Highly Selective Electrochemical Baeyer-Villiger Oxidation through Oxygen Atom Transfer from Water.

The Baeyer-Villiger oxidation of ketones is a crucial oxygen atom transfer (OAT) process used for ester production. Traditionally, Baeyer-Villiger oxidation is accomplished by thermally oxidizing the OAT from stoichiometric peroxides, which are often difficult to handle. Electrochemical methods hold promise for breaking the limitation of using water as the oxygen atom source. Nevertheless, existing demonstrations of electrochemical Baeyer-Villiger oxidation face the challenges of low selectivity. We report in this study a strategy to overcome this challenge. By employing a well-known water oxidation catalyst, Fe2O3, we achieved nearly perfect selectivity for the electrochemical Baeyer-Villiger oxidation of cyclohexanone. Mechanistic studies suggest that it is essential to produce surface hydroperoxo intermediates (M-OOH, where M represents a metal center) that promote the nucleophilic attack on ketone substrates. By confining the reactions to the catalyst surfaces, competing reactions (e.g., dehydrogenation, carboxylic acid cation rearrangements, and hydroxylation) are greatly limited, thereby offering high selectivity. The surface-initiated nature of the reaction is confirmed by kinetic studies and spectroelectrochemical characterizations. This discovery adds nucleophilic oxidation to the toolbox of electrochemical organic synthesis.

Occurrence of gastric cancer in patients with juvenile polyposis syndrome: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The true rate of gastric cancer (GC) in juvenile polyposis syndrome (JPS) is unknown because of its rarity and ascertainment bias in published literature. To better assess this, we conducted a systematic review and meta-analysis. METHODS: MEDLINE, Embase, and Scopus databases were searched for the key words juvenile polyposis syndrome, juvenile polyps, stomach cancer, GC, SMAD4, BMPR1A, hamartomatous polyposis syndrome, hamartomas, and hereditary cancers for studies reporting upper GI manifestations in JPS. The primary outcome was the reported occurrence of GC in JPS. We then compared GC occurrence based on the presence or absence of pathogenic germline variants (PGVs) and in untested patients. RESULTS: Eleven studies including 637 patients were included. The pooled occurrence of GC was 3.5% (95% confidence interval [CI], 1.8-5.2; I2 = 12.3%) at a median age of 42.5 years (range, 15-57.6). The pooled occurrence of GC in patients with SMAD4 PGV was 10.1% (95% CI, 3.2-16.8%; I2 = 54.7%). GC was reported in only 1 BMPR1A PGV carrier and was not reported in patients without an identifiable PGV. In patients with prior germline testing, the risk of GC was higher in SMAD4 PGV carriers (odds ratio, 11.6; 95% CI, 4.6-29.4; I2 = 18.3%) compared with patients without SMAD4 PGV. In JPS patients with unknown status of germline testing, pooled occurrence of GC was 7.5% (95% CI, 0-15.5). There was an overall moderate risk of bias in the studies. CONCLUSIONS: GC is highest in SMAD4-associated JPS and was not reported in patients without identifiable PGVs. The value of GC surveillance in BMPR1A PGV carriers and JPS patients without an identifiable PGV is questionable. Germline testing should be performed in all JPS patients to inform GC risk discussion and utility of surveillance.

Endoscopic submucosal dissection vs. endoscopic mucosal resection for early Barrett's neoplasia in the West: a retrospective study.

BACKGROUND: The difference in clinical outcomes after endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for early Barrett's esophagus (BE) neoplasia remains unclear. We compared the recurrence/residual tissue rates, resection outcomes, and adverse events after ESD and EMR for early BE neoplasia. METHODS: We included patients who underwent EMR or ESD for BE-associated high grade dysplasia (HGD) or T1a esophageal adenocarcinoma (EAC) at eight academic hospitals. We compared demographic, procedural, and histologic characteristics, and follow-up data. A time-to-event analysis was performed to evaluate recurrence/residual disease and a Kaplan-Meier curve was used to compare the groups. RESULTS: 243 patients (150 EMR; 93 ESD) were included. EMR had lower en bloc (43 % vs. 89 %; P < 0.001) and R0 (56 % vs. 73 %; P = 0.01) rates than ESD. There was no difference in the rates of perforation (0.7 % vs. 0; P > 0.99), early bleeding (0.7 % vs. 1 %; P > 0.99), delayed bleeding (3.3 % vs. 2.1 %; P = 0.71), and stricture (10 % vs. 16 %; P = 0.16) between EMR and ESD. Patients with non-curative resections who underwent further therapy were excluded from the recurrence analysis. Recurrent/residual disease was 31.4 % [44/140] for EMR and 3.5 % [3/85] for ESD during a median (interquartile range) follow-up of 15.5 (6.75-30) and 8 (2-18) months, respectively. Recurrence-/residual disease-free survival was significantly higher in the ESD group. More patients required additional endoscopic resection procedures to treat recurrent/residual disease after EMR (EMR 24.2 % vs. ESD 3.5 %; P < 0.001). CONCLUSIONS: ESD is safe and results in more definitive treatment of early BE neoplasia, with significantly lower recurrence/residual disease rates and less need for repeat endoscopic treatments than with EMR.

The Prevalence and Significance of Jejunal and Duodenal Bulb Polyposis After Duodenectomy in Familial Adenomatous Polyposis: Retrospective Cohort Study.

OBJECTIVE: To evaluate the prevalence, natural history, and severity of polyposis of the duodenal bulb and jejunum after duodenectomy in patients with FAP. SUMMARY OF BACKGROUND DATA: Advanced duodenal polyposis stage in FAP requires consideration of duodenal resection to prevent cancer; pylorus-preserving approach of pancreas-sparing duodenectomy (PSD) is preferred. Post-duodenectomy data indicate polyps occur in the duodenal bulb and the post-anastomotic jejunum, but limited data exists regarding their significance. METHODS: We identified consecutive FAP patients After duodenal resection, including pancreaticoduodenectomy, PSD, or segmental duodenectomy, at Cleveland Clinic. Medical records were used to determine time to diagnosis of duodenal bulb or jejunal polyps, length of follow up, and severity of polyposis including maximal Spigelman stage (SS) of jejunal polyposis (neo-SS). RESULTS: 64 patients with FAP underwent duodenectomy and endoscopic follow up. 28% underwent pancreaticoduodenectomy, 61% PSD, and 11% segmental duodenectomy. Postoperatively, 38/64 (59%) were diagnosed with jejunal polyposis, with median time to diagnosis of 55 months and follow up time of 127 months. Jejunal polyposis was advanced in 21% (neo- SS III or IV). Fifty percent were treated endoscopically, 1 patient required surgery. Jejunal polyp-free survival after duodenectomy differed by surgery type (P = 0.008). A total of 55/64 patients underwent a pylorus-preserving procedure, and 6/55 (11%) developed duodenal bulb polyps. All bulb polyps were large (>20 mm) and found after PSD. Endoscopic resection was unsuccessful in 5 patients, but no surgical intervention was required. CONCLUSIONS: Polyposis occurs in the remaining duodenal and jejunal mucosa in the majority of patients after surgical duodenectomy. Jejunal polyposis is advanced in 1 in 5 patients, but rarely requires surgery. Endoscopic management of jejunal polyposis seems feasible but has proven difficult for duodenal bulb polyps.

Risks, Benefits, and Effects on Management for Biopsy of the Papilla in Patients With Familial Adenomatous Polyposis.

BACKGROUND & AIMS: Ampullary and duodenal cancer are the leading causes of death in patients with familial adenomatous polyposis (FAP) after colectomy has been performed. Risk of duodenal cancer is determined based on Spigelman stage (SS) of duodenal polyposis. Guidelines recommend endoscopic surveillance of the duodenum and visualization of the papilla to stage duodenal polyposis. There is no consensus on whether biopsies should be routinely collected from duodenal papilla and findings included in SS. Additionally, there are no data on the risk of pancreatitis after biopsy collection from papilla of patients with FAP. We studied the incidence of pancreatitis after biopsy of the papilla in patients with FAP and effects of biopsy findings on SS. METHODS: We identified consecutive patients with FAP at a single center from January 2011 through December 2018 with ≥1 endoscopy with biopsy of the papilla. Patients with history of foregut surgery were excluded. We identified 273 patients with FAP who had biopsies collected from papilla over 792 EGDs, with 1-8 independent exams with biopsy per patient. We collected demographic, endoscopic, and histology data from patients and calculated SS with vs without biopsy findings. Post-procedural pancreatitis was defined by 2 of the following: abdominal pain, lipase level 3-fold the upper limit of normal, or radiography findings consistent with pancreatitis within 7 days of esophagogastroduodenoscopy (EGD). RESULTS: Pancreatitis developed in 2 patients (0.73%): 1 after biopsy of a normal-appearing papilla and 1 after biopsy of an abnormal appearing papilla. Inclusions of biopsy data increased SS in 36 patients (13.2%), with consideration of prophylactic duodenectomy for 3.3%. CONCLUSIONS: Pancreatitis after biopsy of the duodenal papilla is rare. Histology data obtained from biopsy of the papilla in patients with FAP can change SS and affect patient management.

Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. METHODS: We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. RESULTS: Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. CONCLUSIONS: ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.

Recurrence with malignancy after endoscopic resection of large colon polyps with high-grade dysplasia: incidence and risk factors.

BACKGROUND: In the West, piecemeal endoscopic resection remains the primary treatment for large colon polyps (LCP), as most recurrences are believed to be benign and resectable with follow-up endoscopy. However, invasive malignancy at the site of prior piecemeal endoscopic mucosal resection has been reported in the Asian literature. This study aims to identify the incidence of and the risk factors for local recurrence with malignancy after endoscopic resection of LCP with high-grade dysplasia (HGD). METHODS: In this retrospective cohort study, we identified patients undergoing complete endoscopic resection of LCPs (≥ 20 mm) with HGD at the Cleveland Clinic between January 2000 and December 2016. Demographic, endoscopic, and pathologic data were collected. All subsequent endoscopic and pathology reports were reviewed to identify recurrence. The cumulative incidence of malignancy at the polypectomy site was determined and univariate analysis was performed to assess risk factors. RESULTS: A total of 254 LCPs with HGD were resected in 229 patients. Mean polyp size was 29.2 mm. There were 138 lesions resected in piecemeal fashion and 116 en-bloc. After a median follow-up of 28.7 months for the entire cohort, local recurrence with malignancy was diagnosed in six cases. Median time to malignancy diagnosis was 28.5 months. All malignant cases occurred after piecemeal resection and none after en-bloc resection (HR 11.4; 95% CI 0.48-273). CONCLUSION: Malignancy after endoscopic resection of LCPs with HGD is uncommon and may be associated with piecemeal resection. When possible, en-bloc resection should be the goal for the management of LCPs.

The EMALT Score: An Improved Model for Prediction of Early Mortality in Liver Transplant Recipients.

PURPOSE: Needs, risks, and outcomes of patients admitted to a post liver transplant intensive care unit (POLTICU) differ in important ways from those admitted to pretransplant intensive care units (ICUs). The aim of this study was to create the optimal model to risk stratify POLTICU patients. METHODS: Consecutive patients who underwent first deceased donor liver transplantation (LT) at a large United States center between 2008 and 2014 were followed from admission to LT and to discharge or death. Receiver-operating characteristic analysis was performed to assess the value of various scores in predicting in-hospital mortality. A predictive model was developed using logistic regression analysis. RESULTS: A total of 697 patients underwent LT, and 3.2% died without leaving the hospital. A model for in-hospital mortality was derived from variables available within 24 hours of admission to the POLTICU. Key variables best predicting survival were white blood cell count, 24-hour urine output, and serum glucose. A model using these variables performed with an area under the curve (AUC) of 0.88, compared to the Acute Physiology and Chronic Health Evaluation III and Model for End-Stage Liver Disease, which performed with AUCs of 0.74 and 0.60, respectively. CONCLUSION: An improved model, the early mortality after LT (EMALT) score, performs better than conventional models in predicting in-hospital mortality after LT.

Impact of sleeve gastrectomy and Roux-en-Y gastric bypass on biopsy-proven non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome. Our aim was to study the long-term effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on NAFLD/NASH. METHODS: Between 2008 and 2015, 3813 patients had an intraoperative liver biopsy performed at the time of primary RYGB and SG at a single academic center. Utilizing strict inclusion criteria, 487 patients with biopsy-proven NAFLD who had abnormal alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values (≥ 40 IU/L) at baseline were identified. Matching of SG to RYGB patients (1:4) was performed via logistic regression and propensity scores adjusting for clinical and liver histological characteristics. Changes in liver function tests (LFTs) at least 1 year after surgery were compared to baseline values and between the surgical groups. RESULTS: A total of 310 (weighted) patients (SG n = 62, and RYGB n = 248) with a median follow-up time of 4 years (range, 1-10) were included in the analysis. The distribution of covariates was well-balanced after propensity matching. In 84% of patients, LFT values normalized after bariatric surgery at the last follow-up time. The proportions of patients having normalized LFT values did not differ significantly between the SG and RYGB groups (82% vs. 84%, p = 0.66). The AST decreased from (SG: 49.1 ± 21.5 vs. RYGB: 49.3 ± 22.0, p = 0.93) at baseline to (SG: 28.0 ± 16.5 vs. RYGB: 26.5 ± 15.5, p = 0.33) at the last follow-up. Similarly, a significant reduction in ALT values from (SG: 61.7 ± 30.0 vs. RYGB 59.4 ± 24.9, p = 0.75) at baseline to (SG: 27.2 ± 21.5 vs. RYGB: 26.1 ± 19.2, p = 0.52) at the last follow-up was observed. CONCLUSIONS: In patients with biopsy-proven NAFLD/NASH, abnormal LFTs are normalized in most SG and RYGB patients by the end of the first postoperative year and remain normal until the last follow-up. This study also suggests that both bariatric procedures are similarly effective in improving liver function.

Common bile duct dilation after bariatric surgery.

BACKGROUND: Biliary dilation suggests obstruction and prompts further work up. Our experience with endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in the symptomatic post-bariatric surgery population revealed many patients with radiographically dilated bile ducts, but endoscopically normal studies. It is unclear if this finding is phenomenological or an effect of surgery. Additionally, it is unknown whether the type of bariatric surgery alters biliary pathophysiology. Thus, we studied whether a change occurs in biliary diameter following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: A single-center retrospective study assessing biliary diameter before and after RYGB or SG based on radiographic imaging. All adult patients undergoing RYGB or SG from January 2010 to December 2013 who had imaging studies before and > 3 months after surgery were included. Those with known obstructive etiologies and those without post-operative imaging were excluded. Common bile duct (CBD) diameter was re-read by a radiologist at the same location in the CBD for pre- and post-operative imaging. Baseline clinical factors and cholecystectomy status were collected. RESULTS: 269 patients met inclusion criteria (193 RYGB;76 SG). Between the groups, there were no significant differences in pre-operative characteristics. Average time from surgery to repeat imaging was 24.1 months. After adjusting for pre-operative factors, subjects who underwent an RYGB had an increase in CBD diameter of 1.4 mm (95% CI 0.096, 0.18), which was greater than the change following SG 0.5 mm(95% CI - 0.007, 0.11). The magnitude of this change did not depend on prior cholecystectomy in the RYGB cohort. Within the SG group, for patients without a prior cholecystectomy, there was a significant increase in post-operative CBD diameter of 0.8 mm(95% CI 0.02, 0.14). CONCLUSION: Bariatric surgery results in CBD dilation, with changes more pronounced after RYGB. Biliary dilation occurs irrespective of cholecystectomy status. Further work is necessary to determine the cause and clinical implications of this phenomenon.

Optimal injection solution for endoscopic submucosal dissection: A randomized controlled trial of Western solutions in a porcine model.

BACKGROUND AND AIM: When carrying out endoscopic submucosal dissection (ESD), procedural safety increases with greater tissue elevation and efficiency increases with longer-lasting submucosal cushion. Fluids specifically developed for ESD in Asia are not commercially available in the West, leaving endoscopists to use a variety of injectable fluids off-label. To determine the optimal fluid available in the West, we compared commonly used fluids for Western ESD. METHODS: All phases were carried out in an ex vivo porcine stomach model. Phase 1 compared tissue elevation and duration of submucosal cushions produced by various standard volumes of various injectable solutions used for ESD. The two best-performing solutions used off-label were tested head-to-head in ESD in Phase 2. Phase 3 compared the best solution from Phase 2 to Eleview® , currently the only submucosal injection fluid approved in the USA. In Phases 2 and 3, five ESD were carried out with each solution. The solutions were randomized and the endoscopist blinded to the solution. RESULTS: The best-performing solutions in Phase 1 were 0.4% hyaluronic acid, 6% hydroxyethyl starch (HES), and Eleview® . Phase 2 compared 6% HES and hydroxypropyl methylcellulose (HPMC), showing that ESD with 6% HES was easier (P = 0.007), faster (P = 0.041) and required less injection volume (P = 0.003). In Phase 3, resection speed, ease of ESD and total volume per area resected were comparable between 6% HES and Eleview® . CONCLUSIONS: Of the submucosal injection fluids currently available in the West, Eleview® and 6% HES are the best-performing solutions for ESD in a porcine model.

Advanced endoscopic imaging for detection of Barrett's esophagus.

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC), and is caused by chronic gastroesophageal reflux. BE can progress over time from metaplasia to dysplasia, and eventually to EAC. EAC is associated with a poor prognosis, often due to advanced disease at the time of diagnosis. However, if BE is diagnosed early, pharmacologic and endoscopic treatments can prevent progression to EAC. The current standard of care for BE surveillance utilizes the Seattle protocol. Unfortunately, a sizable proportion of early EAC and BE-related high-grade dysplasia (HGD) are missed due to poor adherence to the Seattle protocol and sampling errors. New modalities using artificial intelligence (AI) have been proposed to improve the detection of early EAC and BE-related HGD. This review will focus on AI technology and its application to various endoscopic modalities such as high-definition white light endoscopy, narrow-band imaging, and volumetric laser endomicroscopy.

Characterizing the extent and morphology of intraductal mucinous biliary neoplasm using a novel cholangioscope and treatment with ampullectomy.

Video 1A case characterizing the extent and morphology of an intraductal mucinous biliary neoplasm using a novel cholangioscope and treatment with ampullectomy.