Fibrosis and AST to platelet ratio index predict post-operative prognosis for solitary small hepatitis B-related hepatocellular carcinoma

Purpose

Although advanced liver fibrosis is crucial in the development of hepatocellular carcinoma (HCC) for patients with chronic hepatitis B, whether it is associated with the recurrence of HCC after resection remains obscure. This study was aimed to compare the outcomes for patients with minimal or advanced fibrosis in solitary small hepatitis B virus (HBV)-related HCC.

Methods

This study enrolled 76 patients with small (<5 cm) solitary HBV-related HCC who underwent resection. The outcomes of patients with minimal and advanced fibrosis in non-tumor areas were compared. Serum markers were tested to assess the stage of hepatic fibrosis and to predict prognosis.

Results

Fourteen patients with an Ishak fibrosis score of 0 or 1 were defined as having minimal fibrosis; the remaining 62 patients were defined as having advanced fibrosis. During a follow-up period of 77.0 ± 50.7 months, 41 patients died. The overall survival rate was significantly higher (P = 0.018) and recurrence rate was lower (P = 0.018) for patients in the minimal fibrosis group. Aspartate aminotransferase–platelet ratio index (APRI) exhibited the most reliable discriminative ability for predicting advanced fibrosis. The overall survival rate was significantly higher (P = 0.003) and recurrence rate was lower (P = 0.005) for patients with an APRI of 0.47 or less.

Conclusions

For patients with solitary small HBV-related HCC who underwent resection, minimal fibrosis is associated with a lower incidence of recurrence and with better survival. APRI could serve as a reliable marker for assessing hepatic fibrosis and predicting survival.     

High CD44s expression is associated with the EMT expression profile and intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy

Background/purpose

Local ablation therapy (LAT) is a widely used treatment for hepatocellular carcinoma (HCC) because it is less invasive than hepatic resection. The precise molecular mechanism underlying local HCC recurrence after LAT is largely unknown. The CD44 standard isoform (CD44s) is involved in epithelial–mesenchymal transition (EMT) in HCC. We investigate the significance of CD44s expression and EMT expression profile in local HCC recurrence after LAT.

Methods

We studied the expression levels of CD44s, EMT expression profile (E-cadherin^low/vimentin^high expression) and their association with clinicopathological factors in 30 HCC samples from patients with locally recurrent HCCs after LAT following hepatic resection. The alterations of CD44s expression was compared with those in initial HCCs from 150 patients without prior any anticancer treatment including LAT.

Results

A high CD44s expression was significantly associated with the EMT expression profile (P = 0.002), and it was also detected with a higher frequency in the locally recurrent HCCs after LAT compared to initial HCCs (P < 0.001). In addition, high CD44s expression was associated with the intrahepatic dissemination of HCC after LAT (P = 0.006).

Conclusions

These results suggest that high CD44s expression is associated with the aggressive recurrence pattern via EMT after LAT for HCC.     

IMP3 combined with CD44s,a novel predictor for prognosis of patients with hepatocellular carcinoma

Purpose

Insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) is reported to be re-expressed in malignant tumors and can regulate the expression of multiple genes related to tumor invasion. CD44 standard isoform (CD44s) has been reported to play an important role in facilitating tumor invasion. In this text, we investigate the regulatory function of IMP3 on CD44s and the role of IMP3 and CD44s in predicting the outcomes of patients with hepatocellular carcinoma.

Methods

IMP3 and CD44s were measured in hepatocellular carcinoma (HCC) tissues by immunohistochemical assay, and survival analysis was conducted among 128 patients. Moreover, we studied the effect of IMP3 on the expression of CD44s and the biological functions of tumor cells in HCC cell lines.

Results

Our results showed that the expression of IMP3 was significantly correlated with CD44s expression (r = 0.505, P < 0.001), and both of them correlated with high AFP level, advanced tumor stage and grade, portal vein tumor thrombus, and early tumor recurrence or metastasis. The results of survival analysis exhibited that the 1-, 3-, 5-year disease-free and overall survival rates significantly reduced in IMP3- and CD44s-positive patients, and IMP3 combined with CD44s was an independent prognostic risk factor for HCC. In vitro assay, our results showed that IMP3 promoted HepG2 and MHCC97H cells invading and migrating via regulating CD44s expression.

Conclusions

Our findings suggest that IMP3 facilitates HCC aggressiveness through regulating CD44s expression, and IMP3 combined with CD44s can be as a new predictor for unfavorable prognosis in HCC patients.     

Thrombocytosis and Hepatocellular Carcinoma

Background

Thrombocytopenia has been reported to be both a risk factor for hepatocellular carcinoma (HCC) development as well as a prognostic factor. Many HCCs also occur in presence of normal platelets.

Aim

To examine a cohort of HCC patients with associated thrombocytosis.

Methods

Records were examined of a cohort of 634 biopsy-proven and randomly presenting HCC patients without thrombocytopenia.

Results

In the total cohort, 52 patients were identified with thrombocytosis (platelet levels >400 × 10⁹/L) and compared with 582 patients with normal platelet values. The average tumor sizes were 13.1 versus 8.8 cm (p < 0.0001), and their total average bilirubin levels were 0.9 versus 1.5 (p = 0.02), comparing thrombocytosis patients versus normal platelet count HCC patients. These differences were even more pronounced in patients with HCC sizes >5 cm. Thrombocytosis patients were younger and had less cirrhosis, but similar percent with hepatitis B or C or alcohol consumption.

Conclusion

Thrombocytosis in association with HCC occurs in patients with larger tumor sizes and better liver function.     

Initial response to sorafenib by using enhancement criteria in patients with hepatocellular carcinoma

Purpose

Sorafenib induces early vascularity reduction in patients with hepatocellular carcinoma (HCC). We sought to identify differences in radiological assessment approaches and to evaluate their usefulness for the prediction of the initial response to sorafenib.

Methods

Forty-eight patients with advanced HCC treated with sorafenib were evaluated by four-phase contrast-enhanced computed tomography. All target lesions were analyzed using the Response Evaluation Criteria in Solid Tumors (RECIST), the EASL criteria, and modified RECIST (mRECIST).

Results

At the initial evaluation at 4–6 weeks, rates of objective response (OR) (including both complete and partial responses), stable disease (SD), and progressive disease (PD) were 2, 71, and 27 %, respectively, according to RECIST; 15, 56, and 29 %, respectively, according to the EASL criteria; and 15, 58, and 27 %, respectively, according to mRECIST. Patients who achieved an OR according to the EASL criteria also achieved an OR according to mRECIST. Patients who achieved an OR according to the EASL criteria or mRECIST had better predicted overall survival (OS) than did patients who achieved SD (p = 0.033 and 0.028, respectively). Patients with SD according to RECIST had different outcomes depending on the response according to enhancement criteria. Patients classified as responders (complete and partial) had better predicted OS than those classified as non-responders (those classified as SD and PD) (p = 0.048).

Conclusions

The enhancement criteria could be useful for prediction of the initial response to sorafenib in patients with HCC. Moreover, mRECIST appears to be simple and convenient.     

Circulating free DNA in the progression of liver damage to hepatocellular carcinoma

Purpose

Circulating free DNA (cfDNA) is an extracellular DNA released in the blood by tumor apoptotic/necrotic cells. cfDNA determination has been proposed as a non-invasive and sensitive marker in the diagnosis of cancer. Our aim was to validate the quantification of cfDNA as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC).

Methods

cfDNA was quantified by real-time PCR amplification of the hTERT gene in 142 plasma samples obtained from 66 patients with HCC, 35 with cirrhosis (CIRR) and 41 with advanced HCV-related chronic hepatitis (CH).

Results

cfDNA was documented in the plasma of 22 % of the CH patients, 57 % of those with CIRR and 61 % of HCC patients. Its concentration was lower in CH with respect to CIRR and HCC (p = 0.02). A cutoff value in the diagnosis of HCC was calculated by the ROC method (area under the curve 0.69, 91 % sensitivity, 43 % specificity) considering HCC versus CH/CIRR, taken together. Patients with multinodular HCC showed significantly higher levels of cfDNA (p = 0.05). A cutoff value for cfDNA was also calculated for discriminating patients with long or short survival. Survival was significantly longer in patients with cfDNA below than in those above the cutoff value (37 vs. 24 months, p = 0.03). Similar results were obtained in the subgroups of patients with viral or with HCV-only etiology, with slightly higher overall diagnostic accuracy.

Conclusions

The role of the quantitative analysis of cfDNA as a diagnostic test is debatable, but cfDNA levels discriminate patients with more advanced stages of disease, demonstrating a prognostic relevance in patients with HCC.     

Incidence and risk factors for surveillance failure in patients with regular hepatocellular carcinoma surveillance

Background

Initial presentation of hepatocellular carcinoma (HCC) at an advanced stage in patients under a regular surveillance program is a devastating problem.

Aims

We assessed the prevalence and factors associated with this surveillance failure.

Methods

A total of 304 HCC patients who received regular surveillance were retrospectively reviewed. Surveillance failure was defined when the tumor was diagnosed at beyond the Milan criteria.

Results

Surveillance failure rate was 5.9 %. Macronodular cirrhosis (MC), ultrasonography-only surveillance (US-S) and infiltrative tumor type were independent factors associated with surveillance failure. The surveillance failure rate was higher in patients with MC (10.3 vs. 3.2 %, p = 0.022), US-S (14.6 vs. 4.3 %, p = 0.013) and when the tumor was infiltrative type (57.1 vs. 2.1 %, p < 0.001). Based on the two baseline factors (MC and US-S), the surveillance failure rates were 35.7, 6.8, 5.9 and 2.6 % for MC(+)/US-S(+), MC(+)/US-S(?), MC(?)/US-S(+) and MC(?)/US-S(?), respectively (p < 0.001).

Conclusion

The HCC surveillance failure was not rare in clinical practice. These data suggest that special attention for surveillance failure might be needed for patients with MC who receive US-S.     

Phase I clinical trial of vaccination with URLC10-derived peptide for patients with advanced esophageal cancer

Background

Up-regulated gene in lung cancer 10 (URLC10), confirmed to be lymphocyte antigen 6 complex locus K and defined as an oncoantigen, has been identified as a tumor-associated antigen by systematic analysis of expression levels of thousands of genes in lung cancer tissues and esophageal squamous cell carcinoma tissues, which were compared with those of normal human tissues by use of cDNA microarray analysis. Human leukocyte antigen (HLA)-A*2402-positive dendritic cells pulsed with URLC10-derived epitope peptide induced CD8⁺ cytotoxic T lymphocytes to exert specific cytotoxicity against the HLA-A*2402-positive URLC10-expressing esophageal carcinoma cell lines.

Methods

In a phase I clinical trial we evaluated the safety and immunogenicity of a URLC10-177 peptide vaccine emulsified with Montanide ISA51 for patients with unresectable advanced esophageal cancer. One milligram of URLC10-177 peptide in 1 mL sterile saline was emulsified with 1 mL incomplete Freund’s adjuvant and administered subcutaneously to the inguinal region or axilla of the patients. One course of treatment comprised four vaccinations, which were performed every week in the first and second treatment courses and subsequently every 2 weeks after the first vaccination in the third treatment course.

Results

Redness and induration of the skin were the only adverse events at the injection site and were believed to be a delayed-type hypersensitivity (DTH) reaction against the peptide vaccine. A URLC10-177-specific immune reaction in the enzyme-linked immunospot assay was detected in three of four DTH-positive patients (75 %) and in one of three DTH-negative patients (33 %). Furthermore, patients who had a DTH reaction seemed to survive longer than those who had no DTH reaction.

Conclusion

URLC10-177 peptide/Montanide vaccine therapy was well tolerated and induced a URLC10-177 peptide-specific immune response. Therapeutic URLC10-177 peptide vaccination is expected to have clinical benefit in prolonging the survival of patients with unresectable advanced esophageal cancer.     

Survival of infiltrative hepatocellular carcinoma patients with preserved hepatic function after treatment with transarterial chemoembolization

Purpose

Transarterial chemoembolization (TACE) is highly effective and safe therapeutic modality for unresectable hepatocellular carcinoma (HCC). However, the role of TACE for infiltrative HCC has never been elucidated owing to the concern about hepatic failure and subsequent mortality after the procedure. In this study, we aimed to document whether patients with infiltrative HCC would benefit from TACE.

Methods

Child-Pugh class A/B patients who were newly diagnosed as infiltrative HCC and treated with curative-intent TACE were enrolled. All radiological images were reviewed by a radiologist with more than 20 years of experience in TACE.

Results

Among 1,184 patients newly diagnosed as HCC, 233 (19.7 %) had infiltrative-type tumors and 128 (54.9 %) underwent curative-intent TACE. Although the median overall survival was 5.4 months (IQR 3.1–13.9 months) and 16 (12.5 %) patients had experienced significant complications, 19 (15.9 %) patients survived more than 2 years after the first diagnosis. In multivariable analysis, age >60 years old (HR 0.54, 95 % CI 0.31–0.92), Child-Pugh class A (HR 0.48, 95 % CI 0.30–0.76), and a major PVT without parasitic supply (HR 0.66, 95 % CI 0.44–0.99) were independent favorable prognostic factors. Development of significant complication after TACE was a significant hazard factor of survival (HR 1.99, 95 % CI 1.09–3.62).

Conclusions

In carefully selected patients with preserved hepatic function and good performance, TACE may achieve long-term survival of infiltrative HCC patients with major PVT without parasitic supply. However, the risk of morbidity and immediate mortality after TACE should be considered to select subjects for the procedure.     

Soluble FGL2, a novel effector molecule of activated hepatic stellate cells,regulates T-cell function in cirrhotic patients with hepatocellular carcinoma

Purpose

To investigate the effects of soluble FGL2 (sFGL2) secreted by hepatic stellate cells (HSCs) on immune suppression in cirrhotic patients with hepatocellular carcinoma (HCC).

Methods

Serum sFGL2 levels were examined by ELISA in 40 patients with HCC, liver cirrhosis (LC) or chronic HBV (CHB) infection. A double staining of the immunofluorescence analysis of α-SMA and FGL2 was performed in two cirrhotic liver specimens. The expression of FGL2 in the LX2 cell line was analyzed by immunofluorescence, Western blot and flow cytometry. T-cells purified from HCC patients using magnetic beads were cultured with LX2 cells at different ratios with anti-CD3-stimulating or FGL2-blocking antibodies. The proliferation index (PI) of CD8 + T cells was assessed by flow cytometry, and the secretion of IFN-γ was measured by ELISA.

Results

sFGL2 levels are significantly higher in patients with HCC or LC compared with those with CHB (p = 0.0039/p = 0.0020). Among HCC patients, those with cirrhosis exhibited significantly higher levels of sFGL2 compared with non-cirrhotic individuals (p = 0.0108). The expressions of FGL2 and α-SMA overlapped in HSCs in liver specimens. FGL2 protein secreted by LX2 cells inhibited T-cell proliferation of HCC patients in a dose-dependent manner in vitro. The PI of CD8 + T cells was significantly enhanced following addition of FGL2 antibody to the culture system (LX2/T-cell ratio of 1:10, p = 0.002). The level of IFN-γ in mixed cultures was inversely correlated with the number of HSCs and was reversed by incubation with FGL2 blocking antibody.

Conclusion

sFGL2 protein is a novel effector molecule of activated HSCs, which suppresses CD8 + T cell proliferation and interferon-γ production, and it subsequently might contribute to immune suppression during fibrosis and tumorigenesis in the liver.     

Strong CD8+ T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma

Aim

We investigated whether tumor-specific CD8⁺ T-cell responses affect tumor-free survival as well as the relationship between CD8⁺ T-cell responses against tumor-associated antigens (TAAs) and the clinical course after tumor treatment in patients with hepatocellular carcinoma (HCC).

Methods

Twenty patients with HCC that were treated by radiofrequency ablation or trans-catheter chemo-embolization (TACE) and in whom HCC was undetectable by ultrasonography, CT, and/or MRI 1 month after treatment were enrolled in the study. Before and after treatment for HCC, analyses of TAA (glypican-3, NY-ESO-1, and MAGE-1)-specific CD8⁺ T-cell responses were evaluated with an interferon-γ enzyme-linked immunospot (ELISpot) assay using peripheral CD8⁺ T-cells, monocytes, and 104 types of 20-mer synthetic peptide overlapping by 10 residues and spanning the entirety of the 3 TAAs.

Results

Sixteen out of 20 patients (80%) showed a positive response (≥10 TAA-specific cells/10⁵ CD8⁺ T-cells) before or after treatment. When we performed univariate analysis of prognostic factors for the tumor-free period in the 20 patients, platelet count, prothrombin time, and the number of TAA-specific CD8⁺ T-cells after treatment were significant factors (P = 0.027, 0.030, and 0.004, respectively). In multivariate analysis, the magnitude of the TAA-specific CD8⁺ T-cell response (≥40 TAA-specific cells/10⁵ CD8⁺ T-cells) was the only significant prognostic factor for a prolonged tumor-free interval (hazard ratio 0.342, P = 0.022).

Conclusions

Our results suggest that strong TAA-specific CD8⁺ T-cell responses suppress the recurrence of HCC. Immunotherapy to induce TAA-specific cytotoxic T lymphocytes by means such as the use of peptide vaccines should be considered for clinical application in patients with HCC after local therapy.     

Detection of TFPI2 Methylation in the Serum of Hepatocellular Carcinoma Patients

Background

DNA methylation plays a key role in hepatocellular carcinogenesis and progression. Analysis of aberrant methylation in serum DNA might provide a strategy for noninvasive detection of hepatocellular carcinoma (HCC).

Methods

To explore the feasibility of this approach, we compared TFPI2 methylation status in serum samples of HCC, chronic hepatitis B (CHB) patients and normal control groups using methylation-specific polymerase chain reaction.

Results

Our results showed that the percentage of serum TFPI2 promoter methylation was significantly higher in the HCC group (46.5 %, 20/43) compared with the CHB group (16.7 %, 4/24; p = 0.015) and the normal control group (19.2 %, 5/26; p = 0.022), respectively, indicating that TFPI2 methylation frequently existed in the serum of HCC patients. In our study, the detection rate of HCC using serum TFPI2 methylation was 46.5 % (20/43), which was quite close to the reported detection rate of α-fetoprotein (54 %). In cases where we combined both markers, the detection rate was 61.0 %, suggesting that serum TFPI2 methylation could be used as a potential marker for noninvasive detection of HCC. Then, we evaluated the correlation between the serum TFPI2 methylation status of HCC patients and their clinicopathological parameters. Patients with advanced TNM stage (III–IV) showed a significantly elevated serum methylation percentage of TFPI2 in comparison with those with early TNM stage (I–II) (p = 0.025). Moreover, TFPI2 methylation was observed more frequently according to the progression of TNM stage.

Conclusions

Our present study suggested that TFPI2 methylation in serum tended to be detected more easily in patients with advanced HCC and might be used as a predictor of HCC progression.     

Comparison of the outcomes between anatomical resection and limited resection for single hepatocellular carcinomas no larger than 5 cm in diameter: a single-center study

Background/Purpose

Liver resection is a widely preferred treatment modality for hepatocellular carcinomas (HCCs). This study aimed to compare the survival impact of anatomical resection with that of limited resection, in patients with single HCCs no larger than 5 cm in diameter.

Methods

A cohort study was carried out on 209 consecutive patients who underwent hepatic resection for a single HCC no larger than 5 cm in diameter between January 1994 and March 2007 at Osaka City General Hospital.

Results

The cumulative 5-year overall survival and disease-free survival rates in the anatomical resection group (n = 111) were 71 and 40%, respectively, both of which were significantly better than the 48 and 25% seen in the limited resection group (n = 98) (P = 0.0043 and P = 0.0232, respectively). Better effects of the anatomical resection on both overall and disease-free survival were seen in patients having HCC larger than 2 cm in diameter and in patients with moderately or poorly differentiated HCC. But no significant difference in either overall or disease-free survival was seen between the groups in patients with a HCC 2 cm or less in diameter or in the patients with well-differentiated HCC. Using Cox’s regression model, anatomical resection was confirmed to be an independent favorable factor for both overall and disease-free survival.

Conclusions

Anatomical resection is therefore recommended for histologically advanced single HCCs ranging from 2 to 5 cm in diameter.     

Positive glypican-3 expression in early hepatocellular carcinoma predicts recurrence after hepatectomy

Background

Glypican-3 (GPC3) is a new prognostic factor after curative hepatectomy in patients with hepatocellular carcinoma (HCC), and the expression of GPC3 is known to be associated with postoperative metastasis. However, the role of GPC3 in patients with early HCC remains unknown.

Methods

We retrospectively studied 55 patients with early HCC (total 99 nodules) who underwent initial hepatectomy between 1995 and 2010. Clinicopathological features and surgical outcomes were compared in relation to GPC3 expression.

Results

The GPC3-positive expression was seen in 28 of 55 patients (50.9 %) with early HCC (44 of 99 nodules). The GPC3-positive expression was significantly associated with hepatitis C virus (HCV) infection (P = 0.0019) and with multiple early HCCs (P < 0.0001). The 5-year disease-free survival rate was significantly lower in patients with GPC3-positive early HCC (27 %) than in patients with GPC3-negative early HCC (62 %, P = 0.0036). The GPC3 expression was a significant independent prognostic factor for disease-free survival. However, it showed no significant difference in overall survival.

Conclusions

The GPC3 expression is capable to be a new prognostic factor for disease-free survival in patients with early HCC.     

Profile of hepatocellular carcinoma in a tertiary care hospital in Punjab in northern India

Purpose/Aim

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in all parts of the world. We analyzed the clinical presentation, etiology, and tumor characteristics of HCC presenting to our hospital.

Methods

All patients diagnosed to have HCC from September 2007 to August 2010 were prospectively enrolled. HCC was diagnosed according to EASL criteria—USG/CT/MRI of the abdomen and/or serum alpha-fetoprotein and/or histology (where indicated). Detailed clinical and laboratory parameters were noted. Barcelona Clinic Liver Cancer (BCLC) staging was done.

Results

One hundred and twenty-eight patients (22 females, mean±SD; age, 49.8?±?10.2 years) were diagnosed to have HCC. Underlying cirrhosis was present in 99.2 %. Hepatitis C virus infection, alone (21.9 %) or with alcohol (22.9 %) was the most common etiological factor, followed by alcohol alone; 33.6 % of the patients had more than one etiological factor. Most patients (83.5 %) presented with features of decompensated cirrhosis. HCC leading to decompensation of cirrhosis was the first presentation of the liver disease in nearly one third of the cases. Serum alpha-fetoprotein was >200 ng/mL in 67.2 % of the patients, while it was normal in 18.7 % of the patients. The mean±SD size of HCC was 5.3?±?2.9 cm. HCC was multicentric in 57 %, and portal vein thrombosis was present in 34.4 %. About 66 % of the patients belonged to BCLC stage C or D.

Conclusions

Hepatitis C virus infection was the most common cause of HCC in Punjab. One-third of the patients had multiple etiological factors and almost all had underlying cirrhosis and presented at advanced stage.     

Pre-S Mutation Is a Significant Risk Factor for Hepatocellular Carcinoma Development: A Long-Term Retrospective Cohort Study

Background

Several cross-sectional studies have shown an association between pre-S mutation and hepatocellular carcinoma (HCC).

Aims

We aim to verify whether pre-S mutation represents a risk for HCC development in a longitudinal way.

Methods

A total of 195 patients with chronic HBV infection [age: 43.7 ± 10.8 years, males: 141 (72.3 %), genotype C: 195 (100 %), hepatitis B e antigen (HBeAg) positive: 109 (55.9 %), cirrhosis: 79 (40.5 %), and pre-S mutation positive: 44 (22.6 %)] were followed up for a median of 7.2 years (range 1.0–7.8 years).

Results

HCC developed in 24 patients during follow-up. The 1-, 3-, and 5-year cumulative incidences of HCC were 0.5, 4.9, and 10.4 %, respectively. Patients with pre-S mutation had significantly higher 5-year cumulative incidences of HCC than those without (26.5 vs. 5.7 %, p < 0.001) and showed higher hazard ratio for HCC [3.04 (95 % CI 1.24–7.42), p = 0.015, adjusted for age, gender, HBeAg, cirrhosis and baseline HBV DNA level]. Notably, in patients aged ≥50 years, the 5-year cumulative incidences of HCC in patients with pre-S mutation were considerably high (58.3 %), compared to those without (16.1 %, p < 0.001).

Conclusions

Patients with pre-S mutations had higher incidence of HCC during follow-up, especially in aged patients. Patients with pre-S mutations, especially older ones, may require careful attention to HCC development.     

High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma

Background

Prognosis of patients with hepatocellular carcinoma (HCC) remains poor because HCC is frequently diagnosed late. Therefore, regular surveillance has been recommended to detect HCC at the early stage when curative treatments can be applied. HCC biomarkers, including Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), are widely used for surveillance in Japan. A newly developed immunoassay system measures AFP-L3 % with high sensitivity. This retrospective study aimed to evaluate clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) as a predictor of early stage HCC in surveillance at a single site.

Methods

Of consecutive 2830 patients in the surveillance between 2000 and 2009, 104 HCC-developed and 104 non-HCC patients were selected by eligibility criteria and propensity score matching. Samples were obtained from the HCC patients who had blood drawn annually for 3 years prior to HCC diagnosis.

Results

In the present study, hs-AFP-L3 was elevated 1 year prior to diagnosis in 34.3 % of patients. The survival rate of patients with the hs-AFP-L3 ≥ 7 % at 1 year prior to diagnosis was significantly lower than that of patients with hs-AFP-L3 < 7 %.

Conclusions

Elevation of hs-AFP-L3 was early predictive of development of HCC even at low AFP levels and in absence of ultrasound findings of suspicious HCC. The hs-AFP-L3 should be added to surveillance programs with US because elevated hs-AFP-L3 may be a trigger to perform enhanced imaging modalities for confirmation of HCC.     

Perioperative change in white blood cell count predicts outcome of hepatic resection for hepatocellular carcinoma

Background

In spite of improvements in surgical management, hepatocellular carcinoma (HCC) still recurs after operation in 60–70% of patients. Therefore, we investigated the relation between perioperative change in white blood cell count (WBC) and tumor recurrence as well as survival in patients with HCC after hepatic resection.

Methods

Subjects were 53 patients who underwent elective hepatic resection for HCC. We retrospectively examined the relation between perioperative change in WBC and recurrence of HCC as well as overall survival.

Results

Advanced tumor stage and increasing of WBC on postoperative day (POD) 1 were positively associated with worse disease-free survival rate on both univariate and multivariate analysis (P < 0.05). Advanced tumor stage, increasing of WBC on POD 1, and blood transfusion were positively associated with worse overall survival rate on univariate analysis (P < 0.05), while change in WBC was the only independent factor on multivariate analysis (P < 0.05).

Conclusions

Perioperative change in WBC after elective hepatic resection for HCC is positively associated with recurrence and worse survival.