Indian consensus statements on irritable bowel syndrome in adults: A guideline by the Indian Neurogastroenterology and Motility Association and jointly supported by the Indian Society of Gastroenterology.

The Indian Neurogastroenterology and Motility Association (INMA), earlier named the Indian Motility and Functional Diseases Association developed this evidence-based practice guidelines for the management of irritable bowel syndrome (IBS). A modified Delphi process was used to develop this consensus containing 28 statements, which were concerning diagnostic criteria, epidemiology, etiopathogenesis and comorbidities, investigations, lifestyle modifications and treatments. Owing to the Coronavirus disease-19 (COVID-19) pandemic, lockdowns and mobility restrictions, web-based meetings and electronic voting were the major tools used to develop this consensus. A statement was regarded as accepted when the sum of "completely accepted" and "accepted with minor reservation" voted responses were 80% or higher. Finally, the consensus was achieved on all 28 statements. The consensus team members are of the view that this work may find use in teaching, patient care, and research on IBS in India and other nations.

Fractional Excretion of Sodium and Urea in Differentiating Acute Kidney Injury Phenotypes in Decompensated Cirrhosis.

Background: Prerenal acute kidney injury (prerenal AKI), hepatorenal syndrome (HRS-AKI), and acute tubular necrosis (ATN-AKI) are the various phenotypes of acute kidney injury, which are described in decompensated cirrhosis. It has therapeutic and prognostic implications. We aimed to evaluate the diagnostic utility of fractional excretion of sodium and urea (FENa and FEUrea) for differentiating AKI phenotypes. Methods: A prospective analysis was performed in 200 patients with decompensated cirrhosis with AKI to derive receiver operating curve, optimal cut-off, sensitivity, and specificity. These findings were validated in an independent cohort (n = 50) to differentiate ATN-AKI, HRS-AKI, and prerenal AKI. Results: The incidence of prerenal AKI, HRS-AKI, and ATN-AKI were 37.5%, 34%, and 28.5% in the derivation cohort and 28%, 38%, and 34% in the validation cohort respectively. The median FENa was significantly different in various phenotypes of AKI in the derivation and validation cohort (P 0.001); FEUrea was significantly different in the derivation cohort (P 0.0001), not in the validation cohort (P 0.106). The AUC for FENa (cut-off, sensitivity/specificity) was 86.6% (0.567, 89/71) and for FEUrea was 60.3% (34.73, 70/58) for ATN-AKI vs. non-ATN-AKI. The area under the curve for FENa to differentiate between HRS-AKI vs. non-HRS-AKI was 74.5%. FEUrea could not differentiate HRS-AKI vs. non-HRS-AKI (AUC 60.4%) satisfactorily. FENa and FEUrea were unable to differentiate between prerenal AKI and HRS-AKI (AUC <70%). Conclusion: Among cirrhotics FENa at admission is a simple, commonly available clinical tool that can be used to differentiate structural AKI from prerenal AKI and HRS-AKI. The newly derived lowered cut-off value of FENa makes the diagnosis of ATN-AKI easier, faster and thus obviates the need for extensive workup in a significant proportion of patients. FENa appears better than FEUrea in decompensated cirrhosis with AKI.

Predictors of Long-Term Outcomes, Recurrent Dysphagia, and Gastroesophageal Reflux After Per-oral Endoscopic Myotomy in Esophageal Motility Disorders.

BACKGROUND: There is limited data on long-term outcomes of per-oral endoscopic myotomy (POEM). In this study, we aim to evaluate the efficacy of POEM in patients who completed a minimum follow-up of 5 years. METHODS: Data of patients who underwent POEM and completed ≥ 5-year follow-up were analyzed, retrospectively. Primary outcome of study was clinical success (Eckardt ≤ 3) at ≥ 5 years after POEM. Secondary outcomes included predictors of dysphagia and symptomatic gastroesophageal reflux disease (GERD) on long-term follow-up. RESULTS: Three hundred nineteen patients (males 182, mean age 40.5 ± 14.2 years) completed a median of 73-(60-89) month follow-up. Esophageal motility disorders included idiopathic achalasia (type I 26.6%, type II 60.8%, type III 5.6%) and Jackhammer esophagus or distal esophageal spasm (2.8%). POEM was technically successful in 307 (96.2%) patients. Long-term success was 92.6% (overall), 92.1% (type I), 94.7% (type II), 87.5% (type III), and 75% (Jackhammer esophagus/distal esophageal spasm). Symptomatic GERD and reflux esophagitis were detected in 28.9% and 35.3% patients, respectively. On multivariate analysis, young age and female gender were independent risk factors for recurrent dysphagia (p = 0.037) and symptomatic GERD after POEM (p = 0.025), respectively. Lower post-POEM lower esophageal sphincter pressure was an independent predictor for reflux esophagitis (p = 0.016). CONCLUSION: POEM is an effective and durable treatment for achalasia and non-achalasia spastic motility disorders. Young patients and females may be at higher risk for recurrent dysphagia and symptomatic GERD, respectively.

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.

Endoscopic full-thickness plication for the treatment of PPI-dependent GERD: results from a randomised, sham controlled trial.

BACKGROUND: The majority of endoscopic antireflux procedures for GERD are cumbersome to use and randomised long-term data are sparse. We conducted such a trial to determine the efficacy and safety of a novel, easy to use endoscopic full-thickness fundoplication (EFTP) device in patients with GERD. DESIGN: Patients with proton pump inhibitor (PPI)-dependent GERD were randomised to either EFTP or a sham procedure in 1:1 ratio. The primary endpoint was ≥50% improvement in the health-related quality of life (GERD-HRQL) score at 3 months. Secondary end points included improvement in GERD-HRQL, reflux symptom scores, PPI usage, oesophageal acid exposure and reflux episodes and endoscopic findings at 3, 6 and 12 months. RESULTS: Seventy patients were randomised; 35 in each group with a median (IQR) age of 36 (29-42) years, 71.4% males. 70% had non-erosive reflux disease on endoscopy with a mean DeMeester score of 18.9 (±19.93). The mean (±SD) duration of EFTP procedure was 17.4 (±4) min. The primary end point was more frequently achieved in the EFTP group (65.7% vs 2.9%; p<0.001). Median (IQR) % improvement in GERD-HRQL was significantly higher in the EFTP group at 6 (81.4 (60.9-100.0) versus 8.0 (2.2-21.6); p<0.001) and 12 (92.3 (84.4-100.0) versus 9.1 (4.8-36.0); p<0.001) months. In the EFTP group, 62.8% patients were off-PPI at 12 months compared with 11.4% in the sham group (p<0.001). pH-metry parameters partially improved at 3 months, (n=70; total reflux episodes in EFTP arm and non-acid reflux episodes for EFTP vs sham) but not at 12 months (n=27); endoscopic oesophagitis was seen in 0% in the treatment (n=18) and 5 (29.4%) in the control group (n=17) at 12 months. No major procedure-related adverse events were encountered in either group. CONCLUSION: EFTP using a novel device is safe and effective in improving quality of life in patients with PPI dependent mostly non-erosive reflux disease at short and long terms; objective parameters showed a limited response rate. TRIAL REGISTRATION NUMBER: NCT03322553.

Choledocholithiasis in acute calculous cholecystitis: guidelines and beyond.

BACKGROUND: Acute calculous cholecystitis (ACC) is the most frequent complication of gallstones requiring cholecystectomy. These patients may have coexisting choledocholithiasis. We aimed to evaluate the role of current guidelines for choledocholithiasis in patients with ACC. METHODS: In this retrospective study, we included all patients diagnosed with ACC between December 2018 and May 2019. These patients were substratified according to the guidelines of the American and European Societies of Gastrointestinal Endoscopy (ASGE and ESGE) as having high, intermediate, or low likelihood of choledocholithiasis, and the diagnostic performance was measured. Binomial logistic regression analysis was applied to ascertain independent risk factors for choledocholithiasis. RESULTS: A total of 173 patients with ACC, mean age (±standard deviation) 49.89±15.74 years and 60.1% male, were included. Sixty-three (36.4%) had confirmed choledocholithiasis. ASGE high likelihood criteria had sensitivity and specificity of 61.9% (95% confidence interval [CI] 48.8-73.9) and 83.4% (95%CI 75.4-90.0) for predicting choledocholithiasis. ESGE high likelihood criteria had sensitivity and specificity of 49.2% (95%CI 36.4-62.1) and 87.3% (95%CI 79.6-92.9). On logistic regression analysis, an alkaline phosphatase level above the upper limit of normal (P=0.003; odds ratio [OR] 4.26, 95%CI 1.66-10.96) and a dilated common bile duct on ultrasound (P=0.001; OR 9.97, 95%CI 4.65-21.36) were independent positive predictors for choledocholithiasis, while acute biliary pancreatitis was an independent negative predictor (P=0.030; OR 0.36, 95%CI 0.14-0.91). CONCLUSIONS: The performance of the ASGE and ESGE guidelines' risk stratification criteria is inadequate in patients with ACC. We suggest the utilization of a separate predictive model for suspected choledocholithiasis in these patients.

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.

Gastroesophageal reflux after per-oral endoscopic myotomy is frequently asymptomatic, but leads to more severe esophagitis: A case-control study.

BACKGROUND AND AIM: The incidence of gastroesophageal reflux disease (GERD) is high after per-oral endoscopic myotomy (POEM). GERD after POEM may be qualitatively different from GERD in patients without motility disorders. In this study, we aimed to analyze and compare different aspects of GERD between patients with post-POEM GERD and nonachalasia GERD. METHODS: The data of patients with GERD after POEM (January 2018 to June 2019) were compared with that of a control group (nonachalasia GERD group), which included patients presenting with typical reflux symptoms without associated major motility disorders. Patients with lower esophageal sphincter pressure lower than 10 mmHg were excluded from the study. GERD was evaluated at 3 months after POEM. Esophageal acid exposure time higher than 4.2% was used to define GERD. The primary outcome of the study was comparison of GERD-related quality of life and reflux symptom severity between the two groups. In addition, the severity of erosive esophagitis and reflux-symptom association were also recorded in the two groups. RESULTS: A total of 100 patients were included in the study, with 50 patients in each group (post-POEM GERD vs. controls). The baseline parameters were comparable between the two groups. Median interquartile range of GERD-related quality of life score was significantly lower in the post-POEM group (11 [0-23.3] versus 34 [24-44]; p < 0.001). The post-POEM GERD group had significantly lower median heartburn (6.0 [0-16.3] versus 15.5 [7.5-24.8]; p = 0.001) and regurgitation scores (0 [0-6.0] versus 20.0 [12.3-25.0]; p < 0.001). Erosive esophagitis was more frequent in the post-POEM group (28 [56%] versus 10 [20.4%], p = 0.001). Only three (6%) patients in the post-POEM group had a positive reflux-symptom association as compared with 28 (56%) patients in the control group (p < 0.001). CONCLUSION: In selected patients with pH positive GERD after POEM, the symptoms are milder and reflux-symptom association is poor in spite of more severe esophagitis as compared with controls.

Long-term Outcomes of Per-oral Endoscopic Myotomy in Spastic Esophageal Motility Disorders: A Large, Single-Center Study.

BACKGROUND AND AIMS: Spastic esophageal motility disorders (SEMD) are a rare group of motility disorders including type III achalasia, distal esophageal spasm (DES), and Jackhammer esophagus (JHE). Limited data suggest that per-oral endoscopic myotomy (POEM) may be effective in these disorders. In this study, we aimed to evaluate the long-term outcomes of POEM in SEMD. METHODS: The data of patients with SEMD who underwent POEM (January 2013 to December 2019) were analyzed, retrospectively. The following outcomes were recorded: POEM procedure details, technical and clinical success, adverse events, and gastroesophageal reflux disease (GERD). Clinical success was classified as immediate (<1 y), short-term (1 to 3 y), medium term (3 to 5 y), and long-term (>5 y). RESULTS: A total of 1115 POEM procedures were performed during the study period for achalasia and nonachalasia spastic motility disorders. POEM was performed for SEMD in 74 (6.6%) patients including type III in 53, DES in 11, and JHE in 10 patients. Technical success was achieved in all the patients. The median follow-up for the entire group was 47.5 months (range: 2 to 77 mo). Clinical success at short-term (1 to 3 y) and long-term follow-up (>5 y) was attained in 85.2% and 82.6% patients, respectively. There was no significant difference in the clinical success between type III achalasia and JHE/DES. Mild and moderate adverse events were recorded in 21 (28.4%) cases. GERD was detected in 23 (56.1%) patients with 24-hour pH study. Erosive esophagitis and symptomatic GERD were found in 36 (48.6%) and 16 (21.6%) patients, respectively. CONCLUSIONS: POEM is a safe, effective, and durable treatment modality for spastic motility disorders of the esophagus. However, GERD is found in about half of the patients mandating close monitoring after POEM.

Perforation following pneumatic dilation of achalasia cardia in a university hospital in northern India: A two-decade experience.

Pneumatic dilation (PD) is a cost-effective first-line treatment for achalasia. The most feared complication of PD is esophageal perforation (EP). As data on EP after PD for achalasia are not widely reported, we present the frequency, risk factors, and treatment-outcome of EP. Records of patients undergoing PD for achalasia (January 1995 to September 2015) were retrospectively reviewed. Of 433 patients (age 38 years, 13-88, 57% male), and 521 dilations, 12 were complicated by EP (2.7% of patients and 2.3% of PD). EP occurred in 7 (3.4%), 4 (1.7%), and 1 (4.1%) with use of balloon diameters 30, 35, and 40 mm, respectively. In most (11/12, 92%), EP occurred during the first PD. No risk factor for EP was identified (p = 0.65 for the first dilation vs. > 1 dilation, and 0.75 for balloon size of 30 mm vs. > 30 mm). Seven patients with contrast leak on esophagogram and/or computed tomography scan underwent surgery. One other with contrast leak was successfully treated with a fully covered self-expandable metal stent (FC-SEMS); the remaining four with small leak/pneumomediastinum were managed conservatively. The median duration of hospital stay following perforation was 13 days (7-26) and 8 days (6-10) in surgery and conservative groups, respectively. No mortality was observed in either group. The frequency of EP with PD was 2.3%. Though most EP (92%) occurred during the first dilation, neither the balloon size nor repeated dilations were identified as risk factors. Both surgical and conservative approaches had a favorable outcome in appropriate settings.

Indian consensus on chronic constipation in adults: A joint position statement of the Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology.

The Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology developed this evidence-based practice guideline for management of chronic constipation. A modified Delphi process was used to develop this consensus containing 29 statements, which were generated by electronic voting iteration as well as face to face meeting and review of the supporting literature primarily from India. These statements include 9 on epidemiology, clinical presentation, and diagnostic criteria; 8 on pathophysiology; and the remaining 12 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The members of the consensus team believe that this would be useful for teaching, clinical practice, and research on chronic constipation in India and in other countries with similar spectrum of the disorders.

Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance Imaging.

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is associated with exaggerated cerebral response including emotional processing following visceral stimulation; though data on this issue is available in female IBS patients, it is scanty among males. Hence, we aimed to study brain response of male IBS patients following rectal balloon distension as compared to healthy controls using functional magnetic resonance imaging (fMRI). Data between diarrhea and constipation predominant IBS (IBS-D and IBS-C) were also compared. METHODS: Rectal balloon distension threshold was assessed in 20 male IBS patients (10 IBS-C and 10 IBS-D) and 10 age-matched male healthy controls. Subsequently, fMRI on all the participants was performed at their respective rectal pain threshold. The fMRI data were analysed using the Statistical Parametric Mapping software. RESULTS: IBS patients showed greater cerebral activations in insula, middle temporal gyrus, and cerebellum in the left hemisphere compared to healthy controls. Neural activation was found in bilateral precuneus/superior parietal lobules in controls but not in patients with IBS. The brain activation differed among IBS-C and IBS-D patients; while the right mid-cingulate cortex was activated in IBS-C, the left inferior orbito-frontal cortex, left calcarine, and bilateral fusiform gyri were activated among patients with IBS-D following rectal balloon distension. CONCLUSIONS: Brain response to rectal balloon distension differed among male patients with IBS and controls and among patients with IBS-C and IBS-D. Differential activation among patients with IBS-C and IBS-D was seen in the brain regions controlling affective motivation, homeostatic emotions, and autonomic responses to pain.

Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Though nocturnal acid-breakthrough (NAB) is common in gastroesophageal reflux disease (GERD) patients, its clinical importance results from esophageal acidification, which has been shown to be uncommon. Ilaprazole, a long-acting proton pump inhibitor, may cause NAB infrequently. Accordingly, we studied prospectively, (1) frequency and degree of esophageal acidification during NAB, and (2) frequency and severity of NAB while on ilaprazole versus omeprazole. METHODS: Fifty-eight consecutive patients with GERD on once daily ilaprazole, 10 mg (n = 28) or omeprazole, 20 mg (n = 30) for > one month underwent 24-hour impedance-pH monitoring prospectively. NAB was defined as intra-gastric pH < 4 for > one hour during night, and esophageal acidification as pH < 4 for any duration. Nocturnal symptoms (heartburn, regurgitation, and chest pain) were also recorded. RESULTS: Of the 58 patients (age 35.5 [inter-quartile range 26.5-46.0] years, 38 [65.5%], 42 (72.4%) had NAB. Though patients with NAB had lower nocturnal intra-gastric pH than without (2.8 [1.9-4.1] vs 5.7 [4.6-6.8], P < 0.001), frequency and duration of nocturnal esophageal acidification (17/42 vs 4/16, P = 0.360 and 0.0 [0.0-1.0] vs 0.0 [0.0-0.3] minutes, P = 0.260, respectively) and symptoms were comparable (13/42 vs 6/16, P = 0.750). Though ilaprazole was associated with less NABs (1 [range 1-2, n = 19] vs 1 [range 1-3, n = 23], P = 0.010) than omeprazole, the frequency, duration, and mean intra-gastric pH during NAB were comparable (19/28 vs 23/30, P = 0.560; 117 [0-315] vs 159 [69-287] minutes, P = 0.500; 1.02 [0.7-1.4] vs 1.04 [0.44-1.3], P = 0.620, respectively). CONCLUSIONS: Though NAB was common while patients were on a proton pump inhibitor, esophageal acidification was uncommon. Frequency and severity of NAB were comparable among patients on ilaprazole and omeprazole, except for the lesser number of NABs with ilaprazole.

Radioiodine therapy in patients with Graves' disease and the effects of prior carbimazole therapy.

UNLABELLED: The use of radioiodine as the first line of treatment in Graves' disease is restricted in India because of its limited availability and an unrealistic risk perception associated with it. Additionally, the effectiveness of radioiodine ablation in Graves' disease is influenced by many factors. Prior medical antithyroid therapy is one such important factor. AIMS: To analyze the efficacy of low dose radioiodine therapy (5 mCi) in treatment of naive patients of Graves' disease in comparison to that in which it was already primed with an antithyroid drug, carbimazole. SETTINGS AND DESIGN: A non-randomized, interventional study conducted in the Department of Medicine and Endocrinology of a tertiary care institute in South India. MATERIALS AND METHODS: The study had two groups; Group A (36 treatment naive, uncomplicated Graves' disease patients) and B (34 Graves' disease patients on carbimazole prior to radioiodine therapy). Both groups had baseline clinical, biochemical evaluation and were reassessed at 3 and 6 months for evaluating the clinical status for possible documentation of cure. RESULTS: The cure rate was 61.1% in drug naive group and 58.8% in pretreated group at 6 months following radioiodine (P = 0.845). Higher baseline 999m technicium (99m Tc) uptake, male gender, BMI and higher baseline free thyroxine (fT4) level predicted treatment failure following radioiodine therapy. CONCLUSIONS: Administration of carbimazole prior to low dose radioiodine therapy does not alter the efficacy of radioiodine. Low fixed dose (5 mCi) of radioactive iodine may be a safe and effective primary therapeutic option in Graves' disease patients pretreated with antithyroid drugs.

Fever of unknown origin in a patient of systemic onset juvenile idiopathic arthritis.

Hemophagocytic lymphohistiocytosis is a potentially fatal condition characterized by pathologic immune activation, which can complicate infections, childhood systemic rheumatologic diseases and malignancies. Here we report a case of reactive hemophagocytic lymphohistiocytosis [macrophage activation syndrome] complicating systemic onset juvenile idiopathic arthritis, which was treated successfully with dexamethasone and cyclosporine. Reactive hemophagocytic lymphohistiocytosis or macrophage activation syndrome should be considered in patients of juvenile idiopathic arthritis with prolonged fever of unknown origin and cytopenias. Early diagnosis with high index of suspicion and prompt, aggressive treatment are needed for successful outcomes.