1.Significance of Molecular Diagnosis using Histopathological Specimens in Cestode Zoonoses
Hiroshi Yamasaki ; Kazuhiro Nakaya ; Minoru Nakao ; Yasuhito Sako ; Akira Ito
Tropical Medicine and Health 2007;35(4):307-321
Cestode zoonosis cases confirmed by PCR-based mitochondrial DNA analysis were investigated. The cestodiosis included taeniasis, cysticercosis, alveolar echinococcosis, cystic echinococcosis, sparganosis mansoni, diphyllobothriasis and diplogonoporiasis. DNA samples were extracted from the ethanol-fixed, formalin-fixed, paraffin-embedded sections, HE-stained, and the PAS- or acetocarmine-stained samples submitted for histopathology. For PCR-based analysis, cytochrome c oxidase subunit 1 and⁄or cytochrome b genes were amplified by multiplex PCR or conventional PCR coupled with DNA sequencing. Although DNA molecules were degraded in most formalin-fixed samples, smaller gene fragments were successfully amplified and the species causing cestodiosis could be identified by DNA sequence analysis of the amplicons. This review describes cestode zoonosis cases in which mitochondrial DNA analysis was useful not only for routine and retrospective diagnosis, but also for genetic polymorphism analysis and molecular identification of the species associated with pathogenicity. The significance of molecular diagnosis using histopathological specimens for cestode zoonoses is also discussed.
2.Diphyllobothriasis and sparganosis in Indonesia
Sri S. Margono ; Rawina W. Sutjahyono ; Agnes Kurniawan ; Minoru Nakao ; Tri Mulyani ; Toni Wandra ; Akira Ito
Tropical Medicine and Health 2007;35(4):301-305
Food-borne zoonotic cestode infections by Diphyllobothrium spp. and Spirometra spp. are relatively uncommon in Indonesia. So far, only one case of diphyllobothriasis was confirmed in 2004 in Jakarta, whereas there were 4 sparganosis cases in Indonesia. Morphology of eggs and gravid proglottids revealed the first case to be caused by Diphyllobothrium species. However, molecular identification of the species was not successful. Sparganosis may not be particularly rare in Indonesia, since Spirometra species have often been found in cats and other animals. These topics in Indonesia are briefly overviewed with reference to historical records and socio-cultural background information.
3.A Proposal on the Curriculum of Behavioral Science
Marie Amitani ; Yoshiki Ishikawa ; Akio Inui ; Shigeru Inoue ; Akihito Shimazu ; Shigeki Suwa ; Akira Tsuda ; Akizumi Tsutsumi ; Koji Tsuboi ; Mutsuhiro Nakao ; Takeo Nakayama ; Masahiro Hashizume ; Kazuhiro Yoshiuchi
Medical Education 2015;46(1):37-40
Introduction: No formal curriculum has been formulated for teaching behavioral science to undergraduate medical students in Japan.
Method: We conducted a survey using the Delphi method to investigate the required competency in behavioral science for graduates in medicine. Then, we developed an outcome-oriented curriculum for teaching behavioral science.
Results: We propose an educational module of behavioral science consisting of 15 sessions of 90-minute lectures, small group discussions, and practice.
Discussion: We recommend including not only lectures but also practices according to problem-based learning as well as team-based learning in the curriculum to achieve the target outcome.
4.Simeprevir-Based Triple Therapy with Reduced Doses of Pegylated Interferon α-2a Plus Ribavirin for Interferon Ineligible Patients with Genotype 1b Hepatitis C Virus.
Hideyuki TAMAI ; Yoshiyuki IDA ; Akira KAWASHIMA ; Naoki SHINGAKI ; Ryo SHIMIZU ; Kosaku MORIBATA ; Tetsushi NASU ; Takao MAEKITA ; Mikitaka IGUCHI ; Jun KATO ; Taisei NAKAO ; Masayuki KITANO
Gut and Liver 2017;11(4):551-558
BACKGROUND/AIMS: The present study aimed to evaluate the safety and efficacy of simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG-IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly and/or cirrhotic patients, and to elucidate the factors contributing to a sustained virologic response (SVR). METHODS: One hundred IFN ineligible patients infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100 mg) was given orally together with reduced doses of PEG-IFN-α 2a (90 μg), and ribavirin (200 mg less than the recommended dose). RESULTS: The patients’ median age was 70 years, and 70 patients were cirrhotic. Three patients (3%) discontinued treatment due to adverse events. The SVR rate was 64%. Factors that significantly contributed to the SVR included the γ-glutamyl transferase and α-fetoprotein levels, interleukin-28B (IL28B) polymorphism status, and the level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed that the IL28B polymorphism status was the only independent factor that predicted the SVR, with a positive predictive value of 77%. CONCLUSIONS: Simeprevir-based triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism status was a useful predictor of the SVR.
Aged
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Genotype*
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Hepacivirus*
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Hepatitis C*
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Hepatitis*
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Humans
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Interferons*
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Multivariate Analysis
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Ribavirin*
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RNA
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Simeprevir
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Transferases
5.Current Situation of Taeniasis and Cysticercosis in Indonesia
Toni Wandra ; Sri S. Margono ; Made S. Gafar ; John M Saragih ; Putu Sutisna ; A.A. Raka Sudewi ; A.A. Depary ; Hemma Yulfi ; Dewi Masyithah Darla ; Munehiro Okamoto ; Marcello Otake Sato ; Yasuhito Sako ; Minoru Nakao ; Kazuhiro Nakaya ; Philip S. Craig ; Akira Ito
Tropical Medicine and Health 2007;35(4):323-328
Three human taeniid species, Taenia solium, Taenia saginata and Taenia asiatica are distributed in Indonesia. A field survey conducted in Bali from 2002 to 2006 showed that the prevalence of taeniasis was highly variable among four districts (1.1-27.5%), and only two cysticercosis cases due to T. solium infection were detected. All tapeworms (n = 66) expelled from 66 tapeworm carriers were confirmed to be T. saginata by mitochondrial DNA analysis. A total prevalence of 13.0% (19⁄146) for T. solium taeniasis was found in Jayawijaya District, Papua (Irian Jaya). It included 14 of 88 (15.9%) in 1999 and 5 of 58 (8.6%) in 2001, while the seroprevalence of cysticercosis in humans by sub-district in Papua ranged from 0.0% in a non-endemic area to 48.5% in an endemic area from 1996 to 2005. The seroprevalence of cysticercosis in pigs and dogs in Jayawijaya ranged from 8.5% to 70.4% (1998-1999) and 4.9% to 33.3% (2000-2002), respectively. A 2003-2006 survey of 371 local people in Samosir island, north Sumatra revealed 6 of 240 (2.5%) to be infected with T. asiatica; 2 of 58 (3.4%) and 4 of 182 (2.2%) cases were detected in 2003 and 2005, respectively. This brief review summarizes the present situation of taeniasis and cysticercosis, the distribution of three human taeniid species, and the risk factors⁄transmission aspects of these tapeworm infections in Bali, Papua, and north Sumatra regions of Indonesia.
6.The Real-World Safety and Efficacy of Daclatasvir and Asunaprevir for Elderly Patients
Shinya TAKI ; Hideyuki TAMAI ; Yoshiyuki IDA ; Naoki SHINGAKI ; Akira KAWASHIMA ; Ryo SHIMIZU ; Kosaku MORIBATA ; Takao MAEKITA ; Mikitaka IGUCHI ; Jun KATO ; Taisei NAKAO ; Masayuki KITANO
Gut and Liver 2018;12(1):86-93
BACKGROUND/AIMS: Although daclatasvir with asunaprevir was approved in Japan for interferon ineligible or intolerant patients, patients aged ≥75 years were excluded in the phase III trial. The present study aimed to evaluate the safety and efficacy of this therapy for elderly patients aged ≥75 years and to clarify whether an extremely high sustained virological response (SVR) rate can be achieved, even in a real-world setting when patients with resistance-associated substitutions (RASs) to nonstructural protein 5A (NS5A) inhibitors or prior simeprevir failure are excluded. METHODS: Daclatasvir (60 mg) and asunaprevir (100 mg) were orally administered daily for 24 weeks. Patients without pre-existing NS5A RASs and simeprevir failure were enrolled in this study. RESULTS: Overall, 110 patients were treated. The median age was 73 years old. The SVR rates of total patients, those aged ≥75 years, and those aged < 75 years were 97% (107/110), 98% (46/47), and 97% (61/63), respectively. The treatment of two patients (2%) was discontinued because of adverse events. CONCLUSIONS: Daclatasvir with asunaprevir was a safe treatment, even in patients aged ≥75 years. When patients without pre-existing NS5A RASs and prior simeprevir failure were selected, an extremely high SVR rate could be achieved irrespective of age.
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Hepacivirus
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Humans
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Interferons
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Japan
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Simeprevir
7.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
8.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
9.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.