外科研究与新技术
外科研究與新技術
외과연구여신기술
SURGICAL RESEARCH AND NEW TECHNIQUE
2014年
3期
161-168
,共8页
胆囊肿瘤%血管生成拟态%诊断%治疗%预后
膽囊腫瘤%血管生成擬態%診斷%治療%預後
담낭종류%혈관생성의태%진단%치료%예후
Gallbladder neoplasm%Vasculogenic minicry%Diagnosis%Treatment%Prognosis
从胆囊癌的一种新的血液供应方式——血管生成拟态（vasculogenic mimicry，VM）论述胆囊癌诊疗观点的改变。1994.1—2000.12同济医院确诊的74例原发性胆囊癌标本及其临床病理学和人口统计学资料；H&E染色+CD31/PAS双重染色（Envision法），胆囊癌VM（+）/（－）临床参数单/多因素、Cox模型风险和Kaplan-Meier生存分析+log-rank检验。细胞、动物实验：胆囊癌GBC-SD、SGC-996细胞二/三维培养，侵袭力、迁移力、VM形成测定和倒置光显微镜、透射/扫描电镜VM形态学观察以及动态磁共振荷瘤鼠胆囊癌移植瘤血流动力学检测。信号通道研究：胆囊癌细胞三维培养和裸鼠移植瘤VM组织切片的免疫组化、免疫荧光、Western blotting、QRT-PCR检测，以探讨相关信号通道。13.5%（10/74）胆囊癌存VM，其中4.3%（13/306）管腔内含红细胞，即胆囊癌VM是高倍光学显微镜下由胆囊癌细胞围成管腔、内衬癌细胞而非血管内皮细胞、有圈PAS阳性界膜分隔、腔内含红细胞的管道结构；VM（+）胆囊癌腺癌居多，有较高的血行转移机会；VM是影响胆囊癌患者预后的独立危险因素，有VM存在胆囊癌患者生存期短，预后差。体外胆囊癌GBC-SD细胞三维培养、荷瘤鼠胆囊癌石蜡切片经H&E染色和CD31/PAS双重染色，光/电镜观察，85.7%存在VM，其VM结构与临床结果一致；MRI增强扫描提示，荷瘤裸鼠胆囊癌移植瘤中心或瘤体周围存在VM血供而不致出现肿瘤坏死而呈现MRI强化信号。发现胆囊癌存在VM-相关PI3-K/MMPs/Ln-5γ2和EphA2/FAK/Paxillin信号通路。高侵袭胆囊癌存在VM这一特殊生物学特性。因高侵袭胆囊癌VM不能被常规病理学检测，故建议对临床恶性程度高、易血行转移、预后差胆囊癌，常规开展胆囊癌标本CD31/PAS双重染色检查。对胆囊癌根治术后复发、辅助化疗+抗血管生成靶向疗效差者，应考虑存在VM，采取针对性的“抗血管生成拟态”辅助治疗。
從膽囊癌的一種新的血液供應方式——血管生成擬態（vasculogenic mimicry，VM）論述膽囊癌診療觀點的改變。1994.1—2000.12同濟醫院確診的74例原髮性膽囊癌標本及其臨床病理學和人口統計學資料；H&E染色+CD31/PAS雙重染色（Envision法），膽囊癌VM（+）/（－）臨床參數單/多因素、Cox模型風險和Kaplan-Meier生存分析+log-rank檢驗。細胞、動物實驗：膽囊癌GBC-SD、SGC-996細胞二/三維培養，侵襲力、遷移力、VM形成測定和倒置光顯微鏡、透射/掃描電鏡VM形態學觀察以及動態磁共振荷瘤鼠膽囊癌移植瘤血流動力學檢測。信號通道研究：膽囊癌細胞三維培養和裸鼠移植瘤VM組織切片的免疫組化、免疫熒光、Western blotting、QRT-PCR檢測，以探討相關信號通道。13.5%（10/74）膽囊癌存VM，其中4.3%（13/306）管腔內含紅細胞，即膽囊癌VM是高倍光學顯微鏡下由膽囊癌細胞圍成管腔、內襯癌細胞而非血管內皮細胞、有圈PAS暘性界膜分隔、腔內含紅細胞的管道結構；VM（+）膽囊癌腺癌居多，有較高的血行轉移機會；VM是影響膽囊癌患者預後的獨立危險因素，有VM存在膽囊癌患者生存期短，預後差。體外膽囊癌GBC-SD細胞三維培養、荷瘤鼠膽囊癌石蠟切片經H&E染色和CD31/PAS雙重染色，光/電鏡觀察，85.7%存在VM，其VM結構與臨床結果一緻；MRI增彊掃描提示，荷瘤裸鼠膽囊癌移植瘤中心或瘤體週圍存在VM血供而不緻齣現腫瘤壞死而呈現MRI彊化信號。髮現膽囊癌存在VM-相關PI3-K/MMPs/Ln-5γ2和EphA2/FAK/Paxillin信號通路。高侵襲膽囊癌存在VM這一特殊生物學特性。因高侵襲膽囊癌VM不能被常規病理學檢測，故建議對臨床噁性程度高、易血行轉移、預後差膽囊癌，常規開展膽囊癌標本CD31/PAS雙重染色檢查。對膽囊癌根治術後複髮、輔助化療+抗血管生成靶嚮療效差者，應攷慮存在VM，採取針對性的“抗血管生成擬態”輔助治療。
종담낭암적일충신적혈액공응방식——혈관생성의태（vasculogenic mimicry，VM）논술담낭암진료관점적개변。1994.1—2000.12동제의원학진적74례원발성담낭암표본급기림상병이학화인구통계학자료；H&E염색+CD31/PAS쌍중염색（Envision법），담낭암VM（+）/（－）림상삼수단/다인소、Cox모형풍험화Kaplan-Meier생존분석+log-rank검험。세포、동물실험：담낭암GBC-SD、SGC-996세포이/삼유배양，침습력、천이력、VM형성측정화도치광현미경、투사/소묘전경VM형태학관찰이급동태자공진하류서담낭암이식류혈류동역학검측。신호통도연구：담낭암세포삼유배양화라서이식류VM조직절편적면역조화、면역형광、Western blotting、QRT-PCR검측，이탐토상관신호통도。13.5%（10/74）담낭암존VM，기중4.3%（13/306）관강내함홍세포，즉담낭암VM시고배광학현미경하유담낭암세포위성관강、내츤암세포이비혈관내피세포、유권PAS양성계막분격、강내함홍세포적관도결구；VM（+）담낭암선암거다，유교고적혈행전이궤회；VM시영향담낭암환자예후적독립위험인소，유VM존재담낭암환자생존기단，예후차。체외담낭암GBC-SD세포삼유배양、하류서담낭암석사절편경H&E염색화CD31/PAS쌍중염색，광/전경관찰，85.7%존재VM，기VM결구여림상결과일치；MRI증강소묘제시，하류라서담낭암이식류중심혹류체주위존재VM혈공이불치출현종류배사이정현MRI강화신호。발현담낭암존재VM-상관PI3-K/MMPs/Ln-5γ2화EphA2/FAK/Paxillin신호통로。고침습담낭암존재VM저일특수생물학특성。인고침습담낭암VM불능피상규병이학검측，고건의대림상악성정도고、역혈행전이、예후차담낭암，상규개전담낭암표본CD31/PAS쌍중염색검사。대담낭암근치술후복발、보조화료+항혈관생성파향료효차자，응고필존재VM，채취침대성적“항혈관생성의태”보조치료。
From the discovery of a new blood supply of gallbladder carcinoma:vasculogenic mimicry(VM), insight into diagnosis and treatment of gallbladder cancer. 74 cases of primary gallbladder carcinoma diagnosed at Tongji Hospital from 1994.1 to 2000.12 and their clinical pathological and demographic data were used;VM of gallbladder carcinoma was detected by H&E staining and CD31-PAS double staining(Envision method),single-or multiple-factor clinical parameters,Cox model,Kaplan-Meier survival analysis and log-rank test for gallbladder carcinoma with VM (+)/(-) were done. Two or three-dimensional cultures of GBC-SD and SGC-996 cells,invasion,migration,VM formation assay and hemodynamic of gallbladder cancer in vitro and in vivo were carried out. VM-related signal pathways were studied by immunohisto- chemistry, immunofluorescence,Western blotting and QRT-PCR. VM in 13.5%(10/74) of gallbladder cancers was found,namely VM of gallbladder cancer is the pipeline structures surrounded by gallbladder cancer cells and non vascular endothelial cells,with the PAS positive,red blood cells inside under the microscope;VM(+)gallbladder cancers being mainly adenocarcinoma with highly blood metastasis;VM is an independent prognostic factor for gallbladder cancer patients with VM,and prognosis of gallbladder cancer patients with VM is poor. VM was found in GBC-SD cell 3-D matrices and xenografts,and the formation of VM through the activation of the PI3K/MMPs/Ln-5γ2 signaling pathway. There is a special biological characteristic of VM in highly aggressive gallbladder carcinoma;because VM cannot be detected by conventional pathology,CD31-PAS double staining for specimens were routinely done in the gallbladder cancer patient with highly malignant,easy to hematogenous metastasis and poor prognosis;the presence of VM should be considered for post-operational recurrence after gallbladder cancer radical resection,poor results of adjuvant chemotherapy and anti-angiogenic targeted therapy,"anti vasculogenic mimicry"adjuvant therapy was adopted.
