肝细胞性肝癌自发破裂出血的治疗策略

【摘要】 目的 探讨肝细胞性肝癌自发性破裂出血患者的治疗策略。方法〓对江门市人民医院两个不同历史阶段收治的肝癌破裂患者的临床资料进行回顾性对比研究,第一阶段(1992~2002年)肝癌破裂患者47例,采取手术或保守治疗;第二阶段(2003~2013年)肝癌破裂患者58例,采用手术、经肝动脉栓塞或保守治疗,对比两阶段患者的30天、1年生存率和累计生存率。结果〓第一阶段保守治疗22例,急诊肝切除25例,30天死亡22例;第二阶段12例保守治疗,急诊肝切除29例,经肝动脉栓塞17例,其中10例栓塞之后行肝切除手术,30天死亡例16例。两阶段中手术治疗患者较非手术治疗患者累积生存率高(P﹤0.05);第二阶段患者累积生存率较第一阶段高(P=0.036),两阶段中手术治疗患者的累积生存率比较无统计学差异(P=0.234)。结论 对于自发性肝癌破裂出血患者,保守治疗预后差,经肝动脉栓塞为有效的急诊止血措施,对合适的患者实施急诊或分期肝切除可延长患者生存时间。     

急诊手助式腹腔镜肝切除治疗原发性肝癌破裂出血

目的 分析总结原发性肝癌破裂出血时急诊行手助式腹腔镜肝切除的方法和经验.方法 回顾性分析15例急诊行手助式腹腔镜肝切除手术治疗的原发性肝癌破裂出血病例的临床资料.结果 15例原发性肝癌破裂出血的病例均顺利完成手术,无手术死亡.13例获得随访,生存时间11～56个月.1、3年生存率分别为84.6%(11/13)、53.8%(7/13).结论 在经过临床选择的病例中,急诊手助式腹腔镜肝部分切除术治疗原发性肝癌破裂出血是安全可行的,疗效显著,如患者的病情允许可作为首选.     

急诊肝切除与急诊肝动脉栓塞联合二期肝切除治疗原发性肝癌破裂出血疗效比较的Meta分析

目的:比较急诊肝切除与急诊肝动脉栓塞联合二期肝切除治疗原发性肝癌破(HCC)裂出血的临床疗效。方法:通过系统检索多个国内外文献数据库,并按照纳入与排除标准,筛选符合标准的文献,用StataSE 12.0进行Meta分析。结果:共纳入11篇文献,581例患者,其中305例行急诊肝切除,276例行急诊肝动脉栓塞+二期肝切除。与急诊肝切除患者比较,急诊肝动脉栓塞联合二期肝切除患者围手术期并发症发生率降低(OR=0.39,95%CI=0.21~0.72,P=0.003),30 d病死率降低(OR=0.21,95%CI=0.08~0.56,P=0.002),1、3年生存率升高(OR=0.48,95%CI=0.32~0.73,P=0.001;OR=0.59,95%CI=0.37~0.95,P=0.031)。结论:对于可切除的HCC自发破裂出血,急诊肝动脉栓塞联合二期肝切除治疗较急诊肝切除可显著降低围手术期并发症、病死率,并明显提高患者生存率。     

终末期肝病模型在肝癌破裂出血急诊术前评估中的应用

目的探讨终末期肝病模型（MELD）评估肝储备功能在原发性肝癌破裂出血中确定急诊手术适应证的应用价值。方法2002年1月至2005年4月间在传统的手术适应证标准的基础上联合MELD评估后,急诊肝切除治疗肝癌破裂出血18例。结果全部病例MELD分值〈18,均值为（13.3±4．2）分。18例患者均顺利完成手术,无围手术期死亡。15例获得随访,生存时间为4～51个月。1、3年生存率分别为66．7％（10／15）、33．3％（5／15）。结论在经过临床选择的病例中,急诊肝切除治疗原发性肝癌破裂出血是安全可行的,疗效显著。MELD评分简单,能够客观地反映肝储备功能,对原发性肝癌破裂出血确定合理的治疗方案有重要的参考价值。     

可切除原发性肝癌破裂出血急诊肝切除与TACE后二期肝切除的临床研究

目的探讨可切除原发性肝癌破裂出血行急诊肝切除与经导管动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)后二期肝切除的疗效及预后。方法回顾性分析南充市中心医院2010年1月至2016年1月期间收治的可切除原发性肝癌破裂出血患者共42例,其中行急诊(入院24～48 h)肝切除术24例,行TACE后二期(TACE后1～2周)手术18例,比较2组患者的术中出血量和输血量、围术期死亡率、术后肝功能不全的发生率、术后1年肝癌复发或腹腔转移率以及术后1年及3年生存率。结果行急诊肝切除术患者和TACE后二期手术患者的术前一般资料比较差异无统计学意义(P0.050)。行急诊肝切除术患者的术中出血量和输血量均明显多于TACE后二期手术患者(P=0.028、P=0.017),二者间的围术期死亡率(P=0.489)、肝功能不全发生率(P=1.000)、1和3年生存率(P=0.650、P=0.463)及1年复发率(P=0.601)比较差异均无统计学意义,均未发现腹腔种植转移。结论对于可切除原发性肝癌破裂出血行急诊肝切除与TACE后二期肝切除均安全有效,应根据患者的具体情况选择合适的治疗方案。     

肝切除治疗原发性肝癌自发性破裂出血

目的: 探讨肝切除治疗原发性肝癌自发性破裂的疗效。方法:回顾性分析1988年以来采用肝切除术治疗肝癌破裂15例的临床资料。结果:全组15例，男12例，女3例；平均年龄48岁。8例行急症肝切除，2例手术止血后40d行二期手术，5例保守治疗40d行择期手术。右肝叶部分切除术8例，中肝切除术1例，左肝外叶切除术2例，左肝内叶切除术2例，左半肝切除术1例，右肝肿瘤切除1例、左肝肿瘤术后综合治疗1例。肝功能Child B级中1例术后5d死于肝衰竭，手术死亡率6.7%，14例生存者12例获得随访，中位生存时间18个月。1，3，5年生存率为58.3%，25.0%，16.7%。其中1例无瘤生存6年2个月。结论:肝切除是治疗肝癌破裂的最好方法，当有可能时应争取施行。肝切除治疗肝癌破裂可能使患者获得长时间生存。     

再次肝切除治疗复发性肝癌疗效及预后因素分析

目的：探讨再次肝切除治疗复发性肝癌的价值并分析影响预后的相关因素。 方法：回顾性分析重庆医科大学附属第一医院2006—2013年26例复发性肝癌施行再次肝切除的临床资料。 结果：首次与再次手术的术中出血量、手术时间差异无统计学意义（均P>0.05）。首次术后中位无瘤生存时间21.0（3~192）个月,1、3、5年无瘤生存率为69.6%、26.1%、8.7%;再次肝切除术后中位无瘤生存时间为19.0（3~35）个月,1、3、5年无瘤生存率为68.4%、0、0,中位生存时间为 40.0个月,1、3、5年累积生存率为83.5%、55.7%、13.0%。26例患者总的生存时间为（87.8±19.3）个月,总中位生存时间为57.0个月,1、3、5年累计生存率100%、60.8%、30.4%。首次术后早期（2年内）复发行再次肝切除患者的生存率明显低于首次术后晚期（2年后）复发行再次切肝除患者（P=0.001）。单因素分析显示,复发间隔、手术方式及病理分期与再次肝切除术后的生存有关（均P<0.05）,三者在多因素分析中的P值分别为0.089、0.006、0.054。 结论：再次肝切除可提高复发性肝癌总生存率,但要严格选择适应证与合理的手术方式。复发间隔越短及肿瘤病理分期越晚,再次肝切除手术预后不良。     

肝切除术治疗肝癌自发性破裂出血

目的：探讨肝切除术治疗肝癌自发性破裂出血的临床效果。方法：对24例肝细胞性肝癌自发性破裂出血患者的临床资料、肝切除方法及随访结果进行回顾性分析。结果：手术止血成功率为100%，手术后病死率为4.1%（1/24），并发症发生率16.7%（4/24），术后肝功能2周内基本恢复正常。平均住院（14.75±6.25）d。21例获随访；其中8例术后10个月内复发死亡，10例生存1年以上，2例生存2年以上，1例生存3年，1年生存率为54.2%（13/24）。结论：肝切除术在治疗肝癌自发性破裂出血时可有效止血并同时切除肿瘤，部分患者可达根治切除，如患者的病情允许应作为首选。     

影响原发性肝癌术后行TACE 肿瘤复发因素的分析

目的:探讨影响原发性肝癌术后行经肝动脉化疗栓塞(TACE)患者无瘤生存的因素.方法:回顾性分析121例手术切除后1～2个月内行TACE治疗的原发性肝癌患者的临床及随访资料,计算患者治疗后的累积无瘤生存率,分析影响无瘤生存的相关因素.结果:121例患者术后1,2,3年的无瘤生存率分别为72.73％,46.21％,28.93％.经单因素分析筛选后,进入COX比例风险模型的各临床变量中,肿瘤的分化程度(P=0.040),肿瘤大小(P=0.002)及有无血管癌栓(P=0.039)对模型贡献有统计学意义.结论:分化程度、肿瘤的大小及有无血管癌栓是影响肝癌术后行TACE近期复发的独立危险因素.     

腹腔镜下射频消融治疗肝癌破裂出血的临床研究

目的:探讨腹腔镜下射频消融(LRFA)治疗原发性肝癌破裂出血的临床价值.方法:选取我院2007年7月-2011年7月确诊为肝癌破裂出血患者49例,其中男30例,女19例;年龄45 ～ 76岁,中位年龄(56.0±5.1)岁;LRFA治疗组(LRFA组)16例,手术切除治疗组(对照组)33例;统计分析两组患者性别、年龄、术前肝功能分级、术中肝门阻断时间、术中出血量、手术时间、止血成功率、术后并发症发生率、再出血率的差异、生存时间及生存率的差异,检验LRFA临床效果.结果:两组患者在性别、年龄、术前肝功能分级、肿瘤大小、数目方面的差异无统计学意义(P＞0.05);而两组患者在肝门阻断时间、术中出血量、手术时间、止血情况、再出血情况、术后并发症发生率及术后1年生存率差异有统计学意义(P＜0.05).结论:LRFA是肝癌破裂出血安全、可靠、有效的治疗手段,或可成为急诊肝癌破裂出血的首选方法.     

Pre-operative predictors of post-hepatectomy recurrence of hepatocellular carcinoma: Can we predict earlier?

Backgrounds and purposeTo determine the predictors for recurrence in patients receiving curative hepatectomy for hepatocellular carcinoma (HCC).MethodsFrom January 2001 to July 2007, all patients having hepatectomy for first occurrence HCC with curative intent were identified from a prospectively collected database. Prognostic factors for recurrence and survival after resection were analyzed.ResultsA total of 235 patients were included. With a median follow-up of 50.2 (0.07–125.1) months, the recurrence rate was 57.0%. The 1-, 3-, and 5-year overall survival rates were 83.9%, 66.0%, and 58.1% respectively. Multivariate analysis demonstrated that multi-focal lesions (HR: 2.93, P < 0.001), alpha-fetoprotein (AFP) level greater than 100 ng/ml (HR: 1.74, P = 0.002) and history of tumor rupture (HR: 2.84, P = 0.003) were independent risk factors for recurrence of HCC after hepatectomy.ConclusionsPredictors for HCC recurrence can be identified before operation. These important parameters should be considered before and after contemplating curative resection for HCC patients and for risk stratification in future clinical trials for neoadjuvant or post-resection adjuvant therapy. The possible use of neoadjuvant or adjuvant treatment to improve survival should be addressed by further trials.     

原发性肝癌自发性破裂的治疗

目的分析原发性肝癌(hepatocellular carcinoma,HCC)自发性破裂的治疗效果。方法26例HCC自发性破裂患者,行一期肝切除9例,一期手术止血4例,二期肝切除11例,另2例行介入治疗。结果二期肝切除和一期肝切除比较,术后并发症发生率分别为27.3%和66.7%,无统计学差异(P=0.175);术后30 d、60 d死亡率分别为0%vs 22.2%,0%vs 44.4%,仅术后60 d死亡率有统计学意义,P=0.026;术后1年、3年生存率比较无统计学意义,分别为90.9%vs 44.4%,3.64%vs 22.2%,P>0.05。结论对于自发性破裂HCC,二期肝切除手术近期效果优于一期肝切除手术,但两者远期生存率并无显著差异。一期切除手术对于部分病人仍可取得较好的效果。     

Spontaneous rupture of hepatocellular carcinoma: a Western experience

BACKGROUND: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening presentation, with an incidence of <3% of HCC patients in Western countries. The reported overall mortality is < or =50% in Asian countries, where the incidence is 12% to 14%. The aim of this study was to report a single center's experience of patients with ruptured HCC during a 11-year period. METHODS: A retrospective review was performed of all patients who presented with ruptured HCC between 1995 and 2005. Data on clinical features, treatment strategies, and survival outcomes were collected. Statistical methods included univariate analysis and Kaplan-Meier survival estimates with log-rank test. RESULTS: A cohort of 21 patients (15 male and 6 female) was identified. Fourteen (66.6%) patients had histologic evidence of underlying cirrhosis, ad the median age at presentation was 68 years (interquartile range [IQR] 61 to 69). Ten of these patients (71.4%) were hemodynamically unstable at presentation. The mean tumor size was 8.5 cm (range 3 to 13), and there was multifocal disease in 6 (42.8%) patients. The etiology of cirrhosis was hepatitis B infection in 3, hepatitis C in 3, alcohol in 4, and cryptogenic in 4 patients. Initial bleeding control was attempted by transarterial embolization (TAE) in 7 (50%) and by emergency surgery in 7 patients (50%). Four of the operations were performed at referring hospitals, and 3 were performed at our institution. Two patients (14.2%) underwent palliative treatment only. Definitive treatment included resection at emergency surgery in 1, staged hepatectomy in 1, and transarterial chemoembolization in 2 patients. There were 7 patients who were noncirrhotic and had a median age of 51 years (IQR 42 to 60). Of these, 6 (87.5%) were hemodynamically unstable at presentation. Mean tumor size was 9 cm (range 6 to 18) and confined to right lobe in all patients. Primary hemostasis was successfully achieved by TAE in 2 and perihepatic packing in 1 patient. Definitive treatment was provided by emergency hepatectomy in 4 and staged hepatectomy in 3 patients. Patients with cirrhosis (n = 14) had a median survival rate of <30 days. Child-Pugh score at presentation (median 7, IQR 5 to 8) correlated strongly with overall survival (P <.0001). Median survival for noncirrhotic patients was 20 months (IQR 2 to 31). One patient without cirrhosis survived for 122 months without disease recurrence. CONCLUSIONS: Spontaneous rupture of HCC is an uncommon presentation in Western countries. Primary hemostasis, followed by emergency or staged hepatic resection, is the treatment of choice. Median survival in patients initially treated with surgery was better than that observed in patients who underwent initial TAE, although this was not statistically significant. Patients who had no underlying liver disease had better prognosis than those who had cirrhosis.     

Impact of Spontaneous Hepatocellular Carcinoma Rupture on Recurrence Pattern and Long-term Surgical Outcomes after Partial Hepatectomy

Background

The clinical significance of spontaneous hepatocellular carcinoma (HCC) rupture association with recurrence pattern and long-term surgical outcomes remains under debate. We investigated the impact of spontaneous HCC rupture on recurrence pattern and long-term surgical outcomes after partial hepatectomy.

Methods

From 2000 to 2012, 119 patients with diagnosed ruptured HCC were reviewed. To compare outcomes between staged hepatectomy in spontaneously ruptured HCC and hepatectomy in non-ruptured HCC, we performed propensity score-matching to adjust for significant differences in patient characteristics. Overall survival, disease-free survival, and recurrence pattern were compared between the matched groups.

Results

Forty-four patients with newly diagnosed ruptured HCC and Child A class were initially treated with transcatheter arterial embolization for hemostasis. Three patients underwent emergency laparotomy, 18 underwent staged hepatectomy, and 23 received transarterial chemoembolization (TACE) alone after transcatheter arterial embolization. Among the 23 patients treated with TACE alone, 10 had resectable tumors. The staged hepatectomy group shows significantly higher overall survival with TACE alone than the resectable tumor group (P < 0.001). After propensity score-matching, overall survival, disease-free survival, and recurrence pattern were not significantly different between the ruptured HCC with staged hepatectomy group and the non-ruptured HCC with hepatectomy group. Peritoneal recurrence rates were similar at 14.3 % versus 10.0 %, respectively (P = 0.632).

Conclusions

Patients with spontaneously ruptured HCC with staged hepatectomy show comparable long-term survival and recurrence pattern as patients with non-ruptured HCC having similar tumor characteristics and liver functional status. Thus, spontaneous HCC rupture may not increase peritoneal recurrence and decrease long-term survival after partial hepatectomy.     

Repeat hepatectomy for recurrent hepatocellular carcinoma

BACKGROUND: Long-term prognosis of patients with hepatocellular carcinoma (HCC) after partial hepatectomy remains unsatisfactory because of the high incidence of recurrence in the liver remnant. Controversy exists about the efficacy of repeat hepatectomy for recurrent HCC patients. The purpose of this study was to retrospectively examine and clarify the significance of repeat hepatectomy in the treatment of recurrent HCC. METHODS: From January 1990 to December 2004, 84 patients with recurrent HCC underwent a second hepatectomy with curative intent. Survival rates in these 84 patients were analyzed retrospectively. RESULTS: After the second hepatectomy, the overall 5-year survival rate was 50% for the 84 patients included in this study; the corresponding recurrence-free survival rate was 10%. Multivariate analysis showed that the second hepatectomy performed between 1997 and 2004 (P < .001) and the absence of microscopic vascular invasion at the second hepatectomy (P = .001) were the significant and independent prognostic factors for overall survival after the second hepatectomy. The overall 5-year survival rate after the second hepatectomy was 80% in 46 patients who had both these prognostic factors. However, even in the subgroup with good long-term survival, the 5-year recurrence-free survival rate was only 6%. The more times hepatectomy was repeated, the shorter the recurrence-free interval became. CONCLUSIONS: Repeat hepatectomy for recurrent HCC had survival benefits, especially for patients without microscopic vascular invasion. However, the incidence of re-recurrence after the second hepatectomy was high, and the recurrence-free interval was short, even in the subgroup with survival benefits. The effectiveness of repeat hepatectomy for curing recurrent HCC is limited.     

原发性肝癌10966例外科治疗分析

目的探讨原发性肝癌外科治疗的临床经验。方法回顾性分析1986年1月至2019年12月南京医科大学第一附属医院肝胆中心手术治疗的10966例原发性肝癌患者的临床资料。采用寿命表法进行生存率和肿瘤复发率的计算,Log-rank检验比较不同组别的差异,采用Cox回归模型进行多因素分析。选取2009—2019年随访数据更详尽的2884例肝细胞癌病例纳入长期生存分析,其中接受肝切除患者2549例,男性2107例,女性442例,年龄(56.6±11.1)岁(范围:20~86岁);接受肝移植患者335例,男性292例,女性43例,年龄(51.0±9.7)岁(范围:21~73岁)。比较肝切除与肝移植的效果、解剖性肝切除与非解剖性肝切除的效果等。结果10966例原发性肝癌患者中,10331例行肝切除,635例行肝移植。根据收治时间,将10331例行肝切除的原发性肝癌患者分为3组:1986—1995年组(712例)、1996—2008年组(3988例)、2009—2019年组(5631例)。1986—1995年组肝细胞癌肝切除患者的5年生存率为32.9%。2009—2019年组原发性肝癌患者肝切除后5年总体生存率为51.7%,其中肝细胞癌、肝内胆管细胞癌和混合性肝癌的5年总体生存率分别为57.4%、26.6%和50.6%。进一步分析行首次肝切除的肝细胞癌患者(2549例),其1、3、5、10年累积总体生存率分别为88.1%、71.9%、60.0%、41.0%,围手术期病死率为1.0%;行一期肝移植的肝细胞癌患者247例,1、3、5、10年累积总体生存率分别为84.0%、64.8%、61.9%、57.6%,行补救性肝移植88例,1、3、5、10年累积总体生存率分别为86.8%、65.2%、52.5%、52.5%,两组患者总体生存率的差异无统计学意义(P>0.05)。2549例接受首次肝切除和247例接受一期肝移植患者的总体生存率和复发率相比,符合米兰标准的肝切除和肝移植患者的1、3、5、10年总体生存率分别为96.3%、87.1%、76.9%、54.7%和95.4%、79.4%、77.4%、71.7%(P=0.754),1、3、5年复发率分别为16.3%、35.9%、47.6%和8.1%、11.7%、13.9%(P<0.01);超米兰标准无大血管侵犯的肝切除和肝移植患者的1、3、5、10年总体生存率分别为87.2%、65.9%、53.0%、33.0%和87.6%、71.8%、71.8%、69.3%(P=0.003),1、3、5年复发率分别为39.2%、57.8%、69.7%和29.7%、36.7%、36.7%(P<0.01);超米兰标准有大血管侵犯的肝切除和肝移植患者的1、3、5、10年总体生存率分别为62.1%、36.1%、22.2%、15.0%和62.9%、31.8%、19.9%、0(P=0.387),1、3、5年复发率分别为61.5%、74.7%、80.8%和59.7%、82.9%、87.2%(P=0.909)。影响肝细胞癌肝切除患者生存率及无复发生存率的独立预后因素有性别、术前辅助治疗、症状、AST、术中或术后输血、肿瘤数目、肿瘤最大径、肝硬化、大血管侵犯、微血管侵犯和病理分化(P值均<0.05)。采用倾向性评分匹配法匹配解剖性肝切除和非解剖性肝切除患者资料,得到443对病例,非解剖性肝切除术后患者的生存率与解剖性肝切除的差异无统计学意义(P=0.895),但非解剖性肝切除术后患者的复发率高于解剖性肝切除(P=0.035)。结论近十年,肝癌手术治疗的生存率较之前明显升高。对于肝功能储备较好的肝细胞癌患者可以先行切除手术,复发后再行补救性肝移植,补救性肝移植的效果与一期肝移植相当。在确保阴性切缘的前提下可以选择保留更多肝脏组织的非解剖性肝切除。     

自发性肝细胞癌破裂的处理策略

世界不同国家和地区肝癌和肝癌破裂发生率差异很大。同肝癌一样,肝癌破裂病死率很高。肝癌破裂的原因,推论很多而且十分具有争议性。肝癌破裂的诊断主要通过临床和影像学检查,确诊率很高。肝癌破裂的治疗主要分为3个处理阶段:(1)急症阶段。主要通过复苏治疗,稳定病人和停止肝癌破裂出血。停止肝癌破裂出血的方法包括改善病人凝血功能障碍,介入治疗(肝动脉栓塞)和手术治疗(围肝脏纱布填塞、肝动脉结扎、使用能量器械或化学制剂直接止血和急症期肝部分切除术)。(2)评估阶段。病人肝癌破裂停止出血后进行评估,包括病人整体情况、肝功能、肿瘤分期、肝癌(包括肿瘤位置)能否切除、剩余肝脏体积情况、是否伴有肝硬化或门静脉高压症。(3)决定性治疗阶段。该阶段主要分为治愈性和非治愈性。由于肝癌破裂是肝移植的禁忌证,肝部分切除术是唯一治愈性手段。术中使用蒸馏水或5-氟尿嘧啶灌洗腹腔,可有效降低术后肝癌腹膜转移率。肝部分切除术可在急症期(出血期间),延迟早期(肝癌破裂时间≤8 d)或延迟晚期(肝癌破裂时间>8 d)施行。在急症期或延迟早期施行肝部分切除术,术后肝癌腹膜转移率比延迟晚期低。肝癌破裂停止出血后,对于无法施行肝部分切除术的病人,其治疗方法与没有肝癌破裂的病人无较大差别。在可施行肝部分切除术的病人中,手术是最好的治疗手段。肝部分切除术病人的远期生存率高于其他任何非手术治疗(包括经肝动脉栓塞或化疗栓塞)。