Improved prognosis following peritonectomy procedures and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from appendiceal carcinoma

EJSO 2001; 27: 286–290
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 P. Piso∗, 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 Aims: 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.
Key words: appendiceal carcinoma; peritonectomy; intraperitoneal chemotherapy.
INTRODUCTION
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 Surgical therapy
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 resection (n=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 Survival
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 DISCUSSION
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=2). One 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. Boston/Dordrecht/London: Kluver particularly during our initial experience with this 6. Sugarbaker PH. Peritonectomy Procedures. Ann Surg 1995; 221:
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 1994; 41: 207–13.
this multimodality treatment. Patients in whom complete 8. Gilly FN, Carry PY, Sayag AC, et al. Regional chemotherapy (with Mitomycin C) and intra-operative hyperthermia for digestive cytoreduction is achieved are most likely to benefit from peritonectomy and intraperitoneal chemotherapy. The Gastroenterology 1994; 41: 124–9.
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 Oncol 2000; 6: 727–31.
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
Surg 1995; 19: 235–40.
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 1999; 384: 576–87.
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. Intraoperative (hypertherme) operative morbidity was increased mainly due to ‘‘non- sicheren intra- und postoperativen Umgang mit Zystostatika.
Langenbecks Arch Chir 1997; 382: 8–14.
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 Hepato-Gastroenterology 1999; 46: 601–609.
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
1998; 63: 1251–61.
16. O’Dwyer PJ, LaCreta F, Hogan M, et al. Pharmacologic study of etoposide and cisplatin by the intraperitoneal route. J Clin Pharmacol REFERENCES
1991; 31: 253–8.
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 1992; 52: 1252–8.
of peritoneal carcinomatosis. PPO Updates 1995; 9: 1–9.
18. Gratz KF, Ja¨hne J, Hamman A, et al. Szintigraphische U 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 1997; 36:
1989; 63: 364–7.
3. Sadeghi B, Arvieux C, Glehen O, et al. Peritoneal carcinomatosis 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 2000; 88: 358–63.
Oncol 1999; 26 (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 1995; 221: 124–32.
technique. Ann Surg Oncol 2000; 6: 790–6.
5. Sugarbaker PH. Observations concerning cancer spread within the Accepted for publication 4 December 2000

Source: http://webserver.barmherzige.de/fileadmin/user_upload/kh_regensburg/Kliniken/Allg_Visz_Chir/Peritoneal/Publikationen_Improved_Prognosis.pdf