Technology of hyperthermic intraperitoneal chemotherapy in the United States, Europe, China, Japan, and Korea

Significant improvements in the understanding of the biologic behavior of peritoneal surface malignancies in addition to the combination of peritonectomy procedures that allow complete eradication of macroscopic peritoneal disease and hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of surgery, directed at residual microscopic disease, have change the therapeutic strategy from a palliative approach to a curative intent in a selected group of patients with peritoneal carcinomatosis. The rationale for adding HIPEC is supported by the strong pharmacological advantage over systemic therapy. Because of the peritoneal-plasma barrier, intraperitoneal administration of chemotherapy results in intraperitoneal levels that are 20 to 1000 times higher than plasma levels. The chemotherapy not only directly destroys tumor cells, but also eliminates viable platelets, neutrophils, and monocytes from the peritoneal cavity. This diminishes the promotion of tumor growth associated with the wound healing process. In addition, combining the intraperitoneal chemotherapy with hyperthermia has several advantages. Heat by itself has more toxicity for cancerous tissue than for normal tissue, and this predominant effect on cancer increases as the vascularity of the malignancy decreases. Also, hyperthermia increases the penetration of chemotherapy into tissues. As tissues soften in response to heat, the elevated interstitial pressure of a tumor mass may decrease and allow improved drug penetration. Lastly, and probably most important, heat increases the cytotoxicity of selected chemotherapy agents. This synergism occurs only at the interface of heat and body tissue at the peritoneal surface. However, despite the wider acceptance to combine extensive cytoreductive surgery with intraoperative intraperitoneal heated chemotherapy, the specifics of the HIPEC administration continue to lack uniformity. The most recent consensus statement issued by the Peritoneal Surface Oncology Group International after the 2006 meeting in Milan concluded that the debate on the best method to deliver HIPEC is still open, and as a group, we declared that there is no sufficient evidence in the literature confirming the superiority of one technique over the other in terms of outcome, morbidity, and safety to the personnel in the operating room.