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International audience; Background: Experienced pancreatic surgeons, for whom complexity is not an issue, must decide at the end of neoadjuvant therapy whether to continue or discontinue surgery, when pancreatectomy with vascular resection is planned in patients with pancreatic ductal adenocarcinoma (PDAC). Objective: Our study aimed to determine preoperative factors that can predict short postoperative survival in such situations. Methods: Overall, 105 patients with borderline or locally advanced PDAC received neoadjuvant FOLFIRINOX (followed by chemoradiation in 22% of patients) and underwent pancreatectomy with segmental venous and/or arterial resection at two high-volume centers. The primary endpoint was overall survival (OS) of < 1 year after surgery for patients who did not die from the surgery. Results: Tumors were classified as borderline in 78% of cases and locally advanced in 22% of cases. Mean CA19-9 at diagnosis was 934 U/mL, which significantly decreased to 213 U/mL (p < 0.01) after a median of six cycles of FOLFIRINOX. Pancreaticoduodenectomy was performed most often (76%). The vast majority of patients underwent venous resection (92%), and a simultaneous arterial resection was performed in 16 patients (15%). The severe morbidity rate and 30- and 90-day mortality rates were 21%, 8.5%, and 10.4%, respectively. The median OS after surgery was 23 months. In the multivariate analysis, preoperative CA19-9 ≥ 450 U/mL was the only preoperative factor independently associated with OS of < 1 year (p = 0.044). Conclusion: The preoperative CA19-9 value should be considered in the clinical decision-making process when complex vascular resection is required. © 2021, Society of Surgical Oncology.

This study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice.From 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment.The 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3-16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P 0.001). In resected patients, the ASA 3 score (P 0.01), venous resection (P 0.01), hemorrhage (P 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P 0.001).Neoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.

Purpose To determine if improvement in imaging reduces the non-resection rate (NRR) among patients with pancreatic ductal adenocarcinoma (PDAC). Methods From 2000 to 2019, 751 consecutive patients with PDAC were considered eligible for a intention-to-treat pancreatectomy and entered the operating room. In April 2011, our institution acquired a dual energy spectral computed tomography (CT) scanner and liver diffusion weighted magnetic resonance imaging (DW-MRI) was included in the imaging workup. We consequently considered 2 periods of inclusion: period #1 (February 2000–March 2011) and period #2 (April 2011–August 2019). Results All patients underwent a preoperative CT scan with a median delay to surgery of 18 days. Liver DW-MRI was performed among 407 patients (54%). Median delay between CT and surgery decreased (21 days to 16 days, P P P P P P Conclusions Due to changes in our therapeutic strategies, the NRR did not decrease during two decades despite imaging improvement.

We evaluated the usefulness of the 2017 definition of borderline pancreatic ductal adenocarcinoma (BR-PDAC) in fit patients (performance status 0-1) based on anatomical (A) and biological dimensions (B).From 2011 to 2018, 139 resected patients with BR-PDAC according to the 2017 definition were included: 18 patients underwent upfront pancreatectomy (CA 19-9 500 U/mL and/or regional lymph node metastasis; BR-B group), and 121 received FOLFIRINOX (FX) induction chemotherapy and were divided into BR-A (CA 19-9 500 U/mL, no regional lymph node metastasis; n = 68) and BR-AB (CA 19-9 500 U/mL and/or regional lymph node metastasis; n = 53) groups.The 3 groups were comparable according to patient characteristics (except for back pain (P .01) and CA 19-9 (P .01)), intraoperative data, and postoperative courses. BR-AB patients required more venous resections (P .01). The 3 groups were comparable on pathologic findings, except that BR-B patients had more lymph node invasions (P = .02). Median overall survival (OS) of the 121 patients was 45 months. In multivariate analysis, venous resection (P = .039) and R1 resection (P = .012) were poorly linked with OS, whereas BR-A classification (P .01) independently favored OS. Median survival times of BR-A, BR-AB, and BR-B groups were undetermined, 27 months, and 20 months (P.001), respectively.The 2017 definition was relevant for sub-classifying patients with BR-PDAC. The anatomical dimension (BR-A) was a favorable prognostic factor, whereas the biological dimension (BR-AB and BR-B) poorly impacted survival.

Central hepatectomy (CH) is technically challenging and seldom-used to treat centrally located tumors. However, CH is a parenchyma-sparing resection that may decrease the risk of postoperative liver failure. This retrospective study presents our technique of CH and assesses the outcomes.All CH performed in our department over two decades (1997-2017) were identified. Indications and short-term outcomes were compared between the two decades. Long-term outcomes were assessed.Sixty-four patients underwent CH using a suprahilar approach for hepatocellular carcinoma (HCC: n = 30), metastasis (n = 23), intrahepatic cholangiocarcinoma (IHCCA: n = 9) or other diseases (n = 2). CH represented 6% of 1004 major hepatectomies, (7.4% (n = 35) before 2007 vs 5.4% (n = 29) after 2007). The mean operating time was 219 ± 56 min. A perioperative blood transfusion was required in 14 patients (22%). Intraoperative bile duct injuries occurred in 5 patients (8%), and they were repaired. One patient died postoperatively (1,5%). Ten patients (16%) experienced a major complication. Nine patients (14%) suffered from bile leakage, of which 6 healed spontaneously. Only one patient had low grade liver failure. The R0-resection rate was 69%. After 2007, there were no bile duct injuries (0/29 vs 5/35, p 0.05), and the average hospital stay was shorter but not significantly (11 vs 14 days). Actuarial 5-year survival was 56% for HCC patients and 34% for those with colorectal metastasis CONCLUSIONS: CH is associated with significant biliary morbidity and may increase positive surgical margins. Nevertheless, it should be recommended in selected patients to avoid the risk of postoperative liver failure.

Two-stage hepatectomy (TSH) strategy is used to treat patients with bilobar colorectal liver metastasis (CLM). However, many patients do not undergo the second hepatectomy owing to disease progression in the future liver remnant (FLR) after portal vein embolization (PVE). This study aimed to assess the impact of disease progression in the FLRs of patients who completed the first hepatectomy.68 consecutive patients underwent the first hepatectomy followed by PVE. Six patients (9%) dropped out after the PVE (two-stage failed [TSF] group) because of unresectable hepatic or general disease progression. Seventeen patients (25%) completed their second hepatectomy despite disease progression in the FLR (new CLM [nCLM] group) as it was considered resectable, while 45 patients (66%) underwent the second hepatectomy (control group).The 5-year overall survival rates in the TSF, nCLM, and control groups were 0%, 7%, and 60%, respectively (P 0.001). The median overall survival times between the TSF and nCLM groups were 26 months and 42 months (P = 0.005). Patients in the nCLM group whose hepatic disease progression was detected preoperatively versus intraoperatively had comparable survival rates.Resectable hepatic disease progression in the FLR after PVE should not be considered a contraindication for the second hepatectomy.

To describe, in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the laparotomy findings, treatments and outcomes before (period 1) and after 2010 (period 2).From 2000 to 2015, patients newly diagnosed with resectable PDAC at Paoli-Calmettes Institute, France, were evaluated. Survival was examined using the Kaplan-Meier method, and statistical comparisons were conducted using log rank tests.Among 1175 patients diagnosed with pancreatic mass, 164 underwent laparotomy with an intention of pancreatic resection. Some of them did not undergo pancreatic resection due to peroperative discovery of advanced disease. For those who were finally resected (n = 119), there were fewer pancreaticoduodenectomies (p = 0.045), shorter operation times (p 0.01), lower mortality rates (p = 0.02), more advanced-stage tumors (T3), more frequent perineural invasion and R1 resection in period 2. This group had a trend of better outcomes after 2010 (51 months vs. 36 months (p = 0.065)).Improvement in surgical procedures and postoperative management led to prolonged survival of those who underwent surgery for resectable pancreatic cancer since 2010, despite a higher frequency of advanced tumors at the diagnosis in our institution.

OBJECTIVE To evaluate the influence of hospital volume on failure-to-rescue (FTR) after pancreatectomy in France. BACKGROUND There are growing evidences that FTR is an important source of postoperative mortality (POM) after pancreatectomy. However, few studies have analyzed the volume-FTR relationship following pancreatic surgery. METHODS All patients undergoing pancreatectomy between 2012 and 2015 were included. FTR is defined as the 90-day POM rate among patients with major complications. According to the spline model, the critical cutoff was 20 resections per year and hospitals were divided into low (

OBJECTIVE The aim of the current study was to assess the short and long-term outcome of total pancreatectomy (TP) for IPMN based on the largest series to date. BACKGROUND Literature data are scarce regarding TP for IPMN, though increasingly performed in this setting. METHODS Data of 888 IPMN patients operated between 2004 and 2013 were collected in a multicentric retrospective AFC database. Ninety-three patients (10.5%) who had TP entered this study. Patient demographics, indications, intraoperative data, 3-month morbi-mortality (Clavien), and long-term outcome were analyzed. RESULTS Most patients had mixed type IPMN (59%) and underwent upfront (56%) or intraoperatively-decided (33%) TP. Morbidity and mortality rates were 47.3% and 4.3%, respectively, with no lethal hypoglycemia; morbidity was higher for intraoperatively-decided TP. Misdiagnoses were frequent regarding main pancreatic duct involvement (12%), invasiveness (33%), or mural nodules (50%), resulting in 12 TPs (13%) performed for asymptomatic IPMN showing only low/moderate dysplasia (LMD). On histopathological examination, there were 54 (58%) invasive IPMN (mostly pT3/T4 (76%), N+ (60%), R0 (75%)), with a significantly worse 5-year survival (21.2%) compared to noninvasive group (85.7%; P < 0.0001). In the former, 24 (58.5%) developed recurrence showing mostly distant metastasis, within 2 years in 92%. CONCLUSION This large series of TP for IPMN reported acceptable morbi-mortality rates with no long-term death from diabetes-related complication. Morphologic assessment was imperfectly reliable with 13% of TP done for LMD only. More than half of patients were operated at an invasive carcinoma stage with poor outcome. Conversely, long-term survival was excellent after TP for noninvasive IPMN.

Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX. Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups). Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1–30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7 months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1 months follow-up, overall survival (OS) and disease-free survival were 45.4 months and 16.2 months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P

Introduction Type II AEG is now considered as oesophageal cancer in the seventh and eighth edition of TNM classification but optimal surgical approach for these tumors remains debated. The objective of the study is to assess and compare surgical and oncological outcomes of two surgical approaches: superior polar oesogastrectomy (SPO) or total gastrectomy (TG) in patients with type II adenocarcinoma of the oesophagogastric junction (AEG). Material and methods 183 patients with type II AEG treated from 1997 to 2010 in 21 French centers by SPO or TG were included in a multicenter retrospective study. The surgical and oncological outcomes were compared between these two surgical approaches. Results A TG was performed in 64 (35%) patients whereas 119 (65%) patients were treated by SPO with transthoracic approach in 100 of them (83.2%) and transhiatal approach with cervicotomy in 19 (16.8%). Surgical outcomes were comparable between the two approaches with a postoperative mortality rate of 4.9% and a severe operative morbidity rate within 30 days of 15.3%. Median survival in patients operated on by TG was of 46 months compared to 27 months in patients treated by SPO (p = 0.118). At multivariate analysis, TG appears to be an independent good prognostic factor compared to SPO (HR = 1.847; p = 0.008). However, TG was also associated with a higher rate of incomplete resection, (12.5% vs 5.9%; p = 0.120). Conclusion When TG allows obtaining tumor-free resection margins, this approach should be preferred to SPO.

The online version of this article ( https://doi.org/10.1007/s00423-018-1702-1) contains supplementary material, which is available to authorized users.; International audience; Background - The benefit of adjuvant chemotherapy (AC) after pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) remains controversial. The study aimed to evaluate the impact of AC after PD for DCC in a large multicentric cohort. Methods - Patients from five French centers who underwent from PD for DCC between 2000 and 2015 and received AC (AC+ group) or surgery only (AC- group) were included in the analysis. Variables associated with AC administration were analyzed by univariate analysis. The Cox regression identified covariates associated with overall survival (OS) and disease-free survival (DFS). The AC+ cohort was matched to the AC- cohort (1:1) by a propensity score (PS) based on the likelihood of AC administration and independent factors associated with decreased OS and DFS. Results - Of the 178 patients included, 56 (31.5%) received AC. In the whole cohort, no difference on OS and DFS between the AC+ and AC- groups was identified (P = 0.15 and P = 0.07, respectively). After PS matching, the AC+ group (n = 49) was comparable to the AC- group (n = 49) on factors associated with AC administration and on factors associated with a decreased survival in the large cohort. After matching, the medians of OS and DFS in the AC+ group and in the AC- group were comparable (26.27 vs 43.33 months, P = 0.34, and 15.47 vs. 14.70 months, P = 0.79, respectively). Conclusion - Our study did not demonstrate a survival benefit of adjuvant chemotherapy (mostly base on gemcitabine regimen) for DCC after PD even after propensity score matching. New trial specially designed for DCC is urgently needed to improve survival after surgical resection.

International audience; BACKGROUND:Postoperative complications influence overall and disease free survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma is still a matter of debate and controversy.METHODS:The outcome of 942 consecutive patients, from the multicentric study of the French Association of Surgery, between January 2004 and December 2009 was analyzed. Perioperative data, including severe complications (grade III and above), were used in univariate and multivariate analysis to assess their influence on overall and disease free survival. Recurrence and its location were investigated as well.RESULTS:Median overall and disease free survival were 24 and 19 months respectively. Postoperative complications occurred in 444 patients (47%) with 18.3% of severe complications. On multivariate analysis, severe complications, positive lymph node status and R1-R2 resection were independent prognostic factors for both overall and disease free survival. The median overall survival decreased from 25 to 22 months (p = 0.005) and disease free survival from 21 to 16 months (p = 0.02) if severe complications occurred. Severe complications were independent prognostic factor of recurrence (p < 0.001).CONCLUSIONS:Severe complications significantly alter both overall and disease free survival and are an independent factor of recurrence.

International audience; OBJECTIVES:Multicenter studies comparing the reverse strategy (RS) with the classical strategy (CS) for the management of stage IVA liver-only colorectal cancer (CCR) are scarce. The aim of this study was to compare long-term survival and recurrence patterns following use of the CS and RS.METHOD:This retrospective multicenter review collected data from all consecutive patients with stage IVA liver-only CCR who underwent staged resection of CCR and liver metastases (LM) at 24 French hospitals between 2006 and 2013 and were retrospectively analyzed. Patients who underwent simultaneous liver and CCR resection, those with synchronous extrahepatic metastasis, and those who underwent emergent CCR resection were excluded. Overall survival (OS) and recurrence-free survival (RFS) rates and recurrence patterns were investigated before and after propensity score matching (PSM).RESULTS:A total of 653 patients were included: 587 (89.9%) in the CS group and 66 (10.1%) in the RS group. Compared with the CS patients, RS patients were more likely to have rectal cancer (43.9 vs. 24.9%; p = 0.006), larger liver tumor size (52.5 ± 38.6 vs. 39.6 ± 30 mm; p = 0.01), and more positive lymph nodes (62.1 vs. 44.8%; p = 0.009). OS was not different between the two groups (75 vs. 72% at 5 years; p = 0.77), while RFS was worse in the RS group (24 vs. 33% at 5 years; p = 0.01). Time to recurrence at any site (1.8 vs. 2.4 years, p = 0.024) and intrahepatic recurrence (1.7 vs. 2.2 years, p = 0.014) were significantly shorter in the RS group than in the CS group. After PSM (63 patients in each group), no significant difference was found between the two groups in OS (p = 0.35), RFS (p = 0.62), time to recurrence at any site (p = 0.19), or intrahepatic recurrence (p = 0.13).CONCLUSIONS:In this study, approximately 10% of patients with CCR and synchronous LM were offered surgery with the RS. Both strategies ensured similar oncological outcomes.

Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival. Moreover, we describe the state of promoters, enhancers, super-enhancers, euchromatic, and heterochromatic regions for each subtype. Further analyses indicate that the distinct epigenomic landscapes are regulated by different membrane-to-nucleus pathways. Inactivation of a basal-specific super-enhancer associated pathway reveals the existence of plasticity between subtypes. Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets., Pancreatic ductal adenocarcinoma (PDAC) is a complex disease and its underlying epigenomic heterogeneity is not fully understood. Here, the authors utilize patient-derived PDAC xenografts to define the epigenomic landscape of PDAC, highlighting chromatin states linked to differing disease aggressiveness and survival.

RAS mutation status is an important prognostic factor after resection of liver metastases (LiM) from colorectal cancer (CRC). The prognostic significance of RAS after resection of lung (LuM) and peritoneal (PM) metastases from CRC is unknown. Between 2005 and 2014, all consecutive patients with known RAS status who underwent potentially curative resection for LiM, LuM, or PM were evaluated. A total of 720 patients with known RAS status underwent resection of LiM (n = 468), LuM (n = 102), and PM (n = 150). RAS mutations were identified in 63 and 58% of patients with LuM and PM, respectively, compared with 41% of patients with LiM (p

While uptake of laparoscopic hepatectomy has improved, evidence on laparoscopic re-hepatectomy (LRH) for colorectal liver metastases (CRLMs) is limited and has never been compared to the open approach. We sought to define outcomes of LRH compared to open re-hepatectomy (ORH). Patients undergoing re-hepatectomy for CRLM at 39 institutions (2006–2013) were identified. Primary outcomes were 30-day post-operative overall morbidity, mortality, and length of stay. Secondary outcomes were recurrence and survival at latest follow-up. LRHs were matched to ORHs (1:3) using a propensity score created by comparing pre-operative clinicopathologic factors (number and size of liver metastases and major hepatectomy). Of 376 re-hepatectomies included, 27 were LRH, including 1 (3.7%) conversion. The propensity-matched cohort included 108 patients. Neither median operative time (252 vs. 230 min; p = 0.82) nor overall 30-day morbidity (48.1 vs. 38.3%; p = 0.37) differed. Non-specific morbidity (including cardiac, respiratory, infectious, and renal events) decreased with LRH (11.1 vs. 30.9%, p = 0.04), while surgical-specific morbidity, including liver insufficiency, was higher (44.4 vs. 22.2%, p = 0.03). One ORH and 0 LRH suffered 30-day mortality. Median length of stay (9 vs. 12 days; p = 0.60) was comparable. At latest follow-up, 26 (96.3%) LRH and 67 (82.7%) ORH patients were alive. Eight (29.6%) LRH and 36 (44.4%) ORH patients were alive without disease. LRH for recurrent CRLM was associated with overall short-term outcomes comparable to ORH, but different morbidity profiles. While it may offer a safe and feasible approach, further insight is necessary to better define patient selection.

Background Transabdominal laparoscopic proctectomy (LAP) for rectal cancer was associated with postoperative recovery improvement. Early studies showed favorable short-term results of endoscopic transanal proctectomy (ETAP), with low conversion rates to open procedures. We aimed to compare efficacy, morbidity, and functional outcomes of ETAP to standard LAP for low rectal cancer. Study Design From 2008 to 2013, 72 consecutive patients received proctectomy and coloanal manual anastomosis for low rectal adenocarcinoma. Thirty-four patients had transanal endoscopic proctectomy, and 38 patients underwent the standard laparoscopic procedure. Results When compared with the LAP group, the ETAP group demonstrated a lower conversion rate to open procedures (23.7% vs 2.9%, respectively; p = 0.015), shorter in-hospital stays (9 vs 8 days, respectively; p = 0.04), and a lower readmission rate (13.2% vs 0%; p = 0.03). Overall postoperative morbidity rates for the LAP and the ETAP groups (36.8% vs 32.4%, respectively; p = 0.69) and functional results (Kirwan score 1/2, 73.7% vs 73.5%, respectively; p = 0.85) were comparable; additionally, we found similar oncologic quality criteria (R1 resection 10.5% vs 5.9%, respectively; p = 0.68; grade 3 mesorectal integrity 52.6% vs 55.9%, respectively; p = 0.66). Disease-free survival of 24 months (Kaplan-Meier estimation) was comparable in the 2 groups: 86% in the ETAP group vs 88% in the LAP group; p = 0.91. At the date of last follow-up, 91.2% of ETAP patients and 92.1% of LAP patients were free of stoma. Conclusions The endoscopic transanal approach could facilitate mesorectal excision and improve short-term outcomes without impairing the oncologic quality of the resection or mid-term functional and oncologic results.

Background The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings. Methods Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan–Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method. Results FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR) = 1.2, 95% confidence interval: 0.86–1.6, P = .03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0–1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR = 1.38, 95% confidence interval: 1–1.9, P Conclusions The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.

OBJECTIVES We aimed to examine whether the improved outcome of a digestive cancer procedure in high-volume hospitals is specific or correlates with that of other digestive cancer procedures, and determine if the discriminant cut-off of hospital volume may influence postoperative mortality (POM) regardless of the procedure. BACKGROUND Performing complex surgeries in tertiary centers is associated with improved outcome. However, the association between POM and hospital volume of nonspecific procedures is unknown. METHODS Patients who underwent colectomy, proctectomy, esophagectomy, gastrectomy, pancreatectomy, and hepatectomy for cancer between 2012 and 2017 were identified in the French nationwide database. Chi-square automatic interaction detector was used to identify the cut-off values of the annual caseload affecting the 90-day POM. A common threshold was estimated by minimization of chi-square distance taking into account the specific mortality of each procedure. RESULTS Overall, 225,752 patients were identified. Hospitals were categorized according to the procedure volume (colectomy: ≥80 cases/yr, proctectomy: ≥35/yr, esophagectomy: ≥41/yr, gastrectomy: ≥16/yr, pancreatectomy: ≥26/yr, and hepatectomy: ≥76/yr). The overall 90-day POM was 5.1% and varied significantly with volume. The benefits of high volume were transferable across procedures. High-volume hospitals for colorectal cancer surgery significantly influenced the risk of death after hepatectomy (P < 0.001) and pancreatectomy (P < 0.001). The common threshold for all procedures that influenced POM was 199 cases/yr (odds ratio 1.29, P < 0.001). CONCLUSION In digestive cancer surgery, the volume-POM relationship of one procedure was associated with the volume of other procedures. Thus, tertiary hospitals should be defined according to the common threshold of different procedures.

Objective To determine the effect of clinical status (weight variation and performance status [PS]) at diagnosis and during induction treatment on resectability and overall survival (OS) rates in patients with borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC). Methods From 2005 to 2017, 454 consecutive patients were diagnosed with LAPC or BRPC. We evaluated the PS (0–1 or 2–3), body mass index at diagnosis, and weight loss (WL) > 5% at initial staging and after induction treatment and separated continuous weight loss (CWL) from weight stabilization. Results A total of 294 patients (64.8%) presented with WL, and 57 patients (12.6%) presented with a PS of 2–3. At restaging, 60 patients (13.2%) presented with CWL. Independent factors that poorly influenced the OS were a PS of 2–3 at diagnosis (P < .01), CWL at restaging (P < .01), and absence of resection (P < .01). Factors independently impeding resection were LAPC (P < .01), PS > 1 at diagnosis (P < .01), and CWL (P = .01). In total, 142 patients (31.3%) underwent pancreatectomy. Independent factors that poorly influenced the OS in the resected group were PS > 0 at diagnosis (P = .01) and obesity (P < .01). For the 312 unresected cancer patients (68.7%), CWL (P < .01) was identified as an independent factor that poorly influenced the OS. Conclusion Clinical parameters that are easy to measure and monitor are independent factors of poor prognosis. The variation of weight during the induction treatment, more than WL at diagnosis, significantly precluded resection and was an independent factor of shorter OS in unresected patients.

A new neoadjuvant regimen, together with more aggressive surgeries, appears to have increased the resectability rate in patients with pancreatic ductal adenocarcinoma (PDAC). Our study aimed to evaluate the outcomes of patients who underwent venous resection (VR) during pancreatectomies for PDAC.Between 2005 and 2017, 130 patients underwent pancreatectomies with type 3 or 4 (i.e., segmental resection without or with graft interposition, respectively) VR for PDAC. Patients' characteristics, surgical techniques, perioperative management, pathological findings, and outcomes were recorded and compared during 2 inclusion periods: the landmark year for the introduction of the FOLFIRINOX regimen and the hyperspecialization of our pancreatic-surgery team was 2010.Performance of pancreatectomies with VR steadily increased through the 2 inclusion periods. In the overall series (n = 130), the median overall survival time and the 5-year survival proportion were 26.3 months and 21%, respectively. Upon multivariate analysis, ASA score 3 (P = 0.01) and R1 resection margins (P 0.01) were found to be negative independent factors influencing survival. Patients who underwent upfront VR (n = 47) had survival rates similar to those of patients who received neoadjuvant treatment (n = 83). After 2010, more complex VR were performed; however, no difference was found between the 2 periods with respect to postoperative courses, pathologic findings, or survival after a matching process based on patients' characteristics and tumor stages.Over the last 2 decades, VR during pancreatectomy has been confirmed as a safe procedure despite the increase in technical complexity. Disappointingly, we did not observe any dramatic survival improvement.

International audience; Pancreatic cancer is one of the most aggressive human cancers. PD1/PDL1-inhibitors recently showed promising results in different cancers with correlation between PDL1 tumor expression and responses. Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in pancreatic cancer. In this retrospective study, we analyzed PDL1 mRNA expression in 453 clinical pancreatic cancer samples profiled using DNA microarrays and RNASeq. Compared to normal pancreatic samples, PDL1 expression was upregulated in 19% of cancer samples. Upregulation was not associated with clinicopathological features such as patients' age and sex, pathological type, tumor size, lymph node status, and grade, but was associated with shorter disease-free survival and overall survival in multivariate analyses. Analysis of correlations with biological parameters showed that PDL1 upregulation was associated with some degree of lymphocyte infiltration and signs of anti-tumor T-cell response, but to a lesser extent than what has been reported in breast cancer and GIST. PDL1-up pancreatic cancers displayed profiles of lymphocyte exhaustion, were more enriched in inhibitory molecules and pro-tumor populations (Tregs with upregulation of FOXP3 and IL10, myeloid-derived suppressor cells with upregulation of CD33 and S100A8/A9), and demonstrated a down-modulation of most MHC class I members (HLA-A/B/C, HLA-E/F/G) suggestive of a defect in antigen processing and presentation. In conclusion, our results suggest that PDL1 expression might refine the prediction of metastatic relapse in operated pancreatic cancer, and that PD1/PDL1 inhibitors might reactivate inhibited T-cells to increase the anti-tumor immune response in PDL1-upregulated tumors.

International audience; BACKGROUND:Recurrence remains frequent after curative-intent hepatectomy for colorectal liver metastases (CRLM). We sought to define short- and long-term outcomes, and identify prehepatectomy factors associated with survival, following rehepatectomy (RH) for recurrence.METHODS:We conducted a multi-institutional cohort study of hepatectomy for CRLM over 2006-2013. Second-stage resections were excluded. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS) assessed using Kaplan-Meier methods. Secondary outcomes included 30-day overall morbidity and mortality, and survival from recurrence. Outcomes of RH and initial hepatectomy (IH) were compared.RESULTS:Of 2771 hepatectomies included in the study, 447 were RH. Median operative time, 30-day morbidity, mortality, and median length of stay did not differ for RH and IH. Five-year OS did not statistically differ, i.e. 56.5 % from RH and 67.6 % from IH [adjusted hazard ratio (HR) 0.9, 95 % confidence interval (CI) 0.5-1.7], and 5-year RFS was inferior after RH (18.5 vs. 28.8 %; adjusted HR 1.3, 95 % CI 1.0-1.7). In patients who eventually recurred, 5-year survival from the time of recurrence did not differ whether it was after RH (46.5 %) or after IH (60.3 %) (adjusted HR 1.1, 95 % CI 0.8-1.8). Rectal primary tumor (HR 1.4, 95 % CI 1.0-2.1) and metastasis ≥3 cm (HR 1.3, 95 % CI 1.1-2.7) were independently associated with RFS, but not OS, after RH.CONCLUSION:Short-term outcomes of RH did not differ from IH. While recurrence was more frequent after RH than IH, it did not impact OS. Survival from the time of recurrence did not differ whether recurrence occurred after RH or after IH. CRLM recurrence can be treated with curative intent with excellent long-term outcomes.

Treating pancreatic cancer is extremely challenging due to multiple factors, including chemoresistance and poor disease prognosis. Chemoresistance can be explained by: the presence of a dense stromal barrier leading to a lower vascularized condition, therefore limiting drug delivery; the huge intra-tumoral heterogeneity; and the status of epithelial-to-mesenchymal transition. These factors are highly variable between patients making it difficult to predict responses to chemotherapy. Nicotinamide phosphoribosyl transferase (NAMPT) is the main enzyme responsible for recycling cytosolic NAD+ in hypoxic conditions. FK866 is a noncompetitive specific inhibitor of NAMPT, which has proven anti-tumoral effects, although a clinical advantage has still not been demonstrated. Here, we tested the effect of FK866 on pancreatic cancer-derived primary cell cultures (PCCs), both alone and in combination with three different drugs typically used against this cancer: gemcitabine, 5-Fluorouracil (5FU) and oxaliplatin. The aims of this study were to evaluate the benefit of drug combinations, define groups of sensitivity, and identify a potential biomarker for predicting treatment sensitivity. We performed cell viability tests in the presence of either FK866 alone or in combination with the drugs above-mentioned. We confirmed both inter- and intra-tumoral heterogeneity. Interestingly, only the in vitro effect of gemcitabine was influenced by the addition of FK866. We also found that NAMPT mRNA expression levels can predict the sensitivity of cells to FK866. Overall, our results suggest that patients with tumors sensitive to FK866 can be identified using NAMPT mRNA levels as a biomarker and could therefore benefit from a co-treatment of gemcitabine plus FK866.

Endotherapy (ET) has replaced surgery as the first-line treatment of high-grade dysplasia (HGD)/superficial ECA (ECAs) from Barrett’s oesophagus (BO). However, long-term follow-up and predictive factors of relapse are not so well studied. The aim of the following study was to evaluate the efficiency of ET for treatment of HGD/ECAs and to determine factors of long-term efficiency. ET procedures were manually reported and registered in a hospital data base from March 2000 to July 2010. Inclusion criteria were HGD/ECA on pre-resection biopsies, complete histological and sufficient oncological resection of HGD/ECAs, and complete macroscopic resection of metaplastic BO. Sixty patients (53 men, mean age = 65 years) were included. Median follow-up was 66 months [range 42–80]. Complete eradication of residual histological metaplastic BO occurred in 29 patients (48 %). Relapse rate at 36 months was 16.6 % (n = 10) and was unchanged at 60 months of follow-up. There was only one relapse (3.4 %) in case of complete eradication of metaplastic BO and 9 (31 %) in case of incomplete eradication. In univaried and multi-varied analysis, complete eradication of metaplastic BO (p

International audience; OBJECTIVES: The aim of this study is to compare at a national level, the early and long-term outcome of distal pancreatectomy (DP) performed by laparoscopy (LapDP) or open surgery (OpenDP) for pancreatic ductal adenocarcinoma (PDAC). BACKGROUND DATA: LapDP is feasible and safe for benign conditions but its use for PDAC is controversial. METHODS: French healthcare databases were screened to identify all patients who had undergone LapDP or OpenDP for PDAC between 2007 and 2012. Endpoints were (i) 90-day mortality, (ii) morbidity, (iii) transfusion rate, (iv) length of hospital stay (LOS), and (v) long-term survival. Logistic regression and adjusted Cox models were used to compare LapDP and OpenDP with regard to these outcomes. Confounders included (i) patients' characteristics; (ii) associated surgical procedures; and (iii) characteristics of the hospital. Performance of the resulting models was determined by the area under the receiver operating characteristic (ROC) curve. RESULTS: Over the 6-year period, there were 2753 operations for PDAC: 2406 OpenDP and 347 LapDP (12.6%). The overall 90-day mortality rate was 5.2%; median LOS was 15 days, and median survival was 38 months. LapDP was not correlated with 90-day mortality but was associated with reduced pleuropulmonary morbidity (odds ratio (OR) 0.73, P = 0.028), blood transfusion (OR 0.44, P = 0.001), and LOS (P = 0.042), and was associated with increased survival (P = 0.0007). CONCLUSIONS: LapDP has not been adopted widely for PDAC. The early and long-term results of LapDP as currently practiced are as good as those of OpenDP. The next step in the evaluation of LapDP should be a randomized controlled trial (RCT), but such a trial is likely to suffer from insufficient recruitment

International audience; Background - Although the peri-operative mortality following pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) has decreased, the post-operative morbidity remains high. The aim of this study was to evaluate the impact of factors that may affect the long term survival for patients with DCC following PD. Methods - All patients who underwent PD for DCC between January 2000 and December 2015 in 5 tertiary referral centers underwent retrospective medical record review. Factors likely to influence overall (OS) and disease-free (DFS) survivals were assessed by univariate and multivariate analysis. Results - A total of 201 on 217 patients who underwent PD for DCC were included for further analysis. The median OS was 39 months, with actuarial survival rates at 1, 3, and 5 years of 85%, 53% and 39%. Recurrence occurred in 123 (61%) patients. The median DFS was 16 months, with actuarial survival rates at 1, 3 and 5 years of 60%, 37% and 28%. Following multivariate analysis, peri-operative blood transfusions (PBT) were associated to worse OS (HR = 2.25 [1.31-3.85], P = 0.003) and DFS (HR = 2.08 [1.24-3.5], P = 0.005). Conclusion - This study confirms the negative impact of PBT on the oncologic result following PD for DCC.

The width of resection margin is still a matter of debate in case of colorectal liver metastasis resection. The aim of this study was to determine the risk factors for R1 resection. Once risk factors had been identified, patients were matched according to Fong’s prognostic criteria, in order to evaluate whether R1 resection still remained a negative prognostic factor impacting overall and disease-free survival. A total of 1784 hepatectomies were analyzed from a multicentric retrospective cohort of hepatectomies. Patients were compared before and after a 1:1 propensity score analysis in order to compare R0 versus R1 resections according to Fong criteria. Primary tumor nodes found positive after colorectal resection (RR = 1.20, p = 0.02), operative time (> 240 min) (RR = 1.26, p = 0.05), synchronous liver metastasis (RR = 1.27, p = 0.02), pedicle clamping (> 40 min) (RR = 1.52, p = 0.001), lesion size larger than 50 mm (RR = 1.54, p = 0.001), rehepatectomy (RR = 1.68, p = 0.001), more than 3 lesions (RR = 1.69, p = 0.0001), and bilateral lesions (RR = 1.74, p = 0.0001) were identified as risk factors in multivariate analysis. After a 1:1 PSM according to Fong criteria, R1 resection still remained a negative prognostic factor impacting overall and disease-free survival, with 1-, 3-, 5-year OS at 94, 81, and 70% in R0 and 92, 75, and 58% in R1, respectively, (p = 0.008), and disease-free survival (DFS) with 1-, 3-, 5-year survival at 64, 41, and 28% in R0 versus 51, 28, and 18% in R1 (p = 0.0002), respectively. Even after using PSM as an oncological prognostic criterion, R1 resection still impacts overall and disease-free survival negatively.

Background To determine predictive factors of postoperative pancreatic fistula (POPF) in patients undergoing enucleation (EN). Methods From 2005 to 2017, 47 patients underwent EN and had magnetic resonance imaging available for precise analysis of tumor location. Three pancreatic zones were delimited by the right side of the portal vein and the main pancreatic head duct (zone #3 comprising the lower head parenchyma and the uncinate process). Results The mortality and morbidity rates were 0% and 62%, respectively. POPF occurred in 23 patients (49%) and was graded as B or C (severe) in 15 patients (32%). Four patients (8.5%) developed a postoperative hemorrhage, and 5 patients (11%) needed a reintervention. In univariate and multivariate analyses, the pancreatic zone was the unique predictive factor of overall (P = .048) or severe POPF (P = .05). We did not observe any difference in postoperative courses when comparing the EN achieved in zones #1 and #2. We noted a longer operative duration (P = .016), higher overall (P = .017) and severe POPF (P = .01) rates, and longer hospital stays (P = .04) when comparing the EN achieved in zone #3 versus that in zones #1 and #2. Patients who underwent EN in zone #3 had a relative risk of developing a severe POPF of 3.22 compared with patients who underwent EN in the two other pancreatic zones. Conclusion Our study identifies the lower head parenchyma and the uncinate process as a high-risk zone of severe POPF after EN. Patients with planned EN in this zone could be selected and benefit from preoperative and/or intraoperative techniques to reduce the severe POPF rate. Electronic supplementary material The online version of this article (10.1186/s12957-018-1476-5) contains supplementary material, which is available to authorized users.

International audience; Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.

Objective To assess the accuracy of pre‐operative staging in patients with peripheral pancreatic cystic neoplasms (pPCNs). Methods From 2005 to 2011, 148 patients underwent a pancreatectomy for pPCNs. The pre‐operative examination methods of computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) were compared for their ability to predict the suggested diagnosis accurately, and the definitive diagnosis was affirmed by pathological examination. Results A mural nodule was detected in 34 patients (23%): only 1 patient (3%) had an invasive pPCN at the final histological examination. A biopsy was performed in 79 patients (53%) during EUS: in 55 patients (70%), the biopsy could not conclude a diagnosis; the biopsy provided the correct and wrong diagnosis in 19 patients (24%) and 5 patients (6%), respectively. A correct diagnosis was affirmed by CT, EUS and pancreatic MRI in 60 (41%), 103 (74%) and 80 (86%) patients (when comparing EUS and MRI; P = 0.03), respectively. The positive predictive values (PPVs) of CT, EUS and MRI were 70%, 75% and 87%, respectively. Conclusions Pancreatic MRI appears to be the most appropriate examination to diagnose pPCNs accurately. EUS alone had a poor PPV. Mural nodules in a PCN should not be considered an indisputable sign of pPCN invasiveness.

Predictors of survival following pancreaticoduodenectomy (PD) are well described for pancreatic cancers but are less detailed in ampullary (AC), bile duct (BDC) and duodenal cancers (DC). We therefore sought to evaluate the long-term results of PD for AC, BDC and DC, and to determine for each tumour the predictive factors of survival. Medical charts of patients operated on between 2001 and 2011 were retrospectively reviewed. Univariate and multivariate analyses were performed to determine predictors of survival. One hundred thirty-five patients were identified. Mean follow-up was 47 ± 33 months. Median survival was not reached for DC and was 66 and 24 months for AC and BDC, respectively. Two-year and five-year survival rates were 80 and 51 % for DC and 69 and 51 % for AC, respectively. BDC had a significantly poorer prognosis, with two-year and five-year survival rates of 51 and 34 %, respectively. Predictors of survival were weight loss, N stage and International Union Against Cancer (UICC) stage for AC, T stage and resection margin status for BDC and N stage for DC. AC, BDC and DC display distinctive predictors of survival related to the biological aggressiveness. Preoperative malnutrition worsens the prognosis. The effect of adapted nutritional management on the survival improvement has to be studied.

Venous resection (VR) during pancreatectomy has been reported to neither increase mortality nor morbidity and to provide similar survival outcomes in same stage tumors. However, controversy remains regarding the indications for up-front surgery according to the degree of venous involvement. From 2004 to 2009, 1,399 patients included in a French multicenter survey underwent pancreaticoduodenectomy or total pancreatectomy for pancreatic adenocarcinoma, either without VR (997 standard resections [SR]) or with VR (402 patients; 29 %). Postoperative and long-term outcomes were compared in both groups. VR was associated with the following factors: larger tumors (p

Previous publications have suggested that endoscopic transanal proctectomy (ETAP) is a promising technique and may be an alternative to conventional low anterior resection for rectal cancer. The aim of this study was to evaluate the technical feasibility of ETAP, with a particular focus on postoperative and oncological results and on functional outcomes.This study was a multicenter prospective study of unselected consecutive patients with low rectal cancer requiring proctectomy and coloanal anastomosis. All patients underwent a standardized procedure. The study endpoints were the safety and adequacy of the oncological resection criteria. All patients were evaluated with the Wexner Fecal Incontinence Questionnaire after stoma closure.Fifty-six consecutive patients (41 men) underwent ETAP between February 2010 and June 2012. The median age was 65 years (39-83), and the median body mass index was 27 (20-42). No intraoperative complications were encountered. There was no postoperative mortality, and the morbidity rate was 26%. The mesorectum was complete in 47 cases (84%) and nearly complete in 9 cases (16%). The median number of lymph nodes retrieved was 12 (range, 7-29) per patient. The median radial and distal margins were 8 mm (0-20) and 10 mm (3-40), respectively. R0 resection was achieved in 53 patients (94.6%). The median Wexner score was 4 (3-12). Thirteen (28%) patients reported stool fragmentation and difficult evacuation.ETAP is a feasible alternative surgical option to conventional laparoscopy for rectal resection and may represent a promising step toward rectal natural orifice transluminal endoscopic surgery (NOTES).

OBJECTIVE Investigate if involving surgeons in outcome prediction-research and having them use a dedicated Electronic-Health-Record that provides feedback, improves patients' outcome. BACKGROUND Improvement of clinical outcome mainly relies on the declaration of adverse events, identification of their predictors, self-assessment, and feedback. METHODS Thirteen French Hepato-Pancreato-Biliary-centers made commitment to include all patients undergoing elective hepatectomies in an observational study. Each center was given access to a dedicated website, where perioperative data were prospectively collected. The website provided real-time individual and comparative feedback of outcome and was also intended to perform prognostication studies. The hypothesis was that by using this strategy, the length-of-stay would be reduced by 10%. Power-calculation implied the inclusion of 1720 patients. Secondary endpoints were 90-day mortality, severe morbidity, and the comprehensive-complication index. RESULTS Only 5 of the 13 participating centers were fully compliant in enrolling their patients and the inclusion period was extended by 1-year (October 2012-October 2015) to meet the objective. During this period, the collaborative group published 9 studies based on the study data (median impact factor = 8.327) that identified quantitative clinical variables, qualitative clinical variables, and nonclinical variables influencing outcome. For patients enrolled by the 5 active centers (n = 1752), there was no improvement in length of stay (13.3 vs 12.4 days, P = 0.287), severe complications (23.6 vs 20.5%, P = 0.134), the complication comprehensive index (24.0 vs 24.9, P = 0.448), mortality (4.1 vs 3.9%, P = 0.903), or unplanned readmissions (7.2 vs 8.4%, P = 0.665), even after adjusting for confounders. CONCLUSION Simply sensitizing surgeons to their outcome has no measurable short-term clinical benefit.

Background Postoperative outcomes following pancreaticoduodenectomy are well described for pancreatic cancers. Due to a lower incidence rate, complication rates and relative predictive factors are less detailed for ampullary, bile duct and duodenal cancers. Methods Medical charts of patients operated on between 2001 and 2011 for an ampullary, bile duct or duodenal cancer were reviewed. Data were retrospectively studied with respect to demographics, surgical management, postoperative complications and histological findings. Specific complication rates were reported, and predictive factors for severe morbidity and mortality were determined by multivariate analysis. Results 135 patients were identified: 55 ampullary, 55 bile duct and 25 duodenal cancers. Twelve patients (8.9%) deceased postoperatively, and 36 others (26.7%) presented severe complications. Sixty-seven percent of the pancreas was soft, and pancreatic hardness was found to be the main protective factor against severe morbidity (HR = 0.36, 95% CI = 0.14–0.94, P = 0.037). Age and postpancreatectomy haemorrhage were independent predictors for death (HR = 14.63, 95% CI = 1.57–135.77, P = 0.018, and HR = 14.71, 95% CI = 2.86–75.62, P = 0.001, respectively). Only the use of an external transanastomotic duct stent significantly reduced both the morbidity (HR = 0.37, 95% CI = 0.16–0.83, P = 0.016), and the mortality (HR = 0.12, 95% CI = 0.02–0.69, P = 0.017). Conclusions Pancreaticoduodenectomy for ampullary, bile duct and duodenal cancers is a high-risk procedure. The systematic use of transanastomotic duct stents would significantly decrease the complication rate. Older patients should beneficiate from specific preoperative evaluation using an adapted index. Omental flap techniques to prevent a postpancreatectomy haemorrhage should be efficient. Effects of preoperative octreotid to harden the pancreas should be clarified.

Background Acute kidney injury (AKI) following major hepatectomy (MH) remains inadequately investigated. This retrospective study aimed to assess the risk factors and prognostic value of AKI on short-term outcomes following MH without portal pedicle clamping. Methods From January 2014 through June 2017, 111 consecutive patients underwent MH without portal pedicle clamping, but with intraoperative low-crystalloid infusion. Kidney Disease Improving Global Outcomes stages II and III were classified as severe AKI. Results A total of 102 patients did not develop AKI or only AKI stage I (92%, control group), whereas 9 patients developed severe AKI (8%, severe AKI group). Hepatectomy (P = 0.002) and surgery (P = 0.011) durations were longer in the severe AKI group. Clavien-Dindo grades 3 to 5 morbidity (55% versus 9%, P = 0.001), liver failure (P = 0.017), and 90-day mortality (33% versus 2%, P = 0.003) were significantly higher in the severe AKI group. After a multivariate analysis, the duration of hepatectomy (cut-off: 250 min; P = 0.029) and urea serum levels on postoperative day 3 (P = 0.006) were identified as independent predictors of severe AKI. Discussion Severe AKI, is common with increased duration of hepatectomy, was associated with poor short-term outcomes, and can be predicted by operative duration greater than 250 minutes.

The aim of the study was to assess the relevance of resection margin status for survival after resection of pancreatic-head ductal adenocarcinoma.The definition and prognostic value of incomplete microscopic resection (R1) remain controversial.Prognostic factors were analyzed in 147 patients included in a prospective multicenter study on the impact of tumor clearance evaluated using a standardized pathology protocol.Thirty patients received neoadjuvant treatment (NAT = 20%); 41 had venous resection (VR = 28%), and 70% received adjuvant chemotherapy. In-hospital mortality was 3% (5/147). Follow-up was 83 months. Tumor clearance was 0,1.0,1.5, and2.0 mm in 35 (25%), 92 (65%), 95 (67%), and 109 (77%) patients, respectively. R0-resection rates decreased from 75% to 35% when changing the definition of R1 status from R1-direct invasion (0 mm) to R11.0 mm. On univariate analysis, clearance1.0 or1.5 mm, pT stage, pN stage, LNR ≥0.2, tumor grade 3, and lymphovascular invasion were significantly associated with 5-year survival. On multivariate analysis, pN was the most powerful independent predictor (P = 0.004). Clearance1.0 or1.5 mm had borderline significance for the entire cohort, but was relevant in certain subgroups (upfront pancreatectomy (n = 117; P = 0.049); without VR or NAT (n = 87; P = 0.003); N+ without VR or NAT (n = 50; P = 0.004). No N0-patient had R1-0 mm. Additional independent risk predictors were (1) R11.0 mm for the SMA-margin in specific subgroups (upfront pancreatectomy, N0 patients without NAT, N+ patients without NAT or VR; (2) R1-0 mm posterior-margin for the NAT group (P = 0.004).Tumor clearance1.0 or1.5 mm was an independent determinants of postresection survival in certain subgroups. To avoid misinterpretation, future trials should specify the clearance margin in millimeter.ClinicalTrials.gov: NCT00918853.

Background Pancreatic carcinoma is one of the most lethal human cancers. In patients with resectable tumors, surgery followed by adjuvant chemotherapy is the only curative treatment. However, the 5-year survival is 20%. Because of a strong metastatic propensity, neoadjuvant chemotherapy is being tested in randomized clinical trials. In this context, improving the selection of patients for immediate surgery or neoadjuvant chemotherapy is crucial, and high-throughput molecular analyses may help; the present study aims to address this. Methods Clinicopathological and gene expression data of 695 pancreatic carcinoma samples were collected from nine datasets and supervised analysis was applied to search for a gene expression signature predictive for overall survival (OS) in the 601 informative operated patients. The signature was identified in a learning set of patients and tested for its robustness in a large independent validation set. Results Supervised analysis identified 1400 genes differentially expressed between two selected patient groups in the learning set, namely 17 long-term survivors (LTS; ≥ 36 months after surgery) and 22 short-term survivors (STS; dead of disease between 2 and 6 months after surgery). From these, a 25-gene prognostic classifier was developed, which identified two classes (“STS-like” and “LTS-like”) in the independent validation set (n = 562), with a 25% (95% CI 18–33) and 48% (95% CI 42–54) 2-year OS (P = 4.33 × 10–9), respectively. Importantly, the prognostic value of this classifier was independent from both clinicopathological prognostic features and molecular subtypes in multivariate analysis, and existed in each of the nine datasets separately. The generation of 100,000 random gene signatures by a resampling scheme showed the non-random nature of our prognostic classifier. Conclusion This study, the largest prognostic study of gene expression profiles in pancreatic carcinoma, reports a 25-gene signature associated with post-operative OS independently of classical factors and molecular subtypes. This classifier may help select patients with resectable disease for either immediate surgery (the LTS-like class) or neoadjuvant chemotherapy (the STS-like class). Its assessment in the current prospective trials of adjuvant and neoadjuvant chemotherapy trials is warranted, as well as the functional analysis of the classifier genes, which may provide new therapeutic targets. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0936-z) contains supplementary material, which is available to authorized users.

Objective Measure the caseload of pancreatectomies that influences their short-term outcome, at a national level, and assess the applicability of a centralization policy. Background There is agreement that pancreatectomies should be centralized. However, previous studies have failed to accurately define a "high-volume" center. Methods French healthcare databases were screened to identify all adult patients who had elective pancreatectomies between 2007 and 2012. The patients' age, comorbidities, indication, and extent of surgery, and also the hospital administrative-type and location were retrieved. The annual-caseload of pancreatectomy was calculated for each hospital facility. The primary endpoint was 90-day mortality. Spline modeling was used to identify the different annual-caseload that influenced mortality. Logistic regressions were performed to assess if their influence was independent of confounders, and the accuracy of the model calculated. Results Overall, 22,366 patients underwent a pancreatectomy and the mortality was 8.1%. Two cut-offs were identified (25 and 65 per year): compared with centers performing >65 resections per year, the adjusted OR of mortality was 1.865 (1.529-2.276) in centers performing ≤25 resections per year and 1.234 (1.031-1.478) in those performing 26 to 65 resections per year. The average number of facilities performing ≤25, 26 to 65, and >65 pancreatectomies per year was 456, 20, and 9, respectively. The percentage of patients operated in these facilities was 56.6%, 19.9%, and 23.3%, respectively.For pancreaticoduodenectomies (12,670 patients; mortality 9.2%), there were 2 cut-offs (16 and 40 pancreaticoduodenectomies per year), and both were independent predictors of mortality (adjusted OR of 1.979 and 1.333). For distal pancreatectomies (7085 patients; 6.2% mortality), there were 2 cut-offs (13 and 25 distal pancreatectomies per year), but neither was an independent predictor of outcome (area under the receiver-operating characteristic curve of the model = 0.778). Conclusions Centralization of pancreatic surgery is theoretically justified, but currently unrealizable. As the incidence of pancreatic cancer increases, there is an urgent need to improve the training of surgeons and develop both intermediate and high-volume centers.

International audience; BACKGROUND:Predictors of recurrence following pancreaticoduodenectomy are well described for ductal periampullary cancers but lack reliability for non-ductal tumors. The purpose of this study is to analyze the disease-free survival (DFS) and to define the predictors of recurrence following resection for ampullary (AC), bile duct (BDC) and duodenal cancers (DC).MATERIALS AND METHODS:Clinico-pathological data of patients operated on between 2001 and 2011 were retrospectively reviewed. The effect of lymphatic invasion was specified using the lymph node ratio (LNR) and the number of positive nodes (NPN), with thresholds calculated with the likelihood ratio. Kaplan-Meier disease-free survival (DFS) curves were compared for all covariates by a log-rank test. Multivariate logistic regression analyses were performed to identify predictors of recurrence.RESULTS:135 patients were identified. Mean follow-up was 49 ± 35 months. Median DFS was not reached for AC and was 36 and 18 months for DC and BDC, respectively. Five-year DFS was 52%, 43% and 32% for AC, DC and BDC, respectively. Predictors of recurrence were T4 tumors, neural invasion and preoperative biliary drainage for DC, ≥3 positive nodes and ≥4% loss of BMI for AC, and T3-T4 tumors for BDC.CONCLUSION:Loss of BMI ≥4% is a strong predictor of recurrence in AC, and the recurrence risk increases with the total number of lymph nodes invaded (0; 1-3; ≥4). Only T stage influences recurrence for BDC. Considering DC, the adverse effect of preoperative biliary drainage should be validated in randomized series.

The occurrence of post-operative pancreatic fistula (POPF) after pancreaticoduodenectomy is a challenging issue. The aim was to identify variables on preoperative computed tomography (CT) scan, useful to predict clinically significant POPF (grades B-C) after pancreaticoduodenectomy.Patients presented POPF after pancreaticoduodenectomy were included from two tertiary referral centres. B/W ratio was defined by ratio of pancreas body thickness (B) to main pancreatic duct (W). The predictive parameters of POPF on CT scan were assessed with a receiving operator characteristics (ROC) curve and intrinsic characteristics.Between 2010 and 2013, 186 patients who underwent pancreaticoduodenectomy were included. POPF occurred in 25% of them, and was clinically significant in 13%. After univariate analysis, endocrine tumours (P = 0.03), main pancreatic duct size (P 0.01) and B/W ratio (P = 0.04) were significantly associated with POPF. ROC curve showed a greater area under curve for B/W ratio (0.68) than for main pancreatic duct size (0.33). A 3.8 threshold displayed 80 and 51% for sensibility and specificity, respectively, and a negative predictive value of 94%. A B/W ratio3.8 increased the rates of post-operative haemorrhage (odds ratio = 4.3 (1.4-13.2), P = 0.01), and reintervention (odds ratio = 3.4 (1.2-9.6), P = 0.02).B/W ratio superior to 3.8 assessed on preoperative CT scan may be an easy tool to predict clinically significant POPF after pancreaticoduodenectomy.

Total mesorectal excision is the standard surgical treatment for mid- and low-rectal cancer. Laparoscopy represents a clear leap forward in the management of rectal cancer patients, offering significant improvements in post-operative measures such as pain, first bowel movement, and hospital length of stay. However, there are still some limits to its applications, especially in difficult cases. Such cases may entail either conversion to an open procedure or positive resection margins. Transanal endoscopic proctectomy (ETAP) was recently described and could address the difficulties of approaching the lower third of the rectum. Early series and case-control studies have shown favourable short-term results, such as a low conversion rate, reduced hospital length of stay and oncological outcomes comparable to laparoscopic surgery. The aim of the proposed study is to compare the rate of positive resection margins (R1 resection) with ETAP versus laparoscopic proctectomy (LAP), with patients randomly assigned to each arm. The proposed study is a multicentre randomised trial using two parallel groups to compare ETAP and LAP. Patients with T3 lower-third rectal adenocarcinomas for whom conservative surgery with manual coloanal anastomosis is planned will be recruited. Randomisation will be performed immediately prior to surgery after ensuring that the patient meets the inclusion criteria and completing the baseline functional and quality of life tests. The study is designed as a non-inferiority trial with a main criterion of R0/R1 resection. Secondary endpoints will include the conversion rate, the minimal invasiveness of the abdominal approach, postoperative morbidity, the length of hospital stay, mesorectal macroscopic assessment, functional urologic and sexual results, faecal continence, global quality of life, stoma-free survival, and disease-free survival at 3 years. The inclusion period will be 3 years, and every patient will be followed for 3 years. The number of patients needed is 226. There is a strong need for optimal evaluation of the ETAP because of substancial changes in the operative technique. Assessment of oncological safety and septic risk, as well as digestive and urological functional results, is particularily mandatory. Moreover, benefits of the ETAP technique could be demonstrated in post-operative outcome. ClinicalTrial.gov: NCT02584985 . Date and version identifier: Version n°2 – 2015 July 6.

The aim of this study was to determine the incidence and predisposing factors of biliary complications (BCs) after pancreaticoduodenectomy (PD) and report our experience in managing these BCs. Pancreatic surgery, particularly PD, has benefited from improvements in operative techniques and postoperative care and is currently safer in terms of mortality. However, the morbidity associated with PD remains high, including frequent complications such as delayed gastric emptying and pancreatic fistulas. Rarer but important BCs are those that manifest as bile leaks (BLs) and biliary strictures (BSs). Between April 2005 and December 2011, a total of 397 patients underwent PD at two centers. All data were retrospectively studied with respect to age, gender, pancreatic pathology, neoadjuvant treatment, preoperative biliary stenting, intraoperative data, postoperative pancreatic fistula, BL and BS rates, and mortality. The management of BCs was also analyzed. Thirty patients experienced a BC: 13 BLs (3.3 %) and 17 BSs (4.3 %). A thin bile duct (

Ampullary carcinoma is a rare tumor. There are neither sufficient available data related to management after resection of the neoplasm of the ampulla of Vater, nor any international recommendations. The aim of this study was to identify factors associated with recurrence and survival after curative resection.A retrospective follow-up study was conducted including patients with ampullary carcinoma who underwent resection with curative intent in 12 French surgical centers between January 1990 and November 2011.In this study, 319 patients underwent surgical resection for an ampullary neoplasm. Disease recurred in 120 patients (37.6%), and the 5- and 10-year disease-free survival rates were 48.9% and 40.4%, respectively. In multivariable Cox regression, preoperative bilirubin, T stage, pancreaticobiliary histology subtype, and lymph node involvement were each significantly associated with the risk of recurrence.Ampullary carcinomas are a heterogeneous group that can be classified as intestinal and pancreaticobiliary subtypes. Our findings indicate that pancreaticobiliary differentiation, advanced stage, and lymph node involvement are predictors of both poor disease-free and poor overall survival. It is still unclear what adjuvant treatment after curative resection of ampullary carcinoma is optimal. It would be informative to evaluate adjuvant therapy according to histological subtype.

ObjectivesThis study aimed to determine the impact of a standardized pathological protocol on resection margin status after pancreaticoduodenectomy (PD) for ductal adenocarcinoma.MethodsA total of 150 patients operated during 2008–2010 were included in a prospective multicentre study using a ‘quality protocol’. Multicolour inking by the surgeon identified three resection margins: the portal vein–superior mesenteric vein margin (PV-SMVm) or mesenterico–portal vein groove; the superior mesenteric artery margin (SMAm), and the posterior margin. Resection margins were stratified by 0.5-mm increments (range: 0–2.0 mm). Pancreatic neck, bile duct and intestinal margins were also analysed. Correlations between histopathological factors and survival in the 0-mm resection margin group were analysed.ResultsThirty-six patients (24%) had a PV-SMV resection (PV-SMVR). An analysis of resections categorized according to margin distances of 0 mm

To assess by prospective randomized controlled trial the feasibility and efficacy of using a bioresorbable hyaluronic acid/carboxymethylcellulose membrane (HA membrane) to prevent abdominal and perihepatic adhesions in metastatic colorectal cancer patients requiring 2-stage hepatectomy.Two-stage hepatectomy offers the possibility of long-term survival to selected patients whose liver metastases cannot be removed in a single procedure. However, the second operation is made more difficult by adhesions arising from the first. HA membrane reduces adhesions in gynecologic and abdominal surgery but this is the first trial in hepatectomy.Fifty-four candidates for 2-stage hepatectomy were randomized at the end of the first procedure to implantation of HA membrane (n = 41) or standard management (n = 13). Thirty patients from the membrane arm and 11 well-matched controls underwent the planned second hepatectomy.Positioning of the HA membranes was feasible in all but one patient and did not increase complications associated with the first hepatectomy. At second hepatectomy, patients in the HA membrane arm required 33% less time than controls to achieve complete liver mobilization (median: 50 vs 75 minutes; primary endpoint). The risk of extensive adhesions was reduced in the HA membrane group (31% had grade 3-4 adhesions vs 55% in controls), as was adhesion severity (17% thick and hypervascular adhesions vs 46%). The proportion of patients with complications at second hepatectomy was higher in the control group (55% vs 23% in the HA membrane group, P = 0.07).Use of 4 HA membranes at the end of first hepatectomy reduced the extent and severity of adhesions and facilitated the second hepatectomy in patients with liver metastases who required a 2-stage hepatectomy. A larger study to confirm these findings is warranted. (NCT01262417).

International audience; BACKGROUND:Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation.METHODS:A retrospective cross-sectional study, from 27 European high-volume HPB units.RESULTS:573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients.DISCUSSION:Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered.