The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope: A multicenter retrospective international study.

BACKGROUND: Duodenoscope-related multidrug-resistant organism (MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography (ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. METHODS: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score (1 to 10) on performance rating of the single-use duodenoscope, and adverse event (AE) rate. RESULTS: A total of 66 patients (26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47 (71.2%) grade 3 and 19 (28.8%) grade 4. The technical success rate was 98.5% (65/66). Procedural duration was 64 (interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66 (1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients (6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis (PEP), 1 cholangitis and 1 bleeding. CONCLUSIONS: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

Early Diagnosis and Prevention of Infections in Cirrhosis.

Strategies to prevent infection and improve outcomes in patients with cirrhosis. HAV, hepatitis A virus; HBV, hepatitis B virus; COVID-19, novel coronavirus disease 2019; NSBB, nonselective ß-blocker; PPI, proton pump inhibitors.Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications, and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection; the incremental preventive strategies for infections and sepsi; and the consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of ß-blockers, and vaccinations for viral diseases including novel coronavirus disease 2019. Secondary prevention includes early diagnosis and a timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable improved outcomes.

In Vitro and In Vivo Metabolism of a Novel Antimitochondrial Cancer Metabolism Agent, CPI-613, in Rat and Human.

CPI-613, an inhibitor of pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH) enzymes, is currently in development for the treatment of pancreatic cancer, acute myeloid leukemia, and other cancers. CPI-613 is an analog of lipoic acid, an essential cofactor for both PDH and KGDH. Metabolism and mass balance studies were conducted in rats after intravenous administration of [14C]-CPI-613. CPI-613 was eliminated via oxidative metabolism followed by excretion of the metabolites in feces (59%) and urine (22%). ß-Oxidation was the major pathway of elimination for CPI-613. The most abundant circulating components in rat plasma were those derived from ß-oxidation. In human hepatocytes, CPI-613 mainly underwent ß-oxidation (M1), sulfur oxidation (M2), and glucuronidation (M3). The Michaelis-Menten kinetics (Vmax and Km) of the metabolism of CPI-613 to these three metabolites predicted the fraction metabolized leading to the formation of M1, M2, and M3 to be 38%, 6%, and 56%, respectively. In humans, after intravenous administration of CPI-613, major circulating species in plasma were the parent and the ß-oxidation derived products. Thus, CPI-613 metabolites profiles in rat and human plasma were qualitatively similar. ß-Oxidation characteristics and excretion patterns of CPI-613 are discussed in comparison with those reported for its endogenous counterpart, lipoic acid. SIGNIFICANCE STATEMENT: This work highlights the clearance mechanism of CPI-613 via ß-oxidation, species differences in their ability to carry out ß-oxidation, and subsequent elimination routes. Structural limitations for completion of terminal cycle of ß-oxidation is discussed against the backdrop of its endogenous counterpart lipoic acid.

Impact of transmural plastic stent on recurrence of pancreatic fluid collection after metal stent removal in disconnected pancreatic duct: a randomized controlled trial.

BACKGROUND: Disconnected pancreatic duct (DPD) after development of walled-off necrosis (WON) predisposes to recurrent (peri)pancreatic fluid collection (PFC). In this randomized controlled trial, we compared plastic stents with no plastic stent after removal of a large-caliber metal stent (LCMS) on incidence of recurrent PFCs in DPD. METHODS : Consecutive patients with WON who underwent endoscopic ultrasound (EUS)-guided drainage with LCMS between September 2017 and March 2020 were screened for eligibility. At LCMS removal (4 weeks after drainage), patients with DPD were randomized to plastic stent or no stent groups. The primary outcome was incidence of recurrent PFC at 3 months. Secondary outcomes were technical success of plastic stent deployment, adverse events, stent migration, and recurrence of PFC at 6 and 12 months. RESULTS: 236 patients with WON underwent EUS-guided drainage using LCMS, and 104 (males 94, median age 34 years (interquartile range [IQR] 26-44.7) with DPD were randomized into stenting (n = 52) and no-stenting (n = 52) groups. Plastic stent deployment was successful in 88.5 %. Migration occurred in 19.2 % at median follow-up of 8 months (IQR 2.5-12). Recurrent PFCs occurred in six patients at 3 months (stent n = 3, no stent n = 3). There was no significant difference in PFC recurrence between the two groups at 3, 6, and 12 months. Reintervention was required in seven patients with recurrent PFCs, with no significant difference between the two groups. CONCLUSION: In patients with WON and DPD, deployment of plastic stents after LCMS removal did not reduce recurrence of PFC.

A new biodegradable stent in bilio-pancreatic diseases: a prospective multi-center feasibility study.

INTRODUCTION: biodegradable stents of various designs are reportedly used in pancreato-biliary conditions with promising results. Their major advantage is the avoidance of repeat endoscopic procedure for stent removal, thereby reducing overall costs and endoscopic retrograde cholangiopancreatography (ERCP) associated adverse events. The aim of the study was to evaluate the feasibility and safety of a new biodegradable stent in patients with pancreato-biliary diseases. METHODS: a prospective multicenter pilot study was performed. All consecutive patients ≥ 18 years old who underwent biliary or pancreatic stenting using the new biodegradable Archimedes stent were included in the study. There were three biodegradation profiles. Technical and clinical success and feasibility and safety were assessed during a pre-established follow-up schedule. RESULTS: fifty-three patients (mean age: 48.54 ± 19.29, 66 % male) with biliary (n = 29, 54.7 %) or pancreatic (n = 24, 45.3 %) indications were included. The distribution of stents used according to degradation properties were as follows: fast (n = 11, 20.8 %), medium (n = 16, 30.2 %) and slow (n = 26, 49.1 %). The technical and clinical success were 100 % and 77.8 %, respectively. Thirty-five patients were followed for a median of 26 weeks (range: 4-56, 66 %). There were nine procedure-related adverse events (17 %), all mild, including one uneventful stent-related event (external migration). CONCLUSION: the biodegradable Archimedes stent placement is feasible and safe in pancreato-biliary diseases.

Early liver transplantation after COVID-19 infection: The first report.

COVID-19 (coronavirus disease 2019) has impacted solid organ transplantation (SOT) in many ways. Transplant centers have initiated SOT despite the COVID-19 pandemic. Although it is suggested to wait for 4 weeks after COVID-19 infection, there are no data to support or refute the timing of liver transplant after COVID-19 infection. Here we describe the course and outcomes of COVID-19-infected candidates and healthy living liver donors who underwent transplantation. A total of 38 candidates and 33 potential living donors were evaluated from May 20, 2020 until October 30, 2020. Ten candidates and five donors were reverse transcriptase-polymerase chain reaction (RT-PCR) positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pretransplant. Four candidates succumbed preoperatively. Given the worsening of liver disease, four candidates underwent liver transplant after 2 weeks due to the worsening of liver disease and the other two candidates after 4 weeks. Only one recipient died due to sepsis posttransplant. Three donors underwent successful liver donation surgery after 4 weeks of COVID-19 infection without any postoperative complications, and the other two were delisted (as the candidates expired). This report is the first to demonstrate the feasibility of elective liver transplant early after COVID-19 infection.

Worldwide Variations in Demographics, Management, and Outcomes of Acute Pancreatitis.

BACKGROUND & AIMS: Few studies have compared regional differences in acute pancreatitis. We analyzed data from an international registry of patients with acute pancreatitis to evaluate geographic variations in patient characteristics, management, and outcomes. METHODS: We collected data from the APPRENTICE registry of patients with acute pancreatitis, which obtains information from patients in Europe (6 centers), India (3 centers), Latin America (5 centers), and North America (8 centers) using standardized questionnaires. Our final analysis included 1612 patients with acute pancreatitis (median age, 49 years; 53% male, 62% white) enrolled from August 2015 through January 2018. RESULTS: Biliary (45%) and alcoholic acute pancreatitis (21%) were the most common etiologies. Based on the revised Atlanta classification, 65% of patients developed mild disease, 23% moderate, and 12% severe. The mean age of patients in Europe (58 years) was older than mean age for all 4 regions (46 years) and a higher proportion of patients in Europe had comorbid conditions (73% vs 50% overall). The predominant etiology of acute pancreatitis in Latin America was biliary (78%), whereas alcohol-associated pancreatitis accounted for the highest proportion of acute pancreatitis cases in India (45%). Pain was managed with opioid analgesics in 93% of patients in North America versus 27% of patients in the other 3 regions. Cholecystectomies were performed at the time of hospital admission for most patients in Latin America (60% vs 15% overall). A higher proportion of European patients with severe acute pancreatitis died during the original hospital stay (44%) compared with the other 3 regions (15%). CONCLUSIONS: We found significant variation in demographics, etiologies, management practices, and outcomes of acute pancreatitis worldwide. ClinicalTrials.gov number: NCT03075618.

Long-term outcomes after temporary placement of a self-expanding fully covered metal stent for benign biliary strictures secondary to chronic pancreatitis.

BACKGROUND AND AIMS: Temporary single, fully covered self-expanding metal stent (FCSEMS) placement for benign biliary strictures (BBSs) associated with chronic pancreatitis (CP) may require fewer interventions than endotherapy with multiple plastic stents and may carry less morbidity than biliary diversion surgery. This study aimed to assess long-term outcomes in CP-associated BBSs after FCSEMS placement and removal. METHODS: In this open-label, multinational, prospective study, subjects with CP and a BBS treated with FCSEMS placement with scheduled removal at 10 to 12 months were followed for 5 years after FCSEMS indwell. Kaplan-Meier analyses assessed BBS resolution and cumulative probability of freedom from recurrent stent placement to 5 years after FCSEMS indwell. RESULTS: One hundred eighteen patients were eligible for FCSEMS removal. At a median of 58 months (interquartile range, 44-64) post-FCSEMS indwell, the probability of remaining stent-free was 61.6% (95% confidence interval [CI], 52.5%-70.7%). In 94 patients whose BBSs resolved at the end of FCSEMS indwell, the probability of remaining stent-free 5 years later was 77.4% (95% CI, 68.4%-86.4%). Serious stent-related adverse events occurred in 27 of 118 patients (22.9%); all resolved with medical therapy or repeated endoscopy. Multivariate analysis identified severe CP (hazard ratio, 2.4; 95% CI, 1.0-5.6; P = .046) and longer stricture length (hazard ratio, 1.2; 95% CI, 1.0-1.4; P = .022) as predictors of stricture recurrence. CONCLUSION: In patients with symptomatic BBSs secondary to CP, 5 years after placement of a single FCSEMS intended for 10 to 12 months indwell, more than 60% remained asymptomatic and stent-free with an acceptable safety profile. Temporary placement of a single FCSEMS may be considered as first-line treatment for patients with CP and BBSs. (Clinical trial registration number: NCT01014390.).

Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group.

Description: This update of the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding (UGIB) refines previous important statements and presents new clinically relevant recommendations. Methods: An international multidisciplinary group of experts developed the recommendations. Data sources included evidence summarized in previous recommendations, as well as systematic reviews and trials identified from a series of literature searches of several electronic bibliographic databases from inception to April 2018. Using an iterative process, group members formulated key questions. Two methodologists prepared evidence profiles and assessed quality (certainty) of evidence relevant to the key questions according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Group members reviewed the evidence profiles and, using a consensus process, voted on recommendations and determined the strength of recommendations as strong or conditional. Recommendations: Preendoscopic management: The group suggests using a Glasgow Blatchford score of 1 or less to identify patients at very low risk for rebleeding, who may not require hospitalization. In patients without cardiovascular disease, the suggested hemoglobin threshold for blood transfusion is less than 80 g/L, with a higher threshold for those with cardiovascular disease. Endoscopic management: The group suggests that patients with acute UGIB undergo endoscopy within 24 hours of presentation. Thermocoagulation and sclerosant injection are recommended, and clips are suggested, for endoscopic therapy in patients with high-risk stigmata. Use of TC-325 (hemostatic powder) was suggested as temporizing therapy, but not as sole treatment, in patients with actively bleeding ulcers. Pharmacologic management: The group recommends that patients with bleeding ulcers with high-risk stigmata who have had successful endoscopic therapy receive high-dose proton-pump inhibitor (PPI) therapy (intravenous loading dose followed by continuous infusion) for 3 days. For these high-risk patients, continued oral PPI therapy is suggested twice daily through 14 days, then once daily for a total duration that depends on the nature of the bleeding lesion. Secondary prophylaxis: The group suggests PPI therapy for patients with previous ulcer bleeding who require antiplatelet or anticoagulant therapy for cardiovascular prophylaxis.

Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Updated August 2018.

ESGE suggests endoscopic therapy and/or extracorporeal shockwave lithotripsy (ESWL) as the first-line therapy for painful uncomplicated chronic pancreatitis (CP) with an obstructed main pancreatic duct (MPD) in the head/body of the pancreas. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team and surgical options should be considered.Weak recommendation, low quality evidence.ESGE suggests, for the selection of patients for initial or continued endoscopic therapy and/or ESWL, taking into consideration predictive factors associated with a good long-term outcome. These include, at initial work-up, absence of MPD stricture, a short disease duration, non-severe pain, absence or cessation of cigarette smoking and of alcohol intake, and, after initial treatment, complete removal of obstructive pancreatic stones and resolution of pancreatic duct stricture with stenting.Weak recommendation, low quality evidence.ESGE recommends ESWL for the clearance of radiopaque obstructive MPD stones larger than 5 mm located in the head/body of the pancreas and endoscopic retrograde cholangiopancreatography (ERCP) for MPD stones that are radiolucent or smaller than 5 mm. Strong recommendation, moderate quality evidence.ESGE suggests restricting the use of endoscopic therapy after ESWL to patients with no spontaneous clearance of pancreatic stones after adequate fragmentation by ESWL.Weak recommendation, moderate quality evidence.ESGE suggests treating painful dominant MPD strictures with a single 10-Fr plastic stent for one uninterrupted year if symptoms improve after initial successful MPD drainage. The stent should be exchanged if necessary, based on symptoms or signs of stent dysfunction at regular pancreas imaging at least every 6 months. ESGE suggests consideration of surgery or multiple side-by-side plastic stents for symptomatic MPD strictures persisting beyond 1 year after the initial single plastic stenting, following multidisciplinary discussion. Weak recommendation, low quality evidence.ESGE recommends endoscopic drainage over percutaneous or surgical treatment for uncomplicated chronic pancreatitis (CP)-related pseudocysts that are within endoscopic reach.Strong recommendation, moderate quality evidence.ESGE recommends retrieval of transmural plastic stents at least 6 weeks after pancreatic pseudocyst regression if MPD disruption has been excluded, and long-term indwelling of transmural double-pigtail plastic stents in patients with disconnected pancreatic duct syndrome.Strong recommendation, low quality evidence.ESGE suggests the temporary insertion of multiple side-by-side plastic stents or of a fully covered self-expandable metal stent (FCSEMS) for treating CP-related benign biliary strictures.Weak recommendation, moderate quality evidence.ESGE recommends maintaining a registry of patients with biliary stents and recalling them for stent removal or exchange.Strong recommendation, low quality evidence.

Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines.

This Guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy (APSDE). It was developed in response to the increasing use of antithrombotic agents (antiplatelet agents and anticoagulants) in patients undergoing gastrointestinal (GI) endoscopy in Asia. After reviewing current practice guidelines in Europe and the USA, the joint committee identified unmet needs, noticed inconsistencies, raised doubts about certain recommendations and recognised significant discrepancies in clinical practice between different regions. We developed this joint official statement based on a systematic review of the literature, critical appraisal of existing guidelines and expert consensus using a two-stage modified Delphi process. This joint APAGE-APSDE Practice Guideline is intended to be an educational tool that assists clinicians in improving care for patients on antithrombotics who require emergency or elective GI endoscopy in the Asian Pacific region.

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018.

Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.

Initial experience of EUS-guided radiofrequency ablation of unresectable pancreatic cancer.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) has been used as a valuable treatment modality for various unresectable malignancies. EUS-guided radiofrequency ablation (EUS-RFA) of the porcine pancreas was reported to be feasible and safe in our previous study, suggesting that EUS-RFA may be applicable as an adjunct and effective alternative treatment method for unresectable pancreatic cancer. This study aimed to assess the technical feasibility and safety of EUS-RFA for unresectable pancreatic cancer. METHODS: An 18-gauge endoscopic RFA electrode and a radiofrequency generator were used for the procedure. The length of the exposed tip of the RFA electrode was 10 mm. After insertion of the RFA electrode into the mass, the radiofrequency generator was activated to deliver 20 to 50 W ablation power for 10 seconds. Depending on tumor size, the procedure was repeated to sufficiently cover the tumor. RESULTS: EUS-RFA was performed successfully in all 6 patients (median age 62 years, range 43-73 years). Pancreatic cancer was located in the head (n = 4) or body (n = 2) of the pancreas. The median diameter of masses was 3.8 cm (range 3cm-9cm). Four patients had stage 3 disease, and 2 patients had stage 4 disease. After the procedure, 2 patients experienced mild abdominal pain, but there were no other adverse events such as pancreatitis or bleeding. CONCLUSIONS: EUS-RFA could be a technically feasible and safe option for patients with unresectable pancreatic cancer.

Artificial intelligence in endoscopy related to inflammatory bowel disease: A systematic review.

BACKGROUND AND OBJECTIVES: In spite of rapid growth of artificial intelligence (AI) in digestive endoscopy in lesion detection and characterization, the role of AI in inflammatory bowel disease (IBD) endoscopy is not clearly defined. We aimed at systematically reviewing the role of AI in IBD endoscopy and identifying future research areas. METHODS: We searched the PubMed and Embase database using keywords ("artificial intelligence" OR "machine learning" OR "computer-aided" OR "convolutional neural network") AND ("inflammatory bowel disease" OR "ulcerative colitis" OR "Crohn's") AND ("endoscopy" or "colonoscopy" or "capsule endoscopy" or "device assisted enteroscopy") between 1975 and September 2023 and identified 62 original articles for detailed review. Review articles, consensus guidelines, case reports/series, editorials, letter to the editor, non-peer-reviewed pre-prints and conference abstracts were excluded. The quality of the included studies was assessed using the MI-CLAIM checklist. RESULTS: The accuracy of AI models (25 studies) to assess ulcerative colitis (UC) endoscopic activity ranged between 86.54% and 94.5%. AI-assisted capsule endoscopy reading (12 studies) substantially reduced analyzable images and reading time with excellent accuracy (90.5% to 99.9%). AI-assisted analysis of colonoscopic images can help differentiate IBD from non-IBD, UC from non-UC and UC from Crohn's disease (CD) (three studies) with 72.1%, 98.3% and > 90% accuracy, respectively. AI models based on non-invasive clinical and radiologic parameters could predict endoscopic activity (three studies). AI-assisted virtual chromoendoscopy (four studies) could predict histologic remission and long-term outcomes. Computer-assisted detection (CADe) of dysplasia (two studies) is feasible along with AI-based differentiation of high from low-grade IBD neoplasia (79% accuracy). AI is effective in linking electronic medical record data (two studies) with colonoscopic videos to facilitate widespread machine learning. CONCLUSION: AI-assisted IBD endoscopy has the potential to impact clinical management by automated detection and characterization of endoscopic lesions. Large, multi-center, prospective studies and commercially available IBD-specific endoscopic AI algorithms are warranted.