复杂肝胆管结石病3D技术指导下外科综合诊疗效果的评价研究
|
摘要
研究背景
复杂肝胆管结石病(Complicated Hepatolithiasis)的概念目前尚未统一。对于肝胆管结石病,尤其对实施再次手术处理持有不同经验者而言,对概念的认识不尽一致。目前国内外多数学者认为,复杂肝胆管结石病是指除去病人全身情况,因为其他系统疾病如心脏、肺、肾脏、糖尿病等构成胆道手术威胁外,存在以下病情者视为复杂肝胆管结石病：(1)肝胆道结石病经历一次或以上胆道手术,但肝内胆管结石残留、复发或反复胆管炎发作需再次接受手术；(2)既往接受不适当的胆道手术,如接受各类胆肠吻合术后吻合口狭窄需要再次手术者；(3)两侧肝叶均弥漫分布肝内胆管结石；(4)肝内胆管结石病合并高位胆道狭窄或Caroli病；(5)肝内胆管结石病合并胆汁性肝硬化、门静脉高压症；(6)肝内胆管结石病合并胆管细胞癌(梁力建,李绍强.复杂肝胆管结石诊断和治疗原则[J].中国实用外科杂志.2009;29(7)：542-544.)。
复杂肝胆管结石病是胆道外科中最难治疗且再手术率最高的良性疾病。复杂肝胆管结石病的基本病理改变是肝内胆管扩张与狭窄,合并胆道机械性梗阻、胆道感染和肝实质组织损害。这一病理本质贯穿于复杂肝胆管结石病病理演变的全过程,与肝胆管结石和胆道狭窄的发生发展有密切的关系。临床上有关肝胆管细胞癌的报告显示：反复多次发作的胆道感染,可能是导致胆道病变性质的改变,诱发胆管细胞癌。根据对复杂肝胆管结石病上述病理演变认识,Ong等早于1962年提出了复杂肝胆管结石病外科治疗原则：“详尽了解胆管病理改变,根除结石、狭窄及包含复发感染灶的病变肝段组织”。其方案与黄志强院士提出的“取尽结石、解除梗阻、去除病灶、通畅引流”可谓不谋而合。因为肝胆管结石病的病灶不仅是肝胆管系统内堆积的结石,往往伴有发生在肝内各级肝管中的狭窄及增生性病灶,这是治疗的核心,而外科治疗则仍是达到这一治疗目的最有效、最常用的方法。手术方案的选择必须个体化,根据肝内胆管结石的数量及分布范围、胆道狭窄的部位和程度、肝脏的病理改变、肝功能状态及患者的全身状况,制定针对性的个体化治疗方案并选择合适的手术方法。
尽管在近20年来对复杂肝胆管结石病的认识和治疗有了明显的进步,但由于其复杂的病理生理过程和术中术后容易出现严重并发症的特点,复杂肝胆管结石病的诊治仍然是困扰胆道外科医生的难题。对于复杂肝内胆管结石病患者应尽量获取详尽的患者影像学资料和肝功能评估等实验室检查资料,做好充足的术前准备工作。术前对胆道系统的解剖,肝内胆管结石的位置、分布、数量,狭窄胆管的部位、形态等应有准确的诊断评估,并且要注意有无变异的肝内胆管,特别是右后叶胆管的变异,如右后叶胆管直接汇入左肝管。对于变异的右后叶胆管结石,由于汇入的角度成锐角,单凭取石钳取石或术中胆道镜取石往往很难取净结石,这是造成术后右后叶结石残留的重要解剖因素(Mori T, Sugiyama M, Atomi Y. Gallstone disease:Management of intrahepatic stones[J]. Best Pract Res Clin Gastroenterol,2006,20(6):1117-1137.)。同时,应充分了解既往手术情况、手术原因和方法,以及目前病变的具体情况极为重要,从而制订出再次手术的个体化外科治疗方案。任何匆忙决定的手术方案可能会导致更多次的手术可能,令病人遭受更大的痛苦。
近年来,伴随着腹腔镜技术、内镜技术及介入技术的发展应用,多种微创性治疗手段已被广泛报道,如经皮经肝穿刺胆道镜碎石术和胆道镜联合钬激光或气压弹道碎石,对一般的肝胆管结石取得了令人瞩目的疗效,但是对于复杂肝胆管结石病其术后残石率却高达20%-50%(Cheng Y F, Lee T Y, Sheen-Chen S M, et al. Treatment of complicated hepatolithiasis with intrahepatic biliary strictureby ductal dilatation and stenting:long-term results[J]. World J Surg,2000,24(6):712-716.).上述内镜治疗技术对于复杂肝胆管结石病的治疗尚有争论,仍然缺乏大宗病例证据。
目前,复杂肝胆管结石病的诊断手段主要依靠B超、CT和MR等无创性影像学检查,以明确结石的部位、大小、数量和分布情况,胆管狭窄的部位及程度,从而进行定位诊断；并结合患者肝功能状况、Oddi括约肌功能、有无肝胆管炎发作、有无梗阻性黄疸、有无肝门部胆管狭窄、有无门静脉高压症和脾肿大等综合因素制定手术方案。但由于复杂肝胆管结石病肝内胆管结石的分布广泛,同时合并不同程度的肝胆管狭窄和肝脏毁损性病变,上述各种影像学检查手段各有优势和不足,常需多种影像学检查方法的综合运用,才能做出较为全面的诊断。目前尚无一种理想的诊断方法能够同时对结石大小、数量和分布,胆管狭窄程度和长度,肝脏病理形态,以及胆管和血管的关系做出系统全面的诊断。
随着计算机科学的发展,基于CT或MRI的三维重建技术已经广泛应用于肝胆外科临床诊治活动中,其虚拟手术规划系统可以帮助肝胆外科医生在术前提前进行手术模拟操作,制定出个体化的手术方案,进而减少实际手术中的无意义损伤,提高实际手术的安全性。目前国内外已有多个数字化肝胆外科虚拟手术系统应用于临床的报道,其指导临床外科治疗效果满意。但是,数字医学技术应用于肝胆管结石病的临床研究仍处于早期应用阶段,相关文献报道不多,缺乏大宗病例临床评价证据。而且,针对大宗病例的复杂肝胆管结石病三维重建技术(3D技术)指导下外科诊疗效果的系统评价尚未见文献报道。
基于上述问题,本课题收集南方医科大学珠江医院肝胆一科2008年6月至2013年12月收治的复杂肝胆管结石病患者高质量亚毫米CT数据基础上,利用具有自主研发的腹部医学图像三维可视化系统(Medical Image Three-Dimensional Visualization System, MI-3DVS)(软件专利号：2008SRl8798),构建针对具体个体的复杂肝胆管结石病程序化3D诊疗模式,系统探讨3D技术指导下外科综合诊疗模式在复杂肝胆管结石病临床应用价值和意义。
一、复杂肝胆管结石病患者三维重建数据库系统的构建
目的：
1.优化CT数据采集方法,获取高质量复杂肝胆管结石病患者亚毫米CT数据；
2.研究基于体绘制交互的分割新算法,构建活人体复杂肝胆管结石病患者模型数据库；
3.利用ResMan临床试验公共管理平台构建复杂肝胆管结石病患者三维重建数据库系统
4.探讨复杂肝胆管结石病患者三维重建数据库系统的临床应用价值
方法：
1.研究对象：逐步收集南方医科大学珠江医院肝胆一科2008年6月至2013年12月收治的复杂肝胆管结石病患者病例资料。
2.数据采集设备：
(1)64排/256层螺旋CT-PHILIPS Brilliance(荷兰PHILIPS公司)；双筒高压注射器及造影剂(碘比乐370mgI/ml)。
(2)图像后处理工作站为PHILIPS Brilliance层螺旋CT自带的Mxview工作站；
(3)南方医科大学数字医学临床中心HP刀片式服务器、高配置计算机；
(4)腹部医学图像三维可视化系统；
3.高质量肝胆管结石亚毫米CT数据采集方法参考(Fang C H, Liu J, Fan Y F, et al. Outcomes of hepatectomy for hepatolithiasis based on3-dimensional reconstruction technique[J]. J Am Coll Surg,2013,217(2):280-288.)。
4.复杂肝胆管结石3D模型构建方法：
(1)基于体绘制交互的图像分割算法：先进行体绘制重建,通过对窗宽和窗位的调节,得到所需胆道结构最清晰的三维图像,直接在体绘制图像上取得三维种子点,进行区域生长,同时在体绘制图像上显示生长的过程,当生长停止时可以通过人机交互,在体绘制三维图像上进行修补。特别对于三级以上胆管,通过局部放大,并对断续胆管进行连接,再进行分割,可以把局部小胆管提取出来。使得组织分割,特别对肝内胆管分割更精细,达到与体绘制相同的分辨率水平。当用户满意当前分割结果时可以立即将当前的分割结果保存,并进行快速的面绘制三维重建。
(2)把基于体绘制交互的分割算法作为一个分割插件整合到腹部医学图像三维可视化系统(MI-3DVS)中,将DICOM格式的亚毫米CT数据导入到MI-3DVS中进行配准、分割、三维重建。
①肝内胆管、胰腺等腹腔脏器重建：使用区域生长法完成分割,采用面绘制方法进行脏器三维重建。
②肝内主要血管三维重建：使用基于体绘制交互的分割算法完成对亚毫米CT断层图像中的血管数据分割,采用面绘制方法进行脏器三维重建。
(3)3D模型的后处理及立体结构观察分析
通过MI-3DVS中的面数据图形处理工具对3D模型进行平滑和去噪,然后将肝内胆管系统3D模型在空间上组合和显示,通过放大、缩小、旋转可视化3D模型来观察、分析肝内胆管病变的分布特点。
5.利用ResMan临床试验公共管理平台构建复杂肝胆管结石病患者三维重建数据库系统
根据中国临床试验中心临床研究电子管理公平台(Research Manager, ResMan)指引(中国临床试验注册中心公告[J].中国循证医学杂志,2007(08)：557-558.),制定复杂肝胆管结石病3D技术指导下外科综合诊疗临床试验的管理流程。利用设计好的流程,将外科诊疗过程中记录的受试者基线资料包括人口学资料和入组时影像学检查及3D基线数据、临床外科试验过程中的实施情况、结果数据等相关资料即“复杂肝胆管结石病3D技术指导下外科综合诊疗临床试验病例记录表(case record form, CRF)'’的所有内容,基于互联网在线记录并传送到中央数据库保存管理。
结果：
1.使用试验注射法采集的亚毫米CT数据图像质量高,胆道系统、肝胆管周围血管、胆道的病变显示清晰。
2.复杂肝胆管结石病患者3D模型立体感强,可清晰地再现患者肝脏的立体形态和有无肥大和萎缩；肝内一、二、三级胆管树立体形态及狭窄或扩张胆管的长度和直径显示清晰,部分肝内胆管结石合并肝内胆管广泛扩张者,甚至四级胆管(亚肝段胆管)也可以得到显示；结石的大小、数量及其在肝内外胆管的分布,门静脉、肝静脉及肝动脉三套血管及其分支在肝内的立体分布等情况也清晰可见。
3.成功建立基于ResMan临床试验公共管理平台的复杂肝胆管结石病3D技术指导下外科综合诊疗公共数据库(public accessable database)。实现试验研究者方便地保存和管理试验资料,免除使用纸张记录,减少集中录入数据的错误可能性和工作量,提高记录可靠性,利于提高临床试验质量。
4.复杂肝胆管结石病3D技术指导下外科综合诊疗公共数据库(public accessable database)达到中国临床试验中心的规范要求,成功完成临床试验的注册。
结论：
1.采集方法优化后的64排/256层螺旋CT可以获得高质量的复杂肝胆管结石病患者亚毫米CT数据,各级胆管系统显影良好,能够区分出微细结构的影像学特征,能满足胆管三维重建分割、三维重建的要求。
2.复杂肝胆管结石病患者3D模型能对肝内结石的分布,胆管狭窄程度和分布,肝脏病理形态改变作出准确系统全面的诊断。
3.基于ResMan I临床试验公共管理平台的复杂肝胆管结石病3D技术指导下外科综合诊疗公共数据库提高记录可靠性,利于提高复杂肝胆管结石病3D技术指导下外科综合诊疗临床试验的评价质量。
二、复杂肝胆管结石病患者3D模型在临床诊疗中的应用研究
目的：
1.探讨复杂肝胆管结石病患者3D模型对肝内病变诊断的应用价值。
2.研究复杂肝胆管结石病患者3D模型在指导复杂肝胆管结石病外科综合治疗术前规划,术式决策的应用价值。
3.研究复杂肝胆管结石病患者3D模型在指导复杂肝胆管结石病综合外科治疗的应用价值。
方法：
1.研究对象：通过南方医科大学珠江医院复杂肝胆管结石病ResMan临床试验公共管理平台(详见第一部分)提取2008年7月至2012年12月南方医科大学复杂肝胆管结石病患者131例进行回顾性研究,根据其是否施行基于3D模型指导复杂肝胆管结石病综合外科治疗,将其分为3D辅助手术组(A组)和非3D辅助手术组(B组)。病例入选标准：(1)18岁以上；(2)符合复杂肝胆管结石的定义；(3)肝功能归类为Child A或B级；(4)能耐受外科治疗。
A组为施行基于3D模型指导复杂肝胆管结石病综合外科治疗,其中男30例,女47例,年龄53.1±11.2岁,病程8个月—15年；B组为施行非3D辅助外科治疗复杂肝胆管结石病组,其中男15例,女39例,年龄54.4±12.7岁,病程7个月—14年。两组患者在性别、年龄、术前肝功能、发病部位、有无合并肝内胆管狭窄及肝脏萎缩等的一般资料方面比较,差异无统计学意义(P>0.05),具有可比性。
2.数据采集设备同第一部分。
3.亚毫米CT数据收集方法同第一部分。
4.复杂肝胆管结石3D模型建立方法同第一部分。
5.根据对肝内结石分布,胆管狭窄程度和分布,肝脏病理形态改变的诊断率,比较3D模型相对于B超,CT, MRI影像检查在临床诊断中的应用优势。
6.复杂肝胆管结石病患者3D模型指导术前规划,术式决策的效果评价：
(1)将重建出的复杂肝胆管结石病患者3D模型导入MI-3DVS系统中,对模型及各组成部分随意进行拆分、放大、缩小、旋转、透明等操作,通过全方位、多角度、多层次地观察各组织结构解剖特点及相互关系,明确：①结石分布的范围；②结石所在肝叶或(和)段有无萎缩；③肝内外胆管有无狭窄、狭窄的部位；④有无合并胆道畸形；⑤有无合并胆道肿瘤；⑥无结石肝叶体积的估算。此外,如果病人合并肝硬化、门静脉高压、阻塞性黄疸等,还应对肝功能代偿能力作出正确的评价。然后利用力反馈设备PHANTOM和自行开发设计的虚拟手术器械对重建模型进行各种类型的仿真手术,通过多种仿真手术方式的模拟和比较确定最终个体化外科综合治疗方案,在实际手术中提供实时指导。
(2)实际手术
观察实际手术中所见肝内外管道解剖结构与结石分布是否与3D模型一致,以及实际手术方式与仿真手术符合情况。术中常规运用胆道镜检查是否残留结石及胆管狭窄,视病情需要放置T管或肝胆管胆道支撑管以用于术后胆道引流、胆道造影及胆道镜检查。术后常规进行胆道造影或胆道镜检查以明确是否有残留结石和胆道狭窄。7.复杂肝胆管结石病患者3D模型在指导综合外科治疗的效果评价
(1)围手术期／短期疗效：实验室数据(血清转氨酶水平,血清胆红素水平,血清白蛋白水平,血清血红蛋白水平,血白细胞水平),外科手术数据(手术时间、术中失血、术中输血),结石清除率,手术并发症率和围手术期死亡率,进行评估。对潜在影响术后并发症发生的因素：性别、年龄、术前并发症,胆道手术史,肝切除术方式,胆肠吻合,术前胆红素、白蛋白水平,术前3D图像分析等,使用logistic回归模型进行统计分析。
(2)远期疗效：术后随访远期肝胆管结石和胆管炎复发率使用Kaplan-Meier方法计算和比较两组间差别。利用多因素Cox回归分析对影响复杂肝胆管结石病患者术后无症状生存的可能因素进行统计分析。8.统计学处理：
对于连续变量采用均数±标准差表示,利用t检验进行统计分析；对于计数资料,则采用X2检验或Fisher's精确检验统计分析。对潜在影响术后并发症发生的相关危险因素：性别、年龄、术前基础疾病、胆道手术史、肝切除术方式、胆肠吻合、术前胆红素、白蛋白水平、术前3D图像分析、术前胆道感染病史、术前基础疾病史,上述11个因素采用多变量Logistic回归分析,用向前法筛选变量,引入变量的检验水准a=0.05。术后随访远期肝内胆管结石复发率和胆管炎复发率采用Log-rank检验比较两组间差别,采用Kaplan-Meier法绘制生存曲线。利用Cox风险模型对影响复杂肝胆管结石病患者术后无症状生存的多因素进行预后分析。假设P<0.05为差异具有统计学意义。所有统计分析均采用SpSS13.0(SPSSInc.,Chicago,IL,USA)统计学软件进行数据分析。
结果
1.复杂肝胆管结石病3D模型的临床诊断结果
通过MI-3DVS软件对复杂肝胆管结石病胆道系统和肝内胆管结石的进行精确分割和重建,A组77例患者肝脏及其内部的各管道系统等三维重建图像形象逼真、立体感强,可清晰地再现患者肝脏的立体形态和有无肥大和萎缩；肝内一、二、三级胆管树立体形态及狭窄或扩张胆管的长度和直径显示清晰,部分肝内胆管结石合并肝内胆管广泛扩张者,甚至四级胆管(亚肝段胆管)也可以得到显示；结石的大小、数量及其在肝内外胆管的分布,门静脉、肝静脉及肝动脉三套血管及其分支在肝内的立体分布等情况也清晰显示。
复杂肝胆管结石病3D模型对肝内胆道狭窄病变的显示率明显高于MRCP, B超、CT,(3D vs. CT,81.8%vs.31.3%, P=0.000,3D vs. MRCP,81.8%vs.58.8%,P=0.039)。在肝脏组织病变的诊断上,复杂肝胆管结石病3D模型诊断显示效果也优于MRCP和B超(3D vs. US,98.7%vs.45.4%, P=0.000,3D vs. MRI/MRCP,98.7%vs.82.4%, P=0.018).3D模型在肝内胆管结石的大小、数量及其在肝内外胆管的分布显示率与MRCP, B超、CT无明显差别。
2.复杂肝胆管结石病3D模型指导术前规划,术式决策的临床结果
(1)3D模型指导术前规划
在MI-3DVS中,通过力反馈设备PHANTOM和虚拟手术器械可方便地对复杂肝胆管结石3D模型进行各种类型的仿真模拟手术规划,包括胆管探查取石术,肝切除术等。通过个体化肝脏分段可准确对结石及胆管狭窄进行定位,术前肝脏体积测量能准确估算肝切除术后残肝体积以规避术后肝功能衰竭发生。可视化仿真手术规划观察肝切除平面内重要血管、胆管及结石的解剖关系,通过多个手术方案的优化筛选确定最佳个体化手术方案。A组77例患者术前规划方案为：1例行胆管探查取石术(包括胆总管切开取石术、肝内胆管切开取石术、狭窄胆管整形术、胆肠吻合术),76例行肝切除术为主的外科手术(包括各种术式的肝部分切除术、肝内外胆管切开取石术、经肝断面胆管探查取石术、术中纤维胆道镜／胆道硬镜取石术、狭窄胆管整形术、胆管支撑管支持引流术、胆肠吻合术)。
(2)实际手术
A组77例患者中l例行胆管探查取石术(包括胆总管切开取石术、肝内胆管切开取石术、狭窄胆管整形术、胆肠吻合术),76例行肝切除术为主的外科手术(包括各种术式的肝部分切除术、肝内外胆管切开取石术、经肝断面胆管探查取石术、狭窄胆管整形术、胆管支撑管支持引流术、胆肠吻合术),与3D模型指导的术前规划相一致。
3.复杂肝胆管结石病3D模型在指导综合外科治疗的评价结果
1.术中手术诊疗效果评价
A组与B组在手术时间、术中输血量、术中出血量和肝脏血流阻断时间的统计比较结果分别为：(269.7±83.0min vs.315.6±81.7min, P=0.002),(77.9±169.0mL vs.192.6±229.7mL, P=0.002),(411±107.9mL vs.517.2±179.4mL, P=0.015)和(12.7±3.2min vs.17.3±4.0min,P=0.001)。A组有1例患者合并肝内胆管细胞癌,与术前3D模型诊断一致。
2.术后早期诊疗效果评价
A组与B组在即刻残石率和最终残石率的统计比较结果分别为：(7.8%vs.38.9%,P<0.001)和(5.2%vs.18.5%,P=0.015)。两组共有25例病人发生结石残留,其中A组6例,B组21例。两组最终结石清除率分别为94.8%和81.5%。两组术后经胆道造影检查证实肝内胆管狭窄残留率分别为(7.8%vs.35.2%,P<0.001)。术后并发症方面,两组间术后常见的并发症统计比较结果为：胸腔积液(13%vs.33.3%,P=0.005),,伤口感染(7.8%vs.20.4%,P=0.035)和肝功能能障碍(2.6%vs.16.7%,P=0.004)。A组与B组术后白蛋白水平比较结果为(38.7±3.0g/L vs.36.9±4.8g/L,P=0.024)。对影响术后并发症(包括切口感染、肺部感染、胸腔积液、膈下感染、肝脓肿、胆瘘、肠瘘、上消化道出血、胆道出血和肝肾综合征等)发生的潜在相关危险因素进行logistic回归分析提示：用向前法筛选变量,引入变量的检验水准α=0.05,在所有的11个考察的有关临床术后并发症发生相关因素,合并胆肠吻合术(OR=2.493,P=0.039,95%CI=1.046-5.943)为术后并发症发生的潜在危险因素；肝切除术(OR=0.629, P=0.016,95%CI=0.431-0.918),术前白蛋白水平(OR=0.926,P=0.033,95%CI=0.862-0.994),3D模型术前规划(OR=0.260, P=0.002,95%CI=0.112-0.602)术后并发症发生的潜在保护因素。
3.术后远期诊疗效果评价
所有病例随访中位时间为28个月,A组9(11.7%)例和B组15(27.8%)例经超声、CT或胆道造影术证实肝内胆管结石复发。两组间肝内胆管结石复发率和胆管炎复发率采用Log-rank检验,A组肝内胆管结石复发率(X2=4.121,P=0.042)和胆管炎复发率(X2=9.866,P=0.002)显著低于B组。
利用Cox风险模型对影响复杂肝胆管结石病患者术后无症状生存的相关因素进行预后分析提示：3D技术进行术前规划是复杂肝胆管结石病患者术后无症状生存的有效保护因素(RR=0.348,95%CI0.185-0.657, P=0.001);但是,性别、年龄、术后并发症、术前胆红素水平、白蛋白水平等相关因素对长期无症状生存无显著性影响。随访期间A组1例术中发现合并胆管细胞癌患者,其术后出现肿瘤复发。除此之外,其余患者无一例进展为胆管细胞癌。
结论：
1.复杂肝胆管结石病患者3D模型真实再现了肝脏内部含有的所有结构包括：胆管、肝动脉、肝静脉、门静脉系统以及结石之间的解剖关系；明确了结石大小、形态、数量、位置及胆管走行；肝内胆管狭窄部位、狭窄程度、狭窄长度,减少术者思考上的模糊性和不稳定性,同时避免侵入性检查如ERCP、PTC等可能诱发出血、胰腺炎、胆管炎的风险。
2.通过复杂肝胆管结石病患者3D模型指导术前规划,制定个体化手术方案,最大程度去除包括萎缩肝叶、肝内胆管结石、肝内胆管狭窄等在内的病灶同时尽量保护术后肝功能,减少并发症发生。A组术后残石率、肝内胆管狭窄残留率、术后结石复发率、术后胆管炎复发率、术后并发症发生率和术后实验室检查指标结果均优于传统B组。
3.复杂肝胆管结石病患者3D模型丰富了传统影像学诊断手段提供的个体化肝内胆管病变信息,指导术前规划,合理制定最佳手术方案,个体化针对性强,避免术中盲目探查导致的结石残留、胆管狭窄残存、正常肝组织损毁、肝内各脉管系统损伤等风险,尽可能缩短手术时间、减少术中失血及术中输血等对病人二次打击,防止术后出现肝功能损伤。
4.复杂肝胆管结石病3D模型指导综合外科诊疗模式能有效减少术后肝内胆管结石和胆管炎的复发,提高患者长期无症状生存率,有效改善复杂肝胆管结石病患者的预后。
三、3D技术联合胆道硬镜外科治疗复杂肝胆管结石病的疗效评价
目的：
1.研究3D技术联合胆道硬镜治疗复杂肝胆管结石病的诊疗价值；
2.比较3D技术联合胆道硬镜治疗模式与现有的外科治疗模式在复杂肝胆管结石病治疗中的临床效果。
方法：
1.研究对象：通过南方医科大学珠江医院复杂肝胆管结石病ResMan临床试验公共管理平台(详见第一部分)提取我院2012年2月至2013年12月期间共25例经3D技术联合术中胆道硬镜外科综合治疗的复杂肝胆管结石病患者进行研究,其中女18例,男7例,年龄31-76岁,平均54岁,定义为C组进行临床研究。同时,提取我院2011年6月至2012年1月期间共27例接受现有外科治疗模式的复杂肝胆管结石病患者资料,其中女22例,男5例,年龄30-83岁,平均53.9岁,定义为D组作为对照组。两组患者在性别、年龄、术前肝功能、肝内胆管结石的分布、既往胆道手术史及术前胆管炎病史等的一般资料方面比较,差异无统计学意义(P>0.05),具有可比性。
2.CT数据的采集所用设备、参数,数据的分割,肝脏和脉管系统的三维重建方法见文献同第二部分。
3.纳入标准：
病例入选标准：(1)18岁以上；(2)符合复杂肝胆管结石的定义；(3)肝功能归类为Child A或B级；(4)能耐受外科治疗；(5)同意接受胆道硬镜治疗。
4.评价指标：
(1)3D模型指导胆道硬镜术前规划
术前通过对复杂肝胆管结石病3D模型进行多角度旋转观察,利用三维可视化技术观察肝内胆管病变情况,明确结石分布的范围；结石所在肝叶或肝段损毁情况；肝内外胆管有无狭窄、狭窄的部位,狭窄的长度；排除有无合并胆道的畸形；通过反复手术演练,制定出个体化的3D技术联合术中胆道硬镜外科治疗的方案。指导制定术中胆道硬镜探查碎石取石的个体化路径。
(2)外科治疗效果评价
术中常规运用胆道硬镜或纤维胆道镜检查是否残留结石及胆管狭窄,视病情需要放置T管或肝胆管胆道支撑管以用于术后胆道引流、胆道造影及胆道镜检查。术后常规进行胆道造影或胆道镜检查以明确是否有残留结石和胆道狭窄。
围手术期效果评价指标：平均手术时间、平均住院时间、即刻结石清除率、术后并发症发生率(肝功能障碍、胆汁瘘、胆道出血)。
远期手术效果评价：远期无症状长期生存率、术后进一步胆道镜取石率、最终残留结石率。
5.统计学处理：
对于连续变量采用均数±标准差表示,利用t检验进行统计分析；对于计数资料,则采用X2检验或Fisher's精确检验统计分析。假设P<0.05为差异具有统计学意义。所有统计分析均使用采用SpSS13.0(SPSSInc.,Chicago,IL,USA)统计学软件进行数据分析。
结果
C组与D组在即刻结石清除率、手术时间和术后住院天数的统计比较结果分别为：(88%vs.66.7%, P=0.012)、(232.4±23.2vs.309.3±87.3min, P=0.010)和(11.1±3.7vs.14.6±3.1days,P=0.001)。
C组24(96%)例患者最终实现完全取尽结石,1例患者因胆汁性肝硬化肝脏损毁严重,肝内胆管双侧弥漫性结石未能完全取尽结石。C组术中合并行右肝部分切除者1例,左外叶切除者l0例。其中l例患者术中发现合并尾状叶胆管细胞癌,术后随访12个月仍存活。
C组出现的围手术期并发症十分轻微。C组2例患者因术中胆道硬镜探查时损伤胆道粘膜而出现术中胆道出血,均通过胆道内注射0.08%的去甲肾上腺盐水保守治疗缓解。其中1例伴有胆汁性肝硬化患者由于术中取石时间较长,术后7天内出现肝功能异常,通过护肝保守治疗后缓解。而D组,共有7例患者因术中采用纤维胆道镜网篮取石出现胆道出血,均通过胆道内注射0.08%的去甲肾上腺盐水保守治疗得到缓解。
D组最后的残石率和术后进一步胆道镜治疗率与C组统计比较结果为：(25.9%vs.4%,P=0.032)和(33.3%vs.12%,P=0.020)。D组有l例患者接受右肝部分切除术,14例患者接受左肝外叶切除术。l例患者出现术后胆瘘。D组与C组统计比较最终残石率为(25.9%vs.4%,P=0.032)。C组和D组中位随访时间分别是13个月和15个月。
结论：
1.3D技术联合术中胆道硬镜外科综合治疗模式有效优化术中胆道硬镜探查取石的路径,缩短手术和住院时间,明显提高复杂肝胆管结石病患者的结石清除率。
2.利用3D技术进行手术规划,对个体化手术方案的制定提供详实的术前指导,能够增加手术成功率,减少术后并发症的发生和术后再次手术率。
Research Background
Complicated Hepatolithiasis concept is not yet unified. For bile duct stones, especially for the surgery again hold unequal treatment in terms of experience, understanding of concepts are not consistent. At present, most scholars believe that the complexity of the removal of bile duct stones is the general condition of the patient, because other diseases such as heart, lung, kidney, diabetes, biliary tract surgery constitutes a threat. In general, hepatolithiasis is divided into "complicated hepatolithiasis" types depending on the presence of bilateral hepatolithiasis or the patients, who received one or more biliary tract surgery, have residue or recurrence stones, bile duct stricture requiring reoperations; the patients combine Caroli'S disease or cholangiocarcinoma and the absence of infections, biliary cirrhosis, portal hypertension,septic manifestations, and intrahepatic abscess (Liang Li Jian, Li Shaoqiang complex diagnosis and treatment of bile duct stones principle [J] Chinese Journal of Surgery2009;..29(7):542-544).
Complicated hepatolithiasis is the most of difficult to treat, the highest rate of reoperation for benign disease. The basical pathologies are complex bile duct stones and intrahepatic bile duct stricture dilation and mechanical biliary obstruction, biliary tract infections, and liver damage. The pathological nature of the entire process of the evolution of the complex pathology of bile duct stones, there is a close relationship with bile duct stones and bile duct narrow. Report on the clinical display of hepatic cholangiocarcinoma:repeated episodes of biliary tract infections, may be a change in the nature of the lesion. According to the complex evolution of bile duct stones above pathological understanding, Ong et al, raises complex surgical treatment of bile duct stones in principle in1962:"With the detailed understanding of the bile duct pathology, the eradication of stones, narrow and contain foci of disease recurrence hepatic tissue." It's programs happens to coincide with the ideal," Take out all of the bile ducts stones, remove all of the bile ducts obstructions, remove all of the liver lesions, unobstructed drainaging ", of Wong Chi Keung Academy's. Because bile duct stones are not only the accumulation of stones, often accompanied occurs in all levels of intrahepatic duct stenosis and hyperplastic lesions, which is the core of treatment, and surgical treatment is still to be one of the most effective means to achieve the therapeutic purposes, which is the most commonly methods. Select surgery programs must be individualized, depending on the number and distribution of intrahepatic bile duct stones, biliary stricture location and extent of the pathological changes in the liver, liver function and general condition of the patient, the development of targeted individualized treatment plan and select appropriate surgical approach.
Despite nearly20years of complicated hepatolithiasis understanding and treatment has been significant progress, but because of its complex pathophysiological process and prone to serious complications characteristic, is still plagued by the problem of biliary surgeon. For complicated hepatolithiasis should make adequate preoperative preparation, try to get detailed imaging data and liver function evaluation. Preoperative biliary anatomy, intrahepatic bile duct stones location, distribution, quantity, bile duct stricture location, shape should have an accurate understanding. And pay attention to whether the variation in intrahepatic bile ducts, especially the posterior lobe of the right bile duct variations, the most common is the right hepatic duct abnormalities, especially in the posterior lobe of the right bile duct directly into the left hepatic bile duct. For the right posterior bile duct stones variation due to an acute angle to import alone stone forceps stone or stone surgery choledochoscopic difficult to take the net calculus, which is an important factor in causing postoperative anatomical right posterior residual stones (Mori T, Sugiyama M, Atomi Y. Gallstone disease:Management of intrahepatic stones[J]. Best Pract Res Clin Gastroenterol,2006,20(6):1117-1137.). At the same time, to fully understand the pathology before surgery, surgical causes and methods, as well as the specific circumstances of the current lesion is extremely important in order to formulate a reoperation individualized surgical treatment. Any hasty decision surgery may cause more surgery times, the patients suffer more pain.
In recent years, with the development of laparoscopic techniques, endoscopy and interventional techniques, a variety of minimally invasive treatment has been widely reported, such as percutaneous transhepatic biliary lithotripsy and holmium laser mirror or pneumatic lithotripsy of bile duct stones in general has made remarkable efficacy, but for complicated hepatolithiasis postoperative residual stone rate of up to20%-50%(Cheng Y F, Lee T Y, Sheen-Chen S M, et al. Treatment of complicated hepatolithiasis with intrahepatic biliary stricture by ductal dilatation and stenting: long-term results[J]. World J Surg,2000,24(6):712-716.). The above technique for endoscopic treatment of bile duct stones complicated treatment is still controversial, evidence is still lacking the bulk of cases.
Currently, the diagnosis of complicated hepatolithiasis mainly rely on B ultrasound, CT and MR and other noninvasive imaging tests to clear stones location, size, number and distribution, location and extent of bile duct stenosis, thereby positioning the diagnosis. Combined liver function in patients, Oddi sphincter function, with or without liver cholangitis episodes, with or without obstructive jaundice, with or without hilar bile duct stricture, portal vein hypertension and splenomegaly combination of factors such as surgical planning. However, due to the widespread distribution of intrahepatic bile duct stones, but with various degrees of bile duct stricture disease and liver damage, these various imaging methods have advantages and disadvantages, and often require the integrated use of several imaging methods, in order to do a more comprehensive diagnosis. There is no ideal diagnostic method to make a comprehensive diagnostic system for stone size, number and distribution, bile duct stenosis and length, pathological liver, bile ducts and blood vessels as well as the relationship.
With the development of computer science, based on three-dimensional reconstruction of CT or MRI technology has been widely used in clinical diagnosis and treatment of hepatobiliary surgery activities, its virtual surgical planning system can help hepatobiliary surgeon in advance of surgery simulation operations before surgery, to develop individualized surgery program, thereby reducing the actual surgery pointless damage, improve the actual safety of surgery. At home and abroad there have been several hepatobiliary virtual surgery systems used in clinical, its clinical effect is satisfied and it has great help for clinical work. However, the diagnosis and treatment of intrahepatic bile duct stones used in digital medicine is still in its early stages, less relevant literature. Moreover, for complex three-dimensional reconstruction of bile duct stones bulk of cases (3D technology) system under the guidance of surgical polyclinics evaluate the effect has not been reported in the literature.
Based on the above issues, this subject collects the patients treated bile duct stones submillimeter CT complex data quality of the collection from June2008to December2013in Division I of Hepatobiliary of Zhujiang Hospital, Southern Medical University, based on the use of abdominal medical images with independent intellectual property rights3D Visualization System (Medical Image Three-Dimensional Visualization System, MI-3DVS)(software patent number:2008SR18798), built for specific individuals complicated hepatolithiasis complicated treatment procedures3D mode, the system discussed under the technical guidance of surgical polyclinics3D mode bile duct stones in complex clinical value and significance.
Part I. Design of three-dimensional reconstruction database system for Complicated Hepatolithiasis
Objective
1. Optimization of CT data acquisition method to obtain high-quality sub-millimeter CT data for complicated hepatolithiasis patients;
2. Interactive volume rendering based segmentation algorithm to construct complicated hepatolithiasis model database;
3Clinical trial based on ResMan public management platform to build a complex three-dimensional reconstruction of bile duct stones database system for comprehensive hepatolithiasis patients;
4Investigate complex clinical value of the database systemin for the patients with complicated hepatolithiasis.
Methods
1. Retrospectively collected the complicated hepatolith disease case information of zhujiang hospital, Southern Medical University from June2008to December2013step by step.64rows/256slice CT
2. The equipments used to collect data include64rows/256slice CT spiral CT scanner (CT PHILIPS Brilliance, made in Dutch); double tube high pressure syringe and contrast agents (Lopamiro in a dose of370mg I/ml); the self attached Mxview workstation for post processing of the images; HP blade server and high configuration computer (from Clinical Center of Digital Medicine, Southern Medical University, Guangzhou, China) and the abdominal three-dimensional visualization system.
3. The procedures for collecting high quality submillimeter CT data of intrahepatic bile duct include:prescanning preparation, plain scanning, trial injection, routine enhanced scanning as well as the transmission and storage of thin layer CT scanning data.(Fang C H, Liu J, Fan Y F, et al. Outcomes of hepatectomy for hepatolithiasis based on3-dimensional reconstruction technique[J]. J Am Coll Surg,2013,217(2):280-288.)
4.3D model building method for complex Hepatolithiasis:
(1)Interactive volume rendering image segmentation algorithm based on:the first reconstruction volume rendering through the window width and window level adjustment to obtain the desired structure of the biliary clear three-dimensional images.
(2)The volume rendering interactive segmentation algorithm as a segmentation plug-in integrated into the abdomen medical image visualization system (MI-3DVS), the import sub-millimeter CT data in DICOM format to MI-3DVS conducted registration, segmentation, three-dimensional reconstruction.
(3)Post-processing of the3D model and observe and analyze the three-dimensional structure.
By MI-3DVS the surface data processing tools for3D graphics model smoothing and de-noising, then the intrahepatic bile duct system is a combination of3D models and display, zoom in, zoom out, rotate the3D model visualization in space to observe, analyze intrahepatic distribution duct lesions.
5. Public use ResMan clinical trial management platform to build complex patients
with bile duct stones dimensional reconstruction of the database system.
Results
1. The quality of submillimeter CT images obtained via trial injection was optimal, with favorable demonstrations of the biliary lesions, peripheral arterial lesions of the extrahepatic bile duct, peripancreatic lesions and periampullar lesions.
2. The3D model of arteries supplying the extrahepatic bile duct can be multidimensionally rotated to clearly demonstrate the origins and distributions of the arteries supplying the extrahepatic bile duct. The arteries supplying the superior segment of extrahepatic bile duct were found to be originated from the right hepatic artery, the gallbladder artery, the left hepatic artery and the proper hepatic artery. However, the arteries supplying the inferior segment of the extrahepatic bile duct were found to be originated from the superioposterior pancreatoduodenal artery, the astroduodenal artery, the gallbladder artery and the retroportal artery.
3. The3D model of arteries supplying the extrahepatic bile duct can be multi-dimensionally observed and analyzed for the anatomical relationships. Traditional sketches can only display the anatomic structures on the surface. However, it has the advantage of demonstrating vascular vessels that the3D model fails to display, such as the artery plexus around the bile duct. The sketches are based on the cadaveric perfusion under a surgical microscope.
Conclusions:
1.64rows/256slice CT spiral CT scanning with optimized data collecting method can obtain high quality submillimeter CT data of the arteries supplying the extrahepatic bile duct, with well demonstrated vasculature. It can facilitate to distinguish the imaging demonstrations of the micro-structures, which satisfies the requirements for segmentation and3D reconstruction of arteries supplying the extrahepatic bile duct.
2. Based on volume rendering of interactive segmentation method, the scanning data of arterioles supplying the extrahepatic bile duct can be extracted and segmented for3D reconstruction. The3D model reconstructed by using MI-3DVS can display the three-dimensional anatomical structures of the extrahepatic bile duct and its blood supplying arteries.
3. The reconstructed3D model is authentic and direct, which facilitates the learning of anatomic knowledge and related researches.
Part II Evaluation of the value in clinical diagnosis and treatment by3D models for Complicated Hepatolithiasis
Purpose:
1. Explore the clinical value on liver lesions using by3D model for complicated hepatolithiasis patients.
2. Study the application value of3D models for complicated hepatolithiasis patients with bile duct stones before guiding complex surgical therapy integrated planning, surgical decision-making.
3. Study the integrated application value of3D models for complicated hepatolithiasis patients in guiding complex surgical treatment.
Method:
1.Study subjects:Zhujiang Hospital, Southern Medical complicated by hepatolithiasis ResMan clinical trials of public management platform (Part I) extraction from July2008to December2012in patients with bile duct stones, Southern Medical complex131cases, according to the whether implementation guidance based on complex3D models integrated surgical treatment of bile duct stones, will be divided into A groupgroup (A) and the non-A groupgroup (group B).
Case inclusion criteria:(1) More than18years of age;(2) Meet the definition of complicated hepatolithiasis;(3) Liver function classified as Child A or B;(4) Can tolerate surgical treatment.
Group A for the purposes of guidance based on3D models integrated surgical treatment of complex bile duct stones, including30males and47females, aged53.1±11.2years, duration of8months-15years; Group B for the purposes of the traditional surgical treatment of complex hepatolithiasis group, including15males and39females, aged54.4±12.7years, duration of7months-14years. Two groups were compared before sex, age, preoperative liver function, disease location, presence or absence of intrahepatic bile duct stricture and liver atrophy and other general information, the difference was not statistically significant (P>0.05), comparable.
2. Data acquisition devices are the same as mentioned in first part.
3. Submillimeter CT data collection methods are the same as the first part.
4. The3D modeling method of complex Hepatolithiasis is same as the first part.
5. According to the distribution of intrahepatic stones diagnosis rate, bile duct stenosis and distribution of pathological changes in the liver, comparing the3D model with respect to B-, CT, MRI imaging application advantages in clinical diagnosis.
6. Evaluate the effect of patient's3D models of complex Hepatolithiasis before surgery to guide the planning, surgical decision-making.
(1) Import the reconstruction3D models of complex hepatobiliary duct stones in patients into MI-3DVS import system, freely split the model and its components, zoom, rotation, transparency, etc, through comprehensive, multi-angle, multi-level structure observed anatomical characteristics and relationships, specifically:①Range of bile duct stones distribution;②Bile duct stones where the lobe or (and) whether the shrinking segment;③Whether the extrahepatic bile duct stenosis, narrow part;④Have biliary abnormalities;⑤Have biliary cancer;⑥No estimate stones lobe volume. In addition, if the patient with cirrhosis, portal hypertension, obstructive jaundice, liver function should also make a correct evaluation of the compensatory ability. Then use the PHANTOM force-feedback device designed and developed a virtual surgical instruments for various types of simulation model reconstruction surgery, through modeling and simulation comparing multiple surgical procedures to determine the final develop individualized surgical comprehensive treatment program, provided the actual surgery Real-time guidance.
(2) The actual surgery
Observe the actual surgery seen in the anatomy and extrahepatic duct stones distribution is consistent with the3D model, and simulation and the actual surgical procedure compliance. Routine using of intraoperative endoscopy diagnose whether residual biliary stones and biliary strictures and conventional T-tube placement for postoperative cholangiography and biliary endoscopy. Routine postoperative cholangiography or biliary endoscopy to confirm whether there is residual stones and biliary stricture.
7. The effect evaluation of patient's3D model of complex bile duct stones in guidance of comprehensive surgical treatment.
(1) Perioperative/short-term effect:laboratory data (serum transaminase levels, serum bilirubin, serum albumin, serum hemoglobin levels, white blood cell levels), surgical data (operative time, intraoperative blood loss, intraoperative blood transfusion), stone clearance rate, the rate of surgical complications and perioperative mortality assessed. The potential impact of the factors of postoperative complications: gender, age, preoperative complications, biliary tract surgery, liver resection way cholangioenterostomy, preoperative bilirubin, albumin level, preoperative3D image analysis, using logistic regression models for statistical analysis.
(2) Long-term effect:long-term follow-up after bile duct stones and cholangitis recurrence rate is calculated using the Kaplan-Meier method and comparing the difference between the two groups. The using of multivariate Cox regression analysis estimate of possible factors in asymptomatic patients after bile duct stones affect the survival of a complex statistical analysis.
8. Statistical analysis:
The perioperative/short-term outcomes, including laboratory data (serum aminotransferase level, serum bilirubin level, serum albumin level, serum hemoglobin level, blood leukocytes level), surgical data (operation time, intraoperative blood loss, intraoperative blood transfusion), stone clearance rate, operative morbidity and mortality, were evaluated. Continuous variables were expressed as mean±standard deviation and compared using the Student's t-test, Chi-squared test, and Fisher's exact tests. The influence of potential factors that may affect operative morbidity, sex, age, preoperative comorbidities, previous biliary tract surgery, type of hepatectomy (left vs. right), concomitant hepaticojejunostomy, preoperative bilirubin, and albumin levels, preoperative3D images analysis, were analyzed using a logistic regression model. Long-term results, including recurrence of biliary stone and cholangitis rate, were also studied. Long-term survival was computed using the Kaplan-Meier method and compared between groups by the log-rank test. Overall survival was measured from the date of surgery to the time of detection of recurrent stones and cholangitis. Cox regression analysis was used to determine which factors significantly influenced long-term asymptomatic survival. A P-value<0.05was considered statistically significant. All statistical analyses were performed using SPSS13.0(SPSSInc.,Chicago,IL,USA) for Windows.
Results:
1. The outcome of3D model for complicated hepatolithiasis patients in clinical diagnosis.
Using by MI-3DVS software, it can segment accurately and reconstruct the biliary system and stones of complex bile duct stones,3D-assisted surgery group of77patients the liver and its internal piping system and other vivid, three-dimensional sense, can be clearly patients with liver reproduce three-dimensional shape and the presence or absence hypertrophy and atrophy; intrahepatic one, two, three bile duct stenosis or establish a body shape and length and diameter of the bile duct dilatation clear display, part of intrahepatic bile duct stones with extensive intrahepatic bile duct dilation, even four bile duct (sub-hepatic bile ducts) can also be displayed; stone size, number and distribution in the case of the three-dimensional distribution in the liver and other extrahepatic bile duct, portal vein, hepatic vein and hepatic artery and its branches three vessels also clearly visible.
The diagnosis rate using by3D model of complex bile duct stones and intrahepatic bile duct stenosis was significantly higher than MRCP, B ultrasonography, CT,(3D vs. CT,81.8%vs.31.3%, P<0.001,3D vs. MRCP,81.8%vs.58.8%, P=0.021). In the diagnosis of liver lesions, the diagnostic performance using by3D model of complex bile duct stones is better than MRCP and B ultrasonography (3D vs. US,98.7%vs.45.4%, P<0.001,3D vs. MRI/MRCP,98.7%vs.82.4%, P=0.018).3D model of intrahepatic bile duct stones the size, quantity and super distribution in extrahepatic bile duct diagnosis rate and MRCP, B ultrasonography, CT was no significant difference.
2The effect of3D model for complicated hepatolithiasis patients on operation planning and decision-making during surgery.
(1) Use3D models to guide the preoperative planning
In MI-3DVS system, by PHANTOM force feedback device and virtual surgical instruments can be easily reconstructed model for the simulation of various types of surgery, including bile duct exploration lithotripsy, liver resection and so on. Accurate to locate bile duct stones and bile duct stricture by individual segments, preoperative volume measurement can accurately estimate the remnant liver volume after hepatectomy to avoid postoperative liver failure. Visual simulation surgery anatomical relationship observed in liver resection plane important blood vessels and bile duct stones, determine the best individualized surgical plan by optimizing multiple surgical screening programs.3D-assisted surgery group77cases of preoperative planning are:1routine bile duct exploration lithotripsy (including choledocholithotomy surgery, lithotomy intrahepatic bile duct, bile duct stricture plastic surgery, biliary-enteric anastomosis),76cases mainly hepatic resection surgery (including surgical procedures partial hepatectomy, extrahepatic bile duct lithotomy, hepatic bile duct exploration lithotomy section, bile duct stricture plastic surgery, biliary drainage support tube support, bile intestinal anastomosis).
(2) The actual surgery
1of77patients in A groupgroup underwent bile duct exploration lithotripsy (including choledocholithotomy surgery, lithotomy intrahepatic bile duct, bile duct stricture plastic surgery, biliary-enteric anastomosis),76underwent hepatic resection is lord surgery (including surgical resection of liver section, extrahepatic bile duct lithotomy, hepatic bile duct exploration lithotomy section, bile duct stricture plastic surgery, biliary drainage support tube support, biliary-enteric anastomosis), it is consistent with the preoperative planning in the guidance of3D models.
3The effect of3D models for complicated hepatolithiasis patients in guiding surgical treatment.
(1) Evaluation of intraoperative surgical treatment
Group A and Group B in operative time, intraoperative blood transfusion, blood loss and liver blood flow occlusion time statistical comparison results are:(269.7±83.0min vs315.6±81.7min, P=0.002.),(77.9±169.0mL vs.192.6±229.7mL, P=0.002),(411±107.9mL vs.517.2±179.4mL, P=0.015) and (12.7±3.2min vs.17.3±4.0min, P=0.001). Group A1patients with intrahepatic cholangiocarcinoma, the3D model is consistent with the preoperative diagnosis.
A set of statistics compared with Group A and Group B in immediate residual stone rate and final residual stone rate results were:(7.8%vs.38.9%, P<0.001), and (5.2%vs.18.5%, P=0.015). A total of25cases of two patients with residual stones occurred, where Group A of six cases,21cases of group B. Two final stone clearance rate was94.8%and81.5%, respectively. Postoperative angiography confirmed by intrahepatic bile duct stricture residual rate was (7.8%vs.35.2%, P<0.001). Postoperative complications between the Group A and Group B a common complication after statistical comparison results:pleural effusion (13%vs.33.3%, P=0.005), wound infection (7.8%vs.20.4%, P=0.035.) and liver dysfunction (2.6%vs.16.7%, P=0.004). Group A and Group B after the comparison of albumin levels (38.7±3.0g/L vs.36.9±4.8g/L, P=0.024). On the impact of postoperative complications (including wound infection, lung infection, pleural effusion, subphrenic infection, liver abscess, biliary fistula, intestinal fistula, upper gastrointestinal bleeding, biliary tract bleeding and hepatorenal syndrome, etc.). Potential risk factors for postoperative complications were logistic regression analysis showed:Screening using forward variable, test level to introduce variable a=0.05, the relevant factors occurred in all11clinical complications related to merger biliary-enteric anastomosis (OR=2.493, P=0.039,95%CI=1.046-5.943) as a potential risk factor for postoperative complications; liver resection (OR=0.629, P=0.016,95%CI=0.431-0.918), preoperative albumin level (OR=0.926, P=0.033,95%CI=0.862-0.994), the3D model before surgery planning (OR=0.260, P=0.002,95%CI=0.112-0.602) after complications potential protective factors occur.(2) Postoperative evaluation of long-term clinical results
All patients were followed a median time of28months,3D-assisted surgery group9(11.7%) patients and the surgical group15(27.8%) patients with ultrasound, CT or angiography confirmed intrahepatic bile duct stone recurrence Between the two groups of intrahepatic bile duct stone recurrence rate and cholangitis recurrence rate using Log-rank test, A groupgroup intrahepatic bile duct stone recurrence rate (x2=4.121, P=4.121) and cholangitis recurrence rate (X2=9.866, P=9.866) was significantly lower than the surgery group.
Cox risk model related to the use of complex factors affecting postoperative bile duct stones in patients with asymptomatic survival prognosis analysis showed:3D technology for preoperative planning is an effective protective factor complex surgery in asymptomatic patients with bile duct stones survival (RR=0.348,95%CI0.185-0.657,.P=0.001); however, the relevant factors such as gender, age, postoperative complications, preoperative bilirubin, albumin level, the position of intrahepatic stones and other long-term symptom-free survival significant effect None of patients subsequently developed cholangiocarcinoma during follow-up, except one patient in A groupgroup for the cholangiocarcinoma recurrence after surgery.
Conclusions
1.3D model of complex bile duct stones in patients with a true representation of all contained within the structure of the liver include:bile duct, hepatic artery, hepatic vein, portal venous system and anatomic relationship between the bile duct stones; clear stone size, shape, number, location and traveling bile duct; intrahepatic bile duct stenosis, stenosis, stricture length, reduce ambiguity and thinking on the stability of the surgeon, while avoiding invasive procedures such as ERCP, PTC which may induce the risk of bleeding, pancreatitis, cholangitis.
2Through complex hepatobiliary surgery patients before the3D model to guide planning duct stones, develop individualized surgical plan, including removing the greatest degree lobe atrophy, intrahepatic bile duct stones, intrahepatic bile duct stricture, etc., while maximizing protection of postoperative liver lesions function and reduce complications. A groupgroup were residual stone rate, residual rate of intrahepatic bile duct stricture, stone recurrence rate after surgery, postoperative cholangitis recurrence rate, incidence of postoperative complications and postoperative laboratory parameters were superior to conventional surgery group results.
3.3D model of complex bile duct stones in patients with intrahepatic bile duct enrich individual lesions traditional imaging diagnostic tools, guidance preoperative planning, reasonable surgical plan to develop the best individualized targeted, avoiding blind exploratory surgery resulting residual stones, bile duct stricture remaining normal liver tissue damage, the risk of intrahepatic vascular system of each injury, as far as possible to shorten the operation time, reduce intraoperative blood loss and intraoperative blood transfusions to patients secondary to combat and prevent postoperative liver function sustained damage.
4.3D model of complex bile duct stones comprehensive guide surgical treatment model can effectively reduce postoperative intrahepatic bile duct stones and cholangitis recurrence and improve survival in patients with long-term symptoms, improve the prognosis of patients with complicated bile duct stones.
Part III Evaluation of the management complicated hepatolithiasis with operative rigid choledochoscope guided by3D reconstruction technique
Purpose:
1. Research on3D technology combined with operative rigid choledochoscope comprehensive therapeutic value of complicated hepatolithiasis;
2. Comparison of the clinical effect between the3D technology combined with operative rigid choledochoscope comprehensive treatment model and the traditional existing surgical treatment model in the treatment of complicated hepatolithiasis.
Method:
l.The object of study:complicated hepatolithiasis ResMan clinical trials of public management platform (Part I) extraction by our hospital, Zhujiang Hospital, Southern Medical University from February2012to December2013period by a total of25cases of3D technology combined with intraoperative biliary bile duct stones in patients with complex surgical comprehensive treatment of the rigid choledochoscope which18females,7males, aged31-76years, mean54years, defined as Group C. Meanwhile, during the extraction hospital from June2011to January2012a total of27cases of patients who received conventional surgical treatment of complex data bile duct stones, including22females,5males, aged30-83years, mean53.9years, is defined as the Group D as a control group. More general information on the two groups of patients before sex, age, preoperative liver function, distribution of intrahepatic bile duct stones, previous history of surgery and preoperative biliary cholangitis medical history, the difference was not statistically significant (P>0.05), comparable.
2. CT data acquisition equipment used for segmentation, parameters, data, three-dimensional reconstruction of the liver and vascular system, see the second part of the same document.
3. Inclusion criteria:
Case inclusion criteria:(1) More than18years of age;(2) Meet the definition of complicated hepatolithiasis;(3) Liver function classified as Child A or B;(4) Can tolerate surgical treatment;(5) Agree accept operative rigid choledochoscope treatment.
4. Evaluation:
All patients were followed up after treatment with the rigid choledochoscope guided by CT-based3D reconstruction technique and traditional method. The follow-up examinations included T-tube cholangiography, ultrasonography and laboratory tests (hemoglobin, white blood cell count, bilirubin, alanine aminotransferase, aspartate aminotransferase, creatinine, serum urea nitrogen, CEA, CA-199), which were performed every three months. Stones detected in the intrahepatic bile duct within3months after therapies were considered as residual stones. Patients were followed up regularly in the hepatobiliary outpatient clinic. Median follow up time was13months, ranging from5-23months.
5. Statistical treatment
Continuous variables were expressed as the mean±standard and compared using Student's test. Categorical variables were expressed as n (%) and compared using the Chi-square or Fisher'
复杂肝胆管结石病(Complicated Hepatolithiasis)的概念目前尚未统一。对于肝胆管结石病,尤其对实施再次手术处理持有不同经验者而言,对概念的认识不尽一致。目前国内外多数学者认为,复杂肝胆管结石病是指除去病人全身情况,因为其他系统疾病如心脏、肺、肾脏、糖尿病等构成胆道手术威胁外,存在以下病情者视为复杂肝胆管结石病：(1)肝胆道结石病经历一次或以上胆道手术,但肝内胆管结石残留、复发或反复胆管炎发作需再次接受手术；(2)既往接受不适当的胆道手术,如接受各类胆肠吻合术后吻合口狭窄需要再次手术者；(3)两侧肝叶均弥漫分布肝内胆管结石；(4)肝内胆管结石病合并高位胆道狭窄或Caroli病；(5)肝内胆管结石病合并胆汁性肝硬化、门静脉高压症；(6)肝内胆管结石病合并胆管细胞癌(梁力建,李绍强.复杂肝胆管结石诊断和治疗原则[J].中国实用外科杂志.2009;29(7)：542-544.)。
复杂肝胆管结石病是胆道外科中最难治疗且再手术率最高的良性疾病。复杂肝胆管结石病的基本病理改变是肝内胆管扩张与狭窄,合并胆道机械性梗阻、胆道感染和肝实质组织损害。这一病理本质贯穿于复杂肝胆管结石病病理演变的全过程,与肝胆管结石和胆道狭窄的发生发展有密切的关系。临床上有关肝胆管细胞癌的报告显示：反复多次发作的胆道感染,可能是导致胆道病变性质的改变,诱发胆管细胞癌。根据对复杂肝胆管结石病上述病理演变认识,Ong等早于1962年提出了复杂肝胆管结石病外科治疗原则：“详尽了解胆管病理改变,根除结石、狭窄及包含复发感染灶的病变肝段组织”。其方案与黄志强院士提出的“取尽结石、解除梗阻、去除病灶、通畅引流”可谓不谋而合。因为肝胆管结石病的病灶不仅是肝胆管系统内堆积的结石,往往伴有发生在肝内各级肝管中的狭窄及增生性病灶,这是治疗的核心,而外科治疗则仍是达到这一治疗目的最有效、最常用的方法。手术方案的选择必须个体化,根据肝内胆管结石的数量及分布范围、胆道狭窄的部位和程度、肝脏的病理改变、肝功能状态及患者的全身状况,制定针对性的个体化治疗方案并选择合适的手术方法。
尽管在近20年来对复杂肝胆管结石病的认识和治疗有了明显的进步,但由于其复杂的病理生理过程和术中术后容易出现严重并发症的特点,复杂肝胆管结石病的诊治仍然是困扰胆道外科医生的难题。对于复杂肝内胆管结石病患者应尽量获取详尽的患者影像学资料和肝功能评估等实验室检查资料,做好充足的术前准备工作。术前对胆道系统的解剖,肝内胆管结石的位置、分布、数量,狭窄胆管的部位、形态等应有准确的诊断评估,并且要注意有无变异的肝内胆管,特别是右后叶胆管的变异,如右后叶胆管直接汇入左肝管。对于变异的右后叶胆管结石,由于汇入的角度成锐角,单凭取石钳取石或术中胆道镜取石往往很难取净结石,这是造成术后右后叶结石残留的重要解剖因素(Mori T, Sugiyama M, Atomi Y. Gallstone disease:Management of intrahepatic stones[J]. Best Pract Res Clin Gastroenterol,2006,20(6):1117-1137.)。同时,应充分了解既往手术情况、手术原因和方法,以及目前病变的具体情况极为重要,从而制订出再次手术的个体化外科治疗方案。任何匆忙决定的手术方案可能会导致更多次的手术可能,令病人遭受更大的痛苦。
近年来,伴随着腹腔镜技术、内镜技术及介入技术的发展应用,多种微创性治疗手段已被广泛报道,如经皮经肝穿刺胆道镜碎石术和胆道镜联合钬激光或气压弹道碎石,对一般的肝胆管结石取得了令人瞩目的疗效,但是对于复杂肝胆管结石病其术后残石率却高达20%-50%(Cheng Y F, Lee T Y, Sheen-Chen S M, et al. Treatment of complicated hepatolithiasis with intrahepatic biliary strictureby ductal dilatation and stenting:long-term results[J]. World J Surg,2000,24(6):712-716.).上述内镜治疗技术对于复杂肝胆管结石病的治疗尚有争论,仍然缺乏大宗病例证据。
目前,复杂肝胆管结石病的诊断手段主要依靠B超、CT和MR等无创性影像学检查,以明确结石的部位、大小、数量和分布情况,胆管狭窄的部位及程度,从而进行定位诊断；并结合患者肝功能状况、Oddi括约肌功能、有无肝胆管炎发作、有无梗阻性黄疸、有无肝门部胆管狭窄、有无门静脉高压症和脾肿大等综合因素制定手术方案。但由于复杂肝胆管结石病肝内胆管结石的分布广泛,同时合并不同程度的肝胆管狭窄和肝脏毁损性病变,上述各种影像学检查手段各有优势和不足,常需多种影像学检查方法的综合运用,才能做出较为全面的诊断。目前尚无一种理想的诊断方法能够同时对结石大小、数量和分布,胆管狭窄程度和长度,肝脏病理形态,以及胆管和血管的关系做出系统全面的诊断。
随着计算机科学的发展,基于CT或MRI的三维重建技术已经广泛应用于肝胆外科临床诊治活动中,其虚拟手术规划系统可以帮助肝胆外科医生在术前提前进行手术模拟操作,制定出个体化的手术方案,进而减少实际手术中的无意义损伤,提高实际手术的安全性。目前国内外已有多个数字化肝胆外科虚拟手术系统应用于临床的报道,其指导临床外科治疗效果满意。但是,数字医学技术应用于肝胆管结石病的临床研究仍处于早期应用阶段,相关文献报道不多,缺乏大宗病例临床评价证据。而且,针对大宗病例的复杂肝胆管结石病三维重建技术(3D技术)指导下外科诊疗效果的系统评价尚未见文献报道。
基于上述问题,本课题收集南方医科大学珠江医院肝胆一科2008年6月至2013年12月收治的复杂肝胆管结石病患者高质量亚毫米CT数据基础上,利用具有自主研发的腹部医学图像三维可视化系统(Medical Image Three-Dimensional Visualization System, MI-3DVS)(软件专利号：2008SRl8798),构建针对具体个体的复杂肝胆管结石病程序化3D诊疗模式,系统探讨3D技术指导下外科综合诊疗模式在复杂肝胆管结石病临床应用价值和意义。
一、复杂肝胆管结石病患者三维重建数据库系统的构建
目的：
1.优化CT数据采集方法,获取高质量复杂肝胆管结石病患者亚毫米CT数据；
2.研究基于体绘制交互的分割新算法,构建活人体复杂肝胆管结石病患者模型数据库；
3.利用ResMan临床试验公共管理平台构建复杂肝胆管结石病患者三维重建数据库系统
4.探讨复杂肝胆管结石病患者三维重建数据库系统的临床应用价值
方法：
1.研究对象：逐步收集南方医科大学珠江医院肝胆一科2008年6月至2013年12月收治的复杂肝胆管结石病患者病例资料。
2.数据采集设备：
(1)64排/256层螺旋CT-PHILIPS Brilliance(荷兰PHILIPS公司)；双筒高压注射器及造影剂(碘比乐370mgI/ml)。
(2)图像后处理工作站为PHILIPS Brilliance层螺旋CT自带的Mxview工作站；
(3)南方医科大学数字医学临床中心HP刀片式服务器、高配置计算机；
(4)腹部医学图像三维可视化系统；
3.高质量肝胆管结石亚毫米CT数据采集方法参考(Fang C H, Liu J, Fan Y F, et al. Outcomes of hepatectomy for hepatolithiasis based on3-dimensional reconstruction technique[J]. J Am Coll Surg,2013,217(2):280-288.)。
4.复杂肝胆管结石3D模型构建方法：
(1)基于体绘制交互的图像分割算法：先进行体绘制重建,通过对窗宽和窗位的调节,得到所需胆道结构最清晰的三维图像,直接在体绘制图像上取得三维种子点,进行区域生长,同时在体绘制图像上显示生长的过程,当生长停止时可以通过人机交互,在体绘制三维图像上进行修补。特别对于三级以上胆管,通过局部放大,并对断续胆管进行连接,再进行分割,可以把局部小胆管提取出来。使得组织分割,特别对肝内胆管分割更精细,达到与体绘制相同的分辨率水平。当用户满意当前分割结果时可以立即将当前的分割结果保存,并进行快速的面绘制三维重建。
(2)把基于体绘制交互的分割算法作为一个分割插件整合到腹部医学图像三维可视化系统(MI-3DVS)中,将DICOM格式的亚毫米CT数据导入到MI-3DVS中进行配准、分割、三维重建。
①肝内胆管、胰腺等腹腔脏器重建：使用区域生长法完成分割,采用面绘制方法进行脏器三维重建。
②肝内主要血管三维重建：使用基于体绘制交互的分割算法完成对亚毫米CT断层图像中的血管数据分割,采用面绘制方法进行脏器三维重建。
(3)3D模型的后处理及立体结构观察分析
通过MI-3DVS中的面数据图形处理工具对3D模型进行平滑和去噪,然后将肝内胆管系统3D模型在空间上组合和显示,通过放大、缩小、旋转可视化3D模型来观察、分析肝内胆管病变的分布特点。
5.利用ResMan临床试验公共管理平台构建复杂肝胆管结石病患者三维重建数据库系统
根据中国临床试验中心临床研究电子管理公平台(Research Manager, ResMan)指引(中国临床试验注册中心公告[J].中国循证医学杂志,2007(08)：557-558.),制定复杂肝胆管结石病3D技术指导下外科综合诊疗临床试验的管理流程。利用设计好的流程,将外科诊疗过程中记录的受试者基线资料包括人口学资料和入组时影像学检查及3D基线数据、临床外科试验过程中的实施情况、结果数据等相关资料即“复杂肝胆管结石病3D技术指导下外科综合诊疗临床试验病例记录表(case record form, CRF)'’的所有内容,基于互联网在线记录并传送到中央数据库保存管理。
结果：
1.使用试验注射法采集的亚毫米CT数据图像质量高,胆道系统、肝胆管周围血管、胆道的病变显示清晰。
2.复杂肝胆管结石病患者3D模型立体感强,可清晰地再现患者肝脏的立体形态和有无肥大和萎缩；肝内一、二、三级胆管树立体形态及狭窄或扩张胆管的长度和直径显示清晰,部分肝内胆管结石合并肝内胆管广泛扩张者,甚至四级胆管(亚肝段胆管)也可以得到显示；结石的大小、数量及其在肝内外胆管的分布,门静脉、肝静脉及肝动脉三套血管及其分支在肝内的立体分布等情况也清晰可见。
3.成功建立基于ResMan临床试验公共管理平台的复杂肝胆管结石病3D技术指导下外科综合诊疗公共数据库(public accessable database)。实现试验研究者方便地保存和管理试验资料,免除使用纸张记录,减少集中录入数据的错误可能性和工作量,提高记录可靠性,利于提高临床试验质量。
4.复杂肝胆管结石病3D技术指导下外科综合诊疗公共数据库(public accessable database)达到中国临床试验中心的规范要求,成功完成临床试验的注册。
结论：
1.采集方法优化后的64排/256层螺旋CT可以获得高质量的复杂肝胆管结石病患者亚毫米CT数据,各级胆管系统显影良好,能够区分出微细结构的影像学特征,能满足胆管三维重建分割、三维重建的要求。
2.复杂肝胆管结石病患者3D模型能对肝内结石的分布,胆管狭窄程度和分布,肝脏病理形态改变作出准确系统全面的诊断。
3.基于ResMan I临床试验公共管理平台的复杂肝胆管结石病3D技术指导下外科综合诊疗公共数据库提高记录可靠性,利于提高复杂肝胆管结石病3D技术指导下外科综合诊疗临床试验的评价质量。
二、复杂肝胆管结石病患者3D模型在临床诊疗中的应用研究
目的：
1.探讨复杂肝胆管结石病患者3D模型对肝内病变诊断的应用价值。
2.研究复杂肝胆管结石病患者3D模型在指导复杂肝胆管结石病外科综合治疗术前规划,术式决策的应用价值。
3.研究复杂肝胆管结石病患者3D模型在指导复杂肝胆管结石病综合外科治疗的应用价值。
方法：
1.研究对象：通过南方医科大学珠江医院复杂肝胆管结石病ResMan临床试验公共管理平台(详见第一部分)提取2008年7月至2012年12月南方医科大学复杂肝胆管结石病患者131例进行回顾性研究,根据其是否施行基于3D模型指导复杂肝胆管结石病综合外科治疗,将其分为3D辅助手术组(A组)和非3D辅助手术组(B组)。病例入选标准：(1)18岁以上；(2)符合复杂肝胆管结石的定义；(3)肝功能归类为Child A或B级；(4)能耐受外科治疗。
A组为施行基于3D模型指导复杂肝胆管结石病综合外科治疗,其中男30例,女47例,年龄53.1±11.2岁,病程8个月—15年；B组为施行非3D辅助外科治疗复杂肝胆管结石病组,其中男15例,女39例,年龄54.4±12.7岁,病程7个月—14年。两组患者在性别、年龄、术前肝功能、发病部位、有无合并肝内胆管狭窄及肝脏萎缩等的一般资料方面比较,差异无统计学意义(P>0.05),具有可比性。
2.数据采集设备同第一部分。
3.亚毫米CT数据收集方法同第一部分。
4.复杂肝胆管结石3D模型建立方法同第一部分。
5.根据对肝内结石分布,胆管狭窄程度和分布,肝脏病理形态改变的诊断率,比较3D模型相对于B超,CT, MRI影像检查在临床诊断中的应用优势。
6.复杂肝胆管结石病患者3D模型指导术前规划,术式决策的效果评价：
(1)将重建出的复杂肝胆管结石病患者3D模型导入MI-3DVS系统中,对模型及各组成部分随意进行拆分、放大、缩小、旋转、透明等操作,通过全方位、多角度、多层次地观察各组织结构解剖特点及相互关系,明确：①结石分布的范围；②结石所在肝叶或(和)段有无萎缩；③肝内外胆管有无狭窄、狭窄的部位；④有无合并胆道畸形；⑤有无合并胆道肿瘤；⑥无结石肝叶体积的估算。此外,如果病人合并肝硬化、门静脉高压、阻塞性黄疸等,还应对肝功能代偿能力作出正确的评价。然后利用力反馈设备PHANTOM和自行开发设计的虚拟手术器械对重建模型进行各种类型的仿真手术,通过多种仿真手术方式的模拟和比较确定最终个体化外科综合治疗方案,在实际手术中提供实时指导。
(2)实际手术
观察实际手术中所见肝内外管道解剖结构与结石分布是否与3D模型一致,以及实际手术方式与仿真手术符合情况。术中常规运用胆道镜检查是否残留结石及胆管狭窄,视病情需要放置T管或肝胆管胆道支撑管以用于术后胆道引流、胆道造影及胆道镜检查。术后常规进行胆道造影或胆道镜检查以明确是否有残留结石和胆道狭窄。7.复杂肝胆管结石病患者3D模型在指导综合外科治疗的效果评价
(1)围手术期／短期疗效：实验室数据(血清转氨酶水平,血清胆红素水平,血清白蛋白水平,血清血红蛋白水平,血白细胞水平),外科手术数据(手术时间、术中失血、术中输血),结石清除率,手术并发症率和围手术期死亡率,进行评估。对潜在影响术后并发症发生的因素：性别、年龄、术前并发症,胆道手术史,肝切除术方式,胆肠吻合,术前胆红素、白蛋白水平,术前3D图像分析等,使用logistic回归模型进行统计分析。
(2)远期疗效：术后随访远期肝胆管结石和胆管炎复发率使用Kaplan-Meier方法计算和比较两组间差别。利用多因素Cox回归分析对影响复杂肝胆管结石病患者术后无症状生存的可能因素进行统计分析。8.统计学处理：
对于连续变量采用均数±标准差表示,利用t检验进行统计分析；对于计数资料,则采用X2检验或Fisher's精确检验统计分析。对潜在影响术后并发症发生的相关危险因素：性别、年龄、术前基础疾病、胆道手术史、肝切除术方式、胆肠吻合、术前胆红素、白蛋白水平、术前3D图像分析、术前胆道感染病史、术前基础疾病史,上述11个因素采用多变量Logistic回归分析,用向前法筛选变量,引入变量的检验水准a=0.05。术后随访远期肝内胆管结石复发率和胆管炎复发率采用Log-rank检验比较两组间差别,采用Kaplan-Meier法绘制生存曲线。利用Cox风险模型对影响复杂肝胆管结石病患者术后无症状生存的多因素进行预后分析。假设P<0.05为差异具有统计学意义。所有统计分析均采用SpSS13.0(SPSSInc.,Chicago,IL,USA)统计学软件进行数据分析。
结果
1.复杂肝胆管结石病3D模型的临床诊断结果
通过MI-3DVS软件对复杂肝胆管结石病胆道系统和肝内胆管结石的进行精确分割和重建,A组77例患者肝脏及其内部的各管道系统等三维重建图像形象逼真、立体感强,可清晰地再现患者肝脏的立体形态和有无肥大和萎缩；肝内一、二、三级胆管树立体形态及狭窄或扩张胆管的长度和直径显示清晰,部分肝内胆管结石合并肝内胆管广泛扩张者,甚至四级胆管(亚肝段胆管)也可以得到显示；结石的大小、数量及其在肝内外胆管的分布,门静脉、肝静脉及肝动脉三套血管及其分支在肝内的立体分布等情况也清晰显示。
复杂肝胆管结石病3D模型对肝内胆道狭窄病变的显示率明显高于MRCP, B超、CT,(3D vs. CT,81.8%vs.31.3%, P=0.000,3D vs. MRCP,81.8%vs.58.8%,P=0.039)。在肝脏组织病变的诊断上,复杂肝胆管结石病3D模型诊断显示效果也优于MRCP和B超(3D vs. US,98.7%vs.45.4%, P=0.000,3D vs. MRI/MRCP,98.7%vs.82.4%, P=0.018).3D模型在肝内胆管结石的大小、数量及其在肝内外胆管的分布显示率与MRCP, B超、CT无明显差别。
2.复杂肝胆管结石病3D模型指导术前规划,术式决策的临床结果
(1)3D模型指导术前规划
在MI-3DVS中,通过力反馈设备PHANTOM和虚拟手术器械可方便地对复杂肝胆管结石3D模型进行各种类型的仿真模拟手术规划,包括胆管探查取石术,肝切除术等。通过个体化肝脏分段可准确对结石及胆管狭窄进行定位,术前肝脏体积测量能准确估算肝切除术后残肝体积以规避术后肝功能衰竭发生。可视化仿真手术规划观察肝切除平面内重要血管、胆管及结石的解剖关系,通过多个手术方案的优化筛选确定最佳个体化手术方案。A组77例患者术前规划方案为：1例行胆管探查取石术(包括胆总管切开取石术、肝内胆管切开取石术、狭窄胆管整形术、胆肠吻合术),76例行肝切除术为主的外科手术(包括各种术式的肝部分切除术、肝内外胆管切开取石术、经肝断面胆管探查取石术、术中纤维胆道镜／胆道硬镜取石术、狭窄胆管整形术、胆管支撑管支持引流术、胆肠吻合术)。
(2)实际手术
A组77例患者中l例行胆管探查取石术(包括胆总管切开取石术、肝内胆管切开取石术、狭窄胆管整形术、胆肠吻合术),76例行肝切除术为主的外科手术(包括各种术式的肝部分切除术、肝内外胆管切开取石术、经肝断面胆管探查取石术、狭窄胆管整形术、胆管支撑管支持引流术、胆肠吻合术),与3D模型指导的术前规划相一致。
3.复杂肝胆管结石病3D模型在指导综合外科治疗的评价结果
1.术中手术诊疗效果评价
A组与B组在手术时间、术中输血量、术中出血量和肝脏血流阻断时间的统计比较结果分别为：(269.7±83.0min vs.315.6±81.7min, P=0.002),(77.9±169.0mL vs.192.6±229.7mL, P=0.002),(411±107.9mL vs.517.2±179.4mL, P=0.015)和(12.7±3.2min vs.17.3±4.0min,P=0.001)。A组有1例患者合并肝内胆管细胞癌,与术前3D模型诊断一致。
2.术后早期诊疗效果评价
A组与B组在即刻残石率和最终残石率的统计比较结果分别为：(7.8%vs.38.9%,P<0.001)和(5.2%vs.18.5%,P=0.015)。两组共有25例病人发生结石残留,其中A组6例,B组21例。两组最终结石清除率分别为94.8%和81.5%。两组术后经胆道造影检查证实肝内胆管狭窄残留率分别为(7.8%vs.35.2%,P<0.001)。术后并发症方面,两组间术后常见的并发症统计比较结果为：胸腔积液(13%vs.33.3%,P=0.005),,伤口感染(7.8%vs.20.4%,P=0.035)和肝功能能障碍(2.6%vs.16.7%,P=0.004)。A组与B组术后白蛋白水平比较结果为(38.7±3.0g/L vs.36.9±4.8g/L,P=0.024)。对影响术后并发症(包括切口感染、肺部感染、胸腔积液、膈下感染、肝脓肿、胆瘘、肠瘘、上消化道出血、胆道出血和肝肾综合征等)发生的潜在相关危险因素进行logistic回归分析提示：用向前法筛选变量,引入变量的检验水准α=0.05,在所有的11个考察的有关临床术后并发症发生相关因素,合并胆肠吻合术(OR=2.493,P=0.039,95%CI=1.046-5.943)为术后并发症发生的潜在危险因素；肝切除术(OR=0.629, P=0.016,95%CI=0.431-0.918),术前白蛋白水平(OR=0.926,P=0.033,95%CI=0.862-0.994),3D模型术前规划(OR=0.260, P=0.002,95%CI=0.112-0.602)术后并发症发生的潜在保护因素。
3.术后远期诊疗效果评价
所有病例随访中位时间为28个月,A组9(11.7%)例和B组15(27.8%)例经超声、CT或胆道造影术证实肝内胆管结石复发。两组间肝内胆管结石复发率和胆管炎复发率采用Log-rank检验,A组肝内胆管结石复发率(X2=4.121,P=0.042)和胆管炎复发率(X2=9.866,P=0.002)显著低于B组。
利用Cox风险模型对影响复杂肝胆管结石病患者术后无症状生存的相关因素进行预后分析提示：3D技术进行术前规划是复杂肝胆管结石病患者术后无症状生存的有效保护因素(RR=0.348,95%CI0.185-0.657, P=0.001);但是,性别、年龄、术后并发症、术前胆红素水平、白蛋白水平等相关因素对长期无症状生存无显著性影响。随访期间A组1例术中发现合并胆管细胞癌患者,其术后出现肿瘤复发。除此之外,其余患者无一例进展为胆管细胞癌。
结论：
1.复杂肝胆管结石病患者3D模型真实再现了肝脏内部含有的所有结构包括：胆管、肝动脉、肝静脉、门静脉系统以及结石之间的解剖关系；明确了结石大小、形态、数量、位置及胆管走行；肝内胆管狭窄部位、狭窄程度、狭窄长度,减少术者思考上的模糊性和不稳定性,同时避免侵入性检查如ERCP、PTC等可能诱发出血、胰腺炎、胆管炎的风险。
2.通过复杂肝胆管结石病患者3D模型指导术前规划,制定个体化手术方案,最大程度去除包括萎缩肝叶、肝内胆管结石、肝内胆管狭窄等在内的病灶同时尽量保护术后肝功能,减少并发症发生。A组术后残石率、肝内胆管狭窄残留率、术后结石复发率、术后胆管炎复发率、术后并发症发生率和术后实验室检查指标结果均优于传统B组。
3.复杂肝胆管结石病患者3D模型丰富了传统影像学诊断手段提供的个体化肝内胆管病变信息,指导术前规划,合理制定最佳手术方案,个体化针对性强,避免术中盲目探查导致的结石残留、胆管狭窄残存、正常肝组织损毁、肝内各脉管系统损伤等风险,尽可能缩短手术时间、减少术中失血及术中输血等对病人二次打击,防止术后出现肝功能损伤。
4.复杂肝胆管结石病3D模型指导综合外科诊疗模式能有效减少术后肝内胆管结石和胆管炎的复发,提高患者长期无症状生存率,有效改善复杂肝胆管结石病患者的预后。
三、3D技术联合胆道硬镜外科治疗复杂肝胆管结石病的疗效评价
目的：
1.研究3D技术联合胆道硬镜治疗复杂肝胆管结石病的诊疗价值；
2.比较3D技术联合胆道硬镜治疗模式与现有的外科治疗模式在复杂肝胆管结石病治疗中的临床效果。
方法：
1.研究对象：通过南方医科大学珠江医院复杂肝胆管结石病ResMan临床试验公共管理平台(详见第一部分)提取我院2012年2月至2013年12月期间共25例经3D技术联合术中胆道硬镜外科综合治疗的复杂肝胆管结石病患者进行研究,其中女18例,男7例,年龄31-76岁,平均54岁,定义为C组进行临床研究。同时,提取我院2011年6月至2012年1月期间共27例接受现有外科治疗模式的复杂肝胆管结石病患者资料,其中女22例,男5例,年龄30-83岁,平均53.9岁,定义为D组作为对照组。两组患者在性别、年龄、术前肝功能、肝内胆管结石的分布、既往胆道手术史及术前胆管炎病史等的一般资料方面比较,差异无统计学意义(P>0.05),具有可比性。
2.CT数据的采集所用设备、参数,数据的分割,肝脏和脉管系统的三维重建方法见文献同第二部分。
3.纳入标准：
病例入选标准：(1)18岁以上；(2)符合复杂肝胆管结石的定义；(3)肝功能归类为Child A或B级；(4)能耐受外科治疗；(5)同意接受胆道硬镜治疗。
4.评价指标：
(1)3D模型指导胆道硬镜术前规划
术前通过对复杂肝胆管结石病3D模型进行多角度旋转观察,利用三维可视化技术观察肝内胆管病变情况,明确结石分布的范围；结石所在肝叶或肝段损毁情况；肝内外胆管有无狭窄、狭窄的部位,狭窄的长度；排除有无合并胆道的畸形；通过反复手术演练,制定出个体化的3D技术联合术中胆道硬镜外科治疗的方案。指导制定术中胆道硬镜探查碎石取石的个体化路径。
(2)外科治疗效果评价
术中常规运用胆道硬镜或纤维胆道镜检查是否残留结石及胆管狭窄,视病情需要放置T管或肝胆管胆道支撑管以用于术后胆道引流、胆道造影及胆道镜检查。术后常规进行胆道造影或胆道镜检查以明确是否有残留结石和胆道狭窄。
围手术期效果评价指标：平均手术时间、平均住院时间、即刻结石清除率、术后并发症发生率(肝功能障碍、胆汁瘘、胆道出血)。
远期手术效果评价：远期无症状长期生存率、术后进一步胆道镜取石率、最终残留结石率。
5.统计学处理：
对于连续变量采用均数±标准差表示,利用t检验进行统计分析；对于计数资料,则采用X2检验或Fisher's精确检验统计分析。假设P<0.05为差异具有统计学意义。所有统计分析均使用采用SpSS13.0(SPSSInc.,Chicago,IL,USA)统计学软件进行数据分析。
结果
C组与D组在即刻结石清除率、手术时间和术后住院天数的统计比较结果分别为：(88%vs.66.7%, P=0.012)、(232.4±23.2vs.309.3±87.3min, P=0.010)和(11.1±3.7vs.14.6±3.1days,P=0.001)。
C组24(96%)例患者最终实现完全取尽结石,1例患者因胆汁性肝硬化肝脏损毁严重,肝内胆管双侧弥漫性结石未能完全取尽结石。C组术中合并行右肝部分切除者1例,左外叶切除者l0例。其中l例患者术中发现合并尾状叶胆管细胞癌,术后随访12个月仍存活。
C组出现的围手术期并发症十分轻微。C组2例患者因术中胆道硬镜探查时损伤胆道粘膜而出现术中胆道出血,均通过胆道内注射0.08%的去甲肾上腺盐水保守治疗缓解。其中1例伴有胆汁性肝硬化患者由于术中取石时间较长,术后7天内出现肝功能异常,通过护肝保守治疗后缓解。而D组,共有7例患者因术中采用纤维胆道镜网篮取石出现胆道出血,均通过胆道内注射0.08%的去甲肾上腺盐水保守治疗得到缓解。
D组最后的残石率和术后进一步胆道镜治疗率与C组统计比较结果为：(25.9%vs.4%,P=0.032)和(33.3%vs.12%,P=0.020)。D组有l例患者接受右肝部分切除术,14例患者接受左肝外叶切除术。l例患者出现术后胆瘘。D组与C组统计比较最终残石率为(25.9%vs.4%,P=0.032)。C组和D组中位随访时间分别是13个月和15个月。
结论：
1.3D技术联合术中胆道硬镜外科综合治疗模式有效优化术中胆道硬镜探查取石的路径,缩短手术和住院时间,明显提高复杂肝胆管结石病患者的结石清除率。
2.利用3D技术进行手术规划,对个体化手术方案的制定提供详实的术前指导,能够增加手术成功率,减少术后并发症的发生和术后再次手术率。
Research Background
Complicated Hepatolithiasis concept is not yet unified. For bile duct stones, especially for the surgery again hold unequal treatment in terms of experience, understanding of concepts are not consistent. At present, most scholars believe that the complexity of the removal of bile duct stones is the general condition of the patient, because other diseases such as heart, lung, kidney, diabetes, biliary tract surgery constitutes a threat. In general, hepatolithiasis is divided into "complicated hepatolithiasis" types depending on the presence of bilateral hepatolithiasis or the patients, who received one or more biliary tract surgery, have residue or recurrence stones, bile duct stricture requiring reoperations; the patients combine Caroli'S disease or cholangiocarcinoma and the absence of infections, biliary cirrhosis, portal hypertension,septic manifestations, and intrahepatic abscess (Liang Li Jian, Li Shaoqiang complex diagnosis and treatment of bile duct stones principle [J] Chinese Journal of Surgery2009;..29(7):542-544).
Complicated hepatolithiasis is the most of difficult to treat, the highest rate of reoperation for benign disease. The basical pathologies are complex bile duct stones and intrahepatic bile duct stricture dilation and mechanical biliary obstruction, biliary tract infections, and liver damage. The pathological nature of the entire process of the evolution of the complex pathology of bile duct stones, there is a close relationship with bile duct stones and bile duct narrow. Report on the clinical display of hepatic cholangiocarcinoma:repeated episodes of biliary tract infections, may be a change in the nature of the lesion. According to the complex evolution of bile duct stones above pathological understanding, Ong et al, raises complex surgical treatment of bile duct stones in principle in1962:"With the detailed understanding of the bile duct pathology, the eradication of stones, narrow and contain foci of disease recurrence hepatic tissue." It's programs happens to coincide with the ideal," Take out all of the bile ducts stones, remove all of the bile ducts obstructions, remove all of the liver lesions, unobstructed drainaging ", of Wong Chi Keung Academy's. Because bile duct stones are not only the accumulation of stones, often accompanied occurs in all levels of intrahepatic duct stenosis and hyperplastic lesions, which is the core of treatment, and surgical treatment is still to be one of the most effective means to achieve the therapeutic purposes, which is the most commonly methods. Select surgery programs must be individualized, depending on the number and distribution of intrahepatic bile duct stones, biliary stricture location and extent of the pathological changes in the liver, liver function and general condition of the patient, the development of targeted individualized treatment plan and select appropriate surgical approach.
Despite nearly20years of complicated hepatolithiasis understanding and treatment has been significant progress, but because of its complex pathophysiological process and prone to serious complications characteristic, is still plagued by the problem of biliary surgeon. For complicated hepatolithiasis should make adequate preoperative preparation, try to get detailed imaging data and liver function evaluation. Preoperative biliary anatomy, intrahepatic bile duct stones location, distribution, quantity, bile duct stricture location, shape should have an accurate understanding. And pay attention to whether the variation in intrahepatic bile ducts, especially the posterior lobe of the right bile duct variations, the most common is the right hepatic duct abnormalities, especially in the posterior lobe of the right bile duct directly into the left hepatic bile duct. For the right posterior bile duct stones variation due to an acute angle to import alone stone forceps stone or stone surgery choledochoscopic difficult to take the net calculus, which is an important factor in causing postoperative anatomical right posterior residual stones (Mori T, Sugiyama M, Atomi Y. Gallstone disease:Management of intrahepatic stones[J]. Best Pract Res Clin Gastroenterol,2006,20(6):1117-1137.). At the same time, to fully understand the pathology before surgery, surgical causes and methods, as well as the specific circumstances of the current lesion is extremely important in order to formulate a reoperation individualized surgical treatment. Any hasty decision surgery may cause more surgery times, the patients suffer more pain.
In recent years, with the development of laparoscopic techniques, endoscopy and interventional techniques, a variety of minimally invasive treatment has been widely reported, such as percutaneous transhepatic biliary lithotripsy and holmium laser mirror or pneumatic lithotripsy of bile duct stones in general has made remarkable efficacy, but for complicated hepatolithiasis postoperative residual stone rate of up to20%-50%(Cheng Y F, Lee T Y, Sheen-Chen S M, et al. Treatment of complicated hepatolithiasis with intrahepatic biliary stricture by ductal dilatation and stenting: long-term results[J]. World J Surg,2000,24(6):712-716.). The above technique for endoscopic treatment of bile duct stones complicated treatment is still controversial, evidence is still lacking the bulk of cases.
Currently, the diagnosis of complicated hepatolithiasis mainly rely on B ultrasound, CT and MR and other noninvasive imaging tests to clear stones location, size, number and distribution, location and extent of bile duct stenosis, thereby positioning the diagnosis. Combined liver function in patients, Oddi sphincter function, with or without liver cholangitis episodes, with or without obstructive jaundice, with or without hilar bile duct stricture, portal vein hypertension and splenomegaly combination of factors such as surgical planning. However, due to the widespread distribution of intrahepatic bile duct stones, but with various degrees of bile duct stricture disease and liver damage, these various imaging methods have advantages and disadvantages, and often require the integrated use of several imaging methods, in order to do a more comprehensive diagnosis. There is no ideal diagnostic method to make a comprehensive diagnostic system for stone size, number and distribution, bile duct stenosis and length, pathological liver, bile ducts and blood vessels as well as the relationship.
With the development of computer science, based on three-dimensional reconstruction of CT or MRI technology has been widely used in clinical diagnosis and treatment of hepatobiliary surgery activities, its virtual surgical planning system can help hepatobiliary surgeon in advance of surgery simulation operations before surgery, to develop individualized surgery program, thereby reducing the actual surgery pointless damage, improve the actual safety of surgery. At home and abroad there have been several hepatobiliary virtual surgery systems used in clinical, its clinical effect is satisfied and it has great help for clinical work. However, the diagnosis and treatment of intrahepatic bile duct stones used in digital medicine is still in its early stages, less relevant literature. Moreover, for complex three-dimensional reconstruction of bile duct stones bulk of cases (3D technology) system under the guidance of surgical polyclinics evaluate the effect has not been reported in the literature.
Based on the above issues, this subject collects the patients treated bile duct stones submillimeter CT complex data quality of the collection from June2008to December2013in Division I of Hepatobiliary of Zhujiang Hospital, Southern Medical University, based on the use of abdominal medical images with independent intellectual property rights3D Visualization System (Medical Image Three-Dimensional Visualization System, MI-3DVS)(software patent number:2008SR18798), built for specific individuals complicated hepatolithiasis complicated treatment procedures3D mode, the system discussed under the technical guidance of surgical polyclinics3D mode bile duct stones in complex clinical value and significance.
Part I. Design of three-dimensional reconstruction database system for Complicated Hepatolithiasis
Objective
1. Optimization of CT data acquisition method to obtain high-quality sub-millimeter CT data for complicated hepatolithiasis patients;
2. Interactive volume rendering based segmentation algorithm to construct complicated hepatolithiasis model database;
3Clinical trial based on ResMan public management platform to build a complex three-dimensional reconstruction of bile duct stones database system for comprehensive hepatolithiasis patients;
4Investigate complex clinical value of the database systemin for the patients with complicated hepatolithiasis.
Methods
1. Retrospectively collected the complicated hepatolith disease case information of zhujiang hospital, Southern Medical University from June2008to December2013step by step.64rows/256slice CT
2. The equipments used to collect data include64rows/256slice CT spiral CT scanner (CT PHILIPS Brilliance, made in Dutch); double tube high pressure syringe and contrast agents (Lopamiro in a dose of370mg I/ml); the self attached Mxview workstation for post processing of the images; HP blade server and high configuration computer (from Clinical Center of Digital Medicine, Southern Medical University, Guangzhou, China) and the abdominal three-dimensional visualization system.
3. The procedures for collecting high quality submillimeter CT data of intrahepatic bile duct include:prescanning preparation, plain scanning, trial injection, routine enhanced scanning as well as the transmission and storage of thin layer CT scanning data.(Fang C H, Liu J, Fan Y F, et al. Outcomes of hepatectomy for hepatolithiasis based on3-dimensional reconstruction technique[J]. J Am Coll Surg,2013,217(2):280-288.)
4.3D model building method for complex Hepatolithiasis:
(1)Interactive volume rendering image segmentation algorithm based on:the first reconstruction volume rendering through the window width and window level adjustment to obtain the desired structure of the biliary clear three-dimensional images.
(2)The volume rendering interactive segmentation algorithm as a segmentation plug-in integrated into the abdomen medical image visualization system (MI-3DVS), the import sub-millimeter CT data in DICOM format to MI-3DVS conducted registration, segmentation, three-dimensional reconstruction.
(3)Post-processing of the3D model and observe and analyze the three-dimensional structure.
By MI-3DVS the surface data processing tools for3D graphics model smoothing and de-noising, then the intrahepatic bile duct system is a combination of3D models and display, zoom in, zoom out, rotate the3D model visualization in space to observe, analyze intrahepatic distribution duct lesions.
5. Public use ResMan clinical trial management platform to build complex patients
with bile duct stones dimensional reconstruction of the database system.
Results
1. The quality of submillimeter CT images obtained via trial injection was optimal, with favorable demonstrations of the biliary lesions, peripheral arterial lesions of the extrahepatic bile duct, peripancreatic lesions and periampullar lesions.
2. The3D model of arteries supplying the extrahepatic bile duct can be multidimensionally rotated to clearly demonstrate the origins and distributions of the arteries supplying the extrahepatic bile duct. The arteries supplying the superior segment of extrahepatic bile duct were found to be originated from the right hepatic artery, the gallbladder artery, the left hepatic artery and the proper hepatic artery. However, the arteries supplying the inferior segment of the extrahepatic bile duct were found to be originated from the superioposterior pancreatoduodenal artery, the astroduodenal artery, the gallbladder artery and the retroportal artery.
3. The3D model of arteries supplying the extrahepatic bile duct can be multi-dimensionally observed and analyzed for the anatomical relationships. Traditional sketches can only display the anatomic structures on the surface. However, it has the advantage of demonstrating vascular vessels that the3D model fails to display, such as the artery plexus around the bile duct. The sketches are based on the cadaveric perfusion under a surgical microscope.
Conclusions:
1.64rows/256slice CT spiral CT scanning with optimized data collecting method can obtain high quality submillimeter CT data of the arteries supplying the extrahepatic bile duct, with well demonstrated vasculature. It can facilitate to distinguish the imaging demonstrations of the micro-structures, which satisfies the requirements for segmentation and3D reconstruction of arteries supplying the extrahepatic bile duct.
2. Based on volume rendering of interactive segmentation method, the scanning data of arterioles supplying the extrahepatic bile duct can be extracted and segmented for3D reconstruction. The3D model reconstructed by using MI-3DVS can display the three-dimensional anatomical structures of the extrahepatic bile duct and its blood supplying arteries.
3. The reconstructed3D model is authentic and direct, which facilitates the learning of anatomic knowledge and related researches.
Part II Evaluation of the value in clinical diagnosis and treatment by3D models for Complicated Hepatolithiasis
Purpose:
1. Explore the clinical value on liver lesions using by3D model for complicated hepatolithiasis patients.
2. Study the application value of3D models for complicated hepatolithiasis patients with bile duct stones before guiding complex surgical therapy integrated planning, surgical decision-making.
3. Study the integrated application value of3D models for complicated hepatolithiasis patients in guiding complex surgical treatment.
Method:
1.Study subjects:Zhujiang Hospital, Southern Medical complicated by hepatolithiasis ResMan clinical trials of public management platform (Part I) extraction from July2008to December2012in patients with bile duct stones, Southern Medical complex131cases, according to the whether implementation guidance based on complex3D models integrated surgical treatment of bile duct stones, will be divided into A groupgroup (A) and the non-A groupgroup (group B).
Case inclusion criteria:(1) More than18years of age;(2) Meet the definition of complicated hepatolithiasis;(3) Liver function classified as Child A or B;(4) Can tolerate surgical treatment.
Group A for the purposes of guidance based on3D models integrated surgical treatment of complex bile duct stones, including30males and47females, aged53.1±11.2years, duration of8months-15years; Group B for the purposes of the traditional surgical treatment of complex hepatolithiasis group, including15males and39females, aged54.4±12.7years, duration of7months-14years. Two groups were compared before sex, age, preoperative liver function, disease location, presence or absence of intrahepatic bile duct stricture and liver atrophy and other general information, the difference was not statistically significant (P>0.05), comparable.
2. Data acquisition devices are the same as mentioned in first part.
3. Submillimeter CT data collection methods are the same as the first part.
4. The3D modeling method of complex Hepatolithiasis is same as the first part.
5. According to the distribution of intrahepatic stones diagnosis rate, bile duct stenosis and distribution of pathological changes in the liver, comparing the3D model with respect to B-, CT, MRI imaging application advantages in clinical diagnosis.
6. Evaluate the effect of patient's3D models of complex Hepatolithiasis before surgery to guide the planning, surgical decision-making.
(1) Import the reconstruction3D models of complex hepatobiliary duct stones in patients into MI-3DVS import system, freely split the model and its components, zoom, rotation, transparency, etc, through comprehensive, multi-angle, multi-level structure observed anatomical characteristics and relationships, specifically:①Range of bile duct stones distribution;②Bile duct stones where the lobe or (and) whether the shrinking segment;③Whether the extrahepatic bile duct stenosis, narrow part;④Have biliary abnormalities;⑤Have biliary cancer;⑥No estimate stones lobe volume. In addition, if the patient with cirrhosis, portal hypertension, obstructive jaundice, liver function should also make a correct evaluation of the compensatory ability. Then use the PHANTOM force-feedback device designed and developed a virtual surgical instruments for various types of simulation model reconstruction surgery, through modeling and simulation comparing multiple surgical procedures to determine the final develop individualized surgical comprehensive treatment program, provided the actual surgery Real-time guidance.
(2) The actual surgery
Observe the actual surgery seen in the anatomy and extrahepatic duct stones distribution is consistent with the3D model, and simulation and the actual surgical procedure compliance. Routine using of intraoperative endoscopy diagnose whether residual biliary stones and biliary strictures and conventional T-tube placement for postoperative cholangiography and biliary endoscopy. Routine postoperative cholangiography or biliary endoscopy to confirm whether there is residual stones and biliary stricture.
7. The effect evaluation of patient's3D model of complex bile duct stones in guidance of comprehensive surgical treatment.
(1) Perioperative/short-term effect:laboratory data (serum transaminase levels, serum bilirubin, serum albumin, serum hemoglobin levels, white blood cell levels), surgical data (operative time, intraoperative blood loss, intraoperative blood transfusion), stone clearance rate, the rate of surgical complications and perioperative mortality assessed. The potential impact of the factors of postoperative complications: gender, age, preoperative complications, biliary tract surgery, liver resection way cholangioenterostomy, preoperative bilirubin, albumin level, preoperative3D image analysis, using logistic regression models for statistical analysis.
(2) Long-term effect:long-term follow-up after bile duct stones and cholangitis recurrence rate is calculated using the Kaplan-Meier method and comparing the difference between the two groups. The using of multivariate Cox regression analysis estimate of possible factors in asymptomatic patients after bile duct stones affect the survival of a complex statistical analysis.
8. Statistical analysis:
The perioperative/short-term outcomes, including laboratory data (serum aminotransferase level, serum bilirubin level, serum albumin level, serum hemoglobin level, blood leukocytes level), surgical data (operation time, intraoperative blood loss, intraoperative blood transfusion), stone clearance rate, operative morbidity and mortality, were evaluated. Continuous variables were expressed as mean±standard deviation and compared using the Student's t-test, Chi-squared test, and Fisher's exact tests. The influence of potential factors that may affect operative morbidity, sex, age, preoperative comorbidities, previous biliary tract surgery, type of hepatectomy (left vs. right), concomitant hepaticojejunostomy, preoperative bilirubin, and albumin levels, preoperative3D images analysis, were analyzed using a logistic regression model. Long-term results, including recurrence of biliary stone and cholangitis rate, were also studied. Long-term survival was computed using the Kaplan-Meier method and compared between groups by the log-rank test. Overall survival was measured from the date of surgery to the time of detection of recurrent stones and cholangitis. Cox regression analysis was used to determine which factors significantly influenced long-term asymptomatic survival. A P-value<0.05was considered statistically significant. All statistical analyses were performed using SPSS13.0(SPSSInc.,Chicago,IL,USA) for Windows.
Results:
1. The outcome of3D model for complicated hepatolithiasis patients in clinical diagnosis.
Using by MI-3DVS software, it can segment accurately and reconstruct the biliary system and stones of complex bile duct stones,3D-assisted surgery group of77patients the liver and its internal piping system and other vivid, three-dimensional sense, can be clearly patients with liver reproduce three-dimensional shape and the presence or absence hypertrophy and atrophy; intrahepatic one, two, three bile duct stenosis or establish a body shape and length and diameter of the bile duct dilatation clear display, part of intrahepatic bile duct stones with extensive intrahepatic bile duct dilation, even four bile duct (sub-hepatic bile ducts) can also be displayed; stone size, number and distribution in the case of the three-dimensional distribution in the liver and other extrahepatic bile duct, portal vein, hepatic vein and hepatic artery and its branches three vessels also clearly visible.
The diagnosis rate using by3D model of complex bile duct stones and intrahepatic bile duct stenosis was significantly higher than MRCP, B ultrasonography, CT,(3D vs. CT,81.8%vs.31.3%, P<0.001,3D vs. MRCP,81.8%vs.58.8%, P=0.021). In the diagnosis of liver lesions, the diagnostic performance using by3D model of complex bile duct stones is better than MRCP and B ultrasonography (3D vs. US,98.7%vs.45.4%, P<0.001,3D vs. MRI/MRCP,98.7%vs.82.4%, P=0.018).3D model of intrahepatic bile duct stones the size, quantity and super distribution in extrahepatic bile duct diagnosis rate and MRCP, B ultrasonography, CT was no significant difference.
2The effect of3D model for complicated hepatolithiasis patients on operation planning and decision-making during surgery.
(1) Use3D models to guide the preoperative planning
In MI-3DVS system, by PHANTOM force feedback device and virtual surgical instruments can be easily reconstructed model for the simulation of various types of surgery, including bile duct exploration lithotripsy, liver resection and so on. Accurate to locate bile duct stones and bile duct stricture by individual segments, preoperative volume measurement can accurately estimate the remnant liver volume after hepatectomy to avoid postoperative liver failure. Visual simulation surgery anatomical relationship observed in liver resection plane important blood vessels and bile duct stones, determine the best individualized surgical plan by optimizing multiple surgical screening programs.3D-assisted surgery group77cases of preoperative planning are:1routine bile duct exploration lithotripsy (including choledocholithotomy surgery, lithotomy intrahepatic bile duct, bile duct stricture plastic surgery, biliary-enteric anastomosis),76cases mainly hepatic resection surgery (including surgical procedures partial hepatectomy, extrahepatic bile duct lithotomy, hepatic bile duct exploration lithotomy section, bile duct stricture plastic surgery, biliary drainage support tube support, bile intestinal anastomosis).
(2) The actual surgery
1of77patients in A groupgroup underwent bile duct exploration lithotripsy (including choledocholithotomy surgery, lithotomy intrahepatic bile duct, bile duct stricture plastic surgery, biliary-enteric anastomosis),76underwent hepatic resection is lord surgery (including surgical resection of liver section, extrahepatic bile duct lithotomy, hepatic bile duct exploration lithotomy section, bile duct stricture plastic surgery, biliary drainage support tube support, biliary-enteric anastomosis), it is consistent with the preoperative planning in the guidance of3D models.
3The effect of3D models for complicated hepatolithiasis patients in guiding surgical treatment.
(1) Evaluation of intraoperative surgical treatment
Group A and Group B in operative time, intraoperative blood transfusion, blood loss and liver blood flow occlusion time statistical comparison results are:(269.7±83.0min vs315.6±81.7min, P=0.002.),(77.9±169.0mL vs.192.6±229.7mL, P=0.002),(411±107.9mL vs.517.2±179.4mL, P=0.015) and (12.7±3.2min vs.17.3±4.0min, P=0.001). Group A1patients with intrahepatic cholangiocarcinoma, the3D model is consistent with the preoperative diagnosis.
A set of statistics compared with Group A and Group B in immediate residual stone rate and final residual stone rate results were:(7.8%vs.38.9%, P<0.001), and (5.2%vs.18.5%, P=0.015). A total of25cases of two patients with residual stones occurred, where Group A of six cases,21cases of group B. Two final stone clearance rate was94.8%and81.5%, respectively. Postoperative angiography confirmed by intrahepatic bile duct stricture residual rate was (7.8%vs.35.2%, P<0.001). Postoperative complications between the Group A and Group B a common complication after statistical comparison results:pleural effusion (13%vs.33.3%, P=0.005), wound infection (7.8%vs.20.4%, P=0.035.) and liver dysfunction (2.6%vs.16.7%, P=0.004). Group A and Group B after the comparison of albumin levels (38.7±3.0g/L vs.36.9±4.8g/L, P=0.024). On the impact of postoperative complications (including wound infection, lung infection, pleural effusion, subphrenic infection, liver abscess, biliary fistula, intestinal fistula, upper gastrointestinal bleeding, biliary tract bleeding and hepatorenal syndrome, etc.). Potential risk factors for postoperative complications were logistic regression analysis showed:Screening using forward variable, test level to introduce variable a=0.05, the relevant factors occurred in all11clinical complications related to merger biliary-enteric anastomosis (OR=2.493, P=0.039,95%CI=1.046-5.943) as a potential risk factor for postoperative complications; liver resection (OR=0.629, P=0.016,95%CI=0.431-0.918), preoperative albumin level (OR=0.926, P=0.033,95%CI=0.862-0.994), the3D model before surgery planning (OR=0.260, P=0.002,95%CI=0.112-0.602) after complications potential protective factors occur.(2) Postoperative evaluation of long-term clinical results
All patients were followed a median time of28months,3D-assisted surgery group9(11.7%) patients and the surgical group15(27.8%) patients with ultrasound, CT or angiography confirmed intrahepatic bile duct stone recurrence Between the two groups of intrahepatic bile duct stone recurrence rate and cholangitis recurrence rate using Log-rank test, A groupgroup intrahepatic bile duct stone recurrence rate (x2=4.121, P=4.121) and cholangitis recurrence rate (X2=9.866, P=9.866) was significantly lower than the surgery group.
Cox risk model related to the use of complex factors affecting postoperative bile duct stones in patients with asymptomatic survival prognosis analysis showed:3D technology for preoperative planning is an effective protective factor complex surgery in asymptomatic patients with bile duct stones survival (RR=0.348,95%CI0.185-0.657,.P=0.001); however, the relevant factors such as gender, age, postoperative complications, preoperative bilirubin, albumin level, the position of intrahepatic stones and other long-term symptom-free survival significant effect None of patients subsequently developed cholangiocarcinoma during follow-up, except one patient in A groupgroup for the cholangiocarcinoma recurrence after surgery.
Conclusions
1.3D model of complex bile duct stones in patients with a true representation of all contained within the structure of the liver include:bile duct, hepatic artery, hepatic vein, portal venous system and anatomic relationship between the bile duct stones; clear stone size, shape, number, location and traveling bile duct; intrahepatic bile duct stenosis, stenosis, stricture length, reduce ambiguity and thinking on the stability of the surgeon, while avoiding invasive procedures such as ERCP, PTC which may induce the risk of bleeding, pancreatitis, cholangitis.
2Through complex hepatobiliary surgery patients before the3D model to guide planning duct stones, develop individualized surgical plan, including removing the greatest degree lobe atrophy, intrahepatic bile duct stones, intrahepatic bile duct stricture, etc., while maximizing protection of postoperative liver lesions function and reduce complications. A groupgroup were residual stone rate, residual rate of intrahepatic bile duct stricture, stone recurrence rate after surgery, postoperative cholangitis recurrence rate, incidence of postoperative complications and postoperative laboratory parameters were superior to conventional surgery group results.
3.3D model of complex bile duct stones in patients with intrahepatic bile duct enrich individual lesions traditional imaging diagnostic tools, guidance preoperative planning, reasonable surgical plan to develop the best individualized targeted, avoiding blind exploratory surgery resulting residual stones, bile duct stricture remaining normal liver tissue damage, the risk of intrahepatic vascular system of each injury, as far as possible to shorten the operation time, reduce intraoperative blood loss and intraoperative blood transfusions to patients secondary to combat and prevent postoperative liver function sustained damage.
4.3D model of complex bile duct stones comprehensive guide surgical treatment model can effectively reduce postoperative intrahepatic bile duct stones and cholangitis recurrence and improve survival in patients with long-term symptoms, improve the prognosis of patients with complicated bile duct stones.
Part III Evaluation of the management complicated hepatolithiasis with operative rigid choledochoscope guided by3D reconstruction technique
Purpose:
1. Research on3D technology combined with operative rigid choledochoscope comprehensive therapeutic value of complicated hepatolithiasis;
2. Comparison of the clinical effect between the3D technology combined with operative rigid choledochoscope comprehensive treatment model and the traditional existing surgical treatment model in the treatment of complicated hepatolithiasis.
Method:
l.The object of study:complicated hepatolithiasis ResMan clinical trials of public management platform (Part I) extraction by our hospital, Zhujiang Hospital, Southern Medical University from February2012to December2013period by a total of25cases of3D technology combined with intraoperative biliary bile duct stones in patients with complex surgical comprehensive treatment of the rigid choledochoscope which18females,7males, aged31-76years, mean54years, defined as Group C. Meanwhile, during the extraction hospital from June2011to January2012a total of27cases of patients who received conventional surgical treatment of complex data bile duct stones, including22females,5males, aged30-83years, mean53.9years, is defined as the Group D as a control group. More general information on the two groups of patients before sex, age, preoperative liver function, distribution of intrahepatic bile duct stones, previous history of surgery and preoperative biliary cholangitis medical history, the difference was not statistically significant (P>0.05), comparable.
2. CT data acquisition equipment used for segmentation, parameters, data, three-dimensional reconstruction of the liver and vascular system, see the second part of the same document.
3. Inclusion criteria:
Case inclusion criteria:(1) More than18years of age;(2) Meet the definition of complicated hepatolithiasis;(3) Liver function classified as Child A or B;(4) Can tolerate surgical treatment;(5) Agree accept operative rigid choledochoscope treatment.
4. Evaluation:
All patients were followed up after treatment with the rigid choledochoscope guided by CT-based3D reconstruction technique and traditional method. The follow-up examinations included T-tube cholangiography, ultrasonography and laboratory tests (hemoglobin, white blood cell count, bilirubin, alanine aminotransferase, aspartate aminotransferase, creatinine, serum urea nitrogen, CEA, CA-199), which were performed every three months. Stones detected in the intrahepatic bile duct within3months after therapies were considered as residual stones. Patients were followed up regularly in the hepatobiliary outpatient clinic. Median follow up time was13months, ranging from5-23months.
5. Statistical treatment
Continuous variables were expressed as the mean±standard and compared using Student's test. Categorical variables were expressed as n (%) and compared using the Chi-square or Fisher'
引文
[1]中华医学会外科学分会胆道外科学组.肝胆管结石病诊断与治疗指南.中华消化外科杂志.2007；6(2)：156-61.
[2]董家鸿,郑树国,陈平,等.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(21)：159-161.
[3]Shoda J, Tanaka N, Osuga T. Hepatolithiasis-epidemiology and pathogenesis update[J]. Front Biosci,2003,8:398-409.
[4]Tazuma S. Gallstone disease:epidemiology, pathogenesis, and classification of biliary stones(common bile duct and intrahepatic)[J]. Best Pract Res Clin Gastroenterol,2006,20(6):1075-1083.
[5]邹声泉,郭伟,秦仁义,等.肝内胆管结石外科手术治疗疗效的分析[J].中华外科杂志.2003；41(7)：509-512.
[6]梁力建,李绍强.复杂肝胆管结石诊断和治疗原则[J].中国实用外科杂志.2009；29(7)：542-544.
[7]黄志强.我国肝内胆管结石外科治疗的发展[J].外科杂志,1996,1(3)：61.
[8]梁力建.肝胆管结石影像学诊断方法的评价和合理选择[J].中国普外基础与临床杂志,2006,13(4).
[9]方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值[J].中华外科杂志,2009,47(12)：909-911.
[10]Fang CH, Xie AW, Chen ML, et al. Application of a visible simulation surgery technique in preoperation planning for intrahepatic calculi[J]. World J Surg, 2010,34(2):327-335.
[11]Han JH, Park DH, Moon SH, et al. Peroral direct cholangioscopic lithotripsy with a standard upper endoscope for difficult bile duct stones (with videos) [J]. Gastrointest Endosc 2009; 70(1):183-5.
[12]Suhocki PV. Commentary on "Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis"[J]. Am J Gastroenterol 2003; 98(12):2589-90.
[13]Huang MH, Chen CH, Yang JC, et al. Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis[J]. Am J Gastroenterol 2003; 98(12):2655-62.
[14]Vetrone G, Ercolani G, Grazi GL, et al. Surgical therapy for hepatolithiasis:a Western experience [J]. J Am Coll Surg 2006; 202(2):306-12.
[15]方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值[J].中华外科杂志,2009,47(12)：909-911.
[16]陈刚,晋云,谭立文,等.三维数字虚拟人体肝脏系统的建立及其应用[J].第三军医大学学报,2008(22)：2103-2106.
[17]方驰华,顾杨.数字医学技术在我国腹部外科临床应用现状、困难和发展前景[J].中国实用外科杂志,2013(01)：25-29.
[18]林科灿,刘景丰,曾金华,等.虚拟肝脏手术规划应用于肝切除术的研究[J].中华外科杂志,2010,48(3)：185-188.
[19]杨世忠,顾万清,段伟东,等.计算机辅助手术规划系统在复杂肝门部胆管癌根治性切除术中的应用[J].中华消化外科杂志,2012,11(2)：124-128.
[20]Rubin GD, Dake MD, Semba CP. Current status of three-demensional spiral CT scanning for the vasculature[J].Radiographics.2002:22(5):3-19.
[21]Fang C H, You J H, Lau W Y, et al. Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects[J]. World J Surg, 2012,36(1):120-124.
[22]Saito S, Yamanaka J, Miura K, et al. A novel 3D hepatectomy simulation based on liver circulation:application to liver resection and transplantation[J]. Hepatology,2005,41(6):1297-1304.
[23]Xie A, Fang C, Huang Y, et al. Application of three-dimensional reconstruction and visible simulation technique in reoperation of hepatolithiasis[J]. J Gastroenterol Hepatol,2013,28(2):248-254.
[1]Buyse M. Centralized Treatment Allocation in Comparative Clinical Trials[J], APPLIED CLINICAL TRIALS,2000,9 (6):32-37.
[2]Krischer JP, Hurley C, Pillalamam M,et al. An automated patient registration and treatment randomization system for muhicenter clinical trials[J].Control Clial Trials,1991,12 (3):367-377.
[3]Papaconstantinou C, Krischer J P. An automated patient registration and treatment randomization system[J]. J Med Syst,1995,19(6):445-456.
[4]ICH. Sixth International Conference on Harmonisation New Horizons and Future Challenges, www.ich.org,2006-11-01.
[5]洪楠主编.SPSS for Windows统计分析教程,北京：电子工业出版社,2000.
[6]何丽云,文天才,刘保延,梁志伟。中医临床研究中数据库管理系统的选择与应用,中医药信息学,Nov.2005 Vol.12 No.11,90-91.
[7]Fang C H, You J H, Lau W Y, et al. Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects[J]. World J Surg,2012,36(1):120-124.
[8]Xie A, Fang C, Huang Y, et al. Application of three-dimensional reconstruction and visible simulation technique in reoperation of hepatolithiasis[J]. J Gastroenterol Hepatol,2013,28(2):248-254.
[9]林科灿,刘景丰,曾金华,等.虚拟肝脏手术规划应用于肝切除术的研究[J].中华外科杂志,2010,48(3)：185-188.
[10]方驰华,顾杨.数字医学技术在我国腹部外科临床应用现状、困难和发展前景[J].中国实用外科杂志,2013(01)：25-29.
[11]Cui F, Li J, Ding A, et al. Conditional QTL mapping for plant height with respect to the length of the spike and internode in two mapping populations of wheat[J]. Theor Appl Genet,2011,122(8):1517-1536.
[12]陆健.临床试验电子化数据管理与统计分析系统的开发及应用.2012.42.
[13方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值[J].中华外科杂志,2009,47(12)：909-9l1.
[14]邹声泉,郭伟,秦仁义,等.肝内胆管结石外科手术治疗疗效的分析[J].中华外科杂志.2003；41(7)：509-512.
[15]梁力建.肝胆管结石影像学诊断方法的评价和合理选择[J].中国普外基础与临床杂志,2006,13(4).
[16]Saito S, Yamanaka J, Miura K, et al. A novel 3D hepatectomy simulation based on liver circulation:application to liver resection and transplantation [J]. Hepatology,2005,41 (6):1297-1304.
[17]陶文强,侯致典,徐达传,等.肝门静脉64排螺旋CT数据Mimics软件三维重建及其解剖变异[J].南方医科大学学报,2011(01)：121-124.
[18]陈刚,晋云,谭立文,等.三维数字虚拟人体肝脏系统的建立及其应用[J].第三军医大学学报,2008(22)：2103-2106.
[19]Fang CH, Xie AW, Chen ML, et al. Application of a visible simulation surgery technique in preoperation planning for intrahepatic calculi[J]. World J Surg, 2010,34(2):327-335.
[20]Rubin GD, Dake MD, Semba CP. Current status of three-demensional spiral CT scanning for the vasculature[J].Radiographics.2002:22(5):3-19.
[2l]翁璇,郑小林,姜海.医学图像分割技术研究进展[J].医疗卫生装备,2007(01)：37-39.
[22]李洪艳,曹建荣,谈文婷,等.图像分割技术综述[J].山东建筑大学学报,2010(01)：85-89.
[23]Chittajallu D R, Paragios N, Kakadiaris I A. An explicit shape-constrained MRF-based contour evolution method for 2-D medical image segmentation [J]. IEEE J Biomed Health Inform,2014,18(1):120-129.
[24]Torbati N, Ayatollahi A, Kermani A. An efficient neural network based method for medical image segmentation[J]. Comput Biol Med,2014,44:76-87.
[25]Wen J, Yan Z, Jiang J. Novel lattice Boltzmann method based on integrated edge and region information for medical image segmentation[J]. Biomed Mater Eng,2014,24(1):1247-1252.
[26]Zhou W, Xie Y. Interactive medical image segmentation using snake and multiscale curve editing[J]. Comput Math Methods Med,2013,2013:325903.
[27]Xu J, Gu L. [A novel validation method based on radial distance error for 3D medical image segmentation][J]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi,2007,24(4):742-747.
[28]Huang J, Huang X, Metaxas D, et al. Adaptive metamorphs model for 3D medical image segmentation [J]. Med Image Comput Comput Assist Interv,2007,10(Pt 1):302-310.
[29]Cramon P, Rasmussen A K, Bonnema S J, et al. Development and implementation of PROgmatic:A clinical trial management system for pragmatic multi-centre trials, optimised for electronic data capture and patient-reported outcomes[J]. Clin Trials,2014.
[30]Suzuki S, Shimada M, Shibata-Hiraizumi Y. Clinical trial of expectant management of severe preeclampsia that develops at<32 weeks'gestation at a Japanese perinatal center[J]. J Matern Fetal Neonatal Med,2014.
[31]Rustoen T, Valeberg B T, Kolstad E, et al. A randomized clinical trial of the efficacy of a self-care intervention to improve cancer pain management J]. Cancer Nurs,2014,37(1):34-43.
[32]孔玉,陆健,贺佳等CompareData Quick I临床数据管理系统的开发与利用[J].中国卫生统计,2007；24(1)：80-81.
[33]柳松青.面向对象在数据库设计中的应用[J].计算机工程与设计,2012,23(9)：5l-54.
[34]Ball G D, Ambler K A, Keaschuk R A, et al. Parents as agents of change (PAC) in pediatric weight management:the protocol for the PAC randomized clinical trial[J]. BMC Pediatr,2012,12:114.
[35]刘保延,文天才,姚晨等.多中心临床试验中的中央随机系统研究[J],中国新药与临床杂志,2006,25(12)：931-934.
[36]闫世艳,夏结来,姚晨.中心随机化系统在临床试验中的应用[J],中国循证医学杂志,2005,5(8)：632-635.
[37]中国临床试验注册中心公告[J].中国循证医学杂志,2007(08)：557-558.
[38]吴泰相,刘关键.关于循证医学的问题与思考[J].中国循证医学杂志,2005(08)：636-640.
[39]谢敖文,方驰华.3D技术在复发性肝胆管结石诊断和手术方式选择中的价值[J].中国实用外科杂志,2013(01)：43-46.
[40]黄志强.3D时代的肝胆胰外科：从“阿童木”到“阿凡达”[J].中华腔镜外科杂志(电子版),2010(03)：218-220.
[1]黄志强.我国肝内胆管结石外科治疗的发展[J].外科杂志,1996,1(3)：61.
[2]Ausawasdi A, Watanapa P. Hepatolithiasis:epidemiology and classification[J]. Hepatogastroenterology 1997; 44(14):314-6.
[3]黄志强,黄晓强.肝胆胰外科聚焦[M].北京：人民军医出版社,2005：189-195.
[4]Nakayama F, Soloway RD, Nakama T, et al. Hepatolithiasis in East Asia. Retrospective study[J]. Dig Dis Sci 1986; 31(1):21-6.
[5][中华医学会外科学分会胆道外科学组.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(2)：156-161.
[6]James Horwood, Fayaz Akbar.Prospective evaluation of a selective approach to cholangiography for suspected common bile duct stones [J]. Ann R Coll Surg Engl,2010,92(3):206-210.
[7]张红卫,彭孝雄,陈亚进,等.肝胆管结石再次手术方式的选择[J].中华普通外科学文献(电子版),2010,5(1)：18-20.
[8]Cheng YF, Lee TY, Sheen-Chen SM, et al. Treatment of complicated hepatolithiasis with intrahepatic biliary stricture by ductal dilatation and stenting: long-term results[J]. World J Surg 2000; 24(6):712-6.
[9]黄志强.《黄志强胆道外科学》[M].山东：科学技术出版社,1999：174-204.
[10]郑惊雷,梁力建,彭宝岗,等.胆道感染病源菌及其对抗生素敏感性变化的研究[J].中国实用外科杂志,2005,25(2)：86-88.
[1l]梁力建.肝胆管结石影像学诊断方法的评价和合理选择[J].中国普外基础与临床杂志,2006,13(4).
[12]Fang CH, Xie AW, Chen ML, et al. Application of a visible simulation surgery technique in preoperation planning for intrahepatic calculi[J]. World J Surg, 2010,34(2):327-335.
[13]林科灿,刘景丰,曾金华,等.虚拟肝脏手术规划应用于肝切除术的研究[J].中华外科杂志,2010,48(3)：185-188.
[14]Rubin GD, Dake MD, Semba CP. Current status of three-demensional spiral CT scanning for the vasculature[J].Radiographics.2002:22(5):3-19.
[15]方驰华,顾杨.数字医学技术在我国腹部外科临床应用现状、困难和发展前景[J].中国实用外科杂志,2013(01)：25-29.
[16]He XD, Liu W, Li BL, et al. Combined surgical therapy for hepatolithiasis[J]. Chin Med Sci J 2005; 20(2):123-5.
[17]Jeng KS, Sheen IS, Yang FS, et al. Percutaneous transhepatic placement of metallic stents in the treatment of complicated intrahepatic biliary stricture with hepatolithiasis:a preliminary report[J]. Am J Gastroenterol 1999; 94(12):3507-12.
[18]Li SQ, Liang LJ, Peng BG, Li DM, Lu MD. The timing of hepatectomy for hepatolithiasis complicated with acute cholangitis[J]. Chinese Journal Surgery 2006; 44:1607-1609.
[19]Suhocki PV. Commentary on "Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis"[J]. Am J Gastroenterol 2003; 98(12):2589-90.
[20]邹声泉,郭伟,秦仁义,等.肝内胆管结石外科手术治疗疗效的分析[J].中华外科杂志.2003；41(7)：509-512.
[21]Jan YY, Chen MF. Percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis--long-term results[J]. Chang Gung Medical Journal 1994; 17(2):149-52.
[22]Vetrone G, Ercolani G, Grazi GL, et al. Surgical therapy for hepatolithiasis:a Western experience[J]. J Am Coll Surg 2006; 202(2).-306-12.
[23]Uenishi T, Hamba H, Takemura S, et al. Outcomes of hepatic resection for hepatolithiasis[J]. Am J Surg,2009,198(2):199-202.
[24]黄志强.胆道外科的现状与未来[J].中国实用外科杂志,1999(01)：17-18.
[25]Krige JE, Beningfield SJ. Liver resection for complicated hepatolithiasis[J]. Arch Surg 2006; 141(7):713-4; author reply 714.
[26]Chen MF, Jan YY, Wang CS, et al. Role of hepatic resection in surgery for bilateral intrahepatic stones[J]. Br J Surg 1997; 84(9):1229-32.
[27]Chiyama K, Kawai M, Ueno M, et al. Reducing residual and recurrent stones by hepatectomy for hepatolithiasis[J]. J Gastrointest Surg 2007;11(5):626-30.
[28]Al-Sukhni W, Gallinger S, Pratzer A, et al. Recurrent pyogenic cholangitis with hepatolithiasis-the role of surgical therapy in North America[J]. J Gastrointest Surg 2008; 12(3):496-503.
[29]梁力建,李绍强.复杂肝胆管结石诊断和治疗原则[]].中国实用外科杂志.2009；29(7)：542-544.
[30]董家鸿,郑树国,陈平,等.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(21)：159一161.
[31]Chen DW, Tung-Ping PR, Liu CL, et al. Immediate and long-term outcomes of hepatectomy for hepatolithiasis[J]. Surgery 2004; 135(4):386-93.
[32]Lee TY, Chen YL, Chang HC, et al. Outcomes of hepatectomy for hepatolithiasis[J]. World J Surg 2007; 31(3):479-82.
[33]Yang T, Lau W Y, Lai E C, et al. Hepatectomy for bilateral primary hepatolithiasis:a cohort study[J]. Ann Surg,2010,251(1):84-90.
[34]梁力建,汤地.肝胆管结石合并无肝左、右管异常的外科治疗[J].中国实用外科杂志,2002,22(7)：400-402
[35]梁力建,李绍强.对胆肠吻合术的再认识[J].中国实用外科杂志,2008,28(6)：450-452.
[36]赖佳明,梁力建,彭宝岗,等.胆道再次手术235例分析[J].中国实用外科杂志,2006,26(3)：181-183.
[37]黄志强.3D时代的肝胆胰外科：从“阿童木”到“阿凡达”[J].中华腔镜外科杂志(电子版),2010(03)：218-220.
[38]Pan W, Xu E, Fang H, et al. Surgical treatment of complicated hepatolithiasis using the ultrasound-guided fiberoptic choledochoscope[J]. Surg Endosc 2011; 25(2):497-502.
[39]Fang CH, Huang YP, Lu CM, et al. Study on the applied value of digital medical technology in diagnosis and treatment of the hepatolithiasis[J]. Chinese Journal Surgery 2009; 47(12):909-11.
[40]Shaikh F, Elazzazi M, Ryan A, Semelka RC. Debris-filled biliary system:a difficult diagnosis on MRI and MRCP[J]. Clin Imaging 2012; 36(2):153-5.
[4l]陈刚,晋云,谭立文,等.三维数字虚拟人体肝脏系统的建立及其应用[J].第三军医大学学报,2008(22)：2103-2106.
[42]Xie A, Fang C, Huang Y, et al. Application of three-dimensional reconstruction and visible simulation technique in reoperation of hepatolithiasis[J]. J Gastroenterol Hepatol,2013,28(2):248-254.
[43]方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值[J].中华外科杂志,2009,47(12)：909-911.
[44]Fang CH, Xie AW, Chen ML, et al. Application of a visible simulation surgery technique in preoperation planning for intrahepatic calculi[J]. World J Surg, 2010,34(2):327-335.
[45]Fang C H, Liu J, Fan Y F, et al. Outcomes of hepatectomy for hepatolithiasis based on 3-dimensional reconstruction technique[J]. J Am Coll Surg,2013,217(2):280-288.
[46]Lee SK, Seo DW, Myung SJ, et al. Percutaneous transhepatic cholangioscopic treatment for hepatolithiasis:an evaluation of long-term results and risk factors for recurrence[J]. Gastrointest Endosc 2001; 53(3):318-23. Kim JH,
[47]Lee SK, Kim MH, et al. Percutaneous transhepatic cholangioscopic treatment of patients with benign bilio-enteric anastomotic strictures[J]. Gastrointest Endosc 2003; 58(5):733-8.
[48]Sun WB, Han BL, Cai JX. The surgical treatment of isolated left-sided hepatolithiasis:a 22-year experience [J]. Surgery 2000; 127(5):493-7.
[49]陈亚进.肝胆管结石病多次手术原因及决策[J].中国实用外科志,2012,32(1)：57-59.
[50]吴伯文.胆道再次手术中几个问题的讨论[J].中国实用外科杂志,2006,26(3)：178-180.
[51]Li SQ, Liang LJ, Peng BG, et al. Outcomes of liver resection for intrahepatic stones:a comparative study of unilateral versus bilateral disease[J]. Ann Surg 2012; 255(5):946-53.
[52]方驰华,陈智翔,范应方,等.腹部医学图像三维可视化系统辅助肝胆管结石诊治决策的价值[J].中国实用外科杂志,2010,30(1)：40-43.
[53]黄志强,黄晓强,张文智,等.肝切除术治疗肝内胆管结石20年的演变[J].中华外科杂志.2008,46(19)：1450-2.
[54]Lee CC, Wu CY, Chen GH. What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma[J]? J Gastroenterol Hepatol 2002; 17(9):1015-20.
[1]Tazuma S. Gallstone disease:Epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic)[J]. Best Pract Res Clin Gastroenterol,2006,20(6):1075-1083.
[2]方驰华,顾杨.数字医学技术在我国腹部外科临床应用现状、困难和发展前景[J].中国实用外科杂志,2013(01)：25-29.
[3]Cheng YF, Lee TY, Sheen-Chen SM, et al. Treatment of complicated hepatolithiasis with intrahepatic biliary stricture by ductal dilatation and stenting: long-term results[J]. World J Surg 2000; 24(6):712-6.
[4]James Horwood, Fayaz Akbar.Prospective evaluation of a selective approach to cholangiography for suspected common bile duct stones [J]. Ann R Coll Surg Engl,2010,92(3):206-210.
[5]中华医学会外科学分会胆道外科学组.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(2)：156-161.
[6]Li SQ, Liang LJ, Peng BG, et al. Outcomes of liver resection for intrahepatic stones:a comparative study of unilateral versus bilateral disease[J]. Ann Surg 2012; 255(5):946-53.
[7]Krige JE, Beningfield SJ. Liver resection for complicated hepatolithiasis[J]. Arch Surg 2006; 141(7):713-4;author reply 714.
[8]中华医学会外科学分会胆道外科学组.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(2)：156-161.
[9]黄志强,黄晓强.肝胆胰外科聚焦[M].北京：人民军医出版社,2005：189-195.
[10]梁力建,李绍强.复杂肝胆管结石诊断和治疗原则[J].中国实用外科杂志. 2009；29(7)：542-544.
[11]Pan W, Xu E, Fang H, et al. Surgical treatment of complicated hepatolithiasis using the ultrasound-guided fiberoptic choledochoscope[J]. Surg Endosc 2011; 25(2):497-502.
[12]董家鸿,郑树国,陈平,等.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(21)：159-161.
[13]Jeng K S, Sheen I S, Yang F S. Percutaneous transhepatic cholangioscopy in the treatment of complicated intrahepatic biliary strictures and hepatolithiasis with internal metallic stent[J]. Surg Laparosc Endosc Percutan Tech,2000,10(5):278-283.
[14]Han J H, Park D H, Moon S H, et al. Peroral direct cholangioscopic lithotripsy with a standard upper endoscope for difficult bile duct stones (with videos)[J]. Gastrointest Endosc,2009,70(1):183-185.
[15]Otani K, Shimizu S, Chijiiwa K, et al. Comparison of treatments for hepatolithiasis:hepatic resection versus cholangioscopic lithotomy[J]. J Am Coll Surg,1999,189(2):177-182.
[16]Cheung M T, Wai S H, Kwok P C. Percutaneous transhepatic choledochoscopic removal of intrahepatic stones[J]. Br J Surg,2003,90(11):1409-1415.
[17]陈开运,高鹏,向国安,等.术中及术后纤维胆道镜在胆管结石治疗中应用[J].肝胆外科杂志,2004,12(4)：285--287.
[18]陈万发,余忠,罗强,等.输尿管硬镜气压弹道碎石治疗胆管结石126例[J].世界华人消化杂志,2004,16(12)：1364-1367.
[19]殷志平,钟少君,孙正富,等.输尿管镜下气压弹道碎石取石术治疗肝内外胆管结石的体会[J].中国内镜杂志,2010,16(9)：95l-952.
[20]Chen C, Huang M, Yang J, et al. Reappraisal of percutaneous transhepatic cholangioscopic lithotomy for primary hepatolithiasis[J]. Surg Endosc,2005,19(4):505-509.
[21]Huang M H, Chen C H, Yang J C, et al. Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis[J]. Am J Gastroenterol,2003,98(12):2655-2662.
[22]何军明,刁竞芳,谭志健.肝切除联合纤维胆道镜治疗复杂肝胆管结石40例[J].实用医学杂志,2010(14)：2607-2608.
[23]Yang T, Lau W Y, Lai E C, et al. Hepatectomy for bilateral primary hepatolithiasis:a cohort study[J]. Ann Surg,2010,251(1):84-90.
[24]陈亚进.肝胆管结石病多次手术原因及决策[J].中国实用外科志,2012,32(1)：57-59.
[25]方驰华,陈智翔,范应方,等.腹部医学图像三维可视化系统辅助肝胆管结石诊治决策的价值[J].中国实用外科杂志,2010,30(1)：40-43.
[26]Fang CH, Huang YP, Lu CM, et al. Study on the applied value of digital medical technology in diagnosis and treatment of the hepatolithiasis[J]. Chinese Journal Surgery 2009; 47(12):909-11.
[27]Li SQ,Liang LJ, Peng BG, et al. Outcomes of liver resection for intrahepatic stones:a comparative study of unilateral versus bilateral disease. Ann Surg, 2012,255(5):946-953.
[1]黄志强,黄晓强.肝胆胰外科聚焦[M].北京：人民军医出版社,2005：189-195.
[2]Catena M, Aldrighetti L, Finazzi R, et al. Treatment of non-endemic hepatolithiasis in a Western country:The role of hepatic resection[J].Ann R Coll Surg Engl.2006; 88:383-9.
[3]Li FY, Cheng NS, Mao H, et al.Significance of controlling chronic proliferative cholangitis in the treatment of hepatolithiasis [J]. World J Surg.2009; 33(10):2155-60.
[4]Mi YT, Li R, Xu KS et al. Modified method of hepatic portal choledochoplasty to treat benign stricture of hilar biliary ducts [J] J. Gastroenterol. Hepatol.2008; 23: 1075-81.
[5]Hwang JH, Yoon YB, Kim YT, et al. Risk factors for recurrent cholangitis after initial hepatolithiasis treatment [J]. J. Clin. Gastroenterol.2004; 38:364-7.
[6]Yang T, Lau WY, Lai EC, et al.Hepatectomy for bilateral primary hepatolithiasis:a cohort study [J]. Ann Surg.2010; 251(1):84-90.
[7]Cheon YK, Cho YD, Moon JH, et al.Evaluation of long-term results and recurrent factors after operative and nonoperative treatment for hepatolithiasis [J]. Surgery. 2009; 146 (5):843-53.
[8]Tabrizian P, Jibara G, Shrager B, et al.Hepatic resection for primary hepatolithiasis: a single-center Western experience [J]. J Am Coll Surg.2012; 215(5):622-6.
[9]James Horwood, Fayaz Akbar.Prospective evaluation of a selective approach to cholangiography for suspected common bile duct stones [J]. Ann R Coll Surg Engl,2010,92(3):206-210.
[10]Fang C H, Huang Y P, Chen M L. Digital medical technology based on 64-slice computed tomography in hepatic surgery [J]. Chin. Med. J.2010; 123:1149-53.
[1l]范应方,方驰华,朱新勇,等.64层螺旋CT胆道三维成像对肝胆管结石病的诊断价值[J].中华消化外科杂志,2007,6(6)：428-432.
[12]巨邦律,方驰华,钟洪才,等.磁共振胆胰管成像在肝内胆管结石外科治疗 中的价值[J].世界华人消化杂志,2005,13(5)：690-691.
[13]Fang CH, Xie AW, Chen M L. Application of a visible surgery technique in preoperation planning for intrahepatic caculi[J]. World J. Surg.2010;34:327-35.
[14]严福华.肝胆管结石的影像诊断[J].临床外科杂志.2005；13(7)：403-404.
[15]Kim HJ,Kim MH,Lee SK.et al.Characterization of primary pure cholesterol hepatolithiasis:Cholangioscopic and selective cholangiographic findings [J] Gastrointest-Endosc.2001; 53(3):324-8.
[16]罗泽斌,赵振国.肝内胆管结石的CT诊断及与超声对照分析[J].中国CT和MRI杂志.2004；2(2)：36-42.
[17]Cetta F. The classification of biliary calculi and the clicico-ther-apeutic implications[J]. Ann Ital Chir,1998,69(6):701-708.
[18]Nakayama F. Hepatolithiasis:Classification of hepatolithiasis and its statistical distribution in Japan[J]. Nippon Rinsho,1987,5(7):560-563.
[19]何小东,贵勇,张振寰,等.肝内胆管结石和狭窄的外科治疗[J].肝胆外科杂志,2000,8(5)：327-328
[20]中华医学会外科学分会胆道外科学组.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(2)：156-160
[21]董家鸿,陈平,韩殿冰.肝胆管结石病诊断治疗指南.济南,全国外科学术会议,2005：8-9.
[22]中华医学会外科学分会胆道外科学组.肝胆管结石病诊断与治疗指南.中华消化外科杂志.2007,6(2)：156-61.
[23]黄志强,刘永雄.肝内胆管结石的的外科治疗(40年回顾)[J].中国实用外科杂志.1997；17(3)：140-144.
[24]Lee SE, Jang JY, Lee JM, et al.Selection of appropriate liver resection in left hepatolithiasis based on anatomic and clinical study [J]. World J Surg.2008; 32(3):413-8.
[25]Uenishi T, Hamba H, Takemura S, et al.Outcomes of hepatic resection for hepatolithiasis [J]. Am J Surg.2009; 198 (2):199-202.
[26]Jarufe N, Figueroa E, Munoz C, et al.Anatomic hepatectomy as a definitive treatment for hepatolithiasis:a cohort study [J]. HPB (Oxford).2012; 14(9):604-10.
[27]Pan W, Xu E, Fang H, et al.Surgical treatment of complicated hepatolithiasis using the ultrasound-guided fiberoptic choledochoscope [J]. Surg Endosc.2011; 25(2):497-502.
[28]Lee TY, Chen YL, Chang HC, et al. Outcomes of hepatectomy for hepatolithiasis [J]. World J. Surg.2007; 31:479-82.
[29]Ono Y, Kaneko K, Ogura Y, et al.Endoscopic resection of intrahepatic septal stenosis:minimally invasive approach to manage hepatolithiasis after choledochal cyst excision [J]. Pediatr Surg Int.2006; 22(11):939-41.
[30]Lai EC, Ngai TC, Yang GP, et al.Laparoscopic approach of surgical treatment for primary hepatolithiasis:a cohort study [J]. Am J Surg.2010; 199(5):716-21.
[31]A1-Sukhni W, Gallinger S, Pratzer A, et al.Recurrent pyogenic cholangitis with hepatolithiasis-the role of surgical therapy in North America [J]. J Gastrointest Surg.2008; 12(3):496-503.
[32]Herman P, Perini M V, Machado MAC, et al. Liver resection as the definitive treatment for unilateral non-oriental primary intrahepatic lithiasis [J]. Am. J. Surg.206; 191:460-4.
[33]Shah OJ, Robbani I, Shah P, et al. Left-sided hepatic resection for hepatolithiasis: a longitudinal study of 110 patients [J]. HPB (Oxford).2012;14(11):764-71.
[34]Chen DW, Tung-Ping Poon R, Liu CL, et al.Immediate and long-term outcomes of hepatectomy for hepatolithiasis [J]. Surgery.2004; 135 (4):386-93.
[35]Uchiyama K, Kawai M, Ueno M, et al. Reducing residual and recurrent stones by hepatectomy for hepatolithiasis. J Gastrointest Surg,2007; 11:626-30.
[36]Nuzzo G, Clemente G, Giovannini I, et al. Liver resection for primary intrahepatic stones:a single-center experience. Arch Surg 2008;143:570-3.
[37]方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值 研究[J].中华外科杂志,2009,47(12)：909-911.
[38]方驰华,项楠.数字化微创技术在肝胆胰外科的应用[J].中国微创外科志,20ll,ll(1)：15-19.
[39]Cheon YK, Cho YD, Moon JH, et al.Evaluation of long-term results and recurrent factors after operative and nonoperative treatment for hepatolithiasis [J]. Surgery. 2009; 146(5):843-53.
[40]Lee SE, Jang JY, Lee JM, et al.Selection of appropriate liver resection in left hepatolithiasis based on anatomic and clinical study [J]. World J Surg.2008; 32(3):413-8.
[2]董家鸿,郑树国,陈平,等.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(21)：159-161.
[3]Shoda J, Tanaka N, Osuga T. Hepatolithiasis-epidemiology and pathogenesis update[J]. Front Biosci,2003,8:398-409.
[4]Tazuma S. Gallstone disease:epidemiology, pathogenesis, and classification of biliary stones(common bile duct and intrahepatic)[J]. Best Pract Res Clin Gastroenterol,2006,20(6):1075-1083.
[5]邹声泉,郭伟,秦仁义,等.肝内胆管结石外科手术治疗疗效的分析[J].中华外科杂志.2003；41(7)：509-512.
[6]梁力建,李绍强.复杂肝胆管结石诊断和治疗原则[J].中国实用外科杂志.2009；29(7)：542-544.
[7]黄志强.我国肝内胆管结石外科治疗的发展[J].外科杂志,1996,1(3)：61.
[8]梁力建.肝胆管结石影像学诊断方法的评价和合理选择[J].中国普外基础与临床杂志,2006,13(4).
[9]方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值[J].中华外科杂志,2009,47(12)：909-911.
[10]Fang CH, Xie AW, Chen ML, et al. Application of a visible simulation surgery technique in preoperation planning for intrahepatic calculi[J]. World J Surg, 2010,34(2):327-335.
[11]Han JH, Park DH, Moon SH, et al. Peroral direct cholangioscopic lithotripsy with a standard upper endoscope for difficult bile duct stones (with videos) [J]. Gastrointest Endosc 2009; 70(1):183-5.
[12]Suhocki PV. Commentary on "Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis"[J]. Am J Gastroenterol 2003; 98(12):2589-90.
[13]Huang MH, Chen CH, Yang JC, et al. Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis[J]. Am J Gastroenterol 2003; 98(12):2655-62.
[14]Vetrone G, Ercolani G, Grazi GL, et al. Surgical therapy for hepatolithiasis:a Western experience [J]. J Am Coll Surg 2006; 202(2):306-12.
[15]方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值[J].中华外科杂志,2009,47(12)：909-911.
[16]陈刚,晋云,谭立文,等.三维数字虚拟人体肝脏系统的建立及其应用[J].第三军医大学学报,2008(22)：2103-2106.
[17]方驰华,顾杨.数字医学技术在我国腹部外科临床应用现状、困难和发展前景[J].中国实用外科杂志,2013(01)：25-29.
[18]林科灿,刘景丰,曾金华,等.虚拟肝脏手术规划应用于肝切除术的研究[J].中华外科杂志,2010,48(3)：185-188.
[19]杨世忠,顾万清,段伟东,等.计算机辅助手术规划系统在复杂肝门部胆管癌根治性切除术中的应用[J].中华消化外科杂志,2012,11(2)：124-128.
[20]Rubin GD, Dake MD, Semba CP. Current status of three-demensional spiral CT scanning for the vasculature[J].Radiographics.2002:22(5):3-19.
[21]Fang C H, You J H, Lau W Y, et al. Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects[J]. World J Surg, 2012,36(1):120-124.
[22]Saito S, Yamanaka J, Miura K, et al. A novel 3D hepatectomy simulation based on liver circulation:application to liver resection and transplantation[J]. Hepatology,2005,41(6):1297-1304.
[23]Xie A, Fang C, Huang Y, et al. Application of three-dimensional reconstruction and visible simulation technique in reoperation of hepatolithiasis[J]. J Gastroenterol Hepatol,2013,28(2):248-254.
[1]Buyse M. Centralized Treatment Allocation in Comparative Clinical Trials[J], APPLIED CLINICAL TRIALS,2000,9 (6):32-37.
[2]Krischer JP, Hurley C, Pillalamam M,et al. An automated patient registration and treatment randomization system for muhicenter clinical trials[J].Control Clial Trials,1991,12 (3):367-377.
[3]Papaconstantinou C, Krischer J P. An automated patient registration and treatment randomization system[J]. J Med Syst,1995,19(6):445-456.
[4]ICH. Sixth International Conference on Harmonisation New Horizons and Future Challenges, www.ich.org,2006-11-01.
[5]洪楠主编.SPSS for Windows统计分析教程,北京：电子工业出版社,2000.
[6]何丽云,文天才,刘保延,梁志伟。中医临床研究中数据库管理系统的选择与应用,中医药信息学,Nov.2005 Vol.12 No.11,90-91.
[7]Fang C H, You J H, Lau W Y, et al. Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects[J]. World J Surg,2012,36(1):120-124.
[8]Xie A, Fang C, Huang Y, et al. Application of three-dimensional reconstruction and visible simulation technique in reoperation of hepatolithiasis[J]. J Gastroenterol Hepatol,2013,28(2):248-254.
[9]林科灿,刘景丰,曾金华,等.虚拟肝脏手术规划应用于肝切除术的研究[J].中华外科杂志,2010,48(3)：185-188.
[10]方驰华,顾杨.数字医学技术在我国腹部外科临床应用现状、困难和发展前景[J].中国实用外科杂志,2013(01)：25-29.
[11]Cui F, Li J, Ding A, et al. Conditional QTL mapping for plant height with respect to the length of the spike and internode in two mapping populations of wheat[J]. Theor Appl Genet,2011,122(8):1517-1536.
[12]陆健.临床试验电子化数据管理与统计分析系统的开发及应用.2012.42.
[13方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值[J].中华外科杂志,2009,47(12)：909-9l1.
[14]邹声泉,郭伟,秦仁义,等.肝内胆管结石外科手术治疗疗效的分析[J].中华外科杂志.2003；41(7)：509-512.
[15]梁力建.肝胆管结石影像学诊断方法的评价和合理选择[J].中国普外基础与临床杂志,2006,13(4).
[16]Saito S, Yamanaka J, Miura K, et al. A novel 3D hepatectomy simulation based on liver circulation:application to liver resection and transplantation [J]. Hepatology,2005,41 (6):1297-1304.
[17]陶文强,侯致典,徐达传,等.肝门静脉64排螺旋CT数据Mimics软件三维重建及其解剖变异[J].南方医科大学学报,2011(01)：121-124.
[18]陈刚,晋云,谭立文,等.三维数字虚拟人体肝脏系统的建立及其应用[J].第三军医大学学报,2008(22)：2103-2106.
[19]Fang CH, Xie AW, Chen ML, et al. Application of a visible simulation surgery technique in preoperation planning for intrahepatic calculi[J]. World J Surg, 2010,34(2):327-335.
[20]Rubin GD, Dake MD, Semba CP. Current status of three-demensional spiral CT scanning for the vasculature[J].Radiographics.2002:22(5):3-19.
[2l]翁璇,郑小林,姜海.医学图像分割技术研究进展[J].医疗卫生装备,2007(01)：37-39.
[22]李洪艳,曹建荣,谈文婷,等.图像分割技术综述[J].山东建筑大学学报,2010(01)：85-89.
[23]Chittajallu D R, Paragios N, Kakadiaris I A. An explicit shape-constrained MRF-based contour evolution method for 2-D medical image segmentation [J]. IEEE J Biomed Health Inform,2014,18(1):120-129.
[24]Torbati N, Ayatollahi A, Kermani A. An efficient neural network based method for medical image segmentation[J]. Comput Biol Med,2014,44:76-87.
[25]Wen J, Yan Z, Jiang J. Novel lattice Boltzmann method based on integrated edge and region information for medical image segmentation[J]. Biomed Mater Eng,2014,24(1):1247-1252.
[26]Zhou W, Xie Y. Interactive medical image segmentation using snake and multiscale curve editing[J]. Comput Math Methods Med,2013,2013:325903.
[27]Xu J, Gu L. [A novel validation method based on radial distance error for 3D medical image segmentation][J]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi,2007,24(4):742-747.
[28]Huang J, Huang X, Metaxas D, et al. Adaptive metamorphs model for 3D medical image segmentation [J]. Med Image Comput Comput Assist Interv,2007,10(Pt 1):302-310.
[29]Cramon P, Rasmussen A K, Bonnema S J, et al. Development and implementation of PROgmatic:A clinical trial management system for pragmatic multi-centre trials, optimised for electronic data capture and patient-reported outcomes[J]. Clin Trials,2014.
[30]Suzuki S, Shimada M, Shibata-Hiraizumi Y. Clinical trial of expectant management of severe preeclampsia that develops at<32 weeks'gestation at a Japanese perinatal center[J]. J Matern Fetal Neonatal Med,2014.
[31]Rustoen T, Valeberg B T, Kolstad E, et al. A randomized clinical trial of the efficacy of a self-care intervention to improve cancer pain management J]. Cancer Nurs,2014,37(1):34-43.
[32]孔玉,陆健,贺佳等CompareData Quick I临床数据管理系统的开发与利用[J].中国卫生统计,2007；24(1)：80-81.
[33]柳松青.面向对象在数据库设计中的应用[J].计算机工程与设计,2012,23(9)：5l-54.
[34]Ball G D, Ambler K A, Keaschuk R A, et al. Parents as agents of change (PAC) in pediatric weight management:the protocol for the PAC randomized clinical trial[J]. BMC Pediatr,2012,12:114.
[35]刘保延,文天才,姚晨等.多中心临床试验中的中央随机系统研究[J],中国新药与临床杂志,2006,25(12)：931-934.
[36]闫世艳,夏结来,姚晨.中心随机化系统在临床试验中的应用[J],中国循证医学杂志,2005,5(8)：632-635.
[37]中国临床试验注册中心公告[J].中国循证医学杂志,2007(08)：557-558.
[38]吴泰相,刘关键.关于循证医学的问题与思考[J].中国循证医学杂志,2005(08)：636-640.
[39]谢敖文,方驰华.3D技术在复发性肝胆管结石诊断和手术方式选择中的价值[J].中国实用外科杂志,2013(01)：43-46.
[40]黄志强.3D时代的肝胆胰外科：从“阿童木”到“阿凡达”[J].中华腔镜外科杂志(电子版),2010(03)：218-220.
[1]黄志强.我国肝内胆管结石外科治疗的发展[J].外科杂志,1996,1(3)：61.
[2]Ausawasdi A, Watanapa P. Hepatolithiasis:epidemiology and classification[J]. Hepatogastroenterology 1997; 44(14):314-6.
[3]黄志强,黄晓强.肝胆胰外科聚焦[M].北京：人民军医出版社,2005：189-195.
[4]Nakayama F, Soloway RD, Nakama T, et al. Hepatolithiasis in East Asia. Retrospective study[J]. Dig Dis Sci 1986; 31(1):21-6.
[5][中华医学会外科学分会胆道外科学组.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(2)：156-161.
[6]James Horwood, Fayaz Akbar.Prospective evaluation of a selective approach to cholangiography for suspected common bile duct stones [J]. Ann R Coll Surg Engl,2010,92(3):206-210.
[7]张红卫,彭孝雄,陈亚进,等.肝胆管结石再次手术方式的选择[J].中华普通外科学文献(电子版),2010,5(1)：18-20.
[8]Cheng YF, Lee TY, Sheen-Chen SM, et al. Treatment of complicated hepatolithiasis with intrahepatic biliary stricture by ductal dilatation and stenting: long-term results[J]. World J Surg 2000; 24(6):712-6.
[9]黄志强.《黄志强胆道外科学》[M].山东：科学技术出版社,1999：174-204.
[10]郑惊雷,梁力建,彭宝岗,等.胆道感染病源菌及其对抗生素敏感性变化的研究[J].中国实用外科杂志,2005,25(2)：86-88.
[1l]梁力建.肝胆管结石影像学诊断方法的评价和合理选择[J].中国普外基础与临床杂志,2006,13(4).
[12]Fang CH, Xie AW, Chen ML, et al. Application of a visible simulation surgery technique in preoperation planning for intrahepatic calculi[J]. World J Surg, 2010,34(2):327-335.
[13]林科灿,刘景丰,曾金华,等.虚拟肝脏手术规划应用于肝切除术的研究[J].中华外科杂志,2010,48(3)：185-188.
[14]Rubin GD, Dake MD, Semba CP. Current status of three-demensional spiral CT scanning for the vasculature[J].Radiographics.2002:22(5):3-19.
[15]方驰华,顾杨.数字医学技术在我国腹部外科临床应用现状、困难和发展前景[J].中国实用外科杂志,2013(01)：25-29.
[16]He XD, Liu W, Li BL, et al. Combined surgical therapy for hepatolithiasis[J]. Chin Med Sci J 2005; 20(2):123-5.
[17]Jeng KS, Sheen IS, Yang FS, et al. Percutaneous transhepatic placement of metallic stents in the treatment of complicated intrahepatic biliary stricture with hepatolithiasis:a preliminary report[J]. Am J Gastroenterol 1999; 94(12):3507-12.
[18]Li SQ, Liang LJ, Peng BG, Li DM, Lu MD. The timing of hepatectomy for hepatolithiasis complicated with acute cholangitis[J]. Chinese Journal Surgery 2006; 44:1607-1609.
[19]Suhocki PV. Commentary on "Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis"[J]. Am J Gastroenterol 2003; 98(12):2589-90.
[20]邹声泉,郭伟,秦仁义,等.肝内胆管结石外科手术治疗疗效的分析[J].中华外科杂志.2003；41(7)：509-512.
[21]Jan YY, Chen MF. Percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis--long-term results[J]. Chang Gung Medical Journal 1994; 17(2):149-52.
[22]Vetrone G, Ercolani G, Grazi GL, et al. Surgical therapy for hepatolithiasis:a Western experience[J]. J Am Coll Surg 2006; 202(2).-306-12.
[23]Uenishi T, Hamba H, Takemura S, et al. Outcomes of hepatic resection for hepatolithiasis[J]. Am J Surg,2009,198(2):199-202.
[24]黄志强.胆道外科的现状与未来[J].中国实用外科杂志,1999(01)：17-18.
[25]Krige JE, Beningfield SJ. Liver resection for complicated hepatolithiasis[J]. Arch Surg 2006; 141(7):713-4; author reply 714.
[26]Chen MF, Jan YY, Wang CS, et al. Role of hepatic resection in surgery for bilateral intrahepatic stones[J]. Br J Surg 1997; 84(9):1229-32.
[27]Chiyama K, Kawai M, Ueno M, et al. Reducing residual and recurrent stones by hepatectomy for hepatolithiasis[J]. J Gastrointest Surg 2007;11(5):626-30.
[28]Al-Sukhni W, Gallinger S, Pratzer A, et al. Recurrent pyogenic cholangitis with hepatolithiasis-the role of surgical therapy in North America[J]. J Gastrointest Surg 2008; 12(3):496-503.
[29]梁力建,李绍强.复杂肝胆管结石诊断和治疗原则[]].中国实用外科杂志.2009；29(7)：542-544.
[30]董家鸿,郑树国,陈平,等.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(21)：159一161.
[31]Chen DW, Tung-Ping PR, Liu CL, et al. Immediate and long-term outcomes of hepatectomy for hepatolithiasis[J]. Surgery 2004; 135(4):386-93.
[32]Lee TY, Chen YL, Chang HC, et al. Outcomes of hepatectomy for hepatolithiasis[J]. World J Surg 2007; 31(3):479-82.
[33]Yang T, Lau W Y, Lai E C, et al. Hepatectomy for bilateral primary hepatolithiasis:a cohort study[J]. Ann Surg,2010,251(1):84-90.
[34]梁力建,汤地.肝胆管结石合并无肝左、右管异常的外科治疗[J].中国实用外科杂志,2002,22(7)：400-402
[35]梁力建,李绍强.对胆肠吻合术的再认识[J].中国实用外科杂志,2008,28(6)：450-452.
[36]赖佳明,梁力建,彭宝岗,等.胆道再次手术235例分析[J].中国实用外科杂志,2006,26(3)：181-183.
[37]黄志强.3D时代的肝胆胰外科：从“阿童木”到“阿凡达”[J].中华腔镜外科杂志(电子版),2010(03)：218-220.
[38]Pan W, Xu E, Fang H, et al. Surgical treatment of complicated hepatolithiasis using the ultrasound-guided fiberoptic choledochoscope[J]. Surg Endosc 2011; 25(2):497-502.
[39]Fang CH, Huang YP, Lu CM, et al. Study on the applied value of digital medical technology in diagnosis and treatment of the hepatolithiasis[J]. Chinese Journal Surgery 2009; 47(12):909-11.
[40]Shaikh F, Elazzazi M, Ryan A, Semelka RC. Debris-filled biliary system:a difficult diagnosis on MRI and MRCP[J]. Clin Imaging 2012; 36(2):153-5.
[4l]陈刚,晋云,谭立文,等.三维数字虚拟人体肝脏系统的建立及其应用[J].第三军医大学学报,2008(22)：2103-2106.
[42]Xie A, Fang C, Huang Y, et al. Application of three-dimensional reconstruction and visible simulation technique in reoperation of hepatolithiasis[J]. J Gastroenterol Hepatol,2013,28(2):248-254.
[43]方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值[J].中华外科杂志,2009,47(12)：909-911.
[44]Fang CH, Xie AW, Chen ML, et al. Application of a visible simulation surgery technique in preoperation planning for intrahepatic calculi[J]. World J Surg, 2010,34(2):327-335.
[45]Fang C H, Liu J, Fan Y F, et al. Outcomes of hepatectomy for hepatolithiasis based on 3-dimensional reconstruction technique[J]. J Am Coll Surg,2013,217(2):280-288.
[46]Lee SK, Seo DW, Myung SJ, et al. Percutaneous transhepatic cholangioscopic treatment for hepatolithiasis:an evaluation of long-term results and risk factors for recurrence[J]. Gastrointest Endosc 2001; 53(3):318-23. Kim JH,
[47]Lee SK, Kim MH, et al. Percutaneous transhepatic cholangioscopic treatment of patients with benign bilio-enteric anastomotic strictures[J]. Gastrointest Endosc 2003; 58(5):733-8.
[48]Sun WB, Han BL, Cai JX. The surgical treatment of isolated left-sided hepatolithiasis:a 22-year experience [J]. Surgery 2000; 127(5):493-7.
[49]陈亚进.肝胆管结石病多次手术原因及决策[J].中国实用外科志,2012,32(1)：57-59.
[50]吴伯文.胆道再次手术中几个问题的讨论[J].中国实用外科杂志,2006,26(3)：178-180.
[51]Li SQ, Liang LJ, Peng BG, et al. Outcomes of liver resection for intrahepatic stones:a comparative study of unilateral versus bilateral disease[J]. Ann Surg 2012; 255(5):946-53.
[52]方驰华,陈智翔,范应方,等.腹部医学图像三维可视化系统辅助肝胆管结石诊治决策的价值[J].中国实用外科杂志,2010,30(1)：40-43.
[53]黄志强,黄晓强,张文智,等.肝切除术治疗肝内胆管结石20年的演变[J].中华外科杂志.2008,46(19)：1450-2.
[54]Lee CC, Wu CY, Chen GH. What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma[J]? J Gastroenterol Hepatol 2002; 17(9):1015-20.
[1]Tazuma S. Gallstone disease:Epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic)[J]. Best Pract Res Clin Gastroenterol,2006,20(6):1075-1083.
[2]方驰华,顾杨.数字医学技术在我国腹部外科临床应用现状、困难和发展前景[J].中国实用外科杂志,2013(01)：25-29.
[3]Cheng YF, Lee TY, Sheen-Chen SM, et al. Treatment of complicated hepatolithiasis with intrahepatic biliary stricture by ductal dilatation and stenting: long-term results[J]. World J Surg 2000; 24(6):712-6.
[4]James Horwood, Fayaz Akbar.Prospective evaluation of a selective approach to cholangiography for suspected common bile duct stones [J]. Ann R Coll Surg Engl,2010,92(3):206-210.
[5]中华医学会外科学分会胆道外科学组.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(2)：156-161.
[6]Li SQ, Liang LJ, Peng BG, et al. Outcomes of liver resection for intrahepatic stones:a comparative study of unilateral versus bilateral disease[J]. Ann Surg 2012; 255(5):946-53.
[7]Krige JE, Beningfield SJ. Liver resection for complicated hepatolithiasis[J]. Arch Surg 2006; 141(7):713-4;author reply 714.
[8]中华医学会外科学分会胆道外科学组.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(2)：156-161.
[9]黄志强,黄晓强.肝胆胰外科聚焦[M].北京：人民军医出版社,2005：189-195.
[10]梁力建,李绍强.复杂肝胆管结石诊断和治疗原则[J].中国实用外科杂志. 2009；29(7)：542-544.
[11]Pan W, Xu E, Fang H, et al. Surgical treatment of complicated hepatolithiasis using the ultrasound-guided fiberoptic choledochoscope[J]. Surg Endosc 2011; 25(2):497-502.
[12]董家鸿,郑树国,陈平,等.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(21)：159-161.
[13]Jeng K S, Sheen I S, Yang F S. Percutaneous transhepatic cholangioscopy in the treatment of complicated intrahepatic biliary strictures and hepatolithiasis with internal metallic stent[J]. Surg Laparosc Endosc Percutan Tech,2000,10(5):278-283.
[14]Han J H, Park D H, Moon S H, et al. Peroral direct cholangioscopic lithotripsy with a standard upper endoscope for difficult bile duct stones (with videos)[J]. Gastrointest Endosc,2009,70(1):183-185.
[15]Otani K, Shimizu S, Chijiiwa K, et al. Comparison of treatments for hepatolithiasis:hepatic resection versus cholangioscopic lithotomy[J]. J Am Coll Surg,1999,189(2):177-182.
[16]Cheung M T, Wai S H, Kwok P C. Percutaneous transhepatic choledochoscopic removal of intrahepatic stones[J]. Br J Surg,2003,90(11):1409-1415.
[17]陈开运,高鹏,向国安,等.术中及术后纤维胆道镜在胆管结石治疗中应用[J].肝胆外科杂志,2004,12(4)：285--287.
[18]陈万发,余忠,罗强,等.输尿管硬镜气压弹道碎石治疗胆管结石126例[J].世界华人消化杂志,2004,16(12)：1364-1367.
[19]殷志平,钟少君,孙正富,等.输尿管镜下气压弹道碎石取石术治疗肝内外胆管结石的体会[J].中国内镜杂志,2010,16(9)：95l-952.
[20]Chen C, Huang M, Yang J, et al. Reappraisal of percutaneous transhepatic cholangioscopic lithotomy for primary hepatolithiasis[J]. Surg Endosc,2005,19(4):505-509.
[21]Huang M H, Chen C H, Yang J C, et al. Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis[J]. Am J Gastroenterol,2003,98(12):2655-2662.
[22]何军明,刁竞芳,谭志健.肝切除联合纤维胆道镜治疗复杂肝胆管结石40例[J].实用医学杂志,2010(14)：2607-2608.
[23]Yang T, Lau W Y, Lai E C, et al. Hepatectomy for bilateral primary hepatolithiasis:a cohort study[J]. Ann Surg,2010,251(1):84-90.
[24]陈亚进.肝胆管结石病多次手术原因及决策[J].中国实用外科志,2012,32(1)：57-59.
[25]方驰华,陈智翔,范应方,等.腹部医学图像三维可视化系统辅助肝胆管结石诊治决策的价值[J].中国实用外科杂志,2010,30(1)：40-43.
[26]Fang CH, Huang YP, Lu CM, et al. Study on the applied value of digital medical technology in diagnosis and treatment of the hepatolithiasis[J]. Chinese Journal Surgery 2009; 47(12):909-11.
[27]Li SQ,Liang LJ, Peng BG, et al. Outcomes of liver resection for intrahepatic stones:a comparative study of unilateral versus bilateral disease. Ann Surg, 2012,255(5):946-953.
[1]黄志强,黄晓强.肝胆胰外科聚焦[M].北京：人民军医出版社,2005：189-195.
[2]Catena M, Aldrighetti L, Finazzi R, et al. Treatment of non-endemic hepatolithiasis in a Western country:The role of hepatic resection[J].Ann R Coll Surg Engl.2006; 88:383-9.
[3]Li FY, Cheng NS, Mao H, et al.Significance of controlling chronic proliferative cholangitis in the treatment of hepatolithiasis [J]. World J Surg.2009; 33(10):2155-60.
[4]Mi YT, Li R, Xu KS et al. Modified method of hepatic portal choledochoplasty to treat benign stricture of hilar biliary ducts [J] J. Gastroenterol. Hepatol.2008; 23: 1075-81.
[5]Hwang JH, Yoon YB, Kim YT, et al. Risk factors for recurrent cholangitis after initial hepatolithiasis treatment [J]. J. Clin. Gastroenterol.2004; 38:364-7.
[6]Yang T, Lau WY, Lai EC, et al.Hepatectomy for bilateral primary hepatolithiasis:a cohort study [J]. Ann Surg.2010; 251(1):84-90.
[7]Cheon YK, Cho YD, Moon JH, et al.Evaluation of long-term results and recurrent factors after operative and nonoperative treatment for hepatolithiasis [J]. Surgery. 2009; 146 (5):843-53.
[8]Tabrizian P, Jibara G, Shrager B, et al.Hepatic resection for primary hepatolithiasis: a single-center Western experience [J]. J Am Coll Surg.2012; 215(5):622-6.
[9]James Horwood, Fayaz Akbar.Prospective evaluation of a selective approach to cholangiography for suspected common bile duct stones [J]. Ann R Coll Surg Engl,2010,92(3):206-210.
[10]Fang C H, Huang Y P, Chen M L. Digital medical technology based on 64-slice computed tomography in hepatic surgery [J]. Chin. Med. J.2010; 123:1149-53.
[1l]范应方,方驰华,朱新勇,等.64层螺旋CT胆道三维成像对肝胆管结石病的诊断价值[J].中华消化外科杂志,2007,6(6)：428-432.
[12]巨邦律,方驰华,钟洪才,等.磁共振胆胰管成像在肝内胆管结石外科治疗 中的价值[J].世界华人消化杂志,2005,13(5)：690-691.
[13]Fang CH, Xie AW, Chen M L. Application of a visible surgery technique in preoperation planning for intrahepatic caculi[J]. World J. Surg.2010;34:327-35.
[14]严福华.肝胆管结石的影像诊断[J].临床外科杂志.2005；13(7)：403-404.
[15]Kim HJ,Kim MH,Lee SK.et al.Characterization of primary pure cholesterol hepatolithiasis:Cholangioscopic and selective cholangiographic findings [J] Gastrointest-Endosc.2001; 53(3):324-8.
[16]罗泽斌,赵振国.肝内胆管结石的CT诊断及与超声对照分析[J].中国CT和MRI杂志.2004；2(2)：36-42.
[17]Cetta F. The classification of biliary calculi and the clicico-ther-apeutic implications[J]. Ann Ital Chir,1998,69(6):701-708.
[18]Nakayama F. Hepatolithiasis:Classification of hepatolithiasis and its statistical distribution in Japan[J]. Nippon Rinsho,1987,5(7):560-563.
[19]何小东,贵勇,张振寰,等.肝内胆管结石和狭窄的外科治疗[J].肝胆外科杂志,2000,8(5)：327-328
[20]中华医学会外科学分会胆道外科学组.肝胆管结石病诊断治疗指南[J].中华消化外科杂志,2007,6(2)：156-160
[21]董家鸿,陈平,韩殿冰.肝胆管结石病诊断治疗指南.济南,全国外科学术会议,2005：8-9.
[22]中华医学会外科学分会胆道外科学组.肝胆管结石病诊断与治疗指南.中华消化外科杂志.2007,6(2)：156-61.
[23]黄志强,刘永雄.肝内胆管结石的的外科治疗(40年回顾)[J].中国实用外科杂志.1997；17(3)：140-144.
[24]Lee SE, Jang JY, Lee JM, et al.Selection of appropriate liver resection in left hepatolithiasis based on anatomic and clinical study [J]. World J Surg.2008; 32(3):413-8.
[25]Uenishi T, Hamba H, Takemura S, et al.Outcomes of hepatic resection for hepatolithiasis [J]. Am J Surg.2009; 198 (2):199-202.
[26]Jarufe N, Figueroa E, Munoz C, et al.Anatomic hepatectomy as a definitive treatment for hepatolithiasis:a cohort study [J]. HPB (Oxford).2012; 14(9):604-10.
[27]Pan W, Xu E, Fang H, et al.Surgical treatment of complicated hepatolithiasis using the ultrasound-guided fiberoptic choledochoscope [J]. Surg Endosc.2011; 25(2):497-502.
[28]Lee TY, Chen YL, Chang HC, et al. Outcomes of hepatectomy for hepatolithiasis [J]. World J. Surg.2007; 31:479-82.
[29]Ono Y, Kaneko K, Ogura Y, et al.Endoscopic resection of intrahepatic septal stenosis:minimally invasive approach to manage hepatolithiasis after choledochal cyst excision [J]. Pediatr Surg Int.2006; 22(11):939-41.
[30]Lai EC, Ngai TC, Yang GP, et al.Laparoscopic approach of surgical treatment for primary hepatolithiasis:a cohort study [J]. Am J Surg.2010; 199(5):716-21.
[31]A1-Sukhni W, Gallinger S, Pratzer A, et al.Recurrent pyogenic cholangitis with hepatolithiasis-the role of surgical therapy in North America [J]. J Gastrointest Surg.2008; 12(3):496-503.
[32]Herman P, Perini M V, Machado MAC, et al. Liver resection as the definitive treatment for unilateral non-oriental primary intrahepatic lithiasis [J]. Am. J. Surg.206; 191:460-4.
[33]Shah OJ, Robbani I, Shah P, et al. Left-sided hepatic resection for hepatolithiasis: a longitudinal study of 110 patients [J]. HPB (Oxford).2012;14(11):764-71.
[34]Chen DW, Tung-Ping Poon R, Liu CL, et al.Immediate and long-term outcomes of hepatectomy for hepatolithiasis [J]. Surgery.2004; 135 (4):386-93.
[35]Uchiyama K, Kawai M, Ueno M, et al. Reducing residual and recurrent stones by hepatectomy for hepatolithiasis. J Gastrointest Surg,2007; 11:626-30.
[36]Nuzzo G, Clemente G, Giovannini I, et al. Liver resection for primary intrahepatic stones:a single-center experience. Arch Surg 2008;143:570-3.
[37]方驰华,黄燕鹏,鲁朝敏,等.数字医学技术在肝胆管结石诊治中的应用价值 研究[J].中华外科杂志,2009,47(12)：909-911.
[38]方驰华,项楠.数字化微创技术在肝胆胰外科的应用[J].中国微创外科志,20ll,ll(1)：15-19.
[39]Cheon YK, Cho YD, Moon JH, et al.Evaluation of long-term results and recurrent factors after operative and nonoperative treatment for hepatolithiasis [J]. Surgery. 2009; 146(5):843-53.
[40]Lee SE, Jang JY, Lee JM, et al.Selection of appropriate liver resection in left hepatolithiasis based on anatomic and clinical study [J]. World J Surg.2008; 32(3):413-8.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |