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.

Benefit of a flash dose of corticosteroids in digestive surgical oncology: a multicenter, randomized, double blind, placebo-controlled trial (CORTIFRENCH).

BACKGROUND: The modulation of perioperative inflammation seems crucial to improve postoperative morbidity and cancer-related outcomes in patients undergoing oncological surgery. Data from the literature suggest that perioperative corticosteroids decrease inflammatory markers and might be associated with fewer complications in esophageal, liver, pancreatic and colorectal surgery. Their benefit on cancer-related outcomes has not been assessed. METHODS: The CORTIFRENCH trial is a phase III multicenter randomized double-blind placebo-controlled trial to assess the impact of a flash dose of preoperative corticosteroids versus placebo on postoperative morbidity and cancer-related outcomes after elective curative-intent surgery for digestive cancer. The primary endpoint is the frequency of patients with postoperative major complications occurring within 30 days after surgery (defined as all complications with Clavien-Dindo grade > 2). The secondary endpoints are the overall survival at 3 years, the disease-free survival at 3 years, the frequency of patients with intraabdominal infections and postoperative infections within 30 days after surgery and the hospital length of stay. We hypothesize a reduced risk of major complications and a better disease-survival at 3 years in the experimental group. Allowing for 5% of drop-out, 1 200 patients (600 per arm) should be included. DISCUSSION: This will be the first trial focusing on the impact of perioperative corticosteroids on cancer related outcomes. If significant, it might be a strong improvement on oncological outcomes for patients undergoing surgery for digestive cancers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03875690, Registered on March 15, 2019, URL: https://clinicaltrials.gov/ct2/show/NCT03875690 .

Ano-rectovaginal fistula after obstetrical anal sphincter injury: Diverting stoma does not improve the surgical results.

AIM: Ano-rectovaginal fistulas (ARVF) are challenging for the surgeon. Most of the series mix aetiologies, leading to confusion with respect to the conclusion. The aim of this study was to assess the factors associated with the success of ARVF management following obstetrical anal sphincter injury (OASIS). METHODS: This retrospective multicentric study included all the patients undergoing surgery for ARVF identified by the hospital codes. Patients for whom the aetiology of ARVF was not OASIS were excluded. The major outcome measure was the success of the procedure. RESULTS: Sixty patients with treated ARVF due to OASIS were identified. The success of overall management was 91.7%. Female patients underwent a mean of 2.5 (±1.7) procedures. A diverting stoma was formed in 29 patients (48.3%) of which 26 were closed at the end of the management period (89.7%). Of the 148 surgical procedures, only 55 were successful (37.2%). The order of the procedures (OR = 1.38; 95% CI: 0.75-2.51) or the diverting stoma (OR = 1.46; 95% CI: 0.31-6.91) were not significantly associated with the success of the surgery. However, Martius flap (OR = 4.13; 95% CI: 1.1-15.54) and Musset procedures (OR = 5.79; 95% CI: 1.77-18.87) produced better results than the endorectal advancement flap (ERAF). The other procedures did not show a significant correlation with management success. CONCLUSION: A diverting stoma is not mandatory in the management of ARVF due to OASIS to improve the success of the surgical procedure. While the Martius flap procedure offers better results, the ERAF procedure may be preferred as a primary intervention in the absence of sphincter injury as it is less invasive. In cases of residual sphincter injury, the Musset procedure is most likely to be the best option.

Establishing Peer Consensus About the Use of Long-Term Biosynthetic Absorbable Mesh for Hernia (Grades 2-3) as the Standard of Care.

BACKGROUND: Standard synthetic and biologic meshes, often used in hernia repair, have commonly been used and each have their strengths but associated drawbacks. Long-term biosynthetic absorbable (LTBA) mesh has been developed to combine the strengths of synthetic and biologic meshes without the associated weaknesses. As a newer type of mesh, the supporting evidence base is still growing, and their optimum use has yet to be defined. This consensus was initiated to provide insight into those situations where a LTBA might be considered the Standard of Care in ventral hernia repair grades 2-3 (original classification, 2010) of the Ventral Hernia Working Group. METHODS: A steering group of expert surgeons identified 35 statements, based around the evidence supporting LTBA, surgical technique, patients type most suitable for LTBA, risk-benefit of LTBA, patient and surgeon considerations, LTBA value. Surgeons involved in hernia repair received an online survey to assess consensus with these statements. Consensus was defined as high if ≥ 70% and very high if ≥ 90% of respondents agreed. Statements that had not achieved consensus agreement were revised and these were then issued for a subsequent round. Finally, 34 statements were included. RESULTS: Two hundred fifty-five surgeons were involved. Fourteen statements (41%) achieved very high consensus, 24 achieved consensuses (≥ 70-< 90%), whilst one (3%) just failed to achieve consensus with an agreement score of 69%. CONCLUSIONS: Expert consensus opinion about the use of LTBA for hernia (Grades 2-3) as the Standard of Care was achieved. Based on the consensus scores, the steering group derived eleven keys.

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.

Simultaneous Versus Delayed Resection for Initially Resectable Synchronous Colorectal Cancer Liver Metastases: A Prospective, Open-label, Randomized, Controlled Trial.

OBJECTIVE: To answer whether synchronous colorectal cancer liver metastases (SLM) should be resected simultaneously with primary cancer or should be delayed. SUMMARY BACKGROUND DATA: Numerous studies have compared both strategies. All were retrospective and conclusions were contradictory. METHODS: Adults with colorectal cancer and resectable SLM were randomly assigned to either simultaneous or delayed resection of the metastases. The primary outcome was the rate of major complications within 60 days following surgery. Secondary outcomes included overall and disease-free survival. RESULTS: A total of 105 patients were recruited. Eighty-five patients (39 and 46 in the simultaneous- and delayed-resection groups, respectively) were analyzed. The percentage of major perioperative complications did not differ between groups (49% and 46% in the simultaneous- and delayed-resection groups, respectively, adjusted OR 0.84, 95% CI 0.35-2.01; P = 0.70, logistic regression). Complications rates were 28% and 13% (P = 0.08, χ2 test) at colorectal site and 15% and 17% (P = 0.80, χ2 test) at liver site, in simultaneous- and delayed-resection groups, respectively. In the delayed-resection group, 8 patients did not reach the liver resection stage, and this was due to disease progression in 6 cases. After 2 years, overall and disease-free survival tended to be improved in simultaneous as compared with delayed-resection groups (P = 0.05), a tendency which persisted for OS after a median follow-up of 47 months. CONCLUSIONS: Complication rates did not appear to differ when colorectal cancer and synchronous liver metastases are resected simultaneously. Delayed resection tended to impair overall survival.

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+.

Indications and Outcomes of a Cross-Linked Porcine Dermal Collagen Mesh (Permacol) for Complex Abdominal Wall Reconstruction: A Multicenter Audit.

INTRODUCTION: To reduce the occurrence of complications in the setting of high-risk patients with contaminated operative field, a wide range of biologic meshes has been developed. Yet, few series have reported outcomes after abdominal wall repair (AWR) using such meshes. Permacol is an acellular porcine dermal collagen matrix with a cross-linked pattern. This study reports short- and long-term outcomes after AWR for incisional hernia using Permacol. MATERIALS AND METHODS: All consecutive patients undergoing single-stage open AWR using Permacol mesh at eight university hospitals were included. Mortality, complication and hernia recurrence rates were assessed. Independent risk factors for complications and hernia recurrence were identified with logistic regression and Fine and Gray analysis, respectively. RESULTS: Overall, 250 patients underwent single-stage AWR with Permacol. Nearly 80% had a VHWG grade 3 or 4 defect. In-hospital mortality and complication rates were 4.8% (n = 12) and 61.6% (n = 154), respectively. Reintervention for complications was required for 74 patients (29.6%). Mesh explantation rate was 4% (n = 10). Independent risk factors for complications were smoking, defect size and VHWG grade. After a mean follow-up time of 16.8 months (± 18.1 months), 63 (25.2%) experienced hernia recurrence. One-, 2- and 3-year RFS were 90%, 74% and 57%, respectively. Previous AWR, mesh location and the need for reintervention were independent predictors of hernia recurrence. DISCUSSION: Single-stage AWR is feasible using Permacol. Mortality and complication rates are high due to patients' comorbidities and the degree of contamination of the operative field. Given the observed recurrence rate, the benefit of biologics remains to be ascertained.

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.

Proposal of a new classification of postoperative ileus based on its clinical impact-results of a global survey and preliminary evaluation in colorectal surgery.

PURPOSE: There is no consensual definition of postoperative ileus (POI), which leads to a lack of reproducibility. The aims of this study were (i) to propose and evaluate a classification of postoperative ileus based on its consequences and (ii) to assess the reproducibility of the classification. METHODS: A national global survey was carried out according to the DELPHI method in order to create a classification of primary POI. The classification was subsequently tested on a cohort of patients who underwent colorectal surgery. Finally, a reproducibility test was performed in five teaching hospitals with junior and senior surgeons. RESULTS: A five-stage classification was proposed: grade A (least) to grade E (worst). For better differentiation, subcategories (D1/D2) were included. Overall, 173 patients were included who underwent colorectal surgery. Forty of them experienced primary postoperative ileus (23.1%). Grade A occurred in 10 cases, grade B in 10 cases, grade C in 14 cases, grade D1 in 2 cases, and grade D2 in 2 cases. POI-related death (grade E) occurred in 2 cases. Patients with grade A POI recovered their gastrointestinal function significantly faster than those with higher grades (p = 0.01), and were more likely to undergo laparoscopic surgery (p = 0.04). The Intraclass Correlation Coefficient (ICC) was 0.83 in the overall population, and 0.83 and 0.82 respectively in the junior and senior surgeon populations. CONCLUSION: This classification is easy to both use and reproduce. It will improve the reproducibility, evaluation, and assessment of POI. These preliminary results should be confirmed in a multi-centric international study.

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 Procalcitonin and C-reactive Protein for the Early Diagnosis of Intra-abdominal Infection After Elective Colorectal Surgery: A Meta-analysis.

OBJECTIVE: Intra-abdominal infections (IAIs) after elective colorectal surgery impact significantly the short- and long-term outcomes. In the era of fast-track surgery, they often come to light after discharge from hospital. Early diagnosis is therefore essential. C-reactive protein levels have proved to be accurate in this setting. Procalcitonin has been evaluated in several studies with conflicting results. This meta-analysis aimed to compare the predictive abilities of C-reactive protein and procalcitonin in the occurrence of IAIs after elective colorectal surgery. METHODS: This meta-analysis included studies analyzing C-reactive protein and/or procalcitonin levels at postoperative days 2, 3, 4, and/or 5 as markers of intra-abdominal infection after elective colorectal surgery. Methodological quality was assessed by the QUADAS2 tool. The area under the curve summary receiver-operating characteristic was calculated for each day and each biomarker, using a random-effects model in cases of heterogeneity. RESULTS: The meta-analysis included 11 studies (2692 patients). An IAI occurred in 8.9% of the patients. On postoperative day 3, area under the curve was 0.80 (95% CI, 0.76-0.85) for C-reactive protein and 0.78 (95% CI, 0.68-0.87) for procalcitonin. On postoperative day 5, their predictive accuracies were 0.87 (95% CI, 0.80-0.93) and 0.90 (95% CI, 0.82-0.98), respectively. The accuracy of C-reactive protein and procalcitonin did not differ at any postoperative day. CONCLUSIONS: Levels of inflammatory markers under the cutoff value between postoperative days 3 and 5 ensure safe early discharge after elective colorectal surgery. Procalcitonin seems not to have added value as compared to C-reactive protein in this setting.

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.

Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin Increases the Risk of Postoperative Hemorrhagic Complications: Analysis of Predictive Factors.

BACKGROUND: Treatment of peritoneal carcinomatosis (PC) using cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended as curative treatment for selected patients. Modalities of HIPEC remain heterogeneous and HIPEC using oxaliplatin (HIPEC-Ox) appears to increase the risk of postoperative hemorrhagic complications (HCs). OBJECTIVE: The aim of this study was to assess the risk of HCs after CRS combined with HIPEC-Ox versus other drugs, and to determine predictive factors for HCs after HIPEC-Ox. METHODS: Data from 701 patients included in the National French Registry who were treated with CRS and HIPEC at 24 centers between 1998 and 2007 were used to evaluate the incidence of HCs following HIPEC with or without oxaliplatin. Overall, 771 patients treated with HIPEC-Ox at five French specialty centers were then analyzed to determine factors associated with the occurrence of HCs. RESULTS: The overall incidence of HCs was 9.8 %. When used with HIPEC, oxaliplatin significantly and independently increased the rate of HCs (15.7 vs. 2.6 % for other drugs; p = 0.004, odds ratio 32.4). Among the 771 patients who underwent HIPEC-Ox, HCs occurred in 14.3 % of patients. The only independent risk factor for HCs was an extended PC with a Peritoneal Cancer Index (PCI) >12 (p = 0.040). CONCLUSION: HIPEC-Ox increases the risk of HCs compared with HIPEC with other drugs. The potential oncologic benefit of oxaliplatin and the risk of HCs should be considered in patients with PC who have a high PCI, as well as in at-risk patients.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis in the Elderly: A Case-Controlled, Multicenter Study.

OBJECTIVE: This study was designed to identify factors associated with morbidity and mortality in patients older than 70 years who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC). BACKGROUND: Major surgery is associated with higher morbidity and mortality in elderly patients. For PC, CRS and HIPEC is the only current potential curative therapy, but the risks inherent to this patient population have called its benefits into question. METHODS: We retrospectively analyzed a multi-center database from 1989 to 2015. All patients who underwent CRS and HIPEC for PC were selected and patients older than 70 years were matched 1:4 with a younger cohort according to cancer origin, peritoneal cancer index (PCI), and completeness of cytoreduction. Major morbidity and mortality were analyzed. RESULTS: Of 2328 patients, 188 patients older than aged 70 years were matched with 704 younger patients. Patients older than aged 70 years demonstrated a higher American Society of Anesthesiologist score (≥ASA III 10.8 vs. 6.6 %, p = 0.008). There was no difference in overall 90-day morbidity (≥70: 45.7 % vs. <70: 44.5 %; p = 0.171); however, patients older than 70 years had significantly more cardiovascular complications (13.8 vs. 9.2 %, p = 0.044). Differences between the older and younger cohorts failed to reach significance for 90-day mortality (5.4 and 2.7 %, respectively; p = 0.052), and failure-to-rescue (11.6 and 6.1 %, respectively; p = 0.078). In multivariate analysis, PCI > 7 (95 % CI 1.051-5.798, p = 0.038) and HIPEC duration (95 % CI 1.106-6.235, p = 0.028) were independent factors associated with morbidity in elderly patients. CONCLUSIONS: CRS and HIPEC appear feasible for selected patients older than aged 70 years, albeit with a higher risk of medical complications associated with increased mortality.

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.