Management and outcomes of hemorrhage after distal pancreatectomy: a multicenter study at high volume centers.

BACKGROUND: Data on clinically relevant post-pancreatectomy hemorrhage (CR-PPH) are derived from series mostly focused on pancreatoduodenectomy, and data after distal pancreatectomy (DP) are scarce. METHODS: All non-extended DP performed from 2014 to 2018 were included. CR-PPH encompassed grade B and C PPH. Risk factors, management, and outcomes of CR-PPH were evaluated. RESULTS: Overall, 1188 patients were included, of which 561 (47.2 %) were operated on minimally invasively. Spleen-preserving DP was performed in 574 patients (48.4 %). Ninety-day mortality, severe morbidity and CR-POPF rates were 1.1 % (n = 13), 17.4 % (n = 196) and 15.5 % (n = 115), respectively. After a median interval of 8 days (range, 0-37), 65 patients (5.5 %) developed CR-PPH, including 28 grade B and 37 grade C. Reintervention was required in 57 patients (87.7 %). CR-PPH was associated with a significant increase of 90-day mortality, morbidity and hospital stay (p < 0.001). Upon multivariable analysis, prolonged operative time and co-existing POPF were independently associated with CR-PPH (p < 0.005) while a chronic use of antithrombotic agent trended towards an increase of CR-PPH (p = 0.081). As compared to CR-POPF, the failure-to-rescue rate in patients who developed CR-PPH was significantly higher (13.8 % vs. 1.3 %, p < 0.001). CONCLUSION: CR-PPH after DP remains rare but significantly associated with an increased risk of 90-day mortality and failure-to-rescue.

Defining Benchmark Outcomes for Distal Pancreatectomy: Results of a French Multicentric Study.

OBJECTIVE: Defining robust and standardized outcome references for distal pancreatectomy (DP) by using Benchmark analysis. BACKGROUND: Outcomes after DP are recorded in medium or small-sized studies without standardized analysis. Therefore, the best results remain uncertain. METHODS: This multicenter study included all patients undergoing DP for resectable benign or malignant tumors in 21 French expert centers in pancreas surgery from 2014 to 2018. A low-risk cohort defined by no significant comorbidities was analyzed to establish 18 outcome benchmarks for DP. These values were tested in high risk, minimally invasive and benign tumor cohorts. RESULTS: A total of 1188 patients were identified and 749 low-risk patients were screened to establish Benchmark cut-offs. Therefore, Benchmark rate for mini-invasive approach was ≥36.8%. Benchmark cut-offs for postoperative mortality, major morbidity grade ≥3a and clinically significant pancreatic fistula rates were 0%, ≤27%, and ≤28%, respectively. The benchmark rate for readmission was ≤16%. For patients with pancreatic adenocarcinoma, cut-offs were ≥75%, ≥69.5%, and ≥66% for free resection margins (R0), 1-year disease-free survival and 3-year overall survival, respectively. The rate of mini-invasive approach in high-risk cohort was lower than the Benchmark cut-off (34.1% vs ≥36.8%). All Benchmark cut-offs were respected for benign tumor group. The proportion of benchmark cases was correlated to outcomes of DP. Centers with a majority of low-risk patients had worse results than those operating complex cases. CONCLUSION: This large-scale study is the first benchmark analysis of DP outcomes and provides robust and standardized data. This may allow for comparisons between surgeons, centers, studies, and surgical techniques.

Impact of hospital volume in liver surgery on postoperative mortality and morbidity: nationwide study.

BACKGROUND: This nationwide retrospective study was undertaken to evaluate impact of hospital volume and influence of liver transplantation activity on postoperative mortality and failure to rescue after liver surgery. METHODS: This was a retrospective study of patients who underwent liver resection between 2011 and 2019 using a nationwide database. A threshold of surgical activities from which in-hospital mortality declines was calculated. Hospitals were divided into high- and low-volume centres. Main outcomes were in-hospital mortality and failure to rescue. RESULTS: Among 39 286 patients included, the in-hospital mortality rate was 2.8 per cent. The activity volume threshold from which in-hospital mortality declined was 25 hepatectomies. High-volume centres (more than 25 resections per year) had more postoperative complications but a lower rate of in-hospital mortality (2.6 versus 3 per cent; P < 0.001) and failure to rescue (5 versus 6.3 per cent; P < 0.001), in particular related to specific complications (liver failure, biliary complications, vascular complications) (5.5 versus 7.6 per cent; P < 0.001). Liver transplantation activity did not have an impact on these outcomes. CONCLUSION: From more than 25 liver resections per year, rates of in-hospital mortality and failure to rescue declined. Management of specific postoperative complications appeared to be better in high-volume centres.

Early detection of anastomotic leak with C-reactive protein increases the chances of anastomotic salvage.

AIM: Anastomotic leak results in increased morbidity and affects functional and oncological outcomes after colectomy. Measurement of C-reactive protein (CRP) allows early detection of anastomotic leaks. The aim of this study was to evaluate the benefit to the patient of earlier diagnosis and management of anastomotic leaks, namely avoiding takedown of the anastomosis. METHOD: Patients with an anastomotic fistula after elective colorectal surgery from 2010 to 2020 were included. Three periods were defined according to progressive adherence to the CRP protocol in our department. A comparison was made between the periods 'before' (2010-2013) and 'after' (2016-2020) in terms of morbidity, mortality, anastomotic salvage, days spent in hospital within the first postoperative month, timely adjuvant chemotherapy and anastomotic stenosis. RESULTS: Out of 2655 elective colorectal operations, 171 patients presented with an anastomotic leak and 123 patients were included in the study. In univariate analysis, patients in the 'after' group had fewer severe complications (Clavien-Dindo Grade III to IV, 66.7% vs. 56.9; p = 0.017); the difference did not reach significance regarding timely postoperative chemotherapy (p = 0.058) and anastomotic stenosis (p = 0.682). In both, univariate and multivariate analysis, the 'after' period increased the chances of preserving the anastomosis (OR = 2.37 [1.08-5.17]) and increased the number of days out of hospital (p = 0.0002). CONCLUSION: A CRP-based protocol for the screening of anastomotic leaks after colorectal surgery was related to increased anastomotic conservation, a decreased impact and severity of the leak and a shorter length of hospital stay.

C-reactive protein identifies patients at low risk of anastomotic leak after esophagectomy.

PURPOSE: Fast-track protocols are increasingly used after digestive surgery. After esophagectomy, the gravity and the fear of anastomotic leak may be an obstacle to generalization of such protocols. C-reactive protein (CRP) might be a reliable tool to identify patients at low risk of anastomotic leak after esophagectomy, so that they can be safely included in a fast-track program. The aim of our retrospective bicentric study is to evaluate the interest of C-reactive protein measurement for the early diagnosis of anastomotic leak after esophagectomy. METHODS: Patients having undergone Ivor-Lewis procedure between January 2009 and September 2017 were included in this bicentric retrospective study. CRP values were recorded between postoperative day 3 (POD 3) and postoperative day 5 (POD 5). All postoperative complications were recorded, and the primary endpoint was anastomotic leak. RESULTS: We included 585 patients. Among them, 241 (41.2%) developed infectious complications and 69 patients (11.8%) developed anastomotic leak. CRP had the best predictive value on POD 5 (AUC = 0.74; 95% CI: 0.67-0.81). On POD 5, a cut-off value of 130 mg/L yielded a sensitivity of 87%, a specificity of 51%, and a negative predictive value of 96% for the detection of anastomotic leak. CONCLUSIONS: CRP may help in identifying patients at very low risk of anastomotic leak after esophagectomy. Patients with CRP values < 130 mg/L on POD 5 can safely undertake an enhanced recovery protocol.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone. METHODS: We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed. FINDINGS: Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035). INTERPRETATION: Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases. FUNDING: Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.

Limited Resection Versus Pancreaticoduodenectomy for Duodenal Gastrointestinal Stromal Tumors? Enucleation Interferes in the Debate: A European Multicenter Retrospective Cohort Study.

BACKGROUND: The optimal surgical procedure for duodenal gastrointestinal stromal tumors (D-GISTs) remains poorly defined. Pancreaticoduodenectomy (PD) allows for a wide resection but is associated with a high morbidity rate. OBJECTIVES: The aim of this study was to compare the short- and long-term outcomes of PD versus limited resection (LR) for D-GISTs and to evaluate the role of tumor enucleation (EN). METHODS: In this retrospective European multicenter cohort study, 100 patients who underwent resection for D-GIST between 2001 and 2013 were compared between PD (n = 19) and LR (n = 81). LR included segmental duodenectomy (n = 47), wedge resection (n = 21), or EN (n = 13). The primary objective was to evaluate disease-free survival (DFS) between the groups, while the secondary objectives were to analyze the overall morbidity and mortality, radicality of resection, and 5-year overall survival (OS) and recurrence rates between groups. Furthermore, the short- and long-term outcomes of EN were evaluated. RESULTS: Baseline characteristics were comparable between the PD and LR groups, except for a more frequent D2 tumor location in the PD group (68.3% vs. 29.6%; p = 0.016). Postoperative morbidity was higher after PD (68.4% vs. 23.5%; p < 0.001). OS (p = 0.70) and DFS (p = 0.64) were comparable after adjustment for D2 location and adjuvant therapy rate. EN was performed more in American Society of Anesthesiologists (ASA) stage III/IV patients with tumors < 5 cm and was associated with a 5-year OS rate of 84.6%, without any disease recurrences. CONCLUSIONS: For D-GISTs, LR should be the procedure of choice due to lower morbidity and similar oncological outcomes compared with PD. In selected patients, EN appears to be associated with equivalent short- and long-term outcomes. Based on these results, a surgical treatment algorithm is proposed.

Ten-year experience with arterial embolization for peptic ulcer bleeding: N-butyl cyanoacrylate glue versus other embolic agents.

OBJECTIVES: To compare our experience with N-butyl cyanoacrylate glue as the primary embolic agent versus other embolic agents for transcatheter arterial embolization (TAE) in refractory peptic ulcer bleeding and to identify factors associated with early rebleeding and 30-day mortality. METHODS: Retrospective study of 148 consecutive patients comparing the clinical success rate in 78 patients managed with Glubran®2 N-butyl cyanoacrylate metacryloxysulfolane (NBCA-MS) alone or with other agents and 70 with other embolic agents only (coils, microspheres, ethylene-vinyl alcohol copolymer, or gelatin sponge) at a university center in 2008-2019. Univariate and multivariate logistic regression analyses were done to identify prognostic factors. RESULTS: The technical success rate was 95.3% and the primary clinical success was 64.5%. The early rebleeding and day-30 mortality rates were 35.4% and 21.3%, respectively. Rebleeding was significantly less common with than without Glubran®2 (OR, 0.47; 95% CI, 0.22-0.99; p = .047) and significantly more common with coils used alone (OR, 20.4; 95% CI, 10.13-50.14; p = .024). The only other factor independently associated with early rebleeding was having two or more comorbidities (OR, 20.14; 95% CI, 10.01-40.52; p = .047). Day-30 mortality was similar in the two treatment groups. A lower initial hemoglobin level was significantly associated with higher day-30 mortality (OR, 10.38; 95% CI, 10.10-10.74; p = .006). Fluoroscopy time was significantly shorter with Glubran®2 (20.8 ± 11.5 min vs. 35.5 ± 23.4 min, p = .002). Both groups (Glubran®2 vs. other agents) had similar rates of overall complications (10.7% vs. 9.1%, respectively, p = .786). CONCLUSIONS: Glubran®2 NBCA-MS as the primary agent allowed for faster and better clinical success compared to other embolic agents when used for TAE to safely stop refractory peptic ulcer bleeding. KEY POINTS: • Choice of embolic agent for arterial embolization of refractory peptic ulcer bleeding is still debated. We compared our experience with N-butyl cyanoacrylate (NBCA) glue vs. other embolic agents. • The use of Glubran®2 NBCA glue in the endovascular management of refractory peptic ulcer bleeding was significantly faster and more effective, and at least as safe compared to other embolic agents. • NBCA glue offers several advantages compared to other embolic agents and provides rapid hemostasis when used for arterial embolization to treat refractory peptic ulcer bleeding. It should be the first-line therapy.

Detecting Hospital Outliers in Post-Pancreatectomy Care Using Funnel Plots from 2009-2018 Based on Nationwide Medico-Administrative Data.

OBJECTIVES: Our objective was to identify hospitals with unusual mortality rates for major pancreatectomies over a period of ten years using 30-day mortality data from the French national database. METHODS: Data for all patients who underwent pancreatectomy were extracted from the national medico-economic database (Programme de Médicalisation des Systèmes d'Information). To identify quality outliers for each hospital, the observed-to-expected 30-day mortality rates were used as a quality indicator. RESULTS: A total of 19 494 patients underwent a major pancreatectomy in France between January 2009 and December 2018. The overall 30-day mortality rate was 4.8% (n = 944). For the 2009-2014 period, the funnel plot showed that 10 of the 176 hospitals lie outside the central 95% region and 7 lie outside the central 99.8% region. For the 2015-2018 period, out of 176 hospitals, 6 lie outside the central 95% region and 2 lie outside the central 99.8% region. The change in standardized mortality ratios between 2009-2014 and 2015-2018 testing for differences from the overall change, they were there 4 hospitals lie outside the central 95% region and 0 lie outside the central 99.8% region. CONCLUSION: Over time, the improvement in hospital quality was weak. This study suggests that there is a pressing need to reorganize the supply of care for pancreatic surgery in France.

Pancreatoduodenectomy for Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: An AFCE (Association Francophone de Chirurgie Endocrinienne) and GTE (Groupe d'étude des Tumeurs Endocrines) Study.

AIM: To assess postoperative complications and control of hormone secretions following pancreatoduodenectomy (PD) performed on multiple endocrine neoplasia type 1 (MEN1) patients with duodenopancreatic neuroendocrine tumors (DP-NETs). BACKGROUND: The use of PD to treat MEN1 remains controversial, and evaluating the right place of PD in MEN1 disease makes sense. METHODS: Thirty-one MEN1 patients from the Groupe d'étude des Tumeurs Endocrines MEN1 cohort who underwent PD for DP-NETs between 1971 and 2013 were included. Early and late postoperative complications, secretory control and overall survival were analyzed. RESULTS: Indication for surgery was: Zollinger-Ellison syndrome (n = 18; 58%), nonfunctioning tumor (n = 9; 29%), insulinoma (n = 2; 7%), VIPoma (n = 1; 3%) and glucagonoma (n = 1; 3%). Mean follow-up was 141 months (range 0-433). Pancreatic fistulas occurred in 5 patients (16.1%), distant metastases in 6 (mean onset of 43 months; range 13-110 months), postoperative diabetes mellitus in 7 (22%), and pancreatic exocrine insufficiency in 6 (19%). Five-year overall survival was 93.3% [CI 75.8-98.3] and ten-year overall survival was 89.1% [CI 69.6-96.4]. After a mean follow-up of 151 months (range 0-433), the biochemical cure rate for MEN-1 related gastrinomas was 61%. CONCLUSION: In MEN1 patients, pancreatoduodenectomy can be used to control hormone secretions (gastrin, glucagon, VIP) and to remove large NETs. PD was found to control gastrin secretions in about 60% of cases.

Failure to rescue in patients with distal pancreatectomy: a nationwide analysis of 10,632 patients.

BACKGROUND: FTR appears as a major cause of postoperative mortality (POM). Hospital volume has an impact on FTR in pancreatic surgery but no study has investigated this relationship more specifically in DP. METHODS: We analysed patients with DP between 2009 and 2018 through a nationwide database. FTR definition was mortality among patients who experiment major complications. The cutoff between high and low volume centers was 20 pancreatectomies per year. RESULTS: Some 10,632 patients underwent DP, 5048 (47.5%) were operated in 602 (95.4%) low volume centers and 5584 (52.5%) in 29 (4.6%) high volume centers. Overall FTR occurred in 11.2% of patients and was significantly reduced in high volume centers compared to low volume centers (10.2% vs 12.5%, p = 0.047). In multivariate analysis, surgery in a high volume center was a protective factor for POM (OR = 0.570, CI95% [0.505-0.643], p < 0.001) and also for FTR (OR = 0.550, CI95% [0.486-0.630], p < 0.001). CONCLUSION: Hospital volume has a positive impact on FTR in DP. Patients with higher risk of FTR are men, with high modified Charlson comorbidity index, malignant conditions and open procedures.

Multicenter phase III randomized trial comparing laparoscopy and laparotomy for colon cancer surgery in patients older than 75 years: the CELL study, a Fédération de Recherche en Chirurgie (FRENCH) trial.

BACKGROUND: Several multicenter randomized controlled trials comparing laparoscopy and conventional open surgery for colon cancer have demonstrated that laparoscopic approach achieved the same oncological results while improving significantly early postoperative outcomes. These trials included few elderly patients, with a median age not exceeding 71 years. However, colon cancer is a disease of the elderly. More than 65% of patients operated on for colon cancer belong to this age group, and this proportion may become more pronounced in the coming years. In current practice, laparoscopy is underused in this population. METHODS: The CELL (Colectomy for cancer in the Elderly by Laparoscopy or Laparotomy) trial is a multicenter, open-label randomized, 2-arm phase III superiority trial. Patients aged 75 years or older with uncomplicated colonic adenocarcinoma or endoscopically unresectable colonic polyp will be randomized to either colectomy by laparoscopy or laparotomy. The primary endpoint of the study is overall postoperative morbidity, defined as any complication classification occurring up to 30 days after surgery. The secondary endpoints are: 30-day and 90-day postoperative mortality, 30-day readmission rate, quality of surgical resection, health-related quality of life and evolution of geriatric assessment. A 35 to 20% overall postoperative morbidity rate reduction is expected for patients operated on by laparoscopy compared with those who underwent surgery by laparotomy. With a two-sided α risk of 5% and a power of 80% (ß = 0.20), 276 patients will be required in total. DISCUSSION: To date, no dedicated randomized controlled trial has been conducted to evaluate morbidity after colon cancer surgery by laparoscopy or laparotomy in the elderly and the benefits of laparoscopy is still debated in this context. Thus, a prospective multicenter randomized trial evaluating postoperative outcomes specifically in elderly patients operated on for colon cancer by laparoscopy or laparotomy with curative intent is warranted. If significant, such a study might change the current surgical practices and allow a significant improvement in the surgical management of this population, which will be the vast majority of patients treated for colon cancer in the coming years. TRIAL REGISTRATION: ClinicalTrials.gov NCT03033719 (January 27, 2017).

Pancreatic ductal adenocarcinoma and paraaortic lymph nodes metastases: The accuracy of intraoperative frozen section.

BACKGROUND: Pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) with paraaortic lymph nodes metastases (PALN +) is associated with poor survival. Still, there are no current guidelines advocating systematic detection of PALN+. METHODS: All consecutive patients who underwent surgical exploration/resection with concurrent paraaortic (group 16) lymphadenectomy for PDAC between 2009 and 2016 were considered for inclusion. Resection was systematically aborted in case of intraoperative PALN + detection. Diagnostic performance of preoperative imaging upon blind review and intraoperative PALN dissection with frozen section (FS) for PALN detection were evaluated. Additionally, the prognostic significance of PALN + on overall survival (OS) was analyzed. RESULTS: Over the study period, among 129 patients undergoing surgery for PDAC, 113 had intraoperative PALN dissection with FS analysis. Median number of resected PALN was 3 (range, 1-15). Overall, PALN+ was found in 19 patients (16.8%). Upon blind review, preoperative imaging performed poorly for PALN + detection with a low agreement between imaging and final pathology (Kappa-Cohen index<0.2). In contrast, PALN FS showed high detection performances and strong agreement with final pathology (Kappa-Cohen index = 0.783, 95%CI 0.779-0.867, p < 0.001). Regarding survival outcomes, there was no difference between patients with PALN+ and patients not resected in the setting of liver metastases or locally unresectable disease found at exploration (p = 0.708). CONCLUSIONS: Before PD for PDAC, intraoperative PALN dissection and FS analysis yields accurate PALN assessment and allows appropriate patient selection. This should be routinely performed and aborting resection should be strongly considered in case of PALN+.

Altered distribution and function of splenic innate lymphoid cells in adult chronic immune thrombocytopenia.

Innate lymphoid cells (ILCs) have been characterized as innate immune cells capable to modulate the immune response in the mucosae. Human ILCs have been rarely described in secondary lymphoid organs except in tonsils. Moreover, their function and phenotype in human secondary lymphoid organs during autoimmune diseases have never been studied. We took advantage of splenectomy as a treatment of immune thrombocytopenia (ITP) to describe and compare splenic ILC from 18 ITP patients to 11 controls. We first confirmed that ILC3 represented the most abundant ILC subset in human non-inflamed spleens, accounting for 90% of total ILC, and that they were mostly constituted of NKp44- cells. On the contrary, proportions of ILC1 and ILC2 in spleens were lower than in blood. Splenic IL-2- and IFN-γ-producing ILC1 were increased in ITP. While the frequencies of total splenic ILC3 were similar in the two groups, splenic GM-CSF-producing ILC3 were increased in ITP. This is the first description of human ILC in a major secondary lymphoid organ during an autoimmune disease, ITP. We observed an expansion of splenic ILC1 that could participate to the Th1 skewing, while the increased production of GM-CSF by splenic ILC3 could stimulate splenic macrophages which play a key role in ITP pathophysiology.

CA 19-9 predicts resectability of pancreatic cancer even in jaundiced patients.

BACKGROUND: Surgical resection remains the only curative option for pancreatic adenocarcinoma. Despite recent improvements in medical imaging, unresectability is still often discovered at the time of surgery. It is essential to identify unresectable patients preoperatively to avoid unnecessary surgery. High serum CA 19-9 levels have been suggested as a marker of unresectability but considered inaccurate in patients with hyperbilirubinemia. AIM OF THE STUDY: To evaluate CA 19-9 serum levels as a predictor of unresectability of pancreatic adenocarcinomas with a special focus on jaundiced patients. METHODS: All patients presenting with histologically-confirmed pancreatic adenocarcinoma and having serum CA 19-9 levels available prior to any treatment were included in this retrospective study. The relationship between serum concentrations of CA 19-9 and resectability was studied by regression analysis and theROC curves obtained. A cut-off value of CA 19-9 was calculated. In jaundiced patients, a CA 19-9 adjusted for bilirubinemia was also evaluated. RESULTS: Of the 171 patients included, 49 (29%) were deemed resectable and 122 (71%) unresectable. Altogether, 93 patients (54%) had jaundice. The area under the ROC curve for CA 19-9 as a predictor of resectability was 0.886 (95%CI:[0.832-0.932]); in jaundiced patients it was 0.880 (95% CI [0.798-0.934]. A cut-off in CA 19-9 at 178 UI/mlyielded 85% sensitivity, 81% specificity and 91% positive predictive value for resectability. There was no correlation between the levels of bilirubin and CA 19-9 (r = 0.149). CONCLUSION: Serum CA 19-9 is a good predictive marker of unresectability of pancreatic adenocarcinoma, even in jaundiced patients. CA 19-9 levels over 178 UI/ml strongly suggest unresectable disease.

B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia.

B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ITP and to support B cell differentiation and antiplatelet antibody-production may participate to RTX inefficiency. Whereas it is well established that the survival of TFH depends on B cells in animal models, nothing is known in humans yet. To determine the effect of B cell depletion on human TFH, we quantified B cells and TFH in the spleen and in the blood from ITP patients treated or not with RTX. We showed that B cell depletion led to a dramatic decrease in splenic TFH and in CXCL13 and IL-21, two cytokines predominantly produced by TFH. The absolute count of circulating TFH and serum CXCL13 also decreased after RTX treatment, whatever the therapeutic response. Therefore, we showed that the maintenance of TFH required B cells and that TFH are not involved in the inefficiency of RTX in ITP.

Inflammatory markers as early predictors of infection after colorectal surgery: the same cut-off values in laparoscopy and laparotomy?

PURPOSE: C-reactive protein and procalcitonin are reliable early predictors of infection after colorectal surgery. However, the inflammatory response is lower after laparoscopy as compared to open surgery. This study analyzed whether a different cutoff value of inflammatory markers should be chosen according to the surgical approach. METHODS: A prospective, observational study included consecutive patients undergoing elective colorectal surgery in three academic centers. All infections until postoperative day (POD) 30 were recorded. The inflammatory markers were analyzed daily until POD 4. Areas under the ROC curve and diagnostic values were calculated in order to assess their accuracy as a predictor of intra-abdominal infection. RESULTS: Five-hundred-one patients were included. The incidence of intra-abdominal infection was 11.8%. The median levels of C-reactive protein (CRP) and procalcitonin (PCT) were lower in the laparoscopy group at each postoperative day (p < 0.0001). In patients without intra-abdominal infection, they were also lower in the laparoscopy group (p = 0.0036) but were not different in patients presenting with intra-abdominal infections (p = 0.3243). In the laparoscopy group, CRP at POD 4 was the most accurate predictor of overall and intra-abdominal infection (AUC = 0.775). With a cutoff of 100 mg/L, it yielded 95.7% negative predictive value, 75% sensitivity, and 70.3% specificity for the detection of intra-abdominal infection. CONCLUSION: The impact of infection on inflammatory markers is more important than that of the surgical approach. Defining a specific cutoff value for early discharge according to the surgical approach is not justified. A patient with CRP values lower than 100 mg/L on POD 4 can be safely discharged.

Robot-Assisted Choledochoduodenostomy: A Safe and Reproducible Procedure for Benign Common Bile Duct Obstruction.

BACKGROUND: Choledochoduodenostomy (CD) is an option for treating choledocholithiasis and benign biliary obstruction after failure of endoscopic treatment. Nevertheless, this procedure is rarely performed using a mini-invasive approach because of its technical complexity. Robotic assistance could be a safer approach to overcome such technical issues. METHODS: All consecutive patients who underwent a robot-assisted CD for benign biliary obstruction were included. RESULTS: Between 2012 and 2016, 12 patients were operated on, 7 of whom had a body mass index over 25 (58%) and 7 were ASA class 3 (58%). The median age was 73 years (range 49-93). Median operative time was 140 min (range 105-208) and median blood loss was 90 mL (range 5-500). One patient presented with cholangitis 1 month after surgery (treated medically, Clavien-Dindo grade 2). Median length of stay was 7 days (range 3-8). None of the patients experienced severe morbidity after a median follow-up of 15 months. CONCLUSION: Robot-assisted CD is safe and feasible in benign biliary obstruction.

Diagnostic Accuracy of Inflammatory Markers As Early Predictors of Infection After Elective Colorectal Surgery: Results From the IMACORS Study.

BACKGROUND: Intra-abdominal infections are frequent and life-threatening complications after colorectal surgery. An early detection could diminish their clinical impact and permit safe early discharge. OBJECTIVE: This study aimed to find the most accurate marker for the detection of postoperative intra-abdominal infection and the appropriate moment to measure it. METHODS: A prospective, observational study was conducted in 3 centers. Consecutive patients undergoing elective colorectal surgery with anastomosis were included. C-reactive protein and procalcitonin were measured daily until the fourth postoperative day. Postoperative infections were recorded according to the definitions of the Centres for Diseases Control. The areas under the receiver operating characteristic curve were analyzed and compared to assess the diagnostic accuracy of each marker. RESULTS: Five-hundred and one patients were analyzed. The incidence of intra-abdominal infection was 11.8%, with 24.6% of patients presenting at least one infectious complication. Overall mortality was 1.2%. At the fourth postoperative day, C-reactive protein was more discriminating than procalcitonin for the detection of intra-abdominal infection (areas under the ROC curve: 0.775 vs 0.689, respectively, P = 0.03). Procalcitonin levels showed wide dispersion. For the detection of all infectious complications, C-reactive protein was also significantly more accurate than procalcitonin on the fourth postoperative day (areas under the ROC curve: 0.783 vs 0.671, P = 0.0002). CONCLUSIONS: C-reactive protein is more accurate than procalcitonin for the detection of infectious complications and should be systematically measured at the fourth postoperative day. It is a useful tool to ensure a safe early discharge after elective colorectal surgery.

Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia.

Antiplatelet-antibody-producing B cells play a key role in immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand (CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in ITP.