Optimizing the Diagnosis and Biomarker Testing for Patients with Intrahepatic Cholangiocarcinoma: A Multidisciplinary Approach

Cholangiocarcinoma (CCA) is a heterogenous group of malignancies originating in the biliary tree, and associated with poor prognosis. Until recently, treatment options have been limited to surgical resection, liver-directed therapies, and chemotherapy. Identification of actionable genomic alterations with biomarker testing has revolutionized the treatment paradigm for these patients. However, several challenges exist to the seamless adoption of precision medicine in patients with CCA, relating to a lack of awareness of the importance of biomarker testing, hurdles in tissue acquisition, and ineffective collaboration among the multidisciplinary team (MDT). To identify gaps in standard practices and define best practices, multidisciplinary hepatobiliary teams from the University of California (UC) Davis and UC Irvine were convened; discussions of the meeting, including optimal approaches to tissue acquisition for diagnosis and biomarker testing, communication among academic and community healthcare teams, and physician education regarding biomarker testing, are summarized in this review.

Therapeutic Opportunities of GPBAR1 in Cholestatic Diseases

GPBAR1, a transmembrane G protein-coupled receptor for bile acids, is widely expressed in multiple tissues in humans and rodents. In recent years, GPBAR1 has been thought to play an important role in bile homeostasis, metabolism and inflammation. This review specifically focuses on the function of GPBAR1 in cholestatic liver disease and summarizes the various pathways through which GPBAR1 acts in cholestatic models. GPBAR1 mainly regulates cholestasis in a holistic system of liver-gallbladder-gut formation. In the state of cholestasis, the activation of GPBAR1 could regulate liver inflammation, induce cholangiocyte regeneration to maintain the integrity of the biliary tree, control the hydrophobicity of the bile acid pool and promote the secretion of bile HCO3−. All these functions of GPBAR1 might be clear ways to protect against cholestatic diseases and liver injury. However, the characteristic of GPBAR1-mediated proliferation increases the risk of proliferation of cholangiocarcinoma in malignant transformed cholangiocytes. This dichotomous function of GPBAR1 limits its use in cholestasis. During disease treatment, simultaneous activation of GPBAR1 and FXR receptors often results in improved outcomes, and this strategy may become a crucial direction in the development of bile acid-activated receptors in the future.

Challenges in treatment of a patient suffering from neuroendocrine tumor G1 of the hilar bile duct: a case report

Background Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are extremely rare in the biliary tract. Currently, there are no guidelines for the diagnosis and treatment of biliary NETs. We presented a case with NETs G1 of the hilar bile duct and the challenges for her treatment. Case presentation A 24-year-old woman was presented to our department with painless jaundice and pruritus, and the preoperative diagnosis was Bismuth type II hilar cholangiocarcinoma. She underwent Roux-en-Y hepaticojejunostomy with excision of the extrahepatic biliary tree and radical lymphadenectomy. Unexpectedly, postoperative pathological and immunohistochemical examination indicated a perihilar bile duct NETs G1 with the microscopic invasion of the resected right hepatic duct. Then the patient received 3 cycles of adjuvant chemotherapy (Gemcitabine and tegafur-gimeracil-oteracil potassium capsule). At present, this patient has been following up for 24 months without recurrence or disease progression. Conclusion We know little of biliary NETs because of its rarity. There are currently no guidelines for the diagnosis and treatment of biliary NETs. We reported a case of perihilar bile duct NETs G1 with R1 resection, as far as we know this is the first report. More information about biliary NETs should be registered.

Multiple Fat- Containing Hepatic Hydatid Cysts: A Case Report in The X- Ray Institute at Medical City Health Directorate in Iraq

Background: Hydatidosis is a zoonotic disease caused by Echinococcus granulosus and Echinococcus multilocularis parasite which is still endemic in many countries all over the world especially in the developing countries. The liver is the primary site to be infested by the parasite with a rate of 60 – 75%. The right lobe of the liver gets infected in about 80% of cases. Hydatid disease of the liver is usually asymptomatic and most cases discovered accidentally on routine clinical or radiological examinations for other illness. Symptoms usually appear in complicated cases either due to rupture, secondary bacterial infection, or due to the large size of the cyst which might cause pain in the right upper quadrant of the abdomen, discomfort, and sometimes swelling. In this case report, we reported the presence of fat globules within the hepatic hydatid cysts which is most probably due to rupture of hepatic hydatid cysts into the biliary tree. Keywords: Hepatic, hydatid cyst, fat globule and CT scan

P-BN39 The perils of MRCP requesting and early associations of data quality and likelihood of a diagnostic result

Background MRCP (Magnetic resonance cholangiopancreatography) is used most to assess the biliary tree for stones or strictures. Recently, MRCP availability has increased, and it is extensively used to detect of common bile duct (CBD)stones although very frequently no stones are seen. Indeed, the currently recruiting sunflower RCT aims to determine the clinical and cost effectiveness of expectant management versus MRCP in patients undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones. However, it is critical when requesting an investigation that adequate information is provided. This work aimed, to describe the adequacy of information provided and correlate this with the MRCP result. We hypothesised that the less information that was provided the more common a normal result would be. Methods For a three month period (January 2021 to April 2021) all MRCP requests to detect the presence of a CBD stone were reviewed and data obtained from the Radiology CRIS (CDN Radiology Information System, CDN, Sydney, Aus.). The requesting information was compared to three pre-defined criteria (CBD diameter, presence of gallstones and LFT details) that were agreed as the optimal information that a reporting radiologist would require. The number of key pieces of information for each request and whether the request identified a CBD stone were identified. The proportion of MRCPs detecting a CBD stone was calculated according to the number of key pieces of information provided. Results 56 patients were identified, of which 16 (29%) patients had CBD stones. In 24/56 (43%) patients the presence of gallstones on a previous ultrasound was provided, 14/56 (25%) of patients had information about LFTs including bilirubin and a trend in LFTs was not stated for any patient (0/56; 0%). The rate of stone detection was calculated by the number of pieces of information provided. The rate was 71% (5/7) when all 3 pieces of data were provided, 31% (2/13) when two piece of information were provided, 30% (8/27) when a single piece of information was provided, and only 11% (1/11) when none of the specified data were provided. Conclusions It is uncommon for adequate clinical information to be provided in MRCP requests and in 16% of request no key information was provided. The LFT results were frequently omitted and the trend in LFTs never stated. The more key data provided in the request saw a higher proportion of MRCPs where a CBD stone was identified. We recommend that maximal clinical information is mandated for MRCP request perhaps using mandatory fields on electronic requesting systems and that these systems are also used to facilitate recruitment to clinical trials such the Sunflower RCT.

P-EGS16 Lemmel Syndrome due to Duodenal Diverticulitis, an Infrequent Cause of Biliary Obstruction

Background Lemmel syndrome, first described in 1934, is the presence of biliary obstruction as a consequence of duodenal diverticula. The precise aetiology remains uncertain. Multiple causative theories have been proposed. These include mechanical biliopancreatic duct occlusion, functional disruption of the sphincter of Oddi and alteration of the course of the distal biliary and pancreatic ducts. We present a case of biliary obstruction caused by diverticulitis of a solitary duodenal diverticulum. Methods A 71-year-old woman with no co-morbidities presented with early satiety, cachexia and upper abdominal pain. An epigastric mass was palpable, alkaline phosphatase was 247 iu/L, alanine transaminase 124iu/L, bilirubin 4umol/L and C-reactive protein 68mg/L. Computed tomography (CT) of the abdomen and pelvis revealed obstructed biliary tree with D2 duodenal diverticulitis. Magnetic resonance cholangiopancreatography (MRCP) displayed a causative enterolith. Treatment with antibiotics was initiated and the patient commenced on liquid diet. Liver function tests and inflammatory markers normalised. After a seven day admission patient was discharged and oral intake normalised. Interval MRCP revealed resolution of obstruction and inflammation. Results Duodenal diverticula occur in 1-20% of individuals. Complications are symptoms are uncommon. Diverticulitis is a rare complication. Malignancy and cholelithiasis should be excluded in diagnostic workup. The mainstay of therapy for duodenal diverticulitis is conservative. CT and MRCP are effective diagnostic tools. Diverticulectomy carries substantial risk of morbidity and mortality. Endoscopic sphincterotomy or lavage have a role in relief of biliary obstruction when present. Comparative prospective studies of management do not exist and retrospective enquiry is sparse. Management is thereby best determined clinically on a case by case basis. Surgery is reserved for failed conservative and medical therapy. Conclusions Duodenal diverticulitis should be considered in patients with unexplained upper abdominal pain and elevated inflammatory markers. In combination with obstructive jaundice, suspicions should be raised for acute inflammation causing obstruction to the biliary tree. Cross sectional imaging is useful in determining the diagnosis. Antibiotics and conservative therapy are prudent first line management in the absence of perforation. Where these measures are inadequate endoscopic and operative strategies may be employed but have no robust evidence basis.