人工肝支持系统治疗肝功能衰竭的Meta分析

目的 探讨人工肝支持系统对肝功能衰竭的治疗效果.方法 检索国内外1970年1月～2008年6月公开发表的人工治疗肝功能衰竭的相关论文,提取生存率或出院时临床好转率等可以反映远期预后的资料,以风险比(RR)为效应量进行异质性检验和统计量合计分析.结果 共有12篇研究论文入选,共包含肝功能衰竭病例304例.治疗组给予机械型人工肝或生物型人工肝联合常规内科治疗.对照组均给予常规内科治疗.10篇文献讨论了人工肝对肝功能衰竭的疗效,另两篇探讨了生物肝的应用.总体而言,人工肝支持系统对肝功能衰竭的预后有一定程度的改善(RR值0.80,可信区间0.664～0.969,P值0.022),对急性肝功能衰竭的预后基本无改善(RR值0.899,可信区间0.72～1.12,P值0.361)对慢性肝功能衰竭急性加重患者的预后改善明显.(RR值0.57,可信区间为0.39～0.84,P值为0.004).结论 人工肝支持治疗对肝功能衰竭的生存率改善轻微,对慢性肝功能衰竭急性加重者明显降低死亡率.人工肝支持系统类型影响生存率.生物肝对急性肝衰竭或慢性肝功能衰竭急性加重患者都可以降低死亡率.开发生物肝支持系统应是该领域重点研发方向.

Abstract：

Objective To evaluate the effect of artificial and bioartificial liver support systems for management of acute and acute-on-chronic liver failure. Methods Articles documenting randomized clinical trials concerning any liver support systems vs standard conservative therapy, published between January, 1970 and June, 2008, were retrieved by database searching. Of the 1134 articles retrieved, 12 randomized trials involving 479 patients were included. The data were extracted and the trial quality was assessed by 2 independent reviewers. The primary outcome measure was all-cause mortality, and the results were combined on the risk ratio (RR) scale. Results Of the 12 trials included, 10 assessed artificial liver support systems for acute or acute-on-chronic liver failure, and 2 assessed bioartificial systems for acute liver failure. Overall, the liver support systems had moderate effect on mortality compared with standard conservative therapy (RR=0.80; 95% CI 0.664-0.969, P=0.022).Meta-regression indicated that the effect of the support systems depended on the type of liver failure (P=0.00). In stratified meta-analyses, the support systems appeared to reduce the mortality by 43% in acute-on-chronic liver failure (RR=0.57; 95% CI 0.39-0.84, P=0.004), but not in acute liver failure (RRl=0.899; 95% CI 0.72-1.12, P=0.361). Conclusion Artificial liver support systems reduce the mortality of acute-on-chronic liver failure as compared with standard conservative therapy, but have no significant effect on the mortality of acute liver failure. Bioartificial liver support systems lower the mortality rates in both acute and acute-on-chronic liver failure, and should be the future focus of development.     

Clinical Observation of Bevacizumab Combined with S-1 in the Treatment of Pretreated Advanced Esophageal Carcinoma

Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation.
Methods Patients with recurrent or metastatic esophageal cancer after chemoradiation were treated with bevacizumab and S-1. Bevacizumab was used by intravenous infusion, 7.5mg/kg body weight on day 1; S-1 was used by oral at 80mg/m2·d on day 1-14, 21 days as a cycle of treatment and repeated until either pro- gressive disease or intolerable toxicity occurred. Chest CT were performed and RECIST 1.1 was used for response evaluation. Kaplan-Meier method was used for survival analysis. Side effects were recorded and analyzed.
Results Totally 78 patients were enrolled in the study, including 67 squamous cell carcinoma and 11 adenocarcinoma histologically. The overall response (CR+PR) rate was 22.4% (17/76) and disease control (CR+PR+SD) rate was 61.8% (47/76) respectively. The median follow-up time was 20 months (range from 9 to 44 months). The median progression-free survival (PFS) was 4.9 months (95%CI 4.4-5.5) and the median overall survival (OS) was 8.1 months (95%CI 7.6-9.2). The median PFS and OS of patients with metastasis diseases were 6.2 months (95%CI 3.3 to 6.3) and 8.5 months (95%CI 5.8 to 11.2), where PFS was longer than that of patients with local regional recurrence (median 5.0 months, 95%CI 3.0 to 5.5, P=0.017) and OS was longer than that of patients with regional disease and metastasis (median 8.0 months, 95%CI 4.6 to 9.5,P=0.010). The common adverse effects were mild to moderate neutropenia (84.2%), grade I-II hand and foot syndrome (51.3%), grade I-II nausea (48.7%), mild epistaxis (30.1%) and mild vomiting (14.5%). Esophageal bleeding occurred in 7.9% of patients. One patient (1.3%) died from massive bleeding which was caused by esophageal perforation.
Conclusion Bevacizumab combined with S-1 was effective and safe for esophageal cancer patients who had recurrent or metastatic diseases after chemoradiation.     

Cohort Study on Prognosis of Patients with Metastatic Colorectal Cancer Treated with Integrated Chinese and Western Medicine

Objective: To investigate the efficacy of integrated Chinese and Western medicine(IM) in the treatment of metastatic colorectal cancer(m CRC) in a cohort study.Methods: The survival outcome of patients receiving IM was compared with that of patients receiving Western medicine alone.The study design was adopted with "continuous administration of Chinese medicine for 3 months" as the exposure factor.Patients who met this exposure factor were assigned to the IM cohort(Group A,110 patients).Patients who did not meet this exposure factor were assigned to the Western medicine cohort(Group B,225 patients).The overall survival(OS),progression-free survival(PFS),and 1 st year,2 nd year,and 3 rd year survival in the two cohorts were compared.Results: The median OS in Group A and B were 18 months [95% confidence interval(CI) 15–21] and 16 months(95% CI 14–18),respectively,and the median PFS in Group A and B were 6 months(95% CI 4–7) and 5 months(95% CI 4–6),respectively.No statistically significant differences were observed between the groups(P=0.186,P=0.223).Group A demonstrated significantly longer OS and PFS than Group B in the following subgroups: female patients,patients with lesions in the right half of the colon,and those who received first-line treatment(P0.05).In the subgroup of elderly patients(age65 years),the OS in Group A was longer than that in Group B(P0.05).Conclusion: IM could prolong the survival of patients with m CRC.(Registry No.Chi CTR-IOR-17010497)     

Effect of resection following downstaging of unresectable hepatocelluar carcinoma by transcatheter arterial chemoembolization

Background  This retrospective study was undertaken to analyze the outcome of hepatic resection in fifty-two patients with unresectable hepatocellular carcinoma (HCC) between January 2004 and December 2008.

Methods  Among these fifty-two patients, the mean diameter of the tumor was 7.9 cm (4.4–15.5 cm, median 8.5 cm) prior to the first transcatheter arterial chemoembolization (TACE). After 1–6 times of TACE (median 2), the median tumor diameter was reduced to 4.2 cm (0–8.4 cm) prior to resection. The duration between the last TACE treatment and sequential resection varied from one to six months (median 2.7 months). Serum α-fetoprotein (AFP) levels were abnormal in thirty-eight out of the fifty-two patients. In AFP producing HCCs, AFP levels returned to normal (≤400 μg /L) in twenty-five out of thirty-eight patients. Hepatic segmentectomy, multiple hepatic segmentectomy or partial hepatic resection were performed in forty-five patients, two underwent extended left hemihepatectomy, and one underwent right posterior branch portal vein thrombectomy. One patient received a right hemihepatectomy and three had left hemihepatectomies.

Results  Complete tumor radiological response (CR) occurred in five patients (9.6%). There were three cases of perioperative mortality in the fifty-two patients (5.8%). One patient underwent salvaged orthotopic liver transplantation, and twenty-one patients observed tumor recurrence within two years. The 1-, 3- and 5-year survival rates of the fifty-two patients were 77.0% (n=40), 55.0% (n=29), and 52.0% (n=28), respectively. The median survival time after surgery was 49 months (95% confidence interval 7.5–52.7 months).

Conclusions  TACE treatment provides a better chance for HCC resection in  patients initially diagnosed with unresectable HCC. Furthermore, liver resection should be performed once the tumor is downstaged to be compatible for successful resection

     

Different Survival Benefits of Chinese Medicine for Pancreatic Cancer: How to Choose?

Objective:To assess the efficacy of Chinese medicine(CM) on patients with pancreatic cancer(PC) in a retrospective population-based study.Methods:Between January 1,2013,and August 30,2016,according to whether received Western medicine treatment,the patients were included into either integrative medicine(IM) group or CM group.All enrolled patients were orally administrated with Gexia Zhuyu Decoction(膈下逐瘀汤) or Liujun Ermu Decoction(六君二母汤) by syndrome differentiation,twice a day,last for at least 2 months.The primary end point was overall survival(OS).Results:A total of 174 patients with PC were enrolled in this study.In stage Ⅰ/Ⅱ,the median OS was 20.5 months in the IM group [95% confidence interval(CI),12.499 to 28.501] and 11.17 months in the CM group(95% CI,5.160 to 17.180,P=0.015).The 1-and 2-year survival rates for the two groups were 47.0%,40.0% and 21.0%,21.0%,respectively.In stage Ⅲ/Ⅳ,median OS was 13.53 months(95% CI,8.665 to 18.395) in the IM group versus 6.4 months(95% CI,0.00 to 15.682) in the CM group,respectively(P=0.32).The 1-and 2-year survival rate for the IM and CM groups were 27.0%,7.0% and 20.0%,2.0%,respectively.Conclusions:Intervention of CM contributes to the different survival benefits for PC in different stages.Multimodality treatment might be a promising strategy for PC patients in early stage.While,in advanced stage,CM might be an alternative candidate for PC patients.     

Efficacy and Safety of Quxie Capsule (祛邪胶囊) in Metastatic Colorectal Cancer: A Double-Blind Randomized Placebo Controlled Trial

Objective:To verify the efficacy and safety of Quxie Capsule(祛邪胶囊) in patients with metastatic colorectal cancer(mC RC).Methods:The present study was a randomized,double-blind,placebo-controlled trial.Sixty patients with mC RC were randomized into two groups at a 1:1 ratio by sealed envelope.The treatment group received conventional therapy combined with Quxie Capsule for 3 months.The control group was treated with conventional therapy combined with placebo for 3 months.Main outcome measures were overall survival(OS) and progression-free survival(PFS).Subgroup analysis was performed according to age,right or left-sided disease,and second-line therapy to determine the differences in PFS and OS between the two groups.Patients were followed up every 3 months until Dec 31 st 2016.Results:The median OS was 23 months in the treatment group [95% confidence interval(CI):15–not calculated] vs.14 months in the control group(95% CI:11–22,P=0.060).The OS of the treatment group tended to be longer than that of the control group(P0.05).In the subgroups of patients 65 years old,left-sided colon,and 2 nd-line therapy,the treatment group showed a significant survival benefit compared with the control group(P=0.006,0.038,0.013,respectively).There were no significant differences between the two groups in PFS(P0.05).Safety analysis showed no severe hematological toxicity or liver and renal function injury in the treatment group.Conclusions:Quxie Capsule showed good safety and efficacy,and could prolong the OS of patients with mC RC.     

Once- versus twice-weekly Bortezomib induction therapy with dexamethasone in newly diagnosed multiple myeloma

In this study,we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m 2 with dexamethasone(BD) and compared it to the standard 1.3 mg/m 2 twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma(MM).We assessed the difference in efficacy,safety profile and survival between the once-weekly and twice-weekly cohorts(13 vs.24 patients).The over response rate was similar with both arms of the study,being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule(P=0.690).The median overall survival was not reached in either schedule.Also,the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule(8 months vs.10 months,P=0.545 and 6 months vs.7 months,P=0.467 respectively).Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule,but there was no statistically significant difference.This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.     

Effect of radiotherpy techniques (IMRT versus 3D-CRT) on clinical outcomes in patients with glioblastoma multiforme

Objective This study aimed to determine whether intensity-modulated radiotherapy (IMRT) improves clinical outcomes compared with three-dimensional conformal radiotherapy (3D-CRT) for patients with glioblastoma multiforme (GBM). Methods and Materials The records of 54 patients with newly-diagnosed GBM from July 2009 to December 2010 were reviewed. The patients underwent postoperative IMRT or 3D-CRT with concurrent and adjuvant temozolomide. Kaplan-Meier method and log rank test were used to estimate differences of patients’ survival. Results The median follow-up was 13 months. Of the 54 patients, fifty (92.6%) completed the combined modality treatment. The 1-year overall survival rate (OS) was 79.6%. The pattern of failure was predominantly local. A comparative analysis revealed that no statistical difference was observed between the IMRT group (n=21) and the 3D-CRT group (n=33) for 1-year OS (89.6% vs. 75.8%, P=0.795), or 1-year progression-free survival (PFS) (61.0% vs. 45.5%, P=0.867). In dosimetric comparison, IMRT seemed to allow better sparing of organs at risk than 3D-CRT did (P=0.05, P=0.055). However, there was no significant difference for toxicities of irradiation between the IMRT group and the 3D-CRT group. Conclusions Our preliminary results demonstrated that delivering standard radiation doses by IMRT is unlikely to improve local control or overall survival for GBM compared with 3D-CRT. Given this lack of survival benefit and increased costs of IMRT, the utilization of IMRT treatment for GBM needs to be carefully rationalized. Future prospective randomized trials are warrant to validate our results.     

A traditional Chinese herbal medicine compound preparation versus interventional therapy after resection of small hepatocellular carcinoma:22-year follow-up

OBJECTIVE:To compare the long-term effectiveness of compound Ruanjianhugan(RJH)tablets and interventional therapy(IT) in patients after resection of small hepatocellular carcinoma(HCC).METHODS:A retrospective study was conducted in 399 patients after resection of small HCC who were admitted between January 1987 and December 2008 in the Department of Hepatobiliary Surgery and Center of Minimlly Invasive Surgery,First Affiliated Hospital of Guangxi Medical University.Four groups were based on different therapy modes:a TCM-only(TCMO) group,a TCM combined with interventional therapy(TCM-IT) group,an interventional therapy-only(ITO) group,and a simple operation(SO) group.Prognostic factors were correlated with overall survival(OS) and OS rates were calculated with the Kaplan-Meier method,and multivariate analyses for factors affecting survival were evaluated by the Cox proportional hazard model.RESULTS:The median OS was 151.20 months in the TCM-IT group,43.87 months in the ITO group,and 20.77 months in the SO group.All survival rates of the TCMO group were higher than those of the other three groups(>50%).The 5-,10-,and 15-year OS in the TCMO and ITO patients were 83.94%,45.50%,and 71.22% and 33.34%,55.58%,and 9.26%,respectively(risk ratio,0.209;95% confidence interval,0.126-0.347;P=0.000).Multivariate analysis revealed that the independent risk factors were therapy mode(P=0.000),sex(P=0.005),family history(P=0.011),TNM Classification of Malignant Tumor staging(P=0.000),medical care-seeking behavior(P=0.021),and maximum diameter(P=0.030).CONCLUSION:Long-term oral use of compound RJH tablets may improve OS for small HCC after resection compared with IT.     

结合免疫组化标志物和临床病理因素预测子宫内膜癌不同类型复发的预后生存

目的 探讨能够有效预测子宫内膜癌复发患者预后生存的影响因素.方法 回顾性收集2013年10月?2019年5月共473例Ⅰ～Ⅲ期接受了标准手术治疗的子宫内膜癌患者的临床病理数据,术后随访患者复发情况.整体复发包括局部区域复发和不良预后复发.本研究的终点指标为整体复发、局部区域复发和不良预后复发患者的无复发生存(recur...     

动脉栓塞化疗与高强度聚焦超声联合治疗大肝癌的临床疗效

目的 探讨动脉栓塞化疗(TACE)与高强度聚焦超声(HIFU)联合治疗大肝癌的临床应用疗效.方法 68例原发性大肝癌患者分为两组:(1)TACE与HIFU联合组38例,在TACE治疗后2～3周,接受HIFU治疗;(2)单纯TACE组30例.肿瘤最大径5.0～14.5 cm,平均(9.3±3.2)cm,总计88个瘤块,多发病灶者选其中最大径肿瘤为观察目标.两组病例的平均年龄、病灶大小、肿瘤TNM分期以及肝功能分级差异无统计学意义.全部患者随访3～24个月,平均(13±7)个月.观察治疗前后患者临床症状、肿瘤标志物(AFP)、肿瘤影像学(CT或MRI或PET)等变化,对患者进行随访以评估治疗后肿瘤凝固性坏死、肿瘤大小、局部复发率和生存预后.结果 TACE与HIFU联合治疗后患者的临床症状缓解率为90.6%(29/32).TACE与HIFU联合组的肿瘤坏死率为73.7%,肿瘤缩小率为68.4%,单纯TACE组分别为26.7%、33.3%,两组比较,差异有统计学意义(P<0.01).两组局部复发率分别为21.1%、33.3%,二者差异无统计学意义(P>0.05).联合组中位生存期为18个月,明显高于TACE组(10个月),二者差异有统计学意义(P<0.05).结论 TACE与HIFU联合治疗大肝癌的疗效明显优于单纯TACE,可提高肿瘤坏死率并延长患者生存期.     

多参数流式细胞术检测白血病微小残留在急性髓细胞性白血病诱导治疗阶段的临床意义

目的研究急性髓细胞性白血病（AML）患者第1次诱导治疗后和第1次完全缓解时多参数流式细胞术（MFC）监测白血病微小残留（MRD）对预测疾病复发和判断预后的作用,探讨MRD监测的临床价值。方法回顾性研究246例成人AML患者治疗及MRD的监测数据,分析MRD水平与疾病复发和预后的相关性。结果（1）第1次标准方案诱导化疗后,ROC分析确定MRD阈值为1．5×10-2,Cox比例风险模型显示相对于MRD阴性组,MRD阳性组的相对危险度（RR）为2．41。在缓解后采用联合方案化疗的患者中,MRD阳性组和MRD阴性组的中位无复发生存时间（RFS）分别为（19．45±3．74）个月和（56．46±4．28）个月,中位总生存时间（os）分别为（29．37±4．47）个月和（77．97±4．30）个月,差异均有高度统计学意义（均P〈0．01）。（2）第1次达完全缓解时,ROC分析所确定的MRD阈值为3．0×10-3,Cox比例风险模型显示相对于MRD阴性组,MRD阳性组的RR值为1．75。缓解后采取联合化疗,MRD阳性组和MRD阴性组患者的中位RFS分别为（28．36±3．40）个月和（55．70±4．32）个月,中位OS分别为（39．30±3．73）个月和（70．19±4．34）个月,差异均有高度统计学意义（均P〈0．01）。结论MFC检测MRD在AML诱导治疗过程中具有预测复发、判断预后的价值。     

肿瘤灭活对肝硬化伴肝癌患者肝移植前后生存率的影响

目的探讨肝硬化伴肝癌肝移植前等待期经过肿瘤灭活对其移植术后生存率的影响。方法对19例肝硬化伴肝癌病人14例术前用动脉化疗栓塞(TACE)或射频消融(RFA)进行肿瘤灭活并与同组5同期未行肿瘤灭活者比较其对术后肿瘤复发及生存率的影响。结果本组19例,随访6~61月,18例获无瘤存活,其中术前行RFA的4例病理见肿瘤坏死;10例TACE中有9例肿瘤有坏死,已平均存活18.1月。未行治疗的6例中1例于术后4个月骨转移,带瘤存活12个月后死亡。结论肝硬化伴肝癌在移植术前等待期用TACE或射频消融行肿瘤灭活,对提高肝癌肝移植远期疗效、提高术后生存率有显著意义。     

肝细胞癌根治性切除术后辅助性经导管肝动脉化疗栓塞价值的前瞻性研究

目的： 肝切除术是肝细胞癌的最有效治疗方法,但根治性切除术后高复发率是影响预后的最主要因素。肝动脉化疗栓塞（transcatheter arterial chemoembolization ,TACE）是常用的预防肝癌术后肝内复发的手段,但是其真实作用存在较多争议,本研究旨在通过前瞻性队列研究进一步探讨辅助性TACE的价值。方法：2008年1月至2008年12月共220例肝细胞癌患者接受肝切除术。104例符合条件的患者纳入本研究。其中治疗组56例,术后1月接受了辅助性TACE治疗,对照组48例,术后不接受任何辅助性治疗。患者接受定期随访,统计分析术后无瘤生存及总生存情况。结果： 治疗组中位无瘤生存时间为11月（2-38月）,对照组为13月（2-59月）,P=0.005。术后1、2、3年复发率治疗组与对照组分别为：50%、85.7%、89.3% vs. 46.8%、58.3%、62.5%,P=0.005。COX回归多因素分析提示：术后辅助性TACE、AFP、完整包膜、肝硬化、合并肉眼癌栓及肿瘤Edmondson-Steiner分级是影响术后肿瘤复发的危险因素（P<0.05）;治疗组中位生存时间为29月（4-41月）,对照组为24月（5-59月）,P=0.789。术后1、2、3年生存率治疗组与对照组分别为：85.6%、59.5%、36.5% vs. 75%、50%、41.7%,P=0.789。COX回归多因素分析提示：AFP、完整包膜及肿瘤Edmondson-Steiner分级是影响术后生存的危险因素（P<0.05）。结论： 根治性肝切除术后辅助性TACE并不能显著改善肝细胞癌患者的无瘤生存及总生存,甚至可能会弊大于利,因此在治疗方案的选择上应慎重考虑。     

钙调磷酸酶抑制剂减量的吗替麦考酚酯免疫抑制方案对改善肝移植术后肾损害的影响

目的 为了了解肝移植术后,基于钙调磷酸酶抑制剂(CNI)减量的吗替麦考酚酯(MMF)免疫抑制方案改善肝移植术后肾损害的临床效果.方法 我们回顾分析3年内资料完整的124例肝移受体术后CNI相关肾损害发生情况,总结基于CNI减量的MMF免疫抑制方案改善肝移植术后肾损害的临床效果.结果 124例肝移植受体中,有14例(11.29%)发生CNI相关肾损害,其中5例(5/22)发生于环孢素A(CsA)组,9例(9/102)发生于他克莫司(TAC)组,术后发生肾损害的时间为(12.92±9.04)个月(1～31个月).TAC剂量降低约55%[(2.6±1.14)mg/d与(1.1±0.22)mg/d;t=3.000,P=0.040],CsA剂量降低约70%(370±179)mg/d与(105±27);t=3.359,P=0.028,MMF平均剂量为(1.05±0.15)g/d(0.5～1.5 g/d).免疫抑制方案调整后平均随访时间(6.00±3.37)个月(3～14个月),14例肾损害受体血清肌酐从(139±46)μmol/L降到第1、2、3个月的(122±46)μmol/L(t=3.152,P=0.004)、(114±53)μmol/L(t=4.180,P=0.001)和(93±18)μmol/L(t=4.721,P=0.000);肌酐清除率从(52±21)ml/min增加到第1、2、3个月的(63±22)ml/min(t=-3.439,P=0.004)、(69±25)ml/min(t=-4.207,P=0.001)和(79±25)ml/min(t=-6.149,P=0.000).71.43%(10/14)CNI相关肾损害受体血清肌酐水平恢复正常,21.43%(3/14)血清肌酐水平显著降低,7.14%(1/14)死于肾功能衰竭.结论 基于CNI减量的MMF免疫抑制方案能持续显著改善肝移植术后CNI相关肾损害,并具有良好的安全性和耐受性.     

肝移植术后肝内弥漫性胆管狭窄的再次肝移植治疗

目的 探讨肝移植术后肝内弥漫性胆管狭窄行再次肝移植治疗的临床经验.方法回顾性分析中山大学附属第一医院2001年1月至2009年12月施行的53例再次肝移植患者的临床资料,其中因首次肝移植术后肝内胆管弥漫性狭窄行再次肝移植手术患者20例(20/53).分析其预后及影响因素.结果 20例术后肝内胆管弥漫性狭窄的发生时间为首次肝移植术后3～16个月,平均6.3个月.胆道狭窄的类型包括肝内弥漫性胆管狭窄16例,肝内外胆管多发性狭窄者4例;20例患者术前均经介入及其他综合治疗无效,行再次肝脏移植.行再次肝移植20例患者中,14例获治愈.6例死于围手术期合并症,其中严重腹腔感染和多脏器衰竭3例,胆瘘 2例,血管合并症(肝动脉栓塞)1例.术后随访1～5年,平均1.8 年;术后1、6个月和1年的累计生存率分别为80.0%、75.0%和70.0%.结论 再次肝移植是挽救肝内弥漫性胆管狭窄无法介人治疗或介入治疗失败的最终治疗手段;把握最佳手术时机和提高手术技巧,以及有效防治围手术期感染是提高该类患者生存率的关键.

Abstract：

Objective To investigate the feasibility and management of retransplantation for diffuse biliary strictures occurring after initial liver transplantation.Methods The clinical data of 53 consecutive liver retransplantation patients at our hospital from January 2001 to December 2009 were collected and analyzed retrospectively. Among them, 20 (37.7%) were due to diffuse biliary strictures.Results Diffuse biliary strictures appeared at 3-16 months after initial transplantation. The mean time was 6.3 months. The specific types included intra-hepatic diffuse biliary strictures (n=16) and multi-strictures involving both intra- & extra-hepatic biliary ducts (n=4). Retransplantation was performed after a failure of intervention or/and other comprehensive treatments. Among them, 14 were cured and 6 died from peri-operative complications including serious abdominal infection & MODS (multiple organ dysfunction syndrome) (n=3, 50%), biliary fistula (n=2, 33.3%) and hepatic artery embolism (n=1, 16.7%). These patients were followed up for a mean time of 1.8 years (range:1-5 years). The accumulative survival rates at 1, 3 and 6 months were 80.0%, 75.0% and 70.0% respectively.Conclusions Liver retransplantation is the ultimate treatment for diffuse biliary strictures after liver transplantation. The survival rate is associated with operative timing, surgical techniques and peri-operative management.     

雷帕霉素对符合米兰标准的肝细胞癌肝移植患者生存的影响

目的探讨雷帕霉素对符合米兰标准的肝细胞癌（HCC）肝移植患者生存的影响。方法回顾性分析2004年11月至2012年1月北京佑安医院移植中心收治的90例符合米兰标准的HCC肝移植患者的临床资料。按患者是否加用雷帕霉素分为两组。对照组45例,初始免疫抑制方案为：他克莫司（FK506）＋吗替麦考酚酯（MMF）＋甲泼尼龙（Pred）;维持期免疫抑制方案为：FK506＋/-MMF。雷帕霉素组45例,初始免疫抑制方案同对照组;维持期免疫抑制方案为：FK506＋雷帕霉素。比较两组患者术后生存时间、生存率、无瘤生存率和肿瘤复发率。结果至随访结束时,对照组45例,死亡11例,其中因肿瘤复发死亡9例;雷帕霉素组45例,死亡4例,其中因肿瘤复发死亡2例。对照组术后平均生存时间（72.6±5.8）月,明显低于雷帕霉素组[（84.0±4.0）月,差异有统计学意义（P〈0.05）。对照组和雷帕霉素组术后1、2、3、5年的生存率分别为86.5%和97.8%（P=0.11）,76.5%和97.8%（P〈0.05）,73.6%和91.2%（P=0.06）,73.6%和87.0%（P=0.20）;术后1、2、3、5年的无瘤生存率分别为81.6%和97.7%（P〈0.05）,73.7%和97.7%（P〈0.05）,73.7%和88.1%（P=0.15）,73.7%和88.1%（P=0.15）;术后1、2、3、5年的肿瘤复发率分别为13.3%和2.2%（P=0.11）,18.6%和2.2%（P〈0.05）,21.6%和2.2%（P〈0.05）,21.6%和6.8%（P=0.06）。结论雷帕霉素能够显著提高符合米兰标准的HCC患者肝转移术后生存时间,降低肿瘤复发率并提高其术后生存率。     

Loss of membranous carcinoembryonic antigen-related cell adhesion molecule 1 expression is related to decreased relapse-free survival of hepatocellular carcinoma following liver transplantation

Background  Loss of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression is an adverse prognostic factor in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival (RFS) following liver transplantation (LT) for HCC.

Methods  Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed.

Results  Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum α-fetoprotein levels (all P <0.05). Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis (P=0.027). Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation (P=0.037).

Conclusion  Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.

     

符合Milan标准肝细胞癌患者行肝移植和肝切除术预后分析

目的比较符合Milan标准肝细胞癌患者行肝移植和肝切除术后的生存和复发情况,分析影响患者肿瘤复发转移的相关危
险因素。方法回顾性分析南方医院从2006年1月~2011年12月88例符合Milan标准肝细胞癌患者行肝移植或肝切除术的临床
资料,比较两种术式的生存率及无瘤生存率;对围手术期的12个变量进行单因素分析,筛选影响术后肿瘤复发和转移的危险因
素。结果移植组患者1、3、5 年生存率与切除组差别无统计学意义（P>0.05）;移植组患者1、3、5年无瘤生存率优于切除组（P<
0.05）;肝移植组肿瘤复发率明显低于肝切除组（P<0.05）;多因素分析提示性别、肿瘤大小、肿瘤病理分化程度、镜下微血管癌栓
是影响无瘤生存率的重要预后因素。结论治疗符合Milan标准肝细胞癌,肝移植比肝切除能获得较长的无瘤生存时间;男性、
肿瘤直径越大、有镜下血管癌栓、肿瘤病理分化程度低的患者术后更容易发生肿瘤复发和转移。