Repeated resection for extrahepatic recurrences after hepatectomy for ruptured hepatocellular carcinoma

In March 1999, a 54-year-old man with chronic hepatitis C was referred to our hospital because of ruptured hepatocellular carcinoma (HCC) located in Couinauds segments 4 and 8. He underwent central bisegmentectomy of the liver with partial resection of the diaphragm. After the first surgery, extrahepatic metastases were found on different occasions in the abdominal wall, thoracic cavity, and greater omentum and were all surgically resected. In February 2001, the serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) level increased markedly to 19000mAU/l. Magnetic resonance imaging showed a massive right subphrenic tumor with invasion to the right diaphragm and posterior segment of the liver. The patient underwent en bloc resection of the tumor, diaphragm, posterior segment of the liver, and right lower pulmonary lobe. After the surgery, the PIVKA-II level rapidly decreased, and it has remained within the normal range to date. Two years after the last surgery, the patient is doing well without any extrahepatic recurrence, although small intrahepatic recurrences have been completely treated by radiofrequency ablation and transcatheter arterial chemoembolization. Ruptured HCC often exacerbates the risk of peritoneal dissemination and is usually difficult to completely resect. This is an extremely rare case of a patient who successfully underwent five repeated resections for extrahepatic recurrences after hepatectomy for ruptured HCC.     

规范化抗乙肝病毒治疗在肝癌肝切除术后癌症复发的回顾性研究

目的研究抗病毒治疗对乙型肝炎相关肝细胞性肝癌切除后复发的影响。方法利用2010年2月至2011年1月在我中心接受部分肝切除治疗的87例乙肝表面抗原阳性的肝癌患者(其中62例接受规范化抗病毒治疗,25例未进行抗病毒治疗)的详细临床资料以及3年的随访资料进行回顾性分析,研究抗乙肝病毒治疗对于患者肝癌切除后复发以及总体生存的影响。结果 87例HBs Ag阳性患者全部具有完整的随访资料。患者3年随访资料表明,抗病毒治疗可以明显降低术后1个月之后的血清转氨酶水平,提供对肝脏的保护。同时,回顾性研究也证实,抗病毒治疗组相对于对照组的3年癌症复发率有明显改善(50%与64%),3年总体生存率也获得显著提高(66.6%与48.7%)。结论针对HBV-DNA大于104/ml的患者进行围手术期和术后规范化抗病毒治疗是一项安全、有效的治疗手段,与手术切除联合,定期复查,严格防控耐药性病毒株的产生,可以明显延缓患者术后肝脏功能,减少肝癌复发、改善患者预后。     

Spontaneous regression of multiple pulmonary recurrences of hepatocellular carcinoma after hepatectomy: report of a case

Spontaneous regression of hepatocellular carcinoma (HCC) is an extremely rare phenomenon. We herein report the case of a 73-year-old man who showed the spontaneous regression of multiple pulmonary recurrences of HCC that had occurred after hepatectomy. The patient was undergoing dialysis due to diabetic renal failure when ultrasonography revealed a liver tumor (diameter ~ 10 cm). A preoperative diagnosis of HCC with hepatic vein thrombosis was made. The liver function was well preserved and then the right hepatic vein area was resected. Two months after hepatectomy the α-fetoprotein level increased, and multiple lung nodules were observed on follow-up computed tomography. A diagnosis of multiple lung metastases was made, but no therapy was started because of the patient’s renal failure. Five months after hepatectomy the α-fetoprotein level normalized, and the metastases regressed completely. The patient is now doing well without any recurrence at 13 months after the surgery. The associated literature on spontaneous HCC regression is also reviewed.     

Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis.

To determine whether a careful evaluation of tumor extension by preoperative computed tomography scan after intra-arterial injection of ultrafluid lipiodol and by intraoperative ultrasound examination reduced the recurrence rate of hepatocellular carcinoma after resection, a series of 47 cirrhotic patients with a single tumor operated on from 1984 was studied. Alphafetoprotein level was less than 100 ng/mL in 26 patients (55%), size of the tumor was less than 5 cm in 28 patients (59%), and capsule was present in 30 patients (63%). The resection was performed with free margin measuring 1 cm or more. The overall cumulative survival rates at 3 and 5 years were 35% and 17%, respectively. Intrahepatic recurrence was observed in 28 patients (60%), located less than 2 cm from the resection margin in only four patients. The cumulative intrahepatic recurrence rate at 3 years was 81% and was significantly higher in patients with tumor greater than or equal to 5 cm and in patients with preoperative alphafetoprotein level of greater than or equal to 100 ng/mL. In this series the cumulative intrahepatic recurrence rate at 5 years was 100%. This high recurrence rate after resection, even with careful evaluation of tumor extension, indicates that liver transplantation might be envisaged for the treatment of cirrhotic patients with resectable hepatocellular carcinoma.     

Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma.

OBJECTIVE: The aims of this study were to identify prognostic factors in patients who developed recurrent hepatocellular carcinoma (HCC) after repeat hepatectomy and to elucidate the role of multicentric occurrence in the second tumor after a first hepatectomy. SUMMARY BACKGROUND DATA: A repeat hepatectomy for recurrent HCC has been established as the most effective treatment modality, whenever it is possible. However, the prognostic factors for recurrent HCC after repeat hepatectomy have yet to be clarified. METHODS: Forty-one patients who underwent a curative repeat hepatectomy were retrospectively studied. Patient survival and disease-free survival after recurrence were univariately and multivariately analyzed using 38 clinicopathologic variables. The histologic grade of HCC at repeat hepatectomy was also compared with that at first hepatectomy. RESULTS: Patient survival after repeat hepatectomy did not differ substantially from that in 312 patients undergoing primary hepatectomy. However, the disease-free survival after repeat hepatectomy was significantly lower than that in patients with only a primary hepatectomy (p < 0.05). Multivariate analysis revealed only portal vein invasion in the first hepatectomy to be an independent and significantly poor prognostic factor. Regarding multicentric occurrence at repeat hepatectomy, only 6 of 40 patients (15%) whose specimens could be evaluated histologically were determined to be Edmondson and Steiner's Grade 1. CONCLUSIONS: The only prognostic factor identified in patients with recurrent HCC after repeat hepatectomy was portal vein invasion in the first hepatectomy. Most second tumors after the first hepatectomy are considered to be caused by metastatic recurrence, not by multicentric occurrence.     

射频消融治疗复发性肝细胞癌疗效分析

目的探讨射频消融对肝细胞癌(HCC)手术切除后复发病例再治疗的效果,比较不同复发时间的疗效差别。方法以行超声引导经皮射频消融(RFA)治疗的手术切除后复发性肝细胞癌(RHCC)患者(RHCC组)和同期行RFA治疗的首发HCC患者(首发HCC组)为研究对象。(1)RHCC组42例患者,男34例,女8例,平均年龄(58±10)岁;复发灶大小1.5~6.6cm,平均(3.8±1.4)cm。RFA治疗前5例伴肝外转移。肝功能A级21例,B级19例,C级2例。手术切除距肝内初次复发时间为1~96个月,平均22.8个月。术后1年内肿瘤复发者20例40灶(RHCC近期组),术后1年以上复发者22例37灶(RHCC远期组)。(2)首发HCC组148例患者,男117例,女31例,平均年龄59岁。肿瘤大小1.2~7.0cm,平均(4.0±1.4)cm。RFA治疗后1个月采用增强CT检查评价消融成功率;比较RHCC近期组、RHCC远期组和首发HCC组的治疗效果、复发转移情况及生存期。结果首发HCC组RFA成功率为87.2%(129例),局部复发率为16.2%(24例),另位复发率为37.8%(56例),平均生存期为(39.0±2.1)个月;RHCC近期组、远期组RFA成功率分别为85.0%和95.5%(P>0.05),局部复发率分别为15.0%和13.6%(P>0.05),另位复发率为60.0%和18·2%(P=0.005),平均生存期为(15.4±2.3)个月和(39.5±4.5)个月(P<0.005)。与首发HCC组相比,RHCC远期组消融成功率与局部复发率均无显著性差异(P>0.05),RHCC近期组生存期低于首发HCC组(P<0.05)。RHCC远期组1例患者治疗后出血,经射频止血、输血等保守治疗缓解。结论RFA治疗RHCC的预后及疗效与复发的时间相关;对于术后远期复发者,行RFA治疗可获得同首发HCC相似的生存期,而手术后近期复发者疗效相对较差。     

Estimation of prognosis after hepatectomy for hepatocellular carcinoma

BACKGROUND: The preferred means of treatment for hepatocellular carcinoma is surgical resection. However, the tumour recurrence rate is high. Accurate estimation of the risk of tumour recurrence after hepatectomy may facilitate the administration of adjuvant therapy after hepatectomy to patients with a high likelihood of tumour recurrence. METHODS: The clinical and pathological profiles of 176 patients undergoing hepatectomy for hepatocellular carcinoma from March 1992 to August 1998 were reviewed. The Kaplan--Meier method and log rank test were used to analyse univariate prognostic factors. The Cox proportional hazard model was used for multivariate analysis. Disease-free and overall cumulative survival rates were estimated with respect to the number of prognostic factors. RESULTS: Independent factors associated with a lower disease-free survival included the presence of venous infiltration, presence of daughter tumours, absence of tumour encapsulation and tumour size exceeding 5 cm. Factors decreasing the overall survival rate included the presence of venous infiltration, absence of tumour encapsulation and surgical resection margin less than 1 cm. The 1-year disease-free survival rate decreased from 77.5(s.e. 5.6) to 14.0(8.5) per cent when the number of risk factors present increased from zero to three. The 5-year survival rate decreased from 60.2(11.7) per cent to zero when the number of risk factors increased from zero to three. CONCLUSION: The deterioration of disease-free or overall survival of patients with hepatocellular carcinoma after hepatectomy correlates with increasing number of risk factors. The number of risk factors can be employed to accurately estimate disease-free and overall survival.     

肝细胞癌切除术后预后因素分析

目的探索影响肝细胞肝癌手术预后的因素。方法回顾性分析2000～2005年76例经病理证实的肝细胞肝癌手术切除患者,选择16项临床、病理学因素,分析其对生存率的影响。结果全组1,3,5年生存率分别为85.53%,48.05%,14.96%。60例获得根治者1,3,5年生存率分别为100%,58.93%和18.35%。影响预后的单因素为:肿瘤根治程度、肝癌结节数目、肝功能分级、肿瘤分期、门脉癌栓、术前血清胆红素、术前白蛋白水平。多因素分析表明:术前肝功能Child-Pugh分级、肿瘤结节数目、门脉癌栓和肿瘤根治程度与生存率有显著相关性。结论肿瘤结节数目、门脉癌栓、术前肝功能分级、肿瘤根治程度是影响肝细胞肝癌术后的高风险因素。     

Intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy

Background/Purpose  We aimed to clarify the histological features of and risk factors for intrahepatic dissemination after local ablation therapy (LAT) for hepatocellular carcinoma (HCC). Methods  Between April 1992 and December 2005, 192 HCC patients underwent hepatic resection at our department, among whom were 17 patients who had local recurrences after LAT. Eight of these 17 patients had intrahepatic dissemination. The clinical and histological characteristics of these 8 surgically treated patients with intrahepatic dissemination were investigated. Results  Histologically, numerous intrahepatic metastases were observed, mainly in the same section as the treated tumor, together with main or sectional portal vein tumor thrombi. Before the ablation therapy, the average tumor diameter was 2.1 cm, and 62.5% of the tumors were adjacent to the main or sectional portal vein. In terms of therapeutic factors, 25% of the patients had a prior needle biopsy and 62.5% had insufficient safety margins. Conclusions  LAT for HCCs (even those less than 3 cm in diameter) adjacent less than 5 mm to the main or sectional portal vein possibly promotes intrahepatic dissemination.     

微管蛋白Transgelin判断肝癌切除术预后的临床价值探讨

目的 研究肝癌中转胶蛋白(Transgelin)表达预测肝癌切除术患者复发及预后的临床意义.方法 应用组织芯片结合免疫组织化学染色检测43例肝癌切除术患者肝癌和癌周组织的Transgelin表达水平.以Logrank检验、Kaplan-Meier分析以及多因素Cox回归分析其表达水平与肝癌患者预后的关系.结果 Tran...     

影响肝细胞肝癌手术切除预后因素的COX模型分析

目的 对影响肝细胞肝癌手术切除预后的因素进行多因素分析。方法 1986－1996年经手术切除的145例肝癌患者,随访至1999年底。单因素分析采用Kaplain-Meier Log-rank时序检验,多因素采用COX比例风险模型。结果 手术后1、3、5、7、10、12年生存期分别为75．0％、44．4％、29．5％、23．5％、21．2％、16．9％;单因素分析影响预后因素为发现方式、肝癌体积、有否门静脉癌栓、卫星结节及肝癌结节数、UICC分期、手术切缘、有否复发及复发后治疗方式、是否根治性切除;多因素分析得出和预后有关的因素为发现方式、UICC分期、手术切缘、有否复发及复发后治疗方式,是否根治性切除。结论 肝癌的预后取决于早期诊断及治疗方式;UICC分期与预后相关,且与卫星结节、结节数、门静脉癌栓相关。1cm以上的手术切缘,可明显提高切除疗效。     

Locoregional recurrences are frequent after radiofrequency ablation for hepatocellular carcinoma

BACKGROUND: Enthusiasm for radiofrequency ablation (RFA) therapy for patients with unresectable hepatocellular carcinoma (HCC) has increased. The data for recurrence after RFA for patients with HCC is not well documented. The purpose of this study was to evaluate tumor recurrence patterns after RFA in patients with unresectable HCC. STUDY DESIGN: Over a 3-year period, 50 patients having RFA for unresectable HCC were identified at a single institution. Medical records and radiologic studies were reviewed and outcomes factors analyzed. RESULTS: Of the entire cohort, 46 patients underwent RFA by a percutaneous approach under CT guidance. Most patients underwent either one (n = 22) or two ablations (n = 23). At the time of this report, 14 patients (28%) were tumor-free by radiologic and biochemical (alpha-fetoprotein) parameters. Eighteen additional patients had persistence of tumor at the ablation site and 14 patients had recurrence in the liver at sites different from the ablation site. An additional four patients had recurrence in extrahepatic sites. Twelve patients underwent orthotopic liver transplantation after RFA. Of these 12, 5 (42%) demonstrated no viable tumor in the explanted liver. Independent predictors of tumor recurrence included tumor size, serum AFP levels, and the presence of hepatitis. CONCLUSIONS: These data suggest that factors such as tumor size should be considered before employing RFA therapy. In addition to treating the primary tumor, other therapies aimed at the liver's inflammatory state might also be important in achieving a durable response after RFA.     

Multidisciplinary therapy after hepatectomy for hepatocellular carcinoma from the view point of tumor recurrence]

This study was performed to elucidate the risk factors of early recurrence after hepatectomy for the 112 patients with hepatocellular carcinoma, excluding absolute non-curative resections and operative deaths, and effects of early prophylactic management were evaluated. In Cox's multivariate analysis, 3 pathological factors of portal vein invasion, intrahepatic metastasis and capsule formation or capsule infiltration as well as the nuclear DNA ploidy pattern were significantly correlated to postoperative recurrence. The patients with 2 or more pathological factors or with DNA aneuploid tumors developed recurrence at early postoperative period. However, even in the DNA aneuploid tumors, the patients with high DNA index and low S-phase fraction showed relatively better prognosis. Argyrophilic proteins of nucleolar organizer regions (AgNOR) were also correlated well to nuclear DNA analysis, showing one of the good indicators for estimating biological malignant nature. Therefore, intra-arterial regional chemolipiodolization therapy should be performed for these high risk patients at early period after hepatectomy. With these managements we have been getting much lower incidence of early recurrence.     

糖尿病对肝癌肝切除术预后的影响

目的分析研究肝细胞癌（HCC）合并糖尿病（DM）实施肝切除术的预后。方法回顾性总结1992年1月至2005年4月间410例肝细胞癌及36例合并糖尿病手术病人临床资料，用SPSS软件对其临床病理资料与术后生存资料进行统计学分析。结果DM的HCC病人的年龄明显高于无DM的HCC病人（P=0．002），合并DM组术后并发症的发生率明显高于无DM组（P=0．001），而术后生存时间的比较无明显的差异（P=0．417）；DM是影响孤立性大肝癌（SLHCC）病人的术后生存独立的危险因素。结论DM并不影响HCC手术的整体预后，因而，也对HCC病人包括手术等治疗方式的选择上影响不大。但对围手术期血糖的控制，可减少术后并发症的发生。     

Subcutaneous metastases after laparoscopic-assisted partial hepatectomy for hepatocellular carcinoma

We reported an unusual case with subcutaneous seeding of hepatocellular carcinoma 12 months after laparoscopic-assisted partial hepatectomy. A 69-year-old woman with hepatitis-C-related liver cirrhosis was found to have hepatocellular carcinoma on routine sonographic examination. The tumor located superficially in the left lateral segment. She received laparoscopic-assisted partial hepatectomy for the tumor in February 2002. She was uneventful after the surgery and serum α-fetoprotein level dropped from 1217 to 275 ng/mL in 3 months. Serum α-fetoprotein level was found to rise 9 months after surgery and a subcutaneous tumor appeared over the surgical wound 12 months after surgery. Resection of lesion showed hepatocellular carcinoma. To our knowledge, seeding of hepatocellular carcinoma on surgical wound has rarely, if ever, been reported after laparoscopic-assisted surgery. The patient died of disseminated recurrence 20 months after the surgery. This case reminded us the risk of tumor seeding after laparoscopic-assisted partial hepatectomy.     

528例原发性肝细胞癌患者肝切除术后1年生存分析

目的 探讨原发性肝细胞癌患者( hepatocellular carcinoma,HCC)肝切除术后1年生存状况及影响因素.方法 回顾性分析1997年1月至2008年12月因HCC行肝切除的528例患者术后1年生存结果和影响因素.结果 本组患者随访期间死亡302例,患者1年累积生存率为84％.1年内死亡原因主要为HCC复发转移(78.1％,75/96)及与原发的肝病相关合并症(19.8％,19/96).大肝癌(P =0.047)、血管癌栓(P=1.118)、组织学中低分化(P =0.001)和病理切缘肿瘤残留(P=0.004)者是HCC患者1年内HCC复发转移死亡的独立危险因素;伴有门静脉高压症(P =0.001)是预示术后肝病相关死亡的独立因素.非RO切除的患者是1年内死亡(占59.3％)最重要的因素.结论 影响HCC切除术后1年生存的主要因素是HCC复发转移与原发的肝病相关因素,非R0切除是导致原发性HCC患者术后早期复发死亡的最主要的因素,术前伴有门静脉高压症是影响HCC患者术后肝病相关死亡的独立危险因素.     

Percutaneous thermal ablation for recurrent hepatocellular carcinoma after hepatectomy

BACKGROUND: Tumour ablation using a thermal energy source has shown promising results, and is particularly suitable for recurrent hepatocellular carcinoma (HCC). The present study evaluated long-term outcomes after percutaneous thermal ablation for recurrent HCC following liver resection. METHODS: Radiofrequency ablation or microwave ablation was used to treat a total of 124 tumour nodules (0.9-7.0 cm in diameter) in 72 patients with recurrent HCC. RESULTS: Complete ablation of 119 (96.0 per cent) of 124 tumour nodules was achieved. There was no treatment-related death and the major complication rate was 4 per cent. During a mean(s.d.) follow-up of 27.9(17.8) months, local recurrence developed in 16 (13.6 per cent) of 118 successfully treated tumour nodules. Distant recurrence developed in 60 (85 per cent) of 71 patients, of whom 26 had repeat metachronous distant recurrence. With repeated ablation for both local and distant recurrence, the 1-, 3- and 5-year overall survival rates after initial ablation were 75, 43 and 18 per cent respectively. Patients with a serum alpha-fetoprotein level greater than 200 ng/ml before treatment had significantly poorer survival than those with a lower level (P = 0.034) and multivariate analysis identified preablation AFP level as an independent prognostic factor (P = 0.054). CONCLUSION: With their advantages of preservation of non-tumorous liver tissue and easy repetition, percutaneous thermal ablative therapies were particularly suitable for recurrent HCC and improved long-term survival.     

Significant influence of accompanying chronic hepatitis status on recurrence of hepatocellular carcinoma after hepatectomy. Result of multivariate analysis.

OBJECTIVE: The aim of this study was to evaluate the correlation between the histologic status of accompanying chronic hepatitis and the recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy by multivariate analysis. SUMMARY BACKGROUND DATA: Recent studies have suggested that a considerable number of intrahepatic recurrence of HCC after hepatectomy might be the results of metachronous multicentric hepatocarcinogenesis. The authors hypothesized that the incidence of recurrence due to metachronous multicentric hepatocarcinogenesis would depend on the histologic status of accompanying chronic viral liver disease, which is a main promoter of HCC. METHODS: One hundred ten patients with HCC who underwent curative resection were studied. Histologic status of accompanying chronic hepatitis was classified into the three categories: 1) normal liver or chronic persistent hepatitis (CPH, n = 13), 2) chronic aggressive hepatitis (CAH, n = 50), and 3) liver cirrhosis (LC, n = 47). RESULTS: The Cox multivariate proportional hazard model showed that the accompanying chronic viral hepatitis status (p = 0.0133), extent of hepatectomy (p = 0.0078), and number of tumors (p = 0.0475) were significantly predictive variables for recurrence-free survival. By the log-rank test, recurrence-free survival rate in patients with CPH was significantly higher than those in patients with CAH (p = 0.0005) and LC (p = 0.0075). Patients with CAH had the lowest recurrence-free survival rate (vs. LC, p = 0.028). CONCLUSIONS: The results of this study indicated the significant influence of histologic activity of hepatitis on recurrence of HCC. This might support the concept of significant contribution of multicentric hepatocarcinogenesis to recurrence of HCC after hepatectomy.     

Intrahepatic cholangiocarcinoma detected by elevated levels of alpha-fetoprotein-L3 after hepatectomy for hepatocellular carcinoma in a patient with Budd-Chiari syndrome

We report the case of a 57-year-old woman with Budd-Chiari syndrome, hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (ICC). She underwent partial hepatectomy for HCC in April 2000. After surgery, alpha-fetoprotein (AFP) and protein induced by vitamin K absence II (PIVKA-II) returned to normal levels, but lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) increased, and ultrasonography showed a nodule 2 cm in greatest dimension in the left lateral segment of the liver. We diagnosed this nodule as recurrence from HCC and performed a partial hepatectomy in October 2001. Microscopic examination showed that tubular adenocarcinoma and immunohistochemical staining was focally positive for AFP. AFP-L3 was 0% and AFP was 5 ng/ml 3 months after re-operation. This case was interesting in that ICC was detected by elevated levels of AFP-L3, and ICC produced AFP from the time it was minute in size.