Buprenorphine Versus Diclofenac for Pain Relief in Acute Pancreatitis: A Double-Blinded Randomized Controlled Trial.

BACKGROUND: Although both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are used for analgesia in acute pancreatitis (AP), the analgesic of choice is not known. We compared buprenorphine, an opioid, and diclofenac, an NSAID, for analgesia in AP. METHODS: In a double-blind randomized controlled trial, AP patients were randomized to receive intravenous diclofenac or intravenous buprenorphine. Fentanyl was used as rescue analgesia, delivered through a patient-controlled analgesia pump. Primary outcome was the difference in the dose of rescue fentanyl required. Secondary outcomes were the number of effective and ineffective demands of rescue fentanyl, pain-free interval, reduction in visual analogue scale (VAS) score, adverse events, and organ failure development. RESULTS: Twenty-four patients were randomized to diclofenac and 24 to buprenorphine. The 2 groups were matched at baseline. The total amount of rescue fentanyl required was significantly lower in the buprenorphine group:130 µg, interquartile range (IQR), 80-255 vs 520 µg, IQR, 380-1065 (P < .001). The number of total demands was 32 (IQR, 21-69) in the diclofenac arm vs 8 (IQR, 4-15) in the buprenorphine arm (P < .001). The buprenorphine group had more prolonged pain-free interval (20 vs 4 hours; P < .001), with greater reduction in the VAS score at 24, 48, and 72 hours compared with the diclofenac group. These findings were confirmed in the subgroup of moderately severe/severe pancreatitis. Adverse events profile was similar in the 2 groups. CONCLUSIONS: Compared with diclofenac, buprenorphine appears to be more effective and equally safe for pain management in AP patients, even in the subcohort of moderately severe or severe pancreatitis (Trial Registration number: CTRI/2020/07/026914).

Liver abnormalities in celiac disease and response to gluten free diet: A systematic review and meta-analysis.

BACKGROUND AND AIM: Liver involvement in celiac disease (CeD) is known but its various etiologies and the effect of gluten free diet (GFD) on it is understudied. METHODS: We searched PubMed, Medline and Embase databases from date of inception to March 7, 2022, to look for studies reporting on CeD and liver abnormalities. Pooled proportion of CeD patients with deranged transaminases, etiologies of various other liver diseases with CeD and the response to GFD were estimated. Subgroup analyses based on the age group, geographic distribution and duration of GFD were also carried out. RESULTS: Total 42 studies (8976 patients) reported hyper-transaminasemia in patients with celiac disease. The pooled proportion of patients with elevated transaminases was 21.42% (95% CI: 17.02-26.59, I2  = 94%) overall, with similar prevalence among adults (21.20%) and children (21.51%). The commonest etiology was celiac hepatitis at 49.23% (95% CI: 30.09-68.59, I2  = 87%). Compliance with GFD was noted in 90.27%. The proportion of CeD patients with liver abnormalities who showed response to GFD was 86.39% (95% CI: 80.04-90.95, I2  = 74%) overall. CONCLUSION: Liver involvement was noted in 21.42% of CeD patients. Celiac hepatitis was reported in nearly half of them. Good compliance and response were noted with GFD.

Role of Peroral Endoscopic Myotomy in Advanced Achalasia Cardia With Sigmoid and/or Megaesophagus: A Systematic Review and Metanalysis.

BACKGROUND/AIMS: Sigmoid esophagus and/or megaesophagus are considered as an advanced stage in the natural history of achalasia cardia. The role of peroral endoscopic myotomy (POEM) in these subset of patients is emerging. We performed a systematic review and metanalysis to study the efficacy of POEM in advanced achalasia cardia with sigmoid and megaesophagus. METHODS: A literature search in PubMed and Embase was done from inception till August 3, 2021 to look for studies reporting exclusively on the role of POEM in advanced achalasia cardia with sigmoid and/or megaesophagus. The random effect method with inverse variance approach was used for the computation of pooled prevalence. For 2 groups' analysis of continuous outcome standardized mean difference was used as the summary measure. RESULTS: Eleven studies with 428 patients were included for analysis. The pooled technical and clinical success was 98.27% (95% CI, 96.19-99.22; I2 = 0%) and 89.38% (95% CI, 84.49-92.86; I2 = 26%) and on subgroup analysis into sigmoid and megaesophagus it was (98.06% [95% CI, 95.41-99.19; I2 = 0%], 98.47% [95% CI, 92.72-99.69; I2 = 0%] and 87.92% [95% CI, 80.68-92.70; I2 = 37%], 88.36% [95% CI, 62.62-97.17; I2 = 77%]) respectively. The clinical success at < 1 year and 1-3 year follow-up was 89.37% (95% CI, 82.82-93.61; I2 = 0%) and 88.66% (95% CI, 81.65-91.22; I2 = 46%) respectively. There was a significant reduction in the post-POEM scores with standardized mean difference for Eckardt score (4.81), for integrated relaxation pressure at 4 seconds (1.93), and for lower esophageal sphincter pressure (2.06). CONCLUSIONS: POEM is an effective modality of treatment even in the subset of patients of advanced achalasia cardia with sigmoid and megaesophagus.

Oesophageal Tuberculosis: A Systematic Review Focusing on Clinical Management.

Oesophageal tuberculosis, an uncommon form of extrapulmonary tuberculosis, has been reported mainly as small case series and the literature is heterogeneous. A systematic review to characterize the clinical presentation, evaluation and management of oesophageal tuberculosis was performed. Electronic databases were searched with keywords: esophagus OR esophageal AND tuberculosis. We included original papers and case series (> 4 patients) with oesophageal tuberculosis. Twenty-two studies reporting 311 patients were included. Mean age in most of the studies was 31-51 years and male gender constituted 50.5% patients. Dysphagia (72.3%), odynophagia (22.4%) and chest pain (31.3%) were predominant symptoms. Mid-oesophagus was the commonest site of involvement (88%). Endoscopic findings included ulcers (59.9%), submucosal bulge (31.7%), extrinsic compression (24.8%) and pseudotumour (5.8%). On endoscopic ultrasound, presence of hypoechoic (69.5%), heteroechoic (47.6%) and matted (86.3%) mediastinal lymph nodes and oesophageal wall involvement (67.3%) were common findings. Computed tomography showed mediastinal lymphadenopathy (76.5%) and oesophageal thickening (52.1%). Diagnosis was confirmed by granuloma (72.3%) and acid fast bacilli positivity (32.5%) in mots patients. Response to antitubercular therapy was excellent; 97.7% patients recovered and 2.3% patients died. Surgery (14.5%) and oesophageal stenting (11.4%) were required infrequently. Oesophageal tuberculosis should be considered in endemic regions as a cause of dysphagia because early treatment is associated with excellent outcomes.

TPMT and NUDT15 polymorphisms in thiopurine induced leucopenia in inflammatory bowel disease: a prospective study from India.

BACKGROUND: Polymorphisms in thiopurine methyltransferase (TPMT) and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine induced leukopenia in the Western countries and East Asia respectively. Exact role of these polymorphisms in South Asian population with inflammatory bowel disease (IBD) is uncertain. METHODS: We included consecutive patients with IBD who were initiated on thiopurines at a center in North India. The dosage of thiopurines was titrated using regular monitoring of hemogram and liver function tests. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) and one NUDT15 polymorphism (c.415 C > T) were assessed. Comparison regarding incidence of leukopenia and maximum tolerated thiopurine dosage was performed between those with wild polymorphism and those with TPMT and NUDT15 polymorphisms, respectively. RESULTS: Of the 119 patients (61 males, mean age 36.8 ± 13.5 years), 105 (88.2%) had ulcerative colitis and 14 (11.8%) had Crohn's disease. Leukopenia was noted in 33 (27.7%), gastrointestinal intolerance in 5 (4.2%) and pancreatitis in 2 (1.6%). TPMT polymorphisms were detected amongst five patients of whom 1 developed leukopenia. NUDT15 polymorphism was noted in 13 patients of whom 7 had leukopenia. The odds of developing leukopenia in TPMT polymorphism were non-significant (0.77, 95% CI:0.0822 to 7.2134, P = 0.819) but were significantly higher in those with NUDT15 polymorphism (3.5933, 1.1041 to 11.6951, P value: = 0.0336). CONCLUSION: NUDT15 polymorphism was more frequent than TPMT polymorphisms and was associated with thiopurine induced leukopenia. However, the tested polymorphisms account for only 24.2% of the risk of thiopurine induced leukopenia.

Diverticular per oral endoscopic myotomy (DPOEM) for esophageal diverticular disease: a systematic review and meta-analysis.

The traditional way to tackle Zenker's diverticulum (ZD) has been flexible endoscopic septum division (FESD). Recently, the concept of per oral endoscopic myotomy has been found useful for managing diverticular diseases of the esophagus and has been termed DPOEM. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of D-POEM in diverticular disease of the esophagus and to compare it with FESD. We systematically searched PubMed and Embase, for studies reporting clinical success, technical success and adverse events in D-POEM alone or D-POEM comparing with FESD. We computed pooled prevalence for D-POEM alone and risk ratio for D-POEM vs FESD using random effect method with inverse variance approach. Subgroup analysis for ZD, non-ZD and mixed diverticulum was conducted. Totally 19 studies including 341 patients were identified reporting on D-POEM. The pooled clinical, technical success and adverse event rates for D-POEM were 87.07%, 95.19% and 10.22%, respectively. The clinical success was significantly better than FESD while the technical success, adverse event rate, procedure time and length of hospital stay were comparable with FESD. The recurrence rate was negligible for D-POEM compared to FESD. On subgroup analysis by dividing into three groups of ZD, non-ZD and mixed, there was no difference between clinical, technical success and adverse event rate among the three groups. D-POEM is an effective and safe technique among both ZD and non-ZD patients and has better clinical success than FESD.

Per-oral Endoscopic Myotomy and Other Applications of Third Space Endoscopy: Current Status and Future Perspectives.

INTRODUCTION: The modification of NOTES (natural orifice transluminal endoscopic surgery) by mucosal safety flap has introduced us to the world of third space endoscopy (TSE). POEM (per-oral endoscopic myotomy) for achalasia cardia being its first vista, the realm expanded so that we can now remove en bloc a subepithelial/intramural tumor by POET (per-oral endoscopic tumor resection), perform G-POEM (gastric per-oral endoscopic myotomy) for refractory gastroparesis, restore esophageal continuity in complete obstruction by performing POETRE (per-oral endoscopic tunneling for the restoration of the esophagus), divide the septum in Zenker diverticulum completely with negligible risk of perforation by Z-POEM (Zenker per-oral endoscopic myotomy) and relieve constipation in Hirschsprung disease by PREM (per-rectal endoscopic myotomy). However, the real potential of TSE became evident with the introduction of POEM with fundoplication. TSE has opened the gates of the peritoneal cavity. Improved expertise and equipment will make the role of endoscopist complimentary to the surgeon with the dawn of a new field in therapeutic endoscopy. AREAS COVERED: This review intends to comprehensively discuss the various aspects of POEM for achalasia studied so far followed by a brief discussion about other applications of TSE and the future perspectives in this exciting field.

Visceral scalloping in pancreatic ascites: An uncommon manifestation of pancreatitis.

Scalloping of visceral organs like liver and spleen can cause certain peritoneal diseases. It has usually been described with pseudomyxoma peritonei and peritoneal carcinomatosis. Occasionally, it has also been described with certain benign conditions like peritoneal tuberculosis. We describe visceral scalloping in setting of pancreatic diseases. We believe that pancreatic fluid collections exert significant pressure on the visceral organs to result in scalloping of the visceral surfaces.