Olivier Gléhen

Peritoneal carcinomatosis (PC) is a common evolution of digestive cancer, associated with a poor prognosis. Yet it is poorly documented in the literature.Three hundred seventy patients with PC from non-gynecologic malignancies were followed prospectively: the PC was of gastric origin in 125 cases, of colorectal origin in 118 cases, of pancreatic origin in 58 cases, of unknown origin in 43 cases, and of miscellaneous origins in 26 cases. A previously reported PC staging system was used to classify these 370 patients.Mean and median overall survival periods were 6.0 and 3.1 months, respectively. Survival rates were mainly affected by the initial PC stage (9.8 months for Stage I with malignant peritoneal granulations less than 5 mm in greatest dimension, versus 3.7 months for Stage IV with large, malignant peritoneal masses more than 2 cm in greatest dimension). The presence of ascites was associated with poor survival of patients with gastric or pancreatic carcinoma. Differentiation of the primary tumor did not influence the prognoses of patients with PC.A better knowledge of the natural history of PC is needed, in view of the many Phase I, II, and III trials currently being conducted to evaluate aggressive multimodal therapeutic approaches to treating patients with PC from non-gynecologic malignancies.

Purpose The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. Patients and Methods A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. Results The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P < .001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. Conclusion The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.

Purpose Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. Patients and Methods A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. Conclusion This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.

Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study.A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International.Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P < .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P < .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001) were independent predictors of a poorer overall survival.The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.

Purpose This multi-institutional registry study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). Patients and Methods A multi-institutional data registry that included 405 patients with DMPM treated by a uniform approach that used CRS and HIPEC was established. The primary end point was overall survival. The secondary end point was evaluation of prognostic variables for overall survival. Results Follow-up was complete in 401 patients (99%). The median follow-up period for the patients who were alive was 33 months (range, 1 to 235 months). The mean age was 50 years (standard deviation [SD], 14 years). Three hundred eighteen patients (79%) had epithelial tumors. Twenty-five patients (6%) had positive lymph nodes. The mean peritoneal cancer index was 20. One hundred eighty-seven patients (46%) had complete or near-complete cytoreduction. Three hundred seventy-two patients (92%) received HIPEC. One hundred twenty-seven patients (31%) had grades 3 to 4 complications. Nine patients (2%) died perioperatively. The mean length of hospital stay was 22 days (SD, 15 days). The overall median survival was 53 months (1 to 235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis: epithelial subtype (P &lt; .001), absence of lymph node metastasis (P &lt; .001), completeness of cytoreduction scores of CC-0 or CC-1 (P &lt; .001), and HIPEC (P = .002). Conclusion The data suggest that CRS combined with HIPEC achieved prolonged survival in selected patients with DMPM.

Peritoneal carcinomatosis (PC) from nonovarian malignancies long has been regarded as a terminal disease. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved that have demonstrated improved survival.A retrospective, multicenter cohort study was performed in French-speaking institutions to evaluate toxicity and principal prognostic factors after cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy [HIPEC] and/or early postoperative intraperitoneal chemotherapy [EPIC]) for PC from nongynecologic malignancies.The study included 1290 patients from 25 institutions who underwent 1344 procedures between February 1989 and December 2007. HIPEC was performed in 1154 procedures. The principal origins of PC were colorectal adenocarcinoma (N = 523), pseudomyxoma peritonei (N = 301), gastric adenocarcinoma (N = 159), peritoneal mesothelioma (N = 88), and appendiceal adenocarcinoma (N = 50). The overall morbidity and mortality rates were 33.6% and 4.1%, respectively. In multivariate analysis, patient age, the extent of PC, and institutional experience had a significant influence on toxicity. The overall median survival was 34 months; and the median survival was 30 months for patients with colorectal PC, not reached for patients with pseudomyxoma peritonei, 9 months for patients with gastric PC, 41 months for patients with peritoneal mesothelioma, and 77 months for patients with PC from appendiceal adenocarcinoma. Independent prognostic indicators in multivariate analysis were institution, origin of PC, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement.A therapeutic approach that combined cytoreductive surgery with PIC was able to achieve long-term survival in a selected group of patients who had PC of nonovarian origin and had acceptable morbidity and mortality. The current results indicated that this treatment should be centralized to institutions with expertise in the management of PC.

The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone.We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed.Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035).Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases.Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin : a consensus statement

Peritoneal carcinomatosis is a common manifestation of digestive-tract cancer and has been regarded a terminal disease with a short median survival. Over the past decade, a new locoregional therapeutic approach combining cytoreductive surgery with intraperitoneal chemohyperthermia (IPCH) has evolved. Because of its limited benefits, high morbidity and mortality, and high cost, this comprehensive management plan requires accurate patient selection. Quantitative prognostic indicators are needed to assess a patient's eligibility for combined treatment, including tumour histopathology, classification of carcinomatosis extent, assessment of completeness of cytoreduction, and determination of the extent of previous surgery. Patients with pseudomyxoma peritonei and those with peritoneal dissemination of digestive-tract cancer have shown promising survival. Complete cytoreduction with no visible disease persisting is a requirement for long-term benefit. In Japan and Korea, use of IPCH as prophylactic treatment in potentially curative gastric-cancer resection has shown improved survival and lower peritoneal recurrence rates. IPCH combined with cytoreductive surgery seems to be an effective therapeutic approach in carefully selected patients, and offers a chance for cure or palliation in this condition with few alternative treatment options.

LBA3503 Background: Promising results have been obtained during the last decade using cytoreductive surgery (CRS) plus HIPEC for selected patients with colorectal PC who are amenable to complete macroscopic resection. This is the first trial to evaluate the specific role of HIPEC, after CRS, for the treatment of PC of colorectal origin. Methods: Prodige 7 is a randomized phase III, multicenter trial. Patients with histologically proven and isolated PC, peritoneal cancer index (PCI) ≤25 were eligible. Randomization (1:1) was stratified by center, complete macroscopic resection (R0/1 vs R2), and neoadjuvant systemic chemotherapy. Patients were treated with CRS plus HIPEC with oxaliplatin or CRS alone, in association with systemic chemotherapy. The primary endpoint was the overall survival (OS). Secondary endpoints were relapse-free survival (RFS) and toxicity. 264 patients were required to show a gain in median OS from 30 to 48 months (HR = 0.625) with a two-sided α = 0,046 and 80% power. Results: 265 patients from 17 centers were included between February 2008 and January 2014: 132 in Arm without HIPEC and 133 in Arm with HIPEC. The median age was 60 years (range: 30-74). Baseline characteristics were well balanced. The overall post-operative mortality rate was 1.5% and was not different between the two arms. The morbidity rates did not differ statistically at 30 days. At 60 days, the grade 3-5 morbidity rate was significantly higher with HIPEC (24.1% vs. 13.6%, p= 0.030). After a median follow up of 63.8 months (95% CI: 58.9-69.8), the median OS was 41.2 months (95% CI 35.1-49.7) in the non-HIPEC Arm and 41.7 months (95% CI: 36.2-52.8) in the HIPEC Arm, HR = 1.00 (95% CI: 0.73-1.37) p = 0.995. The median RFS was 11.1 months (95% CI: 9-12.7) in non-HIPEC Arm and 13.1 months (95% CI: 12.1-15.7) in HIPEC Arm, HR = 0.90 (95% CI: 0.69-1.90) (p = 0.486), whilst the 1-year RFS rates were 46.1% in non-HIPEC Arm and 59 % in the HIPEC Arm. Conclusions: The therapeutic curative management of PC from colorectal cancer by CRS shows satisfactory survival results. While the addition of HIPEC with oxaliplatin does not influence the OS. Clinical trial information: NCT00769405.

Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy.A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included.The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups.For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patient's selection.

PURPOSE Gastric cancer (GC) with peritoneal metastases (PMs) is a poor prognostic evolution. Cytoreductive surgery (CRS) yields promising results, but the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. Here we aimed to compare outcomes between CRS-HIPEC versus CRS alone (CRSa) among patients with PMs from GC. PATIENTS AND METHODS From prospective databases, we identified 277 patients with PMs from GC who were treated with complete CRS with curative intent (no residual nodules &gt; 2.5 mm) at 19 French centers from 1989 to 2014. Of these patients, 180 underwent CRS-HIPEC and 97 CRSa. Tumor burden was assessed using the peritoneal cancer index. A Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) based on propensity score was used to assess the effect of HIPEC and account for confounding factors. RESULTS After IPTW adjustment, the groups were similar, except that median peritoneal cancer index remained higher in the CRS-HIPEC group (6 v 2; P = .003). CRS-HIPEC improved overall survival (OS) in both crude and IPTW models. Upon IPTW analysis, in CRS-HIPEC and CRSa groups, median OS was 18.8 versus 12.1 months, 3- and 5-year OS rates were 26.21% and 19.87% versus 10.82% and 6.43% (adjusted hazard ratio, 0.60; 95% CI, 0.42 to 0.86; P = .005), and 3- and 5-year recurrence-free survival rates were 20.40% and 17.05% versus 5.87% and 3.76% ( P = .001), respectively; the groups did not differ regarding 90-day mortality (7.4% v 10.1%, respectively; P = .820) or major complication rate (53.7% v 55.3%, respectively; P = .496). CONCLUSION Compared with CRSa, CRS-HIPEC improved OS and recurrence-free survival, without additional morbidity or mortality. When complete CRS is possible, CRS-HIPEC may be considered a valuable therapy for strictly selected patients with limited PMs from GC.

Objective To analyze a large series of patients with pseudomyxoma peritonei (PMP) treated with cytoreductive surgery associated with perioperative intraperitoneal chemotherapy (PIC) in 18 French-speaking centers. Patients and methods From March 1993 to December 2007, 301 patients with diffuse PMP were treated by cytoreductive surgery with PIC. Complete cytoreductive surgery was achieved in 219 patients (73%), and hyperthermic intraperitoneal chemotherapy (HIPEC) was performed in 255 (85%), mainly during the latter period of the study. Results Postoperative mortality and morbidity were 4.4% and 40%, respectively. The mean follow-up was 88 months. The 5-year overall and disease-free survival rates were 73% and 56%, respectively. The multivariate analysis identified 5 prognostic factors: the extent of peritoneal seeding (p=0.004), the center (p=0.0004), the pathologic grade (p=0.03), gender (p=0.02), and the use of HIPEC (p=0.04). When only the 206 patients with complete cytoreductive surgery were considered, the extent of peritoneal seeding was the only significant prognostic factor (p=0.004). Conclusion This large multicentric retrospective study confirms that cytoreductive surgery combined with PIC (with the use of hyperthermia) should be considered as the gold standard treatment of PMP and should be performed in specialized centers. It underlines the prognostic impact of the extent of peritoneal seeding, especially in patients treated by complete cytoreductive surgery. This prognostic impact appears to be greater than that of the pathologic grade.

Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies.

Introduction An important component of treatment failure in gastric cancer (GC) is cancer dissemination within the peritoneal cavity and nodal metastasis. Intraperitoneal chemotherapy (IPC) is considered to give a fundamental contribute in treating advanced GC. The purpose of the study is to investigate the effects of IPC in patients with advanced GC. Material and methods A systematic review with meta-analysis of randomized controlled trials (RCTs) of IPC + surgery vs. control in patients with advanced GC was performed. Results Twenty prospective RCTs have been included (2145 patients: 1152 into surgery + IPC arm and 993 into control arm). Surgery + IPC improves: 1, 2 and 3-year mortality (OR = 0.31, 0.27, 0.29 respectively), 2 and 3-year mortality in patients with loco-regional nodal metastasis (OR = 0.28, 0.16 respectively), 1 and 2-year mortality rate in patients with serosal infiltration (OR = 0.33, 0.27 respectively). Morbidity rate was increased by surgery + IPC (OR = 1.82). The overall recurrence and the peritoneal recurrence rates were improved by surgery + IPC (OR = 0.46 and 0.47 respectively). There was no statistically significant difference in lymph-nodal recurrence rate. The rate of haematogenous metastasis was improved by surgery + IPC (OR = 0.63). Conclusions 1, 2 and 3-year overall survival is incremented by the IPC. No differences have been found at 5-year in overall survival rate. 2 and 3-year mortality rates in patients with nodal invasion and 1 and 2-year mortality rates in patients with serosal infiltration are improved by the use of IPC. IPC has positive effect on peritoneal recurrence and distant metastasis. Morbidity rate is incremented by IPC. Loco-regional lymph-nodes invasion in patients affected by advanced gastric cancer is not a contraindication to IPC.

In Europe, gastric cancer remains diagnosed at advanced stage (serosal and/or lymph node involvement). Despite curative management combining perioperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates of T3 and/or N + patients remain under 30%. More than 50% of recurrences are peritoneal and/or locoregional. The use of adjuvant hyperthermic intraperitoneal chemotherapy that eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences, was extensively evaluated by several randomized trials conducted in Asia. Two meta-analysis reported that adjuvant hyperthermic intraperitoneal chemotherapy significantly reduces the peritoneal recurrences and significantly improves the overall survival. As it was previously done for the evaluation of the extension of lymph node dissection, it seems very important to validate on European or caucasian patients the results observed in trials performed in Asia. GASTRICHIP is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of hyperthermic intraperitoneal chemotherapy with oxaliplatin on patients with gastric cancer involving the serosa and/or lymph node involvement and/or with positive cytology at peritoneal washing, treated with perioperative systemic chemotherapy and D1-D2 curative gastrectomy. Peroperatively, at the end of curative surgery, patients will be randomized after preoperatively written consent has been given for participation. Primary endpoint will be overall survival from the date of surgery to the date of death or to the end of follow-up (5 years). Secondary endpoint will be 3- and 5-year recurrence-free survival, site of recurrence, morbidity, and quality of life. An ancillary study will compare the incidence of positive peritoneal cytology pre- and post-gastrectomy in two arms of the study, and assess its impact on 5-year survival. The number of patients to be randomized was calculated to be 306. EudraCT number: 2012-005748-12, ClinicalTrials.gov identifier: NCT01882933 .

Background Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases. Methods We did an open-label, randomised, phase 3 study in 23 hospitals in France. Eligible patients were aged 18–70 years and had a primary colorectal cancer with synchronous and localised colorectal peritoneal metastases removed during tumour resection, resected ovarian metastases, or a perforated tumour. Patients were randomly assigned (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC (oxaliplatin 460 mg/m2, or oxaliplatin 300 mg/m2 plus irinotecan 200 mg/m2, plus intravenous fluorouracil 400 mg/m2), or mitomycin-HIPEC (mitomycin 35 mg/m2) alone in case of neuropathy, after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence. Randomisation was done via a web-based system, with stratification by treatment centre, nodal status, and risk factors for colorectal peritoneal metastases. Second-look surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable. Surveillance after resection of colorectal cancer was done according to the French Guidelines. The primary outcome was 3-year disease-free survival, defined as the time from randomisation to peritoneal or distant disease recurrence, or death from any cause, whichever occurred first, analysed by intention to treat. Surgical complications were assessed in the second-look surgery group only. This study was registered at ClinicalTrials.gov, NCT01226394. Findings Between June 11, 2010, and March 31, 2015, 150 patients were recruited and randomly assigned to a treatment group (75 per group). After a median follow-up of 50·8 months (IQR 47·0–54·8), 3-year disease-free survival was 53% (95% CI 41–64) in the surveillance group versus 44% (33–56) in the second-look surgery group (hazard ratio 0·97, 95% CI 0·61–1·56). No treatment-related deaths were reported. 29 (41%) of 71 patients in the second-look surgery group had grade 3–4 complications. The most common grade 3–4 complications were intra-abdominal adverse events (haemorrhage, digestive leakage) in 12 (23%) of 71 patients and haematological adverse events in 13 (18%) of 71 patients. Interpretation Systematic second-look surgery plus oxaliplatin-HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes. Funding French National Cancer Institute.

Pseudomyxoma Peritonei (PMP) is a rare peritoneal malignancy, most commonly originating from a perforated epithelial tumour of the appendix. Given its rarity, randomized controlled trials on treatment strategies are lacking, nor likely to be performed in the foreseeable future. However, many questions regarding the management of appendiceal tumours, especially when accompanied by PMP, remain unanswered. This consensus statement was initiated by members of the Peritoneal Surface Oncology Group International (PSOGI) Executive Committee as part of a global advisory role in the management of uncommon peritoneal malignancies. The manuscript concerns an overview and analysis of the literature on mucinous appendiceal tumours with, or without, PMP. Recommendations are provided based on three Delphi voting rounds with GRADE-based questions amongst a panel of 80 worldwide PMP experts.

Peritoneal surface malignancies comprise a heterogeneous group of primary tumours, including peritoneal mesothelioma, and peritoneal metastases of other tumours, including ovarian, gastric, colorectal, appendicular or pancreatic cancers. The pathophysiology of peritoneal malignancy is complex and not fully understood. The two main hypotheses are the transformation of mesothelial cells (peritoneal primary tumour) and shedding of cells from a primary tumour with implantation of cells in the peritoneal cavity (peritoneal metastasis). Diagnosis is challenging and often requires modern imaging and interventional techniques, including surgical exploration. In the past decade, new treatments and multimodal strategies helped to improve patient survival and quality of life and the premise that peritoneal malignancies are fatal diseases has been dismissed as management strategies, including complete cytoreductive surgery embedded in perioperative systemic chemotherapy, can provide cure in selected patients. Furthermore, intraperitoneal chemotherapy has become an important part of combination treatments. Improving locoregional treatment delivery to enhance penetration to tumour nodules and reduce systemic uptake is one of the most active research areas. The current main challenges involve not only offering the best treatment option and developing intraperitoneal therapies that are equivalent to current systemic therapies but also defining the optimal treatment sequence according to primary tumour, disease extent and patient preferences. New imaging modalities, less invasive surgery, nanomedicines and targeted therapies are the basis for a new era of intraperitoneal therapy and are beginning to show encouraging outcomes.

Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available.To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP.This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018.HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens.Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models.Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P < .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules.In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.

The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures.Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or M0 with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray.Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P =.004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival.A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.

This article reviews a single institution's experience with 68 patients (21 females, 47 males) prospectively treated over the last 2 decades with an aggressive local-regional approach, combining maximal cytoreductive surgery with heated intraoperative intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. This multimodality treatment has resulted in a median survival of 67 months. Female patients had a significantly better prognosis than males. The other significant predictive factors of survival were: age, diagnosis by incidental findings, tumor extent, pathology, and completeness of cytoreduction.

To evaluate the tolerance of peritonectomy procedures (PP) combined with intraperitoneal chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis (PC), a phase II study was carried out from January 1998 to September 2001.Fifty-six patients (35 females, mean age 49.3) were included for PC from colorectal cancer (26 patients), ovarian cancer (seven patients), gastric cancer (six patients), peritoneal mesothelioma (five patients), pseudomyxoma peritonei (seven patients), and miscellaneous reasons (five patients). Surgeries were performed mainly on advanced patients (40 patients stages 3 and 4 and 16 patients stages 2 and 1) and were synchronous in 36 patients. All patients underwent surgical resection of their primary tumor with PP and IPCH (with mitomycin C, cisplatinum, or both) with a closed sterile circuit and inflow temperatures ranging from 46 degrees to 48 degrees C. Three patients were included twice.A macroscopic complete resection was performed in 27 cases. The mortality and morbidity rates were one of 56 and 16 of 56, respectively. The 2-year survival rate was 79.0% for patients with macroscopic complete resection and 44.7% for patients without macroscopic complete resection (P =.001). For the patients included twice, two are alive without evidence of disease, 54 and 47 months after the first procedure.IPCH and PP are able to achieve unexpected long-term survival in patients with bulky PC. However, one must be careful when selecting the patients for such an aggressive treatment, as morbidity rate remains high even for an experienced team.

Hypothesis:The most common cause of palliative resection and recurrence in gastric cancer is peritoneal seeding.This study evaluates the efficacy of intraperitoneal chemohyperthermia after cytoreductive surgery in patients with peritoneal carcinomatosis arising from gastric cancer.Design: Prospective clinical trial.Setting: Surgical department at a university academic hospital.Patients: Forty-nine consecutive patients with peritoneal carcinomatosis treated between January 1

Abstract Background Colorectal cancer with peritoneal carcinomatosis is usually considered incurable. The purpose of this study was to evaluate the efficacy of intraperitoneal chemohyperthermia (IPCH) following cytoreductive surgery in patients with colorectal carcinomatosis. Methods Between January 1989 and August 2002, 53 patients (mean age 48·6 years) were treated by IPCH with mitomycin C. IPCH was performed in 34 patients following extensive cytoreductive surgery (more than two peritonectomy procedures). Five patients underwent two operations and one patient three operations. Results Operative morbidity and mortality rates were 23 and 4 per cent respectively. At a median follow-up of 59·5 months, the overall median survival was 12·8 months. The extent of carcinomatosis, completeness of cytoreduction and histological differentiation were significant prognostic indicators by univariate analysis. The median survival was 32·9 months for patients whose resection was classified as completeness of cancer resection (CCR) 0 (complete cytoreduction), 12·5 months for those whose operation was CCR-1 (diameter of residual nodules 5 mm or less) and 8·1 months for patients who had a CCR-2 resection (diameter of residual nodules more than 5 mm) (P &amp;lt; 0·001). Completeness of cytoreduction was the only significant independent predictor of survival by multivariate analysis. Conclusion IPCH combined with cytoreductive surgery seems to be an effective therapy for carefully selected patients with carcinomatosis from colorectal cancer. This strategy was most effective in patients with carcinomatosis of limited tumour volume or when cytoreductive surgery allowed sufficient downstaging (residual tumour nodules smaller than 5 mm).

In Brief Objective: To report a large number of patients with peritoneal carcinomatosis (PC) treated with complete cytoreductive (CCR-0) plus intraperitoneal chemotherapy, and to compare the results according to the origin of the primary: colon, rectum, small bowel, and appendix (excluding peritoneal pseudomyxoma). Patients and Methods: Among 615 patients treated for PC originating from these 4 types of primaries in 23 French centers, 440 were retrospectively selected as having undergone complete cytoreductive surgery and with complete data retrieval. Primary sites were: colon (n = 341), rectum (n = 27), appendix (n = 41), and small bowel (n = 31). Results: Postoperative mortality and morbidity (3.9% and 31%, respectively) did not differ according to the origin of the primary tumor. The mean follow-up was 60 months. The 5-year overall survival rates were not statistically different for the colon (29.7%), rectum (37.9%), nor the small bowel (33.8%), but was higher (P = 0.01) for appendix adenocarcinoma (63.2%). The multivariate analysis of prognostic factors singled out the extent of peritoneal seeding (P < 0.0001), positive lymph nodes (P = 0.001), and adjuvant systemic chemotherapy (P = 0.002), whereas the origin of the tumor was borderline (P = 0.06) in favor of appendix tumors. Conclusion: Cytoreductive surgery plus intraperitoneal chemotherapy yields satisfying and similar survival results in the treatment of PC from colon, rectum, and small bowel adenocarcinomas. Results were better for appendix adenocarcinoma. When feasible, this combined approach should become the gold standard treatment of PC. Complete cytoreductive surgery and intraperitoneal chemotherapy results in a 33% 5-year survival rate. Results were similar for peritoneal carcinomatosis originating from colon, rectum, and small bowel adenocarcinomas, but were better for those originating from the appendix.

Abstract 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. Cancer 2011. © 2010 American Cancer Society.

Following international consensus, HIPEC should be the acronym used in the scientific literature to refer to the hyperthermic intraperitoneal chemotherapy. Several modalities of perfusion are used to deliver HIPEC: open abdominal technique (Coliseum), closed abdominal technique, peritoneal cavity expander, semi-opened abdominal technique. There is no sufficient evidence in literature confirming the superiority of one technique over the others in terms of outcome, morbidity and safety to the personnel of the operating theatre. Each option has its own operational advantages and disadvantages and future prospective studies must be conducted to establish which one is the best alternative. Today, the best technique is the one which is routinely used and improved into each specialized institution involved in the management of peritoneal surface malignancy.

Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery. Methods The American Society of Peritoneal Surface Malignancies (ASPSM) examined the overall survival in patients with CRCPC who underwent a complete cytoreduction and HIPEC with Oxaliplatin vs. Mitomycin C (MMC), stratifying them by the Peritoneal Surface Disease Severity Score (PSDSS). Results Median overall survival (OS) of 539 patients with complete cytoreduction was 32.6 months, 32.7 months for the MMC group and 31.4 months for the Oxaliplatin group (P = 0.925). However, when stratified by PSDSS, median OS rates in PSDSS I/II patients were 54.3 months in those receiving MMC vs. 28.2 months in those receiving oxaliplatin (P = 0.012), whereas in PSDSS III/IV patients, median OS rates were 19.4 months in those receiving MMC vs. 30.4 months in those receiving Oxaliplatin (P = 0.427). Conclusion These data suggest that MMC might be a better agent for HIPEC delivery than Oxaliplatin in patients with CRCPC, favorable histologies and low burden of disease (PSDSS I/II) undergoing complete cytoreduction. Propsective studies are warranted, which stratify patients by their PSDSS and randomize them to HIPEC with MMC vs. Oxaliplatin. J. Surg. Oncol. 2014 110:779–785. © 2014 Wiley Periodicals, Inc.

Even in after curative surgery and adequate linfoadenectomy the survival of advanced gastric cancer (AGC) remains poor. At present some data have been published on the effects of NACT and perioperative chemotherapy on AGC and Esophago-gastric cancer (EGC) but not definitive ones. The present meta-analysis aims to evaluate the effects of neoadjuvant chemotherapy (NACT) on the AGC and EGC. A systematic review with meta-analysis of randomized controlled trials (RCTs) of NACT + surgery vs. Surgery in patients with AGC and EGC was performed. 15 RCTs have been included (2001 patients: 977 into NACT + surgery arm and 1024 into control arm). NACT + Surgery reduces the overall mortality at 1, 3 and 5-year in cumulative analysis (RR = 0.78; 0.81; 0.88 respectively), at 1, 2, 3 and 5-years in EGC (RR = 0.79; 0.83; 0.84; 0.91 respectively) and at 3 and 5-years in AGC (RR = 0.74; 0.82 respectively). Morbidity and perioperative mortality rate are not influenced by NACT. Recurrence rate is reduced by NACT + surgery in EGC (RR = 0.80). NACT reduces the mortality in gastric and esophago-gastric cancer. Morbidity and perioperative mortality are not influenced by NACT. The overall recurrence rate is reduced by NACT in esophago-gastric cancer.

Background At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice. Methods HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and countrywide practice. Results It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies. Conclusion This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.

Objective To review our 25‐year experience with hyperthermic intra‐peritoneal chemotherapy (HIPEC). Background Combining cytoreductive surgery (CRS) and HIPEC as local treatments for peritoneal carcinomatosis (PC) was proposed 25 years ago. Methods A prospective database of all patients undergoing HIPEC for PC since 1989 was searched for clinicopathological data, 90‐day morbidity and mortality, and survival. Results Among 1,125 HIPEC procedures, PC origin was colorectal (342; 30%), ovarian (271; 24%), pseudomyxoma peritonei (189; 17%), gastric (127; 11%), malignant mesothelioma (84; 8%), or other (112; 10%). Between 2004–2009 (n = 321) and 2010–2015 (n = 560), the median peritoneal cancer index decreased (11 vs. 8; P &lt; 0.001), fewer patients underwent incomplete cytoreduction (CC2‐3: 4% vs. 0.5%; P &lt; 0.001), and more were included in randomized trials (5% vs. 16%; P &lt; 0.001). Postoperative morbidity (52% vs. 50%, P = 0.672) was not different, but mortality significantly decreased (5% vs. 2%; P = 0.030). Median overall‐survival was 42 months, and improved significantly for each 5‐year period except for 2006–2010 vs. 2011–2015 ( P = 0.097). The 10‐year survival without recurrence was 53%, 14%, 4%, 10%, and 9% for pseudomyxoma, mesothelioma, ovarian, colorectal, and gastric PC, respectively. Conclusion This study demonstrated that CRS and HIPEC provide long‐term survival irrespective of PC origin, and survival improves with experience. J. Surg. Oncol. 2016;113:796–803 . © 2016 Wiley Periodicals, Inc.

BackgroundEnhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part I of the guidelines highlights preoperative and intraoperative management.MethodsThe core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations.ResultsResponse rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items, No consensus could be reached regarding the preemptive use of fresh frozen plasma.ConclusionThe present ERAS recommendations for CRS±HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS±HIPEC and to prospectively evaluate recommendations in clinical practice.

The aim was to determine the incremental value of MRI compared with CT in the preoperative estimation of the peritoneal carcinomatosis index (PCI).CT and MRI examinations of patients with peritoneal carcinomatosis were evaluated. CT images were first analysed by two observers who determined a first PCI (PCICT ). Then, the two observers reviewed MRI examinations in combination with CT and determined a second PCI (PCICT+MRI ). The sensitivity and negative predictive value of the two imaging sets were determined using surgery as a reference standard (PCIRef ).CT plus MRI was more accurate in predicting the surgical PCI than CT alone. The absolute difference between PCICT+MRI and PCIRef was lower than that between PCICT and PCIRef (mean(s.d.) 3·96(4·10) versus 4·89(4·73); P = 0·010). The number of true-positive findings increased from 106 to 125 for reader 1 and from 117 to 132 for reader 2 with the adjunct of MRI. For both readers, an increased sensitivity was obtained when both MRI and CT were used (from 63 to 81 per cent for reader 1; from 44 to 81 per cent for reader 2). The increase in sensitivity was greater for patients with a moderate volume of disease.The combination of CT and MRI improved the preoperative estimation of PCI compared with CT alone.

Recently, Peritoneal Surface Oncology Group International (PSOGI) developed a novel comprehensive treatment consisting of cytoreductive surgery (CRS) and perioperative chemotherapy (POC) for the treatment of peritoneal metastases (PM) from gastric cancer with curative intent. This article reviews the results of this treatment and verifies its indication. In this strategy, peritoneal cancer index (PCI) is determined by laparoscopy, and a peritoneal port is placed. Neoadjuvant bidirectional intraperitoneal/systemic chemotherapy (NIPS) is performed for 3 cycles, and then laparotomy is performed. Cytoreductive surgery with peritonectomy procedures and hyperthermic intraperitoneal chemoperfusion (HIPEC) are performed. Multivariate analyses showed that completeness of cytoreduction, pathologic response to NIPS and PCI level and cytologic status after NIPS, as independent prognostic factors. PCI less than cut-off level after NIPS, negative cytology after NIPS, and positive response to NIPS were identified as the indications for comprehensive treatment. Patients who hold these criteria should be considered as the candidates for CRS and HIPEC.

PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis (PC). We aimed to evaluate the postoperative outcome of PIPAC in patients with non-resectable PC during our initial experience of the technique.All patients who underwent PIPAC for non-resectable PC in three centers were analyzed regarding postoperative outcomes.Seventy-three patients underwent 164 PIPAC. PC was from colorectal, gastric, ovarian, malignant mesothelioma, pseudomyxoma peritonei or other origins in 20, 26, 13, 8, 1 and 5 patients respectively. Forty-five (62%), 31 (42%), 8 (11%), 6 (8%), 1 (1%) patients underwent a second, third, fourth, fifth, and sixth PIPAC respectively. At the time of the first PIPAC, the median PCI was 17 (1-39), 57 patients presented with symptomatic PC (pain: 33; ascites: 35; transit disorder like diarrhea and constipation: 11). PCI improved in 64.5% of patients, 63.5% of patients presented with complete disappearance of symptoms. Major complications occurred as the outcome of 16 PIPAC (9.7%) and 5 (6.8%) patients died within 30 days of the PIPAC procedure. Rate of mortality and major complications 40% and 62% respectively occurred in first 20 treated patients. For 64 (88%) patients, systemic chemotherapy was associated with PIPAC and could be administered after PIPAC with a median delay of 14 days (2-28).Implementing a PIPAC program in association with systemic chemotherapy is feasible and is associated with a risk of postoperative morbidity, even in teams highly experienced in PC management and requires a learning curve in patient selection.

Background: Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear. Methods: Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction. Results: Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3–12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. Mutations of RAS/RAF impaired survival independently of targeted treatment against EGFR. Consequently, a simple point-based risk score termed BIOSCOPE (BIOlogical Score of COlorectal PEritoneal metastasis) based on PCI, N-, G-, and RAS/RAF status was developed, which showed good discrimination [development area under the curve (AUC) = 0.72, validation AUC = 0.70], calibration ( P = 0.401) and allowed categorization of patients into 4 groups with strongly divergent survival outcomes. Conclusion: RAS/RAF mutations impair survival after CRS/HIPEC. The novel BIOSCOPE score reflects tumor biology, adequately stratifies long-term outcomes, and improves patient assessment and selection.

The completeness of cytoreduction has been considerated as fundamental in increasing the life expectancy in patients with peritoneal carcinosis (PC) in gastric cancer. However no definitive data about the real effect of complete cytoreduction (CC) have still been published. Moreover the PCI cut-off to attempt CC with a reasonable risk-benefit ratio still lacks.A systematic review with meta-analysis of trials of complete vs incomplete cytoreduction in patients with peritoneal carcinosis from GC was performed.Nine trials have been included (748 patients: 417 with CC0-CC1 and 324 with CC2-CC3 cytoreduction). 1, 2, 3 and 5 years survival is favorable to CC0-CC1 (Risk Ratio: 2.41, 8.18, 8.66, and 7.96 respectively). CC0 vs. CC1 survival benefit at 1 and 3 years: RR 2.28 and 6.36 respectively, favoring CC0. 1, 2, 3 and 5 years survival changes significantly above and below a PCI of 12.1, 2, 3 and 5-year overall survival is increased by CC0-CC1 cytoreduction in patients with PC from gastric origin. Moreover CC0 increases the 1 and 3 years survival when compared to CC1 cytoreduction.

Background Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method offered in selected patients suffering from non-resectable peritoneal carcinomatosis (PC). As reported experience is still limited, we conducted a survey among active PIPAC centers aiming to report their technical approach and clinical findings. Methods An online survey was sent to active PIPAC centers worldwide. The questionnaire consisted of 34 closed questions and was conducted over a period of 3 months beginning in March 2017. Results Nine out of 15 contacted centers completed the questionnaire totaling 832 PIPAC procedures in 349 patients. Most common indications for PIPAC were PC from gastric, ovarian and colorectal origin. The mean time between each PIPAC procedure was 6–8 weeks. Seven of nine (77.8%) centers evaluate the PCI at every PIPAC procedure. At least four tissue samples for histopathology analysis were retrieved in 5 (55.6%). All centers (100%) use the same chemotherapy protocol: oxaliplatin at a dosage of 92mg/m2 for PC of colorectal origin and a combination of cisplatin and doxorubicin at a dosage of 7.5mg/m2 and 1.5mg/m2, respectively, for other types of PC. Eight centers (88.9%) perform routine radiological evaluation before first PIPAC and after third PIPAC. Conclusion These data confirm that PIPAC procedures are homogeneously performed in established centers. Standardization of the procedure will facilitate future international multicenter prospective clinical trials.

BackgroundEnhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part II of the guidelines highlights postoperative management and special considerations.MethodsThe core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations.ResultsResponse rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items. No consensus could be reached regarding the preemptive use of fresh frozen plasma.ConclusionThe present ERAS recommendations for CRS ± HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS ± HIPEC and to prospectively evaluate recommendations in clinical practice.

<h2>Abstract</h2><h3>Purpose</h3> Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network. <h3>Patients and methods</h3> From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC). <h3>Results</h3> All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (<i>P</i> = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (<i>P</i> = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07–4.94; <i>P</i> = 0.033). <h3>Conclusion</h3> This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.

Background: Perioperative chemotherapy has proven valuable in several tumors, but not in colon cancer (CC). Objective: The aim of this study was to evaluate the efficacy and safety of perioperative chemotherapy in patients with locally advanced nonmetastatic CC. Methods: This is a French multicenter randomized phase II trial in patients with resectable high-risk T3, T4, and/or N2 CC on baseline computed tomography (CT) scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type patients, a third arm testing perioperative FOLFOX-cetuximab was added. Tumor Regression Grade (TRG1) of Ryan et al was the primary endpoint. Secondary endpoints were toxicity, perioperative morbidity, and quality of surgery. Results: A total of 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped (lack of efficacy). The remaining 104 patients (control, n = 52; FOLFOX preop n = 52) represented our intention-to-treat population. In the FOLFOX perioperative group, 96% received the scheduled 4 cycles before surgery. R0 resection and complete mesocolic excision rate were 94% and 93%, respectively. Overall mortality and morbidity rates were similar in both groups. Perioperative FOLFOX chemotherapy did not improve major pathological response rate (TRG1 = 8%) but was associated with a significant pathological regression (TRG1-2 = 44% vs 8%, P &lt; 0.001) and a trend to tumor downstaging as compared to the control group. CT scan criteria were associated with a 33% rate of overstaging in control group. Conclusions: Perioperative FOLFOX for locally advanced resectable CC is feasible with an acceptable tolerability but is not associated with an increased major pathological response rate as expected. However, perioperative FOLFOX induces pathological regression and downstaging. Better preoperative staging tools are needed to decrease the risk of overtreating patients

<h2>Abstract</h2><h3>Background</h3> PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC. <h3>Methods</h3> A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0. <h3>Results</h3> One hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32–74). Median PCI was 17 (1–39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1–12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC. <h3>Conclusions</h3> PIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication.

Peritoneal mesothelioma (PM) is a rare and aggressive primary peritoneal malignancy characterized by widespread multiple metastatic tumour nodules originating from the peritoneum. The conventional classification distinguishes diffuse malignant peritoneal mesothelioma (DMPM) and border-line forms: multicystic peritoneal mesothelioma (MCPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM). Despite the novel achievements in the management of PM, there is difficulty in conducting randomized trials due to its rarity and aggressive biology in many cases. As there is, a necessity to standardize diagnosis and management of PM, the Peritoneal Surface Oncology Group International (PSOGI) commissioned a steering committee to elaborate clinical guidelines.

<h2>Abstract</h2><h3>Background</h3> PIPAC is a recent method of intraperitoneal chemotherapy. The aim of this study was to describe the clinical characteristics of the patients who became amenable to CRS & HIPEC after PIPAC treatment. <h3>Methods</h3> All patients diagnosed with unresectable PM who became resectable throughout PIPAC treatment were included. Outcome criteria were adverse events following PIPAC procedure and rate of secondary CRS and HIPEC. <h3>Results</h3> Four hundred thirty-seven PIPAC were done in 146 consecutive patients. Among them, 26 patients (17.8%) who underwent 76 PIPAC were scheduled for CRS and HIPEC after reduction of the peritoneal burden. PM were from gastric, peritoneal mesothelioma, ovarian, colorectal and small bowel in 13, 7, 4, 1 and 1 patients, respectively. At the time of the first PIPAC, median age was 58.6 years (32–76.3). Median PCI was 16 (1–39). All patients had systemic chemotherapy in between PIPAC session. Median consecutive PIPAC procedure was 3 (1–8). Complications occurred in 3 PIPAC session (4%) and there was no major complication (CTCAE III or higher). Complete CRS and HIPEC was achieved in 21 patients of the 26 scheduled (14.4%). The remaining 5 patients were considered unresectable at the exploratory laparotomy. Among patients who underwent CRS and HIPEC, with median follow-up of 7 (1–26) months, 14 patients (66.7%) were alive without recurrence, 2 patients (9.5%) were alive with recurrence and 5 patients (23.8%) died. <h3>Conclusions</h3> Complete CRS and HIPEC can be achieved in strictly selected patient with unresectable PM at diagnosis after repeated PIPAC session with palliative intent.

Most patients with peritoneal carcinomatosis of digestive tract origin die within 6 months. Intraperitoneal chemohyperthermia (IPCH) associated with surgery has been reported as a possible new therapeutic approach.A prospective Phase II trial was carried out with 83 patients who had digestive tract cancer and peritoneal carcinomatosis to evaluate the tolerance and efficacy of IPCH with mitomycin C (MMC) associated with surgery. Eighty-six IPCH treatments with MMC were given as complementary therapy after surgery (peritoneal perfusate with a 10 mg/L dose of MMC; inflow temperature, 46-49 degrees C; use of a closed circuit; duration, 90 minutes). Primary tumors were mainly gastric (in 42 cases) or colorectal (in 27 cases).Mortality and morbidity occurred in 3 of 83 cases and 8 of 83 cases, respectively. For patients with resectable tumors, the median survival time was 16 months when carcinomatosis was Stage I and II (malignant granulations less than 5 mm in greatest dimension), whereas it was 6 months when carcinomatosis was Stage III and IV (malignant granulations more than 5 mm in greatest dimension). For patients with resectable gastric cancer and Stage I and II carcinomatosis, 1-, 2-, and 3-year actuarial survival rates were 80%, 61%, and 41%, respectively, whereas the rate was 10% at 1 year for patients with bulky disease (Stage III and IV).IPCH appears to be a promising new approach to treating patients with digestive tract cancers and peritoneal carcinomatosis with small, malignant granulations (Stage I and II).

In Brief Objective: The aim of this study was to analyze the survival of patients with peritoneal dissemination of appendiceal malignancy having incomplete cytoreductive surgery. Summary Background Data: Cytoreductive surgery plus perioperative intraperitoneal chemotherapy has emerged as a new and potentially curative treatment option for patients with peritoneal dissemination of appendiceal mucinous tumors. The goal of surgery is to remove all visible disease. Nevertheless, in some patients, complete cytoreduction is not possible. Methods: Over a 30-year period, 645 patients with epithelial peritoneal surface malignancy of appendiceal origin were treated with cytoreductive surgery and intraperitoneal chemotherapy by a single surgeon. One hundred seventy-four (27.1%) of these patients had an incomplete cytoreduction. A critical statistical analysis of the impact of selected clinical features on survival was performed from a prospective database. Results: Mortality and morbidity rates were 0% and 33.3%, respectively. Median survival of these 174 patients was 20.5 months and their 1-year, 3-year, and 5-year survival rates were 71%, 34%, and 15%, respectively. By multivariate analysis, the presence of signet ring cells and lymph node involvement were independent prognostic indicators of poor survival (P = 0.047 and P < 0.001, respectively). Patients who underwent more than 1 cytoreduction or repeat intraperitoneal chemohyperthermia showed significant improvement in survival (P = 0.018 and P < 0.001, respectively) Conclusion: Incomplete cytoreduction plus perioperative intraperitoneal chemotherapy of peritoneal dissemination from appendiceal malignancy results in limited long-term survival. Patients with signet ring histology or lymph node involvement have an especially poor outcome. Repeat cytoreduction and intraperitoneal chemohyperthermia may improve outcome. Incomplete cytoreductive surgery plus intraperitoneal chemotherapy of peritoneal dissemination from appendiceal malignancy results in limited long-term survival. In 174 patients with a median survival of 20.5 months, the presence of signet ring cells and lymph node involvement were independent poor prognostic indicators. Repeat cytoreduction and intraoperative chemohyperthermia may improve outcome.

Pseudomyxoma peritonei is a rare disease. Recently, cytoreductive surgery with intraperitoneal hyperthermic chemotherapy has emerged as a promising treatment for this debilitating condition. The aim of this prospective study was to evaluate this treatment strategy.Twenty-seven patients with pseudomyxoma peritonei who were treated by cytoreductive surgery and intraperitoneal chemohyperthermia between 1997 and 2003 were identified from a prospective database.Clinical presentation included suspected appendicitis (33 percent), increased abdominal girth (30 percent), and a suspected ovarian mass (26 percent). Twenty-two patients underwent surgery elsewhere before referral. Seventeen complications occurred in 12 patients (44 percent). Six were considered major: three anastomotic leaks, two pleural effusions, and one intra-abdominal abscess. Histologic examination demonstrated Grade 1, 2, and 3 disease in 8 (30 percent), 10 (37 percent), and 9 patients (33 percent), respectively. Pathologic grade showed a significant influence on the complication rate (P = 0 0.008). The actuarial five-year survival was 100 percent for patients with Grade 1 disease, whereas actuarial one-, two-, three-, and five-year survival for Grades 2 and 3 were 100, 80, 64, and 32 percent, respectively (P = 0.008).Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy is a feasible treatment for pseudomyxoma peritonei. It is associated with acceptable morbidity when performed by an experienced surgical team. Histologic grade is the major determinant of survival.

The objective of this retrospective study was to evaluate the influence of neoadjuvant systemic chemotherapy on patients with colorectal carcinomatosis before a curative procedure.Peritoneal carcinomatosis (PC) from colorectal cancer may be treated with a curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The role of perioperative systemic chemotherapy for this particular metastatic disease remains unclear.One hundred twenty patients with PC from colorectal cancer were consecutively treated by 131 procedures combining CRS with HIPEC. The response to neoadjuvant systemic chemotherapy was assessed on data from previous explorative surgery and/or radiological imaging.Ninety patients (75%) were treated with neoadjuvant systemic chemotherapy in whom 32 (36%) were considered to have responded, 19 (21%) had stable disease, and 19 (21%) developed diseases progression. Response could not be evaluated in 20 patients (22%). On univariate analysis, the use of neoadjuvant systemic chemotherapy had a significant positive prognostic influence (P = 0.042). On multivariate analysis, the completeness of CRS and the use of adjuvant systemic chemotherapy were the only significant prognostic factors (P < 0.001 and P = 0.049, respectively). Response to neoadjuvant systemic chemotherapy had no significant prognostic impact with median survival of 31.4 months in patients showing disease progression.In patients with PC from colorectal cancer without extraperitoneal metastases, failure of neoadjuvant systemic chemotherapy should not constitute an absolute contraindication to a curative procedure combining CRS and HIPEC.

Tumor involvement of the peritoneum—peritoneal carcinomatosis—is a heterogeneous form of cancer that had been generally regarded as a sign of systemic tumor disease and as a terminal condition. The multimodal treatment approach for patients with peritoneal carcinomatosis, which had been conceived and developed, consists of what is known as cytoreductive surgery, followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Depending on the tumor mass as assessed intraoperatively and the histopathological differentiation, patients who undergo cytoreductive surgery and HIPEC have a significant survival benefit. Mean increases in the survival period ranging from six months to up to four years have now been reported. In view of the substantial logistic effort and the extent of the surgery involved, this treatment approach represents a major challenge both for patients and for surgical oncologists, as well as for the members of the overall interdisciplinary structure required, which includes oncology, anesthesiology and intensive care, psycho-oncology, and patient management. The surgical procedures alone may take 8–14 hr. The present paper provides an overview of the basis for the approach and the use of specialized classifications and quantitative prognostic indicators.

The aim of this study was to assess the outcomes of patients operated on for peritoneal metastases from unusual cancer sites of origin, meaning apart from peritoneal metastases (PM) from colorectal, gastric and epithelial ovarian carcinomas, pseudomyxoma peritonei and mesothelioma.A questionnaire concerning patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for PM arising from unusual cancer sites of origin was sent to all centres, which routinely performed HIPEC, through the Peritoneal Surface Oncology Group International and the RENAPE network.Between September 1990 and June 2016, 850 procedures for unusual cases were performed in 781 patients, in 53 centres worldwide. Nearly two-thirds of the procedures were performed for three indications: rare ovarian carcinoma (n = 224), sarcoma (n = 189) and neuroendocrine tumours (n = 127). The median PCI was 12 [0-39]. Grade III-IV postoperative complications occurred in 272 patients (41%). Nineteen patients (2.9%) died postoperatively. After a median follow-up of 46 months, median overall survival (OS) was 39 months [33.18-44.05]. Five-year OS rate was 38.7%. For the three main indications, 5-year OS was significantly greater in patients with PM from rare ovarian carcinoma (57.7%), than that of patients with PM from neuroendocrine tumours (39.9%), and from sarcoma (29.3%) (p < 0.0001).CRS and HIPEC appear to be safe and effective in patients with peritoneal metastases from unusual cancer sites of origin, especially from rare ovarian carcinomas, PM from neuroendocrine tumours. The respective roles of CRS and HIPEC remain unclear and should be evaluated.

The learning curves for cytoreductive surgery with intraperitoneal chemotherapy for treatment of pseudomyxoma peritonei (PMP) were explored between international centres/surgeons to identify institutional or other factors that might affect performance.Data from patients with PMP treated with the combined procedure across 33 international centres between 1993 and 2012 were analysed retrospectively. A risk-adjusted sequential probability ratio test was conducted after defining the target outcome as early oncological failure (disease progression within 2 years of treatment), an acceptable risk for the target outcome (odds ratio) of 2, and type I/II error rates of 5 per cent. The risk prediction model was elaborated and patients were evaluated sequentially for each centre/surgeon. The learning curve was considered to be overcome and proficiency achieved when the odds ratio for early oncological failure became smaller than 2.Rates of optimal cytoreduction, severe postoperative morbidity and early oncological failure were 84·4, 25·7 and 29·0 per cent respectively. The median annual centre volume was 17 (range 6-66) peritoneal malignancies. Only eight of the 33 centres and six of 47 surgeons achieved proficiency after a median of 100 (range 78-284) and 96 (86-284) procedures respectively. The most important institutional factor affecting surgical performance was centre volume.The learning curve is extremely long, so centralization and/or networking of centres is necessary to assure quality of services. One centre for every 10-15 million inhabitants would be ideal.

BACKGROUND: Self-expanding metallic stents (SEMSs) have been used as a bridge to surgery, relieving dysphagia and maintaining nutrition, in patients with operable but obstructive esophageal cancer (EC). However, the impact of SEMSs on oncologic outcomes is unknown. The aim of this study was to evaluate the impact of SEMS insertion before EC surgery on oncologic outcomes. STUDY DESIGN: From 2000 to 2010, two thousand nine hundred and forty-four patients who underwent an operation for EC with a curative intent were included in a multicenter European cohort. Through propensity score analysis, patients who underwent SEMS insertion (SEMS group, n = 38) were matched 1:4 to control patients who did not undergo SEMS insertion (control group, n = 152). RESULTS: The SEMS and control groups were comparable according to age, sex, tumor location, clinical stage, American Society of Anesthesiologists score, dysphagia, malnutrition, neoadjuvant treatment administration, histology, and surgical procedure. Self-expanding metallic stent insertion was complicated by tumoral perforation in 2 patients. The in-hospital postoperative mortality and morbidity rates for the SEMS vs control groups were 13.2% vs 8.6% (p = 0.370) and 63.2% vs 59.2% (p = 0.658), respectively. The R0 resection rate (71.0% vs 85.5%; p = 0.041), median time to recurrence (6.5 vs 9.0 months; p = 0.040), and 3-year overall survival (25% vs 44%; p = 0.023) were significantly reduced in the SEMS group, and the 3-year locoregional recurrence rate was increased (62% vs 34%; p = 0.049). The results remained significant after excluding SEMS-related esophageal perforations. After adjusting for confounding factors, SEMS insertion was a predictor of poor prognosis (hazard ratio = 1.6; p = 0.038). CONCLUSIONS: Self-expanding metallic stent insertion, as a bridge to surgery, has a negative impact on oncologic outcomes in EC. Clinicaltrials.gov ID: NCT 01927016.

<h2>Abstract</h2><h3>Introduction</h3> Malignant mesothelioma is a deadly disease that is strongly associated with asbestos exposure. Peritoneal mesotheliomas account for 10% of all the cases. BRCA1 associated protein 1 (BAP1) is a deubiquitinating hydrolase that plays a key role in various cellular processes. Germline and somatic inactivation of BRCA1 associated protein 1 gene (<i>BAP1</i>) is frequent in pleural mesothelioma; however, little is known about its status in peritoneal mesothelioma. <h3>Methods</h3> Taking advantage of the extensive French National Network for the Diagnosis of Malignant Pleural Mesothelioma and Rare Peritoneal Tumors and the French National Network for the Treatment of Rare Peritoneal Surface Malignancies, we collected biological material and clinical and epidemiological data for 46 patients with peritoneal mesothelioma. The status of <i>BAP1</i> was evaluated at the mutational and protein expression levels and combined with our previous data on copy number alterations assessed in the same samples. <h3>Results</h3> We detected mutations in 32% of the malignant peritoneal mesotheliomas analyzed. In addition, we have previously reported that copy number losses occurred in 42% of the samples included in this series. Overall, 73% of the malignant peritoneal mesotheliomas analyzed carried at least one inactivated <i>BAP1</i> allele, but only 57% had a complete loss of its protein nuclear expression. Better overall survival was observed for patients with <i>BAP1</i> mutations (<i>p</i> = 0.04), protein expression loss (<i>p</i> = 0.016), or at least one of these alterations (<i>p</i> = 0.007) independently of tumor histological subtype, age, and sex. <h3>Conclusions</h3> As in pleural mesothelioma, inactivation of <i>BAP1</i> is frequent in peritoneal mesotheliomas. We found that BAP1 protein nuclear expression is a good prognostic factor and a more reliable marker for the complete loss of BAP1 activity than mutation or copy number loss.

Aims The aims of this study were to compare short- and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy. Methods Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short- and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics. Results No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short- or long-term outcomes. Conclusion The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.

3531 Background: Complete cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) allow to prolong survival in patients with colorectal peritoneal metastases (CRPM), especially with a low tumor burden. The aim of the PROPHYLOCHIP multicentric randomized phase 3 study was to evaluate the potential survival benefit of a systematic second-look surgery plus HIPEC in patients at high risk of developing CRPM. Methods: Patients at high risk of developing CRPM defined as minimal CRPM resected with the primary, or history of ovarian metastases, or perforated primary tumor, were eligible. After 6 months of adjuvant chemotherapy, patients without sign of recurrence were randomized into 2 arms: (1) surveillance, (2) systematic second-look surgery plus HIPEC (intraperitoneal oxaliplatin). The primary end-point was the 3-year disease-free survival (DFS). Secondary end-points included overall survival (OS), peritoneal DFS and postoperative complications. Results: Between 2012 and 2015, 150 patients were randomized. During the second-look laparotomy (n = 71), CRPM was diagnosed in 52%, with a median peritoneal cancer index of 4 [0-26]. No patient died postoperatively and grade 3-4 complications occurred in 41%. After a median follow-up of 51 [47-55] months, the 3-year DFS of 44% [33-56] in the second-look group and of 51% [40-62] in the surveillance group did not differ (p = 0.75). In the surveillance group, a peritoneal relapse occurred in 25 (33%) patients, which was accessible to CRS-HIPEC in 16, whereas in the second-look group, 24 (32%) patients had a peritoneal relapse of whom 2 were treated with a new CRS-HIPEC. The 3-year OS was not significantly different, 80% [69-88] and 79% [68-87] in the surveillance and in the second-look groups, respectively. Conclusions: This study confirms that criteria for high risk of developing PM are strong, and strengthens the role of a peritoneal-centered surveillance in these patients. However, a pro-active strategy including a systematic second-look surgery plus HIPEC failed to improve survival, in comparison to an adequate surveillance. Clinical trial information: NCT01226394.

Abstract Background The peritoneal cancer index (PCI) is a comparative prognostic factor for colorectal peritoneal metastasis (CRPM). The ability of laparoscopy to determine the PCI in consideration of cytoreductive surgery remains undetermined, and this study was designed to compare it with laparotomy. Methods A prospective multicentre study was conducted for patients with no known CRPM, but at risk of peritoneal disease. Surgery began with laparoscopic exploration followed by open exploration to determine the PCI. Concordance between laparoscopic and open assessment was evaluated for the diagnosis of CRPM and for the PCI. Results Among 50 patients evaluated, CRPM recurrence was found in 29 (58 per cent) and 34 (68 per cent) at laparoscopic and open surgery respectively. Laparoscopy was feasible in 88 per cent (44 of 50) and deemed satisfactory by the surgeon in 52 per cent (26 of 50). Among the 25 evaluable patients with satisfactory laparoscopy, there was concordance of 96 per cent (24 of 25 patients) and 38 per cent (10 of 25) for laparoscopic and open assessment of CRPM and the PCI respectively. Where there were discrepancies, it was laparoscopy that underestimated the PCI. Conclusion Laparoscopy may underestimate the extent of CRPM.

The prognosis and chemoresistance of signet-ring cell (SRC) gastric adenocarcinoma have been reported and debated, and the utility of perioperative chemotherapy for such a tumor has been questioned . This study was performed to assess the impact of the SRC type on survival following resection of gastric adenocarcinoma, and to assess whether the prognostic factors (including perioperative chemotherapy) for non-SRC adenocarcinoma differed from those for SRC adenocarcinoma.1799 cases of adenocarcinoma that were consecutively treated from 1997 to 2010 in 19 French centers by subtotal or total gastrectomy were included in a retrospective study. A D2 lymphadenectomy was performed for antropyloric tumors, and a modified D2 for upper tumors. SRC adenocarcinoma was diagnosed based on the presence of isolated carcinoma cells containing mucin.A total gastrectomy was performed in 979 (54.4 %) patients. SRC adenocarcinoma was diagnosed in 899 (50 %) patients. Patients with an SRC tumor were more frequently female, younger, and malnourished, had lower ASA scores, and had larger tumors than non-SRC patients. Median survival in patients with non-SRC carcinoma was 51 months, as compared to 26 months in patients with SRC carcinoma (p < 0.001). At multivariate analysis, SRC type remained an independent adverse prognostic factor (HR = 1.182). Factors that were prognostic in the SRC subgroup but not in the non-SRC subgroup were age >60 years, linitis, and involvement of adjacent organs. In contrast to non-SRC tumors, pre- and postoperative chemotherapy did not significantly impact on survival following resection of SRC adenocarcinoma.In comparison to non-SRC adenocarcinoma, the SRC type has a worse prognosis, different prognostic factors, and is only poorly sensitive to perioperative chemotherapy. Non-SRC and SRC adenocarcinomas should be considered different entities in future therapeutic trials.

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the only curative treatment for many peritoneal surface malignancies. The purpose of this study was to evaluate feasibility and safety of CRS combined with HIPEC by laparoscopy for patients with limited peritoneal disease and to compare postoperative outcomes with those for an open procedure. Methods Between January 2011 and November 2012, all patients with low-grade pseudomyxoma peritonei (PMP) or multicystic mesothelioma (MM) and limited peritoneal disease (Peritoneal Cancer Index [PCI] less than 10) underwent CRS and HIPEC by a laparoscopic approach. The study cohort was matched with a historical cohort of patients with the same characteristics (completeness of cytoreduction, HIPEC agent, PCI ± 11 and age ± 20 years) treated with CRS and HIPEC by laparotomy. Results Eight patients (five low-grade PMP and three MM) treated by a laparoscopic approach were compared to eight patients treated by laparotomy. All patients underwent complete cytoreductive surgery with HIPEC, and no conversion to laparotomy was needed. The median surgical length was 210 min (150–300) vs 240 (210–360), with a median hospital stay of 12 days (9–18) vs 19 (13–33). One patient had a postoperative complication (intraperitoneal haematoma treated by radiological drainage) vs four in the laparotomy group. Conclusion Laparoscopic CRS combined with HIPEC is feasible and safe for curative treatment of strictly selected patients with peritoneal surface malignancy and might reduce postoperative complications and length of hospital stay.

Introduction Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have demonstrated promising results in the treatment of peritoneal carcinomatosis (PC). The purpose of this study was to assess the impact of this combined procedure on quality of life (QoL). Materials and methods A prospective single centre study of 216 consecutive patients treated with CRS and HIPEC was conducted using the Gastro-Intestinal Quality of Life Index questionnaire (GIQLI), completed preoperatively and at 1, 3, 6 and 12 months. Results Questionnaire compliance was 81%, 90%, 89%, 89% and 74% at baseline, 1, 3, 6 and 12 months respectively. QoL was significantly decreased up to 6 months and returned to baseline at 12 months. In multivariate analysis, factors decreasing QoL were origin of PC at 3 months, presence of stoma at 6 months and length of surgery over 270 min and disease recurrence at 12 months. Conclusions Despite morbidity associated with CRS and HIPEC, QoL returned to baseline at one year after surgery. This treatment strategy should be considered for the treatment of peritoneal carcinomatosis.

The Lyon R90-01 randomized trial investigated whether the interval between preoperative radiation therapy and surgery influenced rectal cancer outcome. Long-term results are reported here after a median follow-up of 17 years.Between February 1991 and December 1995, 210 patients from 29 French centers were randomly assigned (ratio of 1:1) to groups that waited either 2 weeks (short interval [SI]) or 6 to 8 weeks (long interval [LI]) between neoadjuvant radiation therapy and surgery. The primary endpoint was sphincter-preserving surgery.LI group showed a better pathologic response (complete response or few residual cells) after radiation therapy than the SI group (26% vs 10.3%, P=.015). A better pathologic response was associated in multivariate analysis with significant improvement of overall survival (pT: P=.0293 and pN: P=.0048) but it was irrespective of the interval duration. The median follow-up was 17.2 years. The 5-, 10-, 15-, and 17-year overall survival rates were, respectively, 66.8%, 48.7%, 40.0%, and 34.0% for the SI group and, respectively, 67.1%, 53.5%, 41.9%, and 34.0% for the LI group. There were no significant differences between groups in terms of survival (P=.7656) or local recurrence rates (SI: 14.4% vs LI: 12.1%, respectively; P=.6202). Of 24 local disease recurrences, 20 (83%) occurred during the first 2 postoperative years, and all but one (96%) occurred during the first 5 postoperative years. The rate of second new malignancies was 9.4% (19 patients).The radiation-induced sterilization rate of the preoperative cancer specimen was a marker of good prognosis. The interval duration (the treatment being the same) although it is modifying the sterilization rate has no impact on survival. Radiation therapy did not postpone local recurrence, because the rate of local relapse after 5 years was low. Radiation-induced cancers after radiation therapy were unusual and should not influence treatment decisions in adults.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become widely accepted as an effective method of treating peritoneal metastases (PM) from various cancers. CRS performed with the goal of removing all the macroscopic disease and comprises of peritonectomy procedures and visceral resections. CRS is a technically challenging surgery that requires a considerable amount of skill and appropriate patient selection. This article is a review of the techniques and current recommendations for performing CRS.

Despite being associated with a very poor prognosis, long-term survivors across all series of Desmoplastic Small Round Cell Tumor (DSRCT) have been reported.To analyze patients 'characteristics associated with a prolonged survival after DSRCT diagnosis.All consecutive patients treated for DSRCT in nine French expert centers between 1991 and 2018 were retrospectively analyzed. Patients with a follow-up of less than 2 years were excluded and cure defined as being disease-free at least 5 years.100 pts were identified (median age 25 years, 89% male). 27 had distant metastases at diagnosis and 80 pts underwent upfront chemotherapy (CT). 71 pts were operated, 20 pts without prior CT). Surgery was macroscopically complete (CC0/1) in 50 pts. Hyperthermic intraperitoneal Chemotherapy (HIPEC) was administered during surgery in 15 pts 54 pts had postoperative CT and 26 pts had postoperative whole abdomino-pelvic RT (WAP-RT). After a median follow-up of 103 months (range 23-311), the median overall survival (OS) was 25 months. The 1- year, 3-year and 5-year OS rates were 90%, 35% and 4% respectively. 5 patients were considered cured after a median disease-free interval of 100 months (range 22-139). Predictive factors of cure were female sex (HR = 0.49, p = 0.014), median PCI<12 (HR = 0.32, p = 0.0004), MD Anderson stage I (HR = 0.25, p < 0.0001), CC0/1 (HR = 0.34, p < 0.0001), and WAP-RT (HR = 0.36, p = 0.00013). HIPEC did not statistically improve survival.Cure in DSRCT is possible in 5% of patients and is best achieved combining systemic chemotherapy, complete cytoreductive surgery and WAP-RT. Despite aggressive treatment, recurrence is common and targeted therapies are urgently needed.

Multimodal treatment, including systemic treatment and surgery, improved the prognosis of peritoneal metastasis (PM). Despite all efforts, recurrence rates remain high, and little data are available about clinical behavior or molecular patterns of PM in comparison to hematogenous metastasis. Here, we aimed to analyze recurrence patterns after multimodal treatment for PM from colorectal cancer.Patients with colorectal PM undergoing multimodal treatment including systemic chemotherapy and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 2005 and 2017 at 4 centers were analyzed retrospectively.A total of 505 patients undergoing CRS/HIPEC were analyzed. Of the patients, 82.1% received preoperative chemotherapy. Median peritoneal cancer index was 6 (interquartile range = 3-11). Median disease-free and overall survival was 12 (95% confidence interval [CI] = 11 to 14) months and 51 (95% CI = 43 to 62) months, respectively. Disease recurred in 361 (71.5%) patients, presenting as isolated peritoneal recurrence in 24.6%, isolated hematogenous recurrence in 28.3%, and mixed recurrence in 13.9% of patients. Recurrence to the peritoneum was associated with an impaired time from recurrence to death of 21 (95% CI = 18 to 31) months for isolated peritoneal and 22 (95% CI = 16 to 30) months for mixed recurrence, compared with 43 (95% CI = 31 to >121) months for hematogenous recurrence (hazard ratio [HR] = 1.79, 95% CI = 1.27 to 2.53; P = .001; and HR = 2.44, 95% CI = 1.61 to 3.79; P < .001). On multiple logistic regression analysis, RAS mutational status (odds ratio [OR] = 2.42, 95% CI = 1.11 to 5.47; P = .03) and positive nodal stage of the primary (OR = 3.88, 95% CI = 1.40 to 11.86; P = .01) were identified as predictive factors for peritoneal recurrence.This study highlights the heterogeneity of peritoneal metastasis in patients with colorectal cancer. Recurrent peritoneal metastasis after radical treatment represents a more aggressive subset of metastatic colorectal cancer.

5510 Background: Standard treatment for patients with first platinum-sensitive relapse of epithelial ovarian cancer (EOC) is based on surgery and second-line systemic chemotherapy (CT). The role of hyperthermic intra-peritoneal chemotherapy (HIPEC) remains uncertain. Methods: The CHIPOR multicentric randomized phase III trial (NCT01376752), conducted in 31 institutions, enrolled patients with a first platinum-sensitive relapse (platinum-free interval of ≥6 months) of EOC. Patients were treated with 6 cycles of platinum and taxane based CT ± bevacizumab, and those amenable to a complete cytoreductive surgery at the end of CT were enrolled and randomly assigned to receive HIPEC (cisplatin 75 mg/m² at 41°C for 60 min) or not. Randomization was performed during complete cytoreductive surgery, stratified by center, surgical outcome (no residual disease vs residual &lt;0.25 cm), chemotherapy-free interval before relapse, and PARP inhibitor use (yes vs no). The primary endpoint was overall survival (OS). The target sample size was 404 evaluable patients, providing 80% power at 5% alpha after 268 deaths. Secondary endpoints included progression-free survival (PFS), peritoneal PFS, patient-reported outcomes, safety, and postoperative morbidity and mortality (≤60 days after surgery). Results: Between May 11, 2011, and May 14, 2021, 415 patients were randomized. Baseline characteristics were balanced between treatment arms. At the data cutoff (Jan 8, 2023), with a median follow-up of 6.2 years, 268 patients (65%) had died. Efficacy results are summarized below. Conclusions: HIPEC significantly improves OS and peritoneal PFS of women with first platinum-sensitive relapse of EOC treated with second-line platinum-based CT followed by secondary complete cytoreductive surgery. Ongoing analyses, including patient reported outcome, BRCA status, bevacizumab exposure, and subsequent therapy, will be presented. Clinical trial information: NCT01376752 . [Table: see text]

Recently, the number of prehabilitation trials has increased significantly. The identification of key research priorities is vital in guiding future research directions. Thus, the aim of this collaborative study was to define key research priorities in prehabilitation for patients undergoing cancer surgery.The Delphi methodology was implemented over three rounds of surveys distributed to prehabilitation experts from across multiple specialties, tumour streams and countries via a secure online platform. In the first round, participants were asked to provide baseline demographics and to identify five top prehabilitation research priorities. In successive rounds, participants were asked to rank research priorities on a 5-point Likert scale. Consensus was considered if > 70% of participants indicated agreement on each research priority.A total of 165 prehabilitation experts participated, including medical doctors, physiotherapists, dieticians, nurses, and academics across four continents. The first round identified 446 research priorities, collated within 75 unique research questions. Over two successive rounds, a list of 10 research priorities reached international consensus of importance. These included the efficacy of prehabilitation on varied postoperative outcomes, benefit to specific patient groups, ideal programme composition, cost efficacy, enhancing compliance and adherence, effect during neoadjuvant therapies, and modes of delivery.This collaborative international study identified the top 10 research priorities in prehabilitation for patients undergoing cancer surgery. The identified priorities inform research strategies, provide future directions for prehabilitation research, support resource allocation and enhance the prehabilitation evidence base in cancer patients undergoing surgery.

There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM.Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use. Crude data analysis, propensity score matching (PSM) and Cox-proportional hazard modelling was performed.Of 2093 patients, 1613 were included in neoadjuvant crude evaluation with 708 in the PSM cohort (354 patients/arm). In the adjuvant evaluation, 1176 patients were included in the crude cohort with 778 in the PSM cohort (389 patients/arm). The median overall survival (OS) in the PSM cohort receiving no neoadjuvant vs neoadjuvant therapy was 37.0 months (95% CI: 32.6-42.7) vs 34.7 months (95% CI: 31.2-38.8, HR 1.08 95% CI: 0.88-1.32, p = 0.46). The median OS in the PSM cohort receiving no adjuvant therapy vs adjuvant therapy was 37.0 months (95% CI: 32.9-41.8) vs 45.7 months (95% CI: 38.8-56.2, HR 0.79 95% CI: 0.64-0.97, p = 0.022). Recurrence-free survival did not differ in the neoadjuvant evaluation but differed in the adjuvant evaluation - HR 1.04 (95% CI: 0.87-1.25, p = 0.66) and 0.83 (95% CI: 0.70-0.98, p = 0.03), respectively. Multivariable Cox-proportional hazard modelling in the crude cohorts showed hazard ratio 1.08 (95% CI: 0.92-1.26, p = 0.37) for administering neoadjuvant therapy and 0.86 (95% CI: 0.72-1.03, p = 0.095) for administering adjuvant therapy.Neoadjuvant therapy did not confer a benefit to patients undergoing CRS+HIPEC for CRCPM, whereas adjuvant therapy was associated with a benefit in this retrospective setting.None.

The purpose of this study was to assess image quality and dose level using a photon-counting CT (PCCT) scanner by comparison with a dual-source CT (DSCT) scanner on virtual monoenergetic images (VMIs) at low energy levels.A phantom was scanned using a DSCT and a PCCT with a volume CT dose index of 11 mGy, and additionally at 6 mGy and 1.8 mGy for PCCT. Noise power spectrum and task-based transfer function were evaluated from 40 to 70 keV on VMIs to assess noise magnitude and noise texture (fav) and spatial resolution on two iodine inserts (f50), respectively. A detectability index (d') was computed to assess the detection of two contrast-enhanced lesions according to the energy level used.For all energy levels, noise magnitude values were lower with PCCT than with DSCT at 11 and 6 mGy, but greater at 1.8 mGy. fav values were higher with PCCT than with DSCT at 11 mGy (8.6 ± 1.5 [standard deviation [SD]%), similar at 6 mGy (1.6 ± 1.5 [SD]%) and lower at 1.8 mGy (-17.8 ± 2.2 [SD]%). For both inserts, f50 values were higher with PCCT than DSCT at 11- and 6 mGy for all keV levels, except at 6 mGy and 40 keV. d' values were higher with PCCT than with DSCT at 11- and 6 mGy for all keV and both simulated lesions. Similar d' values to those of the DSCT at 11 mGy, were obtained at 2.25 mGy for iodine insert at 2 mg/mL and at 0.96 mGy for iodine insert at 4 mg/mL at 40 keV.Compared to DSCT, PCCT reduces noise magnitude and improves noise texture, spatial resolution and detectability on VMIs for all low-keV levels.

Spontaneous dissection of the celiac artery (CA) is uncommon, considering the number of isolated lesions without associated aortic dissection and exclusive of abdominal trauma. We have treated five cases of isolated spontaneous dissection of the CA or its branches. There were three men and two women with a mean age of 54 years. The presenting manifestation was acute epigastralgia in three cases and chronic abdominal pain in one. In the remaining case, dissecting CA was a coincidental finding. All patients underwent abdominal Doppler ultrasound and CT scan imaging, which demonstrated aneurysm in three cases and dissection in two. Work-up also included arteriography in three cases and magnetic resonance (MR) angiography in one. Management consisted of emergency surgical repair in three cases and close surveillance in two. The repair procedure was resection-anastomosis in one case and prosthetic bypass to the hepatic artery in two cases. Postoperative recovery was uneventful in all three cases and patients were symptom-free at 6, 8, and 18 months. Both patients under surveillance were symptom-free at 1 and 2 years. Because of the risk of ischemic and hemorrhagic complications, surgery should be considered for any patient with CA dissection. However, some patients with uncomplicated asymptomatic lesions may be eligible for medical treatment with regular surveillance.

Delayed surgery does not reduce local recurrance or improve survival

Quantitative prognostic indicators for carcinomatosis and sarcomatosis are essential in the management of peritoneal surface malignancy. This need is greatly accentuated as a new comprehensive therapeutic approach emerges. The assessment of tumor histopathology, prior surgical score, lesion size, and distribution (Gilly classification and peritoneal cancer index) and the completeness of cytoreduction scores are the tools that are currently in use. Although current assessments have greatly facilitated clinical research, more precise comparisons demand improved quantitation and greater precision. Preoperative and intraoperative assessment of peritoneal surface malignancy will improve patient selection. Now more than ever, postoperative distribution and volume assessments using noninvasive modalities are needed for follow-up.

A prospective randomized trial was carried out to evaluate the efficacy of fibrin glue in preventing lymphorrhea after axillary lymphadenectomy in breast cancer. One hundred and eight breast cancer patients, operated on by two senior surgeons, were randomized into two groups: group 1 (n = 58) without fibrin glue and group 2 (n = 50) with 2 ml of fibrin glue applied to the axillary dissection area at the end of the lymphadenectomy procedure. Early postoperative morbidity was 2/58 and 0/50 in groups 1 and 2, respectively. Mean daily postoperative drainage was significantly greater in group 1. The mean cumulative drainage quantity 6 days after the operation was 407.8 ml and 214.4 ml in groups 1 and 2, respectively (p = 0.001). The mean postoperative hospital stay was 10.1 days and 8.0 days in groups 1 and 2, respectively (p = 0.006). One delayed seroma was observed in each group. Fibrin glue seems to reduce daily postoperative drainage and hospital stay, but did not affect delayed seroma formation after axillary lymphadenectomy for breast cancer.

Five different descriptions quantitating peritoneal carcinomatosis are available: the Lyon staging system, the Peritoneal Cancer Index (PCI), the Japanese Research Society for Gastric Cancer carcinomatosis staging (JRSGS), the Dutch simplified peritoneal carcinomatosis assessment and the Completeness of Cytoreduction Score (CCR). These five staging systems are described and discussed. Combinations of these to achieve a complete description of peritoneal lesions prior to and following treatment assist in a correct prognostic assessment for these patients and in a selection of treatment options.

Abstract Background This study was undertaken to measure survival of patients with multicystic peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy through a multi-institutional collaboration. Methods A multi-institutional data registry, established by the Peritoneal Surface Oncology Group, was used to identify patients with peritoneal mesothelioma and the subgroup with multicystic tumours, treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Outcomes for this subgroup are reported. The primary endpoint was overall survival. A secondary endpoint was the incidence of treatment-related complications. Results Of 405 patients with peritoneal mesothelioma, 26 (6·4 per cent) had multicystic tumours. There were 20 women and six men with a mean(s.d.) age of 42(12) years. The median peritoneal carcinomatosis index (PCI) was 14 (range 6–39). There was no perioperative mortality. Six patients developed grade III or IV complications. After a median follow-up of 54 (range 5–129) months, all 26 patients were still alive. Conclusion Multicystic peritoneal mesothelioma appears to be a distinct subtype of peritoneal mesothelioma, where long-term survival may be achieved through cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Abstract Objective Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the best treatment of several peritoneal surface malignancies. Isolated peritoneal recurrence may be treated by iterative procedures. The aim of this study was to evaluate immediate postoperative and long‐term results after iterative CRS‐HIPEC. Methods From 1990 to 2010, 30 patients with isolated peritoneal recurrence underwent iterative procedures combining CRS‐HIPEC. Results Origins of peritoneal carcinomatosis were ovarian, colorectal, pseudomyxoma peritonei, peritoneal mesothelioma, gastric cancer, cholangiocarcinoma, leiomyosarcoma, and primary peritoneal serous carcinoma. Median recurrence‐free survival (RFS) was 16.2 months from the first procedure. After the second procedure, one (3.3%) postoperative death occurred. Severe morbidity following the second procedure was 40% versus 30% after the first procedure ( P = 0.37). At most recent follow up, 11 patients were disease‐free, 10 were alive with recurrence, and 9 were dead with recurrence. Five‐year overall survival after initial CRS with HIPEC was 65%, and overall median survival from diagnosis was 140 months. Conclusion Iterative procedures combining CRS‐HIPEC are feasible and allow long‐term survival but may result in significant morbidity and mortality. Patients must be carefully selected, based on the following criteria: Origin of carcinomatosis, magnitude of first procedure, length of RFS, physiological age, co‐morbidity, and possibility of complete cytoreduction. J. Surg. Oncol. 2012; 106:197–203. © 2012 Wiley Periodicals, Inc.

Journal of Surgical OncologyVolume 110, Issue 7 p. 777-778 Commentary American Society of peritoneal surface malignancies opinion statement on defining expectations from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer Jesus Esquivel MD, Corresponding Author Jesus Esquivel MD Department of Surgical Oncology, Cancer Treatment Centers of America, Philadelphia, Pennsylvania Correspondence to: Jesus Esquivel, MD, Surgical Oncology Cancer Treatment Centers of America, 1331 E. Wyoming Avenue, Philadelphia, PA 19124. Fax: +1-215-537-5945. E-mail: jesusesquivel@yahoo.comSearch for more papers by this authorPompiliu Piso MD, Pompiliu Piso MD Division of Surgical Oncology, Hospital Barmherzige, Regensburg, GermanySearch for more papers by this authorVic Verwaal MD, Vic Verwaal MD National Cancer Institute, Amsterdam, The NetherlandsSearch for more papers by this authorThomas Bachleitner-Hofmann MD, Thomas Bachleitner-Hofmann MD Vienna University Hospital, Vienna, AustraliaSearch for more papers by this authorOlivier Glehen MD, Olivier Glehen MD Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Pierre-Benite, FranceSearch for more papers by this authorSantiago González-Moreno MD, Santiago González-Moreno MD Department of Surgical Oncology, MD Anderson Cancer Center, Madrid, SpainSearch for more papers by this authorMarcello Deraco MD, Marcello Deraco MD Department of Surgery, National Cancer Institute, Milan, ItalySearch for more papers by this authorJoerg Pelz MD, Joerg Pelz MD Department of Surgery, University of Wuerzburg, Wuerzburg, GermanySearch for more papers by this authorRichard Alexander MD, Richard Alexander MD Department of Surgical Oncology, University of Maryland, Baltimore, MarylandSearch for more papers by this authorGabriel Glockzin MD, Gabriel Glockzin MD Department of Surgical Oncology, Regensburg University Hospital, Regensburg, GermanySearch for more papers by this author Jesus Esquivel MD, Corresponding Author Jesus Esquivel MD Department of Surgical Oncology, Cancer Treatment Centers of America, Philadelphia, Pennsylvania Correspondence to: Jesus Esquivel, MD, Surgical Oncology Cancer Treatment Centers of America, 1331 E. Wyoming Avenue, Philadelphia, PA 19124. Fax: +1-215-537-5945. E-mail: jesusesquivel@yahoo.comSearch for more papers by this authorPompiliu Piso MD, Pompiliu Piso MD Division of Surgical Oncology, Hospital Barmherzige, Regensburg, GermanySearch for more papers by this authorVic Verwaal MD, Vic Verwaal MD National Cancer Institute, Amsterdam, The NetherlandsSearch for more papers by this authorThomas Bachleitner-Hofmann MD, Thomas Bachleitner-Hofmann MD Vienna University Hospital, Vienna, AustraliaSearch for more papers by this authorOlivier Glehen MD, Olivier Glehen MD Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Pierre-Benite, FranceSearch for more papers by this authorSantiago González-Moreno MD, Santiago González-Moreno MD Department of Surgical Oncology, MD Anderson Cancer Center, Madrid, SpainSearch for more papers by this authorMarcello Deraco MD, Marcello Deraco MD Department of Surgery, National Cancer Institute, Milan, ItalySearch for more papers by this authorJoerg Pelz MD, Joerg Pelz MD Department of Surgery, University of Wuerzburg, Wuerzburg, GermanySearch for more papers by this authorRichard Alexander MD, Richard Alexander MD Department of Surgical Oncology, University of Maryland, Baltimore, MarylandSearch for more papers by this authorGabriel Glockzin MD, Gabriel Glockzin MD Department of Surgical Oncology, Regensburg University Hospital, Regensburg, GermanySearch for more papers by this author First published: 08 July 2014 https://doi.org/10.1002/jso.23722Citations: 40Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume110, Issue7December 1, 2014Pages 777-778 RelatedInformation

The aim of the study was to compare the postoperative and oncologic outcomes of laparoscopic versus open surgery for gastric gastrointestinal stromal tumors (gGISTs).The feasibility of the laparoscopic approach for gGIST resection has been demonstrated; however, its impact on outcomes, particularly its oncologic safety for tumors greater than 5 cm, remains unknown.Among 1413 patients treated for a GIST in 61 European centers between 2001 and 2013, patients who underwent primary resection for a gGIST smaller than 20 cm (N = 666), by either laparoscopy (group L, n = 282) or open surgery (group O, n = 384), were compared. Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics.In-hospital mortality and morbidity rates in groups L and O were 0.4% versus 2.1% (P = 0.086) and 11.3% vs 19.5% (P = 0.004), respectively. Laparoscopic resection was independently protective against in-hospital morbidity (odds ratio 0.54, P = 0.014). The rate of R0 resection was 95.7% in group L and 92.7% in group O (P = 0.103). After 1:1 propensity score matching (n = 224), the groups were comparable according to age, sex, tumor location and size, mitotic index, American Society of Anesthesiology score, and the extent of surgical resection. After adjustment for BMI, overall morbidity (10.3% vs 19.6%; P = 0.005), surgical morbidity (4.9% vs 9.8%; P = 0.048), and medical morbidity (6.2% vs 13.4%; P = 0.01) were significantly lower in group L. Five-year recurrence-free survival was significantly better in group L (91.7% vs 85.2%; P = 0.011). In tumors greater than 5 cm, in-hospital morbidity and 5-year recurrence-free survival were similar between the groups (P = 0.255 and P = 0.423, respectively).Laparoscopic resection for gGISTs is associated with favorable short-term outcomes without compromising oncologic results.

Based on the importance of assessing the true extent of peritoneal disease, PeRitOneal MalIgnancy Stage Evaluation (PROMISE) internet application (www.e-promise.org) has been developed to facilitate tabulation and automatically calculate surgically validated peritoneal cancer index (PCI), and other surgically validated scores as Gilly score, simplified peritoneal cancer index (SPCI), Fagotti and Fagotti-modified scores. This application offers computer-assistance to produce simple, quick but precise and standardized pre, intra and postoperative reports of the extent of peritoneal metastases and may help specialized and non-specialized institutions in their current practice but also facilitate research and multicentre studies on peritoneal surface malignancies.

The aim of this study is to evaluate whether a parenchymal-sparing strategy provides similar results in terms of morbidity, mortality, and oncological outcome of non-PSH hepatectomies in a propensity score matched population (PSMP) in case of multiple (>3) bilobar colorectal liver metastases (CLM).The surgical treatment of bilobar liver metastasis is challenging due to the necessity to achieve complete resection margins and a sufficient future remnant liver. Two approaches are adaptable as follows: parenchymal-sparing hepatectomies (PSH) and extended hepatectomies (NON-PSH).A total of 3036 hepatectomies were analyzed from a multicentric retrospective cohort of hepatectomies. Patients were matched in a 1:1 propensity score analysis in order to compare PSH versus NON-PSH resections.PSH was associated with a lower number of complications (≥1) (25% vs. 34%, p = 0.04) and a lower grade of Dindo-Clavien III and IV (10 vs. 16%, p = 0.03). Liver failure was less present in PSH (2 vs. 7%, p = 0.006), with a shorter ICU stay (0 day vs. 1 day, p = 0.004). No differences were demonstrated in overall and disease-free survival.In conclusion, PSH resection for bilobar multiple CLMs represents a valid alternative to NON-PSH resection in selected patients with a reduced morbidity and comparable oncological results.

Hyperthermic intraperitoneal chemotherapy (HIPEC) may improve the outcome of patients with initially unresectable ovarian cancer who are eligible for complete cytoreductive surgery (CCRS) after neoadjuvant chemotherapy. The main objective of this multicenter phase-I study was to identify the recommended dose of cisplatin for HIPEC at CCRS after neoadjuvant carboplatin and paclitaxel (CP).Patients were treated with 6cycles of CP followed by CCRS and HIPEC using cisplatin heated for one hour at 42°C+/-1°C. Four cisplatin dose-levels were evaluated: 50, 60, 70, 80mg/m(2). Dose-limiting toxicities (DLTs) were defined as a grade≥IIIb adverse event (Dindo classification). The Continual Reassessment Method was used for this dose-finding study, with a target percentage of DLT set at 20%. Twenty-two cycles (15mg/kg/cycle) of maintenance bevacizumab therapy were planned after surgery.Between June-2011 and September-2012, 30 patients were recruited. No DLT occurred at the first three dose-levels (4, 4 and 5 patients at 50, 60 and 70mg/m(2) respectively). At dose-level 4 (80mg/m(2), 17 patients), four DLTs occurred: renal failure (n=2), peritonitis (n=1) and hemorrhage (n=1). Eight weeks after surgery, creatinine clearance was reduced to <30mL/min in 3 patients, all treated at 80mg/m(2), and between 30 and 60mL/min in 6 patients (2, 1, 1 and 2 at the four dose-levels respectively). Twenty patients started maintenance bevacizumab, and 7 received the 22 courses initially planned.Based on the observed DLTs and prolonged impairment of renal function, we recommend a dose of 70mg/m(2) of cisplatin for HIPEC.

To evaluate computed tomography (CT) and magnetic resonance imaging (MRI) findings for sign of hepatoduodenal ligament and small bowel non-resectability in patients with pseudomyxoma peritonei (PMP) and to compare assessments made by the radiologist based on their experiences.Between January 2009 and June 2014, all consecutive patients with PMP selected for curative surgery were scheduled to undergo CT and MRI examinations within two days of their surgery. Several imaging findings of hepatoduodenal ligament and small bowel involvements were retrospectively evaluated by a senior and a junior radiologist and compared with surgical findings.Of the 82 patients enrolled in the study, 11 had non-resectable lesions with hepatoduodenal ligament infiltration (n = 4) and/or extensive small bowel involvement (n = 9). All patients underwent CT and 73 underwent MRI scan. Infiltration of the adipose tissue of the hepatoduodenal ligament by mucinous tumor was associated with non-resectability. For the senior and junior radiologists, the sensitivity and specificity were 75% and 100%, and 50% and 100% on CT (kappa value (k) = 0.79); 67% and 100%, and 33% and 97% on MRI (k = 0.38), respectively. Diffuse involvement of the mesentery and/or the small bowel serosa was also associated with non-resectability. For the senior and junior radiologists, the sensitivity and specificity were 67% and 100%, and 56% and 99% on CT (k = 0.82); 88% and 100%, and 38% and 100% on MRI (k = 0.58), respectively.CT and MRI can both contribute to the diagnosis of non-resectability in patients with PMP. The use of MRI to identify small bowel involvement, in particular, benefits from a more experienced radiologist.

Background: The post-operative morbidity and mortality after CRS-HIPEC has been widely evaluated. However, there is a major discrepancy between rates reported due to different metrics and time of analysis used.Objective: To evaluate the legitimacy of 90-day morbidity and mortality based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 classification as criteria of quality for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).Methods: A prospective database of all patients undergoing CRS-HIPEC for peritoneal carcinomatosis between 2004 and 2015 was queried for 90-day morbidity and mortality and survival.Results: Among 881 patients, the 90-day major complication rate based on NCI-CTCAE classification and Clavien-Dindo’s classification were 51% (n = 447 patients) and 25% (n = 222 patients), respectively. Among patients who presented with a 90-day complication based on the NCI-CTCAE classification, 50% (n = 225 patients) presented a medical complication not reported by Clavien-Dindo’s classification. After surgery, 24 patients (2.7%) died of post-operative complications, for only 10 (42%) of them the death occurred within 30-day after surgery. Occurrence of major complication based on either NCI-CTCAE classification, Clavien-Dindo’s classification or the medical complication not reported by Clavien-Dindo’s classification all negatively impacts the overall survival.Conclusion: Among commonly reported morbidity’s classification, 90-day morbidity based on NCI-CTCAE classification represents a legitimate metric of CRS-HIPEC quality. Post-operative morbidity after CRS-HIPEC should be reported using 90-day NCI-CTCAE classification.

Ovarian cancer remains the fourth leading cause of cancer death in women in France. It is all too often diagnosed at an advanced stage with peritoneal carcinomatosis (PC), but remains confined to the peritoneal cavity throughout much of its natural history. Because of cellular selection pressure over time, most tumor recurrences eventually develop resistance to systemic platinum. Options for salvage therapy include alternative systemic chemotherapies and further cytoreductive surgery (CRS), but the prognosis remains poor. Over the past two decades, a new therapeutic approach to PC has been developed that combines CRS with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment strategy has already been shown to be effective in non-gynecologic carcinomatosis in numerous reports. There is a strong rationale for the use of HIPEC for PC of ovarian origin. On the one hand, three prospective randomized trials have demonstrated the superiority of intraperitoneal chemotherapy (without hyperthermia) in selected patients compared to systemic chemotherapy. Moreover, retrospective studies and case-control studies of HIPEC have reported encouraging survival data, especially when used to treat chemoresistant recurrence. However, HIPEC has specific morbidity and mortality; this calls for very careful selection of eligible patients by a multidisciplinary team in specialized centers. HIPEC needs to be evaluated by means of randomized trials for ovarian cancer at different developmental stages: as first line therapy, as consolidation, and for chemoresistant recurrence. Several European phase III studies are currently ongoing.

Giant ventral hernias represent a real handicap for patients and constitute a challenge for surgeons. European Hernia Society classification defines all ventral hernia over 10 cm in the same group. However, this group represents different clinical entities with numerous therapeutic possibilities, and no standardized recommendation has been made. The objective of our work was to define consensual criteria that define giant ventral hernias requiring specific management and determine management modalities. A national survey consisting of 21 questions was proposed through a secure, anonymous internet interface and on a voluntary basis to all surgeons practising in France involved in care of patients affected by giant ventral hernias. For more than 68% of respondents, loss of domain and a hernia volume greater than 30% of abdominal volume were mandatory to define giant ventral hernias. Pre-operative screening should include abdominal CT scan, functional respiratory exploration, and a cardiology consultation for 98%, 71% and 50% of the respondents respectively. Respiratory and cutaneous preparations were systematically proposed before surgery by 91% and 56% of respondents. Regarding surgical techniques, none has gained the support of the majority of respondents. However, 71% of respondents use a non-resorbable mesh in retro muscular position for more than 70% of their patients treated for giant ventral hernias. Giant ventral hernias could be defined as ventral hernia larger than 10 cm with loss of domain. A specific management is advocated.

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare disease affecting predominantly children and young adults and for which the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS) remains unknown.To identify patients with DSRCT without extraperitoneal metastases (EPM) who underwent CCRS between 1991 and 2015, a retrospective nation-wide survey was conducted by crossing the prospective and retrospective databases of the French Network for Rare Peritoneal Malignancies, French Reference Network in Sarcoma Pathology, French Sarcoma Clinical Network and French Pediatric Cancer Society.Among the 107 patients with DSRCT, 48 had no EPM and underwent CCRS. The median peritoneal cancer index (PCI) was 9 (range: 2-27). Among these 48 patients, 38 (79%) had pre- and/or postoperative chemotherapy and 23 (48%) postoperative whole abdominopelvic radiotherapy (WAP-RT). Intraperitoneal chemotherapy was administered to 11 patients (23%): two received early postoperative intraperitoneal chemotherapy (EPIC) and nine HIPEC. After a median follow-up of 30 months, the median overall survival (OS) of the entire cohort was 42 months. The 2-y and 5-y OS were 72% and 19%. The 2-y and 5-y disease-free survival (DFS) were 30% and 12%. WAP-RT was the only variable associated with longer peritoneal recurrence-free survival and DFS after CCRS. The influence of HIPEC/EPIC on OS and DFS was not statistically conclusive.The benefit of HIPEC is still unknown and should be evaluated in a prospective trial. The value of postoperative WAP-RT seems to be confirmed.

Pseudomyxoma peritonei (PMP) is a rare clinical condition characterized by mucinous ascites, typically related to appendiceal or ovarian tumours. Current standard treatment involves cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but recurrences occur in 20-30 per cent of patients. The aim of this study was to define the timing and patterns of recurrence to provide a basis for modifying follow-up of these patients.This observational study examined a prospectively developed multicentre national database (RENAPE working group) to identify patients with recurrence after optimal CRS and HIPEC for PMP. Postoperative complications, long-term outcomes and potential prognostic factors were evaluated.Of 1411 patients with proven PMP, 948 were identified who had undergone curative CRS and HIPEC. Among these patients, 229 first recurrences (24·2 per cent) were identified: 196 (20·7 per cent) occurred within the first 5 years (early recurrence) and 30 (3·2 per cent) occurred between 5 and 10 years. Three patients developed a first recurrence more than 10 years after the original treatment. The mean(s.d.) time to first recurrence was 2·36(2·21) years. Preoperative chemotherapy and high-grade pathology were significant factors for early recurrence. Overall survival for the entire group was 77·9 and 63·1 per cent at 5 and 10 years respectively. The principal site of recurrence was the peritoneum.Recurrence of PMP was rare after 5 years and exceptional after 10 years.