Introduction La majorité des récidives après œsophagectomie surviennent dans les deux premières années. En France, la surveillance postopératoire est habituellement conduite pendant cinq ans. Cependant, des rechutes plus tardives ont été rapportées, soulevant la question de la pertinence d’un suivi prolongé. Méthodes Une étude rétrospective bicentrique a été menée au CHU de Lille et à l’hôpital Saint-Antoine. Ont été inclus les patients opérés d’un cancer de l’œsophage à visée curative entre 2009 et 2015, vivants et indemnes de récidive à cinq ans. Les récidives tardives (≥5 ans) et les seconds cancers primitifs ont été recensés et leurs facteurs associés analysés. Résultats Parmi 664 patients opérés, 229 remplissaient les critères d’inclusion. Douze patients (5,2 %) ont présenté une récidive tardive, dont 50 % métastatiques, survenant jusqu’à 107 mois après la chirurgie. En analyse multivariée, cinq variables étaient indépendamment associées à une diminution de la survie sans récidive : le sexe masculin (OR=6,09 ; p=0,001), les antécédents néoplasiques (OR=2,28 ; p=0,048), la radiochimiothérapie néoadjuvante (OR=3,18 ; p=0,002), le carcinome épidermoïde (OR=2,22 ; p=0,022) et les marges de résection non saines (OR=56,32 ; p=0,001). Seize patients (6,9 %) ont développé un second cancer primitif, principalement ORL ou pulmonaire. La radiochimiothérapie néoadjuvante était associée à un risque accru de seconde localisation (OR=2,64 ; p=0,011). Conclusion Un risque évolutif persiste au-delà de cinq ans après œsophagectomie curative, sous forme de récidives tardives (5 %) et de seconds cancers primitifs (6,9 %). Ces résultats remettent en question l’arrêt systématique du suivi à cinq ans et plaident pour une surveillance prolongée et individualisée.

INTRODUCTION:The majority of recurrences after esophagectomy occur within the first two years. In France, postoperative follow-up usually continues for five years. However, later relapses have been reported, raising the question of whether prolonged follow-up is indicated. METHODS:A retrospective, two-center study was conducted at the University Hospital of Lille and Saint-Antoine Hospital in Paris. The study included patients who had undergone curative esophageal cancer surgery between 2009 and 2015, and were alive and free of recurrence at five years. Late recurrences (≥5 years) and second primary cancers were identified and their associated factors analyzed. RESULTS:Of 664 patients who underwent resection of esophageal cancer, 229 met the inclusion criteria. Twelve of these patients (5.2%) experienced a late recurrence, 50% of which were metastatic, occurring up to 107 months after surgery. In multivariable analysis, five variables were independently associated with decreased recurrence-free survival: male sex (OR=6.09; P=0.001), prior cancer history (OR=2.28; P=0.048), neoadjuvant chemoradiotherapy (OR=3.18; P=0.002), squamous cell carcinoma (OR=2.22; P=0.022), and positive-margin resections (OR=56.32; P=0.001). Sixteen patients (6.9%) developed a second primary cancer, mainly head and neck or lung cancer. Neoadjuvant chemoradiotherapy was associated with an increased risk of a second cancer site (OR=2.64; P=0.011). CONCLUSION:A residual risk of disease progression persists beyond five years after curative esophagectomy, in the form of late recurrences (5%) and second primary cancers (6.9%). These findings challenge the systematic discontinuation of follow-up at five years and support a prolonged and individualized surveillance strategy.

Background Diffuse malignant peritoneal mesothelioma (DMPM) is a rare disease for which only selected patients are eligible for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of our study was to evaluate oncologic outcomes of different treatments patterns of DMPM at national level. Methods All patients treated for DMPM between 2012 and 2021 in France were extracted through a national administrative database. Perioperative outcomes were analyzed into 3 groups: upfront-resectable, borderline-resectable (B-R) and inoperable patients. Survival outcomes were performed by Kaplan-Meier method. A multivariate logistic model was used to identify factors affecting survival. Results Of 924 patients, 270, 117 and 537 were identified as upfront-resectable, B-R and inoperable patients. The median age was 53 years with a mean Elixhauser comorbidity index of 3.2. Patients treated with CRS-HIPEC were younger with less comorbidities and had more exploratory laparoscopy compared to inoperable patients (p < 0.001). Majority of surgical patients were mostly treated in expert centers (97.7%). 90-day postoperative mortality (POM) was 2.1%. Major morbidity (MM) occurred in 50.9% with a failure-to-rescue (FTR) rate of 4.1%. Upfront-resectable patients had significantly better 5-year survival compared to B-R and inoperable patients (84.6% vs 55% vs 12.9%, p < 0.0001). After multivariate analysis, male gender (p < 0.0001), age (p = 0.005), B-R group (p < 0.0001), MM (p = 0.003) and adjuvant chemotherapy (p = 0.01) were independently associated with decrease 5-year survival. Conclusion CRS and HIPEC is a safe procedure with a low 90-day POM and FTR. Patients should be address to expert centers to evaluate patients that could benefit from curative strategy.

INTRODUCTION:Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an emerging therapeutic option for peritoneal carcinomatosis, offering improved drug distribution and tissue penetration. Although clinical outcomes have been encouraging, international guidelines for perioperative management - including pain control and thromboprophylaxis - are still lacking. MATERIALS AND METHODS:A global online survey was distributed to PIPAC practitioners to corresponding authors of published PIPAC studies and members of the International Society for the Study of Pleura and Peritoneum (ISSPP). The questionnaire consisted of 24 closed-ended questions covering five domains: institutional experience, perioperative organization, thromboprophylaxis, biological monitoring, and postoperative pain management. Consensus was defined as ≥70% agreement among respondents. RESULTS:Out of 300 contacted experts, 125 responded (42% overall response rate), representing 68 centers across 27 countries (71.2% from Europe). Consensus was reached for four items: performing a surgical or oncological consultation before each PIPAC procedure (74.59%), conducting pre and postoperative laboratory tests (89.43% and 70.73% respectively) and the non-use of non-medicated thromboprophylaxis (70.97%). Pharmacological thromboprophylaxis was prescribed in 63.71% of centers, mainly low-molecular-weight heparin, up to 7 days in 33% of centers, up to 21 days in 33%, and limited to the in-hospital stay in 22%. Otherwise, anesthetic consultations were systematically performed in 57.26% of centers. Outpatient procedures (<24 h) were performed in 11.29%, while 41.94% and 34.68% of patients were hospitalized for one and two days respectively. Paracetamol was the first-line analgesic and was used in more than 80% of cases on postoperative day 1. A significant difference was observed regarding the use of morphine PCA, which was more frequently prescribed after oxaliplatin-based PIPAC (p = 0.013). DISCUSSION:This international survey highlights substantial heterogeneity in perioperative care practices. Although PIPAC and cytoreductive surgery are performed for peritoneal metastases, pharmacological thromboprophylaxis appears to be less frequently prescribed in the PIPAC settings. Pre-PIPAC consultation and perioperative biological monitoring are more standardized, although noteworthy variations persist. These findings underscore the need for evidence-based international guidelines to harmonize perioperative management and improve patient outcomes in PIPAC.

Introduction: Palliative chemotherapy is the current standard among advanced gastric cancer (GC) patients with peritoneal metastasis (PM), while the role of gastrectomy with cytoreductive surgery and HIPEC remains unclear. The current study aimed to assess treatment outcomes among GC patients with PM undergoing gastrectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) using multinational cancer registries. Methods: The analysis (2012-2022) included stage IV GC patients with PM undergoing gastrectomy and HIPEC from the European GASTRODATA Registry (EU cohort) and the American National Cancer Database (NCDB, U.S. cohort). The study outcomes were textbook oncological outcome (TOO) assessment and overall survival (OS). Results: Among 193 patients, 49.7 % were from the EU cohort and 50.3 % from the U.S. cohort. EU cohort had significantly higher rates of pT4 tumors (EU: 50 % vs U.S.: 40.2 %), metastatic lymph nodes (EU: 68.8 % vs U.S.: 54.6 %), and >16 lymph nodes evaluated (EU: 91.7 % vs U.S.: 68%). Postoperatively, the EU cohort had longer hospital stay (EU: 53.1 % vs 22.2 %, p < 0.001), with no significant differences in 30-day readmission (EU: 14.6% vs U.S: 7.2%, p = 0.11) and 90-day mortality (EU: 4.2 % vs U.S.: 9.3%, p = 0.25). TOO rates were 30.2 % and 32 % for EU and U.S. cohorts, respectively. Within the U.S. cohort, TOO achievement was associated with improved 1- (86.7% vs. 57.4 %), 3- (55.8 % vs. 29.7 %), and 5-year OS (50.2 % vs. 29.7%) (p = 0.0025) survival compared with non-TOO. Conclusions: Among patients with GC and PM undergoing gastrectomy and HIPEC, achievement of TOO was associated with decreased risk of postoperative complications (EU cohort) and improved long-term survival (U.S.

Background This retrospective multicenter cohort study compared the feasibility and safety of oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-Ox) with or without intraoperative intravenous 5-fluorouracil (5-FU) and leucovorin (L). Methods Our study included consecutive patients with histologically proven unresectable and isolated colorectal peritoneal metastases (cPM) treated with PIPAC-Ox in seven tertiary referral centers between January 2015 and April 2020. Toxicity events and oncological outcomes (histological response, progression-free survival, and overall survival) were compared between patients who received intraoperative intravenous 5-FU/L (PIPAC-Ox + 5-FU/L group) and patients who did not (PIPAC-Ox group). Results In total, 101 patients (263 procedures) were included in the PIPAC-Ox group and 30 patients (80 procedures) were included in the PIPAC-Ox + 5-FU/L group. Common Terminology Criteria for Adverse Events v4.0 grade 2 or higher adverse events occurred in 48 of 101 (47.5%) patients in the PIPAC-Ox group and in 13 of 30 (43.3%) patients in the PIPAC-Ox + 5-FU/L group ( p = 0.73). The complete histological response rates according to the peritoneal regression grading score were 27% for the PIPAC-Ox + 5-FU/L group and 18% for the PIPAC-Ox group ( p = 0.74). No statistically significant differences were observed in overall or progression-free survival between the two groups. Conclusions The safety and feasibility of PIPAC-Ox + 5-FU/L appears to be similar to the safety and feasibility of PIPAC-Ox alone in patients with unresectable cPM. Oncological outcomes must be evaluated in larger studies.

Background: Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) is a chronic liver disease commonly associated with hepatic fibrosis. NASH patients have an increased risk for hepatocellular carcinoma (HCC). Due to western way of life, NASH incidence is rising and is predicted to become the leading cause of HCC in the next decades. Therefore, there is an urgent need for robust animal models fully recapitulating the NASH-related HCC carcinogenesis. In this study, we develop and characterize specific diet-induced variants from our transgenic HCC mouse model, focusing on immune landscape.Methods: To mimic NASH, ASV-B, a transgenic mouse model (C57BL/6J) that spontaneously develops a reproducible stage-defined HCC (hyperplasia at week(W)8, nodular stage at W12, and diffuse carcinoma at W16-20) was exposed to 5 different diets. Ten ASV-B and 5 control mice were fed as follows: classic diet as control (yellow), or a high-fat diet (blue), a diet enriched with saturated fatty acids + 1.25% cholesterol (green), a diet containing 22% of vegetal oil + 0.2% cholesterol (orange), and a 1.25% cholesterol diet containing 21% of milkfat (red). All mice fed with special diets also received 30% fructose in the drink water. RNA was extracted from frozen livers at W20 for 40 immune markers analysis using qRT-PCR (LightCycler, Roche). Immune populations were assessed using automated immunohistochemistry (IHC) (Bond Max, Leica).Results: ASV-B model shows an increase in liver volume and angiogenesis, ASV-B livers harboring marked arterialization and capillarization as compared to control. Assessing immune markers on 7 evaluable tumor specimens, we observed an increase in CD8, Foxp3, INOS, CD11b, PD-1, PD-L1, IL1β, IFN-γ, TNF-α, IL17A and IL17F mRNA expression, as frequently observed in human inflammatory HCC. In addition, IHC staining showed intratumoral infiltration of lymphocytes (CD8+) and macrophages (F4/80+, a well-characterized and extensively referenced mouse macrophage marker). ASV-B mice receiving yellow, blue, and green regimens showed similar liver volumes and weight. By macroscopic analysis, we observed increased liver steatosis, and fibrosis in the red and orange regimen compared to others. Moreover, we observed a 40% mortality rate in the orange regimen, and a 20% mortality rate in the blue and the green regimens. At the conference, we will show the morphologic changes of the livers using HPS staining and the immune landscape in the livers of the diet-variants.Conclusion: ASV-B transgenic mouse model mimics several characteristics of human HCC developing on healthy liver including inflammatory reaction and immune cell infiltration. In the ASV-B model, we have been able to develop specific-diets variants aiming at mimicking NASH that could be used for drug testing.Citation Format: Annemilaï Tijeras-Raballand, Christian Hobeika, Benoit Rousseau, Patricia Hainaud, Philippe Bonnin, Aurélie Rodrigues, Fouad Ladfil, Marc Pocard, Valérie Paradis, Armand de Gramont, Eric Raymond, Evelyne Dupuy, Clarisse Eveno, Sandrine Faivre. Diet-variants and immune characterization of a stage-defined, transgenic immunocompetent mouse model of HCC (ASV-B) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 91.

BACKGROUND:This case report aims to describe the impact of the bidirectional chemotherapy (BDC) on resecability for initially unresectable malignant peritoneal mesothelioma (MPM). METHODS:We report a case of 55-year-old male with the diagnosis of initially unresecable MPM. The BDC combined intravenous (IV) chemotherapy (Cisplatin-Pemetrexed) and intra peritoneal (IP) chemotherapy (Cisplatin). The response to chemotherapy was assessed by CT - scan and laparoscopy. RESULTS:Initial evaluation classed the disease as unresecable with PCI at 39. At the reevaluation, CT - scan and laparoscopy showed a macroscopic response, allowing surgery consisting of cytoreductive surgery and hyperthermic intra peritoneal chemotherapy (Doxorubicin and Cisplatin). CONCLUSIONS:BDC (IV and IP) has promising results and allows to undergo surgery for selected patients with borderline or initially unresectable MPM.