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The article presents a case study of a 44-year old man who was presented with a large, symptomatic pancreatic fluid collection six weeks after suffering from alcohol-related acute necrotizing pancreatitis. He underwent endoscopic ultrasound-guided drainage to place a dedicated fully covered self-expanding metal stent.

Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Endoscopic retrograde cholangiopancreatography (ERCP) has evolved from mainly a diagnostic tool to a treatment method, thanks to newer noninvasive techniques like magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS). This paper looks at how ERCP is used to treat conditions such as acute gallstone pancreatitis, pancreas divisum (PD), sphincter of Oddi dysfunction (SOD), and chronic pancreatitis (CP). For acute gallstone pancreatitis, early ERCP to reduce severity or mortality is now questioned, except when there is cholangitis or ongoing bile duct blockage. For patients with recurring acute pancreatitis due to PD, endoscopic treatment aims to lower duct pressure, but there is not enough strong evidence to support its long-term success. In SOD cases, recent research suggests being more careful with endoscopic sphincterotomy. ERCP plays a clearer role in CP by helping to manage duct stones and strictures in suitable patients. The rising use of pancreatoscopy-assisted lithotripsy as an alternative to ESWL is also discussed., Competing Interests: Conflict of interest disclosure forms (ICMJE) have been collected for all co-authors and can be accessed as supplementary material here., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

The management of a patient in the peri-transplantation period is highly challenging, and it is even more difficult while the patient is on the transplantation waitlist. Keeping the patient alive during this period involves managing the complications of liver disease and preventing the disease's progression. Based on the pre-transplantation etiology and type of liver failure, there is a difference in the management protocol. The current review is divided into different sections, which include: the management of underlying cirrhosis and complications of portal hypertension, treatment and identification of infections, portal vein thrombosis management, and particular emphasis on the management of patients of hepatocellular carcinoma and acute liver failure in the transplantation waitlist. The review highlights special concerns in the management of patients in the Asian subcontinent also. The review also addresses the issue of delisting from the transplant waitlist to see that futility does not overtake the utility of organs. The treatment modalities are primarily expressed in tabular format for quick reference. The following review integrates the vast issues in this period concisely so that the management during this crucial period is taken care of in the best possible way., (© 2023 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Background: Paracentesis-induced circulatory disturbance (PICD) occurs in 12-20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP)., Methods: This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5 L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5 mg thrice daily for three days, 2 h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD., Results: 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly ( P  = 0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant ( P  = 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms ( P  = 0.851). Midodrine was found to be more cost-effective., Conclusions: Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis., (© 2023 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The COVID-19 pandemic has impacted transplantation worldwide in a major way with infections and post-COVID-19 complications contributing to increased mortality and morbidity. We present a case of a 42-year-old lady who developed rhino-orbital mucormycosis in a postliver transplantation period. The initial presentation of the patient was very subtle. She never had overt COVID-19 infection before surgery and in the recovery period. Though cases of mucormycosis in the wound site have been reported, this would be one of the rare cases of rhino-orbital mucormycosis postliver transplantation. This infection leads to a rapid downhill course and the death of the patient. Atypical infections and presentations need to be monitored in postliver transplantation patients who are getting operated on during this pandemic, and a high level of clinical suspicion is required to pick up these cases at an early stage., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Swapnali Sabhapandit et al.)

Background: Alcohol is the leading cause of acute-on-chronic liver failure (ACLF). Several severity scores predict the outcome of ACLF. However, there is a lack of simple biomarkers in predicting the outcome of these sick patients. Fatty acid-binding proteins (FABPs) are small cytosolic proteins that play a major role in lipid metabolism, energy homeostasis, and inflammation, but, have not been investigated in alcohol-induced ACLF (A-ACLF)., Objectives: The primary objective was to assess the correlation between serum adipocyte-FABP (A-FABP) and liver-FABP (L-FABP) levels on mortality at day 90. Secondary objectives were to compare the levels between controls and A-ACLF, correlate L-FABP, and A-FABP levels on the development of organ failure/sepsis at day 90., Methods: In this prospective observational pilot study, we included patients with A-ACLF and age-matched healthy controls. FABP's were analyzed by enzyme-linked immunosorbent assay method. The patients were followed up for 90 days., Results: Twenty-five patients with A-ACLF (mean age: 40years; mean model for end-stage liver disease NA: 29.8; median Modified Maddrey's discriminant function [mDF]: 95) and 12 controls (mean age: 36.83yrs) were included in the study. A-FABP and L-FABP levels were significantly high in patients with A-ACLF than controls. Forty-four percent of patients with A-ACLF developed sepsis, 48% developed organ failure, and 44% expired by day 90. On multivariate Cox regression analysis, A-FABP (hazard ratio [HR]: 1.27 [ 1.08-1.5 ] ; P = 0.003), Asian Pacific Association for the Study of Liver ACLF research consortium score ( HR : 3.3 [ 1.15-9.54 ] ; P = 0.02 ) , L-FABP ( HR : 0.69 [ 0.52-0.91 ] ; P = 0.009 ), and serum protein levels ( HR : 0.03 [ 0.003-0.36 ] ; P = 0.005 ) predicted mortality. A-FABP ( 1.17 [ 1.07-1.29 ] ; P = 0.001 ) , and serum bilirubin ( 1.05 [ 0.99-1.12 ] ; P = 0.06 ) predicted development of organ failure , and only mDF ( HR : 1.04 [ 1.01-1.07 ] ; P = 0.009 ) predicted the development of sepsis on multivariate analysis. Fifteen patients received steroid therapy, of which 13.34% were nonresponders., Conclusions: In a selected group of patients with A-ACLF, A-FABP is highly sensitive at predicting mortality and outcome. If validated in a large, diverse sample, A-FABP can be used as a simple biomarker for prognostication in A-ACLF., Competing Interests: The authors have none to declare., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Accurately diagnosing indeterminate biliary strictures is challenging but important for patient prognostication and further management. Biopsy sampling under direct cholangioscopic vision might be superior to standard ERCP techniques such as brushing or biopsy sampling. Our aim was to investigate whether digital single-operator cholangioscopy (DSOC) compared with standard ERCP workup improves the diagnostic yield in patients with indeterminate biliary strictures., Methods: Patients with an indeterminate biliary stricture on the basis of MRCP were randomized to standard ERCP visualization with tissue brushing (control arm [CA]) or DSOC visualization and DSOC-guided biopsy sampling (study arm [SA]). This was a prospective, international, multicenter trial with a procedure-blinded pathologist., Results: The first sample sensitivity of DSOC-guided biopsy samples was significantly higher than ERCP-guided brushing (SA 68.2% vs CA 21.4%, P < .01). The sensitivity of visualization (SA 95.5% vs CA 66.7%, P = .02) and overall accuracy (SA 87.1% vs CA 65.5%, P = .05) were significantly higher in the SA compared with the CA, whereas specificity, positive predictive value, and negative predictive value showed no significant difference. Adverse events were equally low in both arms., Conclusions: DSOC-guided biopsy sampling was shown to be safe and effective with a higher sensitivity compared with standard ERCP techniques in the visual and histopathologic diagnosis of indeterminate biliary strictures. (Clinical trial registration number: NCT03140007.)., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Interventional radiology (IR) is an indispensable component of multidisciplinary care in various gastrointestinal (GI) diseases. The literature on safety and utility of IR is limited in children., Objectives: In this study, we aim to analyze the outcomes of IR in various pediatric GI diseases., Methods: The data of children (≤18 years) who underwent radiological interventions for GI disorders (2009-2017) were analyzed, retrospectively. The indications for interventions included vascular (Budd Chiari syndrome [BCS], pseudoaneurysm) and nonvascular (pancreatic fluid collections [PFCs], cholangitis and anastomotic biliary strictures). The outcomes of radiological interventions, including success and adverse events, were assessed., Results: A total of 93 children (mean age 13.45 ± 4.09 years) underwent radiological interventions for vascular (chronic BCS = 14, pseudoaneurysm = 28) or nonvascular (PFCs = 33, hepaticojejunostomy strictures or leaks = 12, cholangitis = 6) indications. Of 33 children who underwent drainage of PFCs, clinical success was noticed in 32 children during a mean follow-up of 32.4 ± 21.66 months; 11 children with persistent external pancreatic fistula were managed with endoscopic pancreatic ductal stenting (8 children) and internalization of transgastric drain (3 children). In children who underwent hepatic vein or inferior vena cava stenting for BCS, mean stent patency was 78.57% during a follow-up of 24.1 ± 13.78 months. In children with pseudoaneurysms, angioembolization was successfully performed in 92.8% patients. Re-bleeding was noticed in two children, one of whom required reintervention. In children who underwent percutaneous transhepatic biliary drainage, resolution of anastomotic strictures was noticed in all during a follow-up of 36.1 ± 13.73 months., Conclusion: Interventional radiology is safe and effective in the management of various pediatric GI diseases.

Background and Aim: The diagnosis of Hirschsprung's disease (HD) relies on anorectal manometry and rectal biopsy. The role of endoscopic biopsy is uncertain for the diagnosis of HD in children. In this study, we evaluated the adequacy of biopsies procured by endoscopic mucosal resection (EMR) for the diagnosis of HD., Methods: Consecutive children with suspected HD from January 2013 to January 2018 were enrolled in the study. EMR was performed using the standard band ligation device at a distance of about 3 cm from dentate line in rectum. All samples were assessed macroscopically and microscopically. An adequate sample was defined as those measuring >3 mm and including adequate submucosa., Results: A total of 132 children underwent evaluation for constipation in the study period. Of these, 10 children (median age, 4.25 years) underwent EMR using the band ligation device for the evaluation of HD. EMR was performed with and without submucosal lifting injection in four and six children, respectively. All the samples were adequate macroscopically (>3 mm). Absence of ganglion cells was noted in six children. Of these, three children underwent full-thickness rectal biopsy followed by surgery. Three children did not undergo surgery. Ganglion cells were identified in four children, thereby excluding the diagnosis of HD., Conclusion: Rectal biopsy using EMR with a band ligation device is feasible, safe, and provides adequate sample for the evaluation of HD in children.

The capabilities of interventional gastrointestinal endoscopy have significantly increased over the past several decades. Improvements in devices and techniques have eased the transfer of novel concepts from bench to bedside. The concept of submucosal endoscopy with mucosal flap safety valve has enabled endoscopists to securely use submucosal space, or third space. Peroral endoscopic myotomy was the initial procedure performed utilizing submucosal space in patients with achalasia. Subsequently, this technique has been used successfully for removal of subepithelial tumors from the esophagus and the stomach. All third-space endoscopy procedures use a similar technique-a submucosal tunnel is created, and then a myotomy is performed or a subepithelial tumor is dissected away from the initial site of the mucosal incision. The other potential indications for third-space endoscopy include refractory gastroparesis, Zenker diverticulum, and restoration of completely obstructed esophageal lumen. Although the emerging data look promising for peroral endoscopic myotomy and pyloromyotomy, randomized studies with long-term follow-up are lacking. Submucosal endoscopy is largely safe, and the occurrence of major adverse events is uncommon. Therefore, the majority of third-space endoscopy procedures can be performed in an endoscopy suite. The most frequently encountered adverse events during submucosal endoscopy include those related to insufflation, bleeding, and perforations., Competing Interests: The authors have no relevant conflicts of interest to disclose.

Competing Interests: Dr Reddy has no relevant conflicts of interest to disclose.

Background/objectives: Pigmentous gallstones occur in South Indians despite significant higher levels of circulating cholesterol. This study was conducted to identify the biochemical and/or genetic causes for the formation of pigmentous gallstones in this ethnic group., Methods: Plasma lipid profile, bile cholesterol, acids, and phospholipid levels were estimated in patients with gall stone disease and age, sex matched controls using standard protocols. Twenty-seven SNPs related to cholesterol and bilirubin metabolism pathway genes were genotyped in the study population using the Sequenom platform. An equilibrium phase diagram involving bile salt-phospholipid-cholesterol was generated to relate phenotype with the genotype., Results: There were no significant differences in the lipid profiles between the patients ( n  = 305) and controls ( n  = 177). Biliary cholesterol, acids, and phospholipids were significantly different between patients and controls. Single locus analysis revealed association of variants in ABCG6, ABCG8 , and UGT1A1 genes with the disease; however when correction was applied as multiple testing was done, only one variant (rs6742078) in UGT1A1 gene was found to be associated with gall stone disease. Equilibrium phase diagram suggested that few samples were in the crystal formation zone. The mutant, but not wild type or heterozygous genotype of SNPs (rs6742078 and rs887829) in UGT1A1 gene, was associated with significantly higher levels of bilirubin., Conclusions: Higher incidence of pigment stones in South Indians could be due to raised serum bilirubin levels that may be ascribed to variant in the UGT1A1 gene involved in glucuronidation of free bilirubin.

Objective: Association of PRSS1-PRSS2 (rs10273639) and CLDN2-MORC4 (rs12688220 and rs7057398) variants with alcohol-related chronic pancreatitis (CP) is established but with nonalcoholic CP is unclear. We addressed this inconsistency using tropical calcific pancreatitis (TCP) as model., Methods: We sequenced 5'-UTR of PRSS1 and genotyped CLDN2-MORC4 variants in 555 patients with TCP and 801 controls and performed association analysis. Gene-gene interaction between PRSS1 and CLDN2-MORC4 variants and with p.Asn34Ser SPINK1 and p.Leu26Val CTSB was also evaluated., Results: We observed significant association of rs10273639/rs4726576 in PRSS1-PRSS2 (odds ratio [OR] = 0.72; P = 3.50 × 10) and CLDN2-MORC4 variants, rs12688220 (OR = 1.54; P = 1.22 × 10) and rs7057398 (OR = 1.50; P = 1.22 × 10) with TCP. Patients carrying p.Asn34Ser SPINK1 were significantly younger than those with rs4726576 risk genotype (30.0 vs 38.0 years; P = 0.015) and those carrying both were even younger (22.0 years; P = 0.001). Presence of risk allele at rs12688220 in patients carrying p.Asn34Ser SPINK1 delayed the age of onset (32.0 vs 24.0 years; P = 0.013)., Conclusions: Our study establishes strong association of PRSS1-PRSS2 and CLDN2-MORC4 variants with TCP and thus with nonalcoholic CP. These variants independently interact with p.Asn34Ser SPINK1 and influence the age of onset in TCP. However, latter results need to be replicated in other cohorts.

Background and Aim: The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis., Methods: In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2 months followed by open-label antioxidants for the next 4 months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows: complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated., Results: We randomized 42 and 45 patients (mean age 29.3 years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2 months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P = 0.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P = 0.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P = 0.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P = 0.01). Needed-to-treat was 4.8. Pain reduction persisted at 6 months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P = 0.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol., Conclusion: Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic naïve patients with chronic calcific pancreatitis., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The incidence of acute pancreatitis (AP) is increasing globally and mortality could be high among patients with organ failure and infected necrosis. The predominant factors responsible for the morbidity and mortality of AP are systemic inflammatory response syndrome and multiorgan dysfunction. Even though preclinical studies have shown antisecretory agents (somatostatin), antioxidants (S-adenosyl methionine [SAM], selenium), protease inhibitors, platelet activating factor inhibitor (Lexipafant), and anti-inflammatory immunomodulators (eg. prostaglandin E, indomethacin) to benefit AP in terms of reducing the severity and/or mortality, most of these agents have shown heterogeneous results in clinical studies. Several years of experimental studies have implicated nuclear factor-kappa B (NF-κB) activation as an early and central event in the progression of inflammation in AP. In this manuscript, we review the literature on the role of NF-κB in the pathogenesis of AP, its early intraacinar activation, and how it results in progression of the disease. We also discuss why anti-protease, antisecretory, and anti-inflammatory agents are unlikely to be effective in clinical acute pancreatitis. NF-κB, being a central molecule that links the initial acinar injury to systemic inflammation and perpetuate the inflammation, we propose that more studies be focussed towards targeted inhibition of NF-κB activity. Direct NF-κB inhibition strategies have already been attempted in patients with various cancers. So far, peroxisome proliferator activator receptor gamma (PPAR-γ) ligand, pyrrolidine dithiocarbamate (PDTC), proteasome inhibitor and calpain I inhibitor have been shown to have direct inhibitory effects on NF-κB activation in experimental AP., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background and Aim: Peroral endoscopic myotomy (POEM) is a recently introduced technique for the treatment of achalasia cardia (AC). Data regarding safety and efficacy are still emerging. We report our experience of POEM emphasizing its safety, efficacy and follow-up data., Methods: Patients with AC (220; mean age 39 years, range 9-74 years) underwent POEM from January 2013 to August 2014 for AC. Retrospective analysis of prospectively collected data was done. POEM was carried out by the standard technique of mucosal incision, submucosal tunneling, and myotomy of the esophageal and gastric muscle bundles followed by closure of the mucosal incision by hemoclips. Eckardt score, high-resolution manometry (HRM) and timed barium esophagogram (TBE) were used to evaluate the results. Post-procedure patients were followed up., Results: Technical success rate of POEM was 96%. At 1 year, clinical success rate was 92%. Mean Eckardt score was 7.2 ± 1.55 prior to POEM and 1.18 ± 0.74 after POEM (P = 0.001). There was significant improvement of esophageal emptying on TBE (38.4 ± 14.0 % vs 71.5 ± 16.1 % (P = 0.001). Pre-procedure and post-procedure mean lower esophageal sphincter pressure was 37.5 ± 14.5 mmHg and 15.2 ± 6.3 mmHg, respectively. (P = 0.001) Erosive esophagitis was seen in 16% of patients who underwent POEM. There were no major adverse events., Conclusions: Study demonstrates excellent safety profile of POEM with significant relief of symptoms, reduced pressure at HRM and improved emptying at TBE. Further prospective studies are required to compare with other treatment modalities., (© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.)

Background: Peroral endoscopic myotomy (POEM) is an evolving therapeutic modality for achalasia. We aim to determine efficacy of POEM for the treatment of achalasia and compare it with laparoscopic Heller's myotomy (LHM)., Materials and Methods: Systematic review and meta-analyses was conducted on 19 studies using POEM for achalasia. Pubmed, Medline, Cochrane, and Ovid databases, were searched using the terms 'achalasia', 'POEM', 'peroral endoscopic myotomy', 'per oral endoscopic myotomy', and 'per-oral endoscopic myotomy'. Reduction in Eckhart's score and lower esophageal sphincter (LES) pressure were the main outcome measures., Results: A total of 1,045 patients underwent POEM in 29 studies. Ninety patients undergoing POEM was compared with 160 undergoing LHM in five studies. Nineteen and 14 studies, respectively, evaluated for Eckhart's score and LES pressure. There was significant reduction in Eckhart's score and LES pressure with effect sizes of -7.95 (p < 0.0001) and -7.28 (p < 0.0001), respectively. There was significant heterogeneity among the studies [(Q = 83.06; I (2) = 78.33 %; p < 0.0001) for Eckhart's score and (Q = 61.44; I (2) = 75.68 %; p < 0.0001) for LES pressure]. There were no differences between POEM and LHM in reduction in Eckhart's score, post-operative pain scores and analgesic requirements, length of hospital stay, adverse events, and symptomatic gastroesophageal reflux/reflux esophagitis. Operative time was significantly lower for POEM., Conclusions: POEM is effective for achalasia and has similar outcomes as LHM. Multicenter randomized trials need to be conducted to further compare the efficacy and safety of POEM between treatment naïve achalasia patients and those who failed treatment.