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Objectives Current recommendations regarding enhanced recovery programs (ERPs) after complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are based on a low level of evidence. The aim of this study is to evaluate the effect of implementing an adapted ERP for CCRS and HIPEC in a referral center. Methods We conducted a study with a prospective group of 44 patients (post-ERP group) who underwent CCRS with HIPEC between July 2016 and June 2018, the period during which ERP was implemented. This group was compared to a second retrospective group of 21 patients who underwent CCRS with HIPEC between June 2015 and June 2016, during which ERP was not yet implemented (pre-ERP group). Results The ERP compliance rate was 65% in the post-ERP group. The hospital length of stay (HLS) was shorter in the post-ERP group: 24.9 days (IQR 11–68, pre-ERP group) vs. 16.1 days (IQR 6–45, post-ERP group), as was the major morbidity rate (pre-ERP group=33.3% vs. post-ERP group=20.5%). The nasogastric tube, urinary catheter and abdominal drains were all retrieved faster in the post-ERP group. Conclusions The implementation of an adapted ERP after CCRS with HIPEC procedures reduces morbidity and shortens the HLS.

Introduction This document is a summary of the French Intergroup guidelines regarding the management of appendicular epithelial tumors (AT) and pseudomyxoma peritonei (PMP) published in March 2020, available on the website of the French Society of Gastroenterology (SNFGE) ( www.tncd.org ). Methods All French medical societies specialized in the management of AT and PMP collaboratively established these recommendations based on literature until December 2019 and the results of a Delphi vote carried out by the Peritoneal Surface Oncology Group International experts, and graded into 4 categories (A, B, C, Expert Agreement) according to their level of evidence. Results AT and PMP are rare but represent a wide range of clinico-pathological entities with several pathological classification systems and different biological behaviors. Their treatment modalities may vary accordingly and range from simple surveillance or laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) and / or systemic chemotherapy. The prognosis of these neoplasms may also largely vary according to their pathological grade and spreading at diagnosis or during the follow-up. Given the rarity of certain situations, the therapeutic strategy adapted to each patient, must be discussed in a specialized multidisciplinary meeting after a specialized pathological and radiological pre-therapeutic assessment and a clinical examination by a surgeon specializing in the management of rare peritoneal malignancies. Conclusion These recommendations are proposed to achieve the most beneficial strategy in a daily practice as the wide range and the rareness of these entities renders their management challenging. These guidelines are permanently being reviewed.

Sarcopenia is recognized as a negative prognostic factor in several cancers. The aim of this study was to investigate the impact of nutritional support with feeding jejunostomy (FJ) on the occurrence of sarcopenia and how it may affect postoperative short-term outcomes and long-term survival outcomes in patients undergoing esophagectomy for oesogastric junction adenocarcinoma (OJA).Patients with OJA were included. The presence of sarcopenia was determined using cutoff values of the total cross-sectional muscle tissue measured on CT scan. We analyzed risk factors for sarcopenia occurrence and the impact of preoperative sarcopenia on postoperative results, overall survival and disease-free survival.A total of 124 patients were eligible for analysis. Ninety-one patients underwent surgery after chemotherapy, and 72 of them received preoperative FJ. Among the 91 patients, 21 patients (23.0%) were sarcopenic after preoperative chemotherapy. Multivariate analysis showed that FJ is a protective factor against sarcopenia occurrence. Overall survival was significantly different between sarcopenic and nonsarcopenic patients (median survival = 33.7 vs. 58.6 months, respectively, p = 0.04), and sarcopenia occurrence was an independent risk factor for overall survival in patients who underwent surgery (HR = 3.02; CI 95% 1.55-5.9; p 0.005). Subgroup analyses showed no differences in overall survival between patients who presented sarcopenia despite nutritional prehabilitation with a FJ and patients excluded from surgery in palliative situations (median survival = 21.9 vs. 17.2 months, respectively, p = 0.46).The persistence of sarcopenia after preoperative chemotherapy despite renutrition with FJ could be a selection factor to propose curative surgery for OJA.

International audience; Objective: To perform a retrospective root-cause analysis of postoperative death after CRS and HIPEC procedures. Background: The combination of CRS and HIPEC is an effective therapeutic strategy to treat peritoneal surface malignancies, however it is associated with significant postoperative mortality. Methods: All patients treated with a combination of CRS and HIPEC between January 2009 and December 2018 in 22 French centers and died in the hospital, were retrospectively analyzed. Perioperative data of the 101 patients were collected by a local senior surgeon with a sole junior surgeon. Three independent experts investigated the typical root cause of death and provided conclusions on whether postoperative death was preventable (PREV group) or not (NON-PREV group). A typical root cause of preventable postoperative death was classified on a cause-and-effect diagram. Results: Of the 5562 CRS+HIPEC procedures performed, 101 in-hospital deaths (1.8%) were identified, of which a total of 18 patients of 70 years old and above and 20 patients with ASA score of 3. Etiology of peritoneal disease was mainly colorectal. A total of 54 patients (53%) were classified in the PREV group and 47 patients (47%) in the NON-PREV group. The results of the study show that in the PREV group, WHO performance status 1-2 was more frequent and the Median Peritoneal Cancer Index was higher compared with those of the NON-PREV group. The cause of death in the PREV group was classified as: (i) preoperatively for debatable indication (59%), (ii) intraoperatively (30%) and (iii) postoperatively in 17 patients (31%). A multifactorial cause of death was found in 11 patients (20%). Conclusion: More than half of the postoperative deaths after combined CRS and HIPEC may be preventable, mainly by following guidelines regarding preoperative selection of the patients and adequate intraoperative decisions.

Objectives To assess the risk perception and the uptake of measures preventing environment-related risks in the operating room (OR) during hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Methods A multicentric, international survey among OR teams in high-volume HIPEC and PIPAC centers: Surgeons (Surg), Scrub nurses (ScrubN), Anesthesiologists (Anest), Anesthesiology nurses (AnesthN), and OR Cleaning staff (CleanS). Scores extended from 0–10 (maximum). Results Ten centers in six countries participated in the study (response rate 100%). Two hundred and eleven responses from 68 Surg (32%), 49 ScrubN (23%), 45 Anest (21%), 31 AnesthN (15%), and 18 CleanS (9%) were gathered. Individual uptake of protection measures was 51.4%, similar among professions and between HIPEC and PIPAC. Perceived levels of protection were 7.57 vs. 7.17 for PIPAC and HIPEC, respectively (p Conclusions Experience with the current practice of safety protocols was similar during HIPEC and PIPAC. The individual uptake of protection measures was rather low. The safety perception was better for PIPAC, but the perceived level of protection remained relatively low. The willingness to obtain more information was high. Intensified, standardized training of all OR team members involved in HIPEC and PIPAC is meaningful.

Background Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections. Methods The RENAPE database (French expert centers network) was analyzed over a 1999–2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed. Results Overall 60 patients (50 women) were included with a median PCI of 10 (4–14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7–95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12–1.42, p = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC). Conclusion MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.

PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy) is a minimally invasive approach relying on physical principles for improving intraperitoneal drug delivery, including optimizing the homogeneity of drug distribution through an aerosol. Feasibility and safety of the new approach are now consolidated and data on its effectiveness are continuously increasing. Although any surgical procedure associated with PIPAC had always been discouraged due to the high risk of complications, surgical practice is constantly changing: with growing expertise, more and more surgical teams associate PIPAC with surgery. PLUS study is part of the retrospective international cohort studies including 10 centers around the world (India, Italy, France, Germany, Belgium, Russia, Saudi Arabia, Switzerland) and 96 cases of combined approaches evaluated through a propensity score analysis. the procedures most frequently associated with PIPAC were not only adhesiolysis, omentectomy, adnexectomy, umbilical/inguinal hernia repairs, but also more demanding procedures such as intestinal resections, gastrectomy, splenectomy, bowel repair/stoma creation. Although the evidence is currently limited, PLUS study demonstrated that PIPAC associated with additional surgical procedures is linked to an increase of surgical time (p < 0.001), length of stay (p < 0.001) and medical complication rate (p < 0.001); the most frequently reported medical complications were mild or moderate in severity, such as abdominal pain, nausea, ileus and hyperthermia. No difference in terms of surgical complications was registered; neither reoperation or postoperative deaths were reported. these results suggest that PIPAC can be safely combined in expert centers with additional surgeries. Widespread change of practice should be discouraged before the results of ongoing prospective studies are available.

Resume Objectif de l’etude L’innocuite de la chimiotherapie intraperitoneale pressurisee par aerosol (PIPAC) est souvent questionnee lors de sa mise en place dans un bloc operatoire, car le risque d’exposition aux cytotoxiques pour le personnel hospitalier peut etre augmente. Il n’existe aucune donnee sur le risque d’exposition dans des salles operatoires sans flux laminaire. Notre objectif etait de garantir la securite de la PIPAC pour les chirurgiens et leurs collegues lors de PIPAC nouvellement mises en place dans un bloc operatoire sans flux laminaire. Patients et methodes Vingt-six prelevements surfaciques sur lingettes provenant d’elements environnementaux du chirurgien et de ses collegues ainsi que 5 prelevements d’air sur filtres de polytetrafluoroethylene ont ete realises de maniere aleatoire lors des deux premieres PIPAC a base de cisplatine et doxorubicine realisees aux Hopitaux universitaires de Strasbourg. La procedure de PIPAC a ete realisee conformement aux protocoles de securite decrit precedemment, mais sans flux laminaire et avec une couverture en plastique et un dispositif d’evacuation de fumees supplementaires. Les echantillonnages et les analyses ont ete effectues par 2 organisations certifiees independantes accreditees. Resultats Toutes les mesures dans l’air etaient negatives pour le cisplatine et la doxorubicine. Un seul echantillon surfacique sur 26 etait positif pour le cisplatine (4 %) sur la seconde paire de gants (exterieure) du chirurgien, mais les dosages sur la premiere paire et les mains du chirurgien etaient negatifs. Conclusion Lorsqu’elle est executee dans des conditions de securite approuvees, meme dans un bloc operatoire sans flux laminaire, la PIPAC semble inoffensive pour le chirurgien et ses collegues avec un risque tres limite d’exposition aux cytotoxiques.

Summary Aim of the study The safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) is often questioned when newly implemented in an operating room (OR); as it may increase the risk of exposure to cytotoxics for healthcare workers. There are no data on the risk of healthcare exposure in OR without laminar airflow. We aimed to ensure the safety of PIPAC for surgeons and their co-workers for newly implemented procedures in an OR without laminar airflow. Patients and methods Twenty-six samples with cellulosic wipes from surgeons and co-workers’ environmental items and 5 specific polytetrafluoroethylene air-filtered collections were randomly performed for the first 2 cisplatin/doxorubicin-based PIPAC procedures in Strasbourg University Hospital. PIPAC was performed according to previously described safety protocol but without a laminar airflow and with an additional plastic cover and smoke evacuation device. Sampling and analyzes were performed by 2 accredited independent certified organizations. Results All air measurements were negative for cisplatin and doxorubicin. Only one wipe sample out of 26 was positive for cisplatin (4%) on the outer surgeon's pair of gloves but dosages on the surgeon's inner pair and hands were negative. Conclusion When performed in approved security conditions, even without laminar airflow, PIPAC might seem harmless for surgeons and their co-workers with very limited risk of exposure to cytotoxics.

BACKGROUND: The incidence of high-output stoma (HOS) was reported to be approximately 3 to 16% in the literature, and HOS can cause dehydration. This complication is often severe enough to warrant hospital readmission and may result in renal failure. The aim of this study was to show a decrease of 50% in ileostomy output in the experimental arm using lanreotide treatment. METHODS: Patients with an ileostomy output ≥ 1.5 l/24 hours were included in this prospective, open, multicentre randomized trial. Patients were randomly allocated between treatment arms with either lanreotide (LAN) and antidiarrhoeal treatments (TAD) (LAN-TAD group) or antidiarrhoeal treatments only (TADS group). The primary outcome was ileostomy output after 72 days. The secondary endpoints were ileostomy output during the first 6 days, blood urea and creatinine values, hospital length of stay and serious adverse events. RESULTS: In the per-protocol analysis, there were nine patients in the control group (TADS) and six patients in the experimental group (TAD-LAN group). The stoma outputs at Day 3 (D3) in the experimental and control groups were 1,900 ± 855.7 mL and 1,728.6 ± 845.5 mL, respectively (p = 0.2). No differences were found concerning stoma output at D6, renal function, or hospital length of stay between the two groups. CONCLUSION: The trial was prematurely stopped due to the low number of patients included. The question of the usefulness of somatostatin analogues in HOS persists, especially as the cost of this treatment is high, and there is a lack of evidence of its effectiveness.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is increasingly used to treat patients with peritoneal cancer. A recent survey demonstrated considerable diversification of current practice of PIPAC raising issues of concern also regarding safety and efficacy. The study aim was to reach consensus on best practice of PIPAC treatment.METHODS: Current practice was critically discussed during an expert meeting and the available evidence was scrutinized to elaborate a 33-item closed-ended questionnaire. All active PIPAC centers were then invited to participate in an online two-round Delphi process with 3 reminders at least. Consensus was defined a priori as >70% agreement for a minimal response rate of 70%.RESULTS: Forty-nine out of 57 invited PIPAC centers participated in Delphi 1 and 2 (86%). Overall, there was agreement for 21/33 items. Consensus was reached for important aspects like advanced OR ventilation system (91.8%), remote monitoring (95.9%), use of the PRGS (85.7%) and use of a safety checklist (98%). The drug regimens oxaliplatin (87.8%) and cisplatin/doxorubicin (81.6%) were both confirmed by the expert panel. Important controversies included number and location of Biopsies during repeated PIPAC and the combination of PIPAC with additional surgical procedures.CONCLUSION: This consensus statement aims to allow for safe and efficacious PIPAC treatment and to facilitate multi-center analyses of the results. Additional preclinical and clinical studies are needed to resolve the remaining controversies.

Etat de la question La prothese biosynthetique Phasix® n’a jamais fait l’objet d’etude comparative avec les protheses biologiques lors de cure d’eventration en milieu contamine. Des donnees complementaires etaient necessaires pour confirmer la transition vers les protheses biosynthetiques resorbables et justifier l’homogeneisation des pratiques chirurgicales. Le but de cette etude etait de comparer, en termes de cout et de complications graves, l’utilisation des protheses parietales biosynthetiques resorbables et biologiques chez les patients beneficiant d’une cure d’eventration contaminee (grade 3 du « Modified Ventral Hernia Working Group »). Materiel et methodes Une analyse cout-efficacite a ete realisee. Elle reposait sur un modele d’analyse decisionnelle ( Fig. 1 ) construit a partir de donnees cliniques et economiques issues d’une etude avant-apres, incluant 94 patients hospitalises pour une cure d’eventration a l’hopital universitaire de Strasbourg (France) de juin 2011 a fevrier 2018. Le critere d’evaluation de l’efficacite etait le nombre de patients presentant une complication grave generale ou specifique a six mois. Les sejours d’hospitalisation, les hospitalisations a domicile et les couts des soins ambulatoires ont ete inclus. Resultats La prothese biosynthetique Phasix® semblait etre l’option la plus efficace et la moins couteuse ( Tableau 1 , Tableau 2 , Tableau 3 ). Moins de complications serieuses ont ete rapportees (21 % contre 33 % avec une prothese biologique) et nous avons determine une economie de 5146 US $. Des analyses de sensibilite deterministes ( Tableau 4 ) et une analyse probabiliste ( Fig. 2 ) ont confirme nos constatations et la robustesse du modele. Conclusion Ces resultats peuvent etre consideres comme le premier pas vers l’elaboration de nouvelles recommandations. Des donnees supplementaires seront necessaires pour confirmer la superiorite des protheses biosynthetiques en termes de reduction du risque de recidive a long terme.

Guidelines recommend that retroperitoneal sarcoma (RPS) be managed in a reference sarcoma center (RSC), but the benefit remains to be demonstrated. This study investigated the impact of initial surgery performed within the NetSarc network on overall survival (OS). NetSarc is a network of 26 RSCs with specialized multidisciplinary tumor boards (MDTs) that is funded by the French NCI. Since 2010, presentation to an MDT and second pathological review are mandatory for sarcoma patients, and data have been collected in a nationwide database. We extracted data for all patients who received surgery in or outside the network and who presented at a NetSarc center (NSC) for primary nonmetastatic RPS between 2010 and 2017. A total of 2945 patients were included: 1078 (36.6%) underwent the first surgery in an NSC, and 1867 (63.4%) in an out-of-network center. The median number of operations at an NSC during the study period was 23 (range: 3–209), and the corresponding median was 1 (range: 1–2) at out-of-network centers. The diagnostic procedures followed significantly more clinical practice guidelines within NetSarc, where there were significantly more first R0 resections [452 (41.9%) vs. 230 (12.3%)]. The OS was significantly superior for patients treated within NetSarc, with a 2-year OS of 87% vs. 70% (p

Background PIPAC is a new treatment modality for peritoneal cancer which has been practiced and evaluated until very recently by few academic centers in a highly standardized manner. Encouraging oncological outcomes and the safety profile have led to widespread adoption. The aim of this study was to assess current PIPAC practice in terms of technique, treatment and safety protocol, and indications. Methods A standardized survey with 82 closed-ended questions was sent online to active PIPAC centers which were identified by help of PIPAC training centers and the regional distributors of the PIPAC-specific nebulizer. The survey inquired about center demographics (n = 8), technique (n = 34), treatment and safety protocol (n = 34), and indications (n = 6). Results Overall, 62 out of 66 contacted PIPAC centers answered the survey (response rate 93%). 27 centers had performed >60 PIPAC procedures. A consensus higher than 70% was reached for 37 items (50%), and higher than 80% for 28 items (37.8%). The topics with the highest degree of consensus were safety and installation issues (93.5% and 80.65%) while chemotherapy and response evaluation were the least consensual topics (63.7 and 59.6%). The attitudes were not influenced by volume, PIPAC starting year, type of activity, or presence of peritoneal metastases program. Conclusion Homogeneous treatment standards of new techniques are important to guarantee safe implementation and practice but also to allow comparison between cohorts and multi-center analysis of merged data including registries. Efforts to avoid diversification of PIPAC practice include regular update of the PIPAC training curriculum, targeted research and a consensus statement.

Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16ink4a status, cTNM classification as well as both CD3+ and CD4+ T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.

The Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care.

Resume La pandemie de COVID-19 modifie profondement l’organisation et l’acces aux soins, en particulier pour les pathologies neoplasiques peritoneales, dont la prise en charge curative mobilise des moyens importants en personnel, bloc operatoire et reanimation. Les groupes BIG-RENAPE et RENAPE proposent des pistes de reflexion et de priorisation pour leur prise en charge. Un renforcement des criteres habituels de selection est necessaire pour une prise en charge a visee curative : patients jeunes, avec peu de co-morbidites et une extension peritoneale limitee. Il est souhaitable de prioriser les pathologies pour lesquelles la chirurgie de cytoreduction associee ou non a une chimiohyperthermie intraperitoneale (CHIP) est le traitement de reference et celles pour lesquelles la chimiotherapie systemique ne peut etre une alternative temporaire ou prolongee : pseudomyxomes peritoneaux ; mesotheliomes peritoneaux malins resecables ; metastases peritoneales d’origine colorectale si resecables, non repondeuses a la chimiotherapie systemique et/ou apres 12 cures, carcinoses ovariennes en 1re intention si resecables et limitees ou en situation intervallaire apres un maximum de 6 cycles de chimiotherapie systemique. L’adjonction d’une CHIP devra etre discutee au cas par cas, en centre expert. La priorisation des indications devra prendre en consideration les conditions locales et la phase de la periode epidemique pour permettre une prise en charge peri-operatoire optimale.

The aim of this study was to evaluate the impact of a preoperative feeding jejunostomy (FJ) on the occurrence of sarcopenia before and after preoperative chemotherapy for patients with an oesogastric adenocarcinoma (OGA). Forty-six patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. Sarcopenia was evaluated by measuring muscle surfaces (psoas, paraspinal and abdominal wall muscles) on abdominal CT images at the level of the 3rd lumbar vertebra. A FJ was placed in 31 patients (67.4%) before the neoadjuvant treatment (FJ group), while 15 patients (32.6%) started neoadjuvant treatments without FJ (control group). After preoperative chemotherapy, there were significantly more sarcopenic patients in the control group, compared to the FJ group. In the FJ group, 13% of the patients (

Ruthenium and osmium complexes have been shown to bypass several resistance mechanisms of platinum anticancer drugs, suggesting that they might represent therapeutic alternatives. However, the resistance mechanisms that may alter the cytotoxicity of ruthenium and osmium complexes have not been identified yet. Here we investigated the mechanisms governing the variability in the cytotoxicity of two ruthenium cyclometalated compounds and their osmium equivalents. We characterized their anticancer properties in vitro and in vivo, and we developed a 4-step approach to identify genes involved in their sensibility/resistance by correlating their cytotoxicity measures with transcriptomic data of 60 cancer cell lines. As previously observed for ruthenium complexes, we showed that osmium compounds target the endoplasmic reticulum stress pathway and that their activity was not hindered by mutation in the tumor suppressor gene TP53. Then, we identified multiple sensibility/resistance genes that correlated with the cytotoxicity of cyclometalated compounds. Docking and functional studies demonstrated that inhibition of some of these resistance mechanisms, namely ABCB1 export and EGFR expression, improved the activity of cyclometalated complexes. Interestingly, switching from ruthenium to osmium favored cytotoxicity while reducing sensibility to the ABCB1 export mechanism. In summary, this study represents the first comprehensive investigation of the resistance mechanisms that alter the biological activity of ruthenium or osmium complexes, and identifies some of the chemical determinants that are important for their activity.

International audience; PURPOSE:To evaluate the impact of a feeding jejunostomy (FJ) on the preoperative management of patients with an oesogastric adenocarcinoma (OGA).METHODS:From January 2007 to December 2014, patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. FJ was performed before starting perioperative treatments in patients presenting with dysphagia or with a nutritional risk index (NRI)

Complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have dramatically changed the prognosis of patients with pseudomyxoma peritonei (PMP). However, recurrences can still occur and no consensus has been reached regarding their optimal treatments. This study aimed to analyze the patterns of recurrence after CCRS plus HIPEC for PMP and potential subsequent treatments of these lesions.Between 1992 and 2014, patients who had relapsed after treatment of PMP were selected from a prospective database of 251 patients who had undergone CCRS plus HIPEC with a curative intent.After a median follow-up of 85 months, 66 patients (26%) had relapsed with a median free interval of 25 months. The first recurrence was mostly located in the peritoneum, isolated in 50 patients (76%) and associated with extraperitoneal disease in 6 patients. Curatively intended treatment of the relapse, combining surgery and chemotherapy was achievable in 76% of the patients, leading to a 5-year overall survival (OS) rate of 83% from the date of treatment of the first recurrence. In contrast, the 5-year OS rate was only 27% (p 0.001) for patients treated with non-curative therapy. An isolated peritoneal recurrence was predictive of greater amenability to curative therapy and a better prognosis.After CCRS plus HIPEC, serosal recurrences were more common than their distant counterparts. Distant relapses' emergence has raised the question of their optimal treatments. Very long-term survival can be obtained after further treatment of recurrent PMP for patients with limited disease and good general status.

International audience; No abstract available

International audience; Purpose: Psammocarcinoma (PK) is a rare disease of unknown origin. We aimed to report the characteristics, management and survival of patients operated on for PK within the French Network for Rare Peritoneal Malignancies (RENAPE) expert centers.Patients and methods: All consecutive cases of PK operated within all 26 RENAPE centers between 1997 and 2018 were retrospectively analyzed.Results: Twenty-five patients were identified. The median age was 53 years [range 17–78]. None of the patients had extra peritoneal metastases at diagnosis. A median of 6 cycles of carboplatin-based systemic chemotherapy was delivered in 52% preoperatively (n = 13) and 56% postoperatively (n = 14); associated with placlitaxel for 12 patients. All patients were operated on. The median PCI was 23 [0–33]. Eighty-four percent had a complete cytoreductive surgery through digestive (n = 7), spleen (n = 3), pancreas (n = 1) resections and/or multiple peritonectomies (n = 11). Five patients (20%) had intraperitoneal chemotherapy. Morbidity (Dindo-Clavien ≥3) was 12%. No postoperative death occurred. After a median follow-up of 42 months (range [2–194]), the median overall (OS) and progression-free (DFS) survival times were respectively 128 months and 31 months. Eighteen patients recurred (72%), mainly in the peritoneum (n = 16). Four of them (22%) were reoperated. The 5 and 10-year DFS rates were both 20.3%. The 5 and 10-year OS rates were 62% and 51.7%, respectively. A complete cytoreductive surgery was associated with a better OS and DFS in a univariate analysis.Conclusion: Complete cytoreductive surgery is the cornerstone of the PK's management as a primary treatment. Recurrence remains common and new adjuvant strategies seem needed.

Background Soft tissue sarcomas are rare and heterogenous tumors that are hard to diagnose. The aim of this study was to evaluate local practices and conformity to clinical practice guidelines (CPGs) for their initial diagnostic management. Materials and Methods Patients were carriers of a soft tissue or visceral tumor, presented at a sarcoma tumor board (STB) between 2010 and 2016. Conformity to CPGs was evaluated using ten criteria designed for this purpose. Associations between different factors and conformity to composite criteria, reflecting the three main diagnostic steps (imaging, biopsy and histological report) were analyzed. Results A total of 643 patients were included. A preoperative tumor imaging assessment and a biopsy were performed according to CPGs in 80.8% and 36.8% of the cases, respectively. When done, the first surgical resection was R0 in 30.3% of cases, R1 in 28.6%, and R2 in 10.9%. The rest of the operated patients with sarcoma had a second surgical excision (11.4%), an intraoperative fragmentation (4.3%), or margins were unknown (14.4%). Six of the ten quality criteria presented a conformity rate higher than 70%. Two criteria with a conformity rate lower than 20% were the most controversial: presentation at a STB before biopsy and freezing of a tumor fragment. A multivariate analysis revealed that the common predictor of nonconformity to composite criteria was the initial management in a nonexpert center. Conclusion Initial diagnostic management requires improvement, especially outside of specialized centers.

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 PCI12 (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.

The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown. The aim of this study was to evaluate the impact of delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation. Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C). Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61 months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (p = 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (p = 0.938); RE (p = 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (p = 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (p = 0.41). Factors influencing LRFS were adjuvant radiotherapy [hazard ratio (HR) 0.21; p = 0.0001], initial R0 resection (HR 0.24, p = 0.0001), and Group A (HR 0.44; p = 0.01). Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.

The optimal treatment for pseudomyxoma peritonei (PMP) combines complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Yet, achieving CRS is challenging in the case of extensive involvement of the peritoneal cavity and the survival benefit in this setting remains uncertain. The present study evaluated the surgical outcomes according to the peritoneal extent.Between 1992 and 2014, 245 patients underwent CRS and HIPEC for PMP in our institution. Their characteristics were reviewed using a prospective database. Extensive PMP was defined as a peritoneal cancer index (PCI) ≥ 28. Sixty-one patients with extensive PMP were compared to 184 with non-extensive PMP.Severe complications were more frequent in the extensive group (46% vs. 23%, p 0.001) but the post-operative mortality was not significantly different (8% vs. 3%, p = 0.1). The 5-year disease-free survival reached 45% in the extensive and 78% in the non-extensive group (p 0.0001). The 5-year overall survival was 70% and 90% in the extensive and non-extensive group respectively (p 0.021).CRS with HIPEC offers prolonged survival even in the case of extensive PMP. Because of the high rate of surgical morbidity in the extensive group, patients should be carefully selected.

Background To assess relevance of ESMO-ESSO-ESTRO treatment guidelines in a retrospective analysis of patients with anal canal or anal margin cancers. Material and methods 155 patients were separated into standard treatment group (STG), treated according to or closely the guidelines, and an altered treatment group (ATG). Results The median follow-up time was 50.7 months. In the STG, the 5- and 10-year LR-DFS rates were 75.2% and 72.7%; in the ATG, they were 66.8% and 61.2%, respectively. In the STG, the 5- and 10-year OS rates were 81.8% and 68%; in the ATG, they were 63.3% and 49.5%, respectively (p = 0.037). In the multivariate analysis, favorable prognostic factors for OS included the standard treatment, age 50.4 Gy. Conclusion This study identifies the superiority of treatment according to standard guidelines compared to altered treatment. Our results corroborate the guidelines.

International audience; Background: The introduction of cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improved the prognosis of selected patients with peritoneal mesothelioma (PM).Objective: The objective of our study was to evaluate whether different HIPEC agents were associated with different outcomes in patients with PM.Methods: From the RENAPE database, we selected all patients with histology-proven PM who underwent CRS + HIPEC from 1989 to 2014. Inclusion criteria were age ≤ 80 years, performance status ≤ 2, and no extraperitoneal metastases.Results: Overall, 249 patients underwent CRS + HIPEC for PM. The HIPEC regimen included five chemotherapeutic agents (CAs), consisting of cisplatin, doxorubicin, mitomycin-C, oxaliplatin, and irinotecan. When considering all CAs (alone or in combination), there was no significant statistical difference in regard to postoperative overall survival (OS). However, OS was better when using two CAs (group 2 drugs) versus one CA (group 1 drug) (p = 0.03). The different CA regimens were equally distributed between the two groups. This association between OS and HIPEC agent, as well as a trend for better progression-free survival, were both observed in the two-drug group versus the one-drug group (p = 0.009) for patients undergoing complete cytoreductive surgery (CC-0) with an epithelioid subtype.Conclusions: This large study seems to show improved OS when combined CAs, especially with platinum-based regimens, are used for HIPEC in patients with PM, but needs to be confirmed by a randomized controlled trial.

Background Colorectal surgery has an important impact on a patient’s quality of life, and postoperative rehabilitation shows large variations. To enhance the understanding of recovery after colorectal cancer, health-related quality of life has become a standard outcome measurement for clinical care and research. Therefore, we aimed to correlate the influence of preoperative global life satisfaction on subjective feelings of well-being with clinical outcomes after colorectal surgery. Methods In this pilot study of consecutive colorectal surgery patients, various dimensions of feelings of preoperative life satisfaction were assessed using a self-rated scale, which was validated in French. Both objective (length of stay and complications) and subjective (pain, subjective well-being and quality of sleep) indicators of recovery were evaluated daily during each patient’s hospital stay. Results A total of 112 patients were included. The results showed a negative relationship between life satisfaction and postoperative complications and a significant negative correlation with the length of stay. Moreover, a significant positive correlation between life satisfaction and the combined subjective indicators of recovery was observed. Conclusion We have shown the importance of positive preoperative mental states and global life satisfaction as characteristics that are associated with an improved recovery after colorectal surgery. Therefore, patients with a good level of life satisfaction may be better able to face the consequences of colorectal surgery, which is a relevant parameter in supportive cancer care.

Resume Contexte et objectif Les techniques associant cytoreduction maximale tumorale a une chimiotherapie hyperthermique intraperitoneale (CHIP) ont permis d’ameliorer la survie des patients atteints de carcinose peritoneale (CP). Les examens morpho-biologiques actuels sont peu rentables pour le diagnostic de CP. L’objectif de cette etude prospective est de determiner l’interet de la laparotomie de second regard (LSR) systematique associee a une CHIP dans le diagnostic et le traitement de la CP chez des patients a haut risque de recidive. Patients et methodes De 2007 a 2011, une LSR a ete effectuee apres 12 cures de chimiotherapie intraveineuse chez 14 patients qui avaient beneficie d’une chirurgie d’exerese carcinologique initiale complete pour CP et/ou metastases ovariennes synchrones d’origine colique de decouverte fortuite lors de la chirurgie du primitif. Lors de la LSR, une CHIP pouvait etre associee. Resultats Soixante et onze pour cent des patients presentaient une CP confirmee histologiquement lors de la LSR avec un peritoneal carcinomatosis index (PCI) median de 10. Il n’y avait aucune mortalite postoperatoire et 7 % des patients ont presente des complications de stade III–IV. A 2 ans, la survie globale et sans recidive etaient respectivement de 91 % et de 38 %. Une recidive peritoneale n’etait observee que chez 8 % des patients avec CHIP. Conclusion La LSR systematique avec CHIP apres exerese initiale de CP synchrone de cancer colique permet le diagnostic et le traitement de CP de faible score, genere peu de complications postoperatoires et ameliore la survie globale.

Summary Background Surgical procedures that combine both complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved the survival of patients with peritoneal carcinomatosis (PC). Current imaging and laboratory investigations are not very useful to diagnose PC. This prospective study sought to determine the usefulness of routine second-look surgery (RSLS) combined with HIPEC in the diagnosis and treatment of patients with PC at high-risk for recurrence. Methods From 2007 to 2011, RSLS was performed on 14 patients who had undergone a complete initial oncological resection for synchronous colonic PC and/or ovarian metastasis with PC discovered during primary colon cancer surgery after a course of 12 cycles of intravenous chemotherapy, eventually associated with HIPEC. Results Pathology confirmed PC in 71% of patients during RSLS, with a median peritoneal carcinomatosis index (PCI) of 10. There was no post-operative mortality, while 7% of patients exhibited Dindo Grade III–IV complications. The 2-year overall survival and disease-free survival rates were 91% and 38%, respectively. Following RSLS and CCRS, peritoneal recurrence was observed in only 8% of patients who had undergone HIPEC. Conclusion RSLS combined with HIPEC after initial resection of synchronous colonic PC allows diagnosis and treatment of low-score PC, with limited post-operative complications and increased overall survival rates.

Blunt bowel and mesenteric injuries (BBMI) are regularly missed by abdominal computed tomography (CT) scans. The aim of this study was to develop a risk assessment tool for BBMI to help clinicians in decision-making for blunt trauma after road traffic crashes (RTCs). Single-center retrospective study of trauma patients from January 2010 to April 2015. All patients admitted to our hospital after blunt trauma following RTCs and CT scan at admission were assessed. Of the 394 patients included, 78 (19.8%) required surgical exploration and 34 (43.6%) of these had a significant BBMI. A univariate and multivariate analysis were performed comparing patients with BBMI (n = 34) and patients without BBMI (n = 360). A score with a range from 0 to 13 was created. Scores from 8 to 9 were associated with 5–25% BBMI risk. The power of this new score ≥ 8 to predict a surgically significant BBMI had a sensitivity of 96%, specificity of 86.4%, positive predictive value (PPV) of 48% and negative predictive value (NPV) of 99.4%. This score could be a valuable tool for the management of blunt trauma patients after RTA without a clear indication for laparotomy but at risk for BBMI. The outcome of this study suggests selective diagnostic laparoscopy for a score ≥ 8 in obtunded patients and ≥ 10 in all other. To assess the value and accuracy of this new score, a prospective validation of these retrospective findings is due.

Background: Surgery for anal canal cancer (ACC) and anal margin cancer (AMC) is the only curative option after failure of chemoradiotherapy (CRT). This study aimed to determine the efficacy of surgery for ACC or AMC after failed CRT. Methods: This was a single-centre, retrospective study of 161 patients initially treated with CRT. We compared the survival rates of patients successfully treated by CRT with those of patients whose CRT failed (both surgically salvaged and treated palliatively). Results: Thirty-one patients underwent surgery with curative intent, 20 received palliative treatment after failure of CRT, and 110 had effective CRT. The 5-year overall survival (OS) rate was significantly higher among patients with successful CRT than among patients who underwent surgery with curative intent (86 vs. 66%, p < 0.001). On the other hand, the 5-year OS of patients treated with curative surgery was significantly better than that of patients who underwent palliative treatment (66 vs. 13.5%, p < 0.001). The postoperative morbidity and mortality rates were 32 and 3%, respectively. Considering patients with failed CRT, curative surgery was the only factor prognostic of favourable OS in the multivariate analysis. Conclusion: Curative surgery after failure of CRT for ACC or AMC remains an effective treatment to improve survival in two-thirds of cases, resulting in high but manageable morbidity.

Pseudozyma aphidis is an environmental Basidiomycete yeast, and has been involved in the ten past years in rare cases of invasive infection. Pseudozyma species are naturally resistant to caspofungin and often present decreased susceptibility or resistance to fluconazole. This fungus may be difficult to recognize and misidentifications are reported with conventional phenotypical methods. We report a case of P. aphidis invasive infection in an adult with a metastatic ampulloma who had gone through digestive surgery., Highlights • Pseudozyma aphidis invasive infection after abdominal surgery. • Identification of Pseudozyma aphidis: mass spectrometry could be promising if databanks include more spectra, whereas conventional phenotypical methods fail. • Resistance to echinocandins and flucytosine and decreased susceptibility to fluconazole.

Background Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC-ox) induces specific morbidity with hemorrhagic complications (HC). The aim of this study was to identify preoperative, intraoperative and postoperative HC predictive factors after HIPEC-ox. Methods A prospective single center study that included all consecutive patients treated with curative-intent HIPEC-ox, whatever the origin of peritoneal disease, was conducted. All patients underwent systematic blood tests exploring primary hemostasis and endothelial activation before surgical incision (D0) and on postoperative days 2 (POD2) and 5 (POD5). Results Between May 2012 and August 2015, 47 patients were enrolled in the study. The overall HC rate was 38%. Major morbidity was significantly higher in patients with HC. Patients presenting HC were significantly more often affected with pseudomyxoma peritonei and had less preoperative chemotherapy. Multivariate analysis showed that a higher plasmatic level of Von Willebrand factor antigen at D0 (D0 VWF:Ag) was a protective predictive factor for HC (p = 0.049, HR: 0.97 CI 95% [0.94–1.00]). A D0 VWF:Ag level below 138% had a sensitivity of 87.5%, a specificity of 67% and an area under the curve of 80.3% (CI 95% [66.5–94], p Conclusions Through the identification of prognostic factors, this study highlighted a subgroup of patients with low risk of HC after HIPEC-ox. Based on these results, we propose a routine preoperative dosage of VWF that would help the surgeon to select the most suitable patients for HIPEC-ox.

The aim of this study is to analyze the outcome of renal angiomyolipomas (AML) at two European institutions.The data were collected from patients with a primary AML who were treated at Gustave Roussy, Villejuif, France and Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy from 1998 to 2014. The specimens were classified as classic AML (C AML) or epithelioid AML (E AML) based on the percentage of epithelioid cells.There were 40 patients identified for the study (35 C AML, 5 E AML). One patient had an associated tuberous sclerosis complex. Six patients (15%) had bilateral AML. The imaging results were significantly different between C/E AML. E AML was associated with fewer bilateral lesions, more renal vein/vena cava extension, and more poor or non-fatty aspects. Surgery/active surveillance (AS)/chemo radiation were applied for 28/11/1 patients, respectively. The median tumor size was significantly smaller (3.75 cm) in patients receiving AS (median 15 cm when surgically resected). The median patient follow-up was 43 months. The three-year overall survival was significantly better for patients with C AML than E AML (100% versus 50%, p 0.0001). The univariate analysis identified the OS prognostic factors were E AML histologic subtype (p 0.001), poor/non fatty features (p = 0.002), and renal vein extension on imaging (p = 0.01).AML manifests as at least two different entities with significantly different outcomes. Epithelioid subtype, poor/non-fatty features, and renal vein involvement are all associated with worse survival.