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https://www.readbyqxmd.com/read/28324028/a-duodenal-sdh-deficient-gastrointestinal-stromal-tumor-in-a-patient-with-a-germline-sdhb-mutation
#1
M S Elston, S Sehgal, M Dray, E Phillips, J V Conaglen, R J Clifton-Bligh, A J Gill
Context: Gastrointestinal Stromal Tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract arising from the interstitial cells of Cajal. Succinate dehydrogenase (SDH) deficient GISTs are a unique class of GIST defined by: loss of immunohistochemical expression of SDHB indicating dysfunction of the mitochondrial complex 2, lack of driver mutations in KIT and PDGFRA, and a distinctive morphology and natural history. To date, all reported SDH-deficient GISTs have arisen in the stomach...
March 15, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28320755/ciliary-mechanisms-of-cyst-formation-in-polycystic-kidney-disease
#2
Ming Ma, Anna-Rachel Gallagher, Stefan Somlo
Autosomal-dominant polycystic kidney disease (ADPKD) is a disease of defective tissue homeostasis resulting in active remodeling of nephrons and bile ducts to form fluid-filled sacs called cysts. The causal genes PKD1 and PKD2 encode transmembrane proteins polycystin 1 (PC1) and polycystin 2 (PC2), respectively. Together, the polycystins localize to the solitary primary cilium that protrudes from the apical surface of most kidney tubule cells and is thought to function as a privileged compartment that the cell uses for signal integration of sensory inputs...
March 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28318494/the-role-of-the-irreversible-electroporation-in-the-hepato-pancreatico-biliary-surgery
#3
Patricia Sánchez-Velázquez, Pierre-Alain Clavien
Irreversible electroporation is a novel technique growing in popularity over the last years among the ablative modalities. Its unique action mechanism produces irreversible nanopores in the membrane of the cell leading to apoptosis; therefore irreversible electroporation can be used to ablate substantial volumes of tissue without the undesirable thermal effects as the "heat sink effect". Moreover the extracellular matrix is left unperturbed, thus sparing the structural architecture of surrounding structures such as bile ducts and blood vessels...
March 16, 2017: Cirugía Española
https://www.readbyqxmd.com/read/28317087/imaging-and-clinicopathological-features-of-nivolumab-related-cholangitis-in-patients-with-non-small-cell-lung-cancer
#4
Hisato Kawakami, Junko Tanizaki, Kaoru Tanaka, Koji Haratani, Hidetoshi Hayashi, Masayuki Takeda, Ken Kamata, Mamoru Takenaka, Masatomo Kimura, Takaaki Chikugo, Takao Sato, Masatoshi Kudo, Akihiko Ito, Kazuhiko Nakagawa
Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3...
March 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28314688/nivolumab-treatment-for-oesophageal-squamous-cell-carcinoma-an-open-label-multicentre-phase-2-trial
#5
Toshihiro Kudo, Yasuo Hamamoto, Ken Kato, Takashi Ura, Takashi Kojima, Takahiro Tsushima, Shuichi Hironaka, Hiroki Hara, Taroh Satoh, Satoru Iwasa, Kei Muro, Hirofumi Yasui, Keiko Minashi, Kensei Yamaguchi, Atsushi Ohtsu, Yuichiro Doki, Yuko Kitagawa
BACKGROUND: Nivolumab is a human monoclonal IgG4 antibody that inhibits programmed cell death protein 1 (PD-1) expressed on activated T cells. We investigated the safety and activity of nivolumab in patients with treatment-refractory oesophageal cancer. METHODS: We did an open-label, single-arm, multicentre phase 2 study. Eligible patients had advanced squamous-cell carcinoma, adenosquamous-cell carcinoma, or adenocarcinoma of the oesophagus refractory or intolerant to fluoropyrimidine-based, platinum-based, and taxane-based chemotherapy...
March 14, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28304404/interactions-between-th1-cells-and-tregs-affect-regulation-of-hepatic-fibrosis-in-biliary-atresia-through-the-ifn-%C3%AE-stat1-pathway
#6
Jie Wen, Ying Zhou, Jun Wang, Jie Chen, Wenbo Yan, Jin Wu, Junkai Yan, Kejun Zhou, Yongtao Xiao, Yang Wang, Qiang Xia, Wei Cai
Regulatory T cells (Tregs) and CD4(+) T helper (Th) cells have important roles in bile duct injury of biliary atresia (BA). However, their impacts on liver fibrosis are undefined. Between 2013 and 2016, 146 patients with various stages of BA were enrolled in this study. Peripheral blood, liver biopsy and lymph node samples were collected. Flow cytometry, magnetic cell sorting and immunostaining were used to characterize lymphocytes from BA patients. Deficiency of Tregs was observed along with increased Th1, Th2 and Th17 frequencies in the peripheral blood and livers of BA patients...
March 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28293742/the-accumulation-of-regulatory-t-cells-in-the-hepatic-hilar-lymph-nodes-in-biliary-atresia
#7
Naoya Sakamoto, Toshihiro Muraji, Haruo Ohtani, Kouji Masumoto
PURPOSE: A proposed etiopathogenesis of biliary atresia (BA) involves T-cell-mediated inflammatory bile duct damage and progressive hepatic fibrosis. Pediatric surgeons often observe swelling of the hepatic hilar lymph nodes during the Kasai procedure. Given the importance of regulatory mechanisms in immune responses, the present study was designed to analyze the quantitative changes of regulatory T cells (T reg cells) in the hepatic hilar lymph nodes (hepatic hilar LNs) and peripheral blood (PB) in BA...
March 14, 2017: Surgery Today
https://www.readbyqxmd.com/read/28293027/genetics-of-primary-sclerosing-cholangitis-and-pathophysiological-implications
#8
REVIEW
Xiaojun Jiang, Tom H Karlsen
Primary sclerosing cholangitis (PSC) is a chronic disease leading to fibrotic scarring of the intrahepatic and extrahepatic bile ducts, causing considerable morbidity and mortality via the development of cholestatic liver cirrhosis, concurrent IBD and a high risk of bile duct cancer. Expectations have been high that genetic studies would determine key factors in PSC pathogenesis to support the development of effective medical therapies. Through the application of genome-wide association studies, a large number of disease susceptibility genes have been identified...
March 15, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28289714/bile-acids-initiate-cholestatic-liver-injury-by-triggering-a-hepatocyte-specific-inflammatory-response
#9
Shi-Ying Cai, Xinshou Ouyang, Yonglin Chen, Carol J Soroka, Juxian Wang, Albert Mennone, Yucheng Wang, Wajahat Z Mehal, Dhanpat Jain, James L Boyer
Mechanisms of bile acid-induced (BA-induced) liver injury in cholestasis are controversial, limiting development of new therapies. We examined how BAs initiate liver injury using isolated liver cells from humans and mice and in-vivo mouse models. At pathophysiologic concentrations, BAs induced proinflammatory cytokine expression in mouse and human hepatocytes, but not in nonparenchymal cells or cholangiocytes. These hepatocyte-specific cytokines stimulated neutrophil chemotaxis. Inflammatory injury was mitigated in Ccl2(-/-) mice treated with BA or after bile duct ligation, where less hepatic infiltration of neutrophils was detected...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28289704/preferential-tnf%C3%AE-signaling-via-tnfr2-regulates-epithelial-injury-and-duct-obstruction-in-experimental-biliary-atresia
#10
Pranavkumar Shivakumar, Tatsuki Mizuochi, Reena Mourya, Sridevi Gutta, Li Yang, Zhenhua Luo, Jorge A Bezerra
Biliary atresia is an obstructive cholangiopathy of infancy that progresses to end-stage cirrhosis. Although the pathogenesis of the disease is not completely understood, previous reports link TNFα to apoptosis of the bile duct epithelium in the presence of IFNγ. Here, we investigate if TNFα signaling regulates pathogenic mechanisms of biliary atresia. First, we quantified the expression of TNFA and its receptors TNFR1 and TNFR2 in human livers and found an increased expression of the receptors at the time of diagnosis...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28276299/immunohistochemical-analysis-of-the-stem-cell-marker-lgr5-in-pediatric-liver-disease
#11
Zahida Khan, Anne Orr, George K Michalopoulos, Sarangarajan Ranganathan
Aims In regenerating liver, hepatic progenitor cells (HPCs) are recruited in response to injury; however, few highly specific human HPC markers exist for the hepatocyte lineage. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a Wnt-associated stem cell marker, has been extensively studied in intestinal stem cells, but little is known about its expression in human liver. We hypothesized that LGR5+ HPCs are induced in the regenerative response to pediatric liver injury. Methods and results Immunohistochemistry was used to characterize LGR5 expression in pediatric liver explants (n = 36)...
January 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28270342/cholelithiasis-and-its-complications-in-sickle-cell-disease-in-a-university-hospital
#12
Raquel Alves Martins, Renato Santos Soares, Fernanda Bernadelli De Vito, Valdirene de Fátima Barbosa, Sheila Soares Silva, Helio Moraes-Souza, Paulo Roberto Juliano Martins
INTRODUCTION: The clinical manifestations of sickle cell disease are related to the polymerization of hemoglobin S. The chronic hemolysis caused by this condition often causes the formation of gallstones that can migrate and block the common bile duct leading to acute abdomen. OBJECTIVE: This study aimed to evaluate the profile of patients with sickle cell disease and cholelithiasis. METHODS: Patients with sickle cell disease were separated into groups according to the presence or absence of cholelithiasis...
January 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/28265840/characterization-of-the-ca1-pyramidal-neurons-in-rat-model-of-hepatic-cirrhosis-insights-into-their-electrophysiological-properties
#13
Mahshid Tahamtan, Iraj Aghaei, Vahid Pooladvand, Vahid Sheibani, Mohammad Khaksari, Mohammad Shabani
Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study...
March 7, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28261592/pathology-of-intrahepatic-cholangiocarcinoma
#14
REVIEW
Sandrine Vijgen, Benoit Terris, Laura Rubbia-Brandt
Intrahepatic cholangiocarcinoma (iCC) is a primary carcinoma of the liver with increasing significance and major pathogenic, clinical and therapeutic challenges. Classically, it arises from malignant transformation of cholangiocytes bordering small portal bile duct (BD) to second-order segmental large BDs. It has three major macroscopic growth pattern [mass-forming (MF), periductal infiltrative (PI), and intraductal growth (IG)] and histologically is a desmoplastic stroma-rich adenocarcinoma with cholangiocyte differentiation...
February 2017: Hepatobiliary Surgery and Nutrition
https://www.readbyqxmd.com/read/28260715/immunoglobulin-g4-related-sclerosing-cholangitis-diagnosed-by-liver-biopsy-a-case-report
#15
Mitsuhiro Furuta, Hiroki Eguchi, Yoshiya Takeda, Kunihiro Fushiki, Takeshi Yasuda, Yuriko Onozawa, Masanobu Katayama, Motoo Tanaka, Tadashi Shigematsu, Masamichi Bamba
Patients with immunoglobulin (Ig) G4-related sclerosing cholangitis typically have a high serum IgG4 level. However, here we describe our experience of a patient with a normal serum IgG4 level for whom the cholangitis was diagnosed by liver biopsy. A 61-year-old male presented with elevated liver enzymes and a normal serum IgG4 level. The hilar, intrahepatic, and upper extrahepatic bile ducts were stenotic, with no evidence of a pancreatic lesion. We therefore performed a liver biopsy to differentiate between cholangiocarcinoma and primary sclerosing cholangitis...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/28258935/the-predominance-of-a-naive-t-helper-cell-subset-in-the-immune-response-of-experimental-acute-pancreatitis
#16
Andrea I Schmidt, Christian Kühlbrey, Robert Lauch, Guido Wolff-Vorbeck, Sophia Chikhladze, Ulrich T Hopt, Uwe A Wittel
INTRODUCTION: In necrotizing acute pancreatitis (NAP), systemic inflammatory response syndrome (SIRS) and the compensatory anti-inflammatory response syndrome (CARS) decide overall outcome and mortality. In patients, low lymphocyte counts were found, but T-helper cells seemed to conversely increase. Our aim was to further categorize T-helper cells within the context of NAP induced SIRS and CARS. METHODS: NAP was induced by injection of sodium-taurocholate into the common bile duct of male BALB/c mice; sham treated animals received saline infusion...
February 22, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28257144/the-anti-hepatic-fibrosis-effects-of-dihydrotanshinone-i-are-mediated-by-disrupting-the-yap-and-tead2-complex-and-stimulating-autophagy
#17
Maoxu Ge, Hong Liu, Yixuan Zhang, Naren Li, Shuangshuang Zhao, Wuli Zhao, Yongzhan Zhen, Jianzhong Yu, Hongwei He, Rong-Guang Shao
BACKGROUND AND PURPOSE: Dihydrotanshinone I (DHI), a lipophilic component of traditional Chinese medicine Salvia miltiorrhiza Bunge, has various therapeutic effects. In this study, we investigated the anti-fibrotic effects of DHI and its underlying mechanisms in vitro and in vivo. EXPERIMENTAL APPROACH: Rats that underwent bile duct ligation (BDL) were treated with DHI (25 mg·kg(-1) ·d(-1) , ip) for 14 d. Serum biochemical and liver tissue morphological analyses were performed...
March 3, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28256736/substance-p-increases-liver-fibrosis-by-differential-changes-in-senescence-of-cholangiocytes-and-hepatic-stellate-cells
#18
Ying Wan, Fanyin Meng, Nan Wu, Tianhao Zhou, Julie Venter, Heather Francis, Lindsey Kennedy, Trenton Glaser, Francesca Bernuzzi, Pietro Invernizzi, Shannon Glaser, Qiaobing Huang, Gianfranco Alpini
Substance P (SP) is involved in the proliferation of cholangiocytes in bile duct ligated (BDL) mice and human cholangiocarcinoma growth by interacting with the neurokinin-1 receptor (NK-1R). To identify whether SP regulates liver fibrosis during cholestasis, wild type (WT) or NK-1R knockout (NK-1R(-/-) ) mice that received BDL or sham surgery and Mdr2(-/-) mice treated with either an NK-1R antagonist (L-733,060) or saline were used. Additionally, WT mice were treated with SP or saline intraperitoneally. In vivo, there was increased expression of TAC1 (coding SP) and NK-1R in both BDL and Mdr2(-/-) mice compared to WT mice...
March 3, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28251449/a20-attenuates-liver-fibrosis-in-nafld-and-inhibits-inflammation-responses
#19
Xiaohan Wang, Luoyan Ai, Qingqing Xu, Changwei Wu, Zhiwei Chen, Dazhi Su, Xiaoke Jiang, Zhuping Fan
We previously reported A20 was able to inhibit lipid accumulation in nonalcoholic steatohepatitis. We want to investigate whether A20 influences liver fibrosis in this study. Liver tissues from patients with hepatic fibrosis (n = 9) and healthy individuals (n = 7) were studied for A20 protein level by immunohistochemistry. A20 messenger RNA (mRNA) and protein level were also analyzed in two murine hepatic fibrosis models: methionine- and choline-deficient (MCD) diet and extrahepatic bile duct ligation (BDL) operation by real-time PCR and western blot...
March 1, 2017: Inflammation
https://www.readbyqxmd.com/read/28249274/the-emerging-role-of-soluble-adenylyl-cyclase-in-primary-biliary-cholangitis
#20
Jung-Chin Chang, Ulrich Beuers, Ronald P J Oude Elferink
BACKGROUND: Primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis) is a chronic fibrosing cholangiopathy with the signature of an autoimmune disease and features of intrahepatic cholestasis. Immunosuppressing treatments are largely unsuccessful. Responsiveness to ursodeoxycholic acid and reduced expression of anion exchanger 2 (AE2) on canalicular membranes and small bile ducts underline the importance of bicarbonate transportation in its disease mechanism...
2017: Digestive Diseases
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