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A case report of vanishing bile duct syndrome after exposure to pexidartinib (PLX3397) and paclitaxel.

ABSTRACT: Pexidartinib (PLX3397) is a small molecule tyrosine kinase and colony-stimulating factor-1 inhibitor with FDA breakthrough therapy designation for tenosynovial giant-cell tumor, and currently under study in several other tumor types, including breast cancer, non-Hodgkin's lymphoma, and glioblastoma. Here, we report a case of severe drug-induced liver injury requiring liver transplantation due to vanishing bile duct syndrome (VBDS) after exposure to pexidartinib in the I-SPY 2 Trial, a phase 2 multicenter randomized neoadjuvant chemotherapy trial in patients with Stage II-III breast cancer. We also review the current literature on this rare, idiosyncratic, and potentially life-threatening entity.

SUBMITTER: Piawah S

PROVIDER: S-EPMC6570645 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A case report of vanishing bile duct syndrome after exposure to pexidartinib (PLX3397) and paclitaxel.

Piawah Sorbarikor S Hyland Colby C Umetsu Sarah E SE Esserman Laura J LJ Rugo Hope S HS Chien A Jo AJ

NPJ breast cancer 20190614

Pexidartinib (PLX3397) is a small molecule tyrosine kinase and colony-stimulating factor-1 inhibitor with FDA breakthrough therapy designation for tenosynovial giant-cell tumor, and currently under study in several other tumor types, including breast cancer, non-Hodgkin's lymphoma, and glioblastoma. Here, we report a case of severe drug-induced liver injury requiring liver transplantation due to vanishing bile duct syndrome (VBDS) after exposure to pexidartinib in the I-SPY 2 Trial, a phase 2 mu ...[more]

PMID: 31240240

Similar Datasets

Histopathological Features Predicting Long-term Clinical Outcomes in Patients with Vanishing Bile Duct Syndrome.

Project description:Background and aimsThe clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome (VBDS) have yet to be elucidated. The study aims to investigate these features and identify factors associated with poor prognosis.MethodsThis multicenter retrospective study recruited patients with liver biopsy-proven VBDS who were followed up at five hospitals in northern China from January 2003 to April 2022. Clinical and pathological data at time of biopsy were reviewed. Clinical outcomes including cirrhosis, decompensation events, liver transplantation (LT), and liver-related death were recorded. Cox regression analysis was used to identify the risk factors associated with poor outcomes.ResultsA total of 183 patients were included. The median age was 47 years, with 77.6% being women. During a median follow-up of 4.8 years, 88 patients developed compensated or decompensated cirrhosis, 27 died, and 15 received LT. Multivariate Cox regression analysis showed that hepatocellular cholestasis (HR 2.953, 95% CI: 1.437-6.069), foam cells (HR 2.349, 95% CI: 1.092-5.053), and advanced fibrosis (HR 2.524, 95% CI: 1.313-4.851) were independent predictors of LT or liver-related deaths. A nomogram formulated with the above factors showed good consistency with a concordance index of 0.746 (95% CI: 0.706-0.785).ConclusionsNearly half of VBDS patients studied progressed to end-stage liver disease and 23% of them had LT or liver-related death within two years of diagnosis. Hepatocellular cholestasis, foam cells and advanced fibrosis rather than the degree of bile duct loss or underlying etiologies were independently associated with poor prognosis in VBDS patients.

| S-EPMC10412695 | biostudies-literature

Non-invasive biomarkers for identification of vanishing bile duct syndrome among children with acute cholestatic hepatitis.

Project description:The identification of vanishing bile duct syndrome (VBDS) is still challenging before liver biopsy. This study tried to explore non-invasive biomarkers for identification of VBDS among children with acute cholestatic hepatitis. Between January 2017 and December 2021, 192 children underwent native-liver biopsy for acute cholestatic hepatitis with onset after 6 months of age. VBDS was diagnosed by liver biopsy. Differences of liver biochemical indices were compared between children with and without VBDS. Diagnostic performances for VBDS were tested by receiver operating characteristic (ROC) curve analyses. Among the 192 patients, 24 (12.5%) were diagnosed with VBDS based on liver biopsy. At biopsy, their levels of total bilirubin (TB), direct bilirubin (DB), γ-glutamyl transpeptidase (GGT), total bile acid, triglyceride, and total cholesterol (TCH) were higher than patients without VBDS (all P<0.05). However, only GGT and TCH could distinguish patients with VBDS from patients without VBDS with an area under ROC curve (AUC) >0.850. Using GGT >446 U/L as a cut-off value, the sensitivity was 87.5%, the specificity was 91.6%, and the AUC was 0.948 (P<0.001). Using TCH >6.4 mmol/L as a cut-off value, the sensitivity was 100.0%, the specificity was 89.8%, and the AUC was 0.983 (P<0.001). A total of 28 patients had both GGT >446 U/L and TCH >6.4 mmol/L, including 21 patients with VBDS and 7 without VBDS (21/28 vs. 3/143, P<0.0001). Three patients with VBDS would be missed for GGT <446 U/L. Both GGT and TCH can be used as non-invasive biomarkers for identification of VBDS among children with acute cholestatic hepatitis.

| S-EPMC10644022 | biostudies-literature

Laparoscopic management of Rhabdomyosarcoma of common Bile duct, Case report

Project description:Introduction Embryonal Rhabdomyosarcoma (ERMS) is a malignant soft tissue musculoskeletal tumor which constitutes about 0.06% of all malignancies affecting children. Biliary tract ERMS is still rare, though it is considered the most common cause of malignant obstructive jaundice in children. Case presentation A report of a 2-year-old boy, who was presented with recurrent episodes of scleral icterus of three months duration, is added to the related literature. His labs went with obstructive jaundice and the radiological investigations were consistent with a diagnosis of choledochal cyst. The found mass was suspected to be an ERMS of common bile duct and turned out to be so by the histopathology. He was managed totally by laparoscope, both excision and hepaticojejunostomy reconstruction, which is an extremely uncommon entity. Conclusion Common Bile Duct Rhabdomyosarcoma is rare and diagnosis at this anatomical site is difficult. Our case highlights the feasibility of laparoscopic resection and hepaticojejunostomy reconstruction with very good results at 16-month follow up and parents' gratitude as well. Highlights • Rhabdomyosarcoma (RMS) is a rare malignant tumor affecting children.• RMS is worth considering when dealing with a choledochal cyst.• Surgical approaches reported for biliary RMS were laparotomies.• Laparoscopic management is feasible for biliary RMS.• Our case is the least invasive surgical approach reported up to date.

| S-EPMC7519210 | biostudies-literature

Primary mucoepidermoid carcinoma of the intrahepatic bile duct: A case report.

Project description:Mucoepidermoid carcinoma (MEC) is the most common salivary gland carcinoma; however, hepatobiliary MEC is extremely rare. A 74-year-old patient was diagnosed with hepatobiliary MEC after hepatectomy. We considered its origin could be the peribiliary glands. Its genome profile was similar to salivary MEC rather than standard biliary tract carcinoma.

| S-EPMC8811179 | biostudies-literature

Giant duodenal diverticulum with mucinous carcinoma of distal bile duct, mimmicking Lemmel syndrome: A rare case report.

Project description:IntroductionGiant duodenal diverticulum is a very rare case. There are only few cases reported. We reported a case of giant duodenal diverticulum with biliary obstruction caused by mucinous carcinoma of distal common bile duct (CBD), that mimicking Lemmel syndrome.Case presentationA 68-years-old man admitted to hospital with recurrent epigastric pain, jaundice and fever. Magnetic resonance cholangiopancreatography showed dilated intrahepatic and extrahepatic biliary tree, dilated gallbladder and cystic mass in pancreatic head that pushed the pancreatic duct ventrally. Emergency laparotomy was performed. Distended edematous gallbladder with necrotic spot, dilated of CBD and compressible bulging of the pancreatic head were found. Duodenotomy in 2nd-3rd part was made and found a giant duodenal diverticulum filled with food and mucus. Tight adhesion to the ampula of Vater, common bile duct, and pancreas due to fibrosis, met difficulties in dissection with a lot of bleeding, hence the diverticulum was not removed. Gastrojejunostomy, cholecystectomy and choledocho-duodenostomy were also done. Pathologic examination of CBD mucus was accordance with mucinous carcinoma.DiscussionPeriampullary duodenal diverticulum can cause obstructive jaundice, known as Lemmel syndrome. This case was different as the giant duodenal diverticulum located in the 3rd part filled with food and mucin that compressed both distal CBD and pancreatic duct. The cause of obstructive jaundice could be fibrotic tissue in distal CBD and mucinous carcinoma.ConclusionGiant duodenal diverticulum with bile obstruction is very rare and challenging in diagnosis and treatment. The other cause of obstruction should be considered such as mucinous carcinoma of distal CBD.

| S-EPMC8760494 | biostudies-literature

Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors.

Project description:PurposeTo evaluate the safety, recommended phase II dose (RP2D) and efficacy of pexidartinib, a colony stimulating factor receptor 1 (CSF-1R) inhibitor, in combination with weekly paclitaxel in patients with advanced solid tumors.Patients and methodsIn part 1 of this phase Ib study, 24 patients with advanced solid tumors received escalating doses of pexidartinib with weekly paclitaxel (80 mg/m2). Pexidartinib was administered at 600 mg/day in cohort 1. For subsequent cohorts, the dose was increased by ⩽50% using a standard 3+3 design. In part 2, 30 patients with metastatic solid tumors were enrolled to examine safety, tolerability and efficacy of the RP2D. Pharmacokinetics and biomarkers were also assessed.ResultsA total of 51 patients reported ≥1 adverse event(s) (AEs) that were at least possibly related to either study drug. Grade 3-4 AEs, including anemia (26%), neutropenia (22%), lymphopenia (19%), fatigue (15%), and hypertension (11%), were recorded in 38 patients (70%). In part 1, no maximum tolerated dose was achieved and 1600 mg/day was determined to be the RP2D. Of 38 patients evaluable for efficacy, 1 (3%) had complete response, 5 (13%) partial response, 13 (34%) stable disease, and 17 (45%) progressive disease. No drug-drug interactions were found. Plasma CSF-1 levels increased 1.6- to 53-fold, and CD14dim/CD16+ monocyte levels decreased by 57-100%.ConclusionsThe combination of pexidartinib and paclitaxel was generally well tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R signaling, indicating potential for mitigating macrophage tumor infiltration.

| S-EPMC6589951 | biostudies-literature

Intrahepatic intraductal papillary cystic neoplasm of the bile duct: A case report.

Project description:Introduction and importanceIntraductal papillary neoplasm of the bile duct (IPNB) is a tumour with a very low incidence in the Western world, characterised by a high risk of malignant transformation and unknown prognosis. It is a new entity which was adopted by the WHO in 2010 as a precursor lesion of cholangiocarcinoma. Intrahepatic bile duct is the most common site of origin for IPNB.Case presentationHereby, we present a case of an asymptomatic 63- year-old man, referred to our department after routine ultrasonography showing a multifocal cystic lesion on the left hepatic lobe. Further screening modalities (CT, MRI abdo) confirmed a complex cystic liver lesion with atypical features. The patient underwent left hepatectomy. Histopathology showed a cystic type intrahepatic IPNB, which was completely resected (R0). The follow up in 2 yrs post-operation showed no signs of recurrence.Clinical discussionThe diagnosis and management of IPNB remain challenging. A multimodality imaging approach is essential in order to diagnose IPNB, assess tumour location and extent and plan the optimal treatment strategy.ConclusionComplete surgical resection (R0) with close postoperative follow-up offers long-term survival.

| S-EPMC7900680 | biostudies-literature

Repeat hepatectomy for liver metastases from bile duct neuroendocrine tumor: a case report.

Project description:BACKGROUND:Primary neuroendocrine tumor (NET) originating from the extrahepatic bile duct is rare, although liver metastasis from gastroenteropancreatic NET is frequently observed. We herein report a case who successfully underwent repeat hepatectomy for liver metastases from bile duct NET grade 2 (G2). CASE PRESENTATION:A 75-year-old man presented with jaundice and was suspected of perihilar cholangiocarcinoma by computed tomography (CT) and magnetic resonance imaging (MRI). He underwent extended left hepatectomy, extrahepatic bile duct resection, and hepaticojejunostomy. Pathological findings showed a NET G2 of the biliary tract arising from the common bile duct. Two years and 11?months after surgery, a liver metastasis was detected and hepatectomy was performed. During the surgery, another liver metastasis was detected, and limited liver resection for the two lesions was performed. Pathological findings showed four liver metastases of NET G2. Five years and 4?months after the first surgery (2?years and 5?months after the second hepatectomy), four liver metastases were detected. Thereafter, he received somatostatin analogues for 1 year. Although the size of tumors increased slightly, the number did not change. He underwent limited liver resections and was diagnosed with 7 liver metastases of NET G2. Finally, another hepatectomy (fourth hepatectomy) was performed and long-term survival without recurrence was obtained for as long as 8?years after the first surgery. CONCLUSIONS:Repeat hepatectomy is a good option to obtain long-term survival for liver metastases from bile duct NET G2 in select patients.

| S-EPMC7415062 | biostudies-literature

Small-cell neuroendocrine carcinoma arising from an extra-hepatic bile duct: a case report.

Project description: Not available

| S-EPMC8460092 | biostudies-literature

Persistent Mullerian duct syndrome with transverse testicular ectopia: A case report.

Project description:Persistent Mullerian duct syndrome (PMDS) is a rare entity of internal male pseudohermaphroditism. Transverse testicular ectopia (TTE) is the condition in which one testis moves to the other side and both testes pass the same inguinal canal. The combination of PMDS with TTE is rarer. Here, we present a case a phenotype male with left inguinal hernia and right undescended testis. On exploration of left inguinal region, uterus like tissue with its tubal structures were found. Both testes were in same side, one in left inguinal region and the other in the left scrotum.

| S-EPMC6503297 | biostudies-literature

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