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Theoretical Considerations for Optimal Cytoreductive Surgery Plus Hyperthermic Perioperative Chemotherapy

Domenico Sabia, Paul H. Sugarbaker

Background: The concepts regarding the definitive management of peritoneal metastases seems straightforward in that surgery is to remove all visible disease and then intraperitoneal chemotherapy is used to eradicate minimal residual disease. However, implementation of this management strategy presents numerous patient-related, methodologic, and pharmacologic variables. Methods: In order to optimize cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC), important theoretical considerations for implementation of this management strategy are presented. The aim of the study is to integrate these modifications in the treatment of abdominal and pelvic malignancy into practice and thereby improve outcomes. Results: Surgical technology to achieve a complete response is necessary but not sufficient to optimally pursue a curative treatment option. Strategies to initiate treatments with the lowest possible peritoneal cancer index (PCI) involve proactive treatments of the primary gastrointestinal cancer, neoadjuvant chemotherapy, initiation of treatments at the first diagnosis of peritoneal metastases, and the use of laparoscopy and radiology to select patients. Tumor cell entrapment should be avoided. Mechanical removal of cancer cells by vigorous irrigation techniques carries minimal risk and may reduce residual disease. Chemotherapy agents that cause a response, result in prolonged intraperitoneal drug retention and show a high peritoneal to plasma concentration ratio are recommended. Finally, long-term bidirectional adjuvant normothermic chemotherapy (BANC) has been shown in randomized trials in ovarian cancer to improve survival and may be of value in other diseases. Conclusions: Despite the complexity of patient management using CRS and HIPEC, application of six basic principles promise to contribute to the results of treatment of peritoneal metastases.