Elsevier

The Lancet Oncology

Volume 5, Issue 4, April 2004, Pages 219-228
The Lancet Oncology

Review
Peritoneal carcinomatosis from digestive tract cancer: new management by cytoreductive surgery and intraperitoneal chemohyperthermia

https://doi.org/10.1016/S1470-2045(04)01425-1Get rights and content

Summary

Peritoneal carcinomatosis is a common manifestation of digestive-tract cancer and has been regarded a terminal disease with a short median survival. Over the past decade, a new locoregional therapeutic approach combining cytoreductive surgery with intraperitoneal chemohyperthermia (IPCH) has evolved. Because of its limited benefits, high morbidity and mortality, and high cost, this comprehensive management plan requires accurate patient selection. Quantitative prognostic indicators are needed to assess a patient's eligibility for combined treatment, including tumour histopathology, classification of carcinomatosis extent, assessment of completeness of cytoreduction, and determination of the extent of previous surgery. Patients with pseudomyxoma peritonei and those with peritoneal dissemination of digestive-tract cancer have shown promising survival. Complete cytoreduction with no visible disease persisting is a requirement for long-term benefit. In Japan and Korea, use of IPCH as prophylactic treatment in potentially curative gastric-cancer resection has shown improved survival and lower peritoneal recurrence rates. IPCH combined with cytoreductive surgery seems to be an effective therapeutic approach in carefully selected patients, and offers a chance for cure or palliation in this condition with few alternative treatment options.

Section snippets

Natural history

The primary peritoneal malignant disorders such as malignant mesothelioma and papillary serous carcinoma are rare. By contrast, peritoneal dissemination from digestive cancers is common. In colorectal cancer, despite advances in early detection of the primary tumour, carcinomatosis is detected in about 10% of patients at the time of primary cancer resection.2, 3 10–20% of patients being investigated for potentially curative resection of gastric cancer will have peritoneal seeding at the time of

Assessment of prognosis

Quantitative prognostic indicators have been used successfully in several surgical disciplines and serve as guidelines to select patients who are most likely to respond to treatment. Often, the major value of the quantitative prognostic assessment is to exclude patients who have little or no chance of benefiting from expensive, high-risk management protocols. Several specialised teams have identified a series of clinical assessments to select patients for cytoreduction plus perioperative

Rationale for locoregional treatment IPCH

Intraperitoneal administration of anticancer drugs has many pharmacokinetic advantages and gives high response rates within the abdomen compared with other treatments because the peritoneal plasma barrier provides dose-intensive therapy. High concentrations of anticancer drugs can be in direct contact with tumour cells, with reduced systemic concentrations and lower systemic toxicity.37 Heat has been shown to be cytotoxic in vitro at 42·5°C.38 Hyperthermia at 42°C has been shown to enhance the

Devices

Several different IPCH devices have been described.45 Constant hyperthermia is obtained by a closed continuous circuit, with pump, heater, heat exchanger, and real-time temperature monitoring. Figure 3 illustrates the Lyon closed circuit. Open circuits (without recirculation and reheating of the instillate) should be avoided.41

Elias and colleagues45 did a prospective phase II trial testing seven different techniques in 32 patients. They found that complete closure of the abdominal wall before

Duration, perfusate, and drugs

The volume of perfusate used in the different protocols is calculated according to the body surface area. Most teams have used isotonic perfusate, since hypotonic solution can cause intraperitoneal haemorrhage.48 Pharmacokinetic studies done at the Washington Cancer Institute showed that use of hypertonic carrier solution enhanced the exposure of peritoneal surfaces and of residual tumour cells to anticancer drugs.49, 50

The duration of the procedure varies according to investigators from 30 min

Cytoreductive surgery and peritonectomy

To be effective, IPCH must be preceded by comprehensive cytoreductive surgery to remove as much tumour as possible. The objective is to clear the entire abdominal cavity of all macroscopic detectable disease. Procedures for cytoreductive surgery and peritonectomy have been described extensively by Sugarbaker.6 When the tumour involves visceral peritoneal surfaces, organ resections (splenectomy, large bowel or small-bowel resection) are needed. When it involves parietal peritoneal surfaces,

Indications

IPCH after cytoreductive surgery has been used with palliative or curative intent as well as prophylactic treatment for gastric cancer in some Japanese and Korean studies. A consensus for its indications has been established within peritoneal-surface-malignancy treatment centres but has not been validated by large prospective studies.

Contraindications

Because of their poor prognosis and difficulty in locoregional control, carcinomatosis of pancreatic or hepatobiliary origin are not suitable for IPCH. Extraabdominal metastases or massive retroperitoneal lymphnode involvement are also an absolute contraindication.37, 41 An aggressive locoregional treatment cannot be envisaged with non-controlled systemic disease. Liver metastases are a classic contraindication for this combined therapeutic approach, but are controversial, especially when

Morbidity and mortality

The main morbidities associated with IPCH combined with cytoreductive surgery are caused by complications of surgery: anastomotic leakages, intraperitoneal sepsis or abscesses. In view of variations in surgical treatment, IPCH devices, and carcinomatosis origin, the analysis of reported studies is difficult (table 3).61, 62, 63, 64

Colorectal carcinomatosis

The survival results reported by many investigators show the importance of residual tumour volume after cytoreductive surgery (table 4). With a median follow-up of more than 4 years, Elias and colleagues,12 who treated 56 patients with complete cytoreductive surgery followed by early postoperative intraperitoneal chemotherapy or IPCH, reported 3-year and 5-year survival rates of 47% and 27%, respectively. All phase II studies reported median survival of longer than 2 years for patients treated

Adjuvant IPCH for gastric cancer

Over the past decade, four randomised studies from Japan and Korea have investigated use of IPCH as adjuvant treatment after potentially curative gastric-cancer resection. The oldest study found no significant difference in survival between the group treated with surgery followed by IPCH and the group treated with surgery alone.73 This finding was probably because of the small number of patients included. The three other studies were positive. Fujimoto and colleagues74 included 141 patients and

Conclusion

IPCH in combination with cytoreductive surgery and peritonectomy procedures is still under investigation for treatment of carcinomatosis from digestive-tract cancer. The IPCH techniques, the surgical procedures, and the indications are not yet standardised. The survival results of many prospective studies are promising despite high morbidity, which emphasises the importance of careful patient selection. IPCH has a potential role as adjuvant treatment for potentially curative gastric-cancer

Search strategy and selection criteria

References were selected from our own collections. We identified additional references by searching MEDLINE and PubMed using the search terms “carcinomatosis”, “intraperitoneal chemotherapy”, and “hyperthermia”. We also searched references from relevant articles and the abstracts of international conferences. Only reports published in French or English and published between January, 1963, and December, 2003, were selected.

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