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.

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.

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.

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.

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.

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.

"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.

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.

The Host Protein Aquaporin-9 is Required for Efficient Plasmodium falciparum Sporozoite Entry into Human Hepatocytes.

Hepatocyte invasion by Plasmodium sporozoites represents a promising target for innovative antimalarial therapy, but the molecular events mediating this process are still largely uncharacterized. We previously showed that Plasmodium falciparum sporozoite entry into hepatocytes strictly requires CD81. However, CD81-overexpressing human hepatoma cells remain refractory to P. falciparum infection, suggesting the existence of additional host factors necessary for sporozoite entry. Here, through differential transcriptomic analysis of human hepatocytes and hepatoma HepG2-CD81 cells, the transmembrane protein Aquaporin-9 (AQP9) was found to be among the most downregulated genes in hepatoma cells. RNA silencing showed that sporozoite invasion of hepatocytes requires AQP9 expression. AQP9 overexpression in hepatocytes increased their permissiveness to P. falciparum. Moreover, chemical disruption with the AQP9 inhibitor phloretin markedly inhibited hepatocyte infection. Our findings identify AQP9 as a novel host factor required for P. falciparum sporozoite hepatocyte-entry and indicate that AQP9 could be a potential therapeutic target.

Atrio-oesophageal fistula following atrial fibrillation ablation: how to manage this dreaded complication?

OBJECTIVES: Atrio-oesophageal fistula is a rare but serious complication of radiofrequency catheter ablation of atrial fibrillation. Therapeutic options are surgery, oesophageal stenting and conservative treatment (antibiotics and anticoagulation). However, there are no guidelines available. Since no article dwells on the technical considerations of this surgery, we aim to present here our experience and share our surgical approach. METHODS: Between January 2012 and March 2020, all consecutive patients treated for atrio-oesophageal fistula following radiofrequency catheter ablation of atrial fibrillation at our institution were analysed retrospectively. The diagnosis was made on a set of clinical and radiological signs. All patients benefitted from a combined approach involving both digestive and cardiac surgeons. Femoro-femoral peripheral cardiopulmonary by-pass was used. The surgical approach was a right posterolateral thoracotomy. Atrial repair was done on fibrillating heart without cross-clamping, using a left atriotomy. Digestive management consisted of a total oesophagectomy. RESULTS: We identified 6 patients with this complication. The median age was 53 [34-72] years. Symptoms were neurological symptoms, fever and chest pain. Diagnostic modalities were cerebral imaging, chest CT and transthoracic echocardiogram. Atrial repair consisted in a suture of the atrium or by using a pericardial patch. With a median follow-up of 3.1 [0.1-7.7] years, only one patient died during the follow-up. CONCLUSIONS: Our experience shows that an aggressive surgery with a large resection of the oesophagus and left atrial repair by right thoracotomy in the same time provides good results. The ability to involve simultaneously both experienced digestive and cardiac surgical teams is the key for this strategy.