肝细胞癌手术方法及特殊类型肝癌的预后研究

发布时间：2017-12-30 21:14

本文关键词：肝细胞癌手术方法及特殊类型肝癌的预后研究　出处：《北京协和医学院》2017年博士论文　论文类型：学位论文

【摘要】：第一部分肝细胞癌合并多原发癌预后分析一26年随访研究研究目的多原发恶性肿瘤(MPM)是同一个体内、不同器官中,同时或先后发生的两种或多种原发性恶性肿瘤。目前,对合并存在肝细胞癌(HCC)的MPM患者相关研究报道罕见。我们对此类患者进行了长达26年的随访,以研究其临床病理特征及预后。研究方法回顾性分析1989年至2010年于北京协和医院外科确诊的40例合并HCC的MPM患者,统计并分析其临床病理特征和术后生存期。对照组为同期于我院确诊并接受手术治疗的448例仅罹患HCC患者。结果在40例MPM患者中,11例为同时性MPM,29例为异时性MPM。合并HCC的常见肝外恶性肿瘤为肺癌(15%)、结直肠癌(12.5%)和甲状腺癌(12.5%)。与仅罹患HCC的患者相比,合并存在HCC的MPM患者乙型病毒性肝炎感染率和甲胎蛋白(AFP)水平显著较低(P=0.013,P=0.001)。MPM患者术后1年、3年和5年总体生存率分别为82.5%、64.5%和38.6%,与仅罹患HCC者相比无显著差异(84.7%、54.2%和38.3%,P=0.726)。随访期间,24例MPM患者死亡,其中17例(70.8%)死因与HCC相关。单因素分析提示,MPM的同时性诊断、较高的Y谷氨酰转移酶和/或AFP水平、HCC直径大于5cm和血管侵犯显著影响患者术后总体生存期。多因素分析提示,仅HCC直径是影响MPM患者预后的独立因素。结论具有肝外恶性肿瘤的患者仍存在罹患HCC可能。多数合并HCC的MPM患者死因与HCC密切相关;而经过手术治疗,患者可获得与仅罹患HCC者无显著差异的术后生存期。肿瘤直径,而非肝外原发恶性肿瘤,是影响此类患者术后生存的独立因素。第二部分Edmondson分级预测原发透明细胞型肝癌患者术后生存期研究目的透明细胞型肝癌是肝细胞癌罕见的亚型。我们对接受根治性肝切除术的透明细胞型肝癌患者进行长期随访并回顾性分析,研究影响透明细胞型肝癌患者术后肿瘤肝内复发及预后的相关因素。研究方法回顾性分析1989年1月至2010年9月于北京协和医院确诊的38例透明细胞型肝癌患者的临床资料及术后生存情况,2015年1月随访截止。同期,400例接受根治性肝切除术的普通肝细胞癌患者的临床资料为对照。结果透明细胞型肝癌患者的平均肿瘤直径小于普通肝细胞癌(P0.001),肿瘤血管侵犯的发生率显著低于普通肝细胞癌(P=0.029)。透明细胞型肝癌患者术后1年、3年和5年总体生存率分别为94.6%、67.3%和58.5%,1年、3年和5年无瘤生存率分别为89.2%、54.1%和48.6%,均显著高于普通肝细胞癌患者(P=0.039,P=0.044)。多因素分析结果提示,与普通肝细胞癌不同,Edmondson分级是唯一影响透明细胞型肝癌患者术后肿瘤复发和生存期的独立因素。结论与普通肝细胞癌相比,透明细胞型肝癌恶性程度较低;透明细胞型肝癌患者术后肿瘤复发时间可能更长,预后可能较好。Edmondson分级是影响透明细胞型肝癌患者术后生存期的独立因素;Edmondson分级较高的透明细胞型肝癌患者,术后可能需要更严密的随访和更积极的辅助治疗。第三部分连续性Pringle手法对肝细胞癌患者预后的影响研究目的探讨肝切除术中应用连续性Pringle手法阻断入肝血流对肝细胞癌患者预后的影响。研究方法回顾性分析1989年1月至2011年1月586例于北京协和医院外科行根治性肝切除术的肝细胞癌患者的临床资料及术后生存情况。290例术中应用连续性Pringle手法(PM组),包括163例入肝血流阻断时间小于15分钟(PM-1组)和127例阻断时间为15至30分钟(PM-2组)。此外,296例术中未进行入肝血流阻断(OF组)。结果PM组患者肝切除术中失血量显著小于OF组(P=0.005);两组患者围手术期并发症发生率无显著差异。PM和OF组、PM-1和PM-2组患者术后总体生存期及无瘤生存期均无显著差异(PM vs.OF,P=0.117,P=0.291;PM-1 vs.PM-2,P=0.344,P=0.103)。肝切除术中入肝血流阻断与阻断时间均不是影响肝细胞癌患者术后总体生存期或无瘤生存期的独立危险因素。结论连续性Pringle手法可有效降低术中出血量,对肝细胞癌患者预后未产生不利影响。即使手术较为复杂,需要适当延长阻断时间,Pringle手法仍然是肝切除术中进行入肝血流阻断安全、有效的方式。第四部分超巴塞罗那临床分期标准肝细胞癌术后早期和晚期肿瘤复发治疗策略研究背景肝切除术可延长巴塞罗那临床肝癌分期(BCLC)B期或C期肝细胞癌(HCC)患者的总体生存期(OS)。本文旨在探讨影响BCLC B期或C期HCC患者术后肿瘤肝内复发、复发肿瘤的治疗方式及预后的相关因素。研究方法回顾性分析1989年1月至2011年10月397例接受根治性肝切除术的BCLC B期或C期患者的临床病理特征及术后生存期。术后肿瘤肝内复发分为早期复发(肿瘤复发时间1年)和晚期复发(复发时间≥1年)。结果BCLC B期或C期HCC患者术后1年、3年和5年总体生存率分别为83.5%、50.1%和28.2%。73例患者确诊肿瘤早期肝内复发;104例晚期复发。单因素变量分析提示,无肿瘤复发的患者OS显著优于复发者(P0.001),晚期复发患者术后OS显著优于早期复发者(P0.001);多因素变量分析提示,肿瘤直径、肿瘤数目、血管侵犯是影响肿瘤肝内复发的危险因素。晚期复发患者接受根治性治疗可获得与未复发者无显著性差异的OS(P=0.311)。结论肿瘤复发时间和对复发肿瘤进行根治性治疗是BCLC B期或C期HCC患者预后的影响因素。对肿瘤晚期复发患者,根治性治疗可能延长其总生存期。
[Abstract]:The first part of hepatocellular carcinoma with multiple primary carcinoma prognosis analysis of a 26 year follow-up study to study multiple primary malignant tumors (MPM) are the same in different organs, simultaneously or successively occurred in two or more primary malignant tumor. At present, with the presence of hepatocellular carcinoma (HCC). MPM patients reported rare. We were followed for 26 years for such patients, in order to study the clinical pathological characteristics and prognosis. Methods a retrospective analysis from 1989 to 2010 in Peking Union Medical College Hospital surgery 40 patients diagnosed with HCC in patients with MPM, statistics and survival analysis of the clinicopathological characteristics and postoperative period in control group. For the same period in our hospital were diagnosed and 448 patients undergoing surgical treatment only in patients with HCC. Results in 40 cases of MPM patients, 11 cases of MPM, 29 cases of common liver for metachronous MPM. with HCC malignant tumors were lung cancer (15%), colorectal Cancer (12.5%) and thyroid carcinoma (12.5%). Compared with HCC patients, with the presence of hepatitis B virus infection rate and alpha fetoprotein MPM in patients with hepatitis HCC protein (AFP) levels were significantly lower (P=0.013, P=0.001).MPM patients after 1 years, 3 years and 5 years overall survival rate respectively. 82.5%, 64.5% and 38.6%, compared with HCC had no significant difference (84.7%, 54.2% and 38.3%, P=0.726). During the follow-up period, 24 cases of death in patients with MPM, including 17 cases (70.8%) of death associated with HCC. Single factor analysis showed that the MPM at the same time of diagnosis, Y glutamyl transferase higher the level of HCC and / or AFP, larger than 5cm in diameter and vascular invasion significantly affect postoperative overall survival. Multivariate analysis showed that only the diameter of HCC is an independent prognostic factor for MPM patients. Conclusion with extrahepatic malignant tumor patients are still suffering from HCC. MPM and HCC may be the cause of death in patients with HCC is closely related with the majority and; After surgery, there was no significant difference between the survival of patients with HCC and can be obtained only after the operation. The diameter of the tumor, and non extrahepatic primary malignant tumors, are independent factors affecting the survival of these patients after operation. The second part of the Edmondson classification of primary clear cell carcinoma of liver in patients with clear cell survival after study liver cancer is a subtype of hepatocellular carcinoma is rare. The clear cell type in patients with hepatocellular carcinoma undergoing radical hepatic resection for long-term follow-up and retrospective analysis, study on the effect of clear cell type of postoperative recurrence and prognosis of intrahepatic tumor related factors. Methods analysis of the clinical data from January 1989 to September 2010 in Peking Union Medical College Hospital diagnosed 38 cases of clear cell hepatocellular carcinoma patients and the postoperative survival situation review, January 2015. The end of the follow-up period, 400 patients received ordinary liver cells radical hepatic resection The clinical data of cancer patients as controls. Results the average tumor diameter of clear cell type in patients with HCC less than ordinary hepatocellular carcinoma (P0.001), the incidence of vascular invasion was significantly lower than that in normal liver cell carcinoma (P=0.029). 1 years after surgery in patients with hepatocellular carcinoma and clear cell type, 3 years and 5 years overall survival rate respectively. 94.6%, 67.3% and 58.5%, 1 years, 3 years and 5 years disease-free survival rates were 89.2%, 54.1% and 48.6%, were significantly higher than in patients with normal liver cell carcinoma (P=0.039, P=0.044). The results of multivariate analysis suggested that, unlike ordinary hepatocellular carcinoma, Edmondson classification is the only effect of clear cell type patients hepatocellular carcinoma after tumor recurrence and survival independent factors. Conclusion compared with normal liver cell carcinoma, clear cell carcinoma of liver malignancy is low; clear cell type of postoperative recurrence time may be longer, better prognosis may be.Edmondson grade is transparent Independent factors for survival in patients with hepatocellular carcinoma cells; clear cell hepatocellular carcinoma patients with high Edmondson grade, postoperative may need closer follow-up and more aggressive treatment. Objective: To explore the effect of the third part continuous Pringle technique on the prognosis of patients with hepatocellular carcinoma by hepatic blood inflow on the prognosis of patients with liver cells the application of continuous Pringle technique of cancer liver resection. Methods Retrospective analysis of the clinical data of 586 cases from January 1989 to January 2011 in Peking Union Medical College Hospital underwent radical hepatectomy for patients with hepatocellular carcinoma and postoperative survival using continuous Pringle technique of.290 patients (PM group), including 163 cases of hepatic blood flow the blocking time is less than 15 minutes (PM-1 group) and 127 cases of blocking time is 15 to 30 minutes (group PM-2). In addition, 296 patients without hepatic blood inflow occlusion (group OF). The patients in the PM group The blood loss in hepatectomy was significantly lower than group OF (P=0.005); the two groups of patients the incidence of perioperative complications had no significant difference between.PM and OF group, PM-1 and PM-2 groups of patients with postoperative overall survival and disease-free survival were not significantly different (PM vs.OF, P=0.117, P=0.291; PM-1 vs.PM-2, P =0.344. P=0.103). Liver resection for hepatic blood inflow occlusion and occlusion time were not affected in patients with hepatocellular carcinoma after overall survival or disease-free survival period independent risk factors. Conclusion continuous Pringle techniques can effectively reduce the amount of bleeding, on the prognosis of patients with hepatocellular carcinoma is not adversely affected even if the surgery is more complex. Need to extend the time, blocking, Pringle technique is still in hepatectomy for hepatic blood inflow occlusion is safe, effective way. The fourth part Barcelona clinical staging of hepatocellular carcinoma after treatment of early and late recurrence. The background liver resection can prolong the Barcelona Clinic Liver Cancer (BCLC) stage B or stage C hepatocellular carcinoma (HCC) patient overall survival (OS). This paper aims to explore the effects of BCLC B or C HCC in patients with postoperative tumor recurrence in the liver, the factors related to recurrence of cancer treatment and prognosis Methods Retrospective analysis from January 1989 to October 2011 397 patients underwent radical resection of the liver BCLC B or C patients with clinical pathological features and postoperative survival. Postoperative tumor recurrence was divided into early recurrence (recurrence time of 1 years) and late recurrence (recurrence time more than 1 years). BCLC B or C HCC patients after 1 years, 3 years and 5 years overall survival rates were 83.5%, 50.1% and 28.2%.73 of tumor patients were diagnosed early intrahepatic recurrence; 104 cases of late recurrence. Single factor analysis showed that patients with OS were significantly better than no recurrence of tumor recurrence (P0.001), late During the period of postoperative recurrence in patients with OS was significantly higher than that of early recurrence (P0.001); multivariate analysis showed that tumor size, tumor number, vascular invasion were risk factors of recurrence. The tumor in the liver of patients with late recurrence underwent radical treatment can be obtained without recurrence and no significant difference between OS (P=0.311). Conclusion the tumor time to recurrence and recurrence of tumor curative treatment is the prognostic factors of patients with BCLC B or C HCC. For patients with advanced cancer recurrence, radical therapy may prolong the overall survival.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R735.7

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