Conventional vs Short Duration of Antibiotics in Patients With Moderate or Severe Cholangitis: Noninferiority Randomized Trial.

INTRODUCTION: Successful biliary drainage and antibiotics are the mainstays of therapy in management of patients with acute cholangitis. However, the duration of antibiotic therapy after successful biliary drainage has not been prospectively evaluated. We conducted a single-center, randomized, noninferiority trial to compare short duration of antibiotic therapy with conventional duration of antibiotic therapy in patients with moderate or severe cholangitis. METHODS: Consecutive patients were screened for the inclusion criteria and randomized into either conventional duration (CD) group (8 days) or short duration (SD) group (4 days) of antibiotic therapy. The primary outcome was clinical cure (absence of recurrence of cholangitis at day 30 and >50% reduction of bilirubin at day 15). Secondary outcomes were total days of antibiotic therapy and hospitalization within 30 days, antibiotic-related adverse events, and all-cause mortality at day 30. RESULTS: The study included 120 patients (the mean age was 55.85 ± 13.52 years, and 50% were male patients). Of them, 51.7% patients had malignant etiology and 76.7% patients had moderate cholangitis. Clinical cure was seen in 79.66% (95% confidence interval, 67.58%-88.12%) patients in the CD group and 77.97% (95% confidence interval, 65.74%-86.78%) patients in the SD group ( P = 0.822). On multivariate analysis, malignant etiology and hypotension at presentation were associated with lower clinical cure. Total duration of antibiotics required postintervention was lower in the SD group (8.58 ± 1.92 and 4.75 ± 2.32 days; P < 0.001). Duration of hospitalization and mortality were similar in both the groups. DISCUSSION: Short duration of antibiotics is noninferior to conventional duration in patients with moderate-to-severe cholangitis in terms of clinical cure, recurrence of cholangitis, and overall mortality.

Transverse versus longitudinal mucosal incision during POEM for esophageal motility disorders: a randomized trial.

BACKGROUND: Longitudinal incision is the commonly used incision for entry into the submucosal space during peroral endoscopic myotomy (POEM) for esophageal motility disorders. Transverse incision is another alternative for entry and retrospective data suggest it has less operative time and chance of gas-related events. METHODS: This was a single-center, randomized trial conducted at a tertiary care hospital. Patients undergoing POEM for esophageal motility disorders were randomized into group A (longitudinal incision) and group B (transverse incision). The primary objective was to compare the time needed for entry into the submucosal space. The secondary objectives were to compare the time needed to close the incision, number of clips required to close the incision, and development of gas-related events. The sample size was calculated as for a non-inferiority design using Kelsey method. RESULTS: Sixty patients were randomized (30 in each group). On comparing the 2 types of incisions, there was no difference in entry time [3 (2, 5) vs 2 (1.75, 5) min, p = 0.399], closure time [7 (4, 13.5) vs 9 (6.75, 19) min, p = 0.155], and number of clips needed for closure [4 (4, 6) vs 5 (4, 7), p = 0.156]. Additionally, the gas-related events were comparable between the 2 groups (capnoperitoneum needing aspiration-5 vs 2, p = 0.228, and development of subcutaneous emphysema-3 vs 1, p = 0.301). CONCLUSION: This randomized trial shows comparable entry time, closure time, number of clips needed to close the incision, and gas-related events between longitudinal and transverse incisions. REGISTRATION NUMBER: CTRI/2021/08/035829.

Role of Biliary Stent in Recurrence of Biliary Stones and Complications After Stone Clearance in Patients Awaiting Cholecystectomy: A Randomized Trial.

INTRODUCTION: The role of prophylactic biliary stenting after clearance of choledocholithiasis in patients awaiting cholecystectomy for concomitant cholelithiasis is controversial. We planned a randomized controlled trial to study the effect of prophylactic biliary stenting after achieving biliary clearance in reducing recurrence of choledocholithiasis and biliary complications in patients awaiting cholecystectomy. METHODS: Patients with concomitant cholelithiasis and choledocholithiasis were included, and those who had evidence of clearance of choledocholithaisis (documented on occlusion cholangiogram during endoscopic retrograde cholangiography [ERC]) were randomized to prophylactic biliary stenting or no stenting. Choledocholithaisis recurrence rate (primary outcome), biliary complications and need for repeat/emergency ERC (secondary outcomes) were compared till 3 months after clearance. RESULTS: Between September 2021 and July 2022, 70 patients were randomized into group A, stenting (n = 35), and group B, no stenting (n = 35). Sixty-six patients were included in the final analysis. Baseline characteristics were comparable between the 2 groups. Ten (15.2%) patients had recurrence of choledocholithiasis, and it was comparable between the 2 groups (7/34 [20.6%] and 3/34 [9.4%], P = 0.306). Five patients (2 cholecystitis and 3 post-ERC pancreatitis) from the stent group while none from the no stent group developed complications, and this difference was statistically significant ( P = 0.024). None of the patients in both the groups needed emergency ERC during the follow-up. DISCUSSION: This randomized trial shows a higher complication rate with prophylactic stenting, while there is no benefit in preventing choledocholithiasis recurrence in patients waiting for cholecystectomy after biliary clearance (CTRI registration number: CTRI/2021/09/036538).

Deep Venous Thrombosis in Acute Pancreatitis Is Associated with High Mortality: A Prospective Study.

BACKGROUND: Incidence and risk factors for the development of extremity deep vein thrombosis (eDVT) in admitted patients of acute pancreatitis have been rarely explored. AIMS: To identify the incidence of eDVT and to explore role of clinical scores for predicting eDVT in admitted patients of acute pancreatitis. METHODS: We prospectively enrolled admitted patients of acute pancreatitis and performed a weekly eDVT screen for the duration of their admission. Well's score and Padua's score were also calculated weekly. The incidence of venous thrombosis (eDVT and splanchnic thrombosis based on contrast-enhanced CT scan abdomen) was noted, and the risk factors were determined using multivariate analysis. The correlation between Well's score, Padua's score, and development of DVT was calculated using Pearson's correlation. RESULTS: Of the 102 patients of acute pancreatitis enrolled, 73.5% of patients had necrotizing pancreatitis. Total of 46 patients (45.1%) developed thrombosis: 43 patients had splanchnic vein thrombosis; 5 patients had eDVT; and 1 patient had pulmonary embolism. Patients with eDVT had higher BISAP score (2.6 ± 0.9 vs 1.7 ± 0.8; p = 0.039), requirement of mechanical ventilation (60% vs 8.2%; p = 0.008), and mortality (60% vs 12.4%; p = 0.022). Well's score of ≥ 2 had sensitivity and specificity of 80% and 96.9% for prediction of eDVT and it had better correlation with the development of eDVT compared to Pauda's score. CONCLUSION: Incidence of DVT is 5% in patients with acute pancreatitis requiring admission. It is associated with higher disease severity and mortality. The Well's score is useful to predict the development of eDVT in routine clinical practice.

Oral Fluconazole Therapy in Patients With Active Ulcerative Colitis Who Have Detectable Candida in the Stool : A Double-Blind Randomized Placebo-controlled Trial.

BACKGROUND: There is an emerging role of fungal dysbiosis in the pathogenesis of inflammatory bowel disease. Prevalence of Candida in patients with active ulcerative colitis (UC) and the effect of fluconazole therapy in reducing disease activity of UC are not known. PATIENTS AND METHODS: All consecutive consenting patients with active UC defined as Mayo score ≥3 were evaluated for presence of Candida by stool culture and predictors for presence of Candida were identified. Those who had evidence of Candida in the stool were randomized to receive oral fluconazole 200 mg daily or placebo for 3 weeks along with standard medical therapy. Patients were assessed by clinical, sigmoidoscopy, and laboratory parameters at baseline and at 4 weeks. The primary outcome was clinical and endoscopic response at 4 weeks defined by a 3-point reduction in Mayo score. Secondary outcomes were reduction in fecal calprotectin, histologic response, and adverse events. RESULTS: Of the 242 patients with active UC, 68 (28%) patients had Candida in stool culture. Independent predictors for presence of Candida in patients with active UC were partial Mayo score of ≥3 and steroid exposure. Among those with Candida on stool culture (n=68), 61 patients fulfilled eligibility criteria and were randomized to receive fluconazole (n=31) or placebo (n=30). Three-point reduction in Mayo score though was numerically higher in the fluconazole group than the placebo group but was not statistically significant [5 (16.1%) vs. 1 (3.33%); P =0.19]. Postintervention median Mayo score was lower in fluconazole than placebo group [4 (3, 5) vs. 5 (4, 6); P =0.034]. Patients in fluconazole group had more often reduction in fecal calprotectin [26 (83.9%) vs. 11 (36.7%); P =0.001] and histologic scores [23 (74.1%) vs. 10 (33.3%); P =0.001] compared with placebo. All patients were compliant and did not report any serious adverse event. CONCLUSION: Candida colonization is found in 28% of patients with UC. Steroid exposure and active disease were independent predictors for the presence of Candida . There was no statistically significant difference in the number of patients who achieved 3-point reduction in Mayo score between 2 groups. However, clinical, histologic, and calprotectin levels showed significant improvement in fluconazole group.

Per Oral Endoscopic Myotomy for the Management of Large Esophageal Diverticula (D-POEM): Safe and Effective Modality for Complete Septotomy.

With the advent of the technique of sub-mucosal tunnelling, peroral endoscopic myotomy (POEM) has been used for the treatment of esophageal diverticulum, which otherwise is a recurring problem with conventional flexible endoscopic treatment due to incompleteness of septotomy. This study reports our experience of the use of diverticular POEM (D-POEM) technique in the management of large esophageal diverticulum. This is a retrospective study of prospectively maintained database including all consecutive patients with symptomatic esophageal diverticulum presenting at a tertiary care academic center. D-POEM was performed using the technique of submucosal tunnelling and septotomy. Besides baseline parameters, technical success, clinical success, size of diverticula, procedure time, complications and symptom recurrence on follow up were noted. A total of five patients (4 males; median age 72) were included with an average Charlson comorbidity index of 3.2 ± 0.8. Of them, three had Zenker's while two had epiphrenic diverticulum. The median symptom duration was 12 months with a mean diverticulum size of 68.8 ± 1.9 mm. The mean procedure time was 64.80 ± 12.6 min. with a mean septotomy/myotomy length of 79.44 ± 12.2 mm. Minor adverse events were noted intra-procedure in two cases. Clinical success achieved in all cases with a significant mean dysphagia score reduction from 2.20 to 0.20 post procedure (p = 0.011). On a median follow up of 280 days (range 98-330), none had recurrence of symptoms. Our data highlighted that complete septotomy by D-POEM technique can be achieved for the management of large esophageal diverticulum and is safe and effective.

Per oral endoscopic myotomy with fundoplication is a technically feasible NOTES for achalasia cardia.

BACKGROUND: Per-oral endoscopic myotomy (POEM) has become the standard of care for the endoscopic management of achalasia but its major long-term adverse effect has been the development of reflux-associated symptoms and sequelae. AIM: This study was conducted to assess the feasibility and reproducibility of the technique of POEM with fundoplication (POEM + F), a pure Natural Orifice Transluminal Endoscopic Surgery (NOTES) procedure in achalasia. MATERIAL AND METHODS: Between November 2019 and January 2020, three patients with achalasia cardia were subjected to POEM + F. Various parameters such as technical feasibility, procedure time, adverse events and post-procedure follow-up were noted. RESULTS: POEM + F was successfully completed in all three patients. Other than intra-operative capno-peritoneum, no major adverse events were noted. On follow-up at one month, maintenance of wrap was noted. CONCLUSION: POEM + F is a technically feasible and a reproducible pure NOTES procedure.

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.

'Rollover' abdominal paracentesis versus standard technique: protocol of a crossover randomized comparative trial.

The sensitivity of single abdominal paracentesis for diagnosis of peritoneal carcinomatosis in patients with malignant ascites is 40-70%. Tumor cells shed from the peritoneum settle preferentially in certain recesses of the peritoneum. We aim to compare the standard technique of abdominal paracentesis versus a rollover technique in a randomized crossover study to assess the cytological yield in patients suspected to have peritoneal carcinomatosis. Each patient will serve as their own control and the outcome assessor (cytopathologist) will be blinded to the method of paracentesis performed. The primary objective will be to compare the tumor cell positivity between the standard paracentesis group and the rollover group among enrolled patients. Clinical Trial registration: CTRI/2020/06/025887 and NCT04232384.

Lay abstract Existing methods of diagnosing cancer-related ascites are dependent on microscopic evaluation of fluid obtained from the ascites. However, this may not diagnose all such cases because the fluid may not contain many tumor cells. This may be due to the settling of tumor cells in certain inaccessible locations of the peritoneum (the lining of the abdominal cavity). This trial will look at whether rolling the patient from side to side could be helpful in increasing the chances of finding tumor cells in the ascites.

FDG-PET-CT Enterography Helps Determine Clinical Significance of Suspected Ileocecal Thickening: A Prospective Study.

BACKGROUND: Ileocecal thickening (ICT) on imaging could result from diverse etiologies but may also be clinically insignificant. AIM: Evaluation of role of combined 2-deoxy-2-fluorine-18-fluoro-D-glucose(18F-FDG)-positron emission tomography and computed tomographic enterography (PET-CTE) for determination of clinical significance of suspected ICT. METHODS: This prospective study enrolled consecutive patients with suspected ICT on ultrasound. Patients were evaluated with PET-CTE and colonoscopy. The patients were divided into: Group A (clinically significant diagnosis) or Group B (clinically insignificant diagnosis) and compared for various clinical and radiological findings. The two groups were compared for maximum standardized uptake values of terminal ileum, ileo-cecal valve, cecum and overall. RESULTS: Of 34 patients included (23 males, mean age: 40.44 ± 15.40 years), 12 (35.3%) had intestinal tuberculosis, 11 (32.4%) Crohn's disease, 3 (8.8%) other infections, 1 (2.9%) malignancy, 4 (11.8%) non-specific terminal ileitis while 3 (8.8%) had normal colonoscopy and histology. The maximum standardized uptake value of the ileocecal area overall (SUVmax-ICT-overall) was significantly higher in Group A (7.16 ± 4.38) when compared to Group B (3.62 ± 9.50, P = 0.003). A cut-off of 4.50 for SUVmax-ICT-overall had a sensitivity of 70.37% and a specificity of 100% for prediction of clinically significant diagnosis. Using decision tree model, the SUVmax-ICT with a cut-off of 4.75 was considered appropriate for initial decision followed by the presence of mural thickening in the next node. CONCLUSION: PET-CTE can help in discrimination of clinically significant and insignificant diagnosis. It may help guide the need for colonoscopy in patients suspected to have ICT on CT.

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.

Use of steroids for abdominal tuberculosis: a systematic review and meta-analysis.

BACKGROUND: The role of adjunctive steroids in abdominal tuberculosis is unclear. OBJECTIVE: To evaluate effect of adjunctive use of steroids for abdominal tuberculosis in reducing/preventing complications. METHODS: We searched electronic databases (Medline, Embase, CENTRAL, Scopus, Web of Science, CINAHL) from inception to 25th June 2018 using the terms "abdominal tuberculosis" OR "intestinal tuberculosis" OR "peritoneal tuberculosis" OR "tuberculous peritonitis" AND steroids OR methylprednisolone OR prednisolone. Bibliography of potential articles was also searched. We included studies comparing adjunctive steroids to antitubercular therapy (ATT) alone. We excluded non-English articles, case reports, reviews and unrelated papers. The primary outcome was a comprehensive clinical outcome including need for surgery or the presence of symptomatic stricture (abdominal pain or intestinal obstruction). Quality assessment of included studies was done using ROBINS-I tool. Random-effects model was used to calculate the summary effect for all the outcomes. RESULTS: Of total 633 records, three studies on peritoneal tuberculosis were included in meta-analysis. These papers were of poor quality (one quasi-randomised study and two retrospective cohort studies). Meta-analyses showed adjunctive steroids, with ATT is more effective than ATT alone in tuberculous peritonitis patients for the prevention of composite end point (RR 0.15 [0.04, 0.62], p = 0.008), symptomatic stricture(RR 0.15 [0.04-0.62] p = 0.008) and intestinal obstruction (RR 0.18 [0.03-0.99] p = 0.05). CONCLUSION: The data on use of steroids for abdominal tuberculosis are limited to peritoneal tuberculosis. Although steroids seem to have some benefit in patients of tubercular peritonitis, the poor quality of studies limits the generalisability of the findings. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42016047347.

Role of conservative management in tubercular abdominal cocoon: a case series.

BACKGROUND: Sclerosing encapsulating peritonitis (Abdominal cocoon) is an uncommon cause of intestinal obstruction and tuberculosis is an important etiology. Appropriate management of this entity is still uncertain. METHODS: We did a retrospective analysis of patients with abdominal cocoon who were seen over a two year period at a tertiary care center in North India. We included patients with tubercular abdominal cocoon (TAC) who were managed primarily with antitubercular therapy in the present report. The diagnosis of TAC was made using combination of criteria (radiological or surgical findings of cocoon with evidence of tuberculosis in form of microbiological, histological or biochemical evidence). The clinical presentation, outcome and need for surgery for these patients were retrieved from the records of these cases maintained in a database. RESULTS: Of 18 patients with abdominal cocoon, 15 patients had underlying tuberculosis. The median age was 28 years (interquartile range 24) and 12 (80%) were males. Three patients had confirmed tuberculosis on basis of microbiological evidence. All had abdominal pain for 1-9 months, and 11 had intestinal obstruction. Twelve patients had positive Mantoux test, none had HIV. Pulmonary tuberculosis was noted in four patients, pleural in five, splenic and intestinal in two each, hepatic and mediastinal lymph-nodal in one each. Thirteen patients were started on usual 4-drug anti-tubercular therapy (ATT) while two cirrhotics needed modified ATT. Three patients were on steroids with ATT and all three improved. One patient was lost to follow up. Of the rest 14 patients, 2 underwent surgery, 1 at initial presentation while another after 4 months of ATT. Overall five patients developed intestinal obstruction while on ATT, one needed surgery and one died of liver failure while others improved with conservative means. CONCLUSION: TAC can be managed conservatively in a subset of patients.