Endothelial autophagy is not required for liver regeneration after partial hepatectomy in mice with fatty liver.

BACKGROUND & AIMS: Patients with non-alcoholic fatty liver disease (NAFLD) have impaired liver regeneration. Liver endothelial cells play a key role in liver regeneration. In non-alcoholic steatohepatitis (NASH), liver endothelial cells display a defect in autophagy, contributing to NASH progression. We aimed to determine the role of endothelial autophagy in liver regeneration following liver resection in NAFLD. METHODS: First, we assessed autophagy in primary endothelial cells from wild type mice fed a high fat diet and subjected to partial hepatectomy. Then, we assessed liver regeneration after partial hepatectomy in mice deficient (Atg5lox/lox ;VE-cadherin-Cre+ ) or not (Atg5lox/lox ) in endothelial autophagy and fed a high fat diet. The role of endothelial autophagy in liver regeneration was also assessed in ApoE-/- hypercholesterolemic mice and in mice with NASH induced by methionine- and choline-deficient diet. RESULTS: First, autophagy (LC3II/protein) was strongly increased in liver endothelial cells following hepatectomy. Then, we observed at 40 and 48 h and at 7 days after partial hepatectomy, that Atg5lox/lox ;VE-cadherin-Cre+ mice fed a high fat diet had similar liver weight, plasma AST, ALT and albumin concentration, and liver protein expression of proliferation (PCNA), cell-cycle (Cyclin D1, BrdU incorporation, phospho-Histone H3) and apoptosis markers (cleaved Caspase-3) as Atg5lox/lox mice fed a high fat diet. Same results were obtained in ApoE-/- and methionine- and choline-deficient diet fed mice, 40 h after hepatectomy. CONCLUSION: These results demonstrate that the defect in endothelial autophagy occurring in NASH does not account for the impaired liver regeneration occurring in this setting.

Local excision after neoadjuvant chemoradiotherapy for mid and low rectal cancer: a multicentric French study from the GRECCAR group.

AIM: A complete or subcomplete tumour response (CTR) is observed in 10%-25% of patients with mid/low rectal cancer after neoadjuvant chemoradiotherapy (CRT). The aim of our study was to report a multicentric French experience in local excision (LE) after CRT. METHOD: All patients who underwent LE for mid/low rectal cancer with suspected CTR after CRT, from 2006 to 2019 in seven GRECCAR centres were included. LE was considered adequate if the specimen showed a ypT0/Tis/T1R0 tumour, otherwise, a completion total mesorectal excision (TME) was discussed. Morbi-mortality, functional results and oncological outcomes were studied. RESULTS: A total of 257 patients were included. LE specimens showed 36% ypT0, 4% ypTis and 19% ypT1. Thus, 108 patients (42%) had theoretical indication of completion TME, which was performed in only 42 patients. Overall, 30-day morbidity after LE was 11%, including 2% Clavien-Dindo grade III or IV complications. After completion TME, 47% described major low anterior resection syndrome versus 5% after LE alone (p < 0.001). After a mean follow-up of 4 years (range 2-6 years), the recurrence rate was 11% after LE, 32% after completion TME and 20% in patients for whom completion TME was indicated but not performed (p = 0.021). CONCLUSION: TME remains the gold standard for mid/low rectal cancer after CRT. LE in selected patients is safe for operative and functional, but also oncological, results. However, completion TME was indicated in 42% of patients after LE, highlighting the difficulty of the preoperative diagnosis of CTR after CRT.

Endoscopic internal drainage and low negative-pressure endoscopic vacuum therapy for anastomotic leaks after oncologic upper gastrointestinal surgery.

BACKGROUND: Endoscopic internal drainage (EID) with double-pigtail stents or low negative-pressure endoscopic vacuum therapy (EVT) are treatment options for leakage after upper gastrointestinal oncologic surgery. We aimed to compare the effectiveness of these techniques. METHODS: Between 2016 and 2019, patients treated with EID in five centers in France and with EVT in Göttingen, Germany were included and retrospectively analyzed using univariate analysis. Pigtail stents were changed every 4 weeks; EVT was repeated every 3-4 days until leak closure. RESULTS: 35 EID and 27 EVT patients were included, with a median (interquartile range [IQR]) leak size of 0.75 cm (0.5-1.5). Overall treatment success was 100 % (95 % confidence interval [CI] 90 %-100 %) for EID vs. 85.2 % (95 %CI 66.3 %-95.8 %) for EVT (P = 0.03). The median (IQR) number of endoscopic procedures was 2 (2-3) vs. 3 (2-6.5; P = 0.003) and the median (IQR) treatment duration was 42 days (28-60) vs. 17 days (7.5-28; P < 0.001), for EID vs. EVT, respectively. CONCLUSION: EID and EVT provide high closure rates for upper gastrointestinal anastomotic leaks. EVT provides a shorter treatment duration, at the cost of a higher number of procedures.

Redo-surgery after failed colorectal or coloanal anastomosis: Morbidity, mortality and factors predictive of success. A retrospective study of 200 patients.

AIM: In cases of anastomotic failure after colorectal (CRA) or coloanal anastomosis (CAA), revision of the anastomosis is an ambitious surgical option that can be proposed in order to maintain bowel continuity. Our aim was to assess postoperative morbidity, risk of failure and risk factor for failure in patients after CRA or CAA. METHODS: All consecutive patients who underwent redo-CRA/CAA in our institution between 2007-2018 were retrospectively included. The success of redo-CRA/CAA was defined by the restoration of bowel continuity 12 months after the surgery. RESULTS: Two hundred patients (114 male: 57%) were analyzed. The indication for redo-CRA/CAA was chronic pelvic infection in 74 patients (37%), recto-vaginal or urinary fistula in 59 patients (30%), anastomotic stenosis in 36 patients (18%) and redo anastomosis after previous anastomosis takedown in 31 patients (15%). Twenty-three percent of the patients developed a severe postoperative complication. Anastomotic leakage was diagnosed in 39 patients (20%). One-year-success of the redo-CRA/CAA was obtained in 80% of patients. In multivariate analysis, only obesity was associated with redo-CRA/CAA failure (p = 0.042). We elaborated a pre-operative predictive score of success using the four variables: male sex, age > 60 years, obesity and history of pelvic radiotherapy. The success of redo-CRA/CAA was 92%, 86%, 80% and 62% for a preoperative predictive score value of 0, 1, 2 and ≥3, respectively (p = 0.010). CONCLUSIONS: In case of failure of primary CRA/CAA, bowel continuity can be saved in 4 out of 5 patients by redo-CRA/CAA despite 23% suffering severe postoperative morbidity.

Laparoscopic pancreaticoduodenectomy with reconstruction of the mesentericoportal vein with the parietal peritoneum and the falciform ligament.

BACKGROUND: With the improvement of the surgical technique of Laparoscopic pancreaticoduodenectomy (LPD), indications will be extended to patients with vascular invasion. With LPD, vascular grafts for reconstruction are more frequently needed because adequate mobilization is not always done and vascular grafts can safely facilitate reconstruction. We describe our experience of reconstruction with the falciform ligament. METHODS: Venous reconstruction is performed after removal of the specimen. The falciform ligament is rapidly harvested within the same surgical field and for any size and used for lateral reconstruction of the mesentericoportal vein. Therapeutic anticoagulation is not needed and venous patency was assessed by postoperative CT scan. Since April 2011 and among the 93 patients who underwent LPD, four patients had this procedure. RESULTS: The mean age was 73 years old (69-77) and 3 were women. Indications for resection were pancreatic adenocarcinoma (n = 3) and IPMN in severe dysplasia (n = 1) and the mean patch size of 13 mm (10-30). The mean operative time was 397 min (330-480); vascular clamping lasted 54 min (45-60), and mean blood loss was 437 ml (150-1000) and one was transfused. Resection was R0 in patients with adenocarcinoma (n = 3). The postoperative course was uneventful in 3 patients and one patient was re-operated for bile leak and partial venous thrombosis and redo venous reconstruction was done. Complete venous patency was demonstrated in patients (n = 2) who still alive 1 year after resection. CONCLUSION: Venous resection will be more frequently done with LPD and vascular grafts more frequently needed. Compared to other available vascular grafts (autogenous, synthetic, cadaveric and bovine pericardium, etc), the parietal peritoneum had the advantages of being rapidly available, easy to harvest by the laparoscopic approach, not expensive, no need for anticoagulation and at lower risk of infection.

Functional outcomes of patients undergoing successful redo surgery after failed primary colorectal or coloanal anastomosis for rectal cancer.

BACKGROUND: After a failure of a colorectal or coloanal anastomosis, redo anastomotic surgery aims to avoid the risk of permanent stoma but, overall, to provide a satisfactory functional result and quality of life. Very limited data exist regarding the long-term results after a successful redo anastomosis. The present study aimed to report the long-term functional outcomes and quality of life in patients after a successful redo colorectal anastomosis or coloanal anastomosis. METHODS: Between 2007 and 2018, all patients who had a successful restoration of bowel continuity after a failed primary anastomosis performed for a rectal cancer were included. Functional outcomes and quality of life were assessed using the low anterior rectal syndrome score and the Gastrointestinal Quality of Life Index. RESULTS: One hundred and twenty-seven patients were eligible for inclusion in this study, with long-term functional outcomes assessed in 73 patients (57%). After a median follow-up of 69 months, 31 patients presented no or minor low anterior rectal syndrome (42%), whereas 31 patients reported a major low anterior rectal syndrome (42%). A definitive stoma was confectioned in 11 patients (15%), despite the technical success of redo anastomosis due to poor functional results. Only operative interval <36 months was associated with a poor functional outcome (P = .001), whereas all other factors such as pelvic radiotherapy were not (P = .848). An absence of major low anterior rectal syndrome was the only factor associated with improved quality of life (P = .001). CONCLUSION: After successful redo colorectal anastomosis or coloanal anastomosis, good functional outcomes can be achieved in almost half of patients with a well-preserved quality of life but requires a prolonged postoperative period of rehabilitation.

Endoscopic management of anastomotic leak after esophageal or gastric resection for malignancy: a multicenter experience.

BACKGROUND: Most anastomotic leaks after surgical resection for esophageal or esophagogastric junction malignancies are treated endoscopically with esophageal stents. Internal drainage by double pigtail stents has been used for the endoscopic management of leaks following bariatric surgery, and recently introduced for anastomotic leaks after resections for malignancies. Our aim was to assess the overall efficacy of the endoscopic treatment for anastomotic leaks after esophageal or gastric resection for malignancies. METHODS: We conducted a multicenter retrospective study in four digestive endoscopy tertiary referral centers in France. We included consecutive patients managed endoscopically for anastomotic leak following esophagectomy or gastrectomy for malignancies between January 2016 and December 2018. The primary outcome was the efficacy of the endoscopic management on leak closure. RESULTS: Sixty-eight patients were included, among which 46 men and 22 women, with a mean ± SD age of 61 ± 11 years. Forty-four percent had an Ivor Lewis procedure, 16% a tri-incisional esophagectomy, and 40% a total gastrectomy. The median time between surgery and the diagnosis of leak was 9 (6-13) days. Endoscopic treatment was successful in 90% of the patients. The efficacy of internal drainage and esophageal stents was 95% and 77%, respectively (p = 0.06). The mortality rate was 3%. The only predictive factor of successful endoscopic treatment was the initial use of internal drainage (p = 0.002). CONCLUSION: Endoscopic management of early postoperative leak is successful in 90% of patients, preventing highly morbid surgical revisions. Internal endoscopic drainage should be considered as the first-line endoscopic treatment of anastomotic fistulas whenever technically feasible.

What is the functional result of a delayed coloanal anastomosis in redo rectal surgery?

BACKGROUND: Delayed coloanal anastomosis (DCAA) may be used in patients with complex rectal conditions, such as chronic pelvic sepsis, low recto-vaginal and recto-vesical fistula; however, limited data are available. The aim is to report the morbidity and functional results of DCAA in redo rectal surgery. METHODS: All patients undergoing DCAA between January 2014 and August 2017 were retrospectively included. Success was defined as a functional anastomosis without stoma, evaluated using the Low Anterior Resection Syndrome (LARS) score and the Gastrointestinal Quality of Life Index (GIQLI) functional assessment tools. RESULTS: Of the 72 redo pelvic surgeries, 29 (40.3%) DCAA were performed over a 4-year period. Indications for redo resection were chronic pelvic sepsis (n = 13, 44.8%), recto-vaginal fistula (n = 11, 37.9%) and recto-vesical fistula (n = 5, 17.2%). Mean interval period between the two procedures was 14 ± 3 days (8-21). Global major morbidity (Clavien-Dindo III or IV) was seen in six patients (20.7%). Stoma closure was feasible for 22 (75.9%) patients after a median period of 78 days (interquartile range 61-98). The 6-month success rate was 79.3%. Mean LARS was 28.8 ± 10.2 (3-41) (minor LARS) for 18 patients with no stoma at the end of follow-up. LARS score was significantly better with a follow-up >2 years (23.3 ± 12.2 versus 32.3 ± 7.9), P = 0.074. Mean GIQLI score was 79.2 ± 14.3 (48-98). CONCLUSIONS: Transanal colonic pull through with delayed anastomosis for redo-surgery in complex pelvic situations had low morbidity and avoided a permanent stoma in three out of four patients with an acceptable quality of life.