Efficacy and Safety of Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy for Patients with Intermediate-Stage Hepatocellular Carcinoma.

INTRODUCTION: We evaluated the efficacy and safety of lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for patients (n = 88) with intermediate-stage hepatocellular carcinoma (HCC). METHODS: Eighty-eight patients who obtained tumor control by LEN treatment were analyzed; 30 received LEN followed by TACE (LEN-TACE sequential therapy), and 58 received LEN monotherapy. Propensity score matching was performed, and the outcomes of 19 patients in the LEN-TACE group and 19 patients in the LEN-alone group were compared. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and change in albumin-bilirubin (ALBI) score were evaluated. RESULTS: After matching, baseline characteristics were similar between the groups. The ORR was 63.2% with LEN-TACE group and 63.2% with the LEN-alone group. Multivariate analysis showed that addition of TACE during LEN treatment (hazard ratio [HR] 0.264, 95% confidence interval [CI] 0.087-0.802, p = 0.019) and Child-Pugh score 5 (HR 0.223, 95% CI 0.070-0.704, p = 0.011) were the significant factors for PFS. Median PFS was 11.6 months with LEN-TACE and 10.1 months with LEN-alone. The survival rate of the LEN-TACE group was significantly higher than that of the LEN-alone group (median survival time; not reached vs. 16.9 months, p = 0.007). The incidence of common LEN-associated AEs was similar between groups. Although elevated aspartate aminotransferase/alanine aminotransferase and fever were more frequent with LEN-TACE group, these events were manageable. CONCLUSION: For patients with intermediate-stage HCC, LEN-TACE sequential therapy may provide a deep response and favorable prognosis.

Comparison of the Clinical Outcome of Ramucirumab for Unresectable Hepatocellular Carcinoma with That of Prior Tyrosine Kinase Inhibitor Therapy.

INTRODUCTION: The clinical outcome of ramucirumab in multi-molecular targeted agent (MTA) sequential therapy for unresectable hepatocellular carcinoma (u-HCC) was assessed in comparison with that of prior tyrosine kinase inhibitor (TKI) therapy. METHODS: Sixteen patients who received ramucirumab as part of multi-MTA sequential therapy for u-HCC were enrolled in a retrospective, cohort study. Ramucirumab was started as 2nd line in 7 patients, 3rd line in 5 patients, and 4th line in 4 patients. RESULTS: The overall response rate was 6.3%, the disease control rate (DCR) was 50.0%, median progression-free survival was 2.0 months (evaluated by mRECIST), median overall survival (OS) with ramucirumab was 7.9 months, and the median OS from 1st-line therapy was 28.1 months. One month after the start of ramucirumab, α-fetoprotein (AFP) decreased in 6 of 12 cases (50.0%), and the DCR in AFP-decreased cases was 83.3%. The DCR of ramucirumab was 66.7% in cases in which disease control was obtained by prior TKI therapy, whereas it was 0.0% in the cases in which disease control was not obtained by prior TKI therapy. Examining the adverse events, no new safety concerns were confirmed. CONCLUSION: The AFP response to ramucirumab and the treatment response to prior TKI therapy are associated with treatment response to ramucirumab.

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma.

INTRODUCTION: This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. METHODS: In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. RESULTS: There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. CONCLUSION: Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.

Efficacy of vonoprazan 10 mg compared with 20 mg for the initial treatment in patients with erosive esophagitis: a randomized pilot study.

BACKGROUND: The study aimed to investigate the efficacy of vonoprazan 10 mg compared with 20 mg in patients with erosive esophagitis. METHOD: Seventy-three patients with erosive esophagitis were randomly divided into two groups either vonoprazan 20 mg (n = 37) or 10 mg (n = 36). They were administered each dose for 4 weeks as the initial treatment followed by maintenance treatment with 10 mg for 8 weeks. The primary endpoints were mucosal healing rate and symptom relief at 4 weeks. The secondary endpoint was symptom relief at 12 weeks after the maintenance treatment. Mucosal healing was assessed endoscopically, and symptom relief was assessed using the FSSG score. RESULTS: At 4 weeks, the endoscopic healing rates of the 20 mg and 10 mg groups were 94.6% and 94.4%, respectively. The FSSG scores of the 20 mg and 10 mg groups were significantly decreased in both treatment groups from 13 (4-39) to 4 (0-25) and 14 (4-40) to 3 (0-29), respectively. At 12 weeks, the scores further decreased to 2 (0-13) and 2 (0-26), respectively. The vonoprazan 10 mg group showed a similar therapeutic effect to the 20 mg group in mucosal healing at 4 weeks and in symptom relief throughout the study period. When stratified by esophagitis grading, these findings were still demonstrated in grade A/B patients but not in grade C/D patients. CONCLUSION: Our findings suggest that initial treatment with vonoprazan 10 mg might be useful especially in patients with mild erosive esophagitis. Large controlled studies are warranted to confirm our investigation.

Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib.

BACKGROUND: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. METHODS: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. RESULTS: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465-18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099-0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07-0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12-0.746, p = 0.01) were significant prognostic factors. CONCLUSION: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.

[A case of liver metastasis 11 years after resection of a gastrointestinal stromal tumor of the duodenum].

A 77-year-old Japanese man with a gastrointestinal stromal tumor (GIST) had undergone a duodenectomy 11 years prior. At that time, he had an incidentally detected left renal cell carcinoma, for which he underwent a nephrectomy and was followed-up at our institution. Twenty-four months after the nephrectomy, a 13-mm low-density mass was found on abdominal computed tomography (CT). Contrast-enhanced ultrasonography indicated an irregular hyperenhancement in the vascular phase and a defect on the post-vascular image. A tumor biopsy for differential diagnosis revealed that the tumor was a GIST. Since positron emission tomography-CT and capsule endoscopy revealed no evidence of a primary lesion, we performed a partial hepatectomy without adjuvant treatment. Microscopic examination revealed that the tumor consisted of uniform spindle cells with a fascicular growth pattern. Immunohistochemical examination revealed c-kit and CD34 expressions, similar to those found in the resected duodenal GIST specimen 11 years prior. We diagnosed metastatic liver tumor from the duodenal GIST resected 11 years prior. The patient remains alive without disease recurrence 24 months after the hepatectomy. Long-term surveillance is required after resection of a high-risk primary GIST.

Liver fibrosis assessment by FibroScan compared with pathological findings of liver resection specimen in hepatitis C infection.

AIM: FibroScan is a tool for the non-invasive diagnosis of hepatic fibrosis. Previous studies have compared liver stiffness to percutaneous liver biopsy findings, but no study has compared liver stiffness to liver resection specimen findings. The aim of this study was to compare FibroScan measurements to resected liver specimen findings. METHODS: From April 2011 to November 2015, a total of 114 patients with liver tumor and hepatitis C were enrolled. We divided them into two groups, the training set and validation set. Liver stiffness was measured by FibroScan before surgery, and specimens obtained by liver resection were evaluated according to the METAVIR system. RESULTS: Using Spearman's rank correlation analysis, a positive correlation between liver stiffness measurement and liver fibrosis stage was observed (r = 0.786, P ≤ 0.0001). In the training set, the area under receiver operating curves for diagnosis of F ≥ 2 was 0.971 (95% confidence interval, 0.928-1.000; cut-off value, 5.9), for diagnosis of F ≥ 3 was 0.911 (0.825-0.997, 9.8), and for diagnosis of F = 4 was 0.917 (0.849-0.985, 15.5). In the validation set, at a cut-off value of 5.9 kPa, sensitivity, specificity, positive predictive values, and negative predictive values for F ≥ 2 were 95.7%, 0.0%, 97.8%, and 0.0%, respectively, of 9.8 kPa for F ≥ 3 were 86.2%, 52.6%, 73.5%, and 71.4%, and of 15.5 kPa for F = 4 were 100%, 71.8%, 45.0%, and 100%. CONCLUSIONS: The stage of stiffness graded by FibroScan has a good correlation with the liver fibrosis of resected liver specimens. It has the ability to diagnose fibrosis stage non-invasively.

Clinical outcome and prognostic factors in hepatocellular carcinoma patients with bone metastases medicated with zoledronic acid.

AIMS: We retrospectively analyzed the clinical outcome and prognostic parameters in patients with hepatocellular carcinoma (HCC) and bone metastases who had received treatment with zoledronic acid (ZOL). METHODS: Ninety-nine HCC patients with bone metastases who had been treated with ZOL were enrolled in this retrospective cohort study. We analyzed the prognostic factors, including serum N-telopeptide of type I collagen (NTX) levels, as bone metabolism markers. RESULTS: The median overall survival (OS) time was 11.5 months. Child-Pugh grade A (P = 0.004) and intrahepatic tumor stage (IHTS) T0-3 (P = 0.010) correlated significantly with favorable OS. In 46 patients with grade A and T0-3, receiver operating characteristic curve analysis defined 16 nmol BCE/L serum NTX as the cut-off level for median OS. Multivariate analysis identified baseline serum NTX <16 nmol BCE/L (P = 0.045) as the only significant and independent determinant of OS. CONCLUSION: Low baseline serum NTX level correlated with favorable outcome in bone metastatic HCC patients with Child-Pugh grade A and IHTS T0-3 treated with ZOL.

Complete response to short-term sorafenib treatment alone for hepatocellular carcinoma with bone, lymph node, and peritoneum metastases.

We report a 60-year-old male patient who developed extrahepatic metastases in bone, peritoneum, and lymph nodes (confirmed by computed tomography and positron emission tomography-computed tomography) after hepatectomy for hepatocellular carcinoma. He was treated with sorafenib (800 mg/day) but developed grade 3 hand-foot syndrome. He continued to be treated with sorafenib but at a lower dose (400 mg/week). The response to sorafenib therapy was graded as complete response at 6 months by the Response Evaluation Criteria in Solid Tumors. Sorafenib was continued for 8 months and the patient remained in complete response for 11 months. Further reporting of similar cases should help design treatment strategies and evaluate predictors of the response to sorafenib therapy.

Influence of the rs738409 polymorphism in patatin-like phospholipase 3 on the treatment efficacy of non-alcoholic fatty liver disease with type 2 diabetes mellitus.

AIM: A genome-wide association study revealed that the single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with non-alcoholic fatty liver disease (NAFLD). Recent pilot studies investigated the effects of dipeptidyl peptidase-4 inhibitors on liver function and glucose metabolism in NAFLD with type 2 diabetes mellitus (DM). We herein evaluated the efficacy of alogliptin in NAFLD patients with type 2 DM as well as the relationship between genotypes at rs738409 in PNPLA3 and treatment efficacy. METHODS: Forty-one biopsy-proven NAFLD patients with type 2 DM treated with 25 mg/day alogliptin were retrospectively enrolled. SNP rs738409 in PNPLA3 was present in all patients. Clinical data were measured before and after the treatment. RESULTS: Average hemoglobin A1c (HbA1c) levels mostly remained unchanged. Moreover, significant changes were not noted in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) during the follow-up period. A positive correlation was observed between improvements in HbA1c (ΔHbA1c) levels and changes in AST (ΔAST) and ALT (ΔALT) levels (r = 0.325 and 0.439, respectively). Patients with the risk allele (G-allele) showed more positive correlation between ΔHbA1c and changes in transaminase. Furthermore, improvements in the levels of total cholesterol, triglycerides and hyaluronic acid were significantly greater in G-allele patients in the weight loss group. CONCLUSION: The treatment of NAFLD with type 2 DM with alogliptin contributed to the amelioration of NAFLD. Our results suggested that differences in the PNPLA3 risk allele affected the therapeutic effects of this treatment.

Improvement of renal dysfunction in a patient with hepatitis C virus-related liver cirrhosis by daclatasvir and asunaprevir combination therapy: A case report.

Recently, treatments for chronic hepatitis C virus (HCV) infection have been drastically improved by the development of direct-acting antiviral agents. In September 2014, dual oral therapy using daclatasvir (DCV) and asunaprevir (ASV) was approved for the treatment of chronic HCV infection in Japan. We treated a patient with HCV-related liver cirrhosis with severe leg edema due to chronic renal dysfunction using this dual oral therapy. Although serum alanine aminotransferase increased rapidly during the first week of treatment, the antiviral therapy was able to continue, and liver function recovered spontaneously. After 1 month of treatment, serum HCV RNA became continuously undetectable, and serum albumin level gradually increased. Throughout the therapy, serum creatinine level nearly normalized, and leg edema gradually improved. These improvements continued after the combination therapy was completed. HCV RNA remained undetectable following the end of therapy, and sustained virological response at 12 weeks was achieved. It has been reported that chronic HCV infection is associated with renal dysfunction and that HCV eradication can improve it. DCV and ASV combination therapy is safe for patients who have renal dysfunction and may be a suitable therapy for chronic hepatitis C patients with renal dysfunction.

Effects of ITPA polymorphism on decrease of hemoglobin during simeprevir, peg-interferon, and ribavirin combination treatment for chronic hepatitis C.

AIM: Polymorphisms in the ITPA gene influence anemia during peg-interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with simeprevir, PEG-IFN, and RBV are not sufficiently known. METHODS: We analyzed 212 patients with genotype 1 chronic hepatitis C, who were treated with simeprevir plus PEG-IFN/RBV triple therapy, and assessed the effect of the ITPA polymorphism on hemoglobin levels and RBV dose reduction. ITPA (rs1127354) and IFNL4 (ss469415590) polymorphisms were genotyped using the Invader assay. A stepwise multivariate regression analysis was carried out to identify factors associated with outcome of the therapy. RESULTS: Reduction of hemoglobin levels was similar between patients treated with simeprevir plus PEG-IFN/RBV and those treated with PEG-IFN/RBV therapy. In simeprevir plus PEG-IFN/RBV-treated patients, decreases in hemoglobin levels were faster and greater, and the cumulative proportion of patients with ribavirin dose reduction was significantly greater in ITPA genotype CC patients than in CA/AA patients. The total dose of simeprevir and PEG-IFN was similar between ITPA genotype CC and CA/AA patients. In contrast, the total dose of RBV was lower in patients with the CC genotype. Multivariate analysis showed that the IFNL4 TT/TT genotype, but not the ITPA SNP genotype, treatment history (treatment-naive or relapse during prior treatment), and treatment completion were significantly associated with outcome of therapy. CONCLUSION: ITPA polymorphism influences hemoglobin levels and incidence of RVB dose reduction during simeprevir triple therapy, indicating the importance of monitoring anemia during treatment, particularly for ITPA genotype CC patients.

Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: A large-scale, long-term cohort study.

BACKGROUND: We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long-term, large-scale cohort study. METHODS: We reviewed 1094 consecutive patients with HCV who achieved sustained virological response (SVR) following IFN therapy between January 1995 and September 2013. RESULTS: During the observation period (median 50 months: range 13-224), 36 (3%) of 1094 patients developed HCC after SVR. The median period from SVR to diagnosis of HCC was 37 months (range 17-141), and the cumulative rates of HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified old age (≥60 years, HR, 3.1: 95%CI, 1.3-6.6: P = 0.009), male sex (HR, 12.0: 95%CI, 2.8-50.0: P < 0.0001), advanced fibrosis stage (F3/4, HR, 3.2: 95%CI, 1.6-7.2: P < 0.0001), and alpha-fetoprotein ≥10 ng/mL at 1 year after SVR (HR, 7.8: 95%CI, 2.9-16.8: P < 0.0001) as significant and independent risk factors for post-SVR HCC. CONCLUSIONS: Older age and male sex (host factors), advanced fibrosis stage (pre-IFN treatment factor), and higher alpha-fetoprotein values (post-treatment factor) were significantly associated with HCC development after HCV eradication.

Preoperative Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Prediction of Microvascular Invasion in Small Hepatocellular Carcinoma.

OBJECTIVES: This study aimed to assess the value of preoperative fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) for predicting microvascular invasion (MVI) in small hepatocellular carcinoma (HCC). METHODS: We retrospectively examined 60 patients who received F-FDG PET-CT prior to hepatic resection for small HCC (≤30 mm) with subsequent MVI confirmation by histopathology. The associations between PET-positive status and tumor factors were assessed. Furthermore, independent predictors for MVI and diagnostic utility of each MVI predictor were assessed. RESULTS: Multivariate analysis revealed the presence of MVI as an independent predictor of PET-positive status (P = 0.023). Maximum standardized uptake value (SUVmax) of 3.2 or greater (P = 0.017) and lens culinaris agglutinin a-reactive α-fetoprotein (AFP-L3) 19% or greater (P = 0.010) were independent predictors of MVI. Areas under the receiver operating characteristic curves for SUVmax of 3.2 or greater, AFP-L3 19% or greater, and both factors combined for predicting MVI were 0.712 (0.493-0.932), 0.755 (0.563-0.947), and 0.856 (0.721-0.991), respectively. The sensitivity and specificity for predicting MVI were 77.8% and 74.5% for SUVmax of 3.2 or greater, 66.7% and 84.3% for AFP-L3 19% or greater, and 88.9% and 82.4% for the combination. CONCLUSIONS: F-FDG PET-CT and AFP-L3 may be useful for predicting MVI in small HCC, and the combination of the 2 factors provided reliable assessment for selection of suitable hepatic resection and liver transplantation candidates.

Assessment of Outcome of Hepatic Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma by the Combination of RECIST and Tumor Markers.

To assess the outcome of stable disease (SD) patients with advanced hepatocellular carcinoma (HCC) by tumor markers after the first course of hepatic arterial infusion chemotherapy (HAIC). The study subjects were 156 HCC patients treated with HAIC and classified as Child Pugh A, with no extrahepatic metastasis, and no history of sorafenib treatment. In the study and validation cohorts, the AFP and DCP ratios of patients who were considered SD to the first course of HAIC were analyzed by AUROC for a prediction of response to the second course of HAIC. The imaging response to the first course of HAIC was classified as partial response (PR), SD and progressive disease (PD) in 29 (18.8%), 80 (51.9%), and 44 (28.6%) patients respectively. For SD patients, the a-fetoprotein (AFP) and des-y-carboxy prothrombin (DCP) ratios of patients who were considered SD to the first course of HAIC were analyzed by the receiver operating characteristic curve for prediction of response to the second course of HAIC in the study cohorts. The area under the curve of AFP ratio was 0.743. The area under the curve of DCP ratio was 0.695. The cut-off values of AFP and DCP ratios were 1.3 and 1.0, respectively. In the validation cohort, the accuracy of the prediction of response in this validation cohort (71.4%) showed no significant difference compared to that in the study cohort (72.4%) (p = 1.0). The results suggested that patients with a high tumor marker ratio could be switched to alternative therapeutic regimens despite the SD response to HAIC.

Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma.

OBJECTIVE: Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs. METHODS: A total of 85 surgically resected nodules (≤30 mm) were analyzed. HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared. RESULTS: Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95% confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682-0.890): CEUS, 0.784 (0.679-0.889), in combination, 0.876 (0.792-0.959). The sensitivity, specificity, and accuracy were 64.1%, 95.7%, and 81.2% in EOB-MRI, 56.4%, 97.8%, and 78.8% in CEUS, and 84.6%, 95.7%, and 90.6% in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS. CONCLUSION: Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs. KEY POINTS: • Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN. • Macroscopic classification is useful to choose the treatment strategy for small HCCs. • Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal. • The diagnosis of macroscopic findings by individual modality has limitations. • Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.

Efficacy and safety of the anticoagulant drug, danaparoid sodium, in the treatment of portal vein thrombosis in patients with liver cirrhosis.

AIM: To assess the efficacy and safety of the anticoagulant drug, danaparoid sodium, in the treatment of portal vein thrombosis (PVT) in patients with liver cirrhosis. METHODS: A consecutive 26 cirrhotic patients with PVT were enrolled in this retrospective cohort study. The etiologies of cirrhosis were hepatitis B virus-related, hepatitis C virus-related, alcoholic and cryptogenic in five, 14, three and four patients, respectively. Child-Pugh grade A, B and C was noted in 13, eight and five patients, respectively. Patients were treated with 2 weeks' administration of danaparoid sodium followed by the evaluation of PVT reduction and adverse events. RESULTS: All patients experienced reduction of PVT through the treatment. The median volume of PVT before and after treatment was 2.40 cm(3) (range, 0.18-16.63) and 0.37 cm(3) (range, 0-5.74), respectively. The median reduction rate of PVT volume was 77.3% (range, 18-100%). According to the reduction rate, complete reduction (CR), partial reduction (PR, ≥50%) and stable disease (SD, <50%) were observed in four (15%), 16 (62%) and six patients (23%), respectively. The median volume of PVT before treatment was significantly different between CR + PR and SD (2.09 vs 4.35 cm(3) , P = 0.045). No severe adverse events such as bleeding symptoms (e.g. gastrointestinal bleeding and cerebral hemorrhage) and thrombocytopenia were encountered. CONCLUSION: Danaparoid sodium for the treatment of PVT in patients with liver cirrhosis was safe and effective. Therefore, anticoagulation therapy with danaparoid sodium could have potential as one of the treatment options in PVT accompanied by cirrhosis.

Disseminated carcinomatosis of the bone marrow originating from hepatocellular carcinoma. A case report.

A 50-year-old male patient was admitted to the hospital for persistent high fever and back pain. He was diagnosed with hepatocellular carcinoma (HCC), bone marrow metastasis and disseminated intravascular coagulation (DIC). Despite the diagnosis and treatment, the general condition deteriorated rapidly and he died of cerebral hemorrhage associated with generalized bleeding tendency. Autopsy showed multiple HCC in the liver and systemic metastasis including bone marrow. The case describes a rare complication of HCC with disseminated carcinomatosis of the bone marrow (DCBM) complicated with DIC, with rapid deterioration and death. This is the first case of DCBM from HCC. Physicians need to be aware of DCBM in patients with HCC.

Role of 3-D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.

AIM: To evaluate the response, survival and safety on 3-D conformal radiotherapy (3D-CRT) for major portal vein tumor thrombosis (PVTT) combined with hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 83 advanced HCC patients treated with HAIC who met the following criteria were enrolled: (i) PVTT of the main trunk or first branch of the portal vein; (ii) no extrahepatic metastasis; (iii) Child-Pugh score of 5-7; (iv) performance status of 0 or 1; and (v) no history of sorafenib treatment. The response, overall survival (OS), time to treatment failure (TTF), post-progression survival (PPS) and safety were compared between HAIC combined with 3D-CRT for PVTT (RT group, n = 41) and HAIC alone (non-RT group, n = 42). RESULTS: The objective response of PVTT was significantly higher in the RT group (56.1%) than in the non-RT group (33.3%), while that of intrahepatic tumor and OS were not significantly different between groups. Median OS, TTF and PPS were significantly longer in the RT group than in the non-RT group (8.6 and 5.0 months, 5.0 and 2.7 months, and 5.3 and 1.5 months, respectively) among intrahepatic tumor non-responders to HAIC, whereas those were not significantly different between groups among intrahepatic tumor responders to HAIC. By multivariate analysis, the combination of 3D-CRT with HAIC was an independent contributing factor for OS (hazard ratio, 3.2; 95% confidence interval, 1.692-6.021; P < 0.001) among intrahepatic HCC non-responders to HAIC. CONCLUSION: 3D-CRT for PVTT combined with HAIC could provide survival benefit to non-responder to HAIC.