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Esophageal lichen planus:Current knowledge,challenges and future perspectives

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World Journal of Gastroenterology 2022年第41期28卷 5893-5909页

作者： Annegrit Decker Franziska Schauer Adhara Lazaro Carmen Monasterio Arthur Robert Schmidt annette schmitt-Graeff Wolfgang Kreisel Department of Medicine II GastroenterologyHepatologyEndocrinology and Infectious DiseasesMedical Center-University of FreiburgFaculty of MedicineFreiburg 79106Germany Department of Dermatology Medical Center-University of FreiburgFaculty of MedicineFreiburg 79104Germany Department of Medicine Institute of Exercise and Occupational MedicineMedical Center–University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany Institute for Dermatohistology Pathologyand Molecular Pathology Prof.Dr.LaafFreiburgGermany and:University of FreiburgFreiburg 79106Germany

Lichen planus(LP)is a frequent,chronic inflammatory disease involving the skin,mucous membranes and/or skin *** involvement in lichen planus(ELP)is a clinically important albeit underdiagnosed inflammatory *** narrative review aims to give an overview of the current knowledge on ELP,its prevalence,pathogenesis,clinical manifestation,diagnostic criteria,and therapeutic options in order to provide support in clinical *** on ELP were collected using PubMed/*** clinical and therapeutical characteristics from published patient cohorts including our own cohort were extracted and *** mainly affects middle-aged *** principal symptom is ***,asymptomatic cases despite progressed macroscopic esophageal lesions may *** pathogenesis is unknown,however an immune-mediated mechanism is ***,ELP is characterized by mucosal denudation and tearing,trachealization,and *** esophageal stenosis may occur in chronic *** findings include mucosal detachment,T-lymphocytic infiltrations,epithelial apoptosis(Civatte bodies),dyskeratosis,and *** immuno-fluorescence shows fibrinogen deposits along the basement membrane *** date,there is no established ***,treatment with topical steroids induces symptomatic and histologic improvement in two thirds of ELP patients in *** severe cases may require therapy with *** symptomatic esophageal stenosis,endoscopic dilation may be *** may be regarded as a precancerous condition as transition to squamous cell carcinoma has been documented in *** is an underdiagnosed yet clinically important differential diagnosis for patients with unclear dysphagia or *** diagnosis and therapy might prevent potential sequelae such as esophageal stenosis or development of invasive squamous cell *** studies are needed to gain

关键词： Lichen planus Esophagitis T-lymphocytes Budesonide Dysphagia Precancerosis

EGFR and HER2 expression in advanced biliary tract cancer

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World Journal of Gastroenterology 2009年第36期15卷 4511-4517页

作者： Jan Harder Oliver Waiz Florian Otto Michael Geissler Manfred Olschewski Brigitte Weinhold Hubert E Blum annette schmitt-Graeff Oliver G Opitz Department of MedicineⅡ University Medical CenterD-79106 Freiburg Germany Tumorzentrum Ludwig Heilmeyer- Comprehensive Cancer Center Freiburg D-79106 Freiburg Germany Tumorzentrum ZeTuP St.GallenSwitzerland and Department of MedicineⅠUniversity Medical Center D-79106 FreiburgGermany Department of Medicine Gastroenterology and OncologyMunicipal Hospital EsslingenGermany Department of Medical Biometry und Statistics University of FreiburgD-79106 FreiburgGermany annette schmitt-Graeff Institute of PathologyUniversity Medical CenterD-79106 Freiburg Germany

AIM:To analyze the pathogenetic role and potential clinical usefulness of the epidermal growth factor receptor(EGFR)and the human epidermal growth factor receptor 2(HER2)in patients with advanced biliary tract cancer(BTC). METHODS:EGFR and HER2 expression was studied in biopsy samples from 124 patients(51%women; median age 64.8 years),with advanced BTC diagnosed between 1997 and *** micrometers sections of paraffin embedded tissue were examined by standard, FDA approved *** with scores of 2+or 3+for HER2 expression on immunochemistry were additionally tested for HER2 gene amplification by fluorescence in situ hybridisation(FISH).RESULTS:34/124 patients(27.4%)had gallbladder cancer,47(37.9%)had intrahepatic BTC and 43(34.7%)had extrahepatic or perihilar *** expression was examined in a subset of 56 samples. EGFR expression was absent in 22/56 tumors(39.3%). Of the remaining samples expression was scored as 1+in 12(21.5%),2+in 13(23.2%)and 3+in 9(16%), ***2 expression was as follows:score 0 73/124(58.8%),score 1+27/124(21.8%),score 2+ 21/124(17%)and score 3+4/124(3.2%).HER2 gene amplification was present in 6/124,resulting in an overall amplification rate of 5%. CONCLUSION:Our data suggest that routine testing and therapeutic targeting of HER2 does not seem to be useful in patients with BTC,while targeting EGFR may be promising.

关键词： Cholangiocarcinoma Gallbladder cancer Chemotherapy Targeted therapy

Protein-losing pseudomembranous colitis with cap polyposis-like features

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World Journal of Gastroenterology 2017年第16期23卷 3003-3010页

作者： Wolfgang Kreisel Guenther Ruf Richard Salm Adhara Lazaro Bertram Bengsch Anna-Maria Globig Paul Fisch Silke Lassmann annette schmitt-Graeff Department of Medicine II GastroenterologyHepatologyEndocrinology and Infectious DiseasesMedical CenterUniversity of FreiburgFaculty of MedicineUniversity of Freiburg79106 FreiburgGermany Department of General and Visceral Surgery Center for SurgeryUniversity of FreiburgFaculty of MedicineUniversity of Freiburg79106 FreiburgGermany Department of Surgery RKK Bruder-Klaus-Krankenhaus79183 WaldkirchGermany Institute for Exercise and Occupational Medicine Center for MedicineMedical Center-University of FreiburgFaculty of MedicineUniversity of Freiburg79106 FreiburgGermany Silke Lassmann Annette Schmitt-GraeffInstitute of Surgical PathologyMedical Center and Faculty of MedicineUniversity of Freiburg79106 FreiburgGermany

Protein-losing enteropathy(PLE) is characterized by loss of serum proteins into the gastrointestinal tract. It may lead to hypoproteinemia and clinically present as protein deficiency edema, ascites, pleural or pericardial effusion and/or malnutrition. In most cases the site of protein loss is the small intestine. Here we present an unusual case of severe PLE in a 55-year old female with a one-year history of recurrent diarrhea, crampy abdominal pain, and peripheral edema. Endoscopy and MRI showed a diffuse inflammatory thickening of the sigmoid colon and the rectum. Surgical resection of the involved colon was performed and the symptoms were significantly resolved. The final histologic evaluation confirmed a diagnosis of a pseudomembranous colitis with cap polyposis-like features. Such a cause of PLE has never been described before.

关键词： Protein-losing enteropathy Cap polyposis Ulcerative colitis Goblet cells Pseudomembranes

Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension

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World Journal of Gastroenterology 2018年第38期24卷 4356-4368页

作者： Denise Schaffner Adhara Lazaro Peter Deibert Peter Hasselblatt Patrick Stoll Lisa Fauth Manfred W Baumstark Irmgard Merfort annette schmitt-Graeff Wolfgang Kreisel Institute for Exercise-und Occupational Medicine Faculty of MedicineUniversity of FreiburgFreiburg 79106Germany Department of Medicine II GastroenterologyHepatologyEndocrinologyand Infectious DiseasesFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany Anaesthesiological Practice Freiburg 79104Germany Institute of Clinical Pathology Faculty of MedicineUniversity of FreiburgFreiburg 79106Germany Department of Pharmaceutical Biology and Biotechnology University of FreiburgFreiburg 79104Germany

AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver *** In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure *** Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpres

关键词： Portal hypertension Thioacetamide Nitric oxide Liver cirrhosis Cyclic guanosine monophosphate Phosphodiesterase-5 Sildenafil Hepatic stellate cells Metabolic zonation

Inhibitor of differentiation proteins do not influence prognosis of biliary tract cancer

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World Journal of Gastroenterology 2013年第48期19卷 9334-9342页

作者： Jan Harder Michael J Müller Matthias Fuchs Vera Gumpp annette schmitt-Graeff Richard Fischer Melanie Frank Oliver Opitz Jens Hasskarl Department of Gastroenterology Hematology and Oncology Hegau-Bodensee-Hochrhein Kliniken 78221 SingenGermany Department of Hematology and Oncology University Medical Center Freiburg 79104 Freiburg Germany Comprehensive Cancer Center Freiburg Tumorzentrum Ludwig Heilmeyer University Medical Center Freiburg 79104 FreiburgGermany Institute of Pathology University Medical Center Freiburg 79104 Freiburg Germany Onkologie Dreil ndereck 79539 L rrach Germany iOMEDICO AG Freiburg 79108 Freiburg im Breisgau Germany

AIM:To investigate the expression and clinical relevance of inhibitor of differentiation(ID)proteins in biliary tract ***:ID protein expression was analyzed in129 samples from patients with advanced biliary tract cancer(BTC)(45 extrahepatic,50 intrahepatic,and 34 gallbladder cancers),compared to normal controls and correlated with clinical an pathological ***:ID1-3 proteins are frequently overexpressed in all BTC subtypes *** correlation between increased ID protein expression and tumor grading,tumor subtype or treatment response was *** was influenced primary tumor localization(extrahepatic vs intrahepatic and gall bladder cancer,OS 1.5 years vs 0.9 years vs 0.7 years,P=0.002),by stage at diagnosis(OS 2.7 years in stageⅠv s 0.6 years in stageⅣ,P<0.001),resection status and response to systemic *** a multivariate model,ID protein expression did not correlate with clinical ***,there was a trend of shorter OS in patients with loss of cytoplasmic ID4 protein expression(P=0.076).CONCLUSION:ID protein expression is frequently deregulated in BTC but does not influence clinical *** usefulness as prognostic biomarkers in BTC is very limited.

关键词： Biliary tract cancer Cholangiocarcinoma Inhibitor of differentiation Prognostic factors

Hepatitis C Virus Infection Sensitizes Human Hepatocytes to TRAIL-Induced Apoptosis in a Caspase 9-Dependent Manner1

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Hepatitis C Virus Infection Sensitizes Human Hepatocytes to ...

Hepatitis C Virus Infection Sensitizes Human Hepatocytes to TRAIL-Induced Apoptosis in a Caspase 9-Dependent Manner1

第五届国际暨全国肝衰竭与人工肝学术会议

作者： Sebastian Gorke Sibylle J.Rau Mirjam B.Zeisel Eberhard Hildt Kiyoshi Himmelsbach Monica Carvajal-Yepes Roman Huber Takaji Wakita annette schmitt-Craeff Cathy Royer Hubert E.Blum Richard Fischer Thomas F.Baumert Department of infectious disease Southwest hospital of Third Military Medical University

＜正＞Apoptosis of infected cells represents a key host defense mechanism against viral *** impact of apoptosis on the elimination of hepatitis C virus（HCV）-infected cells is poorly *** TRAIL has been implicated in ...

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Hepatitis C Virus Infection Sensitizes Human Hepatocytes to ...