Cholestatic jaundice as a paraneoplastic manifestation of prostate adenocarcinoma.

Malignancies may cause cholestatic jaundice through well-recognized mechanisms (e.g., bile duct obstruction or widespread hepatic infiltration). Paraneoplastic syndromes associated with malignancy, particularly with renal cell carcinoma (Stauffer's syndrome) and malignant lymphoproliferative diseases, can induce a reversible form of cholestasis through an unclear pathogenetic mechanism. Prostate cancer presenting initially with cholestatic jaundice without any obvious cause (i.e., obstruction or infiltration) has been reported in 2 cases in the medical literature. We report a patient who presented with pruritus and cholestatic jaundice. During the diagnostic work-up, prostate cancer was diagnosed. Conjugated bilirubin and alkaline phosphatase levels were increased markedly with modest increases of gamma-glutamyltranspeptidase and transaminase levels. The results of appropriate investigations performed during the patient's hospitalizations indicated no evidence of hepatic metastases or extrahepatic biliary obstruction. After treatment with flutamide and leuprolide, the patient's symptoms and the laboratory abnormalities reversed rapidly. We regard the cholestatic jaundice of this patient as part of a paraneoplastic syndrome; the cause of cholestasis remains an enigma. Patients with unexplained cholestasis should be investigated for malignancies, including prostate cancer.     

Paraneoplastic hepatopathy associated with soft tissue sarcoma.

Paraneoplastic syndromes associated with mesodermal tumors are relatively uncommon. An unusual case manifested by fever, anemia, thrombocytosis, coagulopathy, and idiopathic cholestatic liver dysfunction in association with soft tissue sarcoma is reported. A paraneoplastic syndrome is postulated in the absence of anatomic obstruction of bile flow, evidence of an infectious etiology, or neoplastic hepatic involvement.     

Jaundice as a paraneoplastic phenomenon in a T-cell lymphoma

An adolescent male developed severe unexplained cholestatic jaundice 3 mo before diagnosis of mediastinal non-Hodgkin's lymphoma (T-cell, late thymic phenotype). There was no anatomic obstruction to bile flow, no evidence for an infectious etiology, and no neoplastic involvement of the liver or bile ducts. A paraneoplastic phenomenon is postulated because the jaundice resolved after treatment of the lymphoma. We suggest that occult lymphoma must be added to the differential diagnosis of unexplained intrahepatic cholestasis.     

LP-X in cholestasis.

Extrahepatic and intrahepatic biliary obstruction of different etiology were studied in 62 patients, who were investigated for the presence of lipoprotein X (Lp-X). It was found present in 19 of 20 cholestasis by lithiasis, in all three primary biliary cirrhosis patients, in 2 of 4 cirrhosis, in 5 of 13 hepatitis, in all three benign recurrent intrahepatic cholestasis and in 1 of 2 recurrent juandice of pregnancy. It was found in a Dubin Johnson. Lp-X disappeared in 4 patients within two weeks after relief of the obstruction. It was found in patients with cholestatic hepatitis during the first week of jaundice. It was found in the first 48 hours in three patients with cholestasis by lithiasis. Lp-X does not help in differential diagnosis between extrahepatic and intrahepatic biliary obstruction, but the time of its appearance could contribute to it in some cases. A word of caution is raised in indicating surgery in a cholestatic patient without the presence of Lp-X.     

Drug- and chemical-induced cholestasis

Cholestasis caused by medicinal and chemical agents is an increasingly well-recognized cause of liver disease. Clinical drug-induced cholestatic syndromes producing jaundice and bile duct injury can mimic extrahepatic biliary obstruction, primary biliary cirrhosis, and sclerosing cholangitis, among others. This article updates the various forms of drug-induced cholestasis, focusing on the clinicopathologic features of this form of hepatic injury and on the known or putative mechanisms by which drugs and chemicals lead to cholestasis.     

CHOLESTASIS IN ACUTE ALCOHOLIC LIVER DISEASE

10 of a series of 108 patients with alcoholic liver disease presented with cholestasis associated with non-cirrhotic alcoholic liver disease and without evidence of extrahepatic biliary obstruction. In 7 patients liver histology and the associated conditions presenting as cholestasis were heterogeneous. However, in 3 patients who had been drinking excessively before cholestatic jaundice developed, cholestasis was a major feature of liver histology. The term acute alcoholic cholestasis is suggested for this apparently distinct syndrome of cholestatic jaundice in the absence of hepatitis.     

Idiopathic cholestatic jaundice may be a paraneoplastic manifestation of underlying malignancy: a case of prostate cancer

A 68-year-old male was admitted to our hospital because of jaundice. Laboratory examinations revealed elevated total bilirubin (23.4 mg/dl) and hepatobiliary enzymes levels. Abdominal ultrasonography and computed tomography showed no abnormal finding in the liver and biliary ducts. Abdominal imaging examinations revealed a prostate tumor, and paraaortic and iliac lymph nodes enlargement. An elevated prostate-specific antigen (PSA) level of 15,018.0 ng/ml, followed by a positive prostate biopsy, confirmed prostate cancer. Histological examination of the liver biopsy showed non-specific inflammation of the portal area and sinusoid. We regarded the cholestatic jaundice as a paraneoplastic manifestation of the prostate cancer because of parallel dramatic decline of total bilirubin, hepatobiliary enzymes, and PSA levels after the initiation of anti-androgen treatment to the prostate cancer. Paraneoplastic syndrome should be included in the differential diagnosis of idiopathic cholestasis.     

Clinical problems with developmental anomalies of the biliary tract

Cholestatic jaundice defined as conjugated hyperbilirubinemia is a typical feature of neonatal liver disease. Biliary atresia is the most common disorder producing cholestasis during the first 2 months of life. Syndromic and non-syndromic paucity of the intralobular bile ducts and choledochal cysts can also present with cholestasis during early life. Liver dysfunction from obstruction of the biliary tree must be differentiated from numerous disorders affecting hepatocytes such as congenital infection and inborn errors of metabolism. Early recognition and a stepwise diagnostic evaluation of the cholestatic infant are essential in successfully treating many metabolic and infectious liver diseases of the infant as well as surgically relieving obstruction in patients with biliary atresia.     

A case report: nasobiliary drainage inducing remission in benign recurrent intrahepatic cholestasis

Benign recurrent intrahepatic cholestasis is a rare hereditary disorder characterized by recurrent episodes of cholestasis and pruritus without anatomical obstruction. Generally, medical therapy is not effective in benign recurrent intrahepatic cholestasis. Here, we report the case of a young male patient with benign recurrent intrahepatic cholestasis who presented with cholestatic jaundice and pruritus, refractory to standard therapies. He improved on treatment with temporary endoscopic nasobiliary drainage. We propose that temporary endoscopic nasobiliary drainage should be considered in cholestatic benign recurrent intrahepatic cholestasis patients. A 36-year-old male patient admitted to our outpatient clinic with the complaint of pruritus. His anamnesis revealed that he experienced the same symptoms and signs in 2006. He was hospitalized in a hepatology clinic and was thoroughly examined. Liver biopsy was performed, and he was finally diagnosed as having benign recurrent intrahepatic cholestasis. Medical therapy options all proved to be ineffective and we were able to achieve remission in this patient only with the help of nasobiliary drainage. For this patient, we tried nasobiliary drainage in addition to the standard medical therapies. He improved on nasobiliary drainage. In conclusion, we propose that temporary endoscopic biliary drainage should be considered in cholestatic benign recurrent intrahepatic cholestasis patients. We hope that this case report contributes to the topic, since only a few nasobiliary drainage case experiences have been reported to date.     

Histological assessment of cholestasis

The microscopic identification of bile in sections of liver provides an important diagnostic challenge for the histopathologist, particularly in differentiating the many causes of intrahepatic cholestasis from mechanical bile duct obstruction. The pathologist's chief goal in evaluating the cholestatic liver is to distinguish intrahepatic cholestasis (seen in conditions such as drug hepatotoxicity, viral hepatitis, sepsis, or mutations affecting bile transporters) from large bile duct obstruction caused by conditions such as choledocholithiasis, pancreatic carcinoma, biliary stricture, or primary sclerosing cholangitis (PSC). This distinction carries major therapeutic and prognostic significance, because surgical, endoscopic,or radiologically guided intervention is likely to be undertaken if the pathologic features point to mechanical obstruction of the bile ducts. The histologic assessment of cholestasis, in broad terms, therefore, is a morphologic approach to distinguish between medical jaundice and surgical jaundice.     

Fosinopril-induced prolonged cholestatic jaundice and pruritus: first case report

We report a case of fosinopril-induced prolonged cholestatic jaundice and pruritus in a 61-year-old man, with no previous hepatobiliary disease, who presented with asthenia, jaundice and itching 3 weeks after starting fosinopril therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. Liver biopsy showed cholestasis without bile duct damage. The disease ran a severe course during the 2 months of hospitalization, with prolonged itching for 6 months, eventually controlled with oral naltrexone. Jaundice subsided after 4 months, with anicteric cholestasis persisting for more than 18 months. Similar occurrences have been reported with other inhibitors of angiotensin-converting enzyme (mostly captopril), but this is the first case of an important adverse reaction to fosinopril.     

Drug- and chemical-induced cholestasis

Cholestasis resulting from drugs is an increasingly recognized cause of liver disease. It produces a broad clinical-pathologic spectrum of injury that includes simple jaundice, cholestatic hepatitis, and bile duct injury that can mimic extrahepatic biliary obstruction, primary biliary cirrhosis, and sclerosing cholangitis. Although the risk of drug-induced cholestasis leading to a fatal outcome is quite rare, knowledge and recognition of the various forms of cholestatic injury assumes an importance whenever clinicians are confronted with jaundice or other manifestations of liver disease in patients receiving medicinal or chemical agents.     

Stauffer’s syndrome variant with cholestatic jaundice

Cholestasis is a common feature of several malignant diseases, including pancreatic, hepatic, gallbladder, and ampullary carcinomas. It is usually secondary to main bile duct obstruction or widespread hepatic metastasis, but it can also be a paraneoplastic syndrome of other underlying malignancies. Stauffer's syndrome is a rare paraneoplastic manifestation of renal cell carcinoma (RCC) that is characterized by elevated alkaline phosphatase, erythrocyte sedimentation rate, alpha-2-globulin, and gamma-glutamyl transferase, thrombocytosis, prolongation of prothrombin time, and hepatosplenomegaly, in the absence of hepatic metastasis and jaundice. A rare variant of this syndrome with jaundice has recently been described in 3 cases in the literature. We report a patient who presented with abdominal pain and cholestatic jaundice in whom RCC was incidentally found during initial workup. Jaundice and liver dysfunction resolved completely after surgical resection of the tumor. This case illustrates the protean manifestations of RCC, and the importance of considering Stauffer's syndrome and its variant in the differential diagnosis of anicteric and icteric cholestasis, which may allow early recognition and treatment of an underlying malignancy.     

Intraluminal brachytherapy without stenting in intrahepatic papillary cholangiocarcinoma: A case report

A 46-year-old female patient, with mild cholestasis by a large papillary cholangiocarcinoma involving the left hepatic duct, received intraluminal brachytherapy (50 Gy at 1 cm from the source axis) with the aim to relieve biliary obstruction without stent positioning. The patient presented with haemobilia and vegetant lesions in the left main biliary duct, and thus she had a high risk of early stent obstruction. Eighteen months after the treatment the patient presented tumour progression in the controlateral hepatic lobe, but had a patent left hepatic duct, without signs of cholestasis and/or cholangitis.Based on this and other published reports, intraluminal brachytherapy may be tested in a setting different from standard setting with the aim to safely palliate jaundice in patients with intraductal tumour growth in the biliary tract.     

Cholestatic jaundice during infancy: experience at a tertiary-care center in Bangladesh.

BACKGROUND AND OBJECTIVE: Cholestatic jaundice in early infancy is a difficult diagnostic problem. Early diagnosis is important for proper management. This retrospective study was conducted to find out the etiology and clinical profile of neonatal cholestatic disorders in Bangladesh. SETTING: Tertiary-care hospital in a developing country. METHODS: Clinical profile and cause of cholestatic illness were studied in 62 infants with cholestatic jaundice developing before three months of age and persisting for more than two weeks. RESULTS: Neonatal hepatitis (22; 35.5%--17 with TORCH, 5 with urinary infection), followed by biliary atresia (16; 25.8%) and idiopathic neonatal hepatitis (15; 24.2%), were the commonest causes of cholestasis. Mean age at presentation was 3.5 months. Ten (62.5%) of 16 biliary atresia cases were male and jaundice appeared before 14 days in 14 (87.5%) cases. CONCLUSIONS: Neonatal hepatitis, biliary atresia and idiopathic neonatal hepatitis were the common causes of neonatal cholestasis in infancy. Though cholestatic jaundice developed early, most of the cases presented late.     

Hepatic oxidative alterations in patients with extra-hepatic cholestasis. Effect of surgical drainage

BACKGROUND/AIMS: The mechanisms of liver injury in conditions of biliary obstruction are poorly understood. Hepatic oxidative injury has been observed in experimental models of cholestasis. Little is known in humans. This study aimed to gain more insights into the hepatic redox status in human cholestasis. METHODS: Liver concentrations of total glutathione, protein sulfhydryls and malondialdehyde (end-product of lipid peroxidation) were measured in hepatic specimens of 12 patients with obstructive jaundice before and after the application of an external biliary drainage and in six control subjects. RESULTS: Compared to control subjects, biliary obstructed patients showed significantly (P < 0.001) lower concentrations of hepatic glutathione and protein sulfhydryls, and higher (P < 0.001) levels of malondialdehyde, in the presence of comparable protein concentrations. Two-weeks after the application of external biliary drainage, cholestatic indices were significantly improved and the observed changes in glutathione, protein sulfhydryls and malondialdehyde levels, significantly decreased. CONCLUSIONS: This study shows that cholestasis is associated with a decreased protein and non-protein sulfhydryl content in the liver and with an increased lipid peroxidation. These alterations reversed almost completely after biliary drainage, indicating the cholestasis itself as the determining factor for the redox status impairment observed in the liver of patients with extra-hepatic biliary obstruction.     

Benign familial recurrent intrahepatic cholestasis

Three new cases of benign familial recurrent intrahepatic cholestasis in a brother, sister, and mother are reported. These cases emphasize the familial nature of the disorder and the characteristic clinical findings of recurrent attacks, cholestatic jaundice, pruritus with increases in the serum bilirubin, and increased alkaline phosphatase. A normal extrahepatic biliary tree was shown by dye studies, and liver biopsy showed central lobular cholestasis without any inflammation or necrosis. Liver function tests were normal between attacks. This condition must be differentiated from extrahepatic obstruction, parenchymal liver disease, drug-induced cholestatic disease, and other familial types of jaundice.     

Obstructive jaundice caused by hepatocellular carcinoma report of three cases

A cholestatic syndrome secondary to extrahepatic biliary obstruction as the presenting manifestation of hepatocellular caroinoma is aescribed in three cases. The mechanism is related to the invasion of intrahepatic bile ducts by the carcinoma. The consequent mechanical obstruction is due to either a continuous distally growing tumor cast of the biliary tree, distal migration of a necrotic tumor fragment, or hemobilia. In the cirrhotic patient with a predisposition for the deyelopment of liver cancer, the physician should be aware of the presentation with obstructive jaundice as a mechanical complication of hepatocellular carcinoma     

Treatment of cholestasis caused by stenosis of the intrahepatic bile ducts in alveolar echinococcosis. Trial of biliary drainage by the percutaneous transhepatic approach

Six cases of hepatic alveolar echinococcosis with involvement of the hepatic hilum and cholestasis were treated by percutaneous biliary drainage. Clinical and morphological follow-up ranged from 18 to 34 months. A decrease of jaundice and bilirubinemia and the regression of the intrahepatic bile duct dilatation were observed in all cases. Biliary drainage was associated with percutaneous drainage of an hepatic necrotic cavity in four cases. Left hepatectomy was performed later in three cases. These results are encouraging and suggest that percutaneous biliary drainage is an effective and useful procedure for biliary drainage in hepatic alveolar echinococcosis with cholestasis due to obstruction of the intrahepatic bile ducts.     

Cholestatic hepatitis following flutamide

Summary Previous reports have indicated that administration of flutamide—a nonsteroidal antiandrogen drug—may induce hepatic toxicity. However, cholestatic hepatitis following flutamide is a rare event. This case report describes a 72-year-old male with metastatic adenocarcinoma of the prostate who underwent bilateral orchiectomy and treatment with flutamide. After seven weeks he developed jaundice and elevated AST and ALT levels. A liver biopsy showed cholestatic hepatitis without signs of biliary obstruction. The patient's clinical symptoms and elevated bilirubin resolved after the flutamide was discontinued. Monitoring of serum liver enzyme tests is advocated during flutamide administration to identify drug-induced liver injury.