Publications by authors named "Shinichiro Okabe"

19 Publications

  • Page 1 of 1

Posttreatment after Lenvatinib in Patients with Advanced Hepatocellular Carcinoma.

Liver Cancer 2021 Sep 20;10(5):473-484. Epub 2021 Apr 20.

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

Background: There is no standard posttreatment for patients with advanced hepatocellular carcinoma (HCC) in whom lenvatinib therapy has failed. This study aimed to investigate rates of migration to posttreatment after lenvatinib and to explore candidates for second-line agents in the patients with failed lenvatinib therapy.

Methods: We retrospectively collected data on patients with advanced HCC who received lenvatinib as the first-line agent in 7 institutions.

Results: Overall survival and progression-free survival (PFS) of 178 patients who received lenvatinib as the first-line agent were 13.3 months (95% confidence interval [CI], 11.5-15.2) and 6.7 months (95% CI, 5.6-7.8), respectively. Sixty-nine of 151 patients (45.7%) who discontinued lenvatinib moved on to posttreatment. The migration rates from lenvatinib to the second-line agent and from the second-line agent to the third-line agent were 41.7 and 44.4%, respectively. Based on multivariate analysis, response to lenvatinib (complete or partial response according to modified RECIST) and discontinuation of lenvatinib due to radiological progression, as well as male were associated with a significantly higher probability of migration to posttreatment after lenvatinib. On the other hand, alpha-fetoprotein levels of 400 ng/mL or higher was correlated with a significantly lower probability of migration to posttreatment after lenvatinib. Of 63 patients who received second-line systemic therapy, 53 (84.2%) were administered sorafenib. PFS, objective response rate (ORR), and disease control rate (DCR) for sorafenib treatment were 1.8 months (95% CI, 0.6-3.0), 1.8%, and 20.8%, respectively. According to the Cox regression hazard model, Child-Pugh class B significantly contributed to shorter PFS. PFS, ORR, and DCR of 22 patients who received regorafenib after lenvatinib in any lines were 3.2 months (range, 1.5-4.9 months), 13.6%, and 36.3%, respectively. Similarly, PFS, ORR, and DCR of 17 patients who received regorafenib after lenvatinib in the third-line (after sorafenib) were 3.8 months (range, 1.1-6.5 months), 17.6%, and 41.2%, respectively.

Conclusion: Sorafenib may not be a candidate for use as a posttreatment agent after lenvatinib, according to the results of the present study. Regorafenib has the potential to become an appropriate posttreatment agent after lenvatinib.
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http://dx.doi.org/10.1159/000515552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527907PMC
September 2021

Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma.

Liver Cancer 2020 Aug 5;9(4):382-396. Epub 2020 May 5.

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

Background: The present study aimed to assess the efficacy and safety of lenvatinib and verify the possibility of lenvatinib for the expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma (HCC) in real-world practice, primarily focusing on the population that was excluded in the REFLECT trial.

Methods: We retrospectively collected data on patients with advanced HCC who were administered lenvatinib in 7 institutions in Japan.

Results: Of 152 advanced HCC patients, 95 and 57 patients received lenvatinib in first-line and second- or later-line systemic therapies, respectively. The median progression-free survival in Child-Pugh class A patients was nearly equal between first- and second- or later-line therapies (5.2 months; 95% CI 3.7-6.9 for first line, 4.8 months; 95% CI 3.8-5.9 for second or later line, = 0.933). According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate of 27 patients (18%) who showed a high burden of intrahepatic lesions (i.e., main portal vein and/or bile duct invasion or 50% or higher liver occupation) at baseline radiological assessment was 41% and similar with that of other population. The present study included 20 patients (13%) with Child-Pugh class B. These patients observed high frequency rates of liver function-related adverse events due to lenvatinib. The 8-week dose intensity of lenvatinib had a strong correlation with liver function according to both the Child-Pugh and albumin - bilirubin scores.

Conclusion: Lenvatinib had potential benefits for patients with advanced HCC with second- or later-line therapies and a high burden of intrahepatic lesions. Dose modification should be paid increased attention among patients with poor liver function, such as Child-Pugh class B patients.
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http://dx.doi.org/10.1159/000507022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506220PMC
August 2020

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Invest New Drugs 2020 02 6;38(1):172-180. Epub 2019 Jun 6.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.
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http://dx.doi.org/10.1007/s10637-019-00801-8DOI Listing
February 2020

Endoscopic recovery of multiple migrated plastic stents during EUS-guided transmural drainage of pancreatic fluid collections.

Gastrointest Endosc 2017 04 21;85(4):860-861. Epub 2017 Feb 21.

Department of Gastroenterology, Mastudo City Hospital, Chiba, Japan.

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http://dx.doi.org/10.1016/j.gie.2017.02.011DOI Listing
April 2017

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

PLoS One 2016 20;11(9):e0163119. Epub 2016 Sep 20.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029907PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163119PLOS
August 2017

[Successful Surgical Treatment for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus after Favorable Response to Irradiation and Transcatheter Arterial Chemoembolization].

Gan To Kagaku Ryoho 2015 Nov;42(12):1842-4

Dept. of Surgery, Matsudo City Hospital.

Here, we describe the surgical treatment of a patient with hepatocellular carcinoma(HCC)with portal vein tumor thrombus (PVTT) after irradiation and transcatheter arterial chemoembolization (TACE). A 51-year-old man was being followed-up for HBV-related liver cirrhosis and HCC that was previously treated by radio-frequency ablation (RFA) and TACE. A follow up CT study revealed recurrence of HCC in segment 6 of the liver with PVTT extending to the right branch. As early recurrence was likely after resection and due to insufficient hepatic functional reserve, primary radiotherapy for PVTT was performed followed by TACE. After non-surgical treatment, a favorable tumor response was observed with no evidence of intrahepatic disease within the left lobe of the liver, and the volume of the future liver remnant increased, allowing us to perform splenectomy and right hemihepatectomy combined with portal vein resection/reconstruction.
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November 2015

[A case of enterolith ileus secondary to acute pancreatitis associated with a juxtapapillary duodenal diverticulum].

Nihon Shokakibyo Gakkai Zasshi 2015 May;112(5):863-70

Department of Gastroenterology, Matsudo City Hospital.

A 63-year-old woman with abdominal pain was referred to our hospital. Her pancreatic enzymes were elevated, and an abdominal computed tomography (CT) scan showed an enlarged pancreas, consistent with pancreatitis, and gas collection containing an impacted stone adjacent to Vater's papilla. This finding raised the suspicion of a duodenal diverticulum. A subsequent ERCP showed a juxtapapillary duodenal diverticulum (JPDD) filled with calculi and pus. The pancreatitis improved with 2 weeks of conservative treatment. Subsequently, the patient underwent resection of the uterus and bilateral adnexa to remove a large ovarian cyst that was also identified on the admission CT scan. On the third postoperative day, she developed abdominal pain and vomiting. CT revealed small bowel obstruction caused by an enterolith expelled from JPDD. Enterotomy was performed to remove the stone. To our knowledge, only three similar cases have been previously reported in Japan.
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http://dx.doi.org/10.11405/nisshoshi.112.863DOI Listing
May 2015

Natural history of large regenerative nodules and dysplastic nodules in liver cirrhosis: 28-year follow-up study.

Hepatol Int 2015 Apr 3;9(2):330-6. Epub 2015 Mar 3.

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba, 260-8670, Japan,

Background And Aims: Some follow-up studies of large regenerative nodules (LRNs) and dysplastic nodules (DNs) were reported previously. However, the pre-malignant potentiality of LRNs has remained controversial up to now. No LRNs showed malignant transformation in our previous study. We aimed to evaluate the pre-malignant potentiality of LRNs and DNs with a greater number of cases and longer follow-up periods.

Methods: From 1982 to 2005, 1,500 consecutive nodular lesions up to 2 cm in diameter were subjected to US guided thin-needle biopsy in cirrhotic patients at Chiba University Hospital. Of these lesions, 68 LRNs in 60 cases and 20 DNs in 22 cases were followed up for more than 6 months without any anti-cancer therapy. The last US examination was in 2010. The total study period was 28 years. We analyzed the histological findings and the clinical data of all cases retrospectively. The outcome of the lesions was examined.

Results: The mean follow-up period was 38.9 (16-119) months in LRNs and 31.9 (6-101 months) in DNs. Rate of nodule enlargement was higher in DNs (8/24 nodules, 33%) than LRNs (11/68 nodules, 16 %), (p = 0.0743, not significant). Rate of malignant transformation was also higher in DNs (10/24 nodules, 42%) than LRNs (9/68 nodules, 13%), (p = 0.0040, significant). The rate of disappearance in images was similar between LRNs and DNs.

Conclusions: We should recognize LRN as low risk pre-malignant lesions whereas DNs as high risk lesions.
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http://dx.doi.org/10.1007/s12072-015-9620-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387310PMC
April 2015

Clinical features and natural history of portal vein thrombosis after radiofrequency ablation for hepatocellular carcinoma in Japan.

Hepatol Int 2013 Oct 28;7(4):1030-9. Epub 2013 Aug 28.

Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan.

Purpose: Little is known about portal vein thrombosis (PVT) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to determine the incidence, background, and natural history of RFA-related PVT.

Methods: This is a retrospective study of 317 patients (219 males and 98 females) with HCC treated by RFA. Clinical data were compared between patients with and without PVT detected by ultrasound/CT. The median follow-up period after RFA was 15.8 months.

Results: PVT was detected in 6 (1.9 %) of 317 patients, 6 (0.8 %) of 802 treatments for HCC, and 6 (0.6 %) of 964 sessions of RFA. Body mass index was significantly higher in patients with PVT (26.9 ± 3.1 kg/m(2)) than in those without (22.9 ± 3.5 kg/m(2), p = 0.0075). PVT was significantly more frequent in RFA for the left lobe of the liver (2.7 %) than for the other sites (0 %, p < 0.0001). Five of the six patients received no treatment for PVT, with natural outcomes of disappearance in one patient, improvement in one patient, and unchanged appearance in three patients. Anticoagulation was applied in the one remaining patient and resulted in a successful recanalization. In the six patients, there was no significant difference in hepatic functional reserve between baseline and time of detection of PVT.

Conclusions: These results indicated that a high body mass index and RFA for HCC in the left lobe might be significant risk factors for PVT and that RFA-related PVT was rarely progressive with little influence on liver function.
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http://dx.doi.org/10.1007/s12072-013-9470-zDOI Listing
October 2013

Gadoxetic acid-enhanced MRI compared with CT during angiography in the diagnosis of hepatocellular carcinoma.

Magn Reson Imaging 2013 Jun 5;31(5):748-54. Epub 2012 Dec 5.

Department of Medicine and Clinical Oncology, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Purpose: To assess the value of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for the pre-therapeutic detection of hepatocellular carcinoma (HCC) using receiver operating characteristic (ROC) analysis with the combination of computed tomography (CT) arterial portography and CT hepatic arteriography (CTAP/CTHA).

Materials And Methods: A total of 54 consecutive patients with 87 nodular HCCs were retrospectively analyzed. All HCC nodules were confirmed pathologically. Three blinded readers independently reviewed 432 hepatic segments, including 78 segments with 87 HCCs. Each reader read two sets of images: Set 1, CTAP/CTHA; Set 2, gadoxetic acid-enhanced MRI including a gradient dual-echo sequence and diffusion-weighted imaging (DWI). The ROC method was used to analyze the results. The sensitivity, specificity, positive predictive value, negative predictive value and sensitivity according to tumor size were evaluated.

Results: For each reader, the area under the curve was significantly higher for Set 2 than for Set 1. The mean area under the curve was also significantly greater for Set 2 than for Set 1 (area under the curve, 0.98 vs. 0.93; P=.0009). The sensitivity was significantly higher for Set 2 than for Set 1 for all three readers (P=.012, .013 and .039, respectively). The difference in the specificity, positive predictive values and negative predictive values of the two modalities for each reader was not significant (P>.05).

Conclusion: Gadoxetic acid-enhanced MRI including a gradient dual-echo sequence and DWI is recommended for the pre-therapeutic evaluation of patients with HCC.
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http://dx.doi.org/10.1016/j.mri.2012.10.028DOI Listing
June 2013

Linear enhancement after radio-frequency ablation for hepatocellular carcinoma: is it a sign of recurrence?

Ultrasound Med Biol 2012 Nov;38(11):1902-10

Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, Chiba, Japan.

This prospective study was performed in 179 hepatocellular carcinoma (HCC) lesions treated by radio-frequency ablation (RFA) to explore the clinical outcome of "linear enhancement" on contrast-enhanced sonogram. Thirty-three lesions (18.4%) showed linear enhancement, a linear-shaped positive enhancement in the RFA-treated area. Seventeen of them were followed up with no treatment (remaining 16; dropout in eight, additional RFA in six and ineffective treatment in two) and three lesions (3/17, 17.6%) showed local tumor progression corresponding to linear enhancement at 7, 14, 19 months after RFA. Although there was no significant difference in local recurrence rate between the lesions with (3/17) and without linear enhancement (10/35), local tumor progression inside the ablation zone occurred only in the lesions with linear enhancement. In conclusion, linear enhancement inside the RFA-treated area should be followed up within 7 months because it has a risk of local tumor progression. Histology of linear enhancement and its influence on distant recurrence remain to be solved.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2012.07.003DOI Listing
November 2012

Safety and tolerance of sorafenib in Japanese patients with advanced hepatocellular carcinoma.

Hepatol Int 2011 Sep 22;5(3):850-6. Epub 2011 Jan 22.

Department of Medicine and Clinical Oncology, Graduate School of Medicine, University of Chiba, 1-8-1 Inohana, Chuo-ku, 260-8670, Chiba, Japan.

Purpose: Sorafenib provides a survival benefit for patients with advanced hepatocellular carcinoma (HCC). However, there has been little experience with it in Japan. This study evaluated the safety and tolerance of sorafenib in Japanese patients with HCC.

Methods: Clinical data for patients given sorafenib for advanced HCC were captured from eight institutions. All patients were classified as Child-Pugh A and the treatment was started at 400 mg twice daily. We recorded adverse events, treatment duration, and survival retrospectively. Adverse events were graded using Common Terminology Criteria, version 3.0; tumor response was assessed according to Response Evaluation Criteria in Solid Tumor, version 1.1.

Results: Of the 54 patients treated, their median age was 69 years (range 48-82), 91% were males, 52% had HCV infection, and 22% had HBV infection. The most common drug-related adverse events were hand-foot skin reactions (HFSR) (72%), aspartate transaminase elevation (55%), alanine aminotransferase elevation (52%), rash (50%), fatigue (41%), and diarrhea (32%). Liver failure occurred in 19%. The median time to treatment failure was 2 months. Dose reduction was required in 83% of the patients, and this occurred within 2 weeks in 44%. The median overall survival was 6.9 months.

Conclusions: These data suggest that sorafenib is generally tolerated in Japanese patients with HCC. Nevertheless, the majority needed a dose reduction. Adverse events including HFSR, rash, and liver failure occurred more frequently in our patients than those reported elsewhere. Careful attention must be paid to these adverse events during sorafenib administration.
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http://dx.doi.org/10.1007/s12072-010-9249-4DOI Listing
September 2011

Changes in tumor vascularity precede microbubble contrast accumulation deficit in the process of dedifferentiation of hepatocellular carcinoma.

Eur J Radiol 2010 Jul 23;75(1):e102-6. Epub 2009 Sep 23.

Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine 1-8-1, Inohana, Chuou-ku, Chiba 260-8670, Japan.

Purpose: To elucidate the changes in tumor vascularity and microbubble accumulation on contrast-enhanced sonograms, in relation to the dedifferentiation of hepatocellular carcinoma (HCC).

Materials And Methods: This prospective study enrolled 10 patients with histologically proven HCC (14.4-39.0mm, 26.1+/-7.4) showing nodule-in-nodule appearance upon contrast-enhanced computed tomography. Contrast-enhanced ultrasound was performed by harmonic imaging under a low mechanical index (0.22-0.25) during the vascular phase (agent injection to 1 min) and late phase (15 min) following the injection of Sonazoid (0.0075 ml/kg). Contrast enhancement in the inner and outer nodules was assessed in comparison with that in adjacent liver parenchyma as hyper-, iso-, or hypo-enhanced.

Results: Vascular-phase enhancement of all 10 inner nodules was hyper-enhanced, and that of outer nodules was hyper-enhanced in 3, iso-enhanced in 2, and hypo-enhanced in 5. Late-phase enhancement of inner nodules was hypo-enhanced in 8 and iso-enhanced in 2. Furthermore, late-phase enhancement of outer nodules was iso-enhanced in the 7 lesions that showed iso- or hypo-enhancement in the vascular phase, and hypo-enhanced in the 3 with hyper-enhancement in the vascular phase. Late-phase hypo-enhancement was significantly more frequent in the nodules showing early-phase hyper-enhancement (11/13) than in the nodules showing early-phase iso- or hypo-enhancement (0/7) in both the inner and outer nodules.

Conclusion: Dedifferentiation of HCC may be accompanied by changes in tumor vascularity prior to a reduction in microbubble accumulation. Observation of the vascular phase may be more useful than late-phase imaging for the early recognition of HCC dedifferentiation when using contrast-enhanced ultrasound with Sonazoid.
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http://dx.doi.org/10.1016/j.ejrad.2009.08.017DOI Listing
July 2010

Long-term effect of endoscopic injection therapy with combined cyanoacrylate and ethanol for gastric fundal varices in relation to portal hemodynamics.

Abdom Imaging 2010 Feb 9;35(1):8-14. Epub 2009 Jan 9.

Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan.

Background: The understanding on the long-term effect of endoscopic therapy for gastric fundal varices (FV) is still insufficient. The aim of this study was to evaluate the relationship between the long-term effect of the endoscopic injection therapy with combined cyanoacrylate (CA) and absolute ethanol (ET) for FV, and the portal hemodynamics.

Methods: The subjects of this retrospective study were ten consecutive cirrhotic patients with bleeding FV treated by endoscopic injection therapy with combined CA and ET. Percutaneous transhepatic portography was done after the completion of endoscopic treatment to assess portal hemodynamics.

Results: All the patients showed hemostasis by CA injection and complete obturation of FV by combined therapy of 5.6 +/- 2.1 (3-9) times without any severe complications except for gastric ulcer in one case. Five patients had recurrence (50%), and three of them showed rebleeding (30%). The other five patients had no recurrence during a mean observation period of 5.58 years (1190-2735 days). Although recurrence did not correlate with portal venous pressure, it was significantly frequent in patients without advanced portosystemic collateral vessels (5/7, P = 0.0384) compared to patients with them (0/3).

Conclusions: Endoscopic injection therapy combining CA and ET may be effective for FV. Significant development of portosystemic collateral vessels would support long-term therapeutic effect after this treatment.
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http://dx.doi.org/10.1007/s00261-008-9497-0DOI Listing
February 2010

Ultrasound-guided treatments under low acoustic power contrast harmonic imaging for hepatocellular carcinomas undetected by B-mode ultrasonography.

Liver Int 2009 May 18;29(5):708-14. Epub 2008 Sep 18.

Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, Chuou-ku, Chiba, Japan.

Background/aims: The aim was to examine the efficacy of contrast-enhanced ultrasound (US) with Sonazoid to demonstrate ultrasonically unrecognizable hypervascular hepatocellular carcinoma (HCC) and apply percutaneous US-guided treatments.

Methods: The subjects of this prospective study were 44 cirrhotic patients with 55 hypervascular lesions (12.7+/-4.5 mm) found by contrast-enhanced computed tomography but unrecognized by non-contrast US. Contrast-enhanced US was performed to demonstrate these hepatic lesions after an intravenous injection of Sonazoid (0.0075 ml/kg). The sonograms in both the early phase (for 1 min after injection) and the late phase (5-10 min after) were taken in the harmonic imaging mode under a low mechanical index (0.24-0.3).

Results: Fifty-three lesions were demonstrated by contrast-enhanced US, 52 with positive enhancement in the early phase and 44 with negative enhancement in the late phase. Percutaneous US-guided treatments were successfully performed for 42 lesions (ethanol injection in 20 and radiofrequency ablation in 22) in 32 patients with reference to contrast-enhanced US findings. Six patients were treated by transarterial chemoembolization alone because they had more than three lesions in the liver. In the remaining seven lesions in six patients, six were diagnosed as non-HCC lesions: five with vascular abnormalities such as arterioportal or arteriovenous communication and the other one with benign lesion in alcoholic liver disease. These six lesions and one HCC lesion with severe liver damage were followed up without any treatment.

Conclusions: As the detectability of ultrasonically unrecognizable hypervascular HCC improved by contrast-enhanced US with Sonazoid, a wider application of percutaneous US-guided treatments may be possible.
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http://dx.doi.org/10.1111/j.1478-3231.2008.01875.xDOI Listing
May 2009

Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation.

J Hepatol 2005 Sep;43(3):458-64

Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba-shi, Chiba 260-8670, Japan.

Background/aims: To evaluate the therapeutic efficacy of percutaneous ethanol injection (PEI) for patients with < or = 3 lesions of small (< or = 3 cm diameter) hepatocellular carcinoma (HCC).

Methods: PEI was applied to 270 patients with small HCC as the first-line treatment option during a 20-year period.

Results: (1) There was no treatment-related deaths, and only 2.2% of severe complications; (2) PEI induced a complete response of all HCCs according to CT evaluation performed within one month after the procedure, and the local recurrence rate at 3 years was 10%; (3) the overall 3- and 5-year survival rates after treatment were 81.6 and 60.3%, respectively, but the rates were higher, 87.3 and 78.3%, in Child A patients with a solitary tumor < or = 2 cm in diameter; (4) factors significantly influencing survival were liver function (P = 0.0033) and serum alpha-fetoprotein level (P = 0.0014), and (5) the recurrence rate at remote sites in the liver was lower in patients with HCC < or = 2 cm (P = 0.0395) and in those with a solitary HCC (P < 0.0001) according to Cox's proportional hazard model. (6) Radiofrequency ablation would not have been performed in approximately 25% of these patients.

Conclusions: PEI is considered a reliable treatment for small HCC in terms of safety and efficacy.
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http://dx.doi.org/10.1016/j.jhep.2005.03.033DOI Listing
September 2005

Metal contents of liver parenchyma after percutaneous ethanol injection or radiofrequency ablation in patients with hepatocellular carcinoma before and after trientine hydrochloride therapy.

J Lab Clin Med 2004 Jun;143(6):333-9

Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba-shi, Japan.

We administered trientine hydrochloride, a drug used in the treatment of Wilson's disease, to patients with hepatocellular carcinoma after radical treatment with percutaneous ethanol injection or radiofrequency ablation, and examined its effect on the reduction of liver-tissue copper content. We enrolled 24 patients with 3 or fewer primary lesions of Child class A or B hepatocellular carcinoma with diameters of 3 cm or less who had undergone radical treatment with percutaneous ethanol injection or radiofrequency ablation. Trientine hydrochloride was orally administered in a single daily dose of 250 mg to 12 patients before a meal (at fasting, group 1) or at a total daily dosage of 750 mg, divided into 3 doses, to 12 patients (group 2). This study was a randomized between-groups comparative study of 12 weeks' duration. We used the particle-induced x-ray-emission method to determine liver-tissue mineral content. Urine copper and serum mineral levels were also measured, and transaminase levels were examined. Liver-tissue copper content decreased significantly, to 160.1 microg/g dry weight, after treatment, compared with the pretreatment level of 306.8 microg/g dry weight (P <.05). We detected no significant difference in iron or zinc content before and after treatment. The copper content was significantly reduced after treatment in both groups (P <.05). The urine copper level was significantly increased after 1 week of treatment but decreased thereafter. Serum copper levels were significantly reduced after treatment (P <.01). We detected no significant difference in transaminase level before and after treatment. Iron-deficiency anemia in 1 patient after 12 weeks' treatment was the only adverse reaction, and it was improved by the administration of an iron product. We noted no other overt adverse reactions. In patients with hepatocellular carcinoma, trientine hydrochloride therapy may significantly reduce copper content in liver tissue.
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http://dx.doi.org/10.1016/j.lab.2004.02.010DOI Listing
June 2004

Cloning and characterization of the human BAZF gene, a homologue of the BCL6 oncogene.

Biochem Biophys Res Commun 2002 Mar;291(3):567-73

Department of Hematology and Oncology, Tokyo Medical and Dental University, Tokyo, Japan.

The BAZF gene has recently been identified as a novel homologue of the BCL6 oncogene. Here we cloned the human BAZF gene using murine BAZF as a probe. The predicted amino acid sequence was 91% identical to that of murine BAZF. The BTB/POZ and zinc finger domains were almost completely conserved between human and murine BAZF. Fluorescence in situ hybridization analysis revealed that the human BAZF gene is located on chromosome 17p13.1. Although expression of human BAZF mRNA was ubiquitously detected in human tissues, abundant expression was detected in heart and placenta. BAZF mRNA was expressed in some immature B cell lines and erythroleukemia cell lines. The expression in a human erythroleukemia cell line, HEL cells, was upregulated during megakaryocytic differentiation induced by 12-O-tetradecanoyl-phorbol-13-acetate. These expression patterns of BAZF mRNA suggest that BAZF may regulate differentiation in stages or lineages that are different from those regulated by BCL6.
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http://dx.doi.org/10.1006/bbrc.2002.6481DOI Listing
March 2002
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