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.     

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.     

Sirolimus-Based Immunosuppression Therapy in Liver Transplantation for Patients With Hepatocellular Carcinoma Exceeding the Milan Criteria

Aim

Sirolimus (SRL) acts as a primary immunosuppressant or antitumor agent. The aim of the present study was to evaluate the influence of SRL on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) exceeding the Milan criteria.

Materials and Methods

We retrospectively examined 73 consecutive patients who underwent OLT for HCC exceeding the Milan criteria from March 2004 through December 2005. Among them, 27 patients were treated with SRL-based immunosuppressive protocols after OLT, and 46 patients by an FK506-based protocol. Statistical analysis was based on the intent-to-treat method.

Results

The 2 groups were comparable in all clinicopathologic parameters. The mean overall survival was 594 ± 35 days in the SRL group and 480 ± 42 days in the FK506 group (P = .011); the mean disease-free survival period was 519 ± 43 days in the SRL group and 477 ± 48 days in the FK506 group (P = .234). Multivariate analysis revealed Child's status (P = .004) and immunosuppressive protocol (P = .015) were the significant factors affecting overall survival. Only microvascular invasion (P = .004) was significantly associated with disease-free survival. Among 24 surviving patient in the SRL group, 2 patients had SRL discontinued for toxicity; 10 had SRL monotherapy immunosuppression.

Conclusion

The SRL-based immunosuppressive protocol improved the overall survival of patients after OLT for HCC exceeding the Milan criteria, probably by postponing recurrence and with better tolerability.     

Treatment of Hepatocellular Carcinoma With Liver Transplantation: A Single-Center Experience From Brazil

Introduction

Orthotopic liver transplantation (OLT) is the treatment of choice of hepatocellular carcinoma (HCC) for patients with cirrhosis, mainly those with early HCC. Herein we have present the clinical characteristics and outcomes of cirrhotic patients with HCC who underwent OLT from cadaveric donors in our institution.

Methods

From May 2001 to May 2009, we performed 121 OLT including 24 patients (19.8%) with cirrhosis and HCC within the Milan criteria. In 4 cases, HCC was an incidental finding in the explants.

Results

The patients' average age was 55 ± 10 years, including 82% men. Fifty percent of patients were Child class B or C. The average Model for End Stage Liver Disease for Child A, B, and C categories were 11, 15, and 18, respectively. The HCC diagnosis was made by 2 dynamic images in 16 cases; 1 dynamic image plus alphafetoprotein >400 ng/mL in 4; and 4 by histologic confirmation. Twenty patients received a locoregional treatment before OLT: 6 percutaneous ethanol injection, 9 transarterial chemoembolization, 1 transarterial embolization, and 4 a combination of these modalities. The median follow-up after OLT was 19.7 months (range, 1-51). A vascular invasion was observed in the explant of 1 patient, who developed an HCC recurrence and succumbed at 8 months after OLT. Two further patients, without vascular invasion or satellite tumor displayed tumor recurrences at 7 and 3 months after OLT, and death at 2 and 1 month after the diagnosis. The remaining 25 patients have not shown a tumor recurrence.

Conclusion

In the present evaluation, OLT patients with early HCC and no vascular invasion showed satisfactory results and good disease-free survival. Strictly following the Milan criteria for liver transplantation in patients with HCC greatly reduces but does not completely avoid, the chances of tumor recurrence.     

肝癌肝移植术后雷帕霉素与普乐可复为主免疫抑制治疗结果初探

目的 探讨肝癌肝移植手术后使用雷帕霉素(rapamycin,RPM)与普乐可复为主的免疫抑制治疗是否有助于防止肝癌的复发与转移.方法 2004年1月至2005年1月期间19例肝癌行肝移植病人(米兰标准6例,扩大米兰标准13例)随机选取其中10位病人作为治疗组(米兰标准2例,扩大米兰标准8例)手术后使用雷帕霉素与普乐可复为主免疫抑制治疗,9例(米兰标准1例,扩大米兰标准8例),采用普乐可复为主的肝癌肝移植病人作为对照组,比较两组肝癌病人的累计生存率和累计无瘤生存率,并长期随访了解其复发转移情况.结果 肝癌病人肝移植术后生存时间及复发转移情况:至该文报告时,治疗组无死亡病例,仍存活1O例,其中无瘤生存9例,带瘤生存1例;对照组死亡1例,仍存活8例,其中无瘤生存5例,带瘤生存3例.两组经检验差异有显著性.结论 雷帕霉素可能有助于预防肝癌肝脏移植术后的转移与复发.     

挽救性肝移植治疗肝癌切除术后肿瘤复发

目的 分析挽救性肝移植治疗肝癌切除术后肿瘤复发患者的疗效.方法 2004年1月至2008年12月,单中心376例肝癌患者接受了肝移植,其中36例(9.6 %)为行根治性肿瘤切除术后因肿瘤肝内复发而接受挽救性肝移植者(挽救性肝移植组).挽救性肝移植组中男性29例,女性7例;16例接受右半肝切除,10例接受左半肝切除,其余10例接受不规则肝切除或肝段切除.首次肝切除至行挽救性肝移植的时间为(34.9±16.2)个月(1～63个月).以同期符合米兰标准并接受首次肝移植的147例作为对照组,比较两组受者的术中情况及术后生存情况、肿瘤复发情况等.结果 挽救性移植组术中出血量和输血量明显多于对照组(P＜0.05),手术时间也长于对照组(P＜0.05).随访期间,挽救性肝移植组死亡11例,其中围手术期死亡1例;对照组共死亡36例,其中围手术期死亡3例.两组手术后并发症、肿瘤复发率、受者存活率以及无瘤存活率的差异无统计学意义(P＞0.05).结论 挽救性肝移植虽然较首次肝移植手术难度增加,但不影响患者预后,是根治性肝癌切除术后肿瘤复发患者的有效治疗手段.

Abstract：

Objective To summarize the experience with salvage liver transplantation for patients with recurrent hetaptocellular carcinoma(HCC)after primary liver resection.Methods From 2004 to 2008,376 patients with HCC received liver transplantation in our single center.Among these patients,36 (9.6 %)underwent salvage liver transplantation after primary liver curative resection due to intrahepatic recurrence.There were 29 males and 7 females with the mean age of 46 years old.Sixteen received right lobectomy,10 received left lobectomy and the others received sectionectomy or segmentectomy.As a control group for comparison,we used clinical data of the 147 patients who underwent primary OLT for HCC within Milan Criteria.Results The mean interval between initial liver resection and salvage transplantation was 34.9±16.2 months(1-63 months).Intraoperative bleeding volume,transfusion volume and operative time in the salvage group were significantly different from those in control group (P<0.05).There were no significant difference in post-operative complications,tumor recurrence rate,survival rate and tumor-free survival between these two groups(P>0.05).Conclusion In comparison with primary OLT,although salvage liver transplantation would increase the operation difficulties,it still remains a good option for patients with HCC recurrence after curative resection.     

Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma

BackgroundScarce data are available comparing outcomes of hepatic resection vs orthotopic liver transplantation (OLT) for localized hepatocellular carcinoma (HCC) patients both meeting and exceeding the Milan criteria. This study compared the clinical and oncological outcomes of patients undergoing hepatic resection vs transplantation localized HCC.MethodBetween January 2005 and February 2017, clinical and oncological outcomes of patients who underwent liver resection (n = 38) vs OLT (n = 28) for localized HCC were compared using a prospectively maintained database.ResultsA total of 66 patients (with a median age of 62) who met the study criteria were analyzed. Comparable postoperative complications (13.2% vs 28.6%, P = .45) and perioperative mortality rates (7.9% vs 10.7%, P = .2) were noted for the resection vs OLT groups. While Child-Pugh Class A patients were more prevalent in the resection group (78.9% vs 7.1%, P = .0001), the rate of patients who met the Milan criteria was higher in the OLT group (89.3% vs 34.25, P = .0001). Recurrence rates were 36.8% in the resection group and 3.6% in the OLT group at the end of the median follow-up period (32 vs 39 months, respectively). The HCC-related mortality rate was significantly higher in the resection group (39.5% vs 10.7%, P = .034).However, a subgroup analysis of patients who met the Milan criteria revealed similar rates of recurrence and HCC-related mortality (15.4% vs 8%, P = .63). Based on logistic regression analysis, number of tumors (P = .034, odds ratio: 2.1) and “resection”-type surgery (P = .008, odds ratio: 20.2) were independently associated with recurrence.ConclusionCompared to liver transplantation, hepatic resection for localized hepatocellular carcinoma is associated with a higher rate of recurrence and disease-related mortality.     

Adjuvant treatment of hepatocellular carcinoma after orthotopic liver transplantation: do we really need this?

Hepatocellular carcinoma (HCC) continues to rise and is still a major cause of mortality. Orthotopic liver transplantation (OLT) continues to give patients the best chance for cure, but recurrence of the disease remains a problem. Even with the implementation of the Milan criteria, recurrence rates have been shown to be 8–15% in most studies and even higher in patients who are beyond the Milan criteria. Therefore, several investigators have looked into the value of adjuvant therapy using systemic cytotoxic chemotherapy in HCC after OLT. Unfortunately, most of the trials are very small, and the results have been disappointing. But trials using Licartin seem to be promising, and other drugs such as FOLFOX and sorafenib warrant further investigation based on their efficacy in the advanced disease. In this review, we will review the current data on efficacy and rationale of adjuvant treatment for HCC after OLT including novel biomarkers.     

Influence of coexisting cirrhosis on outcomes after partial hepatic resection for hepatocellular carcinoma fulfilling the Milan criteria: an analysis of 293 patients

BACKGROUND: For patients with liver cirrhosis and hepatocellular carcinoma (HCC) satisfying the Milan criteria (single tumor < or =5 cm or 2 or 3 tumors < or =3 cm), orthotopic liver transplantation (OLT) is an effective treatment. Nevertheless, it remains controversial whether OLT is the best treatment strategy for patients with resectable HCC. METHODS: This study included 293 HCC patients (both with and without cirrhosis) oncologically satisfying the Milan criteria who underwent primary and curative liver resection between 1990 and 2003. RESULTS: There were 127 noncirrhotic, 129 Child-Pugh A cirrhotic, and 37 Child-Pugh B cirrhotic patients. Five-year survival rates in each population were 81%, 54%, and 28%, respectively. Coexisting cirrhosis, Child-Pugh classification, alpha-fetoprotein value, tumor burden, and vascular invasion by the tumor were identified as significant prognostic factors. Among these factors, coexisting cirrhosis was the most crucial variable by multivariate analysis. During the initial 3 postoperative years, yearly tumor recurrence rate was 22% in cirrhotic patients and 15% in noncirrhotic patients. In cirrhotic patients, the recurrence rate did not decrease even after three years of tumor-free survival post-resection, whereas in noncirrhotic patients the recurrence rate decreased to 9%. Cirrhosis was associated with a higher probability of recurrence exceeding the Milan criteria. CONCLUSIONS: Hepatic resection offers an acceptable survival result for HCC patients fulfilling the Milan criteria. Coexisting cirrhosis is associated with higher mortality and recurrence rate, possibly due to multicentric carcinogenesis which limits the efficacy of hepatic resection.     

Predictive factors of outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma

Studies to define the optimal upper limits of tumor size and number as predictors of outcome after orthotopic liver transplantation (OLT) have yielded conflicting results. We analyzed 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 12-year period in a single center. Predictive factors for survival and tumor recurrence, according to the Milan criteria, were also examined. Our cohort included 60 men and 12 women of mean age 54 +/- 8 years and mean follow-up of 40 +/- 39 months. Origin of cirrhosis was postviral in 70% and Child class B or C in two thirds of patients. HCC was multifocal in 61%; about one fifth of patients had micro- or macrovascular involvement or positive nodes upon histologic examination. The cumulative size of the lesions was <3 cm in 17 patients; >3 to < or =5 cm in 28 patients; >5 to < or =8 cm in 14 patients; and >8 cm in 13 patients. According to the number and size of tumor nodules, 49 patients met the Milan criteria. During follow-up 25 patients died, 13 due to tumor recurrence. The 1- and 2-year survivals were 90% and 85% for patients who met the Milan criteria versus 57% and 51% for patients exceeding those limits (P = .006). A cumulative tumor size >8 cm was predictive of survival and tumor recurrence upon multivariate analysis. The adoption of Milan criteria for selection of cirrhotic patients has improved survival and reduced the rate of tumor recurrence. The evaluation of cumulative tumor size might further improve patient selection.     

Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed?

Introduction

Liver transplantation (OLT) is considered the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rates, when restrictive selection criteria are applied. Nevertheless, tumor recurrence may occur in 3.5% to 21% of recipients. It usually occurs within 2 years following OLT, having a major negative impact on prognosis. The efficacy of active posttransplantation surveillance for recurrence has not been demonstrated, due to the poor prognosis of recipients with recurrences.

Aim

To analyze the clinical, pathological, and prognostic consequences of late recurrence (>5 years after OLT).

Method

We analyzed the clinical records of 165 HCC patients including 142 males of overall mean age of 58 ± 6.9 years who underwent OLT between July 1994 and August 2011.

Results

Overall survival was 84%, 76%, 66.8%, and 57% at 1, 3, 5, and 10 years, respectively. Tumor recurrence, which was observed in 18 (10.9%) recipients, was a major predictive factor for survival: its rates were 72.2%, 53.3%, 26.7%, and 10% at 1, 3, 5, and 10 years, respectively. HCC recurrence was detected in 77.8% of patients within the first 3 years after OLT. Three recipients (100% males, aged 54-60 years) showed late recurrences after 7, 9, and 10 years. In only one case were Milan criteria surpassed after the examination of explanted liver; no vascular invasion was detected in any case. Recurrence sites were peritoneal, intrahepatic, and subcutaneous abdominal wall tissue. In all cases, immunosuppression was switched from a calcineurin-inhibitor to a mammalian target of rapamycin inhibitor. We surgically resected the extrahepatic recurrences. The remaining recipient was treated with transarterial chemoembolization with doxorubicin-eluting beads and sorafenib. Prognosis after diagnosis of recurrence was poor with median a survival of 278 days (range, 114-704).

Conclusions

Global survival, recurrence rate, and pattern of recurrence were similar to previously reported data. Nevertheless, in three patients recurrence was diagnosed >5 years after OLT. Although recurrence was limited and surgically removed in two cases, disease-free survival was poor. Thus, prolonged active surveillance for HCC recurrence beyond 5 years after OLT may be not useful to provide a survival benefit for these patients.     

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。     

Beyond Milan criteria – chances and risks of expanding transplantation criteria for HCC patients with liver cirrhosis

Abstract:  Orthotopic liver transplantation (OLT) is, apart from resection, one important curative treatment for hepatocellular carcinoma (HCC) in liver cirrhosis, and especially attractive because it eliminates both the tumor and the underlying liver disease. The application of restrictive inclusion criteria for OLT in HCC patients resulted in favorable long-term recurrence-free survival. These criteria, however, exclude a subgroup of patients which, despite advanced tumor size, demonstrate an acceptable outcome. As a consequence, expansion of the strict Milan criteria has been discussed. However, this will also deteriorate the average outcome of OLT in HCC patients. Considering that we run short of donor organs, more sophisticated prediction models for survival after OLT for HCC patients are needed to identify patients who benefit best from OLT. Neoadjuvant treatment that is frequently applied as a bridging technique for patients on the waiting list for OLT could provide useful information on tumor behavior to better predict the risk of post-OLT tumor recurrence. This might also allow expansion of the Milan criteria to patients with good response to downstaging methods without negatively affecting post-OLT survival. Furthermore, alternative scoring systems have been suggested to identify HCC patients that might still benefit from resection instead of OLT, and molecular tools are being explored to provide predictive information on HCC biology. This review discusses the advantages and risks of extended inclusion criteria for OLT and the currently available data on alternative prediction models and bridging methods in HCC patients.     

Orthotopic Liver Transplantation for Hepatocellular Carcinoma: A Thirteen-Year Single-Center Experience

Background

When restrictive selection criteria are applied orthotopic liver transplantation (OLT) is the most efficient option for the treatment of hepatocellular carcinoma (HCC) in terms of survival and recurrence rate. Nevertheless, tumor recurrence may occur in 3.5%-21% of recipients, with a consequent negative impact on prognosis. The aim of this study was to analyze the long-term survival and tumor recurrence rate among a cohort of liver transplant recipients with HCC.

Methods

During the period 1994-2007, 130 HCC patients, including 111 males with a mean overall age of 57.8 ± 7.1 years (range, 38-70), underwent cadaveric donor-OLT. The etiology of liver disease was alcoholic cirrhosis in 66 patients (50.8%) and viral infection in 52 patients (40%). Baseline alpha fetoprotein values were 53.4 ± 280.9 ng/mL (range, 1-2593). Median interval between inclusion date and transplantation was 179.5 days.

Results

After a median follow-up of 40.8 months, 93 recipients (71.5%) were alive. Tumor recurrence was detected in 11 patients (8.5%). Neoplasm recurrence sites were as follows: liver graft (45.4%), bone (36.4%), lymphoadenopathies (27.3%), adrenal glands (27.3%), and lung (27.3%). Overall survival rates at 1, 3, 5, and 10 years were 85.1%, 78.3%, 70.1%, and 57%, respectively. After examination of the explanted liver, Milan criteria were surpassed in 32 recipients (24.6%). Nevertheless, no differences in survival were observed according to fulfilment or not of Milan criteria (log-rank test, P > .05). Hepatitis C virus (HCV) infection, female gender, and tumor recurrence were associated with a worse survival rate (log-rank test, < .05).

Conclusions

OLT is an effective option for the treatment of HCC with good long-term survival and low recurrence rates. In this series, survival was not affected by findings of poor prognostic factors in the explanted liver.     

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (OLT) is usually reserved for Child B and C patients with multiple nodules. The aim of this study was to compare HR and OLT for HCC within the Milan criteria on an intention-to-treat basis. Forty-eight patients were treated by OLT and 38 by HR. Three- and 5-year patient survival rates were significantly higher (P = .0057) in the OLT group (79% and 74%) than after HR (61% and 26%). The 3- and 5-year disease-free survival rate was better (P = .0005) for OLT (74% and 74%) versus HR (41% and 11%). The probability of HCC recurrences after resection was greater (P = .0002) than after transplantation, achieving 31% and 76% for HR and 2% and 2% for OLT at 3 and 5 years after surgery. The median waiting list time was 118 days; two patients dropped out for HCC progression. We concluded that OLT is superior to HR for small HCC in cirrhotic patients assuming that OLT can be performed within 6 to 10 months after listing to reduce dropouts due to tumor progression.     

Risk-Based Long-Term Screening for Hepatocellular Carcinoma Recurrence After Living Donor Liver Transplantation

Background

This study sought to establish an actual risk-based long-term screening protocol for hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT).

Methods

The study was a retrospective review of medical records from 334 HCC patients who underwent primary living donor OLT and followed up for at least 5 years.

Results

Overall 10-year patient survival rate was 67.5%, with a 4.8% perioperative mortality. HCC recurred in 68/318 (21.4%) surviving patients over a mean follow-up of 77 months. HCC recurrence was 20.7% at 5 and 22.2% at 10 years. Annual recurrence rates were 11.4%, 6.6%, and 2.0% during the first, second, and third years, respectively. Among patients within Milan criteria, the annual incidence of HCC recurrence was highest during the first 3 years; thereafter only 6 sporadic recurrences were observed during next 8 years. Among subjects beyond Milan criteria, recurrence was common during, but not after 3 years. In 43 patients (63.2%) increased alpha-fetoprotein (AFP) was an initial indication to perform further imaging studies to diagnosis recurrence, whereas they were detected incidentally on protocol screening imaging among another 25 patients (36.8%) in the absence of an AFP rise. There was a close correlation between pretransplant AFP level and AFP increase after HCC recurrence.

Conclusions

Patients beyond the Milan criteria require frequent tumor marker tests and imaging studies over the first 3 years; and those within Milan criteria require 10-years to follow-up primarily with tumor marker tests.     

Outcome of patients with recurrent hepatocellular carcinoma in liver transplantation

Liver transplantation (OLT) is the treatment of choice for patients with hepatic cirrhosis related hepatocellular carcinoma (HCC). Among 156 liver transplant patients for HCC from June 1996 to February 2005, 23 had recurrent HCC. To evaluate risk factors that affect early recurrence of HCC after OLT, we divided the 23 patients into two groups: early (< or =12 months) and late (>12 months) recurrences. Among them, 15 patients were dead and eight alive patients had been followed to 31 July 2005. The most common recurrence site was the grafted liver (n = 15), next was bone (n = 11), lung (n = 8), lymph node (n = 6), brain (n = 4), skin (n = 2), adrenal gland (n = 1). There were no significant differences between the two groups in age or tumor size, number of tumors, cell differentiation, alpha-feto protein levels, tumor staging, number of patients within Milan criteria, steroid pulse therapy, infectious diseases, and immunostaining of tumor. In our study, there were no risk factors that predict early tumor recurrence. We noticed that more patients in the early recurrence group were excluded by Milan criteria due to a more progressed tumor staging with higher mean levels of serum alpha-feto protein.     

Very late recurrence of hepatocellular carcinoma after liver transplantation: case report and literature review

Hepatocellular carcinoma (HCC) recurs in 10% to 60% of the patients after liver transplantation (OLT) and is associated with increased mortality. The average time to recurrence ranges from 1 to 2 years following OLT, and the median survival from the time of diagnosis is about 1 year. We report a case of a 69-year-old man who underwent OLT for hepatitis C virus-related cirrhosis with HCC, and was diagnosed with recurrent HCC 6.5 years after OLT. Biopsies from the initial and recurrent tumors showed a well-differentiated HCC with foci of clear cell pattern. The patient was still alive and asymptomatic 32 months after the diagnosis despite extensive tumor burden. He expired 9 years, 9 months after OLT and 3 years, 2 months after the detection of recurrence. In conclusion, HCC may recur more than 6 years after OLT and may exhibit an indolent course. This case illustrates the highly variable rate of tumor growth and progression post-OLT. The impact of this information on the need for long-term surveillance for recurrent HCC post-OLT remains to be determined.     

Long-Term Outcome of Liver Transplantation for Combined Hepatocellular Carcinoma and Cholangiocarcinoma

Purpose

Combined hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) is a rare pair of intrahepatic malignancies. Differential diagnosis among combined HCC-CCC, HCC, or CCC can be difficult; thus malignancies other than ordinary HCC are occasionally encountered unexpectedly in explanted liver specimens. The present study analyzed the long-term outcomes of liver transplantation (OLT) among patients with HCC-CCC.

Methods

Between January 1999 and December 2009, we performed 2137 adult OLT at our institution including 15 cases of pathologically confirmed HCC-CCC, who all underwent OLT with a pretransplant diagnosis of HCC. We reviewed retrospectively the medical records of these 15 patients.

Results

Their mean age was 58.9 ± 7.2 years. The median preoperative alpha-fetoprotein level was 32.6 ng/mL. Fourteen patients underwent living donor and one deceased donor OLT. The Milan criteria were met in 12 cases. A single tumor was identified in 8 and multiple lesions in 7 patients. The maximal tumor diameter was 2.9 ± 1.7 cm. Seven patients experienced tumor recurrences: including 6 within the first 12 months. All of the patients who experienced recurrences died at a median 4 months after that diagnosis. The overall patient survival rates were 66.7% at 1 year and 60.0% at 3 and 5 years. Disease-free patient survival rates were 60.0% at 1 year and 53.3% at 3 and 5 years.

Conclusions

Patients with combined HCC-CCC showed a high rate of early recurrences, particularly within the first year.     

An Analysis of Resection vs Transplantation for Early Hepatocellular Carcinoma: Defining the Optimal Therapy at a Single Institution

Background The reported survival after liver transplantation (OLT) for early hepatocellular carcinoma (HCC) is superior to the results of liver resection (LR), but few analyses have considered long waiting times and patient drop-offs due to tumor progression. Methods From 1995–2005, 347 patients with HCC were evaluated at our institution and underwent either LR (n = 174) or placed on the OLT waiting list (n = 173). Patients who only underwent ablation were not included. After eliminating patients with 1) incidental tumors after OLT, 2) tumors outside of Milan criteria, 3) preoperative vascular invasion prior to LR and 4) Child-Pugh Class C cirrhosis prior to OLT, 261 patients (LR = 121; OLT = 140) were included in this analysis. Results Median follow-up time was 35 months. Median waiting time for OLT was 7.7 months; during this time, 30 patients were taken off the waiting list. Overall survival (OS) from time of listing or LR was not different between the two groups; 1, 3, and 5 year OS after LR was 89%, 75%, and 56% compared with 90%, 70%, and 64% for OLT (P = .84). Only patients who waited <4 months for OLT (n = 67) had better survival than those who underwent LR (P = .05). Patients who waited longer that four months for OLT had a 2.5× higher risk of death in a Cox multivariate model [odds ratio (OR) 2.5; 95% confidence interval (CI): 1.3–5; P = .007]. Conclusion Unless waiting time is short (<4 months), the survival of patients with early HCC is similar between LR and LT. Presented at the 2006 Seventh International Hepato-Pancreato-Biliary Association, Edinburgh, Scotland, September 3–7, 2006.