Malignant peritoneal mesothelioma

This paper summarizes the author's thoughts about the use of cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy (CS-IPHC) for treatment of peritoneal malignant mesothelioma. Pleural malignant mesotheliomas are by far more common (about ten- to thirty-fold) than the peritoneal variants (2.2 cases per 1 million in the US). Other locations (pericardium, tunica vaginalis) are very rare. It is well known that chemotherapy for mesothelioma is largely unsatisfactory, and measurement of treatment responses can be difficult. Single agent responses are all less than 20% with currently available agents for systemically administered drugs. Multiple drug combinations are typically more toxic, and have yielded little consistent demonstrable benefit with major studies reporting median survivals consistently under a year. There is currently more attention being paid to the response category of "stable" or absence of disease progression in concert with quality of life measurements; all regimens show poor durability. With peritoneal malignant mesothelioma, malignant ascites is a common presentation and a major factor in disease-related morbidity and mortality. Interperitoneal administration of agents is attractive, but drug distribution is an issue, as are response rates and durability. Multiple treatments are required; further, all neoplasms with peritoneal dissemination are typically understaged by current radiologic tests (CT, MRI), and the variable uptake of sugar by the small bowel limits the use of positron-emission tomography (PET) imaging for peritoneal malignant mesothelioma. Also, symptoms of bowel obstruction are not uncommon, and any mechanical component of obstruction will not improve with any form of chemotherapy. The author's approach relies on surgery to achieve the following: 1) accurate staging; 2) tumor debulking, as possible, and treatment of mechanical obstruction as well as prevention of impending obstruction by resection or bypass; and 3) preparation for the use of intra-operative hyperthermic chemotherapy perfusion. This approach has been associated with rapid clinical symptom improvement, as well as a reliable and durable resolution of ascites with a single therapy. Morbidity and mortality have been acceptable with about 27-month median survival. The inability to provide effective systemic therapy to maintain or consolidate these gains is problematic.