Acute cholecystitis with massive upper gastrointestinal bleed: A case report and review of the literature

BACKGROUND: Cystic artery pseudoaneurysm is a rare complication following cholecystitis. Its presentation with upper gastrointestinal hemorrhage (UGIH) is even rarer. Thirteen patients with cystic artery pseudoaneurysm have been reported in the literature but only 2 of them presented with UGIH alone. CASE PRESENTATION: We report a 43-year-old woman who developed a cystic artery pseudoaneurysm following an episode of acute cholecystitis. She presented with haematemesis and melaena associated with postural symptoms. Upper gastrointestinal endoscopy revealed a duodenal ulcer with adherent clots in the first part of the duodenum. Ultrasonography detected gallstones and a pseudoaneurysm at the porta hepatis. Selective hepatic angiography showed two small pseudoaneurysms in relation to the cystic artery, which were selectively embolized. However, the patient developed abdominal signs suggestive of gangrene of the gall bladder and underwent an emergency laparotomy. Cholecystectomy with common bile duct exploration along with repair of the duodenal rent, and pyloric exclusion and gastrojejunostomy was done. CONCLUSION: This case illustrates the occurrence of a rare complication (pseudoaneurysm) following cholecystitis with an unusual presentation (UGIH). Cholecystectomy, ligation of the pseudoaneurysm and repair of the intestinal communication is an effective modality of treatment

Hepatobiliary and pancreatic tuberculosis: A two decade experience

<p>Abstract</p> <p>Background</p> <p>Isolated hepatobiliary or pancreatic tuberculosis (TB) is rare and preoperative diagnosis is difficult. We reviewed our experience over a period two decades with this rare site of abdominal tuberculosis.</p> <p>Methods</p> <p>The records of 18 patients with proven histological diagnosis of hepatobiliary and pancreatic tuberculosis were reviewed retrospectively. The demographic features, sign and symptoms, imaging, cytology/histopathology, procedures performed, outcome and follow up data were obtained from the departmental records. The diagnosis of tuberculosis was based on granuloma with caseation necrosis on histopathology or presence of acid fast bacilli.</p> <p>Results</p> <p>Of 18 patients (11 men), 11 had hepatobiliary TB while 7 had pancreatic TB. Two-thirds of the patients were < 40 years (mean: 42 yrs; range 19–70 yrs). The duration of the symptoms varied between 2 weeks to 104 weeks (mean: 20 weeks). The most common symptom was pain in the abdomen (n = 13), followed by jaundice (n = 10), fever, anorexia and weight loss (n = 9). Five patients (28%) had associated extra-abdominal TB which helped in preoperative diagnosis in 3 patients. Imaging demonstrated extrahepatic bile duct obstruction in the patients with jaundice and in addition picked up liver, gallbladder and pancreatic masses with or without lymphadenopathy (peripancreatic/periportal). Preoperative diagnosis was made in 4 patients and the other 14 were diagnosed after surgery. Two patients developed significant postoperative complications (pancreaticojejunostomy leak <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> intraabdominal abscess <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>) and 3 developed ATT induced hepatotoxicity. No patient died. The median follow up period was 12 months (9 – 96 months).</p> <p>Conclusion</p> <p>Tuberculosis should be considered as a differential diagnosis, particularly in young patients, with atypical signs and symptoms coming from areas where tuberculosis is endemic and preoperative tissue and/or cytological diagnosis should be attempted before labeling them as hepatobiliary and pancreatic malignancy.</p

Hypoxia-driven oncometabolite L-2HG maintains stemness-differentiation balance and facilitates immune evasion in pancreatic cancer

In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intra-tumoral metabolic pathways and leading to poor survival. One metabolic enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate, an epigenetic modifier, that regulates the tumor transcriptome. However, the role of L-2HG in remodeling the pancreatic tumor microenvironment is not known. Here we used mass spectrometry to detect L-2HG in serum samples from pancreatic cancer patients, comprising tumor cells as well as stromal cells. Both hypoxic pancreatic tumors as well as serum from pancreatic cancer patients accumulated L-2HG as a result of promiscuous activity of LDHA. This abnormally accumulated L-2HG led to H3 hypermethylation and altered gene expression, which regulated a critical balance between stemness and differentiation in pancreatic tumors. Secreted L-2HG inhibited T cell proliferation and migration, suppressing anti-tumor immunity. In a syngeneic orthotopic model of pancreatic cancer, inhibition of LDHA with GSK2837808A decreased L-2HG, induced tumor regression, and sensitized tumors to anti-PD1 therapy. In conclusion, hypoxia-mediated promiscuous activity of LDHA produces L-2HG in pancreatic tumor cells, regulating the stemness-differentiation balance and contributing to immune evasion. Targeting LDHA can be developed as a potential therapy to sensitize pancreatic tumors to checkpoint inhibitor therapy