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   Interventional procedures overview of complete
       cytoreduction and heated intraoperative
intraperitoneal chemotherapy (Sugarbaker technique)
      in patients with peritoneal carcinomatosis

This overview has been prepared to assist members of the Interventional Procedures
Advisory Committee (IPAC) in making recommendations about the safety and
efficacy of an interventional procedure. It is based on a rapid review of the medical
literature and specialist opinion. It should not be regarded as a definitive assessment
of the procedure.

Date prepared
This overview was prepared in July 2004.

Procedure name
•   Complete cytoreduction combined with heated intraoperative intraperitoneal
    chemotherapy (Sugarbaker technique) in patients with peritoneal carcinomatosis.

Specialty societies
•   Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland.
•   British Association of Surgical Oncology.
•   Association of Cancer Physicians.
•   Association of Coloproctology of Great Britain and Ireland.

Peritoneal carcinomatosis.

Peritoneal metastases commonly result from the regional spread of gastrointestinal,
gynaecological and other malignancies. Peritoneal carcinomatosis is an advanced
form of cancer associated with short survival and poor quality of life, which may lead
to bowel obstruction, ascites and pain.

Current treatment and alternatives
There is no curative treatment. Current standard treatment uses systemic
chemotherapy and/or surgery for the short term palliation of complications such as
bowel obstruction.

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis   Page 1 of 14
What the procedure involves
This procedure was developed by Paul Sugarbaker at the Washington Cancer
Institute. A laparotomy is performed under general anaesthesia and all gross tumour
is removed along with the involved organs, peritoneum and tissue. The surgery

•   removal of the right hemicolon, spleen, gall bladder, parts of the stomach, greater
    omentum and lesser omentum
•   stripping of the peritoneum from the pelvis and diaphragm
•   stripping of tumour from the surface of the liver
•   removal of the uterus and ovaries in women
•   removal of the rectum in some cases.

The aim of the surgery is to remove all macroscopic tumour, although residual
tumour is sometimes left behind.

After the organs have been removed, the abdomen is perfused with fluid containing a
chemotherapy agent, heated to between 40 and 48°C. The fluid is perfused for 60 to
120 minutes and then drained from the abdomen, before the laparotomy is closed. A
further course of systemic or intraperitoneal chemotherapy may be administered after
the surgery.

Intraoperative intraperitoneal administration of chemotherapy allows the drug to be
distributed uniformly to all surfaces of the abdomen and pelvis. Potential advantages
of heating the perfusion fluid are that it increases drug penetration and the cytotoxic
effect of drugs such as mitomycin C and cisplatin.

In one randomised controlled trial, 54 patients treated with this procedure had a
significantly longer median survival than 51 patients treated with systemic
chemotherapy with or without surgery (22.4 months versus 12.6 months). Survival
was poorer for those patients left with extensive residual disease after surgery. In
one non-randomised controlled study, 48 patients treated with surgery and
intraoperative heated chemotherapy had a significantly better survival rate than 18
control patients treated with surgery and chemotherapy. In a second non-randomised
controlled trial, there was no significant difference in survival between 27 patients
treated with this procedure and 37 patients treated with surgery and unheated
intraperitoneal chemotherapy.

A case series of 109 patients showed that survival varied according to the primary
cancer site. Patients with peritoneal carcinomatosis arising from stomach cancer had
a median survival of 10 months compared with 63 months for patients with appendix
as the primary site. Overall survival at 1 year was 61%. Overall 5-year survival was
reported in three studies and ranged from 16% in a study of 49 patients with the
stomach as the primary cancer site to 31% in a study of 48 patients also with the
stomach as the primary cancer site.

The Specialist Advisors stated that there are uncertainties regarding survival

The postoperative mortality rate ranged from 4% (2/49) to 12% (9/77) of patients.
The most commonly reported specific complication was a gastrointestinal fistula,
affecting between 4% (2/49) and 18.5% (5/27) of patients. Other complications
included abdominal and systemic sepsis, haemorrhage, heart failure, pulmonary

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis   Page 2 of 14
embolism, pleural effusion and pneumothorax. Four studies reported haematological
complications, affecting between 7% (2/27) and 21% (23/109) of patients.

The Specialist Advisors noted that this is a long and complex procedure. Potential
adverse effects include death, infection, haemorrhage, anastomotic dehiscence and

Literature review

Rapid review of literature
The medical literature was searched to identify studies and reviews relevant to
complete cytoreduction and heated intraperitoneal chemotherapy (Sugarbaker
technique) in patients with peritoneal carcinomatosis. Searches were conducted via
the following databases, covering the period from their commencement to July 2004:
MEDLINE, PREMEDLINE, EMBASE, Cochrane Library and Science Citation Index.
Trial registries and the Internet were also searched. No language restriction was
applied to the searches.

The following selection criteria (Table 1) were applied to the abstracts identified by
the literature search. Where these criteria could not be determined from the abstracts
the full paper was retrieved

Table 1 Inclusion criteria for identification of relevant studies

 Characteristic            Criteria
 Publication type          Clinical studies included. Emphasis was placed on identifying good
                           quality studies.
                           Abstracts were excluded where no clinical outcomes were reported, or
                           where the paper was a review, editorial, laboratory or animal study.
                           Conference abstracts were also excluded because of the difficulty of
                           appraising methodology.
 Patient                   Patients with peritoneal carcinomatosis.
 Intervention/test         Complete cytoreduction and heated intraperitoneal chemotherapy
                           (Sugarbaker technique).
 Outcome                   Articles were retrieved if the abstract contained information relevant to
                           the safety and/or efficacy.
 Language                  Non-English-language articles were excluded unless they were
                           thought to add substantively to the English-language evidence base.

List of studies included in the overview
Case series including fewer than 30 people were excluded. One randomised
controlled trial was identified, comparing complete cytoreduction and heated
intraoperative intraperitoneal chemotherapy with systemic chemotherapy (with or
without surgery).1 Two non-randomised controlled studies comparing surgery and
early intraperitoneal chemotherapy with surgery and intraoperative intraperitoneal
chemohyperthermia, were identified.2,3 Four case series are also described in Table
2.4-7 Other studies that were suitable for inclusion but have not been summarised in
Table 2 are listed in Appendix A.

Existing reviews on this procedure
A systematic review of the Sugarbaker procedure for the treatment of
pseudomyxoma peritonei has been published, but it does not consider the use of the
procedure for the treatment of patients with peritoneal carcinomatosis. 8

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis   Page 3 of 14

Table 2 Summary of key efficacy and safety findings on complete cytoreduction and heated intraoperative intraperitoneal
Abbreviations used: HIPEC = hyperthermic intraperitoneal chemotherapy, EPIC = early intraperitoneal chemotherapy, IPCH = intraperitoneal
Study details                                Key efficacy findings                                    Key safety findings                    Comments
Verwaal VJ (2003)                            Survival after a median follow-up of 21.6 months:        Complications of cytoreduction and     Random allocation of patients.
                                              • Systemic chemotherapy = 39.2% (20/51)                 HIPEC:
Prospective randomised controlled trial       • Cytoreductive surgery and HIPEC = 55.6%                • Postoperative deaths = 8.3%         Follow-up complete for 99%
                                                  (30/54)                                                 (4/48)                             (104/105) patients.
1998–2001                                                                                              • Fever = 6.2% (3/48)
                                             Hazard ratio 0.55 (95% CI 0.32 to 0.95)                   • Leukopenia = 16.7% (8/48)           Patients alive at the time of
The Netherlands                                                                                        • Thrombocytopaenia = 4.2% (2/48)     analysis were censored at their
                                             Median survival:                                          • Neuropathy = 4.2% (2/48)            last follow-up examination.
105 patients                                  • Systemic chemotherapy = 12.6 months                    • Pleural effusion = 2.1% (1/48)
• 51 treated with systemic                       Cytoreductive surgery and HIPEC = 22.4                • Pulmonary embolism within 3         Survival estimated by Kaplan-
  chemotherapy with or without                   months                                                   months of surgery = 4.2% (2/48)    Meier method and tested
  surgery (standard arm)                                                                                                                     following the intention-to-treat
                                                                                                       • Pneumonia = 2.1% (1/48)
• 54 treated with cytoreductive surgery      p = 0.032                                                 • Renal obstruction = 4.2% (2/48)
  and hyperthermic intraperitoneal
                                                                                                       • Anuria = 6.2% (3/48)                Standard arm: 7 patients never
  chemotherapy (HIPEC) followed by           Survival according to success of surgical procedure:      • Cardiac arrhythmia = 2.1% (1/48)    started systemic chemotherapy
  systemic chemotherapy                      Complete resection = 94.4% (17/18)
  (experimental arm)                                                                                   • Heart failure = 12.5% (6/48)        (5 withdrew consent and 2
                                             Limited residual disease = 33.3% (7/21)
                                                                                                       • Gastrointestinal fistula = 14.6%    deteriorated too rapidly).
                                             Extensive residual disease = 30.0% (3/10)
Median age: 54 years (range 28–                                                                           (7/48)
70 years)                                    Median survival according to extent of preoperative       • Pancreatitis = 2.1% (1/48)          HIPEC arm: 5 patients did not
                                             disease in patients treated with cytoreductive surgery    • Catheter infections = 6.2% (3/48)   undergo procedure (2 died, 2
Median follow-up: 21.6 months                and HIPEC:                                                • Haemorrhage = 12.5% (6/48)          developed metastases, 1
                                             0 to 5 regions of disease = >29 months                    • Psychological disorders = 10.4%     withdrew consent).
Inclusion criteria: patients with            6 to 7 regions of disease = 5.4 months                       (5/48)
histologically proven peritoneal                                                                                                             All treatment-related deaths were
metastases of colorectal                     p < 0.0001                                               Complications of systemic              in patients with extensive
adenocarcinoma or positive cytology of                                                                chemotherapy alone not stated          disease.
ascites, no evidence of distant
metastases on CT scan, age < 71 years
old, fit for major surgery

Primary cancer sites: colon (n = 75),
appendix (n = 18), rectum (n = 12)

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis     Page 4 of 14

Study details                                Key efficacy findings                                       Key safety findings   Comments
Fujimoto S (1997)                            Resolution of abdominal effusion:                           None reported         No randomisation.
                                                •     Control group = 5.6% (1/18)
Non randomised controlled study                 •     HIPEC group = 100% (48/48)                                               Some patients had been referred
                                                                                                                               for HIPEC treatment and some
1986–1995                                    Cytologically positive postoperatively                                            patients refused the option of
                                                 •    Control group = 100% (18/18)                                             surgery alone.
Japan                                            •    HIPEC group = 4.2% (2/48)
                                                                                                                               The HIPEC group included 18
66 patients                                  Median survival of control group = 247 days                                       patients with numerous
• 18 treated with surgery and                100% (18/18) patients in control group died within 16                             metastases to the distant
   chemotherapy delivered                    months                                                                            peritoneum. None of the control
   intraperitoneally and/or intravenously                                                                                      group had such extensive
• 48 treated with surgery and                HIPEC group:                                                                      metastatic disease.
   hyperthermic intraperitoneal              1-year survival rate = 54.0%
   chemotherapy (HIPEC)                      3-year survival rate = 41.5%                                                      The histology and types of
                                             5-year survival rate = 31.0%                                                      surgery performed were similar
Primary cancer site: stomach                 8-year survival rate = 25.4%                                                      for both patient groups.

                                             The survival for the HIPEC group was significantly                                Follow-up not described.
                                             better than that for the control group (p = 0.00167)

                                             Incidence of death due to peritoneal recurrence:
                                                  •   Control group = 94.4% (17/18)
                                                  •   HIPEC group = 27.1% (13/48)

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis        Page 5 of 14

Study details                                Key efficacy findings                                      Key safety findings                      Comments
Elias D (2001)                               Cancer recurrence = 65.6% (42/64)                          Complications in patients treated        No randomisation.
                                             Peritoneal recurrence = 31.3% (21/64)                      with surgery and early intraperitoneal
Retrospective non-randomised                                                                            chemotherapy without hyperthermia        Patient selection not described.
controlled study                             Overall survival in entire population:                      • Death = 8.1% (3/37)
                                             2-year = 60.1%                                              • Abdominal fistula = 18.9% (7/37)      Small patient numbers.
1993–1999                                    3-year = 47.1%                                              • Abdominal abscess = 13.5% (5/37)
                                             4-year = 36.0%                                              • Reoperation = 27.0% (10/37)           No patient was lost to follow-up.
France                                       5-year = 27.4%                                              • Pulmonary complication = 24.3%
                                                                                                             (9/37)                              At the beginning of study,
64 patients                                  Disease-free survival in entire population:                 • Aplastic complication = 0% (0/37)     patients with massive diffuse
• 37 treated with surgery and early          2-year = 54.7%                                              • Miscellaneous extraabdominal          peritoneal carcinomatosis were
    intraperitoneal chemotherapy             3-year = 39.4%                                                  complication = 27.0% (10/37)        treated. Such patients were
    (EPIC) without hyperthermia              4-year = 30.1%                                                                                      subsequently excluded because
• 27 treated with surgery and                5-year = 18.4%                                                                                      of their high complication rate
    intraoperative intraperitoneal                                                                      Complications in patients treated        and poor survival.
    chemohyperthermia (IPCH)                 Median survival = 35.9 months                              with surgery and intraoperative
                                                                                                        intraperitoneal chemohyperthermia
Mean age: 47.1 years (range 16–              Survival rates were higher in patients treated with
                                                                                                          • Death = 11.1% (3/27)
75 years)                                    IPCH but not significantly (p = 0.13)
                                                                                                          • Abdominal fistula = 18.5% (5/27)
                                             Presence of associated metastases had a                      • Abdominal abscess = 11.1% (3/27)
Median follow-up: 51.6 months
                                             significantly negative influence on survival (p = 0.04)      • Reoperation = 29.6% (8/27)
Exclusion criteria: lung, liver or lymph                                                                  • Pulmonary complication = 29.6%
metastases, or invaded lymph nodes           Patients with extensive peritoneal carcinomatosis               (8/27)
along the aorta or vena cava                 before surgery had significantly poorer survival than        • Aplastic complication = 7.4%
                                             patients with less extensive disease (p = 0.01)                 (2/27)
Primary cancer site: colon (n = 46),                                                                      • Miscellaneous extraabdominal
rectum (n = 9), appendix (n = 9)                                                                             complication = 25.9% (7/27)

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis       Page 6 of 14

Study details                                Key efficacy findings                                  Key safety findings                       Comments
Shen P (2003)                                Median survival:                                       Complications                             Consecutive patients.
                                                                                                     • Postoperative mortality = 8.3%
Case series                                  Overall = 15.9 months                                     (9/109)                                Nearly a third of patients in this
                                                                                                     • Haematological toxic                   series did not receive the full
1991–1997                                    Primary cancer site appendix = 63.4 months                effects = 21.1% (23/109)               application of heat and
                                             Primary cancer site stomach = 10.1 months               • Blood transfusion = 63.3%              chemotherapy as described in
North Carolina, USA                          Primary cancer site colorectal = 14.4 months              (69/109)                               the protocol.

109 patients                                 Ascites present = 7.9 months                             Overall perioperative morbidity = 36%   Four factors were significant
                                             No ascites = 22.3 months, p = 0.03                                                               independent predictors of
Median follow-up: 52 months                                                                                                                   improved survival by multivariate
                                             Positive post-intraperitoneal chemotherapy cytology                                              analysis: nonadenocarcinoma
Primary cancer sites: colorectal             = 12.7 months                                                                                    histology (p = 0.001), the
(n = 40), appendix (n = 23), stomach         Negative post-intraperitoneal chemotherapy                                                       appendix as a primary site
(n = 19), peritoneum (n = 8), ovary          cytology = 28.1 months, p = 0.06                                                                 (p = 0.003), the absence of
(n = 6), retroperitoneum (n = 4), other                                                                                                       hepatic parenchymal metastases
(n = 4), unknown (n = 5)                     1-year overall survival = 60.6%                                                                  (p = 0.01), and complete
                                             3-year overall survival = 32.7%                                                                  resection of gross disease
                                                                                                                                              (p < 0.001).

Verwaal VJ (2004)5                           Completeness of cytoreduction:                         No safety data were reported              Some patients likely to also be
                                             Macroscopically complete = 51% (54/106)                                                          included in Verwaal et al (2003).
Case series                                  Nearly complete = 35% (37/106)
                                             Grossly incomplete = 14% (15/106)                                                                Signet cell carcinoma and older
1995–2003                                                                                                                                     age were significant risk factors
                                             Recurrence = 65% (69/106)                                                                        for a shorter survival.
The Netherlands
                                             Median survival:
106 patients                                 Complete cytoreduction = 11.1 months
                                             Nearly complete cytoreduction = 5.9 months
Median follow-up: 47.5 months (range         Gross residual tumour = 3.7 months
1.3–88.3 months)
                                             A shorter interval between the initial treatment of
Primary cancer sites: colon (n = 82),        carcinomatosis and recurrence was related to shorter
appendix (n = 15), rectum (n = 5),           survival after recurrence
unknown (n = 4)

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis   Page 7 of 14

Study details                                Key efficacy findings                                  Key safety findings                       Comments
Shen P (2003)                                Recurrence = 67.5% (52/77)                             Complications                             No randomisation.
                                                                                                     • Postoperative mortality = 11.7%
Case series                                  Median overall survival = 15.9 months                     (9/77)                                 Some patients likely to also be
                                                                                                     • Haematological toxic                   included in Shen P et al (2003).
Nebraska, USA                                3-year overall survival = 25.0%                           effects = 19.5% (15/77)
                                             5-year overall survival = 17.3%                         • Blood transfusion = 42.9% (33/77)      Four factors were significant
1991–2002                                                                                                                                     independent predictors of overall
                                                                                                      Overall perioperative morbidity = 30%   survival by multivariate analysis:
77 patients                                                                                                                                   Eastern Cooperative Oncology
                                                                                                                                              Group (ECOG) performance
Median age: 54 years                                                                                                                          status, completeness of
                                                                                                                                              resection, absence of bowel
Median follow-up: 15 months                                                                                                                   obstruction, absence of
                                                                                                                                              malignant ascites.
Primary cancer sites: colon (n = 74),
rectum (n = 3)

Inclusion criteria: histological diagnosis
of adenocarcinoma

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis   Page 8 of 14

Study details                                Key efficacy findings                                       Key safety findings                       Comments
Glehen O (2004)                              Overall median survival = 10.3 months                       Complications                             Consecutive patients.
                                             1-year overall survival = 48.1%                              • 30-day mortality = 4% (2/49)
Case series                                  2-year overall survival = 19.9%                              • Pleuritis = 6.1% (3/49)                During study period, 200 patients
                                             5-year overall survival = 16.0%                              • Occlusion = 6.1% (3/49)                with peritoneal carcinomatosis
1989–2000                                                                                                 • Ileocolic fistula = 4.0% (2/49)        originating from gastric cancer
                                                                                                          • Parietal collection = 2.0% (1/49)      presented to the department –
France                                       Patients with complete resection or limited residual         • Pancreatic fistula = 2.0% (1/49)       only 49 met the selection criteria
                                             disease:                                                     • Biliary peritonitis = 2.0% (1/49)      and gave informed consent. No
49 patients                                  Median survival = 21.3 months                                                                         data regarding the other 151
                                                                                                          • Peritonitis = 2.0% (1/49)
                                             1-year survival = 74.8%                                                                               patients were obtained.
                                                                                                          • Intraperitoneal abscess = 2.0%
Mean age: 53.7 years (range 27–70            2-year survival = 36.8%
years)                                       5-year survival = 29.4%                                                                               2% (1/49) patients lost to follow-
                                                                                                         Delayed complications
Median follow-up: 99 months
                                                                                                          • Retrograde ejaculation after 6         65.3% (32/49) patients did not
Inclusion criteria: age younger than                                                                         months = 2.0% (1/49)                  have extensive cytoreductive
70 years, gastric adenocarcinoma,                                                                         • Intestinal hernia after 2              debulking.
peritoneal carcinomatosis confirmed by                                                                       years = 2.0% (1/49)
cytological or pathological examination,                                                                  • Choledochal stenosis after 11          Intraperitoneal
synchronous or metachronous                                                                                  years = 2.0% (1/49) (attributed to    chemohyperthermia was delayed
peritoneal carcinomatosis, absence of                                                                        late adverse effect of irradiation)   in 42.9% (21/49) patients and
extra-abdominal metastases, no liver                                                                                                               performed after the resection of
metastases, satisfactory                                                                                                                           the primary tumour.
cardiorespiratory and renal status,
signed informed consent                                                                                                                            Completeness of cancer
                                                                                                                                                   resection and the absence of
Exclusion criteria: oesophageal                                                                                                                    preoperative ascites were both
adenocarcinoma, renal or myocardial                                                                                                                significantly associated with
failures, systemic chemotherapy                                                                                                                    improved survival.
1 month before inclusion, central
nervous system disease, World Health
Organisation index score greater than 2

Primary cancer site: stomach (49)

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis        Page 9 of 14
Validity and generalisability of the studies
•   Two studies were reported from the same centre during overlapping time
    periods.4,6 It is not clear how many of the patients were described in both reports.
•   It is difficult to compare outcomes for patients with peritoneal carcinomatosis
    arising from primary cancers at different sites. Studies have shown that the site of
    the primary cancer is an important factor for predicting survival.
•   It is likely that some of these studies included some patients with pseudomyxoma
    peritonei, who may have a better prognosis than patients with peritoneal
•   In the two studies that described the inclusion criteria in detail, patients were only
    included if they were younger than 71 years and fit for major surgery. 1,7 Three
    studies reported that they excluded patients with distant metastases. 1,3,7
•   Reported treatment regimens varied both within and between studies.

Specialist advisors’ opinions
Specialist advice was sought from consultants who have been nominated or ratified
by their Specialist Society or Royal College.

•   This procedure is only suitable for a small proportion of patients with
    carcinomatosis and published efficacy results apply to a highly selected group of
•   The procedure is complex and time consuming.
•   Extensive training and experience are required.

Issues for consideration by IPAC
None other than those described above.

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis   Page 10 of 14
 1   Verwaal VJ, van Ruth S, de Bree E et al. Randomized trial of cytoreduction and
     hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative
     surgery in patients with peritoneal cacinomatosis of colorectal cancer. Journal of Clinical
     Oncology 2003; 21: 3737–43.

 2   Fujimoto S, Takahashi M, Mutou T et al. Improved mortality rate of gastric carcinoma
     patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic
     chemoperfusion combined with surgery. Cancer 1997; 79: 884–91.

 3   Elias D, Blot F, El Otmany A et al. Curative treatment of peritoneal carcinomatosis
     arising from colorectal cancer by complete resection and intraperitoneal chemotherapy.
     Cancer 2001; 92: 71–6.

 4   Shen P, Levine EA, Hall J et al. Factors predicting survival after intraperitoneal
     hyperthermic chemotherapy with mitomycin C after cytoreductive surgery for patients
     with peritoneal carcinomatosis. Archives of Surgery 2003; 138: 26–33.

 5   Verwaal VJ, Boot H, Aleman BMP et al. Recurrences after peritoneal carcinomatosis of
     colorectal origin treated by cytoreduction and hyperthermic intraperitoneal
     chemotherapy: location, treatment, and outcome. Annals of Surgical Oncology 2004; 11:

 6   Shen P, Hawksworth J, Lovato J et al. Cytoreductive surgery and intraperitoneal
     hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis from
     nonappendiceal colorectal carcinoma. Annals of Surgical Oncology 2003; 11: 178–86.

 7   Glehen O, Schreiber V, Cotte E, et al. Cytoreductive surgery and intraperitoneal
     chemohyperthermia for peritoneal carcinomatosis arising from gastric cancer. Archives
     of Surgery 2004; 139: 20–6.

 8   Bryant J, Clegg AJ, Sidhu MK et al. Clinical effectiveness and costs of the Sugarbaker
     procedure for the treatment of pseudomyxoma peritonei, Health Technology Assessment
     2004; 8(7).

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis   Page 11 of 14
Appendix A: Additional papers on complete cytoreduction and heated
intraoperative intraperitoneal chemotherapy not included in the
summary tables (1)

Article title                                                  Number of      Comments         Direction of
                                                               patients/                       conclusions
Glehen O, Osinsky D, Cotte E et al. Intraperitoneal            207            Case series.     Postoperative
chemohyperthermia using a closed abdominal                     patients.      Results for      mortality = 3%.
procedure and cytoreductive surgery for the treatment                         different        Postoperative
of peritoneal carcinomatosis: morbidity and mortality                         treatment        morbidity = 24%.
analysis of 216 consecutive procedures. Annals of                             regimens         No efficacy data.
Surgical Oncology 2003; 10: 863–9.                                            combined.
Stephens AD, Alderman R, Chang D et al. Morbidity              200            Case series.     Treatment
and mortality analysis of 200 treatments with                  patients.      Includes         related
cytoreductive surgery and hyperthermic intraoperative                         patients with    mortality = 1.5%.
intraperitoneal chemotherapy using the Coliseum                               pseudo-          Grade 3/4
technique. Annals of Surgical Oncology 1999; 6: 790–                          myxoma           morbidity = 27%.
6.                                                                            peritonei.
Verwaal VJ, Tinteren HV, Ruth SV et al. Toxicity of            102            Case series.     Treatment
cytoreductive surgery and hyperthermic intra-peritoneal        patients.                       related
chemotherapy. Journal of Surgical Oncology 2004; 85:                                           mortality = 8%.
61–7.                                                                                          Surgical
                                                                                               complications =
                                                                                               Grade 3 toxicity
                                                                                               above = 65%.
Fujimura T, Yonemura Y, Kawamura T et al.                      96             Case series.     Cytoreductive
Cytoreductive surgery and sandwich therapy with                patients.      Includes         resection and/or
chemohyperthermic peritoneal perfusion and intra-                             patients with    chemo-
aortic chemotherapy for peritoneal dissemination in                           different        hyperthermic
gastric cancer. Oncology Reports 1996; 3: 513–7.                              treatment        peritoneal
                                                                              regimens.        perfusion
Loggie BW, Fleming RA, McQuellon RP et al.                     84             Case series.     Overall median
Cytoreductive surgery with intraperitoneal hyperthermic        patients.      Patients also    survival 14.3
chemotherapy for disseminated peritoneal cancer of             27 months      likely to be     months.
gastrointestinal origin. The American Surgeon 2000;            median         included in      1-year survival:
66: 561–8.                                                     follow-up.     Shen P, et al,   59%.
Pestieau SR, Sugarbaker PH. Treatment of primary               77             Compares         Extent of cancer
colon cancer with peritoneal carcinomatosis.                   patients.      patients         in abdomen and
Comparison of concomitant vs delayed management.                              treated at       pelvis at the time
Diseases of the Colon & Rectum 2000; 43: 1341–8.                              different        of treatment
                                                                              times after      correlated
                                                                              primary          directly with
                                                                              cancer.          survival.
Sugarbaker PH, Welch LS, Mohamed F et al. A review             68             Case series.     Postoperative
of peritoneal mesothelioma at the Washington Cancer            patients.      Includes         mortality = 7%.
Institute. Surgical Oncology Clinics of North America.                        patients with    Postoperative
2003; 12: 605–21.                                                             different        morbidity = 24%.
                                                                              treatment        median
                                                                              regimens.        survival = 67
Jacquet P, Stephens AD, Averbach AM et al. Analysis            60 patients    Case series.     Postoperative
of morbidity and mortality in 60 patients with peritoneal      (16 with       Patients also    mortality = 5%.
carcinomatosis treated by cytoreductive surgery and            pseudo-        likely to be     Postoperative
heated intraoperative intraperitoneal chemotherapy.            myxoma         included in      morbidity = 35%.
Cancer 1996; 77: 2622–9.                                       peritonei).    Stephens AD
                                                                              et al, 1999.

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis          Page 12 of 14
Article title                                                  Number of      Comments         Direction of
                                                               patients/                       conclusions
Fujimoto S, Takahashi M, Mutou T et al. Treatment              54             Case series.     At follow-up,
failures after intraperitoneal hyperthermic perfusion          patients.      Patients also    43% (23/54)
combined with surgery for advanced gastric cancer.                            likely to be     patients alive.
Regional Cancer Treatment 1996; 9: 164–9.                                     included in
                                                                              Fujimoto S,
                                                                              et al. 1997.
Glehen O, Cotte E, Schreiber V et al. Intraperitoneal          53             Case series.     Morbidity = 23%
chemohyperthermia and attempted cytoreductive                  patients.                       Mortality = 4%
surgery in patients with peritoneal carcinomatosis of          59.5 month                      Overall median
colorectal origin. British Journal of Surgery 2004; 91:        median                          survival = 12.8
747–54.                                                        follow-up.                      months.
Chen MY, Chiles C, Loggie BW et al. Thoracic                   42             Case series.     Thoracic
complications in patients undergoing intraperitoneal           patients.                       complications in
heated chemotherapy with mitomycin following                                                   86% (36/42)
cytoreductive surgery. Journal of Surgical Oncology                                            patients.
1997; 66: 19–23.
Yonemura Y, Fujimura T, Fushida S et al.                       41             Case series.     3-year
Hyperthermo-chemotherapy combined with                         patients.                       survival = 28%.
cytoreductive surgery for the treatment of gastric
cancer with peritoneal dissemination. World Journal of
Surgery 1991; 15: 530–5.
Cavaliere F, Di Filippo F, Botti C et al. Peritonectomy        35             Case series.     Postoperative
and hyperthermic antiblastic perfusion in the treatment        patients.                       mortality = 11%.
of peritoneal carcinomatosis. European Journal of              17 month                        Postoperative
Surgical Oncology 2000; 26: 486–91.                            mean                            morbidity = 54%.
                                                               follow-up.                      2-year
                                                                                               survival = 55%.
                                                                                               survival = 26
Rossi CR, Foletto M, Mocellin S et al. Hyperthermic            31             Case series.     Postoperative
intraoperative intraperitoneal chemotherapy with               patients.                       mortality = 0%.
cisplatin and doxorubicin in patients who undergo              19 month                        Postoperative
cytoreductive surgery for peritoneal carcinomatosis            median                          morbidity = 25%.
and sarcomatosis. Cancer 2002; 94: 492–9.                      follow-up.                      At follow-up,
                                                                                               29% (9/31)
                                                                                               patients died of
Elias DM and Pocard M. Treatment and prevention of             30             Case series.     Postoperative
peritoneal carcinomatosis from colorectal cancer.              patients.      Patients may     mortality = 8%.
Surgical Oncology Clinics of North America 2003; 12:           27 month       also be in       Postoperative
543–59.                                                        median         Elias D et al,   morbidity = 38%.
                                                               follow-up.     2001. 2          Survival:
                                                                                               1-year = 83%
                                                                                               2-year = 74%
                                                                                               3-year = 65%.

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis          Page 13 of 14
Appendix B: Literature search for complete cytoreduction and
heated intraoperative intraperitoneal chemotherapy
The following search strategy was used to identify papers in Medline. A similar
strategy was used to identify papers in EMBASE, Current Contents, PreMedline and
all EMB databases.

For all other databases a simple search strategy using the key words in the title was

1. exp Peritoneal Neoplasms/
2. exp Combined Modality Therapy/
3. 1 and 2
4. chem$.mp. and cytoreduct$.tw.
5. 3 and 4
6. (intraperitoneal adj chemo$ adj15 cytoreduct$).tw.
7. 6 and 1
8. 5 or 7
9. limit 8 to human

Complete cytoreduction and heated intraperitoneal chemotherapy for peritoneal carcinomatosis   Page 14 of 14

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