Clinical efficacy of liver transplantation for intrahepatic cholangiocarcinoma: a multicenter study / 中华消化外科杂志

Objective:To investigate the clinical efficacy of liver transplantation for intra-hepatic cholangiocarcinoma.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 22 patients with intrahepatic cholangiocarcinoma who underwent liver trans-plantation in the 5 medical centers, including First Hospital of Jilin University, et al, from September 2005 to December 2021 were collected. There were 18 males and 4 females, aged 57(range, 38?71)years. Observing indicators: (1) clinicopathological characteristics of patients with intrahepatic cholangiocarcinoma; (2) follow-up; (3) prognosis. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to draw survival curves. The Log-Rank test was used for survival analysis. Results:(1) Clinicopathological characteristics of patients with intrahepatic cholangio-carcinoma. Of the 22 patients, 20 cases were diagnosed as intrahepatic cholangiocarcinoma before liver transplantation, 7 cases had viral hepatitis type B, 1 case had primary sclerosing cholangitis, 7 cases had tumor treatment before liver transplantation, 7 cases, 6 cases and 9 cases were classified as grade A, grade B and grade C of the Child-Pugh classification, 16 cases had preoperative CA19-9 >40 U/mL, 14 cases had single tumor, 11 cases with tumor located at right lobe of liver, 6 cases with tumor located at both left and right lobe of liver, 5 cases with tumor located at left lobe of liver, 9 cases with tumor vascular invasion. All 22 patients were diagnosed as moderate-poor differentiated tumor. There were 9 cases with liver cirrhosis, 4 cases with tumor lymph node metastasis, 10 cases with tumor burden within Milan criteria. The tumor diameter of 22 patients was 4.5(range, 1.5?8.0)cm. (2) Follow-up. All 22 patients were followed up for 15(range, 3?207)months. Of the 22 patients, 9 cases had tumor recurrence and 8 cases died. (3) Prognosis. The 1-year overall survival rate and 1-year disease-free survival rate of the 22 patients was 72.73% and 68.18%, respectively. Results of subgroup analysis showed there were significant differences in overall survival and disease-free survival between the 10 patients with tumor burden within Milan criteria and the 12 patients with tumor burden beyond Milan criteria who underwent liver transplantation ( hazard ratio=0.13, 0.26, 95% confidence interval as 0.03?0.53, 0.08?0.82, P<0.05). Results of further analysis of the 12 patients with tumor burden beyond Milan criteria showed there were significant differences in overall survival and disease-free survival between the 5 patients with preoperative tumor down-staging treatment and the 7 patients without preoperative tumor down-staging treatment ( hazard ratio=0.18, 0.14, 95% confidence interval as 0.04?0.76, 0.04?0.58, P<0.05). Conclusions:Intrahepatic cholangiocarcinoma patients with tumor burden within Milan criteria have a better prognosis than patients with tumor burden beyond Milan criteria after liver transplantation. For patients with tumor burden beyond Milan criteria, active tumor down-staging treatment before liver transplantation can improve the prognosis.

Role of the criteria based on preoperative serological indexes of AFP and GGT in predicting long-term survival of patients with hepatocellular carcinoma after liver transplantation / 器官移植

Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.

Prognostic outcomes of salvage liver transplantation under different transplantation criteria / 中华器官移植杂志

Objective:To compare the prognoses of salvage liver transplantation fulfilling the Criteria of Milan, University of California San Francisco(UCSF)and Hangzhou.Methods:Clinical data were retrospectively reviewed for 256 patients with recurrent hepatocellular carcinoma(HCC)undergoing donation after citizen death(DCD)liver transplantation(LT)from January 2015 to October 2019.They were divided into two groups of primary(PLT, n=175)and salvage(SLT, n=81). General profiles, tumor pathological characteristics and postoperative complications of two groups were compared by T-test, rank-sum or χ2 test.Kaplan-Meier method and Log rank test were employed for comparing overall survival rate(OS)and recurrence-free survival rate(RFS)between two groups.In SLT group, 31 cases fulfilled Milan criteria, 45 cases UCSF criteria and 69 cases Hangzhou criteria.OS/RFS of three groups were compared.According to there was downstaging or bridging treatment pre-LT, SLT group was divided into downstaging group(n=32)and non-downstaging group(n=49). OS/RFS of two groups were compared.According to the Rescit1.1 criteria, downstaging group were divided into remission group(n=14)and non-remission group(n=18)and OS/RFS of two groups were compared. Results:The operative durations of PLT and SLT groups were(439.5±74.9)and(475.1±83.4)min respectively.There was significant inter-group difference( P<0.05); However, no significant inter-group difference existed in amount of intraoperative bleeding, blood transfusion, postoperative hospital stay or incidence of postoperative complications(all P>0.05). No significant difference existed in OS/RFS between PLT and SLT groups( P>0.05). No significant difference existed in OS at 1/3/5 years post-SLT among Milan, UCSF and Hangzhou criteria groups(all P>0.05); However, RFS in Milan criteria group at 1/3/5 years post-SLT were 93.5%, 81.7% and 81.7% respectively.They were significantly higher than 68.9%, 59.7% and 59.7% in UCSF criteria group and 78.3%, 58.8% and 55.5% in Hangzhou criteria group(all P<0.05). For patients on downstaging therapy, OS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 73% and 73% respectively, which was significantly higher than 83.3%, 49.4% and 0 in non-Remission group( P=0.042). RFS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 62.5% and 46.9% respectively, which was significantly higher than 52.9%, 0 and 0 in no-Remission group( P=0.001). Conclusions:The survival outcome of SLT recipients is similar to that of PLT recipients.The overall survival of SLT recipients shows no significant difference between Milan, UCSF and Hangzhou criteria.However, SLT recipients fulfilling Milan criteria have the longest recurrence-free time.The prognosis of patients with remission after preoperative descending treatment is superior to that of patients without remission.

Clinical study of microvascular invasion on prognosis of recipients after liver transplantation for liver cancer / 器官移植

Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.

Selection criteria for liver transplantation recipients of hepatocellular carcinoma / 中华肝脏病杂志

Liver transplantation is by far the most thorough and effective treatment for liver cancer. However, there is still much controversy about how to select receptors in an effective and equitable manner under the shortage of liver donor. The "Milan Standard" is the most widely used screening standard for liver transplantation recipients in the world. In recent years, many patients with Trans Milan criteria (such as Hangzhou standard) can achieve transplant survival similar to that of Milan patients after transplantation. This article describes the research progress of liver transplantation recipients’ selection criteria in hepatocellular carcinoma.

Comparative effect of salvage liver transplantation and repeated hepatectomy for recurrent hepatocellular carcinoma / 局解手术学杂志

Objective To evaluate the curative effect of salvage liver transplantation and repeated hepatectomy for recurrent hepatocel-lular carcinoma.Methods The data of 72 patients with recurrent hepatocellular carcinoma fulfilling Child-Pugh A and the Milan criteria from September 2004 to August 2010 were retrospectively studied.According to different treatments,53 patients were divided into repeated hepatec-tomy group,and 19 patients were divided into salvage liver transplantation group.The overall survival rates and disease-free survival rates after operation were evaluated by Kaplan-Meier method.COX proportional hazard was used for univariate analysis and multivariate analysis to eval-uate the risk factors for prognosis.Results The 1-year,3-year and 5-year survival rates were 86.79%,62.26% and 45.28% in repeated hepatectomy group,and 89.47%,68.42%and 57.89% in the salvage liver transplantation group respectively.There was no significant differ-ence in the overall survival rates between the two groups (χ2 =2.530,P =0.112).The 1-year,3-year and 5-year disease-free survival rates were 67.92%,47.17% and 35.85%in the repeated hepatectomy group,94.74%,68.42% and 52.63% in the salvage liver transplantation group respectively.There was a significant difference in the disease-free survival rates between the two groups(χ2 =4.395,P =0.036).The univariate analysis and multivariate analysis indicated that microvascular invasion,satellite lesion and multiple tumors were the independent risk factors to influence the survival.Conclusion The salvage liver transplantation obtains a better effect for the patients fulfilling Child-Pugh A and the Milan criteria,which is an effective method in the treatment of hepatocellular carcinoma.

Living Donor Liver Transplantation in a Hepatitis B Patient with Acute on Chronic Liver Failure Accompanying Hepatocellular Carcinoma / 이화의대지

Acute clinical deterioration in patients with chronic liver disease is called acute on chronic liver failure (ACLF). Principles of management of ACLF consist of early identifying etiology of liver disease, rapid intervention of precipitating event and discreet intensive cares. Despite medical intensive cares, if liver failure progresses, liver transplantation could be the other option. Also, liver transplantation is the only treatment that offers a chance of cure for hepatocellular carcinoma (HCC) and the underlying liver cirrhosis simultaneously. Emergent living donor liver transplantation (LDLT) can be performed for patients with acute liver failure and improves survival rate, especially in circumstances which liver graft is often not available because of deceased donors are not affordable. Here, we describe a chronic hepatitis B patient who developed ACLF accompanying early HCC. Because he did not improved with medical care, he received emergent LDLT. After LDLT, he showed great improvement without critical complications.

Clinical significance and predictive factors of early massive recurrence after radiofrequency ablation in patients with a single small hepatocellular carcinoma

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated. METHODS: In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated. RESULTS: During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence. CONCLUSIONS: Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence.

Progress on TACE treatment for primary liver cancer exceeding Milan criteria / 实用肿瘤学杂志

Primary liver cancer ( PLC) is one of the most invasive malignant tumors in the clinics .The PLC within Milan criteria can be cured by liver transplantation or liver resection .However,PLC exceeding Milan criteria has been a question for us to overcome all the time .In recent years ,transcatheter arterial chemoemboliza-tion( TACE) and its combination therapy for PLC exceeding Milan criteria have made some breakthrough .A great deal of literatures have confirmed that TACE and its combined therapy for PLC exceeding Milan criteria can im -prove the survival rate obviously,it also contains many advantages,such as low cost,safe,painless,minimally in-vasive,repetitive operation and so on .The progress of TACE for PLC exceeding Milan criteria in recent years is summarized in this paper .

Impact of sirolimus and tacrolimus on the tumor recurrence after liver transplantation due to HCC beyond milan criteria: randomized controlled clinical trial / 中华器官移植杂志

Objective To compare the impact of the sirolimus and tacrolimus on the tumor recurrence after liver transplantation due to HCC beyond Milan criteria.Method Sixty-one liver transplantation recipients due to HCC beyond Milan criteria,between Jan.2008 and Apri.2012,were randomized,with the informed consent,into two different immunosuppression groups: sirolimus group (n=30) and tacrolimus group (n=31).In tacrolimus group,tacrolimus was used as the basic immunosuppressant,methylprednisolone was discontinued within one month postoperatively,and mycophenolate mofetil was used within the dosage of 1.5 g/d accordingly.In sirolimus group,the immunosuppresive scheme was the same as that of the tacrolimus group within postoperative one month,and from that,tacrolimus was transferred to sirolimus.No antineoplastic agents were given before tumor recurrence.The tumor recurrence rate and the survival rate of the recipients were compared between the two groups.Result The median follow-up duration was 35.2 months (10.3～ 60.2).The tumor recurrence rate at postoperative year 1,2,3 and 4 in the sirolimus group (13.3％,36.7％,43.3％ and 53.3％) was significantly lower than that in the tacrolimus group (38.7％,67.7％,74.2％ and 77.4％),P ＜ 0.05 for all.The one-year survival rate in the recipients postoperation had no significant difference between sirolimus group and tacrolimus group (90.0％ vs.87.1％,P=0.438).The 2-,3-and 4-year survival rate in the recipients was significantly higher in the sirolimus group (53.3％,33.3％ and 20.0％) than that in the tacrolimus group (41.9％,22.6％ and 9.7％),P ＜ 0.05 for all.The liver function and renal function of the recipients at the postoperative year 1,2,3 and 4 showed no significant difference between the two groups,P＞0.05.Conclusion In comparison with tacrolimus,sirolimus could significantly reduce the tumor recurrence rate and increase the survival rate for the liver transplant recipients due to HCC beyond Milan criteria.

Liver transplantation and expanded Milan criteria: does it really work? / Transplante de fígado e critérios de Milão expandidos: isto realmente funciona?

CONTEXT: Orthotopic liver transplantation is an excellent treatment approach for hepatocellular carcinoma in well-selected candidates. Nowadays some institutions tend to Expand the Milan Criteria including tumor with more than 5 cm and also associate with multiple tumors none larger than 3 cm in order to benefit more patients with the orthotopic liver transplantation. METHODS: The data collected were based on the online database PubMED. The key words applied on the search were "expanded Milan criteria" limited to the period from 2000 to 2009. We excluded 19 papers due to: irrelevance of the subject, lack of information and incompatibility of the language (English only). We compiled patient survival and tumor recurrence free rate from 1 to 5-years in patients with hepatocellular carcinoma submitted to orthotopic liver transplantation according to expanded the Milan criteria from different centers. RESULTS: Review compiled data from 23 articles. Fourteen different criteria were found and they are also described in detail, however the University of California - San Francisco was the most studied one among them. CONCLUSION: Expanded the Milan criteria is a useful attempt for widening the preexistent protocol for patients with hepatocellular carcinoma in waiting-list for orthotopic liver transplantation. However there is no significant difference in patient survival rate and tumor recurrence free rate from those patients that followed the Milan criteria.

CONTEXTO: Em pacientes bem selecionados, o transplante ortotópico de fígado é um excelente tratamento para pacientes com carcinoma hepatocelular. Algumas instituições atualmente tendem a expandir os critérios de Milão. São os chamados Critérios de Milão Expandidos, que incluem tumores maiores do que 5 cm e também aqueles associados com múltiplos tumores, não maiores do que 3 cm, a fim de beneficiar o maior número possível de pacientes submetidos ao transplante ortotópico de fígado. MÉTODOS: Os dados foram coletados na base de dados do PubMED. A palavra-chave para procura foi Critérios de Milão expandidos, no período de 2000 a 2009. Foram excluídos 19 trabalhos devido à falta de dados de sobrevida e à recurrência tumoral, não compatíveis com a língua inglesa e fora do assunto em questão. Foram analisadas a sobrevida do paciente e a taxa de recurrência do tumor de 1 a 5 anos de pacientes submetidos ao transplante hepático com critérios de Milão expandidos em diferentes centros internacionais. RESULTADOS: Esta revisão agregou 23 trabalhos. Catorze diferentes critérios foram encontrados e descritos em detalhes. No entanto, os critérios da Universidade da Califórnia em São Francisco foram os mais estudados entre todos os analisados. CONCLUSÃO: Os Critérios de Milão Expandidos são úteis para ampliar os protocolos para adesão de doentes na lista de espera para transplante de fígado, não havendo diferença significante na sobrevida do doente e nem na taxa livre de recurrência tumoral quando comparados aos critérios de Milão.

Comparison of efficacies of hepatectomy and liver transplantation for patients with hepatocellular carcinoma fulfilling the Milan criteria / 中华消化外科杂志

Objective To compare the efficacies of hepatectomy and liver transplantation for patients with hepatocellular carcinoma (HCC) fulfilling the Milan criteria.Methods From July 2002 to February 2009,121 patients with HCC combined with hepatic cirrhosis fulfilling the Milan criteria were admitted to the Fuzhou General Hospital.Eighty-nine patients who received hepatectomy were in the hepatectomy group,and 32 patients who received liver transplantation were in the liver transplantation group.There were no significant difference in the age,gender,etiology of liver disease,the size of the largest tumor,number of tumors,microscopic venous invasion,microsatellite lesion and tumor differentiation between the 2 groups.The clinical data of the patients in the 2 groups were retrospectively analyzed.The overall survival and disease-free survival were evaluated by Kaplan-Meier method,and differences in survival rates between the 2 groups were determined by Log-rank test.COX proportional hazard was used for univariate and multivariate analysis to evaluate the risk factors for prognosis.Results The median period of follow-up was 37 months.The 1-,3-,5-year survival rates were 86％,63％ and 44％ in the hepatectomy group,and 87％,70％ and 62％ in the liver transplantation group.There was no significant difference in the overall survival rate between the 2 groups (x2 =1.092,P ＞ 0.05).The 1-,3-,5-year disease-free survival rates were 68％,44％ and 26％ in the hepatectomy group,and 80％,65％ and 52％ in the liver transplantation group.There was a significant difference in the disease-free survival rate between the 2 groups (x2 =4.712,P ＜ 0.05).The result of univariate analysis revealed that microscopic venous invasion and microsatellite lesion were significantly correlated with the survival (Wald =9.625,7.340,P ＜ 0.05),and the result of multivariate analysis indicated that microscopic venous invasion was the independent risk factor influencing the survival (Wald =5.008,P ＜ 0.05).Conclusions As for patients with HCC fulfilling the Milan criteria,the overall survival rate of patients who received hepatectomy is not different from those who received liver transplantation,but the disease-free survival rate of patients who received liver transplantation is higher than those who received hepatectomy.Microscopic venous invasion is an independent risk factor influencing the survival.

The initial application of sorafenib in liver transplantation patients of primary hepatic carcinoma exceeding Milan criteria / 中华肝胆外科杂志

ObjectiveTo observe the efficacy of using sorafenib in preventing and treating tumor recurrence after liver transplantation for patients with primary hepatic carcinoma exceeding Milan criteria.MethodsFrom March 2008 to June 2010,30 patients of liver transplantation with primary hepatic carcinoma exceeding Milan criteria were randomized into 2 groups,each group of 15 cases.The experimental group received oral administration of sorafenib (400 mg bid) ; the control group received capecitabine (1500 mg bid) for 14 days every 4 weeks.The patient without recurrence in 18 months after transplantation stoped taking the medication.The recurrent patients maintained the original dose until they were not suitable for the medication.Patients with serious adverse reactions must reduce the dose or stop the medication.ResultsThe 1 year recurrence rate of experimental group was 53.3％,the control group was 86.6％,the difference between 2 groups was statistically significant (x2 =3.968,P＜0.05).The 1 year survival rate of experimental group was 93.3％,the control group was 46.6％,the difference between 2 groups was statistically significant (x2 =7.777,P＜0.05).The mean survival time of experimental group was (28.3±2.5)months (7～36 months),the control group was (17.9±3.5)months (5 ～ 41 months),the experimental group patients' survival time was longer than the control group,the differences was statistically significant (x2=5.702,P＜0.05 ).Most adverse reactions in 2 groups were grade Ⅰ - Ⅱ.The incidence of diarrhea and hand-foot syndrome in experimental group was higher than in control group.ConclusionUsing sorafenib for patients with primary hepatic carcinoma exceeding Milan criteria after liver transplantation probably may reduce or delay the process of carcinoma recurrence,can prolong the survival time of those patients,and side effects can be tolerated.

Outcome of Hepatic Resection for Hepatocellular Carcinoma within the Milan Criteria in Child-Pugh Class A Patients

PURPOSE: Hepatic resection and liver transplantation are considered a curative treatment for hepatocellular carcinoma (HCC) within the Milan criteria. In this study, we examine the outcome of hepatic resection for HCC within the Milan criteria, and determine the effectiveness of hepatic resection as the primary treatment for HCC within the Milan criteria in Child-Pugh class A. METHODS: 110 patients underwent curative surgical resection for HCC in Child-Pugh class A between August 1991 and June 2008. Fifty-six patients met Milan criteria (Group M) and the remaining 54 did not (Group N). RESULTS: Overall survival rates at 1, 3, and 5 years were 92.6%, 72.5% and 54.6% versus 70.4%, 43.1%, and 28.7% in Group M and Group N, respectively (P=0.0043). The corresponding disease-free survival rates were 81.5%, 69.7%, and 38.2% versus 46.0%, 32.9%, and 26.9% in Group M and Group N (P=0.0012). HCC recurred in 25 patients in Group M (44.6%) and 35 patients in Group N (64.8%)(P=0.034). Outcomes of hepatic resection in Group M were significantly better compared to Group N. CONCLUSION: Hepatic resection can achieve a comparable 5-year overall survival & disease-free survival to that reported for liver transplantation. Hepatic resection should be considered as the standard therapy for HCC within the Milan criteria in Child-Pugh class A patients.

Results of Hepatectomy as First Treatment for Hepatocellular Carcinoma within the Milan Criteria with Preserved Liver Function

PURPOSE: Hepatic resection and liver transplantation are surgical therapeutic options for small-sized HCC. But, the therapeutic option for patients meeting the Milan criteria with preserved liver function is facing a dilemma. In this study, we examined the outcomes of surgical resection for HCC patients meeting the Milan criteria with preserved liver function and rationale of hepatic resection as the first treatment for HCC meeting the Milan Criteria. METHODS: Between 1991 and 2006, 248 patients with HCC underwent hepatectomy in 158 primary HCC patients meeting Milan criteria (Group M) and in 90 patients beyond Milan criteria (Group N). Median age was 54.5 years in group M and 52.4 years in group N. RESULTS: The tumor size, mean survival months, E-S grade and vascular invasion rate were significantly different between the two groups. 67 patients in group M and 22 patients in group N had intrahepatic recurrence after primary hepatectomy. The cumulative 1, 3, and 5-year survival rates were 91.9%, 74.5%, and 60.5% in intrahepatic recurrence group M after primary hepatectomy and 100%, 96.0%, and 90.5% in repeated hepatic resection for recurrent treatment in group M, respectively. CONCLUSION: Because of the high survival rate and long-term survival after adequate treatment of recurrence, primary hepatectomy is considered a reasonable option as first-line treatment for HCC meeting Milan criteria with preserved liver function.

Indication and Outcome of Liver Transplantation In Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and most commonly associated with hepatitis B infection in Korea. Since HCC arises in cirrhotic livers and is often multicentric, liver transplantation (LT) seems to be a rational and effective approach. Furthermore hepatitis B can be eradicated after LT in more than 90% patients. Current selection criteria of LT for HCC are Milan criteria; single nodule < or = 5cm in diameter, or 3 nodules < or = 3cm each, without major vessel invasion, without extrahepatic metastasis. Patients within Milan criteria showed 75% 5-yeaer survival rate after LT, which was comparable to that of a transplant candidate without HCC. Expanding selection criteria result in more patients with HCC being cured at the expense of a higher incidence of recurrence. Because some, but not all patients with unresectable HCC more than 5cm in diameter have significant vascular invasion and high recurrence rate, this highlights the need to incorporate molecular/biologic information. Pretransplant transarterial chemoembolization and salvage transplantation had a role for down stage or biologic selection of HCC. However, these methods had many controversies about their indication and safety. Iindication of LT for HCC patients is similar in living donor LT. In Korea, living donor LT is more popular in LT for HCC and outcome is comparable to that in deceased donor liver transplantation. In the future, with better understanding of tumor biology, a more and better group of patients with HCC can be selected for LT.

Living donor liver transplantation for Patients with beyond Milan hepatocellular carcinoma

BACKGROUND: To find the patients who have a significant chance of cure with living donor liver transplantation (LDLT) among the patients suffering with beyond-Milan hepatocellular carcinoma (HCC), we retrospectively analyzed the tumor factors that could affect a good prognosis after LDLT for patients who suffer with beyond Milan HCC. METHODS: Between March 2005 and May 2007, 18 cases of LDLT for beyond Milan HCC were performed. None of the patients had preoperative radiological evidence of vascular invasion. Excluding the 3 cases of in-hospital mortality, we analyzed the survival, the disease-free survival and the prognostic factors for recurrence in 15 beyond Milan HCC patients. The mean follow-up period was 18.8degrees +/- 8.8 months (range: 4-34 months). RESULTS: The two-year survival and disease-free survival rates after LDLT were 61.7% and 31.1%, respectively, in 15 beyond-Milan patients. Among them, 9 patients had recurrence of HCC during follow-up. The one-year survival rate after tumor recurrence was 55.5%. An alphafetoprotein (AFP) level < 400 ng/mL, Edmonson-Steiner histology grade I and II and the presence of graft rejection were analyzed as the good prognostic factors of disease-free survival after LDLT for beyond-Milan HCC (p < .05). The patients with negative preoperative positron emission tomography (PET) findings (n = 5) showed a better prognosis than the PET-positive patients (n = 10) with statistical significance (p = .05). CONCLUSION: Allowing that HCC patients exceed the Milan criteria, we can find the potentially curable candidates for LDLT with using tumor biologic markers such as a serum AFP level < 400 ng/mL, negative PET uptake or low grade histology, as assessed by preoperative needle biopsy. Further investigation is needed to evaluate the relation between graft rejection and tumor recurrence after liver transplantation.

Effects of Partial Hepatectomy for Hepatocellular Carcinoma Meeting Milan Criteria Combined with Compensated Liver Cirrhosis

PURPOSE: This study examined the effects a partial hepatectomy through an analysis of survival rates and examine the recurrence pattern after a partial hepatic resection for HCC according to the Milan criteria combined with Child-Pugh A cirrhosis. METHODS: On hundred and twenty seven HCC patients with Child-Pugh A liver cirrhosis undergoing a hepatic resection for HCC from September 1987 through July 2004 in the hospital were retrospectively reviewed. Among them, 85 cases met the Milan criteria (M group). However, the remaining 42 cases did not (N group). The median age was 52 years and males outnumbered females by almost five times. The median follow up period was 39.8 months. RESULTS: No in-hospital mortality occurred in the M group, but there was a single mortality case in the N group. The size of the tumor, multiplicity and major resection rate were different between the two groups. The 5 years overall survival rate of each group was 62.3% and 37.3%, respectively (P=0.002) and the 5 year disease free survival rates were 44.0% and 24.5%, respectively (P=0.023). Forty one patients in the M group developed recurrences, of which 35 had only intrahepatic recurrences. Among them, 28 recurrences still met the Milan criteria. CONCLUSION: A partial hepatic resection should be considered a standard treatment method for a HCC meeting the Milan criteria with compensated liver cirrhosis in terms of safety and long-term survival. A salvage transplantation may play a role after a recurrence because most recurrences are intrahepatic recurrences that meet the Milan criteria.

Outcome of the Liver Resection of the Hepatocellular Carcinoma under Milan Criteria

PURPOSE: Liver resection (LR) has been the treatment of choice for hepatocellular carcinoma (HCC), but resection and survival rates remain low, and recurrence is common in cirrhotic patients. This study was designed to evaluate the outcome after resection of potentially transplantable early HCCs and compare it with that for liver transplantation (LT) as reported in the literature. METHODS: We studied 109 patients with HCC under the Milan criteria who underwent LR at Kyungpook National University Hospital from September 1997 to May 2002. The patients were divided into two groups: group A had a single tumor and group B had two or three tumors. RESULTS: The mean age was 56.1+/-8.1 years and the male-to-female ratio was 4.7: 1. Most of the patients had chronic liver disease due to viral hepatitis, but had preserved hepatic function. Overall survival rates (SR) at 1, 2, 3, and 4 years were 86.7, 69.4, 44.8, and 13.3%, respectively, and the corresponding disease-free survival rates (DFSR) were 74.2, 53.8, 41.6, and 23.7%. SR and DFSR were not significantly different between the two groups, although group B tended to have lower SR and DFSR. At a median follow-up of 25.3 months, 52 patients experienced recurrence, most of whom had intrahepatic recurrence within 2 years after resection. At the time of the diagnosis of recurrence, 34 patients were considered eligible for LT. CONCLUSION: Although most of the patients had preserved hepatic function, LR of early HCC showed low survival rates and high recurrence rates compared with those after LT reported in the literature and in our experiences. Therefore, in the absence of limiting factors, LT may be the better option for surgical treatment of patients with early HCC, even when preserved hepatic function is maintained.