研究等業績 - 原著論文 - 羽渕 友則
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[Primary retroperitoneal carcinoid tumor associated with multiple endcrine neoplasia (men) type 1: a case report].
Syuji Chiba, Kazuyuki Numakura, Kiyofumi Satoyoshi, Mitsuru Saito, Yohei Horikawa, Koichiro Takayama, Taketoshi Nara, Sohei Kanda, Yoshiko Miura, Shinya Maita, Hiroshi Tsuruta, Takashi Obara, Teruaki Kumazawa, Shintaro Narita, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi
Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 102 ( 6 ) 735 - 9 2011年11月
研究論文（学術雑誌）
We report an extremely rare case of a 69-year-old man having a retroperitoneal carcinoid tumor associated with multiple endocrine neoplasia (MEN) type 1. The patient whose son and daughter were previously diagnosed with MEN type 1 was admitted to the Department of Endocrinology at our hospital for evaluation of this disorder. Computed tomography (CT) and ultrasonography revealed a parathyroid and retroperitoneal tumor (43 mm x 34 mm). The patient did not consent to surgical management of the tumor; however three years later, a follow-up CT revealed tumor enlargement (55 mm x 50 mm). We were unable to rule out a malignancy, and subsequently resected the tumor. A pathological diagnosis of retroperitoneal carcinoid was made. No local recurrence or metastasis have been observed for 21 months.
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Overexpression of Fn14 promotes androgen-independent prostate cancer progression through MMP-9 and correlates with poor treatment outcome.
Mingguo Huang, Shintaro Narita, Norihiko Tsuchiya, Zhiyong Ma, Kazuyuki Numakura, Takashi Obara, Hiroshi Tsuruta, Mitsuru Saito, Takamitsu Inoue, Yohei Horikawa, Shigeru Satoh, Tomonori Habuchi
Carcinogenesis 32 ( 11 ) 1589 - 96 2011年11月
研究論文（学術雑誌）
Fibroblast growth factor-inducible 14 (Fn14), a transmembrane receptor binding to the multifunctional cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is known to modulate many cellular activities including cancer progression. Here, we demonstrated the significant role of Fn14 in invasion, migration and proliferation of androgen-independent prostate cancer (AIPC) cells. Fn14 and its ligand TWEAK were highly expressed in two AIPC cell lines, DU 145 and PC-3, whereas expression was weak in androgen-sensitive LNCaP cells. Fn14 knockdown using small-interfering RNAs attenuated migration, invasion and proliferation and enhanced apoptosis in the AIPC cell lines. Both forced overexpression of Fn14 by stable Fn14 complementary DNA transfection to PC-3 cells (PC-3/Fn14) and ligand activation by recombinant TWEAK in PC-3 cells enhanced invasion. Fn14 was shown to modulate expression of matrix metalloproteinase (MMP)-9, and MMP-9 mediated the invasive potential influenced by Fn14 in PC-3 cells. In vivo, subcutaneous xenografts of PC-3/Fn14 grew significantly faster than xenograft of PC-3/Mock, and the invasive capacity in PC-3/Fn14 was found to be higher than that of PC-3/Mock as evaluated in an invasion model of the diaphragm. Furthermore, the messenger RNA expressions of MMP-9 in PC-3/Fn14 xenografts were significantly higher than those in PC-3/Mock xenografts. Clinically, high expression of Fn14 was significantly associated with higher prostate-specific antigen recurrence rate in patients who underwent radical prostatectomy. In conclusion, the overexpression of Fn14 may contribute to multiple malignant cellular phenotypes associated with prostate cancer (PCa) progression, in part via MMP-9. TWEAK-Fn14 signaling may be a novel therapeutic target of PCa.
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The clinical research office of the endourological society audit committee.
Glenn M Preminger, Peter Alken, Tomonori Habuchi, Hessel Wijkstra, Andreas Skolarikos, Chan-Jun Yin
Journal of endourology 25 ( 11 ) 1811 - 3 2011年11月
研究論文（学術雑誌）
The Clinical Research Office of the Endourological Society (CROES) conducts large-scale, international, multicenter clinical trials in the field of endourology. One of the major challenges that these trials pose is to ensure that data collected remotely and online within a very short time frame are valid and reliable. This editorial describes a formal process for auditing the data by the CROES Audit Committee. The audit process presented is largely based on an automatic scoring system, which takes into consideration several parameters to determine the quality of the data and of the participating institution. This process is dynamic in nature and offers live monitoring of both patient data and study centers.
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A case study of metastatic Xp11.2 translocation renal cell carcinoma effectively treated with sunitinib.
Kazuyuki Numakura, Norihiko Tsuchiya, Takeshi Yuasa, Mitsuru Saito, Takashi Obara, Hiroshi Tsuruta, Shintaro Narita, Yohei Horikawa, Shigeru Satoh, Tomonori Habuchi
International journal of clinical oncology 16 ( 5 ) 577 - 80 2011年10月
研究論文（学術雑誌）
We report a case of Xp11.2 translocation renal cell carcinoma (RCC) whose lung metastases were effectively treated with sunitinib. A 43-year-old woman presenting with upper abdominal pain was diagnosed with a left renal tumor. Laparoscopic left radical nephrectomy was performed. Histopathological examination of the surgical specimen revealed a clear-cell carcinoma of the left kidney. Two years later, multiple lung metastases were detected and the patient was treated daily with 50 mg sunitinib. A computed tomography scan performed after 2 cycles of sunitinib treatment revealed partial regression of these metastases. The partial regression has been maintained for >3 years. In retrospective evaluation of the primary RCC, tumor cells showed strong nuclear staining for transcription factor E3 (TFE3) protein and TFE3 split-fluorescence in-situ hybridization revealed translocation involving the TFE3 gene. These findings strongly support diagnosis of Xp11.2 translocation RCC.
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Combination therapy consisting of gemcitabine, carboplatin, and docetaxel as an active treatment for advanced urothelial carcinoma.
Hiroshi Tsuruta, Takamitsu Inoue, Shintaro Narita, Yohei Horikawa, Mitsuru Saito, Takashi Obara, Kazuyuki Numakura, Shinya Maita, Shigeru Satoh, Norihiko Tsuchiya, Tomonori Habuchi
International journal of clinical oncology 16 ( 5 ) 533 - 8 2011年10月
研究論文（学術雑誌）
BACKGROUND: To evaluate the efficacy and toxicity of a combination chemotherapy consisting of gemcitabine, carboplatin, and docetaxel (GCD) in patients with advanced urothelial carcinoma (UC) as a phase II trial. MATERIALS AND METHODS: Patients with metastatic or locally advanced unresectable UC were eligible for this trial. All enrolled patients were considered to be "unfit" for cisplatin-based chemotherapy, or to have methotrexate, vinblastine, doxorubicin, cisplatin (MVAC)-refractory UC. The chemotherapy regimen consisted of gemcitabine 1000 mg/m(2) on days 1 and 8, and carboplatin (with a target area under the curve of 5) and docetaxel 70 mg/m(2) on day 1; this was repeated every 21 days. RESULTS: Thirty-five patients were enrolled, with a median age of 68 years. A total of 89 cycles were administered (median, 2 cycles). Major toxicities were Grade 3/4 neutropenia in 28 (80.0%) patients and Grade 3/4 thrombocytopenia in 18 (51.5%). An objective response rate (ORR) was 11 of 21 patients (52.4%), including a complete response in 1 (4.8%). The median overall survival (OS) was 13.1 months (1-year survival rate, 60%) and the median progression-free survival (PFS) was 5.0 months. Among 16 patients who had previously received MVAC, the ORR, the median PFS, the median OS and 1-year survival rate was 56.3%, 5.0 months, 12.6 months and 54%, respectively. CONCLUSIONS: GCD chemotherapy is active and well tolerated as a first- or second-line therapy for patients with advanced UC. Response rate, duration and survival did not differ between those with and without a history of MVAC treatment.
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Two survivin polymorphisms are cooperatively associated with bladder cancer susceptibility.
Naoko Kawata, Norihiko Tsuchiya, Yohei Horikawa, Takamitsu Inoue, Hiroshi Tsuruta, Shinya Maita, Shigeru Satoh, Yoko Mitobe, Shintaro Narita, Tomonori Habuchi
International journal of cancer 129 ( 8 ) 1872 - 80 2011年10月
研究論文（学術雑誌）
Abnormal survivin expression has been reported to be involved in many types of cancer. A single-nucleotide polymorphism (SNP), C-31G, located in the promoter region of survivin reportedly may alter the mRNA level, while the significance of the nonsynonymous SNP A9194G in exon 4 has not yet been clarified. Here, the association between the two survivin SNPs and bladder cancer susceptibility and progression was investigated in 235 patients with bladder cancer and 346 healthy controls. Regarding the C-31G SNP, subjects with the CC genotype had a significantly higher risk of bladder cancer compared to those with the GG + CG genotype [odds ratio (OR) = 1.85, p = 0.001]. Regarding the A9194G SNP, the presence of the G allele was associated with a significantly reduced risk with a gene dosage effect (OR = 0.69, p = 0.002). Using the C-A haplotype as a reference, the G-G haplotype was associated with a significantly lower risk (OR = 0.11, p = 0.00006), indicating the cooperative effect of the two SNPs. Immunohistological evaluation of surgical specimens showed that cancer cells of the C-31G CC genotype had significantly higher nuclear survivin expression than those of the C-31G GG + CG genotype. With reverse transcriptase-polymerase chain reaction analysis, a significantly higher survivin mRNA expression level was observed in surgical specimens with an increase in the number of the C-31G C allele (p = 0.016). These results indicate that the two SNPs have a significant and cooperative influence on bladder cancer susceptibility.
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Correlations between pretransplant dialysis duration, bladder capacity, and prevalence of vesicoureteral reflux to the graft.
Takamitsu Inoue, Shigeru Satoh, Mitsuru Saito, Kazuyuki Numakura, Hiroshi Tsuruta, Takashi Obara, Shintaro Narita, Yohei Horikawa, Norihiko Tsuchiya, Tomonori Habuchi
Transplantation 92 ( 3 ) 311 - 5 2011年08月
研究論文（学術雑誌）
BACKGROUND: Urinary bladder capacity is reduced in patients undergoing long-term dialysis, which may increase the risk of vesicoureteral reflux (VUR) to a transplanted kidney. This study investigated the correlations between dialysis duration, pretransplant and posttransplant bladder capacity, and prevalence of VUR to the graft. METHODS: Voiding cystography was performed in 101 adult renal transplant recipients without neurogenic disorders immediately before and 1 year after transplantation to evaluate bladder capacity and VUR. Nonstented extravesical antireflux ureteroneocystostomy was performed in all patients. RESULTS: The median dialysis duration and pretransplant bladder capacity were 32 months (range 1-426 months) and 120 mL (range 15-450 mL), and 21 patients (20.8%) underwent dialysis for more than 120 months, and 30 patients (29.7%) had a pretransplant bladder capacity of less than 80 mL. Dialysis duration was correlated with pretransplant bladder capacity (R=0.466, P<0.001). Bladder capacity expanded more than 6-fold from pretransplantation to posttransplantation, and all recipients had a bladder capacity greater than 150 mL at 1 year posttransplantation. Thirty patients had VUR to the graft. Dialysis duration longer than 60 months (P=0.021) and pretransplant bladder capacity of less than 130 mL (P=0.024) were associated with VUR. VUR was associated with lower graft function. CONCLUSIONS: Although bladder capacity decreased because of long-term dialysis, it exceeded 150 mL at 1 year posttransplantation. A small bladder can be used in renal transplantation, but it may increase the risk of VUR.
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[Granulocyte colony stimulating factor-producing spindle cell renal cell carcinoma successfully treated by chemotherapy consisting of gemcitabine and doxorubicin].
Souhei Kanda, Takamitsu Inoue, Hiroshi Tsuruta, Shuji Chiba, Takashi Obara, Mitsuru Saito, Teruaki Kumazawa, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi
Hinyokika kiyo. Acta urologica Japonica 57 ( 7 ) 385 - 9 2011年07月
研究論文（学術雑誌）
A 62-year-old female patient with a chief complaint of back pain and continuous fever was referred to our hospital. A computed tomography scan revealed a left renal tumor (76×54×67 mm) without a metastatic lesion. Laboratory examination showed an elevated white blood cell count of 23,200/μl. The patient underwent left radical nephrectomy and the histopathological diagnosis was spindle cell renal cell carcinoma (G3-4, pT4, pN2) with positive staining for granulocyte colony-stimulating factor. One month later, a computed tomography scan showed an enlarged locally recurrent tumor mass. Three cycles of combination chemotherapy consisting of gemcitabine (1,500 mg/m2, day 1) and doxorubicine (50 mg/m2, day 1) resulted in an 83% reduction of the tumor mass. A follow-up computed tomography scan after 2 weeks revealed rapid regrowth of the recurrent tumor. The patient died 199 days after the surgery. Combination chemotherapy consisting of gemcitabine and doxorubicin is a treatment option for patients with spindle cell renal cell carcinoma.
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Impact of the CYP3A4*1G polymorphism and its combination with CYP3A5 genotypes on tacrolimus pharmacokinetics in renal transplant patients.
Masatomo Miura, Shigeru Satoh, Hideaki Kagaya, Mitsuru Saito, Kazuyuki Numakura, Norihiko Tsuchiya, Tomonori Habuchi
Pharmacogenomics 12 ( 7 ) 977 - 84 2011年07月
研究論文（学術雑誌）
AIM: Tacrolimus is a substrate of CYP3A4 and CYP3A5. The present study investigated the impact of the CYP3A4*1/*1G polymorphism compared with CYP3A5 genotypes on the dose-adjusted pharmacokinetics of tacrolimus. The effects of the polymorphism on the variability in tacrolimus pharmacokinetics among patients with the CYP3A5*1 allele (CYP3A5 expresser) and among those with CYP3A5*3/*3 genotype (nonexpresser) were also studied. MATERIALS & METHODS: A total of 136 renal allograft recipients were given repeated doses of tacrolimus every 12 h. On day 28 after the renal transplantation, blood tacrolimus concentrations were measured, and dose-adjusted pharmacokinetics were determined and compared with the corresponding genotype. RESULTS: The dose-adjusted AUC₀₋₁₂ and C₀ of tacrolimus were significantly lower in patients with the CYP3A4*1G allele and CYP3A5 expressers than those with the CYP3A4*1/*1 genotype and nonexpressers, respectively. In a multiple regression analysis, the dose-adjusted AUC₀₋₁₂ and C₀ values were associated with CYP3A4*1/*1 (p = 0.018 and 0.040, respectively) and CYP3A5*3/*3 (p < 0.001 each). The standardized regression coefficient for the AUC₀₋₁₂ of tacrolimus was approximately twofold less for CYP3A4*1/*1 than CYP3A5*3/*3. The lowest dose-adjusted AUC₀₋₁₂ was found in CYP3A5 expressers with the CYP3A4*1G allele. CONCLUSION: The CYP3A4*1/*1G polymorphism was associated with the pharmacokinetics of tacrolimus, however, its contribution to dose-adjusted pharmacokinetics was approximately twofold less than that of the CYP3A5*1/*3 polymorphism. Although its effect on CYP3A4 activity is not clear, CYP3A4*1/*1G may be a candidate for a polymorphism affecting the interindividual variability in tacrolimus pharmacokinetics among CYP3A5 expressers.
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Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study.
Zsofia Kote-Jarai, Ali Amin Al Olama, Graham G Giles, Gianluca Severi, Johanna Schleutker, Maren Weischer, Daniele Campa, Elio Riboli, Tim Key, Henrik Gronberg, David J Hunter, Peter Kraft, Michael J Thun, Sue Ingles, Stephen Chanock, Demetrius Albanes, Richard B Hayes, David E Neal, Freddie C Hamdy, Jenny L Donovan, Paul Pharoah, Fredrick Schumacher, Brian E Henderson, Janet L Stanford, Elaine A Ostrander, Karina Dalsgaard Sorensen, Thilo Dörk, Gerald Andriole, Joanne L Dickinson, Cezary Cybulski, Jan Lubinski, Amanda Spurdle, Judith A Clements, Suzanne Chambers, Joanne Aitken, R A Frank Gardiner, Stephen N Thibodeau, Dan Schaid, Esther M John, Christiane Maier, Walther Vogel, Kathleen A Cooney, Jong Y Park, Lisa Cannon-Albright, Hermann Brenner, Tomonori Habuchi, Hong-Wei Zhang, Yong-Jie Lu, Radka Kaneva, Ken Muir, Sara Benlloch, Daniel A Leongamornlert, Edward J Saunders, Malgorzata Tymrakiewicz, Nadiya Mahmud, Michelle Guy, Lynne T O'Brien, Rosemary A Wilkinson, Amanda L Hall, Emma J Sawyer, Tokhir Dadaev, Jonathan Morrison, David P Dearnaley, Alan Horwich, Robert A Huddart, Vincent S Khoo, Christopher C Parker, Nicholas Van As, Christopher J Woodhouse, Alan Thompson, Tim Christmas, Chris Ogden, Colin S Cooper, Aritaya Lophatonanon, Melissa C Southey, John L Hopper, Dallas R English, Tiina Wahlfors, Teuvo L J Tammela, Peter Klarskov, Børge G Nordestgaard, M Andreas Røder, Anne Tybjærg-Hansen, Stig E Bojesen, Ruth Travis, Federico Canzian, Rudolf Kaaks, Fredrik Wiklund, Markus Aly, Sara Lindstrom, W Ryan Diver, Susan Gapstur, Mariana C Stern, Roman Corral, Jarmo Virtamo, Angela Cox, Christopher A Haiman, Loic Le Marchand, Liesel Fitzgerald, Suzanne Kolb, Erika M Kwon, Danielle M Karyadi, Torben Falck Orntoft, Michael Borre, Andreas Meyer, Jürgen Serth, Meredith Yeager, Sonja I Berndt, James R Marthick, Briony Patterson, Dominika Wokolorczyk, Jyotsna Batra, Felicity Lose, Shannon K McDonnell, Amit D Joshi, Ahva Shahabi, Antje E Rinckleb, Ana Ray, Thomas A Sellers, Hui-Yi Lin, Robert A Stephenson, James Farnham, Heiko Muller, Dietrich Rothenbacher, Norihiko Tsuchiya, Shintaro Narita, Guang-Wen Cao, Chavdar Slavov, Vanio Mitev, Douglas F Easton, Rosalind A Eeles
Nature genetics 43 ( 8 ) 785 - 91 2011年07月
研究論文（学術雑誌）
Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.
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[Genetic polymorphisms in prostate cancer].
Norihiko Tsuchiya, Tomonori Habuchi
Nihon rinsho. Japanese journal of clinical medicine 69 Suppl 5 79 - 86 2011年06月
研究論文（学術雑誌）
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A novel strategy for evasion of NK cell immunity by tumours expressing core2 O-glycans.
Shigeru Tsuboi, Mihoko Sutoh, Shingo Hatakeyama, Nobuyoshi Hiraoka, Tomonori Habuchi, Yohei Horikawa, Yasuhiro Hashimoto, Takahiro Yoneyama, Kazuyuki Mori, Takuya Koie, Toshiya Nakamura, Hisao Saitoh, Kanemitsu Yamaya, Tomihisa Funyu, Minoru Fukuda, Chikara Ohyama
The EMBO journal 30 ( 15 ) 3173 - 85 2011年06月
研究論文（学術雑誌）
The O-glycan branching enzyme, core2 β-1,6-N-acetylglucosaminyltransferase (C2GnT), forms O-glycans containing an N-acetylglucosamine branch connected to N-acetylgalactosamine (core2 O-glycans) on cell-surface glycoproteins. Here, we report that upregulation of C2GnT is closely correlated with progression of bladder tumours and that C2GnT-expressing bladder tumours use a novel strategy to increase their metastatic potential. Our results showed that C2GnT-expressing bladder tumour cells are highly metastatic due to their high ability to evade NK cell immunity and revealed the molecular mechanism of the immune evasion by C2GnT expression. Engagement of an NK-activating receptor, NKG2D, by its tumour-associated ligand, Major histocompatibility complex class I-related chain A (MICA), is critical to tumour rejection by NK cells. In C2GnT-expressing bladder tumour cells, poly-N-acetyllactosamine was present on core2 O-glycans on MICA, and galectin-3 bound the NKG2D-binding site of MICA through this poly-N-acetyllactosamine. Galectin-3 reduced the affinity of MICA for NKG2D, thereby severely impairing NK cell activation and silencing the NK cells. This new mode of NK cell silencing promotes immune evasion of C2GnT-expressing bladder tumour cells, resulting in tumour metastasis.
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Monitoring of mycophenolic acid predose concentrations in the maintenance phase more than one year after renal transplantation.
Masatomo Miura, Takenori Niioka, Shoutaro Kato, Hideaki Kagaya, Mitsuru Saito, Tomonori Habuchi, Shigeru Satoh
Therapeutic drug monitoring 33 ( 3 ) 295 - 302 2011年06月
研究論文（学術雑誌）
BACKGROUND: Routine therapeutic drug monitoring of mycophenolic acid (MPA) is generally performed using the area under the concentration-time curve from 0 to 12 hours (AUC0-12) with recommended values between 30 and 60 μg·h/mL. OBJECTIVE: The aim of this study was to examine whether the monitoring of the MPA predose concentration (C0) in patients who are stable for >1 year after renal transplantation was practical and to determine factors that cause MPA C0 variability among patients. METHODS: Eighty-six Japanese patients who had undergone renal transplantation and were taking tacrolimus and who had their MPA C0 analyzed >6 times by high-performance liquid chromatography for >1 year posttransplantation were enrolled. RESULTS: Recipients with MPA AUC0-12 levels<30 μg·h/mL on day 28 and 1 year after transplantation had an MPA C0 of <2.0 μg/mL, with a sensitivity of 90.9% and a specificity of 70.7%. There was no significant difference in the mean dose-adjusted MPA C0>1 year after transplantation between subjects with either the UGT (1A1, 1A9, and 2B7) or drug transporter (SLCO1B3, ABCC2, and ABCG2) genotypes. However, in a multiple regression analysis, the dose-adjusted mean MPA C0>1 year after transplantation was significantly associated with age (P=0.0035), creatinine clearance (P=0.0001), and the dose-adjusted MPA AUC0-12 at 1 year (P=0.0147). CONCLUSIONS: To keep the MPA AUC0-12>30 μg·h/mL, the plasma threshold for maintaining the MPA C0 with tacrolimus should be set >2.0 μg/mL as determined by high-performance liquid chromatography. For patients who are stable for >1 year after transplantation, continued monitoring of the MPA C0 using the same samples used to monitor the tacrolimus C0 and the additional assessment of the MPA AUC0-12 at the 1-year time point seem to be a viable option. If a change of the mycophenolate mofetil dose seems necessary based on the routine MPA C0 information, the determination of MPA AUC0-12 using a limited sampling strategy is recommended.
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A case of intratesticular endometrioid papillary cystadenocarcinoma.
Kazuyuki Numakura, Norihiko Tsuchiya, Hiroshi Tsuruta, Takashi Obara, Mitsuru Saito, Takamitsu Inoue, Shintaro Narita, Yohei Horikawa, Shigeru Satoh, Hiroshi Nanjyo, Tomonori Habuchi
Japanese journal of clinical oncology 41 ( 5 ) 674 - 6 2011年05月
研究論文（学術雑誌）
We report a case of intratesticular endometrioid papillary cystadenocarcinoma. A 73-year-old man was admitted for a painless right scrotal swelling. Ultrasonography and computed tomography revealed a large cystic mass in the right testis. Right scrotum puncture revealed xanthochromic fluid with negative cytology. Three months later, follow-up computed tomography showed enlargement of the cystic mass. Right high orchiectomy was performed because a testicular malignancy was suspected. The pathological diagnosis was endometrioid papillary cystadenocarcinoma, and the cells were strongly positive for the estrogen and progesterone receptors. Testicular neoplasms resembling common ovarian-type epithelial tumors are very rare. This is the first report of endometrioid papillary cystadenocarcinoma of the testis.
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Pharmacogenetic determinants for interindividual difference of tacrolimus pharmacokinetics 1 year after renal transplantation
M. Miura, T. Niioka, H. Kagaya, M. Saito, M. Hayakari, T. Habuchi, S. Satoh
Journal of Clinical Pharmacy and Therapeutics 36 ( 2 ) 208 - 216 2011年04月
研究論文（学術雑誌）
What is known and objective: Tacrolimus, a widely used immunosuppressive agent in organ transplantation, has a narrow therapeutic window. It has been suggested that its interaction with lansoprazole could be dependent on polymorphisms of CYP3A5 and CYP2C19. The objective of this study was to investigate how, 1 year after renal transplantation, CYP3A5 and CYP2C19 polymorphisms, biochemical parameters and coadministration with lansoprazole, influenced tacrolimus pharmacokinetics. Methods: The pharmacokinetics of tacrolimus was studied 1 year after renal transplantation, in 75 recipients who were all receiving continuation treatment with 12-hourly oral tacrolimus, and 30 mg lansoprazole daily (Group 1; n = 20) or, 10 mg rabeprazole daily or no proton pump inhibitor (Group 2; n = 55). Results: There were no significant differences in the dose-adjusted area under the plasma concentration-time curve (AUC0-12) and maximum plasma concentration (Cmax) of tacrolimus between CYP2C19 genotype groups, but there were significant differences between CYP3A5 genotypes groups (*1/*1 +*1/*3 vs.*3/*3 = 45·2 ± 20·0 vs. 71·0 ± 34·1 ng·h/mL/mg, P < 0·0001 and 6·3 ± 2·6 vs. 9·3 ± 7·0 ng/mL/mg, P = 0·0017, respectively) and between co-administration with and without lansoprazole (74·5 ± 34·0 vs. 52·4 ± 27·4 ng·h/mL/mg, P = 0·0054 and 10·9 ± 8·8 vs. 6·7 ± 3·0 ng/mL/mg, P = 0·0024, respectively). In a multiple regression analysis, the dose-adjusted AUC 0-12 and Cmax of tacrolimus were associated with CYP3A5*3/*3 and co-administration with lansoprazole. What is new and conclusion: CYP2C19 does not seem to contribute to the interaction between tacrolimus and lansoprazole. The long-term combination of tacrolimus and lansoprazole requires careful monitoring of patients with the CYP3A5*3/*3 genotype. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.
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A case of ureteral malignant lymphoma diagnosed by laparoscopic needle biopsy.
Kazuyuki Numakura, Norihiko Tsuchiya, Takashi Obara, Hiroshi Tsuruta, Mitsuru Saito, Shintaro Narita, Takamitsu Inoue, Yohei Horikawa, Shigeru Satoh, Tomonori Habuchi
Japanese journal of clinical oncology 41 ( 3 ) 440 - 2 2011年03月
研究論文（学術雑誌）
A pathological diagnosis of a lesion in the ureteral wall is often attended with a difficulty. We report a case of a 54-year-old man who presented a thickening of the ureteral wall and diffuse swelling of paraaortic lymph nodes diagnosed as a non-Hodgkin lymphoma by a laparoscopic needle biopsy. This is a safe and useful technique by which target tissues can be surely obtained.
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Factors increasing quantitative interstitial fibrosis from 0 hr to 1 year in living kidney transplant patients receiving tacrolimus.
Yoshiko Miura, Shigeru Satoh, Mitsuru Saito, Kazuyuki Numakura, Takamitsu Inoue, Takashi Obara, Hiroshi Tsuruta, Shintaro Narita, Yohei Horikawa, Norihiko Tsuchiya, Atsushi Komatsuda, Hideaki Kagaya, Masatomo Miura, Tomonori Habuchi
Transplantation 91 ( 1 ) 78 - 85 2011年01月
研究論文（学術雑誌）
BACKGROUND: This study investigated the increase in interstitial fibrosis (IF) from 0 hr to 1 month and 1 year posttransplantation in biopsy sections and assessed the risk of developing IF in 118 living kidney recipients. METHODS: A quantitative analysis of IF was performed using computer-assisted imaging. The percent IF (%IF) in the cortical region at 0 hr was defined as the baseline, and the increases in %IF at 1 month and 1 year were calculated. Demographics, higher (regimen 1) and lower (regimen 2) target trough concentrations of tacrolimus, and the cytochrome P450 (CYP) 3A5 polymorphism were tested as risk factors. RESULTS: The mean %IF at 0 hr, 1 month, and 1 year was 10.3%+/-4.2%, 15.0%+/-5.8%, and 19.0%+/-7.7%, respectively. %IF increased 1.7- and 2.2-fold from 0 hr to 1 month and 1 year posttransplantation, respectively. At 1 year, the increase was higher in patients with the CYP3A5*3/*3 genotype (nonexpressers), those treated with regimen 1, and those with a lower estimated glomerular filtration rate and higher body mass index. In a multivariate analysis, CYP3A5 nonexpression correlated with the development of IF (odds ratio 2.63, P=0.018). Tacrolimus blood levels in the early stage posttransplantation were higher in nonexpressers than CYP3A5 expressers in both regimens 1 and 2, despite therapeutic drug monitoring. CONCLUSIONS: The higher concentrations of tacrolimus, especially in the nonexpressers treated with regimen 1, might influence the development of IF. This study suggested that a new regimen with lower and narrow target trough levels of tacrolimus or a dosing strategy based on the CYP3A5 genotype is needed to reduce the risk of developing IF.
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Clearance and safety of the radiocontrast medium iopamidol in peritoneal dialysis patients.
Shingo Hatakeyama, Akihiko Abe, Takehiro Suzuki, Yasuhiro Hashimoto, Takuya Koie, Tomihisa Funyu, Shigeru Satoh, Tomonori Habuchi, Chikara Ohyama, Shigeki Matsuo
International journal of nephrology 2011 657051 - 657051 2011年
研究論文（学術雑誌）
Although the characteristics and safety of radiocontrast media in peritoneal dialysis (PD) patients are not yet well defined, their use in PD patients is considered generally safe. In this study, we evaluated clearance and adverse events of iopamidol in PD patients. We measured the iopamidol concentration in the plasma, dialysate, and urine of 11 patients. Iopamidol clearance from patient plasma was delayed with a half-life of 33.3 h, and the elimination ratio was 83.6% for 96 h. We retrospectively investigated adverse events occurring in a total of 50 stable PD patients who underwent a total of 64 angiographic computed tomography (CT) scans. In 64 angiographic CT scans, two cases of adverse events were observed. Our results suggest that iopamidol can be eliminated by regular PD and careful observation for adverse events are necessary for the safe use of radiocontrast media.
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What is the most preferred wound site for laparoscopic donor nephrectomy?: a questionnaire assessment.
Mitsuru Saito, Norihiko Tsuchiya, Shinya Maita, Kazuyuki Numakura, Takashi Obara, Hiroshi Tsuruta, Teruaki Kumazawa, Takamitsu Inoue, Shintaro Narita, Yohei Horikawa, Takeshi Yuasa, Shigeru Satoh, Tomonori Habuchi
Journal of laparoendoscopic & advanced surgical techniques. Part A 21 ( 6 ) 511 - 5 2011年
研究論文（学術雑誌）
INTRODUCTION: Although specimen extraction site selection for laparoscopic donor nephrectomy (LDN) is relatively flexible and is mostly selected by surgeons from the patient's standpoint, the patient's request may differ from the medical worker's recommendation. The cosmetic aspect may also differ with age, gender, and the extent of medical knowledge. We performed an unsigned questionnaire assessment of individual preferences for LDN wound sites. MATERIALS AND METHODS: Between August 2007 and October 2008, we surveyed LDN wound site preferences among 148 physicians, 263 nurses, and 266 outpatients of urology at Akita University Hospital. They were questioned for their age, gender, occupation (medical worker or not), and for the most preferred surgical wound site among the following: A, lower vertical midline: B, upper vertical midline: C, anterior subcostal: D, Pfannenstiel: E, Gibson: and F, subcostal flank. The valid response rate was 93.5% (677/724). RESULTS: Wound sites preferred (ranked in descending order) were F (48.3%), D (25.6%), E (10.5%), A (9.0%), C (5.2%), and B (1.4%). The subcostal flank incision was the most preferred in almost all the categories. Second preferences were Pfannenstiel incisions in women and incisions on the lower abdomen in men. Overall, flank and lower abdominal incisions tended to be preferred, and mid and upper abdominal incisions tended to be avoided. Medical workers selected the subcostal flank and Pfannenstiel incisions more frequently than outpatients. With increasing age, the selection rates of the Gibson and the lower vertical midline incisions increased, whereas the subcostal flank and the Pfannenstiel incisions decreased. CONCLUSIONS: The subcostal flank was the most preferred LDN sites. Age, gender, and the extent of medical knowledge may influence the individual preferences for LDN wound sites.