Publications by authors named "Hiroaki Takeoka"

31 Publications

Human T-Cell Leukemia Virus Type 1 Infection Is a Risk Factor for Atherosclerosis.

J Clin Med Res 2021 Mar 19;13(3):164-169. Epub 2021 Mar 19.

General Medicine, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.

Background: Infection, such as by human immunodeficiency virus (HIV), has been reported to cause atherosclerosis by inducing inflammation. Because human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus, as is HIV, we investigated the possible influence of HTLV-1 on the pathogenesis of atherosclerosis by use of established atherosclerosis parameters.

Methods: The study was done on Iki Island, Fukuoka, an area endemic for HTLV-1. The data of 1,424 residents who reported to an annual health check were available for analysis. Anti-HTLV-1 antibody status and factors associated with atherosclerosis were examined, including maximum intima-media thickness (Max-IMT) and brachial-ankle pulse wave velocity (PWV).

Results: HTLV-1 positive participants had significantly higher Max-IMT (1.15 ± 0.55 vs. 1.08 ± 0.61 mm, P = 0.04) and PWV (1,760.6 ± 414.5 vs. 1,657.1 ± 425.5 cm/s, P < 0.01) values than did those negative. Moreover, in multiple regression analysis (odds ratio: 1.39, P < 0.01) of participants with Max-IMT 1.1 mm or over, HTLV-1 was extracted as an independent factor for the development of atherosclerosis.

Conclusion: Our results indicate that HTLV-1 infection confers a high risk of atherosclerosis, although its opposite relation is also possible. It is important to carefully follow the health status of HTLV-1 carriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14740/jocmr4457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016519PMC
March 2021

A deep learning model for the classification of indeterminate lung carcinoma in biopsy whole slide images.

Sci Rep 2021 Apr 14;11(1):8110. Epub 2021 Apr 14.

Medmain Research, Medmain Inc., Fukuoka, 810-0042, Japan.

The differentiation between major histological types of lung cancer, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small-cell lung cancer (SCLC) is of crucial importance for determining optimum cancer treatment. Hematoxylin and Eosin (H&E)-stained slides of small transbronchial lung biopsy (TBLB) are one of the primary sources for making a diagnosis; however, a subset of cases present a challenge for pathologists to diagnose from H&E-stained slides alone, and these either require further immunohistochemistry or are deferred to surgical resection for definitive diagnosis. We trained a deep learning model to classify H&E-stained Whole Slide Images of TBLB specimens into ADC, SCC, SCLC, and non-neoplastic using a training set of 579 WSIs. The trained model was capable of classifying an independent test set of 83 challenging indeterminate cases with a receiver operator curve area under the curve (AUC) of 0.99. We further evaluated the model on four independent test sets-one TBLB and three surgical, with combined total of 2407 WSIs-demonstrating highly promising results with AUCs ranging from 0.94 to 0.99.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-87644-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046816PMC
April 2021

A case of transient global amnesia with hippocampal infarction due to infective endocarditis.

J Infect Chemother 2021 Jun 20;27(6):902-905. Epub 2021 Jan 20.

General Medicine, Fukuoka University Hospital, Fukuoka, Japan.

Transient global amnesia (TGA) is an uncommon disease characterized by sudden onset anterograde amnesia that typically improves within 24 hours. A 35-year-old woman presented with complete disruption of memory that had started on the previous day. She had fever and heart murmur and was diagnosed as having infective endocarditis with Staphylococcus lugdunensis, a coagulase-negative staphylococcus. Septic embolizations were found in the spleen and kidney on CT scan. The patient underwent aortic valve replacement. MRI susceptibility-weighted imaging showed a dotted low intensity area in the right hippocampus. Recently, etiology of TGA is reported to be related to hippocampal disorder. We report a rare case of TGA with hippocampal infarction due to septic embolism from infective endocarditis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jiac.2021.01.001DOI Listing
June 2021

A case report, a case who developed limited cutaneous scleroderma and pulmonary hypertension 8 years after diagnosis of anti-centromere antibody-positive Sjögren syndrome.

Mod Rheumatol Case Rep 2020 07 30;4(2):248-252. Epub 2020 Apr 30.

Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.

A 52-year-old woman was diagnosed as having anti-centromere antibody (ACA)-positive primary Sjögren syndrome (pSS). Eight years later, she visited our hospital because she had developed dyspnoea. She was diagnosed as having pulmonary arterial hypertension (PAH) with pulmonary veno-occlusive disease on the basis of the results of right heart catheterisation, a severe decrease in diffusing capacity of the lung for carbon monoxide (D, 17%) and desaturation (69%) after a 6-minute walk test. She was also diagnosed as having limited cutaneous systemic sclerosis (lcSSc) because she had developed finger sclerosis. The six-minute walk distance had improved by 54 m 3 months after commencing treatment with tadalafil. Clinicians should be alert to the possibility of patients with ACA-positive SS developing lcSSc and PAH during their clinical course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/24725625.2020.1755516DOI Listing
July 2020

Pretreatment prognostic nutritional index as a novel biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

Lung Cancer 2019 10 14;136:45-51. Epub 2019 Aug 14.

Department of Thoracic Surgery, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Japan.

Objectives: Immune checkpoint inhibitors (ICIs) have been established as a novel strategy for non-small cell lung cancer (NSCLC) therapy. However, a definitive biomarker that can predict response to ICI therapy remains unestablished. The prognostic nutritional index (PNI) is used to assess immune-nutritional conditions and is a prognostic factor in patients with various malignancies; however, its usefulness as a biomarker of response to ICI therapy and survival outcomes in NSCLC patients is unknown. Thus, we retrospectively analyzed the clinicopathological features of advanced-stage or recurrent NSCLC patients treated with ICI therapy to identify predictors of response to ICI therapy and investigate the effects of pretreatment PNI levels on survival after ICI therapy.

Materials And Methods: We selected 102 consecutive NSCLC patients who were treated with ICI therapy from November 2015 to February 2019. We measured their pretreatment PNI levels and performed univariate and multivariate Cox regression analyses of progression-free survival (PFS) or overall survival (OS) after ICI therapy.

Results: Pretreatment PNI levels were significantly associated with response to ICI therapy (objective response rate:P = 0.0131; disease control rate: P = 0.0002), PFS (P = 0.0013), and OS (P = 0.0053). In univariate and multivariate analyses of the associations between PNI, C-reactive protein (CRP) or neutrophil-lymphocyte ratio (NLR) and PFS or OS, NLR and PNI, but not CRP, are independent prognostic factors for PFS (NLR: relative risk [RR]=1.655, 95% confidence interval [CI]: 1.012-2.743, P = 0.0449, PNI: RR=1.704, 95% CI: 1.039-2.828, P = 0.0346). Only PNI showed a trend towards being an independent prognostic factor for OS (RR=1.606, 95% CI: 0.952-2.745, P = 0.0761).

Conclusion: The pretreatment PNI has the potential to be a simple and novel predictive biomarker of ICI response in NSCLC patients and might help to identify patients who will obtain a survival benefit from ICI therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2019.08.006DOI Listing
October 2019

Phase II Trial of Carboplatin and Pemetrexed Plus Bevacizumab with Maintenance Bevacizumab as a First-line Treatment for Advanced Non-squamous Non-small Cell Lung Cancer in Elderly Patients.

Anticancer Res 2018 Jun;38(6):3779-3784

Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.

Background/aim: The combination of platinum-doublet chemotherapy with bevacizumab has been established as a first-line treatment option in non-elderly patients with non-squamous (non-sq) non-small cell lung cancer (NSCLC). However, the safety and efficacy of this regimen have not yet been fully established in elderly patients.

Patients And Methods: Chemo-naïve patients with non-sq NSCLC, aged ≥75 years, having a good performance status (Eastern Cooperative Oncology Group performance status 0-1) and adequate organ function were considered eligible. Patients received carboplatin (area under the curve=5 mg/ml/min), pemetrexed (500 mg/m), and bevacizumab (15 mg/kg) every 3 weeks for up to 4 cycles, followed by maintenance bevacizumab. The primary endpoint was the objective response rate (ORR; target=50%, threshold=30%; Simon's two-stage design), and the secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS).

Results: Twelve patients were enrolled from June 2013 to July 2017. The study was closed because of slow patient accrual. The median patient age was 80 years. Eleven patients (92%) completed 4 cycles of induction chemotherapy. Seven patients achieved a partial response (PR), yielding an ORR of 58%. The median PFS was 8.4 [95% confidence interval (CI)=4.4-10.5] months, and the median OS was 33.9 (95%CI=13.2-43.3) months. Toxicities were generally mild and consistent with previous reports. There were no treatment-related deaths.

Conclusion: A regimen comprising carboplatin and pemetrexed plus bevacizumab followed by maintenance bevacizumab is feasible and potentially efficacious in elderly patients with non-sq NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.12661DOI Listing
June 2018

Preventive effect of kampo medicine (hangeshashin-to, TJ-14) plus minocycline against afatinib-induced diarrhea and skin rash in patients with non-small cell lung cancer.

Onco Targets Ther 2017 24;10:5107-5113. Epub 2017 Oct 24.

Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University, Kurume City.

Purpose: Diarrhea and oral mucositis induced by afatinib can cause devastating quality of life issues for patients undergoing afatinib treatment. Several studies have shown that hangeshashin-to (TJ-14) might be useful for chemotherapy-induced diarrhea and oral mucositis. In this study, we investigated the prophylactic effects of TJ-14 for afatinib-induced diarrhea and oral mucositis and minocycline for afatinib-induced skin rash.

Patients And Methods: First- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have become the standard first-line treatment in patients with EGFR-mutated non-small cell lung cancer. The incidence of diarrhea was higher with afatinib than with gefitinib, and we conducted a single-arm Phase II study with afatinib. Patients who had previously undergone treatment with afatinib were ineligible. Both TJ-14 (7.5 g/day) and minocycline (100 mg/day) were administered simultaneously from the start of afatinib administration. The primary end point was the incidence of ≥ grade 3 (G3) diarrhea (increase of ≥7 stools/day over baseline) during the first 4 weeks of treatment. The secondary end points were the incidence of ≥ G3 oral mucositis (severe pain interfering with oral intake) and $ G3 skin toxicity (severe or medically significant but not immediately life-threatening).

Results: A total of 29 patients (nine men and 20 women; median age, 66 years; performance status, 0/1/2: 18/10/1) were enrolled from four centers. Four patients had undergone prior treatment with chemotherapy, including gefitinib or erlotinib. In all, 20 (68.9%) patients and one (3.4%) patient had diarrhea of any grade and ≥ G3, respectively. One (3.4%) patient had ≥ G3 oral mucositis; no patients had ≥ G3 skin rash. A total of 18 (62%) of the 29 patients achieved a partial response.

Conclusion: The present study indicated a trend in which TJ-14 reduced the risk of afatinib-induced diarrhea and minocycline reduced the risk of afatinib-induced skin rash.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S145613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661491PMC
October 2017

Aplastic anemia in a lung adenocarcinoma patient receiving pemetrexed.

Invest New Drugs 2017 10 30;35(5):662-664. Epub 2017 Mar 30.

Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.

Pemetrexed (PEM) is an antimetabolite drug that interferes with enzymes involved in DNA synthesis and also the folate-dependent metabolic processes necessary for DNA replication and homocysteine homeostasis. Continuation maintenance with PEM after induction therapy with PEM plus cisplatin has been the standard form of first-line chemotherapy for advanced non-squamous non-small cell lung cancer. The regimen has a low incidence of bone marrow suppression, and the incidences of anemia, leukopenia, neutropenia and thrombocytopenia exceeding grade 3 are less than 5%. Here we report a 68-year-old Japanese man with stage IIIB (cT4N3M0) lung adenocarcinoma who received 4 cycles of chemotherapy with PEM 500 mg/m and cisplatin 75 mg/m every three weeks, which resulted in a partial response, and then continued to receive maintenance PEM monotherapy. After 11 cycles of PEM maintenance therapy, the patient's platelet count decreased, and progressed to pancytopenia within two months. A bone marrow puncture revealed replacement with fatty marrow. As other diseases possibly responsible for pancytopenia were ruled out, we diagnosed the patient as having aplastic anemia. This is the first reported case of aplastic anemia to have occurred during PEM therapy. Clinicians should bear in mind that PEM can potentially trigger severe pancytopenia, including aplastic anemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-017-0462-zDOI Listing
October 2017

A multicenter phase II trial of S-1 combined with bevacizumab after platinum-based chemotherapy in patients with advanced non-squamous non-small cell lung cancer.

Cancer Chemother Pharmacol 2016 Sep 11;78(3):501-7. Epub 2016 Jul 11.

Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka, 830-0011, Japan.

Objectives: This phase II trial investigated the efficacy and safety of S-1 plus bevacizumab (SB) after failure of platinum-based chemotherapy in patients with non-squamous non-small cell lung cancer (non-sq NSCLC).

Methods: Patients with non-sq NSCLC who had undergone prior platinum-based chemotherapy, regardless of the use of bevacizumab, were eligible. S-1 (80 mg/m(2)) was administered orally twice daily for 14 days, and bevacizumab (15 mg/kg) on day 1 every 3 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS).

Results: Twenty-eight patients (14 males and 14 females; median age 62 years; performance status 0/1/2: 21/7/0) were accrued from 4 centers. Almost half (n = 15, 53.6 %) of these had received prior bevacizumab therapy. The median PFS and overall survival were 3.2 months [95 % confidence interval (CI) 2.2-4.0 months] and 11.4 months (95 % CI 8.9-13.9 months), respectively. Prior exposure to bevacizumab did not affect the PFS. An objective response was observed in 4 patients, the response rate and disease control rate being 14.3 and 85.7 %, respectively. The treatment was well tolerated, the most common treatment-related side effects being anorexia (75 %) and fatigue (68 %).

Conclusion: Although SB was well tolerated, this combination did not provide any additional benefit in terms of PFS for patients with non-sq NSCLC after failure of platinum-based chemotherapy. It will be important to clarify the most suitable agent for use with bevacizumab, and the optimal timing of bevacizumab therapy for lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-016-3101-zDOI Listing
September 2016

A prospective, multicentre phase II trial of low-dose erlotinib in non-small cell lung cancer patients with EGFR mutations pretreated with chemotherapy: Thoracic Oncology Research Group 0911.

Eur J Cancer 2015 Sep 11;51(14):1904-10. Epub 2015 Jul 11.

Thoracic Oncology Research Group, Kanagawa, Japan.

Background: Low-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR) gene.

Methods: Patients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50 mg/d until disease progression or unacceptable toxicities. The dose was escalated to 150 mg/d in patients showing no response (i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours (RECIST)) to the initial dose during the first 4 weeks. The primary end-point was the objective response rate at the dose of 50 mg/d.

Results: Thirty-four patients from seven institutes were enrolled. The study was closed early when no response was confirmed in 15 patients, excluding the possibility that the primary end-point would be met. The objective response and disease control rates at the dose of 50 mg/d as determined by an independent review committee were 54.5% and 84.8%, respectively. Four additional patients achieved partial response with increased 150 mg/d dose. Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5 months, respectively. Treatment-related toxicities were generally mild, the most common being skin disorders and diarrhoea. Only one case experienced grade 3 toxicity, which was transient increase of hepatic enzymes.

Conclusion: The primary end-point was not met; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations. However, it may merit further evaluation for elderly or frail patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2015.06.120DOI Listing
September 2015

Electroless nickel plating on polymer particles.

J Colloid Interface Sci 2014 Sep 29;430:47-55. Epub 2014 May 29.

Department of Applied Chemistry, Faculty of Engineering, Osaka Institute of Technology, 5-16-1 Ohmiya, Asahi-ku, Osaka 535-8585, Japan; Nanomaterials Microdevices Research Center, Osaka Institute of Technology, Japan.

Near-monodisperse, micrometer-sized polypyrrole-palladium (PPy-Pd) nanocomposite-coated polystyrene (PS) particles have been coated with Ni overlayers by electroless plating in aqueous media. Good control of the Ni loading was achieved for 1.0 μm diameter PPy-Pd nanocomposite-coated PS particles and particles of up to 20 μm in diameter could also be efficiently coated with the Ni. Laser diffraction particle size analysis studies of dilute aqueous suspensions indicated that an additional water-soluble colloidal stabilizer, poly(N-vinyl pyrrolidone), in the electroless plating reaction media was crucial to obtain colloidally stable Ni-coated composite particles. Elemental microanalysis indicated that the Ni loading could be controlled between 61 and 78 wt% for the 1.0 μm-sized particles. Scanning/transmission electron microscopy studies revealed that the particle surface had a flaked morphology after Ni coating. Spherical capsules were obtained after extraction of the PS component from the Ni-coated composite particles, which indicated that the shell became rigid after Ni coating. X-ray diffraction confirmed the production of elemental Ni and X-ray photoelectron spectroscopy studies indicated the existence of elemental Ni on the surface of the composite particles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2014.05.041DOI Listing
September 2014

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer.

Jpn J Clin Oncol 2014 May 30;44(5):472-8. Epub 2014 Mar 30.

*Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.

Objective: The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (≥75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer.

Methods: Patients received escalated doses of carboplatin at an area under the concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy.

Results: A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months).

Conclusions: The combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was determined as the recommended dose in chemotherapy-naïve elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyu030DOI Listing
May 2014

Feasibility re-evaluation of 75 mg/m² docetaxel in Japanese patients with previously treated non-small cell lung cancer.

Jpn J Clin Oncol 2014 Apr 30;44(4):338-45. Epub 2014 Jan 30.

*Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka 830-0011, Japan.

Objective: The primary objective of this study was to re-evaluate the feasibility of docetaxel at doses of up to 75 mg/m² in Japanese patients with previously treated non-small cell lung cancer.

Methods: Patients received escalated doses of docetaxel at 70 mg/m² (level 1) or 75 mg/m² (level 2) every 3 weeks until disease progression or unacceptable toxicities. Dose escalation was decided on the basis of dose-limiting toxicity in the first cycle of chemotherapy.

Results: At dose level 1, dose-limiting toxicity--Grade 3 febrile neutropenia--was observed in one of the six patients and at dose level 2, it was seen in one of the first six patients. Therefore, an additional 14 patients were enrolled at dose level 2, as originally planned. Among the total of 20 patients at dose level 2, 6 (<33%) developed dose-limiting toxicity in the first cycle: febrile neutropenia in 5 and pneumonia in 1. Finally, 10 (50%) of the 20 patients experienced toxicities that met the dose-limiting toxicity criteria, including 8 with febrile neutropenia throughout the treatment period, but this was manageable with dose reduction or appropriate supportive care. Other observed toxicities were predictable from the safety profile of decetaxel and were also well managed. Four partial responses were observed, giving an overall response rate of 15.4%. The median progression-free survival period of the patients overall was 4.0 months (95% confidence interval 1.4-6.6 months).

Conclusions: Although docetaxel administration at an initial dose of 75 mg/m² requires careful attention because of the high incidence of febrile neutropenia, this dose is considered feasible according to the protocol definition in Japanese patients with previously treated non-small cell lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyt236DOI Listing
April 2014

Prognostic value of EGFR mutation and ERCC1 in patients with non-small cell lung cancer undergoing platinum-based chemotherapy.

PLoS One 2013 5;8(8):e71356. Epub 2013 Aug 5.

Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Background: In order to improve the outcome of patients with non-small cell lung cancer (NSCLC), a biomarker that can predict the efficacy of chemotherapy is needed. The aim of this study was to assess the role of EGFR mutations and ERCC1 in predicting the efficacy of platinum-based chemotherapy and the outcome of patients with NSCLC.

Methods: We conducted a retrospective study to analyze the relationships between EGFR mutations or ERCC1 expression and progression-free survival (PFS) in patients with NSCLC who received platinum-based chemotherapy. EGFR mutation status was determined using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method, and immunohistochemistry was used to examine the expression of ERCC1 in tumor samples obtained from the patients.

Results: Among the NSCLC patients who received platinum-based chemotherapy, the median PFS was significantly better in those who had never smoked and those with exon 19 deletion, and the median overall survival (OS) was significantly better in those who had never smoked, those with exon 19 deletion, and women. Cox regression analysis revealed that exon 19 deletion and having never smoked were significantly associated with both PFS and OS. Subset analysis revealed a significant correlation between ERCC1 expression and EGFR mutation, and ERCC1-negative patients with exon 19 deletion had a longer PFS than the other patients; ERCC1-positive patients without exon 19 deletion had a shorter PFS than the other patients.

Conclusions: Our results indicate that among NSCLC patients receiving platinum-based chemotherapy, those with exon 19 deletion have a longer PFS and OS. Our findings suggest that platinum-based chemotherapy is more effective against ERCC1-negative and exon 19-positive NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0071356PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734014PMC
April 2014

Phase I, dose-escalation study of AZD7762 alone and in combination with gemcitabine in Japanese patients with advanced solid tumours.

Cancer Chemother Pharmacol 2013 Sep 28;72(3):619-27. Epub 2013 Jul 28.

Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.

Purpose: AZD7762, a potent Chk1/Chk2 inhibitor, has shown chemosensitizing activity with gemcitabine in xenograft models.

Methods: This open-label, Phase I, dose-escalation study evaluated the safety, pharmacokinetics (PK) and preliminary efficacy (RECIST) of AZD7762 alone and in combination with gemcitabine in Japanese patients with advanced solid tumours (NCT00937664). Patients received intravenous AZD7762 alone on days 1 and 8 of a 14-day cycle (cycle 0), followed by AZD7762 plus gemcitabine 1,000 mg/m(2) on days 1 and 8 of 22-day cycles, in ascending AZD7762 dose cohorts.

Results: Twenty patients received AZD7762 at doses of 6 mg (n = 3), 9 mg (n = 3), 21 mg (n = 6) and 30 mg (n = 8). Dose-limiting toxicities occurred in 2/6 evaluable patients in the 30-mg cohort: one, CTCAE grade 3 elevated troponin T (cycle 0: AZD7762 monotherapy); one, neutropenia, thrombocytopenia, and elevated aspartate aminotransferase and alanine aminotransferase (cycle 1: combination therapy). The 30 mg dose was therefore regarded as non-tolerable. The most common adverse events (AEs) in cycle 0 (AZD7762 monotherapy) were bradycardia (50 %), hypertension (25 %) and fatigue (15 %). Overall, the most common AEs were bradycardia (55 %), neutropenia (45 %) and hypertension, fatigue and rash (30 % each). Grade ≥3 AEs were reported in 11 patients, the most common being neutropenia (45 %) and leukopenia (25 %). AZD7762 exposure increased approximately linearly. Gemcitabine did not appear to affect AZD7762 PK. There were no objective responses; five patients (all lung cancer) had stable disease.

Conclusions: The maximum tolerated dose of AZD7762 in combination with gemcitabine, 1,000 mg/m(2) was determined as 21 mg in Japanese patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-013-2234-6DOI Listing
September 2013

A randomized, controlled trial comparing traditional herbal medicine and neuraminidase inhibitors in the treatment of seasonal influenza.

J Infect Chemother 2012 Aug 16;18(4):534-43. Epub 2012 Feb 16.

General Medicine, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

The herbal medicine, maoto, has been traditionally prescribed to patients with influenza in Japan. To better understand the efficacy of maoto for the treatment of influenza, a randomized trial was conducted for comparison with oseltamivir or zanamivir. Adult patients with influenza symptoms, including fever, positive for quick diagnostic kit for influenza within 48 h of fever onset were assessed for enrollment. The data of 28 patients randomly assigned to maoto (n = 10), oseltamivir (n = 8), or zanamivir (n = 10) were analyzed for the duration of fever (>37.5°C) and total symptom score from symptom cards recorded by the patient. Viral isolation and serum cytokine measurements were also done on days 1, 3, and 5. Maoto granules, a commercial medical dosage form, are made from four plants: Ephedra Herb, Apricot Kernel, Cinnamon Bark, and Glycyrrhiza Root. Median durations of fever of patients assigned maoto, oseltamivir, or zanamivir were 29, 46, or 27 h, respectively, significantly different for maoto and oseltamivir. No significant between-group differences were found in total symptom score among three groups. Viral persistent rates and serum cytokine levels (IFN-α, IL-6, IL-8, IL-10, and TNF-α) during the study period showed no differences among three groups. The administration of oral maoto granules to healthy adults with seasonal influenza was well tolerated and associated with equivalent clinical and virological efficacy to neuraminidase inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10156-012-0378-7DOI Listing
August 2012

Clinical practice in management of hydration for lung cancer patients receiving cisplatin-based chemotherapy in Japan: a questionnaire survey.

Jpn J Clin Oncol 2011 Nov 29;41(11):1308-11. Epub 2011 Sep 29.

Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume City, Fukuoka 830-0011, Japan.

A questionnaire survey was performed to investigate the actual hydration methods used with cisplatin-containing regimens at various institutions in Japan to gain an overview of the varieties employed. Replies were received from 368 of 686 institutions board-certified by the Japanese Respiratory Society. In 233 institutions (63%), new lung cancer patients were treated regularly with regimens containing cisplatin at ≥60 mg/m2. In 172 institutions (48%), hydration with <3000 ml of intravenous saline was performed on day 1. In 225 institutions (65%), hydration was performed for up to 3 days at most, but no more than 48 (14%) of the institutions that responded did so on day 1 only. Two to three weeks of hospitalization was needed for the initial course at most institutions (76%). Thirteen institutions (4%) treated patients as outpatients after the second course, whereas none did so from the beginning of treatment. Despite inconsistencies among the methods used by the various institutions, 84% of those surveyed considered their approaches to be appropriate. Some useful objective indices for deciding the volume or duration of hydration are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyr145DOI Listing
November 2011

Signet ring cell adenocarcinoma of the lung with an EML4-ALK fusion gene mimicking mucinous (colloid) adenocarcinoma: a case report.

Lung Cancer 2011 Sep 29;73(3):375-8. Epub 2011 Jun 29.

Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan.

We herein report a case of signet ring cell adenocarcinoma of the lung with an EML4-ALK fusion gene mimicking mucinous (colloid) adenocarcinoma. A 79-year-old female presented with a pulmonary tumor located in the right lower lobe measuring 21 mm in size. A right lower lobectomy was performed. The postoperative pathological examination revealed signet ring cell carcinoma with abundant mucin pools, and a multiplex RT-PCR analysis revealed the variant 2 inversion of the EML4-ALK gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2011.05.016DOI Listing
September 2011

The longitudinal quantitative assessment by transient elastography of chronic hepatitis C patients treated with pegylated interferon alpha-2b and ribavirin.

Antiviral Res 2009 Aug 14;83(2):127-34. Epub 2009 Apr 14.

Department of General Internal Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka, Japan.

The aim of this study was to assess the association between liver stiffness measured by transient elastography (FibroScan) and the efficacy of pegylated interferon alpha-2b plus ribavirin combination treatment for patients with chronic hepatitis C virus (HCV) infection. We prospectively studied 145 Japanese patients with chronic HCV infection. FibroScan was done at baseline, at the end of treatment, and at 48 and 96 weeks after the end of treatment. The FibroScan values were significantly decreased for sustained virological response (SVR) patients (the mean rate of change; -16.2%, -32.2% and -43.5%) in comparison with non-SVR patients (-7.2%, -2.1% and +17.3%) at the end of treatment (P=0.0127), and 48 weeks (P<0.0001) and 96 weeks (P<0.0001) after the end of treatment. Among the non-SVR patients, the FibroScan values were significantly decreased for patients with biochemical response (BR) (-17.9%, -30.0% and -27.1%) in comparison with non-BR (-4.1%, +6.4% and +30.6%) at the end of treatment (P=0.0270), and 48 weeks (P<0.0001) and 96 weeks (P<0.0001) after the end of treatment. The FibroScan values may predict a progressively better clinical outcome for patients with successful virological and biochemical responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2009.04.002DOI Listing
August 2009

Epidemiological study of hepatitis E virus infection in the general population of Okinawa, Kyushu, Japan.

J Gastroenterol Hepatol 2008 Dec;23(12):1885-90

Department of Environmental Medicine and Infectious Disease, Kyushu University, Fukuoka, Japan.

Background And Aim: The aim of this study was to investigate the prevalence of hepatitis E virus (HEV) infection in the general population of Japan by determining presence of the antibody to HEV (anti-HEV).

Methods: The prevalence of HEV infection was determined by positivity of serum antibody to HEV (anti-HEV).

Results: On retrospective analysis, a significant decrease in anti-HEV prevalence was found in Okinawa healthy residents from 1995 (15.8%) to 2005 (5.5%) (P < 0.0001). In 2005, the anti-HEV prevalence was significantly higher in Okinawa wild boar hunters (25.3%) than in the residents (male 7.7% and female 4.1%) (P < 0.0001). A significant difference was found in the history of consumption of undercooked or raw boar meat between anti-HEV positive and negative hunters (100% vs 64.3%) (P = 0.0018).

Conclusions: In conclusion, the anti-HEV prevalence has decreased in the residents of this area, but HEV infection has continued at a high rate in the hunters through the custom of eating undercooked or raw boar meat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1440-1746.2008.05568.xDOI Listing
December 2008

Association factors for atopic dermatitis in nursery school children in Ishigaki islands - Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

Eur J Dermatol 2008 Sep-Oct;18(5):571-4. Epub 2008 Aug 8.

Department of Dermatology, Kyushu University Hospital, Maidashi 3-1-1, Higashiku, Fukuoka, Japan.

Atopic dermatitis (AD) is a multifactorial disease that usually decreases the quality of life of affected patients. The purpose of this study was to evaluate the associated factors for atopic dermatitis, asthma, rhinitis, and food allergy by physical examination of the skin and a questionnaire in nursery school children in Ishigaki Island, Okinawa, Japan. Enrolled in this study were 460 children from 0 to 6 years of age. Physical examination of skin symptoms and blood tests were performed. Information on past history and family history of atopic dermatitis, asthma, rhinitis, and food allergy were collected by questionnaire. The prevalence of atopic dermatitis was 12.2% (56/460). The cumulative prevalence of asthma, rhinitis, and food allergy was 19.9% (91/458), 3.3% (15/457), and 5.5% (25/456), respectively. In multivariate analysis, maternal history of rhinitis, atopic dermatitis siblings, past history of asthma and food allergy, and elevation of total IgE were significantly related to atopic dermatitis. A high total IgE level was a strong risk factor specific for atopic dermatitis in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ejd.2008.0479DOI Listing
December 2008

A hybrid lesion of lung cancer and aspergillosis.

Clin Med Oncol 2008 10;2:113-6. Epub 2008 Apr 10.

Division of Respirology, Neurology and Rheumatology, Department of Medicine.

A 74-year-old man presented with gradual wall thickening of a cystic lung lesion. Serologic tests indicated Aspergillus infection, but neither fungal organisms nor evidence of malignant disease were recovered from repeated sputum collections, a bronchoscopic lung biopsy specimen, or bronchial washings. Treatment with antifungal agents did not result in clinical improvement. Surgical resection of the lesion demonstrated both squamous cell carcinoma and aspergillosis. These distinct disorders share common radiologic manifestations that can present a diagnostic challenge, as in the present case.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161662PMC
November 2011

Thymus and activation regulated chemokines in children with atopic dermatitis: Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

Eur J Dermatol 2007 Sep-Oct;17(5):397-404. Epub 2007 Aug 2.

Department of General Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka, 812-8582 Japan.

The purpose of this population-based study was to investigate the clinical significance of serum thymus and activation-regulated chemokine (TARC) in children with atopic dermatitis (AD). Between 2003 and 2004, 1359 Japanese children aged 5 years and under were prospectively followed. Serum levels of TARC by using an ELISA in each child were monitored throughout the study period. The first tested year, the mean serum level of TARC in children with sustained AD (mean; 691.7 pg/mL) was significantly higher than that of regressed AD children (569.9 pg/mL), newly developed AD children (380.1 pg/ mL), and healthy children (506.3 pg/mL). The changes of TARC levels in sustained AD children found no significance between 2003 (691.7 pg/mL) and 2004 (682.0 pg/mL). The mean levels of TARC of both regressed AD and healthy children significantly decreased from 2003 to 2004 (644.2 pg/mL to 448.7 pg/mL and 506.3 pg/mL to 442.1 pg/mL, respectively). The mean TARC level of newly developed AD children significantly increased from 2003 to 2004 (380.1 pg/mL to 491.8 pg/mL). We demonstrated strong associations between TARC levels and the natural course of childhood AD. Monitoring serum TARC levels of AD children may be useful for the biological evaluation of AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ejd.2007.0237DOI Listing
January 2008

Antibody to the human T-lymphotropic virus type 1 (HTLV-1) envelope protein Gp46 in patients co-infected with HCV and HTLV-1.

Am J Trop Med Hyg 2007 Jul;77(1):192-6

Department of Environmental Medicine and Infectious Diseases, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.

Human T-lymphotropic virus type 1 (HTLV-1) infection is known to affect hepatitis C virus (HCV) clearance and to accelerate the development of hepatocellular carcinoma in HCV-infected patients. In this study, we found the prevalence and titer of an antibody recognizing the central region of the HTLV-1 Gp46 protein to be associated with the severity of chronic liver disease. The antibody prevalence was significantly correlated with the stage of chronic liver disease (P < 0.0001): 3 (14.3%) of 21 patients with minimal-mild chronic hepatitis, 12 (24%) of 50 with moderate-severe chronic hepatitis, 7 (87.5%) of 8 with liver cirrhosis, and 13 (100%) of 13 with hepatocellular carcinoma. These results indicate that the antibody may be a useful marker of the deterioration of liver disease in patients co-infected with HCV and HTLV-1. This antibody may be useful for the diagnosis of liver diseases and the development of more effective treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2007

High molecular weight form of adiponectin levels of Japanese patients with chronic hepatitis C virus infection.

Hepatol Res 2007 Dec 1;37(12):1052-61. Epub 2007 Jul 1.

Department of General Medicine, Kyushu University Hospital, and Department of Environmental Medicine and Infectious Diseases, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.

Aim: The aim of the present study was to clarify the correlation between serum adiponectin level and the properties of hepatitis C virus (HCV).

Methods: A meal test was carried out for insulin resistance assessment in 81 patients with chronic HCV infection. Blood samples were taken before and after the test to measure serum insulin and plasma glucose (PG). The adiponectin level was measured by enzyme-linked immunosorbent assay in each patient.

Results: Serum adiponectin levels were significantly correlated with the area under the insulin curve (AUC-insulin)during the meal test and with serum HCV-RNA level. Multiple regression analysis showed age to be a significant independent parameter associated with an increased adiponectin level, whereas male sex, fasting insulin, and serum HCV-RNA level were significant independent parameters associated with a decreased adiponectin level.

Conclusion: It is possible that insulin resistance in patients with chronic HCV infection is related to adiponectin secretion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1872-034X.2007.00159.xDOI Listing
December 2007

Transient elastography for patients with chronic hepatitis B and C virus infection: Non-invasive, quantitative assessment of liver fibrosis.

Hepatol Res 2007 Dec 1;37(12):1002-10. Epub 2007 Jul 1.

Department of General Medicine, Kyushu University Hospital, Fukuoka, Japan.

Aim/methods: The aim of the present study was to compare the diagnostic performance of transient elastography (FibroScan) with that of serum fibrosis markers and stages of hepatic fibrosis by biopsy in 68 patients with chronic hepatitis B virus (HBV) and in 161 patients with hepatitis C virus (HCV) infection.

Results: The serum levels of hyaluronic acid (r = 0.601) and type IV collagen (r = 0.663) significantly positively associated with the FibroScan values (all P < 0.05). Classified by fibrosis stages, the median values of FibroScan were 3.5 kPa for F0, 6.4 kPa for F1, 9.5 kPa for F2, 11.4 kPa for F3, and 15.4 kPa forF4 in patients with chronic HBV infection, and were 6.3 kPa for F0, 6.7 kPa for F1, 9.1 kPa for F2, 13.7 kPa for F3, and 26.4 kPa for F4 in those with chronic HCV infection. The values were significantly correlated with fibrosis stage for both (HBV, r = 0.559, P = 0.0093, and HCV, r = 0.686, P < 0.0001).

Conclusion: These results suggest that FibroScan is an efficient and simple method for evaluating liver fibrosis in patients with chronic infection, both for HBV and HCV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1872-034X.2007.00160.xDOI Listing
December 2007

Intrafamilial transmission of Helicobacter pylori among the population of endemic areas in Japan.

Helicobacter 2007 Apr;12(2):170-6

Department of General Medicine, Kyushu University Hospital, Fukuoka, Japan.

Background: Helicobacter pylori (H. pylori) infection is a worldwide phenomenon related to several gastrointestinal diseases. However, because many aspects concerning the route of transmission remain unclear, we performed this epidemiologic study to clarify the route of intrafamilial transmission of H. pylori.

Materials And Methods: A retrospective study was performed in three widely separate areas in Japan to investigate the prevalence of H. pylori infection. In 1993, 613 residents were tested as were 4136 in 2002, including 1447 family members of 625 families. Antibody to H. pylori (anti-H. pylori) was determined by enzyme-linked immunosorbent assay.

Results: In 2002, the age-adjusted anti-H. pylori prevalence in Hoshino Village (67.5%) was significantly higher than in Kasuya Town (55.0%) and in Ishigaki City (54.7%) (p < .0001, p = .0039, respectively). The age-adjusted anti-H. pylori prevalence of Ishigaki City significantly decreased from 1993 (68.4%) to 2002 (52.5%), showing an age cohort effect. However, the prevalence did not significantly differ in children aged 0-6 years of Ishigaki City between 1993 (9.6%) and 2002 (10.3%). A familial analysis in 2002 demonstrated that the prevalence of anti-H. pylori was significantly higher in children with anti-H. pylori-positive (21.6%, 22 of 102) than with -negative mothers (3.2%, 3 of 95) (p < .0001, by Mantel-Haenszel test), whereas there was no significant difference between children with anti-H. pylori-positive and -negative fathers. Moreover, the prevalence was significantly higher in wives with anti-H. pylori-positive (64.0%, 208 of 325) than with -negative husbands (46.5%, 80 of 172) (p = .0071, by Mantel-Haenszel test) and in husbands with anti-H. pylori-positive (72.2%, 208 of 288) than with -negative wives (56.0%, 117 of 209) (p = .0106, by Mantel-Haenszel test).

Conclusions: In the last decade, H. pylori infection decreased in the general population of Japan by improvement of general hygiene conditions, but did not differ in young children, most likely because of mother-to-child transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1523-5378.2007.00488.xDOI Listing
April 2007

Incidence of atopic dermatitis in nursery school children - a follow-up study from 2001 to 2004, Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

Eur J Dermatol 2006 Jul-Aug;16(4):416-9

Department of Dermatology, Kyushu University Hospital, Maidashi 3-1-1, Higashiku, 812-8582, Fukuoka, Japan.

Atopic dermatitis (AD) is a multifactorial disease that usually decreases the quality of life of affected patients. We monitored the incidence of AD and serum total IgE levels annually among nursery school children in Ishigaki Island, Okinawa, Japan, from 2001 to 2004. A total of 1731 children were enrolled. The prevalence of AD ranged from 3.7 to 11% in each year, with no significant difference between boys and girls. 869 children were examined at least twice. 71.6% (53/74) of AD patients regressed spontaneously, whereas 5.5% (44/795) of non-AD individuals developed AD during the 3-year follow-up. Increases in total IgE levels were greater and more rapid in children with long-term AD than in those who had spontaneously regressed, had newly-developed AD or did not have AD. The regression rate of AD was > 70% while new-onset AD occurred at a rate of 3.67%/person year in nursery school children of Ishigaki Island.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2007

[Varicella-zoster virus symptoms and polyneuropathy in a patient with human immunodeficiency virus infection not improved until highly active anti-retroviral therapy added to acyclovir therapy].

Kansenshogaku Zasshi 2006 Jan;80(1):46-50

Department of Environmental Medicine and Infectoius Desease, Faculity of Medical Sciences, Kyushu University.

In March 2003, a 34-year-old man with left facial palsy, dysphagia, and hoarseness treated with acyclovir suffered worsened dermatological and neurological problems. A routine blood test in early April showed the patient to be HIV-antibody positive, so he was transferred to our hospital. Blood analysis showed serum HIV-RNA at 96,000 copies/mL and a CD 4 count of 170/microL. Brain MRI taken on admission showed a T 2 high lesion in their left medulla. Acyclovir was thought to be ineffective due to reduced cell-mediated immunity because of the HIV infection, and HAART therapy was begun. After two months of HAART, skin lesions and the T 2 high lesion in left medulla improred. HIV-RNA became undetectable and the CD 4 count exceeded 500/microL. Intracellular cytokine analysis by flow cytometry showed a shift from Th 2 to Th 1 dominance. The elimination of VZV may thus have been promoted by the combination of acyclovir and HAART.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11150/kansenshogakuzasshi1970.80.46DOI Listing
January 2006

Long-term lamivudine treatment for chronic hepatitis B in Japanese patients: a project of Kyushu University Liver Disease Study.

World J Gastroenterol 2006 Jan;12(4):561-7

Department of General Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka 812-8582, Japan.

Aim: To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B.

Methods: In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 (median 21) mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment.

Results: Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL (P<0.0001), HBeAg negativity (P<0.0001), a platelet count of 100 x 10(9)/L or more (P=0.0162) at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment (P=0.0003) to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at >=5 mo. A virological breakthrough was found significantly more often in patients with delayed virological response.

Conclusion: Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066088PMC
http://dx.doi.org/10.3748/wjg.v12.i4.561DOI Listing
January 2006