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Background: Acute pancreatitis (AP) is known to result in endocrine dysfunction (prediabetes, diabetes). The objective of this study was to determine the temporal incidence of endocrine dysfunction after onset of AP and determine the risk factors in Indian patients., Methods: In this prospective study, enrolled patients diagnosed with AP between February 2019 and May 2019 were followed at 3, 6, and 12 months until May 2020. Patients with recurrent AP, chronic pancreatitis, and pre-existing endocrine dysfunction were excluded. Demographic and disease severity (clinical, laboratory, and radiological) data were recorded. Mann-Whitney U and Chi-square tests were used to compare groups. Temporal trend for development of endocrine dysfunction was evaluated using the Extended Mantel Haenszel Chi-square test for trend. Logistic regression was used to identify independent risk factors., Results: Eighty-six patients (males 66, median [IQR] age 33.0 [26.0-44.2] years) who fulfilled enrolment criteria were finally analyzed. The most common etiology was alcohol (n=31 [36%]) followed by gallstones (n=17 [19.8%]). The proportion of patients with moderately severe acute pancreatitis and severe AP were 59.3% and 15.1%, respectively. Overall, the frequency of prediabetes and diabetes increased temporally across the follow-up period. These were 2 (2.33%) and 1 (1.16%) at 3 months, 11 (12.8%) and 5 (5.81%) at 6 months, and 20 (23.2%) and 9 (10.5%) at 1 year, respectively. On multivariable logistic regression, intervention for walled-off necrosis (WON) emerged as the single independent risk factor for endocrine dysfunction (odds ratio 9.01 [2.3-35.5]; p=0.002)., Conclusions: Endocrine dysfunction is frequent after an episode of AP. Intervention for WON is an independent risk factor for endocrine dysfunction., (© 2022. Indian Society of Gastroenterology.)

Background: Pathophysiology of transformation of inflammatory lesions in chronic pancreatitis (CP) to pancreatic ductal adenocarcinoma (PDAC) is not clear., Methods: We conducted a systematic review, meta-analysis of circulating metabolites, integrated this data with transcriptome analysis of human pancreatic tissues and validated using immunohistochemistry. Our aim was to establish biomarker signatures for early malignant transformation in patients with underlying CP and identify therapeutic targets., Results: Analysis of 19 studies revealed AUC of 0.86 (95% CI 0.81-0.91, P < 0.0001) for all the altered metabolites (n = 88). Among them, lipids showed higher differentiating efficacy between PDAC and CP; P-value (< 0.0001). Pathway enrichment analysis identified sphingomyelin metabolism (impact value-0.29, FDR of 0.45) and TCA cycle (impact value-0.18, FDR of 0.06) to be prominent pathways in differentiating PDAC from CP. Mapping circulating metabolites to corresponding genes revealed 517 altered genes. Integration of these genes with transcriptome data of CP and PDAC with a background of CP (PDAC-CP) identified three upregulated genes; PIGC, PPIB, PKM and three downregulated genes; AZGP1, EGLN1, GNMT. Comparison of CP to PDAC-CP and PDAC-CP to PDAC identified upregulation of SPHK1, a known oncogene., Conclusions: Our analysis suggests plausible role for SPHK1 in development of pancreatic adenocarcinoma in long standing CP patients. SPHK1 could be further explored as diagnostic and potential therapeutic target., (© 2022. The Author(s).)

Background/aims: Per-oral endoscopic myotomy (POEM) is an established treatment for achalasia. The technique of POEM is still evolving and the impact of length of esophageal myotomy on the outcomes of POEM is not known. In this study, we aim to compare the outcomes of short (3 cm) versus long (6 cm and above) esophageal myotomy in patients undergoing POEM for achalasia cardia., Methods: Consecutive patients with idiopathic achalasia (type I and II) were randomized to receive short (3 cm) or long esophageal myotomy (≥ 6 cm). Both groups were compared for clinical success, operative time, adverse events, and gastroesophageal reflux disease (GERD)., Results: Seventy-one consecutive patients with type I and II achalasia underwent POEM with short (n = 34) or long (n = 37) esophageal myotomy techniques. Mean length of esophageal myotomy in short and long groups was 2.76 ± 0.41 and 7.97 ± 2.40, respectively ( P < 0.001). Mean operative time was significantly shorter in short myotomy group (44.03 ± 13.78 minutes and 72.43 ± 27.28 minutes, P < 0.001). Clinical success was comparable in both arms at 1-year (Eckardt score 0.935 ± 0.929 vs 0.818 ± 0.983, P = 0.627). Improvement in objective parameters including integrated relaxation pressure and barium column height at 5 minutes was similar in both groups. GERD was detected in 50.88% patients with no significant difference in short and long myotomy groups (44.44% vs 56.67%, P = 0.431)., Conclusions: A short esophageal myotomy is non-inferior to long myotomy with regards to clinical success, adverse events, and GERD in cases with type I and II achalasia. Reduced operating duration favors short esophageal myotomy in these patients.

Background: In severe acute pancreatitis (AP), intravenous glutamine has been shown to reduce the rate of complications, hospital stay, and mortality. In the present randomized trial, we aimed to evaluate the effect of enteral glutamine supplementation on clinical outcomes, gut permeability, systemic inflammation, oxidative stress, and plasma glutamine levels in patients with severe and predicted severe AP., Methods: Patients with AP admitted within 72 h of onset of symptoms were included. The primary outcome measure was development of infected pancreatic and peri-pancreatic necrosis and in-hospital mortality. High-sensitivity C-reactive protein (HS-CRP) and interleukin-6 (IL-6) were evaluated as markers of inflammation; plasma thiobarbituric acid reactive substances (TBARS) and activities of serum superoxide dismutase and glutathione peroxidase were determined to evaluate oxidative stress; serum polyethylene glycol (PEG) was tested for intestinal permeability; subjective global assessment (SGA) was used for nutritional assessment, and an improvement in organ function was measured by the Modified Marshall score. Intention-to-treat analysis was used. A p-value of < 0.05 was considered statistically significant., Results: After power calculation, we enrolled 18 patients in the glutamine and 22 in the control arm. There was no significant improvement in the development of infected necrosis and in-hospital mortality between the groups. Improvement in Modified Marshall score was observed in a higher proportion of patients receiving glutamine (15 [83.3%] vs. 12 [54.5%]; p = 0.05). Plasma glutamine levels improved more in glutamine-treated group (432.72 ± 307.83 vs. 618.06 ± 543.29 μM/L; p = 0.004), while it was lower in controls (576.90 ± 477.97 vs. 528.20 ± 410.45 μM/L; p = 0.003). PEG level was lower after glutamine supplementation (39.91 ± 11.97 vs. 32.30 ± 7.39 ng/mL; p = 0.02). Statistically significant reduction in IL-6 concentration was observed in the glutamine group at the end of treatment (87.44 ± 7.1 vs. 63.42 ± 33.7 μM/L; p = 0.02)., Conclusions: Despite absence of improvement in infected necrosis and in-hospital mortality, enteral glutamine supplementation showed improvement in gut permeability, oxidative stress, and a trend towards improvement in organ function as depicted by improvement in the Modified Marshall score., Trial Registration: NCT01503320.

Introduction: This paper reports preliminary data of an ongoing study that evaluates the association of systemic inflammatory response (SIRS) with early severe acute pancreatitis (ESAP) and compensatory anti-inflammatory response syndrome (characterized by HLA-DR down-regulation) with infected pancreatic necrosis (IPN)., Methods: Consecutive patients presenting within 72 h of symptom onset with organ dysfunction and/or local complications were included. Following parameters were recorded: demographics, etiology, SIRS, APACHE II, creatinine, BUN. Circulating IL-8, IL-6, IL-10, TNF-alpha concentrations and expression of HLA-DR and IL-10 by qRT-PCR in PBMCs were measured. Strength of associations of cytokine concentration and HLA-DR/IL-10 expression with outcomes was expressed as Hedges' G and relative risk (95% CI)., Results: Twenty-eight patients (10 MSAP; 18 SAP) fulfilled inclusion criteria. Twelve patients had ESAP and eight presented with organ failure. Admission SIRS worsened in eight (28.6%) patients over 48 h. Sixteen (57.1%) patients developed primary IPN. Twenty-one (75%) patients had HLA-DR down-regulation during the first week, which persisted to the second week in 12 (42.9%) patients. IL-8, IL-6, and TNF-α progressively increased from healthy controls to MAP to MSAP to SAP. IL-6 and TNF-α was higher in the patients who developed ESAP (p = 0.01 and 0.05, respectively). Patients who died within the first week also had a significantly elevated concentration of IL-6 and TNF-α (p = 0.02 and 0.01, respectively). The relative risk (95% CI) of developing primary IPN with persistent HLA-DR down-regulation till the second week of illness was 11.3 (1.6-82.4; p = 0.01)., Conclusions: Our study objectively demonstrates significant association of ESAP and early mortality with primary cytokine response, and development of IPN with persistent HLA-DR down-regulation.