Pancreatic hemorrhage contributes to late mortality in patients with acute necrotizing pancreatitis.

OBJECTIVES: The frequency, risk factors, and impact on survival of hemorrhage into (peri)pancreatic collections in patients with acute pancreatitis (AP) has not been well studied. The study was designed to evaluate the risk factors for hemorrhage, successful hemostasis and its effect on in-hospital mortality. METHODS: In a prospective cohort study for prediction of severity of AP, the incidence, risk factors, and outcomes of pancreatic hemorrhage were analyzed. Patients with significant hemorrhage were managed according to a predefined protocol including endovascular intervention. RESULTS: Out of 363 patients hospitalized during the study-period, 33(9%) patients developed hemorrhage. Median time from onset of AP to hemorrhage was 59(45-68) days. The cause of hemorrhage was arterial in 19(57.5%) patients and unlocalized in 14(42.5%) patients. Hemorrhage was managed by conservative approach in 7 (21.2%), radiographic angioembolisation in 16 (48.5%), radiographic angioembolisation followed by surgery in 3 (9.1%), and surgery in 7 (21.2%) patients. Persistent organ failure [aHR 2.3 (1.1-5.1), p = 0.03], use of large bore (>20 Fr) catheter for initial drainage [aHR 3.9 (1.7-9.1), p = 0.001] and extensive (>50%) necrosis [aHR 3.1 (1.4-6.9), p = 0.005] were significant risk factors for hemorrhage. Hemorrhage was an independent predictor of mortality [aHR 2.0 (1.2-3.4), p = 0.008] in addition to persistent organ failure (aHR 12.1 (5.7-25.8), p < 0.001). In-hospital mortality in patients with hemorrhage was 22/33 (66.7%) vs. 81/330 (25%) in no hemorrhage group [p <0.001]. CONCLUSION: Pancreatic hemorrhage occurs later in the course of acute pancreatitis in relatively sicker group of patients with organ failure and extensive necrosis, and is independently associated with a higher risk of in-hospital mortality.

Relapse rates after withdrawal of thiopurines in patients with inflammatory bowel disease.

PURPOSE: Withdrawal of thiopurines after remission is associated with an increased risk of relapse in patients with inflammatory bowel disease (IBD). However, long-term data on thiopurine withdrawal is limited, especially from developing countries where the cost of long-term therapy poses a significant burden on patients. METHODS: Patients with IBD on thiopurine monotherapy for ≥ 4 months, who stopped thiopurines while in clinical remission and were not on any other immunomodulator or biologics at the time of withdrawal, were included in this retrospective analysis. RESULTS: Among 1093 patients with IBD on thiopurine monotherapy, 461 patients stopped thiopurine due to various reasons. Among these, 218 (ulcerative colitis (UC) = 179; Crohn's disease (CD) = 39) patients were in clinical remission and were continued on mesalamine. Overall, 36.7% (n = 80) relapsed after a median duration of 20 months (IQR: 9-49). Relapse rate was higher in UC than CD (39.7% vs 23%, p = 0.055). Cumulative probabilities of relapse were 17%, 34%, and 44% at the end of 1, 3, and 5 years, respectively. The relapse rate at 5 years was significantly lower in patients who had stopped azathioprine after 4 years of therapy (31% vs 54%, p = 0.007). On multi-variate cox regression analysis, male sex [HR: 1.6(1.0-2.6), p = 0.02] and short duration of therapy with thiopurines [HR: 1.02 (1.01-1.02), p = 0.004] before withdrawal were associated with increased risk of relapse. CONCLUSION: Approximately 50% patients with IBD in remission would relapse after 5 years of thiopurine withdrawal. Male sex and shorter treatment duration predict relapse. Treatment should be continued in patients who tolerate and maintain remission on long-term thiopurine.

Minimal risk of lymphoma and non-melanoma skin cancer despite long-term use of thiopurines in patients with inflammatory bowel disease: A longitudinal cohort analysis from northern India.

BACKGROUND AND AIM: Thiopurines are widely used to maintain remission in both ulcerative colitis (UC) and Crohn's disease (CD). Reported effectiveness and tolerability rates have been variable across studies. There are only sparse data in Asian population regarding the long-term efficacy and safety of thiopurines. METHODS: Records of 5351 patients followed up at inflammatory bowel disease (IBD) clinic, All India Institute of Medical Sciences, New Delhi from 2004 to 2020 were evaluated retrospectively. Safety was evaluated in terms of long-term adverse events and development of malignancy. RESULTS: Of 5351 patients with IBD, 1093 who received thiopurine for > 3 months (UC = 788 [proctitis-1.9%, left-sided colitis-44.9%, & pancolitis-53.1%] & CD = 305 [inflammatory-42.6%, stricturing-46.9%, & fistulizing-10.5%]) were included (60.8%-male patients). Follow up and treatment duration on thiopurine were 7 (4-12) years and 39.4 ± 40.3 months, respectively, with 254 (23.2%) patients receiving thiopurines for more than 5 and 68 (6.2%) receiving for more than 10 years. Three hundred and fifty-nine (UC: 249 [31.6%]; CD: 110 [36.1%]; P = 0.1) patients developed adverse events; commonest was myelosuppression (23.4%) followed by gastrointestinal intolerance (3%), flu-like illness (1.7%), and arthralgia/myalgia (1.4%). Myelosuppression was the commonest cause of thiopurine withdrawal. No patient (including 254 patients on thiopurine for ≥ 5 years) developed lymphoma or non-melanoma skin cancer. The cumulative probability of staying free from adverse events in overall IBD cohort at 1, 2, and 5 years was 78.6%, 71.9%, and 68.4%, respectively, and this was comparable between UC and CD (P = 0.09). CONCLUSION: Long-term follow up of patients with IBD from northern India on thiopurine monotherapy demonstrated minimal risk of development of lymphoma as well as non-melanoma skin cancer.

Outcome assessment of biliary stricture repair following cholecystectomy in a tertiary care centre.

PURPOSE: Bile duct injuries (BDIs) are the potential grievous complications of cholecystectomy that result in substantial morbidity and mortality. Outcomes of BDI management depend on multiple factors such as the type and extent of injury, timing of repair, and surgical expertise. The present retrospective study was conducted to analyse the risk factors associated with the BDI repair outcomes. METHODS: The data of patients having primary or recurrent bile duct stricture following BDI from 1985 to 2018 were retrospectively evaluated. RESULTS: A total of 268 patients underwent hepaticojejunostomy (HJ). Of the total, 218 patients had primary bile duct stricture, and 50 patients had HJ stricture. The most commonly performed procedure for primary BDI was Roux-en-Y HJ (RYHJ), followed by right hepatectomy, right posterior sectionectomy, and left hepatectomy. All patients with strictured HJ underwent RYHJ, except one who underwent a right hepatectomy. Outcome assessment using the McDonald grading system showed that 62%, 27%, 5%, and 6% of patients with primary bile duct stricture had grade A, grade B, grade C, and grade D complications, respectively, with a mortality rate of 3.21%, whereas 46%, 34%, and 18% patients with strictured HJ had grade A, grade B, and grade C complications, respectively, with a mortality rate of 2%. High-up biliary strictures, early repair, and blood loss > 350 mL are the surrogate markers for failure of repair. CONCLUSION: Management of BDI needs a multidisciplinary approach. The outcomes of both primary biliary stricture and strictured HJ can be improved with management of patients in a tertiary care centre. However, attempts to repair within 2 weeks of injury, Strasberg E4 and E5, and blood loss of > 350 mL may have an adverse effect on the outcome of HJ.

Percutaneous Endoscopic Step-Up Therapy Is an Effective Minimally Invasive Approach for Infected Necrotizing Pancreatitis.

BACKGROUND: Infected pancreatic necrosis (IPN) is a major complication of acute pancreatitis (AP), which may require necrosectomy. Minimally invasive surgical step-up therapy is preferred for IPN. AIM: To assess the effectiveness of percutaneous endoscopic step-up therapy in patients with IPN and identify predictors of its success. METHODS: Consecutive patients with AP hospitalized to our tertiary care academic center were studied prospectively. Patients with IPN formed the study group. The treatment protocol for IPN was percutaneous endoscopic step-up approach starting with antibiotics and percutaneous catheter drainage, and if required necrosectomy. Percutaneous endoscopic necrosectomy (PEN) was performed using a flexible endoscope through the percutaneous tract under conscious sedation. Control of sepsis with resolution of collection(s) was the primary outcome measure. RESULTS: A total of 415 patients with AP were included. Of them, 272 patients had necrotizing pancreatitis and 177 (65%) developed IPN. Of these 177 patients, 27 were treated conservatively with antibiotics alone, 56 underwent percutaneous drainage alone, 53 required underwent PEN as a step-up therapy, 1 per-oral endoscopic necrosectomy, and 52 required surgery. Of the 53 patients in the PEN group, 42 (79.2%) were treated successfully-34 after PEN alone and 8 after additional surgery. Eleven of 53 patients died due to organ failure-7 after PEN and 4 after surgery. Independent predictors of mortality were > 50% necrosis and early organ failure. CONCLUSION: Percutaneous endoscopic step-up therapy is an effective strategy for IPN. Organ failure and extensive pancreatic necrosis predicted a suboptimal outcome in patients with infected necrotizing pancreatitis.