Hepatocellular Carcinoma Meeting Milan Criteria Research Articles

Radiofrequency ablation with or without transarterial chemoembolization for hepatocellular carcinoma meeting Milan criteria: a focus on tumor progression and recurrence patterns.

The aim of this study was to evaluate tumor progression and recurrence patterns of radiofrequency ablation (RFA) with or without transarterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) that meets Milan criteria. This retrospective study included consecutive HCC patients meeting Milan criteria who underwent percutaneous RFA with or without TACE as initial treatment at a tertiary academic center between December 2017 and 2022. Technical success rate, local recurrence-free survival (LRFS), progression-free survival (PFS) and recurrence patterns were recorded. A total of 135 HCC patients (109 male [80.7%]) with a mean age of 62 years and 147 target lesions were retrospectively enrolled. The technical success rate was 99.3%. The median LRFS was 60 months, and the cumulative 1-, 3-, and 5-year LRFS were 88.9%, 70.1%, and 30.0%, respectively. Additionally, the median PFS was 23 months, with cumulative 1-, 3-, and 5-year PFS of 74%, 30%, and 0%, respectively. Multivariate analysis confirmed that age > 60, alpha-fetoprotein (AFP) (> 10), and albumin were associated with PFS (2.34, p = 0.004; 1.96, p = 0.021; 0.94, p = 0.007, respectively). Six recurrence patterns were identified: local tumor progression (LTP) alone (n = 15, 25.0%), intrahepatic distant recurrence (IDR) alone (n = 34, 56.7%), extrahepatic recurrence (ER) alone (n = 2, 3.3%), IDR + ER (n = 2, 3.3%), LTP + IDR (n = 5, 8.8%), and LTP + IDR + ER (n = 2, 3.3%). IDR occurred most frequently as a sign of good local treatment. RFA in combination with TACE does not appear to provide an advantage over RFA alone in improving tumor progression in patients with HCC meeting the Milan criteria. However, further prospective studies are needed to confirm these findings and to determine the optimal treatment approach for this patient population.

Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis.

Organ allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). The National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vsLT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P<.001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vsLT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vsLT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.

Poorly Differentiated Hepatocellular Carcinoma: Resection is Equivalent to Transplantation in Patients with Low Liver Fibrosis

Introduction: Organ allocation criteria for liver transplantation (e.g. Milan) focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). Methods: The National Cancer Database was queried between 2004-2016 for solitary HCC meeting Milan criteria undergoing SX vs. LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. Results: 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P<.001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stay, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs. LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. Discussion: HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs. LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.

Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis

Presenter: Omid Salehi MD | Saint Elizabeth's Medical Center Background: Organ allocation criteria for liver transplantation (e.g. Milan) focus on tumor size and multifocality to determine candidacy, while tumor differentiation and degree of liver damage are omitted. This study investigates a synergistic effect of hepatocellular carcinoma (HCC) differentiation grade with degree of liver fibrosis on survival when comparatively analyzing resection (SX) vs transplantation (LT) and whether these parameters should be included in organ allocation algorithms. Methods: The National Cancer Database was queried between 2004-2016 for patients with solitary HCC meeting Milan criteria undergoing SX vs. LT. Two groups were created based on liver damage (low fibrosis (LF) vs high fibrosis (HF)) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. Results: 1515 patients met inclusion criteria; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months and 5-year survival (5YS) was 58.2%; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001), LT 5YS was 68.7% vs SX 5YS of 44.2% (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital length of stay, and age to be factors associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, type of surgery did not impact survival for poorly differentiated HCC in LF patients. This pattern was independent of tumor size. Conclusion: HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs. LT. Therefore, to optimally allocate organs for HCC transplantation, current criteria should give more weight to tumor grade or liver fibrosis compared to tumor size.

Prolonged post-ablation fever may predict one-year tumor recurrence in hepatocellular carcinoma after radiofrequency ablation

Background The impact of prolonged post-ablation fever (PAF) defined as persistent fever > 24 h after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) had not been described before. This study aims to investigate the impact of prolonged PAF on early tumor recurrence in HCC patients after RFA. Methods From 2013 to 2015, a total of 135 patients with HCC meeting Milan criteria and all the tumors having confirmed complete ablation after RFA were enrolled. Study endpoint was any HCC recurrence within 1 year after ablation. Cox regression analysis was applied for multivariate analysis to determine the independent predictors of 1-year tumor recurrence. Results Post-ablation fever occurred in 42 (31.1%) patients after RFA, while prolonged PAF was found in 22 (16.3%) patients. Fifty-eight (42.8%) patients occurred any tumor recurrence within 1 year after complete ablation. Patients with prolonged PAF had a significantly higher rate of HCC recurrence within 1 year (72.7% vs. 37.1%, p = 0.002) and had a significantly shorter time-to-recurrence interval (19.6 vs. 40.5 months, Log rank test, p = 0.002) than those who had no prolonged PAF. Multivariate analysis by Cox regression showed the previous HCC recurrence history (aHR: 1.792, p = 0.0284), baseline AFP > 20 ng/ml (aHR: 1.868, p = 0.0211) and prolonged PAF (aHR: 2.092, p = 0.0138) were associated with early recurrence. Conclusions Prolonged PAF may associate with early HCC recurrence after complete ablation by RFA. Patients with prolonged PAF need to be more clinical attentions.

Comparison of the outcome of radiofrequency ablation or hepatic resection between solitary hepatocellular carcinoma and oligonodular hepatocellular carcinoma meeting Milan criteria: a systematic review and meta-analysis

There are more literatures on the comparison of the outcome of small HCC between HR and RFA, but rare is about the comparison of the outcome between small solitary HCC and small oligonodular HCC meeting Milan criteria by HR or by RFA. Thus, the aim of the present study is to evaluate the outcome between small solitary HCC and small oligonodular HCC meeting Milan criteria treated by HR or by RFA. Total eighteen studies including 4,823 patients was included in this study. Among them LR group included 2,564 cases, and RFA group included 2,259 cases. We divided them into small solitary HCC sub-group and small oligonodular HCC sub-group and compared the survival difference between them. In the HR group, 1, 3, and 5 years OS of the small solitary HCC sub-group were 93.9%, 81.3%, and 72.0%, and the small oligonodular HCC sub-group were 83.3%, 70.4%, and 45.4%, respectively. For the DFS in the HR group, 1, 3, and 5 years of the small solitary HCC sub-group were 76.4%, 56.0%, and 44.0%, and 65.9%, 40.7%, and 11.1% of the small oligonodular HCC sub-group, respectively. In the RFA group, 1, 3, and 5 years OS of the small solitary HCC sub-group were 91.2%, 74.1%, and 54.5%, and the small oligonodular HCC sub-group were 82.0%, 55.4%, and 38.2%, respectively. For the DFS in the RFA group, 1, 3, and 5years of the small solitary HCC sub-group were 74.1%, 49.8%, and 22.1%, and 62.6% and 37.3%, 8.2% of the small oligonodular HCC sub-group, respectively.

Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant

ImportanceSeveral factors are associated with increased hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but no reliable risk score has been established to determine the individual risk for HCC recurrence.ObjectiveWe aimed to develop and validate a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score for patients with HCC meeting Milan criteria by imaging.Design, Setting, and ParticipantsPredictors of recurrence were tested in a development cohort of 721 patients who underwent LT between 2002 and 2012 at 3 academic transplant centers (University of California–San Francisco; Mayo Clinic, Rochester; and Mayo Clinic, Jacksonville) to create the RETREAT score. This was subsequently validated in a cohort of 341 patients also meeting Milan criteria by imaging who underwent LT at the University of Toronto transplant center using the C concordance statistic and net reclassification index.Main Outcomes and MeasuresCharacteristics associated with post-LT HCC recurrence.ResultsA total of 1061 patients participated in the study; 77.8% (825) were men, and the median (IQR) age was 58.2 (53.3-63.9) years in the development cohort and 56.4 (51.7-61.0) years in the validation cohort (P < .001). In the development cohort of 721 patients (542 men), median α-fetoprotein (AFP) level at the time of LT was 8.3 ng/mL; 9.4% had microvascular invasion (n = 68), and 22.1% were beyond Milan criteria on explant (n = 159) owing to understaging by pretransplantation imaging. Cumulative probabilities of HCC recurrence at 1 and 5 years were 5.7% and 12.8%, respectively. On multivariable Cox proportional hazards regression, 3 variables were independently associated with HCC recurrence: microvascular invasion, AFP at time of LT, and the sum of the largest viable tumor diameter and number of viable tumors on explant. The RETREAT score was created using these 3 variables, with scores ranging from 0 to 5 or higher that were highly predictive of HCC recurrence (C statistic, 0.77). RETREAT was able to stratify 5-year post-LT recurrence risk ranging from less than 3% with a score of 0 to greater than 75% with a score of 5 or higher. The validation cohort (n = 340; 283 men) had significantly higher microvascular invasion (23.8% [n = 81], P < .001), explant beyond Milan criteria (37.3% [n = 159], P < .001), and HCC recurrence at 5 years (17.9% [n = 159], P = .03). RETREAT showed good model discrimination (C statistic, 0.82; 95% CI, 0.77-0.86) and superior recurrence risk classification compared with explant Milan criteria (net reclassification index, 0.40; P = .001) in the validation cohort.Conclusions and RelevanceWe have developed and validated a simple and novel prognostic score that may improve post-LT HCC surveillance strategies and help identify patients who may benefit from future adjuvant therapies.

Race/Ethnicity-specific Disparities in Hepatocellular Carcinoma Stage at Diagnosis and its Impact on Receipt of Curative Therapies.

To evaluate race/ethnicity-specific disparities in hepatocellular carcinoma (HCC) stage at diagnosis and how this impacts receiving curative therapies. HCC is a leading cause of morbidity and mortality worldwide. The highest incidence of HCC is seen among ethnic minorities in the United States. Using the 2003-2011 Surveillance, Epidemiology, and End Results database and United Network of Organ Sharing, population-based registries for cancer and liver transplantation (LT) in the United States, race/ethnicity-specific cancer stage at diagnosis and treatment received among adults with HCC were evaluated. Compared with non-Hispanic whites, blacks had significantly more advanced HCC at diagnosis [odds ratio (OR), 1.20; 95% confidence interval (CI), 1.10-1.30; P<0.001], whereas Asians were less likely to have advanced disease (OR, 0.87; CI, 0.80-0.94; P<0.001). Among patients with HCC meeting Milan criteria, Hispanics (OR, 0.64; 95% CI, 0.57-0.71; P<0.001) and blacks (OR, 0.67; 95% CI, 0.59-0.76; P<0.001) were significantly less likely to receive curative therapy (resection or LT), whereas Asians were more likely to receive curative therapy (OR, 1.22; 95% CI, 1.10-1.35; P<0.001) compared with non-Hispanic whites. However, Asians (OR, 0.49; 95% CI, 0.42-0.58; P<0.001) and Hispanics (OR, 0.51; 95% CI, 0.44-0.60; P<0.001) were less likely to receive LT. Among US adults with HCC, blacks consistently had more advanced stage at diagnosis and lower rates of receiving treatment. After correcting for cancer stage and evaluating the subset of patients eligible for curative therapies, blacks and Hispanics had significantly lower rates of curative HCC treatment.

Sa1023 Liver Transplantation for Hepatocellular Carcinoma Outside of Both Milan and UCSF Criteria: Does Etiology of Liver Disease Impact Outcomes?

Background: Liver transplantation (LT) is the optimal treatment for selected patients with hepatocellular carcinoma (HCC). Survival of >80% at 4 years has been demonstrated for patients with HCC meeting Milan criteria. The UCSF group reported acceptable outcomes using a specific protocol for patients beyond Milan criteria. Proceeding with LT for HCC outside UCSF criteria is very controversial given the concern for recurrent HCC affecting longterm outcomes. Underlying viral disease may influence post-transplant immunosuppression. However, the impact of a viral etiology on patients with HCC at higher risk of recurrence is unknown. We sought to examine the impact of underlying etiology of liver disease on recurrence and outcomes in patients who had explants with HCC beyond Milan and UCSF criteria. Methods: We reviewed 87 patients after LT for HCC from 1998-2009 with explant tumor beyond Milan UCSF criteria. We compared outcomes of patients with cirrhosis due to chronic hepatitis B or C to those from non-viral etiology, with recurrence data up to 11/ 2012. Results: The viral hepatitis group (n=58) had a mean LT age of 56.7 years. Hepatitis C (HCV) was present in 86%, with eleven achieving SVR after transplant and one before. Mean biological MELD and mean alfa-fetoprotein (AFP) at LT were 14.4 and 537.9ng/mL, respectively. Pre-LT locoregional therapy with transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) was given in 81% and 12%, respectively. At explant, mean tumor count (MTC) was 4.3, mean largest tumor size (mLTS) was 4.92cm, and 46.6% had vascular invasion. HCC recurrence occurred in 50%, with a mean patient survival time (PST) of 3.41 years. 10 of the 12 HCV patients with SVR had HCC recurrence. Patient survival at 1 year (1yPS) and 3 years (3yPS) was 81% and 48%, respectfully, both lower than the 2005-2010 Surgical Registry of Transplant Recipient (SRTR) national averages. The non-viral group (n=29) had a mean LT age of 61.3 years. Mean MELD and AFP were 17.3 and 1190.1ng/mL, respectively. Pre-LT TACE and RFA were performed in 85% and 7%, respectively. MTC was 4.7 and mLTS was 4.95cm. 65.5% had vascular invasion. HCC recurrence occurred in 55.2%, with a mean PST of 3.76 years. 1yPS and 3yPS was 79% and 48%, respectively, again lower than the national averages from the 2005-2010 SRTR. Conclusion: In our cohort of patients who had HCC outside of Milan and UCSF criteria that underwent LT, the cause of liver disease did not impact recurrence of HCC or patient survival. Both viral and non-viral groups had similar disease burden, AFP levels, and vascular invasion in the explant as well as cancer recurrence rates. HCV SVR did not appear to impact HCC recurrence. Longer term survival was less favorable for patients transplanted beyond Milan and UCSF criteria and was lower than the national average for the same time period.

Approximately one‐half of patients with early‐stage hepatocellular carcinoma meeting Milan criteria did not receive local tumor destructive or curative surgery in the post‐MELD exception era

Since 2002, priority Model for End-stage Liver Disease (MELD) exception status has been given to patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. Since then, the number of liver transplantations performed in patients with HCC has increased, but to the authors' knowledge, few studies to date have examined the effect of MELD exception recommendations on therapy use and survival rates in a nationwide sample. The current study examines therapy use and long-term survival rates among patients with HCC tumors meeting the Milan criteria in the post-MELD exception era. The current study is a retrospective cohort study of 2179 patients with localized HCC meeting the Milan criteria who were registered between 2004 and 2007 in the Surveillance, Epidemiology, and End Results database. A total of 43% of patients did not receive any specific therapy. Overall, the 5-year relative survival rate for patients receiving only supportive care was dismal at 24% (95% confidence interval [95% CI], 21%-27%), whereas that for patients undergoing liver transplantation was 77% (95% CI, 71%-82%). Long-term survival was found to be dependent on age, race/ethnicity, and type of therapy received. A multivariate Cox proportional hazards model adjusted for age, race/ethnicity, and type of therapy received demonstrated that, compared with white patients, black patients had significantly poorer survival outcomes (hazards ratio, 1.23; 95% CI, 1.03-1.47 [P = .02]), whereas Asian/Pacific Islander patients had significantly better survival rates when compared with white patients (HR, 0.66; 95% CI, 0.57-0.77 [P < .001]). Despite having localized disease that met transplantation criteria, nearly 50% of the large nationwide cohort of patients with HCC in the current study received only supportive care and had dismal 5-year relative survival rates, especially among black patients.

Simeprevir and sofosbuvir: Two new drugs for chronic HCV infection

Simeprevir and sofosbuvir: Two new drugs for chronic HCV infection

Current surgical treatment strategies for hepatocellular carcinoma in North America.

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease. Many patients do not initially manifest any symptoms of HCC and present late when cure with surgical resection or transplantation is no longer possible. For this reason, patients at high risk for developing HCC are subjected to frequent screening processes. The surgical management of HCC is complex and requires an inter-disciplinary approach. Hepatic resection is the treatment of choice for HCC in patients without cirrhosis and is indicated in some patients with early cirrhosis (Child-Pugh A). Liver transplantation has emerged in the past decade as the standard of care for patients with cirrhosis and HCC meeting Milan criteria and in select patients with HCC beyond Milan criteria. Loco-regional therapy with transarterial chemoembolization, transarterial embolization, radiofrequency ablation and other similar local treatments can be used as neo-adjuvant therapy to downstage HCC to within Milan criteria or as a bridge to transplantation in patients on transplant wait list.

Risk Factors for Early Recurrence of HBV-related Hepatocellular Carcinoma Meeting Milan Criteria after Curative Resection

The prognosis of patients with hepatocellular carcinoma (HCC) after curative resection varies greatly. Few studies had investigated the risk factors for early recurrence (recurrence-free time ≤ 1 year) of hepatitis B virus (HBV)-related HCCs meeting Milan criteria. A retrospective analysis was performed on the 224 patients with HCC meeting Milan criteria who underwent curative liver resection in our center between February 2007 and March 2012. The overall survival (OS) rate, recurrence-free survival (RFS) rate and risk factors for early recurrence were analyzed. After a median follow-up of 33.3 months, HCC reoccurred in 105 of 224 patients and 32 died during the period. The 1-, 3- and 5-year OS rates were 97.3%, 81.6% and 75.6% respectively, and the 1-, 3- and 5-year RFS rates were 73.2%, 53.7% and 41.6%. Cox regression showed alpha-fetoprotein (AFP) > 800 ng/ml (HR 2.538, 95% CI 1.464-4.401, P=0.001), multiple tumors (HR 2.286, 95% CI 1.123-4.246, P=0.009) and microvascular invasion (HR 2.518, 95% CI 1.475-4.298, P=0.001) to be associated with early recurrence (recurrence-free time ≤ 1-year) of HCC meeting Milan criteria. AFP > 800 ng/ml, multiple tumors and microvascular invasion are independent risk factors affecting early postoperative recurrence of HCC. In addition resection appears capable of replacing liver transplantation in some situations with safety and a better outcome.

Transplant versus resection for the management of hepatocellular carcinoma meeting Milan Criteria in the MELD exception era at a single institution in a UNOS region with short wait times

Management of hepatocellular carcinoma (HCC) in the Model for End-Stage Liver Disease (MELD) exception era remains regionally variable. Outcomes were compared for patients undergoing transplant versus resection at a single institution in a UNOS region with short wait times for organ availability. All patients who underwent resection of HCC from January 2000 to August 2012 and patients who underwent transplant post-January 2006, during the Milan Criteria (MC)-based MELD exception policy for HCC, were identified. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). Two hundred fifty-seven patients were analyzed, of whom 131 underwent transplant and 126 underwent resection. All transplant patients met MC; 45 (36%) resection patients met MC. Median follow-up time was 30 months. Median wait time to transplant was 55 days; no patients dropped off the waitlist while awaiting an organ. Among patients meeting MC, transplant demonstrated significantly greater 5-year OS (65.7% vs. 43.8%; P = 0.005) and RFS (85.3% vs. 22.7%; P < 0.001) versus resection. For patients with hepatitis C, transplant (n = 87) demonstrated significantly improved 5-year outcomes compared to patients meeting MC who underwent resection (n = 21; OS: 63.5% vs. 23.3%; P = 0.001; RFS: 83.5% vs. 23.7%; P < 0.001). In a region with short waitlist times for organ availability, liver transplant is associated with improved survival compared to resection for HCC within MC and should be considered for all patients meeting MC, particularly those with hepatitis C.

Radiofrequency ablation versus hepatic resection for the treatment of early-stage hepatocellular carcinoma meeting Milan criteria: a systematic review and meta-analysis

Current options for the treatment of the early-stage HCC conforming to the Milan criteria consist of liver transplantation, hepatic resection (HR), transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) .Whether HR or RFA is the better treatment for early HCC has long been debated. The aim of our paper is to compare the therapeutic effects of radiofrequency ablation (RFA) and hepatic resection (HR) in the treatment of early-stage hepatocellular carcinoma (HCC). Controlled trials evaluating the efficacy between RFA and HR for the treatment of early-stage HCC published before June 2013 were searched electronically using MEDLINE, PubMed, Cochrane Library, and EMBASE databases. Using inclusion and exclusion criteria, two randomized controlled trials and 10 nonrandomized controlled trials were included in the meta- analysis. The results showed that the 3,5-year overall survival rates and 1,3,5 disease-free survival rates were significantly lower after RFA than after HR. However, complications after treatment were less common and the length of hospital stay was significantly shorter after RFA. Additionally, there was no significant difference in the 1-year overall survival rate between RFA and HR. The conclusions of the results show that the difference in the short-term effectiveness of RFA and HR in the treatment of small HCC is not notable, but the long-term efficacy of HR is better than that of RFA. However, HR is associated with more complications and a longer hospital stay.

肝がんはどこまで切れますか?

The standard strategy in the surgical treatment of hepatocellular carcinoma (HCC) has been outlined based on my experience involving over operated 3,000 cases. My first line operation for HCC is systematic segmentectomy, which carries towards zero mortality and improved survival. Makuuchi′s criteria with bilirubin value and ICG clearance will afford good surgical indication for resection. In living-related liver transplantation, patients with HCC meeting Milan criteria are good candidates. In this review, I will show the surgical treatment options currently available for patients with HCC.

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.

The Timing of Liver Transplantation After Primary Hepatectomy for Hepatocellular Carcinoma: A Special Reference to Recurrence Pattern and Milan Criteria

Hepatic resection (HR) is commonly applied as first-line treatment of hepatocellular carcinoma (HCC) even in the era of liver transplantation (LT). Outcomes and detailed recurrence pattern of 80 patients, who underwent curative HR for HCC were examined referring to Milan criteria. (I) After HR for HCCs exceeding Milan criteria (n=41), recurrence within the criteria was observed in 13 patients (group-A) and recurrence not-meeting the criteria was observed in 22 patients (group-B). group-A showed better 3-year recurrence-free survival rate than group-B (85.7% vs. 23.9%, P<0.05). Tumor size more than or equal to 6 cm was identified as the significant factor for having recurrence as in group-A pattern (P<0.05). Among the patients in group-A, re-recurrence after treating recurrent HCC was observed in eight patients (61.5%) with increased rate of extra-Milan criteria recurrence at 12 months from the initial recurrence. (II) After HR for HCCs meeting Milan criteria (n=39), recurrences within the criteria was observed in 15 patients (group-C) and recurrence not-meeting the criteria was observed in five patients (group-D). The 3-year recurrence-free survival rate was 62.8% in group-C and 40.0% in group-D (P<0.05). Increased rate of extra-Milan re-recurrence was observed later than 12 months from the recurrence in group-C. For HCCs not meeting Milan criteria, secondary LT after primary HR could be applied for a proportion of cases with less aggressiveness. For those meeting Milan criteria, primary LT should be the first therapeutic option. However, secondary LT could be offered for those with re-recurrence within criteria after primary HR.

Outcomes and Recurrence of Initially Resectable Hepatocellular Carcinoma Meeting Milan Criteria: Rationale for Partial Hepatectomy as First Strategy

Partial hepatectomy and liver transplantation are considered curative treatments for small hepatocellular carcinoma (HCC) meeting the Milan criteria (solitary tumor <5 cm or up to 3 nodules <3 cm). This study was designed to clarify whether partial hepatectomy can be the first option in patients eligible for both treatments. All patients (n = 152) underwent curative surgical operation for primary HCC during 2000 to 2005 at our hospital. Eighty-seven patients met Milan criteria and the remaining 65 did not. Outcomes were examined according to Milan criteria. After partial hepatectomy, 3-year survival rate was 89.6% for the group that met Milan criteria, compared with 60.8% for the group that did not (p = 0.0044). Among patients with HCC who initially met the criteria, tumor recurrences were observed in 30 patients; 23 patients met criteria and 7 patients exceeded the criteria at first diagnosis of recurrence. Patients with recurrence within the criteria showed a higher 3-year survival rate compared with patients with recurrence exceeding the criteria (100% versus 19.8%; p < 0.0001). Analysis of clinicopathologic variables to predict mode of recurrence revealed tumor size (p < 0.0001) and lower histologic differentiation (p = 0.0326) as positive factors for recurrence exceeding Milan criteria. Our results suggest that it is an appropriate strategy to treat HCC patients who meet Milan criteria with partial hepatectomy. It should be noted that approximately one-tenth of patients who initially met Milan criteria experienced postoperative recurrence that exceeded the criteria.