Progress in prevention and treatment of peritoneal metastases by cytoreductive surgery

Armed with a new chemotherapy agent, mitomycin C, developed in Japan and sensitized by heat, three groups in Japan began successful experimental studies to treat gastric cancer patients at high risk of developing subsequent peritoneal metastatic disease 1-3 .At the Surgery Branch, National Institutes of Health, we did not have access to the mitomycin C.However, our pharmacologic studies with intraperitoneal 5-fluorouracil showed a marked local-regional dose intensification with a reduced systemic toxicity 4 .In the 1980s rectal cancer had a 40.0%local recurrence rate; a decision was made to perform an RCT of colorectal cancer patients that had a complete resection of their primary disease but were at high risk for subsequent peritoneal metastases.After carefully evaluating patients with a colorectal cancer resection who had advanced disease, they were randomized to receive either intravenous or intraperitoneal 5-fluorouracil over a one-year period 5 .The data from this trial were favourable regarding the local-regional effects of 5-fluorouracil.Progression of disease on abdominal and pelvic surfaces was significantly reduced.In contrast, the systemic component of colorectal cancer was the same in both groups.For colorectal cancer, despite the marked reduction in the incidence of peritoneal metastases in the intraperitoneal 5-fluorouracil group, there was no survival difference.In an attempt to utilize the positive data from this RCT, we began to recruit patients with pseudomyxoma peritonei for prolonged treatment with intraperitoneal 5-fluorouracil.This strategy is currently referred to as normothermic intraperitoneal chemotherapy long term or NIPEC long term.Pseudomyxoma peritonei patients did not develop liver or systemic metastases.The seemingly insurmountable obstacle to the benefit of our patients was the large volume of tumour on peritoneal surfaces that intraperitoneal chemotherapy failed to penetrate.The only way to utilize intraperitoneal 5-fluorouracil was to resect the extensive peritoneal mucinous tumour.A two-part treatment strategy was pursued.Following complete microscopic resection, the intraperitoneal chemotherapy would be used to eradicate microscopic residual disease.As it turned out, pseudomyxoma peritonei was a good choice for resection of large volumes of peritoneal surface tumour in preparation for flooding the peritoneal space, now visibly free of disease, with chemotherapy.The low-grade and minimally invasive mucinous tumour is characterized by the 'redistribution phenomenon'.The glistening smooth visceral peritoneal surfaces are tightly bonded to underlying organs such as liver, spleen, and