Des-gamma-carboxy prothrombin as an important prognostic indicator in patients with small hepatocellular carcinoma

AIM：To clarify the effect of a high des-gamma-carboxy prothrombin （DCP） level on the invasiveness and prognosis of small hepatocellular carcinoma.
METHODS： Among 142 consecutive patients with known DCP levels, who underwent hepatectomy because of hepatocellular carcinoma, 85 patients met the criteria for small hepatocellular carcinoma, i.e. one ≤ 5 cm sized single tumor or no more than three ≤ 3 cm sized tumors.
RESULTS： The overall survival rate of the 142 patients was 92.1% for 1 year, 69.6% for 3 years, and 56.9% for 5 years. Multivariate analysis showed that microscopic vascular invasion （P = 0.03） and serum DCP ≥ 400 mAU/mL （P = 0.02） were independent prognostic factors. In the group of patients who met the criteria for small hepatocellular carcinoma, DCP ≥ 400 mAU/mL was found to be an independent prognostic factor for recurrence-free （P = 0.02） and overall survival （P = 0.0005）. In patients who did not meet the criteria, the presence of vascular invasion was an independent factor for recurrence-free （P = 0.02） and overall survivals （P = 0.01）. In 75% of patients with small hepatocellular carcinoma and high DCP levels, recurrence occurred extrahepatically.
CONCLUSION： For small hepatocellular carcinoma, a high preoperative DCP level appears indicative fortumor recurrence. Because many patients with a high preoperative DCP level develop extrahepatic recurrence, it is necessary to screen the whole body.     

Long-term outcomes of hepatectomy vs percutaneous ablation for treatment of hepatocellular carcinoma ≤4 cm

AIM: To determine which treatment modality -hepatectomy or percutaneous ablation - is more beneficial for patients with small hepatocellular carcinoma (HCC) (≤ 4 cm) in terms of long-term outcomes.METHODS: A retrospective analysis of 149 patients with HCC ≤4 cm was conducted. Eighty-five patients underwent partial hepatectomy (anatomic in 47 and nonanatomic in 38) and 64 underwent percutaneous ablation (percutaneous ethanol injection in 37, radiofrequency ablation in 21, and microwave coagulation in 6). The median follow-up period was 69 mo.RESULTS: Hepatectomy was associated with larger tumor size (P＜0.001), whereas percutaneous ablation was significantly associated with impaired hepatic functional reserve. Local recurrence was less frequent following hepatectomy (P＜ 0.0001). Survival was better following hepatectomy (median survival time:122 mo) than following percutaneous ablation (median survival time: 66 mo; P=0.0123). When tumor size was divided into ≤ 2 cm vs ＞ 2 cm, the favorable effects of hepatectomy on long-term survival was seen only in patients with tumors ＞2 cm (P= 0.0001). The Cox proportional hazards regression model revealed that hepatectomy (P= 0.006) and tumors ≤ 2 cm (P= 0.017) were independently associated with better survival.CONCLUSION: Hepatectomy provides both better local control and better long-term survival for patients with HCC ≤4 cm compared with percutaneous ablation. Of the patients with HCC ≤ 4 cm, those with tumors ＞ 2 cm are good candidates for hepatectomy, provided that the hepatic functional reserve of the patient permits resection.     

Prediction of recurrence of hepatocellular carcinoma after curative hepatectomy using preoperative Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein

Aim: Lens culinaris agglutinin A‐reactive fraction of α‐fetoprotein (AFP‐L3) status has been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). In this study, we evaluated the clinical usefulness of measuring preoperative AFP‐L3 to predict the recurrence and prognosis of HCC after curative hepatectomy. Methods: One hundred and forty‐two HCC patients who underwent curative hepatectomy were examined for the correlation between preoperative tumor marker, including AFP, des‐γ‐carboxy prothrombin (DCP) and AFP‐L3, and clinicopathological variables. The prognostic factors of disease‐free survival rates and overall survival rates were also determined using clinicopathological variables including these three tumor markers. Results: There were similar tendencies in the relationship between these three markers and malignant behaviors including lower grade tumor differentiation or vascular invasion. In multivariate analysis, increased AFP‐L3 value (P = 0.019) was found to be an independent prognostic factor of disease‐free survival after curative hepatectomy. In addition, elevated DCP (P = 0.013) and AFP‐L3 values (P = 0.012) were found to be independent prognostic factors. Furthermore, the preoperative AFP‐L3 value in the patients with early recurrence (within 1 year after hepatectomy) was significantly higher than that in those without early recurrence (26.9 ± 19.5 % vs 14.2 ± 19.8 %, P = 0.047). Conclusion: Preoperative AFP‐L3 value was strongly correlated to disease‐free and overall survival rate and the timing of recurrence, so it appears that it would be useful to predict the recurrence and prognosis of HCC after curative hepatectomy.     

Prognostic value of pretreatment levels of tumor markers for hepatocellular carcinoma on survival after curative treatment of patients with HCC

BACKGROUND/AIMS: We evaluated the prognostic value of the pretreatment elevation of tumor markers for hepatocellular carcinoma (HCC) in patients who underwent curative treatment. METHODS: We studied 801 patients who had been diagnosed as initial HCC and fulfilled the following criteria: maximum tumor size, < or = 3 cm; number of tumors, < or = 3; remnant liver function, Child-Pugh class A or B; treated by hepatectomy or locoregional thermal ablation (LTA); and alpha-fetoprotein (AFP), Lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma carboxy prothrombin (DCP) were measured at diagnosis. We analyzed the effects of elevated tumor markers on patient survival in these 2 distinct groups with different types of treatment, i.e. hepatectomy and LTA. RESULTS: By multivariate analysis in 345 patients who underwent hepatectomy, no tumor marker significantly affected decreased survival rate. In the 456 patients who underwent LTA, the elevation of AFP-L3 (p=0.0171) and DCP (p=0.0004) significantly affected decreased survival rate; DCP elevation had the strongest effect on patient survival. CONCLUSIONS: The prognostic value of pretreatment tumor marker elevation was different in patients who underwent the curative treatment according to the type of treatment. Pretreatment elevation of AFP-L3 and DCP had prognostic values only in patients treated with LTA.     

应用米兰标准微波消融治疗肝细胞癌患者预后及其影响因素分析*

目的 探讨应用米兰标准施行微波消融术(MWA)治疗肝细胞癌(HCC)患者影响生存的因素。方法 2013年1月～2016年12月我院消化内科住院的94例直径≤5 cm的HCC患者接受超声引导下MWA治疗,随访5年。分析不同HCC结节个数和不同肿瘤直径对总生存率(OS)和无进展生存率(PFS)的影响。结果 随访5年,本组HCC患者OS为64.9%,1 a和2 a 肿瘤复发率分别为12.8%和53.2%;HCC直径> 3 cm患者的PFS显著短于直径≤3 cm的患者(P=0.005),PFS≤2年的HCC患者OS显著低于PFS> 2年的患者(48.0%对 84.1%,P<0.001);多因素回归分析显示HCC直径> 3 cm (HR=0.42,95%CI:0.21～0.83,P=0.01)是MWA术后肿瘤复发的独立危险因素,而白细胞计数< 4.0×10⁹ /L (HR=0.38, 95%CI:0.18～0.84,P=0.017)和PFS≤2 年(HR=0.24, 95%CI:0.10～0.56,P=0.001)是影响HCC患者OS的独立危险因素。结论 直径> 3 cm的HCC患者PFS较短,但似乎不影响OS,因为大多数肝内复发的HCC患者仍然可进行重复MWA治疗。     

Usefulness of serum des-γ-carboxy prothrombin in detection of hepatocellular carcinoma

AIM: To evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC. METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with non-cirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL, respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay. RESULTS: The accuracy, sensitivity, and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77%, and 86.4% re 68.5%, 59%, and 77.3%, respectively). The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CI, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81], P= 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and 50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%, and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm. CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.     

Usefulness of serum des-γ-carboxy prothrombin in detection of hepatocellular carcinoma

AIM: To evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC.METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with noncirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL,respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay.RESULTS: The accuracy, sensitivity, and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77%,and 86.4% vs 68.5%, 59%, and 77.3%, respectively).The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CT, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81],P = 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%,and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm.CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.     

Clinical significance of half‐lives of tumor markers α‐fetoprotein and des‐γ‐carboxy prothrombin after hepatectomy for hepatocellular carcinoma

Aim

The prognostic significance of the half‐lives (HLs) of α‐fetoprotein (AFP) and des‐γ‐carboxy prothrombin (DCP) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) is unclear. We evaluated the HLs of AFP and DCP in a cohort of such patients.

Methods

This study included data on 202 patients with HCC who underwent curative hepatectomy and had preoperative AFP concentrations ≥100 ng/mL or DCP ≥200 mAU/mL. We calculated the HLs of AFP and DCP from their values just before and 1 month after hepatectomy. We identified three groups: a normalization group, tumor marker concentrations within normal range 1 month post‐hepatectomy; a long group, HL of AFP ≥7 days or DCP ≥4 days; and a short group, remaining patients. We evaluated associations between HL and prognosis.

Results

Three‐year recurrence‐free survival (RFS) in the normalization (n = 70), short (n = 71), and long groups (n = 61) was 41.3%, 46.0%, and 16.8%, respectively (P = 0.002). Five‐year overall survival (OS) of normalization, short, and long groups was 72.6, 70.6 and 43.8%, respectively (P = 0.002). Multivariate analysis revealed that long HL is an independent risk factor for poor RFS (hazard ratio [HR] 2.21, P = 0.0006) and poor OS (HR 2.70, P = 0.004). The extrahepatic recurrence rate was 21.3% (13/61) in the long group, which is higher than in the normalization group (8.6%, 6/70) (P = 0.04) and short group (9.9%, 7/71) (P = 0.07).

Conclusion

Post‐hepatectomy HLs of AFP and DCP are predictors of long‐term outcome in patients with HCC.     

Usefulness of serum des-γ-carboxy prothrombin in detection of hepatocellular carcinoma

AIM: Des-gamma-carboxy prothrombin (DCP) has been reported to be more sensitive and specific in diagnosing hepatocellular carcinoma (HCC) when compared with alpha-fetoprotein (AFP). However, its ability to identify small HCC still remains unclear. Thus, we conducted a cross-sectional case control study to evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC. METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with non-cirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL, respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay. RESULTS: The accuracy, sensitivity and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77% and 86.4% vs 68.5%, 59% and 77.3%, respectively). The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CI, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81], P = 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and 50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%, and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm. CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.     

Long-term outcomes of hepatectomy vs percutaneous ablation for treatment of hepatocellular carcinoma ≤ 4 cm

AIM: To determine which treatment modality--hepatectomy or percutaneous ablation--is more beneficial for patients with small hepatocellular carcinoma (HCC) (< or =4 cm) in terms of long-term outcomes. METHODS: A retrospective analysis of 149 patients with HCC < or =4 cm was conducted. Eighty-five patients underwent partial hepatectomy (anatomic in 47 and non-anatomic in 38) and 64 underwent percutaneous ablation (percutaneous ethanol injection in 37, radiofrequency ablation in 21, and microwave coagulation in 6). The median follow-up period was 69 mo. RESULTS: Hepatectomy was associated with larger tumor size (P<0.001), whereas percutaneous ablation was significantly associated with impaired hepatic functional reserve. Local recurrence was less frequent following hepatectomy (P<0.0001). Survival was better following hepatectomy (median survival time: 122 mo) than following percutaneous ablation (median survival time: 66 mo; P=0.0123). When tumor size was divided into < or =2 cm vs >2 cm, the favorable effects of hepatectomy on long-term survival was seen only in patients with tumors>2 cm (P=0.0001). The Cox proportional hazards regression model revealed that hepatectomy (P=0.006) and tumors < or =2 cm (P=0.017) were independently associated with better survival. CONCLUSION: Hepatectomy provides both better local control and better long-term survival for patients with HCC < or =4 cm compared with percutaneous ablation. Of the patients with HCC < or =4 cm, those with tumors >2 cm are good candidates for hepatectomy, provided that the hepatic functional reserve of the patient permits resection.     

Des-gamma-carboxy prothrombin (DCP) ratio is a useful prognostic tumor marker for single nodule hepatocellular carcinoma (HCC)

BACKGROUND/AIMS: Des-gamma-carboxy prothrombin (DCP) is measured by an enzyme immunoassay system with the monoclonal antibody MU-3. A novel DCP antibody named 19B7 recognizes a different epitope against the Gla domain of DCP measured by the MU-3 antibody. Therefore, it is possible that DCP variants can be measured with these two antibodies. The aim of this study was to elucidate the usefulness of the DCP ratio as a new prognostic parameter for patients with hepatocellular carcinoma (HCC). METHODOLOGY: One hundred and eighty-three patients with HCC were enrolled in the current study. The DCP ratio was calculated using the formula: DCP ratio = DCP level measured by the MU-3 (mAU/mL) / DCP level measured by the 19B7 (mAU/mL). RESULTS: There was no statistical correlation between DCP level measured by MU-3 antibody and DCP ratio. Clinical stage, tumor type, portal tumor thrombus and DCP were independent factors in the multivariate analysis for survival of 183 patients. In 67 patients with single nodule HCC, clinical stage and DCP ratio were independent factors in the multivariate analysis for survival rate. CONCLUSIONS: The most useful prognostic tumor marker was the DCP in the 183 HCC patients and the DCP ratio in single nodule HCC.     

Comparison of clinicopathological features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein alone and those seropositive for des-gamma-carboxy prothrombin alone

BACKGROUND: There has been no comparative study of the clinicopathological features of HCC patients who are seropositive for alpha-fetoprotein (AFP) alone and those who are seropositive for des-gamma-carboxy prothrombin (DCP) alone. The authors, thus, performed this comparative study. METHODS: The clinicopathological features of patients with solitary hepatocellular carcinoma (HCC), who underwent a hepatectomy were compared among the four below groups according to the seropositivity of AFP and DCP: group A, seronegative for both AFP below 20 ng/mL and DCP below 40 mAU/mL; group B, seropositive for AFP above 100 ng/mL and seronegative for DCP; group C, seronegative for AFP and seropositive for DCP above 100 mAU/mL; and group D, seropositive for both AFP and DCP. RESULTS: Group B patients showed a higher incidence of HCC with an indistinct margin, and a somewhat higher incidence of small HCC less than 2 cm in greatest dimension compared with group C patients. By contrast, group C patients had a higher frequency of HCC with a distinct margin compared with that of an indistinct margin, large tumors more than 3 cm compared with that of small tumors less than 2 cm, and a somewhat higher frequency of moderately to poorly differentiated HCC compared with that of well-differentiated HCC. Our HCC cases showed advanced clinicopathological features in the order of group C, group B and group A. Groups C and D patients showed similar characteristics. CONCLUSIONS: Hepatocellular carcinoma patients who were seropositive for AFP alone demonstrated clinicopathological features of less advanced HCC compared with those who were seropositive for DCP alone.     

The role of des-gamma-carboxyprothrombin expression in hepatocellular carcinoma

BACKGROUND/AIMS: Des-gamma-carboxyprothrombin (DCP), is a well-known tumor marker of hepatocellular carcinoma (HCC). On the other hand, some reports suggest that tissue expression of DCP is more useful as a prognostic factor than the serum DCP value. The aim of this study is to clarify the clinicopathological role of expression of DCP on HCC, especially when there is a low serum level of DCP. METHODOLOGY: Fifty-one patients with HCC who underwent curative hepatectomy were included in this study. Immunohistochemical staining was performed using anti-DCP monoclonal antibody, which was classified into 2 groups (strong and weak) by a pathologist. The immunohistochemical expression of tumor microvessel density (MVD) was evaluated using CD34 monoclonal antibody, and counted with specific staining of the capillary-like vessels in the tumor. The clinicopathological variables were compared between the strong and weak-staining groups. RESULTS: A strong DCP expression was recognized in 31 patients. DCP expression was associated with tumor size (p < 0.05) and portal vein infiltration (p < 0.01). In addition, serum DCP levels and alpha-fetoprotein levels tended to be higher in the strong group. In 16 patients whose serum DCP level was < 200mAU/ml, the recurrence-free survival rate was significantly lower in the strong group. No correlation was observed between DCP expression and MVD. CONCLUSIONS: DCP expression in HCC is useful for the prediction of early recurrence in patients with a low serum DCP level.     

Adjuvant hepatic arterial infusion chemotherapy after radical hepatectomy for hepatocellular carcinoma--results of long-term follow-up.

BACKGROUND/AIMS: This clinical study aimed to clarify the effectiveness and indication of adjuvant hepatic arterial infusion chemotherapy (HAIC) that is performed to prevent recurrence after radical hepatectomy for hepatocellular carcinoma (HCC). METHODOLOGY: From January 1986 to December 1992, 135 HCC patients, who tolerated curative hepatic resection in which all of the macroscopic HCC was removed, were included in this study. They were divided into two groups. One group was comprised of 68 patients who received HAIC after radical hepatectomy (HAIC (+) group), and the other group was comprised of 67 patients who received radical hepatectomy alone (HAIC (-) group). In the HAIC (+) group, an emulsion of doxorubicin (30-50 mg) and lipiodol (3-5 ml) was injected from a reservoir every 2 or 3 months for 1 year. RESULTS: The cumulative survival rates in the HAIC (+) group (79.1%, 54.5% and 39.9% at 3, 5, and 7 years after hepatectomy, respectively) were better than those in the HAIC (-) group (69.2%, 38.1% and 26.8%, respectively) (p = 0.086). The disease-free survival rates in the HAIC (+) group (50.8%, 31.7% and 25.6% at 3, 5, and 7 years after hepatectomy, respectively) were significantly better than those in the HAIC (-) group (25.7%, 20.6% and 6.4%, respectively) (p = 0.006). This improvement was evident for 3 years after hepatectomy. The adjuvant HAIC was effective especially in patients with good liver function, whose tumor size ranged between 2.1 cm and 5 cm in diameter, and who received a minor hepatic resection. CONCLUSIONS: Adjuvant HAIC was effective in preventing recurrence after radical hepatectomy for HCC. This treatment is especially indicated for patients with good liver function, whose tumor size ranges between 2.1 cm and 5 cm in diameter, and who have received a minor hepatic resection.     

Clinicopathologic features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein-L3 and seronegative for des-gamma-carboxy prothrombin in comparison with those seropositive for des-gamma-carboxy prothrombin alone

BACKGROUND: There has been no study of the clinicopathologic features of patients with hepatocellular carcinoma (HCC) who are seropositive for lectin-reactive alpha-fetoprotein (AFP-L3) alone, or seropositive for AFP-L3 and seronegative for des-gamma-carboxy prothrombin (DCP) in comparison with those who are seropositive for DCP alone. Thus, the present comparative study was performed. METHODS: The clinicopathologic features of HCC patients with either one or two tumors who underwent a hepatectomy (n = 88) were compared among the following five groups according to the seropositivity of AFP, AFP-L3 and DCP: (i) group A, seropositive for AFP above 100 ng/mL, AFP-L3 above 15% and DCP above 100 mAU/mL; (ii) group B, seropositive for AFP-L3 and seronegative for DCP below 40 mAU/mL; (iii) group C, seronegative for AFP below 20 ng/mL, AFP-L3 below 15% and seropositive for DCP; (iv) group D, seropositive for AFP and seronegative for AFP-L3 and DCP; and (v) group E, seronegative for AFP, AFP-L3 and DCP. RESULTS: Group B patients showed a higher incidence of infiltrative-type HCC with an irregular margin (P < 0.05) and a higher frequency of poorly differentiated HCC (P < 0.01) compared with group C patients. Group A patients had larger tumors and more massive-type tumors than group B patients. Our HCC cases showed that advanced clinicopathologic features were demonstrated in the order of group B, group C and group D. Group A and B patients and group D and E patients showed similar characteristics. CONCLUSIONS: Hepatocellular carcinoma patients who were seropositive for AFP-L3 and seronegative for DCP demonstrated clinicopathologic features of more advanced HCC compared with those who were seropositive for DCP alone.     

Is inconsistency of α-fetoprotein level a good prognosticator for hepatocellular carcinoma recurrence?

AIM: To identify the clinical outcomes of hepato-cellular carcinoma (HCC) patients with inconsistent α-fetoprotein (AFP) levels which were initially high and then low at recurrence.METHODS: We retrospectively included 178 patients who underwent liver resection with high preoperative AFP levels (≥ 200 ng/dL). Sixty-nine HCC patients had recurrence during follow-up and were grouped by their AFP levels at recurrence: group Ⅰ, AFP ≤ 20 ng/dL (n = 16); group Ⅱ, AFP 20-200 ng/dL (n = 24); and group Ⅲ, AFP ≥ 200 n...     

Recurrence of primary hepatocellular carcinoma after hepatectomy--differences related to underlying hepatitis virus species

BACKGROUND/AIMS: Studies on post-hepatectomy prognoses by infecting viral species have only been rarely reported. METHODOLOGY: The patients who had undergone hepatectomy for primary hepatocellular carcinoma (HCC) over the past 10 years at our hospital were divided into three groups based on their underlying causal diseases: hepatitis B (B type), hepatitis C (C type), and non-viral hepatitis including alcoholic hepatitis, and their backgrounds and long-term results after hepatectomy were comparatively investigated. RESULTS: As for tumor factors, the tumor diameter was 3.7+/-2.1 cm in C type patients, which was significantly smaller than the 5.2+/-3.3 cm diameter in B type patients (p=0.01) and 7.9+/-5.6 cm in non-viral patients (p=0.001). However, the frequencies of intrahepatic metastasis, portal vein infiltration, capsule formation and capsule infiltration did not differ significantly among the three groups. Although there was no significant difference observed among the three groups for the recurrence-free survival time, HCC had recurred at as early a stage as within 1 postoperative year in 50% of non-viral patients. CONCLUSIONS: The size of a tumor upon hepatectomy and the presence or absence of intrahepatic metastasis were found to be significant factors contributing to the postoperative recurrence of HCC. It is possible that the recurrence-free postoperative survival time may be prolonged by earlier detection of HCC, particularly for the B type and the non-viral type in which the tumor size was already large at the time of surgery.     

Alpha-fetoprotein has no prognostic role in small hepatocellular carcinoma identified during surveillance in compensated cirrhosis

Alpha-fetoprotein is a tumor marker that has been used for surveillance and diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. The prognostic capability of this marker in patients with HCC has not been clearly defined. In this study our aim was to evaluate the prognostic usefulness of serum alpha-fetoprotein in patients with well-compensated cirrhosis, optimal performance status, and small HCC identified during periodic surveillance ultrasound who were treated with curative intent. Among the 3,027 patients included in the Italian Liver Cancer study group database, we selected 205 Child-Pugh class A and Eastern Cooperative Group Performance Status 0 patients with cirrhosis with a single HCC ≤3 cm of diameter diagnosed during surveillance who were treated with curative intent (hepatic resection, liver transplantation, percutaneous ethanol injection, radiofrequency thermal ablation). Patients were subdivided according to alpha-fetoprotein serum levels (i.e., normal ≤20 ng/mL; mildly elevated 21-200 ng/mL; markedly elevated >200 ng/mL). Patient survival, as assessed by the Kaplan-Meier method, was not significantly different among the three alpha-fetoprotein classes (P = 0.493). The same result was obtained in the subgroup of patients with a single HCC ≤2 cm (P = 0.714). An alpha-fetoprotein serum level of 100 ng/mL identified by receiver operating characteristic curve had inadequate accuracy (area under the curve = 0.536, 95% confidence interval = 0.465-0.606) to discriminate between survivors and deceased patients. Conclusion: Alpha-fetoprotein serum levels have no prognostic meaning in well-compensated cirrhosis patients with single, small HCC treated with curative intent. (HEPATOLOGY 2012).     

Undetected hepatocellular carcinoma in patients undergoing liver transplantation: is associated with favorable outcome

BACKGROUND/AIMS: The aim of the study was to define the clinical characteristics and outcome of patients found to have undetected hepatocellular carcinomas (HCC) at liver transplantation. Patients who underwent liver transplantation and were unexpectedly found to have a HCC despite prior workup showing normal alpha-fetoprotein levels and/or no visible radiological lesion were defined as having an undetected HCC. METHODOLOGY: Thirty-two of these patients had a histological diagnosis of HCC in the explanted liver. Undetected HCC was defined as a carcinoma found only on pathological evaluation of the explanted liver, with a pre-OLT workup showing a normal serum alpha-fetoprotein (AFP) level (<20 ng/mL) and/or no suspicious lesion on preoperative radiological evaluation. RESULTS: Nine patients had a tumor that met the criteria for an undetected HCC. The most common cause for transplantation was cryptogenic cirrhosis (44.4%). Tumor size was 2 cm or less in all patients, vascular invasion was detected in 11.1% of the patients, and tumor, node, metastasis (TNM) classification was stage I in 77.8%. Eight patients (88.9%) remained alive at the cessation of the analysis with a mean follow-up of 60 +/- 30.4 months. There was no tumor recurrence in any patient. Statistical analysis showed significant differences between undetected and detected HCCs when causes of pretransplantation liver disease, peak AFP level, tumor size, number of tumors, presence of vascular invasion or pathological differentiation were compared. Undetected HCCs were associated with a better survival rate after liver transplantation (p = 0.008). CONCLUSIONS: Patients with undetected HCCs at OLT have a favorable outcome with tumor-free survival. Most patients had small, early-stage HCCs, but the possibility of finding tumors greater than 2 cm, multifocal lesions, and vascular invasion exist despite thorough investigation. An exhaustive histopathological search of the explant for malignancy will allow for greater accuracy in prognosis.     

The Relationship Between Serum Interleukin-6 and the Recurrence of Hepatitis B Virus Related Hepatocellular Carcinoma after Curative Resection

The aim of this study is to assess whether preoperative serum interleukin-6 (IL-6) can predict recurrence of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).The association between preoperative IL-6 levels and HCC recurrence following curative hepatectomy in 146 patients with chronic HBV infection was determined. Patients were divided into groups based on the presence or absence of HCC recurrence. Serum IL-6 levels were compared between groups, and the association between serum IL-6 level and greatest tumor dimension was also analyzed. Receiver operating characteristics (ROC) curve was used to define the optimal cutoff value for predicting recurrence-free survival (RFS) and overall survival (OS) rates. The OS and RFS rates were calculated using the Kaplan-Meier method.Out of 146 patients, 80 (54.8%) patients were documented as having HCC recurrence during the follow-up period. After adjusting for potential confounders, serum IL-6 levels were significantly associated with HCC recurrence, and a saturation effect existed with serum IL-6 levels up to 3.7 pg/mL. In addition, patients with preoperative serum IL-6 levels over 3.1 pg/mL had lower RFS and OS rates (P < 0.01). There was no significant correlation between preoperative serum IL-6 levels and maximal tumor dimension (r = 0.0003, P = 0.84).Elevated serum levels of IL-6 were significantly associated with an increased risk of HBV-associated HCC recurrence suggesting that preoperative IL-6 serum level is potential biomarker for early prediction of HBV-associated HCC recurrence.