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.

Development of a novel CT-based index for predicting the number of extracorporeal shockwave lithotripsy (ESWL) sessions required for successful fragmentation of obstructing pancreatic duct stones.

BACKGROUND & AIM: Extracorporeal shock wave lithotripsy (ESWL) is used for the treatment of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP). We aimed to develop a CT based index to predict the required number of ESWL sessions for technical success. METHODS: We retrospectively evaluated patients with PDS secondary to CP who underwent ESWL. Technical success was defined as the complete fragmentation of stones to <3 mm. CT features including PDS size, number, location, and density in Hounsfield units (HU) were noted. We analyzed the relationship between PDS characteristics and the number of ESWL sessions required for technical success. A multiple linear regression model was used to combine size and density into the pancreatic duct stone (PDS) index that was translated into a web-based calculator. RESULTS: There were 206 subjects (mean age 38.6 ± 13.7 years, 59.2% male) who underwent ESWL. PDS size showed a moderate correlation with the number of ESWL sessions (r = 0.42, p < 0.01). PDS in the head required a fewer number of sessions in comparison to those in the body (1.4 ± 0.6 vs. 1.6 ± 0.7, p = 0.01). There was a strong correlation between PDS density and the number of ESWL sessions (r = 0.617, p-value <0.01). The PDS index {0.3793 + [0.0009755 x PDS density (HU)] + [0.02549 x PDS size (mm)]} could accurately predict the required number of ESWL sessions with an AUC of 0.872 (p < 0.01). CONCLUSION: The PDS index is a useful predictor of the number of ESWL sessions needed for technical success that can help in planning and patient counseling.

Predictors of persistent pain after extracorporeal shockwave lithotripsy for painful chronic calcific pancreatitis.

BACKGROUND: Extracorporeal shockwave lithotripsy (ESWL) and/or endoscopic retrograde cholangiopancreatography (ERCP) are recommended as first-line therapy for painful uncomplicated chronic pancreatitis with obstructed main pancreatic duct (MPD) in the pancreas head/body. However, predictors of pain relief after ESWL are unknown. We evaluated independent predictors of persistent pain in patients who underwent ESWL for chronic pancreatitis. METHODS: 640 consecutive adult patients with chronic pancreatitis, who underwent successful ESWL with ERCP and pancreatic duct (PD) stent placement, were followed for 12 months. The pain was assessed at baseline and at 12 months using the Izbicki Pain Score, with a score decrease of >50% considered pain relief. Independent predictors of pain relief were derived from logistic regression analysis. RESULTS: Of 640 patients (mean age 36.71 [SD 12.19] years; 60.5% men), 436 (68.1%) had pain relief and 204 (31.9%) had persistent pain. On univariate analysis, older age, male sex, alcohol and tobacco intake, longer duration of symptoms, dilated MPD and MPD stricture were associated with persistent pain at 12 months (P<0.05). Consumption of alcohol (odds ratio [OR] 1.93, 95%CI 1.26-2.97), tobacco (OR 4.09, 95%CI 2.43-6.90), duration of symptoms (OR 1.02, 95%CI 1.01-1.04), MPD size (OR 1.22, 95%CI 1.11-1.33), and MPD stricture (OR 8.50, 95%CI 5.01-14.42) were independent predictors of persistent pain. CONCLUSIONS: Alcohol, tobacco, duration of symptoms, MPD size and stricture were independent predictors of persistent pain after successful ESWL. A multidisciplinary team approach that includes behavioral therapy and surgical options should be considered for such patients.

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.

Evaluation of the Crosstalk Between the Host Mycobiome and Bacteriome in Patients with Chronic Pancreatitis.

The human microbiome is a diverse consortium of microbial kingdoms that play pivotal roles in host health and diseases. We previously reported a dysbiotic bacteriome in chronic pancreatitis patients with diabetes (CPD) compared with patients with it's nondiabetic (CPND) phenotype. In this study, we extended our exploration to elucidate the intricate interactions between the mycobiome, bacteriome, and hosts' plasma metabolome with the disease phenotypes. A total of 25 participants (CPD, n = 7; CPND, n = 10; healthy control, n = 8) were recruited for the study. We observed elevated species richness in both the bacterial and fungal profiles within the CP diabetic cohort compared to the nondiabetic CP phenotype and healthy control cohorts. Notably, the CP group displayed heterogeneous fungal diversity, with only 40% of the CP nondiabetic patients and 20% of the CP diabetic patients exhibiting common core gut fungal profiles. Specific microbial taxa alterations were identified, including a reduction in Bifidobacterium adolescentis and an increase in the prevalence of Aspergillus penicilloides and Klebsiella sp. in the disease groups. In silico analysis revealed the enrichment of pathways related to lipopolysaccharide (LPS), apoptosis, and peptidase, as well as reduced counts of the genes responsible for carbohydrate metabolism in the CP groups. Additionally, distinct plasma metabolome signatures were observed, with CPD group exhibiting higher concentrations of sugars and glycerolipids, while the CPND cohort displayed elevated levels of amino acids in their blood. The fatty acid-binding protein (FABP) concentration was notably greater in the CPD group than in the HC group (4.220 vs. 1.10 ng/ml, p = 0.04). Furthermore, compared with healthy controls, disease groups exhibited fewer correlations between key fungal taxa (Aspergillus sp., Candida sp.) and bacterial taxa (Prevotella copri, Bifidobacteria sp., Rumminococcaceae). Our study unveils, for the first time, a dysbiotic mycobiome and emphasizes unique host bacterial-mycobial interactions in CP patient with diabetes, potentially influencing disease severity. These findings provide crucial insights for future mechanistic studies aiming to unravel the determinants of disease severity in this complex clinical context. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01207-8.

Lactated Ringers Use in the First 24 Hours of Hospitalization Is Associated With Improved Outcomes in 999 Patients With Acute Pancreatitis.

INTRODUCTION: Recent pilot trials in acute pancreatitis (AP) found that lactated ringers (LR) usage may result in decreased risk of moderately severe/severe AP compared with normal saline, but their small sample sizes limit statistical power. We investigated whether LR usage is associated with improved outcomes in AP in an international multicenter prospective study. METHODS: Patients directly admitted with the diagnosis of AP were prospectively enrolled at 22 international sites between 2015 and 2018. Demographics, fluid administration, and AP severity data were collected in a standardized prospective manner to examine the association between LR and AP severity outcomes. Mixed-effects logistic regression analysis was performed to determine the direction and magnitude of the relationship between the type of fluid administered during the first 24 hours and the development of moderately severe/severe AP. RESULTS: Data from 999 patients were analyzed (mean age 51 years, female 52%, moderately severe/severe AP 24%). Usage of LR during the first 24 hours was associated with reduced odds of moderately severe/severe AP (adjusted odds ratio 0.52; P = 0.014) compared with normal saline after adjusting for region of enrollment, etiology, body mass index, and fluid volume and accounting for the variation across centers. Similar results were observed in sensitivity analyses eliminating the effects of admission organ failure, etiology, and excessive total fluid volume. DISCUSSION: LR administration in the first 24 hours of hospitalization was associated with improved AP severity. A large-scale randomized clinical trial is needed to confirm these findings.

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.

Pancreatic duct pressure: A review of technical aspects and clinical significance.

Pancreatic duct pressure (PDP) dynamics comprise an intricately modulated system that helps maintain homeostasis of pancreatic function. It is affected by various factors, including the rate of pancreatic fluid secretion, patency of the ductal system, sphincter of Oddi function, and pancreatic fluid characteristics. Disease states such as acute and chronic pancreatitis can alter the normal PDP dynamics. Ductal hypertension or increased PDP is suspected to be involved in the pathogenesis of pancreatic pain, endocrine and exocrine pancreatic insufficiency, and recurrent pancreatitis. This review provides a comprehensive appraisal of the available literature on PDP, including the methods used in the measurement and clinical implications of elevated PDP.

Long-term Outcome of Peroral Endoscopic Myotomy in Esophageal Motility Disorders: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: Peroral endoscopic myotomy (POEM) is an established treatment for achalasia. In this systematic review and meta-analysis, we aimed to analyze the mid and long-term outcomes of POEM in esophageal motility disorders. METHODS: Literature search was performed in databases including PubMed, Embase, Cochrane databases, and Google scholar from January 2010 to May 2021. The primary objective of the study was the clinical success (Eckardt score ≤3 or <4) at mid-term (30 to 60 mo) and long-term (>60 mo) follow-up after POEM. Secondary objectives included post-POEM gastroesophageal reflux (GER) as evaluated by symptoms, increased esophageal acid exposure, and reflux esophagitis. RESULTS: Seventeen studies with 3591 patients were included in the review. Subtypes of motility disorders were type I (27%), type II (54.5%), type III (10.7%), distal esophageal spasm/Jackhammer esophagus (2%), and esophagogastric junction outflow obstruction (17.5%). Pooled mean follow-up duration was 48.9 months (95% CI, 40.02-57.75). Pooled rate of clinical success at mid-term follow-up was 87% (95% CI, 81-91; I2 , 86%) and long-term was 84% (95% CI, 76-89; I2 , 47%). In nonachalasia motility disorders (esophagogastric junction outflow obstruction, distal esophageal spasm, and Jackhammer esophagus), pooled rate of clinical success was 77% (95% CI, 65-85; I2 , 0%). GER as estimated by symptoms was 23% (95% CI, 19-27; I2 , 74%), erosive esophagitis was 27% (95% CI, 18-38%; I2 , 91%), and increased esophageal acid exposure was 41% (95% CI, 30-52; I2 , 88%). CONCLUSION: POEM is a durable treatment option in cases with achalasia. One-fourth of patients suffer from erosive GER in the long-term and success rates are lower in nonachalasia esophageal motility disorders.

EUS versus MRCP to perform ERCP in patients with intermediate likelihood of choledocholithiasis: a randomised controlled trial.

OBJECTIVE: In patients with an intermediate likelihood of choledocholithiasis, European Society of Gastrointestinal Endoscopy (ESGE) guidelines recommend endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP) to diagnose choledocholithiasis to make the indication for endoscopic retrograde cholangiopancreatography (ERCP) treatment; there is no randomised control trial to compare both in this setting. DESIGN: Patients with suspected choledocholithiasis satisfying ESGE guideline's intermediate likelihood were screened for this single-centre randomised controlled trial between November 2019 and May 2020. The enrolled patients were randomised to either EUS or MRCP. ERCP was performed in stone positive cases or if clinical suspicion persisted during follow-up. Negative cases underwent a further 6-month clinical follow-up. Main outcome was accuracy (sensitivity/specificity) of both tests to diagnose choledocholithiasis, with ERCP or follow-up as a gold standard. RESULTS: Of 266 patients, 224 patients (mean age: 46.77±14.57 years; 50.9 % female) were enrolled; overall prevalence of choledocholithiasis was 49.6%, with a higher frequency in the MRCP group (63/112 vs 46/112 for EUS). Both sensitivity of EUS and MRCP were similarly high (92%-98%), without significant differences between the two groups. The negative predictive value and likelihood ratio + were significantly higher in EUS arm (p<0.05). The percentage of ERCPs either incorrectly halted back (false negatives: EUS: 2 vs MRCP: 5) or performed unnecessarily (false positives: EUS: 1 vs MRCP: 2) was low in both groups. CONCLUSION: The performance parameters of both EUS and MRCP are comparable for detecting choledocholithiasis in the intermediate-risk group of choledocholithiasis and the choice of a test should be based on local expertise, availability of resources and patient preference. TRIAL REGISTRATION NUMBER: NCT04173624.

The Modified Pancreatitis Activity Scoring System Shows Distinct Trajectories in Acute Pancreatitis: An International Study.

BACKGROUND & AIMS: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups. METHODS: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared. RESULTS: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001). CONCLUSION: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.

Optimizing nutrition in chronic pancreatitis.

PURPOSE OF REVIEW: This review aims to discuss recent developments in the nutritional management in chronic pancreatitis. RECENT FINDINGS: Nutritional assessment should be comprehensive and include dietary history, anthropometry, and biochemical nutritional parameters. Micronutrients should be evaluated at least yearly and dual-energy X-ray absorptiometry (DEXA) at every 2-yearly intervals. Studies on pancreatic enzyme replacement therapy (PERT) have primarily evaluated coefficient of fat excretion (CFA), coefficient of nitrogen excretion (CNA), and stool weight. Two RCTs, in which patients were treated with PERT for 7 days in a blinded manner and subsequently extended for 6-12 months in an open-label manner, showed improvement in nutritional parameters. However, two subsequent RCTs failed to show any benefit, and the most recent observational study demonstrated persistence of malnutrition even after PERT. The reason for the latter findings were nonadherence to PERT and poor oral intake of calories. Therefore, it is essential to educate the patients on adherence, counsel on taking high-protein, high-calorie diet, and supplement nutrients in those with inadequate oral intake. Other associated manifestations, such as diabetes and related complications, and anxiety/depression could also contribute to malnutrition directly or indirectly, and should, therefore, be adequately managed. SUMMARY: Nutritional assessment should be performed meticulously. Nutritional therapy should not be restricted to only PERT and nutritional supplementation, but should also include dietary counselling and disease related education.

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.

Rectal INdomethacin, oral TacROlimus, or their combination for the prevention of post-ERCP pancreatitis (INTRO Trial): Protocol for a randomized, controlled, double-blinded trial.

BACKGROUND: Acute pancreatitis remains the most common and morbid complication of endoscopic retrograde cholangiopancreatography (ERCP). The use of rectal indomethacin and pancreatic duct stenting has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP), but these interventions have limitations. Recent clinical and translational evidence suggests a role for calcineurin inhibitors in the prevention of pancreatitis, with multiple retrospective case series showing a reduction in PEP rates in tacrolimus users. METHODS: The INTRO trial is a multicenter, international, randomized, double-blinded, controlled trial. A total of 4,874 patients undergoing ERCP will be randomized to receive either oral tacrolimus (5 mg) or oral placebo 1-2 h before ERCP, and followed for 30 days post-procedure. Blood and pancreatic aspirate samples will also be collected in a subset of patients to quantify tacrolimus levels. The primary outcome of the study is the incidence of PEP. Secondary endpoints include the severity of PEP, ERCP-related complications, adverse drug events, length of hospital stay, cost-effectiveness, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of tacrolimus immune modulation in the pancreas. CONCLUSIONS: The INTRO trial will assess the role of calcineurin inhibitors in PEP prophylaxis and develop a foundation for the clinical optimization of this therapeutic strategy from a pharmacologic and economic standpoint. With this clinical trial, we hope to demonstrate a novel approach to PEP prophylaxis using a widely available and well-characterized class of drugs. TRIAL REGISTRATION: NCT05252754, registered on February 14, 2022.

The relationship between pre-existing diabetes mellitus and the severity of acute pancreatitis: Report from a large international registry.

BACKGROUND/OBJECTIVES: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry. METHODS: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission. RESULTS: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent. CONCLUSION: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP.

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.

Outcomes of Per-Oral Endoscopic Myotomy in Children: A Systematic Review and Meta-analysis.

Per-oral endoscopic myotomy (POEM) is an established treatment modality in adult patients with achalasia cardia. There are limited data regarding the efficacy and safety of POEM in pediatric achalasia. In this systematic review and meta-analysis, we aimed to analyze the outcomes of POEM in children and adolescents with achalasia cardia. Literature search was performed in Embase, PubMed, and Cochrane database for studies evaluating the outcome of POEM in pediatric achalasia between January 2010 and March 2021. Primary objective of the study was clinical success (Eckardt ≤ 3). Secondary outcomes included technical success, procedure duration, adverse events , and gastroesophageal reflux after POEM. A total of 14 studies (419 children, 234 boys) were included in the review. The subtypes of achalasia were type I (30.6%), type II (63.8%), and type III (5.6%). Pooled rate of technical success was 97.1% (95% CI 94.5-98.5%; I2 = 0). Pooled clinical success in intention to treat and per-protocol population was 88% (95% CI 84.4-90.9%; I2 = 0) and 94.4% (95% CI 91.5-96.4%; I2 = 0), respectively. Post-POEM, pooled mean reduction in Eckardt scores was 6.71 (95% CI 6.14 7.28; p < 0.001; I2 = 81%). Pooled rate for overall adverse events was 12.9% (95% CI 7.4-21.7%; I2 64.5%), major adverse events was 4.2% (95% CI 2.4-7.4%), and erosive esophagitis was 26.3% (95% CI 17.5-37.7%; I2 51%). POEM is an effective procedure in children with achalasia. Future studies are required to determine the durability of response and comparative outcomes with other treatment modalities for achalasia.

Risk factors for development of endocrine insufficiency in chronic pancreatitis.

Endocrine insufficiency is a common and frequent complication of chronic pancreatitis. Identifying the role of pancreatic damage in the development of diabetes is important for early identification and appropriate management. METHODS: All consecutive CP patients between January 2019 and May 2020 were retrospectively studied. Relevant statistical tests were performed. A two sided p value < 0.05 was considered statistically significant. RESULTS: Total 587 chronic pancreatitis patients were included of which 118 (20.1%) patients developed diabetes with duration of 12 (IQR 4-48) months. Older age (OR 1.079; 95% CI 1.045-1.113; p < 0.001), presence of pancreatic parenchymal (OR 2.284; 95% CI 1.036-5.038; p = 0.041) and ductal (OR 2.351; 95% CI 1.062-5.207; p = 0.035) calcifications, exocrine insufficiency (OR 6.287; 95% CI 2.258-17.504; p < 0.001), and pancreatic duct stricture (OR 3.358; 95% CI 1.138-9.912; p = 0.028) were independently associated with development of diabetes mellitus in chronic pancreatitis patients. On cox-regression analysis, smoking (HR 2.370; 95% CI 1.290-4.354; p = 0.005) and pancreatic ductal calcification (HR 2.033; 95% CI 1.286-3.212; p = 0.002) were independently associated with earlier onset of diabetes mellitus in patients with chronic pancreatitis. CONCLUSION: Pancreatic calcification, pancreatic duct stricture and pancreatic exocrine insufficiency are associated with development of diabetes mellitus in chronic pancreatitis indicating disease progression. Smoking is the modifiable risk factors associated with early onset of diabetes mellitus in CP patients.

Non-compliance to practice guidelines still exist in the early management of acute pancreatitis: Time for reappraisal?

INTRODUCTION: Earlier national surveys on the management of acute pancreatitis (AP) had reported non-compliance to practice guidelines. In the past decade, several guidelines were revised based on new evidence. In this multicenter international survey, we aimed to evaluate the practice patterns of early management of AP and compliance to the revised treatment guidelines across different disciplines and practice environments. METHODS: A structured questionnaire was sent via email to a target population of 654 that constituted of medical and surgical gastroenterologists, physicians and general surgeons, paediatricians from academic and non-academic centres across 30 countries. Other than demographic variables, the questionnaire contained items pertaining to early management of AP, such as, assessment at admissions and within first 72 h s, details regarding analgesics, IV hydration, oral/enteral feeding and antibiotic use. RESULTS: The response rate was 46.2% and after exclusions, a total of 297 participant's responses were analysed. Majority of the participants were from Asia, followed by Europe and the Americas. 181 (60.9%) claimed to follow practice guidelines, out of which 59 (32.6%) followed more than one. On further probing, only 41.9% were actually compliant to feeding and 59.7% to antibiotic guidelines. Even though participants opted for aggressive hydration, early feeding and avoidance of prophylactic antibiotics, there were non-compliance and discrepancies in titration of fluid therapy, indications of feeding and antibiotic use. DISCUSSION: Discrepancies and non-compliance still appear to exist in the early management of AP due to lack of strong evidence. We discuss ways that could improve compliance to the existing guidelines until stronger evidence comes to the fore.

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.