Are enhanced recovery protocols after pancreatoduodenectomy still efficient when applied in elderly patients? A systematic review and individual patient data meta-analysis.

BACKGROUND: This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD). METHODS: Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included. The main outcomes were postoperative morbidity, length of stay, readmission and postoperative functional recovery elements. To assess an age-dependent effect, the group was divided in septuagenarians (70-79 years) and older patients (≥80 years). RESULTS: IPD were obtained from 15 of 31 eligible studies comprising 1109 patients. The overall complication and major complication rates were comparable in both groups (OR 0.92 [95% CI: 0.65-1.29], p = .596 and OR 1.22 [95% CI: 0.61-2.46], p = .508). Length of hospital stay tended to be shorter in the ERAS group compared to the conventional care group (-0.14 days [95% CI: -0.29 to 0.01], p = .071) while readmission rates were comparable and the total length of stay including days in hospital after readmission tended to be shorter in the ERAS group (-0.28 days [95% CI: -0.62 to 0.05], p = .069). In the subgroups, the length of stay was shorter in octogenarians treated with ERAS (-0.36 days [95% CI: -0.71 to -0.004], p = .048). The readmission rate increased slightly but not significantly while the total length of stay was not longer in the ERAS group. CONCLUSION: ERAS in the elderly is safe and its benefits are preserved in the care of even in patients older than 80 years. Standardized care protocol should be encouraged in all pancreatic centers.

Impact of enhanced recovery protocols after pancreatoduodenectomy: meta-analysis.

BACKGROUND: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy. METHODS: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission. RESULTS: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate. CONCLUSION: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged.

Enhanced recovery protocols consist of interdisciplinary interventions aimed at standardizing care and reducing the impact of surgical stress. They often include a short period of preoperative fasting during the night before surgery, early removal of lines and surgical drains, early food intake and mobilization out of bed on the day of surgery. This study gives a summary of reports assessing such care protocols in patients undergoing pancreatic head surgery, and assesses the impact of these protocols on functional recovery in an analysis of individual-patient data. The study revealed the true benefits of enhanced recovery protocols, including shorter time to food intake, earlier bowel activity, fewer complications after surgery, and a shorter hospital stay compared with conventional care.

Unifying the Hepatopancreatobiliary Surgery Fellowship Curriculum via Delphi Consensus.

BACKGROUND: Hepatopancreatobiliary (HPB) Fellowship training in the Americas consists of 3 distinctive routes with variable curricula: Surgical Oncology Fellowship via the Society of Surgical Oncology (SSO), Abdominal Transplant Surgery Fellowship via the American Society of Transplant Surgeons (ASTS), and HPB Fellowship via the Americas Hepato-Pancreato-Biliary Association (AHPBA). Our objective was to establish a pan-American consensus among HPB surgeons, surgical oncologists, abdominal transplant surgeons, and general surgery residency program directors (GSPDs) on a core knowledge curriculum for HPB fellowship, and to identify topics appropriate for general surgery residency and subspecialty beyond HPB fellowship. STUDY DESIGN: A 3-round modified Delphi process was used. Baseline statements were developed by the Education and Training Committee of the AHPBA, in collaboration with representatives of the SSO, ASTS, and GSPDs. The expert panel, consisting of members of the 3 societies together with GSPDs, rated the statements on a 5-point Likert scale and suggested editing or adding new statements. A statement was included in the final curriculum when Cronbach's alpha value was ≥ 0.8 and ≥ 80% of the panel agreed on inclusion. RESULTS: The response rate was 100% for the first round, and 98% for the second and third rounds. Eighty-nine of 138 proposed statements were included in the final HPB fellowship curriculum. Curricula for general surgery residency and subspecialty beyond HPB fellowship included 50 and 29 statements, respectively. CONCLUSIONS: A multinational consensus on core knowledge for an HPB fellowship curriculum was achieved via the modified Delphi method. This core curriculum may be used to standardize HPB fellowship training across different pathways in the Americas.

An objective approach to evaluate novice robotic surgeons using a combination of kinematics and stepwise cumulative sum (CUSUM) analyses.

BACKGROUND: Current evaluation methods for robotic-assisted surgery (ARCS or GEARS) are limited to 5-point Likert scales which are inherently time-consuming and require a degree of subjective scoring. In this study, we demonstrate a method to break down complex robotic surgical procedures using a combination of an objective cumulative sum (CUSUM) analysis and kinematics data obtained from the da Vinci® Surgical System to evaluate the performance of novice robotic surgeons. METHODS: Two HPB fellows performed 40 robotic-assisted hepaticojejunostomy reconstructions to model a portion of a Whipple procedure. Kinematics data from the da Vinci® system was recorded using the dV Logger® while CUSUM analyses were performed for each procedural step. Each kinematic variable was modeled using machine learning to reflect the fellows' learning curves for each task. Statistically significant kinematics variables were then combined into a single formula to create the operative robotic index (ORI). RESULTS: The inflection points of our overall CUSUM analysis showed improvement in technical performance beginning at trial 16. The derived ORI model showed a strong fit to our observed kinematics data (R2 = 0.796) with an ability to distinguish between novice and intermediate robotic performance with 89.3% overall accuracy. CONCLUSIONS: In this study, we demonstrate a novel approach to objectively break down novice performance on the da Vinci® Surgical System. We identified kinematics variables associated with improved overall technical performance to create an objective ORI. This approach to robotic operative evaluation demonstrates a valuable method to break down complex surgical procedures in an objective, stepwise fashion. Continued research into objective methods of evaluation for robotic surgery will be invaluable for future training and clinical implementation of the robotic platform.

Operative Microwave Ablation for the Multimodal Treatment of Neuroendocrine Liver Metastases.

Background and Purpose: Operative microwave ablation (MWA) is a safe modality for treating hepatic tumors. The aim of this study is to present our 10-year, single-center experience of operative MWA for neuroendocrine liver metastases (NLM). Methods: A single-institution retrospective review of patients who underwent operative MWA for NLM was performed (2008-2018). Demographics, primary tumor site, operative approach, combined surgical operations, and carcinoid symptoms were recorded. Clinical outcomes for major complications, readmission, and mortality were analyzed 30 days postoperatively. Postablation imaging was evaluated for incomplete ablation/missed lesions, and surveillance imaging reviewed for local, regional, and metastatic recurrence. Results: Of the 50 patients (166 targeted lesions) who received MWA for NLM, 41 (82%) were treated with a minimally invasive approach, and 22 (44%) underwent MWA concomitant with hepatectomy and/or primary tumor resection. Within the study cohort 70% of patients were treated with curative intent with a 77% (27/35) success rate. Carcinoid symptoms were reported in 40% (20/50) of patients preoperatively, and MWA treatment improved symptoms in 19/20 patients. Incomplete ablation occurred in 1/166 treated lesions. Recurrence-free survival at 1 and 5 years was 86% and 28%, respectively. Overall survival at 1 and 5 years was 94% and 70%, respectively (median follow-up 32 months, range 0-116 months). Conclusion: Operative MWA is a versatile modality, which can be safe and effectively performed alone or combined with hepatectomy for NLM, preferably using a minimally invasive approach, to achieve symptom control and possibly improve survival.

Effect of Margin Status on Survival After Resection of Hilar Cholangiocarcinoma in the Modern Era of Adjuvant Therapies.

INTRODUCTION: Studies have shown that for patients with hilar cholangiocarcinoma (HC), survival is associated with negative resection margins (R0). This requires increasingly proximal resection, putting patients at higher risk for complications, which may delay chemotherapy. For patients with microscopically positive resection margins (R1), the use of modern adjuvant therapies may offset the effect of R1 resection. METHODS: Patients at our institution with HC undergoing curative-intent resection between January 2008 and July 2019 were identified by retrospective record review. Demographic data, operative details, tumor characteristics, postoperative outcomes, recurrence, survival, and follow-up were recorded. Patients with R0 margin were compared to those with R1 margin. Patients with R2 resection were excluded. RESULTS: Seventy-five patients underwent attempted resection with 34 (45.3%) cases aborted due to metastatic disease or locally advanced disease. Forty-one (54.7%) patients underwent curative-intent resection with R1 rate of 43.9%. Both groups had similar rates of adjuvant therapy (56.5% vs. 61.1%, P = .7672). Complication rates and 30 mortality were similar between groups (all P > .05). Both groups had similar median recurrence-free survival (R0 29.2 months vs. R1 27.8 months, P = .540) and median overall survival (R0 31.2 months vs. R1 38.8 months, P = .736) with similar median follow-up time (R0 29.9 months vs. R1 28.5 months, P = .8864). CONCLUSIONS: At our institution, patients undergoing hepatic resection for HC with R1 margins have similar recurrence-free and overall survival to those with R0 margins. Complications and short-term mortality were similar. This may indicate that with use of modern adjuvant therapies obtaining an R0 resection is not an absolute mandate.

Use of Artificial Intelligence Deep Learning to Determine the Malignant Potential of Pancreatic Cystic Neoplasms With Preoperative Computed Tomography Imaging.

BACKGROUND: Society consensus guidelines are commonly used to guide management of pancreatic cystic neoplasms (PCNs). However, downsides of these guidelines include unnecessary surgery and missed malignancy. The aim of this study was to use computed tomography (CT)-guided deep learning techniques to predict malignancy of PCNs. MATERIALS AND METHODS: Patients with PCNs who underwent resection were retrospectively reviewed. Axial images of the mucinous cystic neoplasms were collected and based on final pathology were assigned a binary outcome of advanced neoplasia or benign. Advanced neoplasia was defined as adenocarcinoma or intraductal papillary mucinous neoplasm with high-grade dysplasia. A convolutional neural network (CNN) deep learning model was trained on 66% of images, and this trained model was used to test 33% of images. Predictions from the deep learning model were compared to Fukuoka guidelines. RESULTS: Twenty-seven patients met the inclusion criteria, with 18 used for training and 9 for model testing. The trained deep learning model correctly predicted 3 of 3 malignant lesions and 5 of 6 benign lesions. Fukuoka guidelines correctly classified 2 of 3 malignant lesions as high risk and 4 of 6 benign lesions as worrisome. Following deep learning model predictions would have avoided 1 missed malignancy and 1 unnecessary operation. DISCUSSION: In this pilot study, a deep learning model correctly classified 8 of 9 PCNs and performed better than consensus guidelines. Deep learning can be used to predict malignancy of PCNs; however, further model improvements are necessary before clinical use.

A Single-Center Experience with Minimally Invasive Transgastric ERCP in Patients with Previous Gastric Bypass: Lessons Learned and Technical Considerations.

As bariatric surgery increases, there is a growing population of patients with biliary obstruction and anatomy which precludes transoral access through endoscopic retrograde cholangiopancreatography (ERCP). Minimally invasive transgastric ERCP (TG-ERCP) offers a feasible alternative for the treatment. A retrospective review was performed of all patients who underwent laparoscopic or robotic-assisted TG-ERCP between 2010 and 2017. Chart abstraction collected demographics, procedural details, success rate, and postoperative outcomes. Forty patients were identified, of which 38 cases were performed laparoscopically and two robotically. Median operative time was 163 minutes, with an estimated blood loss of 50 cc. TG-ERCP was performed successfully in 36 cases (90%); sphincterotomy was completed in 35 patients (97%). Sixty per cent already had a cholecystectomy; in the remaining patients, it was performed concurrently. Major complications included stomach perforation (n = 1), pancreatitis (n = 3), and anemia requiring transfusion (n = 2). In patients with biliary obstruction and anatomy not suitable for ERCP, TG-ERCP can be performed in a minimally invasive fashion, with a high rate of technical success and low morbidity. We describe a stepwise, reproducible technique because it is an essential tool for the shared armamentarium of endoscopists and surgeons.

Prognostic impact of the Bismuth-Corlette classification: Higher rates of local unresectability in stage IIIb hilar cholangiocarcinoma.

BACKGROUND: The Bismuth-Corlette (BC) classification is used to categorize hilar cholangiocarcinoma by proximal extension along the biliary tree. As the right hepatic artery crosses just behind the left bile duct, we hypothesized that BC IIIb tumors would have a higher likelihood of local unresectability due to involvement of the contralateral artery. METHODS: A retrospective review of a prospectively maintained database identified patients with hilar cholangiocarcinoma taken to the operating room for intended curative resection between April 2008 and September 2016. Cases were assigned BC stages based on preoperative imaging. RESULTS: Sixty-eight patients were included in the study. All underwent staging laparoscopy after which 16 cases were aborted for metastatic disease. Of the remaining 52 cases, 14 cases were explored and aborted for locally advanced disease. Thirty-eight underwent attempt at curative resection. After excluding cases aborted for metastatic disease, the chance of proceeding with resection was 55.6% for BC IIIb staged lesions compared to 80.0% of BC IIIa lesions and to 82.4% for BC I-IIIa staged lesions (P < 0.05). About 44.4% of BC IIIb lesions were aborted for locally advanced disease versus 17.6% of remaining BC stages. CONCLUSIONS: When hilar cholangiocarcinoma is preoperatively staged as BC IIIb, surgeons should anticipate higher rates of locally unresectable disease, likely involving the right hepatic artery.

Hepatic steatosis in response to acute alcohol exposure in zebrafish requires sterol regulatory element binding protein activation.

UNLABELLED: Steatosis is the most common consequence of acute alcohol abuse and may predispose to more severe hepatic disease. Increased lipogenesis driven by the sterol response element binding protein (SREBP) transcription factors is essential for steatosis associated with chronic alcohol ingestion, but the mechanisms underlying steatosis following acute alcohol exposure are unknown. Zebrafish larvae represent an attractive vertebrate model for studying alcoholic liver disease (ALD), because they possess the pathways to metabolize alcohol, the liver is mature by 4 days post-fertilization (dpf), and alcohol can be simply added to their water. Exposing 4 dpf zebrafish larvae to 2% ethanol (EtOH) for 32 hours achieves approximately 80 mM intracellular EtOH and up-regulation of hepatic cyp2e1, sod, and bip, indicating that EtOH is metabolized and provokes oxidant stress. EtOH-treated larvae develop hepatomegaly and steatosis accompanied by changes in the expression of genes required for hepatic lipid metabolism. Based on the importance of SREBPs in chronic ALD, we explored the role of Srebps in this model of acute ALD. Srebp activation was prevented in gonzo larvae, which harbor a mutation in the membrane-bound transcription factor protease 1 (mbtps1) gene, and in embryos injected with a morpholino to knock down Srebp cleavage activating protein (scap). Both gonzo mutants and scap morphants were resistant to steatosis in response to 2% EtOH, and the expression of many Srebp target genes are down-regulated in gonzo mutant livers. CONCLUSION: Zebrafish larvae develop signs of acute ALD, including steatosis. Srebp activation is required for steatosis in this model. The tractability of zebrafish genetics provides a valuable tool for dissecting the molecular pathogenesis of acute ALD.