page 15 of 63
PubMed-ID: 20145928
http://dx.doi.org/10.1007/s00268-010-0446-z

Regulatory T Cells in Peripheral Blood, Lymph Node, and Thyroid Tissue in Patients With Medullary
Thyroid Carcinoma.
World J Surg, 34(7):1481-7.
Muller S, Poehnert D, Muller JA, Scheumann GW, Koch M, Luck R. 2010.
BACKGROUND: Immunological response of the human body is controlled by the suppressive characteristics of
regulatory T cells (Tregs). In various diseases a change in the number of Tregs is evident. For example,
whereas Tregs are reduced in auto-immunological processes, an increase of Tregs is found with various
malignant tumors. Regarding medullary thyroid carcinoma (MTC) no such studies have been performed to date.
METHODS: Expression of CD4 and CD25 in CD45+ leukocytes from blood and lymph nodes was studied by
flow cytometry in patients with MTC and patients with benign goiter. We also examined the marker forkhead box
P3 (FoxP3), an intracellular transcription factor, which is supposed to be the most specific marker for Tregs.
Immunohistochemical staining for FoxP3 was performed on lymph node and thyroid tissue. RESULTS: The
number of FoxP3+ lymphocytes in peripheral blood was significantly higher in patients with MTC than in controls
(p = 0.02). This result was confirmed immunohistochemically in lymph node and thyroid tissue, as well as in
carcinoma tissue. No difference in CD4+CD25+ lymphocytes was observed between the two groups. After
clinical staging (International Union against Cancer-UICC-stages) of MTC patients, triplication of FoxP3+
lymphocytes could be observed from MTC < UICC II to MTC > UICC II. CONCLUSIONS: An increase of FoxP3+
lymphocytes could be shown in peripheral blood of patients with MTC but not in patients with benign goiter; this
increase also correlates with findings in lymph nodes and thyroid gland. The number of FoxP3+ cells correlated
with the patients' prognosis. Therefore, FoxP3+ lymphocytes are a good diagnostic criterion for malignancy in
patients with medullary thyroid carcinoma, and their presence at staging may influence therapeutic decisions.
PubMed-ID: 20162276
http://dx.doi.org/10.1007/s00268-010-0484-6

An International Perspective on Ultrasound Training and Use for Thyroid and Parathyroid Disease.
World J Surg , 34(6):1157-63.
Miller BS, Gauger PG, Broome JT, Burney RE, Doherty GM. 2010.
BACKGROUND: Use of ultrasound (USN) by endocrine surgeons has dramatically increased. Presently, optimal
training and certification requirements have not been standardized at any level (resident/fellow/attending). We
sought to define the types of USN training endocrine surgeons receive and how USN is employed in practice.
We hypothesized that in more recent years fellowship-trained endocrine surgeons were more likely to receive
formal training in the use of USN during their endocrine surgery fellowship. METHODS: A survey link was sent
via email to a large group of endocrine surgeons around the world asking about the settings in which they
received USN training, the type of instruction received, current use of USN, and other various questions. chi(2)
analysis was performed and P < 0.05 was considered significant. RESULTS: One hundred twenty-one surveys
were collected from respondents in 27 countries. Median time from completion of residency to the present was
17 years (range = 2-49). Fifty-nine percent of both fellowship- and nonfellowship-trained endocrine surgeons
currently use USN in their practice. Of those currently performing USN, 38% reported no USN training of any
kind (47% international vs. 23% United States). USN experience among international and U.S. residents was not
different (P = 0.27). Fifty-nine percent of respondents reported completing an endocrine surgery fellowship; of
those, 85% reported no formal USN training. Forty-one percent reported not being comfortable performing USN
at the completion of their endocrine surgery fellowships, requiring the presence of someone else to assist with
the exam. CONCLUSIONS: USN training among endocrine surgeons varies widely around the world. Despite an
increase in the number of formal endocrine surgery fellowships offered, it does not appear that the number with
formal USN training and certification has increased. Formal USN certification is achieved in only a minority of
cases among practicing endocrine surgeons. It is currently unknown whether there is a difference in competency
between endocrine surgeons with formal versus informal USN training.
PubMed-ID: 20162277
http://dx.doi.org/10.1007/s00268-010-0481-9

Managing Patients With a Preoperative Diagnosis of AJCC/UICC Stage I (T1N0M0) Papillary Thyroid
Carcinoma: East Versus West, Whose Policy Is Best?
World J Surg, 34(6):1291-3.
Hay ID. 2010.
PubMed-ID: 20162281
http://dx.doi.org/10.1007/s00268-010-0469-5

ESES Review of Recently Published Literature 2010-2                                              Page 16 of 63
How to Approach Thyroid Nodules With Indeterminate Cytology.
Ann Surg Oncol, 17(8):2147-55.
Yoon JH, Kwak JY, Kim EK, Moon HJ, Kim MJ, Kim JY, Koo HR, Kim MH. 2010.
BACKGROUND: Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is an accurate, reliable, and
simple procedure to perform, and it is nowadays accepted as a standard diagnostic method for the differential
diagnosis of thyroid nodules. However, a major limitation of US-FNAB is indeterminate cytology results at a
thyroid nodule. This study investigated the clinical and US characteristics that predict malignancy, as well as the
role of intraoperative frozen sections (FS) in the treatment of thyroid nodules with indeterminate cytology.
METHODS: From September 2002 to December 2007, the medical records of 181 patients (185 nodules) with
indeterminate FNAB cytology results were retrospectively reviewed. Among them, 99 patients (M:F = 13:86;
mean age, 43.71 years) with 99 thyroid nodules underwent subsequent surgery with pathologic confirmation.
Seventy-eight patients (78.8%) underwent intraoperative FS. US findings of the surgically proven thyroid nodules
were retrospectively reviewed. US features, clinical characteristics, and FS results were compared to the
surgically proven pathologic results. RESULTS: Nineteen nodules (19.2%) with indeterminate FNAB cytology
were diagnosed as malignant. Lesion size varied from 4 to 70 mm (mean, 27.0 mm). Male patients (46.2%) were
more significantly associated with malignancy than female patients (15.1%, P < 0.05). Microlobulated or ill-
defined margins (87.5%), microcalcifications (50.0%), and taller-than-wide shape (80.0%) were US features
showing correlations with malignancy (P < 0.05). Intraoperative FS significantly predicted malignancy (P < 0.05).
Of the 78 cases with FS, 29 cases (37.2%) were deferred. Among the remaining 49 cases, 4 (5.1%) were
malignant on FS and subsequent surgical pathology. Forty-five cases (57.7%) were diagnosed as benign on FS,
but only two cases were diagnosed as malignant on surgical pathology. CONCLUSIONS: Ultrasound is a
feasible method in predicting malignancy in thyroid nodules with indeterminate FNAB cytology. Also,
intraoperative FS is a supportive method with high specificity that may guide the treatment of thyroid nodule with
indeterminate cytology.
PubMed-ID: 20217250
http://dx.doi.org/10.1245/s10434-010-0992-5

Medullary Thyroid Cancer: Are Practice Patterns in the United States Discordant From American Thyroid
Association Guidelines?
Ann Surg Oncol, 17(6):1490-8.
Panigrahi B, Roman SA, Sosa JA. 2010.
BACKGROUND: Surgery is the mainstay of treatment for medullary thyroid cancer (MTC), with long-term patient
outcomes associated with adequacy of resection. This study benchmarked national practice patterns against
2009 American Thyroid Association (ATA) guidelines for MTC regarding use of thyroidectomy,
lymphadenectomy, radioactive iodine (RAI), and external-beam radiotherapy (EBRT). METHODS: This is a
cross-sectional, retrospective cohort study of MTC patients in the Surveillance, Epidemiology, and End Results
Program database, 1973 to 2006. ATA recommendations 61 to 66 (extent of surgery), 85 (RAI), and 93 (EBRT)
were analyzed. Outcome of interest was practice accordance with these recommendations. Predictors of
accordance were determined and Kaplan-Meier survival analyses were performed. RESULTS: A total of 2033
patients with MTC were identified. Fifty-nine percent were women; 78% were white. Forty-one percent of
patients did not receive appropriate surgical therapy (recommendations 61 to 63). Most patients with distant
metastatic disease had less aggressive surgery and more EBRT (P < 0.001) (recommendations 64 to 66). Four
percent of patients received inappropriate RAI (recommendation 85). Two hundred nine patients had gross
incomplete resections, with 33% receiving postoperative EBRT (recommendation 93). Statistically significant
predictors of receiving surgery discordant with ATA recommendations in multivariate analysis were patient age
>65, female sex, earlier year of diagnosis (1988 to 1997), geographic region, intrathyroidal tumor extent, and
tumor size of </=1 cm. Patients receiving surgery discordant with recommendations had shorter survival than
those receiving surgery according to recommendations (P < 0.05). CONCLUSIONS: Variation in practice
patterns exist in the United States with regard to extent of surgery and lymphadenectomy for MTC.
Dissemination of standardized guidelines is important to ensure optimal treatment with less variation in quality of
care.
PubMed-ID: 20224861
http://dx.doi.org/10.1245/s10434-010-1017-0

What Would Be Left Behind If Subtotal Thyroidectomy Were Preferred Instead of Total Thyroidectomy?
Am J Surg, 199(6):765-9.
Tekin K, Yilmaz S, Yalcin N, Coban S, Aydin C, Kabay B, Erdem E, Ozbas S, Ozden A. 2010.
BACKGROUND: The choice between subtotal thyroidectomy (STT) and total thyroidectomy (TT) for multinodular
goiter (MNG) remains controversial. METHODS: Thyroid tissue samples of 34 patients who underwent TT for


ESES Review of Recently Published Literature 2010-2                                                 Page 17 of 63
multinodular disease between October 2005 and June 2007 in Pamukkale University Hospital, Department of
General Surgery were evaluated. Thyroid tissues weighing 2 g each from either side were separated from the
main specimen to simulate the tissues that would be left behind if a subtotal resection were performed instead of
a total resection. Ki-67 staining was performed. RESULTS: The mean age of subjects was 49.3 +/- 12 years and
25 (73.5%) were females. Papillary microcarcinomas were found in 4 patients, 1 of which was in a residual
thyroid specimen (RTS). Micronodule formations were found in 73.5% of specimens simulating residual thyroid.
While Ki-67 indexes of residual thyroid tissues were 4.65% in nodules and 1.91% in normal areas (P < .05), they
were 5.42% and 2.84%, respectively, for nodular and normal areas in the main specimens (P < .05).
CONCLUSION: Remnant thyroid tissues, following STT, have a high percentage of micronodule formation with a
remarkable cellular proliferative activity.
PubMed-ID: 20226438
http://dx.doi.org/10.1016/j.amjsurg.2009.02.005

Mild Hypercalcitoninaemia and Sporadic Thyroid Disease.
Br J Surg, 97(5):684-90.
Cherenko M, Slotema E, Sebag F, De MC, Henry JF. 2010.
BACKGROUND: Not operating on patients with mild hypercalcitoninaemia (MHCT) and sporadic thyroid disease
carries the risk of omitting curative surgery for medullary thyroid cancer, but systematic surgery would result in
unnecessary treatment of benign pathology. This study reviewed the management of MCHT and non-hereditary
thyroid disease in one centre. METHODS: MCHT was defined as an increase in basal and stimulated calcitonin
levels not exceeding 30 and 200 pg/ml respectively. Over 15 years, 125 patients who presented with MCHT and
sporadic thyroid disease were followed. Surgery was indicated only if there were local pressure symptoms or
suspicious histomorphological changes in solitary nodules. RESULTS: Fifty-five patients underwent total
thyroidectomy and 18 unilateral total lobectomy. Histological examination revealed medullary microcarcinoma in
six patients (two women and four men). C-cell hyperplasia was found in 54 patients (74 per cent) and 13 (18 per
cent) harboured no C-cell pathology. Calcitonin levels stabilized after lobectomy and became undetectable
following thyroidectomy. They normalized during follow-up in a third of patients who did not have surgery.
CONCLUSION: Not all patients with MHCT and sporadic thyroid disease require surgery.
PubMed-ID: 20235084
http://dx.doi.org/10.1002/bjs.6965

Long-Term Efficacy of Lymph Node Reoperation for Persistent Papillary Thyroid Cancer.
J Clin Endocrinol Metab , 95(5):2187-94.
Al-Saif O, Farrar WB, Bloomston M, Porter K, Ringel MD, Kloos RT. 2010.
OBJECTIVE: The objective of the study was to determine the outcome of surgical resection of metastatic
papillary thyroid cancer (PTC) in cervical lymph nodes after failure of initial surgery and I(131) therapy. DESIGN:
This was a retrospective clinical study. SETTING: The study was conducted at a university-based tertiary cancer
hospital. PATIENTS: A cohort of 95 consecutive patients with recurrent/persistent PTC in the neck underwent
initial reoperation during 1999-2005. All had previous thyroidectomy (+/-nodal dissection) and I(131) therapy.
Twenty-five patients with antithyroglobulin (Tg) antibodies were subsequently excluded. MAIN OUTCOME
MEASURES: Biochemical complete remission (BCR) was stringently defined as undetectable TSH-stimulated
serum Tg. RESULTS: A total of 107 lymphadenectomies were undertaken in these 70 patients through January
2010. BCR was initially achieved in 12 patients (17%). Of the 58 patients with detectable postoperative Tg, 28
had a second reoperation and BCR was achieved in five (18%), seven had a third reoperation, and none
achieved BCR. No patient achieving BCR had a subsequent recurrence after a mean follow-up of 60 months
(range 4-116 months). In addition, two more patients achieved BCR during long-term follow-up without further
intervention. In total, 19 patients (27%) achieved BCR and 32 patients (46%) achieved a TSH-stimulated Tg less
than 2.0 ng/ml. Patients who did not achieve BCR had significant reduction in Tg after the first (P < 0.001) and
second (P = 0.008) operations. No patient developed detectable distant metastases or died from PTC.
CONCLUSIONS: Surgical resection of persistent PTC in cervical lymph nodes achieves BCR, when most
stringently defined, in 27% of patients, sometimes requiring several surgeries. No biochemical or clinical
recurrences occurred during follow-up. In patients who do not achieve BCR, Tg levels were significantly reduced.
The long-term durability and impact of this intervention will require further investigation.
PubMed-ID: 20332244
http://dx.doi.org/10.1210/jc.2010-0063

Bilateral Internal Jugular Venous Sampling for Parathyroid Hormone Determination in Patients With
Nonlocalizing Primary Hyperparathyroidism.
World J Surg, 34(6):1299-303.

ESES Review of Recently Published Literature 2010-2                                                Page 18 of 63
Alvarado R, Meyer-Rochow G, Sywak M, Delbridge L, Sidhu S. 2010.
BACKGROUND: Focused parathyroidectomy (FP) is offered to 60% to 70% of patients presenting to our unit
with primary hyperparathyroidism (PHPT). A recent report identified bilateral internal jugular venous sampling
(BIJVS) as a useful tool for localization of parathyroid adenomas in patients with scan-negative PHPT. The
purpose of this study was to evaluate the utility of this approach in a clinical setting. METHODS: A prospective
case-control trial was undertaken. Bilateral internal jugular venous blood samples were obtained. Patients were
stratified into three groups: Group A consisted of patients with a negative sestamibi scan undergoing bilateral
exploration; group B consisted of patients undergoing FP following a positive sestamibi scan; and group C
patients were a control group undergoing total thyroidectomy. RESULTS: In group A, 17 of 30 patients (56%)
had lateralization of the parathyroid hormone (PTH) levels, with 11 correctly lateralizing to the side of the
adenoma, 5 lateralizing despite bilateral disease, and 1 lateralizing to the contralateral side. Of the remaining 13
patients in whom there was no lateralization, 3 had bilateral multigland disease, and 10 had a single parathyroid
adenoma. In group B, 17 of 30 patients (56%) also had lateralization of PTH levels, with 15 lateralizing to the
side of the adenoma and 2 to the contralateral side. Lateralization failed in the remaining 13 patients, although in
all of these patients the calcium and PTH levels normalized postoperatively. The control group of patients
without parathyroid disease (group C) demonstrated lateralization of PTH levels in 23 of 30 patients (76%).
CONCLUSIONS: In our hands, BIJVS for PTH determination was not a useful adjunctive test facilitating FP. We
continue to offer all patients with PHPT and a negative sestamibi scan a standard bilateral neck exploration.
PubMed-ID: 20372897
http://dx.doi.org/10.1007/s00268-010-0556-7

Clinical and Imaging Assessment of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinomas.
World J Surg, 34(7):1494-9.
Choi YJ, Yun JS, Kook SH, Jung EC, Park YL. 2010.
BACKGROUND: The goals of this study were to analyze clinical factors that affect cervical lymph node
metastasis (LNM) in papillary thyroid cancer (PTC), and to evaluate the diagnostic accuracy of preoperative
ultrasound (US) and computed tomography (CT) of the neck. METHODS: The study sample included 589
consecutive patients who underwent surgery for PTC. Patient age and sex, number, size, and location of tumors,
lymphovascular invasion, and extrathyroidal extension were evaluated as risk factors for central and lateral LNM.
RESULTS: Increased risk of lymph node metastasis was found for male patients, <45 years old, with tumor size
>1 cm, lymphovascular invasion, and extrathyroidal invasion. Cancers located in the upper neck had a higher
relative risk of lateral metastasis than cancers located in the lower neck. Sensitivity of both US and CT imaging
was higher for lateral (70-80%) than for central (42-47%) LNM. Specificity of US and CT was high (92-97%) for
both central and lateral LNM. Using central lymph node size of greater than 5 mm as an indicator of metastasis,
preoperative US had 58.3% sensitivity and 71.4% specificity. CONCLUSIONS: Preoperative US and CT imaging
are useful for identifying features that indicate a high risk of LNM and for determining appropriate management
of PTC.
PubMed-ID: 20372903
http://dx.doi.org/10.1007/s00268-010-0541-1

Intramuscular Injection of Parathyroid Autografts Is a Viable Option After Total Parathyroidectomy.
World J Surg, 34(6):1332-6.
Tan CC, Cheah WK, Tan CT, Rauff A. 2010.
INTRODUCTION: Surgical transplantation of parathyroid gland into muscle is an established technique after
total parathyroidectomy for renal hyperparathyroidism. However, no study has examined the role of injecting
parathyroid tissue in these patients. We compared the outcome of surgical transplantation of parathyroid glands
by implantation ("implant") versus that of intramuscular injection ("inject"). METHODS: Patients who had total
parathyroidectomy for tertiary hyperparathyroidism due to chronic renal failure from 2001-2008 are included in
this study. For the implant group, a parathyroid gland is divided into 10-12 pieces (each of 2-mm in diameter)
before embedding into the deltoid or brachioradialis muscle. Patients in the inject group, each had a finely
minced gland injected into the deltoid. Postoperatively, the graft is deemed to be functioning if 1) serum PTH is
normal, or 2) serum calcium is normal in the absence of calcium supplements or reduced dosage requirements;
these assays are performed at least 1 month after initial surgery. Recurrence is defined by the presence of
hyperparathyroidism requiring autograft excision. RESULTS: A total of 66 patients (23 men, 43 women) were
included in the study. The implant group comprised 31 patients (mean age 49.9 +/- 14.0), and the inject group
had 35 patients (mean age 49.2 +/- 10.4; P = 0.80). The mean follow-up period for implant was longer at 40.1
months compared with 16.2 months for inject (P = 0.001). Operative time for implant was slightly longer at 111
min versus 106 min for inject (P = 0.51). Graft function was achieved in 27 (87.1%) implant patients and 20
(69%) inject patients (P = 0.08). Recurrence was seen in four (12.9%) implant patients compared with one


ESES Review of Recently Published Literature 2010-2                                                  Page 19 of 63
(2.9%) inject patient, after a mean period of 28.8 months. This difference was not statistically significant (P =
0.18). CONCLUSIONS: Intramuscular injection of parathyroid tissue is a feasible alternative to surgical
transplantation by implantation after total parathyroidectomy in tertiary hyperparathyroidism. The injection
method was slightly faster to perform. However, injection achieved a slightly lower graft function rate but the risk
of autograft hyperplasia also was lower.
PubMed-ID: 20372906
http://dx.doi.org/10.1007/s00268-010-0531-3

Secondary and Tertiary Hyperparathyroidism: the Utility of IoPTH Monitoring.
World J Surg, 34(6):1343-9.
Pitt SC, Panneerselvan R, Chen H, Sippel RS. 2010.
BACKGROUND: The aim of the present study was to examine the utility of intraoperative parathyroid hormone
(ioPTH) monitoring in patients with secondary (2) and tertiary (3) hyperparathyroidism (HPT). MATERIALS AND
METHODS: We identified 105 patients with 2HPT (n = 33) and 3HPT (n = 72) who underwent ioPTH monitoring
during parathyroidectomy. Data are reported as mean +/- SEM. RESULTS: The 2HPT patients underwent 17
subtotal, 10 total, and 6 re-exploratory parathyroidectomies, whereas the 3HPT patients underwent 54 subtotal,
15 limited, and 3 re-exploratory parathyroidectomies. The percent decrease from the baseline ioPTH level at 5,
10, and 15 min after parathyroid resection, respectively, were 72% +/- 3%, 76% +/- 3%, and 76% +/- 3% in
patients with 2HPT, and 52% +/- 6%, 60% +/- 4%, and 69% +/- 4% in patients with 3HPT. IoPTH levels failed to
drop >50% from baseline in 5 patients (2HPT: n = 2, 3HPT: n = 3) who were normocalcemic at last follow-up.
IoPTH did not alter the surgical approach in any 2HPT patients, but did alter management in 25% of 3HPT
patients (15 limited resections and 3 supernumerary glands). Normocalcemia was achieved in 97% of 2HPT
patients and 99% of 3HPT patients; 2 patients developed recurrent disease. CONCLUSIONS: Intraoperative
PTH levels fell by >50% in nearly 95% of patients with 2HPT and 3HPT, and the PTH level reliably predicted
postoperative cure. Although the use of ioPTH did not alter surgical management in any patient with 2HPT, this
rapid PTH assay affected the surgical care of a quarter of the patients with 3HPT, and it may prove to be a
useful adjunct in this group of patients.
PubMed-ID: 20386902
http://dx.doi.org/10.1007/s00268-010-0575-4

Normalization of 2-Week Postoperative Parathyroid Hormone Values in Patients With Primary
Hyperparathyroidism: Four-Gland Exploration Compared to Focused-Approach Surgery.
World J Surg, 34(6):1318-24.
Mazzaglia PJ, Milas M, Berber E, Siperstein A, Monchik JM. 2010.
BACKGROUND: Elevation of parathyroid hormone (PTH) levels is commonly seen in patients with primary
hyperparathyroidism (PHPT) who have undergone parathyroidectomy. This study evaluates differences in 2-
week postoperative PTH levels in patients having focused-approach surgery versus four-gland exploration.
METHODS: Over 6 years, patients at Rhode Island Hospital (RIH) and the Cleveland Clinic (CCF) who had
PHPT and underwent localization studies suggestive of single adenoma were analyzed. At RIH patients
underwent focused-approach surgery, and at CCF routine four-gland exploration was performed. Postoperative
calcium supplementation was routine at RIH and selective at CCF. RESULTS: There were 308 patients at RIH
and 370 at CCF. They were similar in age (59.2 +/- 13.0 years at RIH and 60.4 +/- 12.9 years at CCF), and sex
(76.9 and 80.0% female at RIH and CCF, respectively). The mean preoperative serum calcium measured 10.9
+/- 0.7 mg/dl at RIH and 11.1 +/- 0.7 mg/dl at CCF (P < 0.001). Preoperative PTH values were similar,
measuring 143.8 +/- 104.8 pg/ml in the focused-approach group (RIH) and 157.6 +/- 150.3 pg/ml in the four-
gland exploration group (CCF). Preoperative 25-hydroxyvitamin D (vitamin D-25) levels were 24.1 +/- 12.0 ng/ml
at RIH and 27.4 +/- 10.6 ng/ml at CCF; and the prevalence of vitamin D-25 deficiency (level <20 ng/ml) was
43.9% at RIH and 27% at CCF (P = 0.017). The proportion of patients whose intraoperative PTH value dropped
by >or=50% prior to completion of surgery was 95.0% at RIH and 95.5% at CCF. The total gland weight resected
per patient was 942 mg at RIH versus 1,394 mg at CCF (P = 0.003). The 2-week postoperative serum PTH was
>65 pg/ml in 18.8% at RIH and in 38.7% at CCF (P < 0.001). The 2-week postoperative serum calcium values
dropped to 9.2 +/- 0.6 mg/dl at RIH and to 9.5 +/- 0.8 mg/dl at CCF (P < 0.001). The incidence of multigland
disease was 5.8% at RIH and 21.9% at CCF (P <or= 0.001). CONCLUSIONS: Among patients with PHPT who
underwent a localizing study indicating unilateral disease, a significant proportion had eucalcemic PTH elevation
2 weeks after parathyroidectomy. The elevation was more frequent in the four-gland exploration group and
correlated most strongly with greater adenoma mass.
PubMed-ID: 20386907
http://dx.doi.org/10.1007/s00268-010-0557-6



ESES Review of Recently Published Literature 2010-2                                                  Page 20 of 63
Treatment With Tyrosine Kinase Inhibitors for Patients With Differentiated Thyroid Cancer: the M. D.
Anderson Experience.
J Clin Endocrinol Metab, 95(6):2588-95.
Cabanillas ME, Waguespack SG, Bronstein Y, Williams MD, Feng L, Hernandez M, Lopez A, Sherman SI,
Busaidy NL. 2010.
OBJECTIVES: Until recently, treatment options for patients with progressive, radioactive iodine-resistant
differentiated thyroid cancer (DTC) have been limited. In our clinical practice, we have begun to use sorafenib
and sunitinib for patients with progressive DTC who are not able or willing to participate in clinical trials. In this
paper, we describe the University of Texas M. D. Anderson Cancer Center's experience with the off-label use of
these tyrosine kinase inhibitors for DTC. METHODS: Adult patients were included if they had a diagnosis of
radioactive iodine-refractory DTC, were treated with single agent sorafenib or sunitinib, and had both baseline
and at least one follow-up scan for restaging purposes. All imaging data were collected, as well as the TSH-
suppressed thyroglobulin (Tg) levels corresponding to each scan date. The primary endpoints were radiographic
response and progression-free survival (PFS). Secondary objectives were tissue-specific radiographic
responses and correlation of Tg with overall response. RESULTS: We identified 33 patients from our clinical
database. Fifteen patients (nine women, six men) met inclusion criteria, with a median age of 61 yr (range, 38-83
yr). Eight patients had papillary and seven had follicular thyroid carcinoma. Sorafenib was used in 13 and
sunitinib in two, including one patient who failed prior sorafenib therapy. All patients had evidence of progressive
disease (PD) before start of therapy, with a median PFS of only 4 months. Best response in target lesions was:
partial response (PR) in three (20%), stable disease (SD) in nine (60%), and PD in three (20%). Clinical benefit
(PR+SD) was 80%. The sunitinib patient previously refractory to sorafenib had a 38% reduction in tumor size.
The most noticeable organ-specific response was observed in lung (median change, -22%) compared to lymph
nodes (median change, 0%). Pleural disease and nonirradiated bone metastases demonstrated PD. All
histological subtypes had similar responses. The median PFS was 19 months. The median overall survival has
not yet been reached, but at 2 yr of follow-up, overall survival is 67%. Log Tg correlated with radiographic
response (P = 0.0005). CONCLUSIONS: Sorafenib and sunitinib appear to be effective in patients with widely
metastatic, progressive DTC, with most patients achieving SD or PR, despite having PD at baseline. The most
noticeable responses occurred in the lungs in contrast with minimal changes in nodal metastases and PD in
pleural and nonirradiated bone metastases, suggesting a tissue-specific response to therapy. Log Tg
significantly correlated with response to treatment and therefore may have value as a surrogate marker of
response.
PubMed-ID: 20392874
http://dx.doi.org/10.1210/jc.2009-1923

Historical Evolution of Thyroid Surgery: From the Ancient Times to the Dawn of the 21st Century.
World J Surg , 34(8):1793-804.
Sakorafas GH. 2010.
Thyroid diseases (mainly goiter) have been recognized for more than 3500 years. Knowledge of the nature of
these diseases was, of course, limited at that time. Thyroid surgery was conceived by the ancients, but it was
limited to rare attempts to remove part of an enlarged thyroid gland in cases of impending death by suffocation
or, in very rare cases, of a suppurating thyroid. Like other fields of surgery, thyroid surgery was limited by many
problems: the lack of anesthesia and antisepsis, the need for appropriate instruments, mainly artery forceps
(many deaths after thyroid surgery were due to severe postoperative hemorrhage or infection). Much of the
progress in thyroid surgery occurred in Europe during the second half of the 19th century. During the first half of
the 20th century, the evolution of thyroid surgery accelerated significantly, based on the contributions of
pioneering European and American surgeons. The present status of thyroid surgery was established during the
last quarter of the 20th century, when modern imaging methods and technological advances (including progress
in applied molecular biology) brought thyroid surgery into the new millennium.
PubMed-ID: 20401481
http://dx.doi.org/10.1007/s00268-010-0580-7

Outpatient Thyroidectomy Is Safe and Reasonable: Experience With More Than 1,000 Planned Outpatient
Procedures.
J Am Coll Surg, 210(5):575-4.
Snyder SK, Hamid KS, Roberson CR, Rai SS, Bossen AC, Luh JH, Scherer EP, Song J. 2010.
BACKGROUND: Thyroidectomy has traditionally been performed as an inpatient hospital procedure, but low risk
and high patient tolerance make it acceptable as an outpatient procedure. STUDY DESIGN: All thyroidectomies
performed by a single surgeon between March 2003 and June 2009 were retrospectively and prospectively
reviewed as planned outpatient or planned inpatient operations, noting the patient's American Society of


ESES Review of Recently Published Literature 2010-2                                                   Page 21 of 63
Anesthesiologists (ASA) classification, success of completion as an outpatient procedure, time to same-day
discharge, postoperative emergency room visit, hospital admission, and complications. RESULTS: Overall,
1,136 of 1,242 thyroidectomies were planned as outpatient procedures and 1,063 (93.6%) were successfully
completed as such. Including 1 outpatient procedure initially planned as an inpatient procedure, 1,064 outpatient
procedures were performed, of which 613 were total and 451 less-than-total thyroidectomies. These outpatient
procedures had a mean time to day-surgery discharge of 2 hours and 42 minutes. Of discharged outpatients, a
postoperative emergency room visit within 30 days occurred in 83 cases (7.8%), with subsequent hospital
admission in 25 of these patients (2.3%). Excluding 153 cases of isolated and self-limited asymptomatic
hypocalcemia (14.4%), substantial complications occurred in 122 discharged outpatients (11.5%), including 56
symptomatic hypocalcemias (5.2%), 39 transient recurrent laryngeal nerve injuries (3.7%), 4 permanent
recurrent laryngeal nerve injuries (0.4%), and 2 hematomas (0.19%). None of the patients with postoperative
hematoma required bedside decompression and only 1 occurred within 24 hours of the outpatient procedure.
Discharged outpatient thyroidectomy patients were younger (53 years versus 60 years; p < 0.0001) and healthier
(2.3 ASA versus 3.0 ASA; p < 0.0001) than planned inpatient thyroidectomies. CONCLUSIONS: Outpatient
thyroidectomy in experienced hands is safe and reasonable with favorable patient acceptance and the potential
for substantial health care cost savings.
PubMed-ID: 20421007
http://dx.doi.org/10.1016/j.jamcollsurg.2009.12.037

Causes and Treatment of Recurrent Hyperparathyroidism After Subtotal Parathyroidectomy in the
Presence of Multiple Endocrine Neoplasia 1.
World J Surg, 34(6):1325-31.
Salmeron MD, Gonzalez JM, Sancho IJ, Goday A, Perez NM, Zambudio AR, Paricio PP, Serra AS. 2010.
BACKGROUND: Subtotal parathyroidectomy (SPTX) is the treatment of choice for hyperparathyroidism in a
patient with multiple endocrine neoplasia type 1 (HPT-MEN-1). There are scarce data on the causes, timing, and
appropriate surgical treatment of patients with recurrent HPT-MEN-1. The aim of this study was to investigate
the timing, causes, site of recurrence, and surgical treatment of recurrent HPT-MEN-1 in patients who underwent
SPTX. METHODS: The study was a retrospective review of prospectively collected data on patients with HPT-
MEN-1 with SPTX at two referral institutions. The data collected included the following: demographics, duration
of follow-up, weight of resected parathyroid tissue, type of remnant, time to reoperation, cause/site of recurrence,
and surgical treatment. We studied prognostic factors of recurrence. RESULTS: A total of 69 patients underwent
SPTX and were followed for a mean of 75.3 months. After the surgery, 15 patients were left with a single
"normal" gland and 54 with a 50- to 70-mg remnant of a partially excised abnormal gland. Nine patients (13%)
had a recurrence within a mean of 85 months (12-144 months). Patients with a recurrence had been followed
longer (115 vs. 66 months; p = 0.005). Five recurrences occurred in a parathyroid remnant, 3 in a previously
"normal" gland; the fifth recurrence was in both a hyperplastic remnant and a fifth gland. Remedial surgery
included five subtotal resections and four immediate parathyroid autotransplantations. Two patients had a
second recurrence due to a supernumerary gland. Factors related with recurrence are the follow-up time (p <
0.01) and thymectomy (p < 0.003). CONCLUSIONS: Recurrence of HPTP-MEN-1 usually is located in preserved
parathyroid tissue with no preference for a previously normal gland or a remnant. A second recurrence is most
likely seen in a supernumerary gland. Recurrence is associated with the follow-up time and thymectomy.
PubMed-ID: 20431882
http://dx.doi.org/10.1007/s00268-010-0605-2

Total Parathyroidectomy Without Autotransplantation for the Treatment of Secondary
Hyperparathyroidism Associated With Chronic Kidney Disease: Clinical and Laboratory Long-Term
Follow-Up.
Biomed Pharmacother, 64(5):359-62.
Puccini M, Carpi A, Cupisti A, Caprioli R, Iacconi P, Barsotti M, Buccianti P, Mechanick J, Nicolini A, Miccoli P.
2010.
Forty-six consecutive patients who underwent total parathyroidectomy (tPTX) for hyperparathyroidism
associated with end-stage kidney disease (CKD5) in a University Hospital from 1990 to 1999 were included in a
long-term observational study. Outcome parameters included symptoms (bone pain, pruritus and muscle
weakness evaluated by visual analog scales [VAS]) and laboratory data (intact parathyroid hormone [iPTH], total
calcium, and alkaline phosphatase) assessed before, shortly postoperatively and then at a later time point: 40
patients were on maintenance hemodialysis and six on conservative medical therapy. Forty-four patients had
four glands removed, while only three glands were found in the remaining two. Perioperative complications
consisted of acute symptomatic hypocalcemia in 10 (22%) patients and non-specific complaints in three (7%).
No laryngeal nerve palsies occurred. After a median follow-up of eight years, 43 subjects were evaluated: 37


ESES Review of Recently Published Literature 2010-2                                                 Page 22 of 63
(86%) were cured, three (7%) had persistent and three (7%) recurrent disease. Eleven patients underwent
successful renal transplantation and 23 died during the period of observation. iPTH decreased from a mean of
1084+/-505 pg/ml to 120+/-381 pg/ml (p < 0.0001). No subsequent bone fractures, persistent bone pain or
disability were reported; this includes patients who later received a functioning renal graft. tPTX was able to
correct hyperparathyroidism in most of the patients and was associated with a low long-term relapse rate. iPTH
levels remained low in 17 cases without symptoms and no clinically significant side effects. The beneficial effects
of tPTX occurred in the majority of patients while renal transplantation was performed in a minority of patients.
tPTX should be considered a safe and successful procedure for the treatment of severe secondary
hyperparathyroidism associated with chronic kidney disease.
PubMed-ID: 20435429
http://dx.doi.org/10.1016/j.biopha.2009.06.006

Hypercalcemia Secondary to Persistent Hyperparathyroidism in Kidney Transplant Patients: Analysis
After a Year With Cinacalcet.
J Nephrol,
Guerra R, Auyanet I, Fernandez EJ, Perez MA, Bosch E, Ramirez A, Suria S, Checa MD. 2010.
Introduction: The most common cause of hypercalcemia in patients with transplanted kidneys is persistent
hyperparathyroidism, which presents in 10%-30% of patients with functioning renal grafts. In these patients, the
treatment of vitamin D-resistant hyperparathyroidism traditionally required parathyroidectomy. Calcimimetic
agents represent a new therapeutic alternative; they inhibit parathyroid hormone (PTH) secretion, increasing the
sensitivity of the calcium-sensitive receptor in the parathyroid gland. The objective of this study is to evaluate the
efficacy of cinacalcet in renal transplant patients with persistent hyperparathyroidism. Methods: Cinacalcet 30
mg/day was prescribed to 17 renal transplant patients (6 women, 11 men) with a mean age of 49 years and
hypercalcemia secondary to persistent hyperparathyroidism. The treatment started 58.17 +/- 35.16 months
posttransplant, with 1 year of follow-up. Results: Calcium in serum fell from 10.5 +/- 0.74 to 9.4 +/- 0.84 mg/dL
(p<0.001), whereas phosphorous levels were not significantly altered. The fall in PTH was from 204.79 +/- 78 to
148.55 +/- 56 pg/mL (p<0.011). Kidney function remained stable, and immunosuppressant drug levels remained
unchanged. The dose of cinacalcet was increased to 60 mg in 2 patients. No significant adverse effects were
described, and none of the patients had to suspend the treatment. Conclusions: Calcimimetic agents represent a
therapeutic alternative in transplant patients with persistent hyperparathyroidism, as they correct hypercalcemia
and reduce PTH levels with no adverse effects on kidney function. Prospective, controlled studies should be
designed to evaluate the long-term effects and evolution after suspension of the treatment.
PubMed-ID: 20437396

Treatment of Persistent or Recurrent Papillary Carcinoma of the Thyroid--the Good, the Bad, and the
Unknown.
J Clin Endocrinol Metab, 95(5):2061-3.
Udelsman R. 2010.
PubMed-ID: 20444934
http://dx.doi.org/10.1210/jc.2010-0583

Decreasing Tumor Size of Thyroid Cancer in Germany: Institutional Experience 1995-2009.
Eur J Endocrinol, 163(1):111-9.
Machens A, Dralle H. 2010.
OBJECTIVE: Decreasing tumor size in a population over time is widely interpreted as a measure of
effectiveness of cancer screening programs. Nonetheless, thyroid cancer size is rarely analyzed as a function of
time. This study aimed to explore secular trends of thyroid cancer diameter in Germany. DESIGN: Retrospective
analysis of 1644 thyroid cancer patients from a large referral center for thyroid cancer (1995-2009). METHODS:
Calculation of largest tumor diameters for each type of cancer as a function of time periods and birth cohorts.
RESULTS: Over the past 25 years, subdivided into 5-year periods by year of thyroidectomy (1985-1989; 1990-
1994; 1995-1999; 2000-2004; 2005-2009), tumor diameters diminished from 25 to 16 mm (P=0.025) for
medullary thyroid cancer and from 28 to 18 mm (P=0.017) for papillary thyroid cancer. This reduction was
greater for hereditary medullary thyroid cancer (from 27 to 11 mm; P=0.088) than sporadic medullary thyroid
cancer (from 23 to 19 mm; P=0.11). No decline was observed for follicular thyroid cancer (means of 45 to 42
mm; P=0.52). From the first (1921-1940) to the most recent birth cohort (1981-2000), tumor size fell from 22 to
10 mm (P<0.001) for medullary thyroid cancer, from 24 to 22 mm (P<0.001) for papillary thyroid cancer, and
from 49 to 38 mm (P=0.011) for follicular thyroid cancer. The reduction of medullary thyroid cancers affected
exclusively patients with hereditary disease (from 20 to 7 mm; P<0.001). CONCLUSION: The consistency and
robustness of these data signify powerful secular trends toward smaller papillary, follicular, and medullary thyroid

ESES Review of Recently Published Literature 2010-2                                                   Page 23 of 63
cancers. The causes and consequences of these trends warrant further investigation.
PubMed-ID: 20447999
http://dx.doi.org/10.1530/EJE-10-0203

Dosimetry and Thyroid Cancer: the Individual Dosage of Radioiodine.
Endocr Relat Cancer, 17(3):R161-R172.
Lassmann M, Reiners C, Luster M. 2010.
Adjuvant therapy of differentiated thyroid cancer with radioactive iodine ((131)I) is a standard procedure for the
ablation of remnant thyroid tissue following surgery and for the treatment of iodine-avid metastases. Presently,
there are two dosimetric concepts for the treatment of thyroid cancer using radioiodine: a) the bone marrow dose
limited approach and b) lesion-based dosimetry. Both concepts and their clinical applications are described. In
addition, the use of (124)I as a diagnostic and dosimetric agent is discussed. Treatment of children and
adolescents with radioiodine requires special precautions; individualized approaches in this setting are reviewed.
The limitations of treatments aiming at high absorbed doses are addressed as well as the doses to normal
organs. Finally, new concepts for further elaborating the potential of thyroid cancer treatment using (131)I are
introduced.
PubMed-ID: 20448022
http://dx.doi.org/10.1677/ERC-10-0071

Clinical Value of 18-Fluorine-Fluorodihydroxyphenylalanine Positron Emission Tomography/Computed
Tomography in the Follow-Up of Medullary Thyroid Carcinoma.
Thyroid, 20(5):527-33.
Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, Glatting G, Buck AK, Solbach C, Neumaier B,
Reske SN, Mottaghy FM. 2010.
BACKGROUND: 18-Fluorine-fluorodihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET) is
a sensitive method for detecting medullary thyroid carcinoma (MTC). The advent of PET/computed tomography
(CT) has enabled more sensitive and specific lesion identification using various tracers in many other tumors.
The aim of this study was therefore to test the hypothesis that combined (18)F-DOPA PET/CT more accurately
detects MTC lesions than each modality does alone. METHODS: Twenty-eight consecutive (18)F-DOPA PET,
CT, and (18)F-DOPA PET/CT scans of patients followed up for sporadic MTC or multiple endocrine neoplasia 2
syndrome-associated MTC were reviewed retrospectively in randomized sequence by two blinded readers, one
a nuclear medicine physician and the other a radiologist, with extensive experience interpreting such images.
RESULTS: Of 18 lesions detected concurrently by the three modalities, PET identified all as positive for MTC,
but was unable to definitively localize 4 (22%) lesions. CT could definitively localize all 18 lesions, but could not
definitively diagnose or exclude MTC in 6 (33%) lesions. Further, CT falsely identified as MTC-negative one
lesion that was judged to be MTC-positive by both PET and PET/CT. Only PET/CT scans accurately
characterized and localized all 18 lesions. On a per patient basis, the sensitivity of (18)F-DOPA PET/CT for MTC
was 74% and the specificity, 100%. In the present series, no truly MTC-positive (18)F-DOPA PET/CT case was
found in patients with basal human calcitonin (hCt) levels under 60 pg/mL, and conversely, no truly MTC-
negative PET/CT case was found in patients with basal hCt over 120 pg/mL. Between hCt concentrations of 60
and 150 pg/mL true-negative, false-negative, and true-positive scans all were obtained. (18)F-DOPA PET/CT
had 100% sensitivity and specificity when hCt at the time of scanning was over 150 pg/mL, the threshold at
which the 2009 American Thyroid Association guidelines recommend performing additional imaging including
(18)F-DOPA PET/CT. CONCLUSIONS: (18)F-DOPA PET/CT allows for a more accurate diagnosis and
localization of MTC lesions than do (18)F-DOPA PET or CT alone. Supporting the recent American Thyroid
Association recommendations on additional imaging in MTC, (18)F-DOPA PET/CT appears to have 100%
sensitivity in patients with hCt over 150 pg/mL.
PubMed-ID: 20450432
http://dx.doi.org/10.1089/thy.2009.0342

Central Neck Lymph Node Dissection for Papillary Thyroid Cancer: the Reliability of Surgeon Judgment
in Predicting Which Patients Will Benefit.
Surgery, 148(2):398-403.
Shen WT, Ogawa L, Ruan D, Suh I, Duh QY, Clark OH. 2010.
BACKGROUND: The role of routine prophylactic central-neck lymph node dissection (CLND) for papillary thyroid
cancer (PTC) remains controversial. We perform CLND for PTC only in patients with enlarged nodes as
determined by preoperative ultrasound and intraoperative inspection and palpation. METHODS: We identified all
patients with PTC who underwent CLND during thyroidectomy (group 1) at our institution, and then we identified
an equivalent number of demographically matched patients who underwent thyroidectomy without CLND (group

ESES Review of Recently Published Literature 2010-2                                                  Page 24 of 63
2) and compared the outcomes of the 2 groups. RESULTS: In all, 191 patients were identified for each group;
49/191 (26%) patients in group 1 developed locoregional nodal recurrence (12% central neck and 21% lateral
neck), compared with 11/191 (6%) patients in group 2 (3% central neck and 3% lateral neck; P < .05). Overall,
161/191 (84%) patients in group 1 were disease free at last survey, compared with 180/191 (94%) patients in
group 2 (P < .05). Transient hypocalcemia was significantly greater in group 1. No difference was found in
disease-specific mortality. CONCLUSION: Surgeon assessment of the central neck compartment is an accurate
predictor of which patients with PTC will benefit from CLND. Patients with nonenlarged central neck nodes who
undergo total thyroidectomy without CLND have a low risk of developing recurrence.
PubMed-ID: 20451230
http://dx.doi.org/10.1016/j.surg.2010.03.021

Endocrine Complications in Long-Term Survivors of Childhood Cancers.
Endocr Relat Cancer, 17(3):R141-R159.
Chemaitilly W, Sklar CA. 2010.
Endocrine disturbances are among the most frequently reported complications in childhood cancer survivors,
affecting between 20 and 50% of individuals who survive into adulthood. Most endocrine complications are the
result of prior cancer treatments, especially radiotherapy. The objective of the present review is to discuss the
main endocrine complications observed in this population, including disorders of the hypothalamic-pituitary axis,
disorders of pubertal development, thyroid dysfunction, gonadal dysfunction, decreased bone mineral density,
obesity, and alterations in glucose metabolism with a special focus on recent findings reported from the
Childhood Cancer Survivor Study.
PubMed-ID: 20453080
http://dx.doi.org/10.1677/ERC-10-0002

The Death of an Indian Rhinoceros.
World J Surg, 34(8):1805-10.
Felger EA, Zeiger MA. 2010.
In 1834, the London Zoological Society purchased a male Indian Rhinoceros, Rhinoceros unicornis, at the
request of the anatomist, Richard Owen. Fifteen years later, the rhinoceros died from traumatic injuries, and the
necropsy performed by Owen led to the very first discovery of parathyroid glands. Around this time, Richard
Owen and Charles Darwin vehemently disagreed with one another about the theory of natural selection. Their
public feud sparked the public's interest in Darwin and his theory while Owen became less popular despite his
many accomplishments in the scientific world. Not until decades after Owen's death was his contribution to the
identification of parathyroid glands discovered. Because his discovery is considered pivotal to the history of
endocrine surgery, we sought to investigate the circumstances surrounding the rhinoceros' death, its dissection,
and Owen's initial discovery.
PubMed-ID: 20458582
http://dx.doi.org/10.1007/s00268-010-0603-4

Characteristics and Prognosis of Primary Thyroid Non-Hodgkin's Lymphoma in Chinese Patients.
J Surg Oncol, 101(7):545-50.
Sun TQ, Zhu XL, Wang ZY, Wang CF, Zhou XY, Ji QH, Wu Y. 2010.
BACKGROUND AND OBJECTIVES: There exists no universally accepted treatment for primary thyroid non-
Hodgkin's lymphoma (TNHL) due to the rarity of this entity. The aim of this study is to assess the role of surgery
and to explore prognostic factors in Chinese TNHL patients. METHODS: Patient presentations, pathologies,
surgical interventions, multidisciplinary treatment, prognostic factors and the value of fine needle aspiration were
analyzed. RESULTS: Between 1991 and 2007, 40 patients of TNHL were diagnosed. Thirty-eight patients
underwent an initial surgical procedure. Further treatments consisted of radiotherapy or chemotherapy alone,
and the majority of patients were treated with combined chemo-radiation. After a median follow-up of 95 months,
the 5-year overall survival (OS) and relapse-free survival (RFS) was 82% and 74%, respectively. Survival curves
showed no significant difference between therapeutic operations when compared with diagnostic operations. A
univariate analysis showed both International Prognostic Index (IPI) and staging significantly influenced OS and
RFS. In multivariate analysis, IPI was found to be the only prognostic factor. CONCLUSIONS: Combined
chemotherapy and radiotherapy may offer better outcome without the need for extensive resection, and surgery
should be reserved to providing tissue for diagnosis. The patients with low-intermediate risk (IPI = 2) or stage IIE
need be treated more aggressively.
PubMed-ID: 20461759
http://dx.doi.org/10.1002/jso.21543



ESES Review of Recently Published Literature 2010-2                                                  Page 25 of 63
Predictive Factors of Carcinoma in 279 Patients With Hurthle Cell Neoplasm of the Thyroid Gland.
J Surg Oncol , 101(7):582-6.
Strazisar B, Petric R, Sesek M, Zgajnar J, Hocevar M, Besic N. 2010.
BACKGROUND AND OBJECTIVES: Estimation of the risk of malignancy in a Hurthle cell (HC) neoplasm is
important for optimum extent of thyroid surgical treatment. The aim of this retrospective study was to find
predictive factors of carcinoma in patients with HC neoplasm. METHODS: A total of 279 patients (241 females,
38 males; median age 55 years, range 15-86 years) with HC neoplasm in whom carcinoma was only suspected
and who were surgically treated at our Institute in the period 1990-2007, were included in this study. Risk factors
for malignancy were identified by the chi-squared test and logistic regression. RESULTS: The histopatological
diagnoses were carcinoma, benign goiter and adenoma in 71 (25%), 68 (25%) and 140 (50%) patients,
respectively. Predictive factors for carcinoma, shown by chi-square test, were: age of patients, tumor diameter,
thyroid volume and T(g) concentration. The independent predictors of malignancy as shown by multivariate
logistic regression were age of patients and pre-operative T(g) concentration. Carcinoma was more common in
the patients older than 65 years of age and with T(g) concentration over 1,000 ng/ml. CONCLUSIONS: The
independent predictors of malignancy in HC neoplasm were age of patients and pre-operative T(g)
concentration.
PubMed-ID: 20461764
http://dx.doi.org/10.1002/jso.21526

Familial Nonmedullary Thyroid Cancer: a Review of the Genetics.
Thyroid, 20(7):795-801.
Khan A, Smellie J, Nutting C, Harrington K, Newbold K. 2010.
OBJECTIVE: Thyroid cancer, the commonest of endocrine malignancies, continues to increase in incidence with
over 19,000 new cases diagnosed in the European Union per year. Although nonmedullary thyroid cancer
(NMTC) is mostly sporadic, evidence for a familial form, which is not associated with other Mendelian cancer
syndromes (e.g., familial adenomatous polyposis and Cowden's syndrome), is well documented and thought to
cause more aggressive disease. Just over a decade ago, the search for a genetic susceptibility locus for familial
NMTC (FNMTC) began. This review details the genetic studies conducted thus far in the search for potential
genes for FNMTC. DESIGN: An electronic PubMed search was performed from the English literature for
genetics of FNMTC and genetics of familial papillary thyroid carcinoma (subdivision of FNMTC). The references
from the selected papers were reviewed to identify further studies not found in the original search criteria. MAIN
OUTCOME: Six potential regions for harboring an FNMTC gene have been identified: MNG1 (14q32), TCO
(19p13.2), fPTC/PRN (1q21), NMTC1 (2q21), FTEN (8p23.1-p22), and the telomere-telomerase complex.
Important genes reported to have been excluded are RET, TRK, MET, APC, PTEN, and TSHR. CONCLUSION:
The genetics of FNMTC is an exciting field in medical research that has the potential to permit individualized
management of thyroid cancer. Studies thus far have been on small family groups using varying criteria for the
diagnosis of FNMTC. Results have been contradictory and further large-scale genetic studies utilizing emerging
molecular screening tests are warranted to elucidate the underlying genetic basis of FNMTC.
PubMed-ID: 20465534
http://dx.doi.org/10.1089/thy.2009.0216

Determinants of Tc-99m Sestamibi SPECT Scan Sensitivity in Primary Hyperparathyroidism.
Am J Surg, 199(5):614-20.
Swanson TW, Chan SK, Jones SJ, Bugis S, Irvine R, Belzberg A, Levine D, Wiseman SM. 2010.
BACKGROUND: The aim of this study was to evaluate the influence of patient and adenoma characteristics on
(99m)Tc-methoxy isobutyl isonitrile (MIBI) scan performance in individuals diagnosed with primary
hyperparathyroidism (PHP). METHODS: Records of patients undergoing parathyroidectomy for PHP over 6
years at a single center were reviewed. RESULTS: The overall true-positive (TP) rate for (99m)Tc-MIBI scans
was 56%. Adenomas sized 1.9 to 3.5 cm were more likely to have TP scans than 0.3-cm to 1.8-cm adenomas
(74% vs 40%, P < .001). Preoperative ionized calcium levels between 1.49 and 1.72 mmol/L were more likely to
have TPs than levels between 1.27 and 1.48 mmol/L (65% vs 47%, P < .05). No single class of medication was
shown to significantly effect TP rates. A decrease in TP rate was observed for larger adenomas in patients on
>or=1 medication (74% vs 65%, P = .05). CONCLUSIONS: In PHP, (99m)Tc-MIBI scan positivity is most related
to adenoma size and preoperative ionized calcium level.
PubMed-ID: 20466104
http://dx.doi.org/10.1016/j.amjsurg.2010.02.001

Effect of Race on Thyroid Cancer Care in an Equal Access Healthcare System.
Am J Surg, 199(5):685-9.

ESES Review of Recently Published Literature 2010-2                                                 Page 26 of 63
Brown SR, Lee S, Brown TA, Waddell BE. 2010.
BACKGROUND: Thyroid cancer is more likely to present at an advanced age with larger tumor size in black
patients. The aim of this study was to assess the influence of race on the presentation, treatment, and survival in
an equal access healthcare system. METHODS: This retrospective study included all black and white patients
with thyroid cancer who were treated at a Department of Defense facility from 1986 to 2008. Patients' age, tumor
size, lymph node status, treatment, and survival were compared. RESULTS: A total of 4,625 patients were
identified. There was no difference between black and white patients in regards to age at presentation, tumor
size, use of surgical and/or radiation therapy, and overall 5-year survival rate. Black patients had a lower rate of
lymph node involvement. CONCLUSIONS: In an equal access healthcare system, black patients have similar
disease presentation, undergo similar treatment, and have the same survival as white patients.
PubMed-ID: 20466117
http://dx.doi.org/10.1016/j.amjsurg.2010.01.020

Diagnosis and Treatment of Small Follicular Thyroid Carcinomas.
Br J Surg, 97(6):839-44.
Clerici T, Kolb W, Beutner U, Bareck E, Dotzenrath C, Kull C, Niederle B. 2010.
BACKGROUND: Follicular thyroid microcarcinomas (mFTCs) of 10 mm or less in size rarely manifest clinically
and their clinical significance is controversial. This study assessed their characteristics and incidence, and
analysed treatment modalities used for mFTC. METHODS: Members of the German Association of Endocrine
Surgeons were asked to review patients with mFTC operated on between 1990 and 2005. RESULTS: Data for
90 patients from 26 institutions were reported. Histopathological slides were available for re-evaluation in 35
patients. Most initial diagnoses had to be revised because of incorrect size assessment or incorrect diagnosis
(benign adenoma, papillary thyroid carcinoma (PTC), follicular variant of PTC). The diagnosis of mFTC was
confirmed in only four patients. As a result of the incorrect histopathological diagnosis, unnecessary completion
thyroidectomy and radioiodine ablation were performed in 17 and 20 patients respectively. The incidence of
mFTC was calculated to be 0.12 per million population per year. CONCLUSION: mFTC is exceptionally rare.
Such tumours are overdiagnosed, resulting in unnecessary treatment associated with avoidable morbidity.
Histopathological re-evaluation by an experienced pathologist is recommended before embarking on further
treatments when a diagnosis of mFTC is made.
PubMed-ID: 20473996
http://dx.doi.org/10.1002/bjs.6969

American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European
Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of
Thyroid Nodules: Executive Summary of Recommendations.
J Endocrinol Invest, 33(5):287-91.
Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedus L, Vitti P. 2010.
American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid
Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules are
systematically developed statements to assist health care professionals in medical decision making for specific
clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional
judgment was applied. These guidelines are a working document that reflects the state of the field at the time of
publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage
medical professionals to use this information in conjunction with their best clinical judgment. Any decision by
practitioners to apply these guidelines must be made in light of local resources and individual patient
circumstances.
PubMed-ID: 20479572
http://dx.doi.org/10.3275/7048

Role of Thyroidectomy in Advanced Laryngeal and Pharyngolaryngeal Carcinoma.
Otolaryngol Head Neck Surg, 142(6):851-5.
Elliott MS, Odell EW, Tysome JR, Connor SE, Siddiqui A, Jeannon JP, Simo R. 2010.
OBJECTIVE: Total thyroidectomy (TThy) or hemithyroidectomy (HThy) in conjunction with a total laryngectomy
(TL) or pharyngolaryngectomy (PL) for laryngeal carcinoma often results in hypothyroidism requiring life-long
thyroid hormone replacement. The aims were to determine the incidence of thyroid gland (TG) invasion in
patients undergoing TL or TPL with TThy or HThy for laryngeal or hypopharyngeal carcinoma and to assess
predicative factors. STUDY DESIGN: Case series with chart review. SETTING: Guy's Hospital, London, UK.
SUBJECTS AND METHODS: Thirty-five patients from 2004 to 2008 were reviewed. Specimens were examined
to determine the incidence of TG invasion and predicative factors. Preoperative imaging was reviewed to assess

ESES Review of Recently Published Literature 2010-2                                                   Page 27 of 63
the radiological evidence of TG invasion. RESULTS: TL and TThy were performed in 19 patients, TL and HThy
in three patients, and PL and TThy in 13 patients. Surgery was performed for primary and recurrent carcinoma in
28 and eight patients, respectively. Histological evidence of invasion of the TG was found in three patients
(8.5%). No significant relationship was found between TG invasion and patient's sex, subsite of primary
carcinoma, stage of primary disease at surgery, degree of differentiation, or the presence of subglottic extension.
In addition, no significant relationship was found between the presence of TG invasion and recurrent disease.
Definite evidence of radiological invasion of the TG was seen in only one patient. CONCLUSIONS: Invasion of
the TG in patients undergoing TL or TPL is a rare event and limits the need for TThy in most cases.
PubMed-ID: 20493357
http://dx.doi.org/10.1016/j.otohns.2010.02.006

A Study of Resident Proficiency With Thyroid Surgery: Creation of a Thyroid-Specific Tool.
Otolaryngol Head Neck Surg, 142(6):856-62.
Stack BC, Jr., Siegel E, Bodenner D, Carr MM. 2010.
OBJECTIVE: Creation and testing of a tool, Hemithyroidectomy-Specific Scale (HSS), to evaluate performance
of a hemithyroidectomy. STUDY DESIGN: Prospective, multi-center study of our HSS tool versus a Global Scale
(GS). SETTING: Two tertiary care academic medical centers. SUBJECTS AND METHODS: Sixteen unique
residents (postgraduate years [PGY] 2-5) evaluated a total of 97 times with a performance tool by a single
endocrine surgeon evaluator (B.C.S.). RESULTS: Overall, the reliability of both evaluation instruments was
good. Cronbach's alpha was 0.972 for the GS and 0.959 for the HSS. This indicates high internal consistency of
each instrument. In general, the scores increased with increasing PGY level, indicating reasonable construct
validity. CONCLUSION: This study describes a new HSS checklist type of evaluation instrument for
hemithyroidectomy and compares it to a validated GS. HSS offers advantages to GS. Most residents reached
competence in hemithyroidectomy by the PGY4 level. A large, multi-institutional study would be required for
adequate evaluation of our tool prior to its routine use in resident evaluations.
PubMed-ID: 20493358
http://dx.doi.org/10.1016/j.otohns.2010.02.028

Prior Head and Neck Radiation Exposure Is Not a Contraindication to Minimally Invasive
Parathyroidectomy.
J Am Coll Surg, 210(6):942-8.
Rahbari R, Sansano IG, Elaraj DM, Duh QY, Clark OH, Kebebew E. 2010.
BACKGROUND: Most patients with primary hyperparathyroidism can have a minimally invasive
parathyroidectomy based on localization studies showing single-gland disease. In patients with a history of head
and neck irradiation, due to the increased risk of multigland disease and risk of concurrent thyroid cancer,
minimally invasive parathyroidectomy is considered by some to be a contraindication. We postulated that
previous history of head and neck irradiation should not be a contraindication for minimally invasive
parathyroidectomy and tested this hypothesis in a prospective cohort of patients undergoing parathyroidectomy
for primary hyperparathyroidism. STUDY DESIGN: We performed a retrospective analysis of a prospective
database of 491 consecutive parathyroidectomies performed between May 2005 and May 2007 at a tertiary
referral medical center. RESULTS: Fifty-two (12.6%) patients had a history of head and neck irradiation and 360
(87.4%) had no exposure to radiation. The 2 groups had no significant difference in terms of gender or ethnicity.
The radiation group was older, with an average age of 65.1 years versus 58.1 years (p < 0.0009). There was no
significant difference in concurrent benign thyroid neoplasm, thyroid cancer, and type of parathyroid disease
(single vs multigland) in the 2 groups. There was no significant difference in the operative approach used
between the 2 groups (focused vs unilateral or bilateral). CONCLUSIONS: Head and neck irradiation should not
be a contraindication for minimally invasive parathyroidectomy in patients with primary hyperparathyroidism in
the setting of preoperative localization studies showing single-gland disease and no concurrent thyroid
neoplasm. Furthermore, history of head and neck irradiation is associated with a later age of presentation for
parathyroidectomy.
PubMed-ID: 20510803
http://dx.doi.org/10.1016/j.jamcollsurg.2010.02.041

[Intraoperative Neuromonitoring of Thyroid Gland Operations : Surgical Standards and Aspects of
Expert Assessment]
Intraoperatives Neuromonitoring Bei Schilddrusenoperationen : Chirurgische Standards Und
Gutachterliche Aspekte.
Chirurg, 81(7):612-9.
Dralle H, Lorenz K. 2010.

ESES Review of Recently Published Literature 2010-2                                                 Page 28 of 63
Intraoperative neuromonitoring (IONM) was introduced into thyroid surgery approximately 10 years ago for better
identification of recurrent laryngeal nerve palsy. Since then several studies have been performed for evaluation
of this new technology. IONM is superior to visual nerve identification alone for prediction of postoperative local
cord function. Therefore, in bilateral procedures IONM enables intraoperative decision-making concerning
resection of the second side. To avoid misinterpretation of the results of IONM a standardized approach
including preoperative and postoperative laryngoscopy and preresection and postresection vagus stimulation is
recommended. Trouble-shooting requires systematic checking of the device including control of electrode
position (needle or tube electrodes). For expert assessment purposes documentation of the standardized
application of IONM is of utmost importance.
PubMed-ID: 20517586
http://dx.doi.org/10.1007/s00104-009-1882-x

Approach to the Patient With Amiodarone-Induced Thyrotoxicosis.
J Clin Endocrinol Metab, 95(6):2529-35.
Bogazzi F, Bartalena L, Martino E. 2010.
Amiodarone, a benzofuranic iodine-rich antiarrhythmic drug, causes thyroid dysfunction in 15-20% of cases.
Although amiodarone-induced hypothyroidism poses no particular problem, amiodarone-induced thyrotoxicosis
(AIT) is a diagnostic and therapeutic challenge. There are two main forms of AIT: type 1, a form of iodine-
induced hyperthyroidism, and type 2, a drug-induced destructive thyroiditis. However, mixed/indefinite forms
exist that may be caused by both pathogenic mechanisms. Type 1 AIT usually occurs in abnormal thyroid
glands, whereas type 2 AIT develops in apparently normal thyroid glands (or small goiters). Diagnosis of
thyrotoxicosis is easy, based on the finding of increased free thyroid hormone concentrations and suppressed
TSH levels. Thyroid radioactive iodine (RAI) uptake values are usually very low/suppressed in type 2 AIT, most
commonly low or low-normal, but sometimes normal or increased in type 1 AIT despite the iodine load. Color
flow Doppler sonography shows absent hypervascularity in type 2 and increased vascularity in type 1 AIT.
Mixed/indefinite forms may have features of both AIT types. Thionamides represent the first-line treatment for
type 1 AIT, but the iodine-replete gland is not very responsive; potassium perchlorate, by inhibiting thyroid iodine
uptake, may increase the response to thionamides. Type 2 AIT is best treated by oral glucocorticoids. The
response very much depends on the thyroid volume and the severity of thyrotoxicosis. Mixed/indefinite forms
may require a combination of thionamides, potassium perchlorate, and steroids. RAI is usually not feasible in AIT
due to low RAI uptake values. Thyroidectomy represents a valid option in cases resistant to medical therapy.
PubMed-ID: 20525904
http://dx.doi.org/10.1210/jc.2010-0180

[Minimally Invasive Follicular Thyroid Carcinoma : Not Always Total Thyroidectomy]
Minimal-Invasives Follikulares Schilddrusenkarzinom : Eine Thyreoidektomie Ist Nicht Obligat.
Chirurg , 81(7):627-5.
Hermann M, Tonninger K, Kober F, Furtlehner EM, Schultheis A, Neuhold N. 2010.
Current treatment guidelines for follicular thyroid carcinoma (FTC) recommend total thyroidectomy,
lymphadenectomy and radioiodine ablation. Considering the low malignant potential of minimally invasive
follicular thyroid carcinoma (MIFTC), a limited radical therapeutic procedure may be adequate. MIFTC is an
intensely discussed group of tumors and a review of the literature reveals disagreement among experts
concerning the criteria for a distinct definition. Therefore, in 2005 Rosai proposed a clinically more significant
classification of FTC based on the extent of capsular and vascular invasion: MIFTC with capsular invasion only,
with limited (< or =3) vascular invasion, encapsulated FTC with extensive (>3) vascular invasion and broadly
invasive FTC with extensive invasive growth.For the diagnosis of MIFTC a complete investigation of the
encapsulated follicular lesion should be performed by the pathologist and examination of at least 10 tissue
blocks is mandatory. Due to the excellent prognosis hemithyroidectomy constitutes an adequate therapeutic
approach in MIFTC with capsular invasion only and may also be considered for MIFTC with limited vascular
invasion. There are no indications for systematic lymphadenectomy.
PubMed-ID: 20544166
http://dx.doi.org/10.1007/s00104-009-1884-8

[Total Thyroidectomy for Multinodular Goiter]
Totale Thyreoidektomie Bei Knotenstruma.
Chirurg, 81(7):603-11.
Musholt TJ. 2010.
Multinodular goiter is a frequent disease which plays a central role in the daily routine of general and visceral
surgeons. Analyses of the national DRG statistics reveal that total thyroidectomy is increasingly replacing partial

ESES Review of Recently Published Literature 2010-2                                                 Page 29 of 63
thyroid resections. This paradigm shift is substantiated by the comprehension of multinodular goiter as a disease
affecting the whole organ as well as the fact that total thyroidectomy avoids high risk secondary interventions for
incidental thyroid carcinomas and recurrent disease while offering comparable operative risks. However, the
available evidence on operative results originates predominantly from thyroid centers and clinical data regarding
long-term effects of thyroid hormone substitution following total as well as sub-total thyroidectomy are lacking.
Therefore, the preservation of functionally relevant normal thyroid tissue retains its relevancy as an alternative
treatment. If a comparably low operative risk can be guaranteed and considering the patient's compliance, life
situation and wishes, total thyroidectomy represents the optimal therapy for bilateral multinodular goiter.
PubMed-ID: 20544167
http://dx.doi.org/10.1007/s00104-009-1880-z

[Intraoperative Parathyroid Hormone Determination for Primary Hyperparathyroidism]
Intraoperative Parathormonbestimmung Beim Primaren Hyperparathyreoidismus.
Chirurg, 81(7):636, 638-6, 642.
Lorenz K, Dralle H. 2010.
Intraoperative parathyroid hormone measurement (IOPTH) has proved to be an important promoter for focused
and minimally invasive parathyroidectomy procedures in primary hyperparathyroidism. IOPTH enables
multiglandular disease to be excluded with a high degree of certainty at the time of operation. The choice of the
cut-off value for IOPTH as the criterion for success is of utmost importance with respect to the prognosis for
operative success (biochemical healing). Advantages and disadvantages of the variety of existing IOPTH
success criteria are confusing and their assessment is contradictory. Particularly with respect to cost-benefit
aspects the standard application of IOPTH as "biochemical frozen section" even in conventional open
parathyroidectomy remains a matter of controversy. This article gives an up-date on current knowledge and
provides practical guidelines for clinical use of IOPTH.
PubMed-ID: 20549175
http://dx.doi.org/10.1007/s00104-009-1885-7

[Calcitonin Determination for Early Diagnosis of Medullary Thyroid Cancer]
Kalzitoninbestimmung Zur Fruhdiagnose Des Medullaren Schilddrusenkarzinoms.
Chirurg, 81(7):620, 622-0, 626.
Karges W. 2010.
Calcitonin is considered to be a sensitive marker for medullary thyroid cancer (MTC) therefore early detection
and surgical treatment may help to improve the clinical prognosis of MTC. Routine calcitonin measurement has
therefore been recommended in the diagnostic evaluation of patients with nodular thyroid disease. In the case of
elevated serum calcitonin (>20 pg/ml) stimulation testing is recommended to improve the predictive power for
MTC particularly in patients with small nodules. Serum calcitonin measurement cannot reliably discriminate
between micro-MTC (<10 mm) and C cell hyperplasia. In patients with stimulated calcitonin levels exceeding 100
pg/ml thyroidectomy is recommended because of a high inherent risk of MTC. Highly elevated basal and
stimulated serum calcitonin levels are strongly suggestive of MTC with practical implications for surgical
management.
PubMed-ID: 20549176
http://dx.doi.org/10.1007/s00104-009-1883-9

Somatostatin Receptor Scintigraphy As a Potential Diagnostic and Treatment Modality for Thyroid
Follicular-Cell-Derived Cancers.
Thyroid, 20(6):671-2.
Margulies DJ, Blum M. 2010.
PubMed-ID: 20553198
http://dx.doi.org/10.1089/thy.2009.0453

Cardiac Function in Mild Primary Hyperparathyroidism and the Outcome After Parathyroidectomy.
Eur J Endocrinol, 163(3):461-7.
Farahnak P, Ring M, Caidahl K, Farnebo LO, Eriksson MJ, Nilsson IL. 2010.
OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity. The extent of
cardiovascular abnormalities in patients with mild-asymptomatic disease is unclear. Using sensitive
echocardiographic methods, we compared cardiac structure and function in patients with mild PHPT and in
healthy controls, and evaluated the changes after parathyroidectomy (PTX). METHODS: In a prospective case-
control design, we studied 51 PHPT patients without any cardiovascular risk factors/diseases and 51 healthy
matched controls. Cardiac structure, and systolic and diastolic function were evaluated by echocardiography and

ESES Review of Recently Published Literature 2010-2                                                 Page 30 of 63
Doppler tissue imaging (DTI). Blood pressure (BP) and heart rate were measured. RESULTS: We observed no
differences in systolic or diastolic function or in cardiac morphology between the PHPT patients and the age-
matched healthy controls. The regional peak systolic myocardial velocities (S') measured with DTI decreased at
all sites (P<0.05) after PTX (tricuspid annulus 14.23+/-1.85 to 13.48+/-1.79, septal 8.48+/-0.96 to 7.97+/-0.85,
and lateral 9.61+/-2.05 to 8.87+/-1.63 cm/s, part of the mitral annulus). At baseline, systolic BP was higher in
patients compared to controls (127.6+/-17.1 vs 119.6+/-12.6 mmHg, P<0.05). After PTX, both systolic (127.6+/-
17.1 vs 124.6+/-16.6 mmHg, P<0.05) and diastolic (80.3+/-9.6 vs 78.4+/-8.6 mmHg, P<0.05) BP decreased.
CONCLUSIONS: Our results indicate that patients with PHPT without cardiovascular risk factors have a normal
global systolic and diastolic function and cardiac morphology. BP and the systolic velocities were marginally
reduced after PTX, but reflected the values of the control group. Our findings warrant further investigation of the
clinical and prognostic significance of these possibly disease-related inotropic effects.
PubMed-ID: 20562163
http://dx.doi.org/10.1530/EJE-10-0201

Hyperparathyroidism and Pregnancy.
Am Surg, 76(6):648-9.
Vazquez QE, Vazquez DE. 2010.
PubMed-ID: 20583526

Lymph Node Management in Clinically Node-Negative Patients With Papillary Thyroid Carcinoma.
Eur J Surg Oncol , 36(8):777-82.
Vergez S, Sarini J, Percodani J, Serrano E, Caron P. 2010.
AIMS: Systematic lymph node dissection in patients with papillary thyroid carcinoma (PTC) remains
controversial. The objective of this study was to study the pattern of lymph node spread in patients with PTC
clinically node-negative and then to propose a lymph node management strategy. METHODS: We
retrospectively reviewed the records of patients who had undergone total thyroidectomy and a systematic central
neck dissection (CND) and lateral neck dissection. Ninety patients with PTC without lymph nodes metastases
(LNM) detected on preoperative palpation and ultrasonographic examination were included. RESULTS: Forty-
one patients (45.5%) had LNM. Twenty-eight patients (31%) had a central and a lateral involvement. Thirteen
patients (14.5%) had only a central involvement. All the patients without LNM in the central compartment were
also free in the lateral compartment. There was no correlation between LNM status and TNM staging. The
largest LNM in the central compartment was smaller than or equal to 5mm in 66% of the cases, and that could
explain the lack of sensitivity of the preoperative ultrasonographic examination. CONCLUSION: CND could be
considered at preoperative or intraoperative diagnosis of PTC whereas lateral neck dissection should be
performed only in patients with preoperative suspected and/or intraoperatively proven LNM. Systematic CND
allows an objective evaluation of lymph node status in this central cervical area where the LNM are particularly
small and difficult to detect preoperatively.
PubMed-ID: 20584589
http://dx.doi.org/10.1016/j.ejso.2010.06.015

Minimally Invasive Video-Assisted Parathyroidectomy (MIVAP) for Secondary Hyperparathyroidism:
Report of Initial Experience.
Am J Surg, 199(6):851-5.
Alesina PF, Hinrichs J, Kribben A, Walz MK. 2010.
BACKGROUND: Minimally invasive video-assisted parathyroidectomy (MIVAP) has become a well-accepted
procedure for patients with primary hyperparathyroidism. Because it allows bilateral neck exploration, the
authors began using this technique for patients with secondary hyperparathyroidism. In this preliminary study,
the authors report their initial experience. METHODS: From July 2006 to November 2008, 12 patients (6 women,
6 men; mean age, 45.5 +/- 16.9 years (range, 23-71 years) underwent MIVAP with bilateral exploration for
secondary hyperparathyroidism. The operation was performed through a central 2-cm to 3-cm skin incision; a 30
degrees 5-mm endoscope was used for magnification. RESULTS: MIVAP was successfully completed in 11
patients (92%). The mean operative time was 81 +/- 37 minutes (range, 35-130 minutes). No major
complications were registered. After a mean follow-up period of 11.4 months (range, 3-30 months), 1 patient
showed recurrence. CONCLUSIONS: MIVAP appears to be a safe and feasible procedure in patients with
secondary hyperparathyroidism.
PubMed-ID: 20609728
http://dx.doi.org/10.1016/j.amjsurg.2009.05.041




ESES Review of Recently Published Literature 2010-2                                                  Page 31 of 63
Postoperative Calcium Requirements in 6,000 Patients Undergoing Outpatient Parathyroidectomy: Easily
Avoiding Symptomatic Hypocalcemia.
J Am Coll Surg, 211(1):49-54.
Vasher M, Goodman A, Politz D, Norman J. 2010.
BACKGROUND: To determine the amount and duration of supplemental oral calcium for patients with varying
clinical presentations discharged immediately after surgery for primary hyperparathyroidism. STUDY DESIGN: A
4-year, prospective, single-institution study of 6,000 patients undergoing parathyroidectomy for primary
hyperparathyroidism and discharged within 2.5 hours. Based on our previous studies, patients are started on a
sliding scale of oral calcium determined by a number of preoperative measures (ie, serum calcium, body weight,
osteoporosis) beginning 3 hours postoperation and decreasing to a maintenance dose by week 3. Patients
reported all hypocalcemia symptoms daily for 2 weeks. RESULTS: Seven parameters were found to have a
substantial impact on the amount of calcium required to prevent symptomatic hypocalcemia: preoperative serum
calcium >12 mg/dL, >13 mg/dL, and >13.5 mg/dL, bone density T score less than -3, morbid obesity, removal of
>1 parathyroid, and manipulation/biopsy of all remaining glands (all p < 0.05). Each independent variable
increased the daily calcium required by 315 mg/day. Using our scaled protocol, <8% of patients showed
symptoms of hypocalcemia, nearly all of whom were successfully self-treated with additional oral calcium. Only 6
patients (0.1%) required a visit to the emergency room for IV calcium, all occurring on postoperative day 3 or
later. CONCLUSION: After outpatient parathyroidectomy, a specific calcium protocol has been verified that
eliminates development of symptomatic hypocalcemia in >92% of patients, identifies patients at high risk for
hypocalcemia, and allows self-medication with confidence in a predictable fashion for those patients in whom
symptoms develop.
PubMed-ID: 20610248
http://dx.doi.org/10.1016/j.jamcollsurg.2010.03.019

Dual-Energy Computed Tomography Localizes Ectopic Parathyroid Adenoma.
J Clin Endocrinol Metab, 95(7):3092-3.
Gimm O, Juhlin C, Morales O, Persson A. 2010.
PubMed-ID: 20610604
http://dx.doi.org/10.1210/jc.2010-0386

Effect of Parathyroidectomy for Primary Hyperparathyroidism on Bone Mineral Density in
Postmenopausal Women.
Br J Surg, 97(7):1013-9.
Sitges-Serra A, Garcia L, Prieto R, Pena MJ, Nogues X, Sancho JJ. 2010.
BACKGROUND: The bone mineral density (BMD) response to parathyroidectomy is heterogeneous and difficult
to predict. Available data come from mixed populations of men and women, of different age and degrees of
disease severity, and preoperative BMD loss. METHODS: This was a longitudinal, prospective cohort study of
103 postmenopausal women with osteopenia or osteoporosis at the femoral neck site, successfully operated on
for primary hyper parathyroidism. BMD and metabolic variables were recorded before and 1 year after
parathyroidectomy. RESULTS: After surgery, there was a 1.3 per cent increase in the median BMD at the
femoral neck site (0.615 versus 0.623 g/cm(2); P = 0.001). Overall, positive responses were also observed at
total hip (0.4 per cent) and lumbar spine (2.3 per cent) sites. Analysing the individual responses, however, only
45 (46 per cent) of 97 patients showed a significant (at least 3.7 per cent) increase in BMD at the femoral neck
site compared with the preoperative value and 52 had a decreased (15) or unchanged (37) femoral neck BMD.
Patients who gained BMD were younger, had more severe hyperparathyroidism and better renal function.
CONCLUSION: Almost half of the postmenopausal women with hyperparathyroidism and low BMD have a
significant remineralization response 1 year after parathyroidectomy. Differential mineralization responses of
BMD after surgery appear to be related to severity of primary hyperparathyroidism, age and renal function.
PubMed-ID: 20632266
http://dx.doi.org/10.1002/bjs.7044

Serum Thyroglobulin Is a Poor Diagnostic Biomarker of Malignancy in Follicular and Hurthle-Cell
Neoplasms of the Thyroid.
Am J Surg, 200(1):41-6.
Suh I, Vriens MR, Guerrero MA, Griffin A, Shen WT, Duh QY, Clark OH, Kebebew E. 2010.
BACKGROUND: Serum thyroglobulin (Tg) is the most accurate biomarker for thyroid cancer recurrence.
However, some clinicians measure preoperative Tg as a diagnostic cancer marker despite lack of supporting
evidence. We examined whether Tg accurately predicts malignancy in follicular or Hurthle-cell neoplasms.
METHODS: We reviewed 366 patients who underwent thyroidectomies for follicular/Hurthle-cell neoplasms. We

ESES Review of Recently Published Literature 2010-2                                                Page 32 of 63
compared Tg in malignant versus benign tumors by univariate and receiver-operator characteristic analyses. We
also examined several Tg-derived indices that normalized Tg to known confounding factors including nodule
size, thyroid function, and type of Tg assay. RESULTS: Thirty-nine patients met inclusion criteria for analysis.
There were no differences between malignant (n = 16) and benign (n = 23) lesions in Tg or any of the
normalized indexes. Receiver-operator characteristic analysis revealed an area under the curve of .59. Lesions
with Tg levels greater than 500 mug/L had a positive predictive value of .75. CONCLUSIONS: Tg has poor
accuracy for predicting malignancy in follicular or Hurthle-cell thyroid neoplasms.
PubMed-ID: 20637335
http://dx.doi.org/10.1016/j.amjsurg.2009.08.030

Surgical Implications of B-RafV600E Mutation in Fine-Needle Aspiration of Thyroid Nodules.
Am J Surg, 200(1):136-43.
Mekel M, Nucera C, Hodin RA, Parangi S. 2010.
BACKGROUND: Management of patients with thyroid nodules is based on establishing an accurate diagnosis;
however, differentiating benign from malignant lesions preoperatively is not always possible using current
cytological techniques. Novel molecular testing on cytological material could lead to clearer treatment algorithms.
B-Raf(V600E) mutation is the most common genetic alteration in thyroid cancer, specifically found in papillary
thyroid cancer (PTC), and usually reported to be associated with aggressive disease. DATA SOURCE: A
literature search using PubMed identified all the pertinent literature on the identification and utilization of the B-
Raf(V600E) mutation in thyroid cancer. CONCLUSIONS: The utility of using B-Raf mutation testing for nodules
with indeterminate cytology is limited since many of those nodules (benign and malignant) do not harbor B-Raf
mutations. However, when the pathologist sees cytological features suspicious for PTC, B-Raf(V600E) mutation
analysis may enhance the assessment of preoperative risks for PTC, directing a more aggressive initial surgical
management when appropriate.
PubMed-ID: 20637346
http://dx.doi.org/10.1016/j.amjsurg.2009.08.029

Operative Failure in the Era of Focused Parathyroidectomy: a Contemporary Series of 845 Patients.
Arch Surg, 145(7):628-33.
Lew JI, Rivera M, Irvin GL, III, Solorzano CC. 2010.
HYPOTHESIS: Focused parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IPM) may
lead to higher failure rates because of missed multiglandular disease. DESIGN: Retrospective review of
prospectively collected data. SETTING: Tertiary referral center. PATIENTS: From September 8, 1993, through
January 30, 2009, a total of 845 consecutive patients with sporadic primary hyperparathyroidism underwent
focused parathyroidectomy guided by IPM at a single institution. MAIN OUTCOME MEASURES: Parathyroid
hormone dynamics and perioperative data were analyzed for factors affecting outcome. Operative failure was
defined as hypercalcemia with elevated parathyroid hormone levels within 6 months after parathyroidectomy.
Detailed intraoperative data from the failed operations were also reviewed. RESULTS: Of 723 patients followed
up for at least 6 months, 702 (97.1%) had successful parathyroidectomy, and 21 (2.9%) had failed
parathyroidectomy. The major cause of operative failure was the surgeon's inability to find the abnormal
parathyroid gland (16 of 21 patients [76.2%]). In the remaining patients, IPM results were false-positive in 5 of 21
patients (23.8%) or 0.7% overall. Among the cohort, IPM correctly identified missed multiglandular disease in 33
of 38 patients (86.8%). Patients having operative failure were more likely to have a history of thyroidectomy or
parathyroidectomy and were less likely to have correct findings on technetium Tc 99m sestamibi or
ultrasonographic localizing studies compared with patients having operative success. CONCLUSION: Inability of
the surgeon to find the abnormal parathyroid gland-not missed multiglandular disease-is the main cause of
operative failure in focused parathyroidectomy guided by IPM.
PubMed-ID: 20644124
http://dx.doi.org/10.1001/archsurg.2010.104

Utility of Elastography for Differential Diagnosis of Benign and Malignant Thyroid Nodules.
Otolaryngol Head Neck Surg, 143(2):230-4.
Kagoya R, Monobe H, Tojima H. 2010.
OBJECTIVE: 1) To classify the appearance of thyroid nodules displayed on ultrasound elastography; 2) to
explore the sensitivity and specificity of this examination for differentiating benign and malignant nodules, with
histopathologic analysis as the reference standard; and 3) to evaluate its utility for avoiding unnecessary
procedures. STUDY DESIGN: Diagnostic test assessment. SETTING: Community hospital. SUBJECTS AND
METHODS: Forty-seven thyroid nodules in 44 consecutive patients were examined with ultrasound
elastography. The images we obtained were classified into four patterns. In addition, the mean strain index of

ESES Review of Recently Published Literature 2010-2                                                   Page 33 of 63
the thyroid nodule and that of the sternocleidomastoid muscle were measured, and the nodule-to-muscle strain
ratio was calculated. As the reference findings, the presence or absence of calcification, irregular margins, and
hypoechogenicity of the thyroid nodules were examined using B-mode ultrasound. RESULTS: Elastography
patterns 3 and 4 were predictive of malignancy, with 73 percent sensitivity (95% confidence interval [CI]: 39%-
94%) and 64 percent specificity (95% CI: 46%-79%). Additionally, all nodules without calcification and those that
presented with patterns 1 or 2 were benign. A strain ratio greater than 1.5 was set as the predictor of thyroid
malignancy. This criterion showed 90 percent sensitivity (95% CI: 59%-100%) and 50 percent specificity (95%
CI: 33%-67%). CONCLUSION: Although elastography can assist in the differential diagnosis of thyroid nodules,
its diagnostic performance is not ideal at present. Further improvements in the technique and the diagnostic
criteria are necessary for this examination to provide a useful contribution to diagnosis.
PubMed-ID: 20647125
http://dx.doi.org/10.1016/j.otohns.2010.04.006

Thyroid Drains and Postoperative Drainage.
Otolaryngol Head Neck Surg, 143(2):235-8.
Dunlap WW, Berg RL, Urquhart AC. 2010.
OBJECTIVE: To evaluate postoperative drainage in patients undergoing thyroid lobectomy versus total
thyroidectomy and to establish a correlation between intraoperative blood loss and postoperative drainage.
STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary medical center. SUBJECTS AND
METHODS: Consecutive patients (n = 100) undergoing thyroid surgery from October 2006 through November
2008 were examined. Data collected included age, gender, postoperative drainage, estimated intraoperative
blood loss, type of surgery, length of hospital stay, pathology, and postoperative complications. Standard
descriptive statistics were used to summarize characteristics of subjects, surgical procedures, and outcomes.
Spearman rank correlation was used to evaluate association of drainage with blood loss and Kruskal-Wallis test
to compare results by surgery type. RESULTS: There were 100 surgeries performed: 52 lobectomies and 48
total thyroidectomies. Total postoperative drainage ranged from 0 to 230 mL, median was 32 mL. Estimated
intraoperative blood loss ranged from 10 to 300 mL, median was 20 mL. We noted a statistically significant
association of postoperative drainage with intraoperative blood loss (r = 0.39, P < 0.001), but substantial
variability in drainage was observed even among patients with similar blood loss. Although there was
significantly less drainage among thyroid lobectomies (P = 0.012), the distributions were quite similar apart from
10 patients (9 lobectomy) with exceptionally low drainage. CONCLUSION: There was a statistically significant
association of postoperative drainage with intraoperative blood loss and significantly less postoperative drainage
among patients undergoing thyroid lobectomies. However, the observed associations do not appear to be strong
enough to accurately predict patients who will experience substantial drainage.
PubMed-ID: 20647126
http://dx.doi.org/10.1016/j.otohns.2010.04.024

Adjuvant External Beam Radiation for Medullary Thyroid Carcinoma.
J Surg Oncol, 102(2):175-8.
Martinez SR, Beal SH, Chen A, Chen SL, Schneider PD. 2010.
BACKGROUND: Adjuvant radiation is rarely used to treat medullary thyroid carcinoma (MTC). We hypothesized
that external beam radiation therapy (EBRT) would improve overall survival (OS) in MTC patients. METHODS:
The Surveillance, Epidemiology, and End Results (SEER) database identified patients who underwent total
thyroidectomy and lymph nodes excision for MTC between 1988 and 2004. The Kaplan-Meier method was used
for univariate comparisons of OS. Multivariate Cox proportional hazards models controlled for gender, age,
lymph node status, tumor size, extent of disease, and EBRT. RESULTS: After 12 years, EBRT did not
significantly improve OS (log rank, P < 0.14). In node-positive patients, univariate analysis demonstrated an OS
benefit with EBRT (log rank, P < 0.05). In a multivariate model of node-positive patients, only increasing age (P <
0.001) and tumor size (P < 0.001) significantly influenced OS. CONCLUSIONS: The OS benefit attributed to
EBRT in node-positive patients by univariate analysis could not be duplicated when controlling for known
prognostic factors.
PubMed-ID: 20648590
http://dx.doi.org/10.1002/jso.21557

Prospective Study in 3,000 Consecutive Parathyroid Operations Demonstrates 18 Objective Factors That
Influence the Decision for Unilateral Versus Bilateral Surgical Approach.
J Am Coll Surg , 211(2):244-9.
Norman J, Politz D. 2010.
BACKGROUND: Although localizing studies are well-known predictors of which patients are candidates for

ESES Review of Recently Published Literature 2010-2                                                Page 34 of 63
unilateral versus bilateral parathyroid exploration, there are a number of other factors that have positive or
negative influence preoperatively and intraoperatively. STUDY DESIGN: A prospective study was conducted
during 20 months on 3,000 consecutive patients undergoing surgery for primary hyperparathyroidism to
determine which factors caused the surgeons to explore bilaterally or, in contrast, influenced a unilateral
approach. Seventeen preoperative and 5 intraoperative objective points were documented on all patients to see
how decisions were made. RESULTS: Parathyroidectomy was unilateral in 32% and bilateral in 68%.
Preoperative factors that had a positive predictive value in dictating a unilateral approach were (in decreasing
frequency): positive sestamibi, previous parathyroid/thyroid surgery, age older than 80 years, anticoagulation
medications, morbid obesity, and presence of large goiter (all p < 0.001). Preoperative parameters dictating a
bilateral approach included negative sestamibi, more than one focus on sestamibi, contralateral thyroid disease,
family history, lithium use, history of radiation, MEN, age younger than 20 years, and pregnancy (all p < 0.001).
Intraoperative parameters influencing conversion of unilateral to bilateral were false-positive sestamibi, hormone
measures not meeting sufficient levels, abnormal ipsilateral gland, and contralateral thyroid pathology identified
(all p < 0.001). Factors that had no effect were gender, degree of calcium, and/or parathyroid hormone elevation,
and age between 20 and 80 years. Cure rates were 99.9% for bilateral and 99.0% for unilateral (p = 0.057).
CONCLUSIONS: High-volume surgeons use a number of identifiable objective factors to determine the best
candidates for unilateral versus bilateral parathyroid exploration. Localizing studies such as sestamibi scans
ultimately play a minor role in determining how many parathyroid glands are evaluated.
PubMed-ID: 20670863
http://dx.doi.org/10.1016/j.jamcollsurg.2010.03.040

Current Status of Surgical Techniques for Parathyroidectomy for Untreated Primary
Hyperparathyroidism: Is the Technology Worth It?
Am Surg, 76(7):663-71.
Flynn MB, Civelek AC. 2010.
PubMed-ID: 20698367

Postoperative Parathyroid Hormone Testing Decreases Symptomatic Hypocalcemia and Associated
Emergency Room Visits After Total Thyroidectomy.
Surgery, 148(4):841-4.
Youngwirth L, Benavidez J, Sippel R, Chen H. 2010.
BACKGROUND: Symptomatic hypocalcemia, the most common complication of total thyroidectomy, can lead to
postoperative emergency room visits for laboratory testing and intravenous calcium infusion. A method to identify
patients reliably at risk for postoperative hypocalcemia could allow prophylactic treatment to avoid this. We
hypothesized that quick parathyroid hormone testing within 4 hours of thyroidectomy and a protocol to treat
parathyroid-hormone-deficient patients would reduce symptomatic hypocalcemia, eliminating the need for
emergency room visits. METHODS: After January 1, 2006, 271 consecutive patients underwent total
thyroidectomy with postoperative parathyroid hormone testing (group 1). Patients with parathyroid hormone
levels <10 pg/mL were treated according to a newly instituted protocol with 0.25-ug calcitriol twice daily and 2-6
g of calcium carbonate daily for 1 week. Patients with parathyroid hormone levels >/=10 pg/mL were treated with
calcium only. Group 2 consisted of 100 consecutive patients who underwent total thyroidectomy prior to 2006
without parathyroid hormone testing and were treated according to surgeon preference and serum calcium
levels. RESULTS: Patients in the 2 groups were similar with regard to age, sex, and thyroiditis. However,
patients in group 1, who had parathyroid hormone testing, had greater postoperative calcium levels (P < .005).
Also, patients in group 2 had a higher incidence of malignancy (P = .04). Importantly, patients in group 1 had a
lesser incidence of symptomatic hypocalcemia (7% vs 17%; P = .005). Furthermore, the number of patients who
made visits to the emergency room was less in patients who had parathyroid hormone testing compared with
those who did not (1.8% vs 8.0%; P = .008). CONCLUSION: Postoperative parathyroid hormone testing reliably
identifies patients at risk for hypocalcemia after thyroid surgery. Moreover, parathyroid hormone testing and
calcitriol administration to patients at risk decreases the incidence of hypocalcemia and associated emergency
room visits after total thyroidectomy. Therefore, patients with postoperative serum parathyroid hormone levels
<10 pg/mL after thyroid surgery should be treated with calcitriol and calcium to prevent symptomatic
hypocalcemia.
PubMed-ID: 20723956
http://dx.doi.org/10.1016/j.surg.2010.07.038

Recurrent Hyperparathyroidism and Forearm Parathyromatosis After Total Parathyroidectomy.
Surgery, 148(4):867-73.
Melck AL, Carty SE, Seethala RR, Armstrong MJ, Stang MT, Ogilvie JB, Yip L. 2010.

ESES Review of Recently Published Literature 2010-2                                                Page 35 of 63
BACKGROUND: In multiple endocrine neoplasia type I and renal failure, the type of initial parathyroidectomy for
hyperparathyroidism may influence the operative risks and development of recurrence. We compared subtotal
parathyroidectomy with total parathyroidectomy and immediate forearm autotransplantation (TPFA) in a large
series with long-term follow-up. METHODS: The data of patients treated from 1977 to 2009 by initial or
reoperative TPFA or subtotal parathyroidectomy were examined for outcomes including the interval to sites and
tissue patterns of recurrence. RESULTS: Permanent hypoparathyroidism was rare and uninfluenced by disease
type. Neither initial procedure nor underlying disease affected the mean time to reoperation for recurrent
hyperparathyroidism. In renal failure, reoperation was more common after TPFA than subtotal
parathyroidectomy (5/19, 26% vs 11/193, 6%; P = .008). Twelve patients required forearm reoperation after
TPFA, which was often complicated by parathyromatosis (7/12, 58%). Further reoperative forearm surgery was
more likely after explant excision than after en bloc resection (7/11 vs 0/8; P = .01) and occurred sooner in renal
failure than in multiple endocrine neoplasia type I (mean 4.4 vs 9 years; P = .04). Permanent hypoparathyroidism
was rare and uninfluenced by disease type. CONCLUSION: Because of frequent recurrence, TPFA should be
abandoned as a treatment of renal hyperparathyroidism. In multiple endocrine neoplasia type I, subtotal
parathyroidectomy has similar outcomes to TPFA. Forearm autotransplantation can be complicated by
parathyromatosis, and surgeons should be prepared for reoperative en bloc resection.
PubMed-ID: 20800255
http://dx.doi.org/10.1016/j.surg.2010.07.037

Parathyroidectomy for Hypercalcemic Crisis: 40 Years' Experience and Long-Term Outcomes.
Surgery, 148(4):807-12.
Cannon J, Lew JI, Solorzano CC. 2010.
BACKGROUND: Hypercalcemic crisis is a serious and potentially life-threatening complication of markedly
increased serum calcium concentrations most commonly due to severe primary sporadic hyperparathyroidism
(HPT). METHODS: A review of 1,310 consecutive patients with severe sporadic HPT who underwent
parathyroidectomy at a single institution from April 1970 through July 2009 was performed. Of this series, 88
patients were treated operatively for hypercalcemic crisis associated with signs and symptoms of acute calcium
intoxication and/or serum calcium concentrations >/=14 mg/dL (3.5 mmol/L). Clinical presentation, laboratory
values, operative success, operative failure, and disease recurrence were compared to noncrisis patients.
RESULTS: Preoperative calcium and parathyroid hormone (PTH) concentrations were significantly greater
among patients with hypercalcemic crisis. Crisis patients had a greater incidence of mental status changes,
fatigue, ectopic glands, and pancreatitis. Postoperatively, calcium and PTH levels were similar. Overall, crisis
patients had a lesser rate of operative success compared to noncrisis patients (92% vs 97%). With the advent of
intraoperative PTH monitoring-guided focused parathyroidectomy in 1993, success rates equalized (95% vs
97%). There was no difference in disease recurrence. Overall follow-up was 59 months. CONCLUSION:
Hypercalcemic crisis patients are appropriately treated by expeditious parathyroidectomy, but overall have
slightly lesser rates of initial operative success than noncrisis patients. Long-term results reveal similar serum
calcium, PTH concentrations, and recurrence rates at a mean follow-up of nearly 5 years.
PubMed-ID: 20800863
http://dx.doi.org/10.1016/j.surg.2010.07.041

Age and Tumor Size Predicts Lymph Node Involvement in Hurthle Cell Carcinoma.
J Cancer, 1:23-6.
Guerrero MA, Suh I, Vriens MR, Shen WT, Gosnell J, Kebebew E, Duh QY, Clark OH. 2010.
Introduction: Hurthle cell carcinoma (HCC) is a rare tumor that tends to metastasize to the lymph nodes. Some
studies have correlated size of Hurthle cell tumors with the risk of malignancy. Whether the size of HCC
correlates with the risk of lymph node (LN) metastases, to our knowledge has not been addressed.Methods: A
retrospective analysis was performed on all patients diagnosed with HCC on final pathology between 1997 and
2008. The tumor size and lymph node status was obtained for each patient. The data were analyzed utilizing
Student's t-test and the Fisher's exact test to calculate the two-tailed p-value.Results: Out of 39 patients
diagnosed with HCC 3(8%) had LN metastases; 1 had ipsilateral central LN metastasis and 2 had ipsilateral
central and lateral LN metastasis. LN dissection was performed in patients with known metastasis (2 were
evident on preoperative ultrasound and 1 intraoperatively). Patients with LN metastasis were older than those
without (mean age: 86.7 and 56.4 years, respectively), had larger tumors (mean size: 6 and 4 cm) and were
commonly male (2 of 3). No tumor < 5cm presented with lymph node involvement (3/15 with >5cm cancer had
node metastasis, 0/24 with <5cm cancer had node metastasis).Conclusions: Similar to what has been found in
patients with papillary thyroid cancer, older male patients with Hurthle cell carcinomas greater than 5cm are
more likely to have lymph node metastasis. Our data suggest that these patients may benefit from a prophylactic



ESES Review of Recently Published Literature 2010-2                                                Page 36 of 63
ipsilateral central neck dissection at the time of their initial operation.
PubMed-ID: 20842220




ESES Review of Recently Published Literature 2010-2                           Page 37 of 63
Parathyroid

Meta-Analyses
- None -


Randomized controlled trials
- None -


Other Articles
[Primary Hyperparathyroidism. Postoperative Normocalcemic Hyperparathyrinemia After Curative
Parathyroidectomy]
Primarer Hyperparathyreoidismus. Postoperative Normokalzamische Hyperparathyrinamie Nach
Kurativer Parathyreoidektomie.
Chirurg, 81(5):447-53.
Hermann M. 2010.
INTRODUCTION: Normocalcemic hyperparathyrinemia, i.e. elevated parathyroid hormone (PTH) levels after
parathyroidectomy in patients with primary hyperparathyroidism (pHPT) may occur in the course of postoperative
recovery without the development of persistence or relapse. MATERIALS, METHODS AND RESULTS:
Intraoperative and long-term (7 year) postoperative PTH and calcium levels after curative parathyroidectomy are
demonstrated on the basis of a case report of a 62-year-old female patient with severe pHPT and pronounced
osseous and renal manifestations. The intraoperative PTH gradient displayed a decrease from 1072 pg/ml to 13
pg/ml (normal range 11-67 pg/ml) followed by an increase of up to 287 pg/ml. The hyperparathyoid values
decline to subnormal levels on administration of calcium and vitamin D and increase again after tapering these
medications. The inverse calcium/PTH correlation in the course of the 7-year observation period suggests an
intact feed-back mechanism. Preoperative PTH screening was performed in 316 consecutive normocalcemic
thyroid patients to evaluate the rate of incidental hyperparathyroidism in patients with normal serum calcium
levels. Of these patients 31 (9.8%) with normocalcemia (average 2.28 mmol/l, normal range 2.1-2.7 mmol/l)
exhibited increased PTH levels averaging 84.2 pg/ml. A parathyroid adenoma was found intraoperatively as the
cause for normocalcemic pHPT in only 1 of these 31 patients. DISCUSSION AND CONCLUSIONS: A review of
the literature revealed that late postoperative elevated parathyroid hormone levels after successful pHPT surgery
occur in 21.5%. Multiple causes are discussed, e.g. reactive hyperparathyroidism in cases of relative
hypocalcemia, hungry bone syndrome, vitamin D deficiency, renal dysfunction and ethnic or lifestyle differences.
In mild cases of postoperative hyperparathyrinemia observation of the patient may be sufficient. In cases of
reactive hyperparathyroidism due to hypocalcemia, administration of calcium is indicated, in symptomatic
patients, additional administration of vitamin D or calcitriol is necessary. Vitamin D deficiency per se needs
adequate substitution. In cases of ongoing hyperparathyrinemia an interdisciplinary diagnostic and therapeutic
approach is required.
PubMed-ID: 19468699
http://dx.doi.org/10.1007/s00104-009-1717-9

Primary Hyperparathyroidism.
Cancer Treat Res, 153:87-103.
Kelly KJ, Chen H, Sippel RS. 2010.
PubMed-ID: 19957221
http://dx.doi.org/10.1007/978-1-4419-0857-5_6

Comparison of Consumer Information on the Internet to the Current Evidence Base for Minimally
Invasive Parathyroidectomy.
World J Surg, 34(6):1304-11.
McLean T, Delbridge L. 2010.
BACKGROUND: The Internet is increasingly used as a source of health information by patients. Under these
circumstances, the opportunity exists for Internet sites ostensibly providing patient information to act to promote


ESES Review of Recently Published Literature 2010-2                                                  Page 38 of 63
surgical referrals based on exaggerated claims. This study aims to assess quantitatively and qualitatively the
Internet-based consumer health information for minimally invasive parathyroidectomy (MIP) techniques.
METHODS: This is a prospective analysis of Internet web sites. Descriptive information about specific published
claims on each of the web sites was documented and compared to the published evidence base. Web sites
were then rated using a validated composite score (CS) tool and an MIP score tool developed specifically for the
study. RESULTS: The search yielded 308 web sites, which, after assessment by the inclusion criteria left 44
unique web sites suitable for analysis. "Exaggerated," "misleading," or "false" claims were present in 27.3% of
the web sites analyzed. The false claims category had a high negative item-total correlation with the overall
score, and accuracy was found to have a statistically significant (p < 0.05) negative correlation with quality.
However, analysis performed for country of origin and the organization responsible for the web site found no
significant difference. CONCLUSIONS: Web sites offering information in relation to MIP have a surprisingly high
rate of claims that are not in accord with the evidence. Such claims may be posted to attract surgical referrals. It
is difficult for consumers to differentiate quality consumer health web sites from poor ones as there are no hard
and fast rules to differentiate them.
PubMed-ID: 20012291
http://dx.doi.org/10.1007/s00268-009-0306-x

Transoral Thyroid and Parathyroid Surgery.
Surg Endosc, 24(6):1261-7.
Karakas E, Steinfeldt T, Gockel A, Westermann R, Kiefer A, Bartsch DK. 2010.
BACKGROUND: Translumenal endoscopic interventions via so-called natural orifices are gaining increasing
interest because they allow surgical treatment without any incision of the skin. Moreover, minimally invasive
procedures have found their way into thyroid and parathyroid surgery. Our goal was to develop a new access for
thyroid and parathyroid resection via an entirely transoral approach. METHODS: We managed to find an entirely
transoral sublingual access to the thyroid region in pigs and human cadavers. Using a modified rigid rectoscope
(oraloscope) hemithyroidectomies as well as resection of parathyroid glands were performed via this new
approach. Preparation and resection was performed using conventional laparoscopic instruments. In living pigs,
integrity of the recurrent laryngeal nerve after resection could be documented by neuromonitoring. An
absorbable suture was used to seal the mucosal incision. RESULTS: First, hemithyroidectomy was performed
via the transoral access in 10 porcine cadavers, then in 10 living and orally intubated pigs, and finally in five
human corpses. In humans, resection of parathyroid glands also was performed. We gained access to the
thyroid region by blunt dissection of the layer behind the hyoid bone and the strap muscles of the neck. We did
not observe any complication during the insertion, resection, and removal part of the new procedure.
CONCLUSIONS: Entirely transoral thyroid and parathyroid surgery via sublingual access seems to be feasible.
However, further investigations are needed to evaluate the safety of the new technique, especially potential and
clinically relevant contamination of the access route has to be excluded.
PubMed-ID: 20033730
http://dx.doi.org/10.1007/s00464-009-0757-z

Vitamin D3 Deficiency Is Associated With Late-Onset Hypocalcemia After Minimally Invasive
Parathyroidectomy in a Vitamin D Borderline Area.
World J Surg, 34(6):1350-5.
Lang BH, Lo CY. 2010.
BACKGROUND: Concurrent vitamin D(3) deficiency is common in primary hyperparathyroidism (pHPT). We
aimed to examine the clinicopathologic features and short-term outcomes of vitamin D(3)-deficient patients after
minimally invasive parathyroidectomy (MIP). METHODS: Over 2-year period, 80 consecutive MIP patients had
preoperative-fasting 25-hydroxyvitamin D(3) (25OHD(3)) checked. Forty-five patients had a 25OHD(3) level <20
ng/ml and were defined as deficient. Intraoperative parathyroid hormone (IOPTH) assay was used for all MIP.
Postoperative adjusted calcium (Ca) was checked at 6, 16 (with intact PTH), and 24 h. Oral calcium and vitamin
D supplements were given if hypocalcemic symptoms developed or Ca < 2.00 mmol/l. Late-onset hypocalcemia
(LOH) was defined as symptoms developed after 24 h. RESULTS: Both deficient and nondeficient groups had
similar demographic data and bone density scores. The deficient group had significantly higher PTH (190 vs.
121 pg/ml, p = 0.015). Although IOPTH in the deficient group were higher at induction and 0 min after excision,
the percentage drop from induction to 10 min after excision was similar. Ca was similar at 6 and 16 h in the two
groups but was significantly lower in the deficient group at 24 h (2.10 vs. 2.45 mmol/l, p = 0.033). At 1 week, the
proportion of LOH was significantly higher in the deficient group (12/42 vs. 3/34, p = 0.043) and in those with
preoperative PTH > 100 pg/ml (15/57 vs. 0/19, p = 0.013). CONCLUSIONS: Vitamin D(3) deficiency was
associated with a higher preoperative PTH level and a greater risk of LOH after MIP. However, the likely cause
of LOH remains unclear as both low preoperative vitamin D(3) and high PTH levels could be responsible.


ESES Review of Recently Published Literature 2010-2                                                  Page 39 of 63
PubMed-ID: 20054540
http://dx.doi.org/10.1007/s00268-009-0377-8

Should Routine Analysis of the MEN1 Gene Be Performed in All Patients With Primary
Hyperparathyroidism Under 40 Years of Age?
World J Surg, 34(6):1294-8.
Skandarajah A, Barlier A, Morlet-Barlat N, Sebag F, Enjalbert A, Conte-Devolx B, Henry JF. 2010.
BACKGROUND: Familial hyperparathyroidism, especially Multiple Endocrine Neoplasia Type 1, is more likely to
present with primary hyperparathyroidism (1 degrees HPT) at a young age, mandating bilateral exploration of the
parathyroid glands. However, the majority of young patients will not be gene carriers or have a family history.
Recent evidence suggests that young adults under 40, in whom there is no suspicion of family history, can be
managed with the same pre- and perioperative strategy as used for sporadic primary HPT of any age. Our aim
was to evaluate the prevalence of mutations in the MEN1 gene in young adults under 40 who present with
apparent sporadic 1 degrees HPT. METHODS: A retrospective review was undertaken of all patients who
underwent surgery for 1 degrees HPT between 1993 and 2004. From a total of 1253 patients, 87 (6.2%) were
under the age of 40. Thirty-three patients provided informed consent to a detailed personal and family history,
physical examination, and genetic analysis of the MEN1 gene. Twelve patients were subsequently excluded as
they were known gene carriers prior to surgery (10 MEN1 and 2 MEN2A patients). Twenty-one patients
underwent genetic analysis. RESULTS: Of the 21 patients who consented to genetic analysis, the mean age
was 30.8 years (range = 18-39 years with 43% younger than 30). These patients had no suspicious family or
personal histories suggestive of a MEN phenotype. Fifteen patients presented with symptomatic hypercalcemia.
All 21 patients underwent parathyroid surgery by conventional cervicotomy (12) or endoscopic
parathyroidectomy in cases (9) where the parathyroid gland was localized preoperatively. Nineteen patients
(91%) had uniglandular disease. Surgical cure was achieved in all patients. Of the 21 patients, only one patient
(4.7%) was found to have a MEN1 gene mutation (exon 3, at codon 190, c;680_681delGGinsC). This patient
was found to have double adenomas at surgery with subsequent histological confirmation. The overall
prevalence of MEN1 mutation in all patients under 40 was 13%. CONCLUSION: Although young age is often the
only criterion to suspect MEN1, our results do not support routine MEN1 analysis in patients under 40. We
propose that these patients be managed with the same preoperative and surgical approach as those presenting
with sporadic 1 degrees HPT of any age.
PubMed-ID: 20058152
http://dx.doi.org/10.1007/s00268-009-0388-5

Weight Difference Between Double Parathyroid Adenomas Is the Cause of False-Positive IOPTH Test
After Resection of the First Lesion.
World J Surg, 34(6):1337-42.
Sitges-Serra A, az-Aguirregoitia FJ, de la QA, Gil-Sanchez J, Jimeno J, Prieto R, Sancho JJ. 2010.
BACKGROUND: Some patients with double parathyroid adenoma show a greater than 50% decline in
intraoperative parathyroid hormone (IOPTH) after resection of the first lesion. The present study was designed to
test the hypothesis that significant adenoma weight differences may explain this inappropriate decline of IOPTH.
METHODS: We reviewed prospective database records at two tertiary institutions. Patients with a
histopathologic diagnosis of double adenoma and no familial history of hyperparathyroidism were included.
Diagnosis of double adenoma was confirmed either preoperatively (double uptake), intraoperatively (bilateral
exploration), or at reintervention. IOPTH was determined following the Miami protocol. The 10-min postexcision
sample was considered as the 0-min sample for IOPTH determinations at the time of resection of the second
lesion. RESULTS: Thirteen patients met the inclusion criteria. After resection of the first lesion, IOPTH failed to
decline in four patients and a second adenoma was removed. They had similar weight (404 vs. 598 mg). In nine
patients IOPTH showed a false greater than 50% decline. These patients had the largest adenoma removed first
(846 +/- 226 mg), and only two had normal PTH serum concentrations 10 min after resection. The second
adenoma was always smaller (284 +/- 177 mg; P = 0.02) and its resection either during the same operation (7
cases) or at reoperation (2 cases) led to normalization of IOPTH at 10 min in all cases. CONCLUSIONS: Two-
thirds of patients with double parathyroid adenoma show a false-positive decline of IOPTH after resection of the
first adenoma. This appears to be due to the initial removal of the larger lesion.
PubMed-ID: 20107797
http://dx.doi.org/10.1007/s00268-010-0413-8

Removal of Autografted Parathyroid Tissue for Recurrent Renal Hyperparathyroidism in Hemodialysis
Patients.
World J Surg, 34(6):1312-7.

ESES Review of Recently Published Literature 2010-2                                                 Page 40 of 63
Tominaga Y, Matsuoka S, Uno N, Tsuzuki T, Hiramitsu T, Goto N, Nagasaka T, Watarai Y, Uchida K. 2010.
BACKGROUND: Recurrent renal hyperparathyroidism (HPT) is a serious problem after parathyroidectomy
(PTx). We evaluated the frequency of graft-dependent recurrent HPT and the clinical outcomes after removal of
the autograft. METHODS: Between March 1980 and January 2009, 2660 patients underwent total PTx with
forearm autograft. After resection of all parathyroid glands, 30 pieces of 1 x 1 x 3 mm parathyroid tissue from
diffuse hyperplasia, if possible, were autografted into brachioradial muscle. Graft-dependent recurrence of HPT
was diagnosed by a high PTH gradient and detection of swollen autografts by palpation and/or MRI or US.
RESULTS: In 248/2660 (9.3%) patients, removal of the graft was required a total of 327 times (53 patients
required removal of the autograft several times). The cumulative frequency of graft-dependent recurrent HPT
was 17.4% ten years after the initial PTx. Thirty-two patients underwent both resection of missed glands located
in the neck or mediastinum and removal of the graft. En-bloc resection of autograft with surrounding muscle was
required to avoid reoperation. When the intact PTH level dropped under 300 pg/ml, in the majority of patients
renal HPT could be medically managed after the operation. The mean weight of the resected parathyroid tissue
was 1583.7 mg. No specimen had histopathologically malignant features. Three patients suffered from
hematoma in the wound. CONCLUSIONS: Graft-dependent recurrent renal HPT is not negligible. However, in
the majority of patients, renal HPT can be controlled by removal of the autograft noninvasively. Total PTx with
forearm autograft is preferable for hemodialysis patients, especially when long-term survival is expected.
PubMed-ID: 20130870
http://dx.doi.org/10.1007/s00268-010-0412-9

Outcome of Total Parathyroidectomy and Autotransplantation As Treatment of Secondary and Tertiary
Hyperparathyroidism in Children and Adults.
World J Surg, 34(5):993-1000.
Kievit AJ, Tinnemans JG, Idu MM, Groothoff JW, Surachno S, Aronson DC. 2010.
BACKGROUND: Treatment safety and effectiveness of total parathyroidectomy and autotransplantation for
secondary and tertiary hyperparathyroidism have been extensively proven in adults; the evidence for children,
however, is scarce. Children and adolescents cannot simply be seen as young adults in the case of chronic
kidney disease and hyperparathyroidism. The aim of this retrospective study was therefore, to evaluate whether
parathyroidectomy with forearm autograft is as effective and safe in children and adolescents as in adults.
METHODS: A group of 64 adults and 8 children and adolescents treated for secondary or tertiary
hyperparathyroidism were retrieved from our database. The outcomes were compared on patient demographics,
operation results, and blood parameters consisting of parathyroid hormone (PTH) and calcium levels. Our results
were compared with all currently available articles on parathyroidectomy in children with secondary or tertiary
hyperparathyroidism (n = 11). RESULTS: For adults, preoperative mean serum calcium was 2.67 +/- 0.29 mmol/l
and mean parathyroid hormone (PTH) level was 120 +/- 86 pmol/l. For children, preoperative mean serum
calcium was 2.62 +/- 0.20 mmol/l and mean parathyroid hormone (PTH) level was 80 +/- 38 pmol/l.
Postoperative calcium and parathyroid hormone levels for adults dropped to 2.39 +/- 0.23 mmol/l and 30 +/- 53
pmol/l, respectively. Postoperative calcium and parathyroid hormone levels for children dropped to 2.41 +/- 0.16
mmol/l and 26 +/- 33 pmol/l, respectively. The effectiveness of parathyroidectomy with autotransplantation was
75% in children and 72% in adults. Thus, effectiveness did not differ significantly between children and adults.
CONCLUSIONS: Combining the results of our own study with a literature review on pediatric parathyroidectomy,
we conclude that parathyroidectomy and forearm autograft is as effective a treatment for secondary and tertiary
hyperparathyroidism in children and adolescents as it is in adults.
PubMed-ID: 20145928
http://dx.doi.org/10.1007/s00268-010-0446-z

Bilateral Internal Jugular Venous Sampling for Parathyroid Hormone Determination in Patients With
Nonlocalizing Primary Hyperparathyroidism.
World J Surg, 34(6):1299-303.
Alvarado R, Meyer-Rochow G, Sywak M, Delbridge L, Sidhu S. 2010.
BACKGROUND: Focused parathyroidectomy (FP) is offered to 60% to 70% of patients presenting to our unit
with primary hyperparathyroidism (PHPT). A recent report identified bilateral internal jugular venous sampling
(BIJVS) as a useful tool for localization of parathyroid adenomas in patients with scan-negative PHPT. The
purpose of this study was to evaluate the utility of this approach in a clinical setting. METHODS: A prospective
case-control trial was undertaken. Bilateral internal jugular venous blood samples were obtained. Patients were
stratified into three groups: Group A consisted of patients with a negative sestamibi scan undergoing bilateral
exploration; group B consisted of patients undergoing FP following a positive sestamibi scan; and group C
patients were a control group undergoing total thyroidectomy. RESULTS: In group A, 17 of 30 patients (56%)
had lateralization of the parathyroid hormone (PTH) levels, with 11 correctly lateralizing to the side of the


ESES Review of Recently Published Literature 2010-2                                               Page 41 of 63
adenoma, 5 lateralizing despite bilateral disease, and 1 lateralizing to the contralateral side. Of the remaining 13
patients in whom there was no lateralization, 3 had bilateral multigland disease, and 10 had a single parathyroid
adenoma. In group B, 17 of 30 patients (56%) also had lateralization of PTH levels, with 15 lateralizing to the
side of the adenoma and 2 to the contralateral side. Lateralization failed in the remaining 13 patients, although in
all of these patients the calcium and PTH levels normalized postoperatively. The control group of patients
without parathyroid disease (group C) demonstrated lateralization of PTH levels in 23 of 30 patients (76%).
CONCLUSIONS: In our hands, BIJVS for PTH determination was not a useful adjunctive test facilitating FP. We
continue to offer all patients with PHPT and a negative sestamibi scan a standard bilateral neck exploration.
PubMed-ID: 20372897
http://dx.doi.org/10.1007/s00268-010-0556-7

Secondary and Tertiary Hyperparathyroidism: the Utility of IoPTH Monitoring.
World J Surg, 34(6):1343-9.
Pitt SC, Panneerselvan R, Chen H, Sippel RS. 2010.
BACKGROUND: The aim of the present study was to examine the utility of intraoperative parathyroid hormone
(ioPTH) monitoring in patients with secondary (2) and tertiary (3) hyperparathyroidism (HPT). MATERIALS AND
METHODS: We identified 105 patients with 2HPT (n = 33) and 3HPT (n = 72) who underwent ioPTH monitoring
during parathyroidectomy. Data are reported as mean +/- SEM. RESULTS: The 2HPT patients underwent 17
subtotal, 10 total, and 6 re-exploratory parathyroidectomies, whereas the 3HPT patients underwent 54 subtotal,
15 limited, and 3 re-exploratory parathyroidectomies. The percent decrease from the baseline ioPTH level at 5,
10, and 15 min after parathyroid resection, respectively, were 72% +/- 3%, 76% +/- 3%, and 76% +/- 3% in
patients with 2HPT, and 52% +/- 6%, 60% +/- 4%, and 69% +/- 4% in patients with 3HPT. IoPTH levels failed to
drop >50% from baseline in 5 patients (2HPT: n = 2, 3HPT: n = 3) who were normocalcemic at last follow-up.
IoPTH did not alter the surgical approach in any 2HPT patients, but did alter management in 25% of 3HPT
patients (15 limited resections and 3 supernumerary glands). Normocalcemia was achieved in 97% of 2HPT
patients and 99% of 3HPT patients; 2 patients developed recurrent disease. CONCLUSIONS: Intraoperative
PTH levels fell by >50% in nearly 95% of patients with 2HPT and 3HPT, and the PTH level reliably predicted
postoperative cure. Although the use of ioPTH did not alter surgical management in any patient with 2HPT, this
rapid PTH assay affected the surgical care of a quarter of the patients with 3HPT, and it may prove to be a
useful adjunct in this group of patients.
PubMed-ID: 20386902
http://dx.doi.org/10.1007/s00268-010-0575-4

Normalization of 2-Week Postoperative Parathyroid Hormone Values in Patients With Primary
Hyperparathyroidism: Four-Gland Exploration Compared to Focused-Approach Surgery.
World J Surg, 34(6):1318-24.
Mazzaglia PJ, Milas M, Berber E, Siperstein A, Monchik JM. 2010.
BACKGROUND: Elevation of parathyroid hormone (PTH) levels is commonly seen in patients with primary
hyperparathyroidism (PHPT) who have undergone parathyroidectomy. This study evaluates differences in 2-
week postoperative PTH levels in patients having focused-approach surgery versus four-gland exploration.
METHODS: Over 6 years, patients at Rhode Island Hospital (RIH) and the Cleveland Clinic (CCF) who had
PHPT and underwent localization studies suggestive of single adenoma were analyzed. At RIH patients
underwent focused-approach surgery, and at CCF routine four-gland exploration was performed. Postoperative
calcium supplementation was routine at RIH and selective at CCF. RESULTS: There were 308 patients at RIH
and 370 at CCF. They were similar in age (59.2 +/- 13.0 years at RIH and 60.4 +/- 12.9 years at CCF), and sex
(76.9 and 80.0% female at RIH and CCF, respectively). The mean preoperative serum calcium measured 10.9
+/- 0.7 mg/dl at RIH and 11.1 +/- 0.7 mg/dl at CCF (P < 0.001). Preoperative PTH values were similar,
measuring 143.8 +/- 104.8 pg/ml in the focused-approach group (RIH) and 157.6 +/- 150.3 pg/ml in the four-
gland exploration group (CCF). Preoperative 25-hydroxyvitamin D (vitamin D-25) levels were 24.1 +/- 12.0 ng/ml
at RIH and 27.4 +/- 10.6 ng/ml at CCF; and the prevalence of vitamin D-25 deficiency (level <20 ng/ml) was
43.9% at RIH and 27% at CCF (P = 0.017). The proportion of patients whose intraoperative PTH value dropped
by >or=50% prior to completion of surgery was 95.0% at RIH and 95.5% at CCF. The total gland weight resected
per patient was 942 mg at RIH versus 1,394 mg at CCF (P = 0.003). The 2-week postoperative serum PTH was
>65 pg/ml in 18.8% at RIH and in 38.7% at CCF (P < 0.001). The 2-week postoperative serum calcium values
dropped to 9.2 +/- 0.6 mg/dl at RIH and to 9.5 +/- 0.8 mg/dl at CCF (P < 0.001). The incidence of multigland
disease was 5.8% at RIH and 21.9% at CCF (P <or= 0.001). CONCLUSIONS: Among patients with PHPT who
underwent a localizing study indicating unilateral disease, a significant proportion had eucalcemic PTH elevation
2 weeks after parathyroidectomy. The elevation was more frequent in the four-gland exploration group and
correlated most strongly with greater adenoma mass.


ESES Review of Recently Published Literature 2010-2                                                  Page 42 of 63
PubMed-ID: 20386907
http://dx.doi.org/10.1007/s00268-010-0557-6

Causes and Treatment of Recurrent Hyperparathyroidism After Subtotal Parathyroidectomy in the
Presence of Multiple Endocrine Neoplasia 1.
World J Surg, 34(6):1325-31.
Salmeron MD, Gonzalez JM, Sancho IJ, Goday A, Perez NM, Zambudio AR, Paricio PP, Serra AS. 2010.
BACKGROUND: Subtotal parathyroidectomy (SPTX) is the treatment of choice for hyperparathyroidism in a
patient with multiple endocrine neoplasia type 1 (HPT-MEN-1). There are scarce data on the causes, timing, and
appropriate surgical treatment of patients with recurrent HPT-MEN-1. The aim of this study was to investigate
the timing, causes, site of recurrence, and surgical treatment of recurrent HPT-MEN-1 in patients who underwent
SPTX. METHODS: The study was a retrospective review of prospectively collected data on patients with HPT-
MEN-1 with SPTX at two referral institutions. The data collected included the following: demographics, duration
of follow-up, weight of resected parathyroid tissue, type of remnant, time to reoperation, cause/site of recurrence,
and surgical treatment. We studied prognostic factors of recurrence. RESULTS: A total of 69 patients underwent
SPTX and were followed for a mean of 75.3 months. After the surgery, 15 patients were left with a single
"normal" gland and 54 with a 50- to 70-mg remnant of a partially excised abnormal gland. Nine patients (13%)
had a recurrence within a mean of 85 months (12-144 months). Patients with a recurrence had been followed
longer (115 vs. 66 months; p = 0.005). Five recurrences occurred in a parathyroid remnant, 3 in a previously
"normal" gland; the fifth recurrence was in both a hyperplastic remnant and a fifth gland. Remedial surgery
included five subtotal resections and four immediate parathyroid autotransplantations. Two patients had a
second recurrence due to a supernumerary gland. Factors related with recurrence are the follow-up time (p <
0.01) and thymectomy (p < 0.003). CONCLUSIONS: Recurrence of HPTP-MEN-1 usually is located in preserved
parathyroid tissue with no preference for a previously normal gland or a remnant. A second recurrence is most
likely seen in a supernumerary gland. Recurrence is associated with the follow-up time and thymectomy.
PubMed-ID: 20431882
http://dx.doi.org/10.1007/s00268-010-0605-2

Total Parathyroidectomy Without Autotransplantation for the Treatment of Secondary
Hyperparathyroidism Associated With Chronic Kidney Disease: Clinical and Laboratory Long-Term
Follow-Up.
Biomed Pharmacother, 64(5):359-62.
Puccini M, Carpi A, Cupisti A, Caprioli R, Iacconi P, Barsotti M, Buccianti P, Mechanick J, Nicolini A, Miccoli P.
2010.
Forty-six consecutive patients who underwent total parathyroidectomy (tPTX) for hyperparathyroidism
associated with end-stage kidney disease (CKD5) in a University Hospital from 1990 to 1999 were included in a
long-term observational study. Outcome parameters included symptoms (bone pain, pruritus and muscle
weakness evaluated by visual analog scales [VAS]) and laboratory data (intact parathyroid hormone [iPTH], total
calcium, and alkaline phosphatase) assessed before, shortly postoperatively and then at a later time point: 40
patients were on maintenance hemodialysis and six on conservative medical therapy. Forty-four patients had
four glands removed, while only three glands were found in the remaining two. Perioperative complications
consisted of acute symptomatic hypocalcemia in 10 (22%) patients and non-specific complaints in three (7%).
No laryngeal nerve palsies occurred. After a median follow-up of eight years, 43 subjects were evaluated: 37
(86%) were cured, three (7%) had persistent and three (7%) recurrent disease. Eleven patients underwent
successful renal transplantation and 23 died during the period of observation. iPTH decreased from a mean of
1084+/-505 pg/ml to 120+/-381 pg/ml (p < 0.0001). No subsequent bone fractures, persistent bone pain or
disability were reported; this includes patients who later received a functioning renal graft. tPTX was able to
correct hyperparathyroidism in most of the patients and was associated with a low long-term relapse rate. iPTH
levels remained low in 17 cases without symptoms and no clinically significant side effects. The beneficial effects
of tPTX occurred in the majority of patients while renal transplantation was performed in a minority of patients.
tPTX should be considered a safe and successful procedure for the treatment of severe secondary
hyperparathyroidism associated with chronic kidney disease.
PubMed-ID: 20435429
http://dx.doi.org/10.1016/j.biopha.2009.06.006

Hypercalcemia Secondary to Persistent Hyperparathyroidism in Kidney Transplant Patients: Analysis
After a Year With Cinacalcet.
J Nephrol,
Guerra R, Auyanet I, Fernandez EJ, Perez MA, Bosch E, Ramirez A, Suria S, Checa MD. 2010.

ESES Review of Recently Published Literature 2010-2                                                 Page 43 of 63
Introduction: The most common cause of hypercalcemia in patients with transplanted kidneys is persistent
hyperparathyroidism, which presents in 10%-30% of patients with functioning renal grafts. In these patients, the
treatment of vitamin D-resistant hyperparathyroidism traditionally required parathyroidectomy. Calcimimetic
agents represent a new therapeutic alternative; they inhibit parathyroid hormone (PTH) secretion, increasing the
sensitivity of the calcium-sensitive receptor in the parathyroid gland. The objective of this study is to evaluate the
efficacy of cinacalcet in renal transplant patients with persistent hyperparathyroidism. Methods: Cinacalcet 30
mg/day was prescribed to 17 renal transplant patients (6 women, 11 men) with a mean age of 49 years and
hypercalcemia secondary to persistent hyperparathyroidism. The treatment started 58.17 +/- 35.16 months
posttransplant, with 1 year of follow-up. Results: Calcium in serum fell from 10.5 +/- 0.74 to 9.4 +/- 0.84 mg/dL
(p<0.001), whereas phosphorous levels were not significantly altered. The fall in PTH was from 204.79 +/- 78 to
148.55 +/- 56 pg/mL (p<0.011). Kidney function remained stable, and immunosuppressant drug levels remained
unchanged. The dose of cinacalcet was increased to 60 mg in 2 patients. No significant adverse effects were
described, and none of the patients had to suspend the treatment. Conclusions: Calcimimetic agents represent a
therapeutic alternative in transplant patients with persistent hyperparathyroidism, as they correct hypercalcemia
and reduce PTH levels with no adverse effects on kidney function. Prospective, controlled studies should be
designed to evaluate the long-term effects and evolution after suspension of the treatment.
PubMed-ID: 20437396

Endocrine Complications in Long-Term Survivors of Childhood Cancers.
Endocr Relat Cancer, 17(3):R141-R159.
Chemaitilly W, Sklar CA. 2010.
Endocrine disturbances are among the most frequently reported complications in childhood cancer survivors,
affecting between 20 and 50% of individuals who survive into adulthood. Most endocrine complications are the
result of prior cancer treatments, especially radiotherapy. The objective of the present review is to discuss the
main endocrine complications observed in this population, including disorders of the hypothalamic-pituitary axis,
disorders of pubertal development, thyroid dysfunction, gonadal dysfunction, decreased bone mineral density,
obesity, and alterations in glucose metabolism with a special focus on recent findings reported from the
Childhood Cancer Survivor Study.
PubMed-ID: 20453080
http://dx.doi.org/10.1677/ERC-10-0002

The Death of an Indian Rhinoceros.
World J Surg, 34(8):1805-10.
Felger EA, Zeiger MA. 2010.
In 1834, the London Zoological Society purchased a male Indian Rhinoceros, Rhinoceros unicornis, at the
request of the anatomist, Richard Owen. Fifteen years later, the rhinoceros died from traumatic injuries, and the
necropsy performed by Owen led to the very first discovery of parathyroid glands. Around this time, Richard
Owen and Charles Darwin vehemently disagreed with one another about the theory of natural selection. Their
public feud sparked the public's interest in Darwin and his theory while Owen became less popular despite his
many accomplishments in the scientific world. Not until decades after Owen's death was his contribution to the
identification of parathyroid glands discovered. Because his discovery is considered pivotal to the history of
endocrine surgery, we sought to investigate the circumstances surrounding the rhinoceros' death, its dissection,
and Owen's initial discovery.
PubMed-ID: 20458582
http://dx.doi.org/10.1007/s00268-010-0603-4

Determinants of Tc-99m Sestamibi SPECT Scan Sensitivity in Primary Hyperparathyroidism.
Am J Surg, 199(5):614-20.
Swanson TW, Chan SK, Jones SJ, Bugis S, Irvine R, Belzberg A, Levine D, Wiseman SM. 2010.
BACKGROUND: The aim of this study was to evaluate the influence of patient and adenoma characteristics on
(99m)Tc-methoxy isobutyl isonitrile (MIBI) scan performance in individuals diagnosed with primary
hyperparathyroidism (PHP). METHODS: Records of patients undergoing parathyroidectomy for PHP over 6
years at a single center were reviewed. RESULTS: The overall true-positive (TP) rate for (99m)Tc-MIBI scans
was 56%. Adenomas sized 1.9 to 3.5 cm were more likely to have TP scans than 0.3-cm to 1.8-cm adenomas
(74% vs 40%, P < .001). Preoperative ionized calcium levels between 1.49 and 1.72 mmol/L were more likely to
have TPs than levels between 1.27 and 1.48 mmol/L (65% vs 47%, P < .05). No single class of medication was
shown to significantly effect TP rates. A decrease in TP rate was observed for larger adenomas in patients on
>or=1 medication (74% vs 65%, P = .05). CONCLUSIONS: In PHP, (99m)Tc-MIBI scan positivity is most related
to adenoma size and preoperative ionized calcium level.

ESES Review of Recently Published Literature 2010-2                                                   Page 44 of 63
PubMed-ID: 20466104
http://dx.doi.org/10.1016/j.amjsurg.2010.02.001

Prior Head and Neck Radiation Exposure Is Not a Contraindication to Minimally Invasive
Parathyroidectomy.
J Am Coll Surg, 210(6):942-8.
Rahbari R, Sansano IG, Elaraj DM, Duh QY, Clark OH, Kebebew E. 2010.
BACKGROUND: Most patients with primary hyperparathyroidism can have a minimally invasive
parathyroidectomy based on localization studies showing single-gland disease. In patients with a history of head
and neck irradiation, due to the increased risk of multigland disease and risk of concurrent thyroid cancer,
minimally invasive parathyroidectomy is considered by some to be a contraindication. We postulated that
previous history of head and neck irradiation should not be a contraindication for minimally invasive
parathyroidectomy and tested this hypothesis in a prospective cohort of patients undergoing parathyroidectomy
for primary hyperparathyroidism. STUDY DESIGN: We performed a retrospective analysis of a prospective
database of 491 consecutive parathyroidectomies performed between May 2005 and May 2007 at a tertiary
referral medical center. RESULTS: Fifty-two (12.6%) patients had a history of head and neck irradiation and 360
(87.4%) had no exposure to radiation. The 2 groups had no significant difference in terms of gender or ethnicity.
The radiation group was older, with an average age of 65.1 years versus 58.1 years (p < 0.0009). There was no
significant difference in concurrent benign thyroid neoplasm, thyroid cancer, and type of parathyroid disease
(single vs multigland) in the 2 groups. There was no significant difference in the operative approach used
between the 2 groups (focused vs unilateral or bilateral). CONCLUSIONS: Head and neck irradiation should not
be a contraindication for minimally invasive parathyroidectomy in patients with primary hyperparathyroidism in
the setting of preoperative localization studies showing single-gland disease and no concurrent thyroid
neoplasm. Furthermore, history of head and neck irradiation is associated with a later age of presentation for
parathyroidectomy.
PubMed-ID: 20510803
http://dx.doi.org/10.1016/j.jamcollsurg.2010.02.041

[Intraoperative Parathyroid Hormone Determination for Primary Hyperparathyroidism]
Intraoperative Parathormonbestimmung Beim Primaren Hyperparathyreoidismus.
Chirurg, 81(7):636, 638-6, 642.
Lorenz K, Dralle H. 2010.
Intraoperative parathyroid hormone measurement (IOPTH) has proved to be an important promoter for focused
and minimally invasive parathyroidectomy procedures in primary hyperparathyroidism. IOPTH enables
multiglandular disease to be excluded with a high degree of certainty at the time of operation. The choice of the
cut-off value for IOPTH as the criterion for success is of utmost importance with respect to the prognosis for
operative success (biochemical healing). Advantages and disadvantages of the variety of existing IOPTH
success criteria are confusing and their assessment is contradictory. Particularly with respect to cost-benefit
aspects the standard application of IOPTH as "biochemical frozen section" even in conventional open
parathyroidectomy remains a matter of controversy. This article gives an up-date on current knowledge and
provides practical guidelines for clinical use of IOPTH.
PubMed-ID: 20549175
http://dx.doi.org/10.1007/s00104-009-1885-7

Cardiac Function in Mild Primary Hyperparathyroidism and the Outcome After Parathyroidectomy.
Eur J Endocrinol, 163(3):461-7.
Farahnak P, Ring M, Caidahl K, Farnebo LO, Eriksson MJ, Nilsson IL. 2010.
OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity. The extent of
cardiovascular abnormalities in patients with mild-asymptomatic disease is unclear. Using sensitive
echocardiographic methods, we compared cardiac structure and function in patients with mild PHPT and in
healthy controls, and evaluated the changes after parathyroidectomy (PTX). METHODS: In a prospective case-
control design, we studied 51 PHPT patients without any cardiovascular risk factors/diseases and 51 healthy
matched controls. Cardiac structure, and systolic and diastolic function were evaluated by echocardiography and
Doppler tissue imaging (DTI). Blood pressure (BP) and heart rate were measured. RESULTS: We observed no
differences in systolic or diastolic function or in cardiac morphology between the PHPT patients and the age-
matched healthy controls. The regional peak systolic myocardial velocities (S') measured with DTI decreased at
all sites (P<0.05) after PTX (tricuspid annulus 14.23+/-1.85 to 13.48+/-1.79, septal 8.48+/-0.96 to 7.97+/-0.85,
and lateral 9.61+/-2.05 to 8.87+/-1.63 cm/s, part of the mitral annulus). At baseline, systolic BP was higher in
patients compared to controls (127.6+/-17.1 vs 119.6+/-12.6 mmHg, P<0.05). After PTX, both systolic (127.6+/-

ESES Review of Recently Published Literature 2010-2                                                Page 45 of 63
17.1 vs 124.6+/-16.6 mmHg, P<0.05) and diastolic (80.3+/-9.6 vs 78.4+/-8.6 mmHg, P<0.05) BP decreased.
CONCLUSIONS: Our results indicate that patients with PHPT without cardiovascular risk factors have a normal
global systolic and diastolic function and cardiac morphology. BP and the systolic velocities were marginally
reduced after PTX, but reflected the values of the control group. Our findings warrant further investigation of the
clinical and prognostic significance of these possibly disease-related inotropic effects.
PubMed-ID: 20562163
http://dx.doi.org/10.1530/EJE-10-0201

Hyperparathyroidism and Pregnancy.
Am Surg, 76(6):648-9.
Vazquez QE, Vazquez DE. 2010.
PubMed-ID: 20583526

Minimally Invasive Video-Assisted Parathyroidectomy (MIVAP) for Secondary Hyperparathyroidism:
Report of Initial Experience.
Am J Surg, 199(6):851-5.
Alesina PF, Hinrichs J, Kribben A, Walz MK. 2010.
BACKGROUND: Minimally invasive video-assisted parathyroidectomy (MIVAP) has become a well-accepted
procedure for patients with primary hyperparathyroidism. Because it allows bilateral neck exploration, the
authors began using this technique for patients with secondary hyperparathyroidism. In this preliminary study,
the authors report their initial experience. METHODS: From July 2006 to November 2008, 12 patients (6 women,
6 men; mean age, 45.5 +/- 16.9 years (range, 23-71 years) underwent MIVAP with bilateral exploration for
secondary hyperparathyroidism. The operation was performed through a central 2-cm to 3-cm skin incision; a 30
degrees 5-mm endoscope was used for magnification. RESULTS: MIVAP was successfully completed in 11
patients (92%). The mean operative time was 81 +/- 37 minutes (range, 35-130 minutes). No major
complications were registered. After a mean follow-up period of 11.4 months (range, 3-30 months), 1 patient
showed recurrence. CONCLUSIONS: MIVAP appears to be a safe and feasible procedure in patients with
secondary hyperparathyroidism.
PubMed-ID: 20609728
http://dx.doi.org/10.1016/j.amjsurg.2009.05.041

Postoperative Calcium Requirements in 6,000 Patients Undergoing Outpatient Parathyroidectomy: Easily
Avoiding Symptomatic Hypocalcemia.
J Am Coll Surg, 211(1):49-54.
Vasher M, Goodman A, Politz D, Norman J. 2010.
BACKGROUND: To determine the amount and duration of supplemental oral calcium for patients with varying
clinical presentations discharged immediately after surgery for primary hyperparathyroidism. STUDY DESIGN: A
4-year, prospective, single-institution study of 6,000 patients undergoing parathyroidectomy for primary
hyperparathyroidism and discharged within 2.5 hours. Based on our previous studies, patients are started on a
sliding scale of oral calcium determined by a number of preoperative measures (ie, serum calcium, body weight,
osteoporosis) beginning 3 hours postoperation and decreasing to a maintenance dose by week 3. Patients
reported all hypocalcemia symptoms daily for 2 weeks. RESULTS: Seven parameters were found to have a
substantial impact on the amount of calcium required to prevent symptomatic hypocalcemia: preoperative serum
calcium >12 mg/dL, >13 mg/dL, and >13.5 mg/dL, bone density T score less than -3, morbid obesity, removal of
>1 parathyroid, and manipulation/biopsy of all remaining glands (all p < 0.05). Each independent variable
increased the daily calcium required by 315 mg/day. Using our scaled protocol, <8% of patients showed
symptoms of hypocalcemia, nearly all of whom were successfully self-treated with additional oral calcium. Only 6
patients (0.1%) required a visit to the emergency room for IV calcium, all occurring on postoperative day 3 or
later. CONCLUSION: After outpatient parathyroidectomy, a specific calcium protocol has been verified that
eliminates development of symptomatic hypocalcemia in >92% of patients, identifies patients at high risk for
hypocalcemia, and allows self-medication with confidence in a predictable fashion for those patients in whom
symptoms develop.
PubMed-ID: 20610248
http://dx.doi.org/10.1016/j.jamcollsurg.2010.03.019

Dual-Energy Computed Tomography Localizes Ectopic Parathyroid Adenoma.
J Clin Endocrinol Metab, 95(7):3092-3.
Gimm O, Juhlin C, Morales O, Persson A. 2010.



ESES Review of Recently Published Literature 2010-2                                                  Page 46 of 63
PubMed-ID: 20610604
http://dx.doi.org/10.1210/jc.2010-0386

Effect of Parathyroidectomy for Primary Hyperparathyroidism on Bone Mineral Density in
Postmenopausal Women.
Br J Surg, 97(7):1013-9.
Sitges-Serra A, Garcia L, Prieto R, Pena MJ, Nogues X, Sancho JJ. 2010.
BACKGROUND: The bone mineral density (BMD) response to parathyroidectomy is heterogeneous and difficult
to predict. Available data come from mixed populations of men and women, of different age and degrees of
disease severity, and preoperative BMD loss. METHODS: This was a longitudinal, prospective cohort study of
103 postmenopausal women with osteopenia or osteoporosis at the femoral neck site, successfully operated on
for primary hyper parathyroidism. BMD and metabolic variables were recorded before and 1 year after
parathyroidectomy. RESULTS: After surgery, there was a 1.3 per cent increase in the median BMD at the
femoral neck site (0.615 versus 0.623 g/cm(2); P = 0.001). Overall, positive responses were also observed at
total hip (0.4 per cent) and lumbar spine (2.3 per cent) sites. Analysing the individual responses, however, only
45 (46 per cent) of 97 patients showed a significant (at least 3.7 per cent) increase in BMD at the femoral neck
site compared with the preoperative value and 52 had a decreased (15) or unchanged (37) femoral neck BMD.
Patients who gained BMD were younger, had more severe hyperparathyroidism and better renal function.
CONCLUSION: Almost half of the postmenopausal women with hyperparathyroidism and low BMD have a
significant remineralization response 1 year after parathyroidectomy. Differential mineralization responses of
BMD after surgery appear to be related to severity of primary hyperparathyroidism, age and renal function.
PubMed-ID: 20632266
http://dx.doi.org/10.1002/bjs.7044

Operative Failure in the Era of Focused Parathyroidectomy: a Contemporary Series of 845 Patients.
Arch Surg, 145(7):628-33.
Lew JI, Rivera M, Irvin GL, III, Solorzano CC. 2010.
HYPOTHESIS: Focused parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IPM) may
lead to higher failure rates because of missed multiglandular disease. DESIGN: Retrospective review of
prospectively collected data. SETTING: Tertiary referral center. PATIENTS: From September 8, 1993, through
January 30, 2009, a total of 845 consecutive patients with sporadic primary hyperparathyroidism underwent
focused parathyroidectomy guided by IPM at a single institution. MAIN OUTCOME MEASURES: Parathyroid
hormone dynamics and perioperative data were analyzed for factors affecting outcome. Operative failure was
defined as hypercalcemia with elevated parathyroid hormone levels within 6 months after parathyroidectomy.
Detailed intraoperative data from the failed operations were also reviewed. RESULTS: Of 723 patients followed
up for at least 6 months, 702 (97.1%) had successful parathyroidectomy, and 21 (2.9%) had failed
parathyroidectomy. The major cause of operative failure was the surgeon's inability to find the abnormal
parathyroid gland (16 of 21 patients [76.2%]). In the remaining patients, IPM results were false-positive in 5 of 21
patients (23.8%) or 0.7% overall. Among the cohort, IPM correctly identified missed multiglandular disease in 33
of 38 patients (86.8%). Patients having operative failure were more likely to have a history of thyroidectomy or
parathyroidectomy and were less likely to have correct findings on technetium Tc 99m sestamibi or
ultrasonographic localizing studies compared with patients having operative success. CONCLUSION: Inability of
the surgeon to find the abnormal parathyroid gland-not missed multiglandular disease-is the main cause of
operative failure in focused parathyroidectomy guided by IPM.
PubMed-ID: 20644124
http://dx.doi.org/10.1001/archsurg.2010.104

Prospective Study in 3,000 Consecutive Parathyroid Operations Demonstrates 18 Objective Factors That
Influence the Decision for Unilateral Versus Bilateral Surgical Approach.
J Am Coll Surg , 211(2):244-9.
Norman J, Politz D. 2010.
BACKGROUND: Although localizing studies are well-known predictors of which patients are candidates for
unilateral versus bilateral parathyroid exploration, there are a number of other factors that have positive or
negative influence preoperatively and intraoperatively. STUDY DESIGN: A prospective study was conducted
during 20 months on 3,000 consecutive patients undergoing surgery for primary hyperparathyroidism to
determine which factors caused the surgeons to explore bilaterally or, in contrast, influenced a unilateral
approach. Seventeen preoperative and 5 intraoperative objective points were documented on all patients to see
how decisions were made. RESULTS: Parathyroidectomy was unilateral in 32% and bilateral in 68%.
Preoperative factors that had a positive predictive value in dictating a unilateral approach were (in decreasing

ESES Review of Recently Published Literature 2010-2                                                 Page 47 of 63
frequency): positive sestamibi, previous parathyroid/thyroid surgery, age older than 80 years, anticoagulation
medications, morbid obesity, and presence of large goiter (all p < 0.001). Preoperative parameters dictating a
bilateral approach included negative sestamibi, more than one focus on sestamibi, contralateral thyroid disease,
family history, lithium use, history of radiation, MEN, age younger than 20 years, and pregnancy (all p < 0.001).
Intraoperative parameters influencing conversion of unilateral to bilateral were false-positive sestamibi, hormone
measures not meeting sufficient levels, abnormal ipsilateral gland, and contralateral thyroid pathology identified
(all p < 0.001). Factors that had no effect were gender, degree of calcium, and/or parathyroid hormone elevation,
and age between 20 and 80 years. Cure rates were 99.9% for bilateral and 99.0% for unilateral (p = 0.057).
CONCLUSIONS: High-volume surgeons use a number of identifiable objective factors to determine the best
candidates for unilateral versus bilateral parathyroid exploration. Localizing studies such as sestamibi scans
ultimately play a minor role in determining how many parathyroid glands are evaluated.
PubMed-ID: 20670863
http://dx.doi.org/10.1016/j.jamcollsurg.2010.03.040

Current Status of Surgical Techniques for Parathyroidectomy for Untreated Primary
Hyperparathyroidism: Is the Technology Worth It?
Am Surg, 76(7):663-71.
Flynn MB, Civelek AC. 2010.
PubMed-ID: 20698367

Recurrent Hyperparathyroidism and Forearm Parathyromatosis After Total Parathyroidectomy.
Surgery, 148(4):867-73.
Melck AL, Carty SE, Seethala RR, Armstrong MJ, Stang MT, Ogilvie JB, Yip L. 2010.
BACKGROUND: In multiple endocrine neoplasia type I and renal failure, the type of initial parathyroidectomy for
hyperparathyroidism may influence the operative risks and development of recurrence. We compared subtotal
parathyroidectomy with total parathyroidectomy and immediate forearm autotransplantation (TPFA) in a large
series with long-term follow-up. METHODS: The data of patients treated from 1977 to 2009 by initial or
reoperative TPFA or subtotal parathyroidectomy were examined for outcomes including the interval to sites and
tissue patterns of recurrence. RESULTS: Permanent hypoparathyroidism was rare and uninfluenced by disease
type. Neither initial procedure nor underlying disease affected the mean time to reoperation for recurrent
hyperparathyroidism. In renal failure, reoperation was more common after TPFA than subtotal
parathyroidectomy (5/19, 26% vs 11/193, 6%; P = .008). Twelve patients required forearm reoperation after
TPFA, which was often complicated by parathyromatosis (7/12, 58%). Further reoperative forearm surgery was
more likely after explant excision than after en bloc resection (7/11 vs 0/8; P = .01) and occurred sooner in renal
failure than in multiple endocrine neoplasia type I (mean 4.4 vs 9 years; P = .04). Permanent hypoparathyroidism
was rare and uninfluenced by disease type. CONCLUSION: Because of frequent recurrence, TPFA should be
abandoned as a treatment of renal hyperparathyroidism. In multiple endocrine neoplasia type I, subtotal
parathyroidectomy has similar outcomes to TPFA. Forearm autotransplantation can be complicated by
parathyromatosis, and surgeons should be prepared for reoperative en bloc resection.
PubMed-ID: 20800255
http://dx.doi.org/10.1016/j.surg.2010.07.037

Parathyroidectomy for Hypercalcemic Crisis: 40 Years' Experience and Long-Term Outcomes.
Surgery, 148(4):807-12.
Cannon J, Lew JI, Solorzano CC. 2010.
BACKGROUND: Hypercalcemic crisis is a serious and potentially life-threatening complication of markedly
increased serum calcium concentrations most commonly due to severe primary sporadic hyperparathyroidism
(HPT). METHODS: A review of 1,310 consecutive patients with severe sporadic HPT who underwent
parathyroidectomy at a single institution from April 1970 through July 2009 was performed. Of this series, 88
patients were treated operatively for hypercalcemic crisis associated with signs and symptoms of acute calcium
intoxication and/or serum calcium concentrations >/=14 mg/dL (3.5 mmol/L). Clinical presentation, laboratory
values, operative success, operative failure, and disease recurrence were compared to noncrisis patients.
RESULTS: Preoperative calcium and parathyroid hormone (PTH) concentrations were significantly greater
among patients with hypercalcemic crisis. Crisis patients had a greater incidence of mental status changes,
fatigue, ectopic glands, and pancreatitis. Postoperatively, calcium and PTH levels were similar. Overall, crisis
patients had a lesser rate of operative success compared to noncrisis patients (92% vs 97%). With the advent of
intraoperative PTH monitoring-guided focused parathyroidectomy in 1993, success rates equalized (95% vs
97%). There was no difference in disease recurrence. Overall follow-up was 59 months. CONCLUSION:
Hypercalcemic crisis patients are appropriately treated by expeditious parathyroidectomy, but overall have

ESES Review of Recently Published Literature 2010-2                                                Page 48 of 63
slightly lesser rates of initial operative success than noncrisis patients. Long-term results reveal similar serum
calcium, PTH concentrations, and recurrence rates at a mean follow-up of nearly 5 years.
PubMed-ID: 20800863
http://dx.doi.org/10.1016/j.surg.2010.07.041




ESES Review of Recently Published Literature 2010-2                                                   Page 49 of 63
Adrenals

Meta-Analyses
123I-Meta-Iodobenzylguanidine Scintigraphy for the Detection of Neuroblastoma and
Pheochromocytoma: Results of a Meta-Analysis.
J Clin Endocrinol Metab, 95(6):2596-606.
Jacobson AF, Deng H, Lombard J, Lessig HJ, Black RR. 2010.
CONTEXT: (123)I-mIBG scintigraphy has been in clinical use for more than 20 yr for diagnostic assessment of
patients with neural crest and neuroendocrine tumors. Prospective validation of the performance characteristics
of this method has recently been published. OBJECTIVE: A meta-analysis was performed to obtain best
estimates of performance characteristics of (123)I-mIBG imaging for the two most common applications,
evaluation of patients with neuroblastoma and pheochromocytoma. DATA SOURCES: Articles published
between 1980 and 2007 were identified from searches of multiple computer databases, including MEDLINE,
BIOSIS, EMBASE, and SciSearch. STUDY SELECTION: Primary inclusion criteria were: acceptable reference
standard(s) for confirming subjects with disease (histopathology and/or a combination of imaging and
catecholamine results); reference standards applied to all subjects who received (123)I-mIBG; and data on a
minimum of 16 patients confirmed to have or not have the disease(s) under consideration. Two physician
reviewers independently evaluated all articles against the inclusion/exclusion criteria. Twenty-two of 100 articles
reviewed were included in the final analysis. DATA EXTRACTION: The two reviewers extracted the data from
eligible articles using a standardized form, capturing both study quality and efficacy information. Disagreements
were resolved by consensus. DATA SYNTHESIS: Sensitivity of (123)I-mIBG scans for detection of
neuroblastoma was 97% [95% confidence interval (CI), 95 to 99%]; data were insufficient to estimate specificity.
For pheochromocytoma, with application of the random-effects model, sensitivity and specificity were 94% (95%
CI, 91-97%) and 92% (95% CI, 87-98%), respectively. CONCLUSION: Based upon the literature, (123)I-mIBG
scintigraphy has sensitivity and specificity greater than 90% for detection of neuroblastoma and
pheochromocytoma.
PubMed-ID: 20392867
http://dx.doi.org/10.1210/jc.2009-2604




Randomized controlled trials
- None -


Other Articles
Laparoscopic Adrenalectomy for Large Unilateral Pheochromocytoma: Experience in a Large Academic
Medical Center.
Surg Endosc, 24(6):1462-7.
Perry KA, El YR, Pham TH, Sheppard BC. 2010.
BACKGROUND: Laparoscopic adrenalectomy is the treatment of choice for most adrenal lesions. Concerns
have persisted about its application to large pheochromocytomas due to reports of hemodynamic instability,
difficult dissection, and tumor spillage. METHODS: Thirty patients underwent laparoscopic adrenalectomy for
unilateral pheochromocytoma between 1998 and 2006. Outcome measures including operative time, blood loss,
intraoperative hemodynamic instability, conversion rate, complications, and disease recurrence were analyzed
based on tumor size. RESULTS: Twenty-two patients had small tumors and eight had large lesions. These
groups did not differ in terms of operative time, blood loss, conversion rate, length of stay or complication rate.
Intraoperative hemodynamic instability occurred in 56.7% of cases, but was not different between groups. There
were no recurrences in either group. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and effective
treatment for large pheochromocytomas. Intraoperative hemodynamic instability remains a frequent occurrence
regardless of tumor size. There were no cases of disease recurrence or iatrogenic pheochromocytosis.
PubMed-ID: 20033709
http://dx.doi.org/10.1007/s00464-009-0801-z


ESES Review of Recently Published Literature 2010-2                                                 Page 50 of 63
Posterior Retroperitoneoscopic Adrenalectomy for Clinical and Subclinical Cushing's Syndrome.
World J Surg, 34(6):1391-7.
Alesina PF, Hommeltenberg S, Meier B, Petersenn S, Lahner H, Schmid KW, Mann K, Walz MK. 2010.
BACKGROUND: Because of co-morbidity, adrenalectomy for adrenal Cushing's syndrome may be associated
with an increased complication rate and long operating times. In the present study we report our experience with
the posterior retroperitoneoscopic adrenalectomy in a large group of patients with clinical or subclinical
Cushing's syndrome. PATIENTS AND METHODS: Between July 1994 and June 2009, 170 patients (17 males,
153 females age 50 +/- 13 years; range: 12-78 years) affected by Cushing's syndrome underwent operation via
posterior retroperitoneoscopic access. Patients were divided into two groups, those with manifest Cushing's
syndrome (mCS) [99 patients: 6 male, 93 female; age 45 +/- 13 years] and those with subclinical Cushing's
syndrome (sCS) [71 patients: 11 male, 60 female; age: 56 +/- 11 years]. The sCS classification was assumed in
cases without typical clinical symptoms but with a pathological dexamethasone suppression test. Partial
adrenalectomy was performed in 35 cases (24 in the mCS-group and 11 in the sCS-group). RESULTS: Mortality
was zero; major complications did not occur. The incidence of postoperative minor complications was 5.3%.
Mean operating time was 58 +/- 36 min (range: 20-230 min) and did not differ between mCS and sCS patients
(58 versus 59 min; p = ns). Postoperative oral steroids supplementation (POSS) was administered in 136
patients (99 mCS, 37 sCS). If POSS was started, mean duration of therapy was 12.3 months (mCS) and 10.3
months (sCS) [p = 0.08], respectively. After a mean follow-up of 70.9 +/- 46.5 months the cure rate was 99.4%.
CONCLUSIONS: The posterior retroperitoneoscopic approach is fast and safe even in patients with Cushing's
syndrome. Partial adrenalectomy represents a new option in the treatment of cortisol-producing adenomas.
PubMed-ID: 20143066
http://dx.doi.org/10.1007/s00268-010-0453-0

Single-Access Retroperitoneoscopic Adrenalectomy (SARA) Versus Conventional Retroperitoneoscopic
Adrenalectomy (CORA): a Case-Control Study.
World J Surg, 34(6):1386-90.
Walz MK, Groeben H, Alesina PF. 2010.
BACKGROUND: Stimulated by the concept of Natural Orifice Transluminal Endoscopic Surgery (NOTES),
minimizing the access even further has become a new trend in minimally invasive surgery. We compare our
recently described new method of endoscopic single-access adrenalectomy with the conventional
retroperitoneoscopic approach in a matched-pairs study. METHODS: Fifty single-access retroperitoneoscopic
adrenalectomies (SARA) were performed in 47 selected patients suffering from Conn's adenomas (n = 20),
pheochromocytomas (n = 15), Cushing's adenomas (n = 6), and other diseases (n = 6). For SARA, a single 2-cm
skin incision beneath the 12th rib was used. Following creation of the retroperitoneal space with the rigid
endoscope, dissection was carried out single-handed. Another 47 patients served as control group; they were
treated by the traditional retroperitoneoscopic three-port approach (CORA). Patients were matched with respect
to gender, body mass index, diagnoses, tumor size, and tumor site. RESULTS: Mortality was zero and no major
complications occurred in both groups. SARA was completed in 41 cases (86%). The overall complication rate
was 8.5% in SARA and 6.4% in CORA. Operative time was longer for SARA (56 +/- 28 min) than for CORA (40
+/- 12 min) (P < 0.05). Postoperatively, pain medication was administered in 47% of SARA patients and in 75%
of CORA patients (P = 0.01). Mean hospital stay was 2.4 +/- 0.7 days (SARA) and 3.1 +/- 1.2 days (CORA) (P <
0.01). CONCLUSIONS: Because feasibility and safety of SARA could be demonstrated in a large group of
selected patients, this surgical technique may represent a new milestone in minimally invasive endocrine
surgery.
PubMed-ID: 20213204
http://dx.doi.org/10.1007/s00268-010-0494-4

A Current Review of the Etiology, Diagnosis, and Treatment of Pediatric Pheochromocytoma and
Paraganglioma.
J Clin Endocrinol Metab, 95(5):2023-37.
Waguespack SG, Rich T, Grubbs E, Ying AK, Perrier ND, yala-Ramirez M, Jimenez C. 2010.
CONTEXT: Pheochromocytomas and paragangliomas (PHEO/PGL) are neuroendocrine tumors that arise from
sympathetic and parasympathetic paraganglia. Diagnosed rarely during childhood, PHEO/PGL are nonetheless
important clinical entities, particularly given our evolving understanding of their pathophysiology. EVIDENCE
ACQUISITION: We identified articles through the U.S. National Library of Medicine by using the search terms
pheochromocytoma and paraganglioma. Results were narrowed to manuscripts that included children and
studies related to the genetics of PHEO/PGL. Web-based resources for genetic disorders were also used. For all
articles, we performed subsequent reference searches and verification of source data. EVIDENCE SYNTHESIS:
Up to 20% of PHEO/PGL are diagnosed in children. Most are functional tumors, and clinical presentation


ESES Review of Recently Published Literature 2010-2                                              Page 51 of 63
includes symptoms related to catecholamine hypersecretion and/or tumor mass effect. Increasingly, PHEO/PGL
are identified during presymptomatic screening in children with genetic syndromes associated with PHEO/PGL
(multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and the paraganglioma syndromes). Plasma
and/or urine metanephrines are the best diagnostic test for a functional tumor, and the management of pediatric
patients is similar to adults. Genetic counseling should be undertaken in all cases. Although most pediatric
PHEO/PGL are benign, these tumors can occasionally metastasize, a condition for which no curative treatment
exists. CONCLUSIONS: Although PHEO/PGL are rarely diagnosed during childhood, the pediatric provider
should be able to recognize and screen for such tumors, particularly in the context of a known genetic
predisposition. Optimal care of these children includes a multidisciplinary team approach at centers experienced
in the evaluation and treatment of these uncommon yet fascinating endocrine neoplasms.
PubMed-ID: 20215394
http://dx.doi.org/10.1210/jc.2009-2830

6-18F-Fluoro-L-Dihydroxyphenylalanine Positron Emission Tomography Is Superior to 123I-
Metaiodobenzyl-Guanidine Scintigraphy in the Detection of Extraadrenal and Hereditary
Pheochromocytomas and Paragangliomas: Correlation With Vesicular Monoamine Transporter
Expression.
J Clin Endocrinol Metab, 95(6):2800-10.
Fottner C, Helisch A, Anlauf M, Rossmann H, Musholt TJ, Kreft A, Schadmand-Fischer S, Bartenstein P,
Lackner KJ, Kloppel G, Schreckenberger M, Weber MM. 2010.
CONTEXT: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by (18)F-
fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than (123)I-metaiodobenzyl-
guanidine (123-I-MIBG) scintigraphy. OBJECTIVE: The objective of the study was to correlate functional imaging
results with immunohistochemical, molecular-genetic, and biochemical findings. DESIGN AND SETTING: Thirty
consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a
prospective study. PATIENTS: Twenty-five patients had confirmed PHEO/PGL. Thirteen of 25 patients had a
hereditary PHEO/PGL syndrome (two multiple endocrine neoplasia II, six succinate dehydrogenase complex,
subunit D, two succinate dehydrogenase complex, subunit B, one von Hippel Lindau tumor suppressor protein,
two Neurofibromatosis-1), and 12 of 25 were classified as sporadic. Five patients had hormonally inactive
adrenal incidentalomas. MAIN OUTCOME MEASURES: In all patients computed tomography scan and/or
magnetic resonance imaging as well as both 123-I-MIBG scintigraphy and FDOPA-PET were performed.
Resected tumors were examined by immunohistochemistry for expression of the vesicular monoamine
transporter (VMAT)-1 and -2 and other markers. RESULTS: A total of 64 lesions were found with both functional
imaging modalities. FDOPA-PET detected 62 lesions, whereas only 34 lesions were detected by 123-I-MIBG
scintigraphy. This resulted in an overall sensitivity and specificity for FDOPA-PET of 98 and 100% and for MIBG
of 53 and 91%, respectively. Comparable sensitivities were found for adrenal and extraadrenal abdominal
lesions (94 vs. 97%), whereas in thoracic/cervical lesions, the sensitivity for 123-I-MIBG scintigraphy (15%) was
inferior to that of FDOPA-PET imaging (100%). Immunohistochemistry demonstrated a lack of VMAT-1
expression in all MIBG-negative tumors. Clinical predictors for MIBG negativity were a predominant
norepinephrine/normetanephrine secretion, an age less than 45 yr, and a hereditary cause. CONCLUSION:
FDOPA-PET is superior to 123-I-MIBG scintigraphy in patients with extraadrenal, predominantly noradrenaline-
secreting, and hereditary types of PHEO/PGL. The lack of VMAT-1 expression predicts negativity for MIBG-
scintigraphy.
PubMed-ID: 20371665
http://dx.doi.org/10.1210/jc.2009-2352

Laparoscopic Resection Is Inappropriate in Patients With Known or Suspected Adrenocortical
Carcinoma.
World J Surg, 34(6):1380-5.
Miller BS, Ammori JB, Gauger PG, Broome JT, Hammer GD, Doherty GM. 2010.
BACKGROUND: Complete surgical resection is the mainstay of treatment for patients with adrenocortical cancer
(ACC). Use of laparoscopy has been questioned in patients with ACC. This study compares the outcomes of
patients undergoing laparoscopic versus open resection (OR) for ACC. METHODS: A retrospective review
(2003-2008) of patients with ACC was performed. Data were collected for demographics, operative and
pathologic data, adjuvant therapy, and outcome. Chi-square analysis was performed. RESULTS: Eighty-eight
patients (66% women; median age, 47 (range, 18-81) years) were identified. Seventeen patients underwent
laparoscopic adrenalectomy (LA). Median tumor size of those who underwent LA was 7.0 (range, 4-14) cm
versus 12.3 (range, 5-27) cm for OR. Recurrent disease in the laparoscopic group occurred in 63% versus 65%
in the open group. Mean time to first recurrence for those who underwent LA was 9.6 months (+/-14) versus 19.2


ESES Review of Recently Published Literature 2010-2                                               Page 52 of 63
months (+/-37.5) in the open group (p < 0.005). Fifty percent of patients who underwent LA had positive margins
or notation of intraoperative tumor spill versus 18% of those who underwent OR (p = 0.01). Local recurrence
occurred in 25% of the laparoscopic group versus 20% in the open group (p = 0.23). Mean follow-up was 36.5
months (+/-43.6). CONCLUSIONS: ACC continues to be a deadly disease, and little to no progress has been
made from a treatment standpoint in the past 20 years. Careful and complete surgical resection is of the utmost
importance. Although feasible in many cases and tempting, laparoscopic resection should not be attempted in
patients with tumors suspicious for or known to be adrenocortical carcinoma.
PubMed-ID: 20372905
http://dx.doi.org/10.1007/s00268-010-0532-2

Beneficial Metabolic Effects of Prompt Surgical Treatment in Patients With an Adrenal Incidentaloma
Causing Biochemical Hypercortisolism.
J Clin Endocrinol Metab, 95(6):2736-45.
Chiodini I, Morelli V, Salcuni AS, Eller-Vainicher C, Torlontano M, Coletti F, Iorio L, Cuttitta A, Ambrosio A,
Vicentini L, Pellegrini F, Copetti M, Beck-Peccoz P, Arosio M, Ambrosi B, Trischitta V, Scillitani A. 2010.
CONTEXT: In patients with adrenal incidentalomas, subclinical hypercortisolism (SH) is associated with an
increased prevalence of the metabolic syndrome. The effect of surgical/conservative approach is debated.
OBJECTIVE: The objective of the study was to determine the effect of the surgical and conservative approaches
on the metabolic syndrome in patients with adrenal incidentalomas. DESIGN: This was a retrospective
longitudinal study (18-48 months follow-up). SETTING: The study was conducted on an in- and outpatient basis.
PATIENTS: One hundred eight patients with adrenal incidentalomas were studied for the presence of SH, which
was diagnosed in the presence of more than two of the following: urinary free cortisol greater than 70 microg per
24 h (193 nmol per 24 h), cortisol after 1 mg dexamethasone suppression test greater than 3.0 microg/dl (83
nmol/liter), ACTH less than 10 pg/ml (2.2 pmol/liter). INTERVENTIONS: Surgery was performed in 25 patients
with SH (group TrSH+) and 30 without SH (group TrSH-), whereas the conservative approach was chosen by 16
patients with SH (group UntrSH+) and 37 without SH (group UntrSH-). MAIN OUTCOME MEASURES: During
the follow-up, the improvement/worsening of body weight, blood pressure, or glucose and cholesterol levels was
defined in the presence of a greater than 5% weight decrease/increase and following the European Society of
Cardiology or the Adult Treatment Panel III criteria, respectively. RESULTS: In group TrSH+, weight, blood
pressure, and glucose levels improved (32, 56, and 48%, respectively) more frequently than in group UntrSH+
(12.5%, P = 0.05; 0.0%, P < 0.0001; 0.0%, P = 0.001; and 0.0%, P = 0.0014, respectively). In group UntrSH+,
blood pressure, glucose, and low-density lipoprotein levels worsened more frequently (50.0, 37.5, and 50.0%,
respectively) than in group TrSH+ (0.0%, P < 0.0001; 0.0%, P = 0.001; and 20.0%, P = 0.05, respectively).
CONCLUSIONS: Regarding the various components of the metabolic syndrome, in patients with adrenal
incidentalomas and SH, surgery is beneficial.
PubMed-ID: 20375210
http://dx.doi.org/10.1210/jc.2009-2387

18F-FDG PET for the Identification of Adrenocortical Carcinomas Among Indeterminate Adrenal Tumors
at Computed Tomography Scanning.
World J Surg, 34(7):1506-10.
Nunes ML, Rault A, Teynie J, Valli N, Guyot M, Gaye D, Belleannee G, Tabarin A. 2010.
BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has been proposed for
the evaluation of adrenal tumors. However, only scarce data are available to evaluate its usefulness for the
identification of primary adrenal carcinomas in patients with no previous history of cancer and equivocal tumors
on computed tomography (CT) scan. The objective of the present study was to evaluate the diagnostic
performance of 18F-FDG-PET to predict malignancy in such patients. METHODS AND PATIENTS: This was a
retrospective study carried out from 2006 to 2009 in a single university hospital center. Twenty-three consecutive
patients without previous history of cancer investigated for adrenal tumors without features of benign
adrenocortical adenoma on CT scan but no obvious ACC underwent 18F-FDG PET. All patients underwent
adrenalectomy because of CT scan characteristics regardless of the results of 18F-FDG PET. The ratio of
maxSUV adrenal tumor on maxSUV liver (adrenal/liver maxSUV ratio) during 18F-FDG PET was compared to
Weiss pathological criteria. RESULTS: Seventeen patients had an adrenal adenoma, 2 had small size adrenal
carcinomas (<5 cm), 1 had an angiosarcoma, and 3 had noncortical benign lesions. An adrenal/liver maxSUV
ratio above 1.6 provided 100% sensitivity, 90% specificity, and 100% negative predictive value for the diagnosis
of malignant tumor. CONCLUSIONS: Because of its excellent negative predictive value, 18F-FDG-PET may be
of help in avoiding unnecessary surgery in patients with non-secreting equivocal tumors at CT scanning and low
18F-FGD uptake.



ESES Review of Recently Published Literature 2010-2                                                Page 53 of 63
PubMed-ID: 20396886
http://dx.doi.org/10.1007/s00268-010-0576-3

Succinate Dehydrogenase Gene Mutations Are Strongly Associated With Paraganglioma of the Organ of
Zuckerkandl.
Endocr Relat Cancer, 17(3):581-8.
Lodish MB, Adams KT, Huynh TT, Prodanov T, Ling A, Chen C, Shusterman S, Jimenez C, Merino M, Hughes
M, Cradic KW, Milosevic D, Singh RJ, Stratakis CA, Pacak K. 2010.
Organ of Zuckerkandl paragangliomas (PGLs) are rare neuroendocrine tumors that are derived from chromaffin
cells located around the origin of the inferior mesenteric artery extending to the level of the aortic bifurcation.
Mutations in the genes encoding succinate dehydrogenase subunits (SDH) B, C, and D (SDHx) have been
associated with PGLs, but their contribution to PGLs of the organ of Zuckerkandl PGLs is not known. We aimed
to describe the clinical presentation of patients with PGLs of the organ of Zuckerkandl and investigate the
prevalence of SDHx mutations and other genetic defects among them. The clinical characteristics of 14 patients
with PGL of the organ of Zuckerkandl were analyzed retrospectively; their DNA was tested for SDHx mutations
and deletions. Eleven out of 14 (79%) patients with PGLs of the organ of Zuckerkandl were found to have
mutations in the SDHB (9) or SDHD (2) genes; one patient was found to have the Carney-Stratakis syndrome
(CSS), and his PGL was discovered during surgery for gastrointestinal stromal tumor. Our results show that
SDHx mutations are prevalent in pediatric and adult PGLs of the organ of Zuckerkandl. Patients with PGLs of the
organ of Zuckerkandl should be screened for SDHx mutations and the CSS; in addition, asymptomatic carriers of
an SDHx mutation among the relatives of affected patients may benefit from tumor screening for early PGL
detection.
PubMed-ID: 20418362
http://dx.doi.org/10.1677/ERC-10-0004

Clinical and Biochemical Features of Seven Adult Adrenal Ganglioneuromas.
J Clin Endocrinol Metab, 95(7):3118-25.
Rondeau G, Nolet S, Latour M, Braschi S, Gaboury L, Lacroix A, Panzini B, Arjane P, Cohade C, Bourdeau I.
2010.
BACKGROUND: Adrenal ganglioneuroma (GN) is seldom considered in the differential diagnosis of adrenal
lesions, and its clinical presentation is not well known. OBJECTIVE: Our aim was to describe the clinical,
biochemical, and radiological features of adrenal GNs in adults. METHODS: Seven adults underwent endocrine
investigation for adrenal lesions that were confirmed to be adrenal GNs. RESULTS: Mean age of the seven
patients was 49 yr (range, 23 to 71 yr). Average tumor diameter was 5.0 cm (range, 1.5 to 10.4 cm). In five
patients, the adrenal lesions were found incidentally. A 49-yr-old female carried a germline mutation in MSH2
gene. A 57-yr-old female presented with mild virilization and increased testosterone levels. Bilateral adrenal
venous sampling revealed testosterone production from her right adrenal lesion. All tumors showed
nonenhanced attenuation between 25 and 40 Hounsfield units on computed tomography scan. Magnetic
resonance imaging revealed low- to iso-signal intensity on T1-weighted imaging and high-signal intensity on T2-
weighted imaging. [(18)F]-2-Fluoro-deoxy-d-glucose-positron emission tomography scan (n = 5) disclosed a
mean standard uptake value of 2.4. Three tumors were composite pheochromocytoma-GN. Microsatellite
instability study and immunohistochemical analysis of MSH2 protein in a patient carrying a MSH2 mutation
showed normal MSH2 protein expression and low microsatellite instability, indicating that the adrenal GN was
not related to the patient's MSH2 germline defect. CONCLUSIONS: We describe one of the largest series of
adult adrenal GNs. Adrenal GNs may secrete testosterone or be part of a composite tumor with
pheochromocytoma. The association of adrenal GN with MSH2 mutation seems to be a coincidental finding.
PubMed-ID: 20427489
http://dx.doi.org/10.1210/jc.2009-2775

Adrenal Incidentaloma: Does an Adequate Workup Rule Out Surprises?
Surgery, 148(2):392-7.
Grogan RH, Mitmaker E, Vriens MR, Harari A, Gosnell JE, Shen WT, Clark OH, Duh QY. 2010.
BACKGROUND: Adrenal incidentaloma remains a diagnostic challenge. Despite well-established management
guidelines, the long-term results of following these guidelines are unknown. We sought to determine how
accurately these guidelines identify functioning incidentalomas and how often these guidelines result in
adrenalectomy for benign tumors. METHODS: We catalogued adrenal incidentalomas from a retrospective
review of 500 consecutive adrenalectomies at a single institution. The outcome measures studied were patient
demographics, preoperative biochemical analysis, imaging characteristics, tumor size, type of operation
performed, and postoperative histologic diagnosis. RESULTS: Eighty-one of the 500 adrenalectomies performed

ESES Review of Recently Published Literature 2010-2                                                Page 54 of 63
were for incidentalomas. Size was the only significant characteristic that distinguished cortical cancers from
benign adenomas. Only 1 out of 26 functioning tumors was incorrectly identified on preoperative workup. We
also found that 25% of cortisol-secreting incidentalomas were cystic, and that benign adenomas accounted for
42% of all tumors resected. CONCLUSION: Current guidelines accurately predict the functional status of adrenal
incidentalomas. Some cystic lesions may be functioning and should therefore be screened for hormonal
hypersecretion. However, even with the most up-to-date diagnostic tools available, most adrenal incidentalomas
resected are benign tumors.
PubMed-ID: 20576282
http://dx.doi.org/10.1016/j.surg.2010.05.001

Laparoscopic Versus Open Adrenalectomy for Adrenocortical Carcinoma: Surgical and Oncologic
Outcome in 152 Patients.
Eur Urol, 58(4):609-15.
Brix D, Allolio B, Fenske W, Agha A, Dralle H, Jurowich C, Langer P, Mussack T, Nies C, Riedmiller H, Spahn M,
Weismann D, Hahner S, Fassnacht M. 2010.
BACKGROUND: The role of laparoscopic adrenalectomy in the treatment of patients with adrenocortical
carcinoma (ACC) is controversial. OBJECTIVE: Our aim was to compare oncologic outcome in patients with
ACC who underwent either open adrenalectomy (OA) or laparoscopic adrenalectomy (LA) for localised disease.
DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective analysis of 152 patients with stage I-
III ACC with a tumour < or =10 cm registered with the German ACC Registry. INTERVENTION: Patients were
stratified into two groups according to the surgical procedure (LA or OA). For comparison, we used both a
matched pairs approach by selecting for each patient from the LA group (n=35) one corresponding patient from
the OA group (n=117) and multivariate analysis in all 152 patients. MEASUREMENTS: Disease-specific survival
was chosen as the predefined primary end point. Secondary end points were recurrence-free survival, frequency
of tumour capsule violation and postoperative peritoneal carcinomatosis, and incidence and reasons for
conversion from LA to OA. RESULTS AND LIMITATIONS: LA and OA did not differ with regard to the primary
end point using either the matched pairs approach (hazard ratio [HR] for death: 0.79; 95% confidence interval
[CI], 0.36-1.72; p=0.55) or multivariate analysis (HR for death: 0.98; 95% CI, 0.51-1.92; p=0.92). Similarly,
adjusted recurrence-free survival was not different between LA and OA (HR: 0.91; 95% CI, 0.56-1.47; p=0.69).
Frequency of tumour capsule violation and peritoneal carcinomatosis were comparable between groups. In 12 of
35 patients of the LA group, surgery was converted to open surgery with no impact on the clinical outcome.
CONCLUSIONS: For localised ACC with a diameter of < or =10 cm, LA by an experienced surgeon is not inferior
to OA with regard to oncologic outcome.
PubMed-ID: 20580485
http://dx.doi.org/10.1016/j.eururo.2010.06.024

Robotic Posterior Retroperitoneal Adrenalectomy: Operative Technique.
Arch Surg, 145(8):781-4.
Berber E, Mitchell J, Milas M, Siperstein A. 2010.
OBJECTIVE: To describe a robotic technique for posterior retroperitoneal (PR) adrenalectomy. DESIGN:
Prospective study. SETTING: Academic hospital. PATIENTS: Twenty-three patients had robotic adrenalectomy
within a year. Of these, 8 cases were done using a PR approach. MAIN OUTCOME MEASURES: Feasibility of
the robotic approach, patient and tumor characteristics, operative time, and complications. RESULTS: There
were 5 women and 3 men (mean age, 52 years). There were no conversions to laparoscopic or open surgery.
Pathology included benign adrenocortical adenoma in 3 patients, aldosteronoma in 2, and pheochromocytoma,
subclinical Cushing syndrome, and lymphangioma in 1 patient each. The right and left sides were each involved
in 4 patients. The mean (SD) tumor size was 2.9 (1.7) cm. The procedures were done using 3 trocars and 5-mm
robotic instruments. The mean (SD) operative time was 214.8 (40.8) minutes; docking time, 21.7 (16.6) minutes;
and console time, 97.1 (24.2) minutes. Estimated blood loss was 24 (35) mL. All patients were discharged to
home in 24 hours. There were no complications. Subjectively, the dissection was felt to be easier with the robotic
technique compared with the laparoscopic approach owing to the improved dexterity of the instruments.
CONCLUSIONS: To our knowledge, this is the first article describing robotic PR adrenalectomy, and we have
demonstrated the technique to be feasible and safe. Owing to the limitations of a conventional laparoscopic PR
approach, we believe that use of the robot is a refinement of the technique.
PubMed-ID: 20713932
http://dx.doi.org/10.1001/archsurg.2010.148

Consequences of Adrenal Venous Sampling in Primary Hyperaldosteronism and Predictors of Unilateral
Adrenal Disease.

ESES Review of Recently Published Literature 2010-2                                                Page 55 of 63
J Am Coll Surg, 211(3):384-90.
Mathur A, Kemp CD, Dutta U, Baid S, Ayala A, Chang RE, Steinberg SM, Papademetriou V, Lange E, Libutti SK,
Pingpank JF, Alexander HR, Phan GQ, Hughes M, Linehan WM, Pinto PA, Stratakis CA, Kebebew E. 2010.
BACKGROUND: In patients with primary hyperaldosteronism, distinguishing between unilateral and bilateral
adrenal hypersecretion is critical in assessing treatment options. Adrenal venous sampling (AVS) has been
advocated by some to be the gold standard for localization of the responsible lesion, but there remains a lack of
consensus for the criteria and the standardization of technique. STUDY DESIGN: We performed a retrospective
study of 114 patients with a biochemical diagnosis of primary hyperaldosteronism who all underwent CT scan
and AVS before and after corticotropin (ACTH) stimulation. Univariate and multivariate analyses were performed
to determine what factors were associated with AVS lateralization, and which AVS values were the most
accurate criteria for lateralization. RESULTS: Eighty-five patients underwent surgery at our institution for
unilateral hyperaldosteronism. Of the 57 patients who demonstrated unilateral abnormalities on CT, AVS
localized to the contralateral side in 5 patients and revealed bilateral hyperplasia in 6 patients. Of the 52 patients
who showed bilateral disease on CT scan, 43 lateralized with AVS. The most accurate criterion on AVS for
lateralization was the post-ACTH stimulation value. Factors associated with AVS lateralization included a low
renin value, high plasma aldosterone-to plasma-renin ratio, and adrenal mass > or = 3 cm on CT scan.
CONCLUSIONS: Because 50% of patients would have been inappropriately managed based on CT scan
findings, patients with biochemical evidence of primary hyperaldosteronism and considering adrenalectomy
should have AVS. The most accurate measurement for AVS lateralization was the post-ACTH stimulation value.
Although several factors predict successful AVS lateralization, none are accurate enough to perform AVS
selectively.
PubMed-ID: 20800196
http://dx.doi.org/10.1016/j.jamcollsurg.2010.05.006

Adrenocortical Carcinoma and Synchronous Malignancies.
J Cancer, 1:108-11.
Guerrero MA, Kebebew E. 2010.
OBJECTIVE: Adrenocortical carcinoma (ACC) is an aggressive tumor that accounts for 0.02% of all reported
cancers. ACC commonly arises in a sporadic manner, but may also manifest as part of a familial syndrome.
Regardless of the setting, ACC rarely arises concurrent with other malignant tumors.METHODS: In this report
we describe a 32-year-old woman who on work-up for abnormal vaginal bleeding was diagnosed with
synchronous uterine adenocarcinoma, ovarian adenocarcinoma and ACC. We also provide a literature review of
the past 20 years to identify other patients with ACC and synchronous malignant tumors, and those with familial
syndromes associated with an increased risk of developing ACC.RESULTS AND CONCLUSIONS: To our
knowledge this is the first report of a patient with synchronous malignant tumors of the uterus, ovary and adrenal
gland. Review of the literature revealed only 5 other cases in which a patient had concurrent ACC and malignant
tumors in other organs.
PubMed-ID: 20842232




ESES Review of Recently Published Literature 2010-2                                                   Page 56 of 63
NET

Meta-Analyses
- None -


Randomized controlled trials
- None -


Other Articles
[177Lu-DOTA 0-Tyr 3]-Octreotate Treatment in Patients With Disseminated Gastroenteropancreatic
Neuroendocrine Tumors: the Value of Measuring Absorbed Dose to the Kidney.
World J Surg, 34(6):1368-72.
Sward C, Bernhardt P, Ahlman H, Wangberg B, Forssell-Aronsson E, Larsson M, Svensson J, Rossi-Norrlund R,
Kolby L. 2010.
BACKGROUND: Peptide receptor radiation therapy (PRRT) using [(177)Lu-DOTA(0)-Tyr(3)]-octreotate is a new,
promising option for treatment of disseminated gastroenteropancreatic neuroendocrine tumors (GEPNETs).
METHODS: During 2006-2008, 26 patients with disseminated GEPNETs were treated with (177)Lu-octreotate.
Radiologic response (RECIST), biochemical response [plasma chromogranin-A (P-CgA)], hematologic toxicity
[Common Toxicity Criteria (CTC)], absorbed dose to the kidneys (conjugate view method), and glomerular
filtration rate (GFR) were analyzed. RESULTS: (177)Lu-octreotate (8 GBq) was given one to five times (median
= 3) with a 6-week interval between each. Sixteen of the 26 patients were evaluated radiologically; 6 (38%) had
partial response (PR), 8 (50%) had stable disease (SD), and 2 (13%) had progressive disease (PD). Seventeen
of the 26 patients were evaluated biochemically; 6 (35%) showed a >or=30% decrease, 8 (47%) showed a
>or=20% increase, and 3 (18%) showed neither a >or=30% decrease nor a >or=20% increase. The mean
absorbed dose to the kidneys was 24 Gy. With a dose limit of 27 Gy to the kidneys, 10 patients did not receive
the planned four treatments, while four patients had the potential to receive additional treatment. A significant
reduction (p = 0.0013) of GFR was observed at follow-up. Three patients experienced CTC grade 3 hematologic
toxicity. CONCLUSIONS: By using the absorbed dose to the kidneys as a limiting factor, treatment with (177)Lu-
octreotate can be individualized, e.g., overtreatment can be avoided and patients with the potential to receive
additional treatment can be identified. Further studies are needed to define tolerance doses to the kidneys so
that treatment can be optimized.
PubMed-ID: 20066413
http://dx.doi.org/10.1007/s00268-009-0387-6

Stenting of the Superior Mesenteric Vein in Midgut Carcinoid Disease With Large Mesenteric Masses.
World J Surg, 34(6):1373-9.
Hellman P, Hessman O, Akerstrom G, Stalberg P, Hennings J, Bjorck M, Eriksson LG. 2010.
BACKGROUND: Midgut carcinoid (MGC) tumors generally develop in the small intestine and in >50% of cases
also present with lymph node metastases in the mesentery. The majority of these tumors are surgically
resectable, but a fraction are inoperable and may cause obstruction of the superior mesenteric vein (SMV), often
associated with stasis of the intestinal wall and severe symptoms. These symptoms include severe abdominal
pain, attacks of diarrhea, and malnutrition. METHODS: Seven patients with severe MGC including a large fibrotic
inoperable mesenteric mass and severe symptoms were studied. After an obstructed SMV and signs of venous
stasis in the small intestine were demonstrated, an expandable stent was inserted after puncturing an
intrahepatic portal venous branch. The associated venography, patient symptoms, and radiological signs on
computed tomography (CT) scans were evaluated. RESULTS: Four patients demonstrated resolution of their
symptoms. In one patient who had intra-abdominal lymph leakage/chyloperitoneum, a complete normalization of
the circulation followed and the intra-abdominal lymph leakage stalled. The venographies demonstrated
normalization of the venous blood flow through the SMV, and CT scans demonstrated reduction in the thickness
of the intestinal wall. In two cases there were no changes in the symptoms, and in one case a slight worsening
of the symptoms ensued. In general, reductions of symptoms were associated with the degree of normalization
of venous blood flow. CONCLUSIONS: We conclude that in selected patients with MGC stenting of the SMV


ESES Review of Recently Published Literature 2010-2                                               Page 57 of 63
may improve symptoms.
PubMed-ID: 20066417
http://dx.doi.org/10.1007/s00268-009-0361-3

Impairment of Cognitive Function Reported by Patients Suffering From Carcinoid Syndrome.
World J Surg, 34(6):1356-60.
Chambers AJ, Longman RS, Pasieka JL, Dixon E, Rorstad O, Rach-Longman K, Jones J. 2010.
BACKGROUND: Carcinoid syndrome (CS) is characterized by symptoms of diarrhea, flushing, bronchospasm,
and valvular heart disease. It has been our impression that patients with CS also exhibit features of cognitive
impairment. The purpose of this pilot study was to evaluate if symptoms of cognitive impairment were reported
by patients with CS. METHODS: Patients with proven CS completed a 38-question multiple-ability self-report
questionnaire (MASQ) to assess symptoms in five cognitive domains: language skills, attention/concentration
(A/C), visual-perceptual function, visual memory, and verbal memory. Patients subsequently underwent
neurocognitive assessment using a battery of six standardized tests. Results of the MASQ and the cognitive test
were compared to published results for healthy individuals. RESULTS: Twenty-one patients with CS were
studied. MASQ symptom scores were higher than published norms in all five cognitive domains. Patients
reported greatest difficulty with verbal memory (mean +/- SD = 2.74 +/- 0.5), followed by A/C (2.41 +/- 0.65),
language (2.31 +/- 0.55), visual memory (2.30 +/- 0.65), and visual-perceptual function (2.17 +/- 0.59). In
contrast, neurocognitive tests for verbal memory immediate recall, visual memory, language, and executive
function were within the normal range. CS patients, however, scored lower than expected in tests of verbal
memory delayed recall and visual-perceptual function. CONCLUSIONS: Patients with CS report high levels of
symptoms of impairment in all cognitive domains; however, on formal neurocognitive testing, patients scored
lower than expected only in tests of verbal memory delayed recall and visual-perceptual function. These findings
appear to confirm our clinical impression that cognitive impairment may be an additional feature of CS. Further
studies are needed to confirm and elucidate the cause of this cognitive impairment.
PubMed-ID: 20127244
http://dx.doi.org/10.1007/s00268-010-0404-9

Prophylactic Cholecystectomy in Midgut Carcinoid Patients.
World J Surg, 34(6):1361-7.
Norlen O, Hessman O, Stalberg P, Akerstrom G, Hellman P. 2010.
BACKGROUND: Patients with midgut carcinoid (MGC) tumors are commonly treated with somatostatin analogs.
Adverse effects of these drugs include impairment of gallbladder function, formation of gallstones, and
cholecystitis. Prophylactic cholecystectomy has been advocated, but data to support this recommendation are
sparse. We have analyzed a cohort of 235 patients with MGC focusing on the risk for gallstone formation and
complications thereof. METHODS: Forty-eight of the 235 patients had been cholecystectomized before surgery
for MGC. Of the remaining 187 patients, 144 were treated with somatostatin analogs. Eighteen of the 187
patients had their gall bladder removed during the primary carcinoid surgery. RESULTS: Twenty-two of the 144
somatostatin-analog-treated patients developed complications, such as gallbladder empyema (n = 1), cholangitis
(n = 2), acute cholecystitis (n = 6), acute pancreatitis (n = 1) or acute pancreatitis and cholecystitis (n = 1), or
biliary colic (n = 11). Ninety-two of the 144 were examined during surgery, by computed tomography, or by
ultrasound, most for reasons other than gallbladder-related indications, and 63% (58/92) of these examinations
revealed gallstones. Of the 43 patients not treated with somatostatin analogs, only 3 patients suffered from
biliary colic and underwent cholecystectomy. CONCLUSIONS: In our study the incidence of gallstone-related
complications seems to be higher than in the general population. We recommend that prophylactic
cholecystectomy is liberally performed during laparotomy for MGC if patients are planned to undergo treatment
with somatostatin analogs.
PubMed-ID: 20130865
http://dx.doi.org/10.1007/s00268-010-0428-1

Parenchyma-Preserving Resections for Small Nonfunctioning Pancreatic Endocrine Tumors.
Ann Surg Oncol, 17(6):1621-7.
Falconi M, Zerbi A, Crippa S, Balzano G, Boninsegna L, Capitanio V, Bassi C, Di C, V, Pederzoli P. 2010.
BACKGROUND: Parenchyma-preserving resections (PPRs), including enucleation and middle pancreatectomy
(MP), are accepted procedures for insulinomas, but their role in the treatment of nonfunctioning pancreatic
endocrine tumors (NF-PETs) is debated. The aim of this study was to evaluate perioperative and long-term
outcomes after PPRs for NF-PETs. METHODS: All patients who underwent PPRs for NF-PETs between 1990
and 2005 were included. Patients with multiple endocrine neoplasia type 1 were excluded. RESULTS: Overall,
50 patients (23 men, 27 women, median age 59 years) underwent 26 enucleations and 24 MP. A total of 58% of

ESES Review of Recently Published Literature 2010-2                                                 Page 58 of 63
NF-PETs were incidentally discovered. Median size of the tumors was 13.5 mm with no preoperative suspicion
of malignancy in all patients. Overall morbidity and pancreatic fistula rates were 58 and 50%, respectively.
Reoperation rate was 4%, with no mortality. Postoperative complications were higher in the MP group. At
pathology, there were 34 (68%) benign lesions, 13 (26%) neoplasms of uncertain behavior, and 3 (6%) well-
differentiated carcinomas. Forty-one patients (82%) had tumors < or =2 cm in size. Only eight patients (16%)
had at least one lymph node removed. After a median follow-up of 58 months, no patient died of disease.
Overall, four patients (8%) experienced tumor recurrence after a mean of 68 months. The incidence of
exocrine/endocrine insufficiency was 8%. CONCLUSIONS: PPRs are generally safe and effective procedures for
treating small NF-PETs. However, better selection criteria must be identified, and lymph node sampling should
be performed routinely to avoid understaging. Long-term follow-up evaluation (>5 years) is of paramount
importance given the possible risk of late recurrence.
PubMed-ID: 20162460
http://dx.doi.org/10.1245/s10434-010-0949-8

Value of Combined 6-[18F]Fluorodihydroxyphenylalanine PET/CT for Imaging of Neuroendocrine
Tumours.
Br J Surg , 97(5):691-7.
Schiesser M, Veit-Haibach P, Muller MK, Weber M, Bauerfeind P, Hany T, Clavien PA. 2010.
BACKGROUND: Accurate knowledge of tumour presence and location is essential to treat neuroendocrine
tumours (NETs). Standard imaging has been hampered by low sensitivity and lack of spatial resolution. This
study assessed prospectively the diagnostic value and impact of combined 6-[18F]fluorodihydroxyphenylalanine
positron emission tomography-computed tomography (18F-DOPA-PET/CT) in the management of NET.
METHODS: 18F-DOPA-PET/CT findings in 61 patients with suspected NET were compared with a composite
reference standard including somatostatin receptor scintigraphy (SRS), magnetic resonance imaging, computed
tomography, histological examination and clinical follow-up. The impact on clinical management was estimated
by calculating the proportion of patients whose treatment changed as a result of 18F-DOPA-PET/CT findings.
RESULTS: 18F-DOPA-PET/CT correctly identified 32 of 36 patients with NET. The sensitivity and specificity of
18F-DOPA-PET/CT for the detection of NET were 91 and 96 per cent respectively. Sensitivity using SRS was
significantly lower (59 per cent), whereas the specificity was similar (86 per cent). In 16 (26 per cent) of the 61
patients the management was altered as a result of new findings on 18F-DOPA-PET/CT. CONCLUSION: 18F-
DOPA-PET/CT yields a high sensitivity and specificity in the detection of NET. The clinical impact was highly
relevant as changes in therapy were observed in more than a quarter of the patients.
PubMed-ID: 20225244
http://dx.doi.org/10.1002/bjs.6937

Epidemiology of Small Bowel Carcinoids in a Defined Population.
World J Surg, 34(7):1500-5.
Landerholm K, Falkmer S, Jarhult J. 2010.
BACKGROUND: This retrospective study describes the epidemiology of small bowel carcinoids in a
geographically defined population, with no other selection bias. METHODS: All patients (n = 145) resident in
Jonkoping County when diagnosed with carcinoid in the jejunum or ileum from 1960 to 2005 were included.
Medical records were reviewed in detail, and tumor specimens were histopathologically and
immunohistochemically reexamined when required (n = 44). RESULTS: The annual age-adjusted incidence of
small bowel carcinoids was 1.12 (95% confidence interval 0.95-1.31) per 100,000 persons. Median age at
diagnosis was 69 years. The predominating presenting symptom was uncharacteristic abdominal pain (50%),
whereas a smaller number suffered from typical flushes (13%). Surprisingly, 14% presented with overt
gastrointestinal hemorrhage. Most of the patients diagnosed based on their symptoms had metastases at
diagnosis (44% regional, 40% distant). Metastasized tumors by definition belong to World Health Organization
(WHO) histopathologic group 2; and when reexamined, most (83%) of the localized tumors were also found to
belong to WHO group 2. CONCLUSIONS: In comparison to previous reports, a higher age-adjusted incidence of
small bowel carcinoids was observed, and the patients were clearly older at the time of diagnosis. Even with
metastatic disease, the presenting symptoms were usually uncharacteristic, and the carcinoid syndrome was
infrequently seen.
PubMed-ID: 20237925
http://dx.doi.org/10.1007/s00268-010-0519-z

Typical Carcinoids and Neuroendocrine Carcinomas of the Stomach: Differing Clinical Courses and
Prognoses.
Am J Surg, 200(3):328-33.

ESES Review of Recently Published Literature 2010-2                                                 Page 59 of 63
Kim BS, Oh ST, Yook JH, Kim KC, Kim MG, Jeong JW, Kim BS. 2010.
BACKGROUND: Gastric endocrine tumors are usually classified as 3 types of well-differentiated endocrine
tumors (typical carcinoids or carcinoids) and poorly differentiated carcinomas (neuroendocrine carcinomas
[NECs]). METHODS: From 1993 to 2008, 97 patients (73 men and 24 women) were diagnosed with gastric
neuroendocrine tumors at the Asan Medical Center. RESULTS: Of the 45 patients with typical carcinoids, 37
underwent surgery (eg, endoscopic resection). Of the 52 patients with NECs, 43 underwent surgery (eg, radical
gastrectomy). One patient died of recurrence of the typical carcinoids, whereas 26 patients with NECs died of
related diseases (P < .05). The rates of survival and recurrence did not significantly differ by type of typical
carcinoid (P > .05). CONCLUSIONS: Regardless of the type, carcinoids that are not yet advanced can be
effectively treated with minimal endoscopic or laparoscopic surgery. However, all NECs and advanced
carcinoids should be treated with radical gastrectomy.
PubMed-ID: 20385369
http://dx.doi.org/10.1016/j.amjsurg.2009.10.028

VEGF Secretion by Neuroendocrine Tumor Cells Is Inhibited by Octreotide and by Inhibitors of the
PI3K/AKT/MTOR Pathway.
 Neuroendocrinology, 91(3):268-78.
Villaume K, Blanc M, Gouysse G, Walter T, Couderc C, Nejjari M, Vercherat C, Cordier-Bussat M, Roche C,
Scoazec JY. 2010.
Gastroenteropancreatic (GEP) endocrine tumors are hypervascular tumors able to synthesize and secrete high
amounts of VEGF. We aimed to study the regulation of VEGF production in GEP endocrine tumors and to test
whether some of the drugs currently used in their treatment, such as somatostatin analogues and mTOR
inhibitors, may interfere with VEGF secretion. We therefore analyzed the effects of the somatostatin analogue
octreotide, the mTOR inhibitor rapamycin, the PI3K inhibitor LY294002, the MEK1 inhibitor PD98059 and the
p38 inhibitor SB203850 on VEGF secretion, assessed by ELISA and Western blotting, in three murine endocrine
cell lines, STC-1, INS-r3 and INS-r9. Octreotide and rapamycin induced a significant decrease in VEGF
production by all three cell lines; LY294002 significantly inhibited VEGF production by STC-1 and INS-r3 only.
We detected no effect of PD98059 whereas SB203850 significantly inhibited VEGF secretion in INS-r3 and INS-
r9 cells only. By Western blotting analysis, we observed decreased intracellular levels of VEGF and HIF-1alpha
under octreotide, rapamycin and LY294002. For rapamycin and LY294002, this effect was likely mediated by the
inhibition of the mTOR/HIF-1/VEGF pathway. In addition to its well-known anti-secretory effects, octreotide may
also act through the inhibition of the PI3K/Akt pathway, as suggested by the decrease in Akt phosphorylation
detected in all three cell lines. In conclusion, our study points out to the complex regulation of VEGF synthesis
and secretion in neoplastic GEP endocrine cells and suggests that the inhibition of VEGF production by
octreotide and rapamycin may contribute to their therapeutic effects.
PubMed-ID: 20389030
http://dx.doi.org/10.1159/000289569

ENETS Consensus Guidelines for the Management of Patients With Rare Metastases From Digestive
Neuroendocrine Tumors: Rationale and Working Framework. Introduction.
Neuroendocrinology, 91(4):324-5.
O'Toole D, Rindi G, Plockinger U, Wiedenmann B. 2010.
PubMed-ID: 20407213
http://dx.doi.org/10.1159/000287272

ENETS Consensus Guidelines for the Management of Peritoneal Carcinomatosis From Neuroendocrine
Tumors.
Neuroendocrinology, 91(4):333-40.
Kianmanesh R, Ruszniewski P, Rindi G, Kwekkeboom D, Pape UF, Kulke M, Sevilla G, I, Scoazec JY, Nilsson
O, Fazio N, Lesurtel M, Chen YJ, Eriksson B, Cioppi F, O'Toole D. 2010.
PubMed-ID: 20424420
http://dx.doi.org/10.1159/000286700

ENETS Consensus Guidelines for the Management of Brain, Cardiac and Ovarian Metastases From
Neuroendocrine Tumors.
Neuroendocrinology, 91(4):326-32.
Pavel M, Grossman A, Arnold R, Perren A, Kaltsas G, Steinmuller T, de HW, Nikou G, Plockinger U, Lopes JM,
Sasano H, Buscombe J, Lind P, O'Toole D, Oberg K. 2010.



ESES Review of Recently Published Literature 2010-2                                               Page 60 of 63
PubMed-ID: 20453466
http://dx.doi.org/10.1159/000287277

ENETS Consensus Guidelines for the Management of Bone and Lung Metastases From Neuroendocrine
Tumors.
Neuroendocrinology, 91(4):341-50.
Kos-Kudla B, O'Toole D, Falconi M, Gross D, Kloppel G, Sundin A, Ramage J, Oberg K, Wiedenmann B,
Komminoth P, Van CE, Mallath M, Papotti M, Caplin M. 2010.
PubMed-ID: 20484875
http://dx.doi.org/10.1159/000287255




ESES Review of Recently Published Literature 2010-2                                  Page 61 of 63
GI and General

Meta-Analyses
- None -


Randomized controlled trials
- None -


Other Articles
Endocrine Tumors: the Evolving Role of Positron Emission Tomography in Diagnosis and Management.
J Endocrinol Invest, 33(1):54-60.
Naji M, Hodolic M, El-Refai S, Khan S, Marzola MC, Rubello D, Al-Nahhas A. 2010.
Endocrine tumors comprise a range of benign and malignant conditions that produce a spectrum of clinical
symptoms and signs depending on the specific hormones they produce. The symptoms and presentations of
these tumors are often independent of their size and location. Because of their expression of cell membrane
receptors or production of specific types of hormones or peptides, endocrine tumors can be identified with
functional radionuclide imaging much more readily compared to standard cross-sectional imaging. In recent
years, 18F-fluoro-deoxy- D-glucose positron emission tomography (18F-FDG-PET) has emerged as a useful tool
for diagnosing and assessing many tumors. In this review we describe how PET, using 18F-FDG and other
radiopharmaceuticals can be useful in the diagnosis and management of a wide range of endocrine tumors.
PubMed-ID: 19820296
http://dx.doi.org/10.3275/6561

Molecular Markers for Novel Therapies in Neuroendocrine (Carcinoid) Tumors.
Endocr Relat Cancer, 17(3):623-36.
Gilbert JA, Adhikari LJ, Lloyd RV, Rubin J, Haluska P, Carboni JM, Gottardis MM, Ames MM. 2010.
Neuroendocrine (carcinoid) tumors (NETs) are endocrine neoplasms occurring most frequently in
gastrointestinal and bronchopulmonary (BP) systems. The majority of patients present with advanced disease for
which few treatment options exist. We assessed 104 NETs (74 cases) for biomarkers targeted by anticancer
drugs under development for other forms of cancer. Activating mutations were assessed in epidermal growth
factor receptor (EGFR), stem cell factor receptor (KIT), and platelet-derived growth factor receptor alpha
(PDGFRA), as well as non-response mutations in KRAS. Copy number of EGFR and HER-2/neu was quantified
with fluorescence in situ hybridization. Immunohistochemical analyses were performed for EGFR, KIT, PDGFRA,
somatostatin receptor subtypes 2A and 5 (SSTR5), vascular endothelial growth factor receptor 1, mammalian
target of rapamycin (mTOR), insulin-like growth factor 1 receptor (IGF1R), heat shock protein 90 (Hsp90), and
transforming growth factor-beta receptor 1 (TGFBR1). NETs lacked HER2-overexpression predictive of anti-
HER2 response and KIT and PDGFRA activating mutations indicative of imatinib sensitivity. High EGFR
aneusomy (20% of all cases) and elevated EGFR copy number (39%) were found, but few KRAS mutations
associated with non-response to anti-EGFR therapy (3%). Hsp90, TGFBR1, IGF1R, and SSTR5 exhibited
highest levels of immunohistochemical staining in the largest percents of tumors. In subsequent in vitro studies,
anticancer drug 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) (targeting Hsp90) inhibited proliferation of
BP NET lines NCI-H727, NCI-H720, and NCI-H835 with IC(50) values of 70.4, 310, and 788 nM respectively;
BMS-754807 (targeting IGF1R/IR) inhibited growth with IC(50) values of 428 nM, 2.8 microM, and 1 microM. At
growth-inhibiting concentrations, 17-AAG (24 h) induced loss of EGFR and IGF1R in the IGF1R-expressing NCI-
H727 line, and BMS-754807 (24 h) inhibited constitutive IGF1R autophosphorylation. Our results support further
research into Hsp90, IGF1R, and EGFR as targets for developing new anticancer therapeutics for some NETs.
PubMed-ID: 20385747
http://dx.doi.org/10.1677/ERC-09-0318

Paraneoplastic Syndromes Secondary to Neuroendocrine Tumours.
Endocr Relat Cancer, 17(3):R173-R193.
Kaltsas G, Androulakis II, de Herder WW, Grossman AB. 2010.


ESES Review of Recently Published Literature 2010-2                                               Page 62 of 63
Neuroendocrine tumours may be either benign or malignant tumours, and have the ability to synthesise and
secrete biologically active substances characteristic of the cell of origin that can cause distinct clinical
syndromes. The term 'paraneoplastic syndromes' (PNSs) is used to denote syndromes secondary to substances
secreted from tumours not related to their specific organ or tissue of origin and/or production of autoantibodies
against tumour cells; such syndromes are mainly associated with hormonal and neurological symptoms.
Appreciation of the presence of such syndromes is important as clinical presentation, if not identified, may delay
the diagnosis of the underlying neoplasia. Conversely, early recognition can allow for more rapid diagnosis,
particularly as the coexistence of a neoplasm with a clinical or biochemical marker offers an additional
determinant of tumour status/progression. PNSs can complicate the patient's clinical course, response to
treatment, impact prognosis and even be confused as metastatic spread. Their diagnosis involves a
multidisciplinary approach, and detailed endocrinological, neurological, radiological and histological studies are
required. Correct diagnosis is essential as the treatment of choice will be different for each disorder, particularly
in the case of malignant tumours; it is therefore important to develop appropriate means to correctly identify and
localise these tumours. Clinical awareness and the incorporation into clinical practise of (111)In-octreotide
scintigraphy, chromogranin A and other evolving biochemical marker measurement techniques have
substantially contributed to the identification of patients harbouring such syndromes. Disease-specific medical
therapies are mandatory in order to prevent recurrence and/or further tumour growth. Owing to their rarity,
central registration of these syndromes is very helpful in order to be able to provide evidence-based diagnostic
and therapeutic approaches.
PubMed-ID: 20530594
http://dx.doi.org/10.1677/ERC-10-0024




ESES Review of Recently Published Literature 2010-2                                                   Page 63 of 63

								
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