Liver transplantation for hepatocellular carcinoma exceeding the Milan criteria: a single-center experience

Purpose

To establish a prognostic prediction system for patients with hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation (LT).

Methods

A total of 130 patients undergoing LT for HCC exceeding Milan criteria were enrolled into the study. Independent predictors for relapse-free survival (RFS) were adopted to establish a grading system to predict the risk of post-LT tumor recurrence.

Results

Multivariate Cox analysis revealed that tumor size >10 cm [vs. ≤5 cm: relative risk (RR) = 4.214, P < 0.001], preoperative alpha fetoprotein > 400 ng/ml (vs. ≤400 ng/ml: RR = 1.657, P < 0.001), extrahepatic invasion (RR = 2.407, P = 0.005) and vascular invasion (RR = 1.917, P = 0.013) were independent predictors for RFS. The risk index of each patient was defined as the sum of the RR obtained in the Cox analysis for RFS. The risk of tumor recurrence was classified into four grades: grade I—risk index equal to 0, grade II—risk index from 0 to 2, grade III—risk index from 2 to 6 and grade IV—risk index >6. RFS rates of patients with grade I–IV (n = 35, 46, 30 and 19) were 87.5, 57.8, 34.7 and 0 % in 1 year; and 74.4, 41.7, 14.4 and 0 % in 5 years. Both of overall survival (OS) and RFS correlated well with the risk index grade. Patients with grade I achieved comparable prognostic outcomes with the Milan group patients (n = 119) (5-year OS = 73.7 vs. 74.7 %, P = 0.748; 5-year RFS = 74.4 vs. 85.7 %, P = 0.148).

Conclusions

The new grading system was proved to be a promising system in predicting the patient prognosis after LT for HCC exceeding Milan criteria.     

Mitochondrial metabolism in the noncancerous liver determine the occurrence of hepatocellular carcinoma: a prospective study

Background

Recurrence determines the postoperative prognosis with hepatocellular carcinoma (HCC). It is unknown how the liver dysfunction involving organic anion transporter failure causes the occurrence of HCCs. This study was designed to elucidate the link between liver dysfunction and multicentric occurrence (MO) after radical hepatectomy.

Methods

Forty-nine samples of noncancerous liver tissue from HCC patients within the Milan criteria who were treated at our institution between January 2004 and August 2008 were examined as a training set by using genome-wide gene expression analysis. Using the independent 2-institutional cohort of 134 patients between September 2008 and December 2009, we performed a validation study using tissue microarray analysis. Cox proportional hazard regression analyses for MFS were performed to estimate the risk factors.

Results

In the Gene Ontology database (GO:0015711), SLC22A7 expression was the best predictor of MO-free survival [MFS] (Fold, 0.726; P = 0.001). High SLC22A7 gene expression prevented the occurrence of HCC after hepatectomy (odds ratio [OR], 0.2; P = 0.004). Multivariate analyses identified SLC22A7 expression as an independent risk factor (OR, 0.3; P = 0.043). In the validation study, multivariate analyses of MFS identified SLC22A7 expression as an independent risk factor (OR, 0.5; P = 0.012). As judged by gene set enrichment analysis, SLC22A7 down regulation was associated with mitochondrion (P = 0.008) and oxidoreductase activity (P = 0.006). Sirtuin 3 as a regulator of mitochondrial metabolism also determined MFS (P = 0.018).

Conclusions

The mitochondrial pathways may affect SLC 22A7 function to promote the occurrence of HCC. (Word count: 246).     

Correlation of apparent diffusion coefficient measured by diffusion-weighted MRI and clinicopathologic features in pancreatic cancer patients

Background/purpose

The aim of this study was to evaluate the clinical usefulness of diffusion-weighted magnetic resonance imaging (DWI) in patients with pancreatic cancer by comparing the apparent diffusion coefficient (ADC) value with clinicopathologic features.

Methods

Twenty-two consecutive patients (12 men, 10 women; mean age 64.4 years) with pancreatic cancer underwent DWI before surgery. We retrospectively investigated the correlations between tumor ADC value and clinicopathologic features.

Results

Apparent diffusion coefficient value was significantly lower for pancreatic cancer than for noncancerous tissue (P < 0.001). Receiver operating characteristic analysis yielded an optimal ADC cutoff value of 1.21 × 10^?3 mm²/s to distinguish pancreatic cancer from noncancerous tissue. There was a significant negative correlation between ADC value and tumor size (r = ?0.59, P = 0.004) and between ADC value and number of metastatic lymph nodes (r = ?0.56, P = 0.007). Tumors with low ADC value had a significant tendency to show high portal venous system invasion (P = 0.02) and extrapancreatic nerve plexus invasion (P = 0.01).

Conclusions

Apparent diffusion coefficient value appears to be a promising parameter for detecting pancreatic cancer and evaluating the degree of malignancy of pancreatic cancer.     

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.     

The expression of chitinase 3-like 1: a novel prognostic predictor for hepatocellular carcinoma

Objectives

Chitinase 3-like 1 (CHI3L1) is associated with poor prognosis of various human cancers. However, the clinical and prognostic significance of CHI3L1 in hepatocellular carcinoma (HCC) is largely unknown. The aim of the present study is to investigate the expression of CHI3L1 in human HCC cell lines, clinical HCC specimens and its association with expressions of phosphorylated-Akt (p-Akt), E-cadherin and prognostic significance.

Methods

The protein level of CHI3L1 in HCC cell lines was evaluated by western blot. The mRNA and protein levels of CHI3L1 in 19 self-paired HCC specimens were assessed by RT-PCR and western blot assays. The clinical and prognostic significance of CHI3L1 in 70 cases of HCC patients was determined by immunohistochemistry. In addition, expressions of p-Akt and E-cadherin were also assessed.

Results

The protein level of CHI3L1 paralleled with increased malignant potential of HCC cell lines (P < 0.05). The mRNA and protein levels of CHI3L1 in HCC tissues were up-regulated compared with those in adjacent peritumoral tissues and further increased in tumors with metastasis (P < 0.05). Clinicopathological analysis showed that positive CHI3L1 expression was significantly associated with larger tumor size, capsular invasion, advanced TNM stages and status of metastasis (P = 0.035, 0.003, 0.023 and 0.003, respectively). Furthermore, CHI3L1 expression was positively correlated with high level of p-Akt (r = 0.293, P = 0.014), but inversely correlated with expression of E-cadherin (r = ?0.267, P = 0.026). Additionally, Kaplan–Meier survival analysis showed that HCC patients with positive CHI3L1 expression had a worse overall survival and disease-free survival compared with those with negative CHI3L1 expression (P < 0.001, respectively). Multivariate analysis identified CHI3L1 as an independent prognostic predictor for overall survival and disease-free survival of HCC patients (P = 0.044 and 0.031, respectively).

Conclusions

CHI3L1 plays an essential role in HCC malignancies and may be served as a valuable prognostic biomarker for HCC patients.     

Tolerance of radiofrequency ablation by patients of hepatocellular carcinoma

Background

Radiofrequency ablation (RFA) is currently an effective method for ablation of hepatocellular carcinoma (HCC). Early reports have indicated that RFA is safe and virtually free from major complications. Unlike partial hepatectomy for HCC on patients with cirrhosis, there are no data on the safety limit of RFA. However, information is vital for selection of appropriate patients for the procedure. In this study, we analyzed results from use of RFA on HCC patients and determined the lower limit of liver function with which HCC patients can tolerate RFA.

Method

Preoperative variables of 310 patients who underwent RFA for HCC were analyzed to identify the risk factors in RFA intolerance in terms of morbidity associated with stress-induced complications.

Results

Thirty-nine (12.6%) patients developed intolerance of RFA. Postoperative morbidity was mainly because of intractable ascites (n = 13), hyperbilirubinemia (n = 10), massive pleural effusion (n = 7), and other complications (n = 14). Multivariate analysis revealed that serum albumin level (P = 0.001), serum bilirubin level (P = 0.000), tumor number (P = 0.002), and RFA duration (P = 0.017) all played a role in this issue.

Conclusions

Simple data such as serum bilirubin, serum albumin level, and tumor number can be used to predict HCC patients’ tolerance of RFA. Avoidance of excessive RFA time and careful monitoring of patients at risk are important means of reducing the postoperative morbidity rate.     

Hepatitis C viral load predicts tumor recurrence after curative resection of hepatocellular carcinoma regardless of the genotype of hepatitis C virus

Purpose

To clarify the prognostic impact of the hepatitis C virus (HCV) genotype after curative resection for hepatocellular carcinoma (HCC).

Methods

A total of 199 patients who underwent a curative hepatic resection for HCV-related HCC were reviewed. The clinical outcomes were compared between patients infected with HCV genotype 1b (n = 160) and those infected with other genotypes (n = 39).

Results

With a comparable median HCV viral load (6.0 vs. 5.8 log₁₀ IU/mL, p = 0.17), the 3-year recurrence-free survival (RFS) rates (25 vs. 20 %, p = 0.65) and the 5-year overall survival (OS) rates (72 vs. 65 %, p = 0.73) were similar between the two groups. A multivariate analysis confirmed that HCV viral load of +1.0 log₁₀ IU/mL [hazard ratio (HR), 1.48], major vascular invasion (HR, 3.20), recurrent tumor (HR, 1.77), and preoperative des-gamma carboxyprothrombin level >40 mAu/mL (HR, 1.64) were independent predictors of tumor recurrence, while the HCV genotype was not a significant risk factor. When the population was stratified according to the HCV viral load, a significant difference was observed in the RFS rate for both genotype 1b (p = 0.003) and the other genotypes (p = 0.037) at HCV viral load of 5.3 log₁₀ IU/mL.

Conclusions

The HCV genotype does not affect the surgical outcomes of patients with HCC. A lower HCV viral load is advantageous regardless of the HCV genotype.     

Heat shock protein 22 overexpression is associated with the progression and prognosis in gastric cancer

Purpose

The heat shock protein 22 (HSP22) is associated with tumor proliferation and protects tumor cell from apoptosis in many malignancies. However, the role of HSP22 in gastric cancer has not been thoroughly elucidated. The aim was to determine the relationship of HSP22 expression with clinicopathological parameters and prognosis in gastric cancer and estimate the alteration of HSP22 expression after neoadjuvant chemotherapy.

Methods

HSP22 and matrix metallopeptidase 9 (MMP-9) antigen expressions were evaluated by immunohistochemistry in 129 gastric carcinoma samples. Univariate and multivariate analyses were performed to determine the association between HSP22 expression and prognosis. The response of HSP22 was assessed in 47 patients who received neoadjuvant chemotherapy.

Results

HSP22 protein expression was significantly associated with tumor size, depth invasion, lymph node metastasis and stage of disease (all P < 0.05). In univariate and multivariate analyses, HSP22 was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS) (P = 0.003 and P = 0.004, respectively). Furthermore, HSP22 overexpression was associated with a poor prognosis in all patients and in patients subgroups stratified by tumor size, depth invasion and lymph node metastasis. In addition, HSP22 was significantly correlated with MMP-9 among 129 gastric cancer tissues (P < 0.001). Patients who had MMP-9 overexpression had poor OS and shorter RFS. Moreover, the alteration of HSP22 was not comparable in 47 patients who underwent neoadjuvant chemotherapy.

Conclusions

HSP22 plays an important role on tumor aggressiveness and prognosis and may act as a promising target for prognostic prediction.     

Wls Expression Correlates with Tumor Differentiation and TNM Stage in Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. Effective biomarkers are necessary to predict the clinical course and outcome of patients with HCC. Wntless (Wls) is a key modulator of Wnt protein secretion and is overexpressed in various human cancers. However, the mechanism and alteration of Wls expression in HCC have not been clarified.

Aims

The aim of this study was to evaluate expression level of Wls in HCC and its clinical significance.

Methods

The levels of Wls expression were investigated in 84 HCC tissues using immunohistochemistry.

Results

Wls was negatively expressed in normal liver tissue and was negatively or weakly (score 0) expressed in liver cirrhosis. Twenty-eight out of 84 samples (33.3%) were negative or weakly (score 0) expressed Wls, 38 out of 84 (45.2%) moderately (1+) expressed Wls, and 18 out of 84 (21.4%) strongly (2+) expressed Wls. Wls expression was positively associated with tumor size (P = 0.005, r = 0.302), tumor TNM stage (P = 0.017, r = 0.261), AFP (P = 0.051), and HBV infection (P = 0.009, r = 0.283), and was negatively associated with differentiation (P < 0.001, r = ? 0.552). No significant relationship between Wls expression and liver cirrhosis, ALT, GGT, age, sex, or tumor focality was found.

Conclusions

Our data showed that Wls was differentially expressed in HCC. Statistical analysis results suggest that Wls expression might increase as HCC progresses.

     

Liver transplantation for hepatocellular carcinoma: the Baylor experience

Background

Liver transplantation (LTX) is indicated in selected patients with hepatocellular carcinoma (HCC) and cirrhosis.

Methods

We compared the outcome of LTX for patients with and without HCC in 5-year time periods between 1987 and 2007 to reflect the implementation of the Milan tumor selection criteria in 1997 and of the model for end-stage liver disease (MELD) score-based liver allocation in 2002.

Results

Of 2350 patients who underwent primary LTX, 330 had HCC. Five-year patient survival for HCC patients was 28.6% in 1987–1992 and 42.3% in 1992–1997, which was 41.4–31.4% lower than that in non-HCC patients (P < 0.0001). After 1997, 5-year survival was 76% for HCC patients, similar to the survival for non-HCC patients (P = 0.8784). Five-year tumor recurrence dropped from 52.9% (1987–1992) and 48.2% (1992–1997) to 11.4% (1997–2002) and 8.4% (2002–2007) (P < 0.0001). Multivariate analysis for tumor recurrence showed the following significant factors: tumor size >6 cm [hazard ratio (HR) 3.67], ≥5 nodules (HR 3.441), vascular invasion (HR 3.18), transplant in 1987–1992 (HR 6.772), and transplant in 1992–1997 (HR 3.059). MELD-based liver allocation reduced median waiting time for LTX for HCC versus non-HCC (35 vs. 111 days; P = 0.005) without compromise in patient outcome.

Conclusions

The results of LTX for HCC continue to improve and are equal to results in patients without HCC.     

Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease

Objectives

We examined the relationship between disease activity and anti-CADM-140/MDA5 titer measured by enzyme-linked immunosorbent assay (ELISA).

Methods

Sera from 63 patients with dermatomyositis (DM) [46 classic DM, 17 clinically amyopathic DM (CADM)] were screened for autoantibody using immunoprecipitation assay. Anti-CADM-140/MDA5-positive sera were examined for their titer by anti-CADM-140/MDA5 ELISA. Potential associations between anti-CADM-140/MDA5 titer and clinical course or outcome were analyzed.

Results

Sera from 14 patients with DM (2 classic DM, 12 CADM) had anti-CADM-140/MDA5. Of ten patients with DM and rapidly progressive interstitial lung disease (RP-ILD), the mean titer of anti-CADM-140/MDA5 before treatment was significantly lower in patients who responded to therapy and survived (responder group, n = 4) than in those who did not respond and died (nonresponder group, n = 6) (110.3 vs. 356.9, P = 0.019). In the responder group, the mean titer of anti-CADM-140/MDA5 significantly decreased down to below the cutoff level after treatment (n = 3, 113.4 vs. 1.6, P = 0.033), whereas that of the nonresponder group did not decrease sufficiently and sustained high level (n = 4, 372.5 vs. 198.4, P = 0.31).

Conclusions

These results emphasize the clinical importance of anti-CADM-140/MDA5 antibody levels to predict outcomes of RP-ILD as well as to monitor disease activity in patients with DM and RP-ILD.     

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.     

The prognostic significance of preoperative plasma levels of osteopontin in patients with TNM stage-I of hepatocellular carcinoma

Purpose

To evaluate the prognostic value of preoperative plasma osteopontin (OPN) levels in patients with early stage of hepatocellular carcinoma (HCC).

Methods

Preoperative plasma levels of OPN were detected by ELISA in 68 patients with tumor-node-metastasis system stage-I of HBV-related HCC, and their association with tumor recurrence or patients’ survival was analyzed.

Results

The median plasma OPN level of patients was 82.51 ng/ml (25–75% interquartile range, 63.15–110.45 ng/ml). Plasma OPN levels in patients with tumor size ≥5 cm in diameter were significantly higher than that of patients with tumor size <5 cm in diameter (104.76 vs. 75.16 ng/ml, P = 0.003). When the 100 ng/ml was used as a cut-off value to divide the patients into two groups: the higher plasma OPN group and the lower plasma OPN group, the tumor recurrence rate of the higher plasma OPN group was significantly higher than that of the lower plasma OPN group (52.17 vs. 24.44%, P = 0.022). Meanwhile, the recurrence rate of the patients with positive alpha fetoprotein (AFP) (45.5%) was significantly higher than that of those negative AFP patients (12.5%, P = 0.006). A higher plasma OPN level was one leading independent prognostic factor for both overall survival (OS) and relapse-free survival in multivariate Cox models.

Conclusion

The preoperative plasma OPN level and serum AFP level in patients with early stage of HCC can be used as a prognostic marker for early stage of HCC.     

Fractal Analysis of Contrast-Enhanced CT Images to Predict Survival of Patients with Hepatocellular Carcinoma Treated with Sunitinib

Background

Intratumoral heterogeneity is a well-recognized feature of malignancy.

Aims

To assess the heterogeneity of tumor using fractal analysis of contrast-enhanced computed tomography (CE-CT) images for predicting survival of hepatocellular carcinoma (HCC) patients treated with sunitinib.

Methods

The patient cohort comprised 23 patients (19 men, 4 women; mean age 61.5 years) with HCC who underwent CE-CT at baseline and after one cycle of sunitinib. Arterial-phase (AP) and portal-phase (PP) CE-CT images were analyzed using a plugin software for ImageJ (NIH, Bethesda, MD). A differential box-counting method was employed to calculate the fractal dimension (FD) of the tumor. Tumor FD, density, and size were compared with survival.

Results

Median progression-free survival (PFS) was 4.43 months. Patients were grouped into a favorable PFS (PFS >4.43 months; 9 patients) and an unfavorable PFS group (PFS ≤4.43; 13 patients). The baseline FD on both the AP and PP images was lower in the favorable PFS group than in the unfavorable PFS group (both P = 0.03). There was a significant difference in the change of the FD on the AP image between the favorable and unfavorable PFS groups (P = 0.02). Tumor density and size showed no significant correlations with PFS. In the Kaplan–Meier analysis, patients with tumors showing lower FD on the AP image at baseline showed longer PFS (P = 0.002). Patients with tumors showing a greater reduction in the FD on the PP image after one cycle of the therapy showed longer overall survival (P = 0.002).

Conclusion

The FD of the tumor on CE-CT images may be a useful biomarker for HCC patients treated with sunitinib.     

Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation

Background

High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is a strong risk factor of hepatocellular carcinoma (HCC) development, independent of hepatitis B e antigen, serum alanine aminotransferase level, and liver cirrhosis. We evaluated whether serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC treated with radiofrequency ablation (RFA).

Methods

The study population was 69 consecutive patients with HBV-related HCC treated locally completely with RFA between January 2000 and September 2007. The risk factors for HCC recurrence were analyzed based on laboratory data, including serum HBV DNA load, together with tumor size and number using univariate and multivariate proportional hazard regression analyses.

Results

HCC recurrence was observed in 42 of 69 patients during the median observation period of 1.5 years. Cumulative recurrence rates at 1, 3, and 5 years were 26.5, 57.8, and 74.3%, respectively. In univariate analysis, albumin (<3.5 g/dl), platelet count (<150 × 10³/mm³), prothrombin activity (PT) (<70%), Child-Pugh class B, serum HBV DNA load (>4.0 log10 copies/ml), and tumor number (>3) were associated with the recurrence at p ≤ 0.15. Multivariate Cox regression analysis with stepwise variable selection showed that the tumor number (risk ratio, 4.63; 95% CI, 1.50–14.25, P = 0.0076), low PT (3.39, 1.52–5.78, P = 0.0029), and high HBV DNA load (2.67, 1.16–6.14, P = 0.021) were independent risk factors for HCC recurrence.

Conclusion

Serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC after RFA.     

Single HCC smaller than 2 cm: surgery or ablation

Purpose

For hepatocellular carcinoma (HCC), surgical resection and radiofrequency ablation (RFA) are accepted as effective treatments. To clarify the long-term outcome in patients with small HCC, we analyzed data from a nationwide survey of Japan.

Methods

Between 2000 and 2003, a total of 2,550 patients who had undergone resection (n = 1,235) or RFA (n = 1,315) for single small HCC (≤2 cm) were registered to the database of the Liver Cancer Study Group of Japan (LCSGJ).

Results

After a median follow-up period of 37 months, disease-free survival after resection was significantly better than after RFA (1-year, 91 vs. 87%; 2-year, 46 vs. 25%; P = 0.001), but overall survival after resection and RFA were similar (98 vs. 99%; 94 vs. 95%, P = 0.28). In the patients of Child–Pugh class A, disease-free survival was significantly better after resection (n = 1,056) than after RFA (n = 965) (P = 0.001), while overall survival was not significantly different (P = 0.16). In the patients of Child–Pugh class B, both disease-free and overall survival were almost similar (P = 0.63 and P = 0.66) after resection (n = 136) and RFA (n = 303).

Conclusions

For single small HCC (≤2 cm), surgical resection provides better disease-free survival than does RFA. Longer follow-up is needed to regard this indication as conclusive.     

Radiofrequency ablation for hepatocellular carcinoma: the relationship between a new grading system for the ablative margin and clinical outcomes

Background

In our previous study, we classified the radicality (R grading) of percutaneous radiofrequency ablation (RFA) therapy for single hepatocellular carcinoma (HCC) according to the extent of the ablated margin, and demonstrated that this grading system was useful for predicting local tumor progression (LTP) after RFA. The aim of this study was to measure the overall survival (OS), the recurrence free survival (RFS), and the distant recurrence (DR) rate for each R grade (A–D), and to examine the relationship between clinical outcome and R grading.

Methods

This study involved 368 patients with solitary HCC who had undergone RFA. The mean tumor diameter was 2.0 ± 0.7 cm. We calculated the post-RFA cumulative OS, RFS, and DR rate for each R grade and analyzed the factors contributing to clinical outcomes.

Results

In the multivariate analysis, significant factors were as follows: tumor size >2 cm, serum albumin >3.5 g/dL, prothrombin time >70 %, HCC recurrence within 1 year, and R grading (grade A) in OS; cause of liver disease (hepatitis B), gamma glutamyl transpeptidase (GGT) >80 IU/L, platelet count >10 × 10⁴/mm³, and R grading (grade A or B) in RFS; GGT >80 IU/L, platelet count >10 × 10⁴/mm³, and R grading (grade A or B) in DR. In patients with sufficient Lipiodol accumulation (n = 219), very similar results were obtained. However, in patients with grade A and B (n = 232), R grade was not a significant independent factor linked to OS, although grade A patients had lower LTP rate.

Conclusions

Our proposed R grading system appears to be useful for predicting clinical outcomes after RFA.     

Laparoscopic findings of reddish markings predict hepatocellular carcinoma in patients with hepatitis B virus-related liver disease

Background

For patients with chronic hepatitis due to hepatitis B virus (HBV), factors predicting hepatocellular carcinoma (HCC) other than high levels of HBV-DNA and alanine aminotransferase (ALT) are needed to prevent HCC development, as many patients with chronic HBV infection fulfill these conditions. The purpose of this study was to clarify factors predictive of HCC development for those patients.

Methods

The study was a systematic cohort analysis of 303 consecutive patients with hepatitis B e-antigen, receiving laparoscopic examination for assessment of liver disease. Laparoscopic, histological, and clinical characteristics were investigated as related to HCC development.

Results

HCC occurred in 27 patients during a mean follow-up of 8.0 ± 5.0 years, at the age of 37–72 years. Significant associations with HCC development were shown for liver cirrhosis, histological activity grade, reddish markings, and older age. Multivariate analysis revealed that HCC development was strongly associated with older age and male gender (P = 0.002 and P = 0.043, respectively). HCC occurred more frequently in patients of age ≥30 years even with early stage than in patients of age <30 years (P = 0.031). Severe reddish markings, a laparoscopic finding of widespread parenchymal destruction, were highly associated with HCC development in patients of age ≥30 years at diagnosis (odds ratio = 1.67, P = 0.034), while histological activity grade and ALT level were not (P = 0.075 and P = 0.69, respectively).

Conclusions

HCC development is associated with older age, male gender, and liver cirrhosis. Reddish markings, rather than histological activity or ALT level, can be useful to predict HCC for HBV patients of age ≥30 years.     

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.     

Lipiodolized transarterial chemoembolization in hepatocellular carcinoma patients after curative resection

Purpose

To explore the effect of lipiodolized transarterial chemoembolization (lip-TACE) in hepatocellular carcinoma (HCC) patients at different risk of recurrence after curative resection.

Methods

One thousand nine hundred and twenty-four consecutive HCC patients who underwent curative resection were retrospectively analyzed. Patients who underwent resection only were classified into control group, while those received adjuvant lip-TACE were classified into intervention group. Patients were further stratified into 4 groups, that is, tumor ≤5 cm with low or high risk factors, as well as tumor >5 cm with low or high risk factors for recurrence. Tumor number and microscopic tumor thrombus were defined as risk factors for recurrence. The effect of adjuvant lip-TACE on early (<2 year) or late (≥2 year) recurrence was evaluated.

Results

There was no significant difference in recurrence curve between intervention group and control group in each stratum. Adjuvant lip-TACE showed an overall survival benefit in patients with tumor >5 cm and presenting high risk factors, mainly for those with time to recurrence (TTR) <2 years after operation. For them, the median survival was 17 months in the intervention group and 11 months in the control group (P = 0.010). For patients who were confirmed to be recurrence-free at 2 years after operation, it had the negative effect for survival (HR = 1.75, P = 0.004).

Conclusion

Adjuvant lip-TACE had no preventive effect on recurrence, but may be of benefit to detect early recurrence.