Somatostatin vs. Octreotide for Prevention of Postoperative Pancreatic Fistula The PREFIPS Randomized Clinical Trial A FRENCH 007 - ACHBT Study.

OBJECTIVE: Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment. PATIENTS AND METHODS: Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 µg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs. DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis. RESULTS: Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a non-dilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 d). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (Chi-2 test, P=0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis. CONCLUSIONS: Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy.

Lung Ultrasound Score on Postoperative Day 1 Is Predictive of the Occurrence of Pulmonary Complications after Major Abdominal Surgery: A Multicenter Prospective Observational Study.

BACKGROUND: Postoperative pulmonary complications after major abdominal surgery are frequent and carry high morbidity and mortality. Early identification of patients at risk of pulmonary complications by lung ultrasound may allow the implementation of preemptive strategies. The authors hypothesized that lung ultrasound score would be associated with pulmonary postoperative complications. The main objective of the study was to evaluate the performance of lung ultrasound score on postoperative day 1 in predicting pulmonary complications after major abdominal surgery. Secondary objectives included the evaluation of other related measures for their potential prediction accuracy. METHODS: A total of 149 patients scheduled for major abdominal surgery were enrolled in a bicenter observational study. Lung ultrasound score was performed before the surgery and on days 1, 4, and 7 after surgery. Pulmonary complications occurring before postoperative day 10 were recorded. RESULTS: Lung ultrasound score on postoperative day 1 was higher in patients developing pulmonary complications before day 10 (median, 13; interquartile range, 8.25 to 18; vs. median, 10; interquartile range, 6.5 to 12; Mann-Whitney P = 0.002). The area under the curve for predicting postoperative pulmonary complications before day 10 was 0.65 (95% CI, 0.55 to 0.75; P = 0.003). Lung ultrasound score greater than 12 had a sensitivity of 0.54 (95% CI, 0.40 to 0.67), specificity of 0.77 (95% CI, 0.67 to 0.85), and negative predictive value of 0.74 (95% CI, 0.65 to 0.83). Lung ultrasound score greater than 17 had sensitivity of 0.33 (95% CI, 0.21 to 0.47), specificity of 0.95 (95% CI, 0.88 to 0.98), and positive predictive value of 0.78 (95% CI, 0.56 to 0.93). Anterolateral lung ultrasound score and composite scores using lung ultrasound score and other patient characteristics showed similar predictive accuracies. CONCLUSIONS: An elevated lung ultrasound score on postoperative day 1 is associated with the occurrence of pulmonary complications within the first 10 days after major abdominal surgery.

Splenic vein tumor thrombosis is a major prognostic factor in distal pancreatic adenocarcinoma.

BACKGROUND: The prognostic value of splenic vessel involvement in distal pancreatic adenocarcinoma remains controversial. The aim of the study was to assess its prognostic relevance in a large multicenter cohort. METHODS: Patients who underwent pancreatosplenectomy for distal pancreatic adenocarcinoma were identified from 5 pancreatic surgical centers. A pathology review of the surgical specimens was performed to assess splenic vessel involvement, defined as invasion of the vessel's adventitia or deeper, and confirm the presence of splenic vein tumor thrombosis. Prognostic factors associated with overall and relapse-free survival were evaluated. RESULTS: 149 patients underwent upfront surgery. Splenic vascular involvement was observed in 69 of them (46.3%). A parietal infiltration of the splenic artery or splenic vein was observed in 26 (17.5%) and 49 patients (32.8%), respectively. A pathologic tumor thrombosis of the splenic vein was identified in 22 patients (14.8%) and associated with larger tumors (>20 mm) (P = .023), more perineural (P = .017), and lymphovascular (P = .002) invasion, and more positive lymph node (P = .001). After a median follow-up of 50.8 months (95% confidence interval: 44.3-57.3), the cumulative 5-year overall and relapse-free survival were 46.2% and 33%, respectively. In multivariate analysis, in addition to lymph node metastasis (hazard ratio = 1.8; 95% confidence interval [1.1-3.1]; P = .023) and perineural invasion (hazard ratio = 3.5; 95% confidence interval [1.3-9.7]; P = .016), presence of splenic vein tumor thrombosis was the only splenic vascular involvement that affected independently the overall survival (HR = 2.3; 95% confidence interval [ 1.3-4.3]; P = .006). CONCLUSION: In resectable distal pancreatic adenocarcinoma, a pathologic tumor thrombosis of the splenic vein is an independent prognostic factor of overall survival. To define the perioperative oncological strategy, a preoperative evaluation of splenic vessel involvement and thrombosis is needed.

Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

Strategy for Oligometastatic Recurrence of Cardia Adenocarcinoma: Liver Radiofrequency Ablation Associated with PIPAC Inducing Response Permitting Cytoreductive Surgery and HIPEC.

Management of oligometastatic disease (OMD) in esophagogastric junction cancer is complex due to anatomical location and adenocarcinoma pathway. Specific curative strategy is mandatory to increase survival. A multimodal approach combining surgery, systemic and peritoneal chemotherapy, radiotherapy, and radiofrequency could be envisaged. We report a strategy proposed for a 61-year-old male with cardia adenocarcinoma, initially treated with chemotherapy and superior polar esogastrectomy. He developed at later stage an OMD with peritoneal metastasis, single liver metastasis, and single lung metastasis. Considering that peritoneal metastases were unresectable at first, he was given multiple Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with oxaliplatin, associated with intravenous docetaxel. Percutaneous radiofrequency ablation was performed during the first PIPAC procedure. Peritoneal response allowed a secondary Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

Medicinal Plants and Plant-Based Remedies in Grande-Terre: An Ethnopharmacological Approach.

The island of Grande-Terre is a French overseas region that belongs to the Guadeloupean archipelago, a biodiversity hotspot with unique flora. Herbal medicine is widely used in the island for therapeutical purposes; however, there is a significant knowledge gap in the records relating to medicinal plants and their associated uses. Ethnobotanical survey methodology using quantitative parameters (informant consensus factor, species use value, relative frequency of citation, frequency use of a treatment and plant for an ailment) provided insights into the traditional medicinal use of a given plant. Ninety-six different plant species distributed among 56 families were identified and 523 remedies were documented in the survey. After data filtering, 22 plants species were associated with 182 remedies. The most frequent plant families were Poaceae, Myrtaceae, Cucurbitaceae and Rubiaceae. Aerial parts of these plants were the most common parts of the plant used for the remedies and the most frequent mode of administration was oral ingestion. This study highlights a valuable traditional knowledge of folklore medicine and helps to document and preserve the association of a plant with-and its use frequency for-a given ailment. These findings might be the starting point for the identification of biologically active phytocompounds to fight common health debilities.

Follow-Up, Safety, and Satisfaction with Tele-bariatric Follow-Up Implemented During the COVID-19 French Lockdown: a 2-Year Follow-Up Study.

BACKGROUND: The COVID-19 pandemic was initially responsible for a global restricted access to healthcare resources including the follow-up of at-risk populations such as bariatric patients. We substituted face-to-face bariatric follow-up outpatient clinics (FTFC) with teleclinics (TC) during the lockdown. MATERIAL AND METHODS: We retrospectively reviewed data collected on all patients scheduled for TC during the French lockdown period (March 15 to May 15, 2020) (N = 87). Our aims were to present the patients' outcomes at one and 2 years post-TC implementation and describe patient/practitioner satisfaction. RESULTS: Seven (8%) patients required FTFC, and 80 (92%) underwent TC (study population) for preoperative bariatric assessment (N = 3) and postoperative follow-up (N = 77) after 23.6 ± 29 months following surgery. TC was performed with video and audio (N = 46; 57.5%) or audio alone when video was impossible (N = 34; 42.5%). Sixteen (20%) patients presented at least one complication identified at the first TC and were managed accordingly. There were no readmissions at 30/90 days post-TC. At 1-year after the first TC, overall follow-up rate was 94.9% (TC: 73% vs FTFC: 27%). Patients surveyed on the main advantages of TC over FTFC (N = 46) cited: saving time (97.8%) at a mean 3.9 ± 6.4 h saved per TC, work-advantages (94.3%), and comparable relevance of TC (84.8%). At 2 years post-TC implementation, follow-up rate was 93.5% and satisfaction rate was 80%, with 33% of patients preferring to return to FTFC. CONCLUSIONS: TC is a satisfactory substitute for FTFC, enabling continued bariatric follow-up during and beyond the pandemic setting without compromising patient safety. However, the modest satisfaction outcomes at 2 years highlight a need to discuss follow-up preferences in order to achieve optimal outcomes.

Outcomes of rescue procedures in the management of locally recurrent ampullary tumors: A Pancreas 2000/EPC study.

BACKGROUND: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied. METHODS: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018. RESULTS: A total of 103 patients were included, 21 (20.4%) treated with redo endoscopic papillectomy, 14 (13.6%) with transduodenal surgical ampullectomy, and 68 (66%) with pancreaticoduodenectomy. Redo endoscopic papillectomy had low morbidity with 4.8% (n = 1) severe to fatal complications and a R0 rate of 81% (n = 17). Transduodenal surgical ampullectomy and pancreaticoduodenectomy after a first procedure had a higher morbidity with Clavien III and more complications, respectively, 28.6% (n = 4) and 25% (n = 17); R0 resection rates were 85.7% (n = 12) and 92.6% (n = 63), both without statistically significant difference compared to endoscopic papillectomy (P = .1 and 0.2). Pancreaticoduodenectomy had 4.4% (n = 2) mortality. No deaths were registered after transduodenal surgical ampullectomy or endoscopic papillectomy. Recurrences treated with pancreaticoduodenectomy were more likely to be adenocarcinomas (79.4%, n = 54 vs 21.4%, n = 3 for transduodenal surgical ampullectomy and 4.8%, n = 1 for endoscopic papillectomy, P < .0001). Three-year overall survival and disease-free survival were comparable. CONCLUSION: Endoscopy is appropriate for noninvasive recurrences, with resection rate and survival outcomes comparable to surgery. Surgery applies more to invasive recurrences, with transduodenal surgical ampullectomy rather for carcinoma in situ and early cancers and pancreaticoduodenectomy for more advanced tumors.

IL-17A in Human Liver: Significant Source of Inflammation and Trigger of Liver Fibrosis Initiation.

IL-17A is considered to guide liver inflammation and fibrosis. From twenty-two human liver samples of different fibrosis stages (F0 to F4), IL-17A, IL-22, and TGFß1 protein expression in liver tissue lysates were analyzed. Ten paired samples of liver tissue (F0-F1 stage) and blood from the same patient were used to analyze intrahepatic and blood T-lymphoid IL-17A+ cells by flow cytometry. The analyses have been performed regardless of pathology, considering the stage of fibrosis. Human liver tissue was used for the primary human liver slice cultures, followed by subsequent cytokine stimulation and fibrotic markers' analysis by ELISA. IL-17A production in human liver tissue was significantly higher in the early fibrotic stage compared with the advanced stage. Th17 T cells and, to a lesser extent, MAIT cells were the main sources of IL-17A in both compartments, the liver and the blood. Moreover, the presence of liver Th17IL-17A+INFγ+ cells was detected in the liver. IL-17A stimulation of human liver slice culture increased the expression of profibrotic and pro-inflammatory markers. IL-17A, secreted by Th17 and MAIT cells in the liver, triggered fibrosis by inducing the expression of IL-6 and profibrotic markers and could be a target for antifibrotic treatment. Further amplitude studies are needed to confirm the current results.

Encorafenib plus cetuximab treatment in BRAF V600E-mutated metastatic colorectal cancer patients pre-treated with an anti-EGFR: An AGEO-GONO case series.

BACKGROUND: Encorafenib plus cetuximab is efficient in anti-EGFR-naïve patients with BRAFV600E mutated (BRAFm) metastatic colorectal cancer (mCRC). No data are available concerning the efficacy of BRAF inhibitors associated with anti-EGFRs (B + E) in patients previously treated with an anti-EGFR agent. METHODS: We retrospectively collected a series of patients with BRAFm mCRC treated with B + E after previous anti-EGFR treatment, in 14 centers. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment, and we reported objective response and disease control rates (ORR, DCR; RECIST V1.1). RESULTS: Twenty-five BRAFm mCRC patients were enrolled. Prior to B + E treatment, 4/10/11 patients were treated with 1/2/> 2 previous treatment lines. Ten patients received previous panitumumab, 14 cetuximab, 1 both. Immediate progression with previous anti-EGFR was reported for 7 patients. Anti-BRAF was encorafenib for 21 patients, dabrafenib for 4 patients, with cetuximab for 24 patients and panitumumab for 1 patient. ORR was 40% (10 patients) and DCR was 80% (20 patients). Median PFS and OS were 4.8 months (95% CI, 4.01-7.95) and 10.1 months (95% CI, 7.75-NR). DCR amongst patients with previous primary resistance to anti-EGFR (N = 7) was 100%. Two patients discontinued B + E due to drug-related adverse event. CONCLUSIONS: Though in a limited retrospective series of patients, these results show the efficacy of the combination of anti-BRAF and anti-EGFRs in BRAFm mCRC patients previously treated with an anti-EGFR. The use of this combination should thus not be ruled out in this population with limited therapeutic options.

Restrictive intraoperative fluid intake in liver surgery and postoperative renal function: A propensity score matched study.

BACKGROUND: Postoperative acute kidney injury (AKI) is a common complication in hepatic surgery. In hepatic surgery, relative hypovolemia may help to limit blood loss, but the consequences of restrictive fluid intake are unknown. The goal of this study was to determine the influence of intraoperative fluid intake on the incidence of AKI and its consequences. METHODS: Data from 397 consecutive patients who underwent liver resection were prospectively recorded and retrospectively analyszed. We compared the incidence of postoperative acute kidney failure in patients given restrictive (≤ 5 mL/kg/h) versus liberal (> 5 mL/kg/h) fluid therapy. We calculated a 1:1 match propensity score using logistic regression to estimate the likelihood of patients receiving restrictive or liberal intraoperative fluid intakes. The association between the intraoperative fluid intake strategy and occurrence of postoperative AKI were tested using a Cox frailty model on the database of matched patients. RESULTS: Postoperative AKI was diagnosed in 133 of the 397 patients. Fluid intake strategy was restrictive for 121 patients and liberal for 276 patients. After propensity score matching to balance confounding factors, the liberal strategy was associated with a significantly lower risk for postoperative AKI compared to the restrictive strategy (Hazard Ratio 0.40 [0.29; 0.56], P<0.001). Patients with postoperative AKI had longer hospital stays and higher mortality. There were no cases of further blood loss in the liberal fluid intake group. CONCLUSIONS: A restrictive fluid intake strategy is a risk factor for developing postoperative AKI, with serious consequences, without reducing blood loss in liver surgery.

Circulating tumor DNA: a help to guide therapeutic strategy in patients with borderline and locally advanced pancreatic adenocarcinoma?

BACKGROUND: prognostic biomarkers could be useful to better select patients with borderline resectable (BR) or locally advanced (LA) pancreatic adenocarcinoma (PA) for chemoradiotherapy (CRT) and/or secondary resection. AIMS: The main objective of this work was to study characteristics, received treatments and prognostic of patients with BR or LA PA according to their baseline circulating tumor DNA status and, for secondary objective, neutrophil-to-lymphocyte Ratio (NLR). METHODS: ctDNA status at baseline was determined using Next Generation Sequencing in a consecutive monocentric cohort of patients with a BR or LA PA. RESULTS: 69 patients were included, 31 with BR PA and 38 with LA PA. 14 (20.3%) patients had baseline positive ctDNA. Five (7.8%) patients had NLR> 5. Patients with positive ctDNA had 3.7 months shorter progression free survival (p = 0.006). Patients with positive ctDNA had earlier progression after the beginning of CRT (4.4 vs 7.1 months; p = 0.068) and shorter relapse free survival after secondary resection (9.2 vs 22.9 months; p = 0.016). CONCLUSIONS: positive ctDNA at baseline was associated with a worse prognosis in patients with BR or LA PA. These data are exploratory and must be confirmed in further prospective trials.

"De novo" cholangiocarcinoma 20 years after liver transplantation for primary sclerosing cholangitis: Lifelong screening needed!

We report a rare and very late case of de novo cholangiocarcinoma in a patient transplanted for primary sclerosing cholangitis. An exhaustive analysis of the literature and of our case highlight the very poor prognosis of this type of tumor due to the delay in diagnosis and the potential value of a six-monthly MRI surveillance as soon as cholangitis recurs, but also in the presence of chronic digestive inflammation, whatever the mechanism.

Liver transplantation for iatrogenic bile duct injury during cholecystectomy: a French retrospective multicenter study.

BACKGROUND: Major bile duct injuries (BDI) following cholecystectomy require complex reconstructive surgery. The aim was to collect the liver transplantations (LT) performed in France for major BDI following cholecystectomy, to analyze the risk factors and to report the results. METHODS: National multicenter observational retrospective study. All the patients who underwent a LT in France between 1994 and 2017, for BDI following cholecystectomy, were included. RESULTS: 30 patients were included. 25 BDI occurred in non hepato-biliary expert centers, 20 were initially treated in these centers. Median time between injury and LT was 3 years in case of an associated vascular injury (11 injuries), versus 11.7 years without vascular injury (p = 0.006). Post-transplant morbidity rate was 86.7%, mortality 23.5% at 5 years. CONCLUSION: Iatrogenic BDI remains a real concern with severe cases, associated with vascular damages or leading to cirrhosis, with no solution but LT. It is associated with high morbidity and not optimal results. This enlights the necessity of early referral of all major BDI in expert centers to prevent dramatic outcome. Decision to perform transplantation should be taken before dismal infectious situations or biliary cirrhosis and access to graft should be facilitated by Organ Sharing Organizations.

Pulmonary infection after hepatic resection: Associated factors and impact on outcomes.

BACKGROUND AND AIMS: Postoperative pulmonary complications are frequent after hepatectomy. The aim of this retrospective study was to use preoperative and intraoperative data to establish specific factors associated with post-hepatectomy pneumonia (PHPN). METHODS: Patients underwent minor or major hepatectomy for cancer or non-cancer treatment. Surgical procedure was performed by laparoscopy or laparotomy. PHPN was defined as a new radiologic finding associated with fever, leucocytosis and purulent bronchial secretions. The incidence, associated factors and prognosis of PHPN were investigated. RESULTS: In 399 patients undergoing planned hepatectomy, 49 (12.3%) developed pneumonia. Of 81 patients (20.3%) with cirrhosis, 77 were Child-Pugh A and 4 were Child-Pugh B. Hepatectomy indication was cancer in 331 patients (of which metastasis in 213). Laparoscopy rate was 31.3%. In multivariate analysis, the main factors statistically associated with PHPN were: chronic obstructive pulmonary disease (COPD) (odds ratio [OR] = 4.17; 95% confidence interval [CI], 1.60-10.84; P = 0.003), intraoperative blood transfusion (OR = 2.46; 95% CI 1.01-5.70; P = 0.001), laparotomy (OR = 3.01; 95% CI 1.09-8.27; P = 0.03), and nasogastric tube maintained at day 1 (OR = 2.09; 95% CI 1.03-4.22; P = 0.04). Length of stay was significantly different between groups without PHPN (10.2 days) versus with PHPN (26.4 days; P < 0.001). Intra-hospital and one-year mortality were greater in the PHPN group than the pneumonia-free group (8.16 vs 0% and 18.4 vs 3.4%, respectively; P < 0.001). CONCLUSIONS: COPD, transfusion and laparotomy (versus laparoscopy) are factors associated with PHPN and impaired survival.