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Gastroenterology Report 2020年第1期8卷 50-55,I0002页

作者： Dongwei Zhang John Hart Xianzhong Ding Xuchen Zhang Michael Feely lindsay Yassan lindsay alpert Consuelo Soldevila-Pico Xuefeng Zhang Xiuli Liu Jinping Lai Department of Pathology Immunology and Laboratory of MedicineUniversity of Florida College of MedicineGainesvilleFLUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA Department of Pathology University of Chicago Pritzker School of MedicineChicagoILUSA Department of Pathology and Laboratory of Medicine Loyola University Medical CenterMaywoodILUSA Department of Pathology Yale School of MedicineNew HavenCTUSA Department of Medicine University of Florida College of MedicineGainesvilleFLUSA Department of Pathology Duke University Medical CenterDurhamNCUSA Department of Pathology Kaiser Permanente Sacramento Medical CenterSacramentoCAUSA

背景:Nivolumab和pembrolizumab是两种PD-1受体阻断性单克隆抗体,已成功用于多种晚期恶性肿瘤的治疗。抗PD-1治疗诱发的肝脏毒性的组织学变化尚未被深入研究,因此,本研究旨在评估这一组织学模式。方法:回顾性分析来自5个医疗中心(佛罗... 详细信息

背景:Nivolumab和pembrolizumab是两种PD-1受体阻断性单克隆抗体,已成功用于多种晚期恶性肿瘤的治疗。抗PD-1治疗诱发的肝脏毒性的组织学变化尚未被深入研究,因此,本研究旨在评估这一组织学模式。方法:回顾性分析来自5个医疗中心(佛罗里达大学医学院、芝加哥大学Pritzker医学院、Loyola大学医学中心、耶鲁大学医学院、杜克大学医学中心)的8例接受Nivolumab或pembrolizumab治疗的晚期恶性肿瘤患者。这些患者既往均无肝病史,病毒性肝炎检测均为阴性。结果:抗PD-1治疗后,8例患者中有7例出现轻中度的胃肠道症状,如腹痛、疲乏、恶心、呕吐及黄疸。所有患者肝脏化学检测指标均显著升高。6例患者的肝损伤表现为急性小叶性肝炎,另外2例不同的损伤模式分别为脂肪性肝炎合并轻度胆汁淤积和急性胆汁淤积性损伤。无一例出现自身免疫性肝炎的典型特征。所有患者在中止抗PD-1治疗并予以免疫抑制治疗后,肝功能均恢复正常。结论:本研究结果显示,在抗PD-1治疗前对肝功能异常者进行筛选并在治疗期间定期监测肝功能指标,有助于预防严重肝损伤的发生。PD-1抑制剂并不会导致自身免疫性肝炎,而仅仅是引起免疫介导的急性非特异性肝炎。对于部分肝损伤患者,只要中止抗PD-1治疗即可,不必采用类固醇治疗。

关键词： nivolumab pembrolizumab anti-PD-1 liver injury histology hepatitis

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Can pathologists reliably establish ampulla of Vater carcinoma histologic subtype on H&E alone?Concordance of subtype and comparison to immunohistochemistry-established subtype

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Journal of Pancreatology 2019年第4期2卷 152-157页

作者： Tanager Kevin S Li Yueying alpert lindsay Setia Namrata Weber Christopher Hart John Xiao Shu-Yuan Department of Pathology The University of Chicago MedicineChicagoIL Department of Pathology Wuhan University Zhongnan Hospital Wuhan University Center for Pathology and Molecular Diagnostics WuhanHubeiChina

Histologic subtyping of ampulla of Vater carcinoma(ampullary carcinoma,AC)may guide choice of adjuvant chemotherapy for advanced disease,as intestinal(INT)subtype may have a better treatment response and survival as compared to the pancreatobiliary(PB)and mixed(MIX)subtypes.However,ambiguous morphologic features can result in inconsistent subtyping among pathologists.Recently immunohistochemistry(IHC)for cytokeratin(CK)7,CK20,CDX2,and the Mucin(MUC)family proteins had been used to aid in the subtyping.It is important to determine if accurate subtyping can be achieved based on hematoxylin and eosin(H&E)evaluation alone,or if IHC is required.In this study,5 gastrointestinal pathologists evaluated 34 cases of AC for histologic subtype(PB,INT,or MIX)based on H&E stain alone.IHC studies(CK7,CK20,and CDX2)were used to determine a gold standard subtyping for comparison(strong CK7 with weak CK20 and CDX2=PB;strong CK20 or CDX2 and weak CK7=INT;strong CK7 and CK20 or CDX2=MIX).Interobserver concordance(kappa)was calculated.Percent correctness of subtyping was calculated in relation to IHC-established subtype gold standard.Interobserver concordance for subtype was fair(kappa 0.31).Percent correctness for subtype against IHC-established subtype was 50%for a majority(3 or more)of pathologists.In all 11 cases with 4 or 5 pathologists being concordant,the subtype was also correctly identified.In addition,data on chemotherapy regimen and overall survival was gathered from the electronic medical record.Patients who were assigned a subtype at time of diagnosis tended to receive gemcitabine for PB subtype,and FOLFOX-based therapy for INT subtype,with some cases diagnosed as"not-otherwise specified"typically also receiving gemcitabine.Survival data were limited by loss to follow-up.In conclusion,despite 11 cases with strong concordance and correctness,overall subtyping concordance was only fair,and a majority of the 5 pathologists correctly identified the subtype in only 50%of cases.Thus,while some AC cases yield clear-cut subtypin

关键词： Ampulla of Vater Immunohistochemistry Immunophenotyping Prognosis Subtype

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