Summary and Future Directions

Abstract

Primary gastrointestinal neoplasms have the propensity to grow on the peritoneal surfaces. Peritoneal dissemination is a common mode of disease progression and recurrence in gastric (GC) and colorectal cancer (CRC) and represents the characteristic pathophysiological feature of pseudomyxoma peritonei (PMP). Peritoneal carcinomatosis (PC) of gastric (GCPC) and colorectal origin (CRCPC) and PMP are challenging entities in clinical practice. Owing to a grim natural history and poor prognosis, GCPC and CRCPC have been traditionally considered as a universally fatal condition treated with palliative intent. However, a renewed interest and paradigm shift in the treatment of PC developed in the 1980s with the introduction of cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy. This curative approach rests in the concept that PC is a locoregional disease and can thus be treated with locoregional approaches. Since the advent of this combination modality, accumulating evidence has variably supported its use for gastrointestinal PC. In this regard, PMP and PC from the appendiceal mucinous tumors are now recognized as a paradigm of success. The Fourth International Workshop on Peritoneal Surface Malignancy held in Spain in December 2004 determined as one of the key consensus points that “cytoreductive surgery combined with perioperative intraperitoneal chemotherapy is considered the current standard of care for all cases of mucinous appendiceal neoplasms with peritoneal dissemination, in an otherwise fit patient in the absence of distant metastases” (Gonzalez-Moreno, European Journal of Surgical Oncology 32: 593–596, 2006). This treatment option has also been advocated as the current standard of care for select patients with CRCPC. Despite definite benefits of CRS and perioperative intraperitoneal chemotherapy for select patients with gastrointestinal PC, this modality is frequently associated with treatment failure and recurrence. Thus, additional efforts should be made to enhance microscopic cytoreduction by optimizing the peritoneal chemotherapy, as well as by developing novel modalities directed at microscopic residues and peritoneal free cancer cells. The present project aimed to investigate the efficacy of a novel approach in the management of gastrointestinal PC and PMP, based on the merits of single agent or combination therapy with bromelain (BR) and N-acetylcysteine (NAC). The closing chapter of this book provides a brief summary of the study and our findings, and outlines possible directions for future research.