The “Alphabet Soup” of Peritoneal Dissemination From Appendiceal Neoplasms and Other Malignancies

Abstract

Appendiceal neoplasms are a rare clinical entity that typify the real estate adage: location is everything. Similar to the pathophysiology of appendicitis, increasing intraluminal pressure from tumor obstruction or mucin production leads to appendiceal rupture with subsequent peritoneal dissemination (PD). By definition, this is considered stage IV disease for gastrointestinal cancers because of the poor prognosis associated with the clinical inability to control tumor progression. But does PD require the same inherent biological aggressiveness as lymphatic or hematogenous spread? The answer to this question is ‘‘not always.’’ For example, accidental spillage of an appendiceal adenoma will lead to PD despite a negligible risk for hematogenous metastases. This may also be true for an early-stage colorectal cancer. In this issue of the Annals, there are two articles—one by Stewart et al. and one by Sugarbaker et al.—regarding studies that used cytoreductive surgery (CS) and regional peritoneal therapy for PD from appendiceal neoplasms; they illustrate the evolution of a focused regional approach for, primarily, a locoregional problem. As previously noted by other authors, the treatment of PD from appendiceal neoplasms serves as an excellent example of Dr. Blake Cady s philosophy: ‘‘In the field of surgical oncology, tumor biology is king, patient selection is queen, and technical maneuvers are the prince and princess who try, but usually fail, to usurp the throne.’’ Historically, PD from appendiceal neoplasms has been categorized as either a nonmucinous high-grade tumor (similar to colorectal cancer) or as pseudomyxoma peritonei (PMP). Clinically, PMP presents as abundant intra-abdominal mucin secondary to disseminated tumor. Systemic chemotherapy has rarely been effective for this disease as a result of the overall slow growth of PMP in general, the ability of microscopic cells to survive in the peritoneal cavity by diffusion alone (i.e., no established blood supply), and limited drug penetration secondary to the plasma/peritoneal barrier. The majority of appendiceal PMP patients succumb to intra-abdominal complications (obstruction or perforation), malnutrition, or a declining performance status secondary to progressive, symptomatic mucin/tumor. Consequently, palliative surgical debulking initially evolved as the primary treatment modality to maintain a patent, functional gastrointestinal tract. Even after complete debulking of gross disease, microscopic tumor is present that invariably leads to recurrence. Attempts to eradicate this residual subclinical disease have led to the development of regional therapy approaches such as CS with intraperitoneal hyperthermic chemoperfusion (IPHC), also known as hyperthermic intraperitoneal chemotherapy, hyperthermic intraoperative intraperitoneal chemotherapy, continuous hyperthermic peritoneal perfusion chemotherapy, intraperitoneal hyperthermic perfusion, or hyperthermic antiblastic peritoneal perfusion. Biologically, PMP is actually a spectrum of aggressiveness ranging from diffuse peritoneal adenomucinosis (DPAM) to peritoneal mucinous carcinomatosis (PMC or PMCA), with PMCA and intermediate/discordant features in the middle. In the Received January 5, 2006; accepted January 5, 2006; published online March 16, 2006. Address correspondence and reprint requests to: John M. Kane III, MD; E-mail: john.kane@roswellpark.org.