乙肝病毒因素对肝癌肝切除及肝移植术后复发的影响

肝切除术是目前公认的治疗肝癌的首选方式,但术后肿瘤复发率较高.中国肝癌患者多数合并乙肝感染,乙肝病毒(HBV)因素如:病毒基因型、血清e抗原状态、血清HBV DNA水平、肝内HBV DNA水平与肝切除术后肿瘤复发相关.抗病毒治疗,尤其是干扰素治疗可能是预防肝癌复发的有效方式之一.乙肝病毒因素也可影响肝移植术后患者复发率.     

原发性肝细胞癌行肝切除术后复发的预后因素分析

目的探讨HCC行肝切除术后影响患者复发的各预后因素。方法回顾性分析2006年6月～2011年6月行肝切除术治疗HCC的患者临床资料。应用Cox比例风险模型行单因素和多因素分析。结果所有患者均行根治性肝切除术,本组共84例患者出现术后复发,总体1、2、3、5年累积复发率分别为51.96%（53/102）、67.65%（69/102）、76.47%（78/102）、82.35%（84/102）。结论 HCC行肝切除术后复发早、晚期影响因素不同,应进行预后因素等级划分,有助于预测HCC患者术后复发。     

乙肝相关性肝癌和丙肝相关性肝癌的临床病理特征及意义

【摘要】〓目的〓探讨乙肝相关性肝癌和丙肝相关性肝癌在临床病理特征的差异,以及这些差异的临床意义和对预后的影响。方法〓收集2003年12月~2010年10月在南方医科大学附属南方医院行手术治疗C-HCC标本18例和2011年3月~2012年12月行手术治疗的B-HCC标本34例,以及这些肝癌患者的临床病理资料。分析乙肝相关性肝癌和丙肝相关性肝癌在临床病理特征的差异,以及这些差异的临床意义和对预后的影响。结果〓乙肝相关性肝癌平均年龄(46.9±10.5)显著低于丙肝相关性肝癌组(59.0±9.9),平均住院天数(17.9±6.8)显著低于丙肝相关性肝癌组(34.9±16.5),平均术后住院天数(11.5±4.3)显著低于丙肝相关性肝癌组(19.4±11.9),肝功能分级中A级肝功明显较丙肝相关性肝癌组多,最大肿瘤直径明显大于丙肝相关性肝癌组,差异均有统计学意义(P<0.05)。B-HCC组患者中位无瘤生存时间为13个月,1年、2年无瘤生存率分别为56.3%和32.0%;C-HCC组患者中位无瘤生存时间为16.5个月,1年、2年无瘤生存率分别为75%和75%。Cox模型分析提示肝炎类型是肝细胞癌术后复发的独立影响因素。乙肝相关肝细胞癌术后复发的风险是丙肝相关性肝癌的2.35倍(P=0.108)。结论〓乙肝病毒与丙肝病毒相关肝细胞癌的临床病理特征及预后有显著差异。乙肝相关性肝癌术后恢复较丙肝相关性肝癌快,而丙肝相关肝细胞癌术后复发风险低于乙肝相关肝细胞癌。     

丙肝相关性肝癌根治术后复发规律及危险因素分析

目的：分析丙肝相关性肝癌（HCV-HCC）根治术后复发规律及相关危险因素,探讨针对复发时相的个体化临床干预。 方法：回顾98例行HCV-HCC根治术的患者临床病理资料,分析患者根治术后复发规律,对复发的可能影响因素进行单因素及多因素分析,并对病毒因素进行分层分析。 结果：全组根治术后有2个复发高峰,以24个月为界分为早、晚期;COX比例风险模型分析显示,肿瘤低分化、镜下微血管侵犯为术后早期复发的独立危险因素（P<0.001）,病毒载量为晚期复发的独立危险因素（P=0.013）;术后病毒载量持续阴性患者无瘤生存期明显长于术后持续高病毒载量或病毒载量不稳定者（P<0.001）。 结论：HCV-HCC根治术后早、晚期复发影响因素不同;早期复发率较高,预防性TACE可改善早期复发高危者预后;术后抗病毒治疗可改善远期疗效。

     

乙肝相关性肝癌病人在根治术后的复发和生存分析——病例对照研究

目的:探讨乙型肝炎病毒(HBV)感染对原发性肝细胞肝癌病人行根治术后复发和生存的影响。方法:回顾性观察2005年至2008年我科按照HBV抗原阳性和HBV五项(包括丙肝)全阴性,将肝癌病人分为HBV组(n=79)和非HBV组(n=79)。按年龄、性别、肿瘤直径、血管侵犯及肿瘤数目进行1∶1配对研究,分析两组间临床病理资料的特点,以复发和死亡作为终点事件,对外科治疗的复发率、生存率及预后相关危险因素进行分析总结。结果:HBV组1、3和5年总体复发率和生存率分别为48%、80%、85%和75%、41%、35%;非HBV组1、3和5年总体复发率和生存率分别为27%、65%、76%和86%、58%、44%;两者有统计学差异,HBV组复发率高于非HBV组(P=0.012),而生存率低于非HBV组(P=0.010)。经COX风险比例模型分析后发现HBV阳性、肿瘤多发、血管侵犯、包膜侵犯和TNM分期是影响肝癌术后复发的危险因素;HBV阳性、肿瘤多发、术中输血、血管侵犯、包膜侵犯和TNM分期是影响肝癌术后生存的危险因素。结论:HBV相关性肝癌病人比HBV阴性肝癌病人术后的复发率高,生存率低。     

A review of the prognostic factors in patients with recurrence after liver resection for hepatocellular carcinoma

BACKGROUND: Liver transplantation achieves better results when hepatocellular carcinoma fits the Milan criteria. This study investigated predictors of recurrent hepatocellular carcinoma exceeding the Milan criteria. METHODS: Among 285 patients with hepatocellular carcinoma fitting the Milan criteria who underwent curative resection, 143 patients suffered initial recurrence (92 had tumors fitting the criteria) and 71 patients suffered a second recurrence (40 conforming tumors). RESULTS: Survival after hepatectomy was significantly worse when initial recurrence was nonconforming. Similarly, survival after initial recurrence was significantly worse when the second recurrence was nonconforming. A preoperative increase of protein induced by vitamin K absence/antagonist II, a tumor diameter of 3 cm or greater, age of 65 years or younger, and intraoperative blood transfusion increased the risk of nonconforming initial recurrence. CONCLUSIONS: Liver transplantation should be considered initially for younger patients with hepatocellular carcinoma fitting the Milan criteria, larger tumors, and an increase of protein induced by vitamin K absence/antagonist II.     

无肝损伤性肝癌手术的预后影响因素

无肝损伤性肝癌指无肝炎、肝硬化、肝纤维化及酒精肝等基础肝脏疾病的肝癌.其主要治疗手段为手术切除.术后预后影响因素包括:R0切除、肝细胞功能、复发、血管浸润等.此外,输血、肿瘤大小、数目、包膜及卫星灶亦可能影响预后.术前、术中分析以上预后影响因素可大体判断预后,而改善这些不利预后影响因素则可增强手术疗效.     

Systematic hepatectomy for small hepatocellular carcinoma in Korea

Background/Purpose Systematic hepatectomy for small hepatocellular carcinoma (HCC) is a widely preferred modality, but evidence concerning its benefits is lacking. The aim of this study was to document hepatic resection for small HCC in Korea, and to determine whether patient survival or the pattern of tumor recurrence was influenced by the methods used. Methods Ten major hospitals that perform hepatectomy for HCC in Korea were surveyed for surgeons' opinions concerning systematic hepatectomy and current trends in hepatic resection for small HCC. An analysis was also performed of 119 patients who underwent curative hepatectomy for small HCC (size < 5 cm) between January 2000 and December 2002 at Seoul National University Hospital. Seventy-four of these 119 patients underwent anatomical resection (AR) and 45 had a nonanatomical resection (NAR). Recurrence-free survival, recurrence pattern, overall survival rates, and the risk factors for recurrence were analyzed. Results In the survey, eight of ten surgeons preferred systematic hepatectomy and considered it to aid prognosis. No significant difference was found between the AR and NAR groups in terms of the clinicopathologic findings, except that the presence of underlying hepatic cirrhosis was more prevalent in the NAR group. The postoperative morbidity rate was higher in the NAR group (33.3% vs 27.0%), but this difference was not statistically significant. The respective 1- and 3-year recurrence-free survival rates were 78.1% and 49.7% in the AR group, and 68.9% and 46.5% in the NAR group (P > 0.05). The corresponding 1- and 3-year overall survival rates were 88.8% and 80.8% in the AR group and 91.0% and 71.4% in the NAR group (P > 0.05). Conclusions Although systematic hepatectomy seems to be superior to nonanatomical hepatectomy from the oncological and anatomical aspects, this superiority is not reflected by the recurrence patterns or the survival and recurrence rates of the two procedures. Postoperative recurrence appears, rather, to be related to the underlying liver condition.     

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目的 探讨拉米夫定防治乙肝病毒在肝癌围手术期活跃的效果。方法 对７２例肝癌合并ＨＢＶ感染者随机分组,研究组的３８例在围手术期每日１次给予拉米夫定１００mg,进行定量ＨＢＶ ＤＮＡ及其它检查。对照组在围手术期不进行抗乙肝病毒治疗。结果 对照组的ＨＢＶ ＤＮＡ量,在术后１周内、２周内较术前的增高值具显著性意义（Ｐ＜０.０１）,研究组中术后１周内、２周内ＨＢＶ ＤＮＡ量较术前的ＨＢＶ ＤＮＡ量低值亦有显著性意义（Ｐ＜０.０１）,皆低于安全治愈阈值;两组的术前、术后Ｃhild分级,术前、术后ＡＬＴ比较差异无显著性意义（Ｐ＞０.０5）。术后２周内并发症发生率比较,差异有显著性意义（Ｐ＜０.０５）。结论 外科治疗可激活ＨＢＶ的复制能力,须加强肝癌围手术期对ＨＢＶ的防范。拉米夫定有强大的抗ＨＢＶ功能,可短期内迅速降低ＨＢＶ ＤＮＡ的量至安全范围,应用拉米夫定可以预防和治疗肝癌围手术期乙肝病毒的活跃。但其短期内改善肝脏功能的效果不明显。     

Pediatric liver transplantation for primary hepatocellular carcinoma associated with hepatitis virus infection

We report two cases of early primary hepatocellular carcinoma (PHC) in children, after probable maternal transmission of hepatitis B, that were treated with orthotopic liver transplantation (OLT). Both children were 8.5 years old and had elevated levels of serum alpha-fetoprotein. The diagnosis of PHC was made at 8 years and confirmed histologically. Serum hepatitis B surface antigen (HBs Ag) was detected in the mothers and suggested vertical transmission. An attempt at complete liver tumor resection failed, leading to OLT. In order to prevent recurrence of the hepatitis B virus (HBV) infection, hepatitis B immunoprophylaxis was used. Two years after OLT, one child presented with recurrent HBV infection. No tumor recurrence was observed at follow-up in either of the patients. From these two cases we conclude that (1) HBV infection may play an important causal role in PHC in children, with an even shorter incubation period than that in adults; (2) close follow-up is needed for children who are HBs Ag-positive carriers; and (3) liver transplantation should be proposed early after the diagnosis of PHC, when tumor resection is not feasible.     

原发性肝癌肝切除术后复发患者的肝移植治疗

目的观察肝移植治疗原发性肝癌肝切除术后复发患者的疗效。方法回顾性分析11例原发性肝癌肝切除术后复发接受经典原位肝移植治疗的受者的临床资料,观察移植效果。结果在围手术期,1例术后发生移植肝功能不全和凝血功能障碍并发肾功能衰竭死亡;1例术后出现急性胰腺炎,给予生长抑素治疗10d缓解;2例发生急性排斥反应,行大剂量甲泼尼龙冲击治疗3d逆转。10例受者顺利出院。出院后,3例分别于术后第5个月、第7个月、第19个月死于肝癌复发,1、2年受者存活率分别为72．7％（8／11）和63．6％（7／11）,至今最长存活的1例已达4年余。获长期存活的受者肝癌肝切除术前原发病均为小肝癌,肝切除术后复发行肝移植时肝癌均符合Milan标准。结论小肝癌行肝癌肝切除术后应密切随访,如发现肝癌复发且符合Milan标准可考虑行肝移植治疗,患者仍有可能获较长时间生存。     

A 15-year retrospective study of hepatic resection for stage IV-A hepatocellular carcinoma shows value in hepatitis B negative patients

BACKGROUND: The aim of this study is to identify the risk factors of survival and recurrence after curative hepatic resection for stage IV-A hepatocellular carcinoma (HCC). METHODS: Sixty-five patients with stage IV-A HCC who underwent curative hepatic resection and discharged from hospital were enrolled in this retrospective study. Prognostic factors were evaluated by univariate and multivariate analysis. Clinicopathologic features and survival with stage IV-A HCC were compared with those of 290 patients with stage I to III HCC who underwent curative hepatic resection during the same period. RESULTS: Disease-free and overall survival for patients with stage IV-A HCC was significantly lower than for those with stage I to III HCC. Positive hepatitis B virus (HBV) surface antigen was an independent prognostic factor of poor disease-free and overall survivals in patients with stage IV-A HCC. There were no significant differences in the disease-free and overall survivals between non-HBV-related stage IV-A HCC and stage I to III HCC. CONCLUSIONS: Even for patients with highly advanced HCC, curative hepatic resection may be a feasible therapeutic option for those with non-HBV-related HCC.     

Hepatitis B Virus Infection Predicts Extrahepatic Metastasis After Hepatic Resection in Patients With Large Hepatocellular Carcinoma

Background Although extrahepatic metastasis occurs rarely after hepatic resection for hepatocellular carcinoma (HCC), the prognosis of these patients is extremely poor. Predictors of extrahepatic metastasis have not been fully investigated. Methods To identify predictors of extrahepatic metastasis after resection, we retrospectively investigated 77 patients with HCC tumors >50 mm in diameter who underwent hepatic resection. We investigated correlations between postoperative extrahepatic metastasis and clinicopathologic factors as well as extrahepatic metastasis-free survival rate by log rank test and predictors of extrahepatic metastasis by univariate and multivariate logistic regression models. Results Hepatitis B surface antigen (HBs-Ag) was found in 25 (32.5%) of 77 patients, and extrahepatic metastasis occurred in 26 (33.8%). Patients with extrahepatic metastasis showed better liver function and a high occurrence of HBs-Ag positivity than those without. The 5-year extrahepatic metastasis-free survival rate was worse in patients with HBs-Ag positivity, larger tumors (≥70 mm), higher alfa-fetoprotein level (≥300 ng/mL), and lower indocyanine green retention rate at 15 minutes (ICGR₁₅) (<15%) than in those without. By univariate logistic regression analysis, HBs-Ag positivity, larger HCC tumor (≥70 mm), lower ICGR₁₅ (<15%), and lower preoperative lymphocyte count (<1000/mm³) were predictors of extrahepatic metastasis (P < .1). By multivariate analysis, HBs-Ag positivity was an independent predictor of postoperative extrahepatic metastasis (P = .04). Conclusions In patients positive for HBs-Ag, radiologic examination of extrahepatic organs should be performed as a part of the postoperative surveillance. Hepatitis B virus infection may promote establishment of extrahepatic metastasis.     

聚乙二醇化干扰素联合利巴韦林治疗肝移植后丙型肝炎复发四例

目的 探讨聚乙二醇化干扰素(PEG-IFNα-2a)联合利巴韦林(RIB)方案治疗肝移植后丙型肝炎复发的临床疗效.方法 回顾性分析4例肝移植术后丙型肝炎复发患者的临床资料.4例患者中,术前诊断丙型肝炎合并肝硬化3例,丙型肝炎后肝硬化合并肝细胞肝癌1例,术后均采用他克莫司+霉酚酸酯+皮质激素的三联免疫抑制方案.术后8～12周时,患者均经移植肝组织活检证实丙型肝炎复发.复发后,立即采用PFG-IFNα-2a联合RIB方案进行抗丙型肝炎治疗,连续治疗48周.PEG-IFNα-2a的用量为180μg,皮下注射,每周1次;RIB的用量为1000 mg/d,口服.在治疗期间,检查患者的血常规、肝肾功能、丙型肝炎病毒核糖核酸及移植肝组织活检,观察生化学应答、持续病毒学应答及组织学应答等指标.结果 除1例外,其他患者经治疗后出现持续病毒学应答,移植肝功能均恢复正常,在术后0、48和72周,移植肝组织病理学炎症坏死和纤维化情况改善.1例在术后第7天经组织学证实发生急性排斥反应,给予连续3 d皮质激素冲击治疗后,病情好转.无患者因严重的不良反应而停药或退出治疗.结论 PEG-IFNα-2a联合RIB方案是治疗肝移植后丙型肝炎复发的有效方法,患者的耐受性好,不良反应少.     

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目的 介绍用肝门区域血管阻断法切除最大径１０～３０ｃｍ,且经病理证实的肝细胞癌９６例的经验。复发的相关因素和疗效。方法 用肝门务砭解剖法游离阻断相应血管如肝右叶或右叶多亚役切除阻断肝动脉（ＨＡ）和门静脉（ＰＶ）右支（５４例次）,中叶切除阻断睡ＰＶ右前支和ＨＡ和ＰＶ左内支（１０例次）、左叶切除阻断ＨＡ和ＰＶ左支（１１例次）,左外段切除阻断ＨＡ和ＰＶ左外支（１５例次）。结果 （１）手术死亡率３．１％;     

直肠癌局部切除术的外科疗效与预后分析

目的 分析局部切除术治疗直肠癌的疗效及影响复发和预后的因素.方法 回顾性分析采用局部切除术治疗的46例中低位直肠癌患者临床资料,并对其预后影响因素进行单因素及多因素分析.结果 46例患者中经肛门局部切除38例,经骶尾部切除8例;术后并发症发生率为10.9%,围手术期病死率为0;局部复发率为17.4%,Tis、T1及T2期病变的局部复发率分别为0,12.0%,33.3%.肿瘤大体类型、肿瘤直径和分化程度与术后局部复发相关.总体5年生存率为83.3%,Tis、T1、T2期5年生存率分别为100%、90.9%、66.7%.单因素分析显示,肿瘤大小、分化程度、术后放化疗、脉管癌栓和局部复发是影响预后的因素.多因素分析显示,局部复发是影响预后的主要因素.结论 早期（Tis、T1期）高中分化癌,病灶直径≤3 cm,无脉管浸润的隆起型直肠癌,局部切除术是有效的治疗方法.T2期及以上的肿瘤应首选根治性手术,不能耐受根治术者或拒行腹壁人工肛门者,可考虑姑息性局部切除术后加行辅助放、化疗.     

原发性肝癌患者手术切除术后早期复发影响因素分析

目的:探讨原发性肝癌(HCC)患者手术切除后早期复发的影响因素。方法:回顾性分析郑州大学第一附属医院2014年1月—2016年1月期间450例经手术切除的HCC患者的临床与随访资料,通过统计学方法分析HCC术后早期复发的影响因素。结果:450例患者中,2年内复发182例(40.4%)。单因素分析结果显示,HCC术后复发与门脉癌栓、术前血清AFP水平、肿瘤数目、最大直径、肿瘤分化程度有关(均P0.05);Cox比例风险回归分析显示,肿瘤数目(RR=2.148,95%CI=1.175～3.924,P=0.013),肿瘤最大直径(RR=1.591,95%CI=1.006～2.518,P=0.047),门脉有无癌栓(RR=1.835,95%CI=1.242～2.709,P=0.001),血清AFP水平(RR=1.722,95%CI=1.141～2.601,P=0.010),肿瘤分化程度(RR=1.463,95%CI=1.071～1.998,P=0.017)均是HCC术后复发的独立因素。通过以上因素建立函数模型对预测HCC术后早期复发的风险程度有一定价值(似然比检验:χ~2=45.727,P0.001)。结论:HCC患者手术切除术后早期复发的影响因素较多,其中门脉癌栓、肿瘤数目、最大直径、肿瘤分化程度、血清AFP水平可能是造成复发的独立危险因素,术前综合评估这些因素对预防术后复发有一定的指导意义。     

Prognostic impact of anatomical resection on early and late intrahepatic recurrence in patients with hepatocellular carcinoma

Background/Purpose  Little has been addressed regarding the impact of the type of resection, which can be anatomical or nonanatomical, for patients with hepatocellular carcinoma (HCC), from the viewpoint of early (≤2-year) and late (>2-year) intrahepatic recurrence. The aim of the present study was to investigate this issue. Methods  Between 1990 and 2004, we performed 365 potentially curative liver resections. Among these, 233 patients with a solitary tumor were the subjects of this study. They were classified into two groups: anatomical resection (n = 106) and nonanatomical resection (n = 127). We evaluated the following outcomes: (1) early and late recurrence rates; (2) topography of the recurrent tumors; and (3) risk factors for early recurrence. Results  The early recurrence rate after anatomical resection was significantly lower than that after nonanatomical resection: recurrence rates at 1 and 2 years were 13.8% and 29.8%, respectively, in the former group; while they were 22.6% and 46.3%, respectively, in the latter group (P = 0.01; log-rank test). However, late recurrence rates were similar in the two groups (P = 0.36). Local recurrence was observed in 25 of the 89 patients with intrahepatic recurrence after nonanatomical resection (28%), whereas it was observed in 3 of the 64 patients with intrahepatic recurrence after anatomical resection (5%), showing a significantly lower local recurrence rate in the anatomical resection group (P = 0.0002). Cox multivariate analysis identified the type of resection employed as one of the variables contributing to early HCC recurrence (nonanatomical resection: hazard ratio, 1.84; 95% confidence interval [CI], 1.01–3.37). Conclusions  Anatomical resection would be a more appropriate strategy than nonanatomical resection for preventing early intrahepetic recurrence in patients with solitary HCC. However, the type of resection has no significant influence on late recurrence.     

Laparoscopic hepatic resection for hepatocellular carcinoma

Despite recent progress in diagnostics for hepatocellular carcinoma, the rate of resectability remains low, mainly because of the advancement of the underlying liver disease. We report a case of a 54-year-old man with a hepatocellular carcinoma and poor liver function that was treated successfully with a laparoscopic hepatic resection. Laparoscopic hepatic resection is considered to be feasible with the aid of an ultrasonic dissector and a microwave coagulator; however, close attention should be paid to the development of air embolism and hepatic vein injury.     

一种预测肝癌肝移植术后肿瘤复发的术前评分模型

目的 建立一种基于外周血中性粒细胞/淋巴细胞比(NLR)的肝癌肝移植适应证评分模型,评价其预测肝癌肝移植术后肿瘤复发的价值.方法 回顾性分析我院76例有完整随访资料的乙型肝炎相关性肝细胞癌患者临床资料.把肿瘤数目＞3、大血管侵犯和NLR≥2.5三个影响肿瘤复发的术前指标分别赋值1分建立预测复发评分模型,评价该评分模型预测肝癌肝移植术后肿瘤复发的价值.结果 预测复发评分模型ROC曲线下面积(AUC)为0.758.2分和3分的患者肝移植术后肿瘤复发的风险比(HR值)分别是10.038和59.773,10例3分的患者都在6个月内肿瘤复发;0分、1分、2分的患者1年、3年、5年的无瘤生存率分别为95.0％、78.4％、78.4％,76.9％、66.9％、63.2％和51.9％、8.7％、8.7％.无大血管侵犯的55例患者中,5例肿瘤数目＞3且NLR≥2.5的患者都在31个月内肿瘤复发.结论 肿瘤数目＞3且术前NLR≥2.5的患者肝移植术后肝癌复发的风险显著增加.该术前预测复发评分模型可作为肝癌肝移植适应证选择的重要参考.