OBJECTIVE:: To assess the influence of parietal and visceral peritonectomy procedures on moderate/severe morbidity in patients undergoing surgical cytoreducion and hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify subgroups of patients at highest operative risk. BACKGROUND:: Cytoreducion with HIPEC is an effective but potentially morbid treatment option for peritoneal surface malignancies. Although complication rates have recently decreased with increasing experience, risk-factors for adverse operative outcome are still poorly understood. METHODS:: A prospective database of 426 combined procedures was reviewed. Multivariate analysis tested the correlation between major morbidity and 6 peritonectomies (greater and lesser omentectomy, pelvic, parietal anterior, left and right diaphragmatic peritonectomy), 14 visceral resections, 5 other operative factors, and 12 clinical variables. The extent of peritoneal involvement was quantified by peritoneal cancer index (PCI). RESULTS:: Mortality and major morbidity were 2.6% and 28.2%. PCI, number of visceral resections, poor performance status, and cisplatin dose more than 240 mg independently correlated to morbidity. The type and number of parietal peritonectomies and the type of visceral resections did not correlated to complications. Major morbidity rate was 65.7% in 35 (8.2%) patients with at least 2 of the following factors: PCI greater than 30, more than 5 visceral resections, poor performance status. Morbidity was 100% in 9 patients presenting all the risk factors. CONCLUSIONS:: Acceptable morbidity and low mortality may be achieved in high-volume centers. Operative outcome is mainly affected by a complex interplay of tumor, patient, and treatment-related factors. Preoperative and early intraoperative assessment of operative risk may identify a subset of patients unlikely to tolerate aggressive management.

Please cite this paper as: Deraco M, Virzì S, Raspagliesi F, Iusco D, Puccio F, Macrì A, Famulari C, Solazzo M, Bonomi S, Grassi A, Baratti D, Kusamura S. Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi-institutional study. BJOG 2012;119:800-809. Objective  To assess the efficacy and morbidity and mortality of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (EOC). Design  A retrospective study conducted using information extracted from a multi-institutional prospective database on peritoneal surface malignancies (PSMs). Setting Four Italian centres specializing in locoregional treatment of PSM. Population  Patients with recurrent EOC. Methods  Fifty-six patients underwent 57 combined procedures. CRS was performed using peritonectomy procedures and HIPEC using the closed-abdomen technique with cisplatin and doxorubicin or cisplatin and mitomycin-C. Main outcome measures  Overall survival (OS), progression-free survival (PFS), morbidity and mortality rates. Results  The median age of the patients was 55.2 years (range 30-75 years). The median peritoneal cancer index was 15.2 (range 4-30). Forty-seven patients had microscopic residual disease (completeness of cytoreduction, CC-0), seven had residual disease ≤2.5 mm (CC-1) and one had residual disease >2.5 mm (CC>2). Major complications occurred in 15 patients (26.3%), and procedure-related mortality occurred in three patients (5.3%). The median follow-up time was 23.1 months. The median OS and PFS were 25.7 (95% CI 20.3-31.0) and 10.8 (95% CI 5.4-16.2) months, respectively. The 5-year OS and PFS were 23% and 7%, respectively. Independent prognostic factors affecting OS according to the multivariate analysis were Eastern Cooperative Oncology Group performance status, preoperative serum albumin, and completeness of cytoreduction. Conclusions  Patients with recurrent EOC treated with CRS and HIPEC showed promising results in terms of outcome. The combined treatment strategy could benefit subsets of patients wider than that defined for conventional secondary debulking surgery without HIPEC. These data warrant further evaluation in randomised clinical trials.

BACKGROUND: Combined treatment involving peritonectomy procedures, multivisceral resections, and hyperthermic intraperitoneal chemotherapy (HIPEC) has reportedly resulted in survival benefit for peritoneal surface malignancies, including diffuse malignant peritoneal mesothelioma (DMPM). Many unanswered questions remain regarding the surgical options in the management of DMPM. The aim of this case-control study was to assess the impact of the type and extent of parietal peritonectomy on survival and operative outcomes. METHODS: Thirty patients with DMPM undergoing selective parietal peritonectomy (SPP) of macroscopically involved regions, and 30 matched patients undergoing routine complete parietal peritonectomy (CPP), regardless of disease distribution, were retrospectively identified from a prospective database. RESULTS: Groups were comparable for all characteristics, except for a higher proportion of patients treated before July 2003 and undergoing preoperative systemic chemotherapy in the SPP group. Median follow-up was 86.2 months in the SPP group and 50.3 months in the CPP group. Median overall survival was 29.6 months in the SPP group and not reached in the CPP group; 5-year overall survival was 40.0% and 63.9%, respectively (P = 0.0269). At multivariate analysis, CPP versus SPP was recognized as an independent predictor of better prognosis, along with complete cytoreduction, negative lymph nodes, epithelial histology, and lower MIB-1 labelling index. Morbidity and reoperation rates were not different between groups. No operative mortality occurred. In 12 of 24 patients undergoing CPP, pathologic examination detected disease involvement on parietal surfaces with no evident tumor at surgical exploration. CONCLUSIONS: CPP improved survival in patients with DMPM undergoing combined treatment. This information may contribute to standardize surgical options for DMPM and other peritoneal malignancies.

OBJECTIVE:: To evaluate the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal surface malignancies (PSM). SUMMARY AND BACKGROUND:: CRS and HIPEC to treat PSM is a complex procedure with a significant morbidity. A long-lasting training program is required to acquire expertise in this type of operation. METHODS:: We performed CRS using peritonectomy procedures. HIPEC through the closed abdomen technique employed cisplatin and mitomycin-C or cisplatin and doxorubicin. Risk-adjusted sequential probability ratio test was used to assess the learning curve on a series of 420 cases of PSM on the basis of rates of incomplete cytoreduction and G3-5 morbidity (NCI-CTCAE v3). We determined control limits setting the type I/II error rates and unacceptable odds ratios (ORs) for the outcomes being studied. We performed the risk adjustment using logistic regression model. RESULTS:: Rates of incomplete cytoreduction, G3-5 morbidity, and postoperative mortality rates were 10.2%, 28.5%, and 2.1%, respectively. The risk-adjusted sequential probability ratio test curve crossed the lower control limit at the 137th and 149th case, respectively, for incomplete cytoreduction and G3-5 morbidity. At those points, the actual ORs are lower than the prespecified ORs for outcomes being studied. Therefore, we estimated that approximately 140 cases are necessary to ensure surgical proficiency in CRS and HIPEC. CONCLUSIONS:: CRS and HIPEC to treat PSM has a steep learning curve requiring 140 procedures to acquire expertise.

BACKGROUND: Combined therapy involving cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has been shown to improve survival outcomes for patients with diffuse malignant peritoneal mesothelioma (DMPM). The present study aims to investigate gender as a potential prognostic factor on overall survival. PATIENTS AND METHODS: Over a period of two decades, 294 patients who underwent CRS and perioperative intraperitoneal chemotherapy were selected from a large multi-institutional registry to assess the prognostic significance of gender on overall survival. RESULTS: Female patients were shown to have a significantly improved survival outcome than male patients (P < 0.001). Staging according to a recently proposed tumor-node-metastasis categorization system was significant in both genders. Older female patients had significantly worse survival than younger female patients (P = 0.019), a finding that was absent in male patients. Female patients with low-stage disease were found to have a very favorable long-term outcome after combined treatment. CONCLUSIONS: Gender has demonstrated a significant impact on overall survival for patients with DMPM after CRS and perioperative intraperitoneal chemotherapy. An improved understanding of the role of estrogen in the pathogenesis of DMPM may improve the prognostication of patients and determine the role of adjuvant hormonal treatment in the future.

OBJECTIVE The primary end-point of this multi-institutional phase-II trial was to assess results in terms of overall survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment-naive epithelial ovarian cancer (EOC) with advanced peritoneal involvement. Secondary end-points were treatment morbi-mortality and outcome effects of time to subsequent adjuvant systemic chemotherapy (TTC). METHODS Twenty-six women with stage III-IV EOC were prospectively enrolled in 4 Italian centers to undergo CRS and closed-abdomen HIPEC with cisplatin and doxorubicin. Then they received systemic chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m(2)) for 6 cycles. RESULTS Macroscopically complete cytoreduction was achieved in 15 patients; only minimal residual disease (≤2.5 mm) remained in 11. Major complications occurred in four patients and postoperative death in one. After a median follow-up of 25 months, 5-year overall survival was 60.7% and 5-year progression-free survival 15.2%(median 30 months). Excluding operative death, all the patients underwent systemic chemotherapy at a median of 46 days from combined treatment (range: 29-75). The median number of cycles per patient was 6 (range: 1-8). The time to chemotherapy did not affect the OS or PFS. CONCLUSIONS In selected patients with advanced stage EOC, upfront CRS and HIPEC provided promising results in terms of outcome. Morbidity was comparable to aggressive cytoreduction without HIPEC. Postoperative recovery delayed the initiation of adjuvant systemic chemotherapy but not sufficiently to impact negatively on survival. These data warrant further evaluation in a randomized clinical trial.

BACKGROUND Currently, no tumor-node-metastasis (TNM) staging system exists for patients with diffuse malignant peritoneal mesothelioma (DMPM). The primary objective was to formulate a clinicopathological staging system through the identification of significant prognostic parameters. METHODS Eight international institutions with prospectively collected data on patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy contributed to the registry. Two hundred ninety-four patients had complete clinicopathological data and formed the basis of this staging project. RESULTS Peritoneal cancer index (PCI) was categorized into T(1)(PCI 1-10), T(2)(PCI 11-20), T(3)(PCI 21-30), and T(4)(PCI 30-39). Twenty-two patients had positive lymph nodes (N(1)) and 12 patients had extra-abdominal metastases (M(1)). The survival for patients with T(1)(PCI 1-10) N(0) M(0) was significantly superior to the other patients. This group of patients is therefore designated as Stage I. The survival of patients with T(2)(PCI 11-20) and T(3)(PCI 21-30), in absence of N(1) or M(1) disease, was similar. This group of patients was categorized as Stage II. The survival of patients with T(4)(PCI 30-39), N(1,) and/or M(1) was similarly poor. This group of patients was therefore categorized as Stage III. Three prognostic factors were independently associated with survival in the multivariate analysis: histological subtype, completeness of cytoreduction, and the proposed TNM staging. The 5-year survival associated with Stage I, II, and III disease was 87%, 53%, and 29%, respectively. CONCLUSIONS The proposed TNM staging system resulted in significant stratification of survival by stage when applied to the current multi-institutional registry data.

Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon and locally aggressive tumor with poor prognosis. Currently, no standard therapy is available. The biology of this disease is still poorly understood. We performed a systematic search of relevant studies on clinical management and biological research of DMPM. Trials were selected using a predetermined protocol. The current evidence suggests that cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) results in improved survival. Biological understanding of DMPM is currently evolving.