A randomized placebo-controlled trial of prophylactic dexamethasone for transcatheter arterial chemoembolization.

This randomized, double-blind, placebo-controlled trial evaluated dexamethasone efficacy at preventing fever, anorexia, and nausea/vomiting, the most frequent adverse events of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Child-Pugh class A/B patients with HCC and no macrovascular invasion/extrahepatic metastases were randomly assigned to either a dexamethasone regimen (day 1, intravenous dexamethasone [20 mg] and granisetron [3 mg] before TACE; days 2 and 3, intravenous dexamethasone [8 mg]) or a control regimen (day 1, intravenous placebo [saline] and granisetron [3 mg]; days 2 and 3, intravenous placebo). The primary endpoint was complete response, defined as the absence of grade ≥1 fever, anorexia, or nausea/vomiting according to the Common Terminology Criteria for Adverse Events (version 4.0) and no use of rescue therapy for 120 hours after TACE. A total of 120 patients between October 2010 and June 2013 were randomly assigned to treatment groups. Overall the complete response rate was greater with the dexamethasone regimen than with the control regimen (47.5%, 95% confidence interval 34.3%-60.9%, versus 10.2%, 95% confidence interval 3.8%-20.8%; P < 0.001). Cumulative incidences of fever, anorexia, and nausea/vomiting were higher in the control regimen group compared with the dexamethasone group (P < 0.001, P < 0.001, and P = 0.095, respectively). The dexamethasone regimen was generally well tolerated by HCC patients including those with well-controlled diabetes mellitus and those with hepatitis B virus infection. Conclusion: The dexamethasone regimen was more effective than the control regimen at preventing TACE-induced fever, anorexia, and nausea/vomiting in patients with HCC. (Hepatology 2018;67:575-585).

Post-progression survival in patients with advanced hepatocellular carcinoma resistant to sorafenib.

BACKGROUND: Since the approval of sorafenib, no other agent has been proven to show survival benefits in clinical trials involving patients with advanced hepatocellular carcinoma (HCC) resistant to sorafenib. Prognostic factors for survival after tumor progression in sorafenib-treated patients are critical for designing second-line trials. METHODS: To determine the factors affecting the post-progression survival (PPS) after sorafenib treatment, additional analyses were conducted using fixed data obtained from our previous prospective study. Data on patients with advanced HCC treated with sorafenib were analyzed in view of patient characteristics at the time of tumor progression and the progression pattern (intra-/extrahepatic growth or emergence of new intra-/extrahepatic lesions). RESULTS: Of the 89 enrolled patients, 70 were diagnosed with disease progression according to the Response Evaluation Criteria in Solid Tumors version 1.1. Multivariate Cox's regression analysis revealed that Child-Pugh scores of ≥7, macrovascular invasion (MVI), and alpha-fetoprotein of >400 ng/mL were independent predictors of poor PPS. Although both extrahepatic metastasis (EHM) and MVI were characteristics of advanced HCC, EHM was not determined as a prognostic factor. Additionally, the emergence of new extrahepatic lesions also served as an independent indicator of a poor prognosis. The PPS of the patients was well stratified according to the index based on the sum of these prognostic factors, ranging from 0 to 4. CONCLUSIONS: Child-Pugh score of ≥7, AFP of >400 ng/mL, MVI, and new extrahepatic lesions at the time of progression may be utilized to assess the prognosis and taken into consideration when designing second-line trials.

Histone lysine methyltransferase SUV39H1 is a potent target for epigenetic therapy of hepatocellular carcinoma.

Histone H3 lysine 9 trimethylation (H3K9me3) is associated with transcriptional repression and regulated by histone lysine methyltransferases such as SUV39H1 and ESET. However, the functional roles of these enzymes in hepatocellular carcinoma (HCC) remain uncertain. In this study, we conducted loss-of-function assays for HCC cells. SUV39H1 knockdown but not ESET knockdown reduced H3K9me3 levels and impaired HCC cell growth and sphere formation. The pharmacological inhibition of SUV39H1 by chaetocin resulted in cell growth inhibition and inducing cellular apoptosis in culture and xenograft subcutaneous tumors. Real-time polymerase chain reaction analysis indicated high levels of SUV39H1 expression in 24 of 42 (57.1%) HCC surgical samples compared with corresponding nontumor tissues. Immunohistochemistry identified high levels of H3K9me3 and ESET proteins in 23 (54.8%) and 29 (69.0%) tumor tissues, respectively. However, these proteins' expressions were only observed in biliary epithelial cells and periportal hepatocytes of nontumor tissues. Expression levels of SUV39H1 but not those of ESET were significantly correlated with H3K9me3 levels. The cumulative HCC recurrence rate was significantly higher for patients with elevated SUV39H1 expression and H3K9me3 levels. In conclusion, our data indicate that elevated SUV39H1 expression and high levels of H3K9me3 have important roles in HCC development and progression. Therefore, the pharmacological inhibition of SUV39H1 may be a promising therapeutic approach for HCC treatment.

Liver function assessment according to the Albumin-Bilirubin (ALBI) grade in sorafenib-treated patients with advanced hepatocellular carcinoma.

BACKGROUND: The Albumin-Bilirubin (ALBI) grade has been proposed as a new, simple, and objective method of assessing liver function. However, there is lack of data in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). METHODS: We evaluated the correlations between the ALBI grade and Child-Pugh score, adverse events, and survival in 89 patients with advanced HCC who were prospectively treated with sorafenib. RESULTS: Majority of patients with ALBI grade 1 (14/15 patients, 93%) had a Child-Pugh score of 5. Patients with ALBI grade 2 had a wide range of liver function according to the Child-Pugh scores, with scores of 5, 6, 7, and ≥ 8. We divided ALBI grade 2 patients into ALBI grade 2A and 2B groups according to the median ALBI score among patients with ALBI grade 2. Although no significant difference was observed, the incidence of liver dysfunction in sorafenib-treated patients with ALBI grades 1, 2A, and 2B was 7%, 19%, and 35%, respectively. Overall survival in the ALBI grade 2B group was significantly shorter than that in the ALBI grade 1 and 2A groups. Thus, ALBI grade 2B was an independent predictor of poor prognosis in addition to elevated serum aspartate aminotransferase levels, increased serum alpha-fetoprotein level, and macrovascular invasion. CONCLUSION: Sorafenib may be indicated for all patients with advanced HCC and ALBI grade 1 and for some with ALBI grade 2. The subdivision of patients with ALBI grade 2 increases the utility of ALBI in identifying patients indicated for sorafenib therapy.

Sorafenib treatment in Child-Pugh A and B patients with advanced hepatocellular carcinoma: safety, efficacy and prognostic factors.

BACKGROUND: We aimed to evaluate the safety, efficacy and prognostic impact of baseline and early clinical markers in both Child-Pugh A and B patients with advanced hepatocellular carcinoma (HCC). METHODS: We prospectively studied 89 Japanese patients with HCC (Child-Pugh A, n = 59; Child-Pugh B, n = 30) who were started with sorafenib between May 2010 and July 2013. RESULTS: Frequency of sorafenib-related adverse events was almost similar between Child-Pugh score 5, 6, and 7 patients. The rate of liver dysfunction, including any grade encephalopathy, ≥ grade 3 ascites, or ≥ grade 3 bilirubin increased, in Child-Pugh score ≥8 group was significantly higher than that in the other groups. The median overall survival of Child-Pugh score 5, 6, 7 and ≥8 patients were 14.5, 11.1, 8.7 and 4.6 months, respectively. Patients in Child-Pugh score 6 had significantly longer OS than those in Child-Pugh score 7 (P = 0.049). Multivariate analysis identified macrovascular invasion (MVI), alpha-fetoprotein (AFP), Child-Pugh score and aspartate aminotransferase (AST) as baseline predictors of survival. However, extrahepatic metastasis (EHM) was not a significant prognostic factor. In addition, decrease in AFP level and development of hand-foot skin reaction within 4 weeks after sorafenib initiation were closely associated with favorable survival. CONCLUSION: It is possible that not only Child-Pugh score 5 and 6 but also 7 patients are eligible for future clinical trials with sorafenib or similar drugs. Various survival predictors identified in this study might be considered as stratification factor. Although both MVI and EHM is a phenotype of advanced HCC, MVI should be discriminated from EHM because of the prognostic impact on survival in sorafenib-treated advanced HCC patients.

Sustained virologic response achieved after curative treatment of hepatitis C virus-related hepatocellular carcinoma as an independent prognostic factor.

BACKGROUND AND AIM: Whether an antiviral interferon (IFN)-based therapy (IBT) after curative treatment of hepatocellular carcinoma (HCC) improves the prognosis in patients with hepatitis C virus (HCV)-related HCC remains to be elucidated. METHODS: A total of 178 patients within the Milan criteria underwent curative treatment for HCV-related HCC. Both the time to beyond the Milan criteria (TTBMC) and overall survival (OS) were compared between the sustained virologic response (SVR) (IFN with SVR, n = 22), non-SVR (IFN without SVR, n = 19), and non-IBT (control, n = 82) groups using propensity score matching analysis. Prognostic factors to predict survival were also determined by the Cox proportional-hazards model. RESULTS: TTBMC in the IFN with SVR group was significantly longer than those in the control and IFN without SVR groups (P < 0.001 and P = 0.006, respectively), although no significant difference existed between the IFN without SVR and control groups. Similarly, OS of the IFN with SVR group was significantly longer than that of the control and IFN without SVR groups (P < 0.001 and P = 0.029, respectively), although no significant difference existed between the IFN without SVR and control groups. The Cox proportional-hazards model identified SVR as an independent prognostic factor in these patients. The IFN with SVR group showed a 0.096-fold decrease in mortality risk compared with the control group (95% confidence intervals = 0.023-0.405; P = 0.001). CONCLUSION: Elimination of HCV after curative treatment of patients with HCC within the Milan criteria inhibits recurrence and contributes to a preferential prognosis.

A phase I/II trial of capecitabine combined with peginterferon α-2a in Patients with sorafenib-refractory advanced hepatocellular carcinoma.

BACKGROUND: Several pilot studies have demonstrated the effectiveness of combination therapy with pyrimidine fluoride and interferon for advanced hepatocellular carcinoma.This study aimed to determine the recommended dose of capecitabine combined with peginterferon α-2a (Phase I) and evaluate its safety and efficacy for sorafenib-refractory advanced hepatocellular carcinoma (Phase II). METHODS: Capecitabine was administered daily on days 1-14, while peginterferon α-2a was administered on days 1, 8, and 15. The cycle was repeated every 21 days. The patients were scheduled to receive capecitabine [mg/(m(2)∙day)] and peginterferon α-2a (µg/week) at 3 dose levels in phase I: 1200 and 90 (level 1), 1600 and 90 (level 2), and 2000 and 90 (level 3), respectively. RESULTS: A total of 30 patients were enrolled. The recommended dose was level 3. Among the 24 patients receiving the drug at the recommended dosage, 2 (8 %) exhibited a partial response, 9 (38 %) exhibited stable disease, 10 (42 %) exhibited progressive disease, and 3 (13 %) were not evaluated. The median time to progression and overall survival were 3.0 months and 7.2 months, respectively. The most common toxicities were decreased white blood cell (88 %), neutrophil (88 %), and platelet counts (58 %); fatigue (50 %); and palmar-plantar erythrodysesthesia syndrome (42 %). Four patients (17 %) discontinued treatment because of severe adverse events. CONCLUSION: Capecitabine at 2000 mg/(m(2)∙day) combined with peginterferon α-2a (90 µg/week) exhibited moderate, albeit manageable, toxicity and was declared as the recommended phase II dose. Further research is required to refine the efficacy of this combination.

Efficacy of sorafenib in intermediate-stage hepatocellular carcinoma patients refractory to transarterial chemoembolization.

OBJECTIVE: We compared the benefits of sorafenib therapy with continued transarterial chemoembolization (TACE) in TACE-refractory patients with intermediate-stage hepatocellular carcinoma (HCC). METHODS: This retrospective study reviewed intermediate-stage HCC patients who underwent the first TACE. Patients were defined as TACE-refractory and divided into two cohorts: (1) patients who switched from TACE to sorafenib and (2) those who continued TACE. We evaluated the patient overall survival (OS) and time to disease progression (TTDP; the time patients reached Child-Pugh C or developed advanced-stage HCC). RESULTS: A total of 509 patients with HCC underwent TACE. Of 249 intermediate-stage HCC patients undergoing the first TACE, 122 were deemed refractory. At the time they were identified as refractory, 20 patients converted to sorafenib, whereas 36 patients continued TACE. We excluded patients with Child-Pugh scores of ≥ 8, those with advanced-stage HCC, those who had undergone hepatic arterial infusion chemotherapy or other systemic therapy, and those treated with best supportive care alone. The median TTDP and OS were 22.3 and 25.4 months, respectively, in the conversion group, and 7.7 and 11.5 months, respectively, in the continued group (p = 0.001 and p = 0.003, respectively). CONCLUSIONS: It is possible that sorafenib conversion might prolong OS and TTDP in TACE-refractory patients with intermediate-stage HCC.

Effect of previous interferon-based therapy on recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma.

Previous reports have shown that interferon (IFN)-based therapy decreases the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection. However, it remains to be fully elucidated whether elimination of HCV by IFN-based therapy inhibits HCC recurrence after curative treatment, such as surgical resection and local ablation therapies. In this study, we aimed to clarify the influence of a sustained virological response (SVR) after IFN-based therapy on recurrence and survival after curative treatment of HCC. Fifty-one patients who underwent curative treatment of HCV-related HCC after receiving IFN-based therapy were analyzed retrospectively. They were classified into SVR (N = 14) and non-SVR groups (N = 37). In the SVR group, serum levels of aspartate aminotransferase and alanine aminotransferase, the indocyanine green retention rate at 15 min, and the percentages of patients with liver cirrhosis and HCV serotype 1 were significantly lower, whereas serum albumin level and platelet count were significantly higher upon HCC occurrence. Recurrence-free survival (RFS) for the first recurrence was significantly higher in the SVR group (P < 0.01). Multivariate analysis showed that SVR at initial HCC treatment (P < 0.01) and multiple tumors (P < 0.01) are prognostic factors for RFS. Moreover, RFS for the second recurrence showed a similar trend to that for the first recurrence. In conclusion, patients who underwent IFN-based therapy before initial curative treatment of HCC had a favorable clinical outcome compared with non-SVR patients.

Is intra-patient sorafenib dose re-escalation safe and tolerable in patients with advanced hepatocellular carcinoma?

BACKGROUND: Although sorafenib improves survival in patients with hepatocellular carcinoma (HCC), doses have to be reduced in quite a few patients because of adverse events. We investigated whether intra-patient sorafenib dose re-escalations were safe and tolerable in patients with advanced HCC. METHODS: Of the 73 advanced HCC patients treated with sorafenib, 42 achieved a tolerable dose with a dose reduction. We evaluated safety and tolerability in patients who attempted intra-patient dose re-escalations from the reduced dose. RESULTS: Thirteen of 42 patients increased the sorafenib dose from the reduced dose. Ten patients had a tolerable dose of 400 mg on alternate days, and 3 patients had a tolerable dose of 400 mg daily. Dose-limiting toxicity (DLT), defined as toxicity resulting in a dose reduction, was observed in 8 of 13 patients as a hand-foot skin reaction (HFSR), and DLT was noted in 2 of 13 patients as an increase in alanine aminotransferase/aspartate aminotransferase levels. Seven of 13 patients did not exhibit DLT after dose re-escalations. Although 6 patients exhibited DLT, the cause of the adverse event was HFSR in all cases. The median escalation dose ratio, which was calculated as the ratio of the real cumulative dose to the cumulative dose when continued at the tolerable dose after dose re-escalation, was 1.84. CONCLUSIONS: The results of the present study indicated that intra-patient sorafenib dose re-escalations were safe and tolerable. Further prospective analyses are needed to determine in more detail the safety and efficacy of intra-patient sorafenib dose re-escalations.

Coronal reformatted CT images contribute to the precise evaluation of the radiofrequency ablative margin for hepatocellular carcinoma.

OBJECTIVE: The purpose of the present study was to evaluate the usefulness of coronal reformatted images obtained from 64-slice multi-detector computed tomography to assess the ablative margin (AM) in hepatocellular carcinoma (HCC) treated with radio frequency ablation (RFA). METHODS: Ninety-five HCC nodules were analyzed in 66 HCC patients treated with RFA. Two radiologists and one hepatologist independently reviewed axial CT images with or without coronal reformatted images in HCC treated with RFA. Nodules were determined as AM-sufficient (≥5 mm) or AM-insufficient (<5 mm). The level of interobserver agreement was measured using the weighted kappa test. The sensitivity, specificity, and positive and negative predictive values (NPVs) of an insufficient AM (<5 mm) to predict local recurrence were evaluated. RESULTS: The numbers of AM-sufficient nodules judged by readers 1-3 based on axial images and both axial and coronal images were 56, 49, and 58, and 47, 33, and 48, respectively. Excellent agreement and good to excellent agreement were obtained among the three readers on axial image readings and both axial and coronal image readings, respectively. The mean sensitivity, specificity, and positive and NPVs of an insufficient AM on axial images and both axial and coronal images to predict local recurrence were 64%, 60%, 17%, and 93%, and 95%, 50%, 20%, and 97%, respectively. CONCLUSIONS: Coronal reformatted CT images should be utilized to evaluate the AM in HCC treated with RFA in order to decrease the risk of local recurrence following treatment.

Propofol versus midazolam for sedation during radiofrequency ablation in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Standardization of the sedation protocol during radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) is needed. This randomized, single-blind, investigator-initiated trial compared clinical outcomes during and after RFA using propofol and midazolam, respectively, in patients with HCC. METHODS: Few- and small-nodule HCC patients (≤3 nodules and ≤3 cm) were randomly assigned to either propofol or midazolam. Patient satisfaction was assessed using a 100-mm visual analog scale (VAS) (1 mm = not at all satisfied, 100 mm = completely satisfied). Sedation recovery rates 1, 2, 3, and 4 h after RFA were evaluated based on Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores; full recovery was defined as a MOAA/S score of 5. RESULTS: Between July 2013 and September 2017, 143 patients with HCC were enrolled, and 135 patients were randomly assigned to the treatment group. Compared with midazolam, propofol exhibited similar median procedural satisfaction (propofol: 73.1 mm, midazolam: 76.9 mm, P = 0.574). Recovery rates 1 and 2 h after RFA were higher in the propofol group than in the midazolam group. Meanwhile, recovery rates observed 3 and 4 h after RFA were similar in the two groups. The safety profiles during and after RFA were almost identical in the two groups. CONCLUSION: Patient satisfaction was almost identical in patients receiving propofol and midazolam sedation during RFA. Propofol sedation resulted in reduced recovery time compared with midazolam sedation in patients with HCC. The safety profiles of both propofol and midazolam sedation during and after RFA were acceptable.

Prognostic Significance of Concurrent Hypovascular and Hypervascular Nodules in Patients with Hepatocellular Carcinoma.

BACKGROUND: Hypovascular nodules often occur together with hypervascular hepatocellular carcinoma (HCC). However, it remains controversial whether hypovascular nodules associated with hypervascular HCC have any prognostic value. This study evaluated the prognostic impact of hypovascular nodules co-existing with hypervascular HCC as diagnosed by computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), which can sensitively capture the dynamic changes in blood flow through the portal vein and hepatic artery in patients with early stage HCC. METHODS: A total of 152 patients with hypervascular HCC (≤ 30 mm, ≤ 3 nodules), who underwent initial local ablation, were analyzed retrospectively. All patients received CTAP and CTHA prior to treatment. Overall survival (OS) was compared among group A (hypervascular HCC only, 107 patients) and group B (hypovascular nodules and hypervascular HCC, 45 patients). RESULTS: Among all hypovascular nodules, 81% (46 of 57) developed hypervascularization within the follow-up period. The 1- and 2-year hypervascularization rates were 17% and 51%, respectively. OS was significantly longer for group A than for group B (P < 0.001). A Cox proportional-hazards model identified the presence of hypovascular nodules concurrent with hypervascular HCC as an independent poor prognostic factor. CONCLUSION: The prognosis of hypervascular HCC patients with hypovascular nodules detected during CTAP and CTHA is poor. Clinical HCC categories seem to be dissimilar between patients with and without hypovascular nodules.

Transcatheter arterial infusion for advanced hepatocellular carcinoma: Who are candidates?

AIM: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy (TAI) in patients with hepatocellular carcinoma (HCC). METHODS: Data from a total of 95 patients with HCC who received TAI were analyzed retrospectively. The efficacy of TAI was evaluated according to the Response Evaluation Criteria in Cancer of the Liver. Overall survival was calculated from the date of initial treatment to the date of death or last follow-up. Survival curves were calculated by the Kaplan-Meier method, and differences in survival were evaluated by the log rank test. Clinical variables that were identified as statistically different by a univariate analysis were included into the Cox proportional hazard regression model for multivariate analysis. A prognostic index based on the regression coefficients derived from variables identified by the multivariate analysis was constructed. Stratification of the patients was conducted using this prognostic index. RESULTS: The patient group was comprised of 76 men and 19 women with an average age of 68 years (range: 37-82 years). Six patients (6.3%) showed complete response and 18 patients (18.9%) showed partial response, for an overall response rate of 25.2%. The median overall survival was 27.6 mo, and the proportions of survivors at 1, 2, and 5 years were 67.4%, 54.0%, and 17.4%, respectively. Multivariate analysis demonstrated that no prior transcatheter arterial chemoembolization, lactate dehydrogenase < 230 IU/L, and performance status of 0 were the independent favorable prognostic factors. The development of a 0-3-point prognostic score index was based on the sum of these three prognostic factors. Subsequently, the patients were categorized into three groups: those with a good (prognostic index = 0-1; n = 54), intermediate (prognostic index = 2; n = 26), or poor (prognostic index = 3; n = 15) prognosis. The median survival times in these three groups were 41.0, 21.2, and 6.8 mo, respectively (P < 0.01). CONCLUSION: Our simple prognostic index may be helpful for management of patients in determining treatment strategies for advanced HCC in the era of molecularly targeted therapy.

Fatal Diaphragmatic Hernia following Radiofrequency Ablation for Hepatocellular Carcinoma: A Case Report and Literature Review.

An 81-year-old man was admitted to our hospital because of right quadrant abdominal pain. On admission, his liver function was Child-Pugh grade C (10 points). Computed tomography (CT) revealed a diaphragmatic herniation of bowel loops into the right thoracic cavity, accompanied by pleural effusion. Although diaphragmatic hernia was successfully repaired by emergency surgery, he died of liver failure 23 days after the surgery. A retrospective reading of CT images revealed the presence of diaphragmatic injury after radiofrequency ablation (RFA) which had been conducted 33 months before the development of diaphragmatic hernia. Of importance, the lesion of the diaphragmatic injury was located on the estimated needle track of RFA for hepatocellular carcinomas in segment 5 and segment 5/8, but not adjacent to their ablation areas. Subsequently, diaphragmatic perforation had been observed 24 months before admission. This suggests that diaphragmatic hernia caused by RFA is not necessarily due to thermal damage of ablation and is possibly life-threatening, at least in some patients with an impaired liver function.

A prognostic score for patients with intermediate-stage hepatocellular carcinoma treated with transarterial chemoembolization.

BACKGROUND: Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE. METHODS: Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; n = 187) and two affiliated hospitals (validation cohort; n = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child-Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions. RESULTS: The number of lesions and the Child-Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0-7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child-Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0-2 points, 3 points, 4 points, 5 points, and 6-7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; p < 0.0001). These results were confirmed in the external validation cohort (p < 0.0001). CONCLUSIONS: The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.

Transarterial chemoembolization with miriplatin plus epirubicin in patients with hepatocellular carcinoma.

AIM: We aimed to evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using miriplatin plus epirubicin in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The efficacy of TACE was evaluated by dynamic computed tomography (CT) or magnetic resonance imaging (MRI) three months after the procedure according to the Response Evaluation Criteria in Cancer Study Group of Japan. Adverse events (AEs), including clinical symptoms, hematological toxicities and blood chemistry toxicities, were assessed using Common Terminology Criteria Version 4.0. RESULTS: Thirty patients with HCC received TACE with miriplatin (miriplatin group) and 29 patients received TACE with miriplatin plus epirubicin (miriplatin-plus-epirubicin group). AEs, such as anorexia and neutropenia, were observed more frequently in the miriplatin-plus-epirubicin group than in the miriplatin group (p=0.028 and 0.014, respectively). However, there was no significant difference in the incidence of these AEs (grade 3/4) between groups. The objective response rate (ORR), including the complete response (CR) and partial response (PR), was 76.7% in the miriplatin group and 58.6% in the miriplatin-plus-epirubicin group (p=0.224). The median time to progression (TTP) in the miriplatin group and the miriplatin-plus-epirubicin group was 8.2 and 6.1 months, respectively (p=0.123). CONCLUSION: Although TACE with miriplatin plus epirubicin was safe and tolerable, no additional anti-tumor effects were observed compared to TACE with miriplatin. Further analysis is required to refine the efficacy of TACE using miriplatin plus epirubicin.

Incidental tumor necrosis caused by the interventional alteration of hepatic arterial flow in patients with advanced hepatocellular carcinoma.

Hepatic arterial infusion chemotherapy (HAIC) is one of the approaches used to treat advanced hepatocellular carcinoma (HCC). Here, we describe 2 cases involving unexpected tumor necrosis after interventional alteration of the hepatic arterial flow during implantation of a port-catheter system for HAIC. Case 1 involved a 42-year-old man with diffuse HCC accompanied by a tumor thrombus in the main trunk of the portal vein. After the right hepatic artery (RHA) derived from the superior mesenteric artery (SMA) was occluded by coils, a port-catheter system was successfully implanted using the gastroduodenal artery (GDA) coil method. The next day, he developed a fever and had right upper abdominal pain. A marked increase in transaminase and lactate dehydrogenase levels was observed. Contrast-enhanced computed tomography (CT) showed tumor necrosis in both the parenchymal tumor and portal vein tumor thrombus. Case 2 involved a 62-year-old man diagnosed with a large HCC located in segments VII and VIII of the liver and abdominal lymph node metastasis. As in case 1, angiography revealed the RHA branched from the SMA. After the replaced RHA and right gastric artery were embolized with coils, a port-catheter system was successfully implanted. Although he showed neither clinical symptoms nor abnormal laboratory data the next day, contrast-enhanced CT revealed tumor necrosis in a large part of the HCC lesion. In conclusion, careful attention is required in the interventional alteration of hepatic arterial flow for implantation of a port-catheter system for HAIC against advanced HCC.

Partial splenic embolization with transarterial chemoembolization in patients with hepatocellular carcinoma accompanied by thrombocytopenia.

BACKGROUND: Thrombocytopenia often makes the introduction of systemic treatment difficult in patients with cirrhosis and hepatocellular carcinoma (HCC). We retrospectively evaluated the long-term effects of partial splenic embolization (PSE) with transarterial chemoembolization (TACE) in patients with HCC patients accompanied by thrombocytopenia. PATIENTS AND METHODS: Twenty-one patients with HCC complicated by severe thrombocytopenia (platelet count, <5.0 × 10(4)/mm(3)) were treated with PSE and TACE. Both the safety and platelet-increasing effect was evaluated in these patients. RESULTS: Seventeen of 21 patients (81.0%) showed increased platelet counts to ≥5.0 × 10(4)/mm(3). Subsequently, 13 patients (61.9%) successfully received systemic chemotherapy. Platelet counts and serum levels of total bilirubin, as well as neutrophil counts, improved significantly one month after treatment. However, serum levels of albumin and hemoglobin decreased significantly one month after treatment. Severe adverse events, including acute liver failure and portal vein thrombus, were observed in two patients. CONCLUSION: PSE with selective TACE made it possible for patients with HCC and severe thrombocytopenia to receive systemic chemotherapy. Although PSE with TACE was safe and tolerable for most patients, the extent of PSE with TACE in a wide area of the liver may increase the risk for fatal liver failure.