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Esophageal lichen planus:Current knowledge,challenges and future perspectives

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

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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

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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

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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

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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

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

Hepatitis C Virus Infection Sensitizes Human Hepatocytes to ...

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病毒性肝炎慢性化、重症化基础与临床研究进展学术会议

作者： Sebastian Gorke Sibylle J.Rau Mirjam B.Zeisel Eberhard Hildt Kiyoshi Himmelsbach Monica Carvajal-Yepes Roman Huber Takaji Wakita annette schmitt-graeff Cathy Royer Hubert E.Blum Richard Fischer Thomas F.Baumert Department of infectious disease Southwest hospital of Third Military Medical University Department of infectious disease Southwest hospital of Third Military Medical UniversityChongqing 400038 China

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 the death of liver cells in hepatitis-infected but not in normal liver *** determine the impact of TRAIL on apoptosis of virus-infected host cells,we studied TRAIL-induced apoptosis in a tissue culture model system for HCV *** demonstrated that HCV infection sensitizes primary human hepatocytes and Huh7.5 hepatoma cells to TRAIL induced apoptosis in a dose- and time-dependent *** studies identified the HCV nonstructural proteins as key mediators of sensitization to *** a panel of inhibitors targeting different apoptosis pathways,we demonstrate that sensitization to TRAIL is caspase-9 dependent and mediated in part via the mitochondrial *** of hepatocytes to TRAIL-induced apoptosis by HCV infection represents a novel antiviral host defense mechanism that may have important implications for the pathogenesis of HCV infection and may contribute to the elimination of virus-infected hepatocytes.

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

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Klatskin tumor treated by inter-disciplinary therapies including stereotactic radiotherapy: A case report

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World Journal of Gastroenterology 2005年第31期11卷 4923-4926页

作者： Gerhild Becker Felix Momm Henning Schwacha Norbert Hodapp Henning Usadel Michael GeiBler annette Barke annette schmitt-Gr(a|¨)ff Karl Henne Hubert E. Blum Department of Medicine Ⅱ Department of Radiotherapy Institute of Pathology

In view of the poor prognosis of patients with cholangiocarcinoma （CCC）, there is a need for new therapeutic strategies. Inter-disciplinary therapy seems to be most promising. Radiotherapy is an effective alternative to surgery for hilar CCC （Klatskin tumors） if an adequate radiation dose can be delivered to the liver hilus. Here, we describe a patient for whom we used a stereotactic radiotherapy technique in the context of an inter-disdplinary treatment concept. We report a 45-year-old patient with a locally advanced Klatskin tumor. Explorative laparotomy showed that the tumor was not resectable. A metallic stent was implanted and the patient was treated by stereotactic radiotherapy using a body frame. A total dose of 48 Gy （3×4 Gy/wk） was administered. Therapy was well tolerated. After 32 too, local tumor recurrence and a chest wall metastasis developed and were controlled by radio-chemotherapy. After more than 56 mo with a good quality of life, the patient died of advanced neoplastic disease. Stereotactic radiotherapy led to a long-term survival of this patient with a locally advanced Klatskin tumor. In the context of inter-disciplinary treatment concepts, this radiotherapy technique is a promising choice of treatment for patients with hilar CCC.

关键词： Klatskin tumor Stereotactic radiotherapy Inter-disciplinary treatment

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慢性髓性白血病的组织学和血液学检查——对科隆和弗来堡大学病理研究所604例髂嵴活检免疫组化-形态测量及临床的比较研究

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Oncology and Translational Medicine 2000年第6期17卷 52-56页

作者： J.Thiele,H.M.Kvasnicka,A.schmitt-graeff,H.E.Schaefer,阮幼冰 Zentrum fr Pathologie Universitt zu Kln Joseph-Stelzmannstraβe 9 D-50924 Kln Germany Zentrum fr Pathologie Universitt zu Kln Joseph-Stelzmannstraβe 9 D-50924 Kln Germany Zentrum fr Pathologie Universitt zu Kln Joseph-Stelzmannstraβe 9 D-50924 Kln Germany Zentrum fr Pathologie Universitt zu Kln Joseph-Stelzmannstraβe 9 D-50924 Kln Germany 同济医科大学

众所周知,慢性髓性白血病(CML)在髓性增生性系统疾病中具有重要位置。这一方面是由于其好发率,其相对值约占髓性增生疾病的60％,在世界范围内成年人绝对发病数则为0.3×10～5～1.5×10～5人,相当于淋巴性恶性肿瘤(如慢性淋巴性白血病)... 详细信息

众所周知,慢性髓性白血病(CML)在髓性增生性系统疾病中具有重要位置。这一方面是由于其好发率,其相对值约占髓性增生疾病的60％,在世界范围内成年人绝对发病数则为0.3×10～5～1.5×10～5人,相当于淋巴性恶性肿瘤(如慢性淋巴性白血病)的发病数;另一方面显示CML不仅通过多潜能干细胞的克隆性转化,而且还有一种特异遗传标志的出现(phi-染色体,bcr-abl易位),首先酪氨酸激酶活性调节发生改变,

关键词：形态测量粒细胞白细胞骨髓增生异常骨髓纤维化髓性白血病巨核细胞生成免疫组化 CML 巨核母细胞髂嵴病理基础医学血液学显微解剖学解剖学组织学科隆研究所

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骨髓异常增生综合征的血液病理学诊断

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德国医学 2000年第6期17卷 355-358页

作者： A.schmitt-graeff D.Mattern H.Khler J.Hezel M.Lübbert 阮幼冰 Pathologisches Institut des Universittsklinikums Albertstraβe 19D-79106 FreiburgGermany 同济医科大学

骨髓异常增生综合征(MDS)是一组异质性克隆干细胞疾病,其特征为无效血细胞生成,但关于其中造血祖细胞成分中肿瘤克隆的确切来源尚不清楚。其肿瘤性改变及恶性转化也许早在髓样干细胞水平业已发生,造血细胞具有经干细胞水平而达到成熟的... 详细信息

骨髓异常增生综合征(MDS)是一组异质性克隆干细胞疾病,其特征为无效血细胞生成,但关于其中造血祖细胞成分中肿瘤克隆的确切来源尚不清楚。其肿瘤性改变及恶性转化也许早在髓样干细胞水平业已发生,造血细胞具有经干细胞水平而达到成熟的能力,但却呈现成熟障碍及功能缺陷。因为异常的和正常的干细胞同时具有活性,故两者均能造血。

关键词：骨髓异常增生综合征血液病理学诊断 MDS 分类

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

Hepatitis C Virus Infection Sensitizes Human Hepatocytes to ...

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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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