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Background: Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has recently shown promise for the treatment of patients with various types of peritoneal carcinomatosis (PC). However, it is an extensive procedure that is associated with a variety of morbidities. We evaluated the safety and clinical outcomes of CRS-HIPEC performed at our centre., Methods: Patients with abdominal malignancies who underwent CRS-HIPEC between February 2005 and December 2018 at the Centre hospitalier de l'Université de Montréal (CHUM) were retrospectively reviewed., Results: A total of 141 patients were identified (66 with appendiceal cancer, 62 with colorectal cancer, 10 with mesothelioma and 3 with small intestinal tumours). The median age was 55 years. Median overall survival (OS) was not reached for patients with appendiceal tumours; it was 38.3 months for colorectal cancers. Among patients with colorectal cancer, survival was significantly better for those who received intraperitoneal HIPEC with oxaliplatin (74.9 mo) compared with mitomycin C (29.1 mo) ( p = 0.006). Complete cytoreductive surgery and low peritoneal carcinomatosis index were associated with the highest overall survival in patients with appendiceal tumours and those with colorectal tumours., Conclusion: CRS-HIPEC can be performed with acceptable morbidity in patients with PC. These results validate the outcomes of previously reported trials, but further prospective trials are warranted to determine which patients will most benefit from the addition of HIPEC to CRS., Competing Interests: Competing interests: F. Mercier has received grants and personal fees from Ipsen and personal fees from Advanced Accelerator Applications., (© 2022 CMA Impact Inc. or its licensors.)

Modern management of colorectal cancer (crc) with peritoneal metastasis (pm) is based on a combination of cytoreductive surgery (crs), systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy (hipec). Although the role of hipec has recently been questioned with respect to results from the prodige 7 trial, the role and benefit of a complete crs were confirmed, as observed with a 41-month gain in median survival in that study, and 15% of patients remaining disease-free at 5 years. Still, crc with pm is associated with a poor prognosis, and good patient selection is essential. Many questions about the optimal management approach for such patients remain, but all patients with pm from crc should be referred to, or discussed with, a pm surgical oncologist, because cure is possible. The objective of the present guideline is to offer a practical approach to the management of pm from crc and to reflect on the new practice standards set by recent publications on the topic., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none., (2020 Multimed Inc.)

Background: The COVID-19 pandemic has put enormous pressure on hospital resources, and has affected all aspects of patient care. As operative volumes decrease, cancer surgeries must be triaged and prioritized with careful thought and attention to ensure maximal benefit for the maximum number of patients. Peritoneal malignancies present a unique challenge, as surgical management can be resource intensive, but patients have limited non-surgical treatment options. This review summarizes current data on outcomes and resource utilization to help inform decision-making and case prioritization in times of constrained health care resources. Methods: A rapid literature review was performed, examining surgical and non-surgical outcomes data for peritoneal malignancies. Narrative data synthesis was cross-referenced with relevant societal guidelines. Peritoneal malignancy surgeons and medical oncologists reviewed recommendations to establish a national perspective on case triage and mitigating treatment strategies. Results and Conclusions: Triage of peritoneal malignancies during this time of restricted health care resource is nuanced and requires multidisciplinary discussion with consideration of individual patient factors. Prioritization should be given to patients where delay may compromise resectability of disease, and where alternative treatment options are lacking. Mitigating strategies such as systemic chemotherapy and/or surgical deferral may be utilized with close surveillance for disease stability or progression, which may affect surgical urgency. Unique hospital capacity, and ability to manage the complex post-operative course for these patients must also be considered to ensure patient and system needs are aligned.

Background: The impact of the location of colorectal cancer on patient outcomes has been reported in several settings. The objective of this study was to assess the prognostic impact of the location of the primary colon cancer among patients with colorectal cancer peritoneal metastases undergoing complete cytoreductive surgery., Methods: Using the prospectively maintained clinical and biological digestive peritoneal metastasis database of the BIG-RENAPE network, we identified 796 patients treated by a complete cytoreductive surgery between January 2004 and January 2017 for colorectal cancer peritoneal metastases in 16 different institutions. The 2 primary endpoints were overall survival and progression-free survival. To evaluate the impact on overall survival and progression-free survival of potential prognostic factors (including the location of the primary colorectal cancer), these factors were included in univariate and multivariate Cox proportional hazard models., Results: Right-sided colorectal cancers were more often BRAF mutated and had microsatellite instability, whereas the frequency of RAS mutation was similar between right-sided and left-sided colorectal cancers. After a median follow-up time of 3.3 years, there was no significant difference in overall survival or progression-free survival according to tumor side. The lack of effect of tumor location on overall survival and progression-free survival was consistent across subgroups., Conclusion: Among patients undergoing complete cytoreductive surgery for peritoneal metastases, the site of the primary colorectal cancer was not associated with differences in progression-free survival or overall survival. Tumor side should not be used as a stratification factor in trials of colorectal cancer peritoneal metastases and should not be used in the selection process of patients for cytoreductive surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy, HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries., Methods: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected., Results: Twenty-seven questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year., Conclusions: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.

Complete surgical cytoreduction of peritoneal implants and immediate intraperitoneal (lP) chemotherapy offers the greatest survival in selected patients with peritoneal carcinomatosis. This study was undertaken to describe the metabolism and pharmacokinetics of normothermic intraperitoneal CPT-11, free and glucuronized SN-38, in a pig model. Thirteen pigs were used for experimentation. Animals were grouped for IV and IP CPT-1 1 administration. Eleven pigs underwent laparotomy through a midline incision and instillation of 100, 200, and 400mg IP CPT-11. Systemic venous blood, portal blood and peritoneal fluid samples were taken at 5, 10, 20, 30, and 45 min, then every hour up to 8 hr for the 100 mg. For the three groups, peritoneal CPT-11 exposition was on average 4.9 times greater in the peritoneum than in the systemic venous or portal circulations and the systemic CPT-11 fraction absorbed from the peritoneum linearly increased with time. Free SN-38 was measurable in the earliest peritoneal samples taken. The initial instillation dose of CPT-11 did not impact on the SN-38 converted fraction, which remained stable at approximately 0.04% during the first 4 hour. Mean peritoneal SN-38: CPT-11 AUC ratio was 0.043. OPT-11 peritoneal conversion into SN-38 appeared slightly Inferior to the systemic conversion ratio. This norrnothermic IP OPT-11 pharmacokinetic study performed in a pig model confirms the possibility to achieve at least a 30 times higher peritoneal than systemic exposure. Peritoneal exposure to active SN-38 begins at the moment of CPT-11 peritoneal instillation. A fixed and small traction of less than 0.1% of CPT-11 is converted into SN-38, underlying the importance of a sufficient initial IP dose of CPT-11.

At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan, the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal surface malignancy was obtained through the Delphi process. Conflicting points concerning drugs, carrier solution and optimal temperature for hyperthermic intraperitoneal chemotherapy (HIPEC) were discussed.

At the Fifth International Workshop on Peritoneal Surface Malignancy (PSM), held in Milan, December 2006, the consensus on technical aspects of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was obtained through the Delphi process. The following topics were discussed: pre-operative workup; eligibility to CRS + HIPEC; intra-operative staging system; technical aspects of surgery; residual disease classification systems; HIPEC: nomenclature and modalities; drugs, carrier solution and optimal temperature; morbidity grading systems. Conflicting points regarding above-mentioned topics were elaborated and voted in two rounds by a panel of international experts in local-regional therapy. The purpose of this manuscript is to describe the organization and the methodology of the consensus statements and to interpret and discuss the implications of the most striking results.

At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan, the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal surface malignancy was obtained through the Delphi process. Five conflicting points were discussed: radicality of the peritonectomy procedure, cytoreduction of neoplastic nodules <2.5 mm, the timing of bowel anastomoses in relation to hyperthermic intraperitoneal chemotherapy (HIPEC) and indications of protective ostomies. According to the panel of experts a partial parietal peritonectomy restricted to the macroscopically involved regions could be indicated in all listed clinical conditions with the exception of peritoneal mesothelioma. No expert was of the opinion that a radical parietal peritonectomy is advisable irrespective of the disease being treated. All the experts agreed that electrovaporization of small (<2.5 mm) non-infiltrating metastatic nodules in the mesentery would be appropriate, even if theoretically the HIPEC affords microscopic cytoreduction. The panel also agreed that in the closed technique for HIPEC administration the intestinal anastomoses should be fashioned after completion of the perfusion. Finally when considering the place for protective ostomies the experts voted for a flexible approach allowing the surgeon to exercise discretion for individual patients.

To reach a consensus for reporting complications related to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Reporting the adverse events related to CRS + HIPEC is not standardized yet. Post-operative complications can be divided in two categories: the effects of surgical manipulation per se and the toxic effects of the heated intraoperative chemotherapy. Additive and/or synergistic effects also exist. Different centers have published their experience with regard to the complications associated with the procedure. Various classification systems have been used which makes a temptative comparison of the different techniques and results almost impossible. An effort was made here to review the existing major classification systems: The Bozzetti classification, the Clavien classification (and two proposed modifications from Feldman et al. and Elias et al.) and the Common terminology criteria for adverse events (CTCAE) version 3.0 of the National Institute of Health (NIH) criteria. A related document was sent to an international panel of experts. The CTCAE was adopted by the panel of experts as the unique classification system to be used for reporting complications related to CRS + HIPEC.

Introduction: The purpose of this study was to analyze the postoperative pancreatic morbidity of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal surface malignancies (PSM)., Patients and Methods: Two hundred and sixty five patients (87M/178F) with PSM underwent 270 consecutive procedures. The mean age was 52 years (range: 22-79 years). CRS was performed using peritonectomy procedures. HIPEC through the closed abdomen technique was conducted using cisplatin (CDDP 25 mg/m2/L of perfusate)+mitomycin C (MMC 3.3 mg/m2/L of perfusate) or CDDP (43 mg/L of perfusate)+doxorubicin (Dx 15.25 mg/L of perfusate), at 42.5 degrees C. Diagnosis and classification of postoperative pancreatic fistula (POPF) were performed according to the international study group on pancreatic fistula criteria. Serum amylase alterations were graded according to the National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v3., Results: POPF was observed in 13 (4.8%) cases. Three cases were classified as major (grade C). Two cases presented postoperative pancreatitis. G3-4 alteration of amylase was observed in 12.3% of the cases. Performing splenectomy and CDDP dosage for HIPEC >240 mg were proven to be independent risk factors for both G3-4 hyperamylasemia and POPF., Conclusions: CRS+HIPEC presented an acceptable rate of pancreatic morbidity which did not contribute to the mortality related to the procedure. Most of the POPF were mild and/or easily controlled by conservative measures. Although not specific a normal amylasemia could be a useful marker of pancreatic integrity after CRS+HIPEC.

Introduction: The purpose of this study was to analyze the postoperative systemic toxicity and procedure-related mortality (PRM) of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal surface malignancies (PSMs)., Patients and Methods: A total of 242 (84 males/158 females) patients with PSM underwent 247 consecutive procedures. The mean age was 52 years (range 22-79). CRS was performed using peritonectomy procedures. The HIPEC technique through the closed abdomen was conducted with cisplatin (CDDP 25 mg/m(2)/l of perfusate)+mitomycin C (MMC 3.3 mg/m(2)/l perfusate) or CDDP (43 mg/l perfusate)+doxorubicin (Dx 15.25 mg/l perfusate) at 42.5 degrees C. These dosages were reduced by 30% when the patient had received systemic chemotherapy before the CRS+HIPEC. Systemic toxicities were graded according to the NCI CTCAE v3 criteria., Results: G3-5 systemic toxicity rate was 11.7 % and adverse events were bone marrow suppression, 13; nephrotoxicity, 14; neutropenic infection, 2 and pulmonary toxicity, 1. Independent risk factors for G3-5 systemic toxicity after multivariate analysis were a dose of CDDP for HIPEC of 240 mg or more (OR 2.78, CI 95% 1.20-6.45) and CDDP+Dx schedule for HIPEC (OR 2.36, CI 95% 1.02-5.45). PRM was 1.2%., Conclusions: CRS+HIPEC presented acceptable systemic toxicity and PRM rates. Independent risk factors for systemic toxicity were the CDDP+Dx schedule and CDDP dose for HIPEC.

Aims: CDX-2 is a highly sensitive and specific marker of intestinal epithelial cells and their neoplastic counterparts. CDX-2 status in pseudomyxoma peritonei (PMP) has been barely reported. The aim of this study was to investigate the clinicopathological features of 42 cases of PMP with a special emphasis on CDX-2., Methods and Results: All patients were treated by cytoreduction. Immunohistochemistry was performed for CDX-2, MUC-2, MUC-5AC, cytokeratin (CK) 7 and CK20. Statistical correlation was evaluated for age, sex, completeness of cytoreduction and histological subtype with overall and progression-free survival (OS and PFS). PMP consisted of 32 cases of disseminated peritoneal adenomucinosis and 10 cases of peritoneal mucinous carcinomatosis. The appendix evaluated in 25 cases showed two mucinous adenocarcinomas and 21 low-grade appendiceal mucinous neoplasms. CDX-2 was diffusely positive in 40 cases, with the remaining two cases being focally positive. All cases demonstrated diffuse reactions to CK20 and MUC-2, and variable reactions to MUC-5AC, while CK7 was variably positive in 38 cases. Five-year OS was 97%. Histological type was significantly correlated with PFS (P=0.02)., Conclusions: CDX-2 is diffusely and strongly positive in PMP. This is a useful marker to confirm an appendiceal origin of PMP, particularly when used in conjunction with CK7, CK20, MUC-2 and MUC-5AC.

Background: The purpose of this prospective Phase II study was to analyze morbidity and mortality of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP) in the treatment of peritoneal surface malignancies., Methods: A total of 205 patients (50 with peritoneal mesothelioma, 49 with pseudomyxoma peritonei, 41 with ovarian cancer, 32 with abdominal sarcomatosis, 13 with colon cancer, 12 with gastric cancer, and 8 with carcinomatosis from other origins) underwent 209 consecutive procedures. Four patients underwent the intervention twice because of disease relapse. There were 70 men and 135 women. Mean age was 52 years (range, 22-76 yrs). CRS was performed by using peritonectomy procedures. IPHP through the closed abdomen technique was conducted with a preheated (42.5 degrees C) perfusate containing cisplatin + mitomycin C or cisplatin + doxorubicin., Results: Major morbidity rate was 12%. The most significant complications were 23 anastomotic leaks or bowel perforations, 4 abdominal bleeds, and 4 sepses. Operative mortality rate was 0.9%. On logistic regression model multivariate analysis, extent of cytoreduction (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.29-6.40) and dose of cisplatin for IPHP > or = 240 mg (OR, 3.13; 95% CI, 1.24-7.90) were independent risk factors for major morbidity. Ten patients presented with Grade 3 to 4 toxicity., Conclusions: CRS + IPHP presented acceptable morbidity, toxicity, and mortality rates, all of which support prospective Phase III clinical trials.

Background: Diffuse malignant peritoneal mesothelioma (DMPM) is a subset of peritoneal mesothelioma with a poor clinical outcome. We performed a prognostic analysis in a cohort of DMPM patients treated homogeneously by cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP)., Methods: Forty-nine DMPM patients who underwent 52 consecutive procedures were enrolled onto the study. Cytoreductive surgery was performed according to the peritonectomy technique, and the IPHP was performed with cisplatin plus doxorubicin or cisplatin plus mitomycin C. We assessed the correlation of the clinicopathologic variables (previous surgical score, age, sex, performance status, previous systemic chemotherapy, carcinomatosis extension, completeness of cytoreduction, IPHP drug schedule, mitotic count [MC], nuclear grade, and biological markers [epidermal growth factor receptor, p16, matrix metalloproteinase 2 and matrix metalloproteinase 9]) with overall and progression-free survival., Results: The mean age was 52 years (range, 22-74 years). The mean follow-up was 20.3 months (range, 1-89 months). Regarding the biological markers, the rates of immunoreactivity of epidermal growth factor receptor, p16, matrix metalloproteinase 2, and matrix metalloproteinase 9 were 94%, 60%, 100%, and 85%, respectively. The strongest factors influencing overall survival were completeness of cytoreduction and MC, whereas those for progression-free survival were performance status and MC. No biological markers were shown to be of prognostic value., Conclusions: Completeness of cytoreduction, performance status, and MC seem to be the best determinants of outcome. These data warrant confirmation by a further prospective formal trial. No biological markers presented a significant correlation with the outcome. The overexpression of epidermal growth factor receptor, matrix metalloproteinase 2, and matrix metalloproteinase 9 and absent or reduced expression of p16 might be related to the underlining tumor kinetics of DMPM and warrant further investigation with other methods.

Background: In the current study, the authors report the clinicopathologic features of patients with peritoneal diffuse malignant mesothelioma (DMM) who were treated in a uniform fashion at a single institution to assess prognostic factors., Methods: Thirty-five patients were treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). The tumors were classified into epithelial, sarcomatoid, and biphasic types. Immunohistochemistry stains were performed for calretinin, WT-1, pCEA, Ber-EP4, epidermal growth factor receptor (EGFR), p16, matrix metalloprotease-2 (MMP-2), and MMP-9. Statistical correlation was evaluated for age, gender, completeness of cytoreduction (CC), tumor histotype, mitotic count (MC), necrosis, nuclear grade (NG), and biologic markers with regard to overall survival (OS) and progression-free survival (PFS)., Results: The patient group was comprised of 15 men and 20 women with a median age of 52 years (range, 24-73 yrs). Twenty-five patients underwent optimal cytoreduction. There were 32 epithelial tumors and 3 biphasic tumors, and 3 patients had an NG of 1, 19 had an NG of 2, and 13 had an NG of 3. The mean MC was 14.1 (range, 0-160 per 50 high-power fields). Necrosis was present in 11 cases. All the tumors were found to be positive for calretinin and WT-1 and were negative for pCEA and Ber-EP4. The NG and MC were found to be significantly associated with OS (P = 0.02 and P = 0.01, respectively) whereas CC was found to be associated with both OS (P = 0.05) and PFS (P = 0.03). No biologic markers were found to be of prognostic significance., Conclusions: The results of the current study indicate that NG, MC, and CC may be useful prognostic factors in patients treated with CRS and IPHP. The expression of EGFR, MMP-2, and MMP-9 and absent and/or reduced expression of p16 in DMMs confirms the results of previous studies suggesting their role in tumor pathogenesis and kinetics., (Copyright 2005 American Cancer Society)

Background: Peritonectomy and intraperitoneal hyperthermic perfusion (IPHP) are increasingly used in the management of carcinomatosis of various sites of origin. We analyzed the risk factors for bowel complications with primary anastomoses and the closed technique for IPHP., Methods: From 1995 to 2004, 203 consecutive procedures were performed at the National Cancer Institute of Milan. We retrospectively analyzed this series of patients. Treated pathologies included peritoneal mesothelioma; pseudomyxoma peritonei; colorectal, ovarian, or gastric carcinomatosis; and abdominal sarcomatosis. All digestive anastomoses were performed before the IPHP. Only one defunctioning stoma was used., Results: We found a bowel complication rate of 10.8%. The bowel complications:anastomoses ratio was 11.3%. On univariate analysis we found a statistically significant association between bowel complications and the following variables: sex, previous systemic chemotherapy status, number of anastomoses ( fewer than two vs. two or more), duration of the procedure (<8.7 vs. >or=8.7 hours), and extent of cytoreduction. After multivariate analysis, male sex (odds ratio [OR], 4.2), no previous systemic chemotherapy (OR, 3.5), and duration of the procedure >or=8.7 hours (OR, 6.3) were considered independent risk factors for bowel complications., Conclusions: Bowel complications are not increased when primary unprotected anastomoses are performed during peritonectomy and IPHP when the closed technique is used. Male sex, duration of the procedure, and no previous systemic chemotherapy are independent unfavorable risk factors.