腹腔镜肝癌切除对机体细胞免疫功能的影响
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摘要
目的:
1.前瞻性地比较腹腔镜肝癌切除术和开腹肝癌切除术对机体细胞免疫的影响。2.评估围手术期腹腔镜肝癌切除术对机体细胞免疫影响变化,评估其创伤对机体肿瘤免疫抑制的大小。3.有利于腹腔镜肝癌切除术等腹腔镜治疗肿瘤的手术方式的发展。
方法:
将需行肝癌切除术的60例病人随机分入腹腔镜组和开腹组,纳入分析的有54例,每组27例,两组病人性别、年龄、肿瘤大小无统计学差异。腹腔镜组根据肿瘤大小各再分为手助腹腔镜组和完全腹腔镜组两组,所有病人均在全麻下完成。记录每个病人的切口长度、手术时间、麻醉时间、肝门阻断时间、术中出血量、手术方式、病理诊断、肿瘤部位、肿瘤大小、术后肛门排气时间、术后住院天数、并发症有无及术后下地活动时间等;术前、术后第1、4、7天晨7点抽取空腹静脉血,测定肝功能:包括丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)和细胞免疫指标(外周血LCC、MCC、CD3~+、CD4~+、CD8~+、CD4~+/CD8~+、NK、FasL、CD3~+PFP、CD3~+GrB)。
结果:
完全腹腔镜组患者切口长度只有开腹A组的1/7,手助腹腔镜组患者切口长度只有开腹B组的1/3,与开腹组相比,腹腔镜组手术时间、麻醉时间、肝门阻断、术中出血量差异不具有统计学差异。腹腔镜组患者术后肛门排气时间、术后下地活动时间、术后住院天数均较开腹A组短,差异具有统计学意义,在开腹组中出现了2例切口感染,3例少量胸腔积液,1例少量胆漏,两组均无死亡病例。所有肝癌手术患者术后第1天ALT、AST、TBIL升高明显,腹腔镜组患者第7天完全恢复,开腹组尚未完全恢复。
腹腔镜肝癌切除患者围手术期细胞免疫变化:
TLH、HALH术后第1天淋巴细胞总数降到最低值,TLH术后第4天升至术前水平,HALH术后第7天仍低于术前。与开腹组相比无显著差别。
TLH术后第7天单核细胞总数缓上升至最高值,HALH术后第1天单核细胞总数上升至最高值,术后第4、7天虽下降,仍高于术前。
CD3~+淋巴细胞百分比在LH和OH术后第1天均下降显著,术后第4天降到最低值,LH于术后第4天高于OH组。
CD4~+淋巴细胞百分比在LH和OH中术前术后无显著差异,均为术后第1天均下降显著,在TLH和OH中术后第4天均下降到最低值,术后第4天与术前水平一致;在HALH和OH中术后第4天与术前水平一致,术后第7天较术前水平升高显著。
CD8~+淋巴细胞百分比总趋势均为下降趋势,LH组于术后第7天高于OH组。
CD4~+/CD8~+总趋势均为先降后升,术后第1天均下降显著,术后第4天降到最低值,HALH、OHB组变化幅度较TLH和OHA组大,TLH术后第7天低于OHA组,HALH术后第1、4天低于OHB组,术后第7天两组无显著差异。
在LH中NK细胞术后第1天下降显著,第4、7天恢复至术前,TLH与OHA组无显著差异, HALH术后第1、4、7天下降显著,与OHB组显著差异,HALH组高于OHB组。
CD3~+perforin~+、CD3~+GrB~+淋巴细胞在LH和OH术后第1、4、7天均下降显著。患者淋巴细胞FasL表达术后第1、4、7天上升显著,TLH和OHA围手术期组间无显著差别。TLH和OHA两组患者CD3~+淋巴细胞perforin表达、CD3~+淋巴细胞GrB表达术后第4、7天有显著差别。HALH和OHB两组患者淋巴细胞FasL表达第1、4天两组的差异显著,OHB组高于HALH组。HALH和OHB两组术前及术后第1天CD3~+淋巴细胞GrB表达无显著差别,术后第4、7天有显著差别;HALH和OHB两组术前及术后第1、7天两组患者CD3~+淋巴细胞perforin表达无显著差别,术后第4天有显著差别,HALH组高于OHB组。
结论:
腹腔镜肝癌切除术可抑制机体免疫功能,比开腹术影响程度小,恢复速度快,从细胞免疫抑制这一角度表明腹腔镜肝癌切除术治疗原发性肝癌的可行性及优越性。
Objective:
To compare prospectively effects of laparoscopic hepatectomy(LH) and open hepatectomy(OH) for liver cancer on cellular immune function in selected patients with primary hepatocellular carcinoma(PHCC), evaluate the immunosuppression cause by patients' traumatic reaction after LH, and encourage the development of LH for the PHCC and other malignant tumor treated by complicated pelviscopy。
Methods:
60 selected patients with PHCC were randomly divided into LH and OH group, and total 6 cases were eliminated according to our protocol. Data of 27 LH and 27 OH were studied and analyzed and there were no differences on statistics between them on the sexuality, age, tumor size.
Data of patients were recorded, including length of incision, surgical duration, anaesthetic duration, porta-hepatis blockage duration, modus operandi, intraoperative blood loss, pathologic diagnosis,tumor location, tumor size, hospital stay, complications, et al. All patients' peripheral blood was sampled to measure liver function and cell-mediated-immunologic markers (LCC, MCC, CD3~+, CD4~+, CD8~+, CD4~+/CD8~+, NK, FasL, CD3~+PFP~+, CD3~+GrB~+) before operation and on the morning of the 1st, 4rd,7th day after operation. SPSS13.0 was used for statistical analysis.
Results:
The average length of incision in LH group was shorter than that in OH group. Intraoperative blood loss and surgical duration had no statistical significance between the two groups. Postoperative time in LH group was decreased compared with OH group(P<0.05). LH after one day began to get out of bed activities, and OH was the first three days. No pleural effusion occurred in LH group, but pleural effusion, bile leakage and infection of incisional wound occurred in OH group. ALT, AST and TBIL increased in both groups on the 1th day after operation and recovered on the 7th day after operation, and there was no statistical significance between two groups.
In both groups, level of cell-mediated-immunologic markers(LCC, CD3~+, CD4~+, CD8~+, CD4~+/CD8~+, NK, CD3~+PFP~+, CD3~+GrB~+) decreased while level of MCC, FasL increased compared with the preoperative level (P<0.05), which recovered gradually. The decreased level and speed in LH group were less than that in OH group with statistical significance for CD3~+, CD8~+, CD4~+/CD8~+, NK, CD3~+PFP~+, CD3~+GrB~+. The level of LCC and CD4~+ after LH was no statistical significance between LH and OH(P>0.05). MCC and FasL were greater in OH group compared with LH group (P<0.05).
Conclusions:
LH results in the suppression on cell mediated immunity of patients with PHCC, but it is less compared with OH. LH is feasible and safe in selected patients with PHCC.
1.前瞻性地比较腹腔镜肝癌切除术和开腹肝癌切除术对机体细胞免疫的影响。2.评估围手术期腹腔镜肝癌切除术对机体细胞免疫影响变化,评估其创伤对机体肿瘤免疫抑制的大小。3.有利于腹腔镜肝癌切除术等腹腔镜治疗肿瘤的手术方式的发展。
方法:
将需行肝癌切除术的60例病人随机分入腹腔镜组和开腹组,纳入分析的有54例,每组27例,两组病人性别、年龄、肿瘤大小无统计学差异。腹腔镜组根据肿瘤大小各再分为手助腹腔镜组和完全腹腔镜组两组,所有病人均在全麻下完成。记录每个病人的切口长度、手术时间、麻醉时间、肝门阻断时间、术中出血量、手术方式、病理诊断、肿瘤部位、肿瘤大小、术后肛门排气时间、术后住院天数、并发症有无及术后下地活动时间等;术前、术后第1、4、7天晨7点抽取空腹静脉血,测定肝功能:包括丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)和细胞免疫指标(外周血LCC、MCC、CD3~+、CD4~+、CD8~+、CD4~+/CD8~+、NK、FasL、CD3~+PFP、CD3~+GrB)。
结果:
完全腹腔镜组患者切口长度只有开腹A组的1/7,手助腹腔镜组患者切口长度只有开腹B组的1/3,与开腹组相比,腹腔镜组手术时间、麻醉时间、肝门阻断、术中出血量差异不具有统计学差异。腹腔镜组患者术后肛门排气时间、术后下地活动时间、术后住院天数均较开腹A组短,差异具有统计学意义,在开腹组中出现了2例切口感染,3例少量胸腔积液,1例少量胆漏,两组均无死亡病例。所有肝癌手术患者术后第1天ALT、AST、TBIL升高明显,腹腔镜组患者第7天完全恢复,开腹组尚未完全恢复。
腹腔镜肝癌切除患者围手术期细胞免疫变化:
TLH、HALH术后第1天淋巴细胞总数降到最低值,TLH术后第4天升至术前水平,HALH术后第7天仍低于术前。与开腹组相比无显著差别。
TLH术后第7天单核细胞总数缓上升至最高值,HALH术后第1天单核细胞总数上升至最高值,术后第4、7天虽下降,仍高于术前。
CD3~+淋巴细胞百分比在LH和OH术后第1天均下降显著,术后第4天降到最低值,LH于术后第4天高于OH组。
CD4~+淋巴细胞百分比在LH和OH中术前术后无显著差异,均为术后第1天均下降显著,在TLH和OH中术后第4天均下降到最低值,术后第4天与术前水平一致;在HALH和OH中术后第4天与术前水平一致,术后第7天较术前水平升高显著。
CD8~+淋巴细胞百分比总趋势均为下降趋势,LH组于术后第7天高于OH组。
CD4~+/CD8~+总趋势均为先降后升,术后第1天均下降显著,术后第4天降到最低值,HALH、OHB组变化幅度较TLH和OHA组大,TLH术后第7天低于OHA组,HALH术后第1、4天低于OHB组,术后第7天两组无显著差异。
在LH中NK细胞术后第1天下降显著,第4、7天恢复至术前,TLH与OHA组无显著差异, HALH术后第1、4、7天下降显著,与OHB组显著差异,HALH组高于OHB组。
CD3~+perforin~+、CD3~+GrB~+淋巴细胞在LH和OH术后第1、4、7天均下降显著。患者淋巴细胞FasL表达术后第1、4、7天上升显著,TLH和OHA围手术期组间无显著差别。TLH和OHA两组患者CD3~+淋巴细胞perforin表达、CD3~+淋巴细胞GrB表达术后第4、7天有显著差别。HALH和OHB两组患者淋巴细胞FasL表达第1、4天两组的差异显著,OHB组高于HALH组。HALH和OHB两组术前及术后第1天CD3~+淋巴细胞GrB表达无显著差别,术后第4、7天有显著差别;HALH和OHB两组术前及术后第1、7天两组患者CD3~+淋巴细胞perforin表达无显著差别,术后第4天有显著差别,HALH组高于OHB组。
结论:
腹腔镜肝癌切除术可抑制机体免疫功能,比开腹术影响程度小,恢复速度快,从细胞免疫抑制这一角度表明腹腔镜肝癌切除术治疗原发性肝癌的可行性及优越性。
Objective:
To compare prospectively effects of laparoscopic hepatectomy(LH) and open hepatectomy(OH) for liver cancer on cellular immune function in selected patients with primary hepatocellular carcinoma(PHCC), evaluate the immunosuppression cause by patients' traumatic reaction after LH, and encourage the development of LH for the PHCC and other malignant tumor treated by complicated pelviscopy。
Methods:
60 selected patients with PHCC were randomly divided into LH and OH group, and total 6 cases were eliminated according to our protocol. Data of 27 LH and 27 OH were studied and analyzed and there were no differences on statistics between them on the sexuality, age, tumor size.
Data of patients were recorded, including length of incision, surgical duration, anaesthetic duration, porta-hepatis blockage duration, modus operandi, intraoperative blood loss, pathologic diagnosis,tumor location, tumor size, hospital stay, complications, et al. All patients' peripheral blood was sampled to measure liver function and cell-mediated-immunologic markers (LCC, MCC, CD3~+, CD4~+, CD8~+, CD4~+/CD8~+, NK, FasL, CD3~+PFP~+, CD3~+GrB~+) before operation and on the morning of the 1st, 4rd,7th day after operation. SPSS13.0 was used for statistical analysis.
Results:
The average length of incision in LH group was shorter than that in OH group. Intraoperative blood loss and surgical duration had no statistical significance between the two groups. Postoperative time in LH group was decreased compared with OH group(P<0.05). LH after one day began to get out of bed activities, and OH was the first three days. No pleural effusion occurred in LH group, but pleural effusion, bile leakage and infection of incisional wound occurred in OH group. ALT, AST and TBIL increased in both groups on the 1th day after operation and recovered on the 7th day after operation, and there was no statistical significance between two groups.
In both groups, level of cell-mediated-immunologic markers(LCC, CD3~+, CD4~+, CD8~+, CD4~+/CD8~+, NK, CD3~+PFP~+, CD3~+GrB~+) decreased while level of MCC, FasL increased compared with the preoperative level (P<0.05), which recovered gradually. The decreased level and speed in LH group were less than that in OH group with statistical significance for CD3~+, CD8~+, CD4~+/CD8~+, NK, CD3~+PFP~+, CD3~+GrB~+. The level of LCC and CD4~+ after LH was no statistical significance between LH and OH(P>0.05). MCC and FasL were greater in OH group compared with LH group (P<0.05).
Conclusions:
LH results in the suppression on cell mediated immunity of patients with PHCC, but it is less compared with OH. LH is feasible and safe in selected patients with PHCC.
引文
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14. 吴劲松,刘宝华,刘韧,等.腹腔镜直肠癌根治性切除术对中性粒细胞呼吸暴发功能的影响[J].第三军医大学学报,2005,27(8):770-772.
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1. Cherqui D,Husson E,Hammoud R,et al.Laparoscopic liver resections: A feasibility study in 30 patients[J].Ann Surg. 2000,232(6):753-762.
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8. 郭品娥,吴淑梅,花美仙,等.恶性肿瘤与银屑病患者红细胞天然免疫和补体成分变化比较观察[J].中华国际医学杂志,2003,3(2):146-147.
9. 王华丽,孔北华,赵建文,等.腹腔镜手术对卵巢良性肿瘤及瘤样病变患者红细胞和淋巴细胞免疫功能的影响[J].实用妇产科杂志,2005,21(10):612-614.
10. 亓玉忠,胡三元,于文滨,等.腹腔镜手术对红细胞 CR1 基因活性影响的初步研究[J].腹腔镜外科杂志,2002,7(4) :198-200.
11. 黄东平,罗浩.腹腔镜胆囊切除术对老年人 IL-2、IL-6 和 NK 的影响.中国内镜杂志,2000,6(4):9-10.
12. Dunker MS,Ten-Hove T,Bemelman WA,et a1.Interleukin-6 ,C-reactive protein , and expression of human leukocyte antigen-DR on peripheral blood mononuclear cells in patients after laparoscopic vs.conventional bowel resection:a randomized study.Dis Colon Rectum,2003,46(9):1238-1244.
13. 王琛,李徐生.腹腔镜胆囊切除术对细胞因子、内皮素和 C 反应蛋白水平的影响.腹腔镜外科杂志,2006,11(5):416-418.
14. 吴劲松,刘宝华,刘韧,等.腹腔镜直肠癌根治性切除术对中性粒细胞呼吸暴发功能的影响[J].第三军医大学学报,2005,27(8):770-772.
15. Sietses C,Wiezer MJ,Eijsbouts QA,et al.The influence of laparoscopic surgery on postoperative polymorphonuclear leukocyte function.Surg Endosc,2000,14: 812-816.
16. WitkoSarsat V,Rieu P,Descamps2Latscha B,et al.Neutrophils: molecules,functions and pathophysiological aspects[J].Lab Invest,2000,80(5): 617-653.
17. Schietroma M,Carlei F,Lezoche E,et al.Evaluation of immune response in patients after open or laparoscopic cholecystectomy [J].Hepatogastroenterology,2001,48 (39): 642-646.
18.Bolla G,Tuzzato G.Immunologic postoperative competence after laparoscopy versus laparotomy[J].Surg Endosc,2003,13(6): 632-639.
19. Wu FP,Sietses C,Von Blomberg BM,el al.Systemic and peritoneal inflammatory response after laparoscopic or conventional colon resection in cancer patients:a prospective,randomized trial[J].Dis Colon Rectum,2003,46(2): 147-155.
20. Fujii K,Sonoda K,Izumi K,et al.T lymphocyte subsets and Th1/Th2 balance after laparoscopy-assisted distal gastrectomy[J].Surg Endosc,2003,25(6): 821-827.
21.王汉兵,陈月园,扬承祥.腹腔镜结直肠癌根治术围术期免疫功能变化.中国内镜杂志,2005,11(3):303-305.
22. Whelan RL,Franklin M,Holubar SD,et a1.Postoperative cell mediated immune response is better preserved after laparoscopic vs open colorectal resection in humans[J].Surg Endosc,2003,17(6): 972-978.
23. Michelson AD,Barnard MR,Krueger LA,et al.Circulating monocyte-platelet are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin.Studies in baboons,human coronary intervention,and human acute myocardial infarction.Circulation,2001,104: 1533-1537.
24. 朱江帆,单礼成,孙晓明,等.腹腔镜胆囊切除术对血液凝固性的影响[J].中华消化内镜杂志,1998,15(2):75-77.
25.Sheen-Chen SM,Chen HS,Eng HL,et al.Systemic immune response afterlaparoscopic and open cholecystectomy[J].World J Surg,2002,26(12): 1418-1422.
26.Romeo C,Impellizzeri P,Antonuccio P,et al. Peritoneal macrophage activity after laparoscopy or laparotomy[J].Pediatr Surg,2003,38(1): 97-101.
27.Ure BM,Niewold TA,Bax NM,et al.Peritoneal,systemic,and distant organ inflammatory responses are reduced by a lnparascopic approach and carbon dioxide versus air[J].Surg Endosc,2002,l6(5): 836-842.
28.Gutt CN,Riemer V,Kim ZG,et al.Impact of laparoscopic surgery on experimental hepatic metastases.Br J Surg.2001,88 (3): 371-375.
29.Gutt CN,Kim ZG,Schemmer P,et a1.Impact of Laparoscopic and conventional surgery on Kupffer cells,tumor-associated CD44 expression,and intrahepatic tumor spread [J].Arch Surg,2002,137(12): 1408-1412.