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When peritoneal metastases are diagnosed (strong agreement of experts): (i) seek advice from a multidisciplinary coordination meeting (MCM) with large experience in peritoneal disease (e.g. BIG RENAPE network); (ii) transfer (or not) the patient to a referral center with experience in hyperthermic intraperitoneal chemotherapy (HIPEC), according to the advice of the MCM. With regard to systemic chemotherapy (strong agreement of experts): (i) it should be performed both before and after surgery, (ii) for no longer than 6 months; (iii) without postoperative anti-angiogenetic drugs. With regard to cytoreductive surgery (strong agreement of experts): (i) Radical surgery requires a xiphopubic midline incision; (ii) no cytoreductive surgery via laparoscopy. With regard to HIPEC: HIPEC can be proposed for trials outside an HIPEC referral center (weak agreement between experts): (i) if surgery is radical; (ii) if the expected morbidity is "reasonable"; (iii) if the indication for HIPEC was suggested by a MCM, and; (iv) mitomycin is preferred to oxaliplatin (which cannot be recommended) for this indication., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA)., Methods: A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC., Results: Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1-100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1-33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1-100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1-100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS., Conclusion: The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.

Objective: This study was designed to identify factors associated with morbidity and mortality in patients older than 70 years who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC)., Background: Major surgery is associated with higher morbidity and mortality in elderly patients. For PC, CRS and HIPEC is the only current potential curative therapy, but the risks inherent to this patient population have called its benefits into question., Methods: We retrospectively analyzed a multi-center database from 1989 to 2015. All patients who underwent CRS and HIPEC for PC were selected and patients older than 70 years were matched 1:4 with a younger cohort according to cancer origin, peritoneal cancer index (PCI), and completeness of cytoreduction. Major morbidity and mortality were analyzed., Results: Of 2328 patients, 188 patients older than aged 70 years were matched with 704 younger patients. Patients older than aged 70 years demonstrated a higher American Society of Anesthesiologist score (≥ASA III 10.8 vs. 6.6 %, p = 0.008). There was no difference in overall 90-day morbidity (≥70: 45.7 % vs. <70: 44.5 %; p = 0.171); however, patients older than 70 years had significantly more cardiovascular complications (13.8 vs. 9.2 %, p = 0.044). Differences between the older and younger cohorts failed to reach significance for 90-day mortality (5.4 and 2.7 %, respectively; p = 0.052), and failure-to-rescue (11.6 and 6.1 %, respectively; p = 0.078). In multivariate analysis, PCI > 7 (95 % CI 1.051-5.798, p = 0.038) and HIPEC duration (95 % CI 1.106-6.235, p = 0.028) were independent factors associated with morbidity in elderly patients., Conclusions: CRS and HIPEC appear feasible for selected patients older than aged 70 years, albeit with a higher risk of medical complications associated with increased mortality.

Purpose: 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., Patients and Methods: 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)., Results: 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 (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033)., Conclusion: 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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: 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)., Methods: 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., Results: 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., Conclusions: Based on the observed DLTs and prolonged impairment of renal function, we recommend a dose of 70mg/m(2) of cisplatin for HIPEC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Complete surgery with no macroscopic residual disease (RD) at primary (PDS) or interval debulking surgery (IDS) is the main objective of surgery in advanced epithelial ovarian cancer (EOC). The aim of this work was to evaluate the impact on survival of the number of neoadjuvant chemotherapy (NAC) cycles before IDS in EOC patients., Methods: Data from EOC patients (stages IIIC-IV), operated on between 1995 and 2010 were consecutively recorded. NAC/IDS patients were analyzed according to the number of preoperative cycles (<4=group B1; >4=group B2) and compared with patients receiving PDS (group A). Patients with complete resection were specifically analyzed., Results: 367 patients were analyzed, 220 received PDS and 147 had IDS/NAC. In group B, 37 patients received more than 4 NAC cycles (group B2). Group B2 patients presented more frequently stage IV disease at diagnosis (p<0.01) compared to groups A and B1. The rate of complete cytoreduction was higher in group B (p<0.001). Patients with no RD after IDS and who had received more than 4 NAC cycles had poor survival (p<0.001) despite complete removal of their tumor (relative risk of death after multivariate analysis of 3 (p<0.001)) with an independent impact from disease stage and WHO performance status., Conclusions: Patients with advanced EOC receiving complete IDS after more than 4cycles of NAC have poor prognosis. Despite worse prognostic factors observed in this group of patients, our study reinforces the concept of early and complete removal of all macroscopic tumors in the therapeutic sequence of EOC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: This study was designed to evaluate neoadjuvant intensified chemotherapy in potentially resectable or unresectable liver metastases (LM) from colorectal cancer (CRC)., Methods: Criteria for potentially resectable LM were complex hepatectomy and/or risky procedure, close contact with major vascular structures, and for unresectable LM, a future liver remnant predicted to be less than 25-30 % of total liver volume. Between October 2004 and August 2007, 125 patients were randomized to either standard (FOLFIRI/FOLFOX4) or intensified chemotherapy (FOLFIRI-HD/FOLFOX7/FOLFIRINOX). Primary endpoint was objective response rate (ORR) after 4 cycles of chemotherapy. Secondary endpoints included safety, R0 surgical resection, best ORR, progression-free survival (PFS), and overall survival (OS)., Results: A total of 122 patients were treated; 45 % of patients had less than 30 % of remaining liver tissue, 20 % had major vascular contact, and 35 % were potentially resectable. Grade 3/4 toxicities were neutropenia (24, 19, 10, 23 %) diarrhoea (0, 6, 3, 23 %), mucositis (0, 3, 0, 7 %), vomiting (7, 9, 0, 3 %), and neurotoxicity (0, 0, 10, 3 %) in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. ORR was 33, 47, 43, and 57 % after the first 4 cycles in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. FOLFIRINOX offered the best conversion rate to resectability (67 %). Disease-free status after chemotherapy and surgery (R0, R1, Rx) was achieved in 54 of 64 operated patients. Median PFS was 9.2 months in control arms versus 11.9 months in experimental arms (hazards ratio [HR] = 0.76, p = 0.115), and the median OS was 17.7 versus 33.4 months (HR = 0.73, p = 0.297), respectively., Conclusions: FOLFIRINOX showed promising activity in CRC patients with LM compared with standard or intensified bi-chemotherapy regimens.

Objective: To assess the perioperative and long-term results of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) using oxaliplatin+irinotecan (ox-irino) versus oxaliplatin alone (ox-alone)., Background: Treatment of peritoneal carcinomatosis (PC) of colorectal origin with CRS+HIPEC using mitomycin-C or oxaliplatin monotherapy has shown encouraging survival results. This bi-centric study evaluates an intensified intraperitoneal combination of ox-irino and compares it with ox-alone., Patients and Methods: All consecutive patients with PC undergoing CRS+HIPEC using either ox-alone or ox-irino between 1998 and 2007 were evaluated., Results: One hundred forty-six patients underwent CRS+HIPEC for PC, 103 received ox-irino and 43 received ox-alone. The median peritoneal carcinomatosis index (PCI) was 11 in both groups. 90.4% had complete cytoreduction. Overall mortality rate was 4.1%. The overall morbidity rate was 47.2% and was significantly lower with ox-alone (34.9% vs. 52.4%, P = 0.05). After a median follow-up of 48.5 months, the median overall survival (OS) was 41 months (95% CI, 32-60) and median relapse-free survival (RFS) was 15.7 months (95% CI, 12-18). The median RFS of ox-alone (16.8 months; 95% CI, 11-25) was not significantly different from ox-irino (15.7 months; 95% CI, 11-18; P = 0.93). There was no significant difference between median OS of ox-alone (40.83 months; 95% CI, 29-61) and ox-irino (47 months; 95% CI, 32-61; P = 0.94). At 5 years, OS and RFS rates were 41.8% and 13.8% in ox-alone and 42.4% and 14.2% in ox-irino, respectively. Prognostic factors confirmed on multivariate analysis were lymph node metastasis and PCI., Conclusion: Our study showed no advantage of intensification of HIPEC by adding irinotecan, contrary to the results obtained with IV combination. Ox-alone HIPEC should continue as one of the standard HIPEC regimens for PC.

Background: Peritoneal carcinomatosis (PC) from gastric cancer has long been regarded a terminal disease with a short median survival. New locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved and suggest improved survival., Materials and Methods: A retrospective multicentric study was performed in French-speaking centers to evaluate the toxicity and the principal prognostic factors in order to identify the best indications. All patients had cytoreductive surgery and PIC: hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC)., Results: The study included 159 patients from 15 institutions between February 1989 and August 2007. The median follow-up was 20.4 months. HIPEC was the PIC used for 150 procedures. Postoperative mortality and grade 3-4 morbidity rates were 6.5 and 27.8%, respectively. By multivariate analysis, the institution had a significant influence on toxicity. The overall median survival was 9.2 months and 1-, 3-, and 5-year survival rates were 43, 18, and 13%, respectively. The only independent prognostic indicator by multivariate analysis was the completeness of cytoreductive surgery. For patients treated by complete cytoreductive surgery, the median survival was 15 months with a 1-, 3-, and 5-year survival rate of 61, 30, and 23%, respectively., Conclusions: The therapeutic approach combining cytoreductive surgery with PIC for patients with gastric carcinomatosis may achieve long-term survival in a selected group of patients (limited and resectable PC). The high mortality rate underlines this necessarily strict selection that should be reserved to experienced institutions involved in the management of PC and gastric surgery.

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., (Copyright 2010 Elsevier Ltd. All rights reserved.)

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.

We report a case of a locally advanced cardial adenocarcinoma, occurring in a 48-year-old woman, who underwent concomitant radiotherapy and 5 FU-cis-platin based chemotherapy. Surgical tumor resection was then performed, which incidentally revealed an isolated liver nodule measuring 12 mm. This nodule was histologically characterized by an intense sinusoidal dilatation and a central venular occlusion, similar to that seen in veno-occlusive disease. This lesion was not correlated to any clinical or biological dysfunction and was finally considered as a vascular injury linked to the additive effect of the combined chemotherapy and radiotherapy. This observation illustrates some iatrogenic hepatic side effects, that have been rarely described in digestive cancers and mainly in the case of colo-rectal metastases. Vascular damage may remain histological, as in our case. But one should be aware that vascular injuries could influence hepatic function and regeneration after wide hepatectomy as well as extensive fibrosis.

Purpose: Isolated hepatic metastases of colorectal cancer constitute a frequent and serious therapeutic problem that has led to the evaluation of hepatic arterial infusion (HAI) of different drugs. Oxaliplatin combined with fluorouracil (FU) and leucovorin is effective in the treatment of colorectal cancer. In this context, a phase II study was conducted to evaluate concomitant administration of oxaliplatin by HAI and intravenous (IV) FU plus leucovorin according to the LV5FU2 protocol (leucovorin 200 mg/m(2), FU 400 mg/m(2) IV bolus, FU 600 mg/m(2) 22-hour continuous infusion on days 1 and 2 every 2 weeks)., Patients and Methods: Patients had metastatic colorectal cancer that was restricted to the liver and inoperable. The patients were not to have previously received oxaliplatin. After surgical insertion of a catheter in the hepatic artery, patients were treated with oxaliplatin 100 mg/m(2) HAI combined with FU + leucovorin IV according to the LV5FU2 protocol. Treatment was continued until disease progression or toxicity. Response was evaluated every 2 months., Results: Twenty-eight patients were included, and 26 patients were treated. Two hundred courses of therapy were administered, and the median number of courses received was eight courses (range, zero to 20 courses). The most frequent toxicity consisted of neutropenia. The main toxicity related to HAI was pain. The intent-to-treat objective response rate was 64% (95% CI, 44% to 81%; 18 of 28 patients). With a median follow-up of 23 months, the median overall and disease-free survival times were 27 and 27 months, respectively., Conclusion: The combination of oxaliplatin HAI and FU + leucovorin according to the LV5FU2 protocol is feasible and effective in patients presenting with isolated hepatic metastases of colorectal cancer.

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.