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Case report: Bilateral Pneumothoraces due to Targeted Tumor Therapy with regorafenib in a Young Woman with Metastatic Colorectal Cancer

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Case reports in Clinical Medicine 2022年第5期11卷 139-145页

作者： Tobias rachow Tim Sandhaus Thomas Ernst Helmut Schiffl Susanne M. Lang Klinik für innere medizin II Universit&auml tsklinikum Jena Jena Germany Klinik für innere medizin V Universit&auml tsklinikum Jena Jena Germany Klinik für Herz- und Thoraxchirurgie Universit&auml tsklinikum Jena Jena Germany medizinische Klinik iv LMU München München Germany

Background: Colorectal cancer is one of the most common cancer types, frequently metastasizing into the lungs. Treatment options have been vastly improved over the last years. With the increasing use of targeted therapies, novel and rare adverse effects can be seen. Case Presentation: A 43-year-old woman presented in our oncology department with chest pain and dyspnea. The patient was diagnosed with colorectal cancer seven years earlier and had received chemoradiation, surgery, and multiple chemotherapies before she was started on regorafenib because of progressive pulmonary metastases. Computed tomography scans demonstrated cavitation of former nodular bilateral pulmonary metastases. After drainage and resolution of the right-sided pneumothorax, the patient returned eleven days later with recurrent symptoms caused by left-sided tension pneumothorax. Video-assisted thoracoscopy and bilateral pleurodeses were performed. Persistent air leaks with severe pain and pulmonary infiltrates led to the death of the patient. Conclusions: This case demonstrates the efficacy of oral antiangiogenetic therapy in advanced metastatic colorectal cancer. Nevertheless, it also depicts an important potential side effect by transforming multiple solid lung metastases into cavitations which led to recurrent pneumothoraces. Special attention should be paid to this phenomenon as treatment of these complications can be challenging.

关键词： regorafenib Pneumothorax Pulmonary Metastases Colorectal Cancer

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6-硫鸟嘌呤治疗溃疡性或不确定性结肠炎:一项前瞻性、公开标识试验

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世界核心医学期刊文摘（胃肠病学分册） 2006年第5期2卷 56-57页

作者： Teml A. Schwab M. Harrer M. W. reinisch 赵天智 universittsklinik für innere medizin iv Abteilung für Gastroenterologie und Hepatologie Whringer Gürtel 18-20 AT-1090 Vienna Austria Dr.

Objective. 6-thioguanine (6-TG) has emerged as a pro-mising therapeutic alternative in patients with Crohn’ s disease intolerant or resistant to azathioprine (AZA) and/or 6-mercaptopurine (6-MP). The aim of the present study was to evaluate the safety and efficacy of 6-TG in patients with ulcerative colitis (UC) or indeterminate colitis (IC) intolerant or resistant to AZA/6-MP. Material and methods. Twenty patients with an acute flare, steroid-dependent or steroid-refractory disease attending our outpatient department were included in the study. Measurement of 6-TG nucleotide levels was done to check compliance. Complete, partial and non-response were defined by means of the clinical activity index and the daily steroid demand. Secondary outcome parameters included changes in cumulative steroid doses, C-reactive protein (CrP) levels, and an endoscopic score. results. Out of 20 patients 4 were excluded owing to incompliance; 2/16 compliant patients (13% ) had to be prematurely withdrawn because of adverse events, which ceased upon drug discontinuation. By per-protocol analysis, 5/14 patients (36% )were complete, 6/14 (43% ) partial and 3/14 (21% ) non-responders. In addition to the reduction of the cumulative steroid dose over 3 months, CrP decreased in the study population and the endoscopic score decreased in treatment responders. Conclusions. Treatment with 6-TG was effective in patients with UC or IC previously intolerant or resistant to AZA/6-MP. future work is needed to define a subpopulation of patients at low risk for its potential hepatotoxicity, which we assume will benefit from 6-TG.

关键词：溃疡性结肠炎 6-硫鸟嘌呤不确定治疗门诊患者试验标识 6-巯基嘌呤皮质激素 6-TG

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Anti-Tuberculosis Drug Induced Liver Injury and Ursodeoxycholic Acid

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Journal of Tuberculosis research 2020年第2期8卷 66-72页

作者： Susanne M. Lang Emad Al-Nemnem Helmut Schiffl Klinik für innere medizin II Universit&#228 tsklinikum Jena Jena Germany Department of Pulmonary & Critical Care Medicine Clemenceau Medical Center DHCC Dubai United Arab Emirates Department of Internal Medicine iv University Hospital Munich Munich Germany

Hepatotoxicity induced by standard anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide) can result in significant morbidity and, rarely, even mortality. This major adverse side-effect of anti-tuberculosis treatment has a negative impact on patient adherence and patient outcomes as well as on tuberculosis control. Early recognition and prompt withdrawal of the offending drugs are the most critical interventions in the management of anti-tuberculosis drug-induced liver injury. No drug or herbal extract has been shown until recently to prevent or reverse anti-tuberculosis drug-induced hepatotoxicity. Ursodeoxycholic acid is the only fDA approved drug for the treatment of primary biliary cholangitis and has also been successfully used in various cholestatic liver diseases. Although still experimental, recent controlled clinical studies suggested that oral administration of ursodeoxycholic acid may prevent the onset of anti-tuberculosis drug-induced liver injury and accelerate the recovery of liver injury. These clinical data are supported by experimental models of anti-tuberculosis drug-induced hepatotoxicity. There is an urgent need for further randomized clinical trials to document the promising hepatoprotective properties of ursodeoxycholic acid.

关键词： Ursodeoxycholic Acid Hepatotoxicity rifampicin Isoniazid Pyrazinamide Tuberculosis

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肝病患者肿瘤标记物CA19-9与CA125协同升高对重度肝纤维化具有高度特异性

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世界核心医学期刊文摘（胃肠病学分册） 2006年第9期2卷 11-12页

作者： Schniger-Hekele M. Müller C. 王顺涛 universittsklinik für innere medizin iv Klinische Abteilung Gastroenterologie und HepatologieWhringer Gürtel 18-20A-1090 WienAustria Dr.

Increased tumor markers in patients with liver cirrhosis are often considered to be *** use of this unspecific elevation to discriminate minimal fibrosis from severe fibrosis has never been *** aimed to answer the question,Do tumor markers predict severe liver fibrosis? The study group consisted of 125 patients with alcoholic liver disease,hepatitis B,or hepatitis C with available liver *** markers CA 19-9,CA 15-3,and CA 125 were determined using routine laboratory methods and correlated with the extent of liver *** stages 1 and 2 were classified as minimal fibrosis;stages 3 and 4,as severe *** markers CA 19-9,CA 125,and CA 15-3 increased with stage of *** separating patients with mild fibrosis(f1+f2)from patients with severe fibrosis(f3+f4),CA 19-9 had a sensitivity of 70.5%and a specificity of 88.6,CA 125 had 38.1%and 89.7%,and CA 15-3 had 19.0%and 93.0%,*** regression of a combined score of CA19-9 and CA 125 values revealed that an increase of 1 point of the CA 19-9/CA125 score resulted in a 1.6 times increase in likelihood of the presence of severe *** CA 19-9/CA 125 score achieved a similar specificity(97.1%vs.100%)but a higher sensitivity(42.9%vs.33.3%)than the widely used cirrhosis discriminant score of Bonacini.A specificity(98.5%)similar to that of the CA 19-9/CA 125 score was reached by the easier determination of the combined elevation of CA 19-9 and CA 125,which had the best positive predictive value,92.9%.The excellent predictive ability of the combined elevation of CA 19-9 and CA 125 for severe liver fibrosis(f3+f4)was confirmed in an independent group of patients with liver *** combined elevation of CA 19-9 and CA 125 is useful for identifying patients with advanced fibrosis or cirrhosis with high *** without a combined elevation of CA 19-9 and CA 125 still require histological examination to identify severe fibrosis or cirrhosis.

关键词：肿瘤标记物CA19-9 CA125水平肝纤维化程度非特异性重度升高肝病患者 logistic回归分析

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聚乙二醇干扰素α-2a(40kD)/利巴韦林治疗的慢性丙型肝炎患者的持续性病毒应答预测

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世界核心医学期刊文摘（胃肠病学分册） 2005年第12期1卷 48-49页

作者： ferenci P. friedM.W. Shiffman M.L. 李宏宇 Univ. Klinik für innere medizin iv AKH Waehri- nger Guertel 18- 20 A 1090 Wien Austria

Background/Aims: Prediction of sustained virologicalresponse (SVr) during treatment would allow clinicians to identify patients most likely to benefit from therapy. Methods: retrospective analysis of data from 1121 adults with chronic hepatitis C treated for 48 weeks with peginterferon alfa- 2a (40 KD) 180 μ g/week plus placebo or ribavirin (1000/1200 mg/day), or interferon alfa- 2b 3 MIU three times/week plus ribavirin in a randomized, multinational, study. results: 67% of patients treated with peginterferon alfa- 2a (40 KD)/ribavirin with early virological responses (HCV rNA negative or ≥ 2 log10 decrease) at week 12 had SVrs at week 72 (HCV rNA ive predictive value (NPV) was 97% . The probability of an SVr increased with the rapidity of HCV rNA suppression. The highest SVr rates were achieved in patients with rapid virological responses at week 4, but the corresponding NPV (74% ) is too low for a decision criterion. In patients with early virological responses by week 12, the SVr rate was ≈ 20% lower in those who receivedred with patients who received ≥ 80% of the planned ribavirin dose. Conclusions: Early, sustained suppression of HCV replication portends an SVr. Cessation of treatment may be contemplated in patients without a ≥ 2 log10 reduction in HCV rNA after 12 weeks.

关键词：慢性丙型肝炎 kD 干扰素α 病毒应答病毒学应答持续性丙肝患者病毒学反应丙肝病毒阴性预测值

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基因型在德国慢性丙型肝炎病毒感染和丙型肝炎病毒所致肝硬变中的意义

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德国医学 1996年第3期13卷 133-134页

作者： T.Goeser U.Tx H.M.Mler J.C.Arnold L.Theilmann 唐振亚 Abteilung innere medizin iv Medizinische UniversittsklinikBergheimer Str.58D-69115 HeidelbergGermany 同济医科大学附属同济医院

1989年,丙型肝炎病毒(HCV)感染被确认为既往称之为非甲非乙型肝炎(NANBH)最重要的致病因素,肠道外暴露(如输血、静脉药瘾)是 HCV 感染来源,但是仍有大约40%的慢性 HCV 感染者的感染原因不明(称之为散发性丙型肝炎)。

关键词：丙型肝炎病毒感染肝硬变基因型

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干扰素α-2a加利巴韦林联用或不用金刚烷胺对慢性丙型肝炎病毒基因1型感染者的治疗:一项随机、双盲、安慰剂对照研究

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世界核心医学期刊文摘（胃肠病学分册） 2006年第5期2卷 50-51页

作者： ferenci P. formann E. Laferl H. 刘丽娜 Univ. Klinik für innere medizin iv Medical University of Vienna AKH Waehringer Guertel 18-20 A 1090 Wien Austria

Background/Aims: Amantadine may augment virological response rates to interferon-based therapy in chronic hepatitis C patients. Using a novel design, amantadine was studied in na ve genotype 1 patients treated in combination with peginterferon alfa-2a (40KD)/ribavirin. Methods: Patients enrolled in this randomized, placeo-controlled multicenter trial were stratified by single-dose interferon sensitivity (stratum I, 24 h HCV-rNA decline >1.4log 10; II, 0.8-1.39log10; III, reliable means of identifying nonresponders to interferon/ribavirin) and fibrosis grade (f0/1/2 vs. f3/4) at baseline. All patients received peginterferon alfa-2a (40KD) 180 μ g/week plus ribavirin 1000-1200 mg/day and were randomized to receive amantadine 100 mg twice daily (N=114) or placebo (N=95) for 48 weeks. results: Week 24 virological response rates in strata II and III, the primary outcome, were similar in patients treated with amantadine (63.7% ) or placebo (65.7% ), as were sustained virological response rates at week 72 (46.5 and 51.6% , respectively). Adverse event profiles were similar and amantadine did not improve health-related quality of life compared with placebo. Interferon sensitivity was the only significant predictor of treatment outcome. Conclusions: Adding amantadine to peginterferon alfa-2a (40KD)/ribavirin combination therapy does not augment virological response rates in genotype 1 patients. Virological response was almost exclusively determined by interferon sensitivity at baseline.

关键词：干扰素α-2α 慢性丙型肝炎安慰剂对照金刚烷胺利巴韦林治疗基础病毒基因随机对照研究 1型

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fontolizumab,人源化抗干扰素γ抗体治疗中重度克罗恩病的临床研究:一项关于剂量升级、安慰剂对照、双盲、药物单剂量应用和多剂量应用的安全性与耐受性的研究

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世界核心医学期刊文摘（胃肠病学分册） 2006年第12期2卷 42-43页

作者： reinisch W. Hommes D.W. Van Assche G. 王铮 universitaetsklinik innere medizin iv Abteilung Gastroenterologie and HepatologieWaehringer Guertel 18-20A-1090 ViennaAustria Prof.

Introduction:This study was designed to evaluate the safety of fontolizumab,a humanised anti-interferon γ antibody,in patients with moderate to severe Crohn’s disease(CD) .Patients and methods:forty five patients with a CD activity index(CDAI) of 250-450 were randomised in a double blind,placebo controlled,dose escalating fashion to receive single doses of fontolizumab(0.1,1.0,and 4.0 mg/kg) or *** day 29,patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly *** objectives were safety and *** outcomes included assessments of immunogenicity,clinical activity,and potential pharmacodynamic ***:Treatment was generally well *** were slightly more reports of chills,flu-like syndrome,asthenia,nausea,and vomiting in the 1.0 mg and 4.0 mg/kg fontolizumab *** serious adverse events rated as worsening of CD occurred under *** to fontolizumab were confirmed in one *** differences in clinical activity parameters were noted between any of the active treatment groups and placebo,with the placebo group having a particularly favourable outcome(60% response and 40% remission) .By day 29,a more enhanced decrease in median Crohn’s disease endoscopic index of severity(p = 0.02) and serum C reactive protein(prved in the 4.0 mg/kg(n = 14) fontolizumab cohort compared with placebo(n = 10) .Pharmacodynamic effects were observed by ***:fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD.A biological activity of fontolizumab is suggested.

关键词：克罗恩病 fontolizumab 剂量应用干扰素γ 人源化安慰剂对照药效动力学免疫源性免

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first-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen(IPSOS):a phase 3,global,multicentre,open-label,randomised controlled study

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四川生理科学杂志 2023年第8期45卷 1332-1332页

作者： Siow Ming Lee Christian Schulz Kumar Prabhash Department of Oncology University College London Hospitals NHS Foundation Trust CRUK Lung Cancer Centre of Excellence and UCL Cancer Institute London UK Bereich Pneumologie Klinik und Poliklinik für innere medizin II University Hospital Regensburg Regensburg Germany Department of Medical Oncology Tata Memorial Hospital Mumbai India Department of Lung Cancer and Thoracic Tumors Maria Sklodowska-Curie National Research Institute of Oncology Warsaw Poland Department of Lung Diseases Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy Otwock Poland Department of Pulmonary Medicine Shanghai Chest Hospital Shanghai Jiao Tong University Shanghai China Department of Thoracic Oncology LKI Lungenfachklinik Immenhausen Immenhausen Germany Department of Oncology Royal Cornwall Hospitals NHS Trust Truro UK Medical Oncology Department Hospital Universitario Virgen Macarena Seville Spain Department of Medical Oncology The Christie NHS Foundation Trust and Division of Cancer Sciences University of Manchester Manchester UK Department of Medical Oncology AAST H S Gerardo Monza Monza Italy Cho ray Cancer Centre Cho Ray Hospital Ho Chi Minh City Viet Nam Department of Thoracic Oncology National Clinical Research Centre for Cancer Tianjin Medical University Cancer Institute & Hospital Tianjin China Medical Oncology and Hematology Princess Margaret Cancer Centre Toronto ON Canada Department of Oncology National Cancer Institute IRCCS Regina Elena Rome Italy Oncologico Potosino San Luis Potosí Mexico Department of Thoracic Oncology Lungen Clinic Grosshansdorf Airway Research Centre North German Centre for Lung Research Grosshansdorf Germany Department of Medical Oncology Catalan Institute of Oncology Hospital Duran i Reynals L'Hospitalet Barcelona Spain Department of Medical Oncology Instituto do Cancer do Estado de Sao Paulo Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil f Hoffmann-La roche Basel Switzerland Centre Hospita

Background:Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer(NSCLC),pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status(ECOG PS)0-1 and a median age of 65 years or *** aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based ***:This trial was a phase 3,open-label,randomised controlled study conducted at 91 sites in 23 countries across Asia,Europe,North America,and South *** patients had stage IIIB or iv NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3,or alternatively,being 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet *** were randomised 2:1 by permuted-block randomisation(block size of six)to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy(vinorelbine[oral or intravenous]or gemcitabine[intravenous];dosing per local label)at 3-weekly or 4-weekly *** primary endpoint was overall survival assessed in the intention-to-treat *** analyses were conducted in the safety-evaluable population,which included all randomised patients who received any amount of atezolizumab or *** trial is registered with ***,NCT03191786.

关键词： patients platinum random

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