Publications by authors named "Masahiko Nakayama"

16 Publications

  • Page 1 of 1

A case of coronary artery fistula with multiple coronary artery aneurysms diagnosed by transthoracic echocardiography.

J Med Ultrason (2001) 2020 10 23;47(4):641-642. Epub 2020 Jun 23.

Department of Clinical Laboratory, Gunma University Hospital, Maebashi, Gunma, Japan.

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http://dx.doi.org/10.1007/s10396-020-01032-8DOI Listing
October 2020

Shared Decision-Making in Patients With Prostate Cancer in Japan: Patient Preferences Versus Physician Perceptions.

J Glob Oncol 2018 09 13;4:1-9. Epub 2017 Apr 13.

Ulrike Schaede, University of California at San Diego, San Diego, CA; Jörg Mahlich, Janssen Pharmaceutical K.K., Tokyo, Japan, and University of Düsseldorf, Düsseldorf, Germany; Masahiko Nakayama, Hisanori Kobayashi, and Kazutake Yoshizawa, Janssen Pharmaceutical K.K.; Yuriko Takahashi and Katsuhiko Saito, Anterio, Tokyo; Hiroji Uemura, Yokohama City University, Medical Center, Yokohama; and Masayuki Tokumitsu, Kitasaito Hospital, Ashikawa, Japan.

This article adds the Japanese perspective to our knowledge of shared decision-making (SDM) preferences by surveying patients with prostate cancer (PCA) and physicians in Japan. In 2015, 103 Japanese patients with PCA were asked about their SDM preferences by using an Internet-based 5-point-scale questionnaire. Concurrently, 127 Japanese physicians were surveyed regarding their perceptions of patient preferences on SDM. Drivers of preferences and perceptions were analyzed using univariable ordinal logistic regression and graphing the fitted response probabilities. Although 41% of both patients and physicians expressed and expected a desire for active involvement in treatment decisions (a higher rate than in a similar study for the United States in 2001), almost half the Japanese patients preferred SDM, but only 33% of physicians assumed this was their choice. That is, 29% of Japanese physicians underestimated patients' preference for involvement in making treatment decisions. Patients with lower health-related quality of life (as measured by the Functional Assessment of Cancer Therapy-Prostate [FACT-P]) expressed a stronger preference for SDM. The study shows that the worse the medical situation, the more patients with PCA prefer to be involved in the treatment decision, yet physicians tend to underestimate the preferences of their patients. Perhaps in contrast to common assumptions, Japanese patients are as interested in being involved in decision making as are patients in the United States.
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http://dx.doi.org/10.1200/JGO.2016.008045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180796PMC
September 2018

Extent of intraluminal exfoliated malignant cells during surgery for colon cancer: Differences in cell abundance ratio between laparoscopic and open surgery.

Asian J Endosc Surg 2019 Apr 11;12(2):145-149. Epub 2018 Jul 11.

Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Introduction: Laparoscopic colectomy with intracorporeal anastomosis is a minimally invasive surgical procedure for patients with colon cancer. However, there are often concerns about the presence of intraluminal exfoliated malignant cells in the intracorporeal anastomosis. This study investigated the relationship between colon cancer surgery and the incidence of intraluminal exfoliated malignant cells and several factors.

Methods: Eighty-nine consecutive patients who underwent either laparoscopic or open colectomy were prospectively studied in our department between 2007 and 2011. Before anastomosis, the proximal and distal lumens were irrigated with normal saline and subjected to cytological examination.

Results: In 27 patients (30.3%), exfoliated cancer cells were detected. On the distal side, the frequency of positive cytology findings of exfoliated malignant cells was significantly lower in the laparoscopic colectomy group than in the open colectomy group (P = 0.01). In the laparoscopic colectomy group, there were no cases of positive cytology findings for exfoliated malignant cells more than 100 mm from the primary tumor. The incidence of positive cytology more than 100 mm from the primary tumor was significantly lower than the incidence of positive cytology less than 100 mm from the primary tumor (P = 0.04).

Conclusions: Exfoliated malignant cells were detected at anastomosis sites in patients with colon cancer. On the distal side, laparoscopic colectomy may prevent the development of exfoliated malignant cells.
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http://dx.doi.org/10.1111/ases.12617DOI Listing
April 2019

Patient Preferences and Urologist Judgments on Prostate Cancer Therapy in Japan.

Am J Mens Health 2018 07 18;12(4):1094-1101. Epub 2018 May 18.

3 Health Economics Division, Janssen Pharmaceutical K.K., Tokyo, Japan.

The purpose of the present study is to investigate the concordance of treatment preferences between patients and physicians in prostate cancer (PCa) in Japan. An internet-based discrete choice experiment was conducted. Patients and physicians were asked to select their preferred treatment from a pair of hypothetical treatments consisting of four attributes: quality of life (QOL), treatment effectiveness, side effects, and accessibility of treatment. The data were analyzed using a conditional logistic regression model to calculate coefficients and the relative importance (RI) of each attribute. A total of 103 PCa patients and 127 physicians responded. The study looked at 37 patients considered as advanced PCa and 66 who were non-advanced PCa. All of the physicians were urologists. Advanced PCa patients ranked the attributes as follows: treatment effectiveness (RI: 32%), accessibility of treatment (RI: 26%), QOL (RI: 23%), and side effects (RI: 19%). For physicians, the RI ranking was the same as for advanced PCa patients; treatment effectiveness (RI: 29%), accessibility of treatment (RI: 27%), QOL (RI: 26%), and side effects (RI: 18%). For non-advanced PCa patients, accessibility of treatment ranked the highest RI (27%) and treatment effectiveness ranked as the lowest RI (14%). Our study suggests that the ranking of the attributes was consistent between advanced PCa patients and physicians. The most influential attribute was treatment effectiveness. Treatment preferences also vary by disease stage.
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http://dx.doi.org/10.1177/1557988318776123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131454PMC
July 2018

Treatment pathways of Japanese prostate cancer patients - A retrospective transition analysis with administrative data.

PLoS One 2018 25;13(4):e0195789. Epub 2018 Apr 25.

Janssen KK, Health Economics, Tokyo, Japan.

Background: Limited availability of real-world data that describe treatment patterns of Japanese prostate cancer (PCA) patients.

Methods: A biweekly transition analysis of PCA treatment was performed for patients with PCA diagnosis and a specific treatment between 2010 and 2015. To account for different cancer stages, two patient populations were analyzed. The first group consisted of patients on medication for hormone-sensitive prostate cancer (HSPC). The second group is comprised of patients who ended up receiving specific therapy for castration-resistant prostate cancer (CRPC). For each treatment, the average of treatment duration and the portion of patients transitioning to a consecutive treatment was calculated.

Results: We identified 59,626 patients from the Japanese administrative database with a PCA diagnosis and specific treatment. In the first year of our observational study 786 patients commenced a HSPC treatment and 695 received a CRPC specific therapy Among the HSPC group, we found that combination hormonal therapy, comprised of a gonadotrophin releasing hormone agonist or antagonist with an antiandrogen was more common than monotherapy. The results of the CRPC group indicated that chemotherapy administration was for a shorter time period in a real-world setting as compared to published clinical studies.

Conclusion: Utilizing a novel method to visualize real-world treatment pathways for PCA patients we found that real treatment pathways are in line with international guidelines.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195789PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919000PMC
July 2018

Predictive factors for major postoperative complications related to gastric conduit reconstruction in thoracoscopic esophagectomy for esophageal cancer: a case control study.

BMC Surg 2018 Mar 6;18(1):15. Epub 2018 Mar 6.

Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 8528102, Japan.

Background: Regardless of developments in thoracoscopic esophagectomy (TE), postoperative complications relative to gastric conduit reconstruction are common after esophagectomy. The aim of the present study was to evaluate the predictive factors of major complications related to gastric conduit after TE.

Methods: From 2006 to 2015, 75 patients with esophageal cancer who underwent TE were evaluated to explore the predictive factors of major postoperative complications related to gastric conduit.

Results: Patients with major complications related to gastric conduit had a significantly longer postoperative hospital stay than patients without these complications (P <  0.01). Multivariate analysis demonstrated that three-field lymph node dissection (3FLND) and high serum levels of creatine phosphokinase (CPK) and C-reactive protein (CRP) at 1 postoperative day (1POD) after TE were significant predictive factors of major complications related to gastric conduit [odds ratio (OR) 5.37, 95% confidence interval (CI) 1.41-24.33, P = 0.02; OR 5.40, 95% CI 1.60-20.20, P <  0.01; OR 5.07, 95% CI 1.47-20.25, P = 0.01, respectively]. The incidence rates of major complications related to gastric conduit for 0, 1, 2, and 3 predictive factors were 5.3%, 18.8%, 58.8%, and 85.7%, respectively (P <  0.01).

Conclusions: Two or more factors in 3FLND and the high levels of CPK and CRP at 1POD after TE were identified as the risk model for major complications related to gastric conduit after TE.

Trial Registration: UMIN Clinical Trials Registry, ID: UMIN000024436 , Registered date: Oct/17/2016.
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http://dx.doi.org/10.1186/s12893-018-0348-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838941PMC
March 2018

Hematologists' Preferences for First-line Therapy Characteristics for Multiple Myeloma in Japan: Attribute Rating and Discrete Choice Experiment.

Clin Ther 2018 02 1;40(2):296-308.e2. Epub 2018 Feb 1.

Medical Affairs, Janssen KK, Tokyo, Japan.

Purpose: With the progress being made in the treatment of multiple myeloma and other complex cancers, a variety of clinical research and treatment options are being pursued. This study uses a discrete choice experiment (DCE) to estimate treatment characteristic preferences of hematologists in Japan.

Methods: A 2-stage process was applied within this study. The first stage is an attribute-rating exercise in which each of the full list of 21 attributes is rated on its importance by the clinicians when selecting a first-line therapy. The top 8 rated attributes from a stepwise logistic regression model are then used to develop a DCE to estimate hematologists' willingness to trade-off characteristics of the treatment options in their recommendation of a first-line treatment. A logit model was used to identify the attribute levels that were the strongest determinants of the physicians' treatment preferences.

Findings: From among the potential treatment attributes presented, improved overall survival had the most significant impact on the treatment choice of participating Japanese hematologists. Improvement in the ability to promptly reduce M-protein is also a highly prioritized treatment characteristic, with hematologists willing to sacrifice just over 1 month extra overall survival for this. Additionally, the hematologists' value improved suitability for chromosomal abnormalities with poor prognosis, suitability of the mechanism of action in initial treatment, and promptly improving calcium-renal-anemia-bone symptoms each at roughly 0.9 months extended overall survival. The reduction of adverse events is among the other significant factors in choice of treatment, though it was not found to be as strong a determinant as those mentioned.

Implications: This study reinforces the expectation that clinical research and treatment options should continue to focus on overall survival and are key priorities in multiple myeloma treatment development. However, clinicians are willing to consider and trade off other clinical factors and markers in their choice of treatment. The potential improvements presented were also found to have a greater impact on treatment choice than aversion to the potential worse outcomes presented.
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http://dx.doi.org/10.1016/j.clinthera.2017.12.012DOI Listing
February 2018

A comparison of overall survival with 40 and 50mg/m pegylated liposomal doxorubicin treatment in patients with recurrent epithelial ovarian cancer: Propensity score-matched analysis of real-world data.

Gynecol Oncol 2016 Nov 6;143(2):246-251. Epub 2016 Sep 6.

Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo 101-0065, Japan. Electronic address:

Background: In clinical practice, 40mg/m of pegylated liposomal doxorubicin (PLD40) has been used as an initial dosage for treating recurrent epithelial ovarian cancer (OC) instead of the recommended dose of 50mg/m (PLD50). However, no robust evidence is available to support the use of PLD40. This post-hoc study aimed to compare the efficacy and safety of initial PLD dosages in propensity score (P-score)-matched dataset.

Methods: The data source was a PLD postmarketing surveillance dataset (n=2189) conducted in Japan. Eligibility criteria for the present study were as follows: recurrent OC, history of chemotherapy, and treatment with PLD monotherapy at a dosage between 35.5 and 54.4mg/m. Overall survival (OS) was compared between PLD50- and PLD40-treated groups using the log-rank test. Incidences of palmar-plantar erythrodysesthesia (PPE) and stomatitis were also compared between the groups.

Results: Overall, 503 matched pairs were generated using P-score analysis. The median survival time with PLD50 and PLD40 was 383 and 350days, respectively, with a hazard ratio of 1.10 (95% confidence interval, 0.98-1.26; p=0.211), although the difference was not statistically significant in the P-score-matched dataset. However, the incidence and severity of PPE and stomatitis were significantly lower with PLD40.

Conclusions: Our study showed that the efficacy of PLD did not differ based on initial dosages, but the risk of adverse events was reduced with PLD40. Considering the balance between patient benefits and risks, our results support the use of PLD40 in clinical practice.
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http://dx.doi.org/10.1016/j.ygyno.2016.08.331DOI Listing
November 2016

Association of early PSA decline and time to PSA progression in abiraterone acetate-treated metastatic castration-resistant prostate cancer; a post-hoc analysis of Japanese phase 2 trials.

BMC Urol 2016 Jun 8;16(1):27. Epub 2016 Jun 8.

Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan.

Background: Previous studies have demonstrated an association between prostate-specific antigen (PSA) kinetics and predictive value for treatment outcomes. Abiraterone acetate (AA) is a newly approved cytochrome-P450C17 inhibitor for treatment of metastatic castration-resistant prostate cancer (mCRPC), and few studies have evaluated PSA kinetics using AA so far. Results of a study evaluating PSA kinetics in the beginning of AA and enzalutamide responded chemotherapy-treated patients suggested different trends between the drugs. PSA kinetics of AA-treated patients has been reported using large datasets; however, no studies which have fully evaluated PSA kinetics in the beginning treatment. The present study aimed to assess the PSA kinetics and relationship between the PSA kinetics and PSA progression in chemotherapy-naïve and chemotherapy-treated mCRPC patients receiving AA.

Methods: We used two Japanese phase II trial datasets: JPN-201, chemotherapy-naïve mCRPC (n = 48) and JPN-202, chemotherapy-treated mCRPC (n = 46). PSA kinetic parameters were calculated using actual PSA values measured every 4 weeks, and a subgroup analysis was performed to evaluate the influence of early PSA response on time to PSA progression (TTPP). In addition, we used a Cox proportional hazard model to investigate the influence of variables on TTPP.

Results: PSA declined from week 4 but took more time to achieve nadir. PSA kinetic parameters were different between the datasets, mean time to PSA nadir was 5.3 ± 5.6 and 2.0 ± 3.4 months, and TTPP was 9.5 ± 7.4 and 3.8 ± 4.8 months in JPN-201 and JPN-202, respectively. In the subgroup analysis of week 4 PSA decline status, Kaplan-Meier curves for TTPP were similar between early responders and non-progression patients in JPN-201 (median, 9.2 vs. 6.5 months, respectively) but separated in JPN-202 (median, 3.7 vs. 1.9 months, respectively). According to univariate Cox regression analysis, achievement of PSA response (≥50 %) at week 12 was associated with TTPP in the both trials, but the hazard ratio of PSA decline (≥30 %) at week 4 was not significant in JPN-201.

Conclusions: Our results suggest that PSA kinetics were not comparable and early PSA response showed different association to TTPP according to prior history of chemotherapy.

Trial Registration: The original trials are registered at ClinicalTrials.gov. The identifiers are; JNJ-212082-JPN-201 , registered 20 December 2012 and JNJ-212082-JPN-202 , registered 30January 2013.
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http://dx.doi.org/10.1186/s12894-016-0148-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898460PMC
June 2016

Predictive factors for 24 weeks sustained virologic response (SVR24) and viral relapse in patients treated with simeprevir plus peginterferon and ribavirin.

Hepatol Int 2016 Jan 12;10(1):158-68. Epub 2015 Aug 12.

Medical Affairs Division, Janssen Pharmaceutical K.K., 5-2, Nishi-kanda, 3-Chome, Chiyoda-ku, Tokyo, 101-0065, Japan.

Background: Simeprevir with peginterferon and ribavirin has been used for the treatment of chronic hepatitis caused by genotype 1 hepatitis C virus (HCV). We explored the predictive factors for sustained virological response (SVR) and viral relapse using datasets from four Japanese phase 3 studies (CONCERTO).

Methods: We used a multiple logistic regression model. First, an integrated dataset comprising 357 patients was analyzed. Subsequently, prior treatment-naïve and relapser (223 patients) and nonresponder (134 patients) of interferon-based treatment subsets were analyzed to identify predictors of SVR. A subset of nonresponders (106 patients) who were treated ≥24 weeks was also analyzed to identify predictors for viral relapse.

Results: In the integrated dataset, prior treatment response was significantly associated with SVR. In subset analyses, interleukin-28B (IL28B) TT genotype and undetectable plasma HCV RNA level at week 4 were associated in treatment-naïve patients and relapsers [odds ratio (OR); 4.106 and 3.701, respectively]. In the nonresponders, the IL28B TT genotype population was very small, and inosine triphosphatase (ITPA) and undetectable plasma HCV RNA at week 4 were associated (OR; 2.506 and 3.333, respectively). Furthermore, ribavirin dose intensity (RBV-DI) and detectable plasma HCV RNA at week 4 were significantly associated with viral relapse (OR; 0.327 and 2.922, respectively).

Conclusion: IL28B and plasma HCV RNA level at week 4 were clinically relevant predictive factors for SVR in treatment-naïve patients and relapsers. Moreover, RBV-DI and plasma HCV level at week 4 were identified as relevant predictive factors for viral relapse in nonresponders.
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http://dx.doi.org/10.1007/s12072-015-9654-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722076PMC
January 2016

Similar metabolic responses to calorie restriction in lean and obese Zucker rats.

Mol Cell Endocrinol 2009 Oct 14;309(1-2):17-25. Epub 2009 May 14.

Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

Calorie restriction (CR), which is thought to be largely dependent on the neuroendocrine system modulated by insulin/insulin-like growth factor-I (IGF-I) and leptin signaling, decreases morbidity and increases lifespan in many organisms. To elucidate whether insulin and leptin sensitivities are indispensable in the metabolic adaptation to CR, we investigated the effects of CR on obese Zucker (fa/fa) rats and lean control (+/+) rats. CR did not fully improve insulin resistance in (fa/fa) rats. Nonetheless, CR induced neuropeptide Y (NPY) expression in the hypothalamic arcuate nucleus and metabolism related gene expression changes in the liver in (fa/fa) rats and (+/+) rats. Up-regulation of NPY augmented plasma corticosterone levels and suppressed pituitary growth hormone (GH) expression, thereby modulating adipocytokine production to induce tissue-specific insulin sensitivity. Thus, central NPY activation via peripheral signaling might play a crucial role in the effects of CR, even in insulin resistant and leptin receptor deficient conditions.
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http://dx.doi.org/10.1016/j.mce.2009.05.001DOI Listing
October 2009

Pituitary growth hormone suppression reduces resistin expression and enhances insulin effectiveness: relationship with caloric restriction.

Exp Gerontol 2008 Jun 20;43(6):595-600. Epub 2008 Mar 20.

Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki 852-8523, Japan.

Caloric restriction (CR) retards various age-dependent disorders, increases lifespan, and improves insulin activity in laboratory animals. Recently, adipocytes were found to act together as an active endocrine organ that produces various hormones called adipocytokines. The peripheral and central activities of these adipocytokines have been suggested to mediate the anti-aging effects of CR. Here, we tested this notion by analyzing the effect of CR and suppression of growth hormone/insulin-like growth factor-I (GH/IGF-I) axis on the expression of resistin, adiponectin, and adipsin genes by rat white adipose tissue (WAT). We found that CR and GH/IGF-I suppression markedly downregulated resistin gene expression. We also found plasma resistin levels correlated positively with pituitary GH mRNA expression levels. Our observations suggest that CR reduces resistin expression and increases insulin effectiveness in a GH/IGF-I-dependent manner. The beneficial effects of CR and GH/IGF-I suppression appear to be mediated, at least in part, by changes in glucose metabolism that result from reductions in plasma resistin levels.
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http://dx.doi.org/10.1016/j.exger.2008.03.003DOI Listing
June 2008

Treatment of neurodegenerative CNS disease in Langerhans cell histiocytosis with a combination of intravenous immunoglobulin and chemotherapy.

Pediatr Blood Cancer 2008 Feb;50(2):308-11

Division of Pediatrics, Takasago-seibu Hospital, Takasago, Japan.

Background: In rare cases, patients with Langerhans cell histiocytosis (LCH) develop neurodegenerative CNS disease (ND-CNS-LCH). Management of ND-CNS-LCH has not been established.

Methods: We treated five pediatric patients with a combination of intravenous immunoglobulin (IVIG) and chemotherapy (steroid +/- vinblastine +/- 6-mercaptopurine +/- methotrexate). Prior to the therapy, three of the five patients had cerebellar ataxia while the remaining two had abnormal MRI findings without apparent neurological deficits. IVIG was given monthly or twice monthly at the dosage of 250-400 mg/kg/dose.

Results: The four patients administered more than 23 doses of IVIG and chemotherapy remained in a stable condition and did not show significant progression signs in neurological deficits or brain MRI findings during the 30-month follow-up period (median; range: 19+ to 38+) following the initiation of therapy for ND-CNS-LCH.

Conclusion: The IVIG-containing treatment may be promising for ND-CNS-LCH; however, its effectiveness remains to be further tested in more patients as well as in a randomized trial.
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http://dx.doi.org/10.1002/pbc.21259DOI Listing
February 2008

A case with tracheo-innominate artery fistula. Successful management of endovascular embolization of innominate artery.

Auris Nasus Larynx 2005 Jun;32(2):195-8

Department of Otolaryngology, Sasebo City General Hospital, Sasebo, Japan.

Tracheo-innominate artery fistula (TIF) is known as a fatal complication after tracheostomy. We report a 9-year-old girl with early hypoxic encephalopathy who had a tracheo-innominate artery fistula with exsanguinating hemorrhage from her tracheostoma 10 months after tracheostomy. After temporary control of bleeding, embolization of the innominate artery was performed. The patient has remained well 1 year after the procedure. We reviewed the aetiology, diagnosis and management of the tracheo-innominate fistula, and findings suggest that endovascular embolization of the innominate artery may be an appropriate treatment for patients with tracheo-innominate artery fistula.
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http://dx.doi.org/10.1016/j.anl.2004.11.002DOI Listing
June 2005

[A case of brain metastasis of small cell lung cancer improved with nogitecan hydrochloride (topotecan) after prophylactic irradiation].

Gan To Kagaku Ryoho 2004 Jul;31(7):1071-3

Dept. of Respiratory Medicine, Kyoto First Red Cross Hospital.

A 55-year old woman was treated with chemoradiotherapy for limited type small cell lung cancer. She was then treated with prophylactic cranial irradiation. However, local recurrence and metastatic brain tumors were detected after a year. Three courses of chemotherapy with nogitecan (topotecan) ameliorated the size and numbers of the tumors pronouncedly. Nogitecan (topotecan) is suggested to be an effective therapeutic agent for brain metastasis of small cell lung cancer after prophylactic cranial irradiation.
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July 2004

Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan.

Br J Haematol 2003 May;121(3):503-10

Department of Paediatrics, and Department of Clinical Laboratory and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Perforin gene (PRF1) mutations appear to occur in about 30% of patients with haemophagocytic lymphohistiocytosis (HLH). We tested perforin expression and gene mutations in 14 HLH patients and six patients with Epstein-Barr virus-associated HLH (EBV-HLH) in Japan. Five of the 14 HLH patients had perforin abnormalities. The presence of PRF1 genetic abnormality correlated well with the lack of perforin expression as determined by flow cytometry. Sequencing showed that four patients had a compound heterozygous mutation while the fifth patient had a homozygous mutation. Three of the mutations we detected were novel. In contrast, none of the six EBV-HLH patients showed perforin abnormalities. Our data, combined with the PRF1 mutations in three previously reported Japanese patients, suggest that the 1090-1091delCT and 207delC mutations of the perforin gene are frequently present in Japanese HLH patients (62.5% and 37.5% respectively). Examination of the geographical origins of the ancestors in the perforin-mutant HLH patients revealed that they mostly came from the Western part of Japan, suggesting that the present-day cases may largely derive from a common ancestor.
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http://dx.doi.org/10.1046/j.1365-2141.2003.04298.xDOI Listing
May 2003
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