HUCH, J H • S A 01/2005
Helsinki University Central Hospital
Department of Surgery, Jorvi Hospital
Helsinki University Central Hospital
University of Helsinki
Central Hospital of Jyväskylä
HOW TO IMPROVE RESULTS IN RECTAL
A CLINICAL STUDY
To be presented, with the assent of the Faculty of Medicine, University of Helsinki,
for public examination in the Auditorium of Jorvi Hospital, Helsinki University Central
Hospital, Turuntie 150, Espoo, on October 28th, 2005, at 12 noon
Supervised by Docent I K, MD
Central Hospital of Jyväskylä
Reviewed by Professor H J, MD
Helsinki University Central Hospital
Professor J M, MD
Oulu University Central Hospital
Opponent L P, MD, PhD, FRCS, FRCS (Glasg)
Professor of Surgery
Department of Surgery, University Hospital
Publisher Hospital District of Helsinki and Uusimaa
HUCH, Jorvi Hospital
Turuntie • FIN– Espoo • Finland
tel + • telefax +
http://www.hus.fi/jorvi • firstname.lastname@example.org
Editorial Board H A, Editor in chief
ISBN --- (paperback)
ISBN --- (PDF)
http://www.hus.fi/jorvi/julkaisut • http://ethesis.helsinki.fi
Helsinki University Printing House
LIST OF ORIGINAL ARTICLES..................................................................................................4
LIST OF ABBREVIATIONS .........................................................................................................5
REVIEW OF THE LITERATURE ...............................................................................................10
Colorectal cancer screening .........................................................................................10
Faecal occult blood tests ...............................................................................10
Endoscopic screening ...................................................................................10
Biomarkers of neoplastic transformation....................................................11
Surgical treatment .........................................................................................................11
Anatomical aspects .......................................................................................11
Surgical techniques .......................................................................................12
Complications connected to surgery...........................................................................13
Mortality and morbidity................................................................................13
Sexual and urinary dysfunction ..................................................................15
Local recurrence and survival ......................................................................................16
Elderly patients – special considerations ....................................................................17
e role of adjuvant therapies ......................................................................................17
Preoperative radiotherapy and chemoradiotherapy ..................................17
Tumour response ..........................................................................................18
Quality of life after rectal cancer surgery.....................................................................19
AIMS OF THE STUDY...............................................................................................................20
PATIENTS AND METHODS.....................................................................................................21
LIST OF ORIGINAL ARTICLES
is thesis is based on the following original articles, which are referred to in
the text by their Roman numerals:
I V J, K S, A L, K I. A comparison
of peanut agglutinin (PNA) -test and immunochemical faecal occult blood
test in detecting colorectal neoplasia in symptomatic patients. Scand J Clin
Lab Invest ; : –.
II V J, H L, S P, K L, S T, H A,
K I. New approaches in the management of rectal carcinoma
result in reduced local recurrence rate and improved survival. Eur J Surg
; : –.
III V J, S P, H A, K I. Complications and Survival
after surgery for rectal cancer in patients younger than and aged or
older. Dis Colon Rectum ; : –.
IV V J, J M, K M, J I, K I.
Tumor regression grading in the evaluation of tumor response after
different preoperative radiotherapy treatments for rectal carcinoma. Int J
Colorectal Dis ; : –.
V V J, K M, K I. Impact of functional
results on quality of life after rectal cancer surgery. Dis Colon Rectum
4 HUCH, Jorvi Hospital Publications • Series A 01/2005
LIST OF ABBREVIATIONS
APR Abdominoperineal resection
AR Anterior resection
ASA American Society of Anaesthesiologists score
CRM Circumferential resection margin
ERUS Endorectal ultrasound examination
FOBT Faecal occult blood test
Gy Gray (radiation dose)
HAR High anterior resection
HRQoL Health related quality of life
LAR Low anterior resection
PNA Peanut agglutinin
PRT Preoperative radiotherapy
QoL Quality of life
RAND -item Quality of Life questionnaire
distributed by RAND corporation
SF Short Form (Quality of Life questionnaire)
TME Total mesorectal excision
TRG Tumour regression grading
HUCH, Jorvi Hospital Publications • Series A 01/2005 5
e aim of the present study was to examine periods (Study II). A significantly lower
possibilities for improvement of the results -year crude survival was seen in the older
in rectal cancer surgery from detection of age group compared to younger patients
the cancer to outcome in terms of survival ( vs. , P = .). However, -year
and patient satisfaction. cancer-specific survival ( vs. ,
In Study I the sensitivity and specificity P = .) and disease-free -year survival
for detecting colorectal neoplasia of PNA- ( vs. , P = .) were similar in both
rectal mucus test was compared with those groups. e number of complications (
of an immunological test for faecal occult vs. ) and -day mortality ( vs. )
blood (Hemolex) in patients examined were similar in both groups. More elderly
for colorectal symptoms in the Surgical patients were not operated on at all (
Hospital of Helsinki University Central vs. , P = .) compared to patients
Hospital. e sensitivity of the PNA-test younger than (Study III). ese studies
and Hemolex for colorectal neoplasia was show that adopting TME-technique and
vs. and specificity vs. selective use of preoperative radiotherapy
(P = .) showing that a single PNA-test leads to improved survival. Furthermore,
is as sensitive indicator of colorectal neo- in selected elderly patients major curative
plasia as Hemolex completed over three rectal cancer surgery can be done with
days, but lacks specificity. Some commonly similar indications, perioperative morbid-
expressed PNA-binding proteins were iden- ity and mortality as well as -year cancer-
tified both in normal mucosa and colorectal specific and disease-free survival as in
cancer, but expression of kD PNA-bind- younger patients.
ing protein was seen almost exclusively in Patients treated for rectal cancer in the
colorectal cancer. Characterization of that Central Hospital of Jyväskylä during –
cancer-associated antigen may help in de- (N = ) were included in Studies IV
veloping a more specific PNA-test. and V. e usefulness of histologic tumour
e patients treated in the Surgical regression grading (TRG) in quantifying the
Hospital for rectal cancer during – effect of preoperative radiotherapy (PRT)
(conventional surgery, N = ) and dur- or chemoradiation was examined and
ing – (total mesorectal excision, compared with the downstaging defined as
TME, N = ), were included in Studies a change in preoperative T stage obtained
II and III. e effect of refinement of the with endorectal ultrasound examination
surgical technique in complication rate, (uT) and pathologic stage (pT) (Study
local recurrence rate and survival was IV). e histologic tumour regression was
studied, as well as whether elderly patients more marked after long-term chemora-
(≥ years, N = ) can be treated using diation than after short-course radiotherapy
similar indications as younger patients (P = .). Complete response (no residual
(N = ) with acceptable perioperative tumour, TRG ) was seen in of the pa-
morbidity, mortality and survival. e tients and total or major regression (TRG
actuarial local recurrence rate for poten- –) in of the patients treated with
tially curative rectal cancer improved from Gy chemoradiation (N = ). Of those
to and the crude -year survival treated with Gy PRT (N = ),
from to between the two study showed major tumour regression. When
6 HUCH, Jorvi Hospital Publications • Series A 01/2005
comparing uT with pT, of the tumours QoL of rectal cancer patients was not worse
were downstaged, but less than half of than that of general population. Between
the dowstaged tumours showed marked the treatment groups (sphincter-preserv-
response by TRG. In comparison, of ing surgery vs. abdominoperineal resec-
the tumours with no downstaging showed tion) there was no significant difference in
marked response by TRG (P = .). In as- QoL. Major bowel dysfunction impaired
sessing tumour response to preoperative social functioning significantly compared
adjuvant therapy TRG seems to offer a more to patients without such symptoms. e
reliable means than uT-downstaging, which QoL of symptomatic patients was similar
did not correlate with TRG results. to that of patients having undergone APR.
e impact of surgery-related adverse Urinary dysfunction impaired social func-
effects on the quality of life (QoL) was ex- tioning and impotence physical and social
amined using generic RAND- question- functioning. In an attempt to improve QoL
naire and questionnaires assessing urinary, after rectal cancer surgery, minimizing the
sexual and bowel dysfunction. Results incidence of organ dysfunction seems to be
were compared with age and sex-matched at least as important as aiming to sphincter-
Finnish general population (Study V). e sparing surgery.
HUCH, Jorvi Hospital Publications • Series A 01/2005 7
Colorectal cancer is the second lead- surgical technique has an important role
ing cause of cancer mortality in Western in the outcome (Holm ; Porter ).
countries and its incidence and prevalence Increasing evidence shows that refining
are increasing. In , a total of new and standardizing of surgical techniques
cases were detected in Finland (Finnish decreases local recurrence rates as well as
Cancer Registry ). Of them ( ) variability of results between individual sur-
were rectal tumours defined as having the geons (Dahlberg ; e Norwegian Rectal
lower edge within cm of the anus. Rectal Cancer Group ; Kapiteijn ; Martling
cancer is the fifth most common cancer in ). e technique of total mesorectal ex-
men and tenth most common cancer in cision (TME), first introduced by Heald et al.
women with the incidence of ./ in (Heald ), has been reported to
in men and ./ in women. With the decrease the local recurrence rates to –
population ageing the incidence is rising and to improve the overall -year survival
even if the age-adjusted incidence seems to from – with conventional surgery
be stabilizing. to (Enker ; MacFarlane ).
Prognosis depends on the extent of the However, TME surgery seems to be associ-
disease at the time of diagnosis. e ben- ated more often with potentially dangerous
eficial effect of early detection on mortal- anastomotic leakages than the conventional
ity for colorectal cancer has been proved surgery (Karanjia ).
in randomised screening programs (Towler e number of elderly rectal cancer
). Based on an expected reduction patients is increasing but few studies have
of in mortality for colorectal cancer, addressed the ability of elderly patients,
screening strategies are being evaluated for who may have compromised physical ca-
implementation in several European coun- pacity, to recover from adverse events that
tries, including Finland. Currently available may occur in connection of major rectal
methods rely on faecal occult blood (FOB) surgery. Uncertainty persists, as to whether
tests and subsequent endoscopic evalua- elderly patients benefit from the same surgi-
tion in the case of positive test. Bleeding, cal treatment as younger patients (Shankar
however, is not specific for colorectal neo- ).
plasia and may be intermittent in the case Additional benefits of local control can be
of asymptomatic tumours (Ahlquist ). obtained with neoadjuvant treatment. It has
us faecal occult blood tests are hampered been shown that preoperative radiotherapy
by high false positive and false negative (PRT) or chemoradiotherapy increases the
rates. erefore, new non-invasive methods resectability of low and locally advanced
to detect colorectal neoplasia at an early, tumours (Minsky ) and improves local
asymptomatic phase are needed. tumour control and survival (Delaney ;
Today, – of patients can be oper- Kapiteijn ; Swedish Rectal Cancer Trial
ated on with curative intent. However, a ). However, dosage, timing and optimal
major problem after rectal cancer surgery combination of radiotherapy and chemo-
is local recurrence after which outcome is therapy are controversial as well as which
poor. Local recurrence rates vary consider- patients should receive adjuvant treatment
ably between surgeons and institutions (Simunovic ).
ranging from to , suggesting that Both surgery and adjuvant treatments
8 HUCH, Jorvi Hospital Publications • Series A 01/2005
are connected to adverse effects that may Improvements in treatment and early
significantly affect a person’s quality of life. detection indicate that more patients will
Anal sphincter preservation is regarded live with the consequences of the disease.
one of the main goals in rectal cancer Survival and local recurrence rate are im-
surgery to avoid disruption in a patient’s portant but not the only factors contributing
quality of life (QoL) caused by colostomy to good outcome results. Long-term func-
(Sprangers ). However, anal function tional results have a major impact on quality
may be suboptimal after sphincter-saving of life, which has emerged as an important
surgery, especially after coloanal anasto- endpoint. With individualized treatment
moses (Lewis ). Also disturbances in options available, emphasis can be placed
sexual and urinary functions are common also to patient satisfaction and quality of life.
sequelae (Keating ). e effect of these It is of major importance to pay attention to
physical disabilities in quality of life is not details to ensure the best possible outcome
well known. after treatment in all perspectives.
HUCH, Jorvi Hospital Publications • Series A 01/2005 9
REVIEW OF THE LITERATURE
Colorectal cancer screening Rehydration by a drop of deionized water
increases the rate of positive tests from
ere is evidence that benign adenomatous – to – (Mandel ). Rehydration
polyps develop into cancers in the colon. thus increases the sensitivity of a guaiac
Accumulation of multiple genetic altera- test, but is generally not recommended as
tions such as mutational activation of onco- it decreases the specificity leading to high
genes and inactivation of tumour suppres- number of false positive results.
sor genes leads to stepwise progression from e sensitivity of guaiac based faecal
normal to hyperproliferative epithelium occult blood test for detecting colorectal
and adenoma to carcinoma (Bronner ; neoplasia in asymptomatic patients with an
Fearon ; Leslie ). Removing adeno- average risk has been reported to be –
matous polyps have been shown to reduce (Hardcastle ; Kronborg ; Robinson
the incidence of colorectal cancer (Mandel ; omas ) i.e. nearly half of the
; Winawer ). Also, early detection cancers remain undetected with this test. A
of colorectal cancer by mass screening has detection rate of – has been reported
been shown to reduce mortality by (RR for symptomatic cancers (omas ).
., CI . to .) and, when ad- Evidence from four randomised
justed for screening attendance, by (RR controlled trials with Hemoccult II test
., CI .–.) (Towler ). However, (Hardcastle ; Jorgensen ; Kewenter
the best screening method remains contro- ; Kronborg ; Mandel ;
versial. e ideal screening requires high Scholefield ) shows that detecting early
sensitivity and specificity in detecting early stage cancers reduces mortality from the
stage disease and should be acceptable and disease – in the screened population
safe to patients, inexpensive and feasible in (Table ).
general clinical practise (Winawer ). Immunological tests, specific for human
haemoglobin, have been shown to be more
sensitive for symptomatic colorectal cancer
Faecal occult blood tests
than guaiac-based tests (Robinson ;
Guaiac tests based on the pseudoperoxidase omas ). However, the specificity is
activity of haemin are the most commonly lower; vs. in the asymptomatic
used tests both in the preliminary assess- population and vs. in symptom-
ment of subjects with symptoms of colorec- atic patients, respectively (Robinson ;
tal disease and in screening programs. omas ). Randomised population
ese tests involve collection and testing of based studies have not been performed
six samples from three consecutive stools with immunological tests.
of a patient. A specific diet to minimize the
number of false positive results (avoidance
of red and white meat, fish, fresh fruit and
uncooked vegetables i.e. substances with Case-control and uncontrolled cohort
peroxidase or pseudoperoxidase activ- studies suggest that endoscopic screening
ity) is recommended before the testing is with polypectomy reduces the incidence of
performed. Stool samples can be tested in colorectal cancer by – (iis-Evensen
either a dehydrated or rehydrated state. ; Winawer ) and may be even more
10 HUCH, Jorvi Hospital Publications • Series A 01/2005
effective in detecting colorectal neoplasia antigens) (Shamsuddin ) or complex
than FOBT (Segnan ). Furthermore, an macromolecules (Roseth ). ese an-
increase in the proportion of early cancers tigens can be detected using lectin and an-
(Atkin ) and decrease of – in can- tibody immunohistochemistry. Increased
cer mortality compared to non-screened binding of the lectin peanut agglutinin
patients have been reported (Muller ; (PNA) is a common feature in colorectal
Newcomb ; Selby ). However, no carcinoma and hyperplasia (Rhodes ).
results from randomized studies are avail- PNA binds to the disaccharide omsen-
able so far. Friedenreich blood group antigen (galac-
is an oncofetal antigen commonly ex-
Biomarkers of neoplastic transformation
pressed in colorectal cancer but concealed
Specific biomarkers of neoplastic trans- by further glycolysation (sialylation and/or
formation in colorectal mucosa, including fucosylation) in the normal colorectal
mutations in APC (adenomatous polyposis mucosa (Campbell ). Previous studies
coli tumour suppressor gene), K-ras, p have shown that PNA-reactive carbohydrate
and BAT (a marker of microsatellite in- alterations in rectal mucus have a sensi-
stability), have potential to be used as new, tivity of – in detecting colorectal
non-invasive methods to detect colorec- cancer (Kellokumpu ; Sakamoto ;
tal neoplasia (Ahlquist ; Mak ; Shamsuddin ).
Sidranski ). Neoplasm-specific altered
DNA from tumour cells is released into the
bowel lumen more continuously than blood
and is stable in stool having thus potential
to be used as a screening method. However,
colorectal neoplasms are genetically het-
erogeneous and multiple DNA alterations Rectum comprises the terminal cm of
should be targeted to achieve high sensitiv- large bowel. Fatty tissue called mesorectum,
ity (Ahlquist ). containing the terminal branches of the
Besides tumour-derived mutations in superior rectal vessels and the lymphatic
genes the new biomarkers isolated from drainage of the rectum, surrounds the
faecal samples or bowel lumen include rectum and is covered by visceral fascia
secretion of abnormally glycosylated carbo- (fascia propria). Posteriorly rectum is
hydrate structures (e.g. tumour-associated wholly extraperitoneal whereas anteriorly
Table 1. Results of randomised controlled trials of colorectal cancer screening using
Hemoccult II test.
Minnesota Nottingham Funen Goteborg
(Mandel 2000) (Hardcastle 1996) (Kronborg 1996) (Kewenter 1994)
Population size 46 500 150 000 62 000 68 000
Age group (years) 50–80 45–74 45–75 60–64
Study period (years) 18 12 13 8
33* (21**) 15** 18** 12**
RR (CI) 0.80 (0.70–0.90) 0.85 (0.74–0.99) 0.82 (0.69–0.97) 0.88 (0.69–1.12)
* Annual screen
** Biennial testing
HUCH, Jorvi Hospital Publications • Series A 01/2005 11
only the distal third is extraperitoneal and Lateral lymphatic spread to internal iliac
separated from bladder and genital organs nodes on the pelvic sidewalls may occur
by Denonvilliers´ fascia. Posteriorly there especially in case of low rectal cancers in
is an avascular retrorectal space between approximately of patients and in up to
parietal and visceral fascia. Parietal fascia one third of those with positive mesorectal
thickens over sacrum and coccyx forming a nodes (Moriya ; Sugihara ; Ueno
dense Waldeyer´s fascia (Havenga a). ).
e pelvic autonomic nervous system
is located between peritoneum and vis-
ceral fascia and is intimately related to the
rectum. Hypogastric nerves exit bilaterally Radical surgery aims at removing the tu-
from the superior hypogastric plexus at the mour with its all extensions, including the
level of the sacral promontory. Caudally area of vascular and lymphatic drainage
they run parallel to ureter and iliac ves- as well as direct spread to adjacent organs,
sels on each side of the pelvis uniting with with adequate margins of clearance.
the pelvic splanchnic nerves to form the Proximally, the mesorectum is removed
inferior hypogastric (pelvic) plexus, which to the level of aortic bifurcation including
also has connections with sacral roots all lymph nodes distal to the origin of the
(S–). e superior hypogastric plexus and left colic artery. Caudally, the technique of
hypogastric nerves are mainly sympathetic total mesorectal excision (TME) stresses the
whereas pelvic splanchnic nerves are para- importance of removing an intact mesorec-
sympathetic. Pelvic plexus is a dense plaque tal envelope from the promontorium down
of nerve tissue that sends fibers towards to the anal hiatus in pelvic floor by sharp
bladder, urethra and genital organs. Lateral dissection between the visceral and parietal
mesorectum fuses with this structure from planes of the pelvic fascia, confirming that
where some fibers enter anterior rectal wall none of the mesorectal tissue remains in
as well. All nerves and vessels are embed- the pelvis. In case of high tumours, how-
ded in fat and fibrous tissue resembling a ever, mesorectum is transected in -degree
ligament, hence the name lateral ligament angle at least cm below the tumour. Pelvic
(Church ; Havenga a; Maas ). autonomic nerves are carefully visualized
and preserved (Heald ).
Figure shows the difference between
TME and conventional surgery. With con-
Tumour spread along the muscle tube ventional technique there is a tendency to
beyond cm of the palpable edge of the cone the dissection plane towards the rectal
tumour seems to be uncommon, except wall posteriorly and laterally endangering
in poorly differentiated lesions (Williams the radicality. Tumour spread to the lateral
). Instead, tumour growth is more resection margin occurs in approximately
rapid in the transverse than longitudinal of patients treated with conventional
axis of the bowel. Subsequently, submucosa techniques but in less than of patients
and muscle layer of the bowel are invaded treated by TME (Birbeck ; Cawthorn
allowing the tumour growth enter into ; Haas-Kock de ; Quirke ;
the mesorectum. According to modern Wibe ).
understanding, distal and proximal tumour It has been shown that as long as meso-
spread as microscopic foci within the me- rectum is completely removed, the distal
sorectum occur frequently (Heald ; mucosal margin can usually be safely
Reynolds ). reduced to less than cm (Karanjia ;
e main route of lymphatic spread is to Rullier ). Total mobilization of rectum
the chain of glands along the superior hem- to the anal hiatus and utilizing modern
orrhoidal and inferior mesenteric vessels. stapling devices and surgical techniques in
12 HUCH, Jorvi Hospital Publications • Series A 01/2005
creating colorectal or coloanal anastomoses Complications connected to surgery
ensures that sphincter-sparing surgery can
now be performed in – of patients Mortality and morbidity
(Enker ; Tytherleigh ). e tech- Overall morbidity after rectal cancer sur-
nique of intersphincteric resection enables gery varies between – (Arbman ;
sphincter preservation even in patients Carlsen ; Martling ). In addition to
with carcinomas located at the anorectal anastomotic dehiscence and acute urinary
junction, if not invading the anal sphincter retention the most common perioperative
(Rullier ). complications are the same as after any
Abdominoperineal resection is still nec- major abdominal surgery (haemorrhage,
essary for a subset of patients with very low respiratory-, urinary and wound infections,
or advanced tumours. paralytic ileus and cardiovascular events).
After high anterior resection, the bowel Postoperative mortality after elective
continuity is usually re-established by operations is generally less than after
straight end-to-end anastomosis whereas both conventional and TME-surgery (Enker
after low or ultralow anterior resection ; Graf ; Heald ; Marijnen
colorectal or coloanal anastomosis can be ; Martling ). Cardiac complica-
performed using J-pouch (Lazorthes ; tions and anastomotic dehiscence are the
Parc ), side-to-end anastomosis (Huber most common reasons for postoperative
) or coloplasty (Z´graggen ) in- death (Carlsen ; Enker ; Graf ;
stead to restore the reservoir capacity. e Marijnen ).
use of colonic pouch may also enhance e risk for anastomotic dehiscence is
the healing of the anastomosis compared greater after low than high anterior resec-
to straight anastomosis (Hallböök a; tion (Karanjia ; Pakkastie ; Rullier
Hallböök b). ). TME surgery, resulting in more low
Figure 1. Conventional (a) vs. total mesorectal excision (TME) (b) technique in rectal cancer
HUCH, Jorvi Hospital Publications • Series A 01/2005 13
anastomoses, is associated with leakage tients have some degree of incontinence
rates of up to over compared with that compared with – after low anterior
of approximately after conventional sur- resection (Dennet ; Gamagami ;
gery (Nesbakken ). e mortality rate Ortiz ; Rullier ). Ultralow anterior
associated with anastomotic leakage varies resections, extending to the anorectal junc-
between and (Rullier ). tion or more distally into the anal canal, and
e use of a protective stoma after TME coloanal anastomosis, have been associated
surgery and low anastomosis has been with controversial functional results with
shown to lower the rate of clinically relevant – of patients having problems with
leakages from – to – (Carlsen continence (Gamagami ). Functional
; Dehni ; Marijnen ; Marusch results after intersphincteric resections, in-
), especially in men (Law ; Poon cluding removal of internal sphincter, have
; Rullier ), and therefore its routine been reported to be satisfactory with about
use has been recommended (Karanjia ). to of patients having occasional
A defunctioning stoma does not necessarily soiling and – suffering from urgency
prevent leakage, but reduces the need for (Rullier ; Saito ; Schiessel ;
reoperations and the risk for permanent Tiret ). Erratic defecation patterns have
stomas. Some favour selective use of stoma been reported in , urgency in and
only, as complications related directly to obstructed defecation in of patients
stoma have been reported in – of after rectal cancer surgery (Ortiz ).
patients (Heald ; Poon ). Randomised trials that compared
Preoperative radiotherapy utilizing mod- J-pouch anastomosis with straight end-to-
ern techniques does not seem to increase end anastomosis have shown functional
mortality or the risk of anastomotic leakage superiority of the J-pouch, especially in the
(Enker ; Marijnen ; Swedish Rectal early months after surgery (Hallböök b;
Cancer Trial ; Valero ). Lazorthes ; Ortiz ; Rullier ;
Seow-Choen ). Even after one year
urgency is more common and the median
stool frequency per day higher with straight
Anterior resection is associated with a anastomosis than with a J-pouch (Harris
variety of specific symptoms like increased ; Lazorthes ), but may level by two
bowel function, erratic defecation pat- years (Ho ). e majority of patients
terns, urgency, obstructed defecation and with a pouch have a daily frequency of less
impairment of continence (Ortiz ). than three bowel movements. In contrast,
Diminished rectal capacity and compli- evacuation difficulties are more common
ance, impaired internal anal sphincter tone with a pouch occurring in to of
and loss of rectoanal inhibitory reflex are patients. e size of the pouch is critical to
the main causing factors (Lee ). outcome; a – cm pouch seems to be op-
e incidence of early postoperative timal whereas a larger pouch is associated
functional disorders has been reported with incomplete evacuation more often
to be as high as – (Dennet ). (Dennet ). Functional results compa-
Functional deficiencies improve over to rable to J pouch have been obtained using
years (Gamagami ; Ho ; Lee ; end-to-side anastomosis (Machado )
Sailer ), but some degree of permanent or coloplasty (Ho ; Pimentel ;
impairment of sphincter function after Remzi ).
anterior resection seems inevitable (Lee e effect of radiotherapy on anorectal
). function is not fully known. Irradiated
Functional results are worse the closer patients recover slower from defecation
the anastomosis is to the anal canal. After problems than patients treated with sur-
high anterior resection some of pa- gery alone (Marijnen ). ere is some
14 HUCH, Jorvi Hospital Publications • Series A 01/2005
evidence that sphincter-related symptoms tion has lowered the risk for sexual dysfunc-
(incontinence and pouch-related specific tion but has not completely eliminated it
symptoms such as clustering and incom- (Keating ; Kim ; Nesbakken ;
plete evacuation) may also be more com- Pocard ).
mon in irradiated patients than after surgery e dysfunctional outcomes of pel-
alone (Gervaz ; Marijnen ). vic nerve damage in women are poorly
understood. e likely consequences,
impairment of sexual arousal and libido,
Sexual and urinary dysfunction
have been reported to be rare after TME
Disturbances to bladder and sexual func- surgery (Havenga b; Nesbakken ;
tion are well known sequelae of rectal Platell ). Problems related to scarring
cancer surgery. and changed anatomy (shortness or lack of
Damage to the hypogastric nerves or elasticity of vagina during intercourse, dys-
sacral nerves or both, during operation is pareunia) seem to be more common. Faecal
the most likely cause of sexual dysfunction soiling during or after intercourse may also
(Havenga ; Keating ). It has been be a problem.
shown that unilateral sacrifice of inferior Adjuvant radiotherapy may affect on
hypogastric plexus with its parasympathetic sexual functioning of both male and female
component makes failure of erection highly patients. In a randomised study comparing
probable. Bilateral sacrifice makes total Gy preoperative radiotherapy with sur-
impotence certain and often endangers gery alone, decrease in erectile function for
urinary function. Ejaculatory disorders are up to years was noted after PRT (Marijnen
related to sacrifice of the superior hypo- ). Ejaculation disorders occurred more
gastric plexus (Maas ; Pocard ; frequently too. In female patients, sexual ac-
Sugihara ). tivity and functioning deteriorated signifi-
Permanent complete or partial erectile cantly more after PRT than surgery alone.
dysfunction has been reported in – of e rate of reported urinary dysfunction
patients, while – of potent patients are after surgery for rectal cancer ranges from
not able to ejaculate (Enker ; Havenga to (Leveckis ) presenting as
; Maas ; Nesbakken ; Sugihara various complaints. e most common
). After abdominoperineal resection symptoms are stress incontinence, urgency,
the risk for permanent impotence seems elevated frequency of voiding, difficulty
to be – whereas low anterior resec- emptying the bladder, loss of sensation of
tion carries about half the risk of impotence fullness of the bladder and overflow incon-
compared to APR (Enker ; Havenga tinence.
; Keating ). Inadvertent damage to Since most studies have been retrospec-
the pelvic nerves during the perineal phase tive without urodynamic evaluation pre-
of operation particularly at the level of pros- operatively, the incidence of dysfunction
tate may be one of the explanations for that, attributable to surgery is not known. Many
but the altered anatomy of the pelvic floor of these symptoms and latent dysfunction
caused by division of the perineal muscles are very common in the population of
may also play a role. Patient age seems to be same age as rectal cancer patients (Nuotio
the single most important factor affecting ; Pocard ; Schatzl ), whereas
the risk of sexual dysfunction (Keating ). urodynamic studies have shown that the
e risk has been reported to be more than incidence of bladder dysfunction as a result
-fold in the patients over years of age of pelvic nerve injury seems to be fairly
compared with patients younger than that low, – (Del Rio ; Leveckis ).
(Havenga ). In patients, whose disease With TME surgery and nerve preservation,
is confined to the mesorectum, adopting neurogenic bladder requiring catheterisa-
TME-technique with pelvic nerve preserva- tion is rare (Havenga ; Kneist ;
HUCH, Jorvi Hospital Publications • Series A 01/2005 15
Maas ), but occurs in – if pelvic Cancer of the low rectum treatable by ab-
autonomic nerves are completely sacrificed dominoperineal resection is associated with
(Havenga ; Hojo ). ere does not more local recurrences and poorer survival
seem to be any significant correlation be- than anterior resection. After TME surgery,
tween the extent of nerve preservation and -year survival rates of after APR com-
minor urinary symptoms reported by the pared with that of after sphincter pre-
patients (Maas ). serving surgery have been reported (Enker
Postoperative bladder dysfunction is of- ). Similarly, local recurrence rates are
ten temporary (Del Rio ), whereas erec- higher (– vs. – in midrectal can-
tile dysfunction does not seem to improve cers), possibly because cancers of the low
after – months after surgery (Maas ). rectum often present with more adverse risk
factors (positive nodal disease, vascular and
perineural invasion) (Enker ).
Local recurrence and survival
Circumferential resection margin (CRM)
With conventional blunt surgical resection involvement has been shown to be a potent
of rectal cancer, local recurrence rates after predictor of outcome with exponential
potentially curative operation are – increase in the rate of local recurrence,
in reports from special interest centres and metastasis and death with decreasing cir-
up to – in general surgical practice. cumferential margin. As many as of the
With TME technique local recurrence rates patients with margin involvement develop a
of below have been reported consis- local recurrence (Birbeck ; Nagtegaal
tently (Table ). Consequently, five-year ; Quirke ). A disease-free margin
survival rates have improved from to of less than – mm carries a – risk
(Enker ; MacFarlane ; Wibe of local recurrence compared to – af-
a). ter greater margins (Nagtegaal ; Wibe
Table 2. Local recurrence rate (LR) after surgery before and after adopting TME-surgery.
Figures are percents.
Study Conventional surgery TME-surgery*
(Period) Alone With PRT Alone With PRT
1. Arbman et al
(1984–86 vs. 1990–92)
2. Stockholm Study
30 15 9 1.5
(1980–87 vs. 1994–1997)
3. Swedish Trial
4. Dutch Study
22 9 (11) 2.4 (5.8)
(1987–90 vs. 1996–99)
5. Danish Study
(1991–93 vs. 1996–98)
6. Norwegian study
(1986–88 vs. 1993–99)
* Follow-up time since TME-surgery:
1. 4 years (Arbman 1996)
2. 2 years (Martling 2000)
3. (Swedish Rectal Cancer Trial 1997)
4. 2 years (Kapiteijn 2001; Kapiteijn 2002) (5 years(Marr 2005))
5. 3 years (Bulow 2003)
6. 3 years (Wibe 2003a)
16 HUCH, Jorvi Hospital Publications • Series A 01/2005
). About of patients with positive the other hand emergency presentation is
CRM develop metastasis compared with less common in rectal cancer than colon
of patients with negative margins cancer (– vs. ) (Anderson ;
(Nagtegaal ; Wibe ). After a cura- Shankar ). However, studies concern-
tive operation -year survival rate has been ing the outcome of elderly patients with rec-
reported to be vs. in patients with tal cancer are rare. In a retrospective study
and without CRM involvement, respectively including patients aged or older and
(Birbeck ). patients younger than that, the compli-
cation rate was similar in older and younger
age group ( vs. respectively) and
Elderly patients – special
mortality rate . vs. . after elective
considerations curative rectal cancer surgery (Puig-La Calle
Elderly patients with colorectal cancer ). e selection criteria and number of
have a higher incidence of emergency patients deemed to be unfit for major sur-
presentation compared to younger patients gery, however, was not reported.
(Anderson ; Hessman ; Mulcahy
). Perioperative mortality rates of the
elderly in different studies show a large
e role of adjuvant therapies
variability from to (Anderson ;
Chiappa ; Damhuis ; Fielding
Preoperative radiotherapy and
; Hessman ; Kingston ;
Mulcahy ); probably partly depending
on the proportion of emergency operations Two European trials of conventional surgery
in each study. Emergency surgery is more have shown that short-course preoperative
often than elective surgery associated with radiotherapy ( Gy in five days) reduces
high perioperative morbidity and mortality local recurrences from – to –
(Anderson ; Fielding ; Hessman (Holm ; Swedish Rectal Cancer Trial
; Mäkelä ). ) and improves overall -year survival
After elective surgery for colorectal can- rate from – to – (Martling ;
cer, the cancer-specific survival seems to be Swedish Rectal Cancer Trial ). In a ran-
similar to that of younger patients (Shankar domised trial of standardized TME surgery,
). e number of patients deemed a decrease in local recurrence rate from
unfit for curative surgery, however, rises . in non-irradiated patients to . in
with age (Damhuis ; Violi ). e irradiated patients was seen at two years
concomitant diseases and fitness rather after surgery (Kapiteijn ). A Swedish
than the chronological age seem to be the study reported similar results; local recur-
factors affecting the outcome. In some stud- rence rate was vs. . in non-irradi-
ies American Society of Anaesthesiologists ated and irradiated patients, respectively
(ASA) score rather than the age was seen to (Martling ) (Table ).
predict morbidity and mortality (Hessman Population-based studies have shown
), whereas others did not find that clas- that – of rectal cancer patients have
sification useful. primarily nonresectable tumours and only
Rectal cancer has many special features half of them have distant metastases at the
with regard to anatomical boundaries and time of diagnosis (Påhlman ). Locally
surgical strategies compared to cancer in advanced tumours requiring downstaging
other parts of the large bowel. Rectal cancer to be converted into mobile and resect-
surgery is associated with more frequent able, cannot be effectively treated with ×
complications (e.g. anastomotic leaks) than Gy short course preoperative radiother-
cancer surgery for other parts of the large apy (Marijnen ; Påhlman ). Long
bowel (Chiappa ; Hessman ). On course preoperative radiotherapy (– Gy
HUCH, Jorvi Hospital Publications • Series A 01/2005 17
over to weeks) or chemoradiotherapy on treatment modality, also on interval
have been shown to increase the resect- between preoperative adjuvant therapy
ability of low and locally advanced tumours and operative treatment (Elsaleh ;
(Elsaleh ; Frykholm-Jansson ; Moore ), but the optimal interval is yet
Minsky ). In some cases preoperative to be defined. Complete response has been
radiotherapy enables sphincter-saving sur- reported to occur in – of patients and
gery to be performed in patients, who would seems to be associated with improved local
have previously required an abdominoperi- control and survival (Garcia-Aguilar ;
neal resection (Crane ; Francois ; Janjan a; Luna-Perez ; Minsky
Janjan b; Rullier ; Wagman ). ; Ruo ; eodoropoulos )
Also, overall survival rates in patients with but follow-up times are still fairly short.
T low rectal cancers have been reported ree recent studies have reported, after a
to improve from to after PRT com- mean follow-up time of to months, a
pared to those who underwent surgery only disease-free survival of – in patients
(Delaney ). with complete or near-complete response
(Garcia-Aguilar ; Ruo ; Wheeler
). In comparison, the disease-free sur-
vival was in those with partial or no re-
Quantification of tumour response is es- sponse (Garcia-Aguilar ). Another study
sential in comparing the effectiveness reported the advantages of early survival in
of different multimodality treatments. A complete responders to disappear by –
commonly used measure is a change in months after treatment (Onaitis ).
a T stage defined as a difference between Besides complete response, also partial
endorectal ultrasound (ERUS) finding (uT) radiation-induced histological changes
and pathologic T stage (pT). After high-dose in malignant tumours (necrosis, stromal
long-term chemoradiotherapy tumour fibrosis, irradiation vasculopathy, peritu-
downstaging has been reported to occur in morous inflammatory reactions) have been
– of patients when using this criteria well documented and can be quantified
(Garcia-Aguilar ; Janjan a; Moore accurately (Bozzetti ; Bozzetti ;
; Rullier ; eodoropoulos ). Dworak ; Ruo ; Wheeler ). A
Some studies report improved local recur- pathologic staging system, tumour regres-
rence rates and cancer-specific survival in sion grading (TRG) (Table ) has been
responders compared with non-responders suggested (Bozzetti ; Dworak ;
(eodoropoulos ) whereas some have Wheeler ) to enable the comparison of
not observed significant difference between partial response as well and thus improve
the groups (Janjan a). the reliability of outcome comparisons be-
Complete pathologic response i.e. steril- tween different combined-modality treat-
ization of the tumour is a clearly definable ments. is new grading method has not
measure for tumour response. e complete been widely adopted so far.
response rate seems to be dependent except
Table 3. Tumour regression grading (Bozzetti 1996)
TRG1 – Complete regression, absence of residual tumour cells
TRG2 – Presence of rare residual cancer cells and prominent fibrosis
TRG3 – Fibrosis outgrowing residual cancer cells
TRG4 – Residual cancer cells outgrowing fibrosis
TRG5 – Absence of regression
18 HUCH, Jorvi Hospital Publications • Series A 01/2005
Quality of life after (Camilleri-Brennan ) which may con-
rectal cancer surgery tribute to better QoL reported after HAR
than LAR (Engel ; Grumann ).
It has been assumed that permanent co- After LAR, functional results are better with
lostomy after rectal cancer surgery impairs colonic pouch than with straight end-to-end
health related quality of life (HRQoL) more anastomosis and accordingly, the quality of
than sphincter-sparing surgery. A recent life of patients having J-pouch or coloplasty
Cochrane-analysis did not find support has been shown to be better, especially dur-
for this assumption (Pachler ). Several ing the early postoperative period (Hallböök
of the studies that used validated generic b; Remzi ; Sailer ).
and/or disease-specific quality of life in- Urogenital dysfunction after rectal can-
struments, found that people undergoing cer surgery occurs frequently (Camilleri-
APR did not have a poorer QoL than pa- Brennan ). Urinary dysfunction for any
tients undergoing anterior resection (Allal reason seems to worsen social functioning
; Camilleri-Brennan ; Grumann (Nuotio ; Rauch ). e effect of sex-
; Hamashima ) or that stoma only ual dysfunction on quality of life is not very
slightly affected the QoL (Jess ). In well known, as a high percentage of rectal
contrast, a few other studies found a signifi- cancer patients are elderly and often either
cantly poorer QoL after APR than after AR not sexually active or choose not to answer
(Engel ; Grundman ; Kuzu ; the questions concerning sexuality (Engel
Marquis ). Tumor stage and site, level ; Kuzu ; Rauch ). One study
of the anastomosis, surgical technique and showed no difference in sexual dimen-
adjuvant treatment as well as the follow-up sion of QoL between the treatment groups
time after surgery varies between the stud- (Rauch ), whereas another larger study
ies (Pachler ), which may partly explain reported lower scores in sexual functioning
the contradictory results. after APR than HAR or LAR (Engel ).
Longitudinal studies have shown that However, patients in the APR group were
quality of life improves with time (Engel older, which may affect the results. Based on
; Grumann ), especially after low this scarce data it has been suggested that
anterior resection (Engel ). Functional sexual functioning may not affect overall
results after HAR are better than after LAR quality of life (Engel ).
HUCH, Jorvi Hospital Publications • Series A 01/2005 19
AIMS OF THE STUDY
e purpose of this study was to evaluate factors, which can be af-
fected in order to improve results of rectal cancer treatment. e
specific aims were
. to evaluate the usefulness of PNA-test in screening for rectal
neoplasia compared with occult faecal blood test.
. to find out whether total mesorectal excision (TME) technique
alone or combined with preoperative radiotherapy reduces lo-
cal recurrence rate and improves survival;
. to evaluate if elderly patients ( years or older) can be treated
using similar indications and treatment strategy as in younger
patients without increasing complication risk;
. to evaluate the usefulness of tumour regression grading in
comparing histopathologic effects of different neoadjuvant
treatments in rectal cancer patients; and
. to assess the impact of treatment-related adverse effects in
quality of life after rectal cancer surgery.
20 HUCH, Jorvi Hospital Publications • Series A 01/2005
PATIENTS AND METHODS
Patients S II III Between January
and December , a total of patients
is study was carried out at the Surgical with rectal cancer were admitted ( men,
Hospital, Helsinki University Central women, mean age years) to the
Hospital, and at the Central Hospital of IV Clinic of Surgery, Helsinki University
Jyväskylä. e research material in the stud- Central Hospital.
ies I, II and III consists of patients who were Of the patients, were admitted
operated on for rectal cancer or examined during the period – and during
for colorectal symptoms at the Surgical –. Major potentially curative opera-
Hospital, Helsinki University Central tions using a conventional technique were
Hospital between and . Patients in done for of the during –.
the studies IV and V were treated for rectal Between and , major potentially
cancer in Central Hospital of Jyväskylä be- curative resections using the principles of
tween and (Table ). e data of TME-technique were done for of the
patients were gathered retrospectively until patients. e patients, who underwent
year and prospectively thereafter. major potentially curative operations dur-
ing both periods, were included in Study II
S I From to samples of rec- comparing the outcome between treatment
tal mucus were obtained from patients strategies.
undergoing colonoscopy for lower gastroin- All patients, of whom patients
testinal symptoms (e.g. altered bowel habits, ( ) were aged or older and
abdominal pain, anaemia, hemorrhagia ex younger than years, were enrolled in
ano). From to , patients also Study III comparing the treatment strate-
completed Hemolex test over three days pri- gies and outcome between elderly and
or to the outpatient appointment. ese young patients.
patients were selected for Study I. Informed
consent for obtaining mucus samples for S IV V A total of patients
PNA-test was received from all patients and ( men and women, mean age , range
the study was approved by the ethical com- –) with rectal cancer were admitted to
mittee of the hospital. Jyväskylä Central Hospital between January
Table 4. Number of patients included in the different papers
Study Period No of patients
I PNA vs. Hemolex test 1992–94 199
1980–90 144 (Conventional surgery)
II The effect of treatment strategy
1991–97 61 (TME surgery)
199 (< 75 years)
III Treatment strategy of the elderly 1980–97
95 (≥ 75 years)
IV Quality of life 1999–2003 94
V Tumour regression grading 1999–2003 135
HUCH, Jorvi Hospital Publications • Series A 01/2005 21
and December . Of them, PNA Samples of rectal mucus, obtained
patients underwent either curative or pal- prior to colonoscopy with a cotton stick
liative major resection. Nine patients had an through a proctoscope from macroscopi-
inoperable advanced disease. cally normal mucosa, were applied on
Patients with high or midrectal tumours nitrocellulose filters. e presence of PNA-
penetrating the bowel wall (uT) as judged reactive glycoconjugates in rectal mucus
by endorectal ultrasound received a short- was determined by a peroxidase-conju-
course preoperative Gy radiotherapy gated PNA-overlay procedure (Kellokumpu
whereas patients with uT-tumors in ). Two observers unaware of the
proximity to the anal verge necessitating ab- colonoscopy findings examined PNA-re-
dominoperineal resection, or with fixed or activity.
locally advanced tumours, received a long PNA-binding profiles of paired normal
course preoperative radiotherapy ( Gy and malignant colorectal tissue samples
over five weeks) combined with weekly taken from cancer patients during surgery
infusion of -fluorouracil. were analysed by the PNA-overlay proce-
Study IV comprises the patients, who dure. erefore, tissue samples were ground
underwent either curative or palliative ma- in a mortar under liquid nitrogen, and de-
jor resection. e histological response of tergent-solubilize using TX-, mM
the tumours after different preoperative ra- Tris (pH .) supplemented with proteinase
diation treatments was evaluated. Of the inhibitors tablets (Complete, mini, Roche
patients, who underwent curative resection, Diagnostics Gmbh, Mannheim, Germany).
were alive without any sign of recurrent ml of detergent solution was used per
disease after a minimum follow-up of one mg of frozen tissue, and vortexed on ice for
year. For Study V they were sent a RAND- min before clearing with centrifuga-
(SF-) quality of life questionnaire and tion ( × g, + °C). A × concentrated
a specific disease-related questionnaire SDS sample buffer was added and boiled
assessing problems with urinary, sexual or for min. . microliters (about –
defecation-related functions. microgram of protein) from each sample
was subjected to SDS polyacrylamide gel
electrophoresis. e samples were then
transferred to a nitrocellulose filter. e filter
was quenched with BSA (bovine serum
albumin, fraction V, Sigma Chemicals) in
Screening methods of symptomatic blotting buffer overnight, and probed with
patients (Study I) PNA in the same buffer (. microgram /
H Hemolex (Orion Diagnostica, ml of mM Tris/ mM NaCl, . BSA,
Espoo, Finland) is a test based on im- . Tween). e enhanced chemilumines-
munochemical detection of native human ence-method (ECL) and exposure onto the
haemoglobin with a sensitivity of . mL of Fuji RX film for – min was used for the
blood per g of stool. e test kit includes visualization of the proteins on the filter.
a latex reagent consisting of polystyrene
beads coated with antibodies produced in
Preoperative evaluation (studies II–V)
swine against human haemoglobin. ese
agglutinate when haemoglobin is present in Tumours were classified as low (≤ cm),
the specimen in non-digested form giving mid (– cm) or high (– cm) rectal
visually detectable granular agglutination tumours. e distance of the tumour from
(Väänänen ). e patients completed the anal verge was assessed with a rigid sig-
Hemolex test over three days prior to the moidoscope (studies II–III) or colonoscope
outpatient appointment. (studies IV–V) and biopsies were taken.
Chest radiography, liver ultrasonography,
22 HUCH, Jorvi Hospital Publications • Series A 01/2005
and computed tomography when necessary High dose preoperative radiotherapy
were used to rule out distant spread. ( Gy over five weeks) combined with
In Study IV endorectal ultrasound radiosensitizing -fluorouracil (-FU
(ERUS) staging was done according to mg/m/day once a week as an intravenous
Hildebrandt´s criteria (Hildebrandt ) bolus) was delivered using three or four-
using a ° rotating ∕ MHz endoprobe field technique with the same target volume
(type , Bruell & Kjaell Ltg, Sandtoften, as in short-course radiotherapy and includ-
Denmark). Magnetic resonance imaging ing pelvic organs infiltrated by the tumour.
(MRI) and/or computed tomography (CT) High dose preoperative chemoradiotherapy
were performed as complementary studies was indicated in the case of large, fixed
in the case of fixed or locally advanced tu- uT / tumours or with low (< cm from
mours or if ERUS was not successful. the anal verge) uT tumours requiring
abdominoperineal resection. All patients
were planned to undergo surgical resection
within to weeks after completion of PRT.
Conventional surgery (Studies II and III) was Adjuvant postoperative chemotherapy
defined as sharp dissection and excision of consisting of -FU ( mg/m/day) as an
the mesorectum at least cm distally from intravenous bolus in six cycles and low dose
the lower margin of the tumour. In high and leucovorin ( mg/m) (O´Connell ) for
midrectal tumours the mesorectum was di- five consecutive days every to weeks was
vided perpendicularly to the rectum and the prescribed routinely to all patients having
lateral ligaments were ligated and divided. tumours with metastatic lymph nodes.
Blunt dissection was not used.
Since (studies II–V) surgery was per-
formed according to the principles of total
mesorectal excision technique (MacFarlane e tumours were classified according to
) except in high (> cm from the anal the Turnbull modification of Dukes´ clas-
margin) rectal tumours in which a cm sification during –, and according
distal margin was considered adequate. to the UICC TNM categories (Sobin )
Total mesorectal excision was defined as during –. Assessment of the larg-
complete removal of the intact mesorec- est tumour diameter as well as manual
tum down to the pelvic floor, preserving lymph node harvesting was done in fresh
pelvic nerve plexuses. For rectal wall, i.e. specimens.
the muscular tube, a margin of – cm was e operation was considered curative if
considered adequate. no visible tumour was left behind and his-
topathological specimens showed tumour-
free distal margins. Lateral margins were
not assessed during the period –
Short-course preoperative radiotherapy (Studies II–III). In Study IV the circumfer-
( Gy, Gy in five fractions) (Påhlman ential, radial resection margins were mea-
) followed by resection within a week sured in formalin ( ) fixed specimens
was chosen for patients with high (– cm mounted on macroslides. Tumour response
from the anal verge) and midrectal (– cm to radiotherapy was quantified using the
from the anal verge) uT tumours amenable tumour regression grading (TRG, Table )
to anterior resection. External beam ra- (Wheeler ).
diation therapy was delivered using three
or four-field technique. e clinical target
Quality of life assessment (study V)
volume included the mesorectum and the
pelvic sidewalls including the internal iliac Quality of life assessment was done using
lymph nodes. a validated Finnish version (Aalto ) of
HUCH, Jorvi Hospital Publications • Series A 01/2005 23
the RAND -item health survey quality of sample (age – years) was derived from
life questionnaire (Hays ) and a specific the Finnish population registry.
disease-related questionnaire assessing
problems with urinary, sexual or defeca-
e RAND- consists of items as- Chi-square tests or Fishers exact tests were
sessing eight dimensions of health from the used to compare the association between
patient’s viewpoint. ese dimensions mea- categorical variables. Actuarial survival
sure physical functioning, role limitations and local recurrence rates were assessed
because of physical or emotional problems, using Kaplan-Meier plots with log-rank
social functioning, mental health, energy analysis (Study II and III). Mann-Whitney
and vitality, body pain and general health U tests were used to compare continuous
perception. e scoring scale ranges from data and to detect significant differences in
to , with high scores indicating high level health-related quality of life scores between
of functioning and good quality of life. subgroups. Differences in HRQoL between
A sub sample of persons aged – patient and population controls of same age
years from a Finnish population study and sex were analysed by ANCOVA (analysis
(Aalto ) was used as a population con- of covariance) adjusting the HRQoL means
trol group in examining the level of health for sex and age (Study V). A P-value < .
related quality of life (HRQoL) in RAND- was considered statistically significant.
subscales among patients. e population
24 HUCH, Jorvi Hospital Publications • Series A 01/2005
Study I enomas and carcinomas vs. normal mucosa
and hyperplastic polyps) was vs.
Details of the clinical findings in the and specificity vs. (P = .).
symptomatic patients and the sensitiv- e positive predictive values of the PNA
ity for carcinoma of both tests are shown and Hemolex test were vs. and
in Table . e sensitivity of the PNA-test negative predictive value vs. . e
and Hemolex for colorectal neoplasia (ad- accuracy of the PNA-test and Hemolex was
Sensitivity = Proportion of diseased subjects, who have SDS-PAGE and PNA-overlay showed
a positive test
Specificity = Proportion of non-diseased subjects, who
some commonly expressed PNA-bind-
yield a negative test result ing proteins both in normal mucosa and
Positive/negative predictive value = Proportion of all colorectal cancer. Instead, expression of
individuals with positive/negative tests who do/do not
have the disease kD PNA-binding protein was seen sig-
Accuracy = Proportion of true positive and negative nificantly more often (P < .) in colorectal
tests of all those who were tested
cancer than normal mucosa (Figure ).
Table 5. Test positivity according to clinicopathological characteristics.
Total Positive PNA Positive Hemolex
Clinicopathological variable P
N N ( %) N ( %)
Carcinoma 36 30 (83) 26 (72) 0.45
Adenoma 38 21 (55) 18 (50) 0.8
Inflammatory bowel disease 27 14 (52) 13 (48) 1.0
Hyperplastic polyps 21 10 (48) 5 (25) 0.3
Normal/diverticulosis 77 21 (27) 9 (12) 0.3
Figure 2. Peanut agglutinin (PNA)-binding proteins in 12 paired samples of normal colorec-
tal mucosa and colorectal cancer. Notice that both normal (n) and cancer tissues (c) express
PNA-reactive proteins. Only the 160 kD band (marked with arrow) appears to be quite
specific to colorectal cancer tissues. Numbers on the left denote the molecular size stan-
HUCH, Jorvi Hospital Publications • Series A 01/2005 25
Study II–III Local recurrence rate and survival
Table shows the patient and tumour e actuarial local recurrence rate was
characteristics from the two study periods in the first period utilizing conventional
included in studies II and III (– and surgery and after adopting TME surgery
–) as well as the data from the third and selective use of preoperative radiother-
study period (–, N = ). apy (P = ., Fig. ). e actuarial crude
Table 6. Details of patients who underwent potentially curative operations during the three
study periods (1980–90, 1991–97, 1999–2003). Data are number (%) of patients except were
1980–90 1991–97 1999–2003
(N = 144) (N = 61) (N = 113)
Sex (male: female) 69 (48): 75 (52) 22 (36): 39 (64) 78 (69): 35 (31)
Mean age (range) 70 (41–91) 65 (36–82) 68 (41–91)
A 40 (28) 18 (29) 47 (42)
B 79 (54) 28 (46) 40 (35)
C 24 (17) 14 (23) 24 (21)
D* 1 (1) 1 (2) 2 (2)
Site of tumour
Upper rectum (12–15 cm) 33 (23) 10 (16) 28 (25)
Middle rectum (8–11 cm) 51 (35) 18 (30) 31 (27)
Lower rectum (≤ 7 cm) 60 (42) 33 (54) 54 (48)
Anterior resection 76 (53) 43 (71) 73 (65)
Abdominoperineal resection 68 (47) 18 (29) 40 (35)
Preoperative radiotherapy 0 29 (48) 80 (71)
* Liver metastasis resected later
Figure 3. Actuarial cancer-specific survival (upper curves) and local recurrence rates (lower
curves) after major curative surgery during the two study periods.
1980–90 (conventional surgery)
1991–97 (TME surgery)
26 HUCH, Jorvi Hospital Publications • Series A 01/2005
-year survival improved from to Figure 4. Actuarial cancer-specific survival
(P = .) and the cancer-specific survival after major curative surgery according to
from to (P = ., Fig. ) between patient age.
the two study periods.
During –, the five-year crude
survival was significantly lower in the older
age group ( vs. , P = .), but the -
year cancer-specific survival ( vs. ,
P = .) (Fig. ) and the disease-free -year
survival ( vs. , P = .) were similar
in both groups.
More patients in the elderly group (/
, ) than in the younger age group
(/, ) had a poor physical condition
(compromised cardiac and/or respiratory
function, symptoms in mild exercise) and
underwent local excision (P = .). Ten 75 years or older
Below 75 years
elderly patients ( ) were not operated on
at all in contrast to patients ( ) younger
than (P = .). with / patients ( ) after TME surgery
(P = .). Twenty of the elderly patients
( ) and of the patients ( ) in
the younger age group after curative surgery
Overall, of the patients ( ) who had complications (P = .). e overall
underwent major curative surgery during incidence of postoperative complications
– had complications. After conven- after potentially curative major operations
tional surgery / patients ( ) had during the all three study periods is shown
postoperative complications compared in Table .
Table 7. Postoperative complications after potentially curative major operations during the
three study periods. Data are number ( %) of patients.
1980–1990 1991–1997 1999–2003
Postoperative death 1/144 (1) 0 3/113 (3)
Leak 4/76 (5) 8/43 (19) 4/73 (6)
Stenosis 1/76 (1) 8/43 (19) 5/73 (7)
Postoperative bleeding 0 2/61 (3) 1/113 (1)
Abdominal wound 2/144 (1) 0 7/113 (6)
Perineal wound 4/68 (5) 1/18 (6) 8/40 (20)
Systemic sepsis 3/144 (2) 1/61 (2) 1/113 (1)
Pneumonia 4/144 (3) 1/61 (2) 2/113 (2)
Cardiovascular 2/144 (1) 0 3/113 (3)
Urinary 8/144 (6) 4/61 (7) 6/113 (5)
Other 3/144 (2) 1/61 (2) 6/113 (5)
No pts with complications* 32/144 (22) 21/61 (34) 39/113 (35)
* Some patients had more than one complication
HUCH, Jorvi Hospital Publications • Series A 01/2005 27
After curative anterior resection / of patients developed anastomotic leaks. Table
the patients ( ) during the first period and shows the incidence of anastomotic leak-
/ ( ) during the second period devel- ages in respect to the type of anastomosis
oped anastomotic leaks (P = .). During and use of protective stoma.
–, when all low anastomoses were After elective operations during –,
constructed using J-pouch and usually pro- one elderly patient died due to anastomotic
tected with a temporary stoma, / ( ) leakage. us operative -day mortality
Table 8. Incidence of anastomotic leakages after curative resection for rectal cancer during
the three study periods in respect to the type of operation (HAR = high anterior resection,
LAR = low anterior resection).
Leakages / total number of patients
1980–90 1991–97 1999–2003
HAR 4 / 76* 1 / 10* 0 / 20**
Straight anastomosis 0 5 / 23 0
Straight anastomosis + stoma 0 0 0
J-pouch 0 2/4 2/2
J-pouch + stoma 0 0/7 2 / 51
Total*** 4 / 76 (5 %) 8 / 43 (19 %) 4 / 73 (5 %)
* Straight anastomosis without protective stoma
** Straight anastomosis with (7 patients) or without (13 patients) a protective stoma
*** P = 0.02
Table 9. Tumour regression grading (TRG) in different treatment groups.
Tumour regression grade a 5 4 3 2 1
Preoperative radiotherapy (number of patients (%))
No radiotherapy (n = 40) 27 (68) 12 (30) 0 1 (2) b 0
25 Gy (n = 42) 12 (29) 21 (50) 8 (19) 1 (2) 0
50 Gy (n = 44) 4 (9) 8 (18) 15 (34) 14 (32) 3 (7)
TRG 1, 2 and 3 correspond to a regression exceeding 50 % of the tumour mass
This patient had a small polypoid lesion, which was originally removed endoscopically with snare and
electrocoagulation. Only a 7 mm lesion was seen in the resected specimen.
Table 10. Comparison of histopathologic response (TRG) and dowstaging (pT lower than uT
stage) in 83 patients, who had a successful endorectal ultrasound (ERUS) examination and
received either 25 Gy radiotherapy or 50 Gy chemoradiation preoperatively. TRG classes 1 to
3 are considered `marked response´ regression exceeding 50 % of the tumour mass.
TRG Marked response No response
Downstaged Yes 12 14
No 28 29
P = 0.05 40 43
28 HUCH, Jorvi Hospital Publications • Series A 01/2005
was (N = ) and after potentially cura- ere was a marked discordance between
tive conventional and TME surgery, respec- the two methods in estimating tumour
tively. Consequently, the -day mortal- response after Gy radiotherapy or Gy
ity was (N = ) and in the elderly and chemoradiation (P = .). Of the tu-
younger age group. During – the mours, showed marked regression by
mortality rate was (/ patients); one TRG without any change in T-stage and
patient died due to anastomotic leakage. tumours that showed no response in TRG
were downstaged when comparing uT-stage
Tumour regression grading Study V
Results of TRG of the patients according
Quality of life
to treatment group are shown in Table .
Complete regression (TRG ) was present in e patient group reported significantly
three patients ( ) and tumour regression better general health perception and poorer
more than (TRG –; fibrous tissue social functioning than population controls
outgrowing the amount of residual tumour of same age and sex (Table ). Between the
cells) in ( ) of the patients treated treatment groups there were no significant
with high dose ( Gy) chemoradiation. In differences (Figure ). However, after APR
those patients treated with short course physical functioning tended to be lower
( Gy) radiotherapy only ( , P = .) (P = .) compared with low anterior
had tumour regression of TRG –. resection.
Endorectal ultrasound examination Major bowel dysfunction (frequency
(ERUS) was done in patients. Of them, > bowel movements/day, major inconti-
patients underwent surgery alone. In nence (Jorge ), urgency or constipation
them, ERUS had an accuracy (uT-stage (Drossman )) impaired social function-
same as pT-stage) of . e comparison ing significantly (P = .) in patients hav-
of TRG findings and uT vs. pT change after ing undergone anterior resection compared
different treatments is shown in Table . with the patients without such problems
Table 11. Health related quality of life according to RAND 36 (SF36) among general popula-
tion (N=1440) and patients who had curative resection for rectal cancer (N = 71, age < 80
years). The values are adjusted for age and gender.
General population Rectal cancer patients
Mean (95 % CI) Mean (95 % CI)
PF 74.8 73.5–76.0 73.9 67.4–80.2 0.79
RP 62.5 60.4–64.6 54.9 44.2–65.5 0.17
RE 68.7 66.7–70.8 61.9 51.6–72.1 0.20
SF 79.9 78.6–81.2 68.9 62.4–75.4 0.002
MH 73.8 72.8–74.9 77.5 72.9–82.9 0.19
EV 62.7 61.5–64.0 64.0 57.7–70.3 0.70
BP 70.0 68.6–71.4 67.9 60.9–74.8 0.55
HP 55.9 54.8–57.6 63.3 57.7–68.9 0.01
* PF = physical functioning; RP = role limitations due to physical problems; RE = role limitations due to
emotional problems; SF = social functioning; MH = mental health; EV = energy and vitality; BP = body
pain; HP = general health perception.
HUCH, Jorvi Hospital Publications • Series A 01/2005 29
(Figure ). Increased bowel frequency (> ) (P = .) and general health perception
or constipation after low anterior resection (P = .). e patients without urgency or
did not significantly affect the QoL scores. fecal incontinence had a significantly better
Incontinence worsened social functioning physical functioning than the patients, who
significantly (P = .). Urgency impaired underwent abdominoperineal resection
social functioning (P = .), mental health (P = . and ., respectively), whereas
Figure 5. Quality of life after rectal cancer surgery in different treatment groups (HAR=
high anterior resection; LAR = low anterior resection; APR = anterior resection).
PF = physical functioning; RP = role limitations due to physical problems;
RE = role limitations due to emotional problems; SF = social functioning;
MH = mental health; EV = energy and vitality; P = body pain;
HP = general health perception.
Figure 6. Quality of life after anterior resection in patients with (N = 35) or without (N = 18)
major bowel dysfunction. In comparison, values of the patients who underwent APR (n=28)
PF = physical functioning; RP = role limitations due to physical problems;
RE = role limitations due to emotional problems; SF = social functioning;
MH = mental health; EV = energy and vitality; P = body pain;
HP = general health perception.
30 HUCH, Jorvi Hospital Publications • Series A 01/2005
the patients having such problems had no urinary dysfunction. In patients reporting
statistically significant differences in RAND- sexual dysfunction only a complete loss of
QoL scores compared with APR patients. erection was associated with significantly
Patients with urinary dysfunction had worse physical functioning (P = .) and
worse social functioning (P = .) and social functioning (P = .).
more pain (P = .) than patients with no
HUCH, Jorvi Hospital Publications • Series A 01/2005 31
Despite the fact that – of patients for faecal occult blood (Towler ), there
presenting with colorectal cancer may un- is a need for tests with higher sensitivity and
dergo surgical resection for possible cure specificity.
and that recent advances in multimodality In our study, we compared the sensitivity
therapy has improved survival of advanced and specificity of single PNA-rectal mucus
disease, nearly of patients with cancers test with those of Hemolex, a test completed
of the colon and rectum die from their dis- over three days and based on immuno-
ease. More effective preventive measures chemical detection of native human hae-
together with further refinement of surgical moglobin. Immunological tests have been
techniques and adjuvant treatments are shown to be more sensitive for symptomatic
clearly warranted to improve the outcome colorectal cancer than guaiac-based tests
results of this common disease. (Robinson ; omas ). In contrast,
lower specificities ( vs. in symp-
tomatic patients and vs. in the as-
ymptomatic population) has been reported
Advisory Committee on Cancer Prevention using immunological tests than guaiac-tests
recommends screening for colorectal (Robinson ; omas ).
cancer to be considered in the countries of We have found that in symptomatic
European Union (Advisory Committee on patients a single PNA-test is as sensitive for
Cancer Prevention ). Colorectal cancer colorectal carcinoma as a serial Hemolex
is a major health problem, which usually ( vs. ). e PNA-test, however, had
develops from benign adenomatous polyp a lower specificity for colorectal neoplasia
slowly over approximately years provid- than Hemolex ( vs. ), making it
ing an opportunity for early detection and less suitable for screening purposes in its
removal in pre-cancerous stage or as an present form. e reduced specificity of
early stage cancer (Bronner ; Winawer the PNA-test may result from the fact that
). According to recommendation a some of PNA-reactive proteins (e.g. the
method of choice for screening is faecal oc- kD-band and the diffuse bands at the
cult blood tests and colonoscopy in positive molecular size between kD and kD)
cases. Current stool guaiac tests, however, were present both in normal and malignant
appear to be suboptimal in some respects. colorectal tissue. e kD cancer-associ-
Many cancers and most adenomas do not ated antigen we have identified is under
bleed and are thus missed (Ahlquist ). further characterization for development of
e reported sensitivity of serial guaiac a more specific PNA-test.
based FOBT is only approximately
(Hardcastle ; Kronborg ). e posi-
tive predictive value has been reported to
be – (Hardcastle ; Kronborg ;
Local recurrence and survival
Winawer ) leading to high number of
unnecessary colonoscopies, as bleeding is e concept of TME surgery relies on the
not specific for neoplasias (Towler ). observation that tumour deposits may be
Despite the recent documentation of a found to centimetres distal to the main
significantly reduced mortality by screening tumour in the lymphovascular mesorectum
32 HUCH, Jorvi Hospital Publications • Series A 01/2005
(Heald ; Wang ). erefore, it has more frequently after abdominoperineal
been advocated that all cancers of low or than anterior resection. Wider surgery in-
midrectum should be excised with the me- cluding removal of the levator muscles en
sorectum intact. e excellence of this ap- bloc with anal sphincters might reduce the
proach is further supported by the findings risk (Marr ; Wibe b). In the future,
of Quirke et al. showing that tumour spread radioactivity-guided sentinel node map-
to the lateral resection margin occurs in up ping may be one option for finding patients
to of patients treated with conventional with lateral spread and thus greater risk for
techniques but in only – of patients recurrence (Kitagawa ; Saha ).
treated by TME (Quirke ). Others have
confirmed that the circumferential resection
margin involvement is a reliable predictor
of local recurrence, distant metastases and e overall complication rate of about
survival (Wibe ). in all study periods falls well within
Since these observations, surgical and the reported range. Also in line with previ-
pathological workshop projects have been ous reports, the leakage rate was with
organized in several countries in Europe conventional surgery and in the early
to introduce these new methods. National phase of TME surgery. Later, when the rou-
studies have shown that TME surgery tine use of protective stoma and J-pouch in
improves treatment results in a defined low anastomoses was adopted, the clinical
population (Kapiteijn ; Martling ; leakage rate decreased back to .
Påhlman ; Wibe a). ere is some proof that colonic J-pouch
In our study, the actuarial risk for devel- anastomosis has better blood supply than
oping a local recurrence decreased from end-to-end anastomosis and thus may
to after the introduction of TME be less prone to leakage (Hallböök a;
surgery, which is in line with the reports Hallböök b). Some other studies have
from other centres. Accordingly, cancer- found a significant correlation between the
specific five-year survival increased from absence of stoma and anastomotic dehis-
to and disease-free five-year cence (Law ; Peeters ). During the
survival from to between the two TME period between and in our
periods. study, of the patients ( ) who had a J-
However, still more than of the pa- pouch but no protective stoma, developed
tients with Dukes´ C lesions developed lo- an anastomotic leak. Of the patients
cally recurrent disease after TME. As many with end-to-end anastomosis, patients
as of the Dukes´ C carcinomas in the ( ) had a leakage. In comparison, only
second period were low rectal tumours and two of the patients (. ) who had a
four of the five local recurrences occurred J-pouch and a protective stoma developed
after resection of low rectal carcinomas. a leakage. Our results are in line with oth-
It has been shown that some of low ers showing leakage rates of and –
rectal tumours and of low Dukes´ C in patients without and with a protective
tumours spread laterally along the internal stoma, respectively (Dehni ; Karanjia
iliac vessels (Moriya ), which is outside ).
the dissection area covered by TME and
thus may explain the high recurrence rates.
Besides lateral lymph node involvement, an
inadequate surgical resection despite TME- An increasing number of rectal cancer pa-
surgery might explain some of the treatment tients are elderly and have comorbid medi-
failures. Possibly due to tapering of the me- cal diseases. A question has been raised
sorectum toward levators, circumferential whether elderly patients with compromised
resection margin involvement still occurs physical capacity to recover from adverse
HUCH, Jorvi Hospital Publications • Series A 01/2005 33
events can be offered similar treatment than in Finland were years of age or older in
younger patients. (Finnish Cancer Registry ). Also,
In the present study, the crude survival tumour site and stage distribution are simi-
was significantly lower ( vs. ) in lar in both groups, old and young. erefore,
the elderly but the cancer-specific -year probably a very realistic picture of the
survival rate after curative major surgery management policy and treatment possi-
for rectal cancer in carefully selected elderly bilities of the rectal cancer in the elderly is
patients was similar to that found in younger presented in this study. In future, however,
patients ( vs. ). advancements in laparoscopic surgery may
e overall postoperative mortality rate increase the number of patients suitable
including emergency and palliative pro- for major surgery. Preliminary experience
cedures in our study was . ; . in suggests that laparoscopic resections in
the elderly group and . in the younger the elderly can be performed more safely
age group. After curative operations, than standard open surgery (Delgado ;
the mortality in the elderly group was Reissman ).
compared with in the younger age
group. Diligent perioperative care most
certainly had an effect on low mortal-
ity rates. Furthermore, all possible efforts Several different chemotherapeutic regi-
were made to identify and treat comorbid mens and radiotherapy doses have been
conditions before surgery. e American used in an effort to increase the percentage
Society of Anaesthesiologists (ASA) clas- of those responding the treatment. e true
sification of physical health did not help in impact of the adjuvant treatment on out-
assessing the risk of an individual patient. come has been difficult to assess because
Perioperative mortality was low irrespec- of multiple confounding issues such as
tive of ASA score and also, no statistically variability in tumour stage, different tech-
significant difference in the number of niques employed among studies, variability
complications between the ASA groups was in the extent of the follow-up and above all,
noted. According to many reports (Haynes absence of a uniform method to estimate
; Ranta ) there is considerable in- the effect. e most used measures such as
ter-observer inconsistency of classification changes in tumour size, stage or resectabil-
making ASA-scoring alone too imprecise ity are all subjective and dependent on the
an instrument for treatment decisions. reliability of preoperative evaluation.
Other more reliable scoring systems like In the present study, we have shown that
POSSUM score are being developed and assessment of radiation-induced histopath-
tested (Senagore ). ologic changes in tumours is reproducible
A considerable number of high-risk pa- and easily available method for examining
tients in our study was not operated on at all tumour response after preoperative radio-
( ) or underwent local excision ( ), therapy or chemoradiation. After high-dose
which may contribute to acceptable com- chemoradiation patients ( ) showed
plication and mortality figures, and shows complete regression (TRG ) and marked
the utmost importance of careful patient response (TRG –) was seen in of pa-
selection for major surgery. Preoperative tients, which is in line with previous studies
selection is an aspect often excluded from (Bouzourene ; Bozzetti ; Dworak
studies in the elderly, even if it is crucial ; Ruo ). e majority of patients
in the evaluation of long-term results of ( ) who received a short course PRT in
curative surgery. In our study, proportion of our study, showed no tumour regression.
elderly patients is consistent with the report Non-irradiated patients used as a control
of the Finnish Cancer Registry, according group, were all except one classified in TRG
to which of all rectal cancer patients –.
34 HUCH, Jorvi Hospital Publications • Series A 01/2005
Only of patients with marked re- shown that grades – are commonly seen
sponse (TRG –) showed actual downstag- in patients treated without radiotherapy.
ing according to comparison between uT- Comparison of grades – with grades –
stage measured by ERUS and pT-stage. On might have given a more truthful picture of
the other hand, just as many ( ) of those tumour response.
with no histological response to PRT (TRG A more simplified classification combin-
–) seemed to be downstaged. ere was a ing grades – into two grades and grades
significant discordance (P = .) between – into one non-responder group has
the methods in assessing the effect of PRT. been suggested (Wheeler ). ere are
Downstaging defined as a difference preliminary results showing a trend towards
between uT stage and pT stage has been increased survival and decreased local
considered a precise method to measure recurrence rate in grade patients when
tumour response to chemoradiation. using this three-step classification (Wheeler
However, without preoperative radio- ). Furthermore, results from several
therapy, upstaging is more common than studies suggest that complete response cor-
downstaging suggesting that assessment of relates with improved survival (Garcia-
response to radiation with this method over- Aguilar ; Ruo ; eodoropoulos
estimates the rate of tumour downstaging. ). Considering that, it seems likely that
Furthermore, its accuracy for assessing the the new tumour regression grading would
rectal wall invasion is highly user-depen- help in comparing the results of different
dent varying from to (Adams ; combined-modality therapies and might
Akbari ; Kumar ). us, to estimate help in choosing the most effective neoad-
the accuracy of downstaging based on the juvant treatment in the future. Studies on
change of the T stage, the accuracy of ERUS molecular biomarkers between responders
staging in patients without preoperative and non-responders might help in reveal-
radiotherapy should be known, whereas tu- ing the factors correlating with the tumour
mour regression grading (TRG) is a measure sensitivity for chemoradiotherapy.
independent of preoperative evaluation and
Quality of life
It has not been shown as to yet, whether
histological tumour response translates Up until ´s most of the patients with
into improved survival. e follow-up time a carcinoma of the middle or low rectum
in our study is too short and number of were treated by an abdominoperineal
patients too small to draw any conclusions. excision, introduced by Sir Ernest Miles in
A study of patients with T/ tumours, . Today a variety of surgical techniques
treated preoperatively with . Gy ra- are available that preserve sphincter func-
diotherapy over . weeks and operated tion. Maintaining the normal anatomy has
on within days, examined correlation of become one of the main goals in modern
outcome with clinicopathologic variables, rectal cancer surgery in order to avoid se-
one of which was tumour regression grad- vere disruption of the quality of life. Indeed,
ing. In the univariate analysis, absence of a permanent colostomy is rarely necessary
tumour regression (grade ) together with provided that all presently available tech-
N disease, positive resection margin and niques of sphincter salvation and restora-
vascular invasion was correlated with ad- tion are applied. Tumours extending into
verse overall survival and local recurrence anorectal junction or within the anal canal
rate. In the multivariate analysis absence of can be treated with ultralow anterior resec-
tumour regression was not an independent tion or even intersphincteric resection and
prognostic factor (Bouzourene ). In continuity restored with ultra-low colorec-
that study, patients with grades – were tal or coloanal anastomosis using colonic
regarded as responders, whereas we have pouch (Tytherleigh ).
HUCH, Jorvi Hospital Publications • Series A 01/2005 35
However, sphincter preservation without Physical functioning tended to be worse af-
good function is of questionable benefit. ter APR than LAR. Of note is that sphincter-
e functional result after low anterior re- saving surgery resulted in significantly better
section may be disappointing because of an physical functioning in those patients who
increased frequency of defecation, urgency did not have any major problems with bowel
and faecal leakage (Renner ). With the function or continence. e QoL of patients
addition of radiation therapy the results with such problems was similar to that of the
may be further compromised (Hallböök patients who had undergone APR.
b; Marijnen ). In this study, major Social functioning was significantly
bowel dysfunction (urgency, frequency, worse in patients with major bowel dysfunc-
incontinence or constipation) occurred in tion compared with that of patients who did
of patients after high or low anterior not have such problems. Also urinary dys-
resection, which is in line with previous re- function impaired social functioning and
ports (Camilleri-Brennan ). impotence physical and social functioning
Urogenital dysfunction is also common scores. Consequently, the same age general
after surgery for rectal cancer (Camilleri- population scored significantly better in
Brennan ). However, with modern social functioning compared with rectal
operation techniques permanent major uri- cancer patients. In other dimensions the
nary dysfunction is rare (Enker ; Maas QoL of the patient group was not impaired
). Also in this study, the urinary symp- compared with that of general population.
toms were similar to those encountered In contrast, the patients reported better
commonly in general population of same health perception than the population.
age. No major incontinence or neurogenic According to our results, organ dys-
bladder requiring catheterization was en- function is a crucial factor in determining
countered. e incidence of sexual dysfunc- quality of life after rectal cancer surgery.
tion has been reported to be higher after Preoperative information about potential
APR than AR (Allal ; Engel ). In line side effects is mandatory to make a patient’s
with that, impotence occurred in and expectations realistic, and to help to cope
after LAR and APR in our study. with the consequences. Refining surgical
Overall, the differences in the QoL of techniques to minimize the incidence of
patients after sphincter-sacrificing and treatment-related adverse effects is prob-
sphincter-preserving surgery seem to be ably at least as important as aiming to
small (Pachler ). In the present study, sphincter-sparing surgery in an attempt to
no significant difference between the treat- improve the quality of life after rectal cancer
ment groups in the quality of life was seen. surgery.
36 HUCH, Jorvi Hospital Publications • Series A 01/2005
On the basis of the present study, the following conclusions can be
. A single PNA-test in its present form is as sensitive indicator of
colorectal neoplasia as Hemolex completed over three days but
lacks specificity, making it less suitable for screening purposes.
e kD cancer-associated antigen under further character-
ization might help in developing a more specific PNA-test.
. Total mesorectal excision technique (TME) technique in
low and midrectal cancers results in improved survival and
decreased local recurrence rate compared with conventional
surgery. Despite an increased number of anastomotic compli-
cations TME technique is safe. e use of covering stoma and
colonic J-pouch seems to reduce the incidence and severity of
. Identification and treatment of comorbid conditions before
surgery for rectal cancer is mandatory to keep morbidity and
mortality rates acceptable. In carefully selected elderly patients
similar survival rates to those found in younger patients are
. In assessing tumour response to preoperative adjuvant therapy,
histologic tumour regression grading (TRG) seems to offer a
more accurate means than uT-downstaging, which did not cor-
relate with TRG results.
. Bowel and urinary dysfunction and impotence have a major
adverse impact on the quality of life after rectal cancer surgery.
ese adverse effects need to be discussed with the patient and
preoperative function needs to be taken into account when
choosing between treatment options. Refining surgical tech-
niques to minimize the incidence of treatment-related adverse
effects is probably at least as important as aiming to sphincter-
sparing surgery in an attempt to improve the quality of life after
rectal cancer surgery.
HUCH, Jorvi Hospital Publications • Series A 01/2005 37
e present study was carried out at the Professor Jyrki Mäkelä, MD, for their con-
Fourth Department of Surgery, the Helsinki structive comments in accomplishing the
University Central Hospital and the manuscript to its final form.
Jyväskylä Central Hospital. Analyzing the e colleagues at the Jorvi Hospital have
data and writing the papers were done while a special place in my heart as well. Above all,
I was working at the Jorvi Hospital. I am deeply indebted to Jorma Nieminen,
I wish to thank Professor Krister MD, the Surgeon-in-Chief, for his encour-
Höckerstedt, MD, and the late Professor aging, trusting and supporting attitude that
Juhani Ahonen, MD, and all the colleagues helped enormously in bringing this thesis to
with whom I have worked at the Fourth its conclusion. Also, I am very grateful to the
Department of Surgery. e stimulating wonderful staff at the Day Surgery Unit, who
conversations and fine attitude towards had to put up with me in good and bad days
both clinical and scientific work created the during this process.
ground for this thesis. I owe thanks to the staff at the patient
Above all, I wish to express my deepest archives of the Surgical Hospital, the
gratitude to my supervisor, docent Ilmo Helsinki University Central Hospital and the
Kellokumpu, MD, whose skills as a surgeon Jyväskylä Central Hospital, for their prompt
and researcher I highly respect. He guided assistance and positive attitude when I was
me to the world of science and provided collecting data from patient files. Many
resources and subjects for this study. I could warm thanks go also to Mrs Tuula Boström
not have imagined having a better advisor for her always so helpful attitude in litera-
and mentor and without his knowledge and ture haunt, to Mr Jari Simonen for handling
perceptiveness I might have never finished the lay-out of this thesis, and to Mrs Sari
this work. His commitment to good quality Karesvuori and Mrs Eila Karonen for their
work will always inspire me. invaluable help in organizing practical
I owe sincere thanks to all my co-authors things for the dissertation.
of the published manuscripts for their im- My special thanks go to my cousin and
portant contribution. Especially I wish to ex- very dear friend Mrs Tarja Sarvi for help-
press my gratitude to docent Leena Halme, ing me with the English language. My
MD, whose patience and determination in warmest thanks go also to Mrs Jutta Gröhn
solving problems connected to comput- with whom I shared hilarious moments in
ers and statistics was of great help during the miraculous world of science, and her
the early phases of this work. Gratefully husband Mr Heikki Pikkarainen as well as
acknowledged is also Peter Sainio, MD, Mrs and Mr Helle and Erkki Päiviö, who all
PhD, who showed me the importance took a great interest in the study. anks
of preciseness in scientific work. Docent are due to my dear colleague and friend
Matti Kairaluoma, MD, Matti Juhola, MD, Pia Nordström who was a great source of
and Sakari Kellokumpu, PhD, are sincerely strength all through this work. Collectively, I
thanked for collecting data, for examining am deeply grateful to all my dear friends and
histopathologic samples and for laboratory relatives for their caring, support and always
analyses in PNA-tests, respectively. so refreshing company. Special thanks are
My sincere thanks are due to the review- due to each one of them who kept asking
ers, Professor Heikki Järvinen, MD, and me all these years: ”Have you finished your
38 HUCH, Jorvi Hospital Publications • Series A 01/2005
thesis yet?” Silencing that question was a ing attitude to keep me going. is work is
prime motivation when other interests in dedicated to them all.
life enticed. is study was financially supported by
I wish to thank my dear mother Maria the Jorvi Hospital scientific foundation,
for always believing in me. My warmest the University of Helsinki, the Finnish
thanks go also to my wonderful children Medical Society Duodecim and the Finnish
Eveliina and Aleksi for their patience and Research Foundation of Gastroenterology,
interest in what I was doing throughout this which I gratefully acknowledge.
work. Finally, I owe my most loving thanks Looking forward to new challenges
to my husband Pekka who so often during
many lonely hours spent at the computer Jaana Vironen
nourished me with a hot cup of tea and lov- Espoo, th September
HUCH, Jorvi Hospital Publications • Series A 01/2005 39
Aalto A-M, Aro A, Teperi J. RAND- as a measure Uptake, yield of neoplasia, and adverse effects
of health related quality of life. Reliability, of flexible sigmoidoscopy screening. Gut ;
construct validity and reference values in the : –.
Finnish population [RAND- terveyteen
liittyvän elämänlaadun mittarina – Mittarin Birbeck KF, Macklin CP, Tiffin NJ, Parsons W, Dixon
luotettavuus ja suomalaiset väestöarvot]. . MF, Mapstone NP, Abbott CR, Scott N, Finan PJ,
Helsinki, STAKES. Johnston D, Quirke P. Rates of circumferential
resection margin involvement vary between
Adams D, Blatchford J, Lin K, Ternent C, ornson surgeons and predict outcomes in rectal cancer
A, Christensen M. Use of preoperative ultra- surgery. Ann Surg ; : –.
sound staging for treatment of rectal cancer. Dis
Colon Rectum ; : –. Bouzourene H, Bosman F, Matter M, Coucke P.
Predictive factors in locally advanced rectal
Advisory Committee on Cancer Prevention. Recom- cancer treated with preoperative hyperfraction-
mendations on cancer screening in the Europe- ated and accelerated radiotherapy. Hum Pathol
an Union. Eur J Cancer ; : –. ; : –.
Ahlquist DA, McGill DB, Fleming JL, Schwartz Bozzetti F, Andreola S, Baratti D, Mariani L, Stani
S, Wieand HS. Patterns of occult bleeding in SC, Valvo F, Spinelli P. Preoperative chemora-
asymptomatic colorectal cancer. Cancer ; diation in patients with resectable rectal cancer:
: –. results on tumor response. Surg Oncol ; :
Ahlquist DA, Skoletsky JE, Boynton KA, Harrington
JJ, Mahoney DW, Pierceall WE, ibodeau Bozzetti F, Andreola S, Rossetti C, Zucali R, E. M,
SN, Shuber AP. Colorectal cancer screening Baratti D, Bertario L, Doci R, Gennari L. Preop-
by detection of altered human DNA in stool: erative radiotherapy for resectable cancer of the
feasibility of a multitarget assay panel. Gastro- middle-distal rectum: its effect on the primary
enterology ; : –. lesion as determined by endorectal ultrasound
using flexible echo colonoscope. Int J Colorect
Akbari R, Wong W. Endorectal ultrasound and the Dis ; : –.
preoperative staging of rectal cancer. Scand J
Surg ; : –. Bronner M, Haggitt RC. e polyp-cancer sequence:
do all colorectal cancers arise from benign ad-
Allal AS, Bieri B, Pelloni A, Spataro V, Anchisi S, enomas? Gastrointest Endosc Clin N Am ;
Ambrosetti P, Sprangers MA, Kurtz JM, Gertsch : –.
P. Sphincter-sparing surgery after preoperative
radiotherapy for low rectal cancers: feasibility, Bulow S, Christensen IJ, Harling H, Kronborg O,
oncologic results and quality of life outcomes. Fenger C, Nielsen HJ. Recurrence and survival
Br J Cancer ; : –. after mesorectal excision for rectal cancer. Br J
Surg ; : –.
Anderson JH, Hole D, McArdle CS. Elective versus
emergency surgery for patients with colorectal Camilleri-Brennan J, Steele RJ. Quality of life after
cancer. Br J Surg ; : –. treatment for rectal cancer. Br J Surg ; :
Arbman G, Nilsson E, Hallböök O, Sjödahl R. Local
recurrence following mesorectal excision for Camilleri-Brennan J, Steele RJ. Objective assess-
rectal cancer. Br J Surg ; : –. ment of morbidity and quality of life after sur-
gery for low rectal cancer. Colorectal Dis ;
Atkin WS, Hart A, Edwards R, McIntyre P, Aubrey : –.
R, Wardle J, Sutton S, Cuzick J, Northover JMA.
40 HUCH, Jorvi Hospital Publications • Series A 01/2005
Campbell BJ, Finnie IA, Hounsell EF, Rhodes JM. improves survival for patients undergoing total
Direct demonstration of increased expression of mesorectal excision for stage T low rectal can-
omsen-Friedenreich (TF) antigen in colonic cers. Ann Surg ; : –.
adenocarcinoma and ulcerative colitis mucin
and its concealment in normal mucin. J Clin Delgado S, Lacy AM, Valdecasas JC, Balague C, Pera
Invest ; : –. M, Salvador L, Momblan D, Visa J. Could age
be an indication for laparoscopic colectomy in
Carlsen E, Schlichting E, Guldvog I, Johnson E, colorectal cancer? Surg Endosc ; : –.
Heald RJ. Effect of the introduction of total
mesorectal excision for the treatment of rectal Dennet E, Parry B. Misconceptions about the
cancer. Br J Surg ; : –. colonic J-pouch. What the accumulating data
show. Dis Colon Rectum ; : –.
Cawthorn SJ, Parums DV, Gibbs NM. Extent of
mesorectal spread and involvement of lat- Drossman DA, Sandler RS, McKee DC, Lovitz
eral resection margin as prognostic factors AJ. Bowel patterns among subjects not seek-
after surgery for rectal cancer. Lancet ; : ing health care. Gastroenterology ; :
Chiappa A, Zbar AP, Bertani E, Biella F, Audisio RA, Dworak O, Keilholz L, Hoffman A. Pathological fea-
Staudacher C. Surgical outcomes for colorectal tures of rectal cancer after preoperative radio-
cancer patients including the elderly. Hepato- chemotherapy. Colorectal Dis ; : –.
Gastroenterology ; : –.
Elsaleh H, Joseph D, Levitt M, House A, Robbins
Church JM, Raudkivi PJ, Hill GL. e surgical anat- P. Pre-operative chemoradiotherapy in locally
omy of the rectum – a review with particular advanced rectal cancer. Aust N Z J Surg ;
relevance to the hazards of rectal mobilisation. : –.
Int J Colorect Dis ; : –.
Engel J, Kerr J, Sclesinger-Raab A, Eckel R, Sauer H,
Crane C, Skibber J, Feig B, Vauthey J-N, ames HD, Hölzel D. Quality of life in rectal cancer patients.
Curley SA, Rodrigues-Bigas MA, Wolff RA, Ellis A four-year prospective study. Ann Surg ;
LM, Delclos ME, Lin EH, Janjan NA. Response : –.
to preoperative chemoradiation increases the
use of sphincter-preserving surgery in patients Enker WE. Potency, cure and local control in the
with locally advanced low rectal carcinoma. operative treatment of rectal cancer. Arch Surg
Cancer ; : –. ; : –.
Dahlberg M, Glimelius B, Påhlman L. Changing Enker WE. Safety and efficacy of low anterior resec-
strategy for rectal cancer is associated with im- tion for rectal cancer. consecutive cases
proved outcome. Br J Surg ; : –. from a specialty service. Ann Surg ; :
Damhuis RA, Wereldsma JC, Wiggers T. e influ-
ence of age on resection rates and postoperative Enker WE, Havenga K, Polyak T, aler H, Cranor M.
mortality in patients with colorectal can- Abdominoperineal resection via total mesorec-
cer. Int J Colorectal Dis ; : –. tal excision and autonomic nerve preservation
for low rectal cancer. World J Surg ; :
Dehni N, Schlegel D, Cunningham C, Guiguiet M, –.
Tiret E, Parc R. Influence of a defunctioning
stoma on leakage rates after low colorectal Enker WE, aler HT, Cranor ML, Polyak T. Total
anastomosis and colonic J pouch-anastomosis. mesorectal excision for in the operative treat-
Br J Surg ; : –. ment of carcinoma of the rectum. J Am Coll Surg
; : –.
Del Rio C, Sanchez-Santos R, Oreja V, De Oca J,
Biondo S, Pares D, Osorio A, Marti-Raque J, Fearon ER, Vogelstein B. A genetic model for colorec-
Jaurrieta E. Long-term urinary dysfunction after tal tumorigenesis. Cell ; : –.
rectal cancer surgery. Colorectal Dis ; :
–. Fielding LP, Phillips RK, Hittinger R. Factors in-
fluencing mortality after curative resection for
Delaney C, Lavery I, Brenner A, Hammel J, Senagore large bowel cancer in elderly patients. Lancet
A, Noone R, Fazio V. Preoperative radiotherapy ; : –.
HUCH, Jorvi Hospital Publications • Series A 01/2005 41
Finnish Cancer Registry. Cancer statistics at www. Hallböök H, Johansson K, Sjödahl R. Laser Doppler
cancerregistry.fi. last updated on July . blood flow measurement in rectal resection for
carcinoma – comparison between the straight
Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grand- and colonic J pouch reconstruction. Br J Surg
jean J-P, Partensky C, Souquet JC, Adeleine P, a; : –.
Gerard J-P. Influence of the interval between
preoperative radiation therapy and surgery Hallböök H, Påhlman L, Krog M, Wexner SD, Sjö-
on downstaging and on the rate of sphincter- dahl R. Randomised comparison of straight and
sparing surgery for rectal cancer: the Lyon colonic J pouch anastomosis after low anterior
R– randomised trial. J Clin Oncol ; : resection. Ann Surg b; : –.
Hamashima C. Long-term quality of life of postop-
Frykholm-Jansson G, Påhlman L, Glimelius B. erative rectal cancer patients. J Gastroenterol
Combined chemo- and radiotherapy vs. ra- Hepatol ; : –.
diotherapy alone in the treatment of primary,
nonresectable adenocarcinoma of the rectum. Hardcastle JD, Chamberlain JO, Robinson MHE,
Int J Radiat Oncol Biol Phys ; : –. Moss SM, Amar SS, Balfour TW, James PD,
Mangham CM. Randomised controlled trial
Gamagami R, Istvan G, Cabarrot P, Liagre A, Chio- of faecal-occult-blood screening for colorectal
tasso P, Lazorthes F. Fecal continence following cancer. Lancet ; : –.
partial resection of the anal canal in distal rectal
cancer: long-term results after coloanal anasto- Harris GJC, Lavery IC, Fazio VW. Function of a co-
mosis. Surgery ; : –. lonic J pouch continues to improve with time.
Br J Surg ; : –.
Garcia-Aguilar J, Hernandez de Anda E, Sirivongs
P, Lee S-H, Madoff R, Rothenberger D. A Havenga K, DeRuiter MC, Enker WE, Welvaart K.
pathologic complete response to preoperative Anatomical basis of autonomic nerve-preserv-
chemoradiation is associated with lower local ing total mesorectal excision for rectal cancer.
recurrence and improved survival in rectal Br J Surg a; : –.
cancer patients treated by mesorectal excision.
Dis Colon Rectum ; : –. Havenga K, Enker WE, McDermott K. Male and
female sexual and urinary function after total
Gervaz PA, Wexner SD, Pemberton JH. Pelvic mesorectal excision with autonomic nerve
radiation and anorectal function: introducing preservation for carcinoma of the rectum. J Am
the concept of sphincter-preserving radiation Coll Surg b; : –.
therapy. J Am Coll Surg ; : –.
Havenga K, Maas CP, DeRuiter MC, Welvaart K,
Graf W, Glimelius B, Bergström R, Påhlman L. Com- Trimbos JB. Avoiding long-term disturbance to
plications after double and single stapling in bladder and sexual function in pelvic surgery,
rectal surgery. Eur J Surg ; : –. particularly with rectal cancer. Semin Surg
Oncol ; : –.
Grumann M, Noack E, Hoffman I, Schlag P. Com-
parison of quality of life in patients undergo- Haynes SR, Lawler PG. An assessment of the con-
ing abdominoperineal extirpation or anterior sistency of ASA physical status classification
resection for rectal cancer. Ann Surg ; : allocation. Anaesthesia ; : –.
Hays RD, Sherbourne CD, Mazel RM. e RAND
Grundman R, Said S, Krinke S. Quality of life after -Item Health Survey .. Health Economics
rectal resection or extirpation. A comparison ; : –.
using different measurement parametres. Dtsch
Med Wochenschr ; : –. Heald RJ, Husband EM, Ryall RDH. e mesorec-
tum in rectal cancer surgery – the clue to pelvic
Haas-Kock de DFM, Baeten CGM, Jager JJ, Lan- recurrence? Br J Surg ; : –.
gendijk JA, Schouten LJ, Volovics A, Arends
JW. Prognostic significance of radial margins Heald RJ, Karanjia ND. Results of radical surgery for
of clearance in rectal cancer. Br J Surg ; : rectal cancer. World J Surg ; : –.
42 HUCH, Jorvi Hospital Publications • Series A 01/2005
Hessman O, Bergkvist L, Ström S. Colorectal cancer Jorge JM, Wexner SD. Etiology and management of
in patients over years of age – determinants fecal incontinence. Dis Colon Rectum ; :
of outcome. Eur J Surg Onc ; : –. –.
Hildebrandt U, Feifel G. Preoperative staging of rec- Jorgensen OD, Kronborg O, Fenger C. A randomised
tal cancer by intrarectal ultrasound. Dis Colon study of screening for colorectal cancer using
Rectum ; : –. faecal occult blood testing: results after years
and seven biennial screening rounds. Gut ;
Ho Y-H, Brown S, Heah S-M, Tsang C, Seow-Choen : –.
F, Eu K-W, Tang CL. Comparison of J-pouch and
coloplasty pouch for low rectal cancers. Ann Kapiteijn E, Marijnen C, Nagtegaal I, Putter H, Steup
Surg ; : –. W, Wiggers T, Rutten HJ, Pahlman L, Glimelius
B, Krieken J, Leer JWH, van de Velde CJH. Pre-
Ho Y-H, Seow-Choen F, Tan M. Colonic J-pouch operative radiotherapy combined with total
function at six months versus straight coloanal mesorectal excision for resectable rectal cancer.
anastomosis at two years: randomized con- N Engl J Med ; : –.
trolled trial. World J Surg ; : –.
Kapiteijn E, Putter H, van de Velde CJH, Group
Hojo K, Vernava AM, Sugihara K, Katumata K. Pres- DCC. Impact of the introduction and training
ervation of urine voiding and sexual function of total mesorectal excision on recurrence and
after rectal cancer surgery. Dis Colon Rectum survival in rectal cancer in e Netherlands. Br J
; : –. Surg ; : –.
Holm T, Cedermark B, Rutqvist L-E. Local re- Karanjia ND, Corder AP, Bearn P, Heald RJ. Leakage
currence of rectal adenocarcinoma after from stapled low anastomosis after total meso-
`curative´surgery with and without preopera- rectal excision for carcinoma of the rectum. Br J
tive radiotherapy. Br J Surg ; : –. Surg ; : –.
Holm T, Johansson H, Cedermark B, Ekelund Karanjia ND, Schache DJ, North WR, Heald RJ.
G, Rutqvist L-E. Influence of hospital- and `Close shave´ in anterior resection. Br J Surg
surgeon-related factors on outcome after treat- ; : –.
ment of rectal cancer with or without preopera-
tive radiotherapy. Br J Surg ; : –. Keating JP. Sexual function after rectal excision.
ANZ J Surg ; : –.
Huber FT, Herter B, Siewert JR. Colonic pouch vs.
side-to-end anastomosis in low anterior resec- Kellokumpu IH, Andersson LC, Kellokumpu SJ. De-
tion. Dis Colon Rectum ; : –. tection of colorectal neoplasia with peanut-ag-
glutinin (PNA)-reactive carbohydrate structures
Janjan NA, Abbruzzese J, Pazdur R, Khoo VS, Cleary in rectal mucus. Int J Cancer ; : –.
KR, Dubrow R, Ajani J, Rich TA, Goswitch MS,
Evetts PA, Allen PK, Lynch PM, Skibber J. Prog- Kewenter J, Brevinge H, Engaras B, Haglind E,
nostic implications of response to preoperative Ahren C. Results of screening, rescreening, and
infusional chemoradiation in locally advanced follow-up in a prospective randomized study
rectal cancer. Radiother Oncol a; : for detection of colorectal cancer by fecal occult
–. blood testing. Results for , subjects. Scand
J Gastroenterol ; : –.
Janjan NA, Khoo VS, Abbruzzese J, Pazdur R,
Dubrow R, Cleary KR, Allen PK, Lynch PM, Kim NK, Aahn TW, Park JK, Lee KY, Lee WH, Sohn
Glober G, Wolff RA, Rich TA, Skibber J. Tumour SK, Min JS. Assessment of sexual and voiding
downstaging and and sphincter preservation function after total mesorectal excision with
with preoperative chemoradiation in locally pelvic autonomic nerve preservation in males
advanced rectal cancer: the M.D. Anderson with rectal cancer. Dis Colon Rectum ; :
Cancer Center experience. Int J Radiat Oncol –.
Biol Phys b; : –.
Kingston RD, Jeacock J, Walsh S, Keeling F. e
Jess P, Christiansen J, Bech P. Quality of life after outcome of surgery for colorectal cancer in the
anterior resection versus abdominoperineal ex- elderly: a -year review from the Trafford Data-
tirpation for rectal cancer. Scand J Gastroenterol base. Eur J Surg Onc ; : –.
; : –.
HUCH, Jorvi Hospital Publications • Series A 01/2005 43
Kitagawa Y, Watanabe M, Hasegawa H, Yamamoto for carcinoma? Dis Colon Rectum ; :
K, Matsuda J, Mukai M, Kubo A, Kitajima M. –.
Sentinel node mapping for colorectal cancer
with radioactive tracer. Dis Colon Rectum ; Luna-Perez P, Rodriguez-Ramirez S, Rodriguez-Co-
: –. ria DF, Fernandez A, Labastida S, Silva A, Lopez
MJ. Preoperative chemoradiation therapy
Kneist W, Heintz A, Junginger T. Major urinary and anal sphincter preservation with locally
dysfunction after mesorectal excision for rectal advanced rectal adenocarcinoma. World J Surg
carcinoma. Br J Surg ; : –. ; : –.
Kronborg O, Fenger C, Sondergaard O, Pederson Maas CP, Moriya Y, Steup WH, Kiebert GM, Klein
KM, Olsen J. Randomised study of screening Kranenbarg WM, van de Velde CJH. Radical
for colorectal cancer by faecal occult blood test. and nerve-preserving surgery for rectal cancer
Lancet ; : –. in e Netherlands: a prospective study on
morbidity and functional outcome. Br J Surgery
Kumar A, Scholefield J. Endosonography of the ; : –.
anal canal and rectum. World J Surg ; :
–. Maas CP, Moriya Y, Steup WH, Klein Kranenberg
E, van de Velde CJH. A prospective study on
Kuzu M, Topcu O, Ucar K, Ulukent S, Unal E, Erverdi radical and nerve-preserving surgery for rectal
N, Elhan A, Demirci S. Effect of sphincter-sacri- cancer in e Netherlands. Eur J Surg Onc ;
ficing surgery for rectal carcinoma on quality of : –.
life in Muslim patients. Dis Colon Rectum ;
: –. MacFarlane JK, Ryall RDH, Heald RJ. Mesorectal
excision for rectal cancer. Lancet ; :
Law W-L, Chu K-W, Ho J, Chan C-W. Risk factors for –.
anastomotic leakage after low anterior resec-
tion with total mesorectal excision. Am J Surg Machado M, Nygren J, Goldman S, Ljunqvist O.
; : –. Similar outcome after colonic pouch and side-
to-end anastomosis in low anterior resection for
Lazorthes F, Chiotasso P, Gamagami RA, Istvan G, rectal cancer. Ann Surg ; : –.
Chevreau P. Late clinical outcome in a ran-
domised prospective comparison of colonic J Mak T, Lalloo F, Evans DGR, Hill J. Molecular stool
pouch and straight coloanal anastomosis. Br J screening for colorectal cancer. Br J Surg ;
Surg ; : –. : –.
Lazorthes F, Fages P, Chiotasso P, Lemozy J, Bloom Mandel JS, Bond JH, Bradley GM, Snover DC,
E. Resection of the rectum with construction of Church TR, Williams S, Watt G, Schuman LM,
a colonic reservoir and colo-anal anastomosis Ederer F, Gilbertsen V. Sensitivity, specificity,
for carcinoma of the rectum. Br J Surg ; : and positive predictivity of the Hemoccult test
–. in screening for colorectal cancers. e Univer-
sity of Minnesota´s Colon Cancer Control Study
Lee S-J, Park Y-S. Serial evaluation of anorectal Group. Gastroenterology ; : –.
function following low anterior resection of the
rectum. Int J Colorect Dis ; : –. Mandel JS, Bond JH, Church TR, Snover DC, Bradley
GM, Schuman LM, Ederer F. Reducing mortality
Leslie A, Carey FA, Pratt NR, Steele RJ. e colorec- from colorectal cancer by screening for fecal oc-
tal adenoma-carcinoma sequence. Br J Surg cult blood. N Engl J Med ; : –.
; : –.
Mandel JS, Church TR, Bond JH, Ederer F, Geisser
Leveckis L, Boucher NR, Parys PT, Reed MWR, MS, Mongin SJ, Snover DC, Schuman LM. e
Shorthouse AJ, Anderson JB. Bladder and effect of fecal occult blood screening on the in-
erectile dysfunction before and after surgery for cidence of colorectal cancer. N Engl J Med ;
rectal cancer. Br J Urol ; : –. : –.
Lewis WG, Martin IG, Williamson MER, Stephenson Marijnen C, Kapiteijn E, van de Velde CJH, Martijn
BM, Holdsworth PJ, Finan PJ, Johnston D. Why H, Steup WH, Wiggers T, Klein Kranenbarg E,
do some patients experience poor functional Leer JWH. Acute side effects and complications
results after anterior resection of the rectum after short-term preoperative radiotherapy
44 HUCH, Jorvi Hospital Publications • Series A 01/2005
combined with total mesorectal excision in resectable rectal cancer. Int J Radiat Oncol Biol
primary rectal cancer: a report of a multi- Phys ; : –.
center randomized trial. J Clin Oncol ; :
–. Moore HG, Gittleman AE, Minsky BD, Wong D, Paty
PB, Weiser M, Temple L, Saltz L, Shia J, Guil-
Marijnen C, Nagtegaal I, Kranenbarg E, Hermans J, lem JG. Rate of pathologic complete response
van de Velde CJH, Leer JW, van Krieken JHJM. with increased interval between preoperative
No downstaging after short-term preoperative combined modality therapy and rectal cancer
radiotherapy in rectal cancer patients. J Clin resection. Dis Colon Rectum ; : –.
Oncol ; : –.
Moriya Y, Sugihara K, Akasu T, Fujita S. Importance
Marijnen C, van de Velde CJH, Putter H, van den of extended lymphadenectomy with lateral
Brink M, Maas CP, Martijn H, Rutten HJ, Wig- node dissection for advanced lower rectal can-
gers T, Klein Kranenbarg E, Leer JWH, Stig- cer. World J Surg ; : –.
gelbout AM. Impact of short-term preoperative
radiotherapy on health-related quality of life Mulcahy HE, Patchett SE, Daly L, O´Donoghue DP.
and sexual functioning in primary rectal cancer: Prognosis of elderly patients with large bowel
report of a multicenter randomized trial. J Clin cancer. Br J Surg ; : –.
Oncol ; : –.
Muller AD, Sonnenberg A. Prevention of colorectal
Marquis R, Lasry J, Heppel J, Potvin C, Falardeau cancer by flexible endoscopy and polypectomy.
M, Robidoux A. Quality of life after restorative Ann Intern Med ; : –.
surgery for cancer of the rectum. Ann Chir ;
: –. Mäkelä J, Kiviniemi H, Laitinen S. Survival after op-
erations for colorectal cancer in patients aged
Marr R, Birbeck KF, Garvican J, Macklin CP, Tiffin years or over. Eur J Surg ; : –.
NJ, Parsons WJ, Dixon MF, Mapstone NP, Sebag-
Montefiore D, Scott N, Johnston D, Sagar P, Fi- Nagtegaal ID, Marijnen CA, Kranenbarg Klein E,
nan P, Quirke P. e modern abdominoperineal van de Velde CJH, van Krieken JHJM. Circum-
excision. e next challenge after total mesorec- ferential margin involvement is still an impor-
tal excision. Ann Surg ; : –. tant predictor of local recurrence in rectal carci-
noma: not one millimeter but two millimeters is
Martling A, Holm T, Johansson H, Rutqvist L-E, Ce- the limit. Am J Surg Pathol ; : –.
dermark B. e Stockholm II Trial on Preopera-
tive radiotherapy in rectal carcinoma. Cancer Nesbakken A, Nygaard K, Bull-Njaa T, Carlsen E, Eri
; : –. L. Bladder and sexual dysfunction after meso-
rectal excision for rectal cancer. Br J Surg ;
Martling A, Holm T, Rutqvist LE, Johansson H, : –.
Moran BJ, Heald RJ, Cedermark B. Impact of a
surgical training programme on rectal cancer Nesbakken A, Nygaard K, Westerheim O, Lunde
outcomes in Stockholm. Br J Surg ; : OC, Mala T. Audit of intraoperative and early
–. postoperative complications after introduction
of mesorectal excision for rectal cancer. Eur J
Martling A, Holm T, Rutqvist L-E, Moran B, Heald Surg ; : –.
RJ, Cedermark B. Effect of surgical training
programme on outcome of rectal cancer in the Newcomb PA, Storer BE, Morimoto LM, Templeton
County of Stockholm. Lancet ; : –. A, Potter J. Long-term efficacy of sigmoidoscopy
in the reduction of colorectal cancer incidence.
Marusch F, Koch A, Schmidt U, Geissler S, Dralle J Natl Cancer Inst ; : –.
H, Saeger H-D, Wolff S, Nestler G, Pross M,
Gastinger I, Lippert H. Value of protective stoma Nuotio M, Jylhä M, Luukkaala T, Tammela TLJ.
in low anterior resections for rectal cancer. Dis Urgency, urge incontinence and voiding symp-
Colon Rectum ; : –. toms in men and women aged years and
over. BJU Int ; : –.
Minsky B, Cohen A, Enker WE, Saltz L, Guillem J,
Paty P, Kelsen D, Kemeny N, Ilson D, J. B, Conti O´Connell MJ, Maillard JA, Kahn M J, Macdonald
J. Preoperative -FU, low-dose leucovorin, and JS, Haller DG, Mayer RJ, Wieand HS. Controlled
radiation therapy for locally advanced and un- trial of fluorouracil and low-dose leucovorin
given for months as postoperative adjuvant
HUCH, Jorvi Hospital Publications • Series A 01/2005 45
therapy for colon cancer. J Clin Oncol ; : Porter G, Soskolne C, Yakimets W, Newman S.
–. Surgeon-related factors and outcome in rectal
cancer. Ann Surg ; : –.
Onaitis M, Noone R, Fields R, Hurwitz H, Morse M,
Jowell P, McGrath K, Lee C, Anscher MS, Clary Puig-La Calle JJ, Quayle J, aler HT, Shi W, Paty PB,
B, Mantyh C, Pappas TN, Ludvig K, Seigler HF, Quan SHQ, Cohen AM, Guillem JG. Favorable
Tyler DS. Complete response to neoadjuvant short-term and long-term outcome after elec-
chemoradiation for rectal cancer does not influ- tive radical rectal cancer resection in patients
ence survival. Ann Surg Oncol ; : –. years of age or older. Dis Colon Rectum ;
Ortiz H, Armendariz P. Anterior resection: do the
patients perceive any clinical benefit? Int J Col- Påhlman L, Dahlberg M, Glimelius B. Periop-
orect Dis ; : –. erative radiation therapy. World J Surg ;
Ortiz H, De Miguel M, Armendariz P, Rodriguez J,
Chocarro C. Coloanal anastomosis: are func- Påhlman L, Glimelius B. Pre- and postoperative
tional results better with pouch? Dis Colon radiotherapy in rectal and rectosigmoid carci-
Rectum ; : –. noma: Report from a randomized multicentre
trial. Ann Surg ; : –.
Pachler J, Wille-Jorgensen P. Quality of life after
rectal resection for cancer, with or without per- Påhlman L, Gunnarsson U, Karlbom U. e influ-
manent colostomy. e Cochrane Database of ence on treatment outcome of structuring rectal
systematic reviews ; . cancer care. Eur J Surg Oncol ; : –.
Pakkastie T, Luukkonen P, Järvinen H. Anastomotic Quirke P, Dixon MF, Durdey P, Williams NS. Local
leakage after anterior resection of the rectum. recurrence of rectal adenocarcinoma due to
Eur J Surg ; : –. inadequate surgical resection. Histopathologi-
cal study of lateral tumour spread and surgical
Parc R, Tiret E, Frileux P, Moszkowski E, Loygne excision. Lancet ; i: –.
J. Resection and colo-anal anastomosis with
colonic reservoir for rectal carcinoma. Br J Surg Ranta S, Hynynen M, Tammisto T. A survey of the
; : –. ASA physical status classification: significant
variation in allocation among Finnish anaes-
Peeters KCMJ, Tollenaar RAEM, Marijnen CAM, thesiologists. Acta Anaesth Scand ; :
Klein Kranenberg E, Steup WH, Wiggers T, Rut- –.
ten HJ, van de Velde CJH. Risk factors for anas-
tomotic failure after total mesorectal excision of Rauch P, Miny J, Conroy T, Neyton L, Guillemin F.
rectal cancer. Br J Surg ; : –. Quality of life among disease-free survivors of
rectal cancer. J Clin Oncol ; : –.
Pimentel JM, Duarte A, Gregorio C, Souto P, Patricio
J. Transverse coloplasty pouch and colonic J- Reissman P, Agachan F, Wexner SD. Outcome of
pouch for rectal cancer – a comparative study. laparoscopic colorectal surgery in older pa-
Colorectal Dis ; : –. tients. Am Surg ; : –.
Platell CFE, ompson PJ, Makin GB. Sexual health Remzi FH, Fazio VW, Gorgun E, Zutshi M, Church
in women following pelvic surgery for rectal JM, Lavery IC, Hull TL. Quality of life, functional
cancer. Br J Surg ; : –. outcome, and complications of coloplasty
pouch after low anterior resection. Dis Colon
Pocard M, Zinzindohoue F, Haab F, Caplin S, Parc Rectum ; : –.
R, Tiret E. A prospective study of sexual and uri-
nary function before and after total mesorectal Renner K, Rosen H, Novi G, Hölbing N, Schiessel R.
excision with autonomic nerve preservation for Quality of life after surgery for rectal cancer. Do
rectal cancer. Surgery ; : –. we still need a permanent colostomy? Dis Colon
Rectum ; : –.
Poon RT, Chu K-W, Ho JW, Chan C-W, Law W-L,
Wong J. Prospective evaluation of selective Reynolds JV, Joyce WP, Dolan J, Sheahan K, Hyland
defunctioning stoma for low anterior resection JM. Pathological evidence in support of total
with total mesorectal excision. World J Surg mesorectal excision in the management of rec-
; : –. tal cancer. Br J Surg ; : –.
46 HUCH, Jorvi Hospital Publications • Series A 01/2005
Rhodes JM, Black RR, Savage A. Glycoprotein ab- Sailer M, Fuchs K-H, Fein M, iede A. Random-
normalities in colonic carcinomata, adenomata ized clinical trial comparing quality of life after
and hyperplastic polyps shown by lectin-per- straight and pouch coloanal reconstruction. Br J
oxidase histochemistry. J Clin Pathol ; : Surg ; : –.
Saito N, Ono M, Sugito M, Ito M, Morihiro M, Ko-
Robinson MHE, Kronborg O, Williams C, Bostock sugi C, Sato K, Kotaka M, Nomura S, Arai M, Ko-
K, Rooney P, Hunt L, Hardcastle JD. Faecal batake T. Early results of intersphincteric resec-
occult blood testing and colonoscopy in the tion for patients with very low rectal cancer: an
surveillance of subjects at high risk of colorectal active approach to avoid permanent colostomy.
neoplasia. Br J Surg ; : –. Dis Colon Rectum ; : –.
Robinson MHE, Marks C, Farrands P, omas Sakamoto K, Muratani M, Ogawa T, Nagamachi
W, Hardcastle JD. Population screening for Y. Evaluation of a new test for colorectal neo-
colorectal cancer: comparison between guaiac plasms: a prospective study of asymptomatic
and immunological faecal occult blood tests. Br population. Cancer Biother ; : –.
J Surg ; : –.
Schatzl G, Temml C, Waldmuller J, urridl T, Haid-
Roseth AG, Kristinsson J, Fagerhol MK, Schjonsby inger G, Madersbacher S. A comparative cross-
H, Aadland E, Nygaard K, Roald B. Faecal sectional study of lower urinary tract symptoms
calprotectin: a novel test for the diagnosis of in both sexes. Eur Urol ; : –.
colorectal cancer? Scand J Gastroenterol ;
: –. Schiessel R, Karner-Hanusch J, Herbst F, Teleky
B, Wunderlich M. Intersphincteric resection
Rullier E, Goffre B, Bonnel C, Zerbib F, Caudry M, for low rectal tumours. Br J Surg ; :
Saric J. Preoperative radiochemotherapy and –.
sphincter-saving resection for T carcinomas
of the lower third of the rectum. Ann Surg ; Scholefield JH, Moss SM, Sufi F, Mangham CM,
: –. Hardcastle JD. Effect of fecal occult blood
screening on mortality from colorectal cancer:
Rullier E, Laurent C, Bretagnol F, Rullier A, Vendrely results from a randomized controlled trial. Gut
V, Zerbib F. Sphincter-saving resection for all ; : –.
rectal carcinomas. e end of the -cm distal
rule. Ann Surg ; : –. Segnan N, Senore C, Andreoni B, Arrigoni A, Bisanti
L, Cardelli A, Castiglione G, Crosta C, DiPlacido
Rullier E, Laurent C, Garrelon JL, Michel P, Saric J, R, Ferrari A, Ferraris R, Ferrero F, Fracchia M,
Parneix M. Risk factors for anastomotic leakage Gasperoni S, Malfitana G, Recchia S, Risio M,
after resection of rectal cancer. Br J Surg ; Rizzetto M, Saracco G, Spandre M, Turco D,
: –. Tourco P, Zappa M. Randomized trial of differ-
ent screening strategies for colorectal cancer:
Rullier E, Zerbib F, Laurent C, Bonnel C, Caudry M, patient response and detection rates. J Natl
Saric J, Parneix M. Intersphincteric resection Cancer Inst ; : –.
with excision of internal anal sphincter for con-
servative treatment of very low rectal cancer. Selby JV, Friedman GD, Quesenberry CPJ, Weiss
Dis Colon Rectum ; : –. NS. A case-control study of screening sigmoid-
oscopy and mortality from colorectal cancer. N
Ruo L, Tickoo S, Klimstra DS, Minsky BD, Saltz L, Engl J Med ; : –.
Mazumdar M, Paty PB, Wong WD, Larson SM,
Cohen AM, Guillem JG. Long-term significance Senagore AJ, Warmuth AJ, Delaney CP, Tekkis PP,
of extent of rectal cancer response to preop- Fazio VW. POSSUM, p-POSSUM, and Cr-POS-
erative radiation and chemotherapy. Ann Surg SUM: Implementation issues in a United States
; : –. health care system for prediction of outcome for
colon cancer resection. Dis Colon Rectum ;
Saha S, Monson KM, Bilchik A, Beutler T, Dan AG, : –.
Schochet E, Wiese D, Kaushal S, Ganatra B, De-
sai D. Comparative analysis of nodal upstaging Seow-Choen F, Goh HS. Prospective randomised
between colon and rectal cancers by sentinel trial comparing J colonic pouch-anal anasto-
lymph node mapping: a prospective trial. Dis mosis and straight coloanal reconstruction. Br
Colon Rectum ; : –. J Surg ; : –.
HUCH, Jorvi Hospital Publications • Series A 01/2005 47
Shamsuddin AM. New assays for detection of omas WM, Hardcastle JD, Jackson J, Pye G.
colorectal cancer.. Boca Raton, FL, CRC Chemical and immunological testing for fae-
Press. cal occult blood: a comparison of two tests in
symptomatic patients. Br J Cancer ; :
Shamsuddin AM, Elsayed AM. A test for detection of –.
colorectal cancer. Hum Pathol ; : –.
Tiret E, Poupardin B, McNamara D, Dehni N, Parc R.
Shankar A, Taylor I. Treatment of colorectal cancer Ultralow anterior resection with intersphincter-
in patients aged over . Eur J Surg Oncol ; ic dissection – what is the limit of safe sphincter
: –. preservation? Colorectal Dis ; : –.
Sidranski D, Tokino T, Hamilton SR, Kinzler KW, Towler BP, Irwig L, Glasziou P, Kewenter J, Weller D.
Levin B, Frost P, Vogelstein B. Identification of A systematic review of the effects of screening
ras oncogene mutations in the stool of patients for colorectal cancer using the faecal occult
with curable colorectal tumors. Science ; blood test, Hemoccult. BMJ ; : –.
Towler BP, Irwig L, Glasziou P, Weller D, Kewenter J.
Simunovic M, Sexton R, Rempel E, Moran B, Heald Screening for colorectal cancer using the faecal
RJ. Optimal preoperative assessment and sur- occult blood test, Hemoccult. e Cochrane
gery for rectal cancer may greatly limit the need Database of Systematic Reviews ; .
for radiotherapy. Br J Surg ; : –.
Tytherleigh MG, Mortensen NJM. Options for
Sobin LH, Wittekind C. UICC TNM classification of sphincter preservation in surgery for low rectal
malignant tumours.. New York, Wiley-Liss. cancer. Br J Surg ; : –.
Sprangers MAG, Taal BG, Aaronson NK, te Velde Ueno H, Yamauchi C, Hase K, Ichikura T, Mochizuki
A. Quality of life in colorectal cancer.Stoma vs. H. Clinicopathological study of intrapelvic
nonstoma patients. Dis Colon Rectum ; : cancer spread to the iliac area in lower rectal
–. adenocarcinoma by serial sectioning. Br J Surg
; : –.
Sugihara K, Moriya Y, Akasu T, Fujita S. Pelvic au-
tonomic nerve preservation for rectal cancer: Wagman R, Minsky B, Cohen A, Guillem J, Paty P.
oncological and functional outcome. Cancer Sphincter preservation in rectal cancer with
; : . preoperative radiation therapy and coloanal
anastomosis: long term follow-up. Int J Radiat
Swedish Rectal Cancer Trial. Improved survival Oncol Biol Phys ; : –.
with preoperative radiotherapy in resectable
rectal cancer. N Engl J Med ; : –. Valero G, Lujan JA, Hernandez Q, de las Heras M,
Pellicer E, Serrano A, Parrilla P. Neoadjuvant
e Norwegian Rectal Cancer Group. Total meso- radiation and chemotherapy in rectal cancer
rectal excision (TME) in Norway: A national does not increase postoperative complications.
rectal cancer project. Dis Colon Rectum ; Int J Colorect Dis ; : –.
Wang Z, Zhou Z, Wang C, Zhao G, Chen Y, Gao H,
eodoropoulos G, Wise W, Padmanabhan A, Zheng X, Wang R. Microscopic spread of low
Kerner BA, Taylor CW, Aguilar PS, Khanduja KS. rectal cancer in regions of the mesorectum:
T-level downstaging and complete pathologic detailed pathological assessment with whole-
response after preoperative chemoradiation mount sections. Int J Colorect Dis ; :
for advanced rectal cancer result in decreased –.
recurrence and improved disease-free survival.
Dis Colon Rectum ; : –. Wheeler JM, Warren BF, Jones AC, Mortensen NJM.
Preoperative radiotherapy for rectal cancer:
iis-Evensen E, Hoff GS, Sauar J, Langmark F, implications for surgeons, pathologists and
Majak BM, Vatn MH. Population-based surveil- radiologists. Br J Surg ; : –.
lance by colonoscopy: effect on the incidence
of colorectal cancer. Telemark Polyp Study I. Wheeler JMD, Dodds E, Warren BF, Path FRC, Cun-
Scand J Gastroenterol ; : –. ningham C, George BD, Jones AC, Mortensen
NJM. Preoperative chemoradiotherapy and
total mesorectal excision surgery for locally
48 HUCH, Jorvi Hospital Publications • Series A 01/2005
advanced rectal cancer: correlation with rectal Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar
cancer regression grade. Dis Colon Rectum MH, Mulrow CD, Woolf SH, Glick SN, Ganiats
; : –. TG, Bond JH, Rosen L, Zapka JG, Olsen SJ,
Giardiello FM, Sisk JE, Antwerp van R, Brown-
Wheeler JMD, Warren BF, Path MRC, Mortensen Davis C, Marciniak DA, Mayer RJ. Colorectal
NJM, Ekanyaka N, Kulacoglu H, Jones AC, cancer screening: clinical guidelines and ratio-
George BD, Kettlewell MGW. Quantification nale. Gastroenterology ; : –.
of histologic regression of rectal cancer after
irradiation. A proposal for a modified staging Winawer SJ, Zauber AG, Ho MN, O´Brien MJ, Got-
system. Dis Colon Rectum ; : –. tlieb LS, Sternberg SS, Waye JD, Schapiro M,
Bond JH, Panish JF, Ackroyd F, Shike M, Kurtz
Wibe A, Erisen MT, Syse A, Myrvold HE, Söreide RC, Hornsby-Lewis L, Gerdes H, Stewart ET.
O. Total mesorectal excision for rectal cancer Prevention of colorectal cancer by colonoscopic
– what can be achieved by national audit? polypectomy. NEJM ; : –.
Colorectal Dis a; : –.
Violi V, Pietra N, Grattarola M, Sarli L, Choua O,
Wibe A, Rendedal PR, Svensson E, Norstein J, Eide Roncoroni L, Peracchia A. Curative surgery for
TJ, Myrvold HE, Söreide O. Prognostic signifi- colorectal cancer: long term results and life
cance of the circumferential resection margin expectancy in the elderly. Dis Colon Rectum
following total mesorectal excision for rectal ; : –.
cancer. Br J Surg ; : –.
Väänänen P, Tenhunen R. Rapid immunochemical
Wibe A, Syse A, Andersen E, Tretli S, Myrvold HE, detection of fecal occult blood by use of latex-
Söreide O. Oncological outcomes after total agglutination test. Clinical Chemistry ; :
mesorectal excision for cure for cancer of the –.
lower rectum: anterior vs. abdominoperineal
resection. Dis Colon Rectum b; : –. Z´graggen K, Maurer CA, Birrer S, Giachino D, Kern
B, Buchler MW. A new surcigal concept for
Williams NS, Dixon MF, Johnston D. A study of distal rectal replacement after low anterior resection:
intramural spread and of patient survival. Reap- the transverse coloplasty pouch. Ann Surg ;
praisal of the centimetre rule of distal excision : –.
for carcinoma of the rectum. Br J Surg ; :
HUCH, Jorvi Hospital Publications • Series A 01/2005 49