Publications by authors named "Koji Uchino"

36 Publications

Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma.

J Gastroenterol 2021 May 12;56(5):456-469. Epub 2021 Mar 12.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Liquid biopsies, particularly those involving circulating tumor DNA (ctDNA), are rapidly emerging as a non-invasive alternative to tumor biopsies. However, clinical applications of ctDNA analysis in hepatocellular carcinoma (HCC) have not been fully elucidated.

Methods: We measured the amount of plasma-derived cell-free DNA (cfDNA) in HCC patients before (n = 100) and a few days after treatment (n = 87), including radiofrequency ablation, transarterial chemoembolization, and molecular-targeted agents (MTAs), and prospectively analyzed their associations with clinical parameters and prognosis. TERT promoter mutations in cfDNA were analyzed using droplet digital PCR. Furthermore, we performed a comprehensive mutational analysis of post-treatment cfDNA via targeted ultra-deep sequencing (22,000× coverage) in a panel of 275 cancer-related genes in selected patients.

Results: Plasma cfDNA levels increased significantly according to HCC clinical stage, and a high cfDNA level was independently associated with a poor prognosis. TERT promoter mutations were detected in 45% of all cases but were not associated with any clinical characteristics. cfDNA levels increased significantly a few days after treatment, and a greater increase in post-treatment cfDNA levels was associated with a greater therapeutic response to MTAs. The detection rate of TERT mutations increased to 57% using post-treatment cfDNA, suggesting that the ctDNA was enriched. Targeted ultra-deep sequencing using post-treatment cfDNA after administering lenvatinib successfully detected various gene mutations and obtained promising results in lenvatinib-responsive cases.

Conclusions: Post-treatment cfDNA analysis may facilitate the construction of biomarkers for predicting MTA treatment effects.
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http://dx.doi.org/10.1007/s00535-021-01773-4DOI Listing
May 2021

Radiofrequency Ablation of Liver Tumors in Patients on Antithrombotic Therapy: A Case-Control Analysis of over 10,000 Treatments.

J Vasc Interv Radiol 2021 06 6;32(6):869-877. Epub 2021 Mar 6.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Purpose: To evaluate the safety of radiofrequency ablation (RFA) for liver tumors in patients on antithrombotic therapy.

Materials And Methods: A total of 10,653 consecutive RFA treatments in 3,485 patients with liver tumors were analyzed. The incidence of complications was analyzed on a treatment basis. The treatments for patients who had received antithrombotic medication up to 1 week prior to RFA comprised the antithrombotic therapy group (n = 806), and the others comprised the control group (n = 9,847). Antithrombotic agents were ceased prior to RFA (aspirin, ticlopidine, clopidogrel, and prasugrel ceased 7 days before RFA; cilostazol, 2 or 3 days before RFA; warfarin, 3 days before RFA; and direct oral anticoagulants, 1 day before RFA) and resumed as soon as possible after RFA. Logistic regression analysis was performed to assess whether the antithrombotic therapy increased the risk of hemorrhagic complications.

Results: Hemorrhagic complications were diagnosed after 6 treatments (0.7%) in the antithrombotic group and 48 (0.5%) in the control group, and there was no significant difference between the groups (P = .30). In 3 treatments, hemorrhage was diagnosed on or after 8 days of RFA, all of which were in the antithrombotic group. Thrombotic complications were diagnosed after 2 treatments (0.2%) in the antithrombotic group and after 5 (0.1%) in the control group. In a multivariate analysis, receiving antithrombotic therapy was not an independent risk factor for hemorrhagic complications (adjusted odds ratio, 1.52; 95% confidence interval, 0.60-3.87; P = .38).

Conclusions: RFA of liver tumors in patients on antithrombotic therapy is generally safe with appropriate cessation and resumption. Late-onset hemorrhage should be noted in the patients on antithrombotic therapy.
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http://dx.doi.org/10.1016/j.jvir.2021.02.021DOI Listing
June 2021

Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan.

J Gastroenterol 2021 Mar 11;56(3):261-273. Epub 2021 Jan 11.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Although type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates.

Methods: The study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls. Clinical data at the time of and 5 years before HCC diagnosis were collected.

Results: The mean patient age at HCC diagnosis was approximately 73 years, and 80% of the patients were male. The proportion of patients with insulin use increased, whereas the body mass index (BMI), proportion of patients with fatty liver, fasting glucose levels, and hemoglobin A1c (HbA1c) levels decreased significantly in 5 years. In the cohort study, 18 patients developed HCC during the mean follow-up period of 4.7 years with an annual incidence of 0.11%. Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of HCC development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher BMI and gamma-glutamyl transpeptidase levels. Receiver-operating characteristic analyses showed that a FIB-4 cut-off value of 3.61 could help identify high-risk patients, with a corresponding annual HCC incidence rate of 1.1%.

Conclusion: A simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology.
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http://dx.doi.org/10.1007/s00535-020-01754-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932951PMC
March 2021

Improved liver function in patients with cirrhosis due to chronic hepatitis C virus who achieve sustained virologic response is not accompanied by increased liver volume.

PLoS One 2020 20;15(4):e0231836. Epub 2020 Apr 20.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Serum albumin level improves in patients with chronic hepatitis C virus (HCV) infection who achieve sustained virologic response (SVR) with antiviral therapy. However, it remains controversial whether liver volume increases along with SVR.

Methods: Patients with chronic HCV infection with a history of hepatocellular carcinoma (HCC) who achieved SVR with anti-HCV treatment from March 2003 to November 2017 were enrolled. Patients were followed up with periodic computed tomography (CT) scans to detect HCC recurrence. Patients who underwent treatment for HCC recurrence within 1 year after initiation of anti-HCV treatment were excluded. Laboratory data, including alanine aminotransferase (ALT) level, serum albumin level, and platelet count, were collected at baseline and timepoints after treatment initiation. Liver volume was evaluated at baseline and 24 and 48 weeks after treatment initiation using a CT volume analyzer. A linear mixed-effects model was applied to analyze the chronologic change in liver volume. The correlations between changes in ALT level, albumin level, and liver volume were also evaluated.

Results: Of 108 enrolled patients, 78 had cirrhosis. Serum albumin level continued to increase through 48 weeks after treatment initiation. A significant increase in liver volume was observed only in patients without cirrhosis (P = 0.005). There was a significant correlation between ALT level decrease and albumin level increase (P = 0.018).

Conclusions: Improved liver albumin production with SVR was contributed by improved liver cell function rather than increased liver volume in patients with cirrhosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231836PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170262PMC
July 2020

Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients.

J Gastroenterol 2020 Feb 10;55(2):227-243. Epub 2019 Oct 10.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are characterized by the accumulation of excess hepatic fat. However, in the progression from NASH to cirrhosis, hepatic fat is often lost. Our aim was to elucidate the mechanism underlying hepatic fat loss during NASH progression.

Methods: Liver biopsies were performed at The University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD and 14 patients with cryptogenic cirrhosis who were not being treated with any diabetes or dyslipidemia drugs. Among them, 70 patients underwent liver biopsy after an overnight fast, and 90 patients were biopsied 5 h after an oral glucose tolerance test. Expression differences in genes encoding several fatty acid metabolism-related factors were examined and correlated with hepatic histological changes based on NAFLD activity scores. Prospective patient follow-up continued until June 2018.

Results: The level of fatty acid transport protein 5 (FATP5), which is associated with free fatty acid intake, was significantly and inversely correlated with features of histological progression, including ballooning and fibrosis. This was confirmed by immunohistochemical analysis. Transcript levels of genes encoding fatty acid metabolism-related proteins were comparable between NASH with severe fibrosis and cryptogenic cirrhosis. Furthermore, a prospective cohort study demonstrated that low FATP5 expression was the most significant risk factor for hepatic fat loss.

Conclusions: Decreased hepatic FATP5 expression in NAFLD is linked to histological progression, and may be associated with hepatic fat loss during NASH progression to cirrhosis.
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http://dx.doi.org/10.1007/s00535-019-01633-2DOI Listing
February 2020

A Novel Non-invasive Method for Predicting Liver Fibrosis by Quantifying the Hepatic Vein Waveform.

Ultrasound Med Biol 2019 09 12;45(9):2363-2371. Epub 2019 Jul 12.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

The hepatic vein (HV) waveform by Doppler ultrasound reflects the severity of liver fibrosis. We conducted a proof-of-concept study of a new method for quantifying the HV waveform. We calculated the coefficient of variation (CV) of the HV flow velocity and created a new index "q-HV" (quantified HV) and analyzed its performance for predicting histologic liver fibrosis in 114 patients with chronic liver disease. The CV of the HV flow velocity was well associated with flattening of the waveform and the q-HV significantly increased with the progression of liver fibrosis. The areas under the curve for the prediction of fibrosis stage were 0.732 for F2, 0.772 for F3 and 0.805 for F4. Combined q-HV and FIB-4 index (widely used liver fibrosis score) increased the diagnostic accuracy for liver fibrosis. The q-HV showed good accuracy for predicting liver fibrosis; thus, q-HV is feasible and acceptable as a non-invasive tool for predicting liver fibrosis.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2019.05.028DOI Listing
September 2019

Early detection of bone metastases of hepatocellular carcinoma reduces bone fracture and paralysis.

Jpn J Clin Oncol 2019 Jun;49(6):529-536

Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo.

Background: With the improvement in survival of hepatocellular carcinoma patients, extrahepatic metastases have become a more frequent complication. Although pathological fractures or paralysis due to bone metastases deteriorate the quality of life of patients, no treatment guideline for bone metastases has been established. This study aimed to clarify the risk factors for these events and the clinical course of patients with bone metastases.

Methods: Out of 783 hepatocellular carcinoma patients treated in our institution between 2009 and 2016, 76 patients with bone metastases were enrolled. They were divided into two groups by the trigger of bone metastases detection. One was those diagnosed by surveillance (surveillance group), and the other was those based on symptom presentation (non-surveillance group). We investigated the clinical features, risk factors for fractures or paralysis and prognostic factors for survival after bone metastases.

Results: Baseline characteristics and survival were not significantly different between two groups. Fractures or paralysis occurred in 10 patients (13.2%), and the frequency was significantly higher in the non-surveillance group (20.9%) than the surveillance group (3.0%) in univariate analysis (p = 0.036). The median survival after diagnosis of bone metastases was 11.7 months. Age over 75 years (p = 0.002), hepatitis C-virus etiology (p = 0.007) and Child-Pugh class B/C (p < 0.001) were significantly associated with a shorter survival in multivariate analysis, but fractures or paralysis did not affect the survival.

Conclusions: Early diagnosis through surveillance for hepatocellular carcinoma bone metastases may prevent fractures or paralysis and lead to a better quality of life for these patients.
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http://dx.doi.org/10.1093/jjco/hyz028DOI Listing
June 2019

Ischemic complications after percutaneous radiofrequency ablation of liver tumors: Liver volume loss and recovery.

Hepatol Res 2019 Apr 6;49(4):453-461. Epub 2019 Feb 6.

Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Aim: The liver regrows after acute liver injury and liver resection. However, it is not clear whether the liver regenerates in advanced cirrhosis. This study aimed to evaluate the clinical course of, and liver volume change after, ischemic liver complications caused by radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC).

Methods: We enrolled 35 patients with ischemic complications after RFA. Ischemic complications were defined as rapid elevation of aspartate aminotransferase (AST) to over 500 U/L, with typical radiological findings. Patient characteristics and the ischemic liver volume were investigated. Long-term liver volume changes at 3-8 months after ischemic complications were also assessed in 32 patients. We also assessed the overall survival rate after ischemic complications.

Results: The median value of peak AST was 798 U/L (range, 531-4096 U/L). The median ischemic liver volume relative to the functional liver volume before RFA was 13% (range, 3.1-46.5%). There was a strong correlation between the peak AST value and the ischemic liver volume (r = 0.84, P < 0.001). The liver volume recovered to some extent in 18 of 32 (56%) patients after ischemic complications. The survival rate after ischemic complications was 45.7% at 5 years and correlated with the functional liver volume after ischemic complications (P = 0.02).

Conclusions: Ischemic complications after RFA can lead to massive liver parenchymal loss. Although the liver volume recovered to some extent in the majority of our patients, ischemic liver complications after RFA should be avoided to improve the overall survival rate.
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http://dx.doi.org/10.1111/hepr.13302DOI Listing
April 2019

A nationwide survey on non-B, non-C hepatocellular carcinoma in Japan: 2011-2015 update.

J Gastroenterol 2019 Apr 29;54(4):367-376. Epub 2018 Nov 29.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.

Background: We previously reported that the incidence of hepatocellular carcinoma (HCC) with non-viral etiologies increased rapidly between 1991 and 2010 in Japan.

Methods: To update this investigation, we enrolled patients who were initially diagnosed as having non-B, non-C HCC at participating hospitals between 2011 and 2015. In addition to the patient characteristics investigated in the previous report, we also investigated the duration of alcohol consumption. The overall survival rate was analyzed using the Kaplan-Meier method, and the hazard function against the body mass index (BMI) was plotted using cubic splines.

Results: A total of 2087 patients were enrolled. The proportion of patients with non-viral etiologies has continued to increase from 10.0% in 1991 to 32.5% in 2015. Patients were also older (median ages, 70-73 years) and more obese (median BMIs, 23.9-24.2 kg/m), and the proportions of patients with diabetes mellitus (46.1% to 51.6%), hypertension (42.7% to 58.6%), dyslipidemia (14.6% to 22.9%), and fatty liver (24.0% to 28.8%) had all increased significantly. There was a significant inverse relationship between the duration and the amount of daily alcohol consumption. The improvement in the overall survival was relatively small, with a decreased proportion of patients under surveillance (41.3% to 31.6%). A hazard function plot showed a curve similar to that in our previous report, with a lowest hazard of ~ 26 kg/m.

Conclusions: The proportion of HCC patients with non-viral etiologies continues to increase in Japan. Lifetime total amount of alcohol consumption may be a risk factor.
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http://dx.doi.org/10.1007/s00535-018-1532-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437291PMC
April 2019

Liver stiffness measurements in chronic hepatitis C: Treatment evaluation and risk assessment.

J Gastroenterol Hepatol 2019 May 7;34(5):921-928. Epub 2018 Dec 7.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background And Aim: Liver stiffness (LS), measured by transient elastography, has been validated as a non-invasive surrogate for liver fibrosis.

Methods: We investigated the long-term predictive ability of LS for hepatocellular carcinoma (HCC) development and overall survival in 1146 patients with chronic hepatitis C by using LS value at enrollment. We also investigated chronological changes in LS based on antiviral therapy and its outcome in 752 patients.

Results: During the mean follow-up period of 6.6 years, 190 patients developed HCC. Cumulative HCC incidence rates at 5 years were clearly stratified as 1.7% in the ≤ 5 kPa, 3.3% in 5.1-10 kPa, 16.7% in 10.1-15 kPa, 24.4% in 15.1-20 kPa, 36.3% in 20.1-25 kPa, and 43.7% in > 25 kPa subgroups (P < 0.001). Overall survival was also stratified: 10-year survival rates were 99.3% in the ≤ 5 kPa, 95.4% in 5.1-10 kPa, 81.4% in 10.1-15 kPa, 79.5% in 15.1-20 kPa, 66.1% in 20.1-25 kPa, and 49.1% in > 25 kPa subgroups (P < 0.001). LS decreased at a rate of 8.1% per year in those who achieved sustained virological responses, but increased at 0.1% per year in those who could not achieve sustained virological response instead of antiviral therapy, and increased at 3.7% per year in those who did not undergo antiviral therapy.

Conclusions: Liver stiffness measurements can be useful in the prediction of HCC development and overall survival and in the evaluation of chronological changes in liver fibrosis grade during and after antiviral therapy.
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http://dx.doi.org/10.1111/jgh.14530DOI Listing
May 2019

Impact of direct-acting antivirals on early recurrence of HCV-related HCC: Comparison with interferon-based therapy.

J Hepatol 2019 01 16;70(1):78-86. Epub 2018 Oct 16.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan.

Background & Aims: It remains controversial whether direct-acting antivirals (DAAs) accelerate the recurrence of hepatitis C-related hepatocellular carcinoma (HCC) after curative therapy. This study aimed to evaluate HCC recurrence after DAA treatment of chronic hepatitis C.

Methods: We enrolled patients with a history of successful radiofrequency ablation treatment for hepatitis C-related HCC who received antiviral therapy with DAAs (DAA group: 147 patients) or with interferon (IFN)-based therapy (IFN group: 156 patients). We assessed HCC recurrence rates from the initiation of antiviral therapy using the Kaplan-Meier method and evaluated risk factors for HCC recurrence by multivariate Cox proportional hazard regression analysis. The recurrence pattern was categorized as follows: intrahepatic recurrence with a single tumor <2 cm (stage 0), a single tumor or up to 3 tumors ≤3 cm (stage A), multinodular (stage B), and extrahepatic metastasis or macrovascular invasion (stage C).

Results: The recurrence rates at 1 and 2 years were 39% and 61% in the IFN group and 39% and 60% in the DAA group, respectively (p = 0.43). Multivariate analysis identified higher lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level, a history of multiple HCC treatments, and a shorter interval between HCC treatment and initiation of antiviral therapy as independent risk factors for HCC recurrence. HCC recurrence in stage 0, A, B, and C was found in 56 (41%), 60 (44%), 19 (14%), and 1 (0.7%) patients in the IFN group and 35 (44%), 32 (40%), 11 (14%), and 2 (2.5%) patients in the DAA group, respectively (p = 0.70).

Conclusions: HCC recurrence rates and patterns after initiation of antiviral therapy did not differ between patients who received IFN-based therapy and DAA therapy.

Lay Summary: We detected no significant difference in early hepatocellular carcinoma (HCC) recurrence rates and patterns between patients who received interferon-based and direct-acting antiviral therapy after HCC treatment. High lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level, short recurrence-free period, and a history of multiple HCC treatments were independent risk factors for early HCC recurrence after the initiation of antiviral therapy.
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http://dx.doi.org/10.1016/j.jhep.2018.09.029DOI Listing
January 2019

Serum levels of ferritin do not affect the prognosis of patients with hepatocellular carcinoma undergoing radiofrequency ablation.

PLoS One 2018 25;13(7):e0200943. Epub 2018 Jul 25.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background & Aims: Hepatic iron accumulation can accelerate liver injury in patients with various chronic liver diseases and lead to hepatocarcinogenesis. We elucidated the impact of serum levels of ferritin on the prognosis of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) in a large cohort.

Methods: We retrospectively analyzed 578 treatment-naïve HCC patients who underwent RFA. We divided our cohort into four groups by the quartile points of serum ferritin level: G1 (≤55 ng/mL, n = 148), G2 (56-130 ng/mL, n = 142), G3 (131-243 ng/mL, n = 144) and G4 (≥244 ng/mL, n = 144). We analyzed the recurrence and survival of patients using the Kaplan-Meier method. We also evaluated pathological iron deposition among patients with a solitary tumor smaller than 2 cm.

Results: The cumulative rates of overall recurrence and survival at 5 years were 81.6% and 66.3%, respectively. The serum levels of ferritin were correlated with pathological iron deposition. There were no significant differences in recurrence and survival rates according to serum levels of ferritin and pathological hepatic iron deposition.

Conclusions: Serum levels of ferritin do not affect the prognosis of HCC patients undergoing RFA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200943PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059486PMC
January 2019

Biliary epithelial injury-induced regenerative response by IL-33 promotes cholangiocarcinogenesis from peribiliary glands.

Proc Natl Acad Sci U S A 2017 05 24;114(19):E3806-E3815. Epub 2017 Apr 24.

Department of Gastroenterology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.

The carcinogenic mechanism of extrahepatic cholangiocarcinoma (ECC) is unclear, due at least in part to the lack of an appropriate mouse model. Because human studies have reported frequent genetic alterations in the Ras- and TGFβ/SMAD-signaling pathways in ECC, mice with tamoxifen-inducible, duct-cell-specific Kras activation and a TGFβ receptor type 2 (TGFβR2) deletion were first generated by crossing , , and mice ( ). However, mice showed only mild hyperplasia of biliary epithelial cells (BECs) in the extrahepatic bile duct (EHBD) and died within 7 wk, probably a result of lung adenocarcinomas. Next, to analyze the additional effect of E-cadherin loss, mice were crossed with mice ( ). Surprisingly, mice exhibited a markedly thickened EHBD wall accompanied by a swollen gallbladder within 4 wk after tamoxifen administration. Histologically, invasive periductal infiltrating-type ECC with lymphatic metastasis was observed. Time-course analysis of EHBD revealed that recombined BECs lining the bile duct lumen detached due to E-cadherin loss, whereas recombined cells could survive in the peribiliary glands (PBGs), which are considered a BEC stem-cell niche. Detached dying BECs released high levels of IL-33, as determined by microarray analysis using biliary organoids, and stimulated inflammation and a regenerative response by PBGs, leading eventually to ECC development. Cell lineage tracing suggested PBGs as the cellular origin of ECC. IL-33 cooperated with Kras and TGFβR2 mutations in the development of ECC, and anti-IL-33 treatment suppressed ECC development significantly. Thus, this mouse model provided insight into the carcinogenic mechanisms, cellular origin, and potential therapeutic targets of ECC.
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http://dx.doi.org/10.1073/pnas.1619416114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441746PMC
May 2017

A new method for insertion of long intestinal tube for small bowel obstruction: Nonendoscopic over-the-wire method via short nasogastric tube.

Medicine (Baltimore) 2016 Nov;95(47):e5449

Department of Gastroenterology, JR Tokyo General Hospital, Tokyo, Japan.

It is often difficult to insert a long intestinal tube (LT) in patients with small bowel obstruction (SBO). We developed a novel technique for inserting an LT without endoscopy called nonendoscopic over-the-wire method via short nasogastric tube (NEWSt). We evaluated the efficacy and safety of NEWSt.We performed a retrospective study of patients who underwent LT insertion for SBO without any indications of strangulation with either NEWSt (n = 16) or endoscopy (n = 17) between November 2011 and February 2015 at our hospital. Univariate analysis was used to assess the success rate of LT placement beyond the duodenojejunal flexure, time required for the procedure, clinical outcomes, and adverse events.The success rate was 100% in both groups. Procedure time was numerically, but not statistically, shorter in the NEWSt group compared with the endoscopy group (24 ± 13 vs 30 ± 13 min; P = 0.174). There were no statistically significant differences between the 2 groups in terms of surgery rate (31% vs 12%; P = 0.225), fasting period (11.3 ± 6.3 vs 9.9 ± 4.5 days; P = 0.482), hospital stay (26.4 ± 22.1 vs 18.7 ± 7.0 days; P = 0.194), and recurrence rate (19% vs 24%; P = 1.0). No serious adverse event was observed in the NEWSt group, whereas serious aspiration pneumonia was observed in 2 patients after LT insertion in the endoscopy group.Without endoscopy, NEWSt enabled the high success rate and the short procedure time for the LT insertion. Prospective, randomized controlled trials are needed.
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http://dx.doi.org/10.1097/MD.0000000000005449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134882PMC
November 2016

Serum Alpha-Fetoprotein Has High Specificity for the Early Detection of Hepatocellular Carcinoma After Hepatitis C Virus Eradication in Patients.

Medicine (Baltimore) 2015 Jun;94(23):e901

From the Department of Gastroenterology (TM, RT, MK, RN, NF, MS, KU, KE, HN, YA, YK, KK); Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo (KM); Department of Gastroenterology, Juntendo University, Tokyo, Japan (SS).

Alpha-fetoprotein (AFP) has not played a large role in the surveillance of hepatocellular carcinoma due to inadequate sensitivity and specificity for active chronic hepatitis or cirrhosis. The aim of this study was to evaluate the diagnostic accuracy of AFP in small hepatocellular carcinomas after hepatitis C virus eradication to determine the optimal cutoff value. We conducted a case-control study of 29 cases and 58 controls, matched for age, gender, and platelet counts. The AFP cutoff was 5 ng/mL in patients after hepatitis C virus eradication and 17 ng/mL in those without hepatitis C virus eradication. The areas under the receiver operating characteristic curve were 0.86 (95% confidence interval, 0.76-0.96) in patients after hepatitis C virus eradication and 0.83 (95% confidence interval, 0.74-0.91) in those without hepatitis C virus eradication. In patients after hepatitis C virus eradication, the sensitivity and specificity of AFP levels were 24.1% and 100%, respectively, using a cutoff value of 17 ng/mL. Using a lower cutoff value of 5 ng/mL, the sensitivity increased to 75.9%, although the specificity decreased to 89.0%. AFP is a specific tumor marker for the diagnosis of hepatocellular carcinoma after hepatitis C virus eradication when using the optimal cutoff value of 5 ng/mL.
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http://dx.doi.org/10.1097/MD.0000000000000901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616483PMC
June 2015

Impact of serum ferritin level on hepatocarcinogenesis in chronic hepatitis C patients.

Hepatol Res 2016 Apr 15;46(4):259-68. Epub 2015 May 15.

Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Aim: To elucidate the impact of the serum ferritin level, a surrogate indicator of hepatic iron accumulation, on hepatocarcinogenesis in chronic hepatitis C patients.

Methods: Serum ferritin was measured in 487 chronic hepatitis C patients without history of hepatocellular carcinoma (HCC) after excluding patients in phlebotomy, those with overt chronic gastrointestinal bleeding and those who achieved sustained virological response before enrollment. Patients were divided into four groups (G1-G4) by quartile points of serum ferritin, with sexes separated.

Results: The serum ferritin level was positively correlated with total bilirubin, aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyltransferase, hemoglobin and AFP, and inversely correlated with prothrombin activity in both sexes. A significant difference in HCC incidence was observed only in male patients; the incidence was higher in G1 (≤80 ng/mL, n = 54) and G4 (≥323 ng/mL, n = 54) compared with that of G2 (81-160 ng/mL, n = 54) and G3 (161-322 ng/mL, n = 52). The spline curve indicating the relationship between the hazard ratio and serum ferritin level took the form of a J-shape for male patients. In multivariate analysis, G1 and G4 showed higher incidence of HCC among men with a hazard ratio of 2.19 (95% confidence interval, 1.02-4.70; P = 0.045) compared with G2 and G3, together with older age, lower serum albumin and ALT above the normal upper limit.

Conclusion: The serum ferritin level is an independent risk factor for HCC development in male patients with chronic hepatitis C when the level is extremely high or low.
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http://dx.doi.org/10.1111/hepr.12517DOI Listing
April 2016

Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma.

J Hepatol 2015 Jul 24;63(1):131-40. Epub 2015 Feb 24.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan.

Background & Aims: Obesity defined by body mass index (BMI) significantly increases the risk of hepatocellular carcinoma (HCC). In contrast, not only obesity but also underweight is associated with poor prognosis in patients with HCC. Differences in body composition rather than BMI were suggested to be true determinants of prognosis. However, this hypothesis has not been demonstrated conclusively.

Methods: We measured skeletal muscle index (SMI), mean muscle attenuation (MA), visceral adipose tissue index, subcutaneous adipose tissue index, and visceral to subcutaneous adipose tissue area ratios (VSR) via computed tomography in a large-scale retrospective cohort of 1257 patients with different stages of HCC, and comprehensively analyzed the impact of body composition on the prognoses.

Results: Among five body composition components, low SMI (called sarcopenia), low MA (called intramuscular fat [IMF] deposition), and high VSR (called visceral adiposity) were significantly associated with mortality, independently of cancer stage or Child-Pugh class. A multivariate analysis revealed that sarcopenia (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.18-1.96; p=0.001), IMF deposition (HR, 1.34; 95% CI, 1.05-1.71; p=0.020), and visceral adiposity (HR, 1.35; 95% CI, 1.09-1.66; p=0.005) but not BMI were significant predictors of survival. The prevalence of poor prognostic body composition components was significantly higher in underweight and obese patients than in normal weight patients.

Conclusions: Sarcopenia, IMF deposition, and visceral adiposity independently predict mortality in patients with HCC. Body composition rather than BMI is a major determinant of prognosis in patients with HCC.
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http://dx.doi.org/10.1016/j.jhep.2015.02.031DOI Listing
July 2015

Comparison of improved prognosis between hepatitis B- and hepatitis C-related hepatocellular carcinoma.

Hepatol Res 2015 Oct 3;45(10):E99-E107. Epub 2015 Mar 3.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Aim: Treatment strategies for hepatocellular carcinoma (HCC) have been advanced. The aim of this study was to compare the change of the prognosis between hepatitis B-related HCC (B-HCC) and hepatitis C-related HCC (C-HCC) in the last two decades.

Methods: We enrolled 166 B-HCC patients who underwent percutaneous ablation between 1990 and 2009. Patients were divided into three groups according to the treatment time period: 1990-1995 (cohort 1, n = 19), 1996-2002 (cohort 2, n = 49) and 2003-2009 (cohort 3, n = 98). We enrolled 1219 C-HCC patients who underwent percutaneous ablation during the same period (n = 190, 413 and 616, respectively.). Interferon and nucleoside/nucleotide analog use was investigated. Prognosis was evaluated for each cohort using the Kaplan-Meier method and a multivariate Cox proportional hazard regression model.

Results: Two (11%), 24 (49%) and 80 (82%) B-HCC patients received nucleoside/nucleotide analogs during the follow-up period in cohorts 1-3, respectively. Among them 1, 18 and 62 patients achieved viral remission, respectively. Thirty-four (18%), 35 (8%) and 84 (14%) C-HCC patients received interferon therapy, respectively. The 5-year B-HCC (P < 0.001) survival rates were 52.6%, 61.1% and 81.6% for cohorts 1-3, respectively. However, the survival rates were 55.6%, 58.8% and 61.1% for C-HCC (P = 0.12), respectively. The B-HCC prognosis improved dramatically (P < 0.001) over time, whereas the prognosis of C-HCC improved moderately (P = 0.01).

Conclusion: The prognosis of B-HCC has improved dramatically over time, whereas that of C-HCC has improved moderately.
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http://dx.doi.org/10.1111/hepr.12468DOI Listing
October 2015

Recent progress in radiofrequency ablation therapy for hepatocellular carcinoma.

Oncology 2014 22;87 Suppl 1:73-7. Epub 2014 Nov 22.

Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institution of Medical Research, Tokyo, Japan.

In order to attain better ablation and more effective management of hepatocellular carcinoma (HCC), new approaches and devices in radiofrequency ablation (RFA) therapy were presented and discussed in a workshop at the 50th Annual Meeting of the Liver Cancer Study Group of Japan. A novel bipolar RFA apparatus was introduced in Japan in January 2013. Hundreds of subjects with HCC were treated with multipolar RFA with varied devices and plans. Among these, no-touch ablation was one of the most useful procedures in the treatment of HCC with the apparatus. In RFA therapy, a few assisting devices and techniques were applied for convenience and improvement of the thermal ablation procedure. Contrast-enhanced ultrasonography and three-dimensional fusion imaging technique using volume data of CT or MRI could improve exact targeting and shorten the treatment time for RFA procedures under ultrasonographic guidance. A more complicated method using a workstation was also reported as being helpful in planning the ablated shape and volume in multineedle RFA. The effective use of sedatives and antianalgesics as well as a novel microwave apparatus with a cooled-tip electrode was also discussed.
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http://dx.doi.org/10.1159/000368148DOI Listing
January 2015

Frequency of and predictive factors for vascular invasion after radiofrequency ablation for hepatocellular carcinoma.

PLoS One 2014 14;9(11):e111662. Epub 2014 Nov 14.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Vascular invasion in patients with hepatocellular carcinoma (HCC) is representative of advanced disease with an extremely poor prognosis. The detailed course of its development has not been fully elucidated.

Methods: We enrolled 1057 consecutive patients with HCC who had been treated with curative intent by radiofrequency ablation (RFA) as an initial therapy from 1999 to 2008 at our department. We analyzed the incidence rate of and predictive factors for vascular invasion. The survival rate after detection of vascular invasion was also analyzed.

Results: During a mean follow-up period of 4.5 years, 6075 nodules including primary and recurrent lesions were treated by RFA. Vascular invasion was observed in 97 patients. The rate of vascular invasion associated with site of original RFA procedure was 0.66% on a nodule basis. The incidence rates of vascular invasion on a patient basis at 1, 3, and 5 years were 1.1%, 5.9%, and 10.4%, respectively. Univariate analysis revealed that tumor size, tumor number, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein were significant risk predictors of vascular invasion. In multivariate analysis, DCP was the most significant predictor for vascular invasion (compared with a DCP of ≤100 mAu/mL, the hazard ratio was 1.95 when DCP was 101-200 mAu/mL and 3.22 when DCP was >200 mAu/mL). The median survival time after development of vascular invasion was only 6 months.

Conclusion: Vascular invasion occurs during the clinical course of patients initially treated with curative intent. High-risk patients may be identified using tumor markers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111662PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232383PMC
July 2015

Impact of serum levels of interleukin-6 and adiponectin on all-cause, liver-related, and liver-unrelated mortality in chronic hepatitis C patients.

J Gastroenterol Hepatol 2015 Feb;30(2):379-88

Department of Gastroenterology, The University of Tokyo, Tokyo, Japan.

Background And Aim: Various inflammatory cytokines and adipokines have been implicated in hepatitis C virus (HCV)-mediated liver disease, and interleukin-6 (IL-6) and adiponectin may play key roles. In addition, these factors may be associated with chronic hepatitis C (CHC)-induced extrahepatic manifestations. However, little data are available on the role of these factors on future outcomes of CHC patients. This study aims to evaluate the impact of serum levels of IL-6 and adiponectin on all-cause mortality, liver-related mortality, and liver-unrelated mortality.

Methods: A long-term follow-up study was conducted, consisting of 325 CHC patients, for which we previously reported positive associations between these factors (Serum levels of IL-6 and adiponectin) and hepatocellular carcinoma (HCC) development.

Results: During the follow-up period (mean, 13.0 year), there were 92 events consisting of 91 deaths (liver related, 72; liver unrelated, 19) and 1 liver transplantation due to liver failure. High IL-6 and adiponectin levels, defined as being higher than each median value at baseline, were associated with significantly higher incidences of not only HCC development but also all-cause mortality. Interestingly, high IL-6 was strongly associated with only liver-related mortality, whereas high-serum adiponectin was associated with not only liver-related, but also liver-unrelated mortality. Multivariate analysis identified high IL-6 as an independent risk factor for liver-related mortality and high adiponectin as an independent risk factor for liver-unrelated mortality.

Conclusion: High serum levels of IL-6 and adiponectin were associated with higher all-cause and liver-related mortality in CHC patients. In addition, high adiponectin was associated with liver-unrelated mortality. The measurement of these factors may provide information useful for predicting future outcomes in CHC patients.
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http://dx.doi.org/10.1111/jgh.12719DOI Listing
February 2015

Slight elevation of high-sensitivity C-reactive protein to predict recurrence and survival in patients with early stage hepatitis C-related hepatocellular carcinoma.

Hepatol Res 2015 Jun 2;45(6):645-55. Epub 2014 Sep 2.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Aim: Hepatocellular carcinoma (HCC) is associated with chronic inflammation derived from various origins. We investigated whether high-sensitivity C-reactive protein (hsCRP) could predict recurrence and survival after curative treatment for early stage hepatitis C virus-related HCC (C-HCC).

Methods: We enrolled 387 patients with three or fewer C-HCC nodules, none of which exceeded 3 cm, and of Child-Pugh class A or B who underwent radiofrequency ablation. We divided the patients into high and low hsCRP groups based on the optimal cut-off value for recurrence using a split-sample method and maximally selected rank statistics. Differences in recurrence and survival rates were evaluated by the Kaplan-Meier method and the log-rank test. Hazard ratios of hsCRP were adjusted with confounding factors using a multiple Cox regression model. We also assessed the correlations between hsCRP levels and clinical parameters.

Results: The optimal hsCRP cut-off value was 0.08 mg/dL. The cumulative recurrence rates after 5 years in the high and low hsCRP groups were 90.0% and 82.2%, respectively (P = 0.028), and the corresponding survival rates were 50.9% and 71.8%, respectively (P < 0.001). Higher hsCRP was an independent predictor for recurrence (adjusted hazard ratio [aHR], 1.32; 95% confidence interval [CI], 1.03-1.67; P = 0.026) and survival (aHR, 1.59; 95% CI, 1.14-2.22; P = 0.007). hsCRP was correlated with central obesity as well as tumor burden and liver dysfunction.

Conclusion: Slight elevation of the hsCRP level, even within the normal range, can predict recurrence and survival after curative treatment among patients with early stage C-HCC.
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http://dx.doi.org/10.1111/hepr.12398DOI Listing
June 2015

Cause-specific mortality associated with aging in patients with hepatocellular carcinoma undergoing percutaneous radiofrequency ablation.

Eur J Gastroenterol Hepatol 2014 Sep;26(9):1039-46

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Objective: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The aim of this study is to evaluate the efficacy of radiofrequency ablation (RFA) in elderly patients with HCC and to investigate cause-specific excess deaths associated with increasing number of elderly patients.

Materials And Methods: We enrolled 1401 naive patients with HCC who were treated initially by RFA from 1999 to 2011. Patients below 75 years of age were categorized as 'younger' and those at least 75 as 'elderly'. Differences in the demographic and laboratory data of these patients were assessed, along with Kaplan-Meier analysis of survival using the log-rank test. In addition, we assessed the causes of death, defined as liver related and liver unrelated, by competing risk analysis and risk factors for respective causes of death by a proportional subdistribution model.

Results: Overall, 353 patients were categorized as elderly. Elderly patients were more likely to be women, infected with hepatitis C virus, and score better in the Child-Pugh classification. The mortality at 5 years was lower in the elderly than in the younger patients (47.3 vs. 37.1%; P<0.001). Competing risk analysis showed a significant difference in liver-unrelated death (P<0.001) between the two groups, whereas there were no significant differences in liver-related death (P=0.64). By the proportional subdistribution model, age was a significant risk factor only for liver-unrelated death.

Conclusion: RFA provided satisfactory 5-year survival rates in elderly patients with HCC. The elderly tended to die from liver-unrelated causes.
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http://dx.doi.org/10.1097/MEG.0000000000000161DOI Listing
September 2014

Tumor markers are more useful in patients undergoing surveillance for hepatocellular carcinoma with unreliable results by ultrasonography.

Hepatol Res 2015 Apr 19;45(4):415-22. Epub 2014 Jun 19.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Aim: The objectives of this study was to evaluate the utility of tumor markers in hepatocellular carcinoma (HCC) surveillance based on the reliability of ultrasonography.

Methods: We analyzed 313 patients with HCC detected through a surveillance program using ultrasonography combined with three tumor markers from February 2000 to December 2010. The patients were categorized into two groups based on the triggering event: the US group (n = 281) in which a tumor was first detected using ultrasonography and the TM group (n = 32) in which elevated tumor markers led to the diagnosis of a tumor that was undetected using ultrasonography. The reliability of ultrasonography was scored on a 4-point scale based on three items (coarseness of liver parenchyma, patient obesity and liver atrophy). Additionally, patient survival was assessed using the Kaplan-Meier method and log-rank test.

Results: The median tumor size was 20 mm (interquartile range, 15-24). The reliability of ultrasonography was evaluated as good in 208 (66.5%), satisfactory in 80 (8.0%), poor in 21 (6.7%) and unsatisfactory in four (1.2%) patients. The proportion of patients in the TM group increased significantly according to the score, from 7.2% to 25.0% (P = 0.01). The survival rates of patients at 3 and 5 years were 83.7% and 57.2% in the US group, and 79.3% and 59.4% in the TM group, respectively (P = 0.98).

Conclusion: Tumor markers may play a diagnostic role in patients with unreliable ultrasonography results. The survival of patients diagnosed by elevated tumor markers was not significantly different from those diagnosed by ultrasonography.
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http://dx.doi.org/10.1111/hepr.12365DOI Listing
April 2015

Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma.

PLoS One 2013 2;8(10):e76018. Epub 2013 Oct 2.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Background: To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction.

Materials And Methods: We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors' institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions.

Results: There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10(th), 20(th), and 30(th) examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10(th) exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections.

Conclusion: Repeated exposures to iodinated contrast media increase the risk of adverse reaction.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076018PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788769PMC
July 2014

Spontaneous clearance of serum hepatitis C virus RNA during the clinical course of hepatocellular carcinoma in patients with chronic hepatitis C.

Hepatol Res 2014 Oct 7;44(10):E32-7. Epub 2013 Aug 7.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Aim: Spontaneous clearance of serum hepatitis C virus (HCV) RNA in chronic HCV carriers is assumed to be rare especially after development of hepatocellular carcinoma (HCC). We analyzed patients with chronic hepatitis C who spontaneously resolved serum HCV RNA after the treatment for HCC.

Methods: A database search was performed to identify patients with HCC in whom serum HCV RNA was positive before the treatment for HCC and became negative during the clinical course. Those who received interferon therapy were excluded.

Results: A total of 1145 patients with HCC who had not received interferon therapy were positive for HCV RNA before the treatment. Among them, five patients (M/F = 4/1) spontaneously resolved viremia during the clinical course, with the incidence rate of at least 0.11%/person-year (95% confidence interval: 0.05%-0.26%). The mean age at the time of negative test for HCV RNA was 77 (range: 52-84). Three and two were infected with HCV genotype 1 and 2, respectively. The mean initial viral load was 9.0 K IU/mL (range: 1.6-31.6). The alanine aminotransferase level decreased to within the normal range in all patients after the clearance of serum HCV RNA. Fibrosis grade of background liver, evaluated according to METAVIR classification, was F1 in 1, F2 in 1, F4 in 2, and unknown in 1. All patients survived more than 7 years after the initial treatment for HCC.

Conclusion: Spontaneous clearance of serum HCV RNA after HCC development possibly occurs even in elderly patients. The prognosis was good probably due to improved inflammation in the liver.
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http://dx.doi.org/10.1111/hepr.12203DOI Listing
October 2014

Gait-based person identification robust to changes in appearance.

Sensors (Basel) 2013 Jun 19;13(6):7884-901. Epub 2013 Jun 19.

Department of Advanced Information Technology, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.

The identification of a person from gait images is generally sensitive to appearance changes, such as variations of clothes and belongings. One possibility to deal with this problem is to collect possible subjects' appearance changes in a database. However, it is almost impossible to predict all appearance changes in advance. In this paper, we propose a novel method, which allows robustly identifying people in spite of changes in appearance, without using a database of predicted appearance changes. In the proposed method, firstly, the human body image is divided into multiple areas, and features for each area are extracted. Next, a matching weight for each area is estimated based on the similarity between the extracted features and those in the database for standard clothes. Finally, the subject is identified by weighted integration of similarities in all areas. Experiments using the gait database CASIA show the best correct classification rate compared with conventional methods experiments.
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http://dx.doi.org/10.3390/s130607884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715270PMC
June 2013

CT with hepatic arterioportography as a pretreatment examination for hepatocellular carcinoma patients: a randomized controlled trial.

Am J Gastroenterol 2013 Aug 30;108(8):1305-13. Epub 2013 Apr 30.

Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Objectives: The combination of computed tomography with hepatic arteriography and arterial portography (CTHA/CTAP) can detect additional hepatocellular carcinoma (HCC) nodules undetected by conventional dynamic CT.

Methods: In this single-center, randomized, open-label, controlled trial, we randomly assigned 280 patients who were diagnosed as having HCC by conventional dynamic CT, and eligible for radiofrequency ablation (RFA), to undergo CTHA/CTAP before treatment, or to the control group. Newly detected HCC nodules by CTHA/CTAP were intended to be ablated completely. The primary end point was recurrence-free survival and the key secondary end point was overall survival. The analysis was conducted on an intention-to-treat basis. Those with nonablated nodules were treated as for recurrence.

Results: A total of 75 nodules were newly diagnosed as HCC by CTHA/CTAP in 45 patients. Three patients (one in the CTHA/CTAP group and two in the control group) who refused treatment were excluded from all analyses. The cumulative recurrence-free survival rates at 1, 2, and 3 years were 60.1, 29.0, and 18.9% in the CTHA/CTAP group and 52.2, 29.7, and 23.1% in the control group, respectively (P=0.66 by log-rank test; hazard ratio, 0.94 for CTHA/CTAP vs. control; 95% confidence interval (CI), 0.73-1.22). The cumulative overall survival rates at 3 and 5 years were 79.7 and 56.4% in the CTHA/CTAP group and 86.8 and 60.1% in the control group, respectively (P=0.50; hazard ratio, 1.15, 95% CI, 0.77-1.71).

Conclusions: CTHA/CTAP may detect recurrent lesions earlier. However, CTHA/CTAP before RFA did not improve cumulative recurrence-free survival or overall survival.
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http://dx.doi.org/10.1038/ajg.2013.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734528PMC
August 2013

Uninodular combined hepatocellular and cholangiocarcinoma with multiple non-neoplastic hypervascular lesions appearing in the liver of a patient with HIV and HCV coinfection.

J Clin Virol 2013 Jun 19;57(2):173-7. Epub 2013 Feb 19.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

A 42-year-old man suffering from haemophilia A and coinfection of human immunodeficiency virus (HIV) and hepatitis C virus was referred to our institution because of multiple liver tumours. He had been receiving highly active antiretroviral therapy for HIV infection. Ultrasonography showed multiple hypoechoic space-occupying lesions in the liver. Contrast-enhanced dynamic computed tomography (CT) and magnetic resonance imaging revealed multiple ring-enhanced hypervascular lesions in the liver. An ultrasonography-guided biopsy was performed and histological evaluation indicated one of the lesions to be combined hepatocellular and cholangiocarcinoma and others to be non-neoplastic. The patient underwent partial hepatic resection and is currently alive without recurrence for 15 months. Multiple ring-enhanced lesions have been undetectable in postoperative follow-up CT examinations.
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http://dx.doi.org/10.1016/j.jcv.2013.01.012DOI Listing
June 2013

IGF-II Producing Hepatocellular Carcinoma Treated with Sorafenib: Metabolic Complications and a Foresight to Molecular Targeting Therapy to the IGF Signal.

Case Rep Gastroenterol 2012 Sep 22;6(3):784-9. Epub 2012 Dec 22.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan.

Hypoglycemia is a rare paraneoplastic manifestation of patients with neoplasms. Hypoglycemia can be induced by several causes, including an aberrant increase of hypoglycemic agents and adrenal insufficiency. Sorafenib is the first agent to demonstrate a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC). This small molecule inhibits serine/threonine kinase RAF in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature and decreases tumor growth and angiogenesis. In this paper, we report a case of HCC who was treated with sorafenib and showed severe hypoglycemia. This hypoglycemia might be induced by two causes, both adrenal insufficiency as an adverse effect of sorafenib and activation of the insulin-like growth factor (IGF) signal by excessive secretion of incompletely processed precursors of IGF-II. Although the IGF signal is suggested to be involved in aberrant growth of HCC in some cases, there is no other report showing the influence of sorafenib on HCC with active IGF signal. Unfortunately, the effect of sorafenib was limited in the present case. However, emerging drugs that directly inhibit the IGF signal can be expected to be highly effective in the treatment of HCC with hypoglycemia.
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http://dx.doi.org/10.1159/000346462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551420PMC
September 2012
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