Can the Dropout Risk of Candidates with Hepatocellular Carcinoma Predict Survival after Liver Transplantation?

In the last US national conference on liver transplantation for hepatocellular carcinoma (HCC), a continuous priority score, that incorporates model for end‐stage liver disease (MELD), alpha‐fetoprotein and tumor size, was recommended to ensure a more equitable liver allocation. However, prioritizing highest alpha‐fetoprotein levels or largest tumors may select lesions at a higher risk for recurrence; similarly, patients with higher degree of liver failure could have lower postoperative survival. Data from 300 adult HCC recipients were reviewed and the proposed HCC‐MELD equation was applied to verify if it can predict post‐transplantation survival. The 5‐year survival and recurrence rates after transplantation were 72.8 and 13.5%, respectively. Cox regression analysis confirmed HCC‐MELD as predictive of both postoperative survival and recurrence (p < 0.001). The 5‐year predicted survival and recurrence rates were plotted against the HCC‐MELD‐based dropout probability: the higher the dropout probability while on waiting list, the lower the predicted survival after transplantation, that is worsened by hepatitis C positivity; similarly, the higher the predicted HCC recurrence rate after transplantation. The HCC priority score could predict the postoperative survival of HCC recipients and could be useful in selecting patients with greater possibilities of survival, resulting in higher post‐transplantation survival rates of HCC populations.     

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。     

Liver transplantation for unresectable hepatocellular carcinoma in patients without liver cirrhosis

Summary Hepatocellular carcinoma (HCC) arising in noncirrhotic and nonfibrotic liver (NC‐HCC) is a rare type of malignancy frequently found in healthy young individuals. Partial liver resection is the treatment of choice with expected 5‐year survival rates between 40% and 70%. As a result of absence of any symptom, a considerable number of patients are diagnosed when the malignancy has progressed to an advanced stage and the tumor has turned already unresectable. Some other patients suffer from intrahepatic recurrence after previous liver resection that cannot be re‐resected or locally ablated. In these situations, liver transplantation (LT) may be the only potentially curative treatment. The indication for LT in NC‐HCC patients, however, is not well established. The preliminary results of recent analysis of the European Liver Transplant Registry (ELTR) together with a literature review identified over 150 patients transplanted for NC‐HCC during the last 15 years. In contrast to the historical data, these studies showed 5‐year survival rates at 50–70% in well‐selected patients. Important determinants of poor outcome are macrovascular invasion, lymph node involvement, and time interval of <12 months when LT is used as rescue therapy for intrahepatic recurrence after a previous partial liver resection. Interestingly, outcomes after both liver resection and LT for NC‐HCC are much less influenced by tumor size than is the case with cirrhotic HCC. A large tumor size per se should, therefore, not to be seen as a strict contraindication for performing LT in patients with NC‐HCC.     

Partial necrosis on hepatocellular carcinoma nodules facilitates tumor recurrence after liver transplantation

BACKGROUND: The presence of partial necrosis in hepatocellular carcinoma (HCC) nodules is a common histologic finding after liver transplantation, but its correlation with tumor recurrence has never been investigated. METHODS: we retrospectively reviewed the outcome of 54 patients with a single histologically proven HCC after liver transplantation. All cases had a survival of more than 6 months, and patients treated preoperatively had a transarterial chemoembolization (TACE) procedure. Since 1996, our center has applied the Milan criteria. Correlations between tumor recurrences and clinicopathologic variables, including the presence of partial necrosis, were performed. Etiologic factors for HCC partial necrosis were also investigated. RESULTS: Sixteen of 54 (29.6%) HCC nodules presented partial necrosis, and 4 (25%) of them developed HCC recurrence compared with 1 of 38 (2.6%) cases without this histologic finding (P<0.05). Partial necrosis was related to TACE procedure (P<0.05), patient age less than 50 years (P<0.05), and tumor diameter greater than 2 cm (P<0.05). Multivariate analysis showed only TACE as an independent variable. The other variables related to the five (9.3%) tumor recurrences were HCC diameter greater than 2 cm (P<0.05), year of liver transplantation before 1996 (P<0.05), and the presence of satellite nodules (P<0.05). The Cox regression analysis showed the presence of partial necrosis as an independent variable related to tumor recurrence. The analysis of the recurrence-free survival confirmed the results of the recurrence rate. CONCLUSION: Partial necrosis was a risk factor for tumor recurrence after liver transplantation. Patients and procedures should be selected while also bearing in mind the side-effect of incomplete necrosis of the nodules.     

Outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is considered an optimal indication for liver transplantation (LT) because it may eliminate both the tumor and the underlying liver disease. The present study sought to compare cumulative survival, rate of HCC recurrence, and causes of death among patients with cirrhosis and HCC before and after the adoption of more restrictive criteria (Milan selection criteria) at the time of patient listing. Among 226 adult patients who received an elective liver transplantation between 1999 and 2005, 58 (27%) had a diagnosis of HCC at the time. The 38 patients who underwent transplantation for HCC in the period 1989 to 1998 were considered the "historical group." After LT (mean follow-up, 34 + 28 months), the cumulative survival rate was better among HCC versus non-HCC recipients (93% vs 71% at 1 year and 81% vs 67% at 3 years, respectively; P < .046), although the difference tended to attenuate after 5 years (66% vs 67%, respectively). Tumor recurrence (evaluated in patients surviving at least 3 months after LT) was observed in 10/31 in the historical group versus 4/53 among those who underwent transplantation after 1999. Among the causes of death, recurrence represented 50% in the old series and 23% in patients who underwent transplantation after 1999. Cumulative survival significantly improved among HCC patients who underwent transplantation after 1999 (93% vs 66% at 1 year and 81% vs 50% at 3 years; P < .00001). The 58 patients who underwent transplantation with a diagnosis of cirrhosis and concomitant HCC after 1999 showed even better survival than patients who underwent transplantation for end-stage liver disease without malignancy.     

Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation

OBJECTIVE: To evaluate the survival results and pattern of recurrence after resection of potentially transplantable small hepatocellular carcinomas (HCC) in patients with preserved liver function, with special reference to the implications for a strategy of salvage transplantation. SUMMARY BACKGROUND DATA: Primary resection followed by transplantation for recurrence or deterioration of liver function has been recently suggested as a rational strategy for patients with HCC 5 cm or smaller and preserved liver function. However, there are no published data on transplantability after HCC recurrence or long-term deterioration of liver function after resection of small HCC in Child-Pugh class A patients. Such data are critical in determining the feasibility of salvage transplantation. METHODS: From a prospective database of 473 patients with resection of HCC between 1989 and 1999, 135 patients age 65 years or younger had Child-Pugh class A chronic liver disease (chronic hepatitis or cirrhosis) and transplantable small HCC (solitary < or =5 cm or two or three tumors < or = 3 cm). Survival results were analyzed and the pattern of recurrence was examined for eligibility for salvage transplantation based on the same criteria as those of primary transplantation for HCC. RESULTS: Overall survival rates at 1, 3, 5, and 10 years were 90%, 76%, 70%, and 35%, respectively, and the corresponding disease-free survival rates were 74%, 50%, 36%, and 22%. Cirrhosis and oligonodular tumors were predictive of worse disease-free survival. Patients with concomitant oligonodular tumors and cirrhosis had a 5-year overall survival rate of 48% and a disease-free survival rate of 0%, which were significantly worse compared with other subgroups. At a median follow-up of 48 months, 67 patients had recurrence and 53 (79%) of them were considered eligible for salvage transplantation. Decompensation from Child-Pugh class A to B or C without recurrence occurred in only six patients. CONCLUSIONS: For Child-Pugh class A patients with small HCC, hepatic resection is a reasonable first-line treatment associated with a favorable 5-year overall survival rate. A considerable proportion of patients may survive without recurrence for 5 or even 10 years; among those with recurrence, the majority may be eligible for salvage transplantation. These data suggest that primary resection and salvage transplantation may be a feasible and rational strategy for patients with small HCC and preserved liver function. Primary transplantation may be a preferable option for the subset of patients with oligonodular tumors in cirrhotic liver in view of the poor survival results after resection.     

Antiviral therapy for recurrent hepatitis C reduces recurrence of hepatocellular carcinoma following liver transplantation

Recurrence of hepatocellular carcinoma (HCC) is one of the major concerns following liver transplantation (LT). With the potential antitumor properties of interferon (IFN), their role in prevention of HCC recurrence is to be defined. We retrospectively reviewed 46 patients who underwent LT for hepatitis C virus (HCV)‐related HCC between January 2004 and December 2008. Twenty‐four (52.2%) patients with biopsy‐proven HCV recurrence received antiviral therapy (IFN group); their outcomes were compared with 22 patients (control group). There was no significant difference for tumor size, number, and type of neo‐adjuvant therapy between the two groups. The 1‐ and 3‐year overall patient survival (100% vs. 90.9% and 87.3% vs. 71.8%; P = 0.150) and tumor‐free survival (100% vs. 72.7% and 83.1% vs. 67.5%; P = 0.214) between IFN and control group were comparable. HCC recurrence was the most common cause of death (n = 6 of 12, 50%), all in the control group. During follow‐up, seven (15.2%) patients developed HCC recurrence: one (4.1%) in the IFN group and six (27.3%) in the control group (P < 0.05). In conclusions, HCC recurrence rate and related deaths were significantly lower in patients that received post‐transplant antiviral therapy for recurrent HCV.     

Clinical analysis of recurrent hepatocellular carcinoma after living donor liver transplantation

This study aimed to analyze the clinical outcomes and factors influencing the outcome in the recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT). Between October, 1997 and September, 2010, 25 (16.0%) of 156 patients who had undergone LDLT for HCC experienced recurrence. All patients with recurrence, with a single exception, were in the high‐risk group. Among patients with recurrence, 76.0% of patients experienced recurrence within one yr after LDLT. One‐ and five‐yr survival rates of recurred patients were 56.0% and 8.6%, respectively. Among them, 32% of patients were treated with curative‐intent treatment, and their one‐ and five‐yr survival rates were 62.5% and 25.0%, respectively. Beyond the Milan criteria at liver transplantation (LT) (p = 0.032), multiple recurrence (p = 0.001), and palliative treatment for recurrent tumors (p = 0.049) were related to poor survival after recurrence. Additionally, the independent prognostic factors included multiple recurrence (p = 0.005) and the Milan criteria at LT (p = 0.047). Because almost all recurrent cases belonged to the high‐risk group and recurred within two yr, the high‐risk group should undergo close follow‐up for early detection and be treated with liver‐directed therapies. Although the prognosis of recurrent HCC after LDLT is poor, long‐term survival can be expected on a single recurrence and curative treatment.     

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。     

肝癌切除术后复发的补救性肝移植

目的 评估肝癌患者肝癌切除术后肝癌复发行补救性肝移植术的临床治疗效果及预后影响因素.方法 回顾性分析本治疗组自2000年4月至2008年6月间实施的88例肝癌切除术后复发行补救性肝移植术病例,分析该组病例手术特征、生存状况、病理因素对预后影响.结果 肝癌切除术后复发行补救性肝移植病例平均年龄为52.4±9.2岁(26....     

Pre‐transplant therapy for hepatocellular carcinoma is associated with a lower recurrence after liver transplantation

Abstract: Background: Hepatic transplantation has been advocated as an effective treatment for hepatocellular carcinoma (HCC). We seek to determine if pre‐transplant therapies can reduce post‐transplant recurrence. Methods: We conducted a retrospective review of prospective data in patients undergoing transplantation for HCC 2001–2006. Patients were followed for recurrence every six months with abdominal computerized tomography or magnetic resonance imaging. Logistic regression analyzed recipient factors such as prior treatment for HCC, donor, operative, and tumor factors in comparing patients developing HCC recurrence with those without recurrence. Results: During the study period, we performed 124 hepatic transplants for HCC [age: 55 ± 7.6 yr; 104 (85%) male, 81 (66%) white, and 32 (26%) Asian]. Recurrence was found in nine at a mean of 2.6 yr follow‐up. Thirty‐three patients (27%) had pre‐transplant treatment (radiofrequency ablation, transarterial chemoembolization or percutaneous ethanol injection). Univariable logistic regression identified nine factors [body mass index, Asian race, hepatitis B, prior HCC therapy, alpha‐fetoprotein (AFP), model for end‐stage liver disease (MELD) score, bilirubin, and international normalized ratio] predictive of HCC recurrence at a level of p < 0.1. Multiple logistic regression analysis of six of the nine selected factors demonstrated AFP level >1000, calculated pre‐transplant MELD score <14, and the lack of any pre‐transplant treatment were significantly associated with recurrence of HCC. No patient with prior HCC therapy had recurrence. Conclusions: In patients with HCC awaiting hepatic transplantation, there is a reduced rate of recurrence of HCC if tumors are pre‐treated with liver‐directed therapy. By treating HCC tumors with any type of treatment prior to transplant, we can significantly reduce the odds of HCC recurrence after transplant.     

Expanded living‐donor liver transplantation criteria for patients with hepatocellular carcinoma based on the Japanese nationwide survey: the 5‐5‐500 rule ‐ a retrospective study

Expansion of the liver transplantation indication criteria for patients with hepatocellular carcinoma (HCC) has long been debated. Here we propose new, expanded living‐donor liver transplantation (LDLT) criteria for HCC patients based on a retrospective data analysis of the Japanese nationwide survey. A total of 965 HCC patients undergoing LDLT were included, 301 (31%) of whom were beyond the Milan criteria. Here, we applied the Greenwood formula to investigate new criteria enabling the maximal enrollment of candidates while securing a 5‐year recurrence rate (95% upper confidence limit) below 10% by examining various combinations of tumor numbers and serum alpha‐fetoprotein values, and maintaining the maximal nodule diameter at 5 cm. Finally, new expanded criteria for LDLT candidates with HCC, the 5‐5‐500 rule (nodule size ≤5 cm in diameter, nodule number ≤5, and alfa‐fetoprotein value ≤500 ng/ml), were established as a new regulation with a 95% confidence interval of a 5‐year recurrence rate of 7.3% (5.2–9.3) and a 19% increase in the number of eligible patients. In addition, the 5‐5‐500 rule could identify patients at high risk of recurrence, among those within and beyond the Milan criteria. In conclusion, the new criteria – the 5‐5‐500 rule – might provide rational expansion for LDLT candidates with HCC.     

肝细胞癌肝移植术后复发和转移的研究:单中心经验

目的 研究肝细胞癌肝移植术后复发和转移的临床特点及治疗方法.方法 回顾分析2003年1月至2005年11月收治的95例肝细胞癌肝移植术后肝癌复发转移病例的临床资料.结果 在随访期内,42例(43.2%)患者被诊断为肝癌复发.复发部位最多见于移植肝(32例)、肺(21例)、骨(7例).单因素分析结果显示,肿瘤大小、肿瘤分布、肝硬化背景、术前甲胎蛋白浓度、组织学分期、大血管侵犯6项因素对肝移植术后生存和(或)肝癌复发有明显影响.多因素分析结果显示,肿瘤分布、组织学分期、大血管侵犯是影响术后总体生存率和肝癌复发率的独立危险因素.肝癌复发后的介入治疗及内放疗可延缓肿瘤进展,选择合适病例行复发灶手术切除可最大限度地改善预后.结论 合理选择接受肝移植的肝癌患者可能可以大幅度降低移植术后肝癌的复发率.在现阶段,外科治疗应是目前移植术后复发性肝癌的首选治疗手段.     

Impact of neoadjuvant transarterial chemoembolization on tumor recurrence and patient survival after liver transplantation for hepatocellular carcinoma: a retrospective analysis

Transarterial chemoembolization (TACE) has gained wide acceptance as a bridge to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Aim of this analysis was to compare long‐term results with and without neoadjuvant TACE and to identify subgroups, which particularly benefit from TACE. Patients with HCC transplanted at our center were retrospectively analyzed. The following were excluded to increase consistency: incidental‐HCC, Child‐C, living‐related‐LT, other HCC‐specific‐treatment. Of 336 patients, 177 were subject of this analysis, 71 received TACE and 106 no HCC therapy. Patients with and without TACE showed similar five‐yr survival (73/67%) and recurrence rates (23/29%). Progression on the waiting list was associated with a higher recurrence rate in the TACE (50 vs.12%) and the non‐TACE group (40 vs. 22%). HCC recurrence was reduced in patients inside Milan (0.053) and UCSF (0.037) criteria by neoadjuvant TACE but not outside UCSF (0.99). Also a trend towards an improved survival was seen within these criteria. Our large single center experience suggests that TACE lowers the HCC recurrence rate in patients inside the Milan and UCSF criteria. Moreover, the response to TACE is a good indicator of low recurrence rates. The effect of TACE might be more pronounced in patients with longer waiting time than in this cohort (mean, 4.6 months).     

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.     

肝癌肝移植生存情况及预后影响因素分析（附109例报告）

目的了解原发性肝细胞癌（肝癌）患者肝移植术后的生存情况,探讨影响其预后的危险因素。方法回顾性分析2004年1月至2007年12月中山大学附属第三医院肝移植中心的109例肝癌肝移植病例的临床资料。应用Kaplan-Meier法计算累积生存率和无瘤生存率,采用Log-rank检验和Cox回归模型分别进行无瘤生存率单因素、多因素分析。结果 109例肝癌肝移植患者中,37例肿瘤复发,占总数的33.9%,复发时间2～25（中位时间8）个月。全部病例1年、3年、5年累积生存率分别为86.9%、66.1%、56.6%,而1年、3年、5年无瘤生存率分别为78.3%、64.7%、53.1%。单因素分析显示,影响肝癌肝移植术后无瘤生存率的危险因素有肿瘤大小、肿瘤侵犯血管及病理分化程度。Cox风险回归模型多因素分析发现,肿瘤侵犯血管及病理分化程度是影响肝癌肝移植患者术后无瘤生存率的独立危险因素（均为P〈0.05）。结论影响肝癌肝移植患者术后无瘤生存率的独立危险因素是术前肿瘤侵犯血管和术后病理肿瘤分化程度,应严格筛选肝癌肝移植的适应证可有效降低术后肿瘤的复发率。     

Liver Resection for Hepatocellular Carcinoma in a Hepatitis B Endemic Area

Background Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Treatment options include liver resection, tumor ablation, and liver transplantation. Methods We report the results of all patients undergoing partial hepatectomy for HCC with curative intent from a center where all major treatment modalities were available. Results A series of 53 patients were identified, of whom 72% had underlying liver disease, mostly chronic hepatitis B infection. Altogether, 57% of patients underwent major resections, of whom 43% had histologically proven cirrhosis. Postoperative morbidity and mortality occurred in 41.5% and 7.5%, respectively. After a median follow-up of 34 months, the survival probabilities at 1, 3, and 5 years were 74.1%, 54.1%, and 42.6%, respectively. A total of 47% developed recurrent disease over the study period with a median disease-free survival of 13.8 months. The probabilities of recurrence at 1, 3, and 5 years were 35.2%, 49.4%, and 55.9%, respectively. Among those who developed recurrence, 76% died, with a median time to death from the time the recurrence was diagnosed of 7.8 months. There was a good association between the CLIP score and survival following liver resection. Multivariate analysis showed that only tumor recurrence and the presence of cirrhosis was a significant determinant of the risk of tumor-related death. Conclusion These findings confirm that with careful patient selection liver resection for HCC can achieve good long-term patient survival and acceptable risks.     

Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma

The proportion of liver transplantation (LT) for hepatocellular carcinoma (HCC) has kept on increasing over the past years and account for 20%-40% of all LT. Post-transplant HCC recurrence is considered the most important factor affecting the long-term survival of patients. The use of different types of immunosuppressive agents after LT is closely associated with an increased risk for HCC recurrence. The most commonly used conventional immunosuppressive drugs include the calcineurin inhibitors tacrolimus (FK506) and mammalian target of rapamycin inhibitor rapamycin (RAPA). Compared with tacrolimus, RAPA may carry an advantage in survival benefit because of its anti-tumor effects. However, no sufficient evidence to date has proven that RAPA could increase long-term recurrence-free survival and its anti-tumor mechanism of combined therapy remains incompletely clear. In this review, we will focus on recent advances in clinical application experience and basic research results of RAPA in patients undergoing LT for HCC to further guide the clinical practice.     

Liver transplantation for primary and metastatic liver cancers

Liver transplantation for hepatic malignancies has emerged as a well‐documented and proven treatment modality. However, early unsatisfactory results emphasized that only a highly selected patient population would benefit from transplantation. Currently, 15% of all liver transplants performed are for hepatocellular carcinoma (HCC). There is no controversy about the fact that liver transplantation for HCC in the adult population yields good results for patients whose tumour masses do not exceed the Milan criteria. It remains to be determined whether patients with more extensive tumours can be reliably selected to benefit from the procedure. In patients with small HCC at an early stage and preserved liver function, liver resection provides an alternative to transplant. Liver resection may offer similar survival results to orthotopic liver transplantation (OLT) in the short term, and does not carry the long‐term effects of immunosuppression; however, long‐term and disease‐free survival favours liver transplantation. Very promising results have been obtained for cholangiocarcinoma treated by aggressive combination therapies, including chemo‐ and radiotherapy followed by OLT. Survival rate in these selected patients can approach that of patients with cholestatic liver disease, and the role of transplantation now requires re‐evaluation. Similarly, hepatoblastoma is an excellent indication in paediatric patients with unresectable or recurrent tumours. Epithelioid hemangioendothelioma is also an appropriate indication for liver transplantation, even in the presence of extrahepatic metastases, unlike angiosarcoma which is associated with a very poor survival and considered as a contraindication. And finally for metastatic liver disease from neuroendocrine tumours, liver transplantation can result in long‐term survival and even cure in well selected patients. Conversely, the value of transplantation for colorectal liver metastases (currently a contraindication) requires further evaluation by well‐designed trials.