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Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver

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World Journal of Gastroenterology 2005年第8期11卷 1091-1095页

作者： Timm Kirchhoff Lars Zender Sonja Merkesdal Bernd Frericks nisar malek Joerg Bleck Stefan Kubicka Stefan Baus Ajay Chavan Michael P.Manns Michael Galanski Department of Diagnostic Radiology Department of Gastroenterology Division of Rheumatology Department of Radiology and Nuclear Medicine

AIM: In nonresectable cholangiocellular carcinoma (CCC)therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%.Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver.METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m2) and additional transarterial chemoembolization procedures (50 mg/m2cisplatin, 50 mg/m2 doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity.RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO Ⅲ/Ⅳ) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered.Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases,stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo.CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect

关键词：化学疗法胆管细胞癌肝脏全身联合治疗

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Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival

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Hepatobiliary & Pancreatic Diseases International 2007年第3期6卷 259-266页

作者： Timm D Kirchhoff Joerg S Bleck Arne Dettmer Ajay Chavan Herbert Rosenthal Sonja Merkesdal Bernd Frericks Lars Zender nisar P malek Tim F Greten Stefan Kubicka Michael P Manns Michael Galanski Department of Diagnostic Radiology Hannover Medical School Germany Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School Germany Department of Diagnostic and Interventional Radiology Klinikum Oldenburg Germany Division of Rheumatology Hannover Medical School Germany Department of Radiology and Nuclear Medicine Campus B.F-Charité-University Medicine Berlin Germany

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics,toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size ≤75 mm, tumor number ≤5, and tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications

关键词： carcinoma, hepatocellular transarterial chemoembolization degradable starch microspheres Lipiodol tumor response survival

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Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12

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World Journal of Gastroenterology 2016年第35期22卷 8050-8059页

作者： Christoph R Werner Julia M Schwarz Daniel P Egetemeyr Robert Beck nisar P malek Ulrich M Lauer Christoph P Berg Department of Gastroenterology Hepatology and Infectiology University Hospital Tübingen Institute of Medical Virology University Hospital Tübingen

AIM To gather data on the antiviral efficacy and safety of second generation direct acting antiviral(DAA) treatment with respect to sustained virological response(SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this setting.METHODS Two hundred and sixty patients treated with SOF combination partners PR(n = 51), R(n = 10), SMV(n = 30), DCV(n = 81), LDV(n = 73), or 3D(n = 15).144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets < 100/nL, 25/260 had a MELD score ≥ 10 and 17/260 were postliver transplantation patients. 194/260 had HCV GT1, 44/260 HCV GT3.RESULTS Two hundred and forty/256(93.7%) patients achieved SVR12(m ITT); 4/260 were lost to follow-up. SVR12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/PR, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets < 100/n L, 88% post-liver transplantation, 95% for GT1 a, 93% for GT1 b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVR12 were a platelet count < 100/nL, MELD score ≥ 10(P < 0.0001), liver cirrhosis(P = 0.005) at baseline. In Interferonfree treatment GT3 had significantly lower SVR rates than GT1(P = 0.016). Side effects were mild. CONCLUSION Excellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into "real-world". Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/n L and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure.

关键词： Sofosbuvir Simeprevir Ledipasvir 丙肝肝移植持续 virological 反应肝肝硬化副作用抵抗 Daclatasvir

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Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第23期12卷 3707-3715页

作者： Arne Dettmer Timm D Kirchhoff Michael Gebel Lars Zender nisar P malek Bernhard Panning Ajay Chavan Herbert Rosenthal Stefan Kubicka Susanne Krusche Sonja Merkesdal Michael Galanski Michael P Manns Joerg S Bleck Department of Gastroenterology Hepatology and EndocrinologyHannover Medical SchoolGermany Department of Diagnostic Radiology Hannover Medical SchoolGermany Department of Anaesthesiology Hannover Medical SchoolGermany Department of Diagnostic and Interventional Radiology Klinikum OldenburgGermany S Bleck Department of GastroenterologyHepatology and EndocrinologyHannover Medical SchoolGermany Division of Rheumatology Hannover Medical SchoolGermany

瞄准：为病人评估经皮的乙醇注射(PEI ) 的治疗效果与先进， non-resectable HCC 与 transarterial chemoembolisation 的联合相比(不作声) 并且重复单个会议的 PEI，独自重复了单个会议的 PEI，重复不作声独自一个，或最好的支持的照... 详细信息

瞄准：为病人评估经皮的乙醇注射(PEI ) 的治疗效果与先进， non-resectable HCC 与 transarterial chemoembolisation 的联合相比(不作声) 并且重复单个会议的 PEI，独自重复了单个会议的 PEI，重复不作声独自一个，或最好的支持的照顾。方法：在学习时期期间接受了 PEI 治疗的所有病人根据物理地位和肿瘤程度被包括并且成层到下列治疗形式之一：联合不作声并且重复单个会议的 PEI，独自重复了单个会议的 PEI，重复不作声独自一个，或最好的支持的照顾。包括Okuda分类，门静脉血栓的存在，腹水的存在，肿瘤的数字，最大的肿瘤直径，和假胆硷酯酶( CHE )的临床的参数的预示的价值，以及孩子呸上演， alpha-fetoprotein (法新社)，发烧，复杂并发症的发生在这些组之间被估计并且比较。幸存用 Kaplan-Meier 被决定，多，变量回归分析。结果：所有病人的 1 年、 3 年的幸存是 73% 和 47% 。在亚群分析，联合不作声， PEI (1 ) 与更长的幸存被联系(1- ， 3- ， 5 年的幸存：90% ， 52% ，和 43%) 与 PEI 治疗相比独自一个(2 )(1- ， 3- ， 5 年的幸存：65% ， 50% ，和 37%) 。(3 ) 在起始的层化以后的第二等的 PEI 产出可比较的结果不作声(1- ， 3- ， 5 年的幸存：91% ， 40% ，和 30%) 当在到最好的支持的照顾(4 ) 的层化以后的 PEI 与减少的幸存被联系时(1- ， 3- ， 5 年的幸存：50% ， 23% ， 12%) 。除了选择治疗形式，为更好的幸存的预言者是肿瘤数字(n < 5 ) ，肿瘤尺寸(< 5 厘米) ，在 PEI 前的没有腹水，和在 PEI 以后的稳定的假胆硷酯酶(P < 0.05 ) 。在在 PEI 以后的 2 wk 以内的死亡是 2.8%(n = 3 ) 。有 24 (8.9%) 主修在包括部分肝梗塞，焦点的肝坏死，和肝脓肿的 PEI 以后的复杂并发症。所有复杂并发症能非通过手术被管理。结论：重复单个会议的 PEI 在有以可接受、可管理的复杂并发症率的先进 HCC 的病人是有效的。病人们成层到联合不作声， PEI 能比那些独自成层到重复 PEI 期望更长的幸存。而且，有在好临床的地位的大或多重的肿瘤的病人可以也从联合获利不作声并且为第二等的 PEI 的再考虑。

关键词：经皮注射乙醇肝细胞癌疾病预防

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