Improved prognosis following peritonectomy procedures and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from appendiceal carcinoma
doi:10.1053/ejso.2000.1095, available online at http://www.idealibrary.com on
Improved prognosis following peritonectomyprocedures and hyperthermic intraperitonealchemotherapy for peritoneal carcinomatosisfrom appendiceal carcinoma
∗, H. Bektas
∗, U. Werner
∗, H. J. Schlitt, S. Kubicka†,
A. Bornscheuer‡, M. Manns† and J. Klempnauer
∗Klinik fu¨r Viszeral- und Transplantationschirurgie, Zentrum Chirurgie, Medizinische Hochschule Hannover; †Abteilung Gastroenterologieund Hepatologie, Zentrum Innere Medizin, Medizinische Hochschule Hannover; ‡Abteilung Anaesthesiologie I, Zentrum Anaesthesiologie,Medizinische Hochschule Hannover
The prognosis of patients with peritoneal carcinomatosis from gastrointestinal malignancies is poor. The aim
of this study was to analyse the results of multimodality treatment for peritoneal carcinomatosis of appendiceal
carcinoma.Patients and methods:
From 07/95 to 01/00, 17 patients (13 males, 4 female, median age 58 years) underwent
peritonectomy procedures in combination with intraperitoneal hyperthermic chemotherapy. Surgical, pathological
and survival data were analysed retrospectively.Results:
All patients had undergone previous surgical treatment and one patient had received chemotherapy. In all
patients peritonectomy procedures, as described by Sugarbaker, were performed with the aim of achieving a
macroscopically complete cytoreduction (range 2–6, median 4 procedures per patient). Following resection, open
hyperthermic intraperitoneal chemotherapy with cisplatin was performed. Eleven patients had postoperative com-
plications (predominantly ‘‘non-surgical’’) and two patients died postoperatively. The 4-year survival rate was 75%.
Complete cytoreducion had a statistically significant positive influence on long-term survival.Conclusions:
In selected patients (WHO status 0/1, minimal residual disease, no distant metastases, complete
cytoreduction), the prognosis for patients with peritoneal carcinomatosis of appendiceal origin can be improved by
peritonectomy procedures and hyperthermic intraperitoneal chemotherapy. Postoperative morbidity may be increased
due to ‘‘non-surgical’’ complications.
appendiceal carcinoma; peritonectomy; intraperitoneal chemotherapy.
The prognosis of many patients with gastrointestinal
chemotherapy has improved the prognosis of some
malignancies is poor due to peritoneal carcinomatosis,
defined groups of patients, in particular those with
natural history of peritoneal carcinomatosis from non-
Due to the physiological circulation of peritoneal fluid
gynaecological malignancies is dismal, with a median
and tumour cell entrapment, peritoneal carcinomatosis
survival time of 3 to 9 No effective treatment
tends to occur in certain areas of the peritoneal surface,
option is available for patients with extensive peritoneal
preferentially on the undersurface of the diaphragm, the
liver surface, the lesser omentum, the bursa omentalis,
Over the last decade the concept of complete surgical
the mesocolon and in the All peritoneal nodulesin these areas should be removed during resection. Basedon the typical distribution of the nodules, resection typeswere systematized into six so-called ‘‘peritonectomy
Correspondence to: Dr Pompiliu Piso, Klinik fu¨r Viszeral- und
procedures’Thus between one and six peritonectomy
Transplantationschirurgie, Medizinische Hochschule Hannover, Carl-
procedures may be necessary to obtain a complete
Neuberg Str. 1, 30625 Hannover, Germany. Tel: +49-511-5326534;Fax: +49-511-5324010; E-mail: [email protected]
clearance of the peritoneal surface. After resection,
IMPROVED PROGNOSIS FOLLOWING PERITONECTOMY
Demographic characteristics of 17 patients
between the first operation and the multivisceral
treated for peritoneal carcinomatosis from appendiceal
resection was 5.3 months (range 1–22). In one case
peritoneal carcinomatosis was diagnosed by paracentesisand cytological examination of the ascitic fluid, in three
cases by laparoscopy and in 13 patients by laparotomy. All
primary tumours were well differentiated (G1). Distant
peritonectomy procedures as previously defined by
Sugarbaker. A median of four peritonectomy procedures
macroscopically complete tumour resection. Following
chemotherapy with cisplatin (150 mg/m2) was performed.
Previous oncological treatment of all operated
As previously described, we used the Colliseum
technique (Inflow: one Tenckhoff-catheter, Outflow:
three Jackson–Platt drains), with manual distribution ofheated chemotherapy fluid in the abdominal cavity for
from 41° to 42°C and was monitored by two
temperature probes placed in the pelvis and alongside the
Tenckhoff catheter. The fluid containing chemotherapy
(1.5–3 litres) was circulated by a rollerpump, with a heat
exchanger in the circuit. All information was recordedin a peritoneal carcinomatosis database, including
hyperthermic chemotherapy is performed in order to
epidemiological, surgical, pathological and survival data.
destroy free tumour cells or small residual nodules (up
Survival rates were calculated by the Kaplan–Meier
to 2–3 mm). Hyperthermia has an independent cytotoxic
method and statistical significance was assessed with the
effect and also increases the antiproliferative activity of
log-rank test using the Statistical Package for the Social
This treatment was pioneered by Sugarbaker in
Probabilities of less than 0.05 were accepted as significant.
Washington (USA) and the number of patients treatedby his group has now risen to over Adequate
patient selection is important for the success of thistreatment The best results are obtained in
asymptomatic patients with small-volume peritoneal-
In all patients cytoreductive surgery was possible using
surface malignancies in whom complete cytoreduction
the peritonectomy procedures (median 4 procedures
is possible. Low-grade histology and the absence of
per patient, range 2–6) (Table 3). In some cases extended
surgery (separate from the peritonectomy procedures)
In 1995 we started to treat patients with peritoneal
carcinomatosis of appendiceal origin by multimodality
treatment, and the aim of this study was to analyse the
subsegmental liver resection (n
=3), partial diaphragmatic
=9) and ovariectomy (n
=2). The medianoperating time was 9 hours (range 4–12). Six units ofblood per patient were administered during surgery
PATIENTS AND METHODS
(range 3–18). The median number of gastrointestinal
From July 1995 to January 2000, 17 patients with
anastomoses performed was one (range 0–4).
peritoneal carcinomatosis from an appendiceal carcinoma
Macroscopically complete cytoreduction was achieved
were operated upon (Table 1) in the Klinik fu¨r Viszeral-
in 12 patients (70%). In five patients small nodules up to
und Transplantationschirurgie of the Medical School of
2–3 mm, mainly penetrating the small intestine, were not
Hannover. Another seven patients who were referred
resectable so that only incomplete cytoreduction was
to our department were excluded from this protocol
because they had distant metastases or large tumourmasses in the small bowel mesentery.
Postoperative morbidity and mortality
All patients had undergone previous surgery and one
of them had been treated preoperatively with systemic
chemotherapy (Table 2). The median time interval
postoperatively. ‘‘Non-surgical’’ complications occurred
Description of the peritonectomy procedures (according to Sugarbaker) performed in 17 patients with peritoneal
carcinomatosis from appendiceal carcinoma
Surgical and non-surgical complication after
patient died due to peritonitis after small bowel
peritonectomy procedures combined with hyperthermic
perforation and anastomotic leak, the other patient died
The overall mean survival time was 39±4 months and
the 4-year survival rate was 75% (Figure 1). The
completeness of resection influenced the long-term
survival, which was better for patients with complete
Pioneered by Sugarbaker, the therapy of peritoneal
surface malignancies has advanced over the last two
decades, particularly after good results were obtained
demonstrating the efficacy of cytoreductive surgery
peritoneal carcinomatosis of appendiceal Single-institution data for more than 400 patients withthis disease have been reported and the results areencouraging, with a 5-year survival rate of
more often than ‘‘surgical’’ and included morbidity dueto
characteristics of the patients who experienced grade II
we have treated patients with peritoneal carcinomatosis
or III renal toxicity are described in Table 5. In five cases
in a different fashion since 1995. We changed our
further surgery was required (30%), in all other cases
approach by trying to achieve a macroscopically complete
complications were treated medically.
resection of peritoneal nodules, then administering open
The hospital mortality rate was 11% (n
intraperitoneal hyperthermic chemotherapy.
IMPROVED PROGNOSIS FOLLOWING PERITONECTOMY
Characteristics of the four patients who experienced grade II or III renal toxicity after peritonectomy and
intraperitoneal hyperthermic chemotherapy
volume are good candidates for this aggressive treatment.
However, massive tumour involvement of the small-
bowel mesentery, an inability to achieve complete
cytoreduction and the presence of haematogenous
As this selection is usually very difficult,
attempts were made to systematize this procedure, for
instance with the introduction of the Peritoneal Cancer
This also made possible the comparison of results
In our series we re-operated upon these patients with
cytoreduction, an average of 5.3 months after primary
Overall survival of 17 patients with peritoneal
intraperitoneal chemotherapy was performed using
peritonectomy and intraperitoneal chemotherpy.
cisplatin, as reported by although other agentshave also been used for intraperitoneal therapy (e.g.
Chemotherapy was combined with hyperthermia in
temperatures we achieved (41° to 42°C) are similar to
published We preferred the open technique
because by this method a homogeneous distribution of
chemotherapy into the abdominal cavity can be
scintigraphy that some areas of the peritoneal surface
are not reached by chemotherapy during closed
As others have reported, we found an increased
postoperative morbidity and mortality after extended
Influence of the completeness of cytoreduction on
Most of the complications were either haematological
the prognosis of patients with peritoneal carcinomatosis from
or renal, and were reversible. Of the patients who
appendiceal carcinoma treated by cytoreductive surgery and
experienced grade II or III renal toxicity, one patient
complications, with bowel perforation and peritonitis,so that the impaired renal function had multiple causes.
More experienced centres have shown that not every
The use of protective agents such as Amofostine can
patient with peritoneal carcinomatosis can be treated in
this way and that many patients with advanced disease
experienced centres have found that morbidity correlates
have been treated with minimal Patients who
particularly with the extent of and not so
are selected for the treatment should be in a good
much with increased intra-abdominal temperature. It is
general condition so that they will tolerate major surgery.
likely that the results are influenced by the ‘‘learning-
Patients with non-invasive carcinomas and low tumour
curve’’ of this complex treatment strategy. This may
pathophysiology. In: Sugarbaker PH (ed). Peritoneal carcinomatosis
explain why major complications and deaths were noticed
– Principles of Management.
particularly during our initial experience with this
6. Sugarbaker PH. Peritonectomy Procedures. Ann Surg
Our survival data showing improved prognosis for
7. Elias D, Detroz B, Debaene B, et al.
Treatment of peritoneal
appendiceal carcinoma are in line with other
carcinomatosis by intraperitoneal chemo-hyperthermia: reliable
and demonstrate that achieving cure is a realistic aim of
and unreliable concepts. Hepato-Gastroenterology
this multimodality treatment. Patients in whom complete
8. Gilly FN, Carry PY, Sayag AC, et al.
(with Mitomycin C) and intra-operative hyperthermia for digestive
cytoreduction is achieved are most likely to benefit from
peritonectomy and intraperitoneal chemotherapy. The
survival figures are better than our historical control
9. Sugarbaker PH, Chang D. Results of treatment of 385 patients
with peritoneal surface spread of appendiceal malignancy. Ann Surg
data; however, a randomized trial in this patient
population would be very difficult to justify as no real
10. Sugarbaker PH. Patient selection and treatment of peritoneal
alternative treatment strategies exist.
carcinomatosis from colorectal and appendiceal cancer. World J
We conclude that in selected patients (WHO status
11. Sugarbaker PH. Management of peritoneal-surface malignancy: the
0/1, minimal residual disease, no distant metastases,
surgeon’s rule. Langenbecks Arch Surg
complete cytoreduction) with peritoneal carcinomatosis
12. Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive
surgery: Manual for physicians and nurses.
3rd ed. Gran Rapids, MI:
from appendiceal carcinoma, the prognosis can be
13. Ja¨hne J, Piso P, Schmoll E, et al.
operative morbidity was increased mainly due to ‘‘non-
sicheren intra- und postoperativen Umgang mit Zystostatika.Langenbecks Arch Chir
surgical’’ complications. However, changes due to renal
14. Yonemura Y, Fujimura T, Fushida S, et al.
A new surgical approach
and bone marrow toxicity were reversible. Multicentre
(peritonectomy) for the treatment of peritoneal dissemination.
studies have to be designed in order to find the best
15. Barlett DL, Buell JF, Libutti SK, et al.
A Phase I trial of continuous
treatment strategies for these patients, as most centres
hyperthermic peritoneal perfusion with tumor necrosis factor and
deal with only small numbers of cases.
cisplatin in the treatment of peritoneal carcinomatosis. Cancer
16. O’Dwyer PJ, LaCreta F, Hogan M, et al.
Pharmacologic study of
etoposide and cisplatin by the intraperitoneal route. J Clin Pharmacol
17. Los G, Smals AG, van Vugt MJH, et al.
A rationale for carboplatin
1. Alexander HR, Buel JF, Fraker D. Rationale and clinical status of
treatment and abdominal hyperthermia in cancers restricted to
continuous hyperthermic peritoneal perfusion for the treatment
the peritoneal cavity. Cancer Research
of peritoneal carcinomatosis. PPO Updates
18. Gratz KF, Ja¨hne J, Hamman A, et al.
2. Chu DZD, Lang NP, Thompson C, Osteen PK, Westbrook KC.
der Funktion intraperitoneal liegender Katheter zur regionalen
Peritoneal carcinomatosis in nongynecologic malignancy. Cancer
intraabdominellen Chemotherapie. Nuklearmedizin
3. Sadeghi B, Arvieux C, Glehen O, et al.
19. Capizzi RL. Amifostine reducers the incidence of cumulative
from non-gynecologic malignancies: results of the EVOCAPE 1
nephrotoxicity from cisplatin: laboratory and clinical aspects. Semin
multicentric prospective study. Cancer
(suppl. 7): 72–81.
4. Sugarbaker PH, Jablonski KA. Prognostic features of 51 colorectal
20. Stephens AD, Aldermann R, Chang D, et al.
Morbidity and mortality
and 130 appendiceal cancer patients with peritoneal carcinomatosis
analysis of 200 treatments with cytoreductive surgery and
hyperthermic intraoperative chemotherapy using the Coliseum
chemotherapy. Ann Surg
technique. Ann Surg Oncol
5. Sugarbaker PH. Observations concerning cancer spread within the
Accepted for publication 4 December 2000
Tender Document Hardware & Software Products & Specifications National ICT R&D Fund intends to procure the following hardware & software items. Hardware Products S. # Product Specification Quantity Laptop (Category 1) Processor: Intel Core i5, Minimum 2.3 GHz Optical Drive: Blue Ray Reader, CD/ DVD±RW Connectivity: Ethernet, WiFi, USB 2/3, Bluetooth, HD
Mergers and acquisitions When battles commence Feb 19th 2004 | LONDON, NEW YORK AND TOKYO From The Economist print edition Hostile bids are back again. Who should rejoice? Get article background THIS week, in both America and Europe, corporate bosses locked horns as the biggest hostile bids in years twisted and turned their way towards a denouement. Even in gentle