Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C.

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67 patients (36%) died during the follow-up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC.     

Adjuvant chemotherapy for prevention of recurrence of invasive hepatocellular carcinoma after orthotopic liver transplantation

Orthotopic liver transplantation (OLT) is the best treatment for nonresectable hepatocellular carcinoma (HCC), but tumor recurrence reduces long-term and medium-term survival. The effectiveness of adjuvant chemotherapy to prevent tumor recurrence has not been fully established. METHODS: Three hundred eighty-seven consecutive patients, including 43 with HCC superimposed on liver cirrhosis, underwent OLT. Twelve patients with one or more prognostic criteria for HCC recurrence were entered into a prospective prophylaxis protocol with monthly cycles of cisplatin (60 mg/m(2)) and adriamycin (30 mg/m(2)), beginning the fourth week post-OLT for a maximum of seven sessions. RESULTS: The 5-year survival of the non-HCC patients was 65.7% and that of the HCC patients was 60.46% (P = NS). Chemotherapy was reasonably well tolerated, but the 9 patients with hepatitis C- or B-associated cirrhosis showed viral and histological recurrence of the primary disease. A high proportion of patients (7 of 12) developed tumor recurrence during the first year after OLT. Six of these patients died, all but one due to HCC relapse. Five patients remain healthy and tumor free at 58 to 130 months. Post-OLT adjuvant chemotherapy does not avoid tumor recurrence and its fatal consequences but may contribute to prolonged tumor-free survival among a significant proportion of patients with high-risk HCC. However, the uncertain implications on viral recurrence and the lack of control groups do not allow post-OLT chemotherapy to be recommended outside controlled clinical trials, which are clearly warranted.     

Microvascular tumor embolism: independent prognostic factor after liver transplantation in hepatocellular carcinoma

Microscopic tumor cell dissemination may be a more important factor in the recurrence of hepatocellular carcinoma (HCC) after liver transplantation, probably because of posttransplant immunosuppression. The presence of microvascular tumor embolism was undetermined as a factor for HCC recurrence after orthotopic liver transplantation (OLT). This study evaluated whether microvascular tumor embolism affects recurrence-free survival and correlates with other clinicopathologic factors after OLT among patients with HCC. From September 1996 to June 2003, 72 OLTs for HCC were enrolled in this study. Median follow-up was 22.8 months. Among 41 patients without microvascular tumor embolism, 1-year, 2-year, and 5-year recurrence-free survival rates were all 97.6%, while these rates were 77.3%, 68.2%, and 59.7%, respectively, for 31 patients (43.1%) with microvascular tumor embolism (P = .0006). The 5-year recurrence-free survival rate showed significant differences for a pT2 tumor (P = .0073), for maximal tumor size <3 cm (P = .0328), for > or =5 cm solitary tumor (P = .0095), and for the presence of a tumor capsule (P = .0012), within the Milan criteria (P = .0376). At multivariate analysis, significant independent predictors for HCC recurrence were microvascular tumor embolism and histopathologic grade. In conclusion, microvascular tumor embolism is an independent predictor of HCC recurrence after liver transplantation. Although OLT is a safe and effective treatment for HCC within the Milan criteria, the presence of microvascular tumor embolism at pathologic examination can predict its recurrence. In these cases, the feasibility of immunosuppressive therapy or adjuvant chemotherapy must be considered to prevent tumor recurrence.     

肝癌肝移植术后个体化化疗疗效初步分析

目的　探讨肝癌肝移植术后辅助个体化化疗对预防肝癌复发、提高肝癌肝移植疗效的临床意义。方法　回顾分析 2 0 0 1年 4月～ 2 0 0 3年 1月 2 1例肝癌肝移植术后依据ATP TCA结果制定并实施个体化化疗患者的临床资料。 5 2例单纯采用肝移植治疗的肝癌患者作为对照组 ,比较两组肝癌患者的累计生存率和累计无瘤生存率。结果　个体化化疗组和未作化疗组肝移植术后 1年、2年生存率分别为 92 31%、73 85 %和 92 0 6 %、6 3 93% ,两组术后累计生存率比较差异无显著意义 ;个体化化疗组和未作化疗组患者肝移植术后 6、12、18、2 4个月的无瘤生存率分别为 90 0 0 %、80 0 0 %、80 0 0 %、6 0 0 0 %和 6 7 31%、5 1 92 %、4 0 0 3%、37 81% ,二组术后累计无瘤生存率差异有显著意义 (P <0 0 5 )。结论　肝移植术后辅助个体化化疗能显著降低肝癌肝移植术后的肿瘤复发率 ,明显延长肝移植术后的无瘤生存时间。根据ATP TCA技术指导制定的肝癌肝移植术后个体化化疗方案具有临床应用价值。     

影响原发性肝癌肝移植治疗的预后因素分析

目的分析影响肝癌肝移植术后生存率和无瘤生存率的危险因素,探讨国内肝移植治疗肝癌的选择标准。方法对67例接受同种异位原位肝移植治疗的原发性肝癌病人的基本资料和肿瘤相关资料包括术前病情分级、血清AFP水平、术前辅助治疗以及肝癌大小、数目、pTNM分期、肿瘤恶性程度分级等因素进行单因素和多因素分析。结果术后1年、2年累积生存率为77%、67%,6个月和12个月无瘤生存率为66%和58%。单因素分析显示对肝癌肝移植术后累积生存率影响有统计学意义的因素为CHILD分级(MELD积分)和肝外大血管侵犯;多因素分析影响肝癌肝移植术后无瘤生存率有统计学义的因素是肿瘤大小、大血管侵犯和肿瘤分化程度。结论影响肝癌肝移植术后生存率的因素仍是术前患者肝功能状态。对存在大血管侵犯的肝癌患者需严格控制肝移植术适应证,而无血管侵犯的患者在选择肝移植治疗时肿瘤大小指标可较米兰标准适当放宽。     

超出Milan标准肝癌肝移植患者术后预防性化疗的价值

目的 探讨超出Milan标准肝癌肝移植患者术后预防性化疗的价值.方法 回顾性分析2001年4月至2007年7月243例超出Milan标准肝癌肌移植患者的临床资料,其中预防性化疗162例,未化疗81例.结果 预防性化疗与未化疗患者术后1、3年生存率(78.5%、63.7%和56.6%、39.1%)以及无瘤生存率(76.8%、52.5%和69.3%、64.7%)比较差异无统计学意义(X2=3.084,0.444,P>0.05).Cox风险比例分析显示,对无大血管侵犯的肝癌肝移植患者,术后足否化疗不是影响生存率的独立因素;对有大血管侵犯的肝癌肝移植患者,术后是否化疗是影响生存率的独立因素.结论 对于超出Milan标准且伴有大血管侵犯的肝癌肝移植患者,术后早期预防性化疗可以延缓肿瘤复发,明显提高疗效.     

Surgical Treatment of Hepatocellular Carcinoma beyond Milan Criteria. Results of Liver Resection, Salvage Transplantation, and Primary Liver Transplantation

Background There is no clear consensus regarding the best treatment strategy for patients with advanced hepatocellular carcinoma (HCC). Methods Patients with cirrhosis and HCC beyond Milan who had undergone liver resection (LR) or primary orthotopic liver transplantation (OLT) between November 1995 and December 2005 were included in this study. Pathological tumor staging was based on the American Liver Tumor Study Group modified Tumor-Node-Metastasis classification. Results A total of 23 HCC patients were primarily treated by means of LR, 5 of whom eventually underwent salvage OLT. An additional 32 patients underwent primary OLT. The overall actuarial survival rates at 3 and 5 years were 35% after LR, and 69% and 60%, respectively, after primary OLT. Recurrence-free survival at 5 years was significantly higher after OLT (65%) than after LR (26%). Of the patients who underwent LR, 11 (48%) experienced HCC recurrence only in the liver; 6 of these 11 presented with advanced HCC recurrence, poor medical status, or short disease-free intervals and were not considered for transplantation. Salvage OLT was performed in 5 patients with early stage recurrence (45% of patients with hepatic recurrence after LR and 22% of all patients who underwent LR). At a median of 18 months after salvage OLT, all 5 patients are alive, 4 are free of disease, and 1 developed HCC recurrence 16 months after salvage OLT. Conclusion For patients with HCC beyond Milan criteria, multimodality treatment—including LR, salvage OLT, and primary OLT—results in long-term survival in half of the patients. When indicated, LR can optimize the use of scarce donor organs by leaving OLT as a reserve option for early stage HCC recurrence.     

肝移植治疗原发性肝癌103例疗效观察

目的 比较不同受体选择标准肝癌肝移植的远期疗效,分析肝痛肝移植术后肿瘤复发相关因素.方法 总结北京佑安医院2004年4月至2008年3月间的103例肝癌肝移植的临床资料,按照肿瘤的特征将其分为3组:符合米兰标准组(A组)、超出米兰标准但满足UCSF标准组(B组)和超出UCSF标准组(C组),比较3组的总体生存率及无瘤生存率,并分析影响远期预后的相关因素.结果 103例肝癌肝移植总体1、2、3年存活率分别为84.0%、70.5%和60.2%.其中A组50例,1、2、3年生存率和无瘤生存率分别为93.4%、83.8%、73.2%和97.3%、93.9%、88.7%;B组17例,1、2、3年生存率和无瘤生存率分别为93.3%、79.4%、66.2%和86.7%、79.4%、66.2%;C组36例,1、2、3年生存率和无瘤牛存率分别为67.0%、45.5%、34.1%和65.8%、50.0%、41.7%.远期生存率A组与B组比较无差异(P=0.631),A组、B组与C组比较具有统计学差异(P值分别为0.001,0.045).结论 米兰标准是肝癌肝移植最佳适应证,超出米兰标准但满足UCSF标准也可获得满意的远期疗效;肿瘤的分期和微血管侵犯是影响远期预后的风险因素.     

Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy

BACKGROUND: Surgical resection has been the treatment of choice for hepatocellular carcinoma (HCC), but the resection rate remains low in cirrhotic patients and recurrence is common. Unfavorable results compared with benign disease and the shortage of organ donors have led to a restricted indication for orthotopic liver transplantation (OLT) for HCC. STUDY DESIGN: The aim of this study was to analyze the results of our surgical approach to HCC in patients with cirrhosis. The first treatment strategy indicated in these patients was OLT. From January 1990 to May 1999, 85 patients underwent OLT and the remaining 35 had surgical resection. RESULTS: One-, 3-, and 5-year survival rates were 84%, 74%, and 60% versus 83%, 57%, and 51%, respectively, in the OLT and resection groups (p = 0.34). Hepatic tumor recurrence was much less frequent in the OLT group than in the resection group. The 1-, 3-, and 5-year disease-free survival rates were 83%, 72%, and 60% versus 70%, 44%, and 31%, respectively (p = 0.027). In the multivariate Cox regression analysis, macroscopic vascular invasion was the only factor independently associated with death or recurrence after OLT (p = 0.006). After partial liver resection, the tumors significantly associated with mortality and recurrence in the multivariate analysis were solitary or multiple tumors greater than 2cm with microscopic vascular invasion (pathologic pT3) (p = 0.01). CONCLUSIONS: Our results confirm that in cirrhotic patients, OLT may provide better outcomes than liver resection in carefully selected HCC and that longterm survival is similar to the results of OLT in cirrhotic patients without tumors.     

Hepatic Resection for Hepatocellular Carcinoma Meeting Milan Criteria in Child-Turcotte-Pugh Class A Patients With Cirrhosis

This study evaluated whether hepatic resection is a reasonable strategy as an initial treatment for hepatocellular carcinoma (HCC) meeting Milan criteria in patients with compensated cirrhosis. From the database of 435 consecutive patients with resection of HCC between July 1994 and May 2007, 213 patients were found to have Child-Turcotte-Pugh class A cirrhosis and HCC meeting Milan criteria, as shown by preoperative image studies. We examined long-term survivals and patterns of recurrence after hepatic resection among those patients. Overall survival rates at 1, 3, 5, and 10 years were 92%, 78%, 69%, and 52%, respectively, and 1-, 3-, 5-, and 10-year disease-free survival rates were 79%, 57%, 44%, and 19%, respectively. Pathological review indicated that 36/213 patients (16.9%) had another nodule and/or gross vascular invasion. Microvascular invasion, tumor size, and histological grade of cirrhosis were independent risk factors for recurrence. Sixty percent of recurrent cases met the Milan criteria. The six patients who underwent living donor salvage liver transplantation (OLT) for intrahepatic recurrence were alive without recurrence at a median of 24 (range = 8-31) months. These favorable data suggest that hepatic resection is a good option for small HCCs in patients with compensated cirrhosis; and salvage OLT may be reserved for patients with recurrences.     

肝癌肝移植术后应用亚砷酸化疗的临床效果观察

目的 探讨超出米兰标准的肝癌病人肝移植术后应用亚砷酸全身化疗对肿瘤复发的意义.方法 对23例超出米兰标准的肝癌病人肝移植术后采用亚砷酸化疗:静脉滴注10 mg/d,连续使用7 d后间隔7 d,重复4次为1疗程.以上病人接受1～4个疗程治疗.观察化疗病人的生存情况、肿瘤复发情况以及化疗副作用,并与同期16例未使用化疗的肝癌肝移植病人相比较.结果 经过3～32个月随访,共有30例病人出现肝癌复发,化疗组16例,非化疗组14例,复发部位最常见于肺部、移植肝及骨骼.化疗组与非化疗组肿瘤复发率无明显差异,出现肝癌复发的时间分别为移植术后(14.5±7.5)个月和(10.2±4.6)个月,化疗组复发时间明显延迟(P=0.026);6个月、1年生存率分别为91.3%、87.0%和93.7%、87.5%,两组间无明显差异,化疗组2年生存率明显高于非化疗组(73.9% vs 50.0%,P=0.037);6个月无瘤生存率无明显差别(87.0% vs 81.2%)、1、2年无瘤生存率化疗组明显高于非化疗组(82.6% vs 50.0%,P=0.030;65.2% vs 43.7%,P=0.023).亚砷酸使用过程中未发现严重副作用.结论 静脉使用亚砷酸化疗在超出米兰标准的肝癌肝移植病人中可以延迟肿瘤复发,改善病人长期存活情况.     

肝癌临床病理因素与肝移植术后肿瘤复发的关系

目的探讨原发性肝细胞型肝癌患者行原位肝移植后肝癌复发或转移的影响因素。方法回顾性分析31例肝细胞型肝癌患者肝移植的临床资料,探讨临床病理因素与术后肿瘤复发或转移及无瘤存活率的关系。结果31例患者术后随访时间为12~24个月,中位随访时间为15个月,6个月、12个月及18个月的无瘤存活率分别为83.87%、74.19%及59.49%。Child-Pugh分级、肿瘤的数目、病理Edmondson分级对肿瘤的复发或转移无影响;肿瘤的大小、TNM分期、有无脉管浸润、是否符合Milan标准对肿瘤的复发或转移有显著影响;肿瘤有无脉管浸润以及TNM分期对患者的无瘤存活率有显著影响。结论肿瘤的大小、TNM分期、有无脉管浸润、是否符合Milan标准均能反映肿瘤复发的风险,而肿瘤的TNM分期及肿瘤有无脉管浸润能进一步影响患者术后的无瘤存活率。     

Multifocal manifestation does not affect vascular invasion of hepatocellular carcinoma: implications for patient selection in liver transplantation

BACKGROUND AND AIMS: Liver transplantation (OLT) for hepatocellular carcinoma (HCC) improves patient survival when tumor size and number are limited according to the Milan criteria. However, the impact of tumor size vs. the number of lesions for tumor recurrence after OLT is unclear. Microvascular invasion appears to be a significant risk factor for tumor recurrence. Therefore, it was the aim of this study to investigate tumor differentiation and microvascular invasion in relation to tumor number and size and their impact on survival after transplantation. PATIENTS AND METHODS: In 97 adult HCC patients who underwent OLT between June 1985 and December 2005 the incidence of microvascular invasion, tumor differentiation, and the number and size of tumor lesions were analyzed retrospectively. Their impact on survival was studied by multivariate analysis. RESULTS: Microvascular invasion was the only independent negative predictor of survival after OLT for HCC (p = 0.025). Tumor size > 5 cm was predictive for microvascular invasion (p = 0.007). In contrast, tumor number did not affect the incidence of microvascular invasion or cumulative survival. CONCLUSION: The size of the largest HCC lesion, but not the number of tumors, determined microvascular invasion, a predictor of the outcome following OLT for HCC. Thus, the number of HCC lesions should not be applied to patient selection prior to OLT. These data support the extension of the Milan criteria for the selection of HCC patients for OLT with regard to tumor number, but not tumor size.     

Predictors of long-term outcome following liver transplantation for hepatocellular carcinoma: a single-center experience

Orthotopic liver transplantation (OLT) is increasingly being applied for cure in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC). In recipients with limited tumor burden, OLT achieves reasonable long-term outcome. This study sought to identify clinical and pathologic variables predictive of long-term disease-free survival and the presence of vascular invasion. From 1992 to 2006, 130 patients underwent OLT for cirrhosis and HCC. Malignancy was diagnosed in 107 patients prior to OLT and in 23 patients on pathologic examination of the explant. Nine clinical and pathologic variables were considered including: TNM stage, nodularity, vascular invasion, Milan criteria, incidental lesion, differentiation, tumor size, preOLT transarterial chemoembolization (TACE), and administration of sirolimus-based immunosuppression. The overall incidence of HCC recurrence was 17% with the majority (82%) being stage III. Cumulatively, tumor recurrence-free survival (RFS) is 84, 74, and 67% at 1, 3, and 5 years respectively. Independent predictors of RFS included stage III and poorly differentiated lesions (P<0.05). Furthermore, stage III tumors and those >3.5 cm in size were predictive of vascular invasion. Importantly, preOLT, TACE and postOLT sirolimus had no influence on survival. Pathologic variables including tumor stage and grade have a significant impact on outcome. Importantly, it seems that TACE and sirolimus had no beneficial effect.     

Liver transplantation for hepatocellular carcinoma

OBJECTIVE: To analyze patient and tumor characteristics that influence patient survival to select patients who would most benefit from liver transplantation. SUMMARY BACKGROUND DATA: The selection of patients with hepatocellular carcinoma (HCC) for liver transplantation remains controversial. METHODS: One hundred twelve patients with nonfibrolamellar HCC who underwent a liver transplant from 1985 to 2000 were reviewed. Survival was calculated using the Kaplan-Meier method, with differences in outcome assessed using the log-rank procedure. Multivariate analysis was then performed using a Cox regression model. RESULTS: Overall patient survival rates were 78%, 63%, and 57% at 1, 3, and 5 years, respectively. Patients infected with the hepatitis B virus had a worse 5-year survival than those who were not (43% vs. 64%), with most deaths being attributed to recurrent hepatitis B. However, patients with hepatitis B virus who underwent more recent transplants using antiviral therapy fared as well as those who were negative for the virus, showing a 5-year survival rate of 77%. Patients with vascular invasion by tumor had a worse 5-year survival than patients without vascular invasion (33% vs. 68%). Vascular invasion, tumor size greater than 5 cm, and poorly differentiated tumor grade were predictors of tumor recurrence by univariate analysis; however, only vascular invasion remained significant on multivariate analysis: the rate of tumor recurrence at 5 years was 65% in patients with vascular invasion and only 4% for patients without vascular invasion. CONCLUSIONS: For well-selected patients with HCC, liver transplantation in the current era can achieve equivalent results to transplantation for nonmalignant indications. Vascular invasion is an indicator of high risk of tumor recurrence but is difficult to detect before transplantation.     

Liver transplantation for hilar cholangiocarcinoma: Spanish experience

INTRODUCTION: Palliative treatment for nondisseminated irresectable hilar cholangiocarcinoma (HCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than that for other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for HCC and identify prognostic factors for survival. METHODS: We retrospectively reviewed 36 patients undergoing OLT for HCC over 13 years. RESULTS: The actuarial survival rate at 1, 3, and 5 years was 82%, 53%, and 30%, respectively. The main cause of death was tumor recurrence (53%). In the univariate analysis, the factors for a poor prognosis were vascular invasion (P<.001) namely 0% survival at 3 years when present versus 63% and 35% at 3 and 5 years, respectively, when it was not; and stages III to IVA (P<.05), namely 15% survival at 5 years versus 47% for stages I to II. Lymph node and perineural invasion also reduce survival. In the multivariate analysis, the factors for poor prognosis included vascular invasion (P<.01) and stages III to IVA (P<.01). CONCLUSION: OLT for nondisseminated irresectable HCC has higher survival rates at 3 and 5 years than palliative treatments, especially with initial stage tumors, which means that more information is needed to better select cholangiocarcinoma patients for transplantation.     

Liver transplantation for hepatocellular carcinoma in patients without underlying liver disease: a systematic review.

Liver resection is the treatment of choice for hepatocellular carcinoma (HCC) occurring in the absence of underlying chronic liver disease. Orthotopic liver transplantation (OLT) is reserved for patients with unresectable disease but remains controversial. The aim of this study was to review the published literature on OLT for HCC in patients without coexisting chronic liver disease. A Medline-based search identified 126 patients reported in 16 papers over the last 32 years. One third had fibrolamellar HCC (FL-HCC), and two thirds had non-FL-HCC. Recurrence data were given in 55 patients of whom 27 had tumor recurrence. Seventy-five percent of the recurrences occurred within the first 2 years after OLT, although recurrences were reported up to 72 months after OLT for FL-HCC. The 5-year survival rate was greater in patients who underwent transplantation for FL-HCC than for non-FL-HCC (39.4% and 11.2%, respectively). There was insufficient information available to determine the influence of tumor size, distribution, stage, and vascular invasion on survival, although most patients in whom tumor characteristics were specified had advanced disease. This study indicates that FL-HCC carcinoma is a more favorable indication for OLT than non-FL-HCC in patients without underlying liver disease, although more detailed prognostic information is required to improve patient selection.     

Role of adjuvant treatment in liver transplantation for advanced hepatocellular carcinoma

The results of liver transplantation for advanced hepatocellular carcinoma have been disappointing because of high recurrence rates, leading to low long-term survival; this indication remains controversial in an era of organ shortage. To continue to offer this treatment possibility, efforts were made to reduce recurrence and improve survival. The first approach is to maintain a strict selection policy excluding patients with extraheptic disease. The second approach is to test the efficacy of perioperative adjuvant therapies in patients selected for transplantation. The reasons for recurrence include: (1) undetected preoperative micrometastases, (2) intraoperative dissemination by surgical manipulation, and (3) acceleration of tumor growth by immunosuppression. Preoperative treatment, which may include systemic chemotherapy or arterial chemoembolization, seems necessary to limit tumor progression during the waiting period. Systemic chemotherapy has been tested pre-, intra-, and postoperatively. It is considered essential postoperatively and should be used as soon as possible after surgery (i.e., in the 1st postoperative week). Several teams have performed pilot studies that included rather limited numbers of patients, and the results were compared with those for historic controls. Published results show that chemoembolization creates tumor necrosis in most instances. This is efficient in limiting tumor progression but the effect on recurrence and survival is unknown. All authors who used postoperative chemotherapy reported improved survival over controls, with 50%–60% 3-year survival and up to 50% 5-year survival. However, recent results suggest that late recurrence may occur. Chemotherapy was usually well tolerated, although leukopenia, sometimes severe, was observed in most patients. The use of granulocyte colony-stimulating factor seems useful to overcome this problem. Perioperative adjuvant treatments seem to prolong survival in patients undergoing liver transplantation for advanced hepatocellular carcinoma, but delayed recurrence remains possible. Further studies are necessary; these should ideally be multicentric, prospective, and randomized. Received for publication on June 2, 1997; accepted on July 3, 1997     

Liver transplantation for patients with hepatocellular carcinoma

BACKGROUND: Liver transplantation (LT) has been advocated as a salvage treatment for unresectable hepatocellular carcinoma (HCC). Selection criteria still need to be developed in Taiwan. OBJECTIVES: The purpose of our study was to assess the clinical findings and outcome of cirrhotic patients with HCC undergoing liver transplantation. METHODS: Our study consisted of 13 HCC patients who underwent liver transplantation during October 1996 to March 2003. The medical records and pathologic reports were analyzed retrospectively. RESULTS: Overall survival rates at 1 and 3 years were 86% and 61%, respectively. HCC recurrences occurred in three patients, one of whom is still alive with HCC recurrence 2 years after LT. The other two patients died of HCC recurrence 1 and 2 years after LT, respectively. Pretransplant alpha-fetoprotein (AFP) levels of >200 ng/mL were noted in all three patients with HCC recurrence. In contrast, only one of the ten patients without HCC recurrence had pretransplant AFP >200 ng/mL (P = .003). Four patients did not meet Milan criteria, two of whom had HCC recurrence. However, the other two patients with microscopic vascular invasion survived and were free of HCC. The only one patient, who had histologic grade 4 HCC, died of recurrence, although his tumor was AJCC stage 1. CONCLUSIONS: High AFP level is a risk factor for HCC recurrence after LT. In addition to Milan criteria, histologic tumor grading should be considered in patient selection. Microscopic vascular invasion may not affect the outcome of the patients with early HCC.     

First-line liver resection and salvage liver transplantation are increasing therapeutic strategies for patients with hepatocellular carcinoma and child a cirrhosis

AIM: The present study focused on nine patients with hepatocellular carcinoma (HCC) associated with Child A liver cirrhosis undergoing first-line liver resection and salvage liver transplantation (SLT) for liver tumor recurrence. PATIENTS AND METHODS: Forty-six patients with HCC underwent liver transplantation (OLT); 37 (80.5%) were primary liver transplantations (PLTs) and 9 (19.5%) were SLTs. All patients who underwent SLT received minor transabdominal liver resections. RESULTS: The posttransplant 1-, 3-, and 5-year overall survival rates for SLT (88.9%, 88.9%, and 88.9%) were similar to those for PLT (78%, 62.7%, and 62.7%). Four (10.8%) patients in the PLT group had HCC recurrence, while there was zero recurrence in the SLT group. The 1-, 3-, 5-year disease-free survival rates for PLT (89%, 74%, and 74%) were similar to those for SLT (100%, 100%, and 100%). The 1-, 3-, 5-year disease-free survival rates after PLT were 89%, 74%, and 74%, and after SLT were 100%, 100%, and 100%, respectively. The operative mortality, intraperioperative bleeding, operative time, intensive care unit stay, in-hospital stay, and overall incidence of postoperative complications were similar in the two groups. CONCLUSIONS: In our experience, SLT for HCC is a feasible procedure with similar results in terms of overall survival, disease-free survival, and postoperative complications to those reported for patients who underwent PLT at our institute. An important role exists for SLT as shown by the fact that such a strategy has been used in the 20% of the patients undergoing OLT for HCC.