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Sample records for aih primary biliary

  1. The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis.

    PubMed

    Yang, Fan; Wang, Qixia; Wang, Zhaoyue; Miao, Qi; Xiao, Xiao; Tang, Ruqi; Chen, Xiaoyu; Bian, Zhaolian; Zhang, Haiyan; Yang, Yue; Sheng, Li; Fang, Jingyuan; Qiu, Dekai; Krawitt, Edward L; Gershwin, M Eric; Ma, Xiong

    2016-02-01

    Although a variant of primary biliary cirrhosis (PBC) characterized by features of autoimmune hepatitis (AIH) has been recognized for many years, few studies with ample numbers of patients have focused on its natural history. This study aimed to clarify the natural history, prognosis, and response to therapy in a cohort of patients with PBC with AIH features. We retrospectively analyzed 277 PBC patients without AIH features and 46 PBC patients with AIH features seen between September 2004 and April 2014. The 5-year adverse outcome-free survival of PBC patients with AIH features was 58% compared to 81% in PBC patients without AIH features. Multivariate analysis in the patients with AIH features indicated that total bilirubin ≥ 2.70× the upper limit of normal predicted a poor prognosis (p = 0.008, relative risk 8.39, 95% confidence interval (CI) 1.73, 40.73). Combination therapy with ursodeoxycholic acid (UDCA) and immunosuppression provided better short-term responses in PBC patients with AIH features, defined by multiple criteria. Higher aspartate aminotransferase (AST) level at accession suggested better prognosis for PBC patients with AIH features while worse prognosis for PBC patients without AIH features. PBC patients with AIH features differ from those without AIH features in terms of natural history, prognostic indicators, and response to therapy.

  2. Primary biliary cirrhosis.

    PubMed

    Carey, Elizabeth J; Ali, Ahmad H; Lindor, Keith D

    2015-10-17

    Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options. PMID:26364546

  3. Primary biliary carcinoma: CT evaluation

    SciTech Connect

    Thorsen, M.K.; Quiroz, F.; Lawson, T.L.; Smith, D.F.; Foley, W.D.; Steward, E.T.

    1984-08-01

    Fifty-three patients with documented primary biliary carcinoma were studied with computed tomography. Twenty-six patients had gallbladder carcinoma and 27 patients had carcinoma of the biliary ductal system. Ninety percent of patients with gallbladder cancer had an intraluminal mass. Local invasion into the liver was common. The majority of patients with biliary ductal carcinoma had dilated bile ducts, while only 50% of patients with gallbladder cancer had biliary ductal dilatation. The most common location of tumor involving the extrahepatic biliary ductal system was the distal common bile duct. This occurred in eight patients out of 27, or 30% of the cases.

  4. Primary biliary cirrhosis

    PubMed Central

    Kumagi, Teru; Heathcote, E Jenny

    2008-01-01

    Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC

  5. Transplantation for Primary Biliary Cirrhosis

    PubMed Central

    ESQUIVEL, CARLOS O.; VAN THIEL, DAVID H.; DEMETRIS, ANTHONY J.; BERNARDOS, ANGEL; IWATSUKI, SHUNZABURO; MARKUS, BERND; GORDON, ROBERT D.; MARSH, J. WALLIS; MAKOWKA, LEONARD; TZAKIS, ANDREAS G.; TODO, SATORU; GAVALER, JUDITH S.; STARZL, THOMAS E.

    2011-01-01

    Primary biliary cirrhosis is a frequent indication for liver transplantation. The purpose of this report is to present our experience with liver transplantation for primary biliary cirrhosis. Attention is given to the causes of hepatic dysfunction seen in allografts. In addition, we review the postoperative problems encountered and the quality of life at time of last follow-up in patients with transplants for primary biliary cirrhosis. A total of 97 orthotopic liver transplant procedures were performed in 76 patients with advanced primary biliary cirrhosis at the University of Pittsburgh from March 1980 through September 1985. The transplant operation was relatively easy to perform. The most common technical complications experienced were fragmentation and intramural dissection of the recipient hepatic artery, which required an arterial graft in 20% of the cases. Most of the postoperative mortality occurred in the first 6 mo after transplantation, with an essentially flat actuarial life survival curve from that time point to a projected 5-yr survival of 66%. Common causes of death included rejection and primary graft nonfunction. Thirteen of the 76 patients had some hepatic dysfunction at the time of the last follow-up, although none were jaundiced. Recurrence of primary biliary cirrhosis could not be demonstrated in any of the patients. Antimitochondrial antibody was detected in the serum of almost all of the patients studied postoperatively for it. Most important, almost all of the 52 surviving patients have been rehabilitated socially and vocationally. PMID:3280389

  6. Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients

    PubMed Central

    Zografos, Theodoros A; Gatselis, Nikolaos; Zachou, Kalliopi; Liaskos, Christos; Gabeta, Stella; Koukoulis, George K; Dalekos, George N

    2012-01-01

    AIM: To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in first-degree relatives (FDRs) of Greek PBC patients. METHODS: The presence of antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibodies (ANA) were determined using indirect immunofluorescence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymptomatic for liver-related symptoms FDRs of 44 PBC patients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepatitis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The prevalence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI): 12%-28.1% vs 2.5%, 95% CI: 0.1%-14.7%, P = 0.01; 18.8%, 95% CI: 12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI: 1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio: 3.92, 95% CI: 1.25-12.35, P = 0.02). CONCLUSION: In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs. PMID:23002341

  7. Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome concomitant with immune hemolytic anemia and immune thrombocytopenic purpura (Evans syndrome).

    PubMed

    Korkmaz, Huseyin; Bugdaci, Mehmet Sait; Temel, Tuncer; Dagli, Mehmet; Karabagli, Pinar

    2013-04-01

    Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) associated with Evans syndrome; combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) has rarely been reported. We report the case of a 53-year-old patient who presented with weakness, myalgia, arthralgia, shortness of breath and purpura. Initial laboratory investigations revealed liver dysfunction, anemia and thrombocytopenia. Anti-nuclear (ANA) and antimitochondrial M2 (AMA M2) antibodies were positive. Diagnose of PBC-AIH overlap was made by clinical, serological and histological investigations. AIHA and ITP was identified with clinical-laboratory findings and bone marrow puncture. She was treated with IVIG followed by prednisolone and ursodeoxycholic acid. Hemoglobin-thrombocytes increased rapidly and transaminases improved at day 8. We have reported the first case in the literature with AIH-PBC overlap syndrome concurrent by ITP and AIHA which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including AIH, PBC, ITP and AIHA.

  8. De novo autoimmune hepatitis following liver transplantation for primary biliary cirrhosis: an unusual cause of late grafts dysfunction

    PubMed Central

    Ennaifer, Rym; Ayadi, Hend; Romdhane, Haifa; Cheikh, Meriem; Mestiri, Hafedh; Khalfallah, Taher; Hadj, Najet Bel

    2015-01-01

    De novo autoimmune hepatitis (AIH) is a rare disorder first described in 1998. It occurs in patients who underwent liver transplantation for a different etiology. We present the case of a 56-year-old woman who was diagnosed with primary biliary cirrhosis and had liver transplantation for refractory pruritis. Seven years after transplantation, she presented alterations in the hepatic profile with hypertransaminasemia, elevated alkaline phosphatase and gamma-glutamyl-transferase. Her liver functions test also showed elevated IgG levels. Serum autoantibodies were negative except for antimitochondrial antibodies. Histological findings indicated features of AIH without bile duct damage or loss. She had a pretreatment AIH score of 13 points and a post treatment score of 15 points according to the International AIH Group. The patient was treated effectively with prednisolone and her liver function and globulin levels rapidly returned to normal. PMID:26401196

  9. Women and primary biliary cirrhosis.

    PubMed

    Sun, Ying; Haapanen, Krista; Li, Baosen; Zhang, Weici; Van de Water, Judy; Gershwin, M Eric

    2015-06-01

    Primary biliary cirrhosis occurs more frequently in women, and previous studies indicated that the average age of primary biliary cirrhosis (PBC) onset makes pregnancy in PBC patients uncommon. However, more recently, improved diagnostic testing has enabled detection of PBC in younger women, including those of childbearing age. This has led investigators to become increasingly interested in the relationship between the ontogeny of PBC and pregnancy. Published cases indicate that the typical age for pregnant women to be diagnosed with PBC is in the early 30s, and that during gestation, pruritus and jaundice are the most common symptoms. During gestation, susceptible women may experience onset of PBC resulting from the drastic changes in female hormones; this would include not only the mitochondrial damage due to accumulation of bile acids but also changes in the immune response during the different stages of pregnancy that might play an important role in the breakdown of self-tolerance. The mechanisms underlying the potential relationship between PBC and pregnancy warrant further investigation. For women first diagnosed with PBC during gestation, or those for whom first appearance of a flare up occurs during and postpartum, investigation of the immune response throughout gestation could provide new avenues for immunologic therapeutic intervention and the discovery of new treatment strategies for PBC.

  10. Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan

    PubMed Central

    Umemura, Takeji; Joshita, Satoru; Yamazaki, Tomoo; Komatsu, Michiharu; Katsuyama, Yoshihiko; Yoshizawa, Kaname; Tanaka, Eiji; Ota, Masao

    2016-01-01

    Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are liver-specific autoimmune conditions that are characterized by chronic hepatic damage and often lead to cirrhosis and hepatic failure. Specifically, the protein tyrosine phosphatase N22 (PTPN22) gene encodes the lymphoid protein tyrosine phosphatase, which acts as a negative regulator of T-cell receptor signaling. A missense single nucleotide polymorphism (SNP) (rs2476601) in PTPN22 has been linked to numerous autoimmune diseases in Caucasians. In the present series, nine SNPs in the PTPN22 gene were analyzed in 166 patients with AIH, 262 patients with PBC, and 322 healthy controls in the Japanese population using TaqMan assays. Although the functional rs3996649 and rs2476601 were non-polymorphic in all subject groups, the frequencies of the minor alleles at rs1217412, rs1217388, rs1217407, and rs2488458 were significantly decreased in AIH patients as compared with controls (all Pc < 0.05). There were no significant relationships with PTPN22 SNPs in PBC patients. Interestingly, the AAGTCCC haplotype was significantly associated with resistance to both AIH (odds ratio [OR] = 0.58, P = 0.0067) and PBC (OR = 0.58, P = 0.0048). SNPs in the PTPN22 gene may therefore play key roles in the genetic resistance to autoimmune liver disease in the Japanese. PMID:27406031

  11. Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy

    PubMed Central

    Purohit, Treta; Cappell, Mitchell S

    2015-01-01

    Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren’s syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva

  12. Biliary Epithelial Apoptosis, Autophagy, and Senescence in Primary Biliary Cirrhosis

    PubMed Central

    Sasaki, Motoko; Nakanuma, Yasuni

    2010-01-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized serologically by the high prevalence of anti-mitochondrial autoantibodies (AMAs) and histologically by the cholangitis of small bile ducts, eventually followed by extensive loss of the small bile duct. An autoimmune pathogenesis is suggested by clinical and experimental studies, but there remain issues regarding the etiology, the significance of AMAs in the pathogenesis of bile duct lesions, and so on. The unique properties of apoptosis in biliary epithelial cells (BECs), in which there is exposure of autoantigen to the effectors of the immune system, are proposed to be a cause of bile duct lesions in PBC. Recent progress disclosed that cellular senescence and autophagy are involved in bile duct lesions in PBC. Senescent BECs may modulate the periductal microenvironment by expressing senescence-associated secretory phenotypes, including various chemokines, and contribute to the pathogenesis of bile duct lesions in PBC. PMID:21152179

  13. Pulmonary involvement in primary biliary cirrhosis.

    PubMed Central

    Rodriguez-Roisin, R; Pares, A; Bruguera, M; Coll, J; Picado, C; Agusti-Vidal, A; Burgos, F; Rodes, J

    1981-01-01

    The association of pulmonary fibrosis and primary biliary cirrhosis (PBC) remains controversial. To determine the frequency of pulmonary fibrosis in PBC, a carefully selected series of 14 PBC patients, seven patients with Sicca complex, and 14 control subjects have been studied. Seven of the 14 patients with PBC had Sjögren's syndrome, four of whom had some clinical evidence of pulmonary disease. Evaluation of ventilatory capacity, gas transfer factor, arterial blood gases, and lung mechanics were performed. Gas transfer was reduced in patients with PBC associated with Sjögen's syndrome and in patients with the Sicca complex. These results suggest that the respiratory, clinical, ad functional abnormalities found in PBC are related to the presence of an associated Sjögen's syndrome. PMID:7281088

  14. Risk and Surveillance of Cancers in Primary Biliary Tract Disease

    PubMed Central

    Hrad, Valery; Abebe, Yoftahe; Ali, Syed Haris; Velgersdyk, Jared

    2016-01-01

    Primary biliary diseases have been associated in several studies with various malignancies. Understanding the risk and optimizing surveillance strategy of these malignancies in this specific subset of patients are an important facet of clinical care. For instance, primary sclerosing cholangitis is associated with an increased risk for cholangiocarcinoma (which is very challenging to diagnose) and when IBD is present for colorectal cancer. On the other hand, primary biliary cirrhosis patients with cirrhosis or not responding to 12 months of ursodeoxycholic acid therapy are at increased risk of hepatocellular carcinoma. In this review we will discuss in detail the risks and optimal surveillance strategies for patients with primary biliary diseases. PMID:27413366

  15. Primary biliary cirrhosis: From bench to bedside

    PubMed Central

    Kouroumalis, Elias; Notas, George

    2015-01-01

    Primary biliary cirrhosis (PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient’s genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed. PMID:26261733

  16. Primary cancers of extrahepatic biliary passages.

    PubMed

    Mittal, B; Deutsch, M; Iwatsuki, S

    1985-04-01

    We analyzed the records of 22 patients with cancers of extrahepatic biliary passages (EHBP) to understand their natural histories and patterns of failure and to evaluate the effectiveness of various treatments. None of the preoperative investigations consistently defined the entire extent of tumor. Percutaneous transhepatic cholangiography (PTHC) was the most helpful (100%) in accurately defining the site of ductal obstruction. Computed tomography was helpful in diagnosing liver metastases in 53% and primary tumor mass in 23% of patients. The most common sites of tumor failure or persistence were: liver (67%), tumor bed (56%), peritoneum (22%), porta hepatis and lymph nodes (17%). The median survival for the entire group was 6.8 months. Surgery plays an important role in managing these tumors and in defining tumor extent for subsequent adjuvant irradiation. Patients receiving radiation doses greater than or equal to 70 TDF had a longer median survival (11 months) than patients receiving less than 70 TDF (4.4 months). All three patients, who were alive and free of disease greater than 1 year, received radiation doses greater than or equal to 70 TDF. From our data, it is difficult to comment on the effectiveness of chemotherapy. We have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed.

  17. Primary cancers of extrahepatic biliary passages

    SciTech Connect

    Mittal, B.; Deutsch, M.; Iwatsuki, S.

    1985-04-01

    The records of 22 patients with cancers of extrahepatic biliary passages (EHBP) were analyzed to understand their natural histories and patterns of failure and to evaluate the effectiveness of various treatments. None of the preoperative investigations consistently defined the entire extent of tumor. Percutaneous transhepatic cholangiography (PTHC) was the most helpful (100%) in accurately defining the site of ductal obstruction. Computed tomography was helpful in diagnosing liver metastases in 53% and primary tumor mass in 23% of patients. The most common sites of tumor failure or persistence were: liver (67%), tumor bed (56%), peritoneum (22%), porta hepatis and lymph nodes (17%). The median survival for the entire group was 6.8 months. Surgery plays an important role in managing these tumors and in defining tumor extent for subsequent adjuvant irradiation. Patients receiving radiation doses greater than or equal to 70 TDF had a longer median survival (11 months) than patients receiving less than 70 TDF (4.4 months). All three patients, who were alive and free of disease greater than 1 year, received radiation doses greater than or equal to 70 TDF. From the data, it is difficult to comment on the effectiveness of chemotherapy. The authors have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed.

  18. Primary cancers of extrahepatic biliary passages.

    PubMed

    Mittal, B; Deutsch, M; Iwatsuki, S

    1985-04-01

    We analyzed the records of 22 patients with cancers of extrahepatic biliary passages (EHBP) to understand their natural histories and patterns of failure and to evaluate the effectiveness of various treatments. None of the preoperative investigations consistently defined the entire extent of tumor. Percutaneous transhepatic cholangiography (PTHC) was the most helpful (100%) in accurately defining the site of ductal obstruction. Computed tomography was helpful in diagnosing liver metastases in 53% and primary tumor mass in 23% of patients. The most common sites of tumor failure or persistence were: liver (67%), tumor bed (56%), peritoneum (22%), porta hepatis and lymph nodes (17%). The median survival for the entire group was 6.8 months. Surgery plays an important role in managing these tumors and in defining tumor extent for subsequent adjuvant irradiation. Patients receiving radiation doses greater than or equal to 70 TDF had a longer median survival (11 months) than patients receiving less than 70 TDF (4.4 months). All three patients, who were alive and free of disease greater than 1 year, received radiation doses greater than or equal to 70 TDF. From our data, it is difficult to comment on the effectiveness of chemotherapy. We have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed. PMID:3980281

  19. Autotaxin, Pruritus and Primary Biliary Cholangitis (PBC).

    PubMed

    Sun, Ying; Zhang, Weici; Evans, Jilly F; Floreani, Annarosa; Zou, Zhengsheng; Nishio, Yukiko; Qi, Ruizhao; Leung, Patrick S C; Bowlus, Christopher L; Gershwin, M Eric

    2016-08-01

    Autotaxin (ATX) is a 125-kD type II ectonucleotide pyrophosphatase/phosphodiesterase (ENPP2 or NPP2) originally discovered as an unknown "autocrine motility factor" in human melanoma cells. In addition to its pyrophosphatase/phosphodiesterase activities ATX has lysophospholipase D (lysoPLD) activity, catalyzing the conversion of lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). ATX is the only ENPP family member with lysoPLD activity and it produces most of the LPA in circulation. In support of this, ATX heterozygous mice have 50% of normal LPA plasma levels. The ATX-LPA signaling axis plays an important role in both normal physiology and disease pathogenesis and recently has been linked to pruritus in chronic cholestatic liver diseases, including primary biliary cholangitis (PBC). Several lines of evidence have suggested that a circulating puritogen is responsible, but the identification of the molecule has yet to be definitively identified. In contrast, plasma ATX activity is strongly associated with pruritus in PBC, suggesting a targetable molecule for treatment. We review herein the biochemistry of ATX and the rationale for its role in pruritus.

  20. The Diagnosis of Primary Biliary Cirrhosis

    PubMed Central

    Bowlus, Christopher L.; Gershwin, M. Eric

    2014-01-01

    Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by the immune mediated destruction of small intrahepatic bile duct epithelial cells leading to cholestasis and cirrhosis. The autoimmune basis of PBC is supported by the highly specific anti-mitochondrial antibodies (AMA) and autoreactive T cells, the former being the basis for diagnosis in the vast majority of cases. Although a rare disease, the incidence rates of PBC have been increasing, possibly due to increased testing and diagnosis as opposed to a true increase in disease incidence. Presently, most cases are asymptomatic and only suspected based upon routine liver tests. Those with symptoms typically complain of pruritus and fatigue. The diagnosis of PBC is based on the presence of at least 2 of 3 key criteria including a persistently elevated serum alkaline phosphatase, the presence of serum AMA, and liver histology consistent with PBC. Anti-nuclear antibodies specific to PBC are useful in cases in which AMA are not detected and may indicate a more aggressive course. Ursodeoxycholic acid is the only proven therapy for PBC and in most cases can delay or prevent disease progression. However, a subgroup of patients does not adequately respond to ursodeoxycholic acid and for whom new therapies are needed. PMID:24424173

  1. Multivesicular stellate cells in primary biliary cirrhosis.

    PubMed

    Cameron, R G; Neuman, M G; Shear, N H; Blendis, L M

    1997-09-01

    Stellate cells have only recently received attention in patients with primary biliary cirrhosis (PBC). We used electron microscopy and morphometry to perform a qualitative and quantitative examination of lipid-storing activity of stellate cells in liver biopsies of 26 patients with noncirrhotic and cirrhotic PBC. Parallel with this study, a comparative analysis of the morphology of stellate cells in 51 patients with livers of normal histology was performed. There was a marked increase in the total number of lipid vesicles in stellate cells in all PBC patients when compared to livers with normal histology. Multiple multivesicular stellate cells were seen in the livers of 21 out of 26 patients with PBC. There were 11 to 28 lipid vesicles per multivesicular stellate cell from 1 micromol/L to 5 micromol/L in diameter per lipid vesicle. Hepatocytes showed little or no steatosis in 24 out of 26 (92%) PBC patients. Multivesicular stellate cells were not seen in female patients with normal liver histology. These results suggest that there is an alteration in hepatic lipid-storage that involves stellate cells in PBC, which could be an early manifestation of this disease. Its significance remains to be determined.

  2. Multivesicular stellate cells in primary biliary cirrhosis.

    PubMed

    Cameron, R G; Neuman, M G; Shear, N; Blendis, L M

    1997-10-01

    Stellate cells have only recently received attention in patients with primary biliary cirrhosis (PBC). We have used electron microscopy and morphometry to perform a qualitative and quantitative examination of lipid-storing activity of stellate cells in liver biopsies of 26 patients with noncirrhotic and cirrhotic PBC. In parallel with this study, a comparative analysis of the morphology of stellate cells in 51 patients with livers of normal histology was performed. There was a marked increased in the total number of lipid vesicles in stellate cells in all PBC patients when compared with livers with normal histology. Multiple multivesicular stellate cells were seen in the livers of 21 of 26 patients with PBC. There were 11 to 28 lipid vesicles per multivesicular stellate cell in sizes of 1 microm to 5 microm in diameter per lipid vesicle. Hepatocytes showed little or no steatosis in 24 of 26 (92%) PBC patients. Multivesicular stellate cells were not seen in female patients with normal liver histology. These results suggest that there is an alteration in hepatic lipid storage that involves stellate cells in PBC that could be an early manifestation of this disease. Its significance remains to be elucidated.

  3. Geographic Clusters of Primary Biliary Cirrhosis

    PubMed Central

    Abu-Mouch, Saif; Selmi, Carlo; Benson, Gordon D.; Kenny, Thomas P.; Invernizzi, Pietro; Zuin, Massimo; Podda, Mauro; Rossaro, Lorenzo; Gershwin, M. Eric

    2003-01-01

    Genetic and environmental factors have been widely suggested to contribute to the pathogenesis of primary biliary cirrhosis (PBC), an autoimmune disease of unknown etiology leading to destruction of small bile ducts. Interestingly, epidemiologic data indicate a variable prevalence of the disease in different geographical areas. The study of clusters of PBC may provide clues as to possible triggers in the induction of immunopathology. We report herein four such unique PBC clusters that suggest the presence of both genetic and environmental factors in the induction of PBC. The first cluster is represented by a family of ten siblings of Palestinian origin that have an extraordinary frequency of PBC (with 5/8 sisters having the disease). Second, we describe the cases of a husband and wife, both having PBC. A family in which PBC was diagnosed in two genetically unrelated individuals, who lived in the same household, represents the third cluster. Fourth, we report a high prevalence of PBC cases in a very small area in Alaska. Although these data are anedoctal, the study of a large number of such clusters may provide a tool to estimate the roles of genetics and environment in the induction of autoimmunity. PMID:14768943

  4. Serological and histological diagnosis of primary biliary cirrhosis

    PubMed Central

    Goudie, R. B.; Macsween, R. N. M.; Goldberg, D. M.

    1966-01-01

    A simple immunofluorescence test for antibody to a mitochondrial antigen present in many tissues is a reliable method of distinguishing most cases of primary biliary cirrhosis from jaundice due to extrahepatic biliary tract obstruction. Of 30 cases diagnosed as primary biliary cirrhosis, 26 had antimitochondrial antibody whereas none of 77 cases with jaundice due to extrahepatic bile duct obstruction showed this serological abnormality. The antibody was also found in the serum of three of 42 patients who had other forms of cirrhosis and in two of 266 patients with no evidence of liver disease. Clinical, biochemical, and serological findings favour the view that primary biliary cirrhosis is a real entity which, in our present state of knowledge, cannot be defined clearly by any single method of investigation. In particular, the liver may show a variety of histological appearances which, interpreted without regard to the other features of the case, may lead to errors in diagnosis. Images PMID:5333256

  5. Primary biliary cirrhosis--experience in University Hospital, Kuala Lumpur.

    PubMed

    Mohammed, R; Goh, K L; Wong, N W

    1996-03-01

    Primary biliary cirrhosis is an uncommon disease amongst Malaysians. Over a 12-year period, between 1979 and 1991, only seven patients with clinical, biochemical and histologic evidence of primary biliary cirrhosis were identified in University Hospital Kuala Lumpur. All were Chinese females between the ages of 30 to 55 years. The presenting complaint was pruritus in 5 patients. All except one patient was jaundiced when the diagnosis was made. These patients were followed up from 1 to 11 years. Three deaths were reported, one from massive hemetemesis and two from liver failure.

  6. Mononuclear cell complement receptor blockade in primary biliary cirrhosis.

    PubMed Central

    Al-Aghbar, M N; Neuberger, J; Williams, R; Eddleston, A L

    1985-01-01

    Peripheral blood monocyte and lymphocyte receptors for Fc and C3b fragments were examined in vitro in patients with primary biliary cirrhosis and other chronic liver diseases using sheep red blood cells coated with anti-SRBC IgG1 (to detect Fc receptors) and with anti-SRBC IgM and complement (to detect C3b receptors). The number of C3b receptors detected on 100 monocytes was significantly lower in patients with primary biliary cirrhosis (23.0 +/- 12.0, mean +/- 1 SD) compared with normal controls (57.4 +/- 16.9) and other chronic liver disease (HBsAg negative chronic active hepatitis 62.0 +/- 17.0, alcoholic cirrhosis 50.9 +/- 4.0), while the number of Fc receptors detected on 100 monocytes was not significantly different in all the groups (primary biliary cirrhosis 72.8 +/- 28.6, chronic active hepatitis 74.7 +/- 14.0, alcoholic cirrhosis 58.0 +/- 13.5 and normal controls 69.6 +/- 19.9). When mononuclear cells isolated from normal individuals were pre-incubated with serum from patients with primary biliary cirrhosis before testing their receptor function there was a significant reduction in the number of C3b receptors detected per 100 monocytes (27.6 +/- 10.8) compared with pre-incubation with normal serum (72.0 +/- 18.0). This reduction in C3b-receptor function was again observed when the serum used for pre-incubation was depleted of circulating immune complexes; but when complement was further depleted from these sera, the number of C3b-receptors detected after pre-incubation was similar to normal values (64.0 +/- 11.8). Lymphocyte receptors showed a similar pattern of results. This implies a specific C3b receptor blockade on monocytes and lymphocytes from patients with primary biliary cirrhosis which appears to be because of blocking by serum factor(s) including complement fragments. PMID:3155513

  7. Radiation Therapy for Primary Carcinoma of the Extrahepatic Biliary System

    PubMed Central

    Flickinger, John C.; Epstein, Alan H.; Iwatsuki, Shunzaburo; Carr, Brian I.; Starzl, Thomas E.

    2010-01-01

    From 1976 to 1988, 63 patients received radiation therapy for primary cancers of the extrahepatic biliary system (eight gallbladder and 55 extrahepatic biliary duct). Twelve patients underwent orthotopic liver transplantation. Chemotherapy was administered to 13 patients. Three patients underwent intraluminal brachytherapy alone (range, 28 to 55 Gy). Sixty patients received megavoltage external-beam radiation therapy (range, 5.4 to 61.6 Gy; median, 45 Gy), of whom nine received additional intraluminal brachytherapy (range, 14 to 45 Gy; median, 30 Gy). The median survival of all patients was 7 months. Sixty patients died, all within 39 months of radiation therapy. One patient is alive 11 months after irradiation without surgical resection, and two are alive 50 months after liver transplantation and irradiation. Symptomatic duodenal ulcers developed after radiation therapy in seven patients but were not significantly related to any clinical variable tested. Extrahepatic biliary duct cancers, the absence of metastases, increasing calendar year of treatment, and liver transplantation with postoperative radiation therapy were factors significantly associated with improved survival. PMID:2070327

  8. Pulmonary Manifestations among Patients with Primary Biliary Cirrhosis

    PubMed Central

    Koksal, Deniz; Koksal, Aydin Seref; Gurakar, Ahmet

    2016-01-01

    Abstract Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease caused by diffuse inflammation, destruction and fibrosis of the intrahepatic bile ducts, ultimately leading to cirrhosis, portal hypertension and liver failure. The pathogenesis of PBC is incompletely understood, but current data suggest roles for genetic susceptibility and environmental factors. PBC is often thought of as an organ-specific autoimmune disease, which mainly targets the liver; however, lung tissue is also a site for autoimmune involvement of PBC. The pulmonary manifestations of PBC include abnormalities in gas transfer and pulmonary function, subclinical alveolitis, interstitial lung disease, granulomatous lung disease, airway disease, pulmonary hypertension, pulmonary hemorrhage and pleural effusion. PMID:27777894

  9. [Association between chronic urinary tract infection and primary biliary cirrhosis].

    PubMed

    Xu, Y; Wang, J B; Wang, S

    2016-06-01

    The etiology of primary biliary cirrhosis (PBC) remains unclear, and at present, this disease is considered to be caused by the combined effect of genetic factors, infection, autoimmunity, and environmental factors. Since infection is the major cause for PBC, scholars have been focusing on the association between chronic microbial infection. Studies have shown that Escherichia coli is the most common bacterium for urinary tract infection (UTI), and recurrent UTI has been confirmed to be a risk factor for the development and progression of autoimmune liver diseases and is closely associated with PBC. This article investigates the association between UTI and PBC and possible mechanisms. PMID:27465958

  10. [Is ursodeoxycholic acid effective in primary biliary cirrhosis?].

    PubMed

    Rada, Gabriel; Mac-Namara, Macarena

    2014-09-24

    Ursodeoxycholic acid is considered as first line treatment in patients with primary biliary cirrhosis. Its mechanism of action in this disease is unknown and there is controversy about its clinical impact. Searching in Epistemonikos database, which is maintained by screening 19 databases, we identified four systematic reviews including 16 studies. We combined the evidence using tables with summary of findings following the GRADE approach and concluded ursodeoxycholic acid may not have any effect on pruritus, and there is uncertainty about its effect on mortality, need for liver transplantation or on any other important outcome for the patient.

  11. Bronchiolitis obliterans organising pneumonia and primary biliary cirrhosis-like lung involvement in a patient with primary biliary cirrhosis.

    PubMed

    Strobel, E S; Bonnet, R B; Werner, P; Schaefer, H E; Peter, H H

    1998-01-01

    A 55-year-old woman with a 6-year history of primary biliary cirrhosis presented with an acute onset of fever, dyspnoea, crackles over both lower lung fields, and diffuse interstitial and bibasilar patchy pulmonary opacities. After exclusion of an infectious aetiology, an open lung biopsy was performed which revealed two histopathological features: (1) bronchiolitis obliterans organising pneumonia and (2) lympho-histiocytic interstitial pneumonitis and destructive bronchiolitis. Treatment response to corticosteroids and azathioprine followed a bimodal pattern with immediate resolution of her initial presenting symptoms and late resolution of residual gas exchange defects.

  12. B CELL DEPLETION THERAPY EXACERBATES MURINE PRIMARY BILIARY CIRRHOSIS

    PubMed Central

    Dhirapong, Amy; Lleo, Ana; Yang, Guo-Xiang; Tsuneyama, Koichi; Dunn, Robert; Kehry, Marilyn; Packard, Thomas A.; Cambier, John C.; Liu, Fu-Tong; Lindor, Keith; Coppel, Ross L.; Ansari, Aftab A.; Gershwin, M. Eric

    2010-01-01

    Primary biliary cirrhosis (PBC) is considered a model autoimmune disease due to the clinical homogeneity of patients and the classic hallmark of anti-mitochondrial antibodies (AMAS). Indeed, the presence of AMAS is the most highly directed and specific autoantibody in autoimmune diseases. However, the contribution of B cells to the pathogenesis of PBC is unclear. Thus, although AMAs appear to interact with the biliary cell apotope and contribute to biliary pathology, there is no correlation of disease severity and titer of AMA. The recent development of well characterized mAbs specific for the B cell populations, anti-CD20 and anti-CD79, and the development of a well defined xenobiotic induced model of autoimmune cholangitis, prompted us to utilize these reagents and the model to address the contribution of B cells in the pathogenesis of murine PBC. Prior to the induction of autoimmune cholangitis, mice were treated with either anti-CD20, anti-CD79, or isotype matched control mAb and followed for B cell development, the appearance of AMAs, liver pathology and cytokine production. Results of the studies reported herein show that the in vivo depletion of B cells using either anti-CD20 or anti-CD79 led to the development of a more severe form of cholangitis than control mice which is in contrast with results from a number of other autoimmune models which have documented an important therapeutic role of B cell specific depletion. The anti-CD20/CD79 treated mice have increased liver T cell infiltrates and higher levels of pro-inflammatory cytokines. In conclusion, our results reflect a novel disease protective role of B cells in PBC and suggest that B cell depletion therapy in humans with PBC should be approached with caution. PMID:21274873

  13. Primary Biliary Cirrhosis and the Nuclear Pore Complex

    PubMed Central

    Duarte-Rey, Carolina; Bogdanos, Dimitrios; Yang, Chen-Yen; Roberts, Krista; Leung, Patrick S.C.; Anaya, Juan-Manuel; Worman, Howard J.; Gershwin, M. Eric

    2012-01-01

    Experimental models of autoimmune diseases have led to the conclusion that an immune response to nuclear antigens is a sentinel marker for loss of tolerance and potential tissue damage. Various proteins are targets of antinuclear antibodies in a variety of autoimmune diseases, ranging from systemic rheumatologic disorders to diseases affecting specific organs such as the liver. Autoantibodies against specific nuclear constituents have also been used as probes to understand the structure and the function of the targeted components and their relevance to disease pathogenesis. Approximately a quarter of patients with primary biliary cirrhosis (PBC) have antibodies targeting proteins of the nuclear pore complex (NPC), a multi-protein structure that mediates molecular transport across the nuclear envelope. Autoantibodies against the integral membrane glycoprotein gp210 and nucleoporin p62 appear to be highly specific for PBC, an autoimmune disease characterized by progressive destruction of intrahepatic biliary epithelial cells. This review discusses the diagnostic and clinical relevance of anti-NPC antibodies in PBC and the possibility that this autoimmune response may arise as a result of molecular mimicry. PMID:22487189

  14. Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

    PubMed Central

    Toshikuni, Nobuyuki; Yamato, Ryumei; Kobashi, Haruhiko; Nishino, Ken; Inada, Nobu; Sakanoue, Ritsuko; Suehiro, Mitsuhiko; Fujimura, Yoshinori; Yamada, Gotaro

    2008-01-01

    Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year-old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB1*0601 and DRB1*0803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP. PMID:18416479

  15. Xenobiotics and Autoimmunity: Does Acetaminophen Cause Primary Biliary Cirrhosis?

    PubMed Central

    Leung, Patrick S.C.; Lam, Kit; Kurth, Mark J.; Coppel, Ross L.; Gershwin, M. Eric

    2012-01-01

    The serologic hallmark of primary biliary cirrhosis (PBC) is the presence of antimitochondrial autoantibodies (AMA) directed against the E2 subunit of PDC-E2. The PBC-related autoepitope of PDC-E2 contains lipoic acid, and previous work has demonstrated that mimics of lipoic acid following immunization of mice lead to a PBC-like disease. Furthermore, approximately one third of patients who have ingested excessive amounts of acetaminophen (paracetamol) develop AMA of the same specificity as patients with PBC. Quantitative structure-activity relationship (QSAR) data indicates that acetaminophen metabolites are particularly immunoreactive with AMA, and we submit that in genetically susceptible hosts, electrophilic modification of lipoic acid in PDC-E2 by acetaminophen or similar drugs can facilitate a loss of tolerance and lead to the development of PBC. PMID:22920894

  16. The diagnosis and treatment of primary biliary cirrhosis

    PubMed Central

    Kim, Kyung-Ah

    2011-01-01

    Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. The initial presentation of PBC is various from asymptomatic, abnormal liver biochemical tests to overt cirrhosis. The diagnosis of PBC is based on cholestatic biochemical liver tests, presence of antimitochondrial antibody and histologic findings of nonsuppurative destructive cholangitis. Although the diagnosis is straightforward, it could be underdiagnosed because of its asymptomatic presentation, or underrecognition of the disease. UDCA in a dose of 13-15 mg/kg is the widely approved therapy which can improve the prognosis of patients with PBC. However, one-third of patients does not respond to UDCA therapy and may require liver transplantation. Every effort to diagnose PBC in earlier stage and to develop new therapeutic drugs and clinical trials should be made. PMID:22102382

  17. Clinical significance of autoantibodies in primary biliary cirrhosis.

    PubMed

    Nakamura, Minoru

    2014-08-01

    Antimitochondrial, anti-gp210, anti-sp100, and anticentromere antibodies are specifically detected in primary biliary cirrhosis (PBC). In clinical practice, they are useful for the diagnosis of PBC or for evaluating disease severity, clinical phenotype, and long-term outcome. In the typical or classical form of PBC which shows slow progressive loss of small bile ducts with a parallel increase in liver fibrosis, anti-gp210 antibodies are a strong risk factor for progression to jaundice and hepatic failure, whereas the presence of anticentromere antibodies is a risk factor for progression to cirrhosis and portal hypertension. Of note, the autoimmune repertoire, which is established during the early stage of the disease process, can influence the clinical phenotype and the long-term prognosis of PBC. Because the natural course of PBC is being altered by treatment with ursodeoxycholic acid, the clinical significance of these PBC-specific autoantibodies awaits re-evaluation in various ethnicities.

  18. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    SciTech Connect

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E. )

    1988-10-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M{sub r} 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects.

  19. Xenobiotics and loss of tolerance in primary biliary cholangitis

    PubMed Central

    Wang, Jinjun; Yang, Guoxiang; Dubrovsky, Alana Mari; Choi, Jinjung; Leung, Patrick SC

    2016-01-01

    Data from genome wide association studies and geoepidemiological studies established that a combination of genetic predisposition and environmental stimulation is required for the loss of tolerance in primary biliary cholangitis (PBC). The serologic hallmark of PBC are the presence of high titer anti-mitochondrial autoantibodies (AMA) that recognize the lipoyl domain of the mitochondrial pyruvate dehydrogenase E2 (PDC-E2) subunit. Extensive efforts have been directed to investigate the molecular basis of AMA. Recently, experimental data has pointed to the thesis that the breaking of tolerance to PDC-E2 is a pivotal event in the initial etiology of PBC, including environmental xenobiotics including those commonly found in cosmetics and food additives, suggesting that chemical modification of the PDC-E2 epitope may render its vulnerable to become a neo-antigen and trigger an immune response in genetically susceptible hosts. Here, we will discuss the natural history, genetics and immunobiology of PBC and structural constraints of PDC-E2 in AMA recognition which makes it vulnerable to chemical modification. PMID:26755880

  20. Primary biliary cirrhosis: Clinical and laboratory criteria for its diagnosis

    PubMed Central

    Reshetnyak, Vasiliy Ivanovich

    2015-01-01

    Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic granulomatous, and destructive inflammatory lesion of small intralobular and septal bile ducts, which is likely to be caused by an autoimmune mechanism with a the presence of serum antimitochondrial antibodies and a potential tendency to progress to cirrhosis. Despite the fact that the etiology of this disease has been unknown so far, there has been a considerable body of scientific evidence that can reveal the clinical and laboratory signs of PBC and the individual components of its pathogenesis and elaborate diagnostic criteria for the disease and its symptomatic therapy. Deficiencies in autoimmune tolerance are critical factors for the initiation and perpetuation of the disease. The purpose of this review is to summarize the data available in the literature and the author’s findings on clinical and laboratory criteria for the diagnosis of PBC. This review describes the major clinical manifestations of the disease and the mechanisms of its development. It presents the immunological, biochemical, and morphological signs of PBC and their significance for its diagnosis. A great deal of novel scientific evidence for the problem of PBC has been accumulated. However, the inadequate efficiency of therapy for the disease lends impetus to the quest for its etiological factors and to further investigations of its pathogenetic mechanisms and, on this basis, to searches for new methods for its early diagnosis. PMID:26167070

  1. Prolonged treatment with ursodeoxycholic acid for primary biliary cirrhosis.

    PubMed

    Crippa, G; Cagnoni, C; Castelli, A; Concesi, C; Girometta, S; Pancotti, D; Sverzellati, E; Tacchini, G; Pierfranceschi, M G; Carrara, G C

    1995-05-01

    Eighteen patients affected with biopsy-proved primary biliary cirrhosis (PBC) (histological stage III and IV) received ursodeoxicholic acid (UDCA) 600 mg for 1 year. Signs and symptoms and biochemical tests (glutamic and oxalcetic transaminase, glutamic and pyruvic transaminase, bilirubine, gamma-glutamyl transpeptidase, alkaline phosphatase, leucine aminopeptidase, bile acids, plasma proteins electrophoresis, immunoglubulins A, G and M) and antimitochondrial antibodies were evaluated before the treatment and every four months during the treatment. The results were compared with those obtained in 8 untreated patients affected PBC. The control group of patients were comparable (as far as age, histological stage, biochemical tests are concerned) to the group who received UDCA. Bilirubine, ALP, gamma-GT and LAP decreased during the treatment with UDCA and remained lower than baseline values until the end of the observation (12 months), while no changes occurred in the untreated patients. Both in the treated and untreated group plasma protein electrophoresis, serum immunoglubulins A, G and M remained unchanged, as well as anti-mitochondrial antibody. A moderate reduction of transaminases and bile acids was observed in the group of patients receiving UDCA but it did not reach statistical significance. In 16 out of the 18 treated patients pruritus disappeared and resulted diminished in the remaining 2 patients. No significant amelioration of pruritus was observed in the patients who did not receive UDCA. In conclusion, our data show that prolonged treatment with UDCA drastically reduces pruritus and improves cholestasis biochemical tests in patients affected with symptomatic PBC.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Biliary Multifocal Chromosomal Polysomy and Cholangiocarcinoma in Primary Sclerosing Cholangitis

    PubMed Central

    Eaton, John E.; Barr Fritcher, Emily G.; Gores, Gregory J.; Atkinson, Elizabeth J.; Tabibian, James H.; Topazian, Mark D.; Gossard, Andrea A.; Halling, Kevin C.; Kipp, Benjamin R.; Lazaridis, Konstantinos N.

    2015-01-01

    OBJECTIVES Polysomy detected by fluorescence in situ hybridization (FISH) is associated with cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC). However, a subset of PSC patients with polysomy do not manifest CCA even after long-term follow-up. It is unknown if patients with chromosomal gains detected by FISH in multiple areas of the biliary tree (i.e., multifocal polysomy, MFP) are more likely to be diagnosed with CCA than patients with unifocal polysomy (UFP). Therefore, our aim is to determine whether patients with MFP are more likely to manifest CCA compared with patients with other chromosomal abnormalities including UFP and other FISH subtypes. METHODS We performed a retrospective review of PSC patients without a mass lesion who underwent FISH testing at our institution from 1 January 2005 to 1 July 2013. RESULTS Three-hundred and seventy-one PSC patients were included. Compared with patients with UFP, those with MFP were more likely to have weight loss (32 vs. 9%), suspicious cytology (45 vs. 13%) and develop serial polysomy (91 vs. 35%). MFP was associated with CCA (hazard ratio (HR), 82.42; 95% confidence interval (CI), 24.50–277.31) and was the strongest predictor of cancer diagnosis. Suspicious cytology (HR, 26.31; 95% CI, 8.63–80.24) and UFP (HR, 13.27; 95% CI, 3.32–53.08) were also predictive of CCA. MFP, UFP and suspicious cytology remained associated with CCA in the multivariable model. CONCLUSIONS Compared with other FISH subtypes, MFP is the strongest predictor of CCA. However, patients with UFP and suspicious cytology (regardless of FISH status) are also at an increased risk for CCA. PMID:25623660

  3. Primary Biliary Mixed Adenoneuroendocrine Carcinoma (MANEC): A Short Review.

    PubMed

    Acosta, Andres M; Wiley, Elizabeth Louise

    2016-10-01

    Mixed adenoneuroendocrine carcinomas (MANECs) are composite neoplasms with areas of adenocarcinoma or squamous cell carcinoma intermingled with neuroendocrine carcinoma or neuroendocrine tumor, each composing at least 30% of the neoplasm. MANECs are very infrequent overall, and they are more commonly diagnosed in the appendix, colon, and stomach. Biliary MANECs are particularly rare, and their histogenesis is debated because neuroendocrine cells are seldom identified in the normal biliary tract. They can show one of the 3 different architectural patterns described in Lewin's original classification: collision tumors, combined lesions, or amphicrine neoplasms. The neuroendocrine component is usually of a high grade, with small or large cell cytomorphology, whereas the adenocarcinoma component is either an intestinal or biliary type. Clinical presentation is characterized by locally advanced disease at the time of initial diagnosis. Recent studies suggest that treatment should be guided by the most aggressive histologic component. PMID:27684986

  4. Combination antiretroviral studies for patients with primary biliary cirrhosis

    PubMed Central

    Lytvyak, Ellina; Montano-Loza, Aldo J; Mason, Andrew L

    2016-01-01

    Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis (PBC), pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid. In the first open label pilot study, the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year. Whereas, lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score, cholangitis and ductopenia over a 12 mo period. A double blind, multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase, ALT and AST in patients on antiviral therapy. However, none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase. Furthermore, some patients developed biochemical rebound consistent with drug resistance. A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore, provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load. Nevertheless, viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus. The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor, lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection. This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label

  5. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective

    PubMed Central

    Marchioni Beery, Renée M.; Vaziri, Haleh; Forouhar, Faripour

    2014-01-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are two major types of chronic cholestatic liver disease. Each disorder has distinguishing features and variable progression, but both may ultimately result in cirrhosis and hepatic failure. The following offers a review of PBC and PSC, beginning with a general overview of disease etiology, pathogenesis, diagnosis, clinical features, natural course, and treatment. In addition to commonly associated manifestations of fatigue, pruritus, and fat-soluble vitamin deficiency, select disease-related topics pertaining to women's health are discussed including metabolic bone disease, hyperlipidemia and cardiovascular risk, and pregnancy-related issues influencing maternal disease course and birth outcomes. This comprehensive review of PBC and PSC highlights some unique clinical considerations in the care of female patients with cholestatic liver disease. PMID:26357630

  6. Evaluation of Biliary Calprotectin as a Biomarker in Primary Sclerosing Cholangitis

    PubMed Central

    Gauss, Annika; Sauer, Peter; Stiehl, Adolf; Rupp, Christian; Krisam, Johannes; Leopold, Yvonne; Kloeters-Plachky, Petra; Stremmel, Wolfgang; Gotthardt, Daniel

    2016-01-01

    Abstract Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts with limited therapeutic options except liver transplantation. Reliable biomarkers to predict the disease course are unavailable, and currently employed disease activity scores such as the Mayo risk score (MRS) have limitations. The present study aims to evaluate biliary calprotectin as a marker of disease activity and prognosis in PSC. This is a monocentric retrospective observational study. Calprotectin concentrations were measured by an enzyme-linked immunosorbent assay in bile samples collected by endoscopic retrograde cholangiography from 106 PSC patients and 20 controls. Biliary calprotectin concentrations were compared between the 2 groups. In PSC patients, results were evaluated with regard to the presence of dominant bile duct stenoses, bile microbiology, MRS, survival free of liver transplantation, and necessity for bile duct interventions in the further disease course. Median (interquartile ranges) biliary calprotectin concentrations were higher in PSC patients than in controls (3646 ng/mL, 249–9748 vs 116 ng/mL, 104–655; P < 0.001). In the PSC cohort, higher biliary calprotectin concentrations were associated with the presence of microbes in bile (P = 0.02), the occurrence of dominant bile duct stenosis at any time in the disease course (P = 0.005), and the necessity for future bile duct interventions (P = 0.02). Patients with biliary calprotectin concentrations above a cut-off of 11,610 ng/mL displayed significantly shorter transplantation-free survival than those with biliary calprotectin concentrations ≤11,610 ng/mL (P < 0.001). Univariate Cox regression analysis revealed high biliary calprotectin concentration (>11,610 ng/mL) as a risk factor of shorter transplantation-free survival of PSC patients (P < 0.001) beside high plasma alkaline phosphatase (ALP) concentration (>142.5 U/L) (P = 0.006), high MRS (

  7. T cell clonal expansions detected in patients with primary biliary cirrhosis express CX3CR1

    PubMed Central

    Zhang, Weici; Ono, Yoko; Miyamura, Yoshinori; Bowlus, Christopher L.; Gershwin, M. Eric; Maverakis, Emanual

    2014-01-01

    The intrahepatic biliary destruction of primary biliary cirrhosis (PBC) appears secondary to a multi-lineage response that includes autoantibodies, biliary apotopes, and cellular responses. Although there has been considerable effort in defining the role and specificity of anti-mitochondrial autoantibodies, a major challenge has been the characterization of T effector pathways. This difficulty is due in part to the limitation of current technologies for directly isolating and characterizing autoreactive T cells from patients. Herein, we successfully demonstrate a novel technology for characterizing the surface phenotype of T cell oligoclonal expansions directly ex vivo. Using PBC as a prototypic disease we were able to detect clonal T cell expansions in 15/15 patients examined. Although the T cell expansions from different patients expressed different TCR Vβ gene segments, the surface phenotype of the cells was the same. The clonal T cell expansions in PBC patients are CX3CR1+ Fas+ effector-memory T cells, a finding of particular importance given the known up-regulation of fractalkine on injured biliary epithelial cells (BEC). In contrast to the persistent aberrantly expanded T cells observed in the PBC patients, T cell expansions detected in response to a herpes viral infection were very dynamic and resolved over time. This protocol can be used to characterize T cell expansions in other autoimmune diseases. PMID:21636249

  8. A combination of phototherapy and cholestyramine for the relief of pruritus in primary biliary cirrhosis.

    PubMed

    Cerio, R; Murphy, G M; Sladen, G E; MacDonald, D M

    1987-02-01

    A patient with primary biliary cirrhosis is reported in whom UV phototherapy alone was repeatedly effective in controlling severe pruritus. Symptomatic relief was sustained by introducing cholestyramine at a low dosage, despite previous failure of the drug alone to produce any therapeutic benefit, even in large doses. Bile acid concentrations were measured in sera, urine and suction blister fluid from skin exposed to ultraviolet light before, during and following treatment. The findings suggest that phototherapy reduces cutaneous bile acid levels which can subsequently be maintained by low dose cholestyramine. Routine liver function tests remained unaltered. This combination of phototherapy and cholestyramine may be useful in controlling severe pruritus in primary biliary cirrhosis when the drug alone is not tolerated or is ineffective.

  9. Characterisation of patients with primary biliary cirrhosis responding to long term ursodeoxycholic acid treatment

    PubMed Central

    Leuschner, M; Dietrich, C; You, T; Seidl, C; Raedle, J; Herrmann, G; Ackermann, H; Leuschner, U

    2000-01-01

    BACKGROUND—In some patients with primary biliary cirrhosis, ursodeoxycholic acid causes full biochemical normalisation of laboratory data; in others, indexes improve but do not become normal.
AIMS—To characterise complete and incomplete responders.
METHODS—Seventy patients with primary biliary cirrhosis were treated with ursodeoxycholic acid 10-15 mg/kg/day and followed up for 6-13 years.
RESULTS—In 23 patients (33%) with mainly stage I or II disease, cholestasis indexes and aminotransferases normalised within 1-5 years, except for antimitochondrial antibodies. Histological findings improved. Indexes were not normalised in 47 patients (67%) although the improvement of their biochemical functions parallelled the trend in the first group. In these incomplete responders histological findings improved to a lesser extent. The only difference between the two groups before treatment was higher levels of alkaline phosphatase and γ glutamyl transpeptidase in the incomplete responders. At onset of treatment the discriminant value separating responders from incomplete responders was 660 U/l for alkaline phosphatase and 131 U/l for γ glutamyl transpeptidase. One year later it was 239 and 27 U/l (overall predictive value for responders 92%, for incomplete responders 81%). There were no differences between the two groups concerning immune status, antimitochondrial antibody subtypes, liver histology, or any other data. HLA-B39, DRB1*08, DQB1*04 dominated in both groups.
CONCLUSIONS—In patients with mainly early stages of primary biliary cirrhosis, higher values of alkaline phosphatase and γ glutamyl transpeptidase are the only biochemical indexes which allow discrimination between patients who will completely or incompletely respond to ursodeoxycholic acid treatment.


Keywords: primary biliary cirrhosis; prognostic indexes; full response to ursodeoxycholic acid; incomplete responders; anti-p53 autoantibodies; HLA typing PMID:10601067

  10. Grave's Disease and Primary Biliary Cirrhosis-An Unusual and Challenging Association.

    PubMed

    Shetty, Shiran; Rajasekaran, Senthilkumar; Venkatakrishnan, Leela

    2014-03-01

    Jaundice in Grave's diseases is uncommon, but when it does occur, complication of thyrotoxicosis (heart failure/infection) or intrinsic liver disease should be considered. Grave's disease can cause asymptomatic elevation of liver enzymes, jaundice and rarely acute liver failure. It is associated with other autoimmune diseases like autoimmune hepatitis, or primary biliary cirrhosis. The cause of jaundice in Grave's disease is multifactorial. PMID:25755537

  11. Grave's Disease and Primary Biliary Cirrhosis—An Unusual and Challenging Association

    PubMed Central

    Shetty, Shiran; Rajasekaran, Senthilkumar; Venkatakrishnan, Leela

    2013-01-01

    Jaundice in Grave's diseases is uncommon, but when it does occur, complication of thyrotoxicosis (heart failure/infection) or intrinsic liver disease should be considered. Grave's disease can cause asymptomatic elevation of liver enzymes, jaundice and rarely acute liver failure. It is associated with other autoimmune diseases like autoimmune hepatitis, or primary biliary cirrhosis. The cause of jaundice in Grave's disease is multifactorial. PMID:25755537

  12. The epidemiology of primary biliary cirrhosis: A survey of mortality in England and Wales

    PubMed Central

    Hamlyn, A. N.; Sherlock, S.

    1974-01-01

    Primary biliary cirrhosis is a rare disease in the general population. Estimates of its true incidence are difficult but since survival time is unaffected by treatment, mortality may reflect important regional and other variations. One hundred and sixty-five death certificates collected in England and Wales over the five-year period 1967-1971 were inspected and confirmed an overwhelming predilection for females. Deaths rose sharply at ages 50-54 in the latter with a peak of 4·1 million−1 year−1, with perhaps a secondary peak at ages 70-74. No relation of mortality with climate, altitude, soil type, annual temperature range, or occupation was found, although outside the UK a broad correlation exists with total cirrhosis deaths. There was a suggestive excess of deaths among married women. The greater frequency of deaths in the London area, a rise in mortality from country to urban areas, a fall-off in deaths from primary biliary cirrhosis in old age, and predominance for social class I suggest a simple relationship with standards of medical care or diagnosis. An `epidemic' of deaths in 1971 is attributed to greater availability of the mitochondrial antibody test in the regions. The importance of familial primary biliary cirrhosis and various models of pathogenesis are discussed. Both constitutional and environmental factors producing the disease must be widely distributed in the population of this country. PMID:4854819

  13. Infliximab as a treatment option for patients with rheumatoid arthritis and primary biliary cirrhosis.

    PubMed

    Dimopoulou, Despoina; Dimitroulas, Theodoros; Akriviadis, Evangelos; Garyfallos, Alexandros

    2015-11-01

    Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease which commonly requires treatment with biologic agents targeting various inflammatory pathways. Tumor necrosis factor alpha is a proinflammatory cytokine which plays a pivotal role not only in the pathogenesis of RA but also in other autoimmune diseases such as primary biliary cirrhosis. The co-existence of more than one autoimmune disorder in the same individual is very challenging in the daily practice as therapy strategies applicable to one disease setting may cause clinical and/or biochemical relapse of the other clinical entity. As a result, treatment options able to control different diseases are highly desirable among rheumatologists and other specialties. In that respect, we present a case of a 61-year-old female patient with RA and concomitant primary biliary cirrhosis with poor clinical response to conventional disease-modifying drugs for RA. The introduction of tumor necrosis factor alpha antagonist infliximab led to significant clinical improvement of RA and to stabilization of liver function. In this case review study, we discuss aspects of pathophysiology of primary biliary cirrhosis associated with tumor necrosis alpha and we review the available data of similar published cases.

  14. Novel therapeutics for primary biliary cholangitis: Toward a disease-stage-based approach.

    PubMed

    Mousa, Hani S; Carbone, Marco; Malinverno, Federica; Ronca, Vincenzo; Gershwin, M Eric; Invernizzi, Pietro

    2016-09-01

    Primary biliary cholangitis (PBC; previously "primary biliary cirrhosis") is a cholestatic, putatively autoimmune-mediated liver disease with a clear female preponderance affecting the intrahepatic small and medium-size bile ducts and resulting in bile duct destruction, ductopenia and portal fibrosis that progresses slowly to biliary cirrhosis. Despite suboptimal response in one third of patients treated with ursodeoxycholic acid (UDCA), this remains the only FDA-approved agent for this disease. In this review, we cover recent advances in research that have yielded numerous agents currently at different stages of the drug pipeline, some of which are expected to be approved in the near future. We also discuss accumulating evidence supporting the use of older agents (fibrates and glucocorticoids) as an adjunctive therapy to UDCA in non-responsive patients. We suggest that with the imminent expansion of the therapeutic armamentarium for PBC, a more comprehensive approach - ideally taking into account not only biochemical markers of disease stage - is needed to better select patients in whom these strategies might be most useful. Studies are also needed to compare the relative efficacy of different proposed second-line treatments not only against UDCA monotherapy.

  15. Novel therapeutics for primary biliary cholangitis: Toward a disease-stage-based approach.

    PubMed

    Mousa, Hani S; Carbone, Marco; Malinverno, Federica; Ronca, Vincenzo; Gershwin, M Eric; Invernizzi, Pietro

    2016-09-01

    Primary biliary cholangitis (PBC; previously "primary biliary cirrhosis") is a cholestatic, putatively autoimmune-mediated liver disease with a clear female preponderance affecting the intrahepatic small and medium-size bile ducts and resulting in bile duct destruction, ductopenia and portal fibrosis that progresses slowly to biliary cirrhosis. Despite suboptimal response in one third of patients treated with ursodeoxycholic acid (UDCA), this remains the only FDA-approved agent for this disease. In this review, we cover recent advances in research that have yielded numerous agents currently at different stages of the drug pipeline, some of which are expected to be approved in the near future. We also discuss accumulating evidence supporting the use of older agents (fibrates and glucocorticoids) as an adjunctive therapy to UDCA in non-responsive patients. We suggest that with the imminent expansion of the therapeutic armamentarium for PBC, a more comprehensive approach - ideally taking into account not only biochemical markers of disease stage - is needed to better select patients in whom these strategies might be most useful. Studies are also needed to compare the relative efficacy of different proposed second-line treatments not only against UDCA monotherapy. PMID:27393766

  16. Successful Pregnancy in Autoimmune Hepatitis/Primary Biliary Cirrhosis Overlap Syndrome: A Case Report

    PubMed Central

    Mitra, Subarna; Nayak, Prasanta Kumar; Padma, Alaganandam; Kurian, George

    2012-01-01

    Medical literature on pregnancy outcomes in hepatic overlap syndromes is limited. Autoimmune liver diseases are associated with sub-fertility and pregnancy is usually dissuaded in presence of portal hypertension and cirrhosis due to guarded prognosis for the pregnancy as well as the liver disease. We report a 24-year-old primigravida with autoimmune hepatitis/primary biliary cirrhosis overlap syndrome who had a successful pregnancy owing to intensive monitoring and meticulous treatment with drugs like immunosuppressants and ursodeoxycholic acid. She developed preterm prelabour rupture of membranes and delivered at 35 weeks without any major obstetric or hepatic complications.

  17. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

    PubMed Central

    Liu, Xiangdong; Invernizzi, Pietro; Lu, Yue; Kosoy, Roman; Lu, Yan; Bianchi, Ilaria; Podda, Mauro; Xu, Chun; Xie, Gang; Macciardi, Fabio; Selmi, Carlo; Lupoli, Sara; Shigeta, Russell; Ransom, Michael; Lleo, Ana; Lee, Annette T; Mason, Andrew L; Myers, Robert P; Peltekian, Kevork M; Ghent, Cameron N; Bernuzzi, Francesca; Zuin, Massimo; Rosina, Floriano; Borghesio, Elisabetta; Floreani, Annarosa; Lazzari, Roberta; Niro, Grazia; Andriulli, Angelo; Muratori, Luigi; Muratori, Paolo; Almasio, Piero L; Andreone, Pietro; Margotti, Marzia; Brunetto, Maurizia; Coco, Barbara; Alvaro, Domenico; Bragazzi, Maria C; Marra, Fabio; Pisano, Alessandro; Rigamonti, Cristina; Colombo, Massimo; Marzioni, Marco; Benedetti, Antonio; Fabris, Luca; Strazzabosco, Mario; Portincasa, Piero; Palmieri, Vincenzo O; Tiribelli, Claudio; Croce, Lory; Bruno, Savino; Rossi, Sonia; Vinci, Maria; Prisco, Cleofe; Mattalia, Alberto; Toniutto, Pierluigi; Picciotto, Antonio; Galli, Andrea; Ferrari, Carlo; Colombo, Silvia; Casella, Giovanni; Morini, Lorenzo; Caporaso, Nicola; Colli, Agostino; Spinzi, Giancarlo; Montanari, Renzo; Gregersen, Peter K; Heathcote, E Jenny; Hirschfield, Gideon M; Siminovitch, Katherine A; Amos, Christopher I; Gershwin, M Eric; Seldin, Michael F

    2011-01-01

    A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10–11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10–10, OR = 1.63) and 17q12-21 (P = 1.7 × 10–10, OR = 1.38). PMID:20639880

  18. Spontaneous regression of hepatic inflammatory pseudotumor with primary biliary cirrhosis: Case report and literature review

    PubMed Central

    Koide, Hiroshi; Sato, Ken; Fukusato, Toshio; Kashiwabara, Kenji; Sunaga, Noriaki; Tsuchiya, Takafumi; Morino, Saeko; Sohara, Naondo; Kakizaki, Satoru; Takagi, Hitoshi; Mori, Masatomo

    2006-01-01

    Hepatic inflammatory pseudotumor (IPT) is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been well established, a specific relationship with cholangitis is distinctly rare. We report a case of spontaneous regression of hepatic IPT with primary biliary cirrhosis (PBC). To date, only two cases of IPT with PBC have been reported. In our case, however, IPT developed during the course of improvement of cholangitis of PBC induced by effective treatment, differing from two previously reported cases. Our case indicates that the development of IPT does not also relate to the activity of cholangitis and/or hyper gamma-globulinemia, since our case was confirmed radiologically to be free of IPT when biliary enzymes and immunoglobulins were much higher than the corresponding values on admission. Comparison of our case with the two previously reported cases suggests that IPT occurring with PBC does not represent the same disease entity or be a bystander for PBC. PMID:16570364

  19. Primary biliary cirrhosis in patients with breast cancer: studying the link.

    PubMed

    Bergasa, N V

    1998-06-01

    Primary biliary cirrhosis (PBC) is a liver disease of unknown etiology characterized by chronic nonsuppurative destructive cholangitis (CNSDC) of intrahepatic septal and interlobular bile ducts. It is generally defined as an autoimmune disease. Characteristically, patients with PBC have a cholestatic serum hepatic profile and circulating antimitochondrial antibodies (AMA). PBC is progressive and ultimately leads to biliary cirrhosis and liver failure. It occurs at least three times more often in women than in men and it is the most common indication for liver transplantation in women around the world. There is no known cure for PBC. Despite the remarkable progress elucidating the genetics of breast cancer, and the effort placed on breast cancer education and screening methods, the mortality of breast cancer remains unacceptably high. In this essay, we describe the similarities between breast cancer and PBC and how their pathogenesis may be related. The hypothesis stated herein has evolved from reports from the early 1980s that linked an increased risk for breast cancer with PBC, and from the author's clinical experience with patients who suffer from both diseases. The association between these two diseases in the USA merits further investigation. If it is confirmed, risk factors involved in their pathogenesis will be identified. PMID:9710316

  20. Genetic Abnormalities in Biliary Brush Samples for Distinguishing Cholangiocarcinoma from Benign Strictures in Primary Sclerosing Cholangitis

    PubMed Central

    Timmer, Margriet R.; Lau, Chiu T.; Meijer, Sybren L.; Fockens, Paul; Rauws, Erik A. J.; Ponsioen, Cyriel Y.; Calpe, Silvia; Krishnadath, Kausilia K.

    2016-01-01

    Background. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and is strongly associated with cholangiocarcinoma (CCA). The lack of efficient diagnostic methods for CCA is a major problem. Testing for genetic abnormalities may increase the diagnostic value of cytology. Methods. We assessed genetic abnormalities for CDKN2A, TP53, ERBB2, 20q, MYC, and chromosomes 7 and 17 and measures of genetic clonal diversity in brush samples from 29 PSC patients with benign biliary strictures and 12 patients with sporadic CCA or PSC-associated CCA. Diagnostic performance of cytology alone and in combination with genetic markers was evaluated by sensitivity, specificity, and area under the curve analysis. Results. The presence of MYC gain and CDKN2A loss as well as a higher clonal diversity was significantly associated with malignancy. MYC gain increased the sensitivity of cytology from 50% to 83%. However, the specificity decreased from 97% to 76%. The diagnostic accuracy of the best performing measures of clonal diversity was similar to the combination of cytology and MYC. Adding CDKN2A loss to the panel had no additional benefit. Conclusion. Evaluation of MYC abnormalities and measures of clonal diversity in brush cytology specimens may be of clinical value in distinguishing CCA from benign biliary strictures in PSC. PMID:27127503

  1. Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis

    PubMed Central

    Bernuzzi, Francesca; Fenoglio, Daniela; Battaglia, Florinda; Fravega, Marco; Gershwin, M. Eric; Indiveri, Francesco; Ansari, Aftab A.; Podda, Mauro; Invernizzi, Pietro; Filaci, Gilberto

    2011-01-01

    The mechanisms that lead to loss of tolerance in autoimmune disease have remained both elusive and diverse, including both genetic predisposition and generic dysregulation of critical mononuclear cell subsets. In primary biliary cirrhosis (PBC), patients exhibit a multilineage response to the E2 component of pyruvate dehydrogenase involving antibody as well as autoreactive CD4 and CD8 responses. Recent data from murine models of PBC have suggested that a critical mechanism of biliary destruction is mediated by liver-infiltrating CD8 cells. Further, the number of autoreactive liver-infiltrating CD4 and CD8 cells is significantly higher in liver than blood in patients with PBC. Based on this data, we have studied the frequencies and phenotypic characterization of both CD4 and CD8 regulatory T cell components in both patients with PBC and age–sex matched controls. Our data is striking and indicate that CD8 Treg populations from PBC patients, but not controls, have significant phenotypic alterations, including increased expression of CD127 and reduced CD39. Furthermore, in vitro induction of CD8 Tregs by incubation with IL10 is significantly reduced in PBC patients. Importantly, the frequencies of circulating CD4+CD25+ and CD8+ and CD28− T cell subpopulations are not significantly different between patients and controls. In conclusion, these data identify the CD8 Treg subset as a regulatory T cell subpopulation altered in patients with PBC. PMID:20638239

  2. Guillain–Barré syndrome mimics primary biliary cirrhosis-related myopathy

    PubMed Central

    Munday, William R.; DiCapua, Daniel; Vortmeyer, Alexander; Gomez, Jose Luis

    2015-01-01

    Guillain–Barré syndrome (GBS) is an immune-mediated disorder characterized by acute polyneuropathy, ascending paralysis and post infectious polyneuritis. Two-thirds of patients present with a history of recent upper respiratory tract or gastrointestinal infection. The clinical history, neurologic examination and laboratory assessment allow for a straightforward diagnosis in the majority of cases. However, primary biliary cirrhosis (PBC) is known to cause clinically detectable muscular weakness. It is therefore critical to differentiate between PBC-associated muscular weakness and GBS-induced paralysis. Here, we report a patient with a longstanding history of PBC who developed progressive weakness and respiratory failure due to GBS, which clinically mimicked PBC myopathy. This is the first reported association between GBS and PBC. PMID:26634144

  3. A Systems Model for Ursodeoxycholic Acid Metabolism in Healthy and Patients With Primary Biliary Cirrhosis

    PubMed Central

    Dobbins, RL; O'Connor‐Semmes, RL; Young, MA

    2016-01-01

    A systems model was developed to describe the metabolism and disposition of ursodeoxycholic acid (UDCA) and its conjugates in healthy subjects based on pharmacokinetic (PK) data from published studies in order to study the distribution of oral UDCA and potential interactions influencing therapeutic effects upon interruption of its enterohepatic recirculation. The base model was empirically adapted to patients with primary biliary cirrhosis (PBC) based on current understanding of disease pathophysiology and clinical measurements. Simulations were performed for patients with PBC under two competing hypotheses: one for inhibition of ileal absorption of both UDCA and conjugates and the other only of conjugates. The simulations predicted distinctly different bile acid distribution patterns in plasma and bile. The UDCA model adapted to patients with PBC provides a platform to investigate a complex therapeutic drug interaction among UDCA, UDCA conjugates, and inhibition of ileal bile acid transport in this rare disease population. PMID:27537780

  4. [Cesarean Section Under Combined Spinal and Epidural Anesthesia for a Pregnant Woman with Primary Biliary Cirrhosis].

    PubMed

    Hyoda, Akira; Komasawa, Nobuyasu; Matsunami, Sayuri; Minami, Toshiaki

    2015-12-01

    We report the successful anesthetic management of a pregnant woman with primary biliary cirrhosis (PBC) and autoimmune hepatitis who underwent cesarean section. A 35 year-old pregnant woman with PBC was diagnosed with preterm rupture of membranes (PROM). Emergent cesarean section was scheduled. AST and ALT were elevated and she complained of itching due to PBC. Hydrocortisone 50 mg was intravenously administered. Spinal anesthesia was initiated with 2.4 ml of 0.5% bupivacaine hydrochloride and 10 µg fentanyl at L3-4; sensory loss (T2) was confirmed. Morphine was not included in spinal anesthesia to avoid worsening of the itching. Epidural anesthesia at T12-L1 was performed for postoperative pain control. Surgery proceeded uneventfully and postoperative pain control was satisfactory. Combined spinal and epidural anesthesia was beneficial for the perioperative management of a pregnant woman with PBC and autoimmune hepatitis. PMID:26790326

  5. Guillain-Barré syndrome mimics primary biliary cirrhosis-related myopathy.

    PubMed

    Munday, William R; DiCapua, Daniel; Vortmeyer, Alexander; Gomez, Jose Luis

    2015-04-01

    Guillain-Barré syndrome (GBS) is an immune-mediated disorder characterized by acute polyneuropathy, ascending paralysis and post infectious polyneuritis. Two-thirds of patients present with a history of recent upper respiratory tract or gastrointestinal infection. The clinical history, neurologic examination and laboratory assessment allow for a straightforward diagnosis in the majority of cases. However, primary biliary cirrhosis (PBC) is known to cause clinically detectable muscular weakness. It is therefore critical to differentiate between PBC-associated muscular weakness and GBS-induced paralysis. Here, we report a patient with a longstanding history of PBC who developed progressive weakness and respiratory failure due to GBS, which clinically mimicked PBC myopathy. This is the first reported association between GBS and PBC. PMID:26634144

  6. Genetic association of cytokines polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese

    PubMed Central

    Fan, Lie-Ying; Tu, Xiao-Qing; Zhu, Ye; Pfeiffer, Thomas; Feltens, Ralph; Stoecker, Winfried; Zhong, Ren-Qian

    2005-01-01

    AIM: To characterize gene polymorphism of several cytokine gene in-patients with AIH and PBC and to analyze the difference of the polymorphism distribution between Chinese patients and healthy controls. METHODS: The study population consisted of 62 patients with AIH, and 77 patients with PBC. The genetic profile of four cytokines was analyzed by restriction fragment length polymorphism after specific PCR amplification (PCR-RFLP) or sequence-specific primers PCR (SSP-PCR). The analyzed gene polymorphism included interleukin-1 (IL-1) (at position +3 953 and IL-1RN intron 2), IL-6 (at position -174), IL-10 promoter (at position -1082, -819, and -592). The control group consisted of 160 healthy blood donors. RESULTS: The majority of Chinese people including patients and healthy controls exhibited IL-1B 1,1 genotype, and there was no significant difference in AIH, PBC patients and controls. There were highly statistically significant differences in the distribution of the IL-1RN gene polymorphism between the patients with PBC compared with controls. The frequency of IL-1RN 1,1 was significantly higher (90.9% vs 79.4%, P = 0.03) and the frequency of IL-1RN 1,2 was significantly lower in PBC patients (6.5% vs 17.5%, P = 0.01). No statistical difference was observed between AIH patients and controls. All of the 160 healthy controls and 62 cases of AIH patients exhibited IL-6-174GG genotype, and there were four cases, which expressed IL-6-174GC genotype in 77 cases of PBC patients. The frequency of IL-6-174GC was markedly significantly higher in PBC patients compared with controls (5.2% vs 0%, P = 0.004). No statistically significant difference was found in the distribution of IL-10 promoter genotype in AIH and PBC patients compared with controls. CONCLUSION: The polymorphisms of IL-1RN and IL-6 -174G/C appear to be associated with PBC in Chinese patients. PMID:15884119

  7. Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators

    PubMed Central

    Zhang, Hai-Chun; Hu, Rong-Fei; Zhu, Ting; Tong, Ling; Zhang, Qiu-Qin

    2016-01-01

    AIM: To evaluate the assessment of primary biliary cirrhosis degree by acoustic radiation force impulse imaging (ARFI) and hepatic fibrosis indicators. METHODS: One hundred and twenty patients who developed liver cirrhosis secondary to primary biliary cirrhosis were selected as the observation group, with the degree of patient liver cirrhosis graded by Child-Pugh (CP) score. Sixty healthy individuals were selected as the control group. The four indicators of hepatic fibrosis were detected in all research objects, including hyaluronic acid (HA), laminin (LN), type III collagen (PC III), and type IV collagen (IV-C). The liver parenchyma hardness value (LS) was then measured by ARFI technique. LS and the four indicators of liver fibrosis (HA, LN, PC III, and IV-C) were observed in different grade CP scores. The diagnostic value of LS and the four indicators of liver fibrosis in determining liver cirrhosis degree with PBC, whether used alone or in combination, were analyzed by receiver operating characteristic (ROC) curve. RESULTS: LS and the four indicators of liver fibrosis within the three classes (A, B, and C) of CP scores in the observation group were higher than in the control group, with C class > B class > A class; the differences were statistically significant (P < 0.01). Although AUC values of LS within the three classes of CP scores were higher than in the four indicators of liver fibrosis, sensitivity and specificity were unstable. The ROC curves of LS combined with the four indicators of liver fibrosis revealed that: AUC and sensitivity in all indicators combined in the A class of CP score were higher than in LS alone, albeit with slightly decreased specificity; AUC and specificity in all indicators combined in the B class of CP score were higher than in LS alone, with unchanged sensitivity; AUC values (0.967), sensitivity (97.4%), and specificity (90%) of all indicators combined in the C class of CP score were higher than in LS alone (0.936, 92.1%, 83

  8. Scleroderma, primary biliary cirrhosis, and Sjögren's syndrome after cosmetic breast augmentation with silicone injection: a case report of possible human adjuvant disease.

    PubMed Central

    Okano, Y; Nishikai, M; Sato, A

    1984-01-01

    A 52-year-old woman developed scleroderma, primary biliary cirrhosis, and Sjögren's syndrome after cosmetic silicone injections. These conditions may possibly represent 'human adjuvant disease'. Images PMID:6742917

  9. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

    PubMed

    Liu, Jimmy Z; Almarri, Mohamed A; Gaffney, Daniel J; Mells, George F; Jostins, Luke; Cordell, Heather J; Ducker, Samantha J; Day, Darren B; Heneghan, Michael A; Neuberger, James M; Donaldson, Peter T; Bathgate, Andrew J; Burroughs, Andrew; Davies, Mervyn H; Jones, David E; Alexander, Graeme J; Barrett, Jeffrey C; Sandford, Richard N; Anderson, Carl A

    2012-10-01

    We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P<5×10(-8)), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r2>0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2>0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.

  10. Evolving Trends in Female to Male Incidence and Male Mortality of Primary Biliary Cholangitis

    PubMed Central

    Lleo, Ana; Jepsen, Peter; Morenghi, Emanuela; Carbone, Marco; Moroni, Luca; Battezzati, Pier Maria; Podda, Mauro; Mackay, Ian R.; Gershwin, M. Eric; Invernizzi, Pietro

    2016-01-01

    Primary biliary cholangitis (PBC) has been regarded as female-predominant without evidence of gender difference in survival. We aimed to compare the overall survival, incidence and prevalence of PBC in two well defined population-based studies over a recent decade, considering also sex ratios and mortality. We have taken advantage of population-wide records, during 2000–2009, in Lombardia, Northern Italy, and Denmark. We focused on the incident cases of PBC, including gender and outcome, among 9.7 million inhabitants of Lombardia and 5.5 million of Denmark. In Lombardia there were 2,970 PBC cases with a female:male ratio of 2.3:1. The age/sex-adjusted annual incidence of PBC was 16.7 per million. Point prevalence was 160 per million on January 1st 2009. In Denmark there were 722 cases of incident PBC, female:male ratio was 4.2:1, and the annual incidence was 11.4 per million, a point prevalence of 115 per million in 2009. Cox regression multivariate analysis identified male sex as an independent predictor of all-cause mortality in both Italian (HR 2.36) and Danish population (HR 3.04). Our data indicate for PBC a sex ratio significantly lower than previously cited, a reversal of the usual latitudinal difference in prevalence and a surprisingly higher overall mortality for male patients. PMID:27192935

  11. E. coli Induced Experimental Model of Primary Biliary Cirrhosis: At Last.

    PubMed

    Koutsoumpas, Andreas L; Smyk, Daniel S; Bogdanos, Dimitrios P

    2014-01-01

    Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile ducts. Additional support for the link made between PBC and UTI was based on early observations of recurrent episodes of bacteriuria in female patients with PBC. A series of large epidemiological studies demonstrated a strong correlation between recurrent UTI and PBC, initiating a series of studies investigating the role of Escherichia coli (E. coli, the most prevalent organism isolated in women with UTI) as a trigger of PBC. Immunological evidence of B- and T-cell cross-reactive responses implicating PBC-specific autoantigens and E. coli mimics have been clearly demonstrated, adding support to the notion that E. coli is a potential infectious inducer of PBC in susceptible individuals. One of the major limitations in proving the E. coli/PBC association was the lack of reliable E. coli-infected animal models of PBC. This review provides an overview of the evidence linking this infectious agent with PBC and discusses the pros and cons of a recently developed E. coli-infected animal model of PBC.

  12. A decline of LAMP- 2 predicts ursodeoxycholic acid response in primary biliary cirrhosis

    PubMed Central

    Wang, Lu; Guo, Guan-ya; Wang, Jing-bo; Zhou, Xin-min; Yang, Qiong; Han, Zhe-yi; Li, Qiang; Zhang, Jing-wen; Cai, Yun; Ren, Xiao-li; Zhou, Xia; Chen, Rui-rui; Shi, Yong-quan; Han, Ying; Fan, Dai-ming

    2015-01-01

    Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. We have previously reported that augmented expression of lysosome-associated membrane protein 2 (LAMP-2) was correlated with the severity of PBC. This study aimed to determine whether serum LAMP-2 could serve as a predictor of biochemical response to UDCA. The efficiency of serum LAMP-2 to predict biochemical response was assessed after 1 year of UDCA treatment in PBC patients by a retrospective analysis. We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014). Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant. However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders. Further studies showed that the 35% decline of LAMP-2 after treatment for 3 months could be stated as an indicator of UDCA response with the sensitivity of 62.9% and specificity of 75.0% by Paris criteria. Meanwhile the specificity and sensitivity were identified as 63.5% and 64.1% by Barcelona criteria. Together, a decline in LAMP-2 might help to predict the response to UDCA. PMID:25894308

  13. Oral Tolerance and Pyruvate Dehydrogenase in Patients with Primary Biliary Cirrhosis

    PubMed Central

    Suzuki, Ayako; van de Water, Judy; Gershwin, M. Eric; Jorgensen, Roberta; Angulo, Paul; Lindor, Keith

    2002-01-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the immunological destruction of intralobular bile ducts and serum anti-mitochondrial antibodies (AMA). Based upon previous work of oral tolerance and autoimmunity, we hypothesized that feeding the mitochondrial autoantigens of PBC would alter the clinical course and the level of antimitochondrial antibodies. The bovine pyruvate dehydrogenase complex (PDC) was purified and 5 mg fed in gelatin capsules to 6 patients with early stage PBC for 6 months. Antimitochondrial antibodies and liver biochemistries were measured at every 3 months for 12 months. The clinical trial was completed for all patients except for 1 who showed deterioration of pre-existing skin rash during treatment, which disappeared within 2 weeks after treatment was discontinued. However, after 1 year, neither the titers of AMAs nor liver biochemistries were significantly changed by this treatment. This is the first trial to test the efficacy of oral tolerance induction in PBC. However, the data, which limited in scope, did not demonstrate efficacy and further highlights the difficulties in showing continuing evidence of tolerance induction in autoimmunity. PMID:12739782

  14. Primary biliary cirrhosis in female subjects with sicca-associated antibodies.

    PubMed

    Takada, Kunio; Suzuki, Kimihiro; Matsumoto, Mitsuyo; Okada, Makoto; Nakanishi, Takashi; Horikoshi, Hideyuki; Higuchi, Tomoaki; Ohsuzu, Fumitaka

    2007-01-01

    The aim of this study is to clarify the time course of primary biliary cirrhosis (PBC) in subjects possessing anticentromere antibodies (ACA), anti-Ro, and/or anti-La antibodies, and who used alkaline phosphatase (ALP) as a serological marker for PBC. Female subjects (n = 165), who had at least one of ACA, anti-Ro, and/or anti-La, were enrolled in this study. Groups A (ACA alone, n = 44), B (anti-Ro alone, n = 54), E (anti-Ro and anti-La, n = 52), and DFG (ACA with anti-Ro and/or anti-La, n = 14) were analyzed. Healthy females (n = 65) were used as a control. The frequencies of the PBC in groups A (13.6%) and DFG (14.3%) were higher than those in groups B (1.9%) and E (0.0%). The ALP levels increased with age in groups A and DFG and slightly increased with age in groups B and C, and the control group. After correcting for age by analysis of covariance, a comparison of ALP levels among the groups not having anti-M(2) was as follows: group A falling dots group DFG > group B falling dots group E falling dots the control group. The subjects with ACA might thus have PBC more frequently than either those with anti-Ro and/or anti-La, or the control subjects.

  15. Antimitochondrial antibody-negative chronic nonsuppurative destructive cholangitis. Atypical primary biliary cirrhosis or autoimmune cholangitis?

    PubMed

    Sánchez-Pobre, P; Castellano, G; Colina, F; Dominguez, P; Rodriguez, S; Canga, F; Herruzo, J A

    1996-10-01

    We investigated whether autoimmune cholangitis (AC) has specific features that constitute an entity other than primary biliary cirrhosis (PBC). We compared clinical, laboratory, and liver biopsy features; response to treatment; and the follow-up of two groups of patients. The first group comprised seven patients with AC criteria-PBC with negative antimitochondrial antibodies (AMAs) and positive antinuclear antibodies (ANAs)-termed the PBC AMA-negative group; the second was made up of another seven PBC patients with positive AMA, labeled the PBC AMA-positive group. We found that the PBC AMA-negative group had, besides negative AMAs and positive ANAs, a significantly higher incidence of asthenia, a higher and earlier incidence of liver failure, and higher ANA titers and serum immunoglobulin G levels than the PBC AMA-positive group. There were no significant differences in the other laboratory tests, although the PBC AMA-negative group showed higher serum bilirubin and aminotransferase and lower serum alkaline phosphatase and immunoglobulin M levels. Liver histological data were similar in both groups. Patients in the PBC AMA-negative group, with more markedly abnormal liver tests, responded to immunosuppressive therapy. We concluded that patients with criteria for PBC but with negative AMAs and positive ANAs have a few specific features that fall between PBC and autoimmune chronic hepatitis. This finding suggests that these patients have a different disease, for which autoimmune cholangitis seems to be an appropriate name. PMID:8899500

  16. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies

    PubMed Central

    Kar, SP; Seldin, MF; Chen, W; Lu, E; Hirschfield, GM; Invernizzi, P; Heathcote, J; Cusi, D; Gershwin, ME; Siminovitch, KA; Amos, CI

    2013-01-01

    Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P < 0.05). After correcting for multiple comparisons, only the eight most significant pathways in the Italian dataset had FDR < 0.25 with tumor necrosis factor/stress-related signaling emerging as the top pathway (P = 7.38 × 10−4, FDR = 0.18). Two pathways, phosphatidylinositol signaling and hedgehog signaling, were replicated in both datasets (P < 0.05), and subjected to two additional complementary pathway tests. Both pathway signals remained significant in the Italian dataset on modified gene set enrichment analysis (P < 0.05). In both GWAS, variants nominally associated with PBC were significantly overrepresented in the phosphatidylinositol pathway (Fisher exact P < 0.05). These results point to established and novel pathway-level associations with inherited predisposition to PBC that on further independent replication and functional validation, may provide fresh insights into PBC etiology. PMID:23392275

  17. The Significance of Autoantibody Changes Over Time in Primary Biliary Cirrhosis

    PubMed Central

    Tana, Michele M.; Shums, Zakera; Milo, Jay; Norman, Gary L.; Leung, Patrick S.; Gershwin, M. Eric; Noureddin, Mazen; Kleiner, David E.; Zhao, Xiongce; Heller, Theo; Hoofnagle, Jay H.

    2016-01-01

    Objectives In primary biliary cirrhosis (PBC), the antimitochondrial antibody is a cornerstone of diagnosis, but there have been conflicting reports about the correlation of autoantibodies with disease stage and prognosis. We studied whether autoantibody levels changed over time and sought correlations with clinical outcomes in a cohort of patients with PBC. Methods We tested serial serum samples from patients with PBC at a research institution for several autoantibodies. Long-term clinical follow-up data were used to calculate the slopes (change over time) for autoantibodies, platelet count, Ishak fibrosis score, biopsy copper, and number of portal areas with bile ducts. An adverse clinical outcome was defined as hepatic decompensation, development of hepatocellular carcinoma, liver transplantation, or liver-related death. We performed linear or logistic regression or Fisher exact test as appropriate, adjusting for multiple comparisons. Results Twenty-seven patients with PBC with 145 serum samples were studied. Of the cohort, 85% was white, 81% was female, and median follow-up time was 20 years. Of the autoantibodies tested, only sp100 changed significantly over time. The sp100 slope was inversely associated with the Ishak fibrosis slope (parameter estimate, −0.05; P = .0003). Conclusions While changes in most autoantibodies over time do not seem to correlate with clinical outcomes in PBC, a change in the sp100 autoantibody level may have prognostic utility with respect to the development of fibrosis on liver biopsy. PMID:26386081

  18. Environmental pathways to autoimmune diseases: the cases of primary biliary cirrhosis and multiple sclerosis

    PubMed Central

    Selmi, Carlo; Maria Papini, Anna; Pugliese, Piera; Claudia Alcaro, Maria; Gershwin, M. Eric

    2011-01-01

    The pathways leading to autoimmunity remain enigmatic despite numerous lines of experimental inquiry and epidemiological evidence. The mechanisms leading to the initiation and perpetuation of specific diseases such as primary biliary cirrhosis (PBC) or multiple sclerosis (MS) remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. The growing number of genome-wide association studies and the largely incomplete concordance for autoimmune diseases in monozygotic twins concur to support the role of the environment (including infectious agents and chemicals) in the breakdown of tolerance leading to autoimmunity through different mechanisms. In the present article we illustrate the current hypotheses related to an environmental impact on the onset of PBC and MS as two representative conditions investigated with complementary approaches. Indeed, while a role of post-translational antigen modifications has been proposed for MS, this field remain unexplored in PBC where, conversely, most evidence is gathered from geoepidemiology and experimental data on xenobiotics or infectious agents. PMID:22295019

  19. Quantitation of the Rank-Rankl Axis in Primary Biliary Cholangitis.

    PubMed

    Lleo, Ana; Bian, Zhaolian; Zhang, Haiyan; Miao, Qi; Yang, Fang; Peng, Yanshen; Chen, Xiaoyu; Tang, Ruqi; Wang, Qixia; Qiu, Dekai; Fang, Jingyuan; Sobacchi, Cristina; Villa, Anna; Di Tommaso, Luca; Roncalli, Massimo; Gershwin, M Eric; Ma, Xiong; Invernizzi, Pietro

    2016-01-01

    There is substantial data that suggests an abnormality of innate immunity in patients with primary biliary cholangitis (PBC) which includes the transcription factor nuclear factor-kB (NF-kB) and well as downstream inflammatory signaling pathways. In addition, ImmunoChip analysis has identified a novel PBC-associated locus near the receptor activator of NF-kB ligand (RANKL) gene. Based on these observations, we investigated the role of the RANKL axis in the liver of patients with PBC compared to controls. We used immunohistochemistry to quantitate liver expression of RANKL, its receptor (RANK), and importantly the decoy receptor osteoprotegerin (OPG), including a total of 122 liver samples (PBC = 37, primary sclerosing cholangitis = 20, autoimmune hepatitis = 26, chronic hepatitis B = 32 and unaffected controls = 7). In addition, we studied RANKL-RANK-OPG co-localization in CD4 and CD8 T cells, B cells, dendritic cells, macrophages, NK, NKT cells, hepatocytes, and cholangiocytes. We report herein that RANK is constitutively expressed by cholangiocytes in both unaffected and diseased liver. However, cholangiocytes from PBC express significantly higher levers of RANK than either the unaffected controls or liver diseased controls. CD4, CD8 and CD19 cells with in the portal areas around bile ducts in PBC express significantly higher levels of RANKL compared to controls. Importantly, the overall hepatic RANKL level and the ratio of hepatic RANKL/OPG correlated with disease severity in PBC. In conclusion, our data indicate a role of RANK-RANKL axis in the innate immune activation in PBC and we hypothesize that the damaged cholangiocytes, which express high levels of RANK, lead to the recruitment of RANKL positive cells and ultimately the classic portal tract infiltrates. PMID:27631617

  20. Quantitation of the Rank-Rankl Axis in Primary Biliary Cholangitis

    PubMed Central

    Zhang, Haiyan; Miao, Qi; Yang, Fang; Peng, Yanshen; Chen, Xiaoyu; Tang, Ruqi; Wang, Qixia; Qiu, Dekai; Fang, Jingyuan; Sobacchi, Cristina; Villa, Anna; Di Tommaso, Luca; Roncalli, Massimo; Gershwin, M. Eric; Ma, Xiong; Invernizzi, Pietro

    2016-01-01

    There is substantial data that suggests an abnormality of innate immunity in patients with primary biliary cholangitis (PBC) which includes the transcription factor nuclear factor-kB (NF-kB) and well as downstream inflammatory signaling pathways. In addition, ImmunoChip analysis has identified a novel PBC-associated locus near the receptor activator of NF-kB ligand (RANKL) gene. Based on these observations, we investigated the role of the RANKL axis in the liver of patients with PBC compared to controls. We used immunohistochemistry to quantitate liver expression of RANKL, its receptor (RANK), and importantly the decoy receptor osteoprotegerin (OPG), including a total of 122 liver samples (PBC = 37, primary sclerosing cholangitis = 20, autoimmune hepatitis = 26, chronic hepatitis B = 32 and unaffected controls = 7). In addition, we studied RANKL-RANK-OPG co-localization in CD4 and CD8 T cells, B cells, dendritic cells, macrophages, NK, NKT cells, hepatocytes, and cholangiocytes. We report herein that RANK is constitutively expressed by cholangiocytes in both unaffected and diseased liver. However, cholangiocytes from PBC express significantly higher levers of RANK than either the unaffected controls or liver diseased controls. CD4, CD8 and CD19 cells with in the portal areas around bile ducts in PBC express significantly higher levels of RANKL compared to controls. Importantly, the overall hepatic RANKL level and the ratio of hepatic RANKL/OPG correlated with disease severity in PBC. In conclusion, our data indicate a role of RANK-RANKL axis in the innate immune activation in PBC and we hypothesize that the damaged cholangiocytes, which express high levels of RANK, lead to the recruitment of RANKL positive cells and ultimately the classic portal tract infiltrates. PMID:27631617

  1. Liver damage in primary biliary cirrhosis and accompanied by primary Sjögren's syndrome: a retrospective pilot study

    PubMed Central

    Zhu, Yun; Ma, Xiaolei; Tang, Xiaojun

    2016-01-01

    Introduction Primary biliary cirrhosis (PBC) and primary Sjögren's syndrome (pSS) have been referred to as “generalized autoimmune epithelitis”. Indeed, the pathogenic mechanisms, clinical features, and optimal therapeutic approaches for them are not yet fully defined. Material and methods A retrospective analysis was carried out on clinical data obtained from 302 inpatients newly diagnosed with PBC, pSS, or the coexistence of PBC and SS between May 2011 and December 2014. Forty-two patients with abnormal hepatic function were divided into the PBC group (n = 17), the coexistent group (PBC accompanied by SS, n = 13), and the pSS group (n = 12). Their clinical symptoms, laboratory data, and pathological features were collected and analyzed when they were first diagnosed. The clinical and laboratory data were collected at 0, 1, and 3 months after treatment. Results Of the 42 patients with abnormal liver function, 4 were male and 38 were female patients. Compared with the patients in the PBC group, the patients in the other 2 groups were more likely to have an elevated erythrocyte sedimentation rate (ESR) and serum immunoglobulin G (IgG) levels. Abnormal serum immunoglobulin M levels (IgM) were more frequent in the PBC group. Corticosteroids were effective in normalizing elevated liver enzyme levels in patients with SS and in those with coexistent conditions. Conclusions This pilot study suggests that patients with PBC, pSS, and PBC/SS coexistence and having liver function abnormality share similar symptoms, but have different pathogenesis and prognosis. PMID:27536204

  2. Dysregulation of peritoneal cavity B1a cells and murine primary biliary cholangitis

    PubMed Central

    Yang, Yan-Qing; Yang, Wei; Yao, Yuan; Ma, Hong-Di; Wang, Yin-Hu; Li, Liang; Wu, Qingfa; Gershwin, M. Eric; Lian, Zhe-Xiong

    2016-01-01

    Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease with progressive cholestasis and liver fibrosis. Similar to human patients with PBC, p40−/−IL-2Rα−/− mice spontaneously develop severe autoimmune cholangitis. Although there has been considerable work on immune regulation and autoimmunity, there is a relative paucity of work directed at the functional implications of the key peritoneal cavity (PC) B cell subset, coined B1a cells in PBC. We used flow cytometry and high-resolution microarrays to study the qualitative and quantitative characteristics of B cells, particularly B1a cells, in the PC of p40−/−IL-2Rα−/− mice compared to controls. Importantly, B1a cell proliferation was markedly lower as the expression of Ki67 decreased. Meanwhile, the apoptosis level was much higher. These lead to a reduction of B1a cells in the PC of p40−/−IL-2Rα−/− mice compared to controls. In contrast, there was a dramatic increase of CD4+ and CD8+ T cells accompanied by elevated production of IFN-γ. In addition, we found a negative correlation between the frequency of B1a cells and the presence of autoreactive CD8+ T cells in both liver and PC of p40−/−IL-2Rα−/− mice. From a functional perspective, B cells from p40−/−IL-2Rα−/− mice downregulated IL-10 production and CTLA-4 expression, leading to loss of B cell regulatory function. We suggest that the dysfunction of B1a cells in the PC in this murine model of autoimmune cholangitis results in defective regulatory function. This highlights a new potential therapeutic target in PBC. PMID:27105495

  3. Serum cell death biomarkers for prediction of liver fibrosis and poor prognosis in primary biliary cirrhosis.

    PubMed

    Sekiguchi, Tomohiro; Umemura, Takeji; Fujimori, Naoyuki; Shibata, Soichiro; Ichikawa, Yuki; Kimura, Takefumi; Joshita, Satoru; Komatsu, Michiharu; Matsumoto, Akihiro; Tanaka, Eiji; Ota, Masao

    2015-01-01

    The development of simple, noninvasive markers of liver fibrosis is urgently needed for primary biliary cirrhosis (PBC). This study examined the ability of several serum biomarkers of cell death to estimate fibrosis and prognosis in PBC. A cohort of 130 patients with biopsy-proven PBC and 90 healthy subjects were enrolled. We assessed the utility of the M30 ELISA, which detects caspase-cleaved cytokeratin-18 (CK-18) fragments and is representative of apoptotic cell death, as well as the M65 and newly developed M65 Epideath (M65ED) ELISAs, which detect total CK-18 as indicators of overall cell death, in predicting clinically relevant fibrosis stage. All 3 cell death biomarkers were significantly higher in patients with PBC than in healthy controls and were significantly correlated with fibrosis stage. The areas under the receiver operating characteristic curve for the M65 and M65ED assays for differentiation among significant fibrosis, severe fibrosis, and cirrhosis were 0.66 and 0.76, 0.66 and 0.73, and 0.74 and 0.82, respectively. In multivariate analysis, high M65ED (hazard ratio 6.13; 95% confidence interval 1.18-31.69; P = 0.031) and severe fibrosis (hazard ratio 7.45; 95% confidence interval 1.82-30.51; P = 0.005) were independently associated with liver-related death, transplantation, or decompensation. High serum M65ED was also significantly associated with poor outcome in PBC (log-rank test; P = 0.001). Noninvasive cell death biomarkers appear to be clinically useful in predicting fibrosis in PBC. Moreover, the M65ED assay may represent a new surrogate marker of adverse disease outcome.

  4. Clinical characteristics of drug-induced liver injury and primary biliary cirrhosis

    PubMed Central

    Yang, Jun; Yu, Ya-Li; Jin, Yu; Zhang, Ying; Zheng, Chang-Qing

    2016-01-01

    AIM To summarize and compare the clinical characteristics of drug-induced liver injury (DILI) and primary biliary cirrhosis (PBC). METHODS A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data (sex and age), biochemical indexes (total protein, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma glutamyltransferase), immunological indexes [immunoglobulin (Ig) A, IgG, IgM, antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients, untyped DILI patients and patients with different types of DILI (hepatocellular type, cholestatic type and mixed type). RESULTS There were significant differences in age and gender distribution between DILI patients and PBC patients. Biochemical indexes (except ALB), immunological indexes, positive rates of autoantibodies (except SMA), and number of cases of patients with different ANA titers (except the group at a titer of 1:10000) significantly differed between DILI patients and PBC patients. Biochemical indexes, immunological indexes, and positive rate of autoantibodies were not quite similar in different types of DILI. PBC was histologically characterized mainly by edematous degeneration of hepatocytes (n = 30), inflammatory cell infiltration around bile ducts (n = 29), and atypical hyperplasia of small bile ducts (n = 28). DILI manifested mainly as fatty degeneration of hepatocytes (n = 15) and spotty necrosis or loss of hepatocytes (n = 14). CONCLUSION Although DILI and PBC share some similar laboratory tests (biochemical and immunological indexes) and pathological findings, they also show some distinct characteristics, which are helpful to the differential diagnosis of the two diseases. PMID:27672278

  5. Polyurethane-Covered Nitinol Strecker Stents as Primary Palliative Treatment of Malignant Biliary Obstruction

    SciTech Connect

    Kanasaki, Shuzo; Furukawa, Akira; Kane, Teruyuki; Murata, Kiyoshi

    2000-03-15

    Purpose: To evaluate the clinical efficacy of the polyurethane-covered Nitinol Strecker stent in the treatment of patients with malignant biliary obstruction.Methods: Twenty-three covered stents produced by us were placed in 18 patients with malignant biliary obstruction. Jaundice was caused by cholangiocarcinoma (n = 5), pancreatic cancer (n = 6), gallbladder cancer (n = 4), metastatic lymph nodes (n = 2), and tumor of the papilla (n 1).Results: The mean patency period of the stents was 37.5 weeks (5-106 weeks). Recurrent obstructive jaundice occurred in two patients (11%). Adequate biliary drainage over 50 weeks or until death was achieved in 17 of 18 patients (94.4%). Late cholangitis was observed in two patients whose stents bridged the ampulla of Vater. Other late severe complications were not encountered.Conclusion: Although more study is necessary, our results suggest the clinical efficacy of our covered Nitinol Strecker stent in the management of obstructive jaundice caused by malignant diseases.

  6. Deletion of Galectin-3 Enhances Xenobiotic Induced Murine Primary Biliary Cholangitis by Facilitating Apoptosis of BECs and Release of Autoantigens.

    PubMed

    Arsenijevic, Aleksandar; Milovanovic, Marija; Milovanovic, Jelena; Stojanovic, Bojana; Zdravkovic, Natasa; Leung, Patrick S C; Liu, Fu-Tong; Gershwin, M Eric; Lukic, Miodrag L

    2016-01-01

    Galectin-3 (Gal-3) is a carbohydrate binding lectin, with multiple roles in inflammatory diseases and autoimmunity including its antiapoptotic effect on epithelial cells. In particular, increased expression of Gal-3 in epithelial cells is protective from apoptosis. Based on the thesis that apoptosis of biliary epithelial cells (BECs) is critical to the pathogenesis of Primary Biliary Cholangitis (PBC), we have analyzed the role of Gal-3 in the murine model of autoimmune cholangitis. We took advantage of Gal-3 knockout mice and immunized them with a mimotope of the major mitochondrial autoantigen of PBC, 2-octynoic acid (2-OA) coupled to BSA (2OA-BSA) and evaluated the natural history of subsequent disease, compared to control wild-type mice, by measuring levels of antibodies to PDC-E2, immunohistology of liver, and expression of Gal-3. We report herein that deletion of Gal-3 significantly exacerbates autoimmune cholangitis in these mice. This is manifested by increased periportal infiltrations, bile duct damage, granulomas and fibrosis. Interestingly, the BECs of Gal-3 knockout mice had a higher response to apoptotic stimuli and there were more pro-inflammatory lymphocytes and dendritic cells (DCs) in the livers of Gal-3 knockout mice. In conclusion, Gal-3 plays a protective role in the pathways that lead to the inflammatory destruction of biliary epithelial cells. PMID:26996208

  7. Primary cultures of rat hepatocytes as a model system of canalicular development, biliary secretion, and intrahepatic cholestasis. III. Properties of the biliary transport of immunoglobulin A revealed by immunofluorescence.

    PubMed

    Gebhardt, R

    1983-06-01

    The present study was designed to investigate whether or not the vesicle-mediated, biliary transport of polymeric immunoglobulin A operates in primary cultures of rat hepatocytes. Using immunofluorescence techniques, immunoglobulin A of human or rat origin added to a time-dependent process around and within presumptive bile canaliculi. As a transitory event preceding this accumulation, an intensive particulate fluorescence was detected within the cytoplasm of the hepatocytes. Secretory component could be localized by a faint fluorescence in the cytoplasm and at the margin of bile canaliculi, where the fluorescence was accentuated concomitantly to the accumulation of immunoglobulin A. Translocation of immunoglobulin A could be blocked by an antiserum against secretory component, whereas colostral immunoglobulin A already containing secretory component was not transported. These findings suggest that the pathway for the biliary secretion of immunoglobulin A is active in cultured hepatocytes and provide evidence for the reconstruction of a functionally intact biliary polarity by these cells.

  8. Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter.

    PubMed

    Omori, Kaoru; Yoshida, Kanako; Yokota, Masaki; Daa, Tsutomu; Kan, Masahiro

    2016-10-01

    We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. PMID:27503128

  9. Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter.

    PubMed

    Omori, Kaoru; Yoshida, Kanako; Yokota, Masaki; Daa, Tsutomu; Kan, Masahiro

    2016-10-01

    We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family.

  10. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

    PubMed Central

    Cordell, Heather J.; Han, Younghun; Mells, George F.; Li, Yafang; Hirschfield, Gideon M.; Greene, Casey S.; Xie, Gang; Juran, Brian D.; Zhu, Dakai; Qian, David C.; Floyd, James A. B.; Morley, Katherine I.; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Schlicht, Erik M; Lammert, Craig; Atkinson, Elizabeth J; Chan, Landon L; de Andrade, Mariza; Balschun, Tobias; Mason, Andrew L; Myers, Robert P; Zhang, Jinyi; Milkiewicz, Piotr; Qu, Jia; Odin, Joseph A; Luketic, Velimir A; Bacon, Bruce R; Bodenheimer Jr, Henry C; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Gregersen, Peter K; Almasio, Piero L; Alvaro, Domenico; Andreone, Pietro; Andriulli, Angelo; Barlassina, Cristina; Battezzati, Pier Maria; Benedetti, Antonio; Bernuzzi, Francesca; Bianchi, Ilaria; Bragazzi, Maria Consiglia; Brunetto, Maurizia; Bruno, Savino; Casella, Giovanni; Coco, Barbara; Colli, Agostino; Colombo, Massimo; Colombo, Silvia; Cursaro, Carmela; Crocè, Lory Saveria; Crosignani, Andrea; Donato, Maria Francesca; Elia, Gianfranco; Fabris, Luca; Ferrari, Carlo; Floreani, Annarosa; Foglieni, Barbara; Fontana, Rosanna; Galli, Andrea; Lazzari, Roberta; Macaluso, Fabio; Malinverno, Federica; Marra, Fabio; Marzioni, Marco; Mattalia, Alberto; Montanari, Renzo; Morini, Lorenzo; Morisco, Filomena; Hani S, Mousa; Muratori, Luigi; Muratori, Paolo; Niro, Grazia A; Palmieri, Vincenzo O; Picciotto, Antonio; Podda, Mauro; Portincasa, Piero; Ronca, Vincenzo; Rosina, Floriano; Rossi, Sonia; Sogno, Ilaria; Spinzi, Giancarlo; Spreafico, Marta; Strazzabosco, Mario; Tarallo, Sonia; Tarocchi, Mirko; Tiribelli, Claudio; Toniutto, Pierluigi; Vinci, Maria; Zuin, Massimo; Ch'ng, Chin Lye; Rahman, Mesbah; Yapp, Tom; Sturgess, Richard; Healey, Christopher; Czajkowski, Marek; Gunasekera, Anton; Gyawali, Pranab; Premchand, Purushothaman; Kapur, Kapil; Marley, Richard; Foster, Graham; Watson, Alan; Dias, Aruna; Subhani, Javaid; Harvey, Rory; McCorry, Roger; Ramanaden, David; Gasem, Jaber; Evans, Richard; Mathialahan, Thiriloganathan; Shorrock, Christopher; Lipscomb, George; Southern, Paul; Tibble, Jeremy; Gorard, David; Palegwala, Altaf; Jones, Susan; Carbone, Marco; Dawwas, Mohamed; Alexander, Graeme; Dolwani, Sunil; Prince, Martin; Foxton, Matthew; Elphick, David; Mitchison, Harriet; Gooding, Ian; Karmo, Mazn; Saksena, Sushma; Mendall, Mike; Patel, Minesh; Ede, Roland; Austin, Andrew; Sayer, Joanna; Hankey, Lorraine; Hovell, Christopher; Fisher, Neil; Carter, Martyn; Koss, Konrad; Piotrowicz, Andrzej; Grimley, Charles; Neal, David; Lim, Guan; Levi, Sass; Ala, Aftab; Broad, Andrea; Saeed, Athar; Wood, Gordon; Brown, Jonathan; Wilkinson, Mark; Gordon, Harriet; Ramage, John; Ridpath, Jo; Ngatchu, Theodore; Grover, Bob; Shaukat, Syed; Shidrawi, Ray; Abouda, George; Ali, Faiz; Rees, Ian; Salam, Imroz; Narain, Mark; Brown, Ashley; Taylor-Robinson, Simon; Williams, Simon; Grellier, Leonie; Banim, Paul; Das, Debashis; Chilton, Andrew; Heneghan, Michael; Curtis, Howard; Gess, Markus; Drake, Ian; Aldersley, Mark; Davies, Mervyn; Jones, Rebecca; McNair, Alastair; Srirajaskanthan, Raj; Pitcher, Maxton; Sen, Sambit; Bird, George; Barnardo, Adrian; Kitchen, Paul; Yoong, Kevin; Chirag, Oza; Sivaramakrishnan, Nurani; MacFaul, George; Jones, David; Shah, Amir; Evans, Chris; Saha, Subrata; Pollock, Katharine; Bramley, Peter; Mukhopadhya, Ashis; Fraser, Andrew; Mills, Peter; Shallcross, Christopher; Campbell, Stewart; Bathgate, Andrew; Shepherd, Alan; Dillon, John; Rushbrook, Simon; Przemioslo, Robert; Macdonald, Christopher; Metcalf, Jane; Shmueli, Udi; Davis, Andrew; Naqvi, Asifabbas; Lee, Tom; Ryder, Stephen D; Collier, Jane; Klass, Howard; Ninkovic, Mary; Cramp, Matthew; Sharer, Nicholas; Aspinall, Richard; Goggin, Patrick; Ghosh, Deb; Douds, Andrew; Hoeroldt, Barbara; Booth, Jonathan; Williams, Earl; Hussaini, Hyder; Stableforth, William; Ayres, Reuben; Thorburn, Douglas; Marshall, Eileen; Burroughs, Andrew; Mann, Steven; Lombard, Martin; Richardson, Paul; Patanwala, Imran; Maltby, Julia; Brookes, Matthew; Mathew, Ray; Vyas, Samir; Singhal, Saket; Gleeson, Dermot; Misra, Sharat; Butterworth, Jeff; George, Keith; Harding, Tim; Douglass, Andrew; Panter, Simon; Shearman, Jeremy; Bray, Gary; Butcher, Graham; Forton, Daniel; Mclindon, John; Cowan, Matthew; Whatley, Gregory; Mandal, Aditya; Gupta, Hemant; Sanghi, Pradeep; Jain, Sanjiv; Pereira, Steve; Prasad, Geeta; Watts, Gill; Wright, Mark; Neuberger, James; Gordon, Fiona; Unitt, Esther; Grant, Allister; Delahooke, Toby; Higham, Andrew; Brind, Alison; Cox, Mark; Ramakrishnan, Subramaniam; King, Alistair; Collins, Carole; Whalley, Simon; Li, Andy; Fraser, Jocelyn; Bell, Andrew; Wong, Voi Shim; Singhal, Amit; Gee, Ian; Ang, Yeng; Ransford, Rupert; Gotto, James; Millson, Charles; Bowles, Jane; Thomas, Caradog; Harrison, Melanie; Galaska, Roman; Kendall, Jennie; Whiteman, Jessica; Lawlor, Caroline; Gray, Catherine; Elliott, Keith; Mulvaney-Jones, Caroline; Hobson, Lucie; Van Duyvenvoorde, Greta; Loftus, Alison; Seward, Katie; Penn, Ruth; Maiden, Jane; Damant, Rose; Hails, Janeane; Cloudsdale, Rebecca; Silvestre, Valeria; Glenn, Sue; Dungca, Eleanor; Wheatley, Natalie; Doyle, Helen; Kent, Melanie; Hamilton, Caroline; Braim, Delyth; Wooldridge, Helen; Abrahams, Rachel; Paton, Alison; Lancaster, Nicola; Gibbins, Andrew; Hogben, Karen; Desousa, Phillipa; Muscariu, Florin; Musselwhite, Janine; McKay, Alexandra; Tan, LaiTing; Foale, Carole; Brighton, Jacqueline; Flahive, Kerry; Nambela, Estelle; Townshend, Paula; Ford, Chris; Holder, Sophie; Palmer, Caroline; Featherstone, James; Nasseri, Mariam; Sadeghian, Joy; Williams, Bronwen; Thomas, Carol; Rolls, Sally-Ann; Hynes, Abigail; Duggan, Claire; Jones, Sarah; Crossey, Mary; Stansfield, Glynis; MacNicol, Carolyn; Wilkins, Joy; Wilhelmsen, Elva; Raymode, Parizade; Lee, Hye-Jeong; Durant, Emma; Bishop, Rebecca; Ncube, Noma; Tripoli, Sherill; Casey, Rebecca; Cowley, Caroline; Miller, Richard; Houghton, Kathryn; Ducker, Samantha; Wright, Fiona; Bird, Bridget; Baxter, Gwen; Keggans, Janie; Hughes, Maggie; Grieve, Emma; Young, Karin; Williams, D; Ocker, Kate; Hines, Frances; Martin, Kirsty; Innes, Caron; Valliani, Talal; Fairlamb, Helen; Thornthwaite, Sarah; Eastick, Anne; Tanqueray, Elizabeth; Morrison, Jennifer; Holbrook, Becky; Browning, Julie; Walker, Kirsten; Congreave, Susan; Verheyden, Juliette; Slininger, Susan; Stafford, Lizzie; O'Donnell, Denise; Ainsworth, Mark; Lord, Susan; Kent, Linda; March, Linda; Dickson, Christine; Simpson, Diane; Longhurst, Beverley; Hayes, Maria; Shpuza, Ervin; White, Nikki; Besley, Sarah; Pearson, Sallyanne; Wright, Alice; Jones, Linda; Gunter, Emma; Dewhurst, Hannah; Fouracres, Anna; Farrington, Liz; Graves, Lyn; Marriott, Suzie; Leoni, Marina; Tyrer, David; Martin, Kate; Dali-kemmery, Lola; Lambourne, Victoria; Green, Marie; Sirdefield, Dawn; Amor, Kelly; Colley, Julie; Shinder, Bal; Jones, Jayne; Mills, Marisa; Carnahan, Mandy; Taylor, Natalie; Boulton, Kerenza; Tregonning, Julie; Brown, Carly; Clifford, Gayle; Archer, Emily; Hamilton, Maria; Curtis, Janette; Shewan, Tracey; Walsh, Sue; Warner, Karen; Netherton, Kimberley; Mupudzi, Mcdonald; Gunson, Bridget; Gitahi, Jane; Gocher, Denise; Batham, Sally; Pateman, Hilary; Desmennu, Senayon; Conder, Jill; Clement, Darren; Gallagher, Susan; Orpe, Jacky; Chan, PuiChing; Currie, Lynn; O'Donohoe, Lynn; Oblak, Metod; Morgan, Lisa; Quinn, Marie; Amey, Isobel; Baird, Yolanda; Cotterill, Donna; Cumlat, Lourdes; Winter, Louise; Greer, Sandra; Spurdle, Katie; Allison, Joanna; Dyer, Simon; Sweeting, Helen; Kordula, Jean; Gershwin, M. Eric; Anderson, Carl A.; Lazaridis, Konstantinos N.; Invernizzi, Pietro; Seldin, Michael F.; Sandford, Richard N.; Amos, Christopher I.; Siminovitch, Katherine A.

    2015-01-01

    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist. PMID:26394269

  11. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

    PubMed

    Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

    2015-01-01

    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist. PMID:26394269

  12. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

    PubMed

    Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

    2015-01-01

    Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

  13. Environment and Primary Biliary Cirrhosis: Electrophilic Drugs and the Induction of AMA

    PubMed Central

    Leung, Patrick S.C.; Wang, Jinjun; Naiyanetr, Phornnop; Kenny, Thomas P.; Lam, Kit S.; Kurth, Mark J.; Gershwin, M. Eric

    2013-01-01

    Environmental stimulation is a major factor in the initiation and perpetuation of autoimmune diseases. We have addressed this issue and focused on primary biliary cirrhosis (PBC), an autoimmune disease of the liver. Immunologically, PBC is distinguished by immune mediated destruction of the intra hepatic bile ducts and the presence of high titer antimitochondrial autoantibodies (AMA) directed against a highly specific epitope within the lipoic acid binding domain of the pyruvate dehydrogenase E2 subunit (PDC-E2). We submit that the uniqueness of AMA epitope specificity and the conformational changes of the PDC-E2 lipoyl domain during physiological acyl transfer could be the lynchpin to the etiology of PBC and postulate that chemical xenobiotics modification of the lipoyl domain of PDC-E2 is sufficient to break self-tolerance, with subsequent production of AMA in patients with PBC. Indeed, using quantitative structure activity relationship (QSAR) analysis on a peptide-xenobiotic conjugate microarray platform, we have demonstrated that when the lipoyl domain of PDC-E2 was modified with specific synthetic small molecule lipoyl mimics, the ensuing structures displayed highly specific reactivity to PBC sera, at levels often higher than the native PDC-E2 molecule. Hereby, we discuss our recent QSAR analysis data on specific AMA reactivity against a focused panel of lipoic acid mimic in which the lipoyl di-sulfide bond are modified. Furthermore, data on the immunological characterization of antigen and Ig isotype specificities against one such lipoic acid mimic; 6,8-bis(acetylthio)octanoic acid (SAc), when compared with rPDC-E2, strongly support a xenobiotic etiology in PBC. This observation is of particular significance in that approximately one third of patients who have taken excessive acetaminophen (APAP) developed AMA with same specificity as patients with PBC, suggesting that the lipoic domain are a target of APAP electrophilic metabolites such as NAPQI. We submit

  14. Chondrodermatitis nodularis chronica helicis in a patient with systemic sclerosis associated with primary biliary cirrhosis (Reynolds syndrome): A case report

    PubMed Central

    Giraldo, Walter Alberto Sifuentes; González-García, Carmen; de las Heras Alonso, Elena; de la Puente Bujidos, Carlos

    2014-01-01

    Chondrodermatitis nodularis chronica helicis is a rare non-neoplastic inflammatory and degenerative process of the external ear, characterized by necrobiotic changes in the dermis that extend down to the perichondrium. This condition has been occasionally reported in patients with limited cutaneous systemic sclerosis but not in those with concomitant primary biliary cirrhosis; this association is known as Reynolds syndrome. We report a 70-year-old woman diagnosed with primary biliary cirrhosis at age 47 and with limited cutaneous systemic sclerosis at age 54 who developed a painful ulcerated nodule on the helical rim of the left ear shortly after the last diagnosis. The lesion was excised because of the suspicion of malignancy, but the histopathology was consistent with chondrodermatitis nodularis chronica helicis. Although this condition is infrequent, it is necessary to know, because it may occur in patients with systemic sclerosis and be mistaken for neoplasms, such as basal cell and squamous cell carcinoma, and these patients have an increased risk for the development of skin malignancies.

  15. SP140L, an Evolutionarily Recent Member of the SP100 Family, Is an Autoantigen in Primary Biliary Cirrhosis

    PubMed Central

    Saare, Mario; Hämarik, Uku; Venta, Rainis; Panarina, Marina; Zucchelli, Chiara; Pihlap, Maire; Remm, Anu; Kisand, Kai; Toots, Urve; Möll, Kaidi; Salupere, Riina; Musco, Giovanna; Uibo, Raivo; Peterson, Pärt

    2015-01-01

    The SP100 family members comprise a set of closely related genes on chromosome 2q37.1. The widely expressed SP100 and the leukocyte-specific proteins SP110 and SP140 have been associated with transcriptional regulation and various human diseases. Here, we have characterized the SP100 family member SP140L. The genome sequence analysis showed the formation of SP140L gene through rearrangements of the two neighboring genes, SP100 and SP140, during the evolution of higher primates. The SP140L expression is interferon-inducible with high transcript levels in B cells and other peripheral blood mononuclear cells. Subcellularly, SP140L colocalizes with SP100 and SP140 in nuclear structures that are devoid of SP110, PML, or p300 proteins. Similarly to SP100 and SP140 protein, we detected serum autoantibodies to SP140L in patients with primary biliary cirrhosis using luciferase immunoprecipitation system and immunoblotting assays. In conclusion, our results show that SP140L is phylogenetically recent member of SP100 proteins and acts as an autoantigen in primary biliary cirrhosis patients. PMID:26347895

  16. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection

    PubMed Central

    Bowlus, Christopher L

    2016-01-01

    Primary biliary cholangitis (PBC), previously known as primary biliary “cirrhosis”, is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC. PMID:27621676

  17. The role of Tc-99m IDA hepatobiliary and Tc-99m colloid hepatic imaging in primary biliary cirrhosis

    SciTech Connect

    Aburano, T.; Yokoyama, K.; Shuke, N.; Kinuya, S.; Takayama, T.; Tonami, N.; Hisada, K. )

    1991-01-01

    To assess the presence of primary biliary cirrhosis, 15 patients at various histopathologic stages were studied by Tc-99m IDA hepatobiliary and/or Tc-99m colloid hepatic imaging. In the earlier stages (I and II), seven of eight patients (88%) showed uniform hepatic retention of Tc-99m IDA. Of seven patients in the same stage, however, four (57%) showed no abnormality on Tc-99m colliod imaging. In three of these four negative patients (75%), uniform hepatic retention of Tc-99m IDA was noted. In the later stages (III and IV), all seven patients showed decreased clearance with or without delayed tracer appearance in the intestine and prominent hepatic retention on Tc-99m IDA imaging; with Tc-99m colloid imaging there was enlargement of the spleen and increased activity in the spleen and bone marrow. Thus, Tc-99m IDA imaging is considered to be more useful in revealing this functional disorder at the earlier stage of primary biliary cirrhosis and in evaluating progression from an earlier to a later stage of disease. Tc-99m colloid imaging also effectively evaluated progression.

  18. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection.

    PubMed

    Bowlus, Christopher L

    2016-01-01

    Primary biliary cholangitis (PBC), previously known as primary biliary "cirrhosis", is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC. PMID:27621676

  19. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection

    PubMed Central

    Bowlus, Christopher L

    2016-01-01

    Primary biliary cholangitis (PBC), previously known as primary biliary “cirrhosis”, is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC.

  20. Polyorethaoe-covered nitinol strecker stents as primary palliative treatment of malignant biliary obstruction

    SciTech Connect

    Kanasaki, Shuzo; Furukawa, Akira; Kane, Teruyuki; Murata, Kiyoshi

    2000-03-15

    Purpose: To evaluate the clinical efficacy of the polyure-thane-covered Nitinol Strecker stent in the treatment of patients with malignant biliary obstruction.Methods: Twenty-three covered stents produced by us were placed in 18 patients with malignant biliary obstruction. Jaundice was caused by cholangiocarcinoma (n=5), pancreatic Cancer (n=6), gallbladder Cancer (n=4), metastatic lymph nodes (n=2), and tumor of the papilla (n=1).Resulrs: The mean patency period of the Stents was 37.5 weeks (5-106 weeks). Recurrent obstructive jaundice occurred in two patients (11%). Adequate biliary drainage over 50 weeks or until death was achieved in 17 of 18 patients (94.4%). Late cholangitis was observed in two patients whose stents bridged the ampulla of Vater. Other late severe complications were not encountered.Conclusion: Although more study is necessary, our results suggest the clinical efficacy of our covered Nitinol Strecker stent in the management of obstructive jaundice caused by malignant diseases.

  1. An immunohistochemical and serum ELISA study of type I and III procollagen aminopropeptides in primary biliary cirrhosis.

    PubMed Central

    Davis, B. H.; Madri, J. A.

    1987-01-01

    By means of ELISA methodology, the aminopropeptides of Type I and Type III procollagen were measured in the serum of a group of patients with primary biliary cirrhosis. The corresponding liver biopsies were graded blindly for degrees of fibrosis and inflammation. When available, paraffin-embedded liver specimens underwent immunoperoxidase staining for mature Type I and III collagen as well as the aminopropeptides of Type I and III procollagen. Regardless of the degree of fibrosis or inflammation, serum levels of the aminopropeptide of Type I remained within normal limits. In contrast, serum levels of the aminopropeptide of Type III procollagen were elevated uniformly. Immunohistochemistry demonstrated that the aminopropeptide of Type III procollagen persists extracellularly. This finding may explain the previously reported relationship between levels of inflammation and serum levels of the Type III aminopropeptide. Images Figure 7 Figure 8 PMID:3303951

  2. Risk factors for the development of vertebral and total skeleton osteoporosis in patients with primary biliary cirrhosis.

    PubMed

    Bagur, A; Mautalen, C; Findor, J; Sorda, J; Somoza, J

    1998-11-01

    The objectives of this work was to (1) study the bone mineral density (BMD) of the lumbar spine, total skeleton, and body composition in patients with primary biliary cirrhosis (PBC) and (2) evaluate the risk factors (premature menopause, stages of the disease, hyperbilirubinemia) and bone and liver biochemical parameters for the development of osteoporosis. We studied 23 women with a compatible diagnosis of PBC. The BMD and body composition were evaluated by X-ray absorptiometry (Lunar DPX-L). The average age of the population was 56.7 +/- 10.2 years. The BMD of the lumbar spine and of the total skeleton was 1.3 SDs below the normal population matched for sex and age. In the total skeleton, the legs were the most severely affected area (Z score -1.5). The body composition showed no significant difference compared with the normal population. The BMD of 56% of the patients was less than -2.5 SDs from the average normal young values. Patients with a history of vertebral fractures had diminished mineral density of the lumbar spine, as did those who had had no fractures. Of the risk factors studied, patients with premature menopause had a lower bone mass compared with patients with normal menopausal age (Z score of the total skeleton was -2.1 +/- 1.8 versus -1.1 +/- 1.0) but the difference did not reach statistical significance. The bone mass was not affected in patients with regular menstrual cycles. There were no statistically significant differences in high levels of bilirubin, advanced stages of the disease, or the biochemical variables studied. It is concluded that patients with primary biliary cirrhosis present diminished cortical and trabecular bone mass, whereas body composition was unaffected. Premature hormone deficit, possibly triggered by the chronic hepatic pathology, is a contributing factor to the osteoporosis in this population.

  3. Reduced thoracic fluid content in early-stage primary biliary cirrhosis that associates with impaired cardiac inotropy.

    PubMed

    Zalewski, Pawel; Jones, David; Lewis, Ieuan; Frith, James; Newton, Julia L

    2013-09-15

    Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by cholestasis. Recent MRI studies have confirmed the presence of cardiac abnormalities in noncirrhotic PBC patients. However, cardiorespiratory consequences of these abnormalities have not been explored. Thoracic fluid content (TFC) is a noninvasive bioelectrical impedance measure of the electrical conductivity of the chest cavity. We explored TFC and its relationship with cardiac contractility parameters in early-stage PBC patients, compared with chronic liver disease and community controls. TFC was measured in early-stage PBC (noncirrhotic; n = 78), nonalcoholic fatty liver disease (n = 23), and primary sclerosing cholangitis (n = 18) and in a community control population (n = 78). Myocardial contractility was measured as index of contractility, acceleration index, cardiac index, stroke index, left ventricular ejection time, and left ventricular work index. We also measured total arterial compliance and the Heather Index (HI; cardiac inotropy). The PBC group had significantly lower TFC compared with controls and the chronic liver disease groups (P < 0.0001). There was an association between increasing TFC and markers of cardiac function (cardiac index, stroke index, end-diastolic index, index of contractility, and acceleration index), together with indicators of cardiac inotropy and total arterial compliance. Multivariate analysis confirmed that the only parameter that independently associated with TFC was the marker of cardiac inotropy HI (P = 0.037; β 0.5). This study has confirmed that TFC is reduced in those with PBC, that this is specific to PBC, and that it associates independently with markers of cardiac inotropy.

  4. Lack of evidence for association of primary sclerosing cholangitis and primary biliary cirrhosis with risk alleles for Crohn's disease in Polish patients

    PubMed Central

    Gaj, Pawel; Habior, Andrzej; Mikula, Michal; Ostrowski, Jerzy

    2008-01-01

    Background Numerous papers have addressed the association of mutations and polymorphisms of susceptibility genes with autoimmune inflammatory disorders. We investigated whether polymorphisms that confer susceptibility to Crohn's disease could be classified also as predisposing factors for the development of primary sclerosing cholangitis and primary biliary cirrhosis in Polish patients. Methods The study included 60 patients with CD, 77 patients with PSC, of which 61 exhibited IBD (40 UC, 8 CD, and 13 indeterminate colitis), and 144 patients with PBC. All the patients were screened against Crohn's disease associating genetic polymorphisms. The polymorphisms were chosen according to previously confirmed evidence for association with Crohn's disease, including Pro268Ser, Arg702Trp, Gly908Arg and 1007fs in NOD2/CARD15, Leu503Phe/-207G>C in SLC22A4/OCTN1/SLC22A5/OCTN2, Arg30Gln in DLG5, Thr300Ala in ATG16L1, and Arg381Gln, His3Gln and exon-3'UTR in IL23R. Genotyping was carried out using TaqMan SNP genotyping assays. Results We confirmed a strong association between three NOD2/CARD15 gene variants (Pro268Ser, OR = 2.52, 95% CI = 1.34 – 4.75); (Arg702Trp, OR = 6.65, 95% CI = 1.99 – 22.17); (1007fs, OR = 9.59, 95% CI = 3.94 – 23.29), and a weak association between both the protective OCTN1/OCTN2 CC haplotype (OR = 0.28, 95% CI = 0.08 – 0.94), and a variant of ATG16L1 gene (Thr300Ala, OR = 0.468, 95% CI = 0.24 – 0.90) with Crohn's disease. In contrast, none of the polymorphisms exhibited association with susceptibility to primary sclerosing cholangitis and primary biliary cirrhosis, including a group of primary sclerosing cholangitis patients with concurrent IBD. Conclusion Although the clinical data indicate non-random co-occurrence of inflammatory bowel disease and primary sclerosing cholangitis, consistently with the previously published studies, no genetic association was found between the genetic variants predisposing to Crohn's disease and hepatobiliary

  5. HLA and interleukin 1 gene polymorphisms in primary biliary cirrhosis: associations with disease progression and disease susceptibility

    PubMed Central

    Donaldson, P; Agarwal, K; Craggs, A; Craig, W; James, O; Jones, D

    2001-01-01

    BACKGROUND AND AIMS—Twin and family studies suggest that there is a genetic component to primary biliary cirrhosis (PBC) but the genetic associations which have been described are weak with marked variations between centres. PBC is heterogeneous and genetic associations with disease progression may be obscured when the PBC population is analysed only as a whole and not subdivided.
METHODS—We have investigated two candidate gene loci in 164 well characterised patients, 88 (54%) of whom had advanced disease.
RESULTS—There was an increased frequency of the HLA DRB1*0801-DQA1*0401-DQB1*0402 haplotype in patients who had progressed to late stage disease (23% v 2% of controls; p=0000044; odds ratio (OR) 15.5, 95% confidence interval (CI) 3.52-68.4) but not in those with early stage disease (4% v 2%). Patients had a higher frequency of the IL-1B*1,1 genotype and lower frequencies of the IL-1B*1,2 and *2,2 genotypes (p=0.00078; OR 2.37, 95% CI 1.38-4.06), and higher frequency of the IL-1RN*1,1 genotype and lower frequency of the IL-1RN*1,2 genotype (p=0.0011; OR 2.28, 95% CI 1.34-3.89). The difference in the IL-1B*1,1 genotype distribution was most marked in patients with early stage disease (77% v 43% of controls; p=0.000003; OR 4.8, 95% CI 2.31-10) but the IL-1RN genotype distribution was similar in patients with early and late stage disease.
CONCLUSIONS—These data indicate a complex relationship between immunoregulatory genes and PBC. While the IL-1 genes are markers of both disease susceptibility and progression, HLA genes appear to be principally associated with disease progression.


Keywords: human leucocyte antigens; primary biliary cirrhosis; interleukin 1 PMID:11171832

  6. Biliary ascariasis.

    PubMed

    Arcilla, C A; Varilla, A

    1978-01-01

    The presenting clinical features of a series of cases of biliary tract ascariasis are described, in particular the characteristic colicky pain which occurs. The term 'ascaritic biliary pain' is introduced for the symptom diagnostic of live Ascaris adult worms inside the biliary passages. Methods of diagnosis before, and in the course of, operation are discussed and seem adequate. The management of worms discovered in the bile ducts, and those in the proximal small bowel, is described.

  7. 13C-methacetin breath test correlates with clinical indices of liver disease severity in patients with primary biliary cirrhosis.

    PubMed

    Kochel-Jankowska, A; Hartleb, M; Jonderko, K; Kaminska, M; Kasicka-Jonderko, A

    2013-02-01

    This prospective study intended to ascertain if cytochrome P450 dependent liver function is affected in early and late histological stages of primary biliary cirrhosis (PBC). The study included 32 female PBC patients (mean age 55.4 years, range 33-70) and 16 aged-matched healthy women (mean age 52.6 years, range 38-65). In every subject a 13(C)-methacetin breath test (13(C)-MBT) was applied, and the results were related to histological Ludwig's staging system and several indices of liver disease severity comprising the MAYO-1, MAYO-2, MELD, and Child-Pugh score. The 13(C)-MBT differentiated healthy controls from the patients with Ludwig IV and Ludwig III histopathological stages of PBC. The most significant relationships (i.e. explaining >50% of the variance) were found between measurements of the momentary breath 13(C) elimination from 6 to 18 minutes as well as the 15-min or 30-min cumulative elimination and the MAYO-1 or MAYO-2 scores. The breath test poorly correlated with histopathological features of PBC, however, it accurately discriminated cirrhotic from non-cirrhotic patients (momentary breath 13(C) elimination at 40 min, AUROC 0,958). In conclusion, 13(C)-MBT correlates with clinical scoring systems, especially those specifically designed for PBC (Mayo model) and accurately recognizes the disease at the stage of cirrhosis up to 40 minutes of the test duration.

  8. Are transient environmental agents involved in the cause of primary biliary cirrhosis? Evidence from space-time clustering analysis.

    PubMed

    McNally, Richard J Q; Ducker, Samantha; James, Oliver F W

    2009-10-01

    The cause of primary biliary cirrhosis (PBC) is unclear. Both genetic and environmental factors are likely to contribute. Some studies have suggested that one or more infectious agents may be involved. To examine whether infections may contribute to the cause of PBC, we have analyzed for space-time clustering using population-based data from northeast England over a defined period (1987-2003). Space-time clustering is observed when excess cases of a disease are found within limited geographical areas at limited periods of time. If present, it is suggestive of the involvement of one or more environmental components in the cause of a disease and is especially supportive of infections. A second-order procedure based on K-functions was used to test for global space-time clustering using residential addresses at the time of diagnosis. The Knox method determined the spatiotemporal range over which global clustering was strongest. K-function tests were repeated using nearest neighbor thresholds to adjust for variations in population density. Individual space-time clusters were identified using Kulldorff's scan statistic. Analysis of 1015 cases showed highly statistically significant space-time clustering (P < 0.001). Clustering was most marked for cases diagnosed within 1-4 months of one another. A number of specific space-time clusters were identified. In conclusion, these novel results suggest that transient environmental agents may play a role in the cause of PBC.

  9. No Rise in Incidence but Geographical Heterogeneity in the Occurrence of Primary Biliary Cirrhosis in North East England

    PubMed Central

    McNally, Richard J. Q.; James, Peter W.; Ducker, Samantha; Norman, Paul D.; James, Oliver F. W.

    2014-01-01

    In this study, we examined temporal changes in the incidence of primary biliary cirrhosis (PBC) and investigated associations between PBC incidence and sociodemographic factors and spatial clustering. We included 982 patients aged ≥40 years from North East England with incident PBC diagnosed during 1987–2003. Age-standardized incidence rates with 95% confidence intervals were calculated. Negative binomial regression was used to analyze incidence and socioeconomic deprivation. Clustering analysis was performed using point process methods, testing the null hypothesis that disease risk does not vary spatially and that PBC cases occur independently. The age-standardized incidence rate was 53.50 per million persons per year (95% confidence interval: 48.65, 58.35) in 1987–1994 and 45.09 per million persons per year (95% confidence interval: 41.10, 49.07) in 1995–2003. Risk of PBC increased in areas with higher levels of socioeconomic deprivation (P = 0.035). More specifically, risk increased in areas with higher levels of overcrowded homes (P = 0.040), higher levels of households without cars (P < 0.001), and higher levels of non-owner-occupied homes (P < 0.001). Overall, there was evidence of spatial clustering (P = 0.001). The findings confirm that overall incidence of PBC did not rise over time, but sociodemographic variations suggest that certain aspects of deprivation are involved in its etiology. PMID:24401563

  10. Classical HLA-DRB1 and DPB1 Alleles Account for HLA Associations with Primary Biliary Cirrhosis

    PubMed Central

    Invernizzi, Pietro; Ransom, Michael; Raychaudhuri, Soumya; Kosoy, Roman; Lleo, Ana; Shigeta, Russell; Franke, Andre; Bossa, Fabrizio; Amos, Christopher I.; Gregersen, Peter K.; Siminovitch, Katherine A.; Cusi, Daniele; de Bakker, Paul I.W.; Podda, Mauro; Gershwin, M. Eric; Seldin, Michael F.

    2012-01-01

    Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with HLA region polymorphisms. To determine if associations can be explained by classical HLA determinants we studied Italian 676 cases and 1440 controls with genotyped with dense single nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (p = 1.59 × 10−11) was the strongest predisposing allele where as DRB1*11 (p = 1.42 × 10−10) was protective. Additionally DRB1*14 and the DPB1 association (DPB1*03:01) (p = 9.18 × 10−7) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC. PMID:22573116

  11. Crohn's disease of the small bowel, complicated by primary biliary cirrhosis, Hashimoto thyroiditis, and Raynaud's phenomenon: favorable response of all disorders to adalimumab treatment.

    PubMed

    Triantafillidis, John K; Durakis, Spyros; Merikas, Emmanuel

    2013-01-01

    We describe the case of a male patient suffering from long-lasting Crohn's disease of the small bowel who developed thyroiditis Hassimoto, Raynaud's phenomenon, and primary biliary cirrhosis, during the course of the underlying bowel disease. It is not clear whether these co-morbidities appeared coincidentally, or because they share some common immunopathogenetic mechanisms. In this patient, Crohn's disease favorably responded to the treatment with an anti-TNF-α agent (adalimumab). The serum titers of antimitochondrial antibodyies and cholestatic enzymes considerably reduced during the 3-year treatment with the biologic agent. Raynaud's phenomenon, also, completely disappeared. Bearing in mind the possible involvement of TNF-α in the pathogenesis of primary biliary cirrhosis, it could be argued that the clinical and laboratory improvement of liver disease, as well as the reduction in serum titers of antimitochondrial antibodies, might be due to the anti-TNF-α action of adalimumab. We suggest that it would be worth further investigating the role of biologic agents in the treatment of patients with primary biliary cirrhosis.

  12. Biliary sludge.

    PubMed

    Ko, C W; Sekijima, J H; Lee, S P

    1999-02-16

    Biliary sludge was first described with the advent of ultrasonography in the 1970s. It is defined as a mixture of particulate matter and bile that occurs when solutes in bile precipitate. Its composition varies, but cholesterol monohydrate crystals, calcium bilirubinate, and other calcium salts are the most common components. The clinical course of biliary sludge varies, and complete resolution, a waxing and waning course, and progression to gallstones are all possible outcomes. Biliary sludge may cause complications, including biliary colic, acute pancreatitis, and acute cholecystitis. Clinical conditions and events associated with the formation of biliary sludge include rapid weight loss, pregnancy, ceftriaxone therapy, octreotide therapy, and bone marrow or solid organ transplantation. Sludge may be diagnosed on ultrasonography or bile microscopy, and the optimal diagnostic method depends on the clinical setting. This paper proposes a protocol for the microscopic diagnosis of sludge. There are no proven methods for the prevention of sludge formation, even in high-risk patients, and patients should not be routinely monitored for the development of sludge. Asymptomatic patients with sludge can be managed expectantly. If patients with sludge develop symptoms or complications, cholecystectomy should be considered as the definitive therapy. Further studies of the pathogenesis, natural history, and clinical associations of biliary sludge will be essential to our understanding of gallstones and other biliary tract abnormalities.

  13. Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease

    PubMed Central

    Wunsch, Ewa; Milkiewicz, Małgorzata; Wasik, Urszula; Trottier, Jocelyn; Kempińska-Podhorodecka, Agnieszka; Elias, Elwyn; Barbier, Olivier; Milkiewicz, Piotr

    2015-01-01

    Cholestasis induces adaptive mechanisms protecting the liver against bile acids (BA) toxicity including modulation of BA synthesis. Whether fibroblast growth factor 19 (FGF19) or farnesoid X receptor (FXR) dependent signaling are involved in the regulation of BA homeostasis in primary biliary cirrhosis (PBC) remains unknown. Here we analyzed hepatic expression of FGF19 and other genes relevant to the adaptive response to cholestasis in tissues from non-cirrhotic (n = 24) and cirrhotic (n = 21) patients along with control tissues (n = 21). Moreover we searched for relationships between serum FGF19 and laboratory/clinical findings in 51 patients. Hepatic FGF19 mRNA expression was increased in non-cirrhotic and cirrhotic tissues (9-fold,p = 0.01; 69-fold,p < 0.0001, respectively). Protein levels of FGF19, FGF receptor 4, FXR and short heterodimer partner were increased in cirrhotic livers (9-fold, p < 0.001; 3.5-fold,p = 0.007; 2.4-fold,p < 0.0001; 2.8-fold,p < 0.0001 vs controls, respectively) which was accompanied by down-regulation of CYP7A1 (50% reduction, p = 0.006). Serum and liver levels of FGF19 correlated with worse liver biochemistry, BAs, quality of life and Mayo Risk Score. Serum FGF19 was elevated in UDCA non-responders. We conclude that PBC induces characteristic changes in liver expression of BAs synthesis regulatory molecules. FGF19 correlates with severity of liver disease and can potentially serve as an indicator of chronic cholestatic liver injury. PMID:26293907

  14. Human leukocyte antigen polymorphisms in Italian primary biliary cirrhosis: a multicenter study of 664 patients and 1992 healthy controls

    PubMed Central

    Invernizzi, Pietro; Selmi, Carlo; Poli, Francesca; Frison, Sara; Floreani, Annarosa; Alvaro, Domenico; Almasio, Piero; Rosina, Floriano; Marzioni, Marco; Fabris, Luca; Muratori, Luigi; Qi, Lihong; Seldin, Michael F.; Gershwin, M. Eric; Podda, Mauro

    2008-01-01

    Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multi-center case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1,992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and gender, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). Following correction for multiple testing, DRB1*08 (Odds Ratio–OR, 3.3; 95% Confidence Interval–CI, 2.4−4.5) and DRB1*02 (OR 0.9; 95% CI 0.8−1.2) were significantly associated with PBC while alleles DRB1*11 (OR 0.4; 95% CI 0.3−0.4) and DRB1*13 (OR 0.7; 95% CI 0.6−0.9) were protective. When subjects were stratified according to their grandparental geographical origin, only the associations with DRB1*08 and DRB1*11 were common to all three areas. Associated DRB1 alleles were found only in a minority of patients while an additive genetic model is supported by the gene dosage effect for DRB1*11 allele and the interaction of DRB1*11,*13, and *08. Lastly, no significant associations were detected between specific DRB1 alleles and relevant clinical features represented by the presence of cirrhosis or serum autoantibodies. In conclusion, we confirm the role for HLA to determine PBC susceptibility and suggest that the effect of HLA is limited to patient subgroups. We suggest that a large whole-genome approach is required to identify further genetic elements contributing to the loss of tolerance in this disease. PMID:19003916

  15. Association of Estrogen Receptor Gene Polymorphisms and Primary Biliary Cirrhosis in a Chinese Population: A Case–Control Study

    PubMed Central

    Yang, Liu; Zhang, Hong; Jiang, Yan-Fang; Jin, Qing-Long; Zhang, Peng; Li, Xu; Gao, Pu-Jun; Niu, Jun-Qi

    2015-01-01

    Background: Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease characterized by destruction of the interlobular bile ducts and a striking female predominance. The aim of this study was to identify associations between estrogen receptor (ESR) gene polymorphisms with the risk of developing PBC and abnormal serum liver tests in a Chinese population. Methods: Thirty-six patients with PBC (case group) and 35 healthy individuals (control group) from the First Hospital of Jilin University were studied. Whole genomic DNA was extracted from all the participants. Three single-nucleotide polymorphisms (rs2234693, rs2228480, and rs3798577) from ESR1 and two (rs1256030 and rs1048315) from ESR2 were analyzed by a pyrosequencing method. Demographic data and liver biochemical data were collected. Results: Subjects with the T allele at ESR2 rs1256030 had 1.5 times higher risk of developing PBC than those with the C allele (odds ratio [OR] = 2.1277, 95% confidence interval [CI] = 1.1872–4.5517). Haplotypes TGC of ESR1 rs2234693, rs2228480, and rs3798577 were risk factors for having PBC. The C allele at ESR1 rs2234693 was associated with abnormal alkaline phosphatase (OR = 5.2469, 95% CI = 1.3704–20.0895) and gamma-glutamyl transferase (OR = 3.4286, 95% CI = 1.0083–13.6578) levels in PBC patients. Conclusions: ESR2 rs1256030 T allele may be a significant risk factor for the development of PBC. Screening for patients with gene polymorphisms may help to make early diagnoses in patients with PBC. PMID:26608979

  16. Immunoglobulin G4+ B‐cell receptor clones distinguish immunoglobulin G 4‐related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies

    PubMed Central

    Doorenspleet, Marieke E.; Hubers, Lowiek M.; Culver, Emma L.; Maillette de Buy Wenniger, Lucas J.; Klarenbeek, Paul L.; Chapman, Roger W.; Baas, Frank; van de Graaf, Stan F.; Verheij, Joanne; van Gulik, Thomas M.; Barnes, Eleanor; de Vries, Niek

    2016-01-01

    Immunoglobulin G4 (IgG4)‐related disease (IgG4‐RD) of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies (CA). An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4+ B‐cell receptor (BCR) clones determined by next‐generation sequencing accurately distinguish patients with IgG4‐associated cholangitis/autoimmune pancreatitis (n = 34) from those with primary sclerosing cholangitis (n = 17) and CA (n = 17). A novel, more affordable, and widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA ratio in blood also achieves excellent diagnostic accuracy (n = 125). Moreover, this qPCR test performed better than serum IgG4 levels in sensitivity (94% vs. 86%) and specificity (99% vs. 73%) and correlates with treatment response (n = 20). Conclusions: IgG4+ BCR clones and IgG4/IgG RNA ratio markedly improve delineation, early diagnosis, and monitoring of IgG4‐RD of the biliary tree and pancreas. (Hepatology 2016;64:501‐507) PMID:27015613

  17. Network meta-analysis of randomized controlled trials: efficacy and safety of UDCA-based therapies in primary biliary cirrhosis.

    PubMed

    Zhu, Gui-Qi; Shi, Ke-Qing; Huang, Sha; Huang, Gui-Qian; Lin, Yi-Qian; Zhou, Zhi-Rui; Braddock, Martin; Chen, Yong-Ping; Zheng, Ming-Hua

    2015-03-01

    Major ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE).PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09-1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02-4.83), COC plus UDCA (HR 0.39, 95% CI 0.07-2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05-1.63), or OBS (HR 0.49, 95% CI 0.11-2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59-20.67), COT plus UDCA (OR 2.27, 95% CI 0.15-33.36), COC plus UDCA (OR 1.00, 95% CI 0.09-12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23-17.82), or OBS (OR 3.00, 95% CI 0.53-20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment. PMID:25789951

  18. Red Blood Cell Distribution Width to Platelet Ratio is Related to Histologic Severity of Primary Biliary Cirrhosis

    PubMed Central

    Wang, Huan; Xu, Hongqin; Wang, Xiaomei; Wu, Ruihong; Gao, Xiuzhu; Jin, Qinglong; Niu, Junqi

    2016-01-01

    Abstract We aimed to investigate whether red blood cell distribution width (RDW) and RDW to platelet ratio (RPR) were related to the histologic severity of primary biliary cirrhosis (PBC). Seventy-three treatment-naïve PBC patients who had undergone a liver biopsy between January 2010 and January 2015 were enrolled in our study. The patients’ histological stages were based on the classifications of Ludwig and Scheuer. The patients were divided into early stage (Stage I) and advanced stage (Stage II, III, and IV) hepatic fibrosis according to their histological stage. All common patient demographics, clinical characteristics, hematological parameters, liver biochemistry, and antimitochondrial M2 antibody levels (AMA-M2) were retrospectively analyzed, and RDW, RPR, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on the 4 factors (FIB-4) were calculated. A total of 28 (38.4%) patients had early stage PBC, whereas 45 (62.6%) were classified as advanced stage. Regarding age, no significant differences between the early and advanced stages were observed. Patients with advanced stage PBC had significantly higher RDW (13.6 vs 14.4; P = 0.019), conjugated bilirubin (10.1 vs 23.4; P = 0.029), and significantly lower cholinesterase (7901.1 vs 6060.8; P = 0.001) and platelets (212.6 vs 167.0; P = 0.006). However, no significant differences (P > 0.05) in other routine parameters previously evaluated in PBC, including aspartate aminotransferase (AST) and mean platelet volume, were found between the groups. The sensitivity and specificity of RDW were 33.3% and 92.9%, respectively, and the area under the receiver-operating characteristic curve (AUROC) was 0.66. However, the sensitivity and specificity of RPR were 46.7% and 96.4%, respectively, and the corresponding AUROC was 0.74 (P < 0.001). Hence, compared with preexisting indicators, RPR showed a higher AUROC than APRI (0.648; P = 0.035) and FIB-4 (0.682; P

  19. Primary Biliary Cirrhosis

    MedlinePlus

    ... Griffin Rodgers, Director of the NIDDK Clinical Trials Current research studies and how you can volunteer Community Outreach and Health Fairs Science-based information and tips for planning an outreach effort or community event For Health Care Professionals Patient and provider resources ...

  20. Primary biliary cirrhosis

    MedlinePlus

    ... body's immune system mistakenly attacks healthy tissue. The disease more commonly affects middle-aged women. Long-term bile obstruction is believed to lead to liver cirrhosis . The disease may be linked to autoimmune ...

  1. It is time to change primary biliary cirrhosis (PBC): New nomenclature from "cirrhosis" to "cholangitis", and upcoming treatment based on unveiling pathology.

    PubMed

    Shimoda, Shinji; Tanaka, Atsushi

    2016-03-01

    Primary biliary cirrhosis (PBC) is a chronic, organ-specific, autoimmune liver disease characterized by progressive cholestasis, eventually leading to cirrhosis. Several lines of evidence have revealed a crucial role of adaptive as well as innate immune responses in the etiopathogenesis of PBC, and more recently, the biology of bile duct cells and genome-wide association studies (GWAS) demonstrated several key molecules and pathways in this enigmatic disease. Although ursodeoxycholic acid (UDCA) has been the only approved drug for PBC with clinical evidences for improvement of long-term outcomes, a substantial population have suboptimal responses to UDCA, resulting in unfavorable outcomes. In this regard, second-line treatment for patients refractory to UDCA is strongly awaited. In Japan, bezafibrate (BF) has been frequently used for this purpose, yet recent clinical trials failed to clearly demonstrate clinical efficacy of BF. Novel pharmacotherapies targeted to key molecules and pathways in PBC are upcoming. Finally, we sincerely call on all members of the Japan Society of Hepatology to use from this moment on the name "primary biliary cholangitis" for the disease known by its abbreviation PBC, in keeping with a very recent global agreement. PMID:26518139

  2. Melatonin regulation of biliary functions

    PubMed Central

    Glaser, Shannon; Han, Yuyan; Francis, Heather

    2014-01-01

    The intrahepatic biliary epithelium is a three-dimensional tubular system lined by cholangiocytes, epithelial cells that in addition to modify ductal bile are also the targets of vanishing bile duct syndromes (i.e., cholangiopathies) such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) that are characterized by the damage/proliferation of cholangiocytes. Cholangiocyte proliferation is critical for the maintenance of the biliary mass and secretory function during the pathogenesis of cholangiopathies. Proliferating cholangiocytes serve as a neuroendocrine compartment during the progression of cholangiopathies, and as such secrete and respond to hormones, neurotransmitters and neuropeptides contributing to the autocrine and paracrine pathways that regulate biliary homeostasis. The focus of this review is to summarize the recent findings related to the role of melatonin in the modulation of biliary functions and liver damage in response to a number of insults. We first provide a general background on the general function of cholangiocytes including their anatomic characteristics, their innervation and vascularization as well the role of these cells on secretory and proliferation events. After a background on the synthesis and regulation of melatonin and its role on the maintenance of circadian rhythm, we will describe the specific effects of melatonin on biliary functions and liver damage. After a summary of the topics discussed, we provide a paragraph on the future perspectives related to melatonin and liver functions. PMID:24696836

  3. Biopsy - biliary tract

    MedlinePlus

    Cytology analysis - biliary tract; Biliary tract biopsy ... A sample for a biliary tract biopsy can be obtained in different ways. A needle biopsy can be done if you have a well-defined tumor. The biopsy site ...

  4. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

    ClinicalTrials.gov

    2016-03-01

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

  5. Hepatic nodular lymphoid lesion with increased IgG4-positive plasma cells associated with primary biliary cirrhosis: a report of two cases.

    PubMed

    Calvo, Jessica; Carbonell, Nicolas; Scatton, Olivier; Marzac, Christophe; Ganne-Carrie, Nathalie; Wendum, Dominique

    2015-11-01

    The nodular lymphoid lesion of the liver known as reactive lymphoid hyperplasia or pseudolymphoma is rare and its pathogenesis is unknown. We report two cases of nodular lymphoid lesions of the liver with numerous IgG4-positive plasma cells in patients with primary biliary cirrhosis. Histologically, in both cases, the lesion showed a dense lymphoplasmacytic infiltrate with lymphoid follicles and granulomas. Fibrous tissue was scarce and without a storiform pattern. Obliterative phlebitis was not identified. The IgG4+ plasma cell counts were 82 and 76 per high power field, with an IgG4/IgG ratio of 75 and 64 %, respectively, which qualifies the lesions according to the diagnostic criteria for IgG4-related disease as « probable histological feature of IgG4-related disease ». There were no rearrangements of immunoglobulin heavy-chain genes and plasma cells had a polytypic pattern of kappa and lambda light-chain expression. The non-tumor liver showed primary biliary cirrhosis with destructive cholangitis without IgG4 plasma cells. In both cases, IgG4-related disease was not found in other organs neither at the time of diagnosis nor 3 years later. Serum IgG4 levels normalized after local ablation of the lesions. It seems unlikely that these lesions are a manifestation of IgG4-related disease. However, because the pathogenesis of both nodular lymphoid lesions and IgG4-related disease remains unclear, further studies are needed to elucidate a potential link between nodular lymphoid lesions of the liver and an increased number of IgG4 plasma cells. More definite conclusions will be possible when the pathogenesis of IgG4-related disease has been clarified.

  6. HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence of molecular mimicry in human autoimmune diseases

    PubMed Central

    1995-01-01

    We established six T cell clones specific for pyruvate dehydrogenase complex (PDC)-E2 peptides from four different patients with primary biliary cirrhosis using 33 different peptides of 17-20 amino acid residues corresponding to human PDC-E2 as stimulating antigens. The minimal T cell epitopes of these six T cell clones were all mapped to the same region of the PDC-E2 peptide 163-176 (GDLLAEIETDKATI), which corresponds to the inner lipoyl domain of PDC-E2. The HLA restriction molecules for this epitope were all identified as HLA DRB4 0101. The common essential amino acids of this epitope for these T cell clones were E, D, and K at positions 170, 172, and 173, respectively; other crucial amino acids for this epitope differed in each T cell clone. In addition, the alanine-substituted peptides at positions 170 and 173, but not 172, inhibited the proliferation of all T cell clones induced by the original peptide of human PDC-E2 163-176, indicating that amino acid D at position 172 is a critical MHC-binding site for all T cell clones tested. Interestingly, all T cell clones reacted to PDC-E2 peptide 36-49 (GDLIAEVETDKATV), which corresponds to the outer lipoyl domain of human PDC-E2. Furthermore, one T cell clone cross-reacted with exogenous antigens such as Escherichia coli PDC-E2 peptide 31- 44/134-147/235-248 (EQSLITVEGDKASM), which has an EXDK sequence. This is a definite demonstration of the presence of molecular mimicry at the T cell clonal level in human autoimmune diseases. It is also considered possible to design peptide-specific immunotherapy based on the findings of T cell autoepitopes in primary biliary cirrhosis. PMID:7536796

  7. High levels of autoantibodies against drug-metabolizing enzymes in SLA/LP-positive AIH-1 sera.

    PubMed

    Shinoda, Masakazu; Tanaka, Yuta; Kuno, Takuya; Matsufuji, Tamiko; Matsufuji, Senya; Murakami, Yasuko; Mizutani, Takaharu

    2004-01-01

    Autoimmune hepatitis type 1 (AIH-1) is characterized by the detection of smooth muscle autoantibodies, antinuclear antibodies and antineutrophil cytoplasmic autoantibodies, and AIH-2 is characterized by the presence of autoantibodies against LKM, which contain drug-metabolizing enzymes. In this study, we measured the levels of drug-metabolizing enzymes in AIH-1 patients (ANA-positive). We exhaustively investigated the level of autoantibodies against major CYPs and UDP-glucuronosyltransferases of typical phase II drug-metabolizing enzymes, a transporter (MDR1), and NADPH-cytochrome P450 reductase in 4 patients with AIH-1 and 6 controls, as a case report. Two (Patients 3 and 4) of the AIH patients exhibited high levels of autoantibodies, while two (Patients 1 and 2) of the patients and the controls did not. The levels of autoantibodies against CYP2C19, CYP2D6, CYP2E1, UGT1A6 and human liver microsomes in Patients 3 and 4 sera were over 2(3) times the levels in Patient 1, Patient 2 and the control sera. Meanwhile, the levels of autoantibodies against CYP1A2, CYP2A6, CYP2C9, UGT2B7, MDR1 and NADPH-cytochrome P450 reductase were 2-2(2) higher in Patients 3 and 4 than in the other subjects. We found that the pattern of elevation in the Patient 3 serum was not parallel with that in Patient 4. Thus, we found high levels of autoantibodies against drug-metabolizing enzymes in AIH-1 patients.

  8. Synthesis and antitumor mechanisms of a copper(II) complex of anthracene-9-imidazoline hydrazone (9-AIH).

    PubMed

    Qin, Qi-Pin; Liu, Yan-Cheng; Wang, Hai-Lu; Qin, Jiao-Lan; Cheng, Feng-Jie; Tang, Shang-Feng; Liang, Hong

    2015-07-01

    A new anthracycline derivative, anthracene-9-imidazoline hydrazone (9-AIH), was synthesized and selected as an antitumor ligand to afford a copper(II) complex of 9-AIH, cis-[Cu(II)Cl2(9-AIH)] (1). Complex 1 was structurally characterized by IR, elemental analysis, ESI-MS and single crystal X-ray diffraction analysis. By MTT assay, it was revealed that 1 showed overall a higher in vitro cytotoxicity than 9-AIH towards a panel of human tumour cell lines, with IC50 values from 0.94–3.68 μM, in which the BEL-7404 cell line was the most sensitive to 1. By spectral analyses and gel electrophoresis, the DNA binding affinity of 9-AIH and 1 was determined. 9-AIH was suggested to bind with DNA in an intercalative mode, with a quenching constant of 1.04 × 10(4) M(−1) on the EB–DNA complex. While for 1, both intercalative and covalent binding modes were suggested. By flow cytometry, 1 was found to block the cell cycle of BEL-7404 cells in a dose-dependent mode, in which it induced the G2/M phase arrest at 0.5 μM and induced the S phase arrest at higher concentrations of 1.0 or 2.0 μM. From the cellular morphological observations under different fluorescence probe staining, a dose-dependent manner of 1 to induce cell apoptosis in the late stage was suggested. Comparatively, equivalent apoptotic cells, respectively, in the early and late stages were found when incubated with 2.0 μM of 9-AIH. The mitochondrial membrane potential measured by JC-1 staining and the ROS generation in cells detected using a DCFH-DA probe suggested that the cell apoptosis induced by 1 might undergo the ROS-related mitochondrial pathway. Accordingly, the mutant p53 expression was found to be suppressed and the caspase cascade (caspase-9/3) was consequently activated by 1. This action mechanism for 1 in the BEL-7404 cells was unique and was not found in the presence of 9-AIH under the same conditions, indicating their different antitumor mechanism. Furthermore, the in vivo acute toxicity of 1

  9. Are Dysregulated Inflammatory Responses to Commensal Bacteria Involved in the Pathogenesis of Hepatobiliary-Pancreatic Autoimmune Disease? An Analysis Using Mice Models of Primary Biliary Cirrhosis and Autoimmune Pancreatitis

    PubMed Central

    Yanagisawa, Naoko; Haruta, Ikuko; Kikuchi, Ken; Shibata, Noriyuki; Yagi, Junji

    2011-01-01

    The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure in the pathogenesis of primary biliary cirrhosis (PBC) and autoimmune pancreatitis (AIP), both of which are broadly categorized as autoimmune disorders involving hepatobiliary-pancreatic lesions. Avirulent and/or commensal bacteria, which may have important role(s) as initiating factors in the pathogenesis of autoimmune disorders such as PBC and AIP, will be emphasized. PMID:21991516

  10. Role of Lipoylation of the Immunodominant Epitope of Pyruvate Dehydrogenase Complex: Toward a Peptide-Based Diagnostic Assay for Primary Biliary Cirrhosis.

    PubMed

    Pacini, Giulia; Carotenuto, Alfonso; Rentier, Cedric; Nuti, Francesca; Real-Fernandez, Feliciana; Brancaccio, Diego; Sabatino, Giuseppina; Larregola, Maud; Peroni, Elisa; Migliorini, Paola; Novellino, Ettore; Battezzati, Pier Maria; Selmi, Carlo; Papini, Anna Maria; Rovero, Paolo

    2015-08-27

    Primary biliary cirrhosis is an immune-mediated chronic liver disease whose diagnosis relies on the detection of serum antimitochondrial antibodies directed against a complex set of proteins, among which pyruvate dehydrogenase complex is considered the main autoantigen. We studied the immunological role of the lipoyl domain of this protein using synthetic lipoylated peptides, showing that the lipoyl chain chirality does not affect autoantibody recognition and, most importantly, confirming that both lipoylated and unlipoylated peptides are able to recognize specific autoantibodies in patients sera. In fact, 74% of patients sera recognize at least one of the tested peptides but very few positive sera recognized exclusively the lipoylated peptide, suggesting that the lipoamide moiety plays a marginal role within the autoreactive epitope. These results are supported by a conformational analysis showing that the lipoyl moiety of pyruvate dehydrogenase complex appears to be involved in hydrophobic interactions, which may limit its exposition and thus its contribution to the complex antigenic epitope. A preliminary analysis of the specificity of the two most active peptides indicates that they could be part of a panel of synthetic antigens collectively able to mimic in a simple immunoenzymatic assay the complex positivity pattern detected in immunofluorescence. PMID:26214254

  11. Genome-Wide Analysis of DNA Methylation, Copy Number Variation, and Gene Expression in Monozygotic Twins Discordant for Primary Biliary Cirrhosis

    PubMed Central

    Selmi, Carlo; Cavaciocchi, Francesca; Lleo, Ana; Cheroni, Cristina; De Francesco, Raffaele; Lombardi, Simone A.; De Santis, Maria; Meda, Francesca; Raimondo, Maria Gabriella; Crotti, Chiara; Folci, Marco; Zammataro, Luca; Mayo, Marlyn J.; Bach, Nancy; Shimoda, Shinji; Gordon, Stuart C.; Miozzo, Monica; Invernizzi, Pietro; Podda, Mauro; Scavelli, Rossana; Martin, Michelle R.; Seldin, Michael F.; LaSalle, Janine M.; Gershwin, M. Eric

    2014-01-01

    Primary biliary cirrhosis (PBC) is an uncommon autoimmune disease with a homogeneous clinical phenotype that reflects incomplete disease concordance in monozygotic (MZ) twins. We have taken advantage of a unique collection consisting of genomic DNA and mRNA from peripheral blood cells of female MZ twins (n = 3 sets) and sisters of similar age (n = 8 pairs) discordant for disease. We performed a genome-wide study to investigate differences in (i) DNA methylation (using a custom tiled four-plex array containing tiled 50-mers 19,084 randomly chosen methylation sites), (ii) copy number variation (CNV) (with a chip including markers derived from the 1000 Genomes Project, all three HapMap phases, and recently published studies), and/or (iii) gene expression (by whole-genome expression arrays). Based on the results obtained from these three approaches we utilized quantitative PCR to compare the expression of candidate genes. Importantly, our data support consistent differences in discordant twins and siblings for the (i) methylation profiles of 60 gene regions, (ii) CNV of 10 genes, and (iii) the expression of 2 interferon-dependent genes. Quantitative PCR analysis showed that 17 of these genes are differentially expressed in discordant sibling pairs. In conclusion, we report that MZ twins and sisters discordant for PBC manifest particular epigenetic differences and highlight the value of the epigenetic study of twins. PMID:24734033

  12. Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy.

    PubMed

    Sun, Yonghu; Irwanto, Astrid; Toyo-Oka, Licht; Hong, Myunghee; Liu, Hong; Andiappan, Anand Kumar; Choi, Hyunchul; Hitomi, Yuki; Yu, Gongqi; Yu, Yongxiang; Bao, Fangfang; Wang, Chuan; Fu, Xian; Yue, Zhenhua; Wang, Honglei; Zhang, Huimin; Kawashima, Minae; Kojima, Kaname; Nagasaki, Masao; Nakamura, Minoru; Yang, Suk-Kyun; Ye, Byong Duk; Denise, Yosua; Rotzschke, Olaf; Song, Kyuyoung; Tokunaga, Katsushi; Zhang, Furen; Liu, Jianjun

    2016-01-01

    Genetic polymorphism within the 9q32 locus is linked with increased risk of several diseases, including Crohn's disease (CD), primary biliary cholangitis (PBC) and leprosy. The most likely disease-causing gene within 9q32 is TNFSF15, which encodes the pro-inflammatory cytokine TNF super-family member 15, but it was unknown whether these disparate diseases were associated with the same genetic variance in 9q32, and how variance within this locus might contribute to pathology. Using genetic data from published studies on CD, PBC and leprosy we revealed that bearing a T allele at rs6478108/rs6478109 (r(2) = 1) or rs4979462 was significantly associated with increased risk of CD and decreased risk of leprosy, while the T allele at rs4979462 was associated with significantly increased risk of PBC. In vitro analyses showed that the rs6478109 genotype significantly affected TNFSF15 expression in cells from whole blood of controls, while functional annotation using publicly-available data revealed the broad cell type/tissue-specific regulatory potential of variance at rs6478109 or rs4979462. In summary, we provide evidence that variance within TNFSF15 has the potential to affect cytokine expression across a range of tissues and thereby contribute to protection from infectious diseases such as leprosy, while increasing the risk of immune-mediated diseases including CD and PBC. PMID:27507062

  13. Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn’s disease and leprosy

    PubMed Central

    Sun, Yonghu; Irwanto, Astrid; Toyo-oka, Licht; Hong, Myunghee; Liu, Hong; Andiappan, Anand Kumar; Choi, Hyunchul; Hitomi, Yuki; Yu, Gongqi; Yu, Yongxiang; Bao, Fangfang; Wang, Chuan; Fu, Xian; Yue, Zhenhua; Wang, Honglei; Zhang, Huimin; Kawashima, Minae; Kojima, Kaname; Nagasaki, Masao; Nakamura, Minoru; Yang, Suk-Kyun; Ye, Byong Duk; Denise, Yosua; Rotzschke, Olaf; Song, Kyuyoung; Tokunaga, Katsushi; Zhang, Furen; Liu, Jianjun

    2016-01-01

    Genetic polymorphism within the 9q32 locus is linked with increased risk of several diseases, including Crohn’s disease (CD), primary biliary cholangitis (PBC) and leprosy. The most likely disease-causing gene within 9q32 is TNFSF15, which encodes the pro-inflammatory cytokine TNF super-family member 15, but it was unknown whether these disparate diseases were associated with the same genetic variance in 9q32, and how variance within this locus might contribute to pathology. Using genetic data from published studies on CD, PBC and leprosy we revealed that bearing a T allele at rs6478108/rs6478109 (r2 = 1) or rs4979462 was significantly associated with increased risk of CD and decreased risk of leprosy, while the T allele at rs4979462 was associated with significantly increased risk of PBC. In vitro analyses showed that the rs6478109 genotype significantly affected TNFSF15 expression in cells from whole blood of controls, while functional annotation using publicly-available data revealed the broad cell type/tissue-specific regulatory potential of variance at rs6478109 or rs4979462. In summary, we provide evidence that variance within TNFSF15 has the potential to affect cytokine expression across a range of tissues and thereby contribute to protection from infectious diseases such as leprosy, while increasing the risk of immune-mediated diseases including CD and PBC. PMID:27507062

  14. RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial

    PubMed Central

    Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

    2015-01-01

    Introduction Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. Methods and analysis RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. Ethics and dissemination The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants

  15. Increased Risks of Spontaneous Bacterial Peritonitis and Interstitial Lung Disease in Primary Biliary Cirrhosis Patients With Concomitant Sjögren Syndrome

    PubMed Central

    Chen, Chun-Ting; Tseng, Yu-Chen; Yang, Chih-Wei; Lin, Hsuan-Hwai; Chen, Peng-Jen; Huang, Tien-Yu; Shih, Yu-Lueng; Chang, Wei-Kuo; Hsieh, Tsai-Yuan; Chu, Heng-Cheng

    2016-01-01

    Abstract The incidence of Sjögren syndrome (SS) in primary biliary cirrhosis (PBC) patients is high. The influence of SS on the clinical outcomes of PBC patients, however, remains unclear. Our study retrospectively collected data on PBC-only patients and PBC patients with concomitant SS (PBC-SS) to compare the clinical differences of long-term outcomes between them. A total of 183 patients were diagnosed with PBC from January 1999 to December 2014 at our hospital. Of these, the authors excluded patients with diabetes, hypertension, advanced liver cirrhosis at initial diagnosis of PBC (Child–Turcotte–Pugh classification score of ≥7) and other liver diseases (ie, alcoholic liver disease, alpha-antitrypsin deficiency, viral hepatitis, and primary sclerosing cholangitis), and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Of the remaining 125 patients, 77 (61.6%) were PBC-only and 48 (38.4%) were PBC-SS patients. The mean follow-up duration was 8.76 years. During the observation period, the incidence of interstitial lung disease was higher in the PBC-SS group than in the PBC-only group (P = 0.005). The occurrence of spontaneous bacterial peritonitis was significantly different in PBC-SS patients than in PBC-only patients (P = 0.002). The overall survival was lower in PBC-SS patients than in PBC-only patients (P = 0.033). Although the incidence of hepatocellular carcinoma, end-stage renal disease, variceal bleeding, and hypothyroidism were all higher in the PBC-SS group than in the PBC-only group, the differences were not significant. Our study suggests that PBC-SS patients have a higher risk of developing interstitial lung disease and spontaneous bacterial peritonitis and have a poor prognosis. Aggressive surveillance of thyroid and pulmonary functions should therefore be performed in these patients. PMID:26765478

  16. Chemical xenobiotics and mitochondrial autoantigens in primary biliary cirrhosis: identification of antibodies against a common environmental, cosmetic, and food additive, 2-octynoic acid.

    PubMed

    Amano, Katsushi; Leung, Patrick S C; Rieger, Roman; Quan, Chao; Wang, Xiaobing; Marik, Jan; Suen, Yat Fan; Kurth, Mark J; Nantz, Michael H; Ansari, Aftab A; Lam, Kit S; Zeniya, Mikio; Matsuura, Eiji; Coppel, Ross L; Gershwin, M Eric

    2005-05-01

    Emerging evidence has suggested environmental factors as causative agents in the pathogenesis of primary biliary cirrhosis (PBC). We have hypothesized that in PBC the lipoyl domain of the immunodominant E2 component of pyruvate dehydrogenase (PDC-E2) is replaced by a chemical xenobiotic mimic, which is sufficient to break self-tolerance. To address this hypothesis, based upon our quantitative structure-activity relationship data, a total of 107 potential xenobiotic mimics were coupled to the lysine residue of the immunodominant 15 amino acid peptide of the PDC-E2 inner lipoyl domain and spotted on microarray slides. Sera from patients with PBC (n = 47), primary sclerosing cholangitis (n = 15), and healthy volunteers (n = 20) were assayed for Ig reactivity. PBC sera were subsequently absorbed with native lipoylated PDC-E2 peptide or a xenobiotically modified PDC-E2 peptide, and the remaining reactivity analyzed. Of the 107 xenobiotics, 33 had a significantly higher IgG reactivity against PBC sera compared with control sera. In addition, 9 of those 33 compounds were more reactive than the native lipoylated peptide. Following absorption, 8 of the 9 compounds demonstrated cross-reactivity with lipoic acid. One compound, 2-octynoic acid, was unique in both its quantitative structure-activity relationship analysis and reactivity. PBC patient sera demonstrated high Ig reactivity against 2-octynoic acid-PDC-E2 peptide. Not only does 2-octynoic acid have the potential to modify PDC-E2 in vivo but importantly it was/is widely used in the environment including perfumes, lipstick, and many common food flavorings. PMID:15845458

  17. Increased Risks of Spontaneous Bacterial Peritonitis and Interstitial Lung Disease in Primary Biliary Cirrhosis Patients With Concomitant Sjögren Syndrome.

    PubMed

    Chen, Chun-Ting; Tseng, Yu-Chen; Yang, Chih-Wei; Lin, Hsuan-Hwai; Chen, Peng-Jen; Huang, Tien-Yu; Shih, Yu-Lueng; Chang, Wei-Kuo; Hsieh, Tsai-Yuan; Chu, Heng-Cheng

    2016-01-01

    The incidence of Sjögren syndrome (SS) in primary biliary cirrhosis (PBC) patients is high. The influence of SS on the clinical outcomes of PBC patients, however, remains unclear. Our study retrospectively collected data on PBC-only patients and PBC patients with concomitant SS (PBC-SS) to compare the clinical differences of long-term outcomes between them.A total of 183 patients were diagnosed with PBC from January 1999 to December 2014 at our hospital. Of these, the authors excluded patients with diabetes, hypertension, advanced liver cirrhosis at initial diagnosis of PBC (Child-Turcotte-Pugh classification score of ≥7) and other liver diseases (ie, alcoholic liver disease, alpha-antitrypsin deficiency, viral hepatitis, and primary sclerosing cholangitis), and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Of the remaining 125 patients, 77 (61.6%) were PBC-only and 48 (38.4%) were PBC-SS patients.The mean follow-up duration was 8.76 years. During the observation period, the incidence of interstitial lung disease was higher in the PBC-SS group than in the PBC-only group (P = 0.005). The occurrence of spontaneous bacterial peritonitis was significantly different in PBC-SS patients than in PBC-only patients (P = 0.002). The overall survival was lower in PBC-SS patients than in PBC-only patients (P = 0.033). Although the incidence of hepatocellular carcinoma, end-stage renal disease, variceal bleeding, and hypothyroidism were all higher in the PBC-SS group than in the PBC-only group, the differences were not significant.Our study suggests that PBC-SS patients have a higher risk of developing interstitial lung disease and spontaneous bacterial peritonitis and have a poor prognosis. Aggressive surveillance of thyroid and pulmonary functions should therefore be performed in these patients. PMID:26765478

  18. Increased Risks of Spontaneous Bacterial Peritonitis and Interstitial Lung Disease in Primary Biliary Cirrhosis Patients With Concomitant Sjögren Syndrome.

    PubMed

    Chen, Chun-Ting; Tseng, Yu-Chen; Yang, Chih-Wei; Lin, Hsuan-Hwai; Chen, Peng-Jen; Huang, Tien-Yu; Shih, Yu-Lueng; Chang, Wei-Kuo; Hsieh, Tsai-Yuan; Chu, Heng-Cheng

    2016-01-01

    The incidence of Sjögren syndrome (SS) in primary biliary cirrhosis (PBC) patients is high. The influence of SS on the clinical outcomes of PBC patients, however, remains unclear. Our study retrospectively collected data on PBC-only patients and PBC patients with concomitant SS (PBC-SS) to compare the clinical differences of long-term outcomes between them.A total of 183 patients were diagnosed with PBC from January 1999 to December 2014 at our hospital. Of these, the authors excluded patients with diabetes, hypertension, advanced liver cirrhosis at initial diagnosis of PBC (Child-Turcotte-Pugh classification score of ≥7) and other liver diseases (ie, alcoholic liver disease, alpha-antitrypsin deficiency, viral hepatitis, and primary sclerosing cholangitis), and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Of the remaining 125 patients, 77 (61.6%) were PBC-only and 48 (38.4%) were PBC-SS patients.The mean follow-up duration was 8.76 years. During the observation period, the incidence of interstitial lung disease was higher in the PBC-SS group than in the PBC-only group (P = 0.005). The occurrence of spontaneous bacterial peritonitis was significantly different in PBC-SS patients than in PBC-only patients (P = 0.002). The overall survival was lower in PBC-SS patients than in PBC-only patients (P = 0.033). Although the incidence of hepatocellular carcinoma, end-stage renal disease, variceal bleeding, and hypothyroidism were all higher in the PBC-SS group than in the PBC-only group, the differences were not significant.Our study suggests that PBC-SS patients have a higher risk of developing interstitial lung disease and spontaneous bacterial peritonitis and have a poor prognosis. Aggressive surveillance of thyroid and pulmonary functions should therefore be performed in these patients.

  19. Genome-wide Association Study Identifies TNFSF15 and POU2AF1 as Susceptibility Loci for Primary Biliary Cirrhosis in the Japanese Population

    PubMed Central

    Nakamura, Minoru; Nishida, Nao; Kawashima, Minae; Aiba, Yoshihiro; Tanaka, Atsushi; Yasunami, Michio; Nakamura, Hitomi; Komori, Atsumasai; Nakamuta, Makoto; Zeniya, Mikio; Hashimoto, Etsuko; Ohira, Hiromasa; Yamamoto, Kazuhide; Onji, Morikazu; Kaneko, Shuichi; Honda, Masao; Yamagiwa, Satoshi; Nakao, Kazuhiko; Ichida, Takafumi; Takikawa, Hajime; Seike, Masataka; Umemura, Takeji; Ueno, Yoshiyuki; Sakisaka, Shotaro; Kikuchi, Kentaro; Ebinuma, Hirotoshi; Yamashiki, Noriyo; Tamura, Sumito; Sugawara, Yasuhiko; Mori, Akira; Yagi, Shintaro; Shirabe, Ken; Taketomi, Akinobu; Arai, Kuniaki; Monoe, Kyoko; Ichikawa, Tatsuki; Taniai, Makiko; Miyake, Yasuhiro; Kumagi, Teru; Abe, Masanori; Yoshizawa, Kaname; Joshita, Satoru; Shimoda, Shinji; Honda, Koichi; Takahashi, Hiroki; Hirano, Katsuji; Takeyama, Yasuaki; Harada, Kenichi; Migita, Kiyoshi; Ito, Masahiro; Yatsuhashi, Hiroshi; Fukushima, Nobuyoshi; Ota, Hajime; Komatsu, Tatsuji; Saoshiro, Takeo; Ishida, Jinya; Kouno, Hirotsugu; Kouno, Hirotaka; Yagura, Michiyasu; Kobayashi, Masakazu; Muro, Toyokichi; Masaki, Naohiko; Hirata, Keiichi; Watanabe, Yukio; Nakamura, Yoko; Shimada, Masaaki; Hirashima, Noboru; Komeda, Toshiki; Sugi, Kazuhiro; Koga, Michiaki; Ario, Keisuke; Takesaki, Eiichi; Maehara, Yoshihiko; Uemoto, Shinji; Kokudo, Norihiro; Tsubouchi, Hirohito; Mizokami, Masashi; Nakanuma, Yasuni; Tokunaga, Katsushi; Ishibashi, Hiromi

    2012-01-01

    For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10−14 for rs4979462, and combined OR = 1.39, p = 2.38 × 10−8 for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10−8, 3.66 × 10−9, and 3.04 × 10−9, respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10−6 and 1.42 × 10−7, respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals. PMID:23000144

  20. Pediatric Biliary Interventions.

    PubMed

    Atchie, Benjamin; Kalva, Sanjeeva; Josephs, Shellie

    2015-12-01

    An interventional radiologist is frequently called to evaluate and treat biliary diseases in children; a tailored approach specific to this population is required. Imaging with an emphasis on minimizing ionizing radiation is used not only in the initial workup but also to guide interventions. The most common form of intervention generally consists of transhepatic biliary drainage to treat either biliary obstruction or bile leakage, a scenario frequently encountered after pediatric liver transplantation. Other pathologies referred for evaluation and management include biliary atresia and, rarely, symptomatic choledochal cysts. Biliary complications caused by an underlying malignancy are not a frequently encountered problem in the pediatric population. The initial evaluation, role of preprocedural imaging, and interventional management with an emphasis on technique are discussed regarding these common biliary pathologies in children. PMID:26615168

  1. Diagnosis of Liver Involvement in Primary Sjögren Syndrome

    PubMed Central

    Zeron, Pilar Brito; Retamozo, Soledad; Bové, Albert; Kostov, Belchin Adriyanov; Sisó, Antoni

    2013-01-01

    Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sjögren syndrome (SS). In the 1990s, a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of liver disease, liver function and a complete panel of autoantibodies. Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS. The most recent studies have shown that, after eliminating hepatotoxic drugs and fatty liver disease, the two main causes of liver disease in primary SS are chronic viral infections and autoimmune liver diseases. The differential diagnosis of liver disease in primary SS (viral vs autoimmune) is clinically important, since the two processes require different therapeutic approaches and have different prognoses. With respect to viral infections, chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area, while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries. After eliminating viral hepatitis, primary biliary cirrhosis (PBC) should be considered the main cause of liver disease in primary SS. PBC-related SS patients may have a broad spectrum of abnormalities of the liver, including having no clinical or analytical data suggestive of liver disease. Autoimmune hepatitis (AIH) is the second most frequently found autoimmune liver disease to be associated with SS (all reported cases are type I), and nearly 10% of these patients have an AIH-PBC overlap. Finally, IgG4-related disease must be investigated in patients with SS presenting with sclerosing cholangitis, especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present. PMID:26355632

  2. Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its Lactobacillus mimic.

    PubMed

    Bogdanos, Dimitrios-Petrou; Baum, Harold; Okamoto, Manabu; Montalto, Paolo; Sharma, Umesh C; Rigopoulou, Eirini I; Vlachogiannakos, John; Ma, Yun; Burroughs, Andrew K; Vergani, Diego

    2005-08-01

    The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti-PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC-E2(212-226) and hsp's is a cross-reactive target. Having found that this same motif is present only in beta-galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to cross-reactivity. The mimics were tested via ELISA for reactivity and competitive cross-reactivity using sera from 100 AMA-positive and 23 AMA-negative PBC patients and 190 controls. An Escherichia coli (ECOLI) PDC-E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti-BGAL(266-280) LACDE antibodies were restricted to AMA-positive patients (54 of 95, 57%) and belonged to immunoglobulin (Ig) G3. Of the 190 controls, 22 (12%; P < .001) had anti-BGAL(266-280) antibodies, mainly of the IgG4 subclass. ECOLI PDC-E2 reactivity was virtually absent. BGAL(266-280)/PDC-E2(212-226) reactivity of the IgG3 isotype was found in 52 (52%) AMA-positive PBC patients but in only 1 of the controls (P < .001). LACDE BGAL(266-280)/PDC-E2(212-226) reactivity was due to cross-reactivity as confirmed via competition ELISA. Antibody affinity for BGAL(266-280) was greater than for PDC-E2 mimics. Preincubation of a multireactive serum with BGAL(266-280) reduced the inhibition of enzymatic activity by 40%, while marginal effect (12%) or no effect (2%) was observed in human or ECOLI PDC-E2 mimics. In conclusion, IgG3 antibodies to BGAL LACDE cross-react with the major mitochondrial autoepitope and are characteristic of PBC. PMID:16025495

  3. Involvement of cholangiocyte proliferation in biliary fibrosis

    PubMed Central

    Priester, Sally; Wise, Candace; Glaser, Shannon S

    2010-01-01

    Cholangiocytes are the epithelial cells that line the biliary tree. In the adult liver, they are a mitotically dormant cell population, unless ductular reaction is triggered by injury. The ability of cholangiocytes to proliferate is important in many different human pathological liver conditions that target this cell type, which are termed cholangiopathies (i.e. primary biliary cirrhosis, primary sclerosing cholangitis and biliary atresia). In our article, we provide background information on the morphological and functional heterogeneity of cholangiocytes, summarize what is currently known about their proliferative processes, and briefly describe the diseases that target these cells. In addition, we address recent findings that suggest cholangiocyte involvement in epithelial-to-mesenchymal transformation and liver fibrosis, and propose directions for future studies. PMID:21607140

  4. Molecular genetics and targeted therapeutics in biliary tract carcinoma

    PubMed Central

    Marks, Eric I; Yee, Nelson S

    2016-01-01

    The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract. PMID:26819503

  5. Biliary lipid secretion.

    PubMed

    Hişmioğullari, Adnan Adil; Bozdayi, A Mithat; Rahman, Khalid

    2007-06-01

    The liver has many biochemical functions, of which one of the most important is bile formation. Bile is both a secretory and an excretory fluid and two of its most important functions are the delivery to the intestinal tract of: (i) bile acids to assist in fat digestion and absorption; and (ii) liver-derived metabolites of potentially toxic materials prior to their elimination from the body in the feces. Bile contains numerous solutes, including bile acids, phospholipids and cholesterol. Biliary lipids mainly consist of cholesterol and phospholipids and their secretion into bile is affected by the secretion of bile acids. Phospholipids and cholesterol are synthesized in the hepatocytes and are thought to be transferred via vesicle- and non-vesicle-mediated mechanisms into the bile canaliculus. Hepatocytes acquire biliary lipid by three pathways, which are biosynthesis, lipoproteins and existing molecules drawn from intracellular membranes, with the newly synthesized biliary lipid accounting for less than 20% of the total lipids. The hepatic determinants of biliary cholesterol elimination are not limited to total cholesterol homeostasis, but also concern biliary disease conditions, since excess biliary cholesterol secretion is involved in cholesterol gallstone formation, as well as being a major risk factor for gallbladder cancer. The purpose of this review was to highlight some of the major mechanisms involved in biliary lipid secretion.

  6. Extrahepatic biliary obstruction by metastatic colon carcinoma.

    PubMed

    Warshaw, A L; Welch, J P

    1978-11-01

    Extrahepatic biliary obstruction can be caused by cancer metastatic from the colon to the lymph nodes adjacent to the bile duct. This report details our experience with eight such cases treated at the Massachusetts General Hospital in the last seven years. The interval between resection of the primary tumor and appearance of jaundice averaged 13 months. The location of the obstruction, preferably defined preoperatively by cholangiography, was low on the common duct in three cases and high in the porta hepatis in five. Relief of biliary obstruction was accomplished by biliary-enteric bypass (four cases), internal biliary stenting by permanent indwelling tube (two cases), or by portal irradiation (two cases). In addition to palliating the symptoms of obstructive jaundice, the period of comfortable survival appears to have been extended: the bypassed patients lived 13-38 months. Erosion of tumor into the duodenum, with resulting gastrointestinal hemorrhage, was an additional problem in three patients. Our overall experience illustrates the value of distinguishing this subgroup of patients from the larger number whose jaundice results from extensive liver metastases, and of treating aggressively those with extrahepatic biliary obstruction.

  7. Stenting in Malignant Biliary Obstruction.

    PubMed

    Almadi, Majid A; Barkun, Jeffrey S; Barkun, Alan N

    2015-10-01

    Decompression of the biliary system in patients with malignant biliary obstruction has been widely accepted and implemented as part of the care. Despite a wealth of literature, there remains a significant amount of uncertainty as to which approach would be most appropriate in different clinical settings. This review covers stenting of the biliary system in cases of resectable or palliative malignant biliary obstruction, potential candidates for biliary drainage, technical aspects of the procedure, as well as management of biliary stent dysfunction. Furthermore, periprocedural considerations including proper mapping of the location of obstruction and the use of antibiotics are addressed.

  8. Elevated serum levels of a biliary glycoprotein (BGP I) in patients with liver or biliary tract disease.

    PubMed

    Svenberg, T; Wahren, B; Hammarström, S

    1979-05-01

    Human hepatic bile contains a glycoprotein (biliary glycoprotein I, BGP I) which cross-reacts with the carcinoembryonic antigen (CEA). A radioimmunoassay for BGP I was developed. The interference of CEA or 'non-specific cross-reacting antigen' (NCA) in the assay was small. The serum levels of BGP I were determined in healthy subjects, in patients with hepato-biliary diseases and in patients with various infectious or inflammatory disorders. Healthy individuals, including pregnant women, had a serum BGP I concentration of about 0.5-1 mg/l. Diseases of the liver or biliary tract (e.g. hepatitis A or B, cytomegalovirus hepatitis, obstructive jaundice or primary biliary cirrhosis) were associated with elevated serum levels of BGP I, as opposed to infectious diseases not affecting the liver mostly showing values within the normal range. Raised levels of serum BGP I activity may reflect biliary obstruction as a result of interference with normal BGP I secretion to the bile.

  9. Molecular cloning of a cDNA coding biliary glycoprotein I: Primary structure of a glycoprotein immunologically crossreactive with carcinoembryonic antigen

    SciTech Connect

    Hinoda, Y.; Neumaier, M.; Hefta, S.A.; Drzeniek, Z.; Wagener, C.; Shively, L.; Hefta, L.J.F.; Shively, J.E.; Paxton, R.J.

    1988-09-01

    The authors have isolated and sequenced four overlapping cDNA clones from a normal adult human colon library, which together gave the entire nucleotide sequence for biliary glycoprotein I (BGPI). BGPI is a member of the carcinoembryonic antigen (CEA) gene family, which is a subfamily in the immunoglobulin gene superfamily. The deduced amino acid sequence of the combined clones for BGP I revealed a 34-residue leader sequence followed by a 108-residue N-terminal domain, a 178-residue immunoglobulin-like domain, a 108-residue region specific to BGP I, a 24-residue transmembrane domain, and a 35-residue cytoplasmic domain. The nucleotide sequence of BGP I exhibited greater than 80% identity with CEA and nonspecific crossreacting antigen (NCA) in the leader peptide, N-terminal domain, and immunoglobulin-like domain. They propose that BGP I diverged from NCA by acquiring an immunoglobulin-like domain substantially different from the domains found in NCA or CEA and also a new cytoplasmic domain. The latter feature should result in a substantially different membrane anchorage mechanism of BGP I compared to CEA, which lacks the cytoplasmic domain and is anchored via a phosphatidylinositol-glycan structure. Protein structural analysis of BGP I isolated from human bile revealed a blocked N terminus, 129 amino acids of internal sequence that are in agreement with the translated cDNA sequence, and five glycosylation sites in the peptides sequenced.

  10. Biliary extracorporeal shockwave lithotripsy.

    PubMed

    Rawat, B; Burhenne, H J

    1990-01-01

    Biliary extracorporeal lithotripsy has been considered one of the alternatives to surgery for the treatment of gallstones in the bile ducts and in the gallbladder. Although this technique can fragment almost all gallstones, the clinical effectiveness of this new treatment modality must be measured by successful elimination of all fragments. Some physical principles, stone targeting, patient protocol, complications, and clinical results are presented.

  11. Role of stents and laser therapy in biliary strictures

    NASA Astrophysics Data System (ADS)

    Chennupati, Raja S.; Trowers, Eugene A.

    2001-05-01

    The most frequent primary cancers causing malignant obstructive jaundice were pancreatic cancer (57%), hilar biliary cancer (19% including metastatic disease), nonhilar biliary cancer (14%) and papillary cancer (10%). Endoscopic stenting has widely replaced palliative surgery for malignant biliary obstruction because of its lower risk and cost. Self-expandable metal stents are the preferred mode of palliation for hilar malignancies. Plastic stents have a major role in benign biliary strictures. Major complications and disadvantages associated with metallic stents include high cost, cholangitis. malposition, migration, unextractability, and breakage of the stents, pancreatitis and stent dysfunction. Dysfunction due to tumor ingrowth can be relieved by thermal methods (argon plasma coagulator therapy). We present a concise review of the efficacy of metallic stents for palliation of malignant strictures.

  12. Endoscopic ultrasound-guided biliary drainage of hilar biliary obstruction.

    PubMed

    Park, Do Hyun

    2015-09-01

    Only 20-30% of patients with hilar cholangiocarcinoma (CC) are candidates for potentially curative resection. However, even after curative (R0) resection, these patients have a disease recurrence rate of up to 76%. The prognosis of hilar cholangiocarcinoma (CC) is limited by tumor spread along the biliary tree leading to obstructive jaundice, cholangitis, and liver failure. Therefore, palliative biliary drainage may be a major goal for patients with hilar CC. Endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is an established method for palliation of patients with malignant biliary obstruction. However, there are patients for whom endoscopic stent placement is not possible because of failed biliary cannulation or tumor infiltration that limits transpapillary access. In this situation, percutaneous transhepatic biliary drainage (PTBD) is an alternative method. However, PTBD has a relatively high rate of complications and is frequently associated with patient discomfort related to external drainage. Endoscopic ultrasound-guided biliary drainage has therefore been introduced as an alternative to PTBD in cases of biliary obstruction when ERCP is unsuccessful. In this review, the indications, technical tips, outcomes, and the future role of EUS-guided intrahepatic biliary drainage, such as hepaticogastrostomy or hepaticoduodenostomy, for hilar biliary obstruction will be summarized.

  13. Intraluminal biliary obstruction.

    PubMed Central

    Heaton, N D; Davenport, M; Howard, E R

    1991-01-01

    Jaundice caused by intraluminal bile duct obstruction in infancy is rare but may occur in association with biliary sludge, inspissated bile plugs, or gall stones. Nine boys (aged 2 weeks-6 months) with obstruction caused by inspissated bile (n = 7) or gall stones (n = 2) are presented. Haemolysis was not a factor in the patients' histories but an abnormal entry of the common bile duct into the third part of the duodenum was demonstrated in two and one had an asymptomatic haemangioma. Ultrasonography was the most useful investigation. Surgical removal of the bile duct obstruction was necessary in eight cases and included biliary tract drainage in six and cholecystectomy for changes of cholecystitis in four. Obstruction resolved spontaneously in one infant after percutaneous cholangiography. There were no postoperative complications. Images p1396-a PMID:1776884

  14. Biliary ascariasis. A case report.

    PubMed

    Sarihan, H; Gürkök, S; Sari, A

    1995-01-01

    Ascaris lumbricoides is a worldwide intestinal infestation that may cause various complications. Biliary ascariasis, however, is a rare condition. We describe a child with biliary ascariasis. The patient's clinical symptoms were pain, vomiting and abdominal tenderness, and she was thought to have acute appendicitis. However, laboratory examination revealed high serum alkaline phosphatase and amylase levels, and ultrasonography and percutaneous cholangiography demonstrated biliary ascariasis. The patient was successfully treated with mebendazole and antispasmolytic drugs.

  15. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

    PubMed Central

    Saich, Rebecca; Chapman, Roger

    2008-01-01

    Primary sclerosing cholangitis (PSC) is a chronic progressive disorder of unknown aetiology characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include itch and lethargy and in advanced cases cholangitis and end-stage liver disease, however increasing numbers of asymptomatic individuals are being identified. The disease is rare in the general population but is strongly associated with inflammatory bowel disease (IBD) affecting up to 5% of patients with Ulcerative Colitis, with a slightly lower prevalence (up to 3.6%) in Crohn's disease. The strength of this association means that the vast majority (> 90%) of patients with PSC also have IBD, although many may have only mild gastro-intestinal symptoms. Usually IBD presents before PSC, although vice-versa can occur and the onset of both conditions can be separated in some cases by many years. Mean age of diagnosis of PSC is in the fifth decade of life with a strong male predominance. Risk is increased in those with a family history of PSC, suggesting a genetic predisposition and the disease is almost exclusive to non-smokers. The ulcerative colitis associated with PSC is characteristically mild, runs a quiescent course, is associated with rectal sparing, more severe right sided disease, backwash ileitis and has a high risk of pouchitis post-colectomy. Most worrisome is the high risk of colorectal malignancy which necessitates routine colonoscopic surveillance. Cholangiocarcinoma is also a frequent complication of PSC with a 10%-15% lifetime risk of developing this condition. Treatment with high dose ursodeoxycholic acid offers some chemoprotective effects against colorectal malignancy and may decrease symptoms, biochemical and histological progression of liver disease. Small duct PSC patients characteristically have normal cholangiography, and liver biopsy is required for diagnosis, it appears to have a more favourable prognosis. Autoimmune Hepatitis (AIH) is also more prevalent

  16. Transjugular Insertion of Biliary Stents (TIBS) in Two Patients with Malignant Obstruction, Ascites, and Coagulopathy

    SciTech Connect

    Amygdalos, Michael A.; Haskal, Ziv J.; Cope, Constantin; Kadish, Steven L.; Long, William B.

    1996-03-15

    Two patients with pancreatic malignancies presented with biliary obstruction which could not be treated from an endoscopic approach. Standard transhepatic biliary drainage was relatively contraindicated because of moderate ascites and coagulopathy related to underlying liver disease. In one patient, a transjugular, transvenous approach was used to deliver a Wallstent endoprosthesis across the distal common bile duct obstruction in a single step procedure. In the second case, a previously placed biliary Wallstent was revised with an additional stent from a similar approach. Transjugular biliary catheterization offers a valuable alternative approach for primary stent placement or revision in patients with contraindication to standard transhepatic drainage.

  17. Synthesis of diastereomerically pure Lys(Nε-lipoyl) building blocks and their use in Fmoc/tBu solid phase synthesis of lipoyl-containing peptides for diagnosis of primary biliary cirrhosis.

    PubMed

    Rentier, Cédric; Pacini, Giulia; Nuti, Francesca; Peroni, Elisa; Rovero, Paolo; Papini, Anna Maria

    2015-05-01

    Primary Biliary Cirrhosis is an immune-mediated disease in which one of the epitopes recognized by antimitochondrial autoantibodies is a lipoylated fragment of the PDC-E2 protein. Accordingly, the synthesis of lipoylated peptides as diagnostic tools is a relevant target. Up to now, the proper tools for the introduction of lipoylation on building blocks to be used in Fmoc/tBu solid phase peptide synthesis (SPPS) are lacking, and the role of chirality in lipoylation remains poorly studied. In this paper, we present the synthesis of lipoylated lysine derivatives as pure diastereomeric building blocks suitable for Fmoc/tBu SPPS and their introduction in relevant peptide sequences to possibly serve as synthetic probes for the development of novel diagnostic tools for this disease. The optimization of the synthesis of lipoylated building blocks derived from racemic, (R)-, and (S)-α-lipoic acid is described. Synthesis of peptide probes incorporating lipoylation is described. An insight regarding the cleavage of lipoylated peptides is given, as well as a method to oxidize or reduce the 1,2-dithiolane ring of the lipoyl moiety directly on the peptide without any subsequent purification. PMID:25820084

  18. High Uptake of FDG Along a Biliary Stent

    PubMed Central

    Nagasaki, Yasunari; Yamane, Hiromichi; Ochi, Nobuaki; Honda, Yoshihiro; Takigawa, Nagio

    2016-01-01

    Abstract A 66-year-old woman presented with abdominal discomfort. Contrast-enhanced CT revealed a mass in the pancreas and multiple liver metastases. Pathological examination confirmed the mass to be primary pancreatic cancer. Endoscopic insertion of a biliary stent was performed to prevent common bile duct obstruction. Subsequently, she received combination chemotherapy, which resulted in a complete response. FDG-PET-CT after chemotherapy revealed a high uptake of FDG along the outline of the biliary stent, with complete disappearance of both the primary and metastatic tumors. PMID:27607171

  19. Pigment gallstone pathogenesis: slime production by biliary bacteria is more important than beta-glucuronidase production.

    PubMed

    Stewart, L; Ponce, R; Oesterle, A L; Griffiss, J M; Way, L W

    2000-01-01

    Pigment stones are thought to form as a result of deconjugation of bilirubin by bacterial beta-glucuronidase, which results in precipitation of calcium bilirubinate. Calcium bilirubinate is then aggregated into stones by an anionic glycoprotein. Slime (glycocalyx), an anionic glycoprotein produced by bacteria causing foreign body infections, has been implicated in the formation of the precipitate that blocks biliary stents. We previously showed that bacteria are present within the pigment portions of gallstones and postulated a bacterial role in pigment stone formation through beta-glucuronidase or slime production. Ninety-one biliary bacterial isolates from 61 patients and 12 control stool organisms were tested for their production of beta-glucuronidase and slime. The average slime production was 42 for biliary bacteria and 2.5 for stool bacteria (P <0.001). Overall, 73% of biliary bacteria and 8% of stool bacteria produced slime (optical density >3). In contrast, only 38% of biliary bacteria produced beta-glucuronidase. Eighty-two percent of all patients, 90% of patients with common bile duct (CBD) stones, 100% of patients with primary CBD stones, and 93% of patients with biliary tubes had one or more bacterial species in their stones that produced slime. By comparison, only 47% of all patients, 60% of patients with CBD stones, 62% of patients with primary CBD stones, and 50% of patients with biliary tubes had one or more bacteria that produced beta-glucuronidase. Most biliary bacteria produced slime, and slime production correlated better than beta-glucuronidase production did with stone formation and the presence of biliary tubes or stents. Patients with primary CBD stones and biliary tubes had the highest incidence of slime production. These findings suggest that bacterial slime is important in gallstone formation and the blockage of biliary tubes.

  20. Biliary scintigraphy in acute pancreatitis

    SciTech Connect

    Serafini, A.N.; Al-Sheikh, W.; Barkin, J.S.; Hourani, M.; Sfakiankis, G.; Clarke, L.P.; Ashkar, F.S.

    1982-08-01

    A prospective study was carried out in 60 patients to determine the efficacy of /sup 99m/Tc-PIPIDA scintigraphy in differentiating biliary pancreatitis from nonbiliary pancreatitis. Forty patients were classified as having biliary pancreatitis and 20 patients as having the nonbiliary type. Scintigraphic scans were divided into five main types according to the time to visualization of the gallbladder and the time to excretion of /sup 99m/Tc-PIPIDA into the intestinal tract. Normal scans were obtained on 95% of patients (19/20) with nonbiliary pancreatitis; 22.5% of patients (9/40) with biliary pancreatitis had normal scans. It is concluded that elevated amylase levels together with an abnormal biliary scan, as defined by the criteria presented here, indicate biliary pancreatitis, while a normal scan largely excludes such diagnosis.

  1. Biliary scintigraphy in acute pancreatitis

    SciTech Connect

    Serafini, A.N.; Al-Sheikh, W.; Barkin, J.S.; Hourani, M.; Sfakiankis, G.; Clarke, L.P.; Ashkar, F.S.

    1982-08-01

    A prospective study was carried out in 60 patients to determine the efficacy of /sup 99//sup m/Tc-PIPIDA scintigraphy in differentiating biliary pancreatitis from nonbiliary pancreatitis. Forty patients were classified as having biliary pancreatitis and 20 patients as having the nonbiliary type. Scintigraphic scans were divided into five main types according to the time to visualization of the gallbladder and the time to excretion of /sup 99//sup m/Tc-PIPIDA into the intestinal tract. Normal scans were obtained in 95% of patients (19/20) with nonbiliary pancreatitis; 22.5% of patients (9/40) with biliary pancreatitis had normal scans. It is concluded that elevated amylase levels together with an abnormal biliary scan, as defined by the criteria presented here, indicate biliary pancreatitis, while a normal scan largely excludes such diagnosis.

  2. CD8 T cells mediate direct biliary ductule damage in NOD autoimmune biliary disease

    PubMed Central

    Yang, Guo-Xiang; Wu, Yuehong; Tsukamoto, Hiroki; Leung, Patrick S.; Lian, Zhe-Xiong; Rainbow, Daniel B.; Hunter, Kara M.; Morris, Gerard A.; Lyons, Paul A.; Peterson, Laurence B.; Wicker, Linda S.; Gershwin, M.E.; Ridgway, William M.

    2016-01-01

    We previously described the NOD.c3c4 mouse, which is protected from type 1 diabetes (T1D) due to protective alleles at multiple insulin-dependent diabetes (Idd) genes, but develops autoimmune biliary disease (ABD) resembling primary biliary cirrhosis (PBC). Here we characterize the NOD.ABD strain, which is genetically-related to the NOD.c3c4 strain but develops both ABD and T1D. Histologically, NOD.ABD biliary disease is indistinguishable from that in NOD.c3c4 mice. The frequency of effector memory (CD44+CD62L-) and central memory (CD44+CD62L+) CD8 T cells is significantly increased in the intrahepatic lymphocyte fraction of NOD.ABD mice, and NOD.ABD CD8 T cells produce more IFN-γ and TNF-α, compared to controls. NOD.ABD splenocytes can transfer ABD and T1D to NOD.c3c4 scid mice, but only T1D to NOD scid mice, suggesting that the genetic origin of the target organ and/or its innate immune cells is critical to disease pathogenesis. The disease transfer model, importantly, shows that biliary duct damage (characteristic of PBC) and inflammation precede biliary epithelial cell proliferation. Unlike T1D where both CD4 and CD8 T cells are required for disease transfer, purified NOD.ABD CD8 T cells can transfer liver inflammation into NOD.c3c4 scid recipients, and disease transfer is ameliorated by co-transferring T regulatory cells. Unlike NOD.c3c4 mice, NOD.ABD mice do not develop antinuclear or anti-Smith autoantibodies; however, NOD.ABD mice do develop the anti-pyruvate dehydrogenase antibodies typical of human PBC. The NOD.ABD strain is a model of immune dysregulation affecting two organ systems, most likely by mechanisms that do not completely coincide. PMID:21169553

  3. Biliary Complications After Liver Transplantation.

    PubMed

    Jagannath, Sanjay; Kalloo, Anthony N.

    2002-04-01

    The incidence of biliary complications after liver transplant is estimated to be 8% to 20%. Post-liver transplant biliary complications may lead to acute and chronic liver injury. The early recognition and prompt treatment of such complications improves the long-term survival of the patient and graft. An understanding of the type of biliary reconstruction, the rationale for creating a particular anastomosis, and the technical difficulties in reconstructing the biliary tract are important in assessing and managing complications after liver transplant. Because the clinical presentation of these patients may be subtle, the physician must be aggressive and thoughtful in ordering and interpreting the diagnostic tests. Important points to remember are 1) that noninvasive examinations may fail to detect small obstructions or leaks, 2) a liver biopsy often is performed prior to cholangiography to exclude rejection and ischemia, and 3) the liver biopsy can miss an extrahepatic obstruction by misinterpreting portal inflammation as rejection. Biliary leaks and strictures are the most common biliary complications following liver transplant. Less common complications include ampullary dysfunction and stone/sludge formation. The effective management of biliary complications following a liver transplant depends on understanding the natural history, the prognosis, and the available therapeutic options for each type of complication.

  4. Newborn Screening for Biliary Atresia

    PubMed Central

    Wang, Kasper S.

    2016-01-01

    Biliary atresia is the most common cause of pediatric end-stage liver disease and the leading indication for pediatric liver transplantation. Affected infants exhibit evidence of biliary obstruction within the first few weeks after birth. Early diagnosis and successful surgical drainage of bile are associated with greater survival with the child’s native liver. Unfortunately, because noncholestatic jaundice is extremely common in early infancy, it is difficult to identify the rare infant with cholestatic jaundice who has biliary atresia. Hence, the need for timely diagnosis of this disease warrants a discussion of the feasibility of screening for biliary atresia to improve outcomes. Herein, newborn screening for biliary atresia in the United States is assessed by using criteria established by the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children. Published analyses indicate that newborn screening for biliary atresia by using serum bilirubin concentrations or stool color cards is potentially life-saving and cost-effective. Further studies are necessary to evaluate the feasibility, effectiveness, and costs of potential screening strategies for early identification of biliary atresia in the United States. PMID:26620065

  5. Biliary sequelae of endoscopic sphincterotomy.

    PubMed Central

    Greenfield, C.; Cleland, P.; Dick, R.; Masters, S.; Summerfield, J. A.; Sherlock, S.

    1985-01-01

    Twenty five patients were reviewed a mean of 36 months after successful endoscopic sphincterotomy for the removal of bile duct stones. All the patients had improved symptomatically but 20% had episodes of mild abdominal pain and a similar number had elevated serum gamma glutamyltranspeptidase activities (up to 3 times normal). In 12 patients (50%) biliary gas was demonstrated indicating reflux of duodenal contents. Clinical cholangitis did not occur. Aspiration liver biopsy revealed mild portal tract fibrosis and inflammation in patients with biliary reflux. Biliary reflux was significantly associated with mild upper abdominal pain (P less than 0.05). This study has shown that mild abnormalities of biliary function persist after endoscopic sphincterotomy. The long term consequence of these changes is unclear. PMID:2858846

  6. Spontaneous biliary peritonitis in children.

    PubMed

    Kohli, Supreethi; Singhal, Anu; Arora, Anita; Singhal, Sanjeev

    2013-01-01

    Pediatric Spontaneous Bile duct perforation is a rare clinical condition with only around 150 cases reported worldwide. Early management gives excellent prognosis but the condition often presents a diagnostic dilemma. Hepato-biliary Technetium-99m-iminodiacetic acid scintiscan is the diagnostic investigation of choice but its availability in third world countries is limited. We present two cases of spontaneous biliary peritonitis in children, which were diagnosed without scintiscanning. The first case was a one-and -a half-year-old child, who was diagnosed with biliary peritonitis without pneumoperitoneum by a combination of Ultrasound (USG), Contrast enhanced computed tomography (CECT), and Magnetic Resonance Imaging (MRI). The child underwent USG-guided drainage and subsequent cholecystectomy with hepatico-jejunostomy. The second child also had biliary peritonitis without pneumoperitoneum, which was initially suspected on USG. CECT revealed dilated gall bladder and fluid collection in sub-hepatic space and pelvis. Abdominal paracentesis revealed presence of bile. The child responded to conservative therapy. Both are doing well on two-year follow-up. In a patient with jaundice, biliary tract abnormalities and/or free fluid, either generalized or localized to peri-cholecystic/sub-hepatic space on USG/CT/MRI, in the absence of pneumoperitoneum, suggest a diagnosis of biliary perforation even in the absence of scintiscanning.

  7. Spontaneous Biliary Peritonitis in Children

    PubMed Central

    Kohli, Supreethi; Singhal, Anu; Arora, Anita; Singhal, Sanjeev

    2013-01-01

    Pediatric Spontaneous Bile duct perforation is a rare clinical condition with only around 150 cases reported worldwide. Early management gives excellent prognosis but the condition often presents a diagnostic dilemma. Hepato-biliary Technetium-99m-iminodiacetic acid scintiscan is the diagnostic investigation of choice but its availability in third world countries is limited. We present two cases of spontaneous biliary peritonitis in children, which were diagnosed without scintiscanning. The first case was a one-and -a half-year-old child, who was diagnosed with biliary peritonitis without pneumoperitoneum by a combination of Ultrasound (USG), Contrast enhanced computed tomography (CECT), and Magnetic Resonance Imaging (MRI). The child underwent USG-guided drainage and subsequent cholecystectomy with hepatico-jejunostomy. The second child also had biliary peritonitis without pneumoperitoneum, which was initially suspected on USG. CECT revealed dilated gall bladder and fluid collection in sub-hepatic space and pelvis. Abdominal paracentesis revealed presence of bile. The child responded to conservative therapy. Both are doing well on two-year follow-up. In a patient with jaundice, biliary tract abnormalities and/or free fluid, either generalized or localized to peri-cholecystic/sub-hepatic space on USG/CT/MRI, in the absence of pneumoperitoneum, suggest a diagnosis of biliary perforation even in the absence of scintiscanning. PMID:24083062

  8. Biliary calcium and gallstone formation.

    PubMed

    Moore, E W

    1990-09-01

    The purpose of this paper is to present a brief overview of the current status of the field of biliary calcium and the role of calcium in the formation and maturation of gallstones. The study of free Ca+(+) ions in bile by electrochemical potentiometric measurements using Ca+(+)-selective ion-exchange electrodes is a relatively new field, but much progress has been made in the past few years. Using this powerful analytical tool, new concepts and findings have arisen in almost every aspect of biliary calcium. Although the current symposium is targeted primarily toward cholesterol gallstones, there are several areas in which understanding of biliary calcium may significantly contribute to a better understanding of the pathogenesis of cholesterol, as well as "pigment" (calcium salt), gallstones. Five broad areas are considered in relation to biliary calcium: (a) physiology (calcium entry into bile), (b) biophysics (the regulation of biliary free [Ca+(+)] as related to Gibbs-Donnan equilibria, (c) physical chemistry (the physicochemical state of calcium in bile, (d) thermodynamics (calcium solubility in bile), and (e) kinetics (pronucleating and antinucleating factors and metastable states). With more specific reference to cholesterol stones, consideration is also made of (a) the calcium salt "seed" hypothesis in cholesterol stone pathogenesis; (b) the interactions of Ca+(+) with phospholipid-cholesterol vesicles, with consideration of possible structural requirements and (c) thermodynamic and kinetic factors as related to peripheral or "eggshell" calcification of existing cholesterol stones. PMID:2210651

  9. Oldest biliary endoprosthesis in situ

    PubMed Central

    Consolo, Pierluigi; Scalisi, Giuseppe; Crinò, Stefano F; Tortora, Andrea; Giacobbe, Giuseppa; Cintolo, Marcello; Familiari, Luigi; Pallio, Socrate

    2013-01-01

    The advantages of endoscopic retrograde cholangiopancreatography over open surgery have made it the predominant method of treating patients with choledocholithiasis. After sphincterotomy, however, 10%-15% of common bile duct stones cannot be removed with a basket or balloon. The methods for managing “irretrievable stones” include surgery, mechanical lithotripsy, intraductal or extracorporeal shock wave lithotripsy and biliary stenting. The case presented was a referred 82-year-old Caucasian woman with a 7-year-old plastic biliary endoprosthesis in situ. To the best of our knowledge the examined endoprosthesis is the oldest endoprosthesis in situ reported in the literature. Endoscopic biliary endoprosthesis placement remains a simple and safe procedure for patients with stones that are difficult to manage by conventional endoscopic methods and for patients who are unfit for surgery or who are high surgical risks. To date no consensus has been reached regarding how long a biliary prosthesis should remain in situ. Long-term biliary stenting may have a role in selected elderly patients if stones extraction has failed because the procedure may prevent stones impaction and cholangitis. PMID:23858381

  10. Biliary sludge: the sluggish gallbladder.

    PubMed

    Pazzi, P; Gamberini, S; Buldrini, P; Gullini, S

    2003-07-01

    Biliary sludge is a mixture of particulate matter which has precipitated from bile. It generally consists of cholesterol monohydrate crystals, calcium bilirubinate or other calcium salts. In a clinical setting, biliary sludge is almost always an ultrasonographic diagnosis. Although it is less clinically applicable, direct microscopic examination of gallbladder bile is far more sensitive than ultrasonography into sludge detection, and has to be regarded as the diagnostic gold standard. The overall prevalence of sludge in the general population is relatively low. However, several clinical conditions are associated with a particularly high prevalence of biliary sludge, including pregnancy, rapid weight loss, total parenteral nutrition, octreotide therapy, bone marrow or solid organ transplantation. The clinical course of biliary sludge varies, and complete resolution, a waxing and waning course, and progression to gallstones are all possible outcomes. It may cause complications usually associated with gallstones, such as biliary colic, acute cholecystitis, and acute pancreatitis. The main pathogenic mechanism involved in sludge formation is probably gallbladder dismotility, and in selected patients measures aimed to maintain adequate gallbladder contractions has been shown to effectively prevent sludge development.

  11. Biliary scintigraphy: comparison with other modern techniques for evaluation of biliary tract disease

    SciTech Connect

    Serafini, A.N.

    1982-10-01

    The recent availability of iminodiacetic acid analogues labeled with technetium Tc 99m provides a safe and accurate noninvasive test of biliary function. Biliary scintigraphy is a simple and rapid method of detecting acute cholecystitis in particular but also of distinguishing acute biliary pancreatitis from nonbiliary pancreatitis, of evaluating the patency of the common duct in early obstruction, of assessing possible postcholecystectomy syndrome, of evaluating the patency of a biliary enteric bypass, and of detecting postoperative biliary leaks.

  12. Metallic stents in malignant biliary obstruction

    SciTech Connect

    Rieber, Andrea; Brambs, Hans-Juergen

    1997-01-15

    Purpose. Retrospective analysis of our results with metallic stent placement for malignant biliary strictures. We sought to determine parameters that influence stent patency. Methods. A total of 95 Wallstents were implanted in 65 patients (38 men, 27 women; mean age, 65.1 years) with malignant biliary obstruction. Serum bilirubin levels were assessed in 48 patients; the mean value prior to intervention was 15.0 mg/dl. Results. In 12 patients (21%) complications occurred as a result of percutaneous transhepatic drainage. Stent implantation was complicated in 13 patients, but was possible in all patients. A significant decrease in bilirubin level was seen in 83.3% of patients following stent implantation. Approximately 30% of patients developed recurrent jaundice after a mean 97.1 days. In 9 patients (15%) the recurrent jaundice was caused by stent occlusion due to tumor growth. The mean follow-up was 141.8 days, the mean survival 118.7 days. Patients with cholangiocarcinomas and gallbladder carcinomas had the best results. Worse results were seen in patients with pancreatic tumors and with lymph node metastases of colon and gastric cancers. Conclusions. The main predictive factors for occlusion rate and survival are the type of primary tumor, tumor stage, the decrease in bilirubin level, and the general condition of the patient.

  13. [Radiodiagnosis of patients with primary sclerosing cholangitis].

    PubMed

    Sharipov, V Sh

    2001-01-01

    Among diseases of the hepatobiliary system, primary sclerosing cholangitis is an undetectable disorder of the biliary tract rather than a rare nosological entity, complex radiation study is of great importance in its preoperative diagnosis. Among direct methods for contrasting the biliary tract, the authors gave preference to percutaneous transhepatic cholangiography that allows the dilated biliary tract to be contrasted virtually in 100% of cases. The specific features of X-ray semiotics of primary sclerosing cholangitis were identified in 17 patients.

  14. Endoscopic management of benign biliary strictures

    PubMed Central

    Visrodia, Kavel H; Tabibian, James H; Baron, Todd H

    2015-01-01

    Endoscopic management of biliary obstruction has evolved tremendously since the introduction of flexible fiberoptic endoscopes over 50 years ago. For the last several decades, endoscopic retrograde cholangiopancreatography (ERCP) has become established as the mainstay for definitively diagnosing and relieving biliary obstruction. In addition, and more recently, endoscopic ultrasonography (EUS) has gained increasing favor as an auxiliary diagnostic and therapeutic modality in facilitating decompression of the biliary tree. Here, we provide a review of the current and continually evolving role of gastrointestinal endoscopy, including both ERCP and EUS, in the management of biliary obstruction with a focus on benign biliary strictures. PMID:26322153

  15. Percutaneous transhepatic management of complex biliary problems.

    PubMed Central

    Zuidema, G D; Cameron, J L; Sitzmann, J V; Kadir, S; Smith, G W; Kaufman, S L; White, R I

    1983-01-01

    A series of 27 patients with complex biliary problems secondary to previous biliary operations is presented. The patients are divided into two groups: (1) patients with acute perioperative biliary problems; all had biliary leak with abscess, biliary cutaneous fistula, and/or stricture following cholecystectomy or common duct exploration and (2) patients with chronic postoperative biliary problems; all had previous repair of biliary stricture or injuries with late stricture formation. Early management of all patients included placement of a percutaneous biliary stent. Abscesses were drained operatively, and biliary leaks or fistulas were allowed to close spontaneously. Jaundice and cholangitis were allowed to resolve. Following stabilization, management of stricture, if present, was addressed. Eight acute patients had strictures, of which four were partial and three were dilated percutaneously. Four were complete and required operative repair. All 12 chronic patients had strictures, of which six were partial and successfully managed with percutaneous dilatation. Four patients also had common duct stones which were successfully crushed percutaneously. The authors conclude that percutaneous transhepatic drainage offers significant advantages in the early stabilization and treatment of patients with complex biliary problems, and that partial strictures of the biliary tree may be managed successfully by percutaneous dilatation. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. Fig. 11. PMID:6847278

  16. Spontaneously removed biliary stent drainage versus T-tube drainage after laparoscopic common bile duct exploration.

    PubMed

    Xu, Yakun; Dong, Chengyong; Ma, Kexin; Long, Fei; Jiang, Keqiu; Shao, Ping; Liang, Rui; Wang, Liming

    2016-09-01

    Several studies have shown the safety and feasibility of laparoscopic common bile duct exploration (LCBDE) as a minimally invasive treatment options for choledocholithiasis. Use of T-tube or biliary stent drainage tube placement after laparoscopic choledochotomy for common bile duct (CBD) stones is still under debate. This study tried to confirm the safety of spontaneously removable biliary stent in the distal CBD after LCBDE to allow choledochus primary closure. A total of 47 patients with choledocholithiasis underwent LCBDE with primary closure and internal drainage using a spontaneously removable biliary stent drainage tube (stent group, N = 22) or T-tube (T-tube group, N = 25). Operative parameters and outcomes are compared. Surgical time, intraoperative blood loss, length of hospital stay, drainage tube removal time, postoperative intestinal function recovery, and cost of treatment were all significantly lower in the stent group as compared to that in the T-tube group (P < 0.05 for all). Otherwise, Bile leakage between the two groups had no significant difference (P > 0.05). The biliary stent drainage tube was excreted spontaneously 4 to 14 days after surgery with the exception of one case, where endoscopic removal of biliary tube was required due to failure of its spontaneous discharge. LCBDE with primary closure and use of spontaneously removable biliary stent drainage showed advantage over the use of traditional T-tube drainage in patients with choledocholithiasis.

  17. Management of Benign Biliary Strictures

    SciTech Connect

    Laasch, Hans-Ulrich; Martin, Derrick F.

    2002-12-15

    Benign biliary strictures are most commonly a consequence of injury at laparoscopic cholecystectomy or fibrosis after biliary-enteric anastomosis. These strictures are notoriously difficult to treat and traditionally are managed by resection and fashioning of acholedocho- or hepato-jejunostomy. Promising results are being achieved with newer minimally invasive techniques using endoscopic or percutaneous dilatation and/or stenting and these are likely to play an increasing role in the management. Even low-grade biliary obstruction carries the risks of stone formation, ascending cholangitis and hepatic cirrhosis and it is important to identify and treat this group of patients. There is currently no consensus on which patient should have what type of procedure, and the full range of techniques may not be available in all hospitals. Careful assessment of the risks and likely benefits have to be made on an individual basis. This article reviews the current literature and discusses the options available. The techniques of endoscopic and percutaneous dilatation and stenting are described with evaluation of the likely success and complication rates and compared to the gold standard of biliary-enteric anastomosis.

  18. [Biliary atresia and polysplenia syndrome].

    PubMed

    Kerkeni, Yosra; Ksia, Amine; Zitouni, Hayet; Belghith, Mohsen; Lassad, Sahnoun; Krichene, Imed; Mekki, Mongi; Nouri, Abdellatif

    2015-01-01

    Polysplenia syndrome is a rare malformation characterized by the association of multiple rates and other congenital anomalies dominated by cardiac, vascular, intestinal and bile malformations. We report the observation of a patient operated in the neonatal period (3 days) for an upper intestinal obstruction with situs inversus. Surgical exploration noted the presence of multiple rates, a preduodenal vein, a biliary atresia and a duodenal atresia. The surgical procedures performed were a latero-lateral duodeno-duodenostomy and hepatoportoenterostomy of KASAI with simple immediate and delayed outcomes. The follow up was of 23 years. We recall the epidemiological characteristics of this malformative association and we discuss the role played by the prognosis of polysplenia syndrome in the evolution of biliary atresia. The diagnosis and treatment of biliary atresia are always urgent to increase the chances of success of the Kasai, and the chances of prolonged survival with native liver. However, almost all long-term survivors (even anicteric) have biliary cirrhosis, which requires lifelong follow up. PMID:26815511

  19. Influence of the Biliary System on Biliary Bacteria Revealed by Bacterial Communities of the Human Biliary and Upper Digestive Tracts.

    PubMed

    Ye, Fuqiang; Shen, Hongzhang; Li, Zhen; Meng, Fei; Li, Lei; Yang, Jianfeng; Chen, Ying; Bo, Xiaochen; Zhang, Xiaofeng; Ni, Ming

    2016-01-01

    Biliary bacteria have been implicated in gallstone pathogenesis, though a clear understanding of their composition and source is lacking. Moreover, the effects of the biliary environment, which is known to be generally hostile to most bacteria, on biliary bacteria are unclear. Here, we investigated the bacterial communities of the biliary tract, duodenum, stomach, and oral cavity from six gallstone patients by using 16S rRNA amplicon sequencing. We found that all observed biliary bacteria were detectable in the upper digestive tract. The biliary microbiota had a comparatively higher similarity with the duodenal microbiota, versus those of the other regions, but with a reduced diversity. Although the majority of identified bacteria were greatly diminished in bile samples, three Enterobacteriaceae genera (Escherichia, Klebsiella, and an unclassified genus) and Pyramidobacter were abundant in bile. Predictive functional analysis indicated enhanced abilities of environmental information processing and cell motility of biliary bacteria. Our study provides evidence for the potential source of biliary bacteria, and illustrates the influence of the biliary system on biliary bacterial communities.

  20. Influence of the Biliary System on Biliary Bacteria Revealed by Bacterial Communities of the Human Biliary and Upper Digestive Tracts

    PubMed Central

    Ye, Fuqiang; Shen, Hongzhang; Li, Zhen; Meng, Fei; Li, Lei; Yang, Jianfeng; Chen, Ying; Bo, Xiaochen; Zhang, Xiaofeng; Ni, Ming

    2016-01-01

    Biliary bacteria have been implicated in gallstone pathogenesis, though a clear understanding of their composition and source is lacking. Moreover, the effects of the biliary environment, which is known to be generally hostile to most bacteria, on biliary bacteria are unclear. Here, we investigated the bacterial communities of the biliary tract, duodenum, stomach, and oral cavity from six gallstone patients by using 16S rRNA amplicon sequencing. We found that all observed biliary bacteria were detectable in the upper digestive tract. The biliary microbiota had a comparatively higher similarity with the duodenal microbiota, versus those of the other regions, but with a reduced diversity. Although the majority of identified bacteria were greatly diminished in bile samples, three Enterobacteriaceae genera (Escherichia, Klebsiella, and an unclassified genus) and Pyramidobacter were abundant in bile. Predictive functional analysis indicated enhanced abilities of environmental information processing and cell motility of biliary bacteria. Our study provides evidence for the potential source of biliary bacteria, and illustrates the influence of the biliary system on biliary bacterial communities. PMID:26930491

  1. Biliary pain in postcholecystectomy patients without biliary obstruction. A prospective radionuclide study.

    PubMed

    Grimon, G; Buffet, C; André, L; Etienne, J P; Desgrez, A

    1991-03-01

    Biliary pain without obvious biliary obstruction is common in postcholecystectomy patients. We studied 20 symptomatic patients with episodes of biliary-type pain after cholecystectomy (all having undergone endoscopic retrograde cholangiography), and in 18 asymptomatic postcholecystectomy controls. We performed quantitative hepatobiliary radionuclide analysis with dimethyl-imidodiacetic acid. From a series of 90 dynamic images at 1-min intervals using a gamma camera coupled to a computer, time-activity curves were produced in regions of interest in the liver, intrahepatic biliary tree, common duct, and heart, from which quantitative biliary excretion indexes were obtained. The results demonstrate a biliary kinetic dysfunction in patients with postcholecystectomy pain without morphological abnormalities. PMID:1995268

  2. Laparoscopic cholecystectomy in biliary pancreatitis.

    PubMed

    Graham, L D; Burrus, R G; Burns, R P; Chandler, K E; Barker, D E

    1994-01-01

    Laparoscopic cholecystectomy has emerged as the treatment of choice for uncomplicated cholelithiasis. Despite early concerns, many surgeons have applied this new technique to more complicated biliary tract disease states, including biliary pancreatitis. To evaluate the safety of laparoscopic cholecystectomy in this setting, we retrospectively reviewed 29 patients with clinical and laboratory evidence of biliary pancreatitis who underwent this procedure between March 1990 and December 1992. The severity of pancreatitis was determined by Ranson's criteria. Two patients had a Ranson's score of 6, one of 5, one of 4, five scored 3, nine scored 2, nine also scored 1, and two patients scored 0. The mean serum amylase level on admission was 1,610 (range 148 to 7680). All patients underwent laparoscopic cholecystectomy during the same hospital admission for biliary pancreatitis, with the mean time of operation being 5.5 days from admission. Operative time averaged 123 minutes (range 60-220 minutes). Intraoperative cholangiography was obtained in 76 per cent of patients. Three patients had choledocholithiasis on intraoperative cholangiography and were treated with choledochoscopy, laparoscopic common bile duct exploration, and saline flushing of the duct. The mean length of hospital stay was 11 days (range 5-32 days). There were seven postoperative complications requiring prolonged hospitalization with all but one treated non-operatively. One patient with a preoperative Ranson score of 6 developed necrotizing pancreatitis and subsequently required operative pancreatic debridement and drainage. There were no deaths in this series and no postoperative wound infections. The average recovery period for return to work was 2 weeks. These statistics compare favorably with literature reports for open cholecystectomy in biliary pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Autoimmune hepatitis from the paediatric perspective.

    PubMed

    Roberts, Eve A

    2011-11-01

    Autoimmune hepatitis (AIH) is an important entity within the broad spectrum of autoimmune hepatobiliary disease comprised of AIH, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since the 1960s, AIH has been investigated with extensive clinical research aimed at effective therapeutic intervention. It was one of the first liver diseases where treatment was demonstrated to prolong survival. AIH occurs in children, as well as in adults. Its clinical manifestations in children may differ from classic adult AIH. These differences have elucidated certain aspects of AIH and hepatobiliary disease in general. There are two major patterns of AIH: type 1, with anti-smooth muscle antibodies and type 2, with anti-liver/kidney microsomal antibodies. The second type of AIH was first identified in children and is more common in younger patients. AIH often presents as acute disease in children and also in adults: the nomenclature has dropped the allusion to chronicity. Some children who have sclerosing cholangitis present with clinical disease closely resembling AIH; this AIH-like PSC, termed autoimmune sclerosing cholangitis (ASC), is also found in adults. Children with AIH may have identifiable monogenic disorders of immune regulation such as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Like adults with AIH, children with AIH usually respond very favourably to immunosuppressive treatment with corticosteroids ± azathioprine. True cures seem to be rare, although many children achieve a stable remission. Nonetheless children with AIH may develop cirrhosis and some require liver transplantation. Early diagnosis and improved treatment strategies may further improve the outlook for children with AIH.

  4. Radiological interventions in malignant biliary obstruction

    PubMed Central

    Madhusudhan, Kumble Seetharama; Gamanagatti, Shivanand; Srivastava, Deep Narayan; Gupta, Arun Kumar

    2016-01-01

    Malignant biliary obstruction is commonly caused by gall bladder carcinoma, cholangiocarcinoma and metastatic nodes. Percutaneous interventions play an important role in managing these patients. Biliary drainage, which forms the major bulk of radiological interventions, can be palliative in inoperable patients or pre-operative to improve liver function prior to surgery. Other interventions include cholecystostomy and radiofrequency ablation. We present here the indications, contraindications, technique and complications of the radiological interventions performed in patients with malignant biliary obstruction. PMID:27247718

  5. Radiological interventions in malignant biliary obstruction.

    PubMed

    Madhusudhan, Kumble Seetharama; Gamanagatti, Shivanand; Srivastava, Deep Narayan; Gupta, Arun Kumar

    2016-05-28

    Malignant biliary obstruction is commonly caused by gall bladder carcinoma, cholangiocarcinoma and metastatic nodes. Percutaneous interventions play an important role in managing these patients. Biliary drainage, which forms the major bulk of radiological interventions, can be palliative in inoperable patients or pre-operative to improve liver function prior to surgery. Other interventions include cholecystostomy and radiofrequency ablation. We present here the indications, contraindications, technique and complications of the radiological interventions performed in patients with malignant biliary obstruction. PMID:27247718

  6. Hepatic Tuberculosis Mimicking Biliary Cystadenoma: A Radiological Dilemma.

    PubMed

    Sharma, Rajaram; Dey, Amit Kumar; Mittal, Kartik; Udmale, Prasad; Singh, Udai; Mitkar, Sumit; Hira, Priya

    2015-01-01

    Primary involvement of liver in tuberculosis is a rare entity. It is difficult to diagnose in absence of previous history of tuberculosis or concurrent pulmonary involvement. It is usually misdiagnosed as neoplastic liver lesion, which misdirects the treatment protocol and delays proper treatment. Here we are presenting a case of 36-year-old male patient with vague right upper quadrant abdominal pain. All the laboratory values were within normal limits. Radiological investigations were in favor of biliary cystadenoma but final diagnosis was primary focal involvement of liver in tuberculosis which was histopathologically proven to be tuberculous granulomas on biopsy of the resected mass. PMID:26504607

  7. Post-liver Transplant Biliary Complications.

    PubMed

    Atwal, Tegpal; Pastrana, Mariel; Sandhu, Bimaljit

    2012-03-01

    Biliary tract complications remain a common source of morbidity and mortality in liver transplant (LT) recipients with an estimated incidence of 5-30% after orthotopic LT and a mortality rate of up to 10%. Biliary complications after LT may be related to various factors including hepatic artery thrombosis or stenosis, ischemia reperfusion injury, immunologic injury, infections, donor pool, and technical issues which include imperfect anastomosis and T-tube-related complications. Management of the detected biliary complications includes nonsurgical and surgical methods. A majority of these post transplant biliary complications can be treated with endoscopic retrograde cholangiography. If unsuccessful, a percutaneous intervention or surgery may be required. In this article, we review the incidence, clinical presentation, and management of the main types of biliary complications.

  8. Biliary amylase and congenital choledochal dilatation.

    PubMed

    Davenport, M; Stringer, M D; Howard, E R

    1995-03-01

    The relationship between levels of biliary amylase measured at operation and clinical features was studied in a series of 55 children with congenital biliary dilatation (choledochal cyst) who presented between 1976 and 1993. There were 36 cystic and 19 fusiforms dilatations in the series. The most common modes of presentation were painless jaundice (n = 23) and pancreatitis (n = 22). Five infants presented with abnormal antenatal ultrasound examinations. Children with pancreatitis were older than those with painless jaundice (4.2 versus 1.5 years; P = .005), and a higher proportion had raised levels of biliary amylase (100% versus 44%; P < .0001). There was no difference in the age at presentation (P = .32), clinical mode of presentation (P = .3), or the level of biliary amylase (P = .25) between cystic and fusiform dilatations. A correlation was found between age at surgery and biliary amylase in the cystic (rs = 0.55; P = .001) but not in the fusiform group (P = .22). All infants with antenatal diagnoses were cystic dilatations. Choledochal cystic dilatations that were diagnosed antenatally did not have significant amylase reflux, suggesting that the aetiology of this subgroup is truly congenital. Children who present at a later age with pancreatitis invariably have high levels of biliary amylase, which is presumed to occur because of a common channel and reflux of biliary and pancreatic secretions.

  9. Radionuclide imaging of the biliary tract

    SciTech Connect

    Henry, R.E.; Daly, M.J.

    1981-01-01

    Cholescintigraphy with technetium-labeled biliary agents has great value in evaluation of the patient with suspected acute cholecystitis. Visualization of the gall bladder virtually excludes acute cholecystitis and obstruction of the cystic duct. Nonvisualization of the gall bladder, however, is not specific for acute cholecystitis and may also occur in some patients with chronic cholecystitis or pancreatitis. Interpretation of gall bladder nonvisualization, therefore, must be correlated with the clinical presentation. Biliary tract imaging is also useful in evaluation of some focal abnormalities within the liver, neonatal jaundice, detection of bile leaks or bile reflux, and biliary-enteric shunts. The role of technetium-labeled biliary agents in the evaluation of patients with jaundice is less clear. Excretion of tracer into the gut excludes complete biliary tract obstruction, but the test may be nonconclusive at higher serum bilirubin levels. If persistent common bile duct activity is observed with delayed excretion into the gut, the diagnosis of partial obstruction may be made, but this procedure will be inconclusive if the common bile duct is not visualized and/or significant hepatocellular disease is present. Ultrasonography and abdominal CT are the preferred tools for the diagnosis of biliary tract obstruction at present, but newer biliary tract agents which achieve better hepatic extraction and greater bile concentration at high serum bilirubin levels may improve the diagnostic efficacy of cholescintigraphy.

  10. B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia.

    PubMed

    Feldman, Amy G; Tucker, Rebecca M; Fenner, Erika K; Pelanda, Roberta; Mack, Cara L

    2013-01-01

    A leading theory regarding the pathogenesis of biliary atresia (BA) is that bile duct injury is initiated by a virus infection, followed by an autoimmune response targeting bile ducts. In experimental models of autoimmune diseases, B cells have been shown to play an important role. The aim of this study was to determine the role of B cells in the development of biliary obstruction in the Rhesus rotavirus (RRV)-induced mouse model of BA. Wild-type (WT) and B cell-deficient (Ig-α(-/-)) mice received RRV shortly after birth. Ig-α(-/-) RRV-infected mice had significantly increased disease-free survival rate compared to WT RRV-infected BA mice (76.8% vs. 17.5%). In stark contrast to the RRV-infected BA mice, the RRV-infected Ig-α(-/-) mice did not have hyperbilirubinemia or bile duct obstruction. The RRV-infected Ig-α(-/-) mice had significantly less liver inflammation and Th1 cytokine production compared to RRV-infected WT mice. In addition, Ig-α(-/-) mice had significantly increased numbers of regulatory T cells (Tregs) at baseline and after RRV infection compared to WT mice. However, depletion of Tregs in Ig-α(-/-) mice did not induce biliary obstruction, indicating that the expanded Tregs in the Ig-α(-/-) mice were not the sole reason for protection from disease. Conclusion : B cell deficient Ig-α(-/-) mice are protected from biliary obstruction in the RRV-induced mouse model of BA, indicating a primary role of B cells in mediating disease pathology. The mechanism of protection may involve lack of B cell antigen presentation, which impairs T-cell activation and Th1 inflammation. Immune modulators that inhibit B cell function may be a new strategy for treatment of BA.

  11. The Canadian Biliary Atresia Registry: Improving the care of Canadian infants with biliary atresia

    PubMed Central

    Butler, Alison E; Schreiber, Richard A; Yanchar, Natalie; Emil, Sherif; Laberge, Jean-Martin

    2016-01-01

    Biliary atresia is the most common cause of end-stage liver disease and liver cirrhosis in children, and the leading indication for liver transplantation in the paediatric population. There is no cure for biliary atresia; however, timely diagnosis and early infant age at surgical intervention using the Kasai portoenterostomy optimize the prognosis. Late referral is a significant problem in Canada and elsewhere. There is also a lack of standardized care practices among treating centres in this country. Biliary atresia registries currently exist across Europe, Asia and the United States. They have provided important evidence-based information to initiate changes to biliary atresia care in their countries with improvements in outcome. The Canadian Biliary Atresia Registry was initiated in 2013 for the purpose of identifying best standards of care, enhancing public education, facilitating knowledge translation and advocating for novel national public health policy programs to improve the outcomes of Canadian infants with biliary atresia. PMID:27398049

  12. Biliary complications after liver transplantation: a review.

    PubMed

    Verdonk, Robert C; Buis, Carlijn I; Porte, Robert J; Haagsma, Elizabeth B

    2006-01-01

    After liver transplantation, the prevalence of complications related to the biliary system is 6-35%. In recent years, the diagnosis and treatment of biliary problems has changed markedly. The two standard methods of biliary reconstruction in liver transplant recipients are the duct-to-duct choledochocholedochostomy and the Roux-en-Y-hepaticojejunostomy. Biliary leakage occurs in approximately 5-7% of transplant cases. Leakage from the site of anastomosis, the T-tube exit site and donor or recipient remnant cystic duct is well described. Symptomatic bile leakage should be treated by stenting of the duct by endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTCD). Biliary strictures can occur at the site of the anastomosis (anastomotic stricture; AS) or at other locations in the biliary tree (non-anastomotic strictures; NAS). AS occur in 5-10% of cases and are due to fibrotic healing. Treatment by ERCP or PTCD with dilatation and progressive stenting is successful in the majority of cases. NAS can occur in the context of a hepatic artery thrombosis, or with an open hepatic artery (ischaemic type biliary lesions or ITBL). The incidence is 5-10%. NAS has been associated with various types of injury, e.g. macrovascular, microvascular, immunological and cytotoxic injury by bile salts. Treatment can be attempted with multiple sessions of dilatation and stenting of stenotic areas by ERCP or PTCD. In cases of localized diseased and good graft function, biliary reconstructive surgery is useful. However, a significant number of patients will need a re-transplant. When biliary strictures or ischaemia of the graft are present, stones, casts and sludge can develop. PMID:16782628

  13. Endoscopic palliation of malignant biliary strictures

    PubMed Central

    Salgado, Sanjay M; Gaidhane, Monica; Kahaleh, Michel

    2016-01-01

    Malignant biliary strictures often present late after the window for curative resection has elapsed. In such patients, the goal of therapy is typically focused on palliation. While historically, palliative measures were performed surgically, the advent of endoscopic intervention offers minimally invasive options to provide relief of symptoms, improve quality of life, and in some cases, increase survival of these patients. Some of these therapies, such as endoscopic biliary decompression, have become mainstays of treatment for decades, whereas newer modalities, including radiofrequency ablation, and photodynamic therapy offer additional options for patients with incurable biliary malignancies. PMID:26989459

  14. Cholescintigraphy in extrahepatic biliary obstruction

    SciTech Connect

    Klingensmith, W.C.; Kuni, C.C.; Fritzberg, A.R.

    1982-07-01

    The effect of etiology on findings in cholescintigraphy in patients with extrahepatic obstruction was retrospectively evaluated in 29 patients. Of 11 patients with obstruction secondary to cancer, seven (78%) of nine had complete obstruction (delayed images were not obtained in two) and nine (82%) of 11 had a moderate to severe decreases in hepatocyte clearance. Of 12 patients with obstruction secondary to cholelithiasis, only four (36%) had complete obstruction (delayed images were not obtained in one) (p less than 0.05) and all 11 had normal or only midly decreased hepatocyte clearance (p less than 0.05). All five patients with obstruction secondary to pancreatitis had mild partial obstruction and normal or mildly decreased hepatocyte clearance. One patient had partial obstruction secondary to an abscess adjacent to the common bile duct; hepatocyte clearance was mildly decreased. Cancerous and noncancerous causes of biliary tract obstruction produce significantly different findings in hepatobiliary imaging.

  15. Biliary ascariasis: radiological clue to diagnosis.

    PubMed

    Sundriyal, Deepak; Bansal, Satish; Kumar, Naveen; Sharma, Navneet

    2015-03-01

    Ascariasis is caused by Ascaris lumbricoides. It is the most common helminthic infection seen worldwide. Ascariasis is an endemic disease in our country. This is due to the prevailing poor sanitary conditions and low level of education. Biliary ascariasis is an uncommon cause of obstructive jaundice. We report a case of biliary ascariasis in a young labourer who presented with acute abdominal pain. PMID:26634136

  16. Percutaneous endoscopic management of intrahepatic stones in patients with altered biliary anatomy: A case series.

    PubMed

    Bhandari, Suryaprakash; Bathini, Rajesh; Sharma, Atul; Maydeo, Amit

    2016-03-01

    Incidence of primary intrahepatic stones (IHS) in India is very less as compared to the Far East. However patients with altered biliary anatomy are prone for IHS formation secondary to anastomotic stricture formation. Indian data on percutaneous endoscopic management of IHS is scare. Five patients with IHS were managed percutaneously. All patients had undergone Roux-en-Y hepaticojejunostomy and were not suitable for direct endoscopic intervention. All patients underwent percutaneous biliary drainage followed by cholangioscopy-guided laser lithotripsy. Crushed stones were pushed across the anastomotic site using basket/balloon and ductal clearance was achieved. Good stone pulverization could be achieved in five patients (100 %). Complete ductal clearance could be achieved in all patients (100 %). Cholangioscopy-guided treatment of IHS can be valuable alternative to surgery in select group of patients especially those having dilated biliary tree with absence of intrahepatic strictures. However long-term follow up studies are required to see for recurrence of stone formation.

  17. Anaesthetic Management of a Patient with Synchronous Kartagener Syndrome and Biliary Atresia

    PubMed Central

    Kendigelen, Pınar; Tütüncü, Ayşe Çiğdem; Erbabacan, Şafak Emre; Kaya, Güner; Altındaş, Fatiş

    2015-01-01

    Kartagener syndrome is an autosomal recessive disorder characterized by primary ciliary dyskinesia accompanied by sinusitis, bronchiectasis, and situs inversus. Synchronous extrahepatic biliary atresia and Kartagener syndrome are very rare. During the preoperative preparation of patients with Kartagener syndrome, special attention is required for the respiratory and cardiovascular system. It is important to provide suitable anaesthetic management to avoid problems because of ciliary dysfunction in the perioperative period. Further, maintaining an effective pain control with regional anaesthetic methods reduces the risk of pulmonary complications. Infants with biliary atresia operated earlier have a higher chance of survival. Hepatic dysfunction and decrease in plasma proteins are important for the kinetics of drugs. In this presentation, the anaesthetic management of patients with synchronous Kartagener syndrome and biliary atresia, both of which are rare diseases, is evaluated. PMID:27366497

  18. Anaesthetic Management of a Patient with Synchronous Kartagener Syndrome and Biliary Atresia.

    PubMed

    Kendigelen, Pınar; Tütüncü, Ayşe Çiğdem; Erbabacan, Şafak Emre; Kaya, Güner; Altındaş, Fatiş

    2015-06-01

    Kartagener syndrome is an autosomal recessive disorder characterized by primary ciliary dyskinesia accompanied by sinusitis, bronchiectasis, and situs inversus. Synchronous extrahepatic biliary atresia and Kartagener syndrome are very rare. During the preoperative preparation of patients with Kartagener syndrome, special attention is required for the respiratory and cardiovascular system. It is important to provide suitable anaesthetic management to avoid problems because of ciliary dysfunction in the perioperative period. Further, maintaining an effective pain control with regional anaesthetic methods reduces the risk of pulmonary complications. Infants with biliary atresia operated earlier have a higher chance of survival. Hepatic dysfunction and decrease in plasma proteins are important for the kinetics of drugs. In this presentation, the anaesthetic management of patients with synchronous Kartagener syndrome and biliary atresia, both of which are rare diseases, is evaluated. PMID:27366497

  19. [Biliary extracorporeal shockwave lithotripsy. Preliminary communication].

    PubMed

    Garnica, E

    1989-01-01

    Shock wave lithotripsy has been successfully used in the treatment of urinary stones. Since 1985, it has also been applied in the management of gallbladder and biliary duct stones. The preliminary experience in Venezuela with the shock wave technology for the treatment of biliary stone disease is presented. The facilities of the Unit for the Treatment of Lithiasis. UNILIT of Venezuela, in Caracas were used. This unit is equipped with a Siemens Lithostar, that operates with an electromagnetic shock wave generator guided by a very accurate computerized biplane fluoroscopic system. Symptomatic gallstones with functioning gallbladder and radiolucid stones smaller than 3 cm, were the most important inclusion criteria. For duct stones, all cases that could not be managed by endoscopy were included. Fifteen cases have been treated from April 1988. Ten with gallstones and 5 with biliary duct stones. Success rate for gallstones, clarifications of gallbladder within a 12 month follow-up, was achieved in 40%. In the cases of biliary duct lithiasis, the aim was to reduce the stone to smaller fragments that could pass spontaneously or be retrieved by endoscopic maneuvers. In all the five cases treated, the stones could be crushed into small fragments and in four, they were easily withdrawn by endoscopic ballooning. Preliminary results and published data suggest that shockwave lithotripsy is a valuable method of treatment for selected cases of gallbladder stones and it is specially useful in the management of biliary duct stones where the endoscopic maneuvers have failed.

  20. Biliary tract obstruction secondary to cancer: management guidelines and selected literature review.

    PubMed

    Lokich, J J; Kane, R A; Harrison, D A; McDermott, W V

    1987-06-01

    Malignant biliary tract obstruction (MBTO) due to either primary biliary tract cancer or metastasis to the porta hepatis is a common clinical problem. The most common metastatic tumors causing MBTO in order of frequency are gastric, colon, breast, and lung cancers. Radiographic diagnostic procedures should proceed in a cost-effective sequence from ultrasonography, computerized tomography (CT), percutaneous transhepatic cholangiography (PTHC), and endoscopic retrograde pancreatography with the goal of establishing the site of the biliary tract obstruction. The identification of the site of obstruction could be established by ultrasound 70% to 80%, CT scan 80% to 90%, PTHC 100%, and endoscopic retrograde cholangiography (ERCP) 85%. Therapeutic intervention by radiographic decompression (PTHC or endoscopic prosthesis), surgical bypass, or radiation therapy with or without chemotherapy may be selectively used based on (1) the site of obstruction; (2) the type of primary tumor; and (3) the presence of specific symptoms related to the obstruction. ("Prophylactic" biliary tract decompression to prevent ascending cholangitis is not supported by the literature in that the frequency of sepsis in the face of malignant obstruction is small (in contrast to sepsis associated with stone disease). Furthermore, PTHC with drainage as a long-term procedure is associated with a substantial frequency of sepsis and is unnecessary and possibly problematic as a preoperative procedure simply to reduce the bilirubin level. The use of radiation therapy in conjunction with chemotherapy for patients not deemed suitable for a surgical bypass because of the presence of proximal obstruction is an important alternative to PTHC.

  1. Biliary tract obstruction secondary to cancer: management guidelines and selected literature review.

    PubMed

    Lokich, J J; Kane, R A; Harrison, D A; McDermott, W V

    1987-06-01

    Malignant biliary tract obstruction (MBTO) due to either primary biliary tract cancer or metastasis to the porta hepatis is a common clinical problem. The most common metastatic tumors causing MBTO in order of frequency are gastric, colon, breast, and lung cancers. Radiographic diagnostic procedures should proceed in a cost-effective sequence from ultrasonography, computerized tomography (CT), percutaneous transhepatic cholangiography (PTHC), and endoscopic retrograde pancreatography with the goal of establishing the site of the biliary tract obstruction. The identification of the site of obstruction could be established by ultrasound 70% to 80%, CT scan 80% to 90%, PTHC 100%, and endoscopic retrograde cholangiography (ERCP) 85%. Therapeutic intervention by radiographic decompression (PTHC or endoscopic prosthesis), surgical bypass, or radiation therapy with or without chemotherapy may be selectively used based on (1) the site of obstruction; (2) the type of primary tumor; and (3) the presence of specific symptoms related to the obstruction. ("Prophylactic" biliary tract decompression to prevent ascending cholangitis is not supported by the literature in that the frequency of sepsis in the face of malignant obstruction is small (in contrast to sepsis associated with stone disease). Furthermore, PTHC with drainage as a long-term procedure is associated with a substantial frequency of sepsis and is unnecessary and possibly problematic as a preoperative procedure simply to reduce the bilirubin level. The use of radiation therapy in conjunction with chemotherapy for patients not deemed suitable for a surgical bypass because of the presence of proximal obstruction is an important alternative to PTHC. PMID:3295131

  2. [SURGICAL TACTICS IN CHRONIC PANCREATITIS WITH SIGNS OF BILIARY HYPERTENSION].

    PubMed

    Usenko, O Yu; Kopchak, V M; Pylypchuk, V I; Kopchak, K V; Andronik, S V

    2015-08-01

    The results of treatment of 84 patients for chronic pancreatitis with the biliary hypertension signs were depicted. In 83 patients operative interventions were performed, and in 1--positive results were achieved after pancreatic cyst puncture under ultrasonographic control. In 51 patients the conduction of Frey operation have permitted to achieve a lower pressure inside biliary system, in 25--the additional procedures were applied for a biliary hypertension elimination. In 20 patients a method of pressure measurement in biliary system was used.

  3. Aztreonam biliary excretion in bile duct ligated jaundiced rats.

    PubMed

    Rulli, F; Muzi, M; Zanella, E; Cipriani, P; Magni, A; Giordano, A; Filadoro, F

    1991-04-01

    An experimental study was undertaken to assess aztreonam biliary concentrations in bile duct ligated jaundiced rats. The study proved that aztreonam biliary concentrations are sufficient to inhibit Gram-negative bacteria within the first and the second hour after antibiotic administration. The experimental model suggests that clinical conditions such as lithiasis or neoplasms of the biliary tree should not totally inhibit the antibiotic excretion.

  4. Advanced endoscopic imaging of indeterminate biliary strictures

    PubMed Central

    Tabibian, James H; Visrodia, Kavel H; Levy, Michael J; Gostout, Christopher J

    2015-01-01

    Endoscopic evaluation of indeterminate biliary strictures (IDBSs) has evolved considerably since the development of flexible fiberoptic endoscopes over 50 years ago. Endoscopic retrograde cholangiography pancreatography (ERCP) was introduced nearly a decade later and has since become the mainstay of therapy for relieving obstruction of the biliary tract. However, longstanding methods of ERCP-guided tissue acquisition (i.e., biliary brushings for cytology and intraductal forceps biopsy for histology) have demonstrated disappointing performance characteristics in distinguishing malignant from benign etiologies of IDBSs. The limitations of these methods have thus helped drive the search for novel techniques to enhance the evaluation of IDBSs and thereby improve diagnosis and clinical care. These modalities include, but are not limited to, endoscopic ultrasound, intraductal ultrasound, cholangioscopy, confocal endomicroscopy, and optical coherence tomography. In this review, we discuss established and emerging options in the evaluation of IDBSs. PMID:26675379

  5. Percutaneous Management of Malignant Biliary Obstruction.

    PubMed

    Sutter, Christopher M; Ryu, Robert K

    2015-12-01

    Malignancy resulting in impaired biliary drainage includes a number of diagnoses familiar to the interventional radiologist. Adequate drainage of such a system can significantly improve patient quality of life, and can facilitate the further treatment options and care of such patients. In the setting of prior instrumentation, cholangitis can present as an urgent indication for drainage. Current initial interventional management of malignant biliary duct obstruction frequently includes endoscopic or percutaneous intervention, with local practices and preprocedural imaging guiding interventional approaches and subsequent management. This article addresses the indications for percutaneous drainage, technical considerations in performing such drainage, and specific techniques useful in attempting to achieve clinical end points in patients with malignant biliary duct obstruction.

  6. Chronic biliary colic associated with ketamine abuse

    PubMed Central

    Al-Nowfal, Ahmed; Al-Abed, Yahya A

    2016-01-01

    Introduction Biliary colic is a common clinical presentation, with the majority of cases being related to gallstone disease. However, rarely, patients may present with biliary symptoms without evidence of gallbladder stones – referred to as acalculous gallstone disease. This case report details a rare case of chronic biliary colic associated with ketamine abuse. Case presentation A 24-year-old Caucasian female presented to the emergency department with a history of intermittent right upper quadrant pain associated with nausea and malaise. She had experienced bouts of similar symptoms three times a year for the past 4 years. Various investigations had been conducted during her multiple admissions, which showed possible dilatation of the common bile duct, with no evidence of gallstones. Conclusion Patients can present with a dilated common bile duct and an acalculous cholecystitis. This requires considerable investigation, with an emphasis on drug history, especially with the current rise of recreational hallucinogenic drug abuse. PMID:27330331

  7. Burdick's Technique for Biliary Access Revisited.

    PubMed

    Goenka, Mahesh Kumar; Rai, Vijay Kumar

    2015-01-01

    The precut sphincterotomy is used to facilitate selective biliary access in cases of difficult biliary cannulation. Needle-knife precut papillotomy is the standard of care but is associated with a high rate of complications such as pancreatitis, duodenal perforation, bleeding, etc. Sometimes during bowing of the sphincterotome/cannula and the use of guide wire to facilitate biliary cannulation, inadvertent formation of a false passage occurs in the 10 to 11 o'clock direction. Use of this step to access the bile duct by the intramucosal incision technique was first described by Burdick et al., and since then two more studies have also substantiated the safety and efficacy of this non-needle type of precut sphincterotomy. In this review, we discuss this non-needle technique of precut sphincterotomy and also share our experience using this "Burdick's technique." PMID:25674522

  8. A prospective study of radionuclide biliary scanning in acute pancreatitis.

    PubMed Central

    Neoptolemos, J. P.; Fossard, D. P.; Berry, J. M.

    1983-01-01

    Early surgery for biliary pancreatitis has resulted in a need for an accurate method of gallstone detection in acute pancreatitis. Fifty patients with acute pancreatitis were studied prospectively to assess the diagnostic value of Radionuclide Biliary Scanning (RBS) performed within 72 hours of an attack. To assess the general accuracy of RBS a further 154 patients with suspected acute cholecystitis or biliary colic were similarly studied. There were 34 patients with biliary pancreatitis and 18 (53%) had a positive scan (no gallbladder seen). There were 16 patients with non-biliary pancreatitis and 5 (31%) had a positive scan. All 51 patients with acute cholecystitis had a positive scan, as did 82% of the 51 patients with biliary colic. There were 52 patients with no biliary or pancreatic disease and none of these had a positive scan. RBS is highly accurate in confirming a diagnosis of acute cholecystitis or biliary colic. However, it cannot be relied on to differentiate between biliary and non-biliary pancreatitis and should certainly not be used as the basis for biliary surgery in these patients. PMID:6859781

  9. Biliary casts after liver transplantation: Morphology and biochemical analysis

    PubMed Central

    Yang, Yu-Long; Zhang, Cheng; Lin, Mei-Ju; Shi, Li-Jun; Zhang, Hong-Wei; Li, Jing-Yi; Yu, Qiang

    2013-01-01

    AIM: To investigate the pathogenesis of biliary casts after liver transplantation relative to their morphology and biochemical markers. METHODS: The microstructure of biliary casts was assessed using scanning electron microscopy and Hematoxylin and eosin staining assessed their histology. The expression levels of CD3, CD5, CD34, CD68 and CD79a in these biliary casts were evaluated immunohistochemically. RESULTS: Biliary casts differed widely in their microstructure, with some containing blood vessels positive for CD34 and collagen fibers with positive Masson staining. Large numbers of neutrophils and other inflammatory cells were present, but only on the edge of the biliary casts; although the boundaries were clear without crossover. None of the biliary casts contained T-lymphocytes, B-lymphocytes, macrophages and other inflammatory cells. CONCLUSION: The microcostructure of biliary casts differed. Bacteria and acute rejection are not clearly related to their formation. PMID:24282366

  10. Osteopathic manipulative treatment in the management of biliary dyskinesia.

    PubMed

    Heineman, Katherine

    2014-02-01

    Biliary dyskinesia is a functional gastrointestinal disorder of the gallbladder and sphincter of Oddi. Diagnosis is made on the basis of symptoms of biliary colic in the absence of cholelithiasis and gallbladder inflammation. Palpatory findings of tissue texture changes at midthoracic levels (T6-T9) may correspond to visceral dysfunction related to the biliary system. Osteopathic manipulative treatment (OMT) of the T6-T9 segments can remove the feedback related to the somatic component, thereby affecting nociceptive facilitation at the spinal level and allowing the body to restore autonomic balance. Few reports in the current literature provide examples of treatment for patients with biliary dyskinesia using OMT. The author describes the case of a 51-year-old woman who presented with symptoms consistent with biliary dyskinesia. Her biliary colic completely resolved after OMT. Osteopathic evaluation and OMT should be considered a safe and effective option for conservative management of biliary dyskinesia.

  11. The metabolism of methaqualone in patients with biliary cirrhosis or secondary carcinoma of the liver.

    PubMed

    Burnett, D; Reynolds, C N; Wilson, K

    1979-02-19

    The metabolism of methaqualone has been studied in three patients with secondary carcinoma of the liver and two with biliary cirrhosis. The urinary excretion of five C-monohydroxy metabolites and the N-oxide was studies in the 24 h period immediately after oral dosing with 250 mg methaqualone (Melsed). In both patients with biliary cirrhosis and one with primary carcinoma of the bile duct or pancreas with secondaries in the liver the pattern of metabolites was normal. In a patient with oat cell carcinoma with secondaries in the liver some metabolite patterns were disturbed and increased metabolite excretion occurred. A patient with primary carcinoma of the breast with secondaries in the liver gave a completely abnormal metabolite pattern.

  12. Biliary tract infections caused by Aeromonas species.

    PubMed

    Chao, C M; Lai, C C; Tang, H J; Ko, W C; Hsueh, P-R

    2013-02-01

    This study investigated the clinical and microbiological characteristics of patients with Aeromonas infections of the biliary tract. Patients with bile cultures positive for Aeromonas species during the period July 2004 to December 2011 were identified from a computerized database of a hospital in Taiwan. Patients with Aeromonas infections of the biliary tract were further identified. During the study period, a total of 1,142 isolates of Aeromonas species were obtained from 750 patients. Of those patients, 91 (12.1 %) had Aeromonas infections of the biliary tract. The annual incidence (episodes per 10,000 patient-days) of biliary tract infections caused by all Aeromonas species was 0.31 in 2007, 0.12 in 2010, and 0.27 in 2011. A. hydrophila was the most common species isolated (n = 41, 45.1 %), followed by A. caviae (n = 30, 33.0 %), A. veronii biovar sobria (n = 15, 16.5 %), and A. veronii biovar veronii (n = 5, 5.5 %). The majority of patients (n = 77, 84.6 %) had polymicrobial infections. Hepatobiliary stones (n = 50, 54.9 %) and hepatobiliary cancer (n = 38, 41.8 %) were the most common underlying diseases, followed by diabetes mellitus (n = 29, 31.9 %) and liver cirrhosis (n = 7, 7.7 %). The in-hospital mortality rate was 8.8 %. Infection-related mortality was associated with underlying immunocompromised condition (p = 0.044) and use of mechanical ventilation (p = 0.004), but was not associated with inappropriate antibiotic usage or concomitant bacteremia (n = 8, 8.8 %). In conclusion, biliary tract infections caused by Aeromonas species are not uncommon and can develop in both immunocompromised and immunocompetent patients; however, patients with underlying hepatobiliary diseases are particularly susceptible to these infections.

  13. Is biliary lithiasis associated with pancreatographic changes?

    PubMed Central

    Barthet, M; Affriat, C; Bernard, J P; Berthezene, P; Dagorn, J C; Sahel, J

    1995-01-01

    The aetiological role of biliary lithiasis for chronic pancreatitis remains controversial. Previous studies based on pancreatographic studies reported changes in the pancreatic duct system caused by biliary lithiasis. This study analysed retrospectively the endoscopic retrograde cholangiopancreatography of 165 patients presenting with biliary lithiasis and of 53 controls. Among the 165 patients, 113 had choledochal stones (53 with gall bladder stones, 50 had had a cholecystectomy, 10 with a normal gall bladder), 35 had gall bladder stones without choledochal stones, 17 had cholecystectomy for gall bladder stones. Pancreatograms were analysed by measuring the diameter of the pancreatic duct in the head, the body, and the tail of the pancreas, and evaluating the regularity of the main pancreatic duct and the presence of stenosis, the regularity or the dilatation of secondary ducts, and the presence of cysts. In addition, we established a score, based on the above parameters, by which pancreatograms were classified as normal or with mild, intermediate, moderate or severe abnormalities. A multivariate analysis (stepwise multiple discriminant analysis) was performed for age, sex, presence of gall stones, presence of choledochal stones. Patients were comparable with controls for sex, alcohol consumption but were younger (55 v 68 years, p < 0.01). In patients and in controls, the frequency of pancreatographic abnormalities increased significantly with age. The pancreatographic features of patients and controls were not significantly different. In the multivariate analysis, age was the only factor with significant predicting value for pancreatographic abnormalities. In conclusion, biliary lithiasis in itself is not an aetiological factor for chronic pancreatitis, older age being responsible for the abnormalities seen by pancreatography of patients with biliary lithiasis. PMID:7797128

  14. [Multi-technical management of biliary fistula].

    PubMed

    Vargas, F; Barrios, R; Palao, R; Garnica, E

    1991-01-01

    Biliary fistula is an occasional complication of cholecystectomy and are usually associated to retained biliary stones, surgical trauma of the biliary ducts and local infection. They were mainly treated by surgical methods up to the acquisition of the new endoscopic and percutaneous techniques used together with parenteral and enteral nutrition and new antibiotics. A total of seven patients with diagnosis of biliary fistula were seen between 1984 and 1990 at the "Unidad de Gastroenterología y Cirugía Digestiva" of the Clínica Sanatrix en Caracas. Average age was 50 with ranged between 31 and 76, 4 were male and 3 female. The fistulas were in 1 due to necrotizing pancreatitis, in 3 to lost of the ligation of the cystic duct, 2 were due to accidental injury of the common duct and the last case was a partial dehiscence of a choledoco-jejunostomy after the resection of a common duct cyst. Four of the cases were choledoco-cutaneous fistula, one hepatocutaneous, two hepatoduodenal. All the seven patients had subhepatic collections, one had a retroperitoneal collection, two had subdiaphragmatic collections and one had multiple hepatic abscesses. The abdominal collections were treated by percutaneous drainage using mainly the Ring-McLean and Van Sonnenberg tubes. The fistula was occluded with biliary prosthesis in four cases, using either endoscopic, percutaneous or mixed technique to place the stent. Patency of the stents ranged between 2 weeks and 24 months. Control time was from 2 to 40 months.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Review Article: Spectrum of Biliary Infections in the West and in the East

    PubMed Central

    Schwarz, A.

    1995-01-01

    Biliary infections are an important cause of morbidity in the Western world. With regard to epidemiology, etiology, microbiological spectrum, prevalence, location and composition of gallstones, pathogenesis, clinical sign and therapy, there are large differences between the spectrum of biliary infections in the East and in the West (Table 1). In Western countries, gallstones are found in 10 to 40%. In Eastern countries, the incidence of gallstones is only 2 to 6%. Some eighty – five percent of the gallstones in the West are cholesterol stones, in contrast to the East, where 97% are bile pigment stones. The most important difference is characterized by the origin of common bile duct stones. In the West, common bile duct stones generally originate in the gallbladder, in contrast to the East, where primary common bile duct stones are often found – especially in the intrahepatic segments – with no evidence of gallbladder stones. The sex distribution male to female in the West is 1:2, in the East 1:1. In the West, biliary infections occur mainly in an elderly population, 50% being older than 70 years. In the East, biliary infections appear also in younger people, 50% being younger than 40 years. Parasites play an aetiological role in the East, but not in the West. The typical therapy of gallstones in the West is cholecystectomy, and of common bile duct stones endoscopic sphincterotomy. Due to the frequency of intrahepatic stones in Eastern Countries, the therapeutic spectrum there includes even large hepatic resections and biliary enteric anastomoses. PMID:18612470

  16. Development of the intrahepatic biliary tree.

    PubMed

    Crawford, James M

    2002-08-01

    The liver develops from two anlages: the hepatic diverticulum, which buds off the ventral side of the foregut, and the septum transversum, which is the mesenchymal plate that partially separates the embryonic thoracic and abdominal cavities. The endodermal cells of the hepatic diverticulum invade the septum transversum, forming sheets and cords of hepatoblasts arrayed along the sinusoidal vascular channels derived from the vitelline veins emanating from the yolk sac. The vitelline veins fuse to form the portal vein, which ramifies as tributaries within the liver along mesenchymal channels termed portal tracts. Those hepatoblasts immediately adjacent to the mesenchyme of the portal tracts differentiate into a ductal plate, a single circumferential layer of biliary epithelial cells. Mesenchymal cells interpose between the ductal plate and the remaining parenchymal hepatoblasts, which differentiate into hepatocytes. By week 7 the ductal plate begins to reduplicate, forming a double layer of cells around the portal tract. Lumena form between the two cell layers of the ductal plate, forming peripheral biliary tubular structures. These peripheral tubules remodel and, with continued proliferation of the mesenchyme, by the 11th week begin to become more centrally located within portal tracts as terminal bile ducts with a circular cross-section. The remaining ductal plate resorbs, leaving behind only tethers of bile ductules connecting the terminal bile ducts to the parenchyma. Abutting and within the parenchyma are the canals of Hering, ductular structures half-lined by hepatocytes and half-lined by biliary epithelial cells. Maturation of the intrahepatic biliary tree to the mature tubular treelike architecture occurs from the hilum of the liver outward, beginning around the 11th week of gestation and continuing past birth for several months. The architecture of maturation is the same regardless of gestational age or radial location in the liver. Importantly, the immature

  17. Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma

    PubMed Central

    Andresen, Kim; Boberg, Kirsten Muri; Vedeld, Hege Marie; Honne, Hilde; Jebsen, Peter; Hektoen, Merete; Wadsworth, Christopher A.; Clausen, Ole Petter; Lundin, Knut E.A.; Paulsen, Vemund; Foss, Aksel; Mathisen, Øystein; Aabakken, Lars; Schrumpf, Erik; Lothe, Ragnhild A.

    2015-01-01

    Early detection of the highly aggressive malignancy cholangiocarcinoma (CCA) remains a challenge but has the potential to render the tumor curable by surgical removal. This study evaluates a biomarker panel for the diagnosis of CCA by DNA methylation analyses of biliary brush samples. The methylation status of 13 candidate genes (CDO1, CNRIP1, DCLK1, FBN1, INA, MAL, SEPT9, SFRP1, SNCA, SPG20, TMEFF2, VIM, and ZSCAN18) was investigated in 93 tissue samples (39 CCAs and 54 nonmalignant controls) using quantitative methylation‐specific polymerase chain reaction. The 13 genes were further analyzed in a test series of biliary brush samples (15 CCAs and 20 nonmalignant primary sclerosing cholangitis controls), and the methylation status of the four best performing markers was validated (34 CCAs and 34 primary sclerosing cholangitis controls). Receiver operating characteristic curve analyses were used to evaluate the performance of individual biomarkers and the combination of biomarkers. The 13 candidate genes displayed a methylation frequency of 26%‐82% in tissue samples. The four best‐performing genes (CDO1, CNRIP1, SEPT9, and VIM) displayed individual methylation frequencies of 45%‐77% in biliary brushes from CCA patients. Across the test and validation biliary brush series, this four‐gene biomarker panel achieved a sensitivity of 85% and a specificity of 98%, with an area under the receiver operating characteristic curve of 0.944. Conclusion: We report a straightforward biomarker assay with high sensitivity and specificity for CCA, outperforming standard brush cytology, and suggest that the biomarker panel, potentially in combination with cytological evaluation, may improve CCA detection, particularly among primary sclerosing cholangitis patients. (Hepatology 2015;61:1651–1659) PMID:25644509

  18. Endoscopic management of benign biliary strictures.

    PubMed

    Rustagi, Tarun; Jamidar, Priya A

    2015-01-01

    Benign biliary strictures are a common indication for endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic management has evolved over the last 2 decades as the current standard of care. The most common etiologies of strictures encountered are following surgery and those related to chronic pancreatitis. High-quality cross-sectional imaging provides a road map for endoscopic management. Currently, sequential placement of multiple plastic biliary stents represents the preferred approach. There is an increasing role for the treatment of these strictures using covered metal stents, but due to conflicting reports of efficacies as well as cost and complications, this approach should only be entertained following careful consideration. Optimal management of strictures is best achieved using a team approach with the surgeon and interventional radiologist playing an important role.

  19. Endoscopic radiofrequency ablation for malignant biliary strictures

    PubMed Central

    WANG, FEI; LI, QUANPENG; ZHANG, XIUHUA; JIANG, GUOBING; GE, XIANXIU; YU, HONG; NIE, JUNJIE; JI, GUOZHONG; MIAO, LIN

    2016-01-01

    Endoscopic radiofrequency ablation (RFA) is a novel palliation therapy for malignant biliary stricture; however, its feasibility and safety has not yet been clearly defined. The aim of the present study was to evaluate the feasibility and safety of endoscopic RFA for the treatment of malignant biliary strictures. A total of 12 patients treated by endoscopic RFA between December 2011 and October 2013 were retrospectively analyzed. Adverse events within 30 days post-intervention, stricture diameters prior to and following RFA, stent patency and survival time were investigated. A total of 12 patients underwent 20 RFA procedures as a treatment for malignant biliary strictures. Two patients required repeated elective RFA (4 and 6 times, respectively). All 20 RFA procedures were successfully performed without technical problems. During a 30 day period following each RFA procedure, two patients experienced fever (38.2 and 38.9°C, respectively) and another patient exhibited post-endoscopic retrograde cholangiopancreatography pancreatitis. The 30- and 90-day mortality rates were 0 and 8.3%, respectively. Mean stricture diameter prior to RFA was 5.3 mm (standard deviation (SD), 0.9 mm; range, 5–8 mm), and the mean diameter following RFA was 12.6 mm (SD, 3.1 mm; range, 8–15 mm). There was a significant increase of 7.3 mm in the bile duct diameter following RFA in comparison with prior to RFA (t=8.6; P≤0.001). Of the 11 patients with stents inserted following RFA, the median stent patency was 125.0 days [95% confidence interval (CI), 94.7–155.3 days]. Extrapolated median survival following the first RFA was 232 days (95% CI, 94.3–369.7 days). In conclusion, RFA appears to be an efficient and safe treatment strategy for the palliation of unresectable malignant biliary strictures. PMID:27284336

  20. Colon Cancer Metastatic to the Biliary Tree

    PubMed Central

    Clayton, Steven B.; Markow, Michael; Mamel, Jay

    2016-01-01

    Metastasis of colon adenocarcinoma is commonly found in the lung, liver, or peritoneum. Common bile duct (CBD) tumors related to adenomas from familial adenomatous polyposis metastasizing from outside of the gastrointestinal tract have been reported. We report a case of biliary colic due to metastatic colon adenocarcinoma to the CBD. Obstructive jaundice with signs of acalculous cholecystitis on imaging in a patient with a history of colon cancer should raise suspicion for metastasis to CBD. PMID:27144209

  1. Adenocarcinoma of the extrahepatic biliary tree.

    PubMed Central

    Anderson, J. B.; Cooper, M. J.; Williamson, R. C.

    1985-01-01

    Increasing survival rates for carcinoma of the biliary tree could reflect the selection of patients for referral to a specialist centre as well as modern improvements in diagnosis and treatment. To determine the true incidence and outcome of biliary cancer, the records of 243 unselected Bristol patients were reviewed retrospectively over a 15-year period. Mean age was 64 years. Gallstones were associated in 38% of cases. Sixty-nine of 87 patients with gallbladder carcinoma were submitted to laparotomy. The operative (30-day) mortality rate was 56% and the one-year survival rate was 7%; one patient with an unexpected carcinoma is alive 7 years after cholecystectomy (1% five-year survival rate). Among 31 patients with carcinoma of the ampulla the operative mortality rate was 27%; one-year and five-year survival rates were 46% and 15%. Bile duct cancers (n = 125) arose proximal to the entry of the cystic duct (n = 63), distal to that point (n = 46) or diffusely (n = 16). For proximal cholangiocarcinoma the operative mortality rate was 38% and 1-year survival rate 17%; no patient lived for 2 years. For distal cholangiocarcinoma the operative mortality rate was 45% and one-year survival rate 26%; no patient lived for 3 years. Only palliative procedures were undertaken for diffuse cholangiocarcinoma; 2 patients survived 1 year (13%). Overall 5 patients with carcinoma of the extrahepatic biliary tree appear to have been cured (2%). PMID:2988399

  2. Malignant Biliary Obstruction: Evidence for Best Practice

    PubMed Central

    Pu, Leonardo Zorrón Cheng Tao; Singh, Rajvinder; Loong, Cheong Kuan; de Moura, Eduardo Guimarães Hourneaux

    2016-01-01

    What should be done next? Is the stricture benign? Is it resectable? Should I place a stent? Which one? These are some of the questions one ponders when dealing with biliary strictures. In resectable cases, ongoing questions remain as to whether the biliary tree should be drained prior to surgery. In palliative cases, the relief of obstruction remains the main goal. Options for palliative therapy include surgical bypass, percutaneous drainage, and stenting or endoscopic stenting (transpapillary or via an endoscopic ultrasound approach). This review gathers scientific foundations behind these interventions. For operable cases, preoperative biliary drainage should not be performed unless there is evidence of cholangitis, there is delay in surgical intervention, or intense jaundice is present. For inoperable cases, transpapillary stenting after sphincterotomy is preferable over percutaneous drainage. The use of plastic stents (PS) has no benefit over Self-Expandable Metallic Stents (SEMS). In case transpapillary drainage is not possible, Endoscopic Ultrasonography- (EUS-) guided drainage is still an option over percutaneous means. There is no significant difference between the types of SEMS and its indication should be individualized. PMID:26981114

  3. Excretion of biliary compounds during intrauterine life

    PubMed Central

    Macias, Rocio IR; Marin, Jose JG; Serrano, Maria A

    2009-01-01

    In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem. PMID:19230042

  4. Malignant Biliary Obstruction: Evidence for Best Practice.

    PubMed

    Pu, Leonardo Zorrón Cheng Tao; Singh, Rajvinder; Loong, Cheong Kuan; de Moura, Eduardo Guimarães Hourneaux

    2016-01-01

    What should be done next? Is the stricture benign? Is it resectable? Should I place a stent? Which one? These are some of the questions one ponders when dealing with biliary strictures. In resectable cases, ongoing questions remain as to whether the biliary tree should be drained prior to surgery. In palliative cases, the relief of obstruction remains the main goal. Options for palliative therapy include surgical bypass, percutaneous drainage, and stenting or endoscopic stenting (transpapillary or via an endoscopic ultrasound approach). This review gathers scientific foundations behind these interventions. For operable cases, preoperative biliary drainage should not be performed unless there is evidence of cholangitis, there is delay in surgical intervention, or intense jaundice is present. For inoperable cases, transpapillary stenting after sphincterotomy is preferable over percutaneous drainage. The use of plastic stents (PS) has no benefit over Self-Expandable Metallic Stents (SEMS). In case transpapillary drainage is not possible, Endoscopic Ultrasonography- (EUS-) guided drainage is still an option over percutaneous means. There is no significant difference between the types of SEMS and its indication should be individualized. PMID:26981114

  5. Septic Shock Due to Biliary Stones in a Postcholecystectomy Patient.

    PubMed

    Azfar, Mohammad Feroz; Khan, Muhammad Faisal; Khursheed, Moazzum

    2015-10-01

    Septic shock leading to multi-organ failure is not uncommon. Early diagnosis to confirm the source is the distinctive attribute of sepsis management guidelines. Cholangitis as the source of sepsis can become a diagnostic dilemma in patients who have had cholecystectomy in the past. CT abdomen should be the investigation of choice in this group of patients. This report describes two postcholecystectomy patients who presented with septic shock secondary to biliary stones. The source of septic shock in both patients were biliary stones was confirmed with abdominal CT. Ultrasound abdomen failed to report biliary stones in these patients. Both improved on percutaneous transhepatic biliary drainage.

  6. Human intrahepatic biliary epithelial cells engulf blebs from their apoptotic peers

    PubMed Central

    Rong, G-H; Yang, G-X; Ando, Y; Zhang, W; He, X-S; Leung, P S C; Coppel, R L; Ansari, A A; Zhong, R; Gershwin, M E

    2013-01-01

    The phagocytic clearance of apoptotic cells is critical for tissue homeostasis; a number of non-professional phagocytic cells, including epithelial cells, can both take up and process apoptotic bodies, including the release of anti-inflammatory mediators. These observations are particularly important in the case of human intrahepatic biliary cells (HiBEC), because such cells are themselves a target of destruction in primary biliary cirrhosis, the human autoimmune disease. To address the apoptotic ability of HiBECs, we have focused on their ability to phagocytize apoptotic blebs from autologous HiBECs. In this study we report that HiBEC cells demonstrate phagocytic function from autologous HiBEC peers accompanied by up-regulation of the chemokines CCL2 [monocyte chemotactic protein-1 (MCP-1)] and CXCL8 [interleukin (IL)-8]. In particular, HiBEC cells express the phagocytosis-related receptor phosphatidylserine receptors (PSR), implying that HiBECs function through the ‘eat-me’ signal phosphatidylserine expressed by apoptotic cells. Indeed, although HiBEC cells acquire antigen-presenting cell (APC) function, they do not change the expression of classic APC function surface markers after engulfment of blebs, both with and without the presence of Toll-like receptor (TLR) stimulation. These results are important not only for understanding of the normal physiological function of HiBECs, but also explain the inflammatory potential and reduced clearance of HiBEC cells following the inflammatory cascade in primary biliary cirrhosis. PMID:23480189

  7. Management of major biliary complications after laparoscopic cholecystectomy.

    PubMed Central

    Branum, G; Schmitt, C; Baillie, J; Suhocki, P; Baker, M; Davidoff, A; Branch, S; Chari, R; Cucchiaro, G; Murray, E

    1993-01-01

    OBJECTIVE: A total of 50 major bile duct injuries after laparoscopic cholecystectomy were managed by the Duke University Hepatobiliary Service from 1990-1992. The management of these complex cases is reviewed. SUMMARY BACKGROUND DATA: Laparoscopic cholecystectomy is the preferred method for removing the gallbladder. Bile duct injury is the most feared complication of the new procedure. METHODS: Review of videotapes, pathology, and management of the original operations were reviewed retrospectively, and the injuries categorized. Major biliary injury was defined as a recognized disruption of any part of the major extrahepatic biliary system. Biliary leakage was defined as a clinically significant biliary fistula in the absence of major biliary injury, i.e., with an intact extrahepatic biliary system. RESULTS: Thirty-eight injuries were major biliary ductal injuries and 12 patients had simple biliary leakage. Twenty-four patients had the classic type injury or some variant of the classic injury. A standard treatment approach was developed which consisted of ERCP for diagnosis, preoperative PTC with the placement of stents, CT drainage immediately after the PTC for drainage of biliary ascites, and usually Roux-en-Y hepaticojejunostomy with placement of O-rings for future biliary access if necessary. Major ductal injuries were high in the biliary system involving multiple ducts in 31 of the 38 patients. Re-operation was required in 5 of the 38 patients with particularly complex problems. CONCLUSIONS: Successful management of bile duct injury after laparoscopic cholecystectomy requires careful understanding of the mechanisms, considerable preoperative assessment by experts, and a multidisciplinary approach. Images Figure 2. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. PMID:8489316

  8. Association of Preoperative Biliary Drainage With Postoperative Outcome Following Pancreaticoduodenectomy

    PubMed Central

    Povoski, Stephen P.; Karpeh, Martin S.; Conlon, Kevin C.; Blumgart, Leslie H.; Brennan, Murray F.

    1999-01-01

    Objective To determine whether preoperative biliary instrumentation and preoperative biliary drainage are associated with increased morbidity and mortality rates after pancreaticoduodenectomy. Summary Background Data Pancreaticoduodenectomy is accompanied by a considerable rate of postoperative complications and potential death. Controversy exists regarding the impact of preoperative biliary instrumentation and preoperative biliary drainage on morbidity and mortality rates after pancreaticoduodenectomy. Methods Two hundred forty consecutive cases of pancreaticoduodenectomy performed between January 1994 and January 1997 were analyzed. Multiple preoperative, intraoperative, and postoperative variables were examined. Pearson chi square analysis or Fisher’s exact test, when appropriate, was used for univariate comparison of all variables. Logistic regression was used for multivariate analysis. Results One hundred seventy-five patients (73%) underwent preoperative biliary instrumentation (endoscopic, percutaneous, or surgical instrumentation). One hundred twenty-six patients (53%) underwent preoperative biliary drainage (endoscopic stents, percutaneous drains/stents, or surgical drainage). The overall postoperative morbidity rate after pancreaticoduodenectomy was 48% (114/240). Infectious complications occurred in 34% (81/240) of patients. Intraabdominal abscess occurred in 14% (33/240) of patients. The postoperative mortality rate was 5% (12/240). Preoperative biliary drainage was determined to be the only statistically significant variable associated with complications (p = 0.025), infectious complications (p = 0.014), intraabdominal abscess (p = 0.022), and postoperative death (p = 0.037). Preoperative biliary instrumentation alone was not associated with complications, infectious complications, intraabdominal abscess, or postoperative death. Conclusions Preoperative biliary drainage, but not preoperative biliary instrumentation alone, is associated with increased

  9. The inflammatory phenotype of the fibrous plate is distinct from the liver and correlates with clinical outcome in biliary atresia.

    PubMed

    Arva, Nicoleta C; Russo, Pierre A; Erlichman, Jessi; Hancock, Wayne W; Haber, Barbara A; Bhatti, Tricia R

    2015-03-01

    Biliary atresia is an inflammatory cholangiopathy of still undetermined etiology. Correlations between histologic findings and clinical outcome in this disease have largely been based on evaluation of liver parenchyma. This study aimed to characterize the pattern of inflammation within the biliary remnant and identify associations between the type and degree of inflammation and clinical outcome as reflected by the transplant-free interval. The inflammation within the fibrous plates and livers of 41 patients with biliary atresia was characterized using immunohistochemical markers and the cell populations were digitally quantified. The type and quantity of cells within the infiltrate were then correlated with length of time from Kasai portoenterostomy until transplant. Histologic and immunohistochemical features of the biliary remnant allowed stratification of patients into "inflammatory plate" and "fibrotic plate" groups. Overall there was no significant difference in transplant-free interval between the two cohorts; however, there was a trend towards a longer time to transplant among patients in the "fibrotic plate" group. In addition, the composition of the inflammatory infiltrate in the fibrous plate was distinctly different from that present in the liver and only the characteristics of the inflammation in the fibrous plate, in particular the number of Foxp3+ T regulatory lymphocytes correlated with clinical outcome. The results of this study support the view of the extra-hepatic biliary tree as the primary site of injury in BA with the changes seen in the liver as secondary manifestations of outflow obstruction. The association between specific inflammatory cell subtypes within the fibrous plate and the length of transplant-free interval also supports the role of the immune system in the initial process of bile duct damage in biliary atresia.

  10. The inflammatory phenotype of the fibrous plate is distinct from the liver and correlates with clinical outcome in biliary atresia.

    PubMed

    Arva, Nicoleta C; Russo, Pierre A; Erlichman, Jessi; Hancock, Wayne W; Haber, Barbara A; Bhatti, Tricia R

    2015-03-01

    Biliary atresia is an inflammatory cholangiopathy of still undetermined etiology. Correlations between histologic findings and clinical outcome in this disease have largely been based on evaluation of liver parenchyma. This study aimed to characterize the pattern of inflammation within the biliary remnant and identify associations between the type and degree of inflammation and clinical outcome as reflected by the transplant-free interval. The inflammation within the fibrous plates and livers of 41 patients with biliary atresia was characterized using immunohistochemical markers and the cell populations were digitally quantified. The type and quantity of cells within the infiltrate were then correlated with length of time from Kasai portoenterostomy until transplant. Histologic and immunohistochemical features of the biliary remnant allowed stratification of patients into "inflammatory plate" and "fibrotic plate" groups. Overall there was no significant difference in transplant-free interval between the two cohorts; however, there was a trend towards a longer time to transplant among patients in the "fibrotic plate" group. In addition, the composition of the inflammatory infiltrate in the fibrous plate was distinctly different from that present in the liver and only the characteristics of the inflammation in the fibrous plate, in particular the number of Foxp3+ T regulatory lymphocytes correlated with clinical outcome. The results of this study support the view of the extra-hepatic biliary tree as the primary site of injury in BA with the changes seen in the liver as secondary manifestations of outflow obstruction. The association between specific inflammatory cell subtypes within the fibrous plate and the length of transplant-free interval also supports the role of the immune system in the initial process of bile duct damage in biliary atresia. PMID:25624184

  11. Indocyanine-green-loaded microballoons for biliary imaging in cholecystectomy

    PubMed Central

    Mitra, Kinshuk; Melvin, James; Chang, Shufang; Park, Kyoungjin; Yilmaz, Alper; Melvin, Scott

    2012-01-01

    Abstract. We encapsulate indocyanine green (ICG) in poly[(D,L-lactide-co-glycolide)-co-PEG] diblock (PLGA-PEG) microballoons for real-time fluorescence and hyperspectral imaging of biliary anatomy. ICG-loaded microballoons show superior fluorescence characteristics and slower degradation in comparison with pure ICG. The use of ICG-loaded microballoons in biliary imaging is demonstrated in both biliary-simulating phantoms and an ex vivo tissue model. The biliary-simulating phantoms are prepared by embedding ICG-loaded microballoons in agar gel and imaged by a fluorescence imaging module in a Da Vinci surgical robot. The ex vivo model consists of liver, gallbladder, common bile duct, and part of the duodenum freshly dissected from a domestic swine. After ICG-loaded microballoons are injected into the gallbladder, the biliary structure is imaged by both hyperspectral and fluorescence imaging modalities. Advanced spectral analysis and image processing algorithms are developed to classify the tissue types and identify the biliary anatomy. While fluorescence imaging provides dynamic information of movement and flow in the surgical region of interest, data from hyperspectral imaging allow for rapid identification of the bile duct and safe exclusion of any contaminant fluorescence from tissue not part of the biliary anatomy. Our experiments demonstrate the technical feasibility of using ICG-loaded microballoons for biliary imaging in cholecystectomy. PMID:23214186

  12. The role of sonography in imaging of the biliary tract.

    PubMed

    Foley, W Dennis; Quiroz, Francisco A

    2007-06-01

    Sonography is the recommended initial imaging test in the evaluation of patients presenting with right upper quadrant pain or jaundice. Dependent upon clinical circumstances, the differential diagnosis includes choledocholithiasis, biliary stricture, or tumor. Sonography is very sensitive in detection of mechanical biliary obstruction and stone disease, although less sensitive for detection of obstructing tumors, including pancreatic carcinoma and cholangiocarcinoma. In patients with sonographically documented cholelithiasis and choledocholithiasis, laparoscopic cholecystectomy with operative clearance of the biliary stone disease is usually performed. In patients with clinically suspected biliary stone disease, without initial sonographic documentation of choledocholithiasis, endoscopic ultrasound or magnetic resonance cholangiopancreatography is the next logical imaging step. Endoscopic ultrasound documentation of choledocholithiasis in a postcholecystectomy patient should lead to retrograde cholangiography, sphincterotomy, and clearance of the ductal calculi by endoscopic catheter techniques. In patients with clinical and sonographic findings suggestive of malignant biliary obstruction, a multipass contrast-enhanced computed tomography (CT) examination to detect and stage possible pancreatic carcinoma, cholangiocarcinoma, or periductal neoplasm is usually recommended. Assessment of tumor resectability and staging can be performed by CT or a combination of CT and endoscopic ultrasound, the latter often combined with fine needle aspiration biopsy of suspected periductal tumor. In patients whose CT scan suggests hepatic hilar or central intrahepatic biliary tumor, percutaneous cholangiography and transhepatic biliary stent placement is usually followed by brushing or fluoroscopically directed fine needle aspiration biopsy for tissue diagnosis. Sonography is the imaging procedure of choice for biliary tract intervention, including cholecystostomy, guidance for

  13. 21 CFR 876.5010 - Biliary catheter and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Biliary catheter and accessories. 876.5010 Section 876.5010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5010 Biliary...

  14. 21 CFR 876.5010 - Biliary catheter and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Biliary catheter and accessories. 876.5010 Section 876.5010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5010 Biliary...

  15. 21 CFR 876.5010 - Biliary catheter and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Biliary catheter and accessories. 876.5010 Section 876.5010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5010 Biliary...

  16. 21 CFR 876.5010 - Biliary catheter and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Biliary catheter and accessories. 876.5010 Section 876.5010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5010 Biliary...

  17. Indocyanine-green-loaded microballoons for biliary imaging in cholecystectomy

    NASA Astrophysics Data System (ADS)

    Mitra, Kinshuk; Melvin, James; Chang, Shufang; Park, Kyoungjin; Yilmaz, Alper; Melvin, Scott; Xu, Ronald X.

    2012-11-01

    We encapsulate indocyanine green (ICG) in poly[(D,L-lactide-co-glycolide)-co-PEG] diblock (PLGA-PEG) microballoons for real-time fluorescence and hyperspectral imaging of biliary anatomy. ICG-loaded microballoons show superior fluorescence characteristics and slower degradation in comparison with pure ICG. The use of ICG-loaded microballoons in biliary imaging is demonstrated in both biliary-simulating phantoms and an ex vivo tissue model. The biliary-simulating phantoms are prepared by embedding ICG-loaded microballoons in agar gel and imaged by a fluorescence imaging module in a Da Vinci surgical robot. The ex vivo model consists of liver, gallbladder, common bile duct, and part of the duodenum freshly dissected from a domestic swine. After ICG-loaded microballoons are injected into the gallbladder, the biliary structure is imaged by both hyperspectral and fluorescence imaging modalities. Advanced spectral analysis and image processing algorithms are developed to classify the tissue types and identify the biliary anatomy. While fluorescence imaging provides dynamic information of movement and flow in the surgical region of interest, data from hyperspectral imaging allow for rapid identification of the bile duct and safe exclusion of any contaminant fluorescence from tissue not part of the biliary anatomy. Our experiments demonstrate the technical feasibility of using ICG-loaded microballoons for biliary imaging in cholecystectomy.

  18. 21 CFR 876.5010 - Biliary catheter and accessories.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Biliary catheter and accessories. 876.5010 Section 876.5010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5010 Biliary...

  19. Biliary leakage after urgent cholecystectomy: Optimization of endoscopic treatment

    PubMed Central

    Ljubičić, Neven; Bišćanin, Alen; Pavić, Tajana; Nikolić, Marko; Budimir, Ivan; Mijić, August; Đuzel, Ana

    2015-01-01

    AIM: To investigate the results of endoscopic treatment of postoperative biliary leakage occurring after urgent cholecystectomy with a long-term follow-up. METHODS: This is an observational database study conducted in a tertiary care center. All consecutive patients who underwent endoscopic retrograde cholangiography (ERC) for presumed postoperative biliary leakage after urgent cholecystectomy in the period between April 2008 and April 2013 were considered for this study. Patients with bile duct transection and biliary strictures were excluded. Biliary leakage was suspected in the case of bile appearance from either percutaneous drainage of abdominal collection or abdominal drain placed at the time of cholecystectomy. Procedural and main clinical characteristics of all consecutive patients with postoperative biliary leakage after urgent cholecystectomy, such as indication for cholecystectomy, etiology and type of leakage, ERC findings and post-ERC complications, were collected from our electronic database. All patients in whom the leakage was successfully treated endoscopically were followed-up after they were discharged from the hospital and the main clinical characteristics, laboratory data and common bile duct diameter were electronically recorded. RESULTS: During a five-year period, biliary leakage was recognized in 2.2% of patients who underwent urgent cholecystectomy. The median time from cholecystectomy to ERC was 6 d (interquartile range, 4-11 d). Endoscopic interventions to manage biliary leakage included biliary stent insertion with or without biliary sphincterotomy. In 23 (77%) patients after first endoscopic treatment bile flow through existing surgical drain ceased within 11 d following biliary therapeutic endoscopy (median, 4 d; interquartile range, 2-8 d). In those patients repeat ERC was not performed and the biliary stent was removed on gastroscopy. In seven (23%) patients repeat ERC was done within one to fourth week after their first ERC

  20. Rare biliary cystic tumors: a case series of biliary cystadenomas and cystadenocarcinoma.

    PubMed

    Banerjee, Abhirup; Shah, Sudeep R; Singh, Abhiyutthan; Joshi, Anand; Desai, Devendra

    2016-01-01

    Cystic lesions of the liver are common and a major proportion is formed by parasitic cysts and simple cysts. Biliary cystic tumors (BCTs), namely biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC), are rare tumors which usually arise from the intrahepatic biliary tree. BCAs have malignant potential and are difficult to differentiate from BCAC pre-operatively on radiological imaging. Here we have presented 4 patients with BCTs and reviewed the literature pertaining to them.The data of four patients with BCA/BCAC diagnosed and treated at our institute were retrieved from our database and records were reviewed for age, sex, history, imaging, surgery, pathology and follow-up. Mean age of the patients was 53.5 years (range 30-71 years). Two male and two female patients presented with abdominal pain, of which one male patient had pancreatitis at diagnosis. Characteristic features were seen on pre-operative imaging (cystic lesions with internal septations) and biliary communication was identified in the patient with pancreatitis. Three patients were diagnosed with a BCA on final histology, while one patient had a BCAC. Following surgical resection, all the patients are asymptomatic and disease free with a mean follow-up of 24 months (range 10-40 months). In conclusion, BCTs should be suspected in the presence of a well-encapsulated, cystic hepatic lesion with internal septations. Although pre-operative distinction between BCA and BCAC is difficult, the lesion, whenever possible, should be completely resected as long-term outcomes are good, especially with BCA. PMID:27049501

  1. Percutaneous cholangioscopy in obstructed biliary metal stents

    SciTech Connect

    Hausegger, Klaus A.; Mischinger, Hans J.; Karaic, Radenko; Klein, Guenther E.; Kugler, Cristian; Kern, Robert; Uggowitzer, Martin; Szolar, Dieter

    1997-05-15

    Purpose. To reevaluate the reasons for the occlusion of self-expanding biliary metal stents, on the basis of cholangioscopic findings. Methods. Percutaneous transhepatic cholangioscopy (PTCS) was performed in 15 patients with obstructed biliary Wallstents. The reason for stent insertion was a malignant obstruction in 14 patients; 1 had a benign biliary stricture. Conventional noncovered stents had been inserted in 12 patients; in 3 cases a polyurethane-covered prototype Wallstent had been used. Stent occlusions occurred after 1-55 months. PTCS was performed with a 2.3-mm endoscope through an 11 Fr sheath. Biopsies were taken via the working channel of the endoscope. Results. In all patients with noncovered stents the inner surface of the stent was highly irregular with seaweed-like protrusions (biopsy-proven granulation tissue). Stent incorporation varied from absent (n=1) to subtotal (n=8), but was always incomplete, no matter how long the stent had been in place. Tumor ingrowth was histologically proven in 2 patients. One patient had a large occluding concrement at the proximal end of the stent. In patients with covered stents, the inner surface appeared more regular; however, viable granulation tissue was found inside two stents and tumor ingrowth in one of them. Conclusion. PTCS showed that incorporation of the stent is virtually always incomplete. The factors contributing most to stent occlusion are the buildup of granulation tissue, bile sludge, and tumor overgrowth. Stone formation and tumor ingrowth can also be important, although less common causes of occlusion. A polyurethane stent covering could not prevent tumor ingrowth in one patient and the buildup of viable granulation tissue inside the stent in two further patients; mean stent patency in the three patients with such a stent was 3 months.

  2. Amylase creatinine clearance ratio after biliary surgery.

    PubMed

    Donaldson, L A; McIntosh, W; Joffe, S N

    1977-01-01

    The amylase creatinine clearance ratio (ACCR) is considered to be a more sensitive index of acute pancreatitis than the serum amylase level. Serial ACCR estimations were undertaken in 25 patients undergoing an elective cholecystectomy. Using accepted criteria, 28% of these patients developed, in the postoperative period, biochemical evidence of pancreatic gland damage, although the serum amylase level remained normal. This raised ACCR was particularly noted in patients who had undergone an exploration of the common bile duct. The ACCR would appear to be a more sensitive index of pancreatic gland disruption secondary to biliary surgery than the serum amylase level.

  3. Amylase creatinine clearance ratio after biliary surgery.

    PubMed

    Donaldson, L A; McIntosh, W; Joffe, S N

    1977-01-01

    The amylase creatinine clearance ratio (ACCR) is considered to be a more sensitive index of acute pancreatitis than the serum amylase level. Serial ACCR estimations were undertaken in 25 patients undergoing an elective cholecystectomy. Using accepted criteria, 28% of these patients developed, in the postoperative period, biochemical evidence of pancreatic gland damage, although the serum amylase level remained normal. This raised ACCR was particularly noted in patients who had undergone an exploration of the common bile duct. The ACCR would appear to be a more sensitive index of pancreatic gland disruption secondary to biliary surgery than the serum amylase level. PMID:402305

  4. Hemobilia from Biliary Angiodysplasia Diagnosed with Cholangioscopy

    PubMed Central

    Lee, Ashley; Kudakachira, Shaismy; Ramberan, Hemchand

    2016-01-01

    Biliary angiodysplasia is extremely rare. Our background search revealed only a few case reports in the English literature. We present a case of angiodysplasia of the proximal common bile duct in a patient with subacute upper gastrointestinal bleeding and symptomatic anemia. A standard esophagogastroduodenoscopy with subsequent dedicated duodenoscopy revealed blood-stained bile draining from the major ampulla orifice. A contrast-enhanced magnetic resonance cholangiopancreatography was unrevealing for any pancreaticobiliary pathology. The patient subsequently underwent an endoscopic retrograde cholangiopancreatography and SpyGlass® cholangioscopy, which demonstrated intermittent bleeding from angiodysplasia in the proximal common bile duct. PMID:27807584

  5. Update of cholangioscopy and biliary strictures

    PubMed Central

    Chin, Marcus W; Byrne, Michael F

    2011-01-01

    Cholangioscopy remains another modality in the investigation of biliary strictures. At cholangioscopy, the “tumour vessel” sign is considered a specific sign for malignancy. Through its ability to not only visualise mucosa, but to take targeted biopsies, it has a greater accuracy, sensitivity and specificity for malignant strictures than endoscopic retrograde cholangiopancreatography guided cytopathological acquisition. Cholangioscopy however, is time consuming and costly, requires greater technical expertise, and should be reserved for the investigation of undifferentiated strictures after standard investigations have failed. PMID:22025874

  6. Percutaneous endoscopic management of intrahepatic stones in patients with altered biliary anatomy: A case series.

    PubMed

    Bhandari, Suryaprakash; Bathini, Rajesh; Sharma, Atul; Maydeo, Amit

    2016-03-01

    Incidence of primary intrahepatic stones (IHS) in India is very less as compared to the Far East. However patients with altered biliary anatomy are prone for IHS formation secondary to anastomotic stricture formation. Indian data on percutaneous endoscopic management of IHS is scare. Five patients with IHS were managed percutaneously. All patients had undergone Roux-en-Y hepaticojejunostomy and were not suitable for direct endoscopic intervention. All patients underwent percutaneous biliary drainage followed by cholangioscopy-guided laser lithotripsy. Crushed stones were pushed across the anastomotic site using basket/balloon and ductal clearance was achieved. Good stone pulverization could be achieved in five patients (100 %). Complete ductal clearance could be achieved in all patients (100 %). Cholangioscopy-guided treatment of IHS can be valuable alternative to surgery in select group of patients especially those having dilated biliary tree with absence of intrahepatic strictures. However long-term follow up studies are required to see for recurrence of stone formation. PMID:27041379

  7. Trends in pediatric ostomy surgery: intestinal diversion for necrotizing enterocolitis and biliary diversion for biliary hypoplasia syndromes.

    PubMed

    Bastawrous, A A; Torosian, M B; Statter, M B; Arensman, R M

    1995-11-01

    Ostomies are placed in children for different indications than in the older population. Many ostomies of childhood are placed because of congenital or neonatal problems that require temporary or long-term diversion to stabilize the neonatal patient. Necrotizing enterocolitis, the most common reason for placement of neonatal colostomies and ileostomies, is increasing in frequency as more prematurely born infants survive. Recently, there has been an increase in treatment of various biliary hypoplasia syndromes with biliary cutaneous diversion. Children with biliary hypoplasia syndromes are a challenging group of patients who frequently can be helped by ostomies. This article reviews current information on biliary cutaneous diversion for the biliary hypoplasia syndromes and intestinal diversion for necrotizing enterocolitis.

  8. Obstructive Jaundice in Hepatocellular Carcinoma: Response after Percutaneous Transhepatic Biliary Drainage and Prognostic Factors

    SciTech Connect

    Lee, Joon Woo; Han, Joon Koo; Kim, Tae Kyoung; Choi, Byung Ihn; Park, Seong Ho; Ko, Young Hwan; Yoon, Chang Jin; Yeon, Kyung-Mo

    2002-06-15

    Purpose: To evaluate the therapeutic effect of percutaneous transhepatic biliary drainage (PTBD) in patients with obstructive jaundice caused by biliary involvement of hepatocellular carcinomas (HCC) and to determine the prognostic factors. Methods: We retrospectively analyzed the data of 22 consecutive patients (M:F = 20:2, mean age 52.8 years).Inclusion criteria were the patient having obstructive jaundice caused by HCC that invaded the bile ducts and having at least 4 weeks of follow-up data after the PTBD. We defined 'good response' and 'poor response' as whether the level of total bilirubin decreased more than 50% in 4 weeks or not. Total bilirubin level (T-bil),Child-Pugh score and the location of biliary obstruction for the two groups were compared. In addition, the interval between clinical onset of jaundice and PTBD, the degree of parenchymal atrophy and the size of the primary tumor were compared. Results: Of the 22 patients, 13 (59.1%) showed good response. T-bil was significantly lower in the good response group than in the poor (14.2 {+-} 6 mg/dlvs 25.9 {+-} 13.8 mg/dl, p = .017). In the five patients with T-bil <10 mg/dl, four (80%) showed good response,while in nine patients with T-bil > 20 mg/dl, only three (33%)showed good response. Although statistically not significant, patients with Child score <10 showed better results [good response rate of 66.7% (12/18)] than patients with Child score ?10 [good response rate of 25% (1/4)]. Involvement of secondary confluence of the bile duct also served as a poor prognostic factor (p =0.235). The interval between clinical onset of jaundice and PTBD, the presence of parenchymal atrophy and the size of the tumor did not show significant effect. Conclusion: Early and effective biliary drainage might be necessary in this group of patients with limited hepatic function.

  9. Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores.

    PubMed

    Hagey, L R; Crombie, D L; Espinosa, E; Carey, M C; Igimi, H; Hofmann, A F

    1993-11-01

    The biliary bile acid composition of gallbladder bile obtained from six species of bears (Ursidae), the Giant panda, the Red panda, and 11 related carnivores were determined by reversed phase liquid chromatography and gas chromatography-mass spectrometry. Bile acids were conjugated solely with taurine (in N-acyl linkage) in all species. Ursodeoxycholic acid (3 alpha, 7 beta-dihydroxy-5 beta-cholan-24-oic acid) was present in all Ursidae, averaging 1-39% of biliary bile acids depending on the species; it was not detected or present as a trace constituent (< 0.5%) in all other species, including the Giant panda. Ursodeoxycholic acid was present in 73 of 75 American Black bears, and its proportion averaged 34% (range 0-62%). Ursodeoxycholic acid averaged 17% of biliary bile acids in the Polar bear (n = 4) and 18% in the Brown bear (n = 6). Lower proportions (1-8%) were present in the Sun bear (n = 2), Ceylon Sloth bear (n = 1), and the Spectacled bear (n = 1). Bile of all species contained taurine-conjugated chenodeoxycholic acid and cholic acid. In some related carnivores, deoxycholic acid, the 7-dehydroxylation product of cholic acid, was also present. To determine whether the 7 beta hydroxy group of ursodeoxycholic acid was formed by hepatic or bacterial enzymes, bile acids were determined in hepatic bile obtained from bears with chronic biliary fistulae. Fistula bile samples contained ursodeoxycholic acid, chenodeoxycholic acid, and a trace amount of cholic acid, all as taurine conjugates, indicating that ursodeoxycholic acid is a primary bile acid formed in the liver in Ursidae.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Malignant biliary obstruction: From palliation to treatment.

    PubMed

    Boulay, Brian R; Birg, Aleksandr

    2016-06-15

    Malignant obstruction of the bile duct from cholangiocarcinoma, pancreatic adenocarcinoma, or other tumors is a common problem which may cause debilitating symptoms and increase the risk of subsequent surgery. The optimal treatment - including the decision whether to treat prior to resection - depends on the type of malignancy, as well as the stage of disease. Preoperative biliary drainage is generally discouraged due to the risk of infectious complications, though some situations may benefit. Patients who require neoadjuvant therapy will require decompression for the prolonged period until attempted surgical cure. For pancreatic cancer patients, self-expanding metallic stents are superior to plastic stents for achieving lasting decompression without stent occlusion. For cholangiocarcinoma patients, treatment with percutaneous methods or nasobiliary drainage may be superior to endoscopic stent placement, with less risk of infectious complications or failure. For patients of either malignancy who have advanced disease with palliative goals only, the choice of stent for endoscopic decompression depends on estimated survival, with plastic stents favored for survival of < 4 mo. New endoscopic techniques may actually extend stent patency and patient survival for these patients by achieving local control of the obstructing tumor. Both photodynamic therapy and radiofrequency ablation may play a role in extending survival of patients with malignant biliary obstruction.

  11. Endoscopic treatment of malignant biliary strictures.

    PubMed

    Rustagi, Tarun; Jamidar, Priya A

    2015-01-01

    Endoscopic stenting is a widely accepted strategy for providing effective drainage in both extrahepatic and intrahepatic malignant strictures. In patients with extrahepatic malignancies, uncovered self-expanding metal stents (SEMS) provide excellent palliation. Hilar malignancies are probably best palliated by placement of uncovered SEMS although some disagreement exists among experts regarding the type and number of stents for optimal palliation. Preoperative biliary drainage (PBD) is commonly performed although a higher risk of complications and the lack of clear benefit raise questions about this practice. Certain groups of patients such as those with markedly elevated bilirubin levels, and in those in whom neoadjuvant therapy is planned, are good candidates for PBD. Considerable controversy exists regarding the optimal method as well as type of stent for PBD in patients with hilar malignancies. Novel endoscopic therapies, including photodynamic therapy and radiofrequency ablation, have emerged as potential adjuvant therapies in the management of malignant bile duct strictures but need further long-term evaluation to establish survival benefit. This review focuses on the current status of endoscopic therapies for malignant biliary obstructions.

  12. Malignant biliary obstruction: From palliation to treatment.

    PubMed

    Boulay, Brian R; Birg, Aleksandr

    2016-06-15

    Malignant obstruction of the bile duct from cholangiocarcinoma, pancreatic adenocarcinoma, or other tumors is a common problem which may cause debilitating symptoms and increase the risk of subsequent surgery. The optimal treatment - including the decision whether to treat prior to resection - depends on the type of malignancy, as well as the stage of disease. Preoperative biliary drainage is generally discouraged due to the risk of infectious complications, though some situations may benefit. Patients who require neoadjuvant therapy will require decompression for the prolonged period until attempted surgical cure. For pancreatic cancer patients, self-expanding metallic stents are superior to plastic stents for achieving lasting decompression without stent occlusion. For cholangiocarcinoma patients, treatment with percutaneous methods or nasobiliary drainage may be superior to endoscopic stent placement, with less risk of infectious complications or failure. For patients of either malignancy who have advanced disease with palliative goals only, the choice of stent for endoscopic decompression depends on estimated survival, with plastic stents favored for survival of < 4 mo. New endoscopic techniques may actually extend stent patency and patient survival for these patients by achieving local control of the obstructing tumor. Both photodynamic therapy and radiofrequency ablation may play a role in extending survival of patients with malignant biliary obstruction. PMID:27326319

  13. Biliary atresia: Clinical advances and perspectives.

    PubMed

    Nizery, Laure; Chardot, Christophe; Sissaoui, Samira; Capito, Carmen; Henrion-Caude, Alexandra; Debray, Dominique; Girard, Muriel

    2016-06-01

    Biliary atresia (BA) is a rare and severe inflammatory and obliterative cholangiopathy that affects both extra- and intrahepatic bile ducts. BA symptoms occur shortly after birth with jaundice, pale stools and dark urines. The prognosis of BA has dramatically changed in the last decades: before the Kasai operation most BA patients died, while nowadays with the sequential treatment with Kasai operation±liver transplantation BA patient survival is close to 90%. Early diagnosis is very important since the chances of success of the Kasai procedure decrease with time. The causes of BA remain actually unknown but several mechanisms including genetic and immune dysregulation may probably lead to the obliterative cholangiopathy. Current research focuses on the identification of blood or liver factors linked to the pathogenesis of BA that could become therapeutic targets and avoid the need for liver transplantation. No similar disease leading to total obstruction of the biliary tree exists in older children or adults. But understanding the physiopathology of BA may highlight the mechanisms of other destructive cholangiopathies, such as sclerosing cholangitis. PMID:26775892

  14. Interferon-Gamma Directly Mediates Developmental Biliary Defects

    PubMed Central

    Cui, Shuang; EauClaire, Steven F.

    2013-01-01

    Abstract Biliary atresia (BA) is the most common identifiable hepatobiliary disease affecting infants, in which there are defects in intra- and extrahepatic bile ducts and progressive fibrosis. Activation of interferon-gamma (IFNγ) appears to be critical in both patients with BA and in rodent models of BA. We have recently reported a zebrafish model of biliary disease that shares features with BA, in which inhibition of DNA methylation leads to intrahepatic biliary defects and activation of IFNγ target genes. Here we report that ifng genes are hypomethylated and upregulated in zebrafish larvae treated with azacytidine (azaC), an inhibitor of DNA methylation. Injection of IFNγ protein into developing zebrafish larvae leads to biliary defects, suggesting that activation of the IFNγ pathway is sufficient to cause developmental biliary defects. These defects are associated with decreased cholangiocyte proliferation and with a decrease in the expression of vhnf1 (hnf1b, tcf2), which encodes a homeodomain protein with previously reported roles in biliary development in multiple models. These results support an importance of IFNγ in mediating biliary defects, and also demonstrate the feasibility of direct injection of intact protein into developing zebrafish larvae. PMID:23448251

  15. Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats

    SciTech Connect

    Fuhrman-Lane, C.; Fujimoto, J.M.

    1982-09-01

    The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

  16. Biliary epithelial cells proliferate during oxygenated ex situ liver culture

    PubMed Central

    Bian, Congwen; Du, Yiqi; Ding, Rui; Huang, Jun; Dai, Yan; Bao, Sujin; Zhao, Lijuan; Shen, Hefang; Dong, Jing; Xu, Jianjian; Xiong, Qiru; Xu, Lili

    2016-01-01

    Biliary complications remain a major source of morbidity in liver transplant patients. Among these complications, nonanastomotic biliary strictures (NAS) are especially common and they are frequently therapy resistant in part because biliary epithelial cells are more sensitive to warm ischemic injury than hepatocytes. It has been a challenge to maintain the physiological function of biliary epithelial cells during liver transplantation. In this work, we have examined the effect of oxygen on proliferation of biliary epithelial cells in the rat livers obtained from donation after circulatory death (DCD). Twelve rat livers from DCD were divided into two groups. Livers in the control group were isolated following a standard procedure without oxygen supply. Livers in the experimental group were isolated with a constant supply of oxygen. All livers were then connected to an ex situ liver culture system in the presence of bromodeoxyuridine (BrdU), a thymidine analogue and a marker for cell proliferation. After 6 hours of normothermic ex situ liver culture, morphology and DNA replication in hepatocytes and biliary epithelial cells were assessed and compared between the two groups. We found that about 4.5% of the biliary epithelial cells in the experimental group proliferated compared with only 0.4% of cells in the control based on BrdU staining. No significant change in cell morphology was observed in those cells between the two groups. Thus, our results indicate that oxygen supply is required for maintenance of the physiological function of biliary epithelial cells during liver transplant and suggest that a constant oxygen supply during liver isolation along with ex situ liver organ culture can enhance the repair of biliary epithelial cell injury during liver transplantation. PMID:27725875

  17. Recent advances in endoscopic ultrasonography-guided biliary interventions.

    PubMed

    Kawakubo, Kazumichi; Kawakami, Hiroshi; Kuwatani, Masaki; Haba, Shin; Kawahata, Shuhei; Abe, Yoko; Kubota, Yoshimasa; Kubo, Kimitoshi; Isayama, Hiroyuki; Sakamoto, Naoya

    2015-08-28

    Interventional endoscopic ultrasonography (EUS) based on EUS-guided fine-needle aspiration has rapidly spread as a minimally invasive procedure. Especially in patients with failed endoscopic retrograde cholangiopancreatography, EUS-guided biliary intervention is reported to be useful as salvage therapy. EUS-guided biliary interventions are carried out using three techniques: EUS-guided bilioenteric anastomosis, EUS-guided rendezvous procedure, and EUS-guided antegrade treatment. Although interventional EUS is not yet a standardized procedure, there have been recent advances in this field that address various biliary diseases. Here, we summarize the indications, techniques, clinical results of previous studies, and future perspectives.

  18. Recent advances in endoscopic ultrasonography-guided biliary interventions

    PubMed Central

    Kawakubo, Kazumichi; Kawakami, Hiroshi; Kuwatani, Masaki; Haba, Shin; Kawahata, Shuhei; Abe, Yoko; Kubota, Yoshimasa; Kubo, Kimitoshi; Isayama, Hiroyuki; Sakamoto, Naoya

    2015-01-01

    Interventional endoscopic ultrasonography (EUS) based on EUS-guided fine-needle aspiration has rapidly spread as a minimally invasive procedure. Especially in patients with failed endoscopic retrograde cholangiopancreatography, EUS-guided biliary intervention is reported to be useful as salvage therapy. EUS-guided biliary interventions are carried out using three techniques: EUS-guided bilioenteric anastomosis, EUS-guided rendezvous procedure, and EUS-guided antegrade treatment. Although interventional EUS is not yet a standardized procedure, there have been recent advances in this field that address various biliary diseases. Here, we summarize the indications, techniques, clinical results of previous studies, and future perspectives. PMID:26327757

  19. Recent advances in endoscopic ultrasonography-guided biliary interventions.

    PubMed

    Kawakubo, Kazumichi; Kawakami, Hiroshi; Kuwatani, Masaki; Haba, Shin; Kawahata, Shuhei; Abe, Yoko; Kubota, Yoshimasa; Kubo, Kimitoshi; Isayama, Hiroyuki; Sakamoto, Naoya

    2015-08-28

    Interventional endoscopic ultrasonography (EUS) based on EUS-guided fine-needle aspiration has rapidly spread as a minimally invasive procedure. Especially in patients with failed endoscopic retrograde cholangiopancreatography, EUS-guided biliary intervention is reported to be useful as salvage therapy. EUS-guided biliary interventions are carried out using three techniques: EUS-guided bilioenteric anastomosis, EUS-guided rendezvous procedure, and EUS-guided antegrade treatment. Although interventional EUS is not yet a standardized procedure, there have been recent advances in this field that address various biliary diseases. Here, we summarize the indications, techniques, clinical results of previous studies, and future perspectives. PMID:26327757

  20. Timing of cholecystectomy in biliary pancreatitis treatment

    PubMed Central

    Demir, Uygar; Yazıcı, Pınar; Bostancı, Özgür; Kaya, Cemal; Köksal, Hakan; Işıl, Gürhan; Bozdağ, Emre; Mihmanlı, Mehmet

    2014-01-01

    Objective: Gallstone pancreatitis constitutes 40% of all cases with pancreatitis while it constitutes up to 90% of cases with acute pancreatitis. The treatment modality in this patient population is still controversial. In this study, we aimed to compare the results of early and late cholecystectomy for patients with biliary pancreatitis. Material and Methods: Patients treated with a diagnosis of acute biliary pancreatitis in our clinics between January 2000 and December 2011 were retrospectively reviewed. Patients were divided into two groups: Group A, patients who underwent cholecystectomy during the first pancreatitis attack, Group B, patients who underwent an interval cholecystectomy at least 8 weeks after the first pancreatitis episode. The demographic characteristics, clinical symptoms, number of episodes, length of hospital stay, morbidity and mortality data were recorded. All data were evaluated with Statistical Package for the Social Sciences (SPSS) 13.0 for windows and p <0.05 was considered as statistically significant. Results: During the last 12 years, a total of 91 patients with surgical treatment for acute biliary pancreatitis were included into the study. There were 62 female and 29 male patients, with a mean age of 57.9±14.6 years (range: 21–89). A concomitant acute cholecystitis was present in 46.2% of the patients. Group A and B included 48 and 43 patients, respectively. The length of hospital stay was significantly higher in group B (9.4 vs. 6.8 days) (p<0,05). More than half of the patients in Group B were readmitted to the hospital for various reasons. No significant difference was observed between the two groups, one patient died due to heart failure in the postoperative period in group B. Conclusion: In-hospital cholecystectomy after remission of acute pancreatitis is feasible. It will not only result in lower recurrence and complication rates but also shorten length of hospital stay. We recommend performing cholecystectomy during the

  1. Biliary epithelial senescence and plasticity in acute cellular rejection.

    PubMed

    Brain, J G; Robertson, H; Thompson, E; Humphreys, E H; Gardner, A; Booth, T A; Jones, D E J; Afford, S C; von Zglinicki, T; Burt, A D; Kirby, J A

    2013-07-01

    Biliary epithelial cells (BEC) are important targets in some liver diseases, including acute allograft rejection. Although some injured BEC die, many can survive in function compromised states of senescence or phenotypic de-differentiation. This study was performed to examine changes in the phenotype of BEC during acute liver allograft rejection and the mechanism driving these changes. Liver allograft sections showed a positive correlation (p < 0.0013) between increasing T cell mediated acute rejection and the number of BEC expressing the senescence marker p21(WAF1/Cip) or the mesenchymal marker S100A4. This was modeled in vitro by examination of primary or immortalized BEC after acute oxidative stress. During the first 48 h, the expression of p21(WAF1/Cip) was increased transiently before returning to baseline. After this time BEC showed increased expression of mesenchymal proteins with a decrease in epithelial markers. Analysis of TGF-β expression at mRNA and protein levels also showed a rapid increase in TGF-β2 (p < 0.006) following oxidative stress. The epithelial de-differentiation observed in vitro was abrogated by pharmacological blockade of the ALK-5 component of the TGF-β receptor. These data suggest that stress induced production of TGF-β2 by BEC can modify liver allograft function by enhancing the de-differentiation of local epithelial cells.

  2. Biliary tract cancers: SEOM clinical guidelines.

    PubMed

    Benavides, M; Antón, A; Gallego, J; Gómez, M A; Jiménez-Gordo, A; La Casta, A; Laquente, B; Macarulla, T; Rodríguez-Mowbray, J R; Maurel, J

    2015-12-01

    Biliary tract cancer (BTC) is an uncommon and highly fatal malignancy. It is composed of three main different entities; Gall bladder carcinoma (GBC), intrahepatic cholangiocarcinoma (iCC) and extrahepatic cholangiocarcinoma (eCC) sharing different genetic, risk factors and clinical presentation. Multidetector-row computed tomography (MDCT) and magnetic resonance cholangio-pancreatography (MRCP) are the more important diagnostic techniques. Surgery is the only potentially curative therapy but disease recurrence is frequent. Treatment with chemotherapy, radiotherapy or both has not demonstrated survival benefit in the adjuvant setting. Cisplatin plus gemcitabine constitutes the gold standard in metastatic disease. New ongoing studies mainly in the adjuvant and neoadjuvant setting along with molecular research will hopefully help to improve survival and quality of life of this disease. PMID:26607930

  3. Vascular Biology of the Biliary Epithelium

    PubMed Central

    Morell, Carola M.; Fabris, Luca; Strazzabosco, Mario

    2012-01-01

    Cholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are nourished by an own arterial supply, the peribiliary plexus. This capillary network originates from the hepatic artery and is strictly arranged around the intrahepatic bile ducts. Biliary and vascular structures are linked by a close anatomic and functional association necessary for liver development, normal organ physiology and liver repair. This strong association is finely regulated by a range of angiogenic signals, enabling the crosstalk between cholangiocytes and the different vascular cell types. This review will briefly illustrate the “vascular” properties of cholangiocytes, their underlying molecular mechanisms and the relevant pathophysiological settings. PMID:23855292

  4. Primary Bile Duct Melanoma Causing Obstructive Jaundice

    PubMed Central

    Addepally, Naga S.; Klair, Jagpal S.; Lai, Keith; Aduli, Farshad

    2016-01-01

    Malignant melanoma is one of the few malignancies that are well known for unusual behavior. Primary malignant melanoma usually originates from squamous epithelium of skin, mucous membranes, retina, and uvea. Although melanoma can metastasize to any part of the body, including biliary tract, primary malignant melanoma of bile ducts is an extremely rare entity. We present a 52-year-old man who presented with 5-month epigastric pain and 15-pound weight loss, with 1-week duration of jaundice, nausea/vomiting, pale stools, and dark urine, blood work suggested cholestatic jaundice. Imaging revealed a large perihilar/peripancreatic mass involving the portal vein and hepatic artery, and intrahepatic biliary dilation. Biliary brushings revealed neoplastic cells strongly suggestive of malignant melanoma. PMID:27807580

  5. [Biliary mucinous cystadenocarcinoma of the liver].

    PubMed

    Colović, R; Perisić-Savić, M; Havelka, M

    1990-01-01

    Biliary mucinous cystadenocarcinoma is an extremely rare tumour. Less than 50 cases have been reported. It is usually a multilocular cystic tumour covered with mucous producing epithelium, with papillary excrescences containing mucinous mass arising from bile ducts. The size of the tumour varies from 3.5 to 25 cm in diameter. It is more frequent in women. The majority of patients belong to the middle age population. We present a 63-year-old man who had been suffering from an epigastric and right subcostal pain of unknown aetiology for over 35 years. During the last 10 years he suffered from multiple attacks of cholangitis with high temperature, rigor, chills, pain and obstructive jaundice. Five years ago he had the attack of pancreatitis with retroperitoneal fatty necrosis for which he was operated on in another institution and cholecystectomy and pancreatic necrectomy were carried out. The attacks of cholangitis continued they were more serious and more frequent until June 1987, when the "cyst" in the left lobe of the liver, dilated bile ducts and "polyps" in the common bile duct were diagnosed by ultrasonography. During the operation advanced biliary cirrhosis, portal hypertension, splenomegaly, very dilated common bile duct full of jelly and the "cyst" in the liver filled with jelly, were found. The removal of the jelly and choledochojejunostomy resulted in temporary relief. Two months later he was reoperated for recurrent obstructive jaundice during which left lobectomy, partial excision of the cyst and cystojejunostomy between the rest of the cyst and another Roux-en-Y jejunal limb, were carried out.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Management of simultaneous biliary and duodenal obstruction: the endoscopic perspective.

    PubMed

    Baron, Todd H

    2010-09-01

    Obstructive jaundice often develops in patients with unresectable malignancy in and around the head of the pancreas. Duodenal obstruction can also occur in these patients, and usually develops late in the disease course. Palliation of both malignant biliary and duodenal obstruction is traditionally performed with surgical diversion of the bile duct and stomach, respectively. With the advent of nonsurgical palliation of biliary obstruction using endoscopic transpapillary expandable metal stent placement, a similar approach can be used to palliate duodenal obstruction by placement of expandable metal gastroduodenal stents. Endoscopic palliation can be achieved in patients who require relief of both biliary obstruction and duodenal obstruction, although this can be technically difficult to achieve depending on the level of duodenal obstruction in relation to the major papilla. This article reviews the endoscopic approaches for combined palliative relief of malignant biliary and duodenal obstruction.

  7. Biliary complications in right lobe living donor liver transplantation.

    PubMed

    Chok, Kenneth S H; Lo, Chung Mau

    2016-07-01

    Living donor liver transplantation is an alternative to deceased donor liver transplantation in the face of insufficient deceased donor liver grafts. Unfortunately, the incidence of biliary complication after living donor liver transplantation is significantly higher than that after deceased donor liver transplantation using grafts from non-cardiac-death donations. The two most common biliary complications after living donor liver transplantation are bile leakage and biliary anastomotic stricture. Early treatment with endoscopic and interventional radiological approaches can achieve satisfactory outcomes. If treatment with these approaches fails, the salvage measure for prompt rectification will be surgical revision, which is now seldom performed. This paper also discusses risk factors in donor biliary anatomy that can affect recipients. PMID:26932842

  8. Fractionation of livers following diosgenin treatment to elevate biliary cholesterol.

    PubMed

    Roman, I D; Thewles, A; Coleman, R

    1995-03-01

    The plant saponin, diosgenin, is known to induce a marked increase in biliary cholesterol/phospholipid ratio. We reasoned that putative biliary lipid supply vesicles might be similarly enriched with cholesterol. Seven-day diosgenin feeding to rats resulted in significantly increased biliary cholesterol and cholesterol/phospholipid ratio, but had no effect on total cholesterol or phospholipid content of the liver. Subcellular fractionation of livers showed no selective increase in any fraction (nuclear, mitochondrial, lysosomal, microsomal) of the homogenate. Further subfractionation of microsomal or nuclear (plasma membrane) fractions also showed no difference between control and diosgenin groups. Thus, no intracellular vesicle fraction has been identified with the provision of the enhanced biliary cholesterol and the results are discussed in terms of the possible involvement of cytosolic lipid-binding proteins as putative lipid carriers to the canalicular membrane as an alternative to the presence of the lipid in lipid supply vesicles.

  9. Ursodeoxycholic Acid Is Conjugated with Taurine to Promote Secretin-Stimulated Biliary Hydrocholeresis in the Normal Rat

    PubMed Central

    Úriz, Miriam; Sáez, Elena; Prieto, Jesús

    2011-01-01

    Background & Aims Secretin induces bicarbonate-rich hydrocholeresis in healthy individuals, but not in untreated patients with primary biliary cirrhosis (PBC). Ursodeoxycholic acid (UDCA) – the first choice treatment for PBC – restores the secretin response. Compared with humans, secretin has poor effect in experimental normal-rat models with biliary drainage, although it may elicit hydrocholeresis when the bile-acid pool is maintained. In view of the benefits of UDCA in PBC, we used normal-rat models to unravel the acute contribution of UDCA (and/or taurine-conjugated TUDCA) for eliciting the biliary secretin response. Methods Intravascular and/or intrabiliary administration of agonists and inhibitors was performed in normal rats with biliary monitoring. Secretin/bile-acid interplay was analyzed in 3D cultured rat cholangiocytes that formed expansive cystic structures with intralumenal hydroionic secretion. Results In vivo, secretin stimulates hydrocholeresis upon UDCA/TUDCA infusion, but does not modify the intrinsic hypercholeretic effect of dehydrocholic acid (DHCA). The former effect is dependent on microtubule polymerization, and involves PKCα, PI3K and MEK pathways, as shown by colchicine (i.p.) and retrograde biliary inhibitors. In vitro, while secretin alone accelerates the spontaneous expansion of 3D-cystic structures, this effect is enhanced in the presence of TUDCA, but not UDCA or DHCA. Experiments with inhibitors and Ca2+-chelator confirmed that the synergistic effect of secretin plus TUDCA involves microtubules, intracellular Ca2+, PKCα, PI3K, PKA and MEK pathways. Gene silencing also demonstrated the involvement of the bicarbonate extruder Ae2. Conclusions UDCA is conjugated in order to promote secretin-stimulated hydrocholeresis in rats through Ae2, microtubules, intracellular Ca2+, PKCα, PI3K, PKA, and MEK. PMID:22194894

  10. [Fissures in biliary calculi. Personal contribution (author's transl)].

    PubMed

    Nano, M; Potenzoni, F; Camandona, M; Casalegno, P A

    1979-04-01

    In a series of 70 patients suffering from biliary lithiasis, the roentgenologic findings of fissures in the calculi was observed in 5 cases examined by means of cholecystography and in 7 cases who underwent cholangiocholecystography. Fissures were demonstrated 11 times in calculi after surgery. The "Mercedes-Benz" sign was never observed at the abdominal examination without contrast medium. The presence of fissures may be an additional sign in the radiologic diagnosis of biliary calculi, but its value is not determinant.

  11. Complications of the extrahepatic biliary surgery in companion animals.

    PubMed

    Mehler, Stephen J

    2011-09-01

    Surgery of the biliary tract is demanding and is associated with several potentially life-threatening complications. Veterinarians face challenges in obtaining accurate diagnosis of biliary disease, surgical decision-making, surgical hemostasis and bile peritonitis. Intensive perioperative monitoring is required to achieve early recognition of common postoperative complications. Proper treatment and ideally, avoidance of surgical complications can be achieved by gaining a clear understanding physiology, anatomy, and the indications for hepatobiliary surgery.

  12. [Fissures in biliary calculi. Personal contribution (author's transl)].

    PubMed

    Nano, M; Potenzoni, F; Camandona, M; Casalegno, P A

    1979-04-01

    In a series of 70 patients suffering from biliary lithiasis, the roentgenologic findings of fissures in the calculi was observed in 5 cases examined by means of cholecystography and in 7 cases who underwent cholangiocholecystography. Fissures were demonstrated 11 times in calculi after surgery. The "Mercedes-Benz" sign was never observed at the abdominal examination without contrast medium. The presence of fissures may be an additional sign in the radiologic diagnosis of biliary calculi, but its value is not determinant. PMID:550199

  13. Biliary intraepithelial neoplasia (BilIN) is frequently found in surgical margins of biliary tract cancer resection specimens but has no clinical implications.

    PubMed

    Matthaei, Hanno; Lingohr, Philipp; Strässer, Anke; Dietrich, Dimo; Rostamzadeh, Babak; Glees, Simone; Roering, Martin; Möhring, Pauline; Scheerbaum, Martin; Stoffels, Burkhard; Kalff, Jörg C; Schäfer, Nico; Kristiansen, Glen

    2015-02-01

    Biliary tract cancers are aggressive tumors of which the incidence seems to increase. Resection with cancer-free margins is crucial for curative therapy. However, how often biliary intraepithelial neoplasia (BilIN) occurs in resection margins and what its clinical and therapeutic implications might be is largely unknown. We reexamined margins of resection specimens of adenocarcinoma of the biliary tree including the gallbladder for the presence of BilIN. When present, it was graded. The findings were correlated with clinicopathological parameters and overall survival. Complete examination of the resection margin could be performed on 55 of 78 specimens (71%). BilIN was detected in the margin in 29 specimens (53%) and was mainly low-grade (BilIN-1; N = 14 of 29; 48%). In resection specimens of extrahepatic cholangiocarcinoma, BilIN was most frequent (N = 6 of 8; 75%). BilIN was found in the resection margin more frequently in extrahepatic cholangiocarcinomas (P = 0.007) and in large primary tumors (P = 0.001) with lymphovascular (P = 0.006) and perineural invasion (P = 0.049). Patients with cancer in the resection margin (R1) had a significantly shorter overall survival than those with resection margins free of tumor (R0) irrespective of the presence of BilIN (R0 vs R1; P < 0.001) or BilIN grade (BilIN-positive vs BilIN-negative, P = 0.6, and BilIN-1 + 2 vs BilIN-3, P = 0.58). BilIN is frequently found in the surgical margin of resection specimens of adenocarcinoma of the biliary tract. Hepatopancreatobiliary surgeons will be confronted with this recently defined entity when an intraoperative frozen section of a resection margin is requested. However, this diagnosis does not require additional resection and in the intraoperative evaluation of resection, the emphasis should remain on the detection of residual invasive tumor. PMID:25425476

  14. A Phase II Trial of the Proteasome Inhibitor Bortezomib in Patients with Advanced Biliary Tract Cancers*

    PubMed Central

    Denlinger, Crystal S.; Meropol, Neal J.; Li, Tianyu; Lewis, Nancy L.; Engstrom, Paul F.; Weiner, Louis M.; Cheng, Jonathan D.; Alpaugh, R. Katherine; Cooper, Harry; Wright, John J.; Cohen, Steven J.

    2014-01-01

    Background Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers. Patients and Methods Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0–2 prior therapies received bortezomib 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate. A Simon two-stage design was employed (null response rate of < 5% and response rate of ≥ 20% of interest). Results Twenty patients enrolled: bile duct/gallbladder cancer (14/6), prior treatments 0/1/2 (10/6/3). The trial was discontinued early due to lack of confirmed partial responses. No unanticipated adverse events were noted. There was one unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% CI 0.7–77.6 months). Median survival was 9 months (95% CI 4.6–18.5 months). The 6-month and 1-year survival rates were 70% and 38%. There was no difference in survival based on primary disease site. Conclusions Single agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered. PMID:24512954

  15. The association between biliary tract inflammation and risk of digestive system cancers

    PubMed Central

    Tsai, Tsung-Yu; Lin, Che-Chen; Peng, Cheng-Yuan; Huang, Wen-Hsin; Su, Wen-Pang; Lai, Shih-Wei; Chen, Hsuan-Ju; Lai, Hsueh-Chou

    2016-01-01

    Abstract The relationship between biliary tract inflammation (BTI) and digestive system cancers is unclear. This study aimed to evaluate the association between BTI and the risks of digestive system cancers. Using the Taiwan National Health Insurance claims data, information on a cohort of patients diagnosed with BTI (n = 4398) between 2000 and 2009 was collected. A comparison cohort of sex-, age-, and index year-matched persons without BTI (n = 17,592) was selected from the same database. The disease was defined by the ICD-9-CM. Both cohorts were followed until the end of 2010 and incidences of digestive system cancers were calculated. The results revealed an increase in adjusted hazard ratio (aHR) of biliary tract cancer (24.45; 95% confidence interval [CI]: 9.20–65.02), primary liver cancer (1.53; 95% CI: 1.07–2.18), and pancreatic cancer (3.10; 95% CI: 1.20–8.03) in patients with both gallbladder and BTI. The aHR of stomach cancer was also found to be increased (2.73; 95% CI: 1.28–5.81) in patients with gallbladder inflammation only. There were no differences in esophageal cancer (aHR: 0.82; 95% CI: 0.23–2.87) and colorectal cancer (aHR: 0.92; 95% CI: 0.59–1.45). The aHR for digestive system cancers increased by 3.66 times (95% CI: 2.50–5.35) and 12.20 times (95% CI: 8.66–17.17) in BTI visits frequency averaged 2 to 4 visits per year and frequency averaged ≥5 visits per year, respectively. Patients with BTI have significantly higher risk of digestive system cancers, particularly biliary tract, pancreatic, and primary liver cancers, compared with those who are without it. PMID:27495065

  16. A comparison between endoscopic ultrasound-guided rendezvous and percutaneous biliary drainage after failed ERCP for malignant distal biliary obstruction

    PubMed Central

    Bill, Jason G.; Darcy, Michael; Fujii-Lau, Larissa L.; Mullady, Daniel K.; Gaddam, Srinivas; Murad, Faris M.; Early, Dayna S.; Edmundowicz, Steven A.; Kushnir, Vladimir M.

    2016-01-01

    Background and study Aims: Selective biliary cannulation is unsuccessful in 5 % to 10 % of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for malignant distal biliary obstruction (MDBO). Percutaneous biliary drainage (PBD) has been the gold standard, but endoscopic ultrasound guided rendezvous (EUSr) have been increasingly used for biliary decompression in this patient population. Our aim was to compare the initial success rate, long-term efficacy, and safety of PBD and EUSr in relieving MDBO after failed ERC Patients and methods: A retrospective study involving 50 consecutive patients who had an initial failed ERCP for MDBO. Twenty-five patients undergoing EUSr between 2008 – 2014 were compared to 25 patients who underwent PBD immediately prior to the introduction of EUSr at our center (2002 – 2008). Comparisons were made between the two groups with regard to technical success, duration of hospital stay and adverse event rates after biliary decompression. Results: The mean age at presentation was 66.5 (± 12.6 years), 28 patients (54.9 %) were female. The etiology of MDBO was pancreaticobiliary malignancy in 44 (88 %) and metastatic disease in 6 (12 %) cases. Biliary drainage was technically successful by EUSr in 19 (76 %) cases and by PBD in 25 (100 %) (P = 0.002). Median length of hospital stay after initial drainage was 1 day in the EUSr group vs 5 days in PBD group (P = 0.02). Repeat biliary intervention was required for 4 patients in the EUSr group and 15 in the PBD group (P = 0.001). Conclusions: Initial technical success with EUSr was significantly lower than with PBD, however when EUSr was successful, patients had a significantly shorter post-procedure hospital stay and required fewer follow-up biliary interventions. Meeting presentations: Annual Digestive Diseases Week 2015 PMID:27652305

  17. Abnormal Anatomical Variations of Extra-Hepatic Biliary Tract, and Their Relation to Biliary Tract Injuries and Stones Formation

    PubMed Central

    Khayat, Meiaad F.; Al-Amoodi, Munaser S.; Aldaqal, Saleh M.; Sibiany, Abdulrahman

    2014-01-01

    Background To determine the most common abnormal anatomical variations of extra-hepatic biliary tract (EHBT), and their relation to biliary tract injuries and stones formation. Methods This is a retrospective review of 120 patients, who underwent endoscopic retrograde cholangiopancreaticography (ERCP) and/or magnetic resonance cholangiopancreaticography (MRCP), between July 2011 and June 2013. The patients’ ERCP and MRCP images were reviewed and evaluated for the anatomy of EHBT; the medical records were reviewed for demographic data, biliary tracts injuries and stones formation. Results Out of 120 patients, 50 were males (41.7%) and 70 were females (58.3%). The mean age was 54 years old (range 20 - 88). Abnormal anatomy was reported in 30% (n = 36). Short cystic duct (CD) was found in 20% (n = 24), left CD insertion in 5% (n = 6), CD inserted into the right hepatic duct (RHD) in 1.7% (n = 2), duct of Luschka in 3.33% (n = 4) and accessory hepatic duct in also 3.33% (n = 4). Biliary tract injuries were reported in 15% (n = 18) and stones in 71.7% (n = 86). Biliary tract injuries were higher in abnormal anatomy (P = 0.04), but there was no relation between abnormal anatomy and stones formation. Conclusion Abnormal anatomy of EHBT was found to be 30%. The most common abnormality is short CD followed by left CD insertion. Surgeons should be aware of these common abnormalities in our patients, hence avoiding injuries to the biliary tract during surgery. The abnormal anatomy was associated with high incidence of biliary tract injury but has no relation to biliary stone formation.

  18. A comparison between endoscopic ultrasound-guided rendezvous and percutaneous biliary drainage after failed ERCP for malignant distal biliary obstruction

    PubMed Central

    Bill, Jason G.; Darcy, Michael; Fujii-Lau, Larissa L.; Mullady, Daniel K.; Gaddam, Srinivas; Murad, Faris M.; Early, Dayna S.; Edmundowicz, Steven A.; Kushnir, Vladimir M.

    2016-01-01

    Background and study Aims: Selective biliary cannulation is unsuccessful in 5 % to 10 % of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for malignant distal biliary obstruction (MDBO). Percutaneous biliary drainage (PBD) has been the gold standard, but endoscopic ultrasound guided rendezvous (EUSr) have been increasingly used for biliary decompression in this patient population. Our aim was to compare the initial success rate, long-term efficacy, and safety of PBD and EUSr in relieving MDBO after failed ERC Patients and methods: A retrospective study involving 50 consecutive patients who had an initial failed ERCP for MDBO. Twenty-five patients undergoing EUSr between 2008 – 2014 were compared to 25 patients who underwent PBD immediately prior to the introduction of EUSr at our center (2002 – 2008). Comparisons were made between the two groups with regard to technical success, duration of hospital stay and adverse event rates after biliary decompression. Results: The mean age at presentation was 66.5 (± 12.6 years), 28 patients (54.9 %) were female. The etiology of MDBO was pancreaticobiliary malignancy in 44 (88 %) and metastatic disease in 6 (12 %) cases. Biliary drainage was technically successful by EUSr in 19 (76 %) cases and by PBD in 25 (100 %) (P = 0.002). Median length of hospital stay after initial drainage was 1 day in the EUSr group vs 5 days in PBD group (P = 0.02). Repeat biliary intervention was required for 4 patients in the EUSr group and 15 in the PBD group (P = 0.001). Conclusions: Initial technical success with EUSr was significantly lower than with PBD, however when EUSr was successful, patients had a significantly shorter post-procedure hospital stay and required fewer follow-up biliary interventions. Meeting presentations: Annual Digestive Diseases Week 2015

  19. A Case of Malignant Biliary Obstruction with Severe Obesity Successfully Treated by Endoscopic Ultrasonography-Guided Biliary Drainage

    PubMed Central

    Yamasaki, Shuuji

    2016-01-01

    Here, we present a case of malignant biliary tract obstruction with severe obesity, which was successfully treated by endoscopic ultrasonography-guided biliary drainage (EUS-BD). A female patient in her sixties who had been undergoing chemotherapy for unresectable pancreatic head cancer was admitted to our institution for obstructive jaundice. She had diabetes mellitus, and her body mass index was 35.1 kg/m2. Initially, endoscopic retrograde cholangiopancreatography (ERCP) was performed, but bile duct cannulation was unsuccessful. Percutaneous transhepatic biliary drainage (PTBD) from the left hepatic biliary tree also failed. Although a second PTBD attempt from the right hepatic lobe was accomplished, biliary tract bleeding followed, and the catheter was dislodged. Consequently, EUS-BD (choledochoduodenostomy), followed by direct metallic stent placement, was performed as a third drainage method. Her postprocedural course was uneventful. Following discharge, she spent the rest of her life at home without recurrent jaundice or readmission. In cases of severe obesity, we consider EUS-BD, rather than PTBD, as the second drainage method of choice for distal malignant biliary obstruction when ERCP fails.

  20. Is Duct to Duct biliary Anastomosis the Rule in Orthotopic Liver Transplantation?

    PubMed

    Selvakumar, N; Saha, Brig Anupam; Naidu, Surg Capt Sudeep

    2013-10-01

    Biliary complications after Liver Transplantation continue to be the major cause of morbidity in 11-25 % of patients. Biliary complications in patients who underwent orthotopic liver transplantation (OLT) at our institute between March 2007 and June 2010 were analyzed retrospectively. 32 patients underwent Deceased Donor Liver Transplantation (DDLT) and in 12 patients Living Donor Liver Transplantation (LDLT) was done. No patients were lost to follow up. Follow up ranged between 4 and 44 months. During the study period, 44 patients underwent orthotopic liver transplantation. Patients were divided into two groups: Biliary Complications group (BC) n = 5 and Non Biliary Complications group (NBC) n = 39. Biliary complications occurred in 15.9 % of patients. Bile leaks accounted for majority of biliary complications. Fifteen variables were analyzed as possible risk factors for biliary complications. Of these, split grafts, duct to duct biliary anastomosis and total blood loss were statistically significant (P < 0.05) for biliary complications. Endoscopic treatment was successful in managing biliary complications in 75 % of patients. Biliary complications are the most common major complications in orthotopic liver transplantation. Significant risk factors are split liver grafts and duct to duct biliary anastomosis. Increased blood loss is a predictor for post operative biliary complications. These complications should be managed by endoscopic interventions. Surgery is indicated following failure of endoscopic interventions. PMID:24426478

  1. The Timing of Biliary Surgery in Acute Pancreatitis

    PubMed Central

    Ranson, John H. C.

    1979-01-01

    The timing of biliary surgery remains controversial in patients with acute pancreatitis associated with cholelithiasis. Eighty hospital admissions for acute pancreatitis, occurring in 74 patients with cholelithiasis, have therefore been reviewed. Among 22 patients who underwent abdominal surgery during the first week of treatment, there were five deaths (23%) and four patients (18%) who required more than seven days of intensive care. Fifty-eight episodes of pancreatitis were managed nonoperatively during the first week of treatment, with no deaths, although six (10%) required more than seven days of intensive care. Biliary surgery was undertaken later during the same admission in 37 patients, with no deaths. Twenty-one patients were discharged without biliary operation, but seven (33%) developed further pancreatitis. Previously reported prognostic signs were used to divide pancreatitis into 57 “mild” episodes (1.8% mortality) and 23 “severe” episodes (17% mortality). Early (day 0-7) definitive biliary surgery was undertaken in 11 patients with “mild” pancreatitis, with one death (9%), and in six patients with “severe” pancreatitis, with four deaths (67%). In three recent patients with “severe” pancreatitis, early biliary surgery was limited to cholecystostomy, with no deaths. These findings suggest that although early correction of associated biliary disease may be undertaken safely in many patients with “mild” acute pancreatitis, early definitive surgery is hazardous in “severe” pancreatitis and should, if possible, be deferred until pancreatitis has subsided. In most patients biliary surgery should precede hospital discharge. PMID:443917

  2. [Pancreas and biliary tract: recent developments].

    PubMed

    de-Madaria, Enrique

    2014-09-01

    Acute pancreatitis (AP) is a common disease that is associated with significant morbidity and considerable mortality. In this article, developments relating to this disease that were presented in DDW 2014 are reviewed. Pancreatic steatosis could be a cause of recurrent AP. Patients with DM have an increased incidence of AP and pancreatic cancer. The use of anti-TNF drugs in inflammatory bowel disease may protect against the occurrence of AP. The presence of pancreas divisum protects against acute biliary pancreatitis. The PANCODE system for describing local complications of AP has good interobserver agreement, when the new definitions of the revised Atlanta classification are applied. The use of prophylactic antibiotics in early-stage AP predisposes the development of intra-abdominal fungal infections. Fluid sequestration in AP is linked with young age, alcoholism and indicators of systemic inflammatory response syndrome. The most common cause of mortality in AP is early onset of multiple organ failure, not pancreatic necrosis infection. Patients with AP and vitamin D deficiency could benefit from taking vitamin D supplements. Moderate fluid administration in emergencies (500-1000 mL) could be associated with better AP development.

  3. Palliative therapy for pancreatic/biliary cancer.

    PubMed

    House, Michael G; Choti, Michael A

    2005-04-01

    Palliative treatment for unresectable periampullary cancer is directed at three major symptoms: obstructive jaundice, duodenal obstruction, and cancer-related pain. In most cases, the pattern of symptoms at the time of diagnosis in the context of the patient's medical condition and projected survival influence the decision to perform an operative versus a non operative palliative procedure. Despite improvements in preoperative imaging and laparoscopic staging of patients with periampullary cancer and hilar cholangiocarcinoma, surgical exploration is the only modality that can definitively rule out resectability and the potential for curative resection in some patients with nonmetastatic cancer. Furthermore, only surgical management achieves successful palliation of obstructive symptoms and cancer-related pain as a single procedure during exploration. To take advantage of the long-term advantages afforded by surgical palliation,operative procedures must be performed with acceptable morbidity. The average postoperative length of hospital stay for patients who undergo surgical palliation is less than 15 days, even in those who develop minor complications. The average survival of patients who receive surgical palliation alone for nonmetastatic, unresectable pancreatic cancer is approximately 8 months. As with all treatment planning, palliative therapy for pancreatic and biliary cancer should be planned using a multidisciplinary approach, including input from the surgeon, gastroenterologist, radiologist,and medical and radiation oncologist. In this way, quality of life can be optimized in most patients with these diseases.

  4. Palliative transhepatic biliary drainage and enteral nutrition.

    PubMed

    Lerch, M M; Moser, C; Stallmach, A; von Blohn, G; Zeitz, M

    1999-12-01

    Simultaneous intestinal and biliary obstruction is a rare but agonizing complication of metastatic abdominal cancer. Although endoscopic procedures exist that relieve jaundice or restore enteral nutrition, they can be impossible to perform for technical or anatomical reasons. We propose a palliative approach for these patients that includes transcutaneous common bile duct drainage, progressive dilation of the transhepatic channel over 1 wk, and, finally, insertion of a permanent silicon catheter that drains bile into the duodenum and is combined with an enteral feeding line. We report three patients whose metastatic abdominal tumors had led to simultaneous jaundice and gastric outlet obstruction, neither of which could be treated endoscopically. In all patients, the transcutaneous bile drainage catheter combined with the enteral feeding line was inserted and tumor symptoms resolved rapidly. As a result, the patients chose to return to home care with enteral nutrition and pain medication. The creation of a transhepatic access for simultaneous enteral bile drainage and nutrition is a technically simple procedure that causes little discomfort to a terminally ill patient. It relieves the symptoms of tumor obstruction, and the option of enteral nutrition and medication can obviate the need for intravenous infusions.

  5. Incidence of hepatotropic viruses in biliary atresia.

    PubMed

    Rauschenfels, Stefan; Krassmann, Miriam; Al-Masri, Ahmed N; Verhagen, Willem; Leonhardt, Johannes; Kuebler, Joachim F; Petersen, Claus

    2009-04-01

    Biliary atresia (BA) is the most frequent indication for paediatric liver transplantation. We tested the hypothesis of a viral aetiology of this disease by screening liver samples of a large number of BA patients for the common human hepatotropic viruses. Moreover, we correlated our findings to the expression of Mx protein, which has been shown to be significantly up-regulated during viral infections. Seventy-four liver biopsies (taken during Kasai portoenterostomy) were tested by polymerase chain reaction (PCR) for DNA viruses (herpes simplex virus [HSV], Epstein-Barr virus [EBV], varicella zoster virus [VZV], cytomegalovirus [CMV], adenovirus, parvovirus B19 and polyoma BK) and RNA viruses (enteroviruses, rotavirus and reovirus 3). Mx protein expression was assessed by immunohistochemistry. Virus DNA/RNA was found in less than half of the biopsies (8/74 CMV, 1/74 adenovirus; 21/64 reovirus, 1/64 enterovirus). A limited number presented with double infection. Patients that had detectable viral RNA/DNA in their liver biopsies were significantly older than virus-free patients (P = 0.037). The majority (54/59) of the liver biopsies showed expression of Mx proteins in hepatocytes, bile ducts and epithelium. Our data suggest that the known hepatotropic viruses do not play a major role in the aetiology and progression of BA. Their incidence appears to be, rather, a secondary phenomenon. Nonetheless, the inflammatory response in the livers of BA patients mimics that observed during viral infections.

  6. [Pancreas and biliary tract: recent developments].

    PubMed

    de-Madaria, Enrique

    2014-09-01

    Acute pancreatitis (AP) is a common disease that is associated with significant morbidity and considerable mortality. In this article, developments relating to this disease that were presented in DDW 2014 are reviewed. Pancreatic steatosis could be a cause of recurrent AP. Patients with DM have an increased incidence of AP and pancreatic cancer. The use of anti-TNF drugs in inflammatory bowel disease may protect against the occurrence of AP. The presence of pancreas divisum protects against acute biliary pancreatitis. The PANCODE system for describing local complications of AP has good interobserver agreement, when the new definitions of the revised Atlanta classification are applied. The use of prophylactic antibiotics in early-stage AP predisposes the development of intra-abdominal fungal infections. Fluid sequestration in AP is linked with young age, alcoholism and indicators of systemic inflammatory response syndrome. The most common cause of mortality in AP is early onset of multiple organ failure, not pancreatic necrosis infection. Patients with AP and vitamin D deficiency could benefit from taking vitamin D supplements. Moderate fluid administration in emergencies (500-1000 mL) could be associated with better AP development. PMID:25294273

  7. Biliary lipid composition in monozygotic and dizygotic pairs of twins.

    PubMed Central

    Antero Kesäniemi, Y; Koskenvuo, M; Vuoristo, M; Miettinen, T A

    1989-01-01

    The relative contribution of genetic factors to biliary and serum lipid composition was studied in 17 monozygotic and 18 dizygotic middle aged male pairs of twins. Cholesterol precursors, squalene and Methylated sterols which reflect the activity of cholesterol synthesis were also measured. Pairwise intraclass correlations were determined for monozygotic and dizygotic twin pairs and heritability estimates were calculated. Molar % of biliary cholesterol and percentage distribution of biliary cholic acid and particularly deoxycholic acid showed significant pairwise correlations within the monozygotic but not the dizygotic pairs. Similar correlations were found for total biliary methylsterols and of the methylsterol subfractions for the two methostenols but not for squalene, lanosterol and dimethylsterols. In serum, the precursor sterols, but not squalene, showed even higher pairwise correlations in the monozygotic twins than the corresponding precursors in bile. Molar per cent of bile acids and phospholipids and cholesterol saturation index were not correlated significantly in either twin pairs, but the pairwise correlations tended to be higher in the monozygotic than in the dizygotic pairs. Gall stones were found in seven monozygotic and three dizygotic subjects. Two monozygotic twin pairs were concordant for gall stones; all the dizygotic pairs were discordant. Overall, these data suggest that molar percentage of biliary cholesterol, bile acid composition, cholesterol synthesis, bile cholesterol saturation, and gall stone formation may be under a significant genetic control. PMID:2612989

  8. Combined biliary and duodenal stenting for palliation of pancreatic cancer.

    PubMed

    Profili, S; Feo, C F; Meloni, G B; Strusi, G; Cossu, M L; Canalis, G C

    2003-10-01

    The aim of this case report was to evaluate the usefulness of combined biliary and duodenal stenting in the palliation of pancreatic cancer. We report a series of 4 consecutive patients (2 men and 2 women, mean age 58.5 years, range 38-77 years) who underwent combined biliary and duodenal stenting in our department between March 2000 and April 2001. All patients had cancer of the head of the pancreas causing stricture of the common bile duct and second portion of the duodenum. Biliary and duodenal stents were successfully positioned, with relief of symptoms in all cases. No early complications were observed, except for a transient increase in serum lipase and amylase in one case. Mean follow-up was 7.5 months (range 5-14 months). One patient presenting recurrence of vomiting after 4 months because of tumour overgrowth at the distal edge of the prosthesis was successfully treated by insertion of a partially overlapping second coaxial stent. Combined biliary and duodenal stenting for the palliation of pancreatic cancer was performed safely and successfully. Stents allowed effective re-canalization of the biliary tract and duodenum, relieving both jaundice and vomiting. This procedure should be considered as an alternative to palliative surgery, especially in critically ill patients.

  9. Percutaneous minimally invasive treatment of malignant biliary strictures: current status.

    PubMed

    Krokidis, Miltiadis; Hatzidakis, Adam

    2014-04-01

    The concept of percutaneous management of malignant biliary obstruction has not significantly changed in the last two decades and is based on the successful drainage of bile toward the duodenum, which normalizes liver function and prevents the development of cholangitis and sepsis. However, patient survival has changed slightly in the last two decades due to the advance of the diagnostic methods, chemo-radiotherapy protocols, and minimally invasive local control of the disease. Bare metal stents have not improved; however, newly developed covered biliary stents have been designed, and there is now evidence supporting their use in the clinical practice. However, other novel devices that may potentially offer benefit to patients with malignant biliary obstruction have been developed, such as drug-eluting biliary stents and intraductal ablation devices, and first feasibility trials have been published that offer encouraging results. These new technological developments, in combination with increased patient survival, bring new exciting data in this constantly developing area. The purpose of this review article is to investigate the latest published evidence on percutaneous minimal invasive palliation of malignant biliary disease and to delineate current trends.

  10. Quasielastic light scattering evidence for vesicular secretion of biliary lipids.

    PubMed

    Cohen, D E; Angelico, M; Carey, M C

    1989-07-01

    We employed quasielastic light scattering, negative-stain, and freeze-fracture electron microscopy to study the time-dependent physicochemical behavior of biliary lipids in fresh rat bile. Three to five minutes after bile collection, the earliest light scattering measurements and electron microscopy revealed unilamellar vesicles (mean hydrodynamic radius, Rh = 430-740 A) coexisting with mixed micelles (Rh = 20-120 A) in all biles. Both percent biliary vesicles (1 to greater than 70%) and micellar sizes varied inversely with bile salt concentration (range 1.6-72 mM) both during endogenous pool drainage and sodium taurocholate infusion. With bile salt concentrations in the vicinity of or below the estimated critical micellar concentration, biliary vesicle concentrations remained constant or increased slightly with passage of time. However, with micellar bile salt concentrations, complete conversion of vesicles to micelles occurred at rates that were directly proportional to bile salt concentration. Back-extrapolation of weighted Rh averages of micelles plus vesicles as functions of time gave sizes of approximately 470 A at 1 min, suggesting the predominance of homogeneously sized unilamellar vesicles at the earliest stages of bile formation. After micellization of lipids, mixed protein aggregates of vesicle size were demonstrated in all biles. These experiments elucidate the dynamic coexistence of lipid vesicles and mixed micelles in cholesterol unsaturated biles and demonstrate that vesicle-to-micelle interconversions of biliary lipid aggregates are normal physiological phenomena within the biliary tree.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Transhepatic contemporary palliation of biliary and duodenal stenoses by means of metallic stents.

    PubMed

    Cozzi, G; Chiaraviglio, F; Bonfanti, G; Civelli, E M

    2004-01-01

    We describe the treatment of a stenosing lesion of the horizontal duodenum by means of a large-bore metallic stent inserted percutaneously in a patient with transhepatic biliary drainage. In the same session, we used an expandable metallic stent in the biliary tree to relieve jaundice. We recommend the transhepatic approach for duodenal metallic stent insertion in patients with percutaneous biliary drainage.

  12. [Suprapapilar puncture for biliary access to advanced cancer of the papilla and severe coagulopathy].

    PubMed

    Artifon, E; Couto, D S; Navarro, A

    2009-01-01

    Biliary cannulation to perform endoscopic retrograde cholangiopancreatography (ERCP) may be difficult in patients with advanced papillary cancer, due to anatomical and technical reasons. Sphincterotomy may be contraindicated in severe coagulopathy. We report a recently described technique of suprapapillary puncture for biliary access with use of an Artifon's catheter for biliary access in a high-risk patient with coagulopathy and periampullary neoplasm.

  13. Drug-eluting stent in malignant biliary obstruction

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Ki; Jang, Sung Ill

    2012-10-01

    Endoscopic stent insertion is the treatment of choice for patients with malignant biliary obstruction. However, conventional stents enable only mechanical palliation of the obstruction, without any anti-tumor effects. Drugeluting stent (DES), which was first introduced in coronary artery disease, are currently under investigation for sustaining stent patency and prolonging patient survival by inhibiting tumor ingrowth in malignant biliary obstruction. Many factors affecting efficient drug delivery have been studied to determine how drugs with antitumor effects suppress tumor ingrowth, including the specific drugs incorporated, means of incorporating the drugs, mode of drug release, and stent structure. Advances have resulted in the construction of more effective non-vascular DES and ongoing clinical research. Non-vascular DES is expected to play a vital role in prolonging the survival of patients with malignant biliary obstruction.

  14. Liver and biliary tract cancer among chemical workers

    SciTech Connect

    Bond, G.G.; McLaren, E.A.; Sabel, F.L.; Bodner, K.M.; Lipps, T.E.; Cook, R.R. )

    1990-01-01

    A recent cohort mortality study of male, hourly wage employees of a large Michigan chemical production and research facility had found a greater than expected number of deaths coded to liver and biliary tract cancer. In response, an additional investigation was then undertaken of the 44 liver and biliary tract cancer deaths observed between 1940 and 1982. A random sample (N = 1,888) of subjects was selected from the total cohort (N = 21,437) to serve as referents. Company work history records were used to classify cases and referents by work area assignment and potential for exposure to 11 selected chemical agents which have been shown to produce cancer of the liver or biliary passages in experimental animals. Statistically significant associations in both positive and negative directions were found for several work areas within the facility. A suggestive association was found for vinyl chloride monomer, based on five cases with presumed exposure.

  15. Anaesthesia for biliary atresia and hepatectomy in paediatrics

    PubMed Central

    Jacob, Rebecca

    2012-01-01

    The scope of this article precludes an ‘in depth’ description of all liver problems and I will limit this review to anaesthesia for biliary atresia — a common hepatic problem in the very young — and partial hepatectomy in older children. I will not be discussing the problems of anaesthetising children with hepatitis, cirrhosis, congenital storage diseases or liver failure. Extrahepatic biliary obstruction is an obliterative cholangiopathy of infancy which is fatal if untreated. Diagnosis involves exclusion of other causes of neonatal jaundice and treatment involves a hepatico portoenterostomy carried out at the earliest. This is a review of current concepts in anaesthesia and postoperative management of neonates with extrahepatic biliary atresia. Anaesthesia for hepatic resection has seen great changes in recent times with the improvement in surgical techniques, technology and a better understanding of the underlying physiology. These are reviewed along with the problems of postoperative pain management. PMID:23293387

  16. Liver and biliary tract cancer among chemical workers.

    PubMed

    Bond, G G; McLaren, E A; Sabel, F L; Bodner, K M; Lipps, T E; Cook, R R

    1990-01-01

    A recent cohort mortality study of male, hourly wage employees of a large Michigan chemical production and research facility had found a greater than expected number of deaths coded to liver and biliary tract cancer. In response, an additional investigation was then undertaken of the 44 liver and biliary tract cancer deaths observed between 1940 and 1982. A random sample (N = 1,888) of subjects was selected from the total cohort (N = 21,437) to serve as referents. Company work history records were used to classify cases and referents by work area assignment and potential for exposure to 11 selected chemical agents which have been shown to produce cancer of the liver or biliary passages in experimental animals. Statistically significant associations in both positive and negative directions were found for several work areas within the facility. A suggestive association was found for vinyl chloride monomer, based on five cases with presumed exposure.

  17. Endoscopic ultrasound guided biliary and pancreatic duct interventions

    PubMed Central

    Prichard, David; Byrne, Michael F

    2014-01-01

    When endoscopic retrograde cholangio-pancreatography fails to decompress the pancreatic or biliary system, alternative interventions are required. In this situation, endosonography guided cholangio-pancreatography (ESCP), percutaneous radiological therapy or surgery can be considered. Small case series reporting the initial experience with ESCP have been superseded by comprehensive reports of large cohorts. Although these reports are predominantly retrospective, they demonstrate that endoscopic ultrasound (EUS) guided biliary and pancreatic interventions are associated with high levels of technical and clinical success. The procedural complication rates are lower than those seen with percutaneous therapy or surgery. This article describes and discusses data published in the last five years relating to EUS-guided biliary and pancreatic intervention. PMID:25400865

  18. Mechanisms of Biliary Plastic Stent Occlusion and Efforts at Prevention

    PubMed Central

    Kwon, Chang-Il; Lehman, Glen A.

    2016-01-01

    Biliary stenting via endoscopic retrograde cholangiopancreatography has greatly improved the quality of patient care over the last 30 years. Plastic stent occlusion limits the life span of such stents. Attempts to improve plastic stent patency duration have mostly failed. Metal stents (self-expandable metal stents [SEMSs]) have therefore replaced plastic stents, especially for malignant biliary strictures. SEMS are at least 10 times more expensive than plastic stents. In this focused review, we will discuss basic mechanisms of plastic stent occlusion, along with a systematic summary of previous efforts and related studies to improve stent patency and potential new techniques to overcome existing limitations. PMID:27000422

  19. [Congenital broncho-biliary fistula: a case report].

    PubMed

    Pérez, Cinthia G; Reusmann, Aixa

    2016-10-01

    Congenital tracheo-or-bronchobiliary fistula or congenital he-patopulmonary fistula is a rare malformation with high morbidity and mortality if the diagnosis is not made early. The tracheo-or-bronchobiliary fistula is a communication between the respiratory (trachea or bronchus) and biliary tract. To date, only 35 cases have been published worldwide. We report a case of a neonate with right pneumonia and bilious fluid in the endotracheal tube. Diagnosis was made using bronchoscopy with fluoroscopy. Videothoracoscopy was used to remove the bronchobiliary fistula. Subsequently, a left he-patectomy with Roux-en-Y biliary-digestive anastomosis was performed as bile ductus hypoplasia was present. PMID:27606661

  20. Congenital biliary atresia and jaundice in lambs and calves.

    PubMed

    Harper, P; Plant, J W; Unger, D B

    1990-01-01

    An outbreak of congenital biliary atresia and jaundice is described, in which approximately 300 crossbred lambs and 9 crossbred calves died. The affected animals failed to thrive, developed jaundice and white scours and died within 4 weeks of birth. A common feature of this outbreak and a similar occurrence 24 years previously was the grazing of plants growing on the exposed silt foreshores of Burrinjuck Dam by ewes and cows in the early stages of pregnancy. Epidemiological and pathological findings suggested that a toxic insult to the foetus in early gestation caused choledysgenesis and biliary atresia, leading to diffuse, subacute to chronic cholangiohepatopathy and cirrhosis.

  1. [Congenital broncho-biliary fistula: a case report].

    PubMed

    Pérez, Cinthia G; Reusmann, Aixa

    2016-10-01

    Congenital tracheo-or-bronchobiliary fistula or congenital he-patopulmonary fistula is a rare malformation with high morbidity and mortality if the diagnosis is not made early. The tracheo-or-bronchobiliary fistula is a communication between the respiratory (trachea or bronchus) and biliary tract. To date, only 35 cases have been published worldwide. We report a case of a neonate with right pneumonia and bilious fluid in the endotracheal tube. Diagnosis was made using bronchoscopy with fluoroscopy. Videothoracoscopy was used to remove the bronchobiliary fistula. Subsequently, a left he-patectomy with Roux-en-Y biliary-digestive anastomosis was performed as bile ductus hypoplasia was present.

  2. A case of biliary Fascioliasis by Fasciola gigantica in Turkey.

    PubMed

    Goral, Vedat; Senturk, Senem; Mete, Omer; Cicek, Mutallib; Ebik, Berat; Kaya, Beşir

    2011-03-01

    A case of Fasciola gigantica-induced biliary obstruction and cholestasis is reported in Turkey. The patient was a 37- year-old woman, and suffered from icterus, ascites, and pain in her right upper abdominal region. A total of 7 living adult flukes were recovered during endoscopic retrograde cholangiopancreatography (ERCP). A single dose of triclabendazole was administered to treat possible remaining worms. She was living in a village of southeast of Anatolia region and had sheeps and cows. She had the history of eating lettuce, mallow, dill, and parsley without washing. This is the first case of fascioliasis which was treated via endoscopic biliary extraction during ERCP in Turkey. PMID:21461271

  3. [Biochemical features of gallbladder bile in biliary tract diseases].

    PubMed

    Plotnikova, E Iu; Aleksandrova, A Iu; Beloborodova, E I; Didlovslaia, N A

    2007-06-01

    Sixty-two and 58 patients with hypo- and hypermotor biliary tract dysfunction (BTD), respectively, as well as 59 patients with chronic acalculous cholecystitis (CAC) and 63 with opisthorchiasis-complicated CAC were examined. A control group comprised 33 patients of the same sex and age. All the patients underwent fractional duodenal intubation, followed by clinical, biochemical, and serological bile studies. All the examinees were found to increased gallbladder bile lithogenicity, minor changes being observed in biliary tract dysfunction and more pronounced ones being in opisthorchiasis. A biochemical study of gallbladder bile, followed by its lithogenicity correction, is recommended in the treatment of different forms of BTD. PMID:17682480

  4. Intraductal radiofrequency ablation for management of malignant biliary obstruction.

    PubMed

    Rustagi, Tarun; Jamidar, Priya A

    2014-11-01

    Self-expandable metal stents (SEMS) are the current standard of care for the palliative management of malignant biliary strictures. Recently, endoscopic ablative techniques with direct affect to local tumor have been developed to improve SEMS patency. Several reports have demonstrated the technical feasibility and safety of intraductal radiofrequency ablation (RFA), by both endoscopic and percutaneous approaches, in palliation of malignant strictures of the bile duct. Intraductal RFA has also been used in the treatment of occlusion of both covered and uncovered SEMS occlusion from tumor ingrowth or overgrowth. This article provides a comprehensive review of intraductal RFA in the management of malignant biliary obstruction.

  5. Pancreatic Stenting Reduces Post-ERCP Pancreatitis and Biliary Sepsis in High-Risk Patients: A Randomized, Controlled Study

    PubMed Central

    Wu, Hai-En; Li, Qi-Xiang; Wang, Wei; Ou, Wei-Lin; Xia, Harry Hua-Xiang

    2016-01-01

    Background. Endoscopic retrograde cholangiopancreatography (ERCP) is an established treatment modality for bile duct disorders, but patients have a risk of post-ERCP pancreatitis (PEP) and biliary sepsis. Aim. To evaluate the effectiveness and safety of pancreatic stent for prophylaxis of PEP and biliary sepsis in high-risk patients with complicating common bile duct (CBD) disorders. Methods. Two hundred and six patients with complicating confirmed or suspected CBD disorders were randomly assigned to receive ERCP with pancreatic stenting (experimental group) or without stenting (control group). Primary outcome measure was frequency of PEP, and secondary outcome measures included operative time, blood loss, postoperative recovery times, and other ERCP-associated morbidities. Results. Baseline age, sex, CBD etiology, concomitant medical/surgical conditions, cannulation difficulty, and ERCP success were comparable between the two groups (all P > 0.05). Compared to the control group, the experimental group had a significantly lower frequency of PEP (7.7% versus 17.7%, P < 0.05) and positive bile microbial culture (40.4% versus 62.7%, P < 0.05). However, the two groups were similar in operative time, blood loss, postoperative recovery times, and other ERCP-associated morbidities (all P > 0.05). Conclusions. Pancreatic stenting can reduce the occurrence of PEP and biliary sepsis in high-risk patients with complicating CBD disorders but does not increase other ERCP-associated morbidities. This trial is registered with the Chinese Clinical Trial Registry (registration identifier ChiCTR-OCH-14005134). PMID:27057161

  6. Endoscopic Ultrasound-Guided Biliary Drainage Using a Fully Covered Metallic Stent after Failed Endoscopic Retrograde Cholangiopancreatography.

    PubMed

    Guo, Jintao; Sun, Siyu; Liu, Xiang; Wang, Sheng; Ge, Nan; Wang, Guoxin

    2016-01-01

    Background and Study Aims. Endoscopic ultrasound- (EUS-) guided biliary drainage (EUS-BD) is an alternative treatment for biliary obstruction after failed endoscopic retrograde cholangiopancreatography (ERCP). In this study, we present the outcomes of inpatients with obstructive jaundice treated with EUS-BD using a fully covered metallic stent after failed ERCP. Patients and Methods. A total of 21 patients with biliary obstruction due to malignant tumors and prior unsuccessful ERCP underwent EUS via an intra- or extrahepatic approach with fully covered metallic stent between March 2014 and October 2015. A single endoscopist performed all procedures. Results. Seven patients underwent hepatogastrostomy (HGS) and 14 underwent choledochoduodenostomy (CDS). The technical and clinical success rates were both 100%. There was no difference in efficacy between HGS and CDS. Adverse events occurred in three patients, including two in the HGS group (1 bile leakage and 1 sepsis) and one in the CDS group (sepsis). Four patients died as a result of their primary tumors during a median follow-up period of 13 months (range: 3-21 months). No patient presented with stent migration. Conclusion. EUS-BD using a fully covered metallic stent appears to be a safe and effective method for the treatment of obstructive jaundice. PMID:27594881

  7. Endoscopic biliary stent migration with small bowel perforation in a liver transplant recipient.

    PubMed

    Esterl, R M; St Laurent, M; Bay, M K; Speeg, K V; Halff, G A

    1997-03-01

    Intestinal perforation from a migrated biliary stent is a rare complication after endoscopic stent placement for benign biliary stricture. We provide the first description of stent migration and distal small-bowel perforation after stent placement for biliary anastomotic stricture in a liver transplant recipient. We review the current literature on the diagnosis and management of stent migration and intestinal perforation after endoscopic or percutaneous stent placement for benign and malignant biliary strictures. Early diagnosis and treatment of biliary stent migration and subsequent intestinal perforation are essential in transplant patients, in whom immunosuppression sometimes blunts signs and symptoms of intestinal perforation.

  8. EUS-guided choledochoduodenostomy for malignant distal biliary obstruction palliation: an article review.

    PubMed

    Artifon, Everson L A; Perez-Miranda, Manuel

    2012-04-01

    The EUS-guided biliary drainage is a new tool for the palliation of distal obstructive biliary lesions. The EUS-guided access, which creates a fistulization between the duodenal bulb and distal common biliary duct, is an effective method to relieve jaundice and has low morbidity and mortality, in patients with distal biliary obstruction (pancreatic mass or papillary câncer). This technique is called choledochoduodenostomy and is presented promptly in this article. The EUS-guided biliary drainage should be made within protocol conditions and done by very experienced endosonographers.

  9. Transjugular Insertion of Bare-Metal Biliary Stent for the Treatment of Distal Malignant Obstructive Jaundice Complicated by Coagulopathy

    SciTech Connect

    Tsauo Jiaywei Li Xiao Li Hongcui Wei Bo Luo Xuefeng Zhang Chunle Tang Chengwei; Wang Weiping

    2013-04-15

    This study was designed to investigate retrospectively the feasibility of transjugular insertion of biliary stent (TIBS) for the treatment of distal malignant obstructive jaundice complicated by coagulopathy. Between April 2005 and May 2010, six patients with distal malignant obstructive jaundice associated with coagulopathy that was unable to be corrected underwent TIBS at our institution for the palliation of jaundice. Patients' medical record and imaging results were reviewed to obtain information about demographics, procedure details, complications, and clinical outcomes. The intrahepatic biliary tract was successfully accessed in all six patients via transjugular approach. The procedure was technically successfully in five of six patients, with a bare-metal stent implanted after traversing the biliary strictures. One procedure failed, because the guidewire could not traverse the biliary occlusion. One week after TIBS, the mean serum bilirubin in the five successful cases had decreased from 313 {mu}mol/L (range 203.4-369.3) to 146.2 {mu}mol/L (range 95.8-223.3) and had further decreased to 103.6 {mu}mol/L (range 29.5-240.9) at 1 month after the procedure. No bleeding, sepsis, or other major complications were observed after the procedure. The mean survival of these five patients was 4.5 months (range 1.9-5.8). On imaging follow-up, there was no evidence of stent stenosis or migration, with 100 % primary patency. When the risks of hemorrhage from percutaneous transhepatic cholangiodrainage are high, TIBS may be an effective alternative for the treatment of distal malignant obstructive jaundice.

  10. Combined Interventional Radiological and Endoscopical Approach for the Treatment of a Postoperative Biliary Stricture and Fistula

    PubMed Central

    Triller, Jürgen; Schmassmann, Adrian; Czerniak, Abraham

    1995-01-01

    A 43-year old woman was admitted 11 days after open cholecystectomy with a iatrogenic bile duct injury. On admission the patient showed an uncontrolled biliary fistula through an external drain placed at an emergency laparotomy for biliary peritonitis with fever and jaundice. PTC showed a biliary stricture type II (Bismuth). A percutaneous drainage was performed to decompress the biliary system. Three weeks later, percutaneous balloon dilatation of the stricture was performed. However, bile leakage persisted. In a combined transhepatic/ endoscopic procedure, the percutaneous biliary drainage was replaced by a nasobiliary tube. One week later, no stricture was found and the biliary leak was sealed. The patient could be discharged without symptoms or signs of cholestasis. The multidisciplinary management of post-operative biliary fistula is presented, comparing the role of interventional radiology, endoscopy and surgery. PMID:18612478

  11. Lipopolysaccharide (LPS)-Induced Biliary Epithelial Cell NRas Activation Requires Epidermal Growth Factor Receptor (EGFR).

    PubMed

    Trussoni, Christy E; Tabibian, James H; Splinter, Patrick L; O'Hara, Steven P

    2015-01-01

    Cholangiocytes (biliary epithelial cells) actively participate in microbe-induced proinflammatory responses in the liver and contribute to inflammatory and infectious cholangiopathies. We previously demonstrated that cholangiocyte TLR-dependent NRas activation contributes to proinflammatory/ proliferative responses. We test the hypothesis that LPS-induced activation of NRas requires the EGFR. SV40-transformed human cholangiocytes (H69 cells), or low passage normal human cholangiocytes (NHC), were treated with LPS in the presence or absence of EGFR or ADAM metallopeptidase domain 17 (TACE) inhibitors. Ras activation assays, quantitative RT-PCR, and proliferation assays were performed in cells cultured with or without inhibitors or an siRNA to Grb2. Immunofluorescence for phospho-EGFR was performed on LPS-treated mouse samples and specimens from patients with primary sclerosing cholangitis, primary biliary cirrhosis, hepatitis C, and normal livers. LPS-treatment induced an association between the TLR/MyD88 and EGFR/Grb2 signaling apparatus, NRas activation, and EGFR phosphorylation. NRas activation was sensitive to EGFR and TACE inhibitors and correlated with EGFR phosphorylation. The TACE inhibitor and Grb2 depletion prevented LPS-induced IL6 expression (p<0.05) and proliferation (p<0.01). Additionally, cholangiocytes from LPS-treated mouse livers and human primary sclerosing cholangitis (PSC) livers exhibited increased phospho-EGFR (p<0.01). Moreover, LPS-induced mouse cholangiocyte proliferation was inhibited by concurrent treatment with the EGFR inhibitor, Erlotinib. Our results suggest that EGFR is essential for LPS-induced, TLR4/MyD88-mediated NRas activation and induction of a robust proinflammatory cholangiocyte response. These findings have implications not only for revealing the signaling potential of TLRs, but also implicate EGFR as an integral component of cholangiocyte TLR-induced proinflammatory processes.

  12. Late Migration of Covered Metal Stent to the Stomach Through a Spontaneous Choledochoduodenal Fistula in a Patient With Malignant Biliary Obstruction

    PubMed Central

    Katakura, Yoshiki; Asaki, Tsutoshi; Adachi, Seitaro; Yasuda, Ikuma; Toyomizu, Michifumi; Fukita, Yosho

    2012-01-01

    We report a case in which a spontaneous choledochoduodenal fistula occurred after biliary covered self-expanding metal stent (SEMS) placement and a late transfistula migration of the stent in a patient with malignant distal biliary obstruction. A partially covered WallFlex biliary stent (Boston Scientific) was appropriately implanted in the common bile duct. Subsequently the patient received chemotherapy with gemcitabine. After 7 months of the SEMS insertion, the patient presented with frequent vomiting. Abdominal computed tomography revealed the obstruction of the duodenal descending part and the migrated stent in the stomach. A choledochoduodenal fistula was observed endoscopically at the proximal point of the duodenal obstruction. These findings can cleanly account for the SEMS migration through the fistula. The mechanism of formation of the fistula is mostly associated with a mechanical contact between the bile duct wall and the SEMS edge, which is pushed up in the direction of the duodenum because of the enlargement of the primary tumor, finally penetrating through the duodenal wall. To our knowledge, this is an extreme unusual case, which has been unreported previously. Therefore, we emphasize the necessity of being alert to the potential for such complications in cases involving placement of SEMS for malignant biliary obstruction.

  13. Holmium laser lithotripsy of a complicated biliary calculus.

    PubMed

    Monga, M; Gabal-Shehab, L L; Kamarei, M; D'Agostino, H

    1999-09-01

    More than 500,000 cholecystectomies are performed annually. Extracorporeal shockwave lithotripsy and endoscopic laser lithotripsy have been used for the management of common bile duct calculi, which complicate 10% of cases. We report the first successful clinical application of the Ho:YAG laser to a complex biliary calculus case.

  14. [Extracorporeal shockwave biliary lithotripsy. Physical basis and clinical application].

    PubMed

    Méndez-Sánchez, N; Uribe-Esquivel, M; Bosques, F; de la Mora, G; Sánchez, J M; Ponciano, G

    1990-01-01

    Extracorporeal shock waves lithotripsy is a new procedure discovered and applied in the present decade to treat urinary and biliary stones. Shock waves are acoustic waves similar to sonic waves which follow the acoustic laws and therefore the shock waves can be refracted or reflected depending on the medium interface. Due to the high water content, the human body can be crossed by shock waves which eventually may be focused on the target stone. There are several commercially available shock waves generators, i.e. the spark gap emisors which were the first ones, and the piezoceramic and electromagnetic emisors. To focus the shock waves on a biliary stone the machines are provided with fluoroscopic or ultrasound devices or with both in the most advanced machines. Using an electromagnetic emisor (Lithostar plus) our group has treated 78 patients with biliary stones without analgesia or anesthesia. Total stone fragmentation was achieved in 85% of the cases. In patients with cholesterol gallstones who undergo lithotripsy, an adjuvant treatment with oral cholesterol solvent is mandatory. Extracorporeal biliary lithotripsy is free of mortality, and the morbidity is less than 5%.

  15. The forgotten biliary stent: an unusual cause of diarrhea.

    PubMed

    Sran, Harkiran; Sebastian, Joseph; Doughan, Samer

    2016-09-01

    This case highlights the possible complications of biliary stents, which may include migration and impaction in the gastrointestinal tract. It also emphasizes the need for a robust follow-up system after stent placement, to minimize the risks and possible sequelae of a forgotten stent. PMID:27648272

  16. Discordance of sonography and cholescintigraphy in acute biliary obstruction

    SciTech Connect

    Floyd, J.L.; Collins, T.L.

    1983-03-01

    Animal studies have shown that there is a brief interval of several hours after acute biliary obstruction during which sonography will demonstrate only normal-sized bile ducts while /sup 99m/Tc cholescintigraphy will document total obstruction. Serial studies documented this phenomenon in a patient whose case is reported and reviewed.

  17. Effect of pancreatic biliary reflux as a cofactor in cholecystitis.

    PubMed

    Amr, Abdel Raouf; Hamdy, Hussam Mohamed; Nasr, Magid Mahmoud; Hedaya, Mohammed Saied; Hassan, Ahmed Mohamed Abdelaziz

    2012-04-01

    This study assessed the effect of pancreatico-biliary reflux (PBR) as co-factor in the process of chronic cholecystitis by measurement of the levels of active pancreatic enzyme amylase in gallbladder bile and serum of patients undergoing cholecystectomy. Pancreatic Amylase levels in bile from the gallbladder and serum were measured during surgery in 68 patients with chronic calcular cholecystitis subjected to elective open or laparoscopic cholecystectomy in the National Hepatology and Tropical Medicine Research Institution and Theodore Bilharz Research Institute. Bile amylase was detected in 64 patients (94.1%) indicating pancreatico-biliary reflux. Biliary amylase level ranged from 20-50 IU/L in 42 patients (61.76%), below 20 IU/l in 14 patients (20.59%), over 50 IU/L in 8 patients (11.76%) and undetectable in two patients. According to gallbladder bile amylase, the incidence of Occult PBR in patients operated upon for chronic calcular cholecystitis was 94.1%. The reason should be clarified by further research and wider scale study. Routinely investigating biliary amylase in every patient having cholecystitis can be a method for early detection of precancerous lesions.

  18. Biliary manometry in choledochal cyst with abnormal choledochopancreatico ductal junction.

    PubMed

    Iwai, N; Tokiwa, K; Tsuto, T; Yanagihara, J; Takahashi, T

    1986-10-01

    Intraoperative manometry of the biliary tract and measurement of amylase levels in choledochal cysts were performed in seven patients, aged 14 months to 5 years, with choledochal cysts, in an investigation of the pathophysiology of the biliary tract. An abnormal choledochopancreatico ductal junction was observed in these seven patients by preoperative endoscopic retrograde cholangiopancreaticography (ERCP) or intraoperative cholangiograms. All six patients examined showed a high amylase level in the choledochal cyst (5,450 to 46,500 Somogyi Units). The intraoperative manometry of the biliary tract showed that a remarkable high pressure zone as was found in the area of sphincter of Oddi was not found in the area of abnormal choledochopancreatico ductal junction. The pressure recordings also demonstrated that the sphincter of Oddi pressure in the patient with choledochal cyst was increased by gastrin stimulation. On the contrary, no pressure reaction to gastrin or secretin was found in the area of abnormal choledochopancreatic ductal junction. From these results it seems that free reflux of pancreatic juice into the biliary system occurs, and the reflux stream depends upon the pressure gradient between pancreatic ductal pressure and common bile duct pressure because of the lack of a sphincter function at the choledochopancreatico ductal junction.

  19. Osteopontin Deficiency Alters Biliary Homeostasis and Protects against Gallstone Formation.

    PubMed

    Lin, Jing; Shao, Wei-Qing; Chen, Zong-You; Zhu, Wen-Wei; Lu, Lu; Cai, Duan; Qin, Lun-Xiu; Jia, Hu-Liang; Lu, Ming; Chen, Jin-Hong

    2016-01-01

    The precipitation of excess biliary cholesterol as solid crystals is a prerequisite for cholesterol gallstone formation, which occurs due to disturbed biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse and form gallstones. We have previously observed that the levels of osteopontin (OPN) in bile and gallbladder were reduced in gallstone patients. However, the role and mechanism for hepatic OPN in cholesterol gallstone formation is undetermined. In this study, we found that the expression of hepatic OPN was increased in gallstone patients compared with gallstone-free counterparts. Then, we observed that OPN-deficient mice were less vulnerable to cholesterol gallstone formation than wild type mice. Further mechanistic studies revealed that this protective effect was associated with alterations of bile composition and was caused by the increased hepatic CYP7A1 expression and the reduced expression of hepatic SHP, ATP8B1, SR-B1 and SREBP-2. Finally, the correlations between the expression of hepatic OPN and the expression of these hepatic genes were validated in gallstone patients. Taken together, our findings reveal that hepatic OPN contributes to cholesterol gallstone formation by regulating biliary metabolism and might be developed as a therapeutic target for gallstone treatments. PMID:27484115

  20. Management of patients after recovering from acute severe biliary pancreatitis

    PubMed Central

    Dedemadi, Georgia; Nikolopoulos, Manolis; Kalaitzopoulos, Ioannis; Sgourakis, George

    2016-01-01

    Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature. PMID:27678352

  1. Retroperitoneal perforation of the duodenum from biliary stent erosion.

    PubMed

    Miller, George; Yim, Duke; Macari, Michael; Harris, Marsha; Shamamian, Peter

    2005-01-01

    Endoscopically placed biliary stents have supplanted surgical decompression as the preferred treatment option for patients with obstructive jaundice from advanced pancreatic cancer. An unusual complication of indewelling biliary stents is duodenal perforation into the retroperitoneum. We describe the case of a patient with end-stage pancreatic cancer who presented with an acute abdomen from erosion of a previously placed bile duct stent through the wall of the second portion of the duodenum. Although our patient presented with advanced symptoms, clinical presentations can vary from mild abdominal discomfort and general malaise to overt septic shock. Definitive diagnosis is best made with computed tomography (CT) imaging, which can detect traces of retroperitoneal air and fluid. Treatment options vary from nonoperative management with antibiotics, bowel rest, and parenteral alimentation in the most stable patients to definitive surgery with complete diversion of gastric contents and biliary flow from the affected area in patients with clinical symptoms or radiologic evidence suggesting extensive contamination. Complications of management can include duodenal fistulization, residual retroperitoneal or intrabdominal abscess, and ongoing sepsis. This report highlights the salient issues in the presentation, diagnosis, and modern management of patients with this rare complication of indwelling biliary stents.

  2. Management of patients after recovering from acute severe biliary pancreatitis

    PubMed Central

    Dedemadi, Georgia; Nikolopoulos, Manolis; Kalaitzopoulos, Ioannis; Sgourakis, George

    2016-01-01

    Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature.

  3. Absorption of biliary cobalamin in baboons following total gastrectomy

    SciTech Connect

    Green, R.; Jacobsen, D.W.; Van Tonder, S.V.; Kew, M.C.; Metz, J.

    1982-11-01

    Absorption of radiolabeled cobalamin in baboons was assessed by whole body counting. Retention of biliary cobalamin and an aqueous solution of cyanocobalamin was measured in normal baboons and in baboons after total gastrectomy by using /sup 57/Co-labeled biliary cobalamin and /sup 58/C0-cyanocobalamin, with and without baboon gastric juice containing intrinsic factor. Radiolabeled biliary cobalamin was obtained by intravenous injection of /sup 57/Co-cyanocobalamin in baboons and collection of bile through a cannula placed in the common bile duct. Cobalamin absorption was not completely abolished by gastrectomy and biliary cobalamin was better retained than cyanocobalamin; intrinsic factor enhanced absorption of both forms. After gastrectomy there was steady depletion of liver and serum cobalamin levels, which ceased after a new equilibrium was reached between a progressively diminishing cobalamin loss and the impaired but significant residual level of absorption. These studies in the nonhuman primate provide further information concerning the enterohepatic circulation of cobalamin and suggest that the form of cobalamin in bile may be more readily absorbed than is cyanocobalamin or that bile itself may have an enhancing effect on cobalamin absorption. The data also suggest that physiologically significant amounts of cobalamin may be absorbed in the absence of a gastric source of intrinsic factor.

  4. Regional Differences in Hospitalizations and Cholecystectomies for Biliary Dyskinesia

    PubMed Central

    2013-01-01

    Background/Aims Published studies suggest that socioeconomic factors contribute to increasing cholecystectomy rates for biliary dyskinesia (BD). The aim of this study was to identify factors driving admissions and operations for BD by examining regional variability in hospitalizations and cholecystectomies for this disorder. Methods Annual hospitalizations and cholecystectomy rates for biliary diseases were assessed using the State Inpatient Databases of the Agency for Healthcare Research and Quality based on diagnosis codes for biliary dyskinesia, cholecystolithiasis and cholecystitis. Results Annual admissions for BD varied nearly sevenfold among different states within the United States. Hospitalizations for gallstone disease and its complication showed less variability, differing 2-fold between states. Nearly 70% of admissions for BD and about 85% of admissions for gallstone disease resulted in cholecystectomies. Higher admission rates for BD were best predicted by high overall hospitalization rates, admission rate for gallstone disease and the physician workforce within a state. Cholecystectomy rates for BD were higher in states with low population density and high rates of cholecystectomy for gallstone disease. Conclusions These data suggest that established medical practice patterns significantly contribute to the variability in admissions and operations for biliary dyskinesia. The findings also indicate that lower thresholds for operative interventions are an important determinant in the approach to this disorder. Considering the benign course of functional illnesses, the bar for surgical interventions should be raised rather than lowered; in addition active conservative treatment options should be developed for these patients. PMID:23875106

  5. Long-term results of choledochoduodenostomy in benign biliary obstruction

    PubMed Central

    Malik, Ajaz A; Rather, Shiraz A; Bari, Shams UL; Wani, Khursheed Alam

    2012-01-01

    AIM: To determine the long-term results of choledochodudenostomy in patients with benign billiary obstruction. METHODS: This prospective study was conducted at Sheri Kashmir Institute of Medical Sciences Srinagar Kashmir, India over a period of 10 years from January 1997 to December 2007. The total number of patients who underwent choledochoduodenostomy during this period was 270. On the basis of etiology of biliary tract obstruction, patients were divided into a calculus group, an oriental cholangiohepatitis group, a benign biliary stricture group and others. Patients were followed for a variable period of 13 mo to 15 years. RESULTS: Choledochoduodenostomy (CDD) with duo-denotomy was performend in four patients. CDD with removal of T- tube, CDD with left hepatic lobectomy and CDD with removal of intra biliary ruptured hydatid was performed in three patients each. In the remaining patients only CDD was performed. Immediate post operative complications were seen in 63 (23%) patients, while long-term complications were seen in 28 (11%) patients, which were statistically significant. Three patients died during hospitalization while four patients died in the late post-operative period. CONCLUSION: Our conclusion is that CDD is safe and produces good long term results when a permanent biliary drainage procedure is required. PMID:22408717

  6. [Modern approaches to the therapy of biliary system diseases].

    PubMed

    Galiullin, A R; Khakamova, G A; Uliamaeva, V V; Latypova, G A; Gur'ev, D A; Volevach, L V

    2010-01-01

    The therapeutic efficacy of duspatalin was evaluated in 72 patients with chronic cholecystitis and dyskinesia of the biliary tract (BT). Supplementation of duspatalin to the combined therapy in the patients with chronic cholecystitis shown to exert a pronounced therapeutic effect. This caused positive changes in clinical symptoms and BT function and quality of life, diminished the lithogenic properties of bile. PMID:20623959

  7. Osteopontin Deficiency Alters Biliary Homeostasis and Protects against Gallstone Formation

    PubMed Central

    Lin, Jing; Shao, Wei-qing; Chen, Zong-you; Zhu, Wen-wei; Lu, Lu; Cai, Duan; Qin, Lun-xiu; Jia, Hu-liang; Lu, Ming; Chen, Jin-hong

    2016-01-01

    The precipitation of excess biliary cholesterol as solid crystals is a prerequisite for cholesterol gallstone formation, which occurs due to disturbed biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse and form gallstones. We have previously observed that the levels of osteopontin (OPN) in bile and gallbladder were reduced in gallstone patients. However, the role and mechanism for hepatic OPN in cholesterol gallstone formation is undetermined. In this study, we found that the expression of hepatic OPN was increased in gallstone patients compared with gallstone-free counterparts. Then, we observed that OPN-deficient mice were less vulnerable to cholesterol gallstone formation than wild type mice. Further mechanistic studies revealed that this protective effect was associated with alterations of bile composition and was caused by the increased hepatic CYP7A1 expression and the reduced expression of hepatic SHP, ATP8B1, SR-B1 and SREBP-2. Finally, the correlations between the expression of hepatic OPN and the expression of these hepatic genes were validated in gallstone patients. Taken together, our findings reveal that hepatic OPN contributes to cholesterol gallstone formation by regulating biliary metabolism and might be developed as a therapeutic target for gallstone treatments. PMID:27484115

  8. Current status of preoperative drainage for distal biliary obstruction.

    PubMed

    Sugiyama, Harutoshi; Tsuyuguchi, Toshio; Sakai, Yuji; Mikata, Rintaro; Yasui, Shin; Watanabe, Yuto; Sakamoto, Dai; Nakamura, Masato; Sasaki, Reina; Senoo, Jun-Ichi; Kusakabe, Yuko; Hayashi, Masahiro; Yokosuka, Osamu

    2015-08-28

    Preoperative biliary drainage (PBD) was developed to improve obstructive jaundice, which affects a number of organs and physiological mechanisms in patients waiting for surgery. However, its role in patients who will undergo pancreaticoduodenectomy for biliary obstruction remains controversial. This article aims to review the current status of the use of preoperative drainage for distal biliary obstruction. Relevant articles published from 1980 to 2015 were identified by searching MEDLINE and PubMed using the keywords "PBD", "pancreaticoduodenectomy", and "obstructive jaundice". Additional papers were identified by a manual search of the references from key articles. Current studies have demonstrated that PBD should not be routinely performed because of the postoperative complications. PBD should only be considered in carefully selected patients, particularly in cases where surgery had to be delayed. PBD may be needed in patients with severe jaundice, concomitant cholangitis, or severe malnutrition. The optimal method of biliary drainage has yet to be confirmed. PBD should be performed by endoscopic routes rather than by percutaneous routes to avoid metastatic tumor seeding. Endoscopic stenting or nasobiliary drainage can be selected. Although more expensive, the use of metallic stents remains a viable option to achieve effective drainage without cholangitis and reintervention. PMID:26328029

  9. A sign of symptomatic chronic cholecystitis on biliary scintigraphy

    SciTech Connect

    Al-Sheikh, W.; Hourani, M.; Barkin, J.S.; Clarke, L.P.; Ashkar, F.S.; Serafini, A.N.

    1983-02-01

    Five hundred patients with acute right-upper-quadrant pain underwent biliary scintigraphy with /sup 99m/Tc paraisopropyliminodiacetic acid. One hundred and thirty-four studies were reported normal (both gallbladder and activity in bowel are noted in 1 hr). Of the 134 studies reported as normal, 32 showed intestinal activity before gallbladder visualization during the first hour of the study. Sonography and/or oral cholecystography revealed that 24 patients had gallstones, and eight patients had no demonstrable pathology in the biliary system. Of the 134 studies, 102 showed visualization of the gallbladder before intestinal activity during the first hour of the study. Sonography and/or oral cholecystography showed that 73 patients had normal biliary system. The remaining 29 patients had gallstones. The overall sensitivity of this finding is 45%, the specificity is 90%, and the accuracy is 73%. In this group of symptomatic patients, the appearance of intestinal activity before gallbladder activity on biliary scintigraphy warrants further evaluation of these patients by sonography and/or oral cholecystography.

  10. Management of patients after recovering from acute severe biliary pancreatitis.

    PubMed

    Dedemadi, Georgia; Nikolopoulos, Manolis; Kalaitzopoulos, Ioannis; Sgourakis, George

    2016-09-14

    Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature. PMID:27678352

  11. Interval Biliary Stent Placement Via Percutaneous Ultrasound Guided Cholecystostomy: Another Approach to Palliative Treatment in Malignant Biliary Tract Obstruction

    SciTech Connect

    Harding, James Mortimer, Alex; Kelly, Michael; Loveday, Eric

    2010-12-15

    Percutaneous cholecystostomy is a minimally invasive procedure for providing gallbladder decompression, often in critically ill patients. It can be used in malignant biliary obstruction following failed endoscopic retrograde cholangiopancreatography when the intrahepatic ducts are not dilated or when stent insertion is not possible via the bile ducts. In properly selected patients, percutaneous cholecystostomy in obstructive jaundice is a simple, safe, and rapid option for biliary decompression, thus avoiding the morbidity and mortality involved with percutaneous transhepatic biliary stenting. Subsequent use of a percutaneous cholecystostomy for definitive biliary stent placement is an attractive concept and leaves patients with no external drain. To the best of our knowledge, it has only been described on three previous occasions in the published literature, on each occasion forced by surgical or technical considerations. Traditionally, anatomic/technical considerations and the risk of bile leak have precluded such an approach, but improvements in catheter design and manufacture may now make it more feasible. We report a case of successful interval metal stent placement via percutaneous cholecystostomy which was preplanned and achieved excellent palliation for the patient. The pros and cons of the procedure and approach are discussed.

  12. Health Related Quality of Life in Patients with Biliary Atresia Surviving with their Native Liver

    PubMed Central

    Sundaram, Shikha S.; Alonso, Estella M.; Haber, Barbara; Magee, John C.; Fredericks, Emily; Kamath, Binita; Kerkar, Nanda; Rosenthal, Philip; Shepherd, Ross; Limbers, Christine; Varni, James W.; Robuck, Patricia; Sokol, Ronald J.; Liver, Childhood

    2014-01-01

    Objectives To quantify health related quality of life (HRQOL) of patients with biliary atresia with their native livers and compare them with healthy children and patients with biliary atresia post-liver transplant (LT) and to examine the relationship between HRQOL and medical variables. Study design A cross-sectional HRQOL study of patients with biliary atresia with their native livers (ages 2-25 years) was conducted and compared with healthy and post-LT biliary atresia samples using PedsQL™ 4.0 child self and parent proxy reports, a validated measure of physical/psychosocial functioning. Results 221 patients with biliary atresia with native livers (54% female, 67% white) were studied. patient self and parent proxy reports showed significantly poorer HRQOL than healthy children across all domains (p < 0.001), particularly in emotional and psychosocial functioning. Child self and parent proxy HRQOL scores from patients with biliary atresia with their native livers and post-LT biliary atresia were similar across all domains (p=NS). Child self and parent proxy reports showed moderate agreement across all scales, except social functioning (poor to fair agreement). On multivariate regression analysis, black race and elevated total bilirubin were associated with lower Total and Psychosocial HRQOL summary scores. Conclusions HRQOL in patients with biliary atresia with their native livers is significantly poorer than healthy and similar to post-LT biliary atresia children. These findings identify significant opportunities to optimize the overall health of patients with biliary atresia. PMID:23746866

  13. Plasma Lipidomics as a Tool for Diagnosis of Extrahepatic Cholangiocarcinoma in Biliary Strictures: a Pilot Study.

    PubMed

    Prachayakul, Varayu; Thearavathanasingha, Phataraphong; Thuwajit, Chanitra; Roytrakul, Sittiruk; Jaresitthikunchai, Janthima; Thuwajit, Peti

    2016-01-01

    Biliary obstruction is a common clinical manifestation of various conditions, including extrahepatic cholangiocarcinoma. However, a screening test for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction is not yet available. According to the rationale that the biliary system plays a major role in lipid metabolism, biliary obstruction may interfere with lipid profiles in the body. Therefore, plasma lipidomics may help indicate the presence or status of disease in biliary obstruction suspected extrahepatic cholangiocarcinoma. This study aimed to use plasma lipidomics for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction. Plasma from healthy volunteers, patients with benign biliary obstruction extrahepatic cholangiocarcinoma, and other related cancers were used in this study. Plasma lipids were extracted and lipidomic analysis was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Lipid profiles from extrahepatic cholangiocarcinoma patients showed significant differences from both normal and benign biliary obstruction conditions, with no distinction between the latter two. Relative intensity of the selected lipid mass was able to successfully differentiate all extrahepatic cholangiocarcinoma samples from patient samples taken from healthy volunteers, patients with benign biliary obstruction, and patients with other related cancers. In conclusion, lipidomics is a non-invasive method with high sensitivity and specificity for identification of extrahepatic cholangiocarcinoma in patients with biliary obstruction. PMID:27644677

  14. Use of Corticosteroids After Hepatoportoenterostomy for Bile Drainage in Infants With Biliary Atresia

    PubMed Central

    Bezerra, Jorge A.; Spino, Cathie; Magee, John C.; Shneider, Benjamin L.; Rosenthal, Philip; Wang, Kasper S.; Erlichman, Jessi; Haber, Barbara; Hertel, Paula M.; Karpen, Saul J.; Kerkar, Nanda; Loomes, Kathleen M.; Molleston, Jean P.; Murray, Karen F.; Romero, Rene; Schwarz, Kathleen B.; Shepherd, Ross; Suchy, Frederick J.; Turmelle, Yumirle P.; Whitington, Peter F.; Moore, Jeffrey; Sherker, Averell H.; Robuck, Patricia R.; Sokol, Ronald J.

    2015-01-01

    IMPORTANCE Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome. OBJECTIVE To determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver. DESIGN, SETTING, AND PATIENTS The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013. INTERVENTIONS Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of hepatoportoenterostomy. MAIN OUTCOMES AND MEASURES The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events. RESULTS The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy (58.6% [41/70] of steroids group vs 48.6% [34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P = .43). The adjusted absolute risk difference was 8.7% (95% CI, −10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4% [57/70] of the steroids group and 80.0% [56/70] of the placebo group (P > .99); however

  15. The Role of ARF6 in Biliary Atresia

    PubMed Central

    Glessner, Joseph; Ashokkumar, Chethan; Ranganathan, Sarangarajan; Min, Jun; Higgs, Brandon W.; Sun, Qing; Haberman, Kimberly; Schmitt, Lori; Vilarinho, Silvia; Mistry, Pramod K.; Vockley, Gerard; Dhawan, Anil; Gittes, George K.; Hakonarson, Hakon; Jaffe, Ronald; Subramaniam, Shankar; Shin, Donghun; Sindhi, Rakesh

    2015-01-01

    Background & Aims Altered extrahepatic bile ducts, gut, and cardiovascular anomalies constitute the variable phenotype of biliary atresia (BA). Methods To identify potential susceptibility loci, Caucasian children, normal (controls) and with BA (cases) at two US centers were compared at >550000 SNP loci. Systems biology analysis was carried out on the data. In order to validate a key gene identified in the analysis, biliary morphogenesis was evaluated in 2-5-day post-fertilization zebrafish embryos after morpholino-antisense oligonucleotide knockdown of the candidate gene ADP ribosylation factor-6 (ARF6, Mo-arf6). Results Among 39 and 24 cases at centers 1 and 2, respectively, and 1907 controls, which clustered together on principal component analysis, the SNPs rs3126184 and rs10140366 in a 3’ flanking enhancer region for ARF6 demonstrated higher minor allele frequencies (MAF) in each cohort, and 63 combined cases, compared with controls (0.286 vs. 0.131, P = 5.94x10-7, OR 2.66; 0.286 vs. 0.13, P = 5.57x10-7, OR 2.66). Significance was enhanced in 77 total cases, which included 14 additional BA genotyped at rs3126184 only (p = 1.58x10-2, OR = 2.66). Pathway analysis of the 1000 top-ranked SNPs in CHP cases revealed enrichment of genes for EGF regulators (p<1 x10-7), ERK/MAPK and CREB canonical pathways (p<1 x10-34), and functional networks for cellular development and proliferation (p<1 x10-45), further supporting the role of EGFR-ARF6 signaling in BA. In zebrafish embryos, Mo-arf6 injection resulted in a sparse intrahepatic biliary network, several biliary epithelial cell defects, and poor bile excretion to the gall bladder compared with uninjected embryos. Biliary defects were reproduced with the EGFR-blocker AG1478 alone or with Mo-arf6 at lower doses of each agent and rescued with arf6 mRNA. Conclusions The BA-associated SNPs identify a chromosome 14q21.3 susceptibility locus encompassing the ARF6 gene. arf6 knockdown in zebrafish implicates early biliary

  16. Percutaneous Embolization of Transhepatic Tracks for Biliary Intervention

    SciTech Connect

    Lyon, Stuart M.; Terhaar, Olaf; Given, Mark F.; O'Dwyer, Helena M.; McGrath, Frank P.; Lee, Michael J.

    2006-12-15

    Significant pain can occur after removing transhepatic catheters from biliary access tracks, after percutaneous biliary drainage (PBD) or stenting. We undertook a randomized prospective study to ascertain whether track embolization decreases the amount of pain or analgesic requirement after PBD. Fifty consecutive patients (M:F, 22:28; age range:29-85 years; mean age: 66.3 years) undergoing PBD were randomized to receive track embolization or no track embolization after removal of biliary drainage catheters. A combination of Lipoidol and n-butyl cyanoacrylate were used to embolize transhepatic tracks using an 8F dilator. The patients who did not have track embolization performed had biliary drainage catheters removed over a guide wire. A visual analog scoring (VAS) system was used to grade pain associated with catheter removal, 24 h afterward. A required analgesic score (RAS) was devised to tabulate the analgesia required. No analgesia had a score of 0, oral or rectal nonopiate analgesics had a score of 1, oral opiates had a score of 2, and parenteral opiates had a score of 3. The average VAS and RAS for both groups were calculated and compared.Seven patients were excluded for various reasons, leaving 43 patients in the study group. Twenty-one patients comprised the embolization group and 22 patients comprised the nonembolization group. The mean biliary catheter dwell time was not significantly different (p > 0.05) between the embolization group and nonembolization (mean: 5.4 days vs 6.9 days, respectively). In the nonembolization group, the mean VAS was 3.4. Eight patients required parenteral opiates, three patients required oral opiates, and five patients required oral or rectal analgesics, yielding a mean RAS of 1.6. In the embolization group, the mean VAS was 0.9. No patient required parenteral opiates, six patients required oral opiates, and two patients had oral analgesia. The average RAS was 0.6. Both the VAS and the RAS were significantly lower in the

  17. Development of a Swine Benign Biliary Stricture Model Using Endoscopic Biliary Radiofrequency Ablation.

    PubMed

    Park, Jin Seok; Jeong, Seok; Kim, Joon Mee; Park, Sang Soon; Lee, Don Haeng

    2016-09-01

    The large animal model with benign biliary stricture (BBS) is essential to undergo experiment on developing new devices and endoscopic treatment. This study conducted to establish a clinically relevant porcine BBS model by means of endobiliary radiofrequency ablation (RFA). Endoscopic retrograde cholangiography (ERC) was performed on 12 swine. The animals were allocated to three groups (60, 80, and 100 W) according to the electrical power level of RFA electrode. Endobiliary RFA was applied to the common bile duct for 60 seconds using an RFA catheter that was endoscopically inserted. ERC was repeated two and four weeks, respectively, after the RFA to identify BBS. After the strictures were identified, histologic evaluations were performed. On the follow-up ERC two weeks after the procedure, a segmental bile duct stricture was observed in all animals. On microscopic examination, severe periductal fibrosis and luminal obliteration with transmural inflammation were demonstrated. Bile duct perforations occurred in two pigs (100 W, n = 1; 80 W, n = 1) but there were no major complications in the 60 W group. The application of endobiliary RFA with 60 W electrical power resulted in a safe and reproducible swine model of BBS. PMID:27510388

  18. Prospective study of outcomes after percutaneous biliary drainage for malignant biliary obstruction

    PubMed Central

    Robson, P. C.; Heffernan, N.; Gonen, M.; Thornton, R.; Brody, L. A.; Holmes, R.; Brown, K. T.; Covey, A. M.; Fleischer, D.; Getrajdman, G. I.; Jarnagin, W.; Sofocleous, C.; Blumgart, L.; D’Angelica, M.

    2015-01-01

    Purpose Percutaneous biliary drainage (PBD) is used to relieve malignant bile duct obstruction (MBO) when endoscopic drainage is not feasible. Little is known about the effects of PBD on the quality of life (QoL) in patients with MBO. The aim of this study was to evaluate changes in QoL and pruritus after PBD and to explore the variables that impact these changes. Patients and Methods Eligible patients reported their QoL and pruritus before and after PBD using the Functional Assessment of Cancer Therapy – Hepatobiliary instrument (FACT-HS) and the Visual Analog Scale for Pruritus (VASP). Instruments were completed pre-procedure and at one and four weeks following PBD. Results One hundred and nine (60 male/49 female) patients enrolled, 102 (94%) had unresectable disease. PBD was technically successful (hepatic ducts cannulated at the conclusion of procedure) in all patients. There were two procedure-related deaths. All-cause mortality was 10% (N=11) at 4 weeks and 28% (N=31) at 8 weeks post PBD with a median survival of 4.74 months. The mean FACT-HS scores declined significantly (P<.01) over time (101.3, 94.8, 94.7 at baseline, 1 week, 4 weeks, respectively). The VASP scores showed significant improvement at 1 week with continued improvement at 4 weeks (P<.01). Conclusion PBD improves pruritus but not QoL in patients with MBO and advanced malignancy. There is high early mortality in this population. PMID:20358300

  19. Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay.

    PubMed

    Miyakawa, Hiroshi; Kawashima, Yumi; Kitazawa, Eriko; Kawaguchi, Naomi; Kato, Takashi; Kikuchi, Kentaro; Imai, Erika; Fujikawa, Hirotoshi; Hashimoto, Etsuko; Schlumberger, Wolfgang

    2003-08-01

    Anti-soluble liver antigen/liver pancreas (SLA/LP) autoantibody has been proposed to be one of the autoantibodies characterizing autoimmune hepatitis (AIH). Recently, one of the autoantigens to anti-SLA/LP was identified as a UGA suppressor tRNA-associated protein. Although the function of this protein remains unknown, the recombinant protein has been prokaryotically expressed. Using this protein as an antigen, a recombinant immunoassay for anti-SLA/LP autoantibody has been established and the frequency and significance of this autoantibody have been discussed in European countries. So, in the present study, we investigated anti-SLA/LP autoantibodies in Japanese patients with autoimmune liver diseases using the recombinant antigen ELISA and Western blot assay. Seventy-five patients with AIH type 1, 5 with AIH type 2, 46 with primary biliary cirrhosis, 10 with primary sclerosing cholangitis, 47 with chronic hepatitis C, 48 with systemic lupus erythematosus, 3 with cryptogenic hepatitis, and 40 normal controls were the subjects of the present study. Anti-SLA/LP autoantibodies were detected in only 5 of 75 (6.7%) patients with AIH type 1, but in none of the other 159 patients or 40 normal controls. The clinicopathologic features of anti-SLA/LP-positive AIH type 1, including carriers of HLA DR locus variations, were not significantly different from anti-SLA/LP-negative patients except for the mortality rate. Anti-SLA/LP autoantibody was detected at a low frequency in Japanese patients with AIH type 1 and did not significantly influence clinical features. However, since it has high disease-specificity to AIH type 1, further analysis of SLA/LP may contribute to help clarify the pathogenesis of AIH type 1.

  20. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

    Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT. PMID:26689244

  1. Recognition of Major Histocompatibility Complex Antigens on Cultured Human Biliary Epithelial Cells by Alloreactive Lymphocytes

    PubMed Central

    Saidman, Susan L.; Duquesnoy, Rene J.; Zeevi, Adriana; Fung, John J.; Starzl, Thomas E.; Demetris, A. Jake

    2010-01-01

    We have developed an in vitro system to study the interactions between biliary epithelium and lymphocytes using cultured human biliary epithelial cells. No class II antigens were detected by immunoperoxidase staining of the normal biliary epithelial cells, but alloactivated lymphocyte culture supernatants were able to induce class II expression. The activity of the supernatants was blocked with an anti-γ-interferon monoclonal antibody. In addition, recombinant human γ-interferon alone induced the expression of class II antigens and increased the intensity of class I staining of cultured biliary epithelial cells. Biliary epithelial cell–induced proliferation of alloreactive T lymphocytes demonstrated that the major histocompatibility complex molecules carry functional lymphocyte-activating determinants. The recognition of major histocompatibility complex determinants was confirmed by monoclonal antibody–blocking studies and by stimulation of an alloreactive T-cell clone. However, the biliary epithelial cells were much less potent stimulators than arterial endothelial cells tested in the same assay system. PMID:1704868

  2. Primary sclerosing cholangitis

    PubMed Central

    Silveira, Marina G; Lindor, Keith D

    2008-01-01

    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a ‘beaded’ appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day) is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC. PMID:18701947

  3. [PRIMARY SCLEROSING CHOLANGITIS

    PubMed

    Dantas, Waldomiro

    2000-01-01

    Primary sclerosing cholangitis (PSC) is a chronic cholestatic and progressive disease, of unknown etiology, characterized by inflammation and fibrosis of intra-hepatic and extra-hepatic biliary tree. Two thirds of the patients have, simultaneously, ulcerative colitis (UC); on the other hand, PSC is the most common chronic hepatic disease in patients with inflammatory bowel disease (IBD). Patients who have both diseases simultaneously are prone to develop colorectal carcinoma and cholangiocarcinoma. The disease predominantly affects young men, may be asymptomatic or presented as fluctuating jaundice, pruritus and increased levels of the cholestasis biochemical markers, or as secondary billiary cirrhosis. The diagnostic gold standard are the cholangiographic abnormalities, consisting of multifocal stenosis and dilatations, involving both the intrahepatic and the extrahepatic biliary tree. Liver biopsy is useful only for staging the disease and to confirm the diagnosis, in the atypical forms. Ursodeoxycholic acid is a promising drug, nowadays, mainly in the first stages of the disease, in spite of doubtful efficacy. Combination therapy, using ursodeoxicolic acid, methotrexate and alternating antibiotics monthly may be sucessfull in PSC before bile strictures occur. Liver transplantation is the only life-saving therapeutic alternative, able to improve significantly the survival and the life quality of the patients. PMID:12140588

  4. Improved biliary detection and diagnosis through intelligent machine analysis.

    PubMed

    Logeswaran, Rajasvaran

    2012-09-01

    This paper reports on work undertaken to improve automated detection of bile ducts in magnetic resonance cholangiopancreatography (MRCP) images, with the objective of conducting preliminary classification of the images for diagnosis. The proposed I-BDeDIMA (Improved Biliary Detection and Diagnosis through Intelligent Machine Analysis) scheme is a multi-stage framework consisting of successive phases of image normalization, denoising, structure identification, object labeling, feature selection and disease classification. A combination of multiresolution wavelet, dynamic intensity thresholding, segment-based region growing, region elimination, statistical analysis and neural networks, is used in this framework to achieve good structure detection and preliminary diagnosis. Tests conducted on over 200 clinical images with known diagnosis have shown promising results of over 90% accuracy. The scheme outperforms related work in the literature, making it a viable framework for computer-aided diagnosis of biliary diseases.

  5. Post-biliary sphincterotomy bleeding despite covered metallic stent deployment

    PubMed Central

    Donatelli, Gianfranco; Cereatti, Fabrizio; Dumont, Jean-Loup; Dhumane, Parag; Tuszynski, Thierry; Vergeau, Bertrand Marie; Meduri, Bruno

    2016-01-01

    Objectives: Several endoscopic techniques have been proposed for the management of post-sphincterotomy bleeding. Lately, self-expandable metal stents deployment has gained popularity especially as a rescue therapy when other endoscopic techniques fail. Methods-results: We report the case report of a massive post-sphincterotomy bleeding in a patient with a self-expandable metal stent in the biliary tree. Despite the presence of a correctly positioned self-expandable metal stent, a new endoscopic session was required to control the bleeding. Conclusions: Self-expandable metal stent may be useful to manage post-endoscopic sphincterotomy bleeding. However, up to now there is no specifically designed self-expandable metal stent for such complication. Large new designed self-expandable metal stent may be a useful tool for biliary endoscopist. PMID:27489716

  6. Postoperative pancreatitis as a complication of biliary surgery.

    PubMed

    Ingram, D M; House, A K; Garcia-Webb, P

    1979-08-01

    Forty patients who underwent biliary surgery were investigated for postoperative pancreatic disturbance as measured by the amylase creatinine clearance ration (ACCR). Its relevance to preoperative pancreatitis, exploration of the common bile duct, and operative cholangiography were examined. The results suggested that a recent clinically proven episode of pancreatitis did not predispose to a postoperative recurrence following biliary surgery. Similarly, cholecystectomy alone did not produce a postoperative pancreatic disturbance. However, exploration of the common bile duct did frequently cause a postoperative elevated ACCR, and hence we recommend that duct exploration should be performed as carefully and as atraumatically as possible. The small number of patients who did not have operative cholangiograms prevented statistical evaluation of the effect of this procedure on the pancreas. However, information from elsewhere suggests that the plasma amylase level is not likely to be raised by cholangiography. PMID:291412

  7. Combined radiologic and endoscopic treatment (using the "rendezvous technique") of a biliary fistula following left hepatectomy.

    PubMed

    Gracient, Aurélien; Rebibo, Lionel; Delcenserie, Richard; Yzet, Thierry; Regimbeau, Jean-Marc

    2016-08-14

    Despite the ongoing decrease in the frequency of complications after hepatectomy, biliary fistulas still occur and are associated with high morbidity and mortality rates. Here, we report on an unusual technique for managing biliary fistula following left hepatectomy in a patient in whom the right posterior segmental duct joined the left hepatic duct. The biliary fistula was treated with a combined radiologic and endoscopic procedure based on the "rendezvous technique". The clinical outcome was good, and reoperation was not required. PMID:27570431

  8. Acceptable Toxicity After Stereotactic Body Radiation Therapy for Liver Tumors Adjacent to the Central Biliary System

    SciTech Connect

    Eriguchi, Takahisa; Takeda, Atsuya; Sanuki, Naoko; Oku, Yohei; Aoki, Yousuke; Shigematsu, Naoyuki; Kunieda, Etsuo

    2013-03-15

    Purpose: To evaluate biliary toxicity after stereotactic body radiation therapy (SBRT) for liver tumors. Methods and Materials: Among 297 consecutive patients with liver tumors treated with SBRT of 35 to 50 Gy in 5 fractions, patients who were irradiated with >20 Gy to the central biliary system (CBS), including the gallbladder, and had follow-up times >6 months were retrospectively analyzed. Toxicity profiles, such as clinical symptoms and laboratory and radiologic data especially for obstructive jaundice and biliary infection, were investigated in relation to the dose volume and length relationship for each biliary organ. Results: Fifty patients with 55 tumors were irradiated with >20 Gy to the CBS. The median follow-up period was 18.2 months (range, 6.0-80.5 months). In the dose length analysis, 39, 34, 14, and 2 patients were irradiated with >20 Gy, >30 Gy, >40 Gy, and >50 Gy, respectively, to >1 cm of the biliary tract. Seven patients were irradiated with >20 Gy to >20% of the gallbladder. Only 2 patients experienced asymptomatic bile duct stenosis. One patient, metachronously treated twice with SBRT for tumors adjacent to each other, had a transient increase in hepatic and biliary enzymes 12 months after the second treatment. The high-dose area >80 Gy corresponded to the biliary stenosis region. The other patient experienced biliary stenosis 5 months after SBRT and had no laboratory changes. The biliary tract irradiated with >20 Gy was 7 mm and did not correspond to the bile duct stenosis region. No obstructive jaundice or biliary infection was found in any patient. Conclusions: SBRT for liver tumors adjacent to the CBS was feasible with minimal biliary toxicity. Only 1 patient had exceptional radiation-induced bile duct stenosis. For liver tumors adjacent to the CBS without other effective treatment options, SBRT at a dose of 40 Gy in 5 fractions is a safe treatment with regard to biliary toxicity.

  9. Liver failure posthepatectomy and biliary fistula: multidisciplinar treatment.

    PubMed

    Calleja Kempin, Javier; Colón Rodríguez, Arturo; Machado Liendo, Pedro; Acevedo, Agustín; Martín Gil, Jorge; Sánchez Rodríguez, Teresa; Zorrilla Matilla, Laura

    2016-05-01

    The main cause of morbimor-mortality after major liver surgery is the development of liver failure posthepatectomy(LFPH). Treatment must involve multiple options and will be aggressive from the beginning. We report a case of a patient with cholangiocarcinoma perihilar treated with surgery: right hepatectomy extended to sI + IVb with develop of LFPH and biliary fistula and being management successfully in a multidisciplinary way.

  10. Physical chemistry of biliary lipids during bile formation.

    PubMed

    Cohen, D E; Carey, M C

    1990-09-01

    Present concepts suggest that the canalicular secretion of bile salts is monomeric, which in turn drives the hepatic secretion of lecithin and cholesterol presumably as unilamellar vesicles into bile. As biliary lipids are concentrated within the biliary tree and gallbladder, bile salts structurally alter lecithin-cholesterol vesicles to form a variety of metastable aggregates whose structures and phase transformations are predicted by phase equilibria considerations. These structural transformations ultimately result in the dispersion of biliary lipids as thermodynamically stable micelles or micelles plus thermodynamically unstable vesicles in common duct and gallbladder biles. The experiments reviewed herein represent experimental simulations of these processes. We used pure aqueous lipid systems to model the putative stages of biliary lipid aggregation on the basis of interactions of small unilamellar vesicles of lecithin-cholesterol with bile salts as the latter's concentrations were varied from below to well above the critical micellar concentration. With submicellar bile salt concentrations likely to be found within hepatocytes, vesicle structures are not appreciably altered. However, perimicellar bile salt concentrations possibly occurring in canaliculi and bile ductules induce the formation of a hexagonal rodlike phase. On further increases in bile salt concentration, the hexagonal rods (formed from lecithin-rich and cholesterol-poor vesicles) are dissolved into mixed micelles as bile salt concentrations exceed their critical micellar concentrations. In slightly cholesterol-"supersaturated" biles, the rapid dissolution of this intermediate phase results in the formation of cholesterol-supersaturated mixed micelles that, in time, give rise to a new population of cholesterol-rich vesicles that coexist with saturated micelles.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. A Survival Analysis of Patients with Malignant Biliary Strictures Treated by Percutaneous Metallic Stenting

    SciTech Connect

    Brountzos, Elias N. Ptochis, Nikolaos; Panagiotou, Irene; Malagari, Katerina; Tzavara, Chara; Kelekis, Dimitrios

    2007-02-15

    Background. Percutaneous metal stenting is an accepted palliative treatment for malignant biliary obstruction. Nevertheless, factors predicting survival are not known. Methods. Seventy-six patients with inoperable malignant biliary obstruction were treated with percutaneous placement of metallic stents. Twenty patients had non-hilar lesions. Fifty-six patients had hilar lesions classified as Bismuth type I (n = 15 patients), type II (n = 26), type III (n = 12), or type IV (n = 3 patients). Technical and clinical success rates, complications, and long-term outcome were recorded. Clinical success rates, patency, and survival rates were compared in patients treated with complete (n = 41) versus partial (n = 35) liver parenchyma drainage. Survival was calculated and analyzed for potential predictors such as the tumor type, the extent of the disease, the level of obstruction, and the post-intervention bilirubin levels. Results. Stenting was technically successful in all patients (unilateral drainage in 70 patients, bilateral drainage in 6 patients) with an overall significant reduction of the post-intervention bilirubin levels (p < 0.001), resulting in a clinical success rate of 97.3%. Clinical success rates were similar in patients treated with whole-liver drainage versus partial liver drainage. Minor and major complications occurred in 8% and 15% of patients, respectively. Mean overall primary stent patency was 120 days, while the restenosis rate was 12%. Mean overall secondary stent patency was 242.2 days. Patency rates were similar in patients with complete versus partial liver drainage. Mean overall survival was 142.3 days. Survival was similar in the complete and partial drainage groups. The post-intervention serum bilirubin level was an independent predictor of survival (p < 0.001). A cut-off point in post-stenting bilirubin levels of 4 mg/dl dichotomized patients with good versus poor prognosis. Patient age and Bismuth IV lesions were also independent predictors

  12. Species differences in biliary excretion of benzo(a)pyrene

    SciTech Connect

    Weyand, E.H.; Bevan, D.R.

    1986-05-01

    Biliary excretion of benzo(a)pyrene (B(a)P) was investigated in rats, hamsters, and guinea pigs following intratracheal administration. (/sup 3/H)-B(a)P, in amounts of approximately 150 ng or 350 ..mu..g, was instilled into lungs and amounts of radioactivity excreted in bile were monitored for six hrs following administration. Differences in biliary excretion of (/sup 3/H)-B(a)P and/or metabolites among species were observed at low doses but not at high doses. Six hours after instillation of a low dose of B(a)P, 70, 54, and 62% of the dose was excreted in bile of rats, hamsters, and guinea pigs, respectively. Upon administration of the higher dose of B(a)P, approximately 50% of the dose was excreted in bile in six hrs by all species. Thus, rats and guinea pigs exhibit differences in biliary excretion of low and high doses of B(a)P whereas hamsters do not. Profiles of phase II metabolites in rats and hamsters were similar at both low and high doses, with the majority of metabolites being glucuronides and thioether conjugates. However, differences in relative amounts of these conjugates were observed between the two doses, with a shift towards a greater proportion of glucuronides at the higher dose. Metabolites in bile from guinea pigs were primarily thioether conjugates, which accounted for 88% of metabolites at the low dose and 95% at the high dose.

  13. The Radiological Management of Biliary Complications Following Liver Transplantation

    SciTech Connect

    Rieber, Andrea; Brambs, Hans-Juergen; Lauchart, Werner

    1996-04-15

    Purpose: Biliary complications contribute significantly to morbidity and mortality in the liver transplant recipient. Surgery has been the mainstay of therapy, but interventional radiological techniques have made significant progress. Methods: Diagnostic percutaneous transhepatic cholangiography (PTC) was performed in 12 patients; percutaneous transhepatic drainage (PTD) was performed in 10 patients. Additional interventional procedures included laser lithotripsy, biopsy, dilatation, and stent implantation. Results: In 6 patients PTC revealed anastomotic, and in 6 patients nonanastomotic biliary strictures. Four patients had intrahepatic stones. Biliary strictures were treated by implantation of Palmaz stents in 5 of 6 patients with anastomotic strictures, and in 3 of 6 patients with nonanastomotic strictures. The intrahepatic stones were fragmented with dye laser lithotripsy under cholangioscopic control in 3 of 4 patients. One spontaneous stent migration after 24 months and one stent occlusion were observed; the remaining stents are still patent. Patients with anastomotic strictures had a more favorable outcome: 5 of 6 of these patients are still alive and symptom-free after an average of 27.4 months, but only 3 of 6 patients with nonanastomotic strictures are alive after an average of 9.8 months. Conclusion: The different outcomes in patients with anastomotic versus nonanastomotic strictures may be explained by the different causes of these types of stricture.

  14. Kinetic analysis of biliary lipid excretion in man and dog.

    PubMed Central

    Wagner, C I; Trotman, B W; Soloway, R D

    1976-01-01

    To understand better the mechanisms involved in biliary lipid excretion and to evaluate their role in cholesterol gallstone formation, the rates of biliary excretion of bile salts, cholesterol, and phospholipids were measured in two species, man and dog. Seven cholecystectomized patients with balloon-occludable reinfusion T-tubes were studied during intact and interrupted enterohepatic circulation and four cholecystectomized dogs were studied during interrupted enterohepatic circulation. In man and dog both cholesterol and phospholipid outputs were hyperbolically related to bile salt output by the equation y = x/(a + bx). The output curves intersected the origin and showed an initial rapid rise, followed by a slower increase to a maximum, suggesting a rate-limited mechanism. The shape of the curves permitted calculation of the theoretical maximal outputs and the rates of rise to those outputs. Comparison of these values showed that in both man and dog phospholipid output was greater than cholesterol output and that cholesterol and phospholipid were excreted at different rates. These studies (a) indicate that cholesterol, phospholipids, and bile salts are not excreted in a fixed relationship and (b) demonstrate the usefulness of the derived theoretical maximal lipid output, and the rate of rise of lipid excretion to a maximum, in evaluating the kinetics of biliary lipid excretion. PMID:943421

  15. Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

    PubMed Central

    Asai, Akihiro; Miethke, Alexander; Bezerra, Jorge A.

    2016-01-01

    Biliary atresia is a severe cholangiopathy of early infancy that destroys extrahepatic bile ducts and disrupts bile flow. With a poorly defined disease pathogenesis, treatment consists of the surgical removal of duct remnants followed by hepatoportoenterostomy. Although this approach can improve the short-term outcome, the liver disease progresses to end-stage cirrhosis in most children. Further improvement in outcome will require a greater understanding of the mechanisms of biliary injury and fibrosis. Here, we review progress in the field, which has been fuelled by collaborative studies in larger patient cohorts and the development of cell culture and animal model systems to directly test hypotheses. Advances include the identification of phenotypic subgroups and stages of disease based on clinical, pathological and molecular features. Stronger evidence exists for viruses, toxins and gene sequence variations in the aetiology of biliary atresia, triggering a proinflammatory response that injures the duct epithelium and produces a rapidly progressive cholangiopathy. The immune response also activates the expression of type 2 cytokines that promote epithelial cell proliferation and extracellular matrix production by nonparenchymal cells. These advances provide insight into phenotype variability and might be relevant to the design of personalized trials to block progression of liver disease. PMID:26008129

  16. Biliary parasitic diseases including clonorchiasis, opisthorchiasis and fascioliasis.

    PubMed

    Lim, Jae Hoon; Mairiang, Eimorn; Ahn, Geung Hwan

    2008-01-01

    Parasitic infection of the biliary tree is caused by liver flukes, namely Clonorchis sinensis and Opisthorchis viverrini. These flukes reside in the peripheral small bile ducts of the liver and produce chronic inflammation of the bile duct, bile duct dilatation, mechanical obstruction, and bile duct wall thickening. On imaging, peripheral small intrahepatic bile ducts are dilated, but the large bile ducts and extrahepatic bile ducts are not dilated or slightly dilated. There is no visible caused of obstruction. Sometimes, in heavy infection, adult flukes are demonstrated on sonography, CT or MR cholangiography as small intraluminal lesions. The flukes in the gallbladder may appear as floating, small objects on sonography. Chronic infection may result in cholangiocarcinoma of the liver parenchyma or along the bile ducts. Human infection of Fasciola hepatica, a cattle flukes, may occur inadvertently, and the flukes migrate in the liver (hepatic phase) and reside the bile ducts (biliary phase). Image findings in the hepatic phase present with multiple, small, clustered, necrotic cavities or abscesses in the peripheral parts of the liver, showing "tunnels and caves" sign, reflecting parasite migration in the liver parenchyma. In the biliary phase, the flukes are demonstrated in the intra- and extrahepatic bile ducts and the gallbladder as small intraluminal flat objects, sometimes moving spontaneously. Bile ducts are dilated.

  17. Photodynamic therapy for pancreatic and biliary tract carcinoma

    NASA Astrophysics Data System (ADS)

    Pereira, Stephen P.

    2009-02-01

    Patients with non-resectable pancreatic and biliary tract cancer (cholangiocarcinoma and gallbladder cancer) have a dismal outlook with conventional palliative therapies, with a median survival of 3-9 months and a 5 year survival of less than 3%. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then is associated with a 5-year survival of less than 30%. Although most applications of photodynamic therapy (PDT) in gastroenterology have been on lesions of the luminal gut, there is increasing experimental and clinical evidence for its efficacy in cancers of the pancreas and biliary tract. Our group has carried out the only clinical study of PDT in pancreatic carcinoma reported to date, and showed that PDT is feasible for local debulking of pancreatic cancer. PDT has also been used with palliative intent in patients with unresectable cholangiocarcinoma, with patients treated with stenting plus PDT reporting improvements in cholestasis, quality of life and survival compared with historical or randomized controls treated with stenting alone. Further controlled studies are needed to establish the influence of PDT and chemotherapy on the survival and quality of life of patients with pancreatic and biliary tract carcinoma.

  18. Role of Adjuvant Chemoradiotherapy for Resected Extrahepatic Biliary Tract Cancer

    SciTech Connect

    Kim, Tae Hyun; Han, Sung-Sik; Park, Sang-Jae Lee, Woo Jin; Woo, Sang Myung; Moon, Sung Ho; Yoo, Tae; Kim, Sang Soo; Kim, Seong Hoon; Hong, Eun Kyung; Kim, Dae Yong; Park, Joong-Won

    2011-12-01

    Purpose: To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. Methods and Materials: The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. Results: For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p = .007; 32.1% vs. 26.1%, p = .041; 36.5% vs. 28.2%, p = .049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p < .05). Conclusion: Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer.

  19. Multidrug resistance p-glycoprotein 2 is essential for the biliary excretion of indocyanine green.

    PubMed

    Huang, L; Vore, M

    2001-05-01

    Multidrug resistance P-glycoprotein 2 (Mdr2) is a phospholipid translocator in the canalicular membrane that is essential for the formation of biliary phospholipid vesicles and mixed lipid/bile salt micelles. Incorporation into biliary vesicles and micelles is thought to contribute to the hepatobiliary excretion of certain hydrophobic organic anions, such as indocyanine green (ICG). The present studies characterized the biliary excretion of two hydrophobic organic anions, ICG and estradiol-17beta(beta-D-glucuronide) (E(2)17G), in the single-pass isolated perfused liver and the biliary excretion of glutathione (GSH) in vivo in wild-type and Mdr2-/- female mice. The biliary excretion of ICG (0.4 micromol) was reduced by 90%, while the biliary excretion of total GSH was decreased by 65% in Mdr2-/- mice relative to wild-type mice. In contrast, the biliary excretion of E(2)17G (0.1 micromol) was increased by 30% in Mdr2-/- mice. These data indicate that the absence of Mdr2 differentially influences the biliary excretion of these organic anions and suggest that phospholipid vesicles and mixed micelles in bile are essential for the biliary excretion of ICG.

  20. Outcome of stenting in biliary and pancreatic benign and malignant diseases: A comprehensive review

    PubMed Central

    Mangiavillano, Benedetto; Pagano, Nico; Baron, Todd H; Luigiano, Carmelo

    2015-01-01

    Endoscopic stenting has become a widely method for the management of various malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents are devices made of plastic or metal used primarily to establish patency of an obstructed bile or pancreatic duct and may also be used to treat biliary or pancreatic leaks, pancreatic fluid collections and to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. In this review, relevant literature search and expert opinions have been used to evaluate the outcome of stenting in biliary and pancreatic benign and malignant diseases. PMID:26290631

  1. A new framework for reverse cholesterol transport: Non-biliary contributions to reverse cholesterol transport

    PubMed Central

    Temel, Ryan E; Brown, J Mark

    2010-01-01

    Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-mediated delivery of peripheral cholesterol to the liver for biliary excretion out of the body. However, recent studies have revealed a novel pathway for RCT that does not rely on biliary secretion. This non-biliary pathway rather involves the direct excretion of cholesterol by the proximal small intestine. Compared to RCT therapies that augment biliary sterol loss, modulation of non-biliary fecal sterol loss through the intestine is a much more attractive therapeutic strategy, given that excessive biliary cholesterol secretion can promote gallstone formation. However, we are at an early stage in understanding the molecular mechanisms regulating the non-biliary pathway for RCT, and much additional work is required in order to effectively target this pathway for CHD prevention. The purpose of this review is to discuss our current understanding of biliary and non-biliary contributions to RCT with particular emphasis on the possibility of targeting the intestine as an inducible cholesterol secretory organ. PMID:21157970

  2. Classification of biliary tract cancers established by the Japanese Society of Hepato-Biliary-Pancreatic Surgery: 3(rd) English edition.

    PubMed

    Miyazaki, Masaru; Ohtsuka, Masayuki; Miyakawa, Shuichi; Nagino, Masato; Yamamoto, Masakazu; Kokudo, Norihiro; Sano, Keiji; Endo, Itaru; Unno, Michiaki; Chijiiwa, Kazuo; Horiguchi, Akihiko; Kinoshita, Hisafumi; Oka, Masaaki; Kubota, Keiichi; Sugiyama, Masanori; Uemoto, Shinji; Shimada, Mitsuo; Suzuki, Yasuyuki; Inui, Kazuo; Tazuma, Susumu; Furuse, Junji; Yanagisawa, Akio; Nakanuma, Yasuni; Kijima, Hiroshi; Takada, Tadahiro

    2015-03-01

    The 3(rd) English edition of the Japanese classification of biliary tract cancers was released approximately 10 years after the 5(th) Japanese edition and the 2(nd) English edition. Since the first Japanese edition was published in 1981, the Japanese classification has been in extensive use, particularly among Japanese surgeons and pathologists, because the cancer status and clinical outcomes in surgically resected cases have been the main objects of interest. However, recent advances in the diagnosis, management and research of the disease prompted the revision of the classification that can be used by not only surgeons and pathologists but also by all clinicians and researchers, for the evaluation of current disease status, the determination of current appropriate treatment, and the future development of medical practice for biliary tract cancers. Furthermore, during the past 10 years, globalization has advanced rapidly, and therefore, internationalization of the classification was an important issue to revise the Japanese original staging system, which would facilitate to compare the disease information among institutions worldwide. In order to achieve these objectives, the new Japanese classification of the biliary tract cancers principally adopted the 7(th) edition of staging system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). However, because there are some points pending in these systems, several distinctive points were also included for the purpose of collection of information for the future optimization of the staging system. Free mobile application of the new Japanese classification of the biliary tract cancers is available via http://www.jshbps.jp/en/classification/cbt15.html. PMID:25691463

  3. Classification of biliary tract cancers established by the Japanese Society of Hepato-Biliary-Pancreatic Surgery: 3(rd) English edition.

    PubMed

    Miyazaki, Masaru; Ohtsuka, Masayuki; Miyakawa, Shuichi; Nagino, Masato; Yamamoto, Masakazu; Kokudo, Norihiro; Sano, Keiji; Endo, Itaru; Unno, Michiaki; Chijiiwa, Kazuo; Horiguchi, Akihiko; Kinoshita, Hisafumi; Oka, Masaaki; Kubota, Keiichi; Sugiyama, Masanori; Uemoto, Shinji; Shimada, Mitsuo; Suzuki, Yasuyuki; Inui, Kazuo; Tazuma, Susumu; Furuse, Junji; Yanagisawa, Akio; Nakanuma, Yasuni; Kijima, Hiroshi; Takada, Tadahiro

    2015-03-01

    The 3(rd) English edition of the Japanese classification of biliary tract cancers was released approximately 10 years after the 5(th) Japanese edition and the 2(nd) English edition. Since the first Japanese edition was published in 1981, the Japanese classification has been in extensive use, particularly among Japanese surgeons and pathologists, because the cancer status and clinical outcomes in surgically resected cases have been the main objects of interest. However, recent advances in the diagnosis, management and research of the disease prompted the revision of the classification that can be used by not only surgeons and pathologists but also by all clinicians and researchers, for the evaluation of current disease status, the determination of current appropriate treatment, and the future development of medical practice for biliary tract cancers. Furthermore, during the past 10 years, globalization has advanced rapidly, and therefore, internationalization of the classification was an important issue to revise the Japanese original staging system, which would facilitate to compare the disease information among institutions worldwide. In order to achieve these objectives, the new Japanese classification of the biliary tract cancers principally adopted the 7(th) edition of staging system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). However, because there are some points pending in these systems, several distinctive points were also included for the purpose of collection of information for the future optimization of the staging system. Free mobile application of the new Japanese classification of the biliary tract cancers is available via http://www.jshbps.jp/en/classification/cbt15.html.

  4. Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy

    PubMed Central

    Lamarca, Angela; Rigby, Christina; McNamara, Mairéad G; Hubner, Richard A; Valle, Juan W

    2016-01-01

    AIM: To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). CONCLUSION: SREs are common and impact on patient’s morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs. PMID

  5. Biliary self-expandable metallic stent for unresectable malignant distal biliary obstruction: which is better: covered or uncovered?

    PubMed

    Isayama, Hiroyuki; Nakai, Yousuke; Kogure, Hirofumi; Yamamoto, Natsuyo; Koike, Kazuhiko

    2013-05-01

    Self-expandable metallic stents (SEMS) are a widely accepted biliary endoprosthesis for patients with unresectable malignant distal biliary obstruction. There are two types of SEMS: covered and uncovered. Uncovered SEMS (UCSEMS) embed into the biliary wall due to their mesh structure and self-expandability, and are resistant to migration. However, the disadvantage of UCSEMS is occlusion due to tumor ingrowth (TI) via the stent mesh, and TI is the main cause of UCSEMS occlusion. To overcome this, covered SEMS (CSEMS) were developed and showed longer patency than UCSEMS. However, migration due to the non-embedded stent body is the main cause of CSEMS dysfunction. There are some randomized studies comparing CSEMS and UCSEMS; however, the results are different according to each study. From one meta-analysis, CSEMS showed longer patency than UCSEMS. A literature review revealed that covered SEMS showed longer patency than UCSEMS. Some studies cannot clearly demonstrate the superiority of CSEMS, as the CSEMS used did not prevent TI or migration. Mechanical properties of SEMS may influence the occurrence of complications. A recent clinical study comparing the Covered Wallstent and the Covered WallFlex revealed superiority of the WallFlex for the prevention of migration. Reducing the axial force and increasing the radial force may lead to good results. Migration of CSEMS should be prevented by taking into consideration the mechanical properties of stents and development of anti-migration systems.

  6. Influence of curcumin on cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion and on biliary excretion of cyclosporin and its metabolites.

    PubMed

    Deters, M; Siegers, C; Hänsel, W; Schneider, K P; Hennighausen, G

    2000-06-01

    We investigated the ability of curcumin, which can be extracted from different Curcuma species, to prevent cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion, and its influence on biliary excretion of cyclosporin (CS) and its metabolites in the bile fistula model in rats. I.v. injection of curcumin (25 and 50 mg/kg) after 30 min increased dose-dependently basal bile flow (30 microliters/kg/min) up to 200%, biliary bilirubin excretion (3000 pmol/kg/min) up to 150%, and biliary cholesterol excretion (22 nmol/kg/min) up to 113%. CS (30 mg/kg) reduced bile flow to 66% and biliary excretion of bilirubin and of cholesterol to 33% of the basal value 30 min after i.v. injection. I.v. administration of curcumin (25 and 50 mg/kg) 30 min after CS increased bile flow dose dependently again to 130% for 1 hour and biliary excretion of cholesterol and of bilirubin to 100% of the basal value for 30 and 150 min, respectively. Injection of curcumin 15 min before CS prevented the CS-induced drop of bile flow at 50 mg/kg and reduction of biliary bilirubin excretion already at 25 mg/kg until the end of the experiment (180 min). The CS-induced reduction of biliary cholesterol excretion, however, was not prevented by curcumin. Finally, the biliary excretions of CS (1200 ng/kg/min) and its metabolites (1200 ng/kg/min) were slightly reduced by curcumin at a dose of 50 mg/kg (to 83% of the initial values). The clinical importance of these controversial effects remains to be shown.

  7. Autoimmune reactivity of sera to hepatocyte plasma membrane in type 1 autoimmune hepatitis.

    PubMed

    Matsuo, I; Ikuno, N; Omagari, K; Kinoshita, H; Oka, M; Yamaguchi, H; Kohno, S; Mackay, I R

    2000-01-01

    Type 1 autoimmune hepatitis (AIH-1) is an organ-specific autoimmune liver disease for which no tissue-specific autoantigen has yet been identified. We examined the reactivity by sensitive immunoblotting with enhanced chemiluminescence (IB-ECL) of 43 sera from patients with AIH-1 and 182 sera from patients with other diseases on hepatocyte plasma membrane derived from rat or human liver (RHPM, HHPM) and separated by aqueous two-phase partition. The sera studied were from patients with AIH-1, primary biliary cirrhosis, chronic viral hepatitis, and systemic lupus erythematosus (SLE); and from normal subjects. Specificity of reactivity by IB-ECL was sought: (i) by testing sera on human or rat liver membrane; (ii) by testing sera on liver or kidney membrane; (iii) by serial titration of reactive sera; and (iv) by testing reactive sera from AIH-1 before and after successful treatment with prednisolone. The results were that in AIH-1 there were multiple reactive components which were not species-specific, since they were detected with both RHPM and HHPM, but were mostly tissue-specific for liver. There was no significant correlation between antinuclear antibodies (ANA) titer and the frequencies of sera reactivities against RHPM. Most of these reactive components were demonstrable at a lesser frequency in other liver diseases and in SLE. There was a striking decrease in reactivity by IB-ECL of AIH-1 sera with liver membrane after clinical remission, further suggesting that differences between AIH-1 and other inflammatory liver diseases and SLE are predominantly quantitative rather than qualitative. However, our study did point to candidate liver membrane antigens with molecular sizes of 136, 116, 81, and 49 kDa, additional to components previously described by others. The molecular identification of these prominent reactants with AIH-1 sera could prove informative for ascertaining pathogenesis.

  8. Medical and endoscopic therapy of primary sclerosing cholangitis.

    PubMed

    Weismüller, Tobias J; Lankisch, Tim O

    2011-12-01

    Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease mainly affecting young male patients. PSC is characterised by chronic inflammation and fibrotic strictures of the intra- and extrahepatic biliary system, which eventually lead to cholestasis and biliary cirrhosis. However, the clinical course remains very variable. As the aetiology remains unknown, the development of a causative treatment is challenging and today no specific medical therapy is available. Ursodeoxycholic acid has been widely used for the treatment of PSC, but improved only biochemistry and/or symptoms in low- or medium dosages and is probably harmful in higher dosages. Other drugs such as immunosuppressive, antifibrotic or antibiotic agents have not been proven to be effective in large clinical trials. The endoscopic therapy encompasses balloon-dilatation and/or stenting of strictures, relieves clinical symptoms and improves a cholestatic enzyme profile. However, endoscopic therapy is limited to patients in advanced stages of PSC with biliary obstruction.

  9. Regulation of biliary cholesterol secretion in the rat. Role of hepatic cholesterol esterification.

    PubMed Central

    Nervi, F; Bronfman, M; Allalón, W; Depiereux, E; Del Pozo, R

    1984-01-01

    Although the significance of the enterohepatic circulation of bile salts in the solubilization and biliary excretion of cholesterol is well established, little is known about the intrahepatic determinants of biliary cholesterol output. Studies were undertaken to elucidate some of these determinants in the rat. Feeding 1% diosgenin for 1 wk increased biliary cholesterol output and saturation by 400%. Bile flow, biliary bile salt, phospholipid and protein outputs remained in the normal range. When ethynyl estradiol (EE) was injected into these animals, biliary cholesterol output decreased to almost normal levels under circumstances of minor changes in the rates of biliary bile salt and phospholipid outputs. Similarly, when chylomicron cholesterol was intravenously injected into diosgenin-fed animals, biliary cholesterol output significantly decreased as a function of the dose of chylomicron cholesterol administered. Relative rates of hepatic cholesterol synthesis and esterification were measured in isolated hepatocytes. Although hepatic cholesterogenesis increased 300% in diosgenin-fed animals, the contribution of newly synthesized cholesterol to total biliary cholesterol output was only 19 +/- 9%, compared with 12 +/- 6% in control and 15 +/- 5% in diosgenin-fed and EE-injected rats. The rate of oleate incorporation into hepatocytic cholesterol esters was 30% inhibited in diosgenin-fed rats. When EE was injected into these animals, the rate of cholesterol esterification increased to almost 300%. To investigate further the interrelationship between hepatic cholesterol esterification and biliary cholesterol output, we studied 21 diosgenin-fed rats. Six of them received in addition EE and 10 received chylomicron cholesterol. The relationships between biliary cholesterol output as a function of both microsomal acyl-CoA:cholesterol acyltransferase (ACAT) activity and hepatic cholesterol ester concentration were significantly correlated in a reciprocal manner. From these

  10. The origin of biliary ductular cells that appear in the spleen after transplantation of hepatocytes.

    PubMed

    Fukuda, Kenji; Sugihara, Ayako; Nakasho, Keiji; Tsujimura, Tohru; Yamada, Naoko; Okaya, Atsuhito; Sakagami, Masafumi; Terada, Nobuyuki

    2004-01-01

    Transplantation of rat hepatocytes into the syngeneic rat spleen results in the appearance of cytokeration (CK)-19-positive biliary cells that form ductules. The exact origin of CK-19-positive cells is not known and the possibility that they are derived from biliary cells or precursors of oval cells in transplanted hepatocyte preparations has been raised. In the present study, we found that the number of CK-19-positive biliary cells increased rapidly after transplantation of hepatocytes, reached the maximum at 4 weeks, and then gradually decreased. However, a Ki-67 labeling index of CK-19-positive biliary cells was low and showed no significant changes throughout the experimental period. In addition, no or few CK-19-positive cells appeared in the spleen after transplantation of nonparenchymal liver cells enriched with biliary cells. These results showed that biliary cells were not the source of CK-19-positive cells in the spleen. Impairment of precursors of oval cells in the liver by administration of 4,4'-diaminodiphenylmethane 24 h before transplantation of hepatocytes did not prevent the appearance of CK-19-positive biliary cells in the spleen. Moreover, transplantation of nonparenchymal cells carrying an increased number of oval cells by means of treatment with 2-acetylaminofluorene and partial hepatectomy resulted in no appearance of CK-19-positive biliary cells in the spleen. These results ruled out oval cells as the origin of CK-19-positive biliary cells in the spleen. Because CK-19-positive biliary cells appeared in the spleen only when hepatocyte fractions were transplanted, we suggest transdifferentiation of heptocytes may be the mechanism by which CK-19-positive biliary cells are generated.

  11. Sequential algorithm analysis to facilitate selective biliary access for difficult biliary cannulation in ERCP: a prospective clinical study

    PubMed Central

    2014-01-01

    Background Numerous clinical trials to improve the success rate of biliary access in difficult biliary cannulation (DBC) during ERCP have been reported. However, standard guidelines or sequential protocol analysis according to different methods are limited in place. We planned to investigate a sequential protocol to facilitate selective biliary access for DBC during ERCP. Methods This prospective clinical study enrolled 711 patients with naïve papillae at a tertiary referral center. If wire-guided cannulation was deemed to have failed due to the DBC criteria, then according to the cannulation algorithm early precut fistulotomy (EPF; cannulation time > 5 min, papillary contacts > 5 times, or hook-nose-shaped papilla), double-guidewire cannulation (DGC; unintentional pancreatic duct cannulation ≥ 3 times), and precut after placement of a pancreatic stent (PPS; if DGC was difficult or failed) were performed sequentially. The main outcome measurements were the technical success, procedure outcomes, and complications. Results Initially, a total of 140 (19.7%) patients with DBC underwent EPF (n = 71) and DGC (n = 69). Then, in DGC group 36 patients switched to PPS due to difficulty criteria. The successful biliary cannulation rate was 97.1% (136/140; 94.4% [67/71] with EPF, 47.8% [33/69] with DGC, and 100% [36/36] with PPS; P < 0.001). The mean successful cannulation time (standard deviation) was 559.4 (412.8) seconds in EPF, 314.8 (65.2) seconds in DGC, and 706.0 (469.4) seconds in PPS (P < 0.05). The DGC group had a relatively low successful cannulation rate (47.8%) but had a shorter cannulation time compared to the other groups due to early switching to the PPS method in difficult or failed DGC. Post-ERCP pancreatitis developed in 14 (10%) patients (9 mild, 1 moderate), which did not differ significantly among the groups (P = 0.870) or compared with the conventional group (P = 0.125). Conclusions Based on the sequential protocol

  12. Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: a systematic review.

    PubMed

    Fiteni, Frédéric; Nguyen, Thierry; Vernerey, Dewi; Paillard, Marie-Justine; Kim, Stefano; Demarchi, Martin; Fein, Francine; Borg, Christophe; Bonnetain, Franck; Pivot, Xavier

    2014-12-01

    Cisplatin/gemcitabine association has been a standard of care for first-line regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine regimen is frequently preferred. Because comparative effectiveness in clinical outcomes of cisplatin- versus oxaliplatin-containing chemotherapy is not available, a systematic review of studies assessing cisplatin/gemcitabine or oxaliplatin/gemcitabine chemotherapies in advanced biliary tract cancer was performed. Published studies evaluating cisplatin/gemcitabine or oxaliplatin/gemcitabine in advanced biliary tract cancer were included. Each study was weighted according to the number of patients included. The primary objective was to assess weighted median of medians overall survival (mOS) reported for both regimens. Secondary goals were to assess weighted median of medians progression-free survival (mPFS) and toxic effects were pooled and compared within each arm. Thirty-three studies involving 1470 patients were analyzed. In total, 771 and 699 patients were treated by cisplatin/gemcitabine and oxaliplatin/gemcitabine, respectively. Weighted median of mOS was 9.7 months in cisplatin group and 9.5 months in oxaliplatin group. Cisplatin-based chemotherapy was significantly associated with more grade 3 and 4 asthenia, diarrhea, liver toxicity, and hematological toxicity. Sensitivity analysis including only the studies with the standard regimen of cisplatin (25-35 mg/m(2) administered on days 1 and 8) showed that the weighted median of mOS increased from 9.7 to 11.7 months but Gem/CDDP regimen remained more toxic than Gemox regimen. These results suggest that the Gem/CDDP regimen with cisplatin (25-35 mg/m(2)) administered on days 1 and 8 is associated with survival advantage than Gemox regimen but with addition of toxicity.

  13. Activation of the renin-angiotensin system stimulates biliary hyperplasia during cholestasis induced by extrahepatic bile duct ligation.

    PubMed

    Afroze, Syeda H; Munshi, Md Kamruzzaman; Martínez, Allyson K; Uddin, Mohammad; Gergely, Maté; Szynkarski, Claudia; Guerrier, Micheleine; Nizamutdinov, Damir; Dostal, David; Glaser, Shannon

    2015-04-15

    Cholangiocyte proliferation is regulated in a coordinated fashion by many neuroendocrine factors through autocrine and paracrine mechanisms. The renin-angiotensin system (RAS) is known to play a role in the activation of hepatic stellate cells and blocking the RAS attenuates hepatic fibrosis. We investigated the role of the RAS during extrahepatic cholestasis induced by bile duct ligation (BDL). In this study, we used normal and BDL rats that were treated with control, angiotensin II (ANG II), or losartan for 2 wk. In vitro studies were performed in a primary rat cholangiocyte cell line (NRIC). The expression of renin, angiotensin-converting enzyme, angiotensinogen, and angiotensin receptor type 1 was evaluated by immunohistochemistry (IHC), real-time PCR, and FACs and found to be increased in BDL compared with normal rat. The levels of ANG II were evaluated by ELISA and found to be increased in serum and conditioned media of cholangiocytes from BDL compared with normal rats. Treatment with ANG II increased biliary mass and proliferation in both normal and BDL rats. Losartan attenuated BDL-induced biliary proliferation. In vitro, ANG II stimulated NRIC proliferation via increased intracellular cAMP levels and activation of the PKA/ERK/CREB intracellular signaling pathway. ANG II stimulated a significant increase in Sirius red staining and IHC for fibronectin that was blocked by angiotensin receptor blockade. In vitro, ANG II stimulated the gene expression of collagen 1A1, fibronectin 1, and IL-6. These results indicate that cholangiocytes express a local RAS and that ANG II plays an important role in regulating biliary proliferation and fibrosis during extraheptic cholestasis.

  14. [The treatment of external biliary fistulae by means of lavage and continuous aspiration].

    PubMed

    Katergiannakis, V; Manouras, A; Xepapadakis, G; Pierrakakis, S; Papadopoulou, A; Karkanias, G; Apostolidis, N

    1990-10-15

    In 99% of cases external biliary fistulas are caused by liver and biliary tract surgery. The paper describes a new continuous aspiration of the fistula. This method was used to treat 18 patients and full closure of the fistula was achieved in 15 out of 18 patients.

  15. Double Sigmoid colon perforation due to migration of a biliary stent.

    PubMed

    Malgras, B; Pierret, C; Tourtier, J-P; Olagui, G; Nizou, C; Duverger, V

    2011-10-01

    Migration of pancreatico-biliary stents is a rare event, usually benign, but which can lead to severe complications such as digestive tube perforation. We report the case of a patient with double sigmoid perforation due to distal migration of a biliary stent placed to decompress a pancreatic head carcinoma.

  16. Duodenal diversion of percutaneous biliary drain through a percutaneous endoscopic gastrostomy: report of a case.

    PubMed

    Mohandas, K M; Swaroop, V S; Desai, D C; Nagral, A; Jagannath, P; Desouza, L J; Kamble, M

    1991-10-01

    Occasionally, percutaneous biliary drainage is the only possible form of treatment in a patient with a malignant obstruction at the porta hepatis. We report on a case of gallbladder carcinoma with a complete block at the porta hepatis, which was palliated with a percutaneous biliary drain. Enteral reinfusion of bile was accomplished through a duodenal tube placed through a percutaneous endoscopic gastrostomy.

  17. Biomarkers in bile-complementing advanced endoscopic imaging in the diagnosis of indeterminate biliary strictures

    PubMed Central

    Lourdusamy, Vennisvasanth; Tharian, Benjamin; Navaneethan, Udayakumar

    2015-01-01

    Biliary strictures present a diagnostic challenge and a conundrum, particularly when an initial work up including abdominal imaging and endoscopic retrograde cholangiopancreatography based sampling are non-diagnostic. Advances in endoscopic imaging have helped us diagnose these strictures better. However, even with modern technology, some strictures remain a diagnostic challenge. The proximity of bile fluid to the bile duct epithelia makes it an attractive option to investigate for bio-markers, which might be representative of the functions/abnormal changes taking place in the biliary system. A number of biomarkers in bile have been discovered recently in approaching biliary strictures with their potential future diagnostic utility, further supported by the immunohistochemical analysis of the resected tissue specimens. Novel biliary biomarkers especially carcinoembryonic cell adhesion molecule 6 and neutrophil gelatinase-associated lipocalin seem promising in differentiating malignant from benign biliary strictures. Recent developments in lipidomic profiling of bile are also very promising. Biliary biomarkers appear to complement endoscopic imaging in diagnosing malignant etiologies of biliary stricture. Future studies addressing these biomarkers need to be incorporated to the current endoscopic techniques to determine the best approach in determining the etiology of biliary strictures. PMID:25901209

  18. Biliary stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.

    PubMed

    Dumonceau, J-M; Tringali, A; Blero, D; Devière, J; Laugiers, R; Heresbach, D; Costamagna, G

    2012-03-01

    This article is part of a combined publication that expresses the current view of the European Society of Gastrointestinal Endoscopy about endoscopic biliary stenting. The present Clinical Guideline describes short-term and long-term results of biliary stenting depending on indications and stent models; it makes recommendations on when, how, and with which stent to perform biliary drainage in most common clinical settings, including in patients with a potentially resectable malignant biliary obstruction and in those who require palliative drainage of common bile duct or hilar strictures. Treatment of benign conditions (strictures related to chronic pancreatitis, liver transplantation, or cholecystectomy, and leaks and failed biliary stone extraction) and management of complications (including stent revision) are also discussed. A two-page executive summary of evidence statements and recommendations is provided. A separate Technology Review describes the models of biliary stents available and the stenting techniques, including advanced techniques such as insertion of multiple plastic stents, drainage of hilar strictures, retrieval of migrated stents and combined stenting in malignant biliary and duodenal obstructions.The target readership for the Clinical Guideline mostly includes digestive endoscopists, gastroenterologists, oncologists, radiologists, internists, and surgeons while the Technology Review should be most useful to endoscopists who perform biliary drainage.

  19. Interventional Endoscopy Database for Pancreatico-biliary, Gastrointestinal and Esophageal Disorders

    ClinicalTrials.gov

    2015-06-01

    Ampullary Cancer; Duodenal Cancer; Bile Duct Cancer; Bile Duct Disorders; Gallstones; Obstructive Jaundice; Pancreatic Disorders (Noncancerous); Colorectal Cancer; Esophageal Cancer; Barrett's Esophagus; Gastric Malignancies; Pancreatic Cancer; Pediatric Gastroenterology; Cholangiocarcinoma; Pancreatic Pseudocysts; Acute and Chronic Pancreatitis; Recurrent Pancreatitis; Cholangitis; Bile Leak; Biliary Strictures; Pancreatic Divisum; Biliary and Pancreatic Stones; Choledocholithiasis

  20. Prolonged exposure of cholestatic rats to complete dark inhibits biliary hyperplasia and liver fibrosis

    PubMed Central

    Han, Yuyan; Onori, Paolo; Meng, Fanyin; DeMorrow, Sharon; Venter, Julie; Francis, Heather; Franchitto, Antonio; Ray, Debolina; Kennedy, Lindsey; Greene, John; Renzi, Anastasia; Mancinelli, Romina; Gaudio, Eugenio; Glaser, Shannon

    2014-01-01

    Biliary hyperplasia and liver fibrosis are common features in cholestatic liver disease. Melatonin is synthesized by the pineal gland as well as the liver. Melatonin inhibits biliary hyperplasia of bile duct-ligated (BDL) rats. Since melatonin synthesis (by the enzyme serotonin N-acetyltransferase, AANAT) from the pineal gland increases after dark exposure, we hypothesized that biliary hyperplasia and liver fibrosis are diminished by continuous darkness via increased melatonin synthesis from the pineal gland. Normal or BDL rats (immediately after surgery) were housed with light-dark cycles or complete dark for 1 wk before evaluation of 1) the expression of AANAT in the pineal gland and melatonin levels in pineal gland tissue supernatants and serum; 2) biliary proliferation and intrahepatic bile duct mass, liver histology, and serum chemistry; 3) secretin-stimulated ductal secretion (functional index of biliary growth); 4) collagen deposition, liver fibrosis markers in liver sections, total liver, and cholangiocytes; and 5) expression of clock genes in cholangiocytes. In BDL rats exposed to dark there was 1) enhanced AANAT expression/melatonin secretion in pineal gland and melatonin serum levels; 2) improved liver morphology, serum chemistry and decreased biliary proliferation and secretin-stimulated choleresis; and 4) decreased fibrosis and expression of fibrosis markers in liver sections, total liver and cholangiocytes and reduced biliary expression of the clock genes PER1, BMAL1, CLOCK, and Cry1. Thus prolonged dark exposure may be a beneficial noninvasive therapeutic approach for the management of biliary disorders. PMID:25214401

  1. A novel biliary stent coated with silver nanoparticles prolongs the unobstructed period and survival via anti-bacterial activity

    PubMed Central

    Yang, Fuchun; Ren, Zhigang; Chai, Qinming; Cui, Guangying; Jiang, Li; Chen, Hanjian; Feng, Zhiying; Chen, Xinhua; Ji, Jian; Zhou, Lin; Wang, Weilin; Zheng, Shusen

    2016-01-01

    Symptomatic biliary stricture causes life-threatening complications, such as jaundice, recurrent cholangitis and secondary biliary cirrhosis. Fully covered self-expanding metal stents (FCSEMSs) are gaining acceptance for treatments of benign biliary stricture and palliative management of malignant biliary obstructions. However, the high rate of FCSEMS obstruction limits their clinic use. In this study, we developed a novel biliary stent coated with silver nanoparticles (AgNPs) and investigated its efficacy both in vitro and in vivo. We first identified properties of the AgNP complex using ultraviolet detection. The AgNP complex was stable without AgNP agglomeration, and Ag abundance was correspondingly increased with an increased bilayer number. The AgNP biliary stent demonstrated good performance in the spin-assembly method based on topographic observation. The AgNP biliary stent also exhibited a long-term anti-coagulation effect and a slow process of Ag+ release. In vitro anti-bacteria experiments indicated that the AgNP biliary stent exhibited high-efficiency anti-bacterial activity for both short- and long-term periods. Importantly, application of the AgNP biliary stent significantly prolonged the unobstructed period of the biliary system and improved survival in preclinical studies as a result of its anti-microbial activity and decreased granular tissue formation on the surface of the anastomotic biliary, providing a novel and effective treatment strategy for symptomatic biliary strictures. PMID:26883081

  2. Efficacy of Covered Metallic Stents in the Treatment of Unresectable Malignant Biliary Obstruction

    SciTech Connect

    Miyayama, Shiro Matsui, Osamu; Akakura, Yukari; Yamamoto, Toru; Nishida, Hiroto; Yoneda, Kenji; Kawai, Keiichi; Toya, Daisyu; Tanaka, Nobuyoshi; Mitsui, Takeshi; Asada, Yasuyuki

    2004-08-15

    We evaluated the efficacy of covered stents for malignant biliary obstruction. We studied 62 patients with obstruction distal to the hilar confluence who survived longer than 10 weeks and divided them into a covered stent group (group 1, n = 22), a Z stent group (group 2, n = 19), and a mesh stent group (group 3, n = 21), according to their type of the stent. Patency rates of each group were compared. Early stent revision was required after 3 days in 18% (4/22) of group 1, 26% (5/19) of group 2, and 0% (0/21) of group 3. The 10, 20, and 40-week primary patency rates were 77%, 77%, and 59% (group 1), 42%, 25%, and 8% (group 2), and 76%, 71%, and 55% (group 3), respectively. Primary patency rates of groups 1 and 3 were significantly higher than those of group 2 (p < 0.05), and there was no statistically difference between those of group 1 and group 3. The 10, 20, and 40-week assisted primary (secondary) patency rates were 96%, 96%, and 96% (group 1), 68%, 49%, and 39% (group 2), and 86%, 74%, and 58% (group 3), respectively. Assisted primary patency (secondary) rates of group 1 were significantly higher than those of groups 2 and 3 (p < 0.01 and p < 0.05, respectively). Our study suggests that the primary patency rates of the covered stents are equal to those of mesh stents, but these may be improved further if covered stents, which avoid the need for early revision, are used.

  3. Role of endoscopy in the conservative management of biliary complications after deceased donor liver transplantation

    PubMed Central

    Lisotti, Andrea; Fusaroli, Pietro; Caletti, Giancarlo

    2015-01-01

    The clinical outcome of patients receiving liver transplantation could be significantly affected by biliary complications, including strictures, leaks, stones and bilomas; early diagnosis and treatment of these conditions lead to markedly reduction in morbidity and mortality. Therapeutic gold standard is represented by conservative approaches, both endoscopic and percutaneous, based on the type of biliary reconstruction, the local availability of the procedures and specific expertise. In patients with previous transplantation, the difficult biliary access and the possible presence of concomitant complications (mainly strictures) further restrict the efficacy of the endoscopic and percutaneous treatments; on the other hand, surgery should generally be avoided because of the even increased morbidity and mortality due to technical and clinical issues. Here we review the most common biliary complications occurring after liver transplantation and discuss available treatment options including future perspectives such as endoscopic ultrasound-guided biliary access in patients with Roux-en-Y choledocho-jejunostomy or extracorporeal shock wave lithotripsy for difficult stones. PMID:26730271

  4. Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling.

    PubMed

    Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru

    2016-01-01

    Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity. PMID:27431614

  5. Decreased gallbladder emptying in dogs with biliary sludge or gallbladder mucocele.

    PubMed

    Tsukagoshi, Taro; Ohno, Koichi; Tsukamoto, Atsushi; Fukushima, Kenjiro; Takahashi, Masashi; Nakashima, Ko; Fujino, Yasuhito; Tsujimoto, Hajime

    2012-01-01

    Biliary sludge in dogs is dismissed commonly as an incidental finding. On the other hand, gallbladder mucocele is reported increasingly in dogs and can lead to biliary obstruction or gallbladder rupture. Cholestasis is suspected to play a role in development of sludge and mucoceles, though there are no data in dogs to support this. We investigated gallbladder emptying, a key factor in biliary flow, in dogs with mobile sludge, immobile sludge, or gallbladder mucocele and in healthy controls. Gallbladder ejection fraction estimated by ultrasonography was used as the index of gallbladder emptying. The ejection fraction at 60 min after eating was significantly decreased in all three abnormal groups. Moreover, all dogs with sludge or a mucocele had gallbladder distension. These changes were the greatest in the mucocele group. Thus, biliary stasis occurs not only in dogs with gallbladder mucocele but also in dogs with biliary sludge. Cholestasis may play a role in the pathogenesis or progression of these diseases in dogs.

  6. Effect of diethyl ether on the biliary excretion of acetaminophen.

    PubMed

    Watkins, J B; Siegers, C P; Klaassen, C D

    1984-10-01

    The biliary and renal excretion of acetaminophen and its metabolites over 8 hr was determined in rats exposed to diethyl ether by inhalation for 1 hr. Additional rats were anesthetized with urethane (1 g/kg ip) while control animals were conscious throughout the experiment (surgery was performed under hexobarbital narcosis: 150 mg/kg ip; 30-min duration). The concentration of UDP-glucuronic acid was decreased 80% in livers from ether-anesthetized rats but was not reduced in urethane-treated animals when compared to that in control rats. The concentration of reduced glutathione was not affected by either urethane or diethyl ether. Basal bile flow was not altered by the anesthetic agents. Bile flow rate after acetaminophen injection (100 mg/kg iv) was increased slightly over basal levels for 2 hr in hexobarbital-treated control rats, was unaltered in urethane-anesthetized animals, and was decreased throughout the 8-hr experiment in rats exposed to diethyl ether for 1 hr. In control and urethane-anesthetized animals, approximately 30-35% of the total acetaminophen dose (100 mg/kg iv) was excreted into bile in 8 hr, while only 16% was excreted in rats anesthetized with diethyl ether. Urinary elimination (60-70% of the dose) was not altered by exposure to ether. Separation of metabolites by reverse-phase high-pressure liquid chromatography showed that ether decreased the biliary elimination of unchanged acetaminophen and its glucuronide, sulfate, and glutathione conjugates by 47, 40, 49, and 73%, respectively, as compared to control rats. Excretion of unchanged acetaminophen and the glutathione conjugate into bile was depressed in urethane-anesthetized animals by 45 and 66%, respectively, whereas elimination of the glucuronide and sulfate conjugates was increased by 27 and 50%, respectively. These results indicate that biliary excretion is influenced by the anesthetic agent and that diethyl ether depresses conjugation with sulfate and glutathione as well as glucuronic

  7. Management of biliary tract stones in heart transplant patients.

    PubMed Central

    Milas, M; Ricketts, R R; Amerson, J R; Kanter, K

    1996-01-01

    OBJECTIVE: The authors report their experience with biliary tract stones in adult and pediatric heart transplant patients, and review the current literature relative to this problem. SUMMARY BACKGROUND DATA: Prior studies in adults have noted that heart transplant patients frequently have cholelithiasis, but offer no consensus about treatment strategy. Few studies exist for pediatric heart transplant patients. A higher rate of hemolysis and cyclosporine-induced changes in bile metabolism may contribute to lithogenesis in this population. METHODS: A chart review was conducted for 211 patients who had heart transplants between January 1988 and September 1994 to determine prevalence of biliary tract stones, management strategies used, and outcome. RESULTS: Of 175 long-term heart transplant survivors, 52 (29.7%) had stones detected: 32.8% of adults (47/143) and 15.6% of children (5/32). The majority of patients (31) were diagnosed 4 months (mean) after transplantation; cholelithiasis developed in 10 of these patients (32%) within 11 months (median) after a negative ultrasound. Symptoms developed in 45% of patients. All patients underwent either elective (36) or urgent (6) cholecystectomy via an open (32) or laparoscopic (10) approach, or endoscopy for common bile duct stones (2). There were no deaths or complications during a follow-up period of up to 7 years. CONCLUSION: Heart transplant patients have a high prevalence of symptomatic biliary tract stone disease. They can be treated safely via an open or laparoscopic approach after transplantation. The authors recommend routine gallbladder ultrasound screening and elective cholecystectomy in the post-transplant period if stones are detected. Images Figure 4. PMID:8645048

  8. Unusual biliary myoepithelial carcinoma in liver-case report and immunohistochemical study

    PubMed Central

    Hassan, Wael; Nishi, Junko; Tomiyasu, Shinjiro; Urakado, Tadahito; Haraoka, Katsuki; Yamanaka, Tuyoshi; Fujiyama, Shigetoshi; Ito, Takaaki

    2014-01-01

    Myoepithelial carcinoma is a well-known tumor of salivary gland, representing 1% of all salivary gland tumors. They have also been reported in other sites as skin/soft tissue, breast and lung. This paper reports a rare case of primary myoepithelial carcinoma in the liver, as well as discusses the findings of immunohistochemistry. The clinical manifestations, imaging characteristics, and histopathological changes of myoepithelial carcinoma in this case were described. The patient was a 33 years old female presented with a cystic tumor in the right lobe of the liver. As the liver tumor increased in size within six months, malignant neoplasm was suspected and thus anterior hepatic segmentectomy was performed. The mass composed of glandular-like structures and trabecular sheets of spindled shaped cells and epithelioid cells which were positive for myoepithelial markers. The tumor recurred within one year, in the left lobe of the liver and partial left lobe lobectomy was performed. The tumor resected showed similar histology to the primary tumor. Three months later, another recurrence was noted for which radiofrequency ablation was performed. This report presents a recurrent case of myoepithelial carcinoma in the liver and suggests the possibility of biliary origin of such tumor. PMID:24966980

  9. Aetiology of biliary atresia: what is actually known?

    PubMed Central

    2013-01-01

    Biliary atresia (BA) is a rare disease of unknown etiology and unpredictable outcome, even when there has been timely diagnosis and exemplary surgery. It has been the commonest indication for liver transplantation during childhood for the past 20 years. Hence much clinical and basic research has been directed at elucidating the origin and pathology of BA. This review summarizes the current clinical variations of BA in humans, its occasional appearance in animals and its various manifestations in the laboratory as an experimental model. PMID:23987231

  10. [RENTGENOENDOSCOPIC INTERVENTIONS FOR BILIARY OBSTRUCTION OF NON-TUMOR GENESIS].

    PubMed

    Nastashenko, L

    2015-06-01

    We analyzed the immediate and long-term results of endoscopic diagnostic and therapeutic interventions in patients on the non-tumor obstruction of the bile ducts. Application of the developed diagnostic algorithm using ultrasound, fistulocholangiography, computer and magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, diagnostic endoscopic papillosphincterotomy, instrumental revision of bile ducts, transduodenal holedohoscopy provided sensitive diagnostic reasons of non-tumor biliary obstruction to (94.2 +/- 1.7)%. Optimization of treatment strategy developed with the introduction of the clinic endobiliary endoscopic intervention has achieved positive results in 83.7% of patients, reducing the morbidity of 1.7%, mortality--0.9%.

  11. Autoimmune Pancreatitis Presenting with Mass and Biliary Obstruction.

    PubMed

    Frank, Amber A; Morse, Michael D; Smith, Benjamin R; Shaffer, Kitt

    2008-01-01

    We report a case of autoimmune pancreatitis in a 31-year-old man with signs and symptoms of biliary tract obstruction. Evaluation with sonography, computed tomography, and ultimately endoscopic retrograde cholangiopancreatography, demonstrated a 5 by 2 cm hypoechoic, hypodense mass near the head of the pancreas that extended into the porta hepatis. Common bile duct obstruction with proximal dilatation was present. Following fine needle aspiration of the mass, cytology showed findings consistent with autoimmune pancreatitis. Treatment with common bile duct stent was followed by resolution of the patient's symptoms.

  12. Endoscopic management of biliary leaks after laparoscopic cholecystectomy.

    PubMed

    Rustagi, Tarun; Aslanian, Harry R

    2014-09-01

    Laparoscopic cholecystectomy has become the procedure of choice for management of symptomatic cholelithiasis. Although it has distinct advantages over open cholecystectomy, bile leak is more common. Endoscopic retrograde cholangiopancreatography is the diagnostic and therapeutic modality of choice for management of postcholecystectomy bile leaks and has a high success rate with the placement of plastic biliary stents. Repeat endoscopic retrograde cholangiopancreatography with placement of multiple plastic stents, a covered metal stent, or possibly cyanoacrylate therapy may be effective in refractory cases. This review will discuss the indications, efficacy, and complications of endoscopic therapy.

  13. Impacted and Fractured Biliary Basket: A Second Basket Rescue Technique.

    PubMed

    Benatta, Mohammed Amine; Desjeux, Ariane; Barthet, Marc; Grimaud, Jean Charles; Gasmi, Mohamed

    2016-01-01

    A 59-year-old woman was treated with ERCP, ES, and biliary plastic stent, for large and multiple common bile duct stones. During a second ERCP basket extraction was impacted with a round entrapped stone. The basket handle was cut off; a metal sheath of extraendoscopic lithotriptor was advanced over the basket. The mechanical lithotripsy was complicated with basket traction wires fracturing, without breakage of the stone. A rescue standard basket was pushed until it caught the basket/stone complex. Using this method disengagement of the whole fractured basket/stone complex was achieved without need of surgery. It is the third case reported in the English literature. PMID:27293442

  14. Current diagnosis and treatment of benign biliary strictures after living donor liver transplantation

    PubMed Central

    Chang, Jae Hyuck; Lee, Inseok; Choi, Myung-Gyu; Han, Sok Won

    2016-01-01

    Despite advances in surgical techniques, benign biliary strictures after living donor liver transplantation (LDLT) remain a significant biliary complication and play an important role in graft and patient survival. Benign biliary strictures after transplantation are classified into anastomotic or non-anastomotic strictures. These two types differ in presentation, outcome, and response to therapy. The leading causes of biliary strictures include impaired blood supply, technical errors during surgery, and biliary anomalies. Because patients usually have non-specific symptoms, a high index of suspicion should be maintained. Magnetic resonance cholangiography has gained widespread acceptance as a reliable noninvasive tool for detecting biliary complications. Endoscopy has played an increasingly prominent role in the diagnosis and treatment of biliary strictures after LDLT. Endoscopic management in LDLT recipients may be more challenging than in deceased donor liver transplantation patients because of the complex nature of the duct-to-duct reconstruction. Repeated aggressive endoscopic treatment with dilation and the placement of multiple plastic stents is considered the first-line treatment for biliary strictures. Percutaneous and surgical treatments are now reserved for patients for whom endoscopic management fails and for those with multiple, inaccessible intrahepatic strictures or Roux-en-Y anastomoses. Recent advances in enteroscopy enable treatment, even in these latter cases. Direct cholangioscopy, another advanced form of endoscopy, allows direct visualization of the inner wall of the biliary tree and is expected to facilitate stenting or stone extraction. Rendezvous techniques can be a good option when the endoscopic approach to the biliary stricture is unfeasible. These developments have resulted in almost all patients being managed by the endoscopic approach. PMID:26819525

  15. Long-term effects of forgotten biliary stents: a case series and literature review

    PubMed Central

    Odabasi, Mehmet; Arslan, Cem; Akbulut, Sami; Abuoglu, Haci Hasan; Ozkan, Erkan; Yildiz, Mehmet Kamil; Eris, Cengiz; Gunay, Emre; Tekesin, Kemal; Muftuoglu, Tolga

    2014-01-01

    There are many studies about the biliary stents, however there is a little information about the long-term stayed forgotten biliary stents except a few case reports. We have reported the results of a number of cases with biliary stents that were forgotten or omitted by the patient and the endoscopist. During February 2010 to May 2013, five patients were referred to the general surgery clinic of Haydarpasa Numune Training and Research Hospital, Istanbul Turkey. Past history and medical documents submitted by the patient did not indicate a replacement of the biliary stent in 3 patients. Two patients knew that they had biliary stents. We also conducted a literature review via the PubMed and Google Scholar databases of English language studies published until March 2014 on forgotten biliary stent. There were 3 men and 2 women ranging in age from 22 to 68 years (mean age 41.6 years). Patients presented with pain in the upper abdomen, jaundice, fever, abnormal liver function tests or dilatation of the biliary tract alone or in combination. Patients’ demographic findings are presented in Table 1. A review of three cases reported in the English medical literature also discussed. The mean duration of the patency of the stent is about 12 months. The biliary stenting is performed either with plastic or metal stents, studies recommending their replacement after 3-6 months. Patients with long stayed forgotten biliary stents are inevitably treated with surgical intervention. We recommend for all endoscopic retrograde cholangiopancreatography units provide a stent registry system that the stents placed for various therapeutic procedures are not forgotten both by the patient as well as the physician. There should be a deadline for biliary stents in the registry system for each patient. PMID:25232385

  16. Isolation and purification of human biliary vesicles with potent cholesterol-nucleation-promoting activity.

    PubMed

    Miquel, J F; Rigotti, A; Rojas, E; Brandan, E; Nervi, F

    1992-02-01

    1. Cholesterol nucleation is a critical step in the formation of cholesterol gallstones. This nucleation takes place after aggregation and fusion of cholesterol-rich biliary vesicles, a process probably modulated by biliary proteins. The present study was conducted to identify specific proteins associated with native cholesterol-rich biliary vesicles and to explore their effect on the cholesterol-nucleation time of supersaturated artificial bile. 2. Hepatic bile was obtained from six patients with cholesterol gallstone disease. Biliary vesicles were isolated by ultracentrifugation and were purified by gel filtration chromatography. A small amount of protein (less than 1% by weight) remained associated with the purified cholesterol-rich biliary vesicles. The electrophoretic profile of these proteins was remarkably similar in all six patients, showing the presence of at least six polypeptides (of molecular mass from 52 to 200 kDa), five of them having carbohydrate residues (except the 52 kDa one). The effect of reconstituted biliary vesicle solutions, containing their specific vesicular proteins, on cholesterol-nucleation time was studied by mixing the vesicle solution with artificial supersaturated bile. A potent cholesterol-pronucleating activity, reflected in a 20-70% reduction in nucleation time, was present in the biliary vesicle solutions compared with control solutions having a similar lipid composition. The pronucleating activity disappeared on heating and was not detected in the micellar fraction containing the major proportion of biliary proteins. 3. These results indicate that cholesterol-rich biliary vesicles containing a unique and defined glycoprotein profile can be isolated and purified from human hepatic bile. The potent cholesterol-pronucleating activity of the biliary vesicles from patients with gallstones was unrelated to their lipid composition or cholesterol content.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Current diagnosis and treatment of benign biliary strictures after living donor liver transplantation.

    PubMed

    Chang, Jae Hyuck; Lee, Inseok; Choi, Myung-Gyu; Han, Sok Won

    2016-01-28

    Despite advances in surgical techniques, benign biliary strictures after living donor liver transplantation (LDLT) remain a significant biliary complication and play an important role in graft and patient survival. Benign biliary strictures after transplantation are classified into anastomotic or non-anastomotic strictures. These two types differ in presentation, outcome, and response to therapy. The leading causes of biliary strictures include impaired blood supply, technical errors during surgery, and biliary anomalies. Because patients usually have non-specific symptoms, a high index of suspicion should be maintained. Magnetic resonance cholangiography has gained widespread acceptance as a reliable noninvasive tool for detecting biliary complications. Endoscopy has played an increasingly prominent role in the diagnosis and treatment of biliary strictures after LDLT. Endoscopic management in LDLT recipients may be more challenging than in deceased donor liver transplantation patients because of the complex nature of the duct-to-duct reconstruction. Repeated aggressive endoscopic treatment with dilation and the placement of multiple plastic stents is considered the first-line treatment for biliary strictures. Percutaneous and surgical treatments are now reserved for patients for whom endoscopic management fails and for those with multiple, inaccessible intrahepatic strictures or Roux-en-Y anastomoses. Recent advances in enteroscopy enable treatment, even in these latter cases. Direct cholangioscopy, another advanced form of endoscopy, allows direct visualization of the inner wall of the biliary tree and is expected to facilitate stenting or stone extraction. Rendezvous techniques can be a good option when the endoscopic approach to the biliary stricture is unfeasible. These developments have resulted in almost all patients being managed by the endoscopic approach. PMID:26819525

  18. A case of biliary stones and anastomotic biliary stricture after liver transplant treated with the rendez - vous technique and electrokinetic lithotritor

    PubMed Central

    Pisa, Marta Di; Traina, Mario; Miraglia, Roberto; Maruzzelli, Luigi; Volpes, Riccardo; Piazza, Salvatore; Luca, Angelo; Gridelli, Bruno

    2008-01-01

    The paper studies the combined radiologic and endoscopic approach (rendez vous technique) to the treatment of the biliary complications following liver transplant. The “rendez-vous” technique was used with an electrokinetic lithotripter, in the treatment of a biliary anastomotic stricture with multiple biliary stones in a patient who underwent orthotopic liver transplant. In this patient, endoscopic or percutaneous transhepatic management of the biliary complication failed. The combined approach, percutaneous transhepatic and endoscopic treatment (rendez-vous technique) with the use of an electrokinetic lithotritor, was used to solve the biliary stenosis and to remove the stones. Technical success, defined as disappearance of the biliary stenosis and stone removal, was obtained in just one session, which definitively solved the complications. The combined approach of percutaneous transhepatic and endoscopic (rendez-vous technique) treatment, in association with an electrokinetic lithotritor, is a safe and feasible alternative treatment, especially after the failure of endoscopic and/or percutaneous trans-hepatic isolated procedures. PMID:18473423

  19. Cirrhosis and autoimmune liver disease: Current understanding

    PubMed Central

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  20. Interleukin-32 production associated with biliary innate immunity and proinflammatory cytokines contributes to the pathogenesis of cholangitis in biliary atresia

    PubMed Central

    Okamura, A; Harada, K; Nio, M; Nakanuma, Y

    2013-01-01

    Biliary atresia (BA) is thought to be associated with infections by viruses such as Reoviridae and is characterized histologically by fibrosclerosing cholangitis with proinflammatory cytokine-mediated inflammation. Interleukin (IL)-32 affects the continuous inflammation by increasing the production of proinflammatory cytokines. In this study, the role of IL-32 in the cholangitis of BA was examined. Immunohistochemistry for IL-32 and caspase 1 was performed using 21 samples of extrahepatic bile ducts resected from BA patients. Moreover, using cultured human biliary epithelial cells (BECs), the expression of IL-32 and its induction on stimulation with a Toll-like receptor [(TLR)-3 ligand (poly(I:C)] and proinflammatory cytokines was examined. BECs composing extrahepatic bile ducts showing cholangitis expressed IL-32 in BA, but not in controls. Caspase 1 was expressed constantly on BECs of both BA and control subjects. Furthermore, poly(I:C) and proinflammatory cytokines [(IL-1β, interferon (IFN)-γ and tumour necrosis factor (TNF)-α] induced IL-32 expression strongly in cultured BECs, accompanying the constant expression of TLR-3 and caspase 1. Our results imply that the expression of IL-32 in BECs was found in the damaged bile ducts of BA and induced by biliary innate immunity via TLR-3 and proinflammatory cytokines. These findings suggest that IL-32 is involved initially in the pathogenic mechanisms of cholangitis in BA and also plays an important role in the amplification and continuance of periductal inflammatory reactions. It is therefore tempting to speculate that inhibitors of IL-32 could be useful for attenuating cholangitis in BA. PMID:23607494

  1. Serial insertion of bilateral uncovered metal stents for malignant hilar obstruction using an 8 Fr biliary system: a case series of 17 consecutive patients

    PubMed Central

    Thosani, Amar; Grunwald, Matthew; Nagula, Satish; Bucobo, Juan Carlos; Buscaglia, Jonathan M.

    2015-01-01

    Controversy exists over the need for unilateral versus bilateral stent placement in patients with malignant obstruction at the biliary hilum. Placement of bilateral uncovered self-expanding metal stent (UCSEMS) at this location is technically challenging, and generally associated with lower rates of procedural success. Serial insertion of side-by-side UCSEMS may be especially difficult when simultaneous deployment is not possible using larger stent delivery catheters. In this single-center, retrospective case series of all patients who underwent bilateral placement of uncovered WallflexTM biliary stents between July 2008 and July 2014, we evaluate the feasibility, technical success, and safety of patients undergoing serial insertion of bilateral UCSEMS using the 8 Fr WallflexTM biliary system for malignant hilar obstruction. A total of 17 patients were included. Primary cholangiocarcinoma, Bismuth IV, was the most common diagnosis. Mean procedure time was 54.4 minutes. Overall procedural technical success was achieved in 17/17 patients. Stricture dilation was necessary prior to WallflexTM insertion in 8/17 patients (47.1%). Transpapillary extension of two stents was performed in all patients. There were no cases of stent deployment malfunction, or inability to insert or deploy the 2nd stent. Nine of 17 patients (52.9%) required inpatient hospitalization following ERCP; the most common indications were abdominal pain and need for IV antibiotics. There was one case of ERCP-related cholangitis otherwise; there were no other major complications. Bilateral, serial insertion of UCSEMS using the 8 Fr WallflexTM biliary system in malignant hilar obstruction is feasible with an excellent technical success profile. Using this device for side-by-side deployment of UCSEMS appears to be safe in the majority of patients. PMID:26605283

  2. Increased MMP-7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia.

    PubMed

    Kerola, Anna; Lampela, Hanna; Lohi, Jouko; Heikkilä, Päivi; Mutanen, Annika; Hagström, Jaana; Tervahartiala, Taina; Sorsa, Timo; Haglund, Caj; Jalanko, Hannu; Pakarinen, Mikko P

    2016-07-01

    The molecular mechanisms underlying progressive liver fibrosis following surgical treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic gene and protein expression and serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after successful portoenterostomy (PE), and relate them to histological signs of liver injury, clinical follow-up data and biochemical markers of hepatic function. LIver biopsies and serum samples were obtained from 25 children after successful PE at median age of 3.3 years. Serum MMP concentrations were determined by enzyme-linked immune sorbent assay. Hepatic gene expression of MMPs and TIMPs was analyzed using real-time reverse-transcription PCR. Liver expression of MMP-7 and cytokeratin-7 was studied using immunohistochemistry. Despite effective clearance of biochemical and histological cholestasis following PE, BA patients showed increased hepatic gene expression of MMP-7 (29-fold, p < 0.001), MMP-2 (3.1-fold, p < 0.001), MMP-14 (1.7-fold, p = 0.007), and TIMP-1 (1.8-fold, p < 0.001), when compared to controls. Similar to a biliary epithelial marker cytokeratin-7, expression of MMP-7 localized in biliary epithelium of bile ducts and ductal proliferations and periportal hepatocytes and was increased (p < 0.001) in relation to controls. BA patients had 6-fold higher serum levels of MMP-7 (p < 0.001), which correlated positively with hepatic MMP-7 gene (r = 0.548, p = 0.007) and protein (r = 0.532, p = 0.007) expression. Patients showed a positive correlation between biliary MMP-7 expression and Metavir fibrosis stage (r = 0.605, p = 0.001) and portal fibrosis grade (r = 0.606, p = 0.001). Neither similarly increased MMP-7 expression nor correlation with liver fibrosis was observed in patients with intestinal failure-associated liver disease and comparable Metavir stage. In conclusion, our findings support an unique role of altered

  3. Pathophysiologic effects of biliary shockwave lithotripsy in a canine model.

    PubMed

    Chapman, W C; Parish, K L; Kaufman, A J; Stephens, W H; Anderson, S; Woodward, S; Williams, L F

    1991-01-01

    At least 10 extracorporeal shockwave lithotripters are under investigation in the United States for treatment of biliary stone disease. Few reports, however, have documented the potential side effects of this new treatment method. In this study, we performed a series of acute and chronic studies in dogs exposed to varying numbers of shockwaves directed at the gallbladder wall via a transthoracic or transabdominal targeting approach. When shockwaves were directed transthoracically, pulmonary hemorrhagic contusions were found which were sometimes large in size. When a transabdominal approach was used, however, only focal areas of hemorrhage were found in the gallbladder wall and adjacent liver with no alterations in postlithotripsy pancreatic or liver enzymes, and normal cholecystokinin-octapeptide stimulated oral cholecystograms were obtained 6 days after treatment. Biliary shockwaves appear to cause few side effects under normal conditions but should be used with caution in patients with potential bleeding disorders. Until further studies are performed, lung tissue should be avoided in the shockwave beam path during treatment. PMID:1796795

  4. The Sea Lamprey as an Etiological Model for Biliary Atresia

    PubMed Central

    Chung-Davidson, Yu-Wen; Yeh, Chu-Yin; Li, Weiming

    2015-01-01

    Biliary atresia (BA) is a progressive, inflammatory, and fibrosclerosing cholangiopathy in infants that results in obstruction of both extrahepatic and intrahepatic bile ducts. It is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult with steatohepatitis and fibrosis in the liver. In this paper, we present new histological evidence and compare the sea lamprey to existing animal models to highlight the advantages and possible limitations of using the sea lamprey to study the etiology and compensatory mechanisms of BA and other liver diseases. Understanding the signaling factors and genetic networks underlying lamprey BA can provide insights into BA etiology and possible targets to prevent biliary degeneration and to clear fibrosis. In addition, information from lamprey BA can be used to develop adjunct treatments for patients awaiting or receiving surgical treatments. Furthermore, the cholestatic adult lamprey has unique adaptive mechanisms that can be used to explore potential treatments for cholestasis and nonalcoholic steatohepatitis (NASH). PMID:26101777

  5. Single-incision laparoscopic surgery for biliary tract disease

    PubMed Central

    Chuang, Shu-Hung; Lin, Chih-Sheng

    2016-01-01

    Single-incision laparoscopic surgery (SILS), or laparoendoscopic single-site surgery, has been employed in various fields to minimize traumatic effects over the last two decades. Single-incision laparoscopic cholecystectomy (SILC) has been the most frequently studied SILS to date. Hundreds of studies on SILC have failed to present conclusive results. Most randomized controlled trials (RCTs) have been small in scale and have been conducted under ideal operative conditions. The role of SILC in complicated scenarios remains uncertain. As common bile duct exploration (CBDE) methods have been used for more than one hundred years, laparoscopic CBDE (LCBDE) has emerged as an effective, demanding, and infrequent technique employed during the laparoscopic era. Likewise, laparoscopic biliary-enteric anastomosis is difficult to carry out, with only a few studies have been published on the approach. The application of SILS to CBDE and biliary-enteric anastomosis is extremely rare, and such innovative procedures are only carried out by a number of specialized groups across the globe. Herein we present a thorough and detailed analysis of SILC in terms of operative techniques, training and learning curves, safety and efficacy levels, recovery trends, and costs by reviewing RCTs conducted over the past three years and two recently updated meta-analyses. All existing literature on single-incision LCBDE and single-incision laparoscopic hepaticojejunostomy has been reviewed to describe these two demanding techniques. PMID:26811621

  6. A simple method for the quantification of biliary reflux.

    PubMed

    Nicolai, J J; Silberbusch, J; van Roon, F; Schopman, W; vd Berg, J W

    1980-01-01

    99mTc-diethyl-IDA is completely excreted into the bile. When cholecystokinin is given after priming of the biliary tract with this tracer, gallbladder contraction leads to expulsion of bile into the duodenum. At the same time cholecystokinin causes contraction of the pylorus, which should normally prevent substantial reflux of tracer into the stomach. We have applied these physiological characteristics in a method to quantify biliary gastric reflux. Fourteen controls had a median reflux of 4.3% of the intravenous dose (93% of controls had values less than 9%). In 18 patients with Billroth II gastrectomies the median reflux was 46% (p less than 0.001). Patients with chronic gastritis (no. = 18) had also increased reflux (median 18.1%, p less than 0.001). The same was found in gastric ulcer (no. = 18, median 11.8%, p less than 0.003). In duodenal ulcer (no. = 7) increased reflux existed in only two patients with pyloric deformation. Patients with hiatal hernia did not show increased reflux (no. = 10, median 2.2%). Bilirubin measurements tended to underestimate reflux in pathological cases, whereas bile acid measurements and reflux percentages of tracer showed a close relationship (r = 0.87, p less than 0.001). PMID:7209386

  7. Circulating MicroRNAs as Biomarkers in Biliary Tract Cancers

    PubMed Central

    Letelier, Pablo; Riquelme, Ismael; Hernández, Alfonso H.; Guzmán, Neftalí; Farías, Jorge G.; Roa, Juan Carlos

    2016-01-01

    Biliary tract cancers (BTCs) are a group of highly aggressive malignant tumors with a poor prognosis. The current diagnosis is based mainly on imaging and intraoperative exploration due to brush cytology havinga low sensitivity and the standard markers, such as carcinoembryonic antigen (CEA) and carbohydrate 19-9 (CA19-9), not having enough sensitivity nor specificity to be used in a differential diagnosis and early stage detection. Thus, better non-invasive methods that can distinguish between normal and pathological tissue are needed. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules of ~20–22 nucleotides that regulate relevant physiological mechanisms and can also be involved in carcinogenesis. Recent studies have demonstrated that miRNAs are detectable in multiple body fluids, showing great stability, either free or trapped in circulating microvesicles, such as exosomes. miRNAs are ideal biomarkers that may be used in screening and prognosis in biliary tract cancers, aiding also in the clinical decisions at different stages of cancer treatment. This review highlights the progress in the analysis of circulating miRNAs in serum, plasma and bile as potential diagnostic and prognostic markers of BTCs. PMID:27223281

  8. Pathophysiologic effects of biliary shockwave lithotripsy in a canine model.

    PubMed

    Chapman, W C; Parish, K L; Kaufman, A J; Stephens, W H; Anderson, S; Woodward, S; Williams, L F

    1991-01-01

    At least 10 extracorporeal shockwave lithotripters are under investigation in the United States for treatment of biliary stone disease. Few reports, however, have documented the potential side effects of this new treatment method. In this study, we performed a series of acute and chronic studies in dogs exposed to varying numbers of shockwaves directed at the gallbladder wall via a transthoracic or transabdominal targeting approach. When shockwaves were directed transthoracically, pulmonary hemorrhagic contusions were found which were sometimes large in size. When a transabdominal approach was used, however, only focal areas of hemorrhage were found in the gallbladder wall and adjacent liver with no alterations in postlithotripsy pancreatic or liver enzymes, and normal cholecystokinin-octapeptide stimulated oral cholecystograms were obtained 6 days after treatment. Biliary shockwaves appear to cause few side effects under normal conditions but should be used with caution in patients with potential bleeding disorders. Until further studies are performed, lung tissue should be avoided in the shockwave beam path during treatment.

  9. [Morphological study of bile in the diagnosis of biliary diseases].

    PubMed

    Potekhina, Iu P

    2003-01-01

    The purpose of this work was to study principles of bile structurization in healthy people and patients with various biliary diseases. 160 patients with different biliary diseases and other diseases of the hepatopancreaticoduodenal zone were examined. Samples of gallbladder bile were taken from corpses of young men, who did not have any diseases of the hepatopancreaticoduodenal zone. Their diagnoses were confirmed by an ultrasound morphological study. Bile was studied by the cuneate dehydration and viscosimetric methods. The structure of facies of gallbladder bile under conditions of absence of diseases of the hepatopancreaticoduodenal zone was shown. The facies have a wide convex peripheral zone (a cushion) without any well-defined border. The central part of the facies is amorphous or fine-grained, sometimes with occasional inclusions of larger crystals. Markers of exacerbation of chronic cholecystitis (dendrites in the central zone of bile facies) as well as signs of the presence of a malignant neoplasm touching the bile (large diamond-shaped crystals in the central zone of bile facies where dendrites begin) were discovered. PMID:14556555

  10. Percutaneous Management of Biliary Strictures After Pediatric Liver Transplantation

    SciTech Connect

    Miraglia, Roberto Maruzzelli, Luigi; Caruso, Settimo; Riva, Silvia; Spada, Marco; Luca, Angelo; Gridelli, Bruno

    2008-09-15

    We analyze our experience with the management of biliary strictures (BSs) in 27 pediatric patients who underwent liver transplantation with the diagnosis of BS. Mean recipient age was 38 months (range, 2.5-182 months). In all patients percutaneous transhepatic cholangiography, biliary catheter placement, and bilioplasty were performed. In 20 patients the stenoses were judged resolved by percutaneous balloon dilatation and the catheters removed. Mean number of balloon dilatations performed was 4.1 (range, 3-6). No major complications occurred. All 20 patients are symptom-free with respect to BS at a mean follow-up of 13 months (range, 2-46 months). In 15 of 20 patients (75%) one course of percutaneous stenting and bilioplasty was performed, with no evidence of recurrence of BS at a mean follow-up of 15 months (range, 2-46 months). In 4 of 20 patients (20%) two courses of percutaneous stenting and bilioplasty were performed; the mean time to recurrence was 9.8 months (range, 2.4-24 months). There was no evidence of recurrence of BS at a mean follow-up of 12 months (range, 2-16 months). In 1 of 20 patients (5%) three courses of percutaneous stenting and bilioplasty were performed; there was no evidence of recurrence of BS at a mean follow-up of 10 months. In conclusion, BS is a major problem following pediatric liver transplantation. Radiological percutaneous treatment is safe and effective, avoiding, in most cases, surgical revision of the anastomosis.

  11. Autocrine regulation of biliary pathology by activated cholangiocytes

    PubMed Central

    Jensen, Kendal; Marzioni, Marco; Munshi, Kamruzzaman; Afroze, Syeda

    2012-01-01

    The bile duct system of the liver is lined by epithelial cells (i.e., cholangiocytes) that respond to a large number of neuroendocrine factors through alterations in their proliferative activities and the subsequent modification of the microenvironment. As such, activation of biliary proliferation compensates for the loss of cholangiocytes due to apoptosis and slows the progression of toxic injury and cholestasis. Over the course of the last three decades, much progress has been made in identifying the factors that trigger the biliary epithelium to remodel and grow. Because a large number of autocrine factors have recently been identified as relevant clinical targets, a compiled review of their contributions and function in cholestatic liver diseases would be beneficial. In this context, it is important to define the specific processes triggered by autocrine factors that promote cholangiocytes to proliferate, activate neighboring cells, and ultimately lead to extracellular matrix deposition. In this review, we discuss the role of each of the known autocrine factors with particular emphasis on proliferation and fibrogenesis. Because many of these molecules interact with one another throughout the progression of liver fibrosis, a model speculating their involvement in the progression of cholestatic liver disease is also presented. PMID:22194419

  12. Biliary Microbiota, Gallstone Disease and Infection with Opisthorchis felineus

    PubMed Central

    Saltykova, Irina V.; Petrov, Vjacheslav A.; Logacheva, Maria D.; Ivanova, Polina G.; Merzlikin, Nikolay V.; Sazonov, Alexey E.; Ogorodova, Ludmila M.; Brindley, Paul J.

    2016-01-01

    Background There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia. Methodology/Principal Findings Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum, bile from participants with opisthorchiasis showed greater numbers of Synergistetes, Spirochaetes, Planctomycetes, TM7 and Verrucomicrobia. Numbers of > 20 phylotypes differed in bile of the O. felineus-infected compared to non-infected participants, including presence of species of the genera Mycoplana, Cellulosimicrobium, Microlunatus and Phycicoccus, and the Archaeans genus, Halogeometricum, and increased numbers of Selenomonas, Bacteroides, Rothia, Leptotrichia, Lactobacillus, Treponema and Klebsiella. Conclusions/Significance Overall, infection with the liver fluke O. felineus modified the biliary microbiome, increasing abundance of bacterial and archaeal phylotypes. PMID:27447938

  13. Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake

    SciTech Connect

    Cotting, J.; Zysset, T.; Reichen, J.

    1989-02-01

    To study immediate events during extrahepatic cholestasis, we investigated the effect of short-term biliary obstruction on the bioelectrical sinusoidal-canalicular barrier in the rat using molecular weight-matched uncharged and negatively charged inert solute pairs. The bioelectrical barrier averaged -22 +/- 5 and -18 +/- 4 mV (NS) using the pair carboxy-/methoxyinulin and ferrocyanide/sucrose, respectively. After a 20-min biliary obstruction both decreased by 61 and 11%, respectively, but only the large molecular weight pair (the inulins) returned to base line after release of the obstruction. Inert solute clearances were increased after short biliary obstruction depending on molecular size and negative charge (ferrocyanide greater than sucrose greater than carboxyinulin greater than inulin), suggesting that both permeability and bioelectrical barriers were affected by obstruction. The hepatic extraction in vivo of a passively transported drug not excreted into bile (D-propranolol) was not affected by obstruction, whereas that of an actively transported drug (glycocholate) decreased from 66 +/- 8 to 41 +/- 20% during biliary obstruction (P less than 0.01). Unidirectional transfer of glycocholate was not affected by short-term biliary obstruction in the situ perfused rat liver; however, 2 min after (14C)glycocholate administration, increased return was observed in hepatic venous effluent in obstructed animals. Our findings demonstrate a loss of the bioelectrical barrier immediately after short-term biliary obstruction. Decreased hepatic extraction in the view of unaltered sinusoidal uptake demonstrates regurgitation of bile into blood during short-term biliary obstruction.

  14. Depression of biliary glutathione excretion by chronic ethanol feeding in the rat

    SciTech Connect

    Vendemiale, G.; Jayatilleke, E.; Shaw, S.; Lieber, C.S.

    1984-03-12

    The effects of chronic alcohol feeding on biliary glutathione excretion were studied in rats pair fed diets containing either ethanol (36% of total energy) or isocaloric carbohydrate for 4-6 weeks. An exteriorized biliary-duodenal fistula was established and total glutathione (GSH) and oxidized glutathione (GSSG) were measured. A significant decrease was observed in rats fed alcohol chronically compared to their pair fed controls in the biliary excretion of GSH (55.7 +/- 37.0 vs 243.1 +/- 29.0 ..mu..g/ml bile, p < 0.025) as well as biliary GSSG (12.5 +/- 5.0 vs 49.9 +/- 8.0 ..mu..g/ml bile, p < 0.05) and in bile flow (23.1 +/- 1.6 vs 29.2 +/- 1.3 ..mu..g/min, p < 0.05). An acute dose of ethanol tended to exaggerate the decrease on biliary GSH and GSSG in the two groups of animals. The depression in biliary GSH could not be attributed to decreased GSH synthesis since S/sup 35/-L-methionine incorporation into hepatic and biliary GSH was unchanged or even increased after chronic ethanol feeding. 22 references, 4 figures.

  15. Comparative study of biliary trace elements and clinical phenotypes in Wilson’s disease

    PubMed Central

    Ren, Ming-Shan; Fan, Yu-Xin; Yang, Ren-Min; Han, Yong-Zhu; Wu, Guo-Jun; Xin, Yu-Rong; Yu, Long

    1997-01-01

    AIM: To further explore the etiological mechanism of Wilson’s disease (WD) by comparing the changes of biliary trace elements and its clinical phenotype. METHODS: WD patients with different types and conditions (n = 20), non-WD patients with chronic liver damage (n = 22), and healthy volunteers (n = 10; used as controls) were studied. Biliary samples were taken by duodenal drainage. Atom absorption spectrophotometer was used to assay the copper and zinc content of each sample. RESULTS: In WD, the copper content and copper/zinc ratio of biliary juice were evidently lower than those of non-WD patients with chronic liver damage and of healthy controls (F = 14.76, 25.4; 14.92, 26.2 respectively; P < 0.01), while the biliary zinc level had no significant difference from the two non-WD control groups (P > 0.05). There were significant differences in biliary copper excretion among patients with different types and conditions (F = 3.75, P < 0.05; F = 6.20, P < 0.01). CONCLUSION: Copper excretion by liver and the biliary system decreases obviously in WD, which plays a key role in the phenotypic copper retention, and the biliary copper retention is closely related with the severity of hepatic injury and illness. PMID:27053888

  16. Biliary tract perforation following percutaneous endobiliary radiofrequency ablation: A report of two cases

    PubMed Central

    ZHOU, CHUANGUO; WEI, BAOJIE; GAO, KUN; ZHAI, RENYOU

    2016-01-01

    Endobiliary radiofrequency ablation (RFA) has recently been recognized as a beneficial treatment option for malignant biliary obstruction using percutaneous or endoscopic approaches. The feasibility and safety of this method has been demonstrated in clinical studies, with pain, cholangitis and asymptomatic biochemical pancreatitis reported as relatively common complications. By contrast, hepatic coma, newly diagnosed left bundle branch block and partial liver infarction have been reported as uncommon complications. Biliary tract perforation is a serious potential complication of percutaneous intraductal RFA, which may result in severe infection, peritonitis or even mortality, and which has not been previously reported in clinical research. The current study presents the first reports of biliary tract perforation in two patients with unresectable malignant biliary obstruction following percutaneous intraductal RFA. Although the patient in case 1 succumbed 12 days after RFA, the minor biliary tract perforation in case 2 was successfully treated by the deployment of a self-expanding metal stent. This study demonstrates that biliary tract perforation should be recognized as a serious potential complication of endobiliary RFA, and that metal stent deployment should be considered as a treatment option for minor biliary tract perforation. PMID:27313699

  17. A new clarification method to visualize biliary degeneration during liver metamorphosis in sea lamprey (Petromyzon marinus)

    USGS Publications Warehouse

    Chung-Davidson, Yu-Wen; Davidson, Peter J.; Scott, Anne M.; Walaszczyk, Erin J.; Brant, Cory O.; Buchinger, Tyler; Johnson, Nicholas S.; Li, Weiming

    2014-01-01

    Biliary atresia is a rare disease of infancy, with an estimated 1 in 15,000 frequency in the southeast United States, but more common in East Asian countries, with a reported frequency of 1 in 5,000 in Taiwan. Although much is known about the management of biliary atresia, its pathogenesis is still elusive. The sea lamprey (Petromyzon marinus) provides a unique opportunity to examine the mechanism and progression of biliary degeneration. Sea lamprey develop through three distinct life stages: larval, parasitic, and adult. During the transition from larvae to parasitic juvenile, sea lamprey undergo metamorphosis with dramatic reorganization and remodeling in external morphology and internal organs. In the liver, the entire biliary system is lost, including the gall bladder and the biliary tree. A newly-developed method called “CLARITY” was modified to clarify the entire liver and the junction with the intestine in metamorphic sea lamprey. The process of biliary degeneration was visualized and discerned during sea lamprey metamorphosis by using laser scanning confocal microscopy. This method provides a powerful tool to study biliary atresia in a unique animal model.

  18. Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload.

    PubMed Central

    Gross, J B; Myers, B M; Kost, L J; Kuntz, S M; LaRusso, N F

    1989-01-01

    We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles was confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload. Images PMID:2910913

  19. Palliation of Malignant Biliary and Duodenal Obstruction with Combined Metallic Stenting

    SciTech Connect

    Akinci, Devrim Akhan, Okan; Ozkan, Fuat; Ciftci, Turkmen; Ozkan, Orhan S.; Karcaaltincaba, Musturay; Ozmen, Mustafa N.

    2007-11-15

    Purpose. The purpose of this study is to evaluate the efficacy of palliation of malignant biliary and duodenal obstruction with combined metallic stenting under fluoroscopy guidance. Materials and Methods. A retrospective analysis of 9 patients (6 men and 3 women) who underwent biliary and duodenal stenting was performed. The mean age of patients was 61 years (range: 42-80 years). The causes of obstruction were pancreatic carcinoma in 7 patients, cholangiocellular carcinoma in one, and duodenal carcinoma in the other. Biliary and duodenal stents were placed simultaneously in 4 patients. In other 5 patients dudodenal stents were placed after biliary stenting when the duodenal obstruction symptoms have developed. In two patients duodenal stents were advanced via transgastric approach. Results. Technical success rate was 100 %. After percutaneous biliary drainage and stenting bilirubin levels decreased to normal levels in 6 patients and in remaining 3 patients mean reduction of 71% in bilirubin levels was achieved. Tumoral ingrowth occurred in one patient and percutaneous biliary restenting was performed 90 days after the initial procedure. Of the 9 patients, 6 patients were able to tolerate solid diet, whereas 2 patients could tolerate liquid diet and one patient did not show any improvement. Mean survival periods were 111 and 73 days after biliary and duodenal stenting, respectively. Conclusion. Combined biliary and duodenal stent placement which can be performed under fluoroscopic guidance without assistance of endoscopy is feasible and an effective method of palliation of malignant biliary and duodenal obstructions. If transoral and endoscopic approaches fail, percutaneous gastrostomy route allows duodenal stenting.

  20. Surgical Management of Benign Biliary Stricture in Chronic Pancreatitis: A Single-Center Experience.

    PubMed

    Ray, Sukanta; Ghatak, Supriyo; Das, Khaunish; Dasgupta, Jayanta; Ray, Sujay; Khamrui, Sujan; Sonar, Pankaj Kumar; Das, Somak

    2015-12-01

    Biliary stricture in chronic pancreatitis (CP) is not uncommon. Previously, all cases were managed by surgery. Nowadays, three important modes of treatment in these patients are observation, endoscopic therapy, and surgery. In the modern era, surgery is recommended only in a subset of patients who develop biliary symptoms or those who have asymptomatic biliary stricture and require surgery for intractable abdominal pain. We want to report on our experience regarding surgical management of CP-induced benign biliary stricture. Over a period of 5 years, we have managed 340 cases of CP at our institution. Bile duct stricture was found in 62 patients. But, surgical intervention was required in 44 patients, and the remaining 18 patients were managed conservatively. Demographic data, operative procedures, postoperative complications, and follow-up parameters of these patients were collected from our prospective database. A total 44 patients were operated for biliary obstruction in the background of CP. Three patients were excluded, so the final analysis was based on 41 patients. The indication for surgery was symptomatic biliary stricture in 27 patients and asymptomatic biliary stricture with intractable abdominal pain in 14 patients. The most commonly performed operation was Frey's procedure. There was no inhospital mortality. Thirty-five patients were well at a mean follow-up of 24.4 months (range 3 to 54 months). Surgery is still the best option for CP-induced benign biliary stricture, and Frey's procedure is a versatile operation unless you suspect malignancy as the cause of biliary obstruction. PMID:26730073

  1. Surgical Management of Benign Biliary Stricture in Chronic Pancreatitis: A Single-Center Experience.

    PubMed

    Ray, Sukanta; Ghatak, Supriyo; Das, Khaunish; Dasgupta, Jayanta; Ray, Sujay; Khamrui, Sujan; Sonar, Pankaj Kumar; Das, Somak

    2015-12-01

    Biliary stricture in chronic pancreatitis (CP) is not uncommon. Previously, all cases were managed by surgery. Nowadays, three important modes of treatment in these patients are observation, endoscopic therapy, and surgery. In the modern era, surgery is recommended only in a subset of patients who develop biliary symptoms or those who have asymptomatic biliary stricture and require surgery for intractable abdominal pain. We want to report on our experience regarding surgical management of CP-induced benign biliary stricture. Over a period of 5 years, we have managed 340 cases of CP at our institution. Bile duct stricture was found in 62 patients. But, surgical intervention was required in 44 patients, and the remaining 18 patients were managed conservatively. Demographic data, operative procedures, postoperative complications, and follow-up parameters of these patients were collected from our prospective database. A total 44 patients were operated for biliary obstruction in the background of CP. Three patients were excluded, so the final analysis was based on 41 patients. The indication for surgery was symptomatic biliary stricture in 27 patients and asymptomatic biliary stricture with intractable abdominal pain in 14 patients. The most commonly performed operation was Frey's procedure. There was no inhospital mortality. Thirty-five patients were well at a mean follow-up of 24.4 months (range 3 to 54 months). Surgery is still the best option for CP-induced benign biliary stricture, and Frey's procedure is a versatile operation unless you suspect malignancy as the cause of biliary obstruction.

  2. Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload

    SciTech Connect

    Gross, J.B. Jr.; Myers, B.M.; Kost, L.J.; Kuntz, S.M.; LaRusso, N.F.

    1989-01-01

    We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles was confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload.

  3. A Double-Layered Covered Biliary Metal Stent for the Management of Unresectable Malignant Biliary Obstruction: A Multicenter Feasibility Study

    PubMed Central

    Park, Jin-Seok; Jeong, Seok; Lee, Don Haeng; Moon, Jong Ho; Lee, Kyu Taek; Dong, Seok Ho

    2016-01-01

    Background/Aims The covered self-expandable metal stent (CMS) was developed to prevent tumor ingrowth-induced stent occlusion during the treatment of malignant biliary obstruction. However, complications such as cholecystitis, pancreatitis, and stent migration can occur after the endoscopic insertion of CMSs. The aim of the present study was to assess the efficacy and safety of a double-layered CMS (DCMS) for the management of malignant bile duct obstruction. Methods DCMSs were endoscopically introduced into 59 patients with unresectable malignant extrahepatic biliary obstruction at four tertiary referral centers, and the patient medical records were retrospectively reviewed. Results Both the technical and functional success rates were 100%. Procedure-related complications including pancreatitis, cholangitis, stent migration, and liver abscess occurred in five patients (8.5%). The median follow-up period was 265 days (range, 31 to 752 days). Cumulative stent patency rates were 68.2% and 40.8% at 6 and 12 months, respectively. At the final follow-up, the rate of stent occlusion was 33.9% (20/59), and the median stent patency period was 276 days (range, 2 to 706 days). Conclusions The clinical outcomes of DCMSs were comparable to the outcomes previously reported for CMSs with respect to stent patency period and complication rates. PMID:27172927

  4. Utility of Stent-Grafts in Treatment of Porto-Biliary Fistula

    SciTech Connect

    Peynircioglu, Bora; Cwikiel, Wojciech

    2006-12-15

    A porto-biliary fistula causing hemobilia is a known complication of percutaneous transhepatic biliary drainage (PTBD). We present two patients with hemobilia secondary to porto-biliary fistula, treated successfully by percutaneous placement of stent-grafts. In one case, the stent-graft was placed in the bile duct, and in the other case, it was placed in the intrahepatic portal vein branch. Hemobilia stopped and there were no complications except a small area of hepatic infarction, distal to the stent-graft in the portal vein.

  5. Multimodality imaging of hepato-biliary disorders in pregnancy: a pictorial essay.

    PubMed

    Ong, Eugene M W; Drukteinis, Jennifer S; Peters, Hope E; Mortelé, Koenraad J

    2009-09-01

    Hepato-biliary disorders are rare complications of pregnancy, but they may be severe, with high fetal and maternal morbidity and mortality. Imaging is, therefore, essential in the rapid diagnosis of some of these conditions so that appropriate, life-saving treatment can be administered. This pictorial essay illustrates the multimodality imaging features of pregnancy-induced hepato-biliary disorders, such as acute fatty liver of pregnancy, preeclamsia and eclampsia, and HELLP syndrome, as well as those conditions which occur in pregnancy but are not unique to it, such as viral hepatitis, Budd-Chiari syndrome, focal hepatic lesions, biliary sludge, cholecystolithiasis, and choledocholithiasis. PMID:19225816

  6. Drug eluting biliary stents to decrease stent failure rates: A review of the literature

    PubMed Central

    Shatzel, Joseph; Kim, Jisoo; Sampath, Kartik; Syed, Sharjeel; Saad, Jennifer; Hussain, Zilla H; Mody, Kabir; Pipas, J Marc; Gordon, Stuart; Gardner, Timothy; Rothstein, Richard I

    2016-01-01

    Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy. PMID:26839648

  7. Successful Treatment with a Covered Stent and 6-Year Follow-Up of Biliary Complication After Liver Transplantation

    SciTech Connect

    Doros, Attila Nemeth, Andrea; Deak, Akos Pal; Hartmann, Erika; Gerlei, Zsuzsa; Fazakas, Janos; Kobori, Laszlo

    2010-04-15

    The role of covered stent in the management of biliary complications is not yet defined in liver transplant recipients. This Case Report presents a patient with anastomotic stricture and leakage with biloma treated with a covered stent 32 months following liver transplantation. Signs of in-stent restenosis developed 52 months following covered stent placement, which was resolved by balloon dilation. There were no complications during the interventions. The latest follow-up, at 69 months following primary and 19 months following secondary percutaneous intervention, shows a patent covered stent without any clinical or morphological sign of further restenosis. The clinical success with long-term follow-up data suggests that covered stent implantation can be a rational, minimally invasive option for simultaneous treatment of bile duct stenosis and bile leak following liver transplantation in selected cases.

  8. Trimming a Metallic Biliary Stent Using an Argon Plasma Coagulator

    SciTech Connect

    Rerknimitr, Rungsun Naprasert, Pisit; Kongkam, Pradermchai; Kullavanijaya, Pinit

    2007-06-15

    Background. Distal migration is one of the common complications after insertion of a covered metallic stent. Stent repositioning or removal is not always possible in every patient. Therefore, trimming using an argon plasma coagulator (APC) may be a good alternative method to solve this problem. Methods. Metallic stent trimming by APC was performed in 2 patients with biliary Wallstent migration and in another patient with esophageal Ultraflex stent migration. The power setting was 60-100 watts with an argon flow of 0.8 l/min. Observations. The procedure was successfully performed and all distal parts of the stents were removed. No significant collateral damage to the nearby mucosa was observed. Conclusions. In a patient with a distally migrated metallic stent, trimming of the stent is possible by means of an APC. This new method may be applicable to other sites of metallic stent migration.

  9. Biliary atresia: Will blocking inflammation tame the disease?

    PubMed Central

    Bessho, Kazuhiko; Bezerra, Jorge A.

    2014-01-01

    Biliary atresia is the most common cholangiopathy of childhood. With complete obstruction of segments or the entire length of extrahepatic bile ducts, the timely pursuit of hepatoportoenterostomy is the best strategy to restore bile drainage. However, even with prompt surgical intervention, ongoing injury of intrahepatic bile ducts and progressive cholangiopathy lead to end-stage cirrhosis. The pace of disease progression is not uniform; it may relate to clinical forms of disease and/or staging of liver pathology at diagnosis. Although the etiology of disease is not yet defined, several biological processes have been linked to pathogenic mechanisms of bile duct injury. Among them, there is increasing evidence that the immune system targets the duct epithelium and disrupts bile flow. In this review, we discuss how careful clinical phenotyping, staging of disease, and pre-clinical research give insight into response to ongoing trials and rational design of new therapies to block progression of disease. PMID:21226614

  10. Hepatic progenitor cells of biliary origin with liver repopulation capacity

    PubMed Central

    Boulter, Luke; Tsuchiya, Atsunori; Cole, Alicia M; Hay, Trevor; Guest, Rachel V; Wojtacha, Davina; Man, Tak Yung; Mackinnon, Alison; Ridgway, Rachel A; Kendall, Timothy; Williams, Michael J; Jamieson, Thomas; Raven, Alex; Hay, David C; Iredale, John P; Clarke, Alan R; Sansom, Owen J; Forbes, Stuart J

    2015-01-01

    Summary Hepatocytes and cholangiocytes self renew following liver injury. Following severe injury hepatocytes are increasingly senescent, whether Hepatic Progenitor Cells (HPCs) then contribute to liver regeneration is unclear. Here, we describe a mouse model where Mdm2 is inducibly deleted in over 98% of hepatocytes, causing apoptosis, necrosis and senescence with nearly all hepatocytes expressing p21. This results in florid HPC activation, which is necessary for survival, followed by complete, functional liver reconstitution. HPCs isolated from genetically normal mice, using cell surface markers, were highly expandable and phenotypically stable in vitro. These HPCs were transplanted into adult mouse livers where hepatocyte Mdm2 was repeatedly deleted, creating a non-competitive repopulation assay. Transplanted HPCs contributed significantly to restoration of liver parenchyma, regenerating hepatocytes and biliary epithelia, highlighting their in vivo lineage potency. HPCs are therefore a potential future alternative to hepatocyte or liver transplantation for liver disease. PMID:26192438

  11. Manometric characteristics of the extrahepatic biliary tract in dogs.

    PubMed

    Miranda, M; Espinoza, M; Csendes, A

    1981-05-01

    Pressure measurements of the whole extrahepatic biliary tract were performed in dogs using constant perfusion techniques. Studies were done during general anesthesia and in conscious trained dogs. Gallbladder intraluminal fasting pressure was significantly lower than common bile duct pressure. No motor activity was demonstrated in the common bile duct. At the cysticocholedochal junction a static high-pressure zone was observed, probably due to mechanical factors. At the level of the choledochoduodenal junction, a high-pressure zone with a sphincter behavior was demonstrated, with a resting pressure of 38 cm H2O above intraduodenal pressure and with rhythmic contractions with a mean amplitude of 88 cm H2O above duodenal pressure. Duodenal motility was completely different from sphincter dynamics. No differences in pressure values were seen during general anesthesia or in conscious state.

  12. Hepatic progenitor cells of biliary origin with liver repopulation capacity.

    PubMed

    Lu, Wei-Yu; Bird, Thomas G; Boulter, Luke; Tsuchiya, Atsunori; Cole, Alicia M; Hay, Trevor; Guest, Rachel V; Wojtacha, Davina; Man, Tak Yung; Mackinnon, Alison; Ridgway, Rachel A; Kendall, Timothy; Williams, Michael J; Jamieson, Thomas; Raven, Alex; Hay, David C; Iredale, John P; Clarke, Alan R; Sansom, Owen J; Forbes, Stuart J

    2015-08-01

    Hepatocytes and cholangiocytes self-renew following liver injury. Following severe injury hepatocytes are increasingly senescent, but whether hepatic progenitor cells (HPCs) then contribute to liver regeneration is unclear. Here, we describe a mouse model where the E3 ubiquitin ligase Mdm2 is inducibly deleted in more than 98% of hepatocytes, causing apoptosis, necrosis and senescence with nearly all hepatocytes expressing p21. This results in florid HPC activation, which is necessary for survival, followed by complete, functional liver reconstitution. HPCs isolated from genetically normal mice, using cell surface markers, were highly expandable and phenotypically stable in vitro. These HPCs were transplanted into adult mouse livers where hepatocyte Mdm2 was repeatedly deleted, creating a non-competitive repopulation assay. Transplanted HPCs contributed significantly to restoration of liver parenchyma, regenerating hepatocytes and biliary epithelia, highlighting their in vivo lineage potency. HPCs are therefore a potential future alternative to hepatocyte or liver transplantation for liver disease.

  13. The extended Kasai portoenterostomy for biliary atresia: A preliminary report

    PubMed Central

    Ramachandran, Priya; Safwan, Mohamed; Srinivas, Sankaranarayanan; Shanmugam, Naresh; Vij, Mukul; Rela, Mohamed

    2016-01-01

    Aims: In 1955, Professor Morio Kasai first performed a hepatic portoenterostomy. Since then, the procedure has changed the lives of children with biliary atresia (BA). We report our initial experience in performing “extended” Kasai portoenterostomy (KPE), a modification of the original procedure. Materials and Methods: Since 2013, we have used the technique of “extended KPE” and prospectively recorded data on all children undergoing this operation. Data on demographics, clinical features, liver function tests, and perioperative cholangiogram findings were collected. Outcome of KPE was measured by Jaundice Disappearance Rate (JDR) and Native Liver Survival Rate (NLSR). We present our preliminary results from a 30-month period (February 2013 to May 2015). Results: Thirty-one children underwent KPE during this period (19 males) and only 1 child had biliary atresia splenic malformation (BASM). The mean age at KPE was 73 ± 24 days. Five (16.1%) children were more than 90 days old at the time of KPE. Fourteen children cleared jaundice (JDR 45.2%). Eleven (35.5%) children developed episodes of cholangitis, of whom 8 had early cholangitis (within 3 months of the operation). The proportion of children who survived with their own liver 6 months after KPE (NLSR) was 84.2%. Of those children older than 90 days, 2 cleared jaundice and have survived with their native livers for more than 16 months. Conclusion: In our preliminary report of 31 children, we conclude that the extended KPE leads to increased jaundice clearance and improved NLSR in children with BA. PMID:27046977

  14. Biliary lipid secretion in health and in cholesterol gallstone disease.

    PubMed

    Carey, M C; Mazer, N A

    1984-01-01

    The secretory compartment for biliary lecithin and cholesterol secretion probably resides in the smooth endoplasmic reticulum of the hepatocyte. The secretory compartment for bile salts lies predominantly in the enterohepatic circulation which fluxes bile salts continuously through the smooth endoplasmic reticulum compartment and extracts lipids for secretion into bile. Most of bile lecithin is newly synthesized by the liver; most of bile cholesterol is derived from extrahepatic sources. Both cholesterol and lecithin secretion are coupled to bile salt secretion and describe output curves which can be fitted by rectangular hyperbolae: since bile salt secretion is a linear function of input, the relative proportions of cholesterol to bile salts plus lecithin in bile increase at low bile salt outputs. In health, an adequate bile salt (+ lecithin) secretion coupled with normal cholesterol secretion maintains the relative composition of bile in a stable state: fasting compositions usually lie within the micellar zone or metastable supersaturated zone of a triangular coordinate-phase diagram plot. In cholesterol gallstone disease, mean bile salt (+ lecithin) secretion rates are subnormal and/or mean cholesterol secretion rates are supranormal, especially in the fasting state. If individuals are obese there is also enhanced hypersecretion of biliary cholesterol. Either or both secretory defects lead to an elevation and persistence of cholesterol supersaturation of bile. The physical state of the secreted lipids in bile is complex and fluctuant, and probably involves vesicle structures and mixed micelles at high water and cholesterol concentrations and predominantly micellar structures at low water and cholesterol concentrations. In lithogenic bile, the physical state, proportions and nucleation potential of the lipid aggregates are probably different.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. [COMPARATIVE CHARACTERISTIC OF VARIOUS METHODS OF SIMULATION OF BILIARY PERITONITIS IN EXPERIMENT].

    PubMed

    Nichitaylo, M Yu; Furmanov, Yu O; Gutsulyak, A I; Savytska, I M; Zagriychuk, M S; Goman, A V

    2016-02-01

    In experiment on rabbits a comparative analysis of various methods of a biliary peritonitis simulation was conducted. In 6 animals a biliary peritonitis was simulated, using perforation of a gallbladder, local serous-fibrinous peritonitis have occurred in 50% of them. In 7 animals biliary peritonitis was simulated, applying intraabdominal injection of medical sterile bile in a 5-40 ml volume. Diffuse peritonitis with exudates and stratification of fibrin was absent. Most effective method have appeared that, when intraabdominal injection of bile was done together with E. coli culture in the rate of 0.33 microbal bodies McF (1.0 x 10(8) CFU/ml) on 1 kg of the animal body mass. Diffuse biliary peritonitis have occurred in all 23 animals, including serous-fibrinous one--in 17 (76%), and purulent-fibrinous--in 6 (24%). PMID:27244928

  16. Managing malignant biliary obstruction in pancreas cancer: choosing the appropriate strategy.

    PubMed

    Boulay, Brian R; Parepally, Mayur

    2014-07-28

    Most patients with pancreatic cancer develop malignant biliary obstruction. Treatment of obstruction is generally indicated to relieve symptoms and improve morbidity and mortality. First-line therapy consists of endoscopic biliary stent placement. Recent data comparing plastic stents to self-expanding metallic stents (SEMS) has shown improved patency with SEMS. The decision of whether to treat obstruction and the means for doing so depends on the clinical scenario. For patients with resectable disease, preoperative biliary decompression is only indicated when surgery will be delayed or complications of jaundice exist. For patients with locally advanced disease, self-expanding metal stents are superior to plastic stents for long-term patency. For patients with advanced disease, the choice of metallic or plastic stent depends on life expectancy. When endoscopic stent placement fails, percutaneous or surgical treatments are appropriate. Endoscopic therapy or surgical approach can be used to treat concomitant duodenal and biliary obstruction.

  17. Transnasal endoscopic biliary drainage as a rescue management for the treatment of acute cholangitis

    PubMed Central

    Itoi, Takao; Sofuni, Atushi; Itokawa, Fumihide; Tsuchiya, Takayoshi; Kurihara, Toshio; Ishii, Kentaro; Tsuji, Shujiro; Ikeuchi, Nobuhito; Moriyasu, Fuminori

    2010-01-01

    Endoscopic biliary drainage has been established to provide effective treatment for acute obstructive jaundice and cholangitis. A recently developed ultrathin transnasal videoendoscope (TNE) is minimally invasive even for critically ill patients and can be performed without conscious sedation. Transnasal endoscopic biliary drainage (TNE-BD) is performed using a front-viewing TNE with approximately 5 mm outer diameter and 2 mm working channel diameter. Finally, 5F naso-biliary tube or plastic stent are placed. Technical success rates are approximately 100% and 70% for post-endoscopic sphincterotomy or placement of self-expandable metallic stent, and intact papilla, respectively. There are no serious complications. In conclusion, although further cases should be accumulated, TNE-BD and in particular, one-step naso-biliary drainage using TNE may be a useful and novel technique for the treatment of acute cholangitis. PMID:21160690

  18. Surgical treatment of incarcerated calculi via laparoscopic bile duct exploration using laparotomy biliary lithotomy forceps

    PubMed Central

    Jiang, H.; Wang, S. Y.; Jin, X. L.; Jin, J. C.; Gu, H. B.; Zhang, F. M.

    2016-01-01

    The present study aimed to investigate the practicability and clinical value of applying laparotomy biliary lithotomy forceps to laparoscopic bile duct exploration (LCBDE) for the surgical treatment of incarcerated calculi. A total of 63 patients were diagnosed with cholecystolithiasis and choledocholithiasis. The present study performed a retrospective analysis of clinical samples from 16 of these patients who had incarcerated calculi at the terminus of the common bile duct, and who had been treated with laparoscopic cholecystectomy and LCBDE. During the procedure, laparotomy biliary lithotomy forceps were used to gently remove the calculi from the common bile duct. Of the surgical procedures that used laparotomy biliary lithotomy forceps, one case was unsuccessful and 15 cases were successful. The results of the present study suggested that it may be clinically advisable to use laparotomy biliary lithotomy forceps to remove incarcerated calculi from the common bile duct during a laparoscopy, since it is easy, economical and effective. PMID:27698730

  19. [The surgical treatment of hepatic echinococcosis and of its biliary complications].

    PubMed

    Agnifili, A; Gola, P; Ibi, I; Verzaro, R; Carducci, G; Marino, M; Gianfelice, F; De Bernardinis, G

    1993-09-30

    The authors report the experience of 47 patients submitted to surgery for hepatic hydatidosis. Results from different therapeutic procedures are then compared. Finally, possible biliary complications of the hepatic echinococcosis and their surgical treatment are discussed.

  20. Surgical treatment of incarcerated calculi via laparoscopic bile duct exploration using laparotomy biliary lithotomy forceps

    PubMed Central

    Jiang, H.; Wang, S. Y.; Jin, X. L.; Jin, J. C.; Gu, H. B.; Zhang, F. M.

    2016-01-01

    The present study aimed to investigate the practicability and clinical value of applying laparotomy biliary lithotomy forceps to laparoscopic bile duct exploration (LCBDE) for the surgical treatment of incarcerated calculi. A total of 63 patients were diagnosed with cholecystolithiasis and choledocholithiasis. The present study performed a retrospective analysis of clinical samples from 16 of these patients who had incarcerated calculi at the terminus of the common bile duct, and who had been treated with laparoscopic cholecystectomy and LCBDE. During the procedure, laparotomy biliary lithotomy forceps were used to gently remove the calculi from the common bile duct. Of the surgical procedures that used laparotomy biliary lithotomy forceps, one case was unsuccessful and 15 cases were successful. The results of the present study suggested that it may be clinically advisable to use laparotomy biliary lithotomy forceps to remove incarcerated calculi from the common bile duct during a laparoscopy, since it is easy, economical and effective.

  1. Value of early cholescintigraphy in detection of biliary complications after laparoscopic cholecystectomy.

    PubMed

    Kulber, D A; Berci, G; Paz-Partlow, M; Ashok, G; Hiatt, J R

    1994-03-01

    Cholescintigraphy using technetium-99m disofenin tracer is accepted as a routine component of preoperative evaluation of the biliary tract in selected patients but is not used regularly in postoperative management. This is a retrospective analysis of the utility of the nuclide scan in 27 patients after laparoscopic cholecystectomy (LC). Most patients had vague postoperative symptoms such as nausea, pain, and low grade fever. Two patients developed jaundice. Seven of the 27 patients had biliary leaks, and two had common bile duct obstructions. We conclude that cholescintigraphy is a sensitive noninvasive test for the evaluation of biliary complications after LC and is a pivotal component of an algorithmic approach to postoperative complications. Because of the subtle clinical findings and the potential for delayed diagnosis of biliary complications after LC, early performance of this test will minimize patient morbidity. PMID:8116979

  2. [COMPARATIVE CHARACTERISTIC OF VARIOUS METHODS OF SIMULATION OF BILIARY PERITONITIS IN EXPERIMENT].

    PubMed

    Nichitaylo, M Yu; Furmanov, Yu O; Gutsulyak, A I; Savytska, I M; Zagriychuk, M S; Goman, A V

    2016-02-01

    In experiment on rabbits a comparative analysis of various methods of a biliary peritonitis simulation was conducted. In 6 animals a biliary peritonitis was simulated, using perforation of a gallbladder, local serous-fibrinous peritonitis have occurred in 50% of them. In 7 animals biliary peritonitis was simulated, applying intraabdominal injection of medical sterile bile in a 5-40 ml volume. Diffuse peritonitis with exudates and stratification of fibrin was absent. Most effective method have appeared that, when intraabdominal injection of bile was done together with E. coli culture in the rate of 0.33 microbal bodies McF (1.0 x 10(8) CFU/ml) on 1 kg of the animal body mass. Diffuse biliary peritonitis have occurred in all 23 animals, including serous-fibrinous one--in 17 (76%), and purulent-fibrinous--in 6 (24%).

  3. Prevalence, risk factors, and biochemical markers in dogs with ultrasound-diagnosed biliary sludge.

    PubMed

    Secchi, P; Pöppl, A G; Ilha, A; Kunert Filho, H C; Lima, F E S; García, A B; González, F H D

    2012-12-01

    Regarded as an incidental finding, biliary sludge is often diagnosed in dogs on abdominal ultrasound. The aims of the present study were to assess the risk factors, biochemical markers and ultrasonographic findings and to estimate the prevalence and influence of different breeds, sexes, and ages on biliary sludge in dogs. Results demonstrate that the prevalence of biliary sludge is high, especially in senior dogs. The biochemical markers did not have a significant correlation with biliary sludge, and the type of diet was not considered to be the major risk factor. Hepatomegaly was frequently observed on the ultrasound scan of affected animals and of dogs on different systemic drugs and with cardiopathies, which have been referred to as risk groups for the development of inspissated bile.

  4. Diagnosis of bile duct cancer by bile cytology: usefulness of post-brushing biliary lavage fluid

    PubMed Central

    Sugimoto, Shinya; Matsubayashi, Hiroyuki; Kimura, Hirokazu; Sasaki, Keiko; Nagata, Kaori; Ohno, Sachiyo; Uesaka, Katsuhiko; Mori, Keita; Imai, Kenichiro; Hotta, Kinichi; Takizawa, Kohei; Kakushima, Naomi; Tanaka, Masaki; Kawata, Noboru; Ono, Hiroyuki

    2015-01-01

    Background: Pathologic evidence of biliary diseases can be obtained from cytology in addition to endoscopic retrograde cholangiopancreatography (ERCP); however, the diagnostic effectiveness is not satisfactory. Study aim: This retrospective, single-center study evaluated the efficacy of various sampling methods for the cytologic diagnosis of bile duct cancer. Patients and methods: Biliary samples included bile that was simply aspirated, brush smear, brush-rinsed saline, and post-brushing biliary lavage fluid. A set of samples was compared for cytologic efficacy in 76 patients with surgically proven bile duct cancer and in 50 patients with benign biliary stricture. Results: The cytologic sensitivity for diagnosing biliary cancer was 34 % with aspirated bile, 32 % with brush smear, 43 % with brush-rinsed saline, and 70 % with post-brushing biliary lavage fluid, in contrast to the null false-positive result in the benign cases. The sensitivity of cytology was significantly higher with post-brushing lavage fluid than with the other three sampling methods (P < 0.0001), and post-brushing lavage fluid improved the cumulative sensitivity by 24 % (P = 0.002). The sensitivity of biliary cytology was also associated with the amount of aspirated bile (P = 0.01) and with the aspiration site (P = 0.03). The rate of cancer positivity in a cytology set differed according to the tumor macroscopic type (85 % in the protruding type vs. 40 % in the flat type; P = 0.003), and according to the size of the cancer (87 % for tumors ≥ 50 mm vs. 66 % for tumors < 50 mm; P = 0.02). Conclusions: Post-brushing biliary lavage fluid cytology provides superior diagnostic efficacy, and its addition to ERCP procedures is recommended for obtaining cytologic evidence of bile duct cancer. PMID:26357678

  5. National assessment of early biliary complications following liver transplantation: incidence and outcomes.

    PubMed

    Axelrod, David A; Lentine, Krista L; Xiao, Huiling; Dzebisashvilli, Nino; Schnitzler, Mark; Tuttle-Newhall, Janet E; Segev, Dorry L

    2014-04-01

    Despite improved overall liver transplant outcomes, biliary complications remain a significant cause of morbidity. A national data set linking transplant registry and Medicare claims data for 17,012 liver transplant recipients was used to identify all recipients with a posttransplant biliary diagnosis code within the first 6 months after transplantation. Patients were further categorized as follows: a diagnosis without a procedure, a diagnosis and an associated radiological or endoscopic procedure, or a diagnosis treated with surgery. Overall, 15.0% had a biliary diagnosis, 11.2% required a procedure, and 2.2% had a surgical revision. Factors independently associated with biliary complications included donation after cardiac death (DCD), donor age, recipient age, split grafts, and long cold ischemia times. Graft loss was significantly more common for patients with biliary diagnoses [adjusted hazard ratio (aHR) = 1.89, confidence interval (CI) = 1.63-2.19], interventions (aHR = 2.08, CI = 1.77-2.44), and surgical procedures (aHR = 1.80, CI = 1.31-2.49). Mortality after transplantation was also markedly increased for patients with biliary diagnoses (aHR = 2.18, CI = 1.97-2.40), procedures (aHR = 2.21, CI = 1.99-2.46), and surgeries (aHR = 1.77, CI = 1.41-2.23). In stratified analyses, the impact of early biliary complications was greater for DCD liver recipients, but they remained highly significant for recipients of allografts from brain-dead donors as well. Reducing biliary complications should improve posttransplant survival and reduce graft loss. PMID:24478266

  6. Treatment of biliary complications after liver transplant: results of a single center.

    PubMed

    Yildirim, Sedat; Ayvazoglu Soy, Ebru Hatice; Akdur, Aydincan; Kirnap, Mahir; Boyvat, Fatih; Karakayali, Feza; Torgay, Adnan; Moray, Gokhan; Haberal, Mehmet

    2015-04-01

    Biliary complications are major sources of morbidity after liver transplant due to vulnerable vascularization of the bile ducts. Biliary complications are the "Achilles' heel" of liver transplant with their high incidence, need for repeated and prolonged treatment, and potential effects on graft and patient survival. Although standardization of reconstruction techniques and improvements in immunosuppression and organ preservation have reduced the incidence of biliary complications, in early reports the morbidity rates are 50%, with related mortality rate 25% to 30%. Prophylaxis is a major issue. Although many risk factors (old donor age, marginal graft, prolonged ischemia time, living-donor liver transplant, partial liver transplant, donation after cardiac death, hepatic arterial thrombosis, organ preservation, chronic rejection, and other donor and recipient characteristics) do not directly affect biliary complications, accumulation of the factors mentioned above, should be avoided. However, no accepted standard has been established. Treatment strategy is a subject of debate. Recently, nonoperative treatment of biliary complications have been preferred for diagnosis and therapy, because percutaneous or endoscopic treatment may prevent the need for surgical intervention. In this study, we reviewed our treatment of early and late biliary complications after liver transplant.

  7. Circadian rhythmic hepatic biliary flow, constituents, concentrations and excretory rates in patients after cholecystectomy.

    PubMed

    Ho, K J

    1994-01-01

    Twelve adult patients with indwelling common bile duct T-tube were selected for the study of circadian fluctuation of biliary excretion. From the 10th postoperative day on when the enterohepatic circulation was well reestablished a 5 ml bile sample was collected at the end of each 4-h interval for 3 to 4 days for determination of the concentrations of various biliary constituents. This was followed by measurement of bile flow rate by collecting the bile continuously through the T-tube at 4-h intervals for another 3 to 4 days. One quarter of the twelve patients showed no persistent daily fluctuation of all the variables studied. A circadian rhythm was demonstrated by single cosinor rhythmometry in the biliary concentrations of bile acid, cholesterol, phospholipid, bilirubin, alkaline phosphatase, and lactate dehydrogenase in the remaining nine patients. Among them six also showed a circadian fluctuation of hepatic bile flow. The lack of synchronization of the rhythm of the concentrations of various biliary constituents with the bile flow rate resulted in undetectability of a circadian rhythm for their excretory rate in the great majority of patients. Those few patients in whom a rhythm remained to be detectable had a much reduced amplitude but the same acrophase. We concluded that bile flow rate played a major role in the circadian rhythm of biliary excretion and might coordinate the fluctuation of the concentrations of various biliary constituents. However, a true circadian rhythm for their concentrations also existed at least in certain subjects.

  8. Endoscopic ultrasound-guided biliary drainage as an alternative to percutaneous drainage and surgical bypass

    PubMed Central

    Prachayakul, Varayu; Aswakul, Pitulak

    2015-01-01

    Endoscopic retrograde cholangiopancreatography had been a treatment modality of choice for both benign and malignant biliary tract obstruction for more than half century, with a very high clinical success rate and low complications. But in certain circumstances, such as advanced and locally advanced pancreatobiliary malignancies (pancreatic cancer, cholangiocarcinoma, ampullary tumor) and tight benign strictures, endoscopic retrograde cholangiopancreatography (ERCP) fails. Up to this point, the only alternative interventions for these conditions were percutaneous transhepatic biliary drainage or surgery. Endoscopic ultrasound guided interventions was introduced for a couple decades with the better visualization and achievement of the pancreatobiliary tract. And it’s still in the process of ongoing development. The inventions of new techniques and accessories lead to more feasibility of high-ended procedures. Endoscopic ultrasound guided biliary drainage was a novel treatment modality for the patient who failed ERCP with the less invasive technique comparing to surgical bypass. The technical and clinical success was high with acceptable complications. Regarded the ability to drain the biliary tract internally without an exploratory laparotomy, this treatment modality became a very interesting procedures for many endosonographers, worldwide, in a short period. We have reviewed the literature and suggest that endoscopic ultrasound-guided biliary drainage is also an option, and one with a high probability of success, for biliary drainage in the patients who failed conventional endoscopic drainage. PMID:25610532

  9. Mutagenicity of bile and pancreatic juice from patients with pancreatico-biliary maljunction.

    PubMed

    Matsubara, T; Tsuji, T; Miyama, A; Yamaguchi, H; Funabiki, T

    1995-04-01

    We attempted to detect mutagenic activity in bile and pancreatic juice from patients with biliary tract disease using the spore rec assay and wild (H17) and mutant (M45) strains. Three bile samples out of 5 obtained from patients with pancreatico-biliary maljunction showed positive reaction in the spore rec assay, and all contained a high level of amylase activity, while 300 microliters of bile samples obtained from 10 control patients without pancreatico-biliary maljunction did not show any positive reaction. Moreover, 300 microliters of the in vitro mixture of bile with an equal volume of pancreatic juice also showed a positive reaction after treatment for 12 days at 37 degrees C or for 10 min at 100 degrees C, suggesting that they were very stable and long-acting in vivo. These data suggest that possible mutagens might be formed by the mixing of bile with pancreatic juice regurgitated into the biliary tract, and that there might be a relationship to biliary tract cancer which often accompanies pancreatico-biliary maljunction.

  10. Percutaneous Intraductal Radiofrequency Ablation is a Safe Treatment for Malignant Biliary Obstruction: Feasibility and Early Results

    SciTech Connect

    Mizandari, Malkhaz; Pai, Madhava Xi Feng; Valek, Vlastimil; Tomas, Andrasina; Quaretti, Pietro; Golfieri, Rita; Mosconi, Cristina; Ao Guokun; Kyriakides, Charis; Dickinson, Robert; Nicholls, Joanna; Habib, Nagy

    2013-06-15

    Purpose. Previous clinical studies have shown the safety and efficacy of this novel radiofrequency ablation catheter when used for endoscopic palliative procedures. We report a retrospective study with the results of first in man percutaneous intraductal radiofrequency ablation in patients with malignant biliary obstruction. Methods. Thirty-nine patients with inoperable malignant biliary obstruction were included. These patients underwent intraductal biliary radiofrequency ablation of their malignant biliary strictures following external biliary decompression with an internal-external biliary drainage. Following ablation, they had a metal stent inserted. Results. Following this intervention, there were no 30-day mortality, hemorrhage, bile duct perforation, bile leak, or pancreatitis. Of the 39 patients, 28 are alive and 10 patients are dead with a median survival of 89.5 (range 14-260) days and median stent patency of 84.5 (range 14-260) days. One patient was lost to follow-up. All but one patient had their stent patent at the time of last follow-up or death. One patient with stent blockage at 42 days postprocedure underwent percutaneous transhepatic drain insertion and restenting. Among the patients who are alive (n = 28) the median stent patency was 92 (range 14-260) days, whereas the patients who died (n = 10) had a median stent patency of 62.5 (range 38-210) days. Conclusions. In this group of patients, it appears that this new approach is feasible and safe. Efficacy remains to be proven in future, randomized, prospective studies.

  11. Risk factors and surgical management of anastomotic biliary complications after pediatric liver transplantation.

    PubMed

    Darius, Tom; Rivera, Jairo; Fusaro, Fabio; Lai, Quirino; de Magnée, Catherine; Bourdeaux, Christophe; Janssen, Magdalena; Clapuyt, Philippe; Reding, Raymond

    2014-08-01

    Biliary complications (BCs) still remain the Achilles heel of liver transplantation (LT) with an overall incidence of 10% to 35% in pediatric series. We hypothesized that (1) the use of alternative techniques (reduced size, split, and living donor grafts) in pediatric LT may contribute to an increased incidence of BCs, and (2) surgery as a first treatment option for anastomotic BCs could allow a definitive cure for the majority of these patients. Four hundred twenty-nine primary pediatric LT procedures, including 88, 91, 47, and 203 whole, reduced size, split, and living donor grafts, respectively, that were performed between July 1993 and November 2010 were retrospectively reviewed. Demographic and surgical variables were analyzed, and their respective impact on BCs was studied with univariate and multivariate analyses. The modalities of BC management were also reviewed. The 1- and 5-year patient survival rates were 94% and 90%, 89% and 85%, 94% and 89%, and 98% and 94% for whole, reduced size, split, and living donor liver grafts, respectively. The overall incidence of BCs was 23% (n = 98). Sixty were anastomotic complications [47 strictures (78%) and 13 fistulas (22%)]. The graft type was not found to be an independent risk factor for the development of BCs. According to a multivariate analysis, only hepatic artery thrombosis and acute rejection increased the risk of anastomotic BCs (P < 0.001 and P = 0.003, respectively). Anastomotic BCs were managed primarily with surgical repair in 59 of 60 cases with a primary patency rate of 80% (n = 47). These results suggest that (1) most of the BCs were anastomotic complications not influenced by the type of graft, and (2) the surgical management of anastomotic BCs may constitute the first and best therapeutic option. PMID:24809592

  12. Carrier-mediated mechanism for the biliary excretion of the quinolone antibiotic grepafloxacin and its glucuronide in rats.

    PubMed

    Sasabe, H; Tsuji, A; Sugiyama, Y

    1998-03-01

    Grepafloxacin (GPFX) has a comparatively greater hepatobiliary transport than other quinolone antibiotics. The biliary excretion mechanism of GPFX was investigated in a series of in vivo and in vitro studies with Sprague-Dawley rats and the mutant strain Eisai-hyperbilirubinemia rats (EHBR), which have a hereditary defect in their bile canalicular multispecific organic anion transport system (cMOAT). The biliary excretion of the parent drug in EHBR was 38% of that in normal rats, whereas the 3-glucuronide, a main metabolite of GPFX, was scarcely excreted into the bile in EHBR. To clarify the biliary excretion mechanism of GPFX, studies of uptake by bile canalicular membrane vesicle (CMV) were performed. ATP dependence was observed in the uptake of GPFX by CMV, although the extent was not very marked, whereas no ATP-dependent uptake was observed by CMV prepared from EHBR. An inhibition study of the ATP-dependent uptake of the glutathione conjugate, 2,4-dinitrophenyl-S-glutathione (DNP-SG), a typical substrate for cMOAT, was performed in order to differentiate among the affinities of six quinolone antibiotics for this transporter. All quinolone antibiotics inhibited the ATP-dependent uptake of DNP-SG with different half-inhibition concentrations (IC50), and GPFX had the lowest IC50 value. The uptake of GPFX-glucuronide by CMV from normal rats showed a marked ATP dependence, whereas there was little ATP-dependent uptake in EHBR. The K(m) value (7.2 microM) for the higher-affinity component of the glucuronide uptake was comparable to the Ki value (9.2 microM) of the glucuronide in terms of inhibition of the ATP-dependent uptake of DNP-SG, which indicates that DNP-SG and the glucuronide may share the same transporter, cMOAT. The Ki value of the glucuronide observed in this inhibition was less than 1/200 that of the parent, which suggests that the glucuronide had a much higher affinity than the parent drug. These results lead us to conclude that at least a part of the

  13. Ultracentrifugal isolation of vesicular carriers of biliary cholesterol in native human and rat bile.

    PubMed

    Ulloa, N; Garrido, J; Nervi, F

    1987-01-01

    We have utilized ultracentrifugation of native bile-Metrizamide density gradients to isolate a vesicular transport system of biliary lipids in both man and rat. We identified vesicular structures by electron microscopy. Fresh bile specimens were obtained from bile fistula rats (unsaturated bile) and from patients 1 week after bile duct surgery (supersaturated bile). Metrizamide was dissolved in bile (33% w/v), and continuous density gradients were performed with undiluted bile (density limits = 1.020 to 1.300 gm per ml). The relative distribution of biliary cholesterol, phospholipid and bile salt was studied as a function of the density of the fractions. Approximately 50% of total rat biliary cholesterol and between 61 and 90% of human biliary cholesterol was concentrated in the lightest fractions of the gradients (density less than 1.060 gm per ml). In contrast, less than 20% of bile salts was present in fractions with densities lower than 1.060 gm per ml. The highest amounts of bile salts and phospholipids of the bile-Metrizamide density gradients were found in the density range of 1.075 to 1.100 gm per ml in both human and rat bile. More than 80% of biliary proteins was found in fractions with densities greater than 1.075 gm per ml, and only 2% was found in the cholesterol-rich fraction with density less than 1.060 gm per ml in both species. When bile salt concentration was raised in rat bile from 38 to 97 mM by adding taurocholate, the low density cholesterol-rich fraction almost disappeared. Electron microscopy of negatively stained preparations of the fractions with density less than 1.060 gm per ml showed 40 to 120 nm vesicles, which were not apparent in the other fractions. Similar vesicles were demonstrated also in fresh rat bile and within the canaliculi after acute depletion of the bile salt pool (biliary bile salt concentration of 3.45 mM; total biliary lipid concentration of 0.25 gm%). The structure of these vesicles was shown in thin sections of liver

  14. [Current concepts of lithogenetic mechanism in the gallbladder and the role of biliary sludge in this process].

    PubMed

    Tsimmerman, Ia S

    2010-01-01

    A review of current data on cholelithiasis is presented. The concept of staged development of the pathological process in the biliary system is considered starting from dysfunction of gallbladder and sphincter apparatus of extrahepatic biliary ducts via chronic acalculous cholecystitis to chronic calculous cholecystitis. Other issues discussed include biliary acid metabolism; varieties, composition and formation of calculi in the gallbladder; biliary sludge and its role in cholelithogenesis. Debatable questions of sludge nature and composition as well as certain terminological problems are considered. PMID:21089450

  15. [Biliary atresias operated with favourable results: predictable outcome].

    PubMed

    Broto, J; Gil Vernet, J M; Ormaechea, M

    2005-01-01

    Since 1975, our experience in the treatment of biliary atresia with Kasai's technique has improved little by little, achieving 65% favourable outcome in the last five years. We define "good results" as the complete restoration of biliary flow and normalization of bilirrubin levels. The long-term evolution of these good results can be diverse. The objective of the present work is to analyze the outcome of patients in our series in whom a favourable initial response was achieved, as well as evaluating their present situation and future perspectives. The authors present a total of 17 patients operated by Kasai's technique since 1985, that constitutes the group with good results in our series. The controls were based on general analysis, liver function and periodic ultrasound explorations. All received a standardized medical treatment consisting of vitamin supplements (A, D3, E, K) minerals (zinc, calcium, phosphate, iron) ursodexoxicolic acid, luminal,as well as close control of calorie intake. In two patients the levels of bilirrubine were progressively increased with time, stabilizing at between 5/6 mgs/100 ml, with progressive hepatic hardening, appearance of splenomegalia, indirect signs of portal hypertension and a slight deterioration of hepatic function. One received a transplant at age 12 with Quick levels below 50%. The other, aged 16, continues with an acceptable hepatic function and good quality of life under recommendation of transplant. Eleven patients with ages ranging from fourteen months to seventeen years presented slight and firm hepatomegalia, moderate portal hypertension, GOT 71 +/- 8 mg/100 ml, GPT 97 +/- 11 mg/100 ml and normal bilirrubine levels. From this group, 3 patients, all under five years of age, experienced bleeding from esophageal varices which were controlled by sclerosis and medical treatment (propanolol and isosorbide dinitrate). Recently, one three year-old patient developed a hepatocarcinoma of rapid, mortal evolution. Since then

  16. Association between green tea/coffee consumption and biliary tract cancer: A population-based cohort study in Japan.

    PubMed

    Makiuchi, Takeshi; Sobue, Tomotaka; Kitamura, Tetsuhisa; Ishihara, Junko; Sawada, Norie; Iwasaki, Motoki; Sasazuki, Shizuka; Yamaji, Taiki; Shimazu, Taichi; Tsugane, Shoichiro

    2016-01-01

    Green tea and coffee consumption may decrease the risk of some types of cancers. However, their effects on biliary tract cancer (BTC) have been poorly understood. In this population-based prospective cohort study in Japan, we investigated the association of green tea (total green tea, Sencha, and Bancha/Genmaicha) and coffee consumption with the risk for BTC and its subtypes, gallbladder cancer, and extrahepatic bile duct cancer. The hazard ratios and 95% confidence intervals were calculated using the Cox proportional hazard model. A total of 89 555 people aged 45-74 years were enrolled between 1995 and 1999 and followed up for 1 138 623 person-years until 2010, during which 284 cases of BTC were identified. Consumption of >720 mL/day green tea was significantly associated with decreased risk compared with consumption of ≤120 mL/day (hazard ratio = 0.67 [95% confidence interval, 0.46-0.97]), and a non-significant trend of decreased risk associated with increased consumption was observed (P-trend = 0.095). In the analysis according to the location of the primary tumor, consuming >120 mL green tea tended to be associated with decreased risk of gallbladder cancer and extrahepatic bile duct cancer. When Sencha and Bancha/Genmaicha were analyzed separately, we observed a non-significant trend of decreased risk of BTC associated with Sencha but no association with Bancha/Genmaicha. For coffee, there was no clear association with biliary tract, gallbladder, or extrahepatic bile duct cancer. Our findings suggest that high green tea consumption may lower the risk of BTC, and the effect may be attributable to Sencha consumption.

  17. Compensatory role of inducible annexin A2 for impaired biliary epithelial anion-exchange activity of inflammatory cholangiopathy.

    PubMed

    Kido, Osamu; Fukushima, Koji; Ueno, Yoshiyuki; Inoue, Jun; Jefferson, Douglas M; Shimosegawa, Tooru

    2009-12-01

    The peribiliary inflammation of cholangiopathy affects the physiological properties of biliary epithelial cells (cholangiocyte), including bicarbonate-rich ductular secretion. We revealed the upregulation of annexin A2 (ANXA2) in cholangiocytes in primary biliary cirrhosis (PBC) by a proteomics approach and evaluated its physiological significance. Global protein expression profiles of a normal human cholangiocyte line (H69) in response to interferon-gamma (IFNgamma) were obtained by two-dimensional electrophoresis followed by MALDI-TOF-MS. Histological expression patterns of the identified molecules in PBC liver were confirmed by immunostaining. H69 cells stably transfected with doxycyclin-inducible ANXA2 were subjected to physiological evaluation. Recovery of the intracellular pH after acute alkalinization was measured consecutively by a pH indicator with a specific inhibitor of anion exchanger (AE), 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Protein kinase-C (PKC) activation was measured by PepTag Assay and immunoblotting. Twenty spots that included ANXA2 were identified as IFNgamma-responsive molecules. Cholangiocytes of PBC liver were decorated by the unique membranous overexpression of ANXA2. Apical ANXA2 of small ducts of PBC was directly correlated with the clinical cholestatic markers and transaminases. Controlled induction of ANXA2 resulted in significant increase of the DIDS-inhibitory fraction of AE activity of H69, which was accompanied by modulation of PKC activity. We, therefore, identified ANXA2 as an IFNgamma-inducible gene in cholangiocytes that could serve as a potential histological marker of inflammatory cholangiopathy, including PBC. We conclude that inducible ANXA2 expression in cholangiocytes may play a compensatory role for the impaired AE activity of cholangiocytes in PBC in terms of bicarbonate-rich ductular secretion and bile formation through modulation of the PKC activity. PMID:19823170

  18. Association between green tea/coffee consumption and biliary tract cancer: A population-based cohort study in Japan.

    PubMed

    Makiuchi, Takeshi; Sobue, Tomotaka; Kitamura, Tetsuhisa; Ishihara, Junko; Sawada, Norie; Iwasaki, Motoki; Sasazuki, Shizuka; Yamaji, Taiki; Shimazu, Taichi; Tsugane, Shoichiro

    2016-01-01

    Green tea and coffee consumption may decrease the risk of some types of cancers. However, their effects on biliary tract cancer (BTC) have been poorly understood. In this population-based prospective cohort study in Japan, we investigated the association of green tea (total green tea, Sencha, and Bancha/Genmaicha) and coffee consumption with the risk for BTC and its subtypes, gallbladder cancer, and extrahepatic bile duct cancer. The hazard ratios and 95% confidence intervals were calculated using the Cox proportional hazard model. A total of 89 555 people aged 45-74 years were enrolled between 1995 and 1999 and followed up for 1 138 623 person-years until 2010, during which 284 cases of BTC were identified. Consumption of >720 mL/day green tea was significantly associated with decreased risk compared with consumption of ≤120 mL/day (hazard ratio = 0.67 [95% confidence interval, 0.46-0.97]), and a non-significant trend of decreased risk associated with increased consumption was observed (P-trend = 0.095). In the analysis according to the location of the primary tumor, consuming >120 mL green tea tended to be associated with decreased risk of gallbladder cancer and extrahepatic bile duct cancer. When Sencha and Bancha/Genmaicha were analyzed separately, we observed a non-significant trend of decreased risk of BTC associated with Sencha but no association with Bancha/Genmaicha. For coffee, there was no clear association with biliary tract, gallbladder, or extrahepatic bile duct cancer. Our findings suggest that high green tea consumption may lower the risk of BTC, and the effect may be attributable to Sencha consumption. PMID:26530716

  19. Endoscopic multiple metal stenting for the treatment of enteral leaks near the biliary orifice: A novel effective rescue procedure

    PubMed Central

    Mutignani, Massimiliano; Dioscoridi, Lorenzo; Dokas, Stefanos; Aseni, Paolo; Carnevali, Pietro; Forti, Edoardo; Manta, Raffaele; Sica, Mariano; Tringali, Alberto; Pugliese, Francesco

    2016-01-01

    Between April 2013 and October 2015, 6 patients developed periampullary duodenal or jejunal/biliary leaks after major abdominal surgery. In all patients, percutaneous drainage of the collection or re-operation with primary surgical repair was attempted at first but failed. A fully covered enteral metal stent was placed in all patients to seal the leak. Subsequently, we cannulated the common bile duct and, in some cases, and the main pancreatic duct inserting hydrophilic guidewires through the stent after dilating the stent mesh with a dilatation balloon or breaking the meshes with Argon Plasma Beam. Finally, we inserted a fully covered biliary metal stent to drain the bile into the lumen of the enteral stent. In cases of normal proximal upper gastrointestinal anatomy, a pancreatic plastic stent was also inserted. Oral food intake was initiated when the abdominal drain outflow stopped completely. Stent removal was scheduled four to eight weeks later after a CT scan to confirm the complete healing of the fistula and the absence of any perilesional residual fluid collection. The leak resolved in five patients. One patient died two days after the procedure due to severe, pre-existing, sepsis. The stents were removed endoscopically in four weeks in four patients. In one patient we experienced stent migration causing small bowel obstruction. In this case, the stents were removed surgically. Four patients are still alive today. They are still under follow-up and doing well. Bilio-enteral fully covered metal stenting with or without pancreatic stenting was feasible, safe and effective in treating postoperative enteral leaks near the biliopancreatic orifice in our small series. This minimally invasive procedure can be implemented in selected patients as a rescue procedure to repair these challenging leaks.

  20. Endoscopic multiple metal stenting for the treatment of enteral leaks near the biliary orifice: A novel effective rescue procedure

    PubMed Central

    Mutignani, Massimiliano; Dioscoridi, Lorenzo; Dokas, Stefanos; Aseni, Paolo; Carnevali, Pietro; Forti, Edoardo; Manta, Raffaele; Sica, Mariano; Tringali, Alberto; Pugliese, Francesco

    2016-01-01

    Between April 2013 and October 2015, 6 patients developed periampullary duodenal or jejunal/biliary leaks after major abdominal surgery. In all patients, percutaneous drainage of the collection or re-operation with primary surgical repair was attempted at first but failed. A fully covered enteral metal stent was placed in all patients to seal the leak. Subsequently, we cannulated the common bile duct and, in some cases, and the main pancreatic duct inserting hydrophilic guidewires through the stent after dilating the stent mesh with a dilatation balloon or breaking the meshes with Argon Plasma Beam. Finally, we inserted a fully covered biliary metal stent to drain the bile into the lumen of the enteral stent. In cases of normal proximal upper gastrointestinal anatomy, a pancreatic plastic stent was also inserted. Oral food intake was initiated when the abdominal drain outflow stopped completely. Stent removal was scheduled four to eight weeks later after a CT scan to confirm the complete healing of the fistula and the absence of any perilesional residual fluid collection. The leak resolved in five patients. One patient died two days after the procedure due to severe, pre-existing, sepsis. The stents were removed endoscopically in four weeks in four patients. In one patient we experienced stent migration causing small bowel obstruction. In this case, the stents were removed surgically. Four patients are still alive today. They are still under follow-up and doing well. Bilio-enteral fully covered metal stenting with or without pancreatic stenting was feasible, safe and effective in treating postoperative enteral leaks near the biliopancreatic orifice in our small series. This minimally invasive procedure can be implemented in selected patients as a rescue procedure to repair these challenging leaks. PMID:27606045

  1. Endoscopic multiple metal stenting for the treatment of enteral leaks near the biliary orifice: A novel effective rescue procedure.

    PubMed

    Mutignani, Massimiliano; Dioscoridi, Lorenzo; Dokas, Stefanos; Aseni, Paolo; Carnevali, Pietro; Forti, Edoardo; Manta, Raffaele; Sica, Mariano; Tringali, Alberto; Pugliese, Francesco

    2016-08-10

    Between April 2013 and October 2015, 6 patients developed periampullary duodenal or jejunal/biliary leaks after major abdominal surgery. In all patients, percutaneous drainage of the collection or re-operation with primary surgical repair was attempted at first but failed. A fully covered enteral metal stent was placed in all patients to seal the leak. Subsequently, we cannulated the common bile duct and, in some cases, and the main pancreatic duct inserting hydrophilic guidewires through the stent after dilating the stent mesh with a dilatation balloon or breaking the meshes with Argon Plasma Beam. Finally, we inserted a fully covered biliary metal stent to drain the bile into the lumen of the enteral stent. In cases of normal proximal upper gastrointestinal anatomy, a pancreatic plastic stent was also inserted. Oral food intake was initiated when the abdominal drain outflow stopped completely. Stent removal was scheduled four to eight weeks later after a CT scan to confirm the complete healing of the fistula and the absence of any perilesional residual fluid collection. The leak resolved in five patients. One patient died two days after the procedure due to severe, pre-existing, sepsis. The stents were removed endoscopically in four weeks in four patients. In one patient we experienced stent migration causing small bowel obstruction. In this case, the stents were removed surgically. Four patients are still alive today. They are still under follow-up and doing well. Bilio-enteral fully covered metal stenting with or without pancreatic stenting was feasible, safe and effective in treating postoperative enteral leaks near the biliopancreatic orifice in our small series. This minimally invasive procedure can be implemented in selected patients as a rescue procedure to repair these challenging leaks. PMID:27606045

  2. Endoscopic management of biliary complications after liver transplantation: An evidence-based review

    PubMed Central

    Macías-Gómez, Carlos; Dumonceau, Jean-Marc

    2015-01-01

    Biliary tract diseases are the most common complications following liver transplantation (LT) and usually include biliary leaks, strictures, and stone disease. Compared to deceased donor liver transplantation in adults, living donor liver transplantation is plagued by a higher rate of biliary complications. These may be promoted by multiple risk factors related to recipient, graft, operative factors and post-operative course. Magnetic resonance cholangiopancreatography is the first-choice examination when a biliary complication is suspected following LT, in order to diagnose and to plan the optimal therapy; its limitations include a low sensitivity for the detection of biliary sludge. For treating anastomotic strictures, balloon dilatation complemented with the temporary placement of multiple simultaneous plastic stents has become the standard of care and results in stricture resolution with no relapse in > 90% of cases. Temporary placement of fully covered self-expanding metal stents (FCSEMSs) has not been demonstrated to be superior (except in a pilot randomized controlled trial that used a special design of FCSEMSs), mostly because of the high migration rate of current FCSEMSs models. The endoscopic approach of non-anastomotic strictures is technically more difficult than that of anastomotic strictures due to the intrahepatic and/or hilar location of strictures, and the results are less satisfactory. For treating biliary leaks, biliary sphincterotomy and transpapillary stenting is the standard approach and results in leak resolution in more than 85% of patients. Deep enteroscopy is a rapidly evolving technique that has allowed successful treatment of patients who were not previously amenable to endoscopic therapy. As a result, the percutaneous and surgical approaches are currently required in a minority of patients. PMID:26078829

  3. Bile Culture and Susceptibility Testing of Malignant Biliary Obstruction via PTBD

    SciTech Connect

    Yu Haipeng; Guo Zhi Xing Wenge; Guo Xiuying; Liu Fang; Li Baoguo

    2012-10-15

    Purpose: To assess the information obtained by bile culture and susceptibility testing for malignant biliary obstruction by a retrospective one-center study. Methods: A total of 694 patients with malignant biliary obstruction received percutaneous transhepatic biliary drainage during the period July 2003 to September 2010, and subsequently, bile specimens were collected during the procedure. Among the 694 patients, 485 were men and 209 were women, ranging in age from 38 to 78 years (mean age 62 years). Results: A total of 42.9% patients had a positive bile culture (298 of 694). Further, 57 species of microorganisms and 342 strains were identified; gram-positive bacteria accounted for 50.9% (174 of 342) and gram-negative bacteria accounted for 41.5% (142 of 342) of these strains. No anaerobes were obtained by culture during this study. The most common microorganisms were Enterococcus faecalis (41 of 342, 11.9%), Escherichia coli (34 of 342, 9.9%), Klebsiella pneumoniae (28 of 342, 8.2%), Staphylococcus epidermidis (19 of 342, 5.5%), Enterococcus (18 of 342, 5.3%), and Enterobacter cloacae (16 of 342, 4.7%). The percentage of {beta}-lactamase-producing gram-positive bacteria was 27.6% (48 of 174), and the percentage of gram-negative bacteria was 19.7% (28 of 142). The percentage of enzyme-producing Escherichia coli was 61.7% (21 of 34). Conclusion: The bile cultures in malignant biliary obstruction are different from those in the Tokyo Guidelines and other benign biliary obstruction researches, which indicates that a different antibacterial therapy should be applied. Thus, knowledge of the antimicrobial susceptibility data could aid in the better use of antibiotics for the empirical therapy of biliary infection combined with malignant biliary obstruction.

  4. Pathogenesis of Primary Sclerosing Cholangitis and Advances in Diagnosis and Management

    PubMed Central

    Eaton, John E.; Talwalkar, Jayant A.; Lazaridis, Konstantinos N.; Gores, Gregory J.; Lindor, Keith D.

    2013-01-01

    Primary sclerosing cholangitis (PSC), first described in the mid-1850’s, is a complex liver that is heterogeneous in its presentation. PSC is characterized by chronic cholestasis, associated with chronic inflammation of the biliary epithelium, resulting in multi-focal bile duct strictures that can affect the entire biliary tree. Chronic inflammation leads to fibrosis involving the hepatic parenchyma and biliary tree, which can lead to cirrhosis and malignancy. The etiology of PSC is not fully understood which in part explains a lack of effective medical therapy for this condition. However, we have begun to better understand the molecular pathogenesis of PSC. The recognition of specific clinical subtypes and their pattern of progression could improve phenotypic and genotypic classification of the disease. We review our current understanding of this enigmatic disorder and discuss important topics for future studies. PMID:23827861

  5. Primary hypertrophic osteoarthropathy (pachydermoperiostosis): a case report.

    PubMed

    Karkucak, Murat; Erturk, Engin; Capkin, Erhan; Akyazi, Hikmet; Ozden, Gonca; Tosun, Mehmet

    2007-02-01

    Hypertrophic osteoarthropathy is characterized by digital clubbing and periosteal reaction of long bones. Most cases are associated with malignancy or other conditions such as congenital heart disease, liver cirrhosis, pulmonary fibrosis, biliary atresia, and gastrointestinal polyps. We report a 19-year-old man presenting with arthritis, broadening of the fingers and clubbing of the fingers and toes for the previous 3 years. The ankles and knees were swollen. X-rays showed periosteal apposition. The search for a secondary cause remained negative. In cases of arthralgia/arthritis together with clubbed fingers, consideration must be given to hypertrophic osteoarthropathy. The primary or idiopathic form is rare and has a good prognosis.

  6. Brain abscess in hepatopulmonary syndrome associated with biliary atresia.

    PubMed

    Morita, Keiichi; Fukuzawa, Hiroaki; Maeda, Kosaku

    2015-12-01

    The first-choice therapy for biliary atresia (BA) is Kasai hepatoportoenterostomy, which has been shown to greatly improve outcome. Various long-term complications, however, such as portal hypertension and hepatopulmonary syndrome (HPS), can occur in patients with native liver. A rare case of brain abscess in an 11-year-old girl with HPS associated with BA is reported. The patient underwent hepatoportoenterostomy for BA at 53 days of age, with resolution of hyperbilirubinemia. At 10 years of age, she was diagnosed with severe HPS with right-to-left shunting, and preparations for liver transplantation proceeded. Three months after the diagnosis, she had a right parietal brain abscess. Given that the brain abscess enlarged in size, surgical drainage of the brain abscess was performed. The postoperative course was uneventful, but a slight left hemiplegia remained at discharge. The presumed mechanism of abscess formation in HPS may be right-to-left bacterial transit through intrapulmonary vascular dilatations and/or arteriovenous fistulae. PMID:26711920

  7. Molecular profiling of biliary tract cancer: a target rich disease

    PubMed Central

    Jain, Apurva

    2016-01-01

    Biliary tract cancers (BTCs) are relatively uncommon orphan tumors that have an aggressive disease course and a poor clinical outcome. Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival. Gemcitabine and cisplatin based chemotherapy has been the only widely accepted standard systemic therapy regimen in these patients but these tumors can be chemoresistant, further complicating their management. In recent times, there has been considerable research in the genetics of BTC and with the advent of new, advanced technologies like next-generation sequencing (NGS) we are achieving a greater understanding of its disease biology. With the help of NGS, we have now been able to identify actionable mutations such as in the isocitrate dehydrogenase 1 (IDH1), FGFR2, BRAF and HER2/neu genes for targeted therapeutics and correlate the genetic variations with distinct clinical prognoses. This recent genetic information has the potential to make precision medicine a part of routine clinical practice for the management of BTC patients. PMID:27747093

  8. Transjugular Intrahepatic Portosystemic Shunts in Children with Biliary Atresia

    SciTech Connect

    Huppert, Peter E.; Goffette, Pierre; Sokal, Emil M.; Schweizer, Paul; Claussen, Claus D.

    2002-12-15

    Purpose: We retrospectively evaluated the technical and long-term clinical results of transjugularintrahepatic portosystemic shunts (TIPS) in children with portal hypertension and biliary atresia (BA). Methods: Nine children with BA and recurrent bleeding from esophagogastric and/or intestinal varices were treated by TIPS at the age of 34-156 months and followed-up in two centers. Different types of stents were used. Results: Shunt insertion succeeded in all patients, but in two a second procedure was necessary. Seven procedures lasted more than 3 hr, mainly due to difficult portal vein puncture.Variceal bleeding ceased in all patients; however, 16 reinterventions were performed in eight patients for clinical reasons (n =11) and sonographically suspected restenosis (n =5). Four patients underwent successful liver transplantation 4-51 months after TIPS and five are in good clinical conditions 64-75 months after TIPS. Conclusions: TIPS in children with BA is technically difficult, mainly due to periportal fibrosis and small portal veins. Frequency of reinterventions seems to be higher compared with adults.

  9. [Biliary sludge: diagnosis and treatment at an outpatient's clinic].

    PubMed

    Manushkin, O N; Burdina, E G; Novozhenova, E V; Vasil'chenko, S A; Gurova, N Iu

    2013-01-01

    The purpose of the study--to develop a diagnostic and management tactics for patients with biliary sludge (BS) in an outpatient setting. The study included 115 patients who, according to the ultrasound revealed a BS. Own methodological approach used by ultrasound scan of the gall bladder and the interpretation of ultrasonographic BS types: Type 1 (suspension echo-positive particles) was set at 59.1%, type 2 (low level of mobile like putty echo-positive bile)--23.5%, 3 type (like putty bile in the form of mobile and/or fixed clots)--17.4%. For the treatment of BS used drugs ursodeoxycholic acid. The daily dosage depends upon the type BS. For the treatment of type 1 requires a minimum of 1 month, 2 types--not less than 3 months. Sludge was the most resistant type 3, which is the duration of treatment was 6-12 months or more. Allocation of risk factors forming the BS is the basis for the formation of risk groups and prevention activities (including pharmacotherapeutic).

  10. Feasibility and safety of using Soehendra stent retriever as a new technique for biliary access in endoscopic ultrasound-guided biliary drainage

    PubMed Central

    Prachayakul, Varayu; Aswakul, Pitulak

    2015-01-01

    AIM: To assess the feasibility and safety of the use of soehendra stent retriever as a new technique for biliary access in endoscopic ultrasound-guided biliary drainage. METHODS: The medical records and endoscopic reports of the patients who underwent endoscopic ultrasound-guided biliary drainage (EUS-BD) owing to failed endoscopic retrograde cholangiopancreatography in our institute between June 2011 and January 2014 were collected and reviewed. All the procedures were performed in the endoscopic suite under intravenous sedation with propofol and full anaesthetic monitoring. Then we used the Soehendra stent retriever as new equipment for neo-tract creation and dilation when performing EUS-BD procedures. The patients were observed in the recovery room for 1-2 h and transferred to the regular ward, patients’ clinical data were reviewed and analysed, clinical outcomes were defined by using several different criteria. Data were analysed by using SPSS 13 and presented as percentages, means, and medians. RESULTS: A total of 12 patients were enrolled. The most common indications for EUS-BD in this series were failed common bile duct cannulation, duodenal obstruction, failed selective intrahepatic duct cannulation, and surgical altered anatomy for 50%, 25%, 16.7%, and 8.3%, respectively. Seven patients underwent EUS-guided hepaticogastrostomy (58.3%), and 5 underwent EUS-guided choledochoduodenostomy (41.7%). The technical success rate was 100%, while the clinical success rate was 91.7%. Major and minor complications occurred in 16.6% and 33.3% of patients, respectively, but there were no procedure-related death. CONCLUSION: Soehendra stent retriever could be used as an alternative instrument for biliary access in endoscopic ultrasound guided biliary drainage. PMID:25759542

  11. Long-Term Placement of Subcutaneous Ruesch-Type Stents for Double Biliary Stenosis in a Living-Donor Liver Transplant Recipient

    SciTech Connect

    Adani, Gian Luigi Baccarani, Umberto; Lorenzin, Dario; Risaliti, Andrea; Como, Giuseppe; Gasparini, Daniele; Sponza, Massimo; Bresadola, Vittorio; Bresadola, Fabrizio

    2007-04-15

    Biliary reconstruction continues to be a major source of morbidity following liver transplantation. The spectrum of biliary complications is evolving due to the increasing number of split-liver and living-donor liver transplantation, which are even associated with a higher incidence of biliary complications. Bile duct strictures are the most common cause of late biliary complications and account for up to 40% of all biliary complications. Optimal therapy for posttransplantation anastomotic biliary strictures remains uncertain and requires a multidisciplinary approach. We report the case of a 54-year-old Caucasian male affected by hepatocarcinoma and hepatitis C-related cirrhosis who underwent right-lobe living-donor liver transplantation from his son complicated by double anastomotic stenosis of the main right hepatic duct and of an accessory biliary duct draining segments 6 and 7 of the graft that was successfully treated by percutaneous transhepatic cholangiography with long-term subcutaneous placement of two internal Ruesch-type biliary stents.

  12. Sanguineous normothermic machine perfusion improves hemodynamics and biliary epithelial regeneration in DCD porcine livers

    PubMed Central

    Liu, Qiang; Nassar, Ahmed; Farias, Kevin; Buccini, Laura; Baldwin, William; Mangino, Martin; Bennett, Ana; O'Rourke, Colin; Okamoto, Toshiro; Uso, Teresa Diago; Fung, John; Abu-Elmagd, Kareem; Miller, Charles; Quintini, Cristiano

    2014-01-01

    The effect of normothermic machine perfusion (NMP) on post-reperfusion hemodynamics and extrahepatic biliary duct histology of donors after cardiac death (DCD) livers after transplantation has not been addressed thoroughly and represented the object of this study. Ten livers (n=5/group) with 60’ of warm ischemia were preserved by cold storage (CS) or sanguineous NMP for 10 hours, and then reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, arterial and portal venous flows were stable in NMP group during the entire simulated reperfusion, while decreased dramatically in CS group after 16 hours post-reperfusion (P<.05), findings consistent with severe parenchymal injury. Similarly, significant differences existed between CS and NMP group on hepatocellular enzyme release, bile volume produced, and enzyme released into bile (P<.05). On histology CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhage, denudated biliary epithelium and submucosal bile duct necrosis, while NMP liver showed very mild injury in liver parenchyma and biliary architecture. Most importantly, Ki67 staining in extrahepatic bile duct showed biliary epithelial regeneration. Our findings advance the knowledge of post-reperfusion events that characterize DCD livers and propose NMP as a beneficial preservation modality able to improve biliary regeneration after a major ischemic event, which may prevent in clinical transplantation the development of ischemic cholangiopathy. PMID:24805852

  13. Methods to Evaluate Biliary Excretion of Drugs in Humans: an Updated Review

    PubMed Central

    Ghibellini, Giulia; Leslie, Elaine M.; Brouwer, Kim L.R.

    2008-01-01

    Determining the biliary clearance of drugs in humans is very challenging because bile in not readily accessible due to the anatomy of the hepatobiliary tract. The collection of bile usually is limited to post-surgical patients with underlying hepatobiliary disease. In healthy subjects, feces typically are used as a surrogate to quantify the amount of drug excreted via non-urinary pathways. Nevertheless, it is very important to characterize hepatobiliary elimination because this is a potential site of drug interactions that might result in significant alterations in systemic or hepatic exposure. In addition to the determination of in vivo biliary clearance values of drugs, the availability of in vitro models that can predict the extent of biliary excretion of drugs in humans may be a powerful tool in the pre-clinical stages of drug development. In this review, recent advances in the most commonly used in vivo methods to estimate biliary excretion of drugs in humans are outlined. Additionally, in vitro models that can be employed to investigate the molecular processes involved in biliary excretion are discussed to present an updated picture of the new tools and techniques that are available to study the complex processes involved in hepatic drug transport. PMID:16749853

  14. Biliary secretion of copper in healthy man. Quantitation by an intestinal perfusion technique.

    PubMed

    van Berge Henegouwen, G P; Tangedahl, T N; Hofmann, A F; Northfield, T C; LaRusso, N F; McCall, J T

    1977-06-01

    A duodenal perfusion technique which permitted a normal daytime eating pattern of three liquid meals and an overnight fast was used to measure the 24-hr output of copper in bile in 19 studies in 14 persons with normal hepatic and gallbladder function. Daily biliary output was also determined by direct measurement on four 24-hr bile collections obtained from 3 patients with complete biliary diversion, and in 4 patients measurements of dietary copper intake and fecal copper output were also made. A mean bile copper output of 25 +/- 13 microng per kg-day (1.7 mg +/- 0.8) (mean +/- SD) was obtained in 19 perfusion studies; the range was 9.0 to 53.0 microng per kg-day. The values in the 24-hr bile collections were similiar to those obtained using the perfusion method. Biliary copper output was similar during the day and night, and there was no correlation between hourly rates of copper output and hourly rates of bile acid output, nor was there any correlation between daily copper output and daily bile acid output. The similar values for dietary intake, biliary output, and fecal output provide additional support for the current view that in healthy man copper balance is maintained by biliary secretion and subsequent fecal excretion of copper which has been absorbed in the stomach and proximal duodenum.

  15. Hepatocyte-specific ablation in zebrafish to study biliary-driven liver regeneration.

    PubMed

    Choi, Tae-Young; Khaliq, Mehwish; Ko, Sungjin; So, Juhoon; Shin, Donghun

    2015-05-20

    The liver has a great capacity to regenerate. Hepatocytes, the parenchymal cells of the liver, can regenerate in one of two ways: hepatocyte- or biliary-driven liver regeneration. In hepatocyte-driven liver regeneration, regenerating hepatocytes are derived from preexisting hepatocytes, whereas, in biliary-driven regeneration, regenerating hepatocytes are derived from biliary epithelial cells (BECs). For hepatocyte-driven liver regeneration, there are excellent rodent models that have significantly contributed to the current understanding of liver regeneration. However, no such rodent model exists for biliary-driven liver regeneration. We recently reported on a zebrafish liver injury model in which BECs extensively give rise to hepatocytes upon severe hepatocyte loss. In this model, hepatocytes are specifically ablated by a pharmacogenetic means. Here we present in detail the methods to ablate hepatocytes and to analyze the BEC-driven liver regeneration process. This hepatocyte-specific ablation model can be further used to discover the underlying molecular and cellular mechanisms of biliary-driven liver regeneration. Moreover, these methods can be applied to chemical screens to identify small molecules that augment or suppress liver regeneration.

  16. Pancreaticobiliary reflux as a high-risk factor for biliary malignancy: Clinical features and diagnostic advancements

    PubMed Central

    Sugita, Reiji

    2015-01-01

    Pancreaticobiliary junction is composed of complex structure with which biliary duct and pancreatic duct assemble and go out into the ampulla of Vater during duodenum wall surrounding the sphincter of Oddi. Although the sphincter of Oddi functionally prevents the reflux of pancreatic juice, pancreaticobiliary reflux (PBR) occurs when function of the sphincter of Oddi halt. The anatomically abnormal junction is termed pancreaticobiliary maljunction (PBM) and is characterized by pancreatic and bile ducts joining outside of the duodenal wall. PBM is an important anatomical finding because many studies have revealed that biliary malignancies are related due to the carcinogenetic effect of the pancreatic back flow on the biliary mucosa. On the other hand, several studies have been published on the reflux of pancreatic juice into the bile duct without morphological PBM, and the correlation of such cases with biliary diseases, especially biliary malignancies, is drawing considerable attention. Although it has long been possible to diagnose PBM by various imaging modalities, PBR without PBM has remained difficult to assess. Therefore, the pathological features of PBR without PBM have not been yet fully elucidated. Lately, a new method of diagnosing PBR without PBM has appeared, and the features of PBR without PBM should soon be better understood. PMID:26167246

  17. Notch Signaling Coordinates Progenitor Cell-Mediated Biliary Regeneration Following Partial Hepatectomy

    PubMed Central

    Lu, Jie; Zhou, Yingqun; Hu, Tianyuan; Zhang, Hui; Shen, Miao; Cheng, Ping; Dai, Weiqi; Wang, Fan; Chen, Kan; Zhang, Yan; Wang, Chengfeng; Li, Jingjing; Zheng, Yuanyuan; Yang, Jing; Zhu, Rong; Wang, Jianrong; Lu, Wenxia; Zhang, Huawei; Wang, Junshan; Xia, Yujing; De Assuncao, Thiago M.; Jalan-Sakrikar, Nidhi; Huebert, Robert C.; Bin Zhou; Guo, Chuanyong

    2016-01-01

    Aberrant transcriptional regulation contributes to the pathogenesis of both congenital and adult forms of liver disease. Although the transcription factor RBPJ is essential for liver morphogenesis and biliary development, its specific function in the differentiation of hepatic progenitor cells (HPC) has not been investigated, and little is known about its role in adult liver regeneration. HPCs are bipotent liver stem cells that can self-replicate and differentiate into hepatocytes or cholangiocytes in vitro. HPCs are thought to play an important role in liver regeneration and repair responses. While the coordinated repopulation of both hepatocyte and cholangiocyte compartment is pivotal to the structure and function of the liver after regeneration, the mechanisms coordinating biliary regeneration remain vastly understudied. Here, we utilized complex genetic manipulations to drive liver-specific deletion of the Rbpj gene in conjunction with lineage tracing techniques to delineate the precise functions of RBPJ during biliary development and HPC-associated biliary regeneration after hepatectomy. Furthermore, we demonstrate that RBPJ promotes HPC differentiation toward cholangiocytes in vitro and blocks hepatocyte differentiation through mechanisms involving Hippo-Notch crosstalk. Overall, this study demonstrates that the Notch-RBPJ signaling axis critically regulates biliary regeneration by coordinating the fate decision of HPC and clarifies the molecular mechanisms involved. PMID:26951801

  18. Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling

    PubMed Central

    Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru

    2016-01-01

    Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity. DOI: http://dx.doi.org/10.7554/eLife.15034.001 PMID:27431614

  19. Minimally Invasive Treatment of Acute Intrahepatic Fluid Collections With Acute Biliary Pancreatitis

    PubMed Central

    Ambrosi, Antonio; Fersini, Alberto; Tartaglia, Nicola; Valentino, Tiziano Pio

    2009-01-01

    Background: Peripancreatic fluid collection suggests the anatomical-clinical scenario of necrotizing acute pancreatitis. However, intrahepatic fluid collection is a rare occurrence with fewer than 30 cases being reported in the medical literature. We describe 2 cases of intrahepatic fluid collection in 2 patients with acute biliary pancreatitis and discuss the therapeutic possibilities. Case Reports: The first case report is that of a 68-year-old female with a diagnosis of acute biliary pancreatitis with several necrotizing fluid collections and a large infected intrahepatic collection in the left lobe. The patient was successfully treated by percutaneous US/CT guided drainage. The second case report is that of a 72-year-old female with a diagnosis of acute biliary pancreatitis with several peripancreatic fluid collections and a voluminous intrahepatic fluid collection in the left lobe that caused epigastric pain. This patient was also successfully treated with percutaneous US/CT guided drainage. Conclusion: Intrahepatic fluid collection in the course of acute biliary pancreatitis is a rare occurrence. The therapeutic approach is the same as that for pancreatic and peripancreatic fluid collections. In case of infection, the patient undergoes percutaneous US/CT guided drainage. This therapeutic procedure can be added to the therapeutic program for necrotizing acute biliary pancreatitis together with ERCP/ES and videolaparocholecystectomy (VLC). PMID:19660231

  20. Acute renal failure in obstructive diseases of the extrahepatic biliary ducts.

    PubMed

    Acalovschi, I; Chirileanu, T

    1984-01-01

    A series of 46 patients with obstructive disease of the bile ducts complicated by acute renal failure (ARF) is presented. The patients exhibited obstructive jaundice with prevalence of conjugated bilirubine. In 80% of the cases biliary obstruction was associated with cholangitis. Disturbances of the liver function (from mild cholestasis to biliary cirrhosis) were also present. The renal damage was due to biliary disorders and was either present on admission (33 cases) or developed postoperatively (13 cases). Most of the patients presented nonoliguric ARF as well as poor perfusion resulting from decreased circulating blood volume (dehydration and electrolyte loss). Among the criteria used to determine the type of ARF, the urinary/plasma creatinine ratio less than 10 and urinary/plasma osmolarity ratio less than 1.1 were the most valuable. Management of ARF by dialysis alone was not satisfactory. Attention is called to the surgical treatment of the biliary disorder as being essential to prognosis. Patients not treated by radical surgery died in proportion of 87 to 100%. From the rest of 18 patients in whom the operation provided an adequate biliary drainage, in 15 the renal function was restored and 12 survived. Better prognosis in these patients was dependent not only on the ability to cure the cholestasis and infection, but on the early surgical treatment. The ultimate prognosis depends on the improvement of the liver function.

  1. Biliary Adenofibroma with Invasive Carcinoma: Case Report and Review of the Literature

    PubMed Central

    Godambe, Anjali; Brunt, Elizabeth M.; Fulling, Keith H.; Reza Kermanshahi, Taher

    2016-01-01

    We report a case of biliary adenofibroma with an invasive carcinoma in a 71-year-old female who presented with bilateral upper abdominal pain. Imaging revealed a 6.3 cm heterogeneously enhancing mass in the left lateral segment of the liver. Histologically, the adenofibroma showed the characteristic components as previously described of biliary adenofibromata, namely, cystic and tubular structures lined by cuboidal to low columnar biliary type epithelium and a dense fibrous stroma composed of spindled cells. Intimately admixed with the adenofibroma was a distinct tumor composed of malignant clear cells which demonstrated stromal and vascular invasion. Although mitotic figures were inconspicuous, Ki67 was brisk and p53 demonstrated 25–50% positivity. Sections also showed a von Meyenberg complex located adjacent to the tumor. This case expands the understanding of this rare tumor and proves two important assertions from previous case reports. First, the presence of an associated von Meyenberg complex with similar morphology and immunohistochemical staining pattern suggests that biliary adenofibromata and von Meyenberg complexes may share related histogenesis. Second, biliary adenofibromata harbor malignant potential and may show malignant transformation. Furthermore, this case highlights the need for these rare tumors to be followed aggressively, as their biological behavior is poorly understood. PMID:26885426

  2. Primary sclerosing cholangitis

    PubMed Central

    Worthington, Joy; Chapman, Roger

    2006-01-01

    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology characterised by inflammation and fibrosis of the biliary tree. The mean age at diagnosis is 40 years and men are affected twice as often as women. There is a reported annual incidence of PSC of 0.9–1.31/100,000 and point prevalence of 8.5–13.6/100,000. The onset of PSC is usually insidious and many patients are asymptomatic at diagnosis or have mild symptoms only such as fatigue, abdominal discomfort and pruritus In late stages, splenomegaly and jaundice may be a feature. In most, the disease progresses to cirrhosis and liver failure. Cholangiocarcinoma develops in 8–30% of patients. PSC is thought to be immune mediated and is often associated with inflammatory bowel disease, especially ulcerative colitis. The disease is diagnosed on typical cholangiographic and histological findings and after exclusion of secondary sclerosing cholangitis. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Liver transplantation remains the only effective therapeutic option for patients with end-stage liver disease from PSC, although high dose ursodeoxycholic acid may have a beneficial effect. PMID:17062136

  3. Late Migration of Two Covered Biliary Stents Through a Spontaneous Bilioenteric Fistula in a Patient with Malignant Biliary Obstruction

    SciTech Connect

    Krokidis, Miltiadis E.; Hatzidakis, Adam A. Manousaki, Eirini G.; Gourtsoyiannis, Nicholas C.

    2008-01-15

    We report a case of simultaneous late migration of two ePTFE-FEP covered biliary endoprostheses (Viabil, W.L. Gore, Flagstaff, AZ, USA) that were percutaneously implanted for the treatment of malignant obstructive jaundice. The first Viabil covered stent was placed successfully without any evidence of dislocation or other complication during follow-up. Occlusion of the stent occurred 4 months later and was treated with the placement of a second stent of the same type. Thirteen months later the patient became symptomatic. Percutaneous transhepatic cholangiography (PTC) revealed the presence of a choledocho-duodenal fistula and the disappearance of the two endoprostheses previously implanted. A third metallic stent was then percutaneously positioned through the bilioenteric fistula. The computed tomography scan that followed for the detection of the metallic bodies did not reveal the dislocated metallic stents. Stent migration is a well-known complication of uncovered metallic stents, though Viabil stent migration is assumed to be most unlikely to happen due to the stent's anchoring barbs. Furthermore, the stent had already been tightly fixed by tumor over- and ingrowth, as recognized in previous imaging. This is a very unusual case, describing the disappearance of two metallic foreign bodies encapsulated by tumor.

  4. Endoscopic pancreatic and biliary manometry in pancreatic, biliary, and papillary disease, and after endoscopic sphincterotomy and surgical sphincteroplasty.

    PubMed Central

    Gregg, J A; Carr-Locke, D L

    1984-01-01

    Endoscopic manometry was used to measure pancreatic duct, common bile duct, pancreatic duct sphincter and bile duct sphincter pressures in 43 healthy volunteers and 162 patients with a variety of papillary, pancreatic and biliary disorders. Common bile duct pressure was significantly raised after cholecystectomy, with common bile duct stones and papillary stenosis but pancreatic duct pressure only in papillary stenosis. After endoscopic sphincterotomy mean common bile duct pressure fell from 11.2 to 1.1 mmHg and pancreatic duct pressure from 18.0 to 11.2 mmHg. Distinct pancreatic duct sphincter and bile duct sphincter zones were identified as phasic pressures of 3-12 waves/minute on pull-through from pancreatic duct and common bile duct to duodenum. Pancreatic duct sphincter pressures were higher with common bile duct stones and stenosis whereas bile duct sphincter pressures were higher in pancreatitis and stenosis. Bile duct sphincter activity was present in 60% of patients after surgical sphincteroplasty but 21% of patients after endoscopic sphincterotomy. Endoscopic manometry facilitated the diagnosis of papillary stenosis, has allowed study of papillary pathophysiology and has shown a functional inter-relationship between the two sphincteric zones. PMID:6500363

  5. Investigation of Spatial Clustering of Biliary Tract Cancer Incidence in Osaka, Japan: Neighborhood Effect of a Printing Factory

    PubMed Central

    Ito, Yuri; Nakaya, Tomoki; Ioka, Akiko; Nakayama, Tomio; Tsukuma, Hideaki; Uehara, Shinichiro; Kogawa Sato, Kyoko; Endo, Ginji; Hayashi, Tomoshige

    2016-01-01

    Background In 2013, an unusually high incidence of biliary tract cancer among current or former workers of the offset color proof printing department of a printing company in Osaka, Japan, was reported. The purpose of this study was to examine whether distance from the printing factory was associated with incidence of biliary tract cancer and whether incident biliary tract cancer cases clustered around the printing factory in Osaka using population-based cancer registry data. Methods We estimated the age-standardized incidence ratio of biliary tract cancer according to distance from this printing factory. We also searched for clusters of biliary tract cancer incidence using spatial scan statistics. Results We did not observe statistically significantly high or low standardized incidence ratios for residents in each area categorized by distance from the printing factory for the entire sample or for either sex. The scan statistics did not show any statistically significant clustering of biliary tract cancer incidence anywhere in Osaka prefecture in 2004–2007. Conclusions There was no statistically significant clustering of biliary tract cancer incidence around the printing factory or in any other areas in Osaka, Japan, between 2004 and 2007. To date, even if some substances have diffused outside this source factory, they do not appear to have influenced the incidence of biliary tract cancer in neighboring residents. PMID:26902168

  6. Biliary excretion of foreign compounds. Benzene and its derivatives in the rat

    PubMed Central

    Abou-El-Makarem, M. M.; Millburn, P.; Smith, R. L.; Williams, R. T.

    1967-01-01

    1. The extent of the excretion in the bile of the rat of benzene and 21 of its simple derivatives was studied. 2. Some 16 compounds of molecular weight less than 200, and including neutral molecules (benzene and toluene), aromatic acids, aromatic amines and phenols, were injected in solution intraperitoneally into biliary-cannulated rats. Metabolites in the bile were identified and estimated. The extent of biliary excretion of these compounds was low, i.e. 0–10% of the dose in 24hr., and most a