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

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 (<400 ng/ml) (Odds ratio=3.3) and PR as best response to TACE (Odds ratio=6.7) were significantly associated with long term survival (>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 were managed conservatively. The mortality within 6 weeks after TACE was 2.1% (one patient). CONCLUSIONS: DSM and Lipiodol were combined successfully in the palliative TACE treatment of advanced HCC resulting in high rates of tumor response and survival at limited toxicity. Favourable tumor response was associated with tumor extent and vascularization. TACE using DSM and Lipiodol can be considered a suitable palliative measure in patients who might not tolerate long acting embolizing agents.

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

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。

Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma

瞄准：与肝细胞癌(HCC ) 从病人分析树枝状的房间(DC ) 的显型和功能以便在这疾病理解他们的角色。方法：骨髓的的树枝状的房间在 HCC 病人的外部血被枚举。从外部血的天真、刺激的骨髓的的树枝状的房间上的 CD80， CD83， CD86 和 HLA 医生表示被分析。骨髓的的树枝状的房间从外部血被孤立，他们的功能被测试。吞噬作用用 FITC 葡聚糖祷告被分析，肽特殊刺激，在多形核白细胞 dI:dC 之上刺激 allogeneic T 房间和 cytokines 的分泌物的能力被测试。结果：骨髓的的树枝状的房间与 HCC 在病人被减少。在 CD80， CD83， CD86 和 HLA 医生表示的差别都没从 HCC 病人和健康控制在天真、刺激的骨髓的的树枝状的房间上被发现。肽 specific T 房间的正常吞噬作用或刺激与一个损害 allo-stimulatory 能力和减少的 IL-12 分泌物相对照被观察。结论：在病人的 mDCs 的损害 IL-12 生产能导致建议指导治疗可以提高的那 IL-12 的天真的 T 房间的一个损害 stimulatory 能力在 HCC 病人的肿瘤 specific 免疫者回答。

FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus

AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE～TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan～ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P < 0.001).Combined FS/TE had 97% accuracy in Asians(n = 33).Baseline FS(0.38 vs 0.51,P < 0.001)and TE(8.0 kPa vs 11.9 kPa,P = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV.

Successful treatment of cervical esophageal leakage by endoscopic-vacuum assisted closure therapy

AIM: To evaluate the efficacy and safety of endoscopic-vacuum assisted closure (E-VAC) therapy in the treatment of cervical esophageal leakage. METHODS: Between May and November 2012, three male patients who developed post-operative cervical esophageal leakage were treated with E-VAC therapy. One patient had undergone surgical excision of a pharyngo-cervical liposarcoma with partial esophageal resection, and the other two patients had received surgical treatment for symptomatic Zenker's diverticulum. Following endoscopic verification of the leakage, a trimmed polyurethane sponge was fixed to the distal end of a nasogastric silicone tube and endoscopically positioned into the wound cavity, and with decreasing cavity size the sponge was positioned intraluminally to cover the leak. Continuous suction was applied, and the vacuum drainage system was changed twice a week.RESULTS: The initial E-VAC placement was technically successful for all three patients, and complete closure of the esophageal leak was achieved without any procedure-related complications. In all three patients, the insufficiencies were located either above or slightly below the upper esophageal sphincter. The median duration of the E-VAC drainage was 29 d (range: 19-49 d), with a median of seven sponge exchanges (range: 5-12 sponge exchanges). In addition, the E-VAC therapy reduced inflammatory markers to within normal range for all three patients. Two of the patients were immediately fitted with a percutaneous enteral gastric feeding tube with jejunal extension, and the third patient received parenteral feeding. All three patients showed normal swallow function and no evidence of stricture after completion of the E-VAC therapy. CONCLUSION: E-VAC therapy for cervical esophageal leakage was well tolerated by patients. This safe and effective procedure may significantly reduce morbidity and mortality following cervical esophageal leakage.

Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model

AIM To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout(Fah-/-) mice by homologous-recombination-mediated targeted addition of the Fah gene.METHODS C57 BL/6 Fah?exon5 mice served as an animal model for human tyrosinaemia type 1 in our study. The vector was created by amplifying human Fah c DNA including the TTR promoter from a lentivirus plasmid as described. The Fah expression cassette was flanked by homologous arms(620 bp and 749 bp long) of the Rosa26 gene locus. Mice were injected with 2.1 × 108 VP of this vector(r AAV8-ROSA26.HAL-TTR.FahROSA26.HAR) via the tail vein. Mice in the control group were injected with 2.1 × 108 VP of a similar vector but missing the homologous arms(r AAV8-TTR.Fah). Primary hepatocytes from Fah-/-recipient mice, treated with our vectors, were isolated and 1 × 106 hepatocytes were transplanted into secondary Fah-/-recipient mice by injection into the spleen. Upon either vector application or hepatocyte transplantation NTBC treatment was stopped in recipient mice. RESULTS Here, we report successful HR-mediated genome editing by integration of a Fah gene expression cassette into the "safe harbour locus" Rosa26 by recombinant AAV8. Both groups of mice showed long-term survival, weight gain and FAH positive clusters as determined by immunohistochemistry analysis of liver sections in the absence of NTBC treatment. In the group of C57 BL/6 Fah?exon5 mice, which have been transplanted with hepatocytes from a mouse injected with r AAV8-ROSA26.HAL-TTR.Fah-ROSA26.HAR 156 d before, 6 out of 6 mice showed long-term survival, weight gain and FAH positive clusters without need for NTBC treatment. In contrast only 1 out 5 mice, who received hepatocytes from r AAV8-TTR.Fah treated mice, survived and showed few and smaller FAH positive clusters. These results demonstrate that homologous recombinationmediated Fah gene transfer corrects the phenotype in a mouse model of human tyrosinaemia type 1(Fah-/-mice) and is long lasting in a proliferating state of the liver as shown by withdrawal of NTBC treatment and serial transplantation of isolated hepatocytes from primary Fah-/-recipient mice into secondary Fah-/-recipient mice. This long term therapeutic efficacy is clearly superior to our control mice treated with episomal r AAV8 gene therapy approach.CONCLUSION HR-mediated r AAV8 gene therapy provides targeted transgene integration and phenotypic correction in Fah-/-mice with superior long-term efficacy compared to episomal r AAV8 therapy in proliferating livers.

Changes of duplex parameters and splenic size in liver transplant recipients during a long period of observation

AIM: To assess the changes of portal and arterial velocities, resistance index, spleen and liver size during a long observation period (13.7 years) after orthotopic liver transplantation (OLT).METHODS: Two hundred and sixty patients were recruited retrospectively for this study and divided into groups with defined time intervals after OLT. The cross-sectional changes of portal and arterial velocities,resistance index, spleen and liver size between the defined time intervals were studied. The complications detected by ultrasound were compared to gold standard methods.RESULTS: The mean values for liver size were all within the normal range. The splenic size decreased between the time intervals 100 and 1 000 d after OLT (t;P＜0.01).While portal and arterial flow velocities decreased up to 5.5 years (t; portal velocity P＜0.01, maximal systolic velocity P=0.05, maximal end diastolic velocity P＜0.01),RI increased during this interval (t:P＜0.01). Higher RIvalues were found in older patients (r = 0.24, P＜0.001).CONCLUSION: The arterial and portal velocities show adaptation processes continuing over the course of many years after OLT and are reported for the first time. The vascular complications detected by ultrasound occur mostly up to 100 d after OLT.