Unexpected anti-tumor effect of immune checkpoint inhibitors followed by transcatheter arterial chemoembolization for hepatocellular carcinoma.

The abscopal effect has recently attracted much attention because this effect is enhanced by immune checkpoint inhibitors (ICIs). However, little is known about the association between induction of the abscopal effect and local treatment against hepatocellular carcinoma (HCC). We describe a patient with advanced HCC who underwent selective transcatheter arterial chemoembolization (TACE) after treatment with an ICI that was found to remarkably regress in lesions in areas outside that targeted by selective TACE. An 82-year-old man had multiple recurrences in both lobes of the liver despite of repeated TACE and radiofrequency ablation, after resection of an HCC five years previously. After chemotherapy with atezolizumab and bevacizumab, his des-gamma-carboxy prothrombin (DCP) increased. CT during hepatic arteriography revealed multiple recurrent HCCs in both lobes of the liver. TACE with selective embolization at the level of the medial segmental arteries was performed against an approximately 50 mm-diameter tumor in the right lobe. Hepatic arterial phase imaging of contrast-enhanced CT performed 6 days after TACE showed hypo-enhancement of tumors in segment II and III in the left lobe. This case highlights that abscopal effects can be induced by local treatment against HCCs in combination with treatment with ICIs.

Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Alpha-fetoprotein (AFP) response (relative decline in AFP) is associated with imaging response evaluated by response evaluation criteria in solid tumors ver1.1 (RECIST) and survival in treatment for hepatocellular carcinoma (HCC). However, the optimal threshold of AFP response is still unknown, especially in atezolizumab and bevacizumab (Atez/Bev) treatment. In this prospective multicenter study, we aimed to investigate an optimal threshold of AFP response in Atez/Bev treatment. Out of 284 patients with unresectable HCC who were treated with Atez/Bev, 91 patients with AFP ≥ 10 ng/ml were enrolled in the multicenter study. We investigated the relationship between various AFP response thresholds (relative decline ≥ 20%, ≥ 50%, and ≥ 75%) and treatment response and progression-free survival (PFS). An AFP relative decrease of ≥ 50% was associated with an overall response rate (ORR) with an odds ratio (95% confidence interval [CI]) of 5.7 (1.9-17). Disease control rate (DCR) was associated with an AFP relative decrease of ≥ 20%, with a 100% positive predictive value and a 52.0% sensitivity. AFP relative decreases of ≥ 50% and ≥ 20% were significantly associated with PFS with a hazard ratio (HR) of 5.60 (95% CI: 1.6-19, p = 0.006) and a HR of 4.44 (95% CI: 1.9-10, p < 0.001), respectively. AFP response of ≥ 50% and ≥ 20% were related to ORR and DCR, respectively, and both of these responses were also associated with PFS. AFP can be used as a real-time monitor during Atez/Bev treatment and is helpful for treatment optimization.

Prospective comparison of diagnostic performance of magnifying endoscopy and biopsy for sessile serrated adenoma/polyp.

Background: Magnifying narrow-band imaging (M-NBI) has recently improved the accuracy of endoscopic diagnosis of gastrointestinal tumors, including colorectal polyps. However, it can be difficult to distinguish between sessile serrated adenoma/polyps (SSA/Ps) and other polyps, especially hyperplastic polyps (HPs), by histological biopsy, because diagnostic features of SSA/Ps can be detected around the colon crypt bases. We aimed to evaluate the accuracy of endoscopic diagnosis of SSA/Ps using M-NBI compared with histological biopsy. Methods: We prospectively enrolled patients diagnosed with SSA/Ps by preoperative endoscopy and assessed the diagnostic accuracy. The primary outcome was the diagnostic accuracy of endoscopy and biopsy. Results: Between August 2015 and October 2017, 295 lesions were resected by polypectomy or endoscopic mucosal resection, and 79 endoscopically resected specimens that were endoscopically diagnosed as SSA/P underwent biopsy for histological examination. Two lesions were excluded because the specimens were too small for histological examination. Finally, 77 endoscopically resected specimens and 77 biopsy specimens were included in the analysis. Histopathological examination showed 67 SSA/Ps, 8 HPs, and 2 adenomas. The sensitivity, specificity and accuracy of endoscopic M-NBI diagnosis for SSA/Ps were 95.7%, 95.5% and 95.6%, respectively. The sensitivity, specificity and accuracy of histological diagnosis of a single biopsy specimen were 71.6%, 90.0% and 74.0%, respectively. The McNemar test showed significant differences between biopsy and endoscopy diagnoses (P=0.001). Conclusion: This study shows that biopsy may be avoided by using M-NBI in patients with suspected SSA/Ps.

The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study.

BACKGROUND: Lenvatinib (LEN) has been approved for patients with unresectable hepatocellular carcinoma (u-HCC) since March 2018 in Japan. We performed a retrospective nationwide multicenter study to clarify the clinical characteristics of LEN in real-world practice. METHODS: A total of 343 u-HCC patients who received LEN from March 2018 to May 2020 at 23 sites in Japan were registered. RESULTS: During the median observation period of 10.5 months, 143 patients died. In Child-Pugh A (n = 276) and Child-Pugh B (n = 67) patients, the median overall survival (OS) was 21.0 and 9.0 months. The median progression-free survival (PFS) was 8.8 months in Child-Pugh A patients. The objective response rate (ORR) and disease control rate (DCR) according to modified response evaluation criteria in solid tumors (RECIST criteria) were 42.1% and 82.1%. The independent pretreatment factors associated with mortality in all patients were AFP ≥ 400 ng/mL (hazard ratio (HR) 2.00, 95% confidential interval (95% CI) 1.08-2.09, p < 0.0001), modified albumin-bilirubin (ALBI) grade 2b or 3 (HR 1.56, 95% CI 1.09-2.17, p = 0.012), major vascular invasion (HR 1.91, 95% CI 1.26-2.89, p = 0.0022), PS > 0 (HR 1.50, 95% CI 1.09-2.08, p = 0.014), and MTT (molecular targeted therapy) experience (HR 2.22, 95% CI 1.56-3.13, p = 0.00038). In the MTT naïve patients with ALBI grade 1 or modified ALBI 2a and BCLC stage B (n = 68), median OS and PFS were 25.3 and 12.3 months. Liver-related adverse events during LEN were the only significant adverse event associated with OS (HR 2.74, 95% CI 1.93-3.88, p < 0.0001). Among the Child-Pugh A patients with extrahepatic metastasis and no major vascular invasion, median PFS in the patients with bone metastasis was significantly shorter than those with lung or adrenal grand metastasis (6.3 vs. 12.5 months, p = 0.0025). CONCLUSION: LEN showed a high response rate in real-world practice. Pretreatment factors, including ALBI score, AFP, and major vascular invasion are important in making a treatment strategy for patients with u-HCC. The patients with bone metastasis would be candidates for new therapeutic approaches.

Underwater endoscopic mucosal resection: a new endoscopic method for resection of rectal neuroendocrine tumor grade 1 (carcinoid) ≤ 10 mm in diameter.

Background and study aims Rectal neuroendocrine tumors grade 1 (NET G1; carcinoid) ≤ 10 mm in diameter often extend into the submucosa, making their complete histological resection difficult using endoscopic techniques. Endoscopic submucosal resection with a ligation device (ESMR-L) and endoscopic submucosal dissection (ESD) are commonly used to overcome these difficulties. We also previously reported that underwater endoscopic mucosal resection (UEMR) could facilitate resection of rectal NET G1. This study aimed to evaluate the safety and efficacy of UEMR for removing rectal NET G1 ≤ 10 mm in diameter. 6 consecutive patients with rectal NET G1 ≤ 10 mm in diameter underwent UEMR at our hospital. The rate of en bloc resection was 100 %, and the rate of R0 resection was 83 %. The median procedure time was 8 min (range 5 - 12 min). No perforations or delayed bleeding occurred in this study. In conclusion, UEMR allows the safe and reliable resection of rectal NET G1 ≤ 10 mm in diameter with comparable results to ESMR-L or ESD, including high en bloc and R0 resection rates with no increase in significant adverse events. A multicenter trial is required to confirm the validity of the present results.

Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy.

The present study aimed to examine the impact of sarcopenia, defined as low muscle mass on computed tomography (CT), prior to sorafenib therapy on the clinical outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib therapy. In total, 232 patients with unresectable HCC (median age, 72 years) were analyzed, and the extent of sarcopenia was assessed using CT. Cross-sectional areas (cm2) of the skeletal muscles at the third lumbar vertebra level were determined by manual outlining on the CT images. The cross-sectional areas were normalized for height [skeletal muscle index (SMI), cm2/m2]. Based on the findings of previous studies, male patients with SMI ≤36.2 cm2/m2 and female patients with SMI ≤29.6 cm2/m2 were defined as having sarcopenia. The baseline characteristics, overall survival (OS) rates, progression-free survival (PFS) rates and best treatment response of the sarcopenia group were retrospectively compared with those of the non-sarcopenia group, and the factors associated with OS and PFS were examined. Sarcopenia was observed in 151 patients (65.1%). There were 165 patients with Child-Pugh A and 67 with Child-Pugh B cirrhosis. In the sarcopenia group, the median treatment duration was 66 days, whereas in the non-sarcopenia group it was 103 days (P=0.001). The median OS time was 174 days in the sarcopenia group and 454 days in the non-sarcopenia group (P<0.0001). The median PFS was 77 days in the sarcopenia group and 106 days in the non-sarcopenia group (P=0.0131). Multivariate analysis identified sarcopenia to be an independent predictor of OS (hazard ratio, 0.365; P<0.0001). The objective response rate and disease control rate in the sarcopenia group were significantly lower, compared with those in the non-sarcopenia group (P=0.0146 and P=0.0151, respectively). In conclusion, sarcopenia may be an indicator of poor clinical course in patients with HCC receiving sorafenib.

Cold snare polypectomy reduced delayed postpolypectomy bleeding compared with conventional hot polypectomy: a propensity score-matching analysis.

BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) for small colorectal polyps has lower incidence of adverse events, especially delayed postpolypectomy bleeding (DPPB). However, few data are available on comparisons of the incidence of DPPB of CSP and hot polypectomy (HP). The aim of this study was to evaluate the incidence of DPPB after CSP and compare it with that of HP. A propensity score model was used as a secondary analysis. PATIENTS AND METHODS: This was a retrospective cohort study conducted in a single municipal hospital. We identified 539 patients with colorectal polyps from 2 mm to 11 mm in size who underwent CSP (804 polyps in 330 patients) or HP (530 polyps in 209 patients) between July 2013 and June 2015. RESULTS: There were no cases of DPPB in the CSP group. Conversely, DPPB occurred in 4 patients (1.9 %) after HP, resulting in a significant difference between the CSP and HP groups (0.008 % vs 0 %, P  = 0.02). Propensity score-matching analysis created 402 matched pairs, yielding a significantly higher DPPB rate in the HP group than CSP group (0.02 % vs 0 %, P  = 0.04). However, significantly more patients in the CSP group had unclear horizontal margins that precluded assessment (83 vs 38 cases, P  < 0.001). The retrieval failure rate was significantly higher in the CSP group than in the HP group (3 % vs 0.7 %, P  = 0.01). CONCLUSIONS: DPPB was less frequent with CSP than HP, as selected by the propensity score-matching model. Our findings indicate that CSP is recommended polypectomy in daily clinical setting. However, special care should be taken during polyp retrieval and horizontal margin assessment, and these issues could be taken into account in follow-up after CSP.

Comparison of FIB-4 index and aspartate aminotransferase to platelet ratio index on carcinogenesis in chronic hepatitis B treated with entecavir.

AIMS: We sought to compare the effects of FIB-4 index and aspartate aminotransferase to platelet ratio index (APRI) on hepatocellular carcinoma (HCC) incidence in chronic hepatitis B (CHB) patients undergoing entecavir (ETV) therapy. PATIENT AND METHODS: A total of 338 nucleosides analogue therapy naïve CHB patients initially treated with ETV were analyzed. The optimal cutoff points in each continuous variable were determined by receiver operating curve (ROC) analysis. The effects of FIB-4 index and APRI on HCC incidence were compared using time-dependent ROC analysis and factors linked to HCC incidence were also examined using univariate and multivariate analyses. RESULTS: There were 215 males and 123 females with the median age of 52 years and the median baseline HBV-DNA level of 6.6 log copies/ml. The median follow-up interval after the initiation of ETV therapy was 4.99 years. During the follow-up period, 33 patients (9.8%) developed HCC. The 3-, 5- 7-year cumulative HCC incidence rates in all cases were 4.4%, 9.2% and 13.5%, respectively. In the multivariate analysis, FIB-4 index revealed to be an independent predictor associated with HCC incidence, while APRI was not. In the time-dependent ROC analyses for all cases and for all subgroups analyses stratified by viral status or cirrhosis status, all area under the ROCs in each time point (2-, 3-, 4-, 5-, 6-, and 7-year) of FIB-4 index were higher than those of APRI. CONCLUSION: FIB-4 index rather than APRI can be a useful predictor associated with HCC development for CHB patients undergoing ETV therapy.

Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis.

AIMS: To investigate variables before sorafenib therapy on the clinical outcomes in hepatocellular carcinoma (HCC) patients receiving sorafenib and to further assess and compare the predictive performance of continuous parameters using time-dependent receiver operating characteristics (ROC) analysis. PATIENTS AND METHODS: A total of 225 HCC patients were analyzed. We retrospectively examined factors related to overall survival (OS) and progression free survival (PFS) using univariate and multivariate analyses. Subsequently, we performed time-dependent ROC analysis of continuous parameters which were significant in the multivariate analysis in terms of OS and PFS. Total sum of area under the ROC in all time points (defined as TAAT score) in each case was calculated. RESULTS: Our cohort included 175 male and 50 female patients (median age, 72 years) and included 158 Child-Pugh A and 67 Child-Pugh B patients. The median OS time was 0.68 years, while the median PFS time was 0.24 years. On multivariate analysis, gender, body mass index (BMI), Child-Pugh classification, extrahepatic metastases, tumor burden, aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) were identified as significant predictors of OS and ECOG-performance status, Child-Pugh classification and extrahepatic metastases were identified as significant predictors of PFS. Among three continuous variables (i.e., BMI, AST and AFP), AFP had the highest TAAT score for the entire cohort. In subgroup analyses, AFP had the highest TAAT score except for Child-Pugh B and female among three continuous variables. CONCLUSION: In continuous variables, AFP could have higher predictive accuracy for survival in HCC patients undergoing sorafenib therapy.

A predictive model for carcinogenesis in patients with chronic hepatitis B undergoing entecavir therapy and its validation.

We created a model to predict the development of liver carcinogenesis in patients with chronic hepatitis B (CHB) undergoing entecavir (ETV) therapy and to validate the accuracy using an independent dataset.A total of 328 CHB subjects were analyzed. Subjects were randomly assigned into 2 groups: the training group (n = 164) and the validation group (n = 164). Using data from the training group, we built a predictive model for liver carcinogenesis by performing univariate and multivariate analyses using variables associated with liver carcinogenesis. We subsequently assessed the applicability of the constructed model in the validation group.The median (range) follow-up periods in the training and the validation groups were 5.03 years (1.03-9.98) and 4.84 years (1.10-9.97), respectively. The proportion of hepatitis B virus-DNA at 24 weeks <1.9 log IU/mL in the training group was 70.7% (116/164), while that in the validation group was 71.3% (117/164). For the entire cohort (n = 328), the median alpha-fetoprotein (AFP) value at 24 weeks (3.45 ng/mL; range, 0.9-102.7 ng/mL) significantly decreased compared to the baseline values (5.55 ng/mL; range, 0.9-1039.5 ng/mL), while the median alanine aminotransferase (ALT) value at 24 weeks (24 IU/mL; range, 6-251 IU/mL) also significantly decreased compared to baseline values (57 IU/mL; range, 7-1450 IU/mL). During the observation period, hepatocellular carcinoma (HCC) developed in 15 (9.1%) patients in the training group and in 17 (10.4%) patients in the validation group. The 3- and 5-year cumulative HCC incidence rates in the entire cohort were 4.48% and 9.52%, respectively. In the multivariate analysis of the training group, age ≥54 years (P = 0.0273), ALT level at 24 weeks (P = 0.0456), and AFP at 24 weeks (P = 0.0485) were found to be significant predictors linked to HCC. Using these independent predictors, the risk for HCC development was well stratified in the validation group (overall significance, P < 0.0001). Similar results were observed in subgroup analyses of patients with or without cirrhosis and HBe antigen positivity.In conclusion, our predictive model was well verified; hence, it may be a promising model for the prediction of the development of liver carcinogenesis in CHB patients undergoing ETV therapy.

Comparison of five staging systems in hepatocellular carcinoma treated with sorafenib: A single-center experience.

To the best of our knowledge, none of the prognostic staging systems for hepatocellular carcinoma (HCC) patients who underwent sorafenib therapy is universally adopted or preferred. In the present study, we aimed to compare prognostic ability among five prognostic systems, including the Japan Integrated Staging (JIS) system, the Barcelona Clinic Liver Cancer classification system, the tumor-node-metastasis classification system, the Cancer of the Liver Italian Program scoring system and the Chinese University Prognostic Index (CUPI) scoring system for HCC patients who received sorafenib therapy. A total of 143 HCC patients treated with sorafenib were analysed. We compared prognostic ability among the five prognostic systems using the likelihood ratio (LR) χ2 test, linear trend χ2 test and concordance index (c-index). Our cohort included 114 men and 29 women. The median patient age was 71 years (range, 45-89 years). A total of 102 patients were classified as Child-Pugh A and 41 as Child-Pugh B, whereas 31 patients (21.7%) had portal vein invasion and 63 (44.1%) extrahepatic metastases. The median survival time was 6.9 months. In the LR χ2 test, the CUPI scoring system had the highest value (35.804), followed by the JIS system (17.469). In the linear trend χ2 test, the CUPI scoring system had the highest value (17.523), followed by the JIS system (15.819). In addition, the JIS system had the highest value in the 6-month c-index (0.659) as well as in the 1-year c-index (0.674). However, the CUPI classification system had the lowest value in the 1-year c-index (0.590). In conclusion, the JIS system may be an appropriate staging system for HCC patients undergoing sorafenib therapy.

Proposal of the performance status combined Japan Integrated Staging system in hepatocellular carcinoma complicated with cirrhosis.

The present study examined the prognostic ability of our proposed performance status combined Japan Integrated Staging (PS-JIS) system in hepatocellular carcinoma (HCC) patients with liver cirrhosis (LC) comparing with other four prognostic systems including original JIS system, the Barcelona Clinic Liver Cancer classification system, TNM classification system and the Cancer of the Liver Italian Program (CLIP) scoring system. A total of 1,170 HCC patients complicated with LC were analysed. The disease was staged for all analysed patients by means of the five staging systems. The cumulative overall survival (OS) rate was calculated by Kaplan-Meier method and tested by log-rank test. We also examined prognostic factors associated with OS using univariate and multivariate analyses and compared the prognostic ability in each prognostic system using concordance index (c-index) at 1-, 3- and 5-year time-points. Overall significance in each prognostic system was P<0.001. In the multivariate analyses, tumor number, Child-Pugh classification, PS, initial treatment modality and several laboratory parameters were significant independent predictors linked to OS. For all cases, in each time-point, the c-index of PS-JIS system was the highest among five staging systems (0.847, 0.816 and 0.808, respectively), indicating that PS-JIS system has the best predictability among these staging systems. According to subgroup analyses stratified by initial treatment modality, in patients treated with surgical resection (n=205), CLIP scoring system had the highest c-index at every time-point, whereas in patients treated with percutaneous ablative therapies (n=632) at 3- and 5-year time-point and in those with transcatheter arterial therapies (n=281) at every time-point, the c-index of PS-JIS system was the highest. In conclusion, the proposed PS-JIS score can be a useful prognostic system for HCC patients complicated with liver cirrhosis.

Hyponatremia in hepatocellular carcinoma complicating with cirrhosis.

BACKGROUND AND AIMS: We aimed to investigate the effect of serum sodium level on survival in hepatocellular carcinoma (HCC) patients complicating with liver cirrhosis (LC). METHODS: A total of 1170 HCC patients with LC were analysed. We classified these patients into three groups according to serum sodium level at HCC diagnosis: group A (n=96); serum sodium ≤135 mmol/L, group B (n=520); 135 mmol/L < serum sodium ≤140 mmol/L, group C (n=554); serum sodium >140 mmol/L. We compared the baseline characteristics and overall survival (OS) among these three groups. Furthermore, we examined the factors linked to OS using univariate and multivariate analyses. RESULTS: In our results, decreased baseline serum sodium level was significantly associated with Child-Pugh classification and HCC stage along with several laboratory parameters in groups A, B and C. The median follow-up period was 1.1 years in group A, 2.4 years in group B and 3.3 years in group C. The 1-, 3- and 5-year cumulative OS rates in groups A, B and C were 64.8%, 46.9% and 25.7%, respectively, in group A, 85.5%, 60.5% and 41.1%, respectively, in group B and 90.7%, 66.6% and 48.2%, respectively, in group C (P<0.001). The multivariate analyses showed that Child-Pugh classification (P<0.001), HCC stage (P<0.001), serum sodium (P<0.001), aspartate aminotransferase ≥57 IU/L (P=0.002), alkaline phosphatase ≥348 IU/L (P<0.001), alpha-fetoprotein ≥29.2 ng/mL (P=0.019) and des-γ-carboxy prothrombin ≥55 mAU/mL (P<0.001) were significant independent predictors linked to OS. CONCLUSION: Lower serum sodium concentration is a useful predictor in HCC patients complicating with LC.

Clinical implication of performance status in patients with hepatocellular carcinoma complicating with cirrhosis.

BACKGROUND AND AIMS: The aims of our study were to elucidate the relationship between baseline characteristics of hepatocellular carcinoma (HCC) patients complicating with liver cirrhosis (LC) and performance status (PS) and to investigate the impact of PS on survival in patients with HCC complicating with LC. METHODS: In a total of 1003 patients diagnosed with HCC complicating with LC, we divided into two groups of PS ≥1 (n=251) and PS 0 (n=752) as evaluated by using the Eastern Cooperative Oncology Group criteria at the time of HCC diagnosis. Baseline characteristics between these two groups were compared. We also performed univariate and multivariate analyses of factors contributing to overall survival (OS). RESULTS: The median follow-up period was 1.6 years in the PS ≥1 group and 3.1 years in the PS 0 group. The 1-, 3- and 5-year OS rates after each initial therapy for HCC were 90.3%, 67.4% and 49.8%, respectively, in the PS 0 group and 73.4%, 42.0% and 17.7%, respectively, in the PS ≥1 group (P<0.001). A worse PS was significantly associated with age, gender, Child-Pugh classification, HCC stage, Japan Integrated Staging score, initial treatment option for HCC, maximum tumor size, alanine aminotransferase value, hypoalbuminemia, hyperbilirubinemia, renal insufficiency, hyponatremia, prothrombin time prolongation, platelet count and tumor marker level. In multivariate analyses, poorer PS was an independent predictor linked to OS with a hazard ratio of 1.773 (P<0.001). CONCLUSIONS: PS was closely associated with status of HCC patients with LC and could be an important predictor for these populations.

Clinical significance of the FIB-4 index for non-B non-C hepatocellular carcinoma treated with surgical resection.

The aims of the present study were to examine the relationship between the preoperative FIB-4 index and background liver fibrosis in non-tumor parts obtained from surgical specimens and to investigate whether the FIB-4 index can be a useful predictor for non-B non-C hepatocellular carcinoma (NBNC-HCC) patients treated with surgical resection (SR). A total of 118 patients with NBNC-HCC treated with SR with curative intent were analyzed. Receiver operating characteristic (ROC) curve analysis was performed for calculating the area under the ROC (AUROC) for the FIB-4 index, aspartate aminotransferase (AST) to platelet ratio index, AST to alanine aminotransferase ratio, serum albumin, total bilirubin and platelet count for cirrhosis. We also examined predictors linked to overall survival (OS) and recurrence-free survival (RFS) after SR. The mean patient age was 68.9±9.0 years (93 males and 25 females) with a median observation period of 3.2 years. In extracted surgical specimens, background liver cirrhosis (F4) was observed in 39 patients (33.1%). The mean maximum tumor size was 5.7±3.2 cm. The mean body mass index was 24.3±3.9 kg/m2. The FIB-4 index yielded the highest AUROC for cirrhosis with a level of 0.887 at an optimal cut-off value of 2.97 (sensitivity, 92.3; specificity, 69.6%). In the multivariate analysis, serum α-fetoprotein >40 ng/ml (P=0.026) was the only significant independent predictor linked to OS, while tumor number (P=0.002) and FIB-4 index >2.97 (P=0.044) were significant factors linked to RFS. In conclusion, preoperative FIB-4 index can be a useful predictor for NBNC-HCC patients who undergo SR.

Clinical implication of the preoperative GSA index in 99mTc-GSA scintigraphy in hepatitis C virus-related hepatocellular carcinoma.

We aimed to examine the relationship between the preoperative GSA index [uptake ratio of the liver to the liver plus heart at 15 min (LHL15) to uptake ratio of the heart at 15 min to that at 3 min (HH15) ratio] calculated from 99mTc­labeled diethylene triamine pentaacetate-galactosyl human serum albumin (99mTc-GSA) scintigraphy and background liver fibrosis and to investigate whether the GSA index can be a useful predictor in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) patients treated with surgical resection (SR). A total of 213 HCV-related HCC patients were analyzed. Receiver operating characteristic (ROC) curve analysis was performed for calculating the area under the ROC (AUROC) for nine noninvasive parameters including GSA index, indocyanine green retention at 15 min, aspartate aminotransferase (AST) to platelet ratio index, FIB-4 index, AST to alanine aminotransferase ratio, serum albumin, total bilirubin, platelet count and prothrombin time for cirrhosis. We also examined predictive factors associated with overall survival (OS) and recurrence-free survival (RFS) after SR in univariate and multivariate analyses. There were 153 males and 60 females with the mean age of 69.9 years. The median observation periods were 2.8 years. The mean maximum tumor size was 4.1 cm. HH15 ranged from 0.452 to 0.897. LHL15 ranged from 0.669 to 0.982. The mean value of the GSA index was 1.41. Among the nine parameters, the GSA index yielded the highest AUROC for cirrhosis with a level of 0.786 at an optimal cut-off value of 1.37 (sensitivity, 65.9%; specificity, 79.0%). In multivariate analyses, the GSA index was an independent predictor (P<0.001) linked to RFS and it had a marginal significance in terms of OS (P=0.074). In conclusion, the preoperative GSA index can be a useful predictor in HCV-related HCC patients treated with SR.

Transcatheter arterial chemoembolization for intermediate-stage hepatocellular carcinoma: clinical outcome and safety in elderly patients.

AIM: The aim of our study was to compare clinical outcomes between elderly patients aged ≥75 years (elderly group, n=66) with intermediate hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE) and younger patients aged <75 years (control group, n=84) with intermediate HCC undergoing TACE. METHODS: Clinical outcomes, including overall survival (OS) and tumor response rate at initial therapy, were compared between these two groups. RESULTS: The median survival time and the 1- and 3-year cumulative OS rates were 2.90 years and 84.1% and 48.0%, respectively, in the elderly group and 2.44 years and 78.2% and 39.3%, respectively, in the control group (p=0.887). The objective response rate in the elderly group was 81.8% (54/66 patients), while that in the control group was 78.6% (66/84 patients) (p=0.227). CONCLUSION: Elderly patients with intermediate HCC undergoing TACE had a prognosis comparable with that of younger patients with intermediate HCC undergoing TACE.

Clinical significance of early interventional therapy of branched-chain amino acid granules in patients with hepatocellular carcinoma: propensity score matching analysis.

We examined whether supplementation of branched-chain amino acid (BCAA) granules in an early stage of underlying liver disease (pretreatment serum albumin levels ≥ 3.6 g/dl) can improve overall survival (OS) after therapy for hepatocellular carcinoma (HCC) using propensity score matching analysis. We compared OS between patients treated with BCAA granules and control group patients in two propensity score matched cohorts (cohort 1: pretreatment serum albumin levels ≥ 3.6 g/dl and <4.0 g/dl, 111 pairs; cohort 2: pretreatment serum albumin levels ≥ 4.0 g/dl, 61 pairs). We also performed subgroup analyses according to HCC stage. In cohort 1 patients, the OS rate in the BCAA group (median follow-up period, 2.9 years) tended to be higher compared to that in the control group (median follow-up period, 2.6 years) (1- and 3-year OS rates; 97.2 and 75.5% in the BCAA group and 87.2 and 64.5% in the control group, P=0.072), whereas in cohort 2 patients, the difference in the two groups did not reach significance in terms of OS [1- and 3-year OS rates; 83.2 and 60.7% in the BCAA group (median follow-up period, 2.3 years) and 91.8 and 66.0% in the control group (median follow-up period, 2.9 years), P=0.871]. In subgroup analyses, in cohort 1, in patients with HCC stage III or IV, the OS rate in the BCAA group (n=37) was significantly higher compared to that in the control group (n=34) (P=0.017). In other subgroup analyses, no significant difference in the two groups was found in terms of OS. In conclusion, early interventional therapies using BCAA granules may be effective in some selected HCC patients.

Clinical efficacy of non-transplant therapies in patients with hepatocellular carcinoma with Child-Pugh C liver cirrhosis.

AIM: To compare clinical outcome in patients with Child-Pugh C hepatocellular carcinoma (HCC) treated with non-transplant therapies and those treated with best supportive care. PATIENTS AND METHODS: A total of 182 patients with HCC with Child-Pugh C cirrhosis were analyzed. Patients were classified into two groups: patients treated with non-transplant therapies (n=113, treated group) and untreated patients (n=69, untreated group). Furthermore, for reducing the bias in patient selection, a propensity score matching analysis was performed (55 pairs). RESULTS: The median survival time in the treated group was significantly longer than that in the untreated group (1.16 years vs. 0.21 years, p<0.001). After propensity score matching, the median survival time in the treated group remained significantly longer than that in the untreated group (0.95 years vs. 0.17 years, p=0.01). CONCLUSION: In patients with HCC with Child-Pugh C cirrhosis, those treated with non-transplant therapies might have longer survival than untreated patients.

[Three cases of hepatocellular carcinoma with nodules showing different signal intensities in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI].

We report three cases of resected hepatocellular carcinomas with nodules showing different signal intensities in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI (EOB-MRI). One case involved a nodule-in-nodule type hepatocellular carcinoma that showed high signal intensity for the outer tumor and low intensity for the inner tumor in the hepatobiliary phase of EOB-MRI. The inner tumor was more dedifferentiated than the outer. The other two cases involved similar nodules, which showed different signal intensities in the hepatobiliary phase of EOB-MRI. In all three cases, the expression of OATP8 showed good correlation with high signal intensity in the hepatobiliary phase of EOB-MRI, whereas MRP2, MRP3, or both were also highly expressed. However, in the two nodules showing low intensities, the expression of one excreting transporter was independently high even though that of OATP8 was not high. The expression of excreting transporters is usually characterized by passive correspondence to OATP8 expression levels; nevertheless, it sometimes shows expression independent of OATP8.