Biflanged metal stents versus plastic stents in the endoscopic ultrasound-guided drainage of walled-off necrosis: a randomized controlled trial.

OBJECTIVE: Endoscopic ultrasound(EUS) guided drainage of walled off necrosis(WON) with either plastic stents or metal stents is the mainstay of WON management. This is a single center randomized controlled study evaluating the efficacy of bi-flanged metal stent(BFMS) and plastic stents for WON drainage. DESIGN: Patients with symptomatic WON amenable for EUS guided drainage were randomized to either BFMS or plastic stents. Primary outcome was reintervention free clinical success at 4 weeks. Secondary outcomes were overall clinical success(complete resolution of symptoms and significant reduction in size of WON (<50% of original size and <5 cm largest diameter size at 4-week follow-up)), number of re-interventions, adverse events, hospital stay for first admission and medium term outcomes at 6 months (recurrence, disconnected pancreatic duct, chronic pancreatitis and new onset diabetes mellitus). RESULTS: 92 patients were randomized - 46 in each arm. The reintervention free clinical success was significantly higher in BFMS group(67.4% vs 43.5%; P: 0.021; ITT analysis). Overall clinical success at one month was similar in both groups. There were significantly lower number of reinterventions (median 0(IQR 0-1) vs 1(0-2) P:0.028)and hospital stay duration in BFMS group(7.04 ± 3.36 days vs 9.09 ± 5.53 days; P:0.035). There was no difference in procedure-related adverse events, mortality and medium-term outcomes. CONCLUSIONS: The BFMS provides higher reintervention free clinical success at 4 weeks with shorter hospital stay without increased risk of adverse events compared to plastic stents for EUS-guided drainage of WON. Medium term outcomes are however similar in both BFMS, and plastics stents.

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.

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.

Small Bowel Capsule Endoscopy: Experience from a single large tertiary care centre.

Background and study aims Capsule endoscopy (CE) has transformed examination of the small bowel (SB), once considered a dark continent. The present study aimed to describe the indications, diagnostic yield, practical issues and complications of CE in one of the largest tertiary center in India. Patients and methods This retrospective analysis from a prospectively maintained database, conducted from January 2013 to June 2021 included 1155 CEs performed during this period. Patient medical records were reviewed for indications, results, and complications of CE. Results A total of 1154 patients (809 males and 345 females), mean age 53 years (range 6-87 years), one capsule got stuck in the esophagus, were included in the study. Active SB bleeding had no effect on SB transit time (324.7±161 minutes, n = 137 patients with active bleed vs 310.6±166.9 minutes, n = 1017 patients without active bleed; P = 0.35). The indication and diagnostic yield (DY) of CE were potential overt SB bleed (68.6% & 43.9%), potential occult SB bleed (8.2% and 40%), chronic diarrhea (7.9% and 28.4%), abdominal pain (6.5% and 21.3%), anemia (5.9% and 57.9%), and suspected/known case of Crohn's disease (2.3% & 56.5%) respectively. The DY for patients with age ≥60 years was similar to those with age < 60 years (61.9% vs. 51.8% respectively; P = 0.4). 21 patients (1.8%) had capsule retention of which six (0.5%) had to be referred for surgery. Conclusions CE is a safe and effective investigation with ever increasing range of indications. Potential SB bleed remains the most common indication for CE with high detection rate.

Healthcare utilization and outcomes of living donor liver transplantation for patients with APASL-defined acute-on-chronic liver failure.

BACKGROUND: Liver transplantation (LT) is associated with excellent survival in patients with acute-on-chronic liver failure (ACLF). There is a lack of data assessing the healthcare utilization and outcomes of patients with APASL-defined ACLF undergoing living donor liver transplantation (LDLT). Our aim was to assess pre-LT healthcare utilization and post-LT outcomes in such patients. METHODS: Patients with ACLF who underwent LDLT at our center between 1st April 2019 and 1st October 2021 were included. RESULTS: Seventy-three ACLF patients willing to undergo LDLT were listed; eighteen patients died within 30 days. Fifty-five patients underwent LDLT (age:38.05 ± 14.76 years; alcohol:52.7%; males:81.8%). Most were in grade II ACLF (87.3%) at the time of LDLT (APASL ACLF Research Consortium [AARC] score: 9.05 ± 1; MELD NA: 28.15 ± 4.13). Survival rate was 72.73%; mean follow-up period of 925.21 days; 58.2% (32/55) developed complications during the first year post-LT; 45% (25/55) and 12.7% (7/55) developed infections within and after 3 months. Pre-LT, each patient required a median of 2 (1-4) admissions for 17 (4-45) days. Fifty-six percent (31/55) of patients underwent plasma exchange pre-LDLT. A median amount of Rs. 8,25,090 (INR 26,000-43,58,154) was spent to stabilize the patient (who were sicker and waited longer to undergo LDLT); though post-LT survival benefit was not observed. CONCLUSIONS: LDLT was associated with 73% survival and, thus, is a viable option in those with APASL-defined ACLF. There was a pre-LT high healthcare resource utilization of plasma exchange, with the intention of optimization, while survival benefit has not been demonstrated.

EUS-guided left lobe liver biopsy: Safer modality with similar diagnostic yield as right lobe: a pilot study.

Background and study aims Percutaneous liver biopsy is traditionally done on the right lobe of the liver. Endoscopic ultrasound-guided liver biopsy (EUS-LB) can be performed on either the left or right lobe or as a combined bi-lobar biopsy. Earlier studies did not compare the benefit of bi-lobar biopsies to single-lobe biopsy for reaching a tissue diagnosis. The current study compared the degree of agreement of pathological diagnosis between the left lobe of the liver compared to right-lobe and with bi-lobar biopsy. Patients and methods Fifty patients fulfilling the inclusion criteria were enrolled in the study. EUS-LB with a 22G core needle was performed separately on both the liver lobes. Three pathologists, who were blinded to the site of biopsy independently reviewed the liver biopsies. Sample adequacy, safety, and concordance of pathological diagnosis between left- and right-lobe biopsy of the liver were analyzed. Results The pathological diagnosis was made in 96 % of patients. Specimen lengths from the left lobe and the right lobe were 2.31 ±â€Š0.57 cm and 2.28 ±â€Š0.69 cm, respectively ( P  = 0.476). The respective number of portal tracts were 11.84 ±â€Š6.71 versus 9.58 ±â€Š7.14; P  = 0.106. Diagnosis between the two lobes showed substantial (κ = 0.830) concordance. Left-lobe (κ value 0.878) and right-lobe (κ = 0.903) biopsies showed no difference when compared with bi-lobar biopsies. Adverse events were observed in two patients, both of whom had biopsies of the right lobe. Conclusions EUS-guided left-lobe liver biopsy is safer than right-lobe biopsy with similar diagnostic yield.

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

Introduction: biodegradable stents of various designs arereportedly used in pancreato-biliary conditions with promising results. Their major advantage is the avoidance ofrepeat endoscopic procedure for stent removal, therebyreducing overall costs and endoscopic retrograde cholangiopancreatography (ERCP) associated adverse events. Theaim of the study was to evaluate the feasibility and safetyof a new biodegradable stent in patients with pancreato-biliary diseases.Methods: a prospective multicenter pilot study was performed. All consecutive patients ≥ 18 years old whounderwent biliary or pancreatic stenting using the new biodegradable Archimedes stent were included in the study.There were three biodegradation profiles. Technical andclinical success and feasibility and safety were assessedduring 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 stentsused 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 followedfor a median of 26 weeks (range: 4-56, 66 %). There werenine procedure-related adverse events (17 %), all mild,including one uneventful stent-related event (externalmigration).Conclusion: the biodegradable Archimedes stent placementis feasible and safe in pancreato-biliary diseases. (AU)

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.

Prophylactic Perioperative Terlipressin Therapy for Preventing Acute Kidney Injury in Living Donor Liver Transplant Recipients: A Systematic Review and Meta-Analysis.

Background: Acute kidney injury (AKI) is common in the perioperative transplant period and is associated with poor outcomes. Few studies reported a reduction in AKI incidence with terlipressin therapy by counteracting the hemodynamic alterations occurring during liver transplantation. However, the effect of terlipressin on posttransplant outcomes has not been systematically reviewed. Methods: A comprehensive search of electronic databases was performed. Studies reporting the use of terlipressin in the perioperative period of living donor liver transplantation were included. We expressed the dichotomous outcomes as risk ratio (RR, 95% confidence interval [CI]) using the random effects model. The primary aim was to assess the posttransplant risk of AKI. The secondary aims were to assess the need for renal replacement therapy (RRT), vasopressors, effect on hemodynamics, blood loss during surgery, hospital and intensive care unit (ICU) stay, and in-hospital mortality. Results: A total of nine studies reporting 711 patients (309 patients in the terlipressin group and 402 in the control group) were included for analysis. Terlipressin was administered for a mean duration of 53.44 ± 28.61 h postsurgery. The risk of AKI was lower with terlipressin (0.6 [95% CI, 0.44-0.8]; P = 0.001). However, on sensitivity analysis including only four randomized controlled trials (I2 = 0; P = 0.54), the risk of AKI was similar in both the groups (0.7 [0.43-1.09]; P = 0.11). The need for RRT was similar in both the groups (0.75 [0.35-1.56]; P = 0.44). Terlipressin therapy reduced the need for another vasopressor (0.34 [0.25-0.47]; P < 0.001) with a concomitant rise in mean arterial pressure and systemic vascular resistance by 3.2 mm Hg (1.64-4.7; P < 0.001) and 77.64 dyne cm-1.sec-5 (21.27-134; P = 0.007), respectively. Blood loss, duration of hospital/ICU stay, and mortality were similar in both groups. Conclusions: Perioperative terlipressin therapy has no clinically relevant benefit.

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.

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.

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.

Outcomes of Endoscopic Submucosal Dissection in Duodenal Neuroendocrine Tumors.

BACKGROUND AND AIM: Endoscopic resection is recommended for small duodenal neuroendocrine tumors DNETs. However, there is limited data on the outcomes of endoscopic submucosal dissection (ESD) in DNETs. In this study, we aimed to evaluate the outcomes of ESD in DNETs. METHODS: Data of consecutive patients who underwent ESD for DNETs from January 2018 to December 2019 were analyzed, retrospectively. All the cases of ESD were performed with or without traction using rubber band and two endoclips. En-bloc resection, complete endoscopic resection (C-ER), complete pathological resection (C-PR), adverse events, and recurrence were evaluated. RESULTS: Twenty patients (19 males, 57.50 ± 9.32 years) underwent ESD for DNETs. DNETs measured ≤ 10 mm (7), 10-15 mm (12), and > 15 mm (1). ESD was performed with and without traction in 10 cases each. Mean operating time was 61 ± 17.38 min. En-bloc resection, C-ER, and C-PR were recorded in 90%, 95%, and 75%, respectively. Vertical margins were positive in five patients. Adverse events included perforations in 4 (20%) cases and major bleeding in one case. There was no recurrence at a mean follow-up of 17.20 ± 7.37 months. CONCLUSION: ESD is feasible and effective for the management of DNETs. However, caution is advised due to a high risk of adverse events and pathologically incomplete resection.

Gastric outlet obstruction with ascites: EUS-guided gastro-enterostomy is feasible.

Background and study aims Endoscopic ultrasound-guided gastro-enterostomy(EUS-GE) is a recently described novel minimally invasive endoscopic procedure for patients having malignant gastric outlet obstruction (GOO). The safety of EUS-GE in the presence of ascites with GOO is not known. The objective of the study was to evaluate the feasibility and safety of EUS-GE in patients with GOO and ascites. Patients and methods Consecutive patients with GOO who underwent EUS-GE between January 2019 and March 2021 constituted the study population. EUS-GE was performed using either EPASS or free-hand technique. The technical success, clinical success, adverse events, and survival times were evaluated. The outcomes were compared between patients with and without ascites. Results A total of 31 patients with GOO underwent EUS-GE of whom 29 (93.5 %) had malignant and two (6.4 %) had benign etiologies. Ascites was observed in 12 out of 31 (38.7%) patients and all had underlying malignancy. Majority (27, 87 %) of the EUS-GE procedures were performed using EPASS technique, and 4 (13 %) underwent free-hand technique. Eleven of 12 patients with ascites and GOO underwent EUS GE using EPASS technique. The technical success (91.6 % vs. 89.4 %; P  = 0.841), clinical success (83.3 % vs. 89.4 %; P  = 0.619), mean procedure time (32 vs. 31.6 min; P  = 0.968) and adverse events (0 % vs. 10.5 %; P =  0.245) were not significantly different between patients with or without ascites. However, the median survival time was significantly low in patients with ascites when compared to without ascites (36 vs. 290 days; P < 001 ). Conclusions Ascites is a common occurrence in patients with malignant GOO. EUS GE is feasible in presence of ascites with EPASS technique.

Double tunnel technique reduces technical failure during POEM in cases with severe submucosal fibrosis.

Background and study aims Submucosal fibrosis (SMF) is one of the major reasons for technical failure during per-oral endoscopic myotomy (POEM). In this study, we aimed to evaluate the impact of double tunnel technique (DT-POEM) on the technical success of POEM in cases with severe SMF. Patients and methods Data from patients with achalasia in whom SMF was encountered during POEM from Jan 2013 to Jan 2020 at our center were retrospectively evaluated. The technical success and adverse events (AEs) were analyzed and compared between cases with SMF who underwent POEM via single tunnel versus DT-POEM technique. Results A total of 1,150 patients underwent POEM during the study period. There were 14 technical failures (1.2 %). SMF and severe SMF was found in 104 (9 %) and 21 (1.8 %) patients, respectively. The majority of patients (17, 80.9 %) with severe SMF had type I achalasia. Overall, technical failures occurred in 14 cases (1.2 %) and severe SMF resulted in the majority of the technical failures (10, 71.4 %). DT-POEM was utilized in 11 cases (52.4 %) with severe SMF. The median procedure time with DT-POEM was 150 minutes (85-210). There were no major AEs and DT-POEM was technically successful in all the patients. The technical success of POEM in cases with SMF improved after the adoption of the double tunnel technique (98.4 % vs 68.3 %, P  = 0.0001). Conclusions Severe SMF is the most common reason for technical failure during POEM. DT-POEM improves the technical success rates of POEM in patients with severe SMF.