中国《胰腺癌诊疗规范(2011年版)》解读——几个外科相关问题

2011年底,为规范我国胰腺癌临床诊疗行为,进一步提高我国医疗机构胰腺癌诊疗水平,保障医疗质量和医疗安全,提高我国胰腺癌患者的生存率,降低病死率,卫生部组织专家制定并颁布了《胰腺癌诊疗规范(2011年版)》.本文针对此规范的几个外科相关问题予以解读. 一、关于《胰腺癌诊疗规范(2011年版)》 本规范的制定以基于循证研究的各种指南及共识为背景,尽可能与之接轨,但考虑到国情及可操作性,亦者在不一致处.由于对疾病本身的认知有限,不确定的因素较多,对很多学术问题的认识尚存很大争议,需要将来的临床研究予以明确,因而由学术角度,本规范之内容有可能存在不确切或不准确之处,有待于将来的进一步完善、更新乃至更正.     

肝移植术后远期胆道并发症的研究进展

胆道并发症被称为肝移植患者的"阿喀琉斯之踵",是严重影响患者生活质量和远期生存的重要因素.国外报道发生率为5％～15％[1],我国的大多数中心在开展肝移植初期都经历了胆道并发症发生率高的过程,文献报道发生率可达40％[2].近年来随着对胆道并发症发病机制的深入理解和预防措施的实施,胆道并发症的发生率已经有了显著下降.我们结合北京大学人民医院肝移植中心的工作经验,对远期胆道并发症做一综述.     

卫生部《原发性肝癌诊疗规范(2011年版)》解读

原发性肝癌是严重危害人类生命健康的重大疾病之一.据2008年最新统计,每年全球新患肝癌人数为74.8万人,因肝癌死亡者高达69.6万人,位居全球男性和女性恶性肿瘤发病率的第5位和第7位,而死亡原因高居第2位和第6位[1].全球新发肝癌病例中有50％发生在中国[2],我国的肝癌诊疗形势十分严峻.根据卫生部统计,我国肝癌死亡率在各种癌症死亡率中居第2位.国际上有多个治疗原发性肝癌的指南,例如,美国国立综合癌症网络( National Comprehensive Cancer Network,NCCN)、美国肝病学会(American Association for the Study of Liver Diseases,AASLD)、巴塞罗那肝癌小组(Barcelona-Clinic Liver Cancer Group,BCLC)、亚太肝病学会(Asian Pacific Association for the Study of the Liver,APASL)、日本肝病学会(Japan Society of Hepatology,JSH)制定的治疗指南等,但由于中国肝癌患者的特殊性,这些指南没有一个能被我国医生完全接受[3].     

大鼠库普弗细胞分离培养方法的改良

目的建立一种稳定、高效的大鼠库普弗细胞(KCs)分离培养方法。方法采用大鼠肝脏离体链酶蛋白酶E消化和胶原酶循环灌注消化。低速离心去除肝细胞,Histodenz不连续密度梯度离心和选择性贴壁的方法分离KCs。采用ED2 CD163、兔抗大鼠溶酶体膜相关蛋白2(LAMP2)免疫细胞化学．latex-beads吞噬实验和电镜观察来鉴定 KCs。结果KCs得率为5×107个,活率为98％,经鉴定ED2阳性细胞大于98％,LAMP2阳性细胞大于99％,吞噬试验及电镜观察证明分离所得为KCs。结论改良的分离培养方法稳定、高效,为进一步的研究打下了基础。     

他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.     

重组腺病毒Ad-PD-L1转染供体小鼠树突状细胞对受体小鼠淋巴细胞激活的影响

目的:观察重组腺病毒载体Ad-PD-L1转染供体C57BL/6(H-2b)小鼠树突状细胞(DC)对受体DBA/2(H-2d)小鼠淋巴细胞增殖和激活的影响.方法:构建腺病毒穿梭质粒pShuttle-GFPCMV(-)-PD-L1和腺病毒骨架质粒pAdxsi-GFP-CMV-PD-L1,重组腺病毒Ad-PD-L1进行包装、扩增和纯化.分离培养供体C57BL/6小鼠的DC,分为3组:腺病毒载体Ad-PD-L1转染组(A组),空载体转染组(B组)和对照组(C组).Western blot检测转染后各组细胞PD-L1的表达.分离受体DBA/2小鼠的淋巴细胞,用羧基荧光素二醋酸琥珀酰亚胺酯(CFSE)标记,将供体C57BL/6小鼠的DC和受体DBA/2小鼠淋巴细胞混合培养,流式细胞仪观察淋巴细胞的增殖情况.结果:酶切及测序证实含PD-L1的重组腺病毒载体Ad-PD-L1构建成功.转染供体C57BL/6小鼠的DC后其PD-L1的表达升高37% (P<0.05),将转染了PD-L1的DC与受体DBA/2小鼠的淋巴细胞进行共培养.与对照组相比,PD-L1表达升高后,明显地抑制了淋巴细胞的增殖和活化.受体DBA/2小鼠的淋巴细胞增殖降低41% (P<0.01).结论:转染供体C57BL/6小鼠DC后通过共刺激通路PD-1/PD-L1抑制了受体DBA/2小鼠淋巴细胞的增殖和激活.     

他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.     

通过PD-1/PD-L1共刺激通路诱导小鼠胰岛移植免疫耐受的研究

目的 观察重组腺病毒Ad-PD-L1对诱导小鼠胰岛移植免疫耐受的作用.方法 酶切含有小鼠全长PD-L1 cDNA的pSport 1-mCD274质粒,亚克隆到穿梭质粒pShuale-GFP-CMV(-)上,再通过酶切、连接等方法构建腺病毒骨架质粒pAdxsi-GFP-CMV-PD-L1,转化DH5α感受态细菌,筛选阳性克隆.经酶切、测序鉴定正确,线性化后脂质体法转染293细胞进行包装、扩增,氯化铯密度梯度离心纯化病毒.链脲霉素(250 mg/kg)腹腔注射诱导C57BL/6(H-2b)小鼠糖尿病模型,将C57BL/6小鼠随机分为3组,A为对照组,B为Ad-EGFP处理组,C为Ad-PD-L1处理组,在进行胰岛移植的前1天,经尾静脉输注5×108 pfu的Ad-PD-L1.将DBA/2(H-2d)小鼠的胰岛移植在糖尿病小鼠肾被膜下.术后监测不同时间各组小鼠的血糖变化及胰岛移植物的存活时间,并观察混合淋巴细胞反应的特异性.结果 酶切及测序证实Ad-PD-L1构建成功.Ad-PD-L1在小鼠体内可以高效地表达PD-L1,Ad-PD-L1治疗组胰岛移植物的存活时间明显延长到27.63±3.51 d(P<0.01),混合淋巴细胞反应表明小鼠对供体反应特异性降低. 结论通过PD-L1/PD-1共刺激通路可以抑制T细胞的活化,从而延长了胰岛移植物的存活时间.     

腹腔镜肝切除术中螺旋水刀的应用

目的 评价螺旋水刀在腹腔镜肝切除术中应用的可行性.方法 回顾性分析18例行腹腔镜肝切除患者的临床资料.结果 本组患者18例,其中肝海绵状血管瘤9例,原发件肝癌5例,肝局灶性结节样增生2例,结肠癌肝转移1例,左肝胆管囊腺瘤1例.本组17例患者行腹腔镜下水刀肝切除术,1例左肝癌患者因术中出血而中转开腹.手术方式为肝部分切除术14例,肝左外叶切除3例.手术时间平均170 min.无巾转开腹的17例病例术中平均出血最230 ml.伞组患者无术后出血、肝功能衰竭等严重并发症,有1例患者术后第3天出现少量胆漏,保守治疗后痊愈.2例患者术后出现少量胸腔积液未做特殊处理.术后平均住院5.6 d.5例肝癌病例术后平均随访17个月,中转开腹的患者术后13个月肝内其他部位复发,所有切门均未见种植转移.结论 腹腔镜下应用螺旋水刀行肝切除时创面清晰,可以保证足够的安全切除边界,术后无严重并发症,是一种安全可行的切肝方法.     

肝移植术后并发移植后淋巴增生性疾病

1临床资料患者男,14岁.因原位肝移植术后1年、皮肤和巩膜黄染1周入院.患者于1年前因乙型病毒性肝炎后肝硬化失代偿,门静脉高压症于我院行原位背驮式肝移植术,术后恢复顺利.1年以来患者肝功能正常,他克莫司( FK506)血药浓度维持在6 ～ 10 μg/L,入院前每日服用FK506 2 mg.患者1周前无明显诱因出现皮肤和巩膜黄染,伴皮肤瘙痒,尿色加深,大便颜色变浅,为求进一步诊断和治疗遂来我院.发病以来患者精神、睡眠好,食欲稍差,体质量无明显变化.