Outcome of Liver Transplantation in Hepatocellular Carcinoma Patients at Siriraj Hospital

Background

Liver transplantation (LT) is one of the standard treatments for hepatocellular carcinoma (HCC), and the outcomes have become better after introduction of strict patient selection, such as the Milan criteria. However, several expanded criteria, such as the University of California San Francisco (UCSF) criteria, have demonstrated similar survival outcomes. The aim of this study was to verify survival outcomes of LT for HCC at Siriraj Hospital.

Combination of Morphologic Criteria and α-Fetoprotein in Selection of Patients With Hepatocellular Carcinoma for Liver Transplantation Minimizes the Problem of Posttransplant Tumor Recurrence

Background

Serum α-fetoprotein concentration (AFP) might be a useful addition to morphologic criteria for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). The aim of this study was to evaluate the role of AFP in selecting HCC patients at minimal risk of posttransplant tumor recurrence in the setting of existing criteria.

Methods

This retrospective cohort study was based on 121 HCC patients after LT performed at a single institution. AFP was evaluated as a predictor of posttransplant tumor recurrence with respect to fulfillment of the Milan, University of California, San Francisco (UCSF), and Up-to-7 criteria.

Results

There was a nearly linear association between AFP and the risk of HCC recurrence (p < 0.001 for linear effect; p = 0.434 for nonlinear effect). AFP predicted HCC recurrence in patients (1) beyond the Milan criteria (p < 0.001; optimal cutoff 200 ng/ml); (2) within the UCSF criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.015; optimal cutoff 200 ng/ml); and (3) within the Up-to-7 criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.023; optimal cutoff 100 ng/ml) but not in patients within the Milan criteria (p = 0.834). Patients within either UCSF and Up-to-7 criteria with AFP level <100 ng/ml exhibited superior (100 %) 5-year recurrence-free survival—significantly higher than those within UCSF (p = 0.005) or Up-to-7 (p = 0.001) criteria with AFP levels higher than the estimated cutoffs or beyond with AFP levels less than the estimated cutoffs.

Conclusions

Combining the UCSF and Up-to-7 criteria with an AFP level <100 ng/ml is associated with minimal risk of tumor recurrence. Hence, this combination might be useful for selecting HCC patients for LT.     

Can we direct organ allocation based on predicted outcome? Hepatocellular carcinoma outside of UCSF criteria or retransplant?

Background

In this study, we ask between patients with graft failure listed for retransplant and patients with hepatocellular carcinoma (HCC) outside of UCSF criteria, who has the greater survival benefit with transplantation?

Methods

This is a retrospective analysis, of liver transplant (LT) patients, done between February 2002 and December 2009 at our center. Patients were included in the “extended HCC” group if their tumor was pathologically beyond UCSF criteria at LT and in the “redo” group if they underwent LT for graft failure occurring more than 3?months after the initial LT. Extended criteria donors (ECDs) were defined as donors above 70?years old, DCD, serology positive for HCV, and split grafts.

Results

There were 25 redos and 37 extended HCC patients. Use of ECDs or high donor risk index organs was associated with poor outcome in both groups (P?=?0.005). Overall, the extended HCC population had a much better survival than redos, both at 1 and 3?years.

Conclusion

These two very different but high risk patient populations have very different survival rates. At a time where regulatory agencies demand more and more with regards to transplant outcomes, we think the transplant community has to reflect on whether allocation justice and fair access to transplant are respected if we start allocating organs based on outcomes.     

Microvascular Infiltration has Limited Clinical Value for Treatment and Prognosis in Hepatocellular Carcinoma

Background

Microvascular infiltration (MVI) is considered a necessary step in the metastatic evolution of hepatocellular carcinoma (HCC), but its prognostic value after liver resection (LR) is uncertain. We studied the clinical value of MVI compared to the Milan criteria in a consecutive series of patients submitted to radical LR.

Methods

A total of 441 patients were retrospectively evaluated. MVI and the Milan criteria were analyzed and compared as prognostic factors for overall and disease-free survival (DFS).

Results

MVI was present in 189 patients (42.8 %). Grading, satellitosis, size of cancer, and alfa fetoprotein value were significantly related to MVI, which was present in 34.3 and 53.2 % of Milan+ and Milan? patients, respectively (p = 0.00001). Both MVI and the Milan criteria were associated with a lower overall and DFS, but only the Milan criteria were associated with the rate of early recurrence and the feasibility of a curative treatment of the recurrence. The application of MVI parameters to patients classified by the Milan criteria further selects the outcome in Milan+ patients (5-year survival rate of 54.1 and 67.9 %, respectively, in the presence or absence of MVI) but not in Milan? patients.

Conclusions

MVI is related to survival after LR for HCC, but the clinical value of this information is limited. In Milan+ patients, the absence of MVI selects the cases with better prognosis. In the presence of a liver recurrence, the Milan criteria related to the primary HCC show a better prognostic accuracy and have clinical relevance in the decision-making process.     

Rate of tumor growth predicts recurrence of hepatocellular carcinoma after liver transplantation in patients beyond Milan or UCSF criteria

Background

It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC).

Methods

We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr³, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed.

Results

Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7–30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P = .001), poorly differentiated tumors (HR 13; P = .039), the presence of microvascular invasion (HR 7.9; P = .001), higher TTV (HR 1.03; P < .001), and faster tumor growth (HR 1.09; P < .001) were significantly associated with the risk of recurrence. A cutoff value of tumor growth of 1.61 cm³/mo was chosen on the basis of the risk of recurrence with the use of a receiver operating characteristic curve. Patients beyond the Milan criteria with tumor growth <1.61 cm³/mo experienced less recurrence (11% vs 58%; P = .023) than those beyond the Milan criteria with tumor growth >1.61 cm³/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria.

Conclusions

Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome.     

Impact of the preoperative des-gamma-carboxy prothrombin level on prognosis after hepatectomy for hepatocellular carcinoma meeting the Milan criteria

Purpose

Hepatectomy is feasible for patients with hepatocellular carcinoma (HCC) who are eligible for liver transplantation according to the Milan criteria if they have good hepatic function. This retrospective study investigates the prognostic factors of hepatectomy in HCC patients meeting the Milan criteria.

Methods

Between 1991 and 2005, 175 patients underwent hepatectomy for HCC at our institute; 111 met and 64 exceeded the Milan criteria. The prognostic factors for hepatectomy were investigated using a Cox regression model.

Results

Operative mortality and morbidity were significantly lower in the patients who met the criteria than in those who exceeded the criteria. After a median follow-up of 51.5 months, the 5-year survival rate was significantly better for the patients who met the criteria than for those who exceeded the criteria (77.8% vs 35.7%; P < 0.0001). The factors predictive of poor prognosis were poor differentiation, microscopic vasculobiliary invasion, and a high serum des-gamma-carboxy prothrombin (DCP) level (>100 mAU/ml) for the patients who met the Milan criteria; and only the presence of a microsatellite lesion for the patients who did not meet the Milan criteria.

Conclusions

Hepatectomy is safe and beneficial for HCC patients who meet the Milan criteria, but a high preoperative serum DCP level may be predictive of a poor prognosis.     

Super-selection of a Subgroup of Hepatocellular Carcinoma Patients at Minimal Risk of Recurrence for Liver Transplantation

Background

A majority of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT) meet the Milan criteria, but these are still regarded as the narrowest criteria for transplantation. Prognostic analysis of incidentally detected HCC after LT suggests that a subgroup of HCC patients is at very low risk of recurrence. To determine the criteria defining this super-selection group, we retrospectively analyzed survival data of 593 adult living-donor LT recipients with HCC in the explanted liver

Discussion

Tumor features of incidental HCC in 38 patients not showing recurrence were analyzed. Of these patients, 34 (89.5%) each had ≤2 tumors and tumors ≤2.0 cm in size. Applying these criteria to 555 patients with pretransplant known HCC (pkHCC) allowed us to identify 79 patients with untreated pkHCCs ≤2.0 cm in size. To date, only two of these patients have shown recurrence, making the conditions for super-selection the presence of tumors ≤2.0 cm in size, ≤2 tumors, alpha-fetoprotein ≤200 ng/mL, and no pretransplant treatment. In 87 patients satisfying these criteria, the 10-year recurrence and survival rates were 1.3% and 92.1%, respectively. After excluding patients meeting these criteria, the 5-year recurrence rates in patients satisfying the Milan, University of California at San Francisco, and Asan criteria were increased by 2.9–4.0%. In conclusion, this super-selection or super-Milan category may be used for validation assessment of various indication criteria and for the development of cost-effective post-transplantation HCC surveillance protocols. Further studies should be followed for deceased-donor LT and patients who have undergone pretransplant treatment.     

Outcome Comparisons Among the Hangzhou, Chengdu, and UCSF Criteria for Hepatocellular Carcinoma Liver Transplantation after Successful Downstaging Therapies

Background

In Mainland China, many selection criteria for hepatocellular carcinoma (HCC) liver transplantation, such as the Hangzhou, the Chengdu, and the Fudan criteria, have been established. No comparisons have been made among the outcomes using the Hangzhou, Chengdu, and University of California, San Francisco (UCSF) criteria in patients who underwent successful downstaging therapies.

Methods

After successful downstaging therapies, 72 patients met the UCSF criteria, 86 met the Chengdu criteria, and 102 met the Hangzhou criteria. The data on these HCC patients were retrospectively analyzed, and various outcomes, such as survival and the tumor-free survival rate, were compared among the three groups.

Results

No significant differences were observed among the three groups with regard to the downstaging protocols, baseline characteristics, or liver function. However, the patients who met the Hangzhou criteria had significantly larger tumor targets than those who met the Chengdu or UCSF criteria (P?<?0.05). The three groups showed similar 1-, 3-, and 5-year survival rates (90.9, 80.0, and 78.6 %, respectively, for the UCSF criteria; 91.6, 81.9, and 75.6 %, respectively, for the Hangzhou criteria; and 91.1, 83.3, and 79.4 %, respectively, for the Chengdu criteria); 1-, 3-, and 5-year tumor-free survival rates (83.3, 77.5, and 75 %, respectively, for the UCSF criteria; 86.3, 78.8, and 75.6 %, respectively, for the Hangzhou criteria; and 87.3, 79.2, and 76.4 %, respectively, for the Chengdu criteria); and 1-, 3-, and 5-year tumor recurrence rates (9.2, 17.5, and 21.4 %, respectively, for the UCSF criteria; 8.4, 16.4, and 20 % for the Hangzhou criteria; and 8.9, 14.6, and 17.6 % for the Chengdu criteria).

Conclusion

Because they have contributed to similar outcomes but to larger HCC patient pools, the Hangzhou criteria for HCC transplantation should be comprehensively accepted in China for HCC patients after successful downstaging therapies.     

Patients with Multiple Hepatocellular Carcinomas Within the UCSF Criteria Have Outcomes After Curative Resection Similar to Patients Within the BCLC Early-Stage Criteria

Background

Surgical strategies for the treatment of multiple hepatocellular carcinomas (HCC) remain controversial. This study compared the prognostic power of the University of California, San Francisco (UCSF) criteria with the Barcelona Clinic Liver Cancer (BCLC) early-stage criteria.

Methods

Clinical and survival data of 162 multiple-HCC patients in Child-Pugh class A who underwent curative resection were retrospectively reviewed. Prognostic risk factors were analyzed using univariate and multivariate analyses.

Results

UCSF criteria were shown to independently predict overall and disease-free survival. In patients within the UCSF criteria, 3-year overall and disease-free survivals were significantly better than in those exceeding the UCSF criteria (68 vs. 34?% and 54 vs. 26?%, respectively; both p?p?=?0.506 and 57 vs. 50?%, p?=?0.666, respectively). Tumors within the UCSF criteria were associated with a lower incidence of high-grade tumor (p?=?0.009), microvascular invasion (p?=?0.005), 3-month death (p?=?0.046), prolonged Pringle’s maneuver (p?=?0.005), and surgical margin <0.5?cm (p?Conclusions Multiple HCC patients within the UCSF criteria benefit from curative resection. Expansion of curative treatment is justified.     

Liver Transplantation for Hepatitis B Virus-Related Hepatocellular Carcinoma: One Center's Experience in China

Background

Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly cancer worldwide, with more than half a million identified cases and about a similar number of subjects succumb to it each year. This study sought to evaluate our results of liver transplantation for HCC to identify prognostic factors.

Methods

Between December 2001 and December 2006, 224 patients (205 men, 19 women; age range, 15-75 years) with HCC underwent orthotopic liver transplantation (OLT) at our center. All grafts were from deceased donors. There were 68 cases within Milan criteria (30.3%), 32 cases beyond Milan criteria but within UCSF (University of California, San Francisco) criteria (14.3%), and 124 cases beyond UCSF criteria (55.4%).

Results

The overall 1-, 3-, and 5-year patient cumulative survival rates were 82.5%, 60.1%, and 51.5%, respectively. The survival rates were comparable between patients within Milan and UCSF criteria, but were significantly greater than that of patients beyond UCSF criteria. Multivariate analysis revealed alpha fetoprotein (AFP) ≥ 800 μg/L, vascular invasion, and poor tumor differentiation to be independent prognostic factors.

Conclusion

OLT is a safe and effective treatment for hepatitis B virus-related HCC. Compared with Milan criteria, UCSF criteria successfully expanded the indication without deteriorating the prognosis significantly, while preoperative AFP ≥ 800 μg/L, vascular invasion, and poor tumor differentiation indicated poor survival.     

Downstaging Advanced Hepatocellular Carcinoma to the Milan Criteria May Provide a Comparable Outcome to Conventional Milan Criteria

Background and Aims

Many hepatocellular carcinoma (HCC) patients met the appropriate criteria and accepted liver transplantation after successful downstaging therapies; however, the outcome in these patients is unclear. We aim to compare the outcome of patients meeting the Milan criteria at the beginning and after successful downstaging therapies.

Patients and Methods

Between July 2001 and January 2013, 112 patients were diagnosed with early-stage HCC that met the Milan criteria. Of these patients, 58 patients did not meet the Milan criteria initially but did after successful downstaging therapies. We retrospectively collected and then compared the baseline characteristics, postoperative complications, survival rate, and tumor recurrence rate of these two groups. Kaplan–Meier analyses were used to estimate the long-term overall survival and tumor-free survival in these patients.

Results

No significant differences were observed between the two groups with respect to baseline donor and recipient characteristics. The downstaging Milan group showed similar tumor characteristics compared to the conventional Milan group, except the downstaging group had better tumor histopathologic grading (P?=?0.027). The 1-, 3-, and 5-year overall survival rates were comparable at 91.4, 82.8, and 70.7 %, respectively, in the downstaging Milan criteria and 92.0, 85.7, and 74.1 %, respectively, according to the initial Milan criteria (P?=?0.540). The 1-, 3-, and 5-year tumor-free survival rates between the two groups were not statistically significant (P?=?0.667).

Conclusion

Successful downstaging therapies can provide a comparable posttransplantation overall survival and tumor-free survival rates after liver transplantation.     

Analysis of the Risk Factors of Untransplantable Recurrence After Primary Curative Resection for Patients with Hepatocellular Carcinoma

Purpose

To determine the prognostic factors that predict recurrence of hepatocellular carcinoma (HCC) exceeding the University of California at San Francisco (UCSF) criteria after primary resection.

Methods

HCC patients who underwent curative liver resections between 2001 and 2007 and who were within the UCSF criteria (n = 716) were examined. Independent prognostic factors were examined by the Cox proportional hazard model.

Results

A total of 285 patients (39.8 %) developed recurrences. Of the patients who developed recurrences, 180 had HCC still within the UCSF criteria (63.2 %), and 105 developed HCC beyond this criteria (36.8 %). Among the population with primary transplantable HCC, patients with larger primary tumor sizes, serum α-fetoprotein (AFP) levels over 400 ng/mL, satellite nodules, vascular invasion, or undifferentiated HCC had a risk of untransplantable recurrence, as shown by univariate analysis. In multivariate analysis, undifferentiated HCC and vascular invasion were identified as the significant predictors with adjusted hazard ratios of 9.25 [95 % confidence interval (CI) 2.13–40.21] and 2.19 (95 % CI 1.34–3.58), respectively. When only preoperative factors were considered in multivariate analysis, primary tumor size and serum AFP levels over 400 ng/mL were identified as significant predictors with adjusted hazard ratios of 1.24 (95 % CI 1.07–1.45) and 1.72 (95 % CI 1.05–2.82), respectively.

Conclusions

For primary HCC patients within the UCSF criteria, larger tumor sizes and AFP levels over 400 ng/mL were associated with postresection recurrence of HCC exceeding the UCSF criteria. Because these are clearly markers for aggressive tumor biology, whether early primary transplant will alter the aggressive tumor behaviors warrant further investigation.     

Comparison of Surgical Resection and Transarterial Chemoembolization for Hepatocellular Carcinoma beyond the Milan Criteria: A Propensity Score Analysis

Background

Treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) is controversial. This study compared the long-term survival of patients beyond the Milan criteria who received surgical resection (SR) or transarterial chemoembolization (TACE).

Methods

A total of 268 and 455 HCC patients beyond the Milan criteria undergoing SR and TACE, respectively, were retrospectively evaluated. After propensity score analysis to adjust for baseline differences, 146 pairs of matched patients were selected from each treatment arm. Long-term survival was compared by the Kaplan?CMeier method. Independent prognostic predictors were determined by the Cox proportional hazards model.

Results

Long-term survival was significantly better for the SR group by univariate survival analysis (P?P?P?P?Conclusions For HCC patients beyond the Milan criteria, SR is considered equally safe as TACE and provides better long-term survival. SR may be regarded as the priority treatment for these patients.     

Liver transplantation is an alternative treatment of hepatocellular carcinoma beyond the Milan criteria

Background

The decision to perform liver transplantation (LT) or liver resection (LR) for patients with hepatocellular carcinoma (HCC) who are beyond the Milan criteria remains controversial.

Methods

We retrospectively analyzed outcome data for 179 patients with HCC beyond the Milan criteria who were treated with LR (n = 135) or LT (n = 44). Univariate and multivariate Cox proportional hazard models were established. Kaplan-Meier survival curves were generated, and a log-rank test was performed to compare group survival status.

Results

Patients who underwent LR group were significantly older, had a lower TNM stage, and were more likely to have unilateral disease and noncirrhotic liver. Significantly more patients in the LR group had recurrence (53.3% vs 29.5%) or died (61.5% vs 43.2%) than patients in the LT group. Recurrence-free survival rates were 11.9% for the LR group and 61.5% for the LT group. The median overall survival duration showed no statistically difference between the LR group (28.0 months) and the LT group (50.0 months).

Conclusions

LT may be the better choice for patients with HCC beyond the Milan criteria.     

Milan Criteria, Multi-nodularity, and Microvascular Invasion Predict the Recurrence Patterns of Hepatocellular Carcinoma After Resection

Aims

This study aims to evaluate the risk factors for tumor recurrence beyond the Milan criteria (MC) for patients with hepatocellular carcinoma (HCC) after surgical resection (SR) in which salvage liver transplantation is relatively contraindicated.

Methods

A total of 447 patients who underwent SR for HCC were enrolled consecutively. Among them, 248 and 199 patients were within the Milan criteria and beyond the Milan criteria (BMC group), respectively. Overall survival, recurrence, and disease-free survival were analyzed by multivariate analysis.

Results

After a median follow-up of 34.4 months, 130 patients died. Microvascular invasion, higher Edmondson stage of tumor cell differentiation, BMC group, and no anti-viral therapy were associated with poor overall survival. Multi-nodularity, higher Edmondson stage, BMC group, and no anti-viral therapy were independent risk factors for tumor recurrence, while BMC group and no anti-viral therapy were independent risk factors for disease-free survival. The Milan criteria, multi-nodularity, and microvascular invasion were used to stratify the patients into low-, medium-, and high-risk groups for tumor recurrence outside the MC and showed statistical significance (low vs. medium, p?=?0.011; low vs. high, p?<?0.001; medium vs. high, p?=?0.009).

Conclusions

The combination of the MC, multi-nodularity, and microvascular invasion predict the post-operative recurrence of HCC and may provide a roadmap for further treatment.     

Comparison Between Living Donor Liver Transplantation Recipients Who Met the Milan and UCSF Criteria After Successful Downstaging Therapies

Background and Aims

Various downstaging therapies were introduced to liver recipients who could not meet the relative criteria for liver transplantation, and many endpoints were reported. The most common criteria used were the Milan criteria and the University of California, San Francisco (UCSF) criteria. However, no comparison was made between them, and we attempted to find possible differences between the living donor liver transplantation (LDLT) patients who met the Milan criteria and those who met the UCSF criteria after accepting preoperative downstaging therapies.

Materials and Methods

We performed a retrospective study of all 72 patients at our center from January 2003 to March 2009 who were diagnosed with advanced hepatocellular carcinoma but accepted various downstaging therapies. Some patients met the Milan criteria (group 1), and some met the UCSF criteria (group 2) but not the Milan criteria. We collected the data from the two groups and then compared the preoperative demographic data, downstaging therapies, intraoperative data from LDLT, and the recovery and complications after LDLT. Survival rates were compared using Kaplan?CMeier analysis.

Results

Only 44 patients (61.1?%) met the criteria for liver transplantation, 21 cases met the Milan criteria (group 1), and 23 cases met the UCSF criteria (group 2) but not the Milan criteria. All of the 44 patients accepted right lobe living liver donor liver transplantation in our center. The difference in the baseline characteristics between the two groups did not reach statistical significance. The mean number of downstaging treatments per patient was 1.81?±?0.35 in group 1 and 1.83?±?0.41 in group 2 (P?=?0.928). Most of the patients received only one downstaging treatment, and transcatheter arterial chemoembolization (TACE) was the most common downstaging therapy. Four patients suffered complications after downstaging therapies: intra-abdominal hemorrhage after right hepatectomy, upper gastrointestinal hemorrhage after TACE, biliary fistula after resection, and hand?Cfoot syndrome after taking sorafenib. All complications after LDLT, classified according to the Clavien?CDindo system, were compared within the two groups, and the calculated score of the complications in group 1 was 1.48?±?1.63, which was greater than that of group 2 (1.39?±?1.64), but this difference did not reach statistical significance (P?=?0.865). The 1-, 3-, and 5-year survival rates were 90.4, 76.2, and 71.4?% in group 1 and 91.3, 73.9, and 69.6?% in group 2, respectively (P?>?0.05). Seven patients (three in group 1 and four in group 2) had tumor recurrence after a median follow-up period of 72?months. The pathology findings were not different between the two groups.

Conclusion

Recipients who meet the Milan or UCSF criteria after accepting successful preoperative downstaging therapy in LDLT can achieve the same result.     

Immediate Radical Therapy or Conservative Treatments When Meeting the Milan Criteria for Advanced HCC Patients After Successful TACE

Background and aims

Many advanced hepatocellular carcinoma (HCC) cases can be successfully downstaged into the Milan criteria; however, immediate radical therapy cannot be applied to all such patients for various reasons. Of the patients who are not eligible for immediate radical therapy, some accept repeated downstaging therapies and some undergo persistent observation. The aim of the present study was to compare long-term survival between these two groups of patients.

Patients and Methods

Between August 2003 and October 2008, 156 HCC patients successfully received downstaging therapy resulting in compliance with the Milan criteria. Of those, 98 cases accepted radical therapies, including liver transplantation (LT), resection, or radiofrequency ablation (RFA) (group 1), and 58 cases underwent repeated transcatheter arterial chemoembolization (TACE) or persistent observation (group 2). The baseline characteristics, demographic data, downstaging protocol, and information on long-term outcomes were collected and compared.

Results

No significant differences were observed in the patient demographic data, downstaging protocols, or tumor characteristics between the two groups. The 1-, 3-, and 5-year overall survival rates were 92.9, 82.7, and 78.6 %, respectively, in group 1, whereas these rates were 82.8, 65.5, and 48.3 %, respectively, in group 2 (P?=?0.046). Among the 58 patients in group 2, the 1-, 3-, and 5-year overall survival rates were 92.3, 65.4, and 46.2 %, respectively, in the repeated TACE group, and 81.3, 65.6, and 50 %, respectively, in the persistent observation group (P?=?0.783).

Conclusion

Immediate radical therapy should be the first choice for advanced HCC patients who undergo successful TACE, and repeated TACE is unnecessary.     

Survival Benefit of Transplantation for Recurrence of Hepatocellular Carcinoma After Liver Resection

Background

Liver transplantation (LT) for hepatocellular carcinoma (HCC) can be used for tumor recurrence after liver resection (LR) both for initially transplant-eligible patients as conventional salvage therapy (ST) and for non–transplant-eligible patients (beyond Milan criteria) with a goal of downstaging (DW). The aim of this study was to compare the intention-to-treat (ITT) survival rates of patients who are listed for LT, according to these two strategies.

Methods

We analyzed a prospective database of 399 consecutive patients who underwent hepatic resection for HCC from 2002 to 2011 to identify patients included in the waiting list for tumor recurrence. Intention-to-treat (ITT) survivals were compared with those of patients resected for HCC within and beyond Milan criteria in the same period and not included in the LT waiting list.

Results

The study group consisted of 42 patients, 28 in the ST group (within Milan) and 14 in the DW group (beyond Milan). The 5-year ITT survival rate was similar between the 2 groups, being 64% for ST and 60% for DW (P = .84). Twenty-five patients (15 ST and 10 DW) underwent LT, 13 (10 ST and 3 DW) were still awaiting LT, 4 (3 ST and 1 DW) dropped out of the waiting list because of tumor progression, and 7 (5 ST [33%] and 2 DW [20%]) had tumor recurrence. The 5-year ITT survival of ST patients was similar to that of 252 in-Milan HCC patients resected only (P = .3), whereas 5-year ITT survival of DW patients was significantly higher (P < .01) than that of 105 beyond-Milan HCC patients resected only.

Conclusions

LR seems to be a safe and effective therapy both as alternative to transplantation and as downstaging strategy for intermediate-advanced HCC. The survival benefit of salvage LT, however, seems to be higher in the 2nd than in the 1st group.     

Surgical Resection versus Open-Approach Radiofrequency Ablation for Small Hepatocellular Carcinomas within Milan Criteria after Successful Transcatheter Arterial Chemoembolization

Aims

The aim of this study was to compare the effectiveness and safety of hepatic resection versus open-approach RFA (ORFA) for small hepatocellular carcinomas (HCC) within Milan criteria after successful downstaging therapy by transcatheter arterial chemoembolization.

Material and Methods

Between February 2005 and February 2008, a total of 110 patients with advanced HCC met the Milan criteria after successful downstaging therapy; 58 patients then underwent hepatic resection and 52 received ORFA. Outcomes, including short- and long-term morbidity, 1-, 3-, and 5-year mortality and HCC-free survival, were analyzed and compared between the two groups.

Results

Patients in the hepatic resection and ORFA groups showed similar baseline characteristics and downstaging protocols. The ORFA group showed less blood loss, lower hospital costs, shorter surgical time, and fewer hospital stay days (P?<?0.05). The 1-, 3-, and 5-year overall survival rates were 94.8, 86.2, and 79.3 %, respectively, with liver resection and 96.2, 82.7, and 76.9 % with ORFA (P?=?0.772). The 1-, 3-, and 5-year recurrence-free survival rates were 93.1, 81.0, and 77.6 % with resection and 94.2, 76.9, and 73.1 % with ORFA (P?=?0.705). The ORFA patients suffered fewer postoperative complications (P?=?0.09), particularly among the cases of central HCC (P?=?0.015).

Conclusion

Resection and ORFA achieved similar survival benefits in the management of HCC within Milan criteria after successful downstaging. The decreased blood loss, hospital costs, surgical time, and hospital stay days, and lower complication rates in central cases render ORFA a preferred treatment option.