Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors

OBJECTIVE: This study aimed to evaluate the long-term results of treatment and prognostic factors in patients with intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Recent studies have demonstrated the usefulness of re-resection, transarterial oily chemoembolization (TOCE), or percutaneous ethanol injection therapy (PEIT) in selected patients with intrahepatic recurrent HCC. The overall results of a treatment strategy combining these modalities have not been fully evaluated, and the prognostic factors determining survival in these patients remain to be clarified. METHODS: Two hundred and forty-four patients who underwent curative resection for HCC were followed for intrahepatic recurrence, which was treated aggressively with a strategy including different modalities. Survival results after recurrence and from initial hepatectomy were analyzed, and prognostic factors were determined by univariate and multivariate analysis using 27 clinicopathologic variables. RESULTS: One hundred and five patients (43%) with intrahepatic recurrence were treated with re-resection (11), TOCE (71), PEIT (6), systemic chemotherapy (8) or conservatively (9). The overall 1-year, 3-year, and 5-year survival rates from the time of recurrence were 65.5%, 34.9%, and 19.7%, respectively, and from the time of initial hepatectomy were 78.4%, 47.2%, and 30.9%, respectively. The re-resection group had the best survival, followed by the TOCE group. Multivariate analysis revealed Child's B or C grading, serum albumin < or = 40 g/l, multiple recurrent tumors, recurrence < or = 1 year after hepatectomy, and concurrent extrahepatic recurrence to be independent adverse prognostic factors. CONCLUSIONS: Aggressive treatment with a multimodality strategy could result in prolonged survival in patients with intrahepatic recurrence after curative resection for HCC. Prognosis was determined by the liver function status, interval to recurrence, number of recurrent tumors, any concurrent extrahepatic recurrence, and type of treatment.     

Surgical margin and recurrence after resection of hepatocellular carcinoma in patients with cirrhosis. Further evaluation of limited hepatic resection.

This report attempts to elucidate the manner in which the surgical margin is linked to a recurrence after curative hepatectomy for hepatocellular carcinoma (HCC) in patients with cirrhosis. Forty patients were divided into two groups: those in whom the margin from the cut surface to HCC in the fresh resected specimen was less than 10 mm wide, and patients in whom the surgical margin was equal to or exceeded 10 mm. These margins were expressed as tumor wedge positive [TW(+)], and tumor wedge negative [TW(-)], respectively. There were 24 and 16 patients in the TW(+) and TW(-) groups, respectively. There was no statistically significant difference in clinicopathologic variables, except for age and values of serum albumin between the two groups. There was a recurrence in ten of 24 patients (42%) of the TW(+) group and in eight of 16 patients (50%) of the TW(-) group. Mean disease-free periods were 21.4 months in the TW(+) group and 23.6 months in TW(-) group. These 40 patients were also divided with regard to the time of recurrence, the early recurrence within 24 months, and the late recurrence after 24 months. There was no statistically significant difference in the rate of recurrence and mean disease-free period between the TW(+) and TW(-) groups in the early and late recurrence groups. In both the TW(+) and TW(-) groups, there were no recurrences in 13 of 16 patients (81.3%) with a tumor less than 4 cm in diameter, yet there were recurrences in seven of eight patients (87.5%) with a tumor exceeding 4 cm in diameter, regardless of the time to recurrence. These results suggest that in patients with a tumor less than 4 cm, the extent of TW is not linked to an early recurrence. However, when the tumor size exceeds 4 cm, 10 mm of TW is inadequate to achieve curability. When a wide resection is not feasible, then adjuvant chemotherapy should be aggressive.     

肝细胞癌切除术后复发再手术治疗

目的　探讨肝细胞癌手术后复发的治疗经验。方法　回顾性分析 1995～ 2 0 0 3年手术治疗 38例肝癌切除术后复发的临床资料。结果　再次手术切除 32例 ,姑息性手术 6例 ,手术后平均生存期超过 14个月。结论　肝细胞癌术后复发是影响病人长期生存的重要原因 ,选择有适应证的病例再次手术切除能延长病人的生存时间。     

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。     

Predictors and patterns of recurrence after resection of hepatocellular carcinoma

BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) who undergo complete tumor resection subsequently develop tumor recurrence. The objectives of this study were to determine the risk factors for recurrence of HCC after hepatectomy and to examine the outcomes once tumor recurrence occurs. STUDY DESIGN: From February 1990 to May 2001 a total of 164 patients underwent liver resection for HCC at our institution and were prospectively followed. Time to recurrence and survival after recurrence were determined by Kaplan-Meier analysis. Patient, tumor, and treatment characteristics were tested for their prognostic significance by univariate and multivariate analysis using the logrank test and the Cox proportional hazards model, respectively. RESULTS: The median patient age was 64 years (range 21 to 87 years) and 106 patients (65%) were male. After a median followup of 26 months, 90 patients (55%) have developed recurrent cancer. Among them, 75 patients (83%) had tumor detectable in the liver, which was the only site of disease in 67 (74%). In all, 15 patients (20%) had extrahepatic disease (7 lung, 4 peritoneum, 2 pancreas, 1 bone, and 1 brain). The median time to recurrence was 24 months (range 1 to 274 months). Predictors of recurrence on univariate analysis were tumor size greater than 5 cm, more than one tumor, cirrhosis, vascular invasion (microscopic or macroscopic), and tumor satellites. On multivariate analysis only tumor size greater than 5 cm (p = 0.04) and vascular invasion (p = 0.01) predicted recurrence. The median survival after recurrence was 11 months (range 0 to 60 months). Of the 90 patients who developed tumor recurrence 49 (67%) were able to undergo additional ablative or surgical therapy (33 embolization, 9 ethanol injection, and 14 re-resection). On multivariate analysis vascular invasion in the original tumor predicted poor survival after recurrence (p = 0.009). CONCLUSIONS: The liver is the predominant site of first recurrence after resection of hepatocellular carcinoma, and once recurrence occurs survival is limited. The current study underscores the need for effective adjuvant therapy for patients with HCC treated with partial hepatectomy.     

肝细胞癌切除术后复发的RFA微创治疗

目的:探讨肝细胞癌切除术后复发患者采用射频消融术(RFA)治疗的临床效果。方法:选取2008—2012年收治的97例肝细胞癌切除术后复发患者作为观察对象,其中再次治疗采用射频消融术者58例(射频组)、选择采用无水酒精注射治疗者39例(无水酒精组),比较两组肿瘤复发治疗效果。结果:病灶≤3 cm和3 cm者,射频组的治疗次数均低于无水酒精组,差异有统计学意义(P0.05);病灶≤3 cm者,射频组灭活率为90.24%,无水酒精组为80.00%,组间比较无统计学差异(P0.05);病灶3 cm者,射频组病灶灭活率明显高于无水酒精组(82.61%vs.50.00%,P0.05)。射频组并发症率低于无水酒精组但无统计学差异(31.03%vs.41.03%,P0.05);射频组末次治疗后的1、2、3年存活率分别为84.48%、62.07%、43.01%均明显高于无水酒精组的64.10%、42.03%、20.51%,差异均有统计学意义(P005);射频组总生存中位时间明显长于无水酒精组(18个月vs.13个月,Log-rankχ2=5.566,P=0.018)。结论:肝细胞癌切除术后复发采用射频消融术治疗临床疗效良好。     

肝细胞肝癌切除后复发（欧洲经验）

目的 探讨肝细胞肝癌切除后复发的预后相关因素及合理治疗方法。方法 １９８３年１月至１９９７年１月２７１例肝癌切除后有１３４例复发，对其一般情况，肿瘤特性及外科措施进行多因素分析，同时比较复发后不同治疗方法的结果。结果 复发时间在术后１年内，首次手术时ＡＦＰ〉１０００μｇ／Ｌ肿瘤直径〉５ｃｍ，门静脉有癌栓，外科切缘为０及术前行肝动脉插管化疗者等６大因素直接影响复发的预后，同时发现，复发肿瘤可行再次切     

Hepatic resection for hepatocellular carcinoma in cirrhosis

Hepatocellular carcinoma is one of the most common cancers worldwide. Several treatment modalities have been proposed, but hepatic resection is still considered the first-line therapeutic option for most of the patient carries of HCC. The proper selection of patients candidate to hepatic resection for HCC and the eradication whenever is possible of the intrahepatic metastases are the most crucial steps for improving the surgical outcome in HCC. This article reviews the current state of the art of the surgical treatment of HCC.     

Factors associated with early recurrence after resection for hepatocellular carcinoma and outcomes

BACKGROUND: Early recurrence (ER) (<1 year) after liver resection is one of the most important factors that impact the prognosis of patients with hepatocellular carcinoma (HCC). We sought to determine factors associated with ER of HCC and examine the outcomes thereafter. STUDY DESIGN: From March 2001 to June 2003, 56 patients underwent hepatic resection for HCC at University of Toronto and were prospectively followed with median followup of 24 months. Patients with ER were compared with those who remained disease free for more than 1 year. Patient characteristics, tumor stage, and operative procedures were evaluated for their prognostic significance by univariate and multivariable analysis. Time to recurrence and time to death were analyzed using Kaplan-Meier survival curves and compared using log-rank analysis. RESULTS: The initial procedure in all patients was surgical hepatectomy. ER occurred in 21 patients (38%), 31 (55%) remained disease free for more than 1 year, and 4 (7%) were omitted from evaluation because of early (<30 days) death. Median survival after initial hepatic resection for those with ER was 27 months, and 2-year survival was 54%. There were no deaths in the group that remained disease free for more than 1 year (100% 2-year survival, p < 0.05). By multivariate analysis, vascular invasion and positive microscopic margins were significant predictors when all 4 variables were considered in the model (p < 0.05). After ER, 11 of 21 patients (52%) underwent additional therapy with significant improvement in median survival (33 months) compared with those not eligible for conventional therapy (18 months, p = 0.05). CONCLUSIONS: ER after liver resection for HCC is the leading cause of death during the first 2 years after potentially curative resection. ER will develop in approximately 75% of patients with either vascular invasion or positive margins. For patients with these predictive factors additional treatment might be advised.     

Survival and recurrence rates after resection for hepatocellular carcinoma in noncirrhotic livers

BACKGROUND: Hepatocellular carcinoma occurring in noncirrhotic livers is rare. The purpose of this article was to evaluate the outcomes and prognostic factors after hepatectomy in this setting. STUDY DESIGN: Between June 1998 and May 2005, 83 patients underwent liver resection for hepatocellular carcinoma in noncirrhotic livers at our institution. Preoperative treatment data, intraoperative details, pathologic findings, and information on tumor recurrence, treatment of recurrence, and survival were available for 80 of these patients. RESULTS: Postresection, the 3- and 5-year-survival rates were 48% and 30%, respectively. After R0 resection (n=66), the calculated 3- and 5-year-survivals were 54% and 39%, compared with 23% and 0%, respectively, after R1/2-resection (p<0.005). After a median followup of 25 months, tumor recurred in 40 of 63 (63%) patients after R0 resection. In univariate analysis, Union Internationale Contre le Cancer (UICC) stage, vascular invasion, and tumor grading were identified as important findings for recurrence and poor survival after R0 resection. For tumors without vascular invasion, the 3- and 5-year-survivals were 79% and 65%, respectively, which compared favorably with 21% and 7%, respectively, for tumors with vascular invasion (p<0.0001). Similarly, 3- and 5-year-survival rates (95% each) were considerably better for G1 tumors than the corresponding 36% and 22% rates in G2 and 60% and 30% in G3 tumors, respectively. CONCLUSIONS: The 3- and 5-year survivals of 54% and 39%, respectively, after R0 resections suggest that surgery is an option in hepatocellular carcinoma arising in noncirrhotic livers. Longterm results, however, are hampered by high recurrence rates. Union Internationale Contre le Cancer stage, vascular invasion, and tumor grades are predictors of tumor recurrence and diminished survival, and may help to identify candidates for potential adjuvant therapies.     

Prognostic factors and survival after hepatic resection for hepatocellular carcinoma without cirrhosis

BACKGROUND: Detailed follow-up of patients with chronic hepatitis has resulted in increased diagnosis of hepatocellular carcinoma (HCC) in patients without cirrhosis. Despite numerous studies on hepatic resection, the prognostic factors for intrahepatic recurrence and survival are not well known for patients with HCC without cirrhosis. METHODS: Among 349 patients with HCC treated in the past 13 years, cirrhosis was absent in 126 patients (36 per cent). Curative hepatic resection was carried out in 100 (79 per cent) of these patients. Risk factors for intrahepatic recurrence and prognostic factors for survival were evaluated by univariate and multivariate analyses. RESULTS: Postoperative morbidity and mortality rates were 22 and 3 per cent respectively. The 5- and 10-year disease-free and overall survival rates were 31 and 50 per cent, and 22 and 47 per cent respectively. Blood loss, surgical resection margin, intrahepatic metastasis, portal vein invasion and extent of hepatic resection were independently associated with overall survival. However, the only risk factors for intrahepatic recurrence were portal vein invasion and hepatitis C virus (HCV) infection. The former was related to early recurrence while the latter was related to later recurrence. The 5-year disease-free survival rate was 58 per cent in patients with hepatitis B virus infection while it was 6 per cent in patients with HCV infection (P < 0.001). CONCLUSION: In the treatment of HCC without cirrhosis, major hepatectomy is advocated to prevent early recurrence. Liver transplantation may be required for patients with HCV infection.     

肝细胞癌根治性切除术后肝内复发的危险因素分析

目的探讨肝细胞癌根治性切除术后肝内复发的独立危险因素,为肝细胞癌的临床综合治疗提供依据。方法回顾性分析实施肝癌根治性切除的194例肝细胞癌患者的临床资料,将全部病例以术后复发时间2年为界,划分为2年内复发组和2年内未复发组,比较两组之间21项可能影响肝细胞癌术后肝内复发的临床指标的差异。结果单因素分析结果示：2年内复发组的术前血清AFP浓度〉20ng／ml、术前血清AST浓度〉40U／L、术前血清ALP浓度〉135U／L、术前血清GGT浓度〉50U／L、血清HBsAg测定为阳性、肿瘤最大直径〉5cm、肿瘤病灶数目为2个、手术持续时间≥180min、手术中总失血量≥1000ml、手术中有输血的病例数的构成比高于2年内未复发组,且差异有统计学意义。多因素分析结果显示术前血清ALP浓度、肿瘤最大直径、肿瘤病灶数目、手术中总失血量是影响肝细胞癌术后肝内复发的有统计学意义的因素。结论肝细胞癌术后肝内复发是多种因素的共同作用的结果,术前血清ALP浓度、肿瘤最大直径、肿瘤病灶数目、手术中总失血量是影响肝细胞癌术后肝内复发的独立的危险因素。     

Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection

BACKGROUND: Little is known about the metastatic pattern in patients with extrahepatic metastasis after the removal of primary hepatocellular carcinoma (HCC). The aim of the present study was to determine the clinicopathologic characteristics and prognosis of patients with extrahepatic metastasis from HCC according to the recurrence pattern. METHODS: Among the patients who underwent hepatic resection for HCC between 1981 and 2001, 80 patients had no recurrence; 221 patients had intrahepatic recurrence, and 47 patients experienced extrahepatic metastasis within a mean follow-up period of 4.8 +/- 3.7 years (+/-SD; range, 2-15 years). The pattern of extrahepatic metastasis after hepatic resection was divided into pattern I (first recurrence in the liver and then spread outside the liver after repetitive intrahepatic recurrences and repetitive locoregional treatments), pattern II (simultaneous recognition of intrahepatic and extrahepatic recurrences), and pattern III (extrahepatic, but no intrahepatic, lesions at first recurrence). RESULTS: There were significant differences in proportions of patients with invasion of the portal vein, hepatic vein, or inferior vena cava, intrahepatic metastases, and tumor stage between patients with intra- and extrahepatic metastases. The disease-free survival and extrahepatic metastasis-free survival in pattern I were better than pattern II. Survival after extrahepatic metastasis did not correlate with the 3 patterns. CONCLUSION: Although long-term overall survival was better in patients with pattern I of extrahepatic recurrences, prognosis was poor in all patterns once extrahepatic metastasis developed.     

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。     

Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma

BackgroundExtrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection.MethodsThe participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping.ResultsExtrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively.ConclusionWe have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.     

Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma

BACKGROUND: Although hepatic resection is one of the most effective treatments for hepatocellular carcinoma (HCC), the longterm results of hepatic resection of this malignancy are far from satisfactory. The potential benefits of hepatectomy for patients with HCC have not been fully delineated. This study aimed to identify surgical outcomes of 386 consecutive patients with HCC undergoing hepatic resection. STUDY DESIGN: The retrospective study looked at records of 293 men and 93 women. The mean age was 63.2 years. Preoperative transarterial chemoembolizaton and portal vein embolization were performed in 138 patients (35.8%) and 8 patients (2.1%), respectively. Sixty-two patients (16.1 %) had major hepatectomy and the other 324 (83.9%) had minor hepatectomy. Thirty-seven of 386 patients (9.6%) had a noncurative operation. RESULTS: The 30-day (operative) mortality rate was 4.1%, and there were 11 additional late deaths (2.9%). Two hundred fourteen of 327 patients (65.4%) had recurrence after curative resection. Unfavorable factors for survival and recurrence were resection between 1983 and 1990, Child class B or C, cirrhosis, a high value of indocyanine green retention-15, a large amount of intraoperative blood loss, stage IV disease, positive surgical margin, vascular invasion, and postoperative complications. Preoperative transarterial chemoembolization increased the recurrence rate and showed no contribution to prognosis. Currently, 106 patients (27.5%) are alive: 7 (1.8%) after more than 10 years and 43 (11.1%) after more than 5 years. Mean and median overall survivals after operation were 38 months and 29 months, respectively. The 5-year and 10-year overall or disease-free survival rates after hepatic resection were 34.4% and 10.5% or 23.3% and 7.8%, respectively. CONCLUSIONS: The longterm survival rate after operation remains unsatisfactory mainly because of the high recurrence rate. Preoperative transarterial chemoembolization should be avoided because of a high risk of postoperative recurrence. Treatment strategies for recurrent HCC may play an important role in achieving better prognosis after operation, especially in patients with more than Child class B, cirrhosis, high values of indocyanine green retention-15, massive intraoperative blood loss, stage IV disease, positive surgical margin, vascular invasion, and postoperative complications.     

原发性肝细胞癌根治性切除术后肝外复发的危险因素分析

目的 探讨影响原发性肝细胞癌(hepatocelluar carcinoma,HCC)根治性切除术后肝外复发的危险因素.方法 回顾性分析行根治性切除的238例HCC患者的临床资料,确定影响术后肝外复发的危险因素.结果 本组患者随访7-78个月,随访中位时间为34个月,32例(13.4%)出现肝外复发.依据单因素分析结果,术前血清甲胎蛋白(α fetoprotein,AFP)>1000 ng/ml、天冬氨酸氨基转移酶>50 IU/L、肝静脉侵犯、周围脏器侵犯、子灶、肿瘤包膜缺失是HCC根治性切除术后肝外复发的危险因素.多因素分析显示血清AFP>1000 ng/ml、肝静脉侵犯、周围脏器侵犯是肝外复发的独立危险因素.结论 HCC根治性切除术后肝外复发与术前血清AFP>1000 ng/ml、肝静脉侵犯、周围脏器侵犯有关.对具有这些危险因素的患者术后应加强随访.