Number and Tumor Size Are Not Sufficient Criteria to Select Patients for Liver Transplantation for Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is an indication for liver resection or transplantation (LT). In most centers, patients whose HCC meets the Milan criteria are considered for LT. The first objective of this study was to analyze whether there is a correlation between the pathologic characteristics of the tumor, survival and recurrence rate. Second, we focused our attention on vascular invasion (VI).

Methods

From January 1997 to December 2007, a total of 196 patients who had a preoperative diagnosis of HCC were included. The selection criteria for LT satisfied both the Milan and the San Francisco criteria (UCSF). Demographic, clinical, and pathologic information were recorded.

Results

HCC was confirmed in 168 patients (85.7%). The median follow-up was 74?months. The pathologic findings showed that 106 patients (54.1%) satisfied the Milan criteria, 134 (68.4%) the UCSF criteria of whom 28 (14.3%) were beyond the Milan criteria but within the UCSF criteria, and 34 (17.3%) beyond the UCSF criteria. VI was detected in 41 patients (24%). The 1-, 3-, and 5-year overall survival rates were 90%, 85%, and 77%, respectively, according to the Milan criteria and 90%, 83%, and 76%, respectively, according to the UCSF criteria (P?=?NS). In univariate and multivariate analyses, tumor size and VI were significant prognostic factors affecting survival (P?400?ng/ml and tumor grade G3.

Conclusions

Tumor size and VI were the only significant prognostic factors affecting survival of HCC patients. Primary liver resection could be a potential selection treatment before LT.     

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.     

The Clinical Behavior of Transplantable Recurrent Hepatocellular Carcinoma After Curative Resection: Implications for Salvage Liver Transplantation

Background

This study aimed to classify transplantable recurrent hepatocellular carcinoma (HCC) after resection into subgroups according to the pattern of progression and to identify risk factors for each subgroup to select optimal candidates for salvage liver transplantation (LT).

Methods

The patients that met the Milan criteria (MC) and were child-pugh class A at initial hepatectomy were included in the study. Of these patients, the patients with transplantable recurrence were identified and further divided into two groups according to the recurrent HCC progression pattern. Group 1 contained patients with controlled tumors within the MC. Group 2 contained patients with progressive tumors that spread beyond the MC. A controlled tumor was defined as the absence of tumor recurrence after locoregional treatment for ≥12 months or control of a recurrent tumor within the MC by active locoregional treatment.

Results

After curative resection of HCC, 114 patients with transplantable recurrence were identified: 70 were classified as group 1 and 44 as group 2. Overall survival after recurrence was significantly higher in group 1 compared to group 2 (65.4 vs 35.7 %, respectively; P < 0.003). Multiple logistic regression analysis showed that risk factors in group 1 were age >50 years and an indocyanine green retention at 15 min >10 %. The presence of a satellite nodule (SN) and/or microscopic portal vein invasion (mPVI) was the only independent risk factor identified in group 2. Among the 15 patients that underwent salvage LT, 2 of 3 patients (66.7 %) with SN and/or mPVI at initial hepatectomy developed extrahepatic recurrence.

Conclusions

The patients with SN and/or mPVI at initial hepatectomy may not be candidates for salvage LT, and an extended observation time is required to determine tumor biology.     

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.     

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.     

The Postresection Alpha-Fetoprotein in Cirrhotic Patients with Hepatocellular Carcinoma. An Independent Predictor of Outcome

Background

The postresection alpha-fetoprotein (AFP) in cirrhotic patients with hepatocellular carcinoma (HCC) may predict overall survival (OS) and recurrence beyond Milan criteria (MC) among the subgroup of initially transplantable patients.

Methods

All patients with cirrhosis resected for HCC between January 1990 and December 2010 in a single institution and presenting a serum AFP value?>?15 ng/ml at diagnosis were included. The postresection AFP was analyzed as a dichotomized variable: normalization (norm + group) or not (norm ? group) within the 90-day postresection period.

Results

Among 271 resected patients, 141 patients (52 %) had a level of serum AFP?≥?15 ng/ml at diagnosis. Five-year OS and median survival were 42 % and 52 months in group norm + versus 20 % and 23 months in the group norm ? (P?=?0.009). On multivariate analysis, the absence of AFP normalization was an independent factor of poor OS as well as microvascular invasion, and satellites nodules. Among theoretically transplantable patients, independent predictors of recurrence beyond MC were the absence of AFP normalization (risk ratio (RR) 5.02 [1.53–16.34]) and microvascular invasion (RR 4.76 [1.42–15.34]).

Conclusion

The postresection AFP has an independent prognostic value. Transplantable patients resected for HCC without 90-day AFP normalization should be discussed for early liver transplantation.     

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.     

Total Tumor Volume Is a Better Marker of Tumor Burden in Hepatocellular Carcinoma Defined by the Milan Criteria

Background

The Milan criteria are used to define small hepatocellular carcinoma (HCC) and to select patients for curative treatments. Total tumor volume (TTV) is an alternative parameter for tumor burden. We aimed to evaluate whether TTV is a feasible prognostic marker in HCC patients with upper boundary TTV of 65.5 cm³, which is equivalent to a single 5 cm tumor nodule defined by the Milan criteria.

Methods

A total of 774 HCC patients with TTV <65.5 cm³ receiving surgical resection, liver transplantation, or radiofrequency ablation (RFA) as the primary treatment were retrospectively analyzed.

Results

Of these patients, 50 (6.5 %) did not fulfill the Milan criteria. Patients beyond the Milan criteria more often had larger tumor size and TTV, as well as more tumor nodules (p values all <0.01). There was no significant survival difference between patients within and beyond the Milan criteria (p = 0.205). Patients with TTV >15 cm³ had a significantly poorer survival than patients with TTV <15 cm³ (p = 0.007). There was no survival difference between patients receiving surgical treatments versus RFA (p = 0.932). In the Cox proportional hazards model, TTV >15 cm³ [risk ratio (RR): 1.474, p = 0.005], serum bilirubin ≥1.5 mg/dL (RR: 1.663, p = 0.003), serum sodium <135 mmol/L (RR: 2.016, p = 0.01), and α-fetoprotein (AFP) ≥100 ng/mL (RR: 1.37, p = 0.033) were independent predictors of poor prognosis.

Conclusions

Total tumor volume, is an independent and better prognostic marker than the Milan criteria to indicate tumor burden in HCC patients who had tumor volume defined by the Milan criteria and underwent curative therapies.     

The Significance of Classifying Microvascular Invasion in Patients with Hepatocellular Carcinoma

Background

Microvascular invasion (MVI) has been recognized as a risk factor for outcome following curative resection in hepatocellular carcinoma (HCC). Because MVI can range from few to many invaded vessels, we evaluated the significance of MVI classification in this study.

Methods

Between January 1995 and December 2010, 207 consecutive patients who underwent curative resection for HCC within Milan criteria were included in this retrospective study. Patients were classified into mild and severe MVI groups based on the number of vessels invaded. This study evaluated whether MVI classification can help to predict recurrence and survival after curative resection.

Results

Of the total 207 patients, 103 (50 %) patients had no detectable MVI, whereas 59 (28 %) had mild MVI, and 45 (22 %) had severe MVI. Recurrence-free survival rates at 2 years for patients without MVI, with mild MVI, and severe MVI were 75.9, 47.2, and 32.7 %, respectively. Patients with severe MVI experienced a high frequency of fatal recurrence, such as multiple tumors, macroscopic vascular invasion, and extrahepatic metastasis after curative resection. Multivariate analysis revealed age, number of tumors, mild MVI, and severe MVI as independent predictors of recurrence-free survival. Disease-specific survival rates at 5 years for patients without MVI, with mild MVI, and severe MVI were 91.5, 70.4, and 51.4, respectively. Multivariate analysis also revealed cirrhosis, tumor size, mild MVI, and severe MVI as independent predictors of disease-specific survival.

Conclusions

We demonstrated that MVI classification can stratify HCC patients by different patterns of recurrence and risk of survival after curative resection.     

Locoregional Therapy-Induced Tumor Necrosis as a Predictor of Recurrence after Liver Transplant in Patients with Hepatocellular Carcinoma

Background

Patients with hepatocellular carcinoma (HCC) often undergo locoregional therapy before liver transplant either to downstage the tumor or as bridge therapy. Our goal was to assess the risk factors for posttransplant tumor recurrence, specifically the extent of necrosis induced by locoregional therapy.

Methods

We conducted a hospital-based retrospective analysis of 100 patients with HCC who received a liver transplant, 86 of whom had received pretransplant locoregional therapy. We evaluated various patient- and tumor-related parameters to determine the risk factors for recurrence. Furthermore, we grouped patients by the degree of tumor necrosis after locoregional therapy and identified the factors that were associated with a favorable tumor response.

Results

Initial tumor extent beyond the University of San Francisco (UCSF) criteria, microvascular invasion, and attainment of less than 90% tumor necrosis after locoregional therapy were independent risk factors for tumor recurrence. In addition, there was a significant correlation between the tumor necrosis percentage and disease-specific survival rate. Among patients whose tumors initially exceeded the UCSF criteria, those with extensive locoregional therapy-induced tumor necrosis had lower recurrence rates. All recurrences after transplant occurred within 3 years, and recurrence rates in patients with extensive tumor necrosis at 1, 2, and 3 years were 3%, 6%, and 10%, respectively. Female gender and a solitary tumor were independently associated with extensive tumor necrosis.

Conclusions

In HCC patients who are transplant candidates and undergo pretransplant locoregional therapy, the degree of induced tumor necrosis affects both tumor recurrence and survival rate.     

Performance Status Enhances the Selection of Treatment for Patients with Hepatocellular Carcinoma Within the Milan Criteria

Background

Performance status (PS) is closely linked with survival in patients with hepatocellular carcinoma (HCC). We investigated its impact on treatment strategy for small HCC(s).

Methods

A total of 360 and 362 HCC patients within the Milan criteria undergoing surgical resection (SR) and radiofrequency ablation (RFA), respectively, were prospectively enrolled. Patients were classified into PS 0 (n = 558) and PS ≥1 (n = 164) groups. Propensity score analysis was performed, and 168 and 35 matched pairs were selected from patients with PS 0 and ≥1, respectively.

Results

The SR group was younger and had a higher male-to-female ratio, higher prevalence of hepatitis B, lower prevalence of hepatitis C, better PS, better liver functional reserve, and larger tumor burden than the RFA group (all p < 0.05). Among patients with PS 0, the SR group was consistently younger, less cirrhotic, and had larger tumor burden (all p < 0.05). The long-term survival was comparable between SR and RFA group in patients with PS 0. After propensity score matching, SR provided significantly better long-term survival than RFA for patients within the Milan criteria classified as PS 0 (p = 0.016); the Cox proportional hazards model showed consistent results. There was no significant difference of overall survival between the SR and RFA group in patients with PS ≥1 before or after propensity score matching (both p > 0.05).

Conclusions

For HCC patients within the Milan criteria and classified as PS 0, SR provides a better long-term survival compared with RFA. Performance status may enhance treatment selection and stratify the risk of survival in these patients.     

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.

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.     

Effects of Genomic Changes in Hepatitis B Virus on Postoperative Recurrence and Survival in Patients with Hepatocellular Carcinoma

Purpose

To determine whether the genomic changes in hepatitis B virus (HBV) affect the clinical outcomes of hepatocellular carcinoma (HCC) in patients with HBV-associated HCC treated with curative surgical resection.

Methods

A total of 247 patients with HBV-associated HCC were treated with curative surgical resection. They were followed regularly for a median of 30 months. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced.

Results

The genomic changes such as the G1896A at precore, the A1762T/G1764A at BCP, the C1653T and the T1753V at X gene, and pre-S2 deletion were not significantly associated with postoperative recurrence of HCC or survival of patients after curative resection. However, in univariate analysis, younger age, elevated serum α-fetoprotein level, elevated serum alanine aminotransferase level, larger tumor size, microvascular invasion, and advanced Cancer of the Liver Italian Program stage were closely associated with shorter survival after surgical resection. In multivariate analysis, only microvascular invasion revealed to be an independent risk factor of postoperative recurrence (relative risk [RR] 5.406; P < 0.001); the independent risk factors of shorter survival appeared to be infiltrative type (RR 5.110; P = 0.032), larger tumor size (RR 1.976; P = 0.047), and microvascular invasion (RR 6.118; P < 0.001).

Conclusions

The postoperative recurrence or survival period may not be affected by the genomic changes at the precore, BCP, X, and pre-S2 regions in HBV of genotype C2 in patients with HBV-associated HCC treated with curative surgical resection. Rather, it may be closely associated with tumor characteristics, such as the size and type of HCC or presence of microvascular invasion.     

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.     

High risk of lung metastasis after resection of hepatocellular carcinoma more than 7 cm in diameter

Purpose

The relationship between the tumor size and organs of recurrence was analyzed to identify a high-risk group for the extrahepatic recurrence of hepatocellular carcinoma (HCC) after resection.

Methods

A total of 544 patients with HCC underwent primary surgical resection for HCC between 2001 and 2010. Of these, 293 patients had a solitary tumor but no macroscopic vascular invasion. The prognostic factors for the overall survival and relapse-free survival were analyzed among these 293 patients. The recurrent organs and frequency of recurrence were also examined.

Results

The analysis of the 293 patients showed that both the overall and relapse-free survival rates of the patients with a large tumor (>7 cm in diameter) were significantly worse than those of the patients with a tumor <7 cm. The incidence of lung metastasis was remarkably high in the group of patients with tumors more than 7 cm (24.0 %), in comparison to those with tumors <7 cm. A multivariate analysis revealed that the tumor size was the only independent risk factor for lung metastasis.

Conclusions

The patients with large HCC tumors more than 7 cm in diameter were at high-risk for a poor prognosis due to a high percentage of lung metastasis, even if there was no macroscopic vascular invasion.     

Protein Induced by Vitamin K Antagonist-II (PIVKA-II) Is a Reliable Prognostic Factor in Small Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) <2 cm in diameter has a favorable prognosis. Therefore surgical resection of small HCC is associated with good outcomes. However, the predisposing factors of prognosis following resection of HCC remain ill-defined. The aims of the present study were to identify the clinicopathologic characteristics and outcomes of patients with small HCC and analyze the predisposing factors for tumor recurrence after surgery.

Methods

We retrospectively reviewed 180 patients with small HCC who underwent hepatectomy between 2006 and 2010. Independent predictors of tumor recurrence were identified with Cox regression analysis.

Results

The 1-year, 3-year, and 5-year disease-free survival rates and overall survival rates were 83.7, 68.0, 65.3, and 98.9, 96.5, 92.7 %, respectively. Multivariate analysis reported that protein induced by the vitamin K antagonist-II (PIVKA-II) ≥200 mAU/mL, alkaline phosphatase (ALP) ≥80 IU/mL, and microvascular invasion were important predisposing factors for tumor recurrence. Elevated serum PIVKA-II level was associated with microvascular invasion in small HCC, which was a powerful predisposing factor.

Conclusions

Although small HCC is generally associated with a good prognosis, serum PIVKA-II level ≥200 mAU/mL, ALP ≥ 80 IU/L, and microvascular invasion were predisposing factors for tumor recurrence. These factors can be used to stratify patients with respect to recurrence after resection. Elevated PIVKA-II was closely associated with microvascular invasion in small HCC. These data emphasize the importance of PIVKA-II in small HCC.