[Esophageal and esophago-gastric junction cancer†: management and multimodal treatment]. / Cancer de l'œsophage et de la jonction œsogastrique†: prise en charge et traitement multidisciplinaire.

Esophageal cancer remains an oncological burden with a low survival rate. Multidisciplinary management is essential to offer an adjusted treatment to the patient general condition and the tumor stage. New minimally invasive surgical treatments help to reduce the surgical trauma and improve post-operative patient recovery. Oncological treatments have also evolved and definitive treatment by radio-chemotherapy can be proposed in specific cases.

Le cancer de l'œsophage reste un fardeau oncologique avec un taux de survie bas. Une prise en charge multidisciplinaire est primordiale afin d'offrir un traitement adapté à l'état général du patient et au stade de la tumeur. De nouvelles prises en charge minimalement invasives chirurgicales permettent de diminuer le traumatisme d'une chirurgie majeure et améliorent la récupération des patients en postopératoire. Les traitements oncologiques ont également évolué et un traitement définitif par radiochimiothérapie peut être proposé dans des cas précis.

A comparison of the da Vinci Xi vs. the da Vinci Si Surgical System for Roux-En-Y gastric bypass.

PURPOSE: The da Vinci Surgical System family remains the most widely used surgical robotic system for laparoscopy. Data about gastric bypass surgery with the Xi Surgical System are not available yet. We compared Roux-en-Y gastric bypass surgery performed at our institution with the da Vinci Xi and the da Vinci Si Surgical System. METHODS: All robotic gastric bypass procedures performed between January 2013 and September 2016 were analyzed retrospectively. Patient demographics and operative and postoperative outcomes up to 30 days were compared for the da Vinci Xi and Si Surgical System. Robotic costs per procedure were modeled including posts for a standard set of robotic instruments, capital investment, and yearly maintenance. RESULTS: One-hundred forty-four Xi Surgical System and 195 Si Surgical System procedures were identified. Mean age (p = 0.9), gender distribution (p = 0.8), BMI (p = 0.6), and ASA scores (p > 0.5) were similar in both cohorts. Operating room times were similar in both groups (219.4 ± 58.8 vs. 227.4 ± 60.5 min for Xi vs. Si, p = 0.22). Docking times were significantly longer with the Xi compared with the Si Surgical System (9 ± 4.8 vs. 5.8 ± 4 min, p < 0.0001). There was no difference in incidence of minor (13.9 vs. 10.3%, p = 0.3) and major complications (5.6 vs. 5.1%, p = 1 for Xi vs. Si). Costs were higher for the Xi Surgical System caused by higher capital investment and yearly maintenance. CONCLUSIONS: Roux-en-Y gastric bypass surgery can be safely performed with the Xi Surgical System, while drawbacks include longer docking times and higher costs.

Pancreas preservation fluid microbial contamination is associated with poor islet isolation outcomes - a multi-centre cohort study.

The microbiological safety of islet preparations is paramount. Preservation medium contamination is frequent, and its impact on islet yield and function remains unclear. Microbiological samples collected during islet isolations from 2006 to 2016 were analyzed and correlated to isolation and allo- and autotransplantation outcomes. Microbial contamination of preservation medium was found in 64.4% of processed donor pancreases (291/452). We identified 464 microorganisms including Staphylococcus (253/464, 54.5%), Streptococcus (31/464, 6.7%), and Candida species (25/464, 5.4%). Microbial contamination was associated with longer warm and cold ischemia times and lower numbers of postpurification islet equivalents, purity, transplant rate, and stimulation index (all P < 0.05). Six percent of the preparations accepted for transplantation showed microbial contamination after isolation (12/200); 9 of 12 were Candida species. Six patients were transplanted with a sample with late microbial growth discovered after the infusion. Insulin independence rate was not affected. This risk of transplanting a contaminated islets preparation was reduced by half following the implementation of an additional sampling after 24 h of islet culture. Pancreas preservation fluid microbial contamination is associated with lower transplant rate and poorer in vitro function, but not with changes in graft survival. Culture medium testing 1 day after isolation reduces the risk of incidental transplantation with contaminated islets.

[Diagnosis and management of gastro-esophageal junction tumor]. / Diagnostic et prise en charge du cancer de la jonction œsogastrique.

At the border between the esophagus and the stomach, gastro-esophageal junction tumors require a specific management that cannot be simplified to either of these two organs. Staging work-up with endoscopy, CT-Scan and PET-Scan, is essential because it will condition the choice of neo-adjuvant treatment. Surgery remains the only curative treatment and should be undergone in specialized center.

A la frontière entre l'œsophage et l'estomac, les tumeurs de la jonction œsogastrique nécessitent une prise en charge spécifique ne pouvant être simplifiée à l'un ou l'autre de ces deux organes. Le bilan complémentaire par endoscopie, CT-scan et PET-scan, est capital car il va conditionner le traitement néoadjuvant. La chirurgie reste le seul traitement curatif et doit être effectuée dans un centre spécialisé.

Impact of graft implantation order on graft survival in simultaneous pancreas-kidney transplantation.

The optimal order of revascularization for pancreas and kidney grafts in simultaneous pancreas-kidney transplantation has not been established. In this study, we investigate the influence of graft implantation order on graft survival in SPK. 12 700 transplantations from the Scientific Registry of Transplant Recipients were analyzed retrospectively. Graft implantation order was determined based on the reported ischemia times of pancreas and kidney grafts. Pancreas and kidney graft survivals were analyzed depending on graft implantation order at 3 months and 5 years using Kaplan-Meier plots. Significance was tested with log-rank test and Cox regression model. In 8454 transplantations, the pancreas was implanted first (PBK), and in 4246 transplantations, the kidney was implanted first (KBP). The proportion of lost pancreas grafts at 3 months was significantly lower in PBK (9.4% vs. 10.8%, P = 0.011). Increasing time lag (>2 h) between kidney and pancreas graft implantation in KBP accentuated the detrimental impact on pancreas graft survival (12.5% graft loss at 3 months, P = 0.001). Technical failure rates were reduced in PBK (5.6 vs. 6.9%, P = 0.005). Graft implantation order had no impact on kidney graft survival. In summary, although observed differences are small, pancreas graft implantation first increases short-term pancreas graft survival and reduces rates of technical failure.

Teaching and learning robotic surgery at the dual console: a video-based qualitative analysis.

Robotic-assisted surgery (RAS) involves training processes and challenges that differ from open or laparoscopic surgery, particularly regarding the possibilities of observation and embodied guidance. The video recording and the dual-console system creates a potential opportunity for participation. Our research, conducted within the department of visceral surgery of a big Swiss, public, academic hospital, uses a methodology based on the co-analysis of video recordings with surgeons in self-confrontation interviews, to investigate the teaching activity of the lead surgeon supervising a surgeon in training at the dual console. Three short sequences have been selected for the paper. Our analysis highlights the skills-in-construction of the surgeon in training regarding communication with the operating team, fluency of working with three hands, and awareness of the whole operating site. It also shows the divergent necessities of enabling verbalization for professional training, while ensuring a quiet and efficient environment for medical performance. To balance these requirements, we argue that dedicated briefing and debriefing sessions may be particularly effective; we also suggest that the self-confrontation video technique may be valuable to support the verbalization on both the mentor's and the trainee's side during such debriefing, and to enhance the mentor's reflexivity regarding didactic choices.

Novel Biomarkers of Gastric Adenocarcinoma: Current Research and Future Perspectives.

Overall survival of gastric cancer remains low, as patients are often diagnosed with advanced stage disease. In this review, we give an overview of current research on biomarkers in gastric cancer and their implementation in treatment strategies. The HER2-targeting trastuzumab is the first molecular targeted agent approved for gastric cancer treatment. Other promising biomarkers for targeted therapies that have shown relevance in clinical trials are VEGF and Claudin 18.2. Expression of MET has been shown to be a negative prognostic factor in gastric cancer. Targeting the PD-1/PD-L1 pathway with immune checkpoint inhibitors has proven efficacy in advanced gastric cancer. Recent technology advances allow the detection of circulating tumor cells that may be used as diagnostic and prognostic indicators and for therapy monitoring in gastric cancer patients. Prognostic molecular subtypes of gastric cancer have been identified using genomic data. In addition, transcriptome profiling has allowed a comprehensive characterization of the immune and stromal microenvironment in gastric cancer and development of novel risk scores. These prognostic and predictive markers highlight the rapidly evolving field of research in gastric cancer, promising improved treatment stratification and identification of molecular targets for individualized treatment in gastric cancer.

[Pancreas and islets of Langerhans transplantation: current status in 2009 and perspectives]. / Transplantation de pancréas et d'ilots de Langerhans: le point en 2009 et le futur.

Type 1 diabetes currently affects 15,000 patients in Switzerland with a rising incidence worldwide. Pancreas or islet of Langerhans transplantation are alternatives to intensive insulin treatment, which decreases long-term complications at the cost of an increase of severe hyoglycemia. Pancreas transplantation, indicated mainly to diabetic patients with simultaneous kidney transplantation, has a high success rate, but is accompanied by high morbidity due to general surgery. Islet transplantation, a cell-therapy for type 1 diabetes, is in full development. It is mainly indicated as islet transplant alone in patients suffering from brittle diabetes, and is associated with a very low risk due to minimally invasive technique, but a lower rate of long-term success. New potential sources of beta cell replacement are beta-cell lines, stem cells and xenotransplantation.

Minimal length of proximal resection margin in adenocarcinoma of the esophagogastric junction: a systematic review of the literature.

The minimal length of proximal margin (PM) in esophagogastric junction cancer has not been established yet and its impact on patient survival remains unclear. Pubmed, Embase and Scopus databases were searched for "adenocarcinoma of the esophagogastric junction", "adenocarcinoma of the gastroesophageal junction" and "cardia cancer", each combined with "proximal margin". English written studies that specified PM length in AEG were included. Survival data in relation to PM were extracted. 13 studies, that were all retrospective case series, with a total number of 2648 patients met inclusion criteria and were analyzed. While 93% of 230 patients with Siewert type I had esophagectomy, 69% of 1270 patients with Siewert type II and 93% of 872 patients with Siewert type III had transhiatal extended gastrectomy. Minimal PM length was treated by five studies and ranged between 2 and 6 cm. While three studies defined minimal PM by the necessary length to obtain R0 resection, two studies found minimal PM length significantly associated with survival. Multivariate analyses revealed in two studies an independent impact of PM on survival, whereas one study did not found any significant relation between PM and survival. One study showed that PM length was significantly associated with survival in T2-4N0-2 tumors, but not in T1 or N3 tumors. In conclusion, available retrospective studies did not allow a conclusion for a minimal length of PM and showed no clear evidence for an impact of PM length on survival. Taking into consideration available data and the shrinkage phenomen, a PM > 2 cm might be necessary to obtain a sufficient PM.

Early esophageal cancer: the significance of surgery, endoscopy, and chemoradiation.

Early carcinomas of the esophagus are histologically classified as adenocarcinoma or squamous cell carcinoma and microscopically subdivided into mucosal and submucosal carcinomas depending on infiltration depth. The prevalence of lymph node metastasis in mucosal carcinoma remains low. However, lymph node metastases arise frequently from tumors with submucosal infiltration, with increasing prevalence in the deeper submucosal sublayers. According to current German guidelines, endoscopic resection is the recommended treatment in mucosal adenocarcinoma without histologic risk factors (lymphatic invasion 1, vascular invasion 1, >grade 2, R1-margin). In superficial submucosal infiltration without histologic risk factors, endoscopic resection can be considered. In squamous cell carcinoma, endoscopic resection is indicated up to middle layer mucosal carcinoma. Beyond these criteria, surgical resection should be considered. The gold standard is a subtotal transthoracic esophagectomy with two-field lymphadenectomy. Total esophagectomy is performed in cervical esophageal carcinoma and transhiatal extended gastrectomy in carcinoma of the cardia. Minimally invasive procedures show good oncologic results and reduce the morbidity of radical esophagectomy. Reduced morbidity might be an argument for surgical resection in borderline cases between endoscopic and surgical resection. In early squamous cell cancer, the combination of endoscopic resection and adjuvant chemoradiotherapy is a therapeutic option with promising results.

Comparison of three radioligands for the labelling of human beta-adrenoceptor subtypes.

We have compared the ability of three radioligands, [(125)I]-cyanopindolol, [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, to label the three human beta-adrenoceptor subtypes. Saturation and competition binding experiments were performed using membrane preparations from Chinese hamster ovary cells stably transfected with the three subtypes. While [(3)H]-CGP 12,177 had very similar affinity for beta(1)- and beta(2)-adrenoceptors (about 40 pM), [(125)I]-cyanopindolol and [(3)H]-dihydroalprenolol had 4- to 6-fold higher affinity for beta(2)- as compared to beta(1)-adrenoceptors (10 vs 45 and 187 vs 1,021 pM, respectively). The affinity of [(125)I]-cyanopindolol at beta(3)-adrenoceptors was considerably lower (440 pM) than at the other two subtypes. The beta(3)-adrenoceptor affinity of [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol was so low that it could not be estimated within the tested range of radioligand concentrations (up to 4,000 pM and 30,000 pM for [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, respectively). We conclude that all three radioligands are ill-suited to label beta(3)-adrenoceptors, particularly in preparations co-expressing multiple subtypes. In the absence of alternatives, [(125)I]-cyanopindolol appears the least unsuitable to label beta(3)-adrenoceptors. There is a need for high-affinity radioligands which are either selective for beta(3)-adrenoceptors or reasonably non-selective among all three beta-adrenoceptor subtypes.

Beta-Cell Replacement: Pancreas and Islet Cell Transplantation.

Pancreas and islet transplantation are 2 types of beta-cell replacement therapies for type 1 diabetes mellitus. Since 1966, when pancreas transplantation was first performed, it has evolved to become a highly efficient procedure with high success rates, thanks to advances in surgical technique and immunosuppression. Pancreas transplantation is mostly performed as simultaneous pancreas-kidney transplantation in patients with end-stage nephropathy secondary to diabetes. In spite of its efficiency, pancreas transplantation is still a major surgical procedure burdened by high morbidity, which called for the development of less invasive and hazardous ways of replacing beta-cell function in the past. Islet transplantation was developed in the 1970s as a minimally invasive procedure with initially poor outcomes. However, since the report of the 'Edmonton protocol' in 2000, the functional results of islet transplantation have substantially and constantly improved and are about to match those of whole pancreas transplantation. Islet transplantation is primarily performed alone in nonuremic patients with severe hypoglycemia. Both pancreas transplantation and islet transplantation are able to abolish hypoglycemia and to prevent or slow down the development of secondary complications of diabetes. Pancreas transplantation and islet transplantation should be seen as two complementary, rather than competing, therapeutic approaches for beta-cell replacement that are able to optimize organ donor use and patient care.

Impact of recipient body mass index on short-term and long-term survival of pancreatic grafts.

BACKGROUND: The impact of recipient body mass index on graft and patient survival after pancreas transplantation is not well known. METHODS: We have analyzed data from all pancreas transplant recipients reported in the Scientific Registry of Transplant Recipients between 1987 and 2011. Recipients were categorized into BMI classes, as defined by the World Health Organization. Short-term (90 days) and long-term (90 days to 5 years) patient and graft survivals were analyzed according to recipient BMI class using Kaplan-Meier estimates. Hazard ratios were estimated using Cox proportional hazard models. RESULTS: A total of 21,075 adult recipients were included in the analysis. Mean follow-up was 5 ± 1.1 years. Subjects were overweight or obese in 39%. Increasing recipient BMI was an independent predictor of pancreatic graft loss and patient death in the short term (P<0.001), especially for obese class II patient survival (hazard ratio, 2.07; P=0.009). In the long term, obesity, but not overweight, was associated with higher risk of graft failure (P=0.01). Underweight was associated with a higher risk of long-term death (P<0.001). CONCLUSION: These results question the safety of pancreas transplantation in obese patients and suggest that they may be directed to alternate therapies, such as behavioral modifications or bariatric surgery, before pancreas transplantation is considered.

Has the gap between pancreas and islet transplantation closed?

Both pancreas and islet transplantations are therapeutic options for complicated type 1 diabetes. Until recent years, outcomes of islet transplantation have been significantly inferior to those of whole pancreas. Islet transplantation is primarily performed alone in patients with severe hypoglycemia, and recent registry reports have suggested that results of islet transplantation alone in this indication may be about to match those of pancreas transplant alone in insulin independence. Figures of 50% insulin independence at 5 years for either procedure have been cited. In this article, we address the question whether islet transplantation has indeed bridged the gap with whole pancreas. Looking at the evidence to answer this question, we propose that although pancreas may still be more efficient in taking recipients off insulin than islets, there are in fact numerous "gaps" separating both procedures that must be taken into the equation. These "gaps" relate to organ utilization, organ allocation, indication for transplantation, and morbidity. In-depth analysis reveals that islet transplantation, in fact, has an edge on whole pancreas in some of these aspects. Accordingly, attempts should be made to bridge these gaps from both sides to achieve the same level of success with either procedure. More realistically, it is likely that some of these gaps will remain and that both procedures will coexist and complement each other, to ensure that ß cell replacement can be successfully implemented in the greatest possible number of patients with type 1 diabetes.

Calcineurin inhibitor-free immunosuppressive regimen in type 1 diabetes patients receiving islet transplantation: single-group phase 1/2 trial.

BACKGROUND: Our final objective is to develop an adoptive therapy with tolerogenic donor-specific type 1 T regulatory cells for patients with type 1 diabetes undergoing islet transplantation. The achievement of this objective depends on the availability of an immunosuppressive treatment compatible with the survival, function, and expansion of type 1 T regulatory cells. METHODS: For this purpose, we designed a single-group, phase 1 to 2 trial with an immunosuppression protocol including: (i) rapamycin treatment before the first islet infusion (starting ≥ 30 days before transplantation); (ii) induction therapy with anti-thymocyte globulin (ATG) instead of anti-interleukin-2Ra monoclonal antibody (after the first islet infusion only); (iii) short-term treatment with steroids and interleukin-1Ra (right before and for 2 weeks after each infusion); rapamycin+mycophenolate mofetil treatment as maintenance therapy. The target enrollment was 10 patients. RESULTS: Ten of 15 patients who started the pretransplant rapamycin treatment completed it. Nine of 10 patients did not complete the induction therapy with ATG, and three of 10 required adaptation of maintenance immunosuppression caused by side effects. Four of 10 patients acquired insulin independence which can be maintained up to year 3 after last infusion. All six other patients have lost their graft, and the early graft loss was associated with lower dose of ATG during induction. CONCLUSION: This protocol resulted feasible, safe but less efficient in maintaining graft survival during the time than other T-cell depletion-based protocols. An adequate induction at the first infusion should be considered to improve the overall clinical outcome.

Comparative impact on islet isolation and transplant outcome of the preservation solutions Institut Georges Lopez-1, University of Wisconsin, and Celsior.

BACKGROUND: Institut Georges Lopez-1 (IGL-1) is a preservation solution similar to University of Wisconsin (UW) with reversed Na/K contents. In this study, we assessed the impact of IGL-1, UW, and Celsior (CS) solutions on islet isolation and transplant outcome. METHODS: We retrospectively analyzed 376 islet isolations from pancreases flushed and transported with IGL-1 (n=95), UW (n=204), or CS (n=77). We determined isolation outcome and ß-cell function in vitro. Transplanted patients were divided into three groups depending on preservation solution of pancreas, and islet graft function was assessed by decrease in daily insulin needs, C-peptide/glucose ratios, ß-scores, and transplant estimated function at 1- and 6-month follow-up. RESULTS: IGL-1, UW, and CS groups were similar according to donor age, body mass index, and pancreas weight. There was no difference in islet yields between the three groups. Success rates, transplant rates, ß-cell secretory function, and viability were similar for all three groups. We observed no difference in decreased insulin needs, C-peptide glucose ratios, ß-scores, and transplant estimated function at 1- and 6-month follow-up between IGL-1, UW, and CS groups. CONCLUSIONS: Our study shows that IGL-1 is equivalent to UW or CS solutions for pancreas perfusion and cold storage before islet isolation and transplantation.

Rapamycin impairs proliferation of transplanted islet ß cells.

BACKGROUND: The cause for a progressive attrition of islet graft function observed over the years after islet transplantation is not well defined but may be in part the result of adverse effects of immunosuppressive agents. In this study, we examined the effect of rapamycin, a key component of the immunosuppressive regimen, on ß-cell replication of transplanted islets. METHODS: Mice transplanted with rat islets under kidney capsule received bromodeoxyuridine for 7 days. Mice were treated with rapamycin or appropriate vehicle. ß-cell replication was determined by double immunofluorescence staining for insulin and bromodeoxyuridine. For in vitro studies, apoptosis, glucose-stimulated insulin secretion, and proliferation were determined in islet cells incubated with EdU in the presence or absence of rapamycin. RESULTS: In our islet transplant model, rapamycin impaired glucose tolerance and ß-cell proliferation of transplanted and host islets. In vitro, rapamycin reduced glucose-stimulated insulin secretion and reversibly decreased ß-cell replication. The inhibitory effect of rapamycin on ß-cell proliferation was not due to the decrease in insulin release. Additionally, in islet cells, expression of cell cycle proteins was significantly modified by rapamycin, suggesting a blockade of cell cycle progression. Inhibition of p38MAPK partially reverted rapamycin effect on ß-cell proliferation. CONCLUSION: Rapamycin, at concentration usually used to prevent islet graft rejection, is able to reduce the rate of ß-cell proliferation in transplanted rat islets but also in host murine islets. These data suggest that the progressive islet graft dysfunction observed under immunosuppressive therapy may result in part from an impairment of ß-cell regeneration.

Islet autotransplantation after extended pancreatectomy for focal benign disease of the pancreas.

BACKGROUND: Extended pancreatectomy is associated with the risk of surgical diabetes. Islet autotransplantation is successful in the prevention of diabetes after pancreas resection for chronic pancreatitis (CP), with insulin independence rates of 50% at 1 year. The aim of the present study is to demonstrate the safety and efficiency of islet autotransplantation after extended left pancreatectomy for benign disease. METHODS: Between 1992 and 2009, 25 patients underwent extended pancreatectomy and islet autotransplantation for benign disease. Of these, 15 patients were operated for focal lesions located at the neck of the pancreas (14 benign tumors and 1 traumatic pancreatic section), the remainder being CP cases. After unequivocal diagnosis of benignity, the rest of the pancreas was processed and infused into the portal vein. Metabolic results were analyzed and isolation results were compared with those obtained from patients with CP or donors with brain death (DBD). RESULTS: There was no mortality and a low morbidity (Streptococcus mitis bacteremia in 1 patient), no portal thrombosis or pancreatic fistula occurred. Median follow-up was 90 months. Actuarial patient survival was 100% at 10 years. Actuarial insulin independence was 94% at 10 years. All patients had positive basal and stimulated C-peptide levels and normal HbA1c. Mean islet yields were 5455 IEQ/gram vs. 1457 in CP (P=0.001) and 3738 in DBD (P=0.003). CONCLUSIONS: Islet autotransplantation after extensive pancreatic resection for benign disease is a safe and successful procedure. Islet yields after isolation, which are equivalent to the live donor situation, are significantly better than those from DBD donors.

Interleukin-1 receptor antagonist modulates the early phase of liver regeneration after partial hepatectomy in mice.

BACKGROUND: Cytokine administration is a potential therapy for acute liver failure by reducing inflammatory responses and favour hepatocyte regeneration. The aim of this study was to evaluate the role of interleukin-1 receptor antagonist (IL-1ra) during liver regeneration and to study the effect of a recombinant human IL-1ra on liver regeneration. METHODS: We performed 70%-hepatectomy in wild type (WT) mice, IL-1ra knock-out (KO) mice and in WT mice treated by anakinra. We analyzed liver regeneration at regular intervals by measuring the blood levels of cytokines, the hepatocyte proliferation by bromodeoxyuridin (BrdU) incorporation, proliferating cell nuclear antigen (PCNA) and Cyclin D1 expression. The effect of anakinra on hepatocyte proliferation was also tested in vitro using human hepatocytes. RESULTS: At 24h and at 48 h after hepatectomy, IL-1ra KO mice had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-1ß and MCP-1) and a reduced and delayed hepatocyte proliferation measured by BrdU incorporation, PCNA and Cyclin D1 protein levels, when compared to WT mice. IGFBP-1 and C/EBPß expression was significantly decreased in IL-1ra KO compared to WT mice. WT mice treated with anakinra showed significantly decreased levels of IL-6 and significantly higher hepatocyte proliferation at 24h compared to untreated WT mice. In vitro, primary human hepatocytes treated with anakinra showed significantly higher proliferation at 24h compared to hepatocytes without treatment. CONCLUSION: IL1ra modulates the early phase of liver regeneration by decreasing the inflammatory stress and accelerating the entry of hepatocytes in proliferation. IL1ra might be a therapeutic target to improve hepatocyte proliferation.