Extracorporeal Shock-Wave Lithotripsy and Endoscopy for the Treatment of Pain in Chronic Pancreatitis : A Sham-Controlled, Randomized Trial.

BACKGROUND: No randomized controlled trials have substantiated endoscopic decompression of the pancreatic duct in patients with painful chronic pancreatitis. OBJECTIVE: To investigate the pain-relieving effect of pancreatic duct decompression in patients with chronic pancreatitis and intraductal stones. DESIGN: 24-week, parallel-group, randomized controlled trial (ClinicalTrials.gov: NCT03966781). SETTING: Asian Institute of Gastroenterology in India from February 2021 to July 2022. PARTICIPANTS: 106 patients with chronic pancreatitis. INTERVENTION: Combined extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde pancreatography (ERP) compared with sham procedures. MEASUREMENTS: The primary end point was pain relief on a 0- to 10-point visual analog scale (VAS) at 12 weeks. Secondary outcomes were assessed after 12 and 24 weeks and included 30% pain relief, opioid use, pain-free days, questionaries, and complications to interventions. RESULTS: 52 patients in the ESWL/ERP group and 54 in the sham group were included. At 12 weeks, the ESWL/ERP group showed better pain relief compared with the sham group (mean difference in change, -0.7 [95% CI, -1.3 to 0] on the VAS; P = 0.039). The difference between groups was not sustained at the 24-week follow-up, and no differences were seen for 30% pain relief at 12- or 24-week follow-up. The number of pain-free days was increased (median difference, 16.2 days [CI, 3.9 to 28.5 days]), and the number of days using opioids was reduced (median difference, -5.4 days [CI, -9.9 to -0.9 days]) in the ESWL/ERP group compared with the sham group at 12-week follow-up. Safety outcomes were similar between groups. LIMITATION: Single-center study and limited duration of follow-up. CONCLUSION: In patients with chronic pancreatitis and intraductal stones, ESWL with ERP provided modest short-term pain relief. PRIMARY FUNDING SOURCE: Asian Institute of Gastroenterology and Aalborg University Hospital.

Kynurenine pathway alteration in acute pancreatitis and its role as a biomarker of infected necrosis.

INTRODUCTION: Infected pancreatic necrosis (IPN) is a major cause of mortality in acute pancreatitis (AP). Currently, no specific strategies are available to predict the development of IPN. Earlier we reported that persistent down-regulation of HLA-DR increases risk of developing IPN. Altered kynurenine pathway (KP) metabolites showed poor prognosis in sepsis. Here we evaluated the role of HLA-DR and KP in IPN. METHODS: Patients with ANP and healthy controls were enrolled. Demographic and clinical parameters were recorded. Circulating interleukin (IL)-8, 6, 1ß, 10, Tumor necrosis factor-α were quantified using flowcytometry. Plasma procalcitonin, endotoxin, and KP (tryptophan, kynurenine) concentrations were estimated using ELISA. qRT-PCR was conducted to evaluate mRNA expression of HLA-DR, IL-10, Toll like receptor-4 (TLR-4), and kynurenine-3-monooxygenase (KMO) genes on peripheral blood mononuclear cells. Plasma metabolites were quantified using gas chromatography mass spectrometry (GC-MS/MS). Standard statistical methods were used to compare study groups. Metaboanalyst was used to analyse/visualize the metabolomics data. RESULTS: We recruited 56 patients in Cohort-1 (IPN:26,Non-IPN:30), 78 in Cohort-2 (IPN:57,Non-IPN:21), 26 healthy controls. Increased cytokines, endotoxin, and procalcitonin were observed in patients with IPN compared to Non-IPN. HLA-DR and KMO gene expressions were significantly down-regulated in IPN groups, showed positive correlation with one another but negatively correlated with IL-6 and endotoxin concentrations. Increased IDO and decreased plasma tryptophan were observed in IPN patients. Metabolome analysis showed significant reduction in several essential amino acids including tryptophan in IPN patients. Tryptophan, at a concentration of 9 mg/ml showed an AUC of 91.9 (95%CI 86.5-97.4) in discriminating IPN. CONCLUSION: HLA-DR downregulation and KP alteration are related to IPN. The KP metabolite plasma tryptophan can act as a potential biomarker for IPN.

Pain, depression, and poor quality of life in chronic pancreatitis: Relationship with altered brain metabolites.

BACKGROUND: To evaluate if altered brain metabolites are connected to pain, depression and affective responses in CP. METHODS: In this prospective study we evaluated pain characteristics, QOL (EORTC QLQc30+PAN28), depression (Beck depression inventory [BDI] II) in 558 patients with CP and 67 healthy controls. Brain metabolites were evaluated using magnetic resonance spectroscopy (MRS) in 49 patients and 5 healthy controls. We measured plasma metabolites using gas chromatography-mass spectrometry (GC-MS/MS). Relationship between metabolomic alterations, pain, depression and QOL components were assessed using statistical/bioinformatics methods. Benjamini-Hochberg FDR correction was applied for multiple testing. RESULTS: 261 (46.8%) patients had depression compared to 5 (7.5%) among healthy controls [n = 67](p < 0.0001). Risk [OR (95% CI) of developing depression in the presence of pain was 1.9 (1.33-1.68); p = 0.0004. The depression scores correlated negatively with functional components and positively with symptom components of EORTC QLQ30. Significant negative correlation, though based on a small sample size, was observed between N-acetyl aspartate in the left hippocampus and choline in the left prefrontal cortex with emotional and cognitive functions. PLS-DA modelling revealed significant alteration in the plasma metabolomic profile among patients with CP who had depression. Six metabolites were significantly different between CP with depression and healthy controls, of which glycine contributed most significantly to the PLS-DA model (VIP score of 3.5). CONCLUSIONS: A significant proportion of patients with CP develops depression that correlate with poor QOL functions. Pain, depression, and emotional components of QOL in patients with CP correlated with N-acetyl aspartate and choline in the left hippocampus and left prefrontal cortex of the brain.

The gut microbiome in pancreatogenic diabetes differs from that of Type 1 and Type 2 diabetes.

We hypothesized that the gut microbiome in patients with diabetes secondary to chronic pancreatitis (Type 3c) is different from those with Type 1 and Type 2 diabetes. This was a cross-sectional preliminary study that included 8 patients with Type 1, 10 with Type 2, 17 with Type 3c diabetes and 9 healthy controls. Demographic, clinical, biochemical, imaging and treatment data were recorded and sequencing of the V3-V4 region of the bacterial 16SrRNA was done on fecal samples. Bioinformatics and statistical analyses was performed to evaluate the differences in the diversity indices, distance matrices, relative abundances and uniqueness of organisms between the types of diabetes. There was significant difference in the species richness. Beta diversity was significantly different between patients with Type 3c diabetes and the other groups. 31 genera were common to all the three types of diabetes. There was significant differences in the species level taxa between Type 3c diabetes and the other groups. The unique bacterial species signature in Type 3c diabetes compared to Type 1 and Type 2 diabetes included Nesterenkonia sp. AN1, Clostridium magnum, Acinetobacter lwoffii, Clostridium septicum, Porphyromonas somerae, Terrabacter tumescens, and Synechococus sp.

Malnutrition after pancreatic enzyme replacement therapy in chronic pancreatitis: Risk factors in real world practice.

BACKGROUND: RCTs that have shown improvement in coefficient of fat absorption with pancreatic enzyme replacement therapy (PERT) have seldom evaluated the impact on overall nutritional status. OBJECTIVE: In this study we evaluated factors responsible for persistence of malnutrition after PERT. METHODS: In this cross-sectional observational study, patients were enrolled based on predefined enrolment criteria. Patients were divided into those taking PERT regularly (Group A), irregularly (Group B) and not taking (Group C) for at least 3 months. Comprehensive evaluation of anthropometric measurements, nutritional assessment and dietary intake was performed. Malnutrition was measured using the Subjective Global Assessment (SGA) tool. Relationship between PERT status, dietary intake and nutritional status were evaluated using standard statistical methods. Logistic regression was performed to identify factors associated with persistence of malnutrition after PERT. RESULTS: 377 patients with CP and 50 controls were included. 95 (25.2%) patients with CP were in Group A, 106 (28.1%) in Group B and 176 (46.7%) in Group C. 130 (34.5%) patients were malnourished, of which 76 (58.5%) were continuing PERT. There were no differences in clinical and biochemical nutritional markers between Groups A, B, and C. Calorie deficit and daily intake of calorie, protein, carbohydrates and fats were not different between those with and without PERT, but was significantly less in those with malnutrition. Logistic regression demonstrated inadequate dietary intake as independent risk factor for persistence of malnutrition. CONCLUSION: Even though PERT is effective in PEI, comprehensive nutritional assessment, personalized nutritional counselling and therapy along with PERT is mandatory.

The Indian gut microbiota-Is it unique?

Colonization of the gut by microbes depends on a number of factors including age, diet, genetic makeup, gender, geographic location, and health status of an individual. India is a megadiverse country and includes 4 biodiversity hot spots. These features, along with the transitioning Indian sociodemographic profile, make the gut microbiota of Indian subjects an interesting area to study. In this review, we critically discuss the present status of the gut microbiome in the Indian population and its difference from other populations. We also discuss the aberrations in the available study designs that could introduce heterogeneity. An ideal study to evaluate the core gut microbiota of healthy Indians should involve a large homogeneous population across the country and use the same technology and data analytics tools. The "Landscape of Gut Microbiome-Pan India Exploration" (LogMPIE) is such a study that confirmed the most predominant organisms in Indians to be Prevotella copri and Faecalibacterium prausnitzii.