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.
ReviewPeritoneal carcinomatosis from digestive tract cancer: new management by cytoreductive surgery and intraperitoneal chemohyperthermia
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
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