Hemosuccus Pancreaticus: A systematic approach.

BACKGROUND AND AIM: Hemosuccus pancreaticus is considered as one of the rare cause of upper gastrointestinal bleeding. Intermittent nature of bleeding and lack of standardized approach for diagnosis has resulted in significant delay in definitive management. METHODS: We retrospectively analyzed prospectively maintained data of patients with suspected hemosuccus pancreaticus between January 2010 and December 2019. RESULTS: Out of 114 patients, 87 patients were diagnosed with hemosuccus pancreaticus. Mean age was 35.7 ± 11.7 years with 89.7% men. Median duration of bleeding before diagnosis was 10 days, with 40.2%, 10.3%, and 5.7% patients had symptoms beyond 1, 6, and 12 months, respectively. Visceral artery aneurysm was noted in 62% of cases with splenic artery aneurysm (37.9%) being the common source of bleed. Rarer causes noted were superior mesenteric artery aneurysm, pancreatic adenocarcinoma, gastrointestinal stromal tumor, and post-endoscopic retrograde cholangiopancreatography (2.3% each). Santorinirrhage was seen in 3.4% patients. Endoscopic diagnosis was possible in 64.4% of patients, and angiogram localization of bleeding source was noted in 94.2%. A 56.3% of patients underwent conventional angioembolization with 95.9% success and 28.7% underwent surgery, with overall rebleeding rate of 11.5%. CONCLUSIONS: Early diagnosis of hemosuccus pancreaticus avoids prolonged suffering, multiple hospital admissions, and multiple blood transfusions. It is not uncommon in the absence of aneurysm. In cases of high suspicion, repeating the endoscopy with proper technique and proper timing increases the yield. Angioembolization remains the most preferred first line therapeutic approach in majority of cases.

Interferon γ and glycemic status in diabetes associated with chronic pancreatitis.

BACKGROUND/AIMS: Although the role of cytokines in the etiopathology of chronic pancreatitis (CP) is well recognized, information on pancreatic tissue cytokines in CP with/without associated diabetes is unavailable. The aim of the present study was to identify the differences in pancreatic cytokines and observe their correlations with the glycemic status in CP. METHODS: Pancreata were obtained from CP patients (n = 44), with/without associated diabetes and non-diabetic control subjects (n= 20). Patients with CP were classified into two groups after ascertaining their diabetic status. Pancreatic cytokines (IL 1ß, IL 6, IL 8, IL 10, IL 12P70, TNF α, IFN γ) were analyzed by flow cytometer. The influence of individual and cocktail of cytokines on glucose stimulated insulin release (GSIR) was examined by challenging the islets from control subjects. RESULTS: The pancreatic IFN γ levels in diabetic and non diabetic CP patients were significantly higher in comparison to controls. The glucose stimulated insulin release (GSIR) in response to high glucose concentration in control islets, islets from non-diabetic and diabetic CP patients was 8.2, 5.67 and 3.15 µU × 10(-3)/min/islet equivalent respectively. IFN γ resulted in 82.35% decrease in GSIR from the control islet cells at a concentration of >20 pg/ml which was reversed by epigallocatechin-3-gallate (EGCG). CONCLUSION: These results suggest that IFN γ among other cytokines, play a major role in ß-cell dysfunction associated with CP.

A new partially covered nitinol stent for palliative treatment of malignant bile duct obstruction: a multicenter single-arm prospective study.

BACKGROUND AND STUDY AIMS: Covered self-expanding metal stents (SEMSs) have proven effective for managing malignant bile duct strictures and may reduce risk of tumor ingrowth. A new nitinol partially covered biliary SEMS was prospectively evaluated. PATIENTS AND METHODS: 70 patients with inoperable extrahepatic biliary obstructions were enrolled in a prospective multicenter trial, and followed up to 6 months or death, whichever came first. Primary endpoint was adequate palliation defined as absence of recurrent biliary obstruction from partly covered SEMS placement to end of follow-up. RESULTS: Mean age of the patients was 69 years and 52 % were men. Pancreatic carcinoma was present in 68 %. One stent was placed in 67 patients, two patients received two, and in one patient a guide wire could not traverse the stricture. In 55 % of patients the SEMS was inserted de novo and in 45 % for exchange with a plastic stent. Technical success was 97 %. At 6 months, 62 % of patients were free of obstructive symptoms; compared with baseline the mean number of symptoms per patient was significantly reduced (3.1 at baseline, 0.6 at 6 months; P < 0.0001) and total bilirubin levels dropped by 73 %. There were four cases of recurrent biliary obstruction, due to stent migration (2), tumor overgrowth (1), and sludge formation (1). Device-related complications included cholecystitis (3), right upper quadrant pain (1), and moderate pancreatitis (1). No tumor ingrowth was reported. CONCLUSIONS: This new partially covered nitinol SEMS is easily inserted, and safe and effective in the palliation of biliary obstruction secondary to malignant bile duct strictures.

Vascular anatomy of strictured small bowel.

AIM: To investigate the role of ischemia in the pathogenesis of small bowel strictures. METHODS: Vascular anatomy of 39 small bowel strictures was studied using modified Spalteholtz method. Ten normal small bowel segments were studied as controls. RESULTS: 71.8% of small bowel strictures showed block in the mesenteric vessels (p=0.008). Subset analysis of tuberculous strictures showed block in the mesenteric vessels in 70.8% of strictures (p=0.0098). CONCLUSIONS: Ischemia plays a significant role in the pathogenesis of small bowel strictures. Mesenteric vasculopathy has a significant association with tuberculous strictures of the intestine.

Primary Pancreatic Leiomyosarcoma: A Rare Malignant Transformation of Primary Pancreatic Head Leiomyoma.

Primary pancreatic leiomyosarcoma and primary pancreatic leiomyoma are rare tumors of the pancreas. Primary pancreatic leiomyoma is a benign tumor and its conversion to leiomyosarcoma has never been reported. We report a case of malignant transformation of pancreatic leiomyoma. In this case, a 75-year-old male, who presented with a mass in the head of the pancreas, was diagnosed with primary pancreatic leiomyoma. The patient maintained well on symptomatic treatment for 13 years. However, later the patient presented with loss of appetite, significant weight loss, and an abdominal lump, which was diagnosed to be locally advanced primary pancreatic leiomyosarcoma. The patient was provided the best supportive care and died after 11 months of diagnosis. Hence, we conclude that a more radical treatment approach is needed in patients with primary pancreatic leiomyoma.

Is It Safe to Perform Endoscopic Retrograde Cholangiopancreatography in Decompensated Cirrhosis?

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is treatment modality of choice for management of pancreatobiliary disorders. However, safety of ERCP in the patients with cirrhosis is not adequately studied. This study was aimed to evaluate adverse events in the patients with cirrhosis undergoing ERCP and the predictors of adverse events and mortality. METHODS: The present study was a retrospective analysis of patients with cirrhosis who underwent ERCP from January 2012 to December 2016. Binary logistic regression analysis was performed to ascertain the risk factors for adverse events and mortality at 1 month. RESULTS: A total of 261 patients underwent ERCP (80.8% men, mean age 53.49 ± 12.6years). There were 36 (16.1%) overall adverse events in patients undergoing ERCP for biliary indication, whereas no adverse event in pancreatic indication. On univariate analysis, ascites, encephalopathy, high Child-Pugh-Turcotte (CTP) and model for end-stage liver disease (MELD) score, and creatinine levels were significantly associated; however, on multivariable analysis, CTP class C (p value 0.033; odds ratio [OR] 3.5, 95% confidence interval [CI] 1.1-11.5) and MELD > 18 (p value 0.004; OR 5.6, 95% CI 1.7-17.9) were independent risk factors for adverse events. There were 19 (8.5%) mortalities. On univariate analysis, presence of ascites, encephalopathy, cholangitis, biliary sphincterotomy, high CTP, low albumin, and high creatinine were significantly associated, whereas, on multivariable analysis, presence of cholangitis (p 0.017; OR 3.8, 95% CI 1.3-11.4) was associated increased mortality. CONCLUSION: Although endoscopic sphincterotomy might be safe for the patients with cirrhosis undergoing ERCP; advanced liver cirrhosis may be independent risk factor for post-ERCP adverse events. Cholangitis at admission is an independent risk factor for mortality.

Clinical trial: oral feeding with a soft diet compared with clear liquid diet as initial meal in mild acute pancreatitis.

BACKGROUND: In mild acute pancreatitis, traditional treatment has been initial fasting and oral refeeding with clear liquids to prevent adverse gastrointestinal events such as pain. The diet is gradually progressed to soft solids and hospital discharge is planned based on patients' tolerance to a solid diet. AIM: To determine the length of hospitalization and tolerance to oral refeeding when initiated on a soft diet as compared to a clear liquid diet. METHODS: One hundred and one patients with mild acute pancreatitis were randomized to receive either a clear liquid diet or soft diet when oral feeding was initiated. Frequency of pain, total and postrefeeding length of hospitalization, and dietary intake were monitored. Hospital discharge was decided by the medical team without input from the study coordinators. RESULTS: A statistically significant decrease in the length of hospitalization (total and postrefeeding) of a median of 2 days was seen in patients receiving a soft diet (P < 0.001). No significant difference in the need for cessation of diet because of pain was observed between the two groups. Patients initiated on a soft diet consumed significantly more calories and fats on study day 1 (P < 0.001). CONCLUSION: Oral refeeding with a soft diet in patients with mild acute pancreatitis can be considered safe and can result in shorter length of hospitalization.

Risk factors for diagnostic delay in Crohn's disease and their impact on long-term complications: how do they differ in a tuberculosis endemic region?

BACKGROUND: The diagnosis of Crohn's disease (CD) can be delayed in clinical practice. In tuberculosis endemic areas, empirical anti-tubercular therapy further delays treatment. AIM(S): To assess risk factors for diagnostic delay and its impact on the long-term complications of Crohn's disease in India where tuberculosis is endemic. METHODS: Data from a large prospectively established inflammatory bowel disease registry were analysed retrospectively. The time from onset of symptoms to diagnosis (diagnostic delay) was calculated and categorised into two groups based on median diagnostic delay. The risk factors for delay including anti-tubercular therapy were analysed. Logistic regression analysis was done to assess impact of diagnostic delay on development of stenotic and fistular complications including need for surgery. RESULTS: Seven hundred and twenty Crohn's disease patients (60.3% male, median: 28 years) were included. Main outcome measures were stenosis, fistula and need for surgery. Subjects with diagnostic delay >18 months (median) developed significantly higher stenotic complications and surgery (OR 4.12; 95% CI: 2.74-6.33, P < 0.001 and OR 2.41, 95% CI: 1.68-3.42, P < 0.001), respectively, compared to those ≤18 months. There was no difference in the development of fistulous complications. 193/720 (27%) received anti-tubercular therapy which significantly contributed to diagnostic delay (OR: 2.47; 95% CI: 1.76-3.47, P < 0.001) with 47% showing initial clinical response (Crohn's disease activity index- CDAI decrease >100). Moreover, the incidence of stenotic complications was significantly higher in patients who had received prior anti-tubercular therapy (55/193 (28.49%) vs 78/527 (14.8%), P < 0.001, OR: 2.60, 95% CI: 1.64-4.12). CONCLUSIONS: Diagnostic delay in Crohn's disease is associated with significantly higher stenotic complications and need for surgery. Empirical anti-tubercular therapy is the single largest contributor to diagnostic delay in tuberculosis endemic areas. Despite initial clinical response to anti-tubercular therapy, long-term stenotic complications are higher.

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.

Eosinophilic pancreatitis with pseudocyst.

Eosinophilic pancreatitis is a rare entity in patients having underlying systemic manifestations such as peripheral eosinophilia, elevated serum IgE levels and/ or eosinophilic infiltrates in other organs, including the gastrointestinal tract. We report a 38-year-old woman with peripheral eosinophilia in association with acute pancreatitis, pancreatic ascites and pseudocyst.

Gastrointestinal manifestations of melioidosis: A single center experience.

Melioidosis, being increasing, is reported from India. Gastrointestinal manifestations are typically reported as unusual cause of liver and/or splenic abscess. We aimed to describe various gastrointestinal manifestation of melioidosis in the present study. We retrospectively collected data of culture positive melioidosis cases from hospital database during August 2014-October 2016 at Asian Institute of Gastroenterology, Hyderabad. A total of nine culture positive cases (8 male) of melioidosis with median age of 40 years (range 23-66) were analyzed. Median duration of symptoms was 45 days. Two patients were being treated as tuberculosis. Three patients presented with liver abscess with two of them having simultaneous splenic abscess, and one had prostatic abscess. Three patients (43%) with history of acute pancreatitis had infected pancreatic collection, and one patient had left empyema with splenic abscess. One patient had wound infection with left lower limb cellulitis, presented as acute in chronic liver failure and another as spontaneous bacterial peritonitis (SBP). Diabetes and/or alcoholism was present in all patients. Seven patients had disseminated organ involvement. Seven patients underwent percutaneous intervention for drainage of abscess. Induction therapy as ceftazidime (n=4) or meropenem (n=5) followed by continuation therapy as oral cotrimoxazole (n=6) and doxycycline (n=1) was given. Six patients completed therapy and asymptomatic at end of follow up. Two patients died in the study period. One patient died due to acute-on-chronic liver failure (ACLF) with acute kidney injury and the other due to cardiac failure. One patient with SBP had lost to follow up. Apart from being unusual cause of liver/splenic abscess, melioidosis can present with infection of pancreatic collection, SBP, and infection in a compensated cirrhosis which can precipitate ACLF. Early recognition and specific therapy can improve prognosis.

Budd-Chiari syndrome: outcomes of endovascular intervention-A single-center experience.

AIM: Outcomes of endovascular intervention in Budd-Chiari syndrome (BCS) have been reported with varied results. Clinical outcomes of endovascular interventions in BCS and role of various prognostic scores were critically evaluated in this study. METHODS: This study retrospectively analyzed consecutive patients of BCS who underwent endovascular intervention between January 2007 and May 2016 at our center. Technical, clinical successes and complications were documented. The role of the prognostic scores such as Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), Rotterdam index, and original Clichy score in predicting mortality, clinical success, and need for re-interventions were also assessed. RESULTS: A total of 88 patients were analyzed. The median follow up was 12 months (range 1-96 months). Thirteen (14.8%) patients had combined inferior vena cava (IVC) and hepatic vein (HV) obstruction; HV obstruction in 33 (37.5%) and inferior vena cava IVC obstruction in 42 (47.7%) patients. The following interventions were done: IVC angioplasty alone (n = 11), IVC angioplasty with stenting (n = 36), HV angioplasty with stenting (n = 26), combined HV and IVC stent (n = 2), and direct intrahepatic porto-systemic shunt (DIPS) (n = 13). Overall technical success was 87/88 (98.86%), and clinical success was 76/88 (86.36%). Immediate complications were noted in 8 patients (10%). The 1-, 2-, 3-, and 4-year stent patency rates were 90.91%, 81.08%, 74.59%, and 70.45%, respectively. Re-interventions were required in 15 (17%). Overall mortality was 6 (6.8%). Apart from MELD >14, none of the other prognostic score could predict mortality, clinical success, and need for re-interventions. CONCLUSION: Endovascular interventions play an important role in the management of BCS, in properly selected patients, even if prognostic score is unfavorable.

Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene with tropical calcific pancreatitis.

BACKGROUND: The genetic basis of tropical calcific pancreatitis (TCP) is different and is explained by mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. However, mutated SPINK1 does not account for the disease in all the patients, neither does it explain the phenotypic heterogeneity between TCP and fibro-calculous pancreatic diabetes (FCPD). Recent studies suggest a crucial role for pancreatic renin-angiotensin system during chronic hypoxia in acute pancreatitis and for angiotensin converting enzyme (ACE) inhibitors in reducing pancreatic fibrosis in experimental models. We investigated the association of ACE gene insertion/deletion (I/D) polymorphism in TCP patients using a case-control approach. Since SPINK1 mutations are proposed a modifier role, we also investigated its interaction with the ACE gene variant. METHODS: We analyzed the I/D polymorphism in the ACE gene (g.11417_11704del287) in 171 subjects comprising 91 TCP and 80 FCPD patients and compared the allelic and genotypic frequency in them with 99 healthy ethnically matched control subjects. RESULTS: We found 46% and 21% of TCP patients, 56% and 19.6% of FCPD patients and 54.5% and 19.2% of the healthy controls carrying the I/D and D/D genotypes respectively (P>0.05). No significant difference in the clinical picture was observed between patients with and without the del allele at the ACE in/del polymorphism in both categories. No association was observed with the presence or absence of N34S SPINK1 mutation in these patients. CONCLUSION: We conclude that the ACE insertion/deletion variant does not show any significant association with the pathogenesis, fibrosis and progression of tropical calcific pancreatitis and the fibro-calculous pancreatic diabetes.

Isolation and characterization of impurities in docetaxel.

During the process development of docetaxel, two polar impurities (Impurities I and II) and two non-polar impurities (Impurities III and IV) were detected by high performance liquid chromatography (HPLC). All the impurities were isolated by Medium Pressure Liquid Chromatography (MPLC). The Impurities I, II, III and IV were identified as 13-[(4S,5R)-2-oxo-4-phenyl-oxazolidine-5-carboxy]-10-deacetyl baccatin III ester, 2'-epi docetaxel, 7-epi docetaxel and 13-[(4S,5R)-2-oxo-4-phenyl-oxazolidine-3,5-dicarboxyl-3-tert-butyl)]-10-deacetyl baccatin III ester, respectively, based on one- (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy data. The Impurity IV was crystallized and the structure was solved by single crystal X-ray diffraction (XRD). Two impurities (Impurities II and III) were found to be process related, while the remaining two impurities (Impurities I and IV) turned out to be isomers. The formation of these impurities was discussed.

Portal biliopathy.

A young male with portal venous thrombosis presented with obstructive jaundice, due to common bile duct stricture secondary to portal biliopathy.

Safety of therapeutic ERCP in pregnancy - an Indian experience.

INTRODUCTION: Only limited data are available regarding the safety of therapeutic ERCP in pregnancy. We report our experience with therapeutic ERCP in pregnant women. METHODS: Medical records of 18 pregnant women (first trimester 4, second 6, third 8) who underwent ERCP between July 1994 and December 2004 were reviewed. Patients and their families were contacted to assess the well being of mother and baby. RESULTS: All the women underwent therapeutic ERCP and biliary sphincterotomy for common bile duct (CBD) stones. In 4 patients, 10-Fr CBD stents were inserted; three of these four cases required mechanical lithotripsy after delivery. Median procedure time was 17 min and median fluoroscopy time was 8 seconds. One patient each developed mild post ERCP pancreatitis and post sphincterotomy bleed. One woman had a preterm delivery. At follow up after a median of 6 years, all the babies were healthy. CONCLUSION: Therapeutic ERCP can be performed safely in all the trimesters of pregnancy provided appropriate precautions are taken.