Peritoneal Surface Disease (PSD) from Appendiceal Cancer Treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Overview of 481 Cases

Abstract

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) used to treat peritoneal surface disease (PSD) from appendiceal cancer have shown variability in survival outcomes. The primary goal of this study was to determine predictors of surgical morbidity and overall survival. The secondary goal was to describe the impact of nodal status on survival after CRS/HIPEC for PSD from low-grade appendiceal (LGA) and high-grade appendiceal (HGA) primary lesions. Methods A retrospective analysis of 1,069 procedures from a prospective database was performed. Patient characteristics, tumor grade, nodal status, performance status, resection status, morbidity, mortality, and survival were reviewed. Results The study identified 481 CRS/HIPEC procedures: 317 (77.3 %) for LGA and 93 (22.7 %) for HGA lesions. The median follow-up period was 44.4 months, and the 30-day major morbidity and mortality rates were respectively 27.8 and 2.7 %. Major morbidity was jointly predicted by incomplete cytoreduction (p = 0.0037), involved nodes (p < 0.0001), and comorbidities (p = 0.003). Multivariate negative predictors of survival included positive nodal status (p = 0.003), incomplete cytoreduction (p < 0.0001), and preoperative chemotherapy (p = 0.04) in LGA patients and incomplete cytoreduction (p = 0.0003) and preoperative chemotherapy (p = 0.0064) in HGA patients. After complete cytoreduction, median survival was worse for patients with positive nodes than for those with negative nodes in LGA (85 months vs not reached [82 % alive at 90 months]; p = 0.002) and HGA (30 vs 153 months; p < 0.0001). Conclusions Positive nodes are associated with decreased survival not only for HGA patients but also for LGA patients even after complete cytoreduction. Nodal status further stratifies histologic grade as a prognostic indicator of survival. Patients with node-negative HGA primary lesions who receive a complete cytoreduction may experience survival comparable with that for LGA patients.

Appendiceal goblet cell carcinomatosis treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

“…In addition, we did observe a lower rate of complete cytoreduction (35.5% versus 44.4%) than we have published in patients with peritoneal carcinomatosis from appendiceal primaries other than goblet cell [14]. We attribute these deviations from our previously reported outcomes to the notoriously desmoplastic nature specific to goblet cell tumors, making surgical resection challenging.…”

“…Mahteme and Sugarbaker, on the other hand, did identify a significant difference in survival based on the completeness of cytoreduction score in patients receiving CRS and intraperitoneal chemotherapy (median OS 28.5 mo for CC0-1, 18.1 mo for CC2, and 5.9 for CC3, P = 0.007) [11,12]. In a larger cohort of patients with appendiceal carcinomatosis, our group identified completeness of cytoreduction as an independent prognosticator, and we believe that given increased power in the present study, we would have been able to identify a significant difference in survival based on completeness of cytoreduction [14]. …”

A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in Patients with Appendiceal Tumors

“…Although the incidence has been increasing for over a decade, 1 several issues have made completing clinical trials difficult 20 . While prospective randomized trials have been attempted in the past (NCT00052962), none, at any stage, had completed planned accrual.…”

“…Appendiceal cancer has been the leading indication for cytoreductive surgery and HIPEC since its original description 22 . Peritoneal dissemination from appendiceal mucinous cancer has been treated with CRS/HIPEC for many years, with acceptable and decreasing morbidity and mortality 6,15,16,20 . As previously reported, surgical complications were associated with increased volume of disease, pre-existing medical comorbidities, poor functional status, and suboptimal nutrition.…”

“…This is in agreement with prior reports that have demonstrated that long term survival is possible, even for high grade disease, if a complete cytoreduction is obtained. 3-6-15,16,20 …”