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Hiroshi Hayami,
Satoshi Takahashi,
Kiyohito Ishikawa,
Mitsuru Yasuda,
Shingo Yamamoto,
Shinya Uehara,
Ryoichi Hamasuna,
Tetsuro Matsumoto,
Shinichi Minamitani,
Akira Watanabe, [......],
Kengo Tsuneyoshi,
Shinji Matsushita,
Takashi Yamane,
Takaoki Hirose,
Shigeru Fujihiro,
Katsuhisa Endo,
Yasuhiko Oka,
Koh Takeyama,
Takahiro Kimura,
Tetsuji Uemura
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ABSTRACT: The Japanese surveillance committee conducted the first nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for female acute uncomplicated cystitis at 43 hospitals throughout Japan from April 2009 to November 2010. In this study, the causative bacteria (Escherichia coli and Staphylococcus saprophyticus) and their susceptibility to various antimicrobial agents were investigated by isolation and culturing of bacteria from urine samples. In total, 387 strains were isolated from 461 patients, including E. coli (n = 301, 77.8 %), S. saprophyticus (n = 20, 5.2 %), Klebsiella pneumoniae (n = 13, 3.4 %), and Enterococcus faecalis (n = 11, 2.8 %). S. saprophyticus was significantly more common in premenopausal women (P = 0.00095). The minimum inhibitory concentrations of 19 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute manual. At least 87 % of E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, and 100 % of S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant E. coli strains and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 13.3 % and 4.7 %, respectively. It is important to confirm the susceptibility of causative bacteria for optimal antimicrobial therapy, and empiric antimicrobial agents should be selected by considering patient characteristics and other factors. However, the number of isolates of fluoroquinolone-resistant or ESBL-producing strains in gram-negative bacilli may be increasing in patients with urinary tract infections (UTIs) in Japan. Therefore, these data present important information for the proper treatment of UTIs and will serve as a useful reference for future surveillance studies.
Journal of Infection and Chemotherapy 05/2013; · 1.80 Impact Factor
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Takeshi Ueda,
Hirotsugu Uemura,
Yoshihiko Tomita, Taiji Tsukamoto,
Hiroomi Kanayama,
Nobuo Shinohara,
Jamal Tarazi,
Connie Chen,
Sinil Kim,
Seiichiro Ozono,
Seiji Naito,
Hideyuki Akaza
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ABSTRACT: OBJECTIVE: Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. The efficacy and safety of axitinib in Japanese patients with metastatic renal cell carcinoma were evaluated. METHODS: A subgroup analysis was conducted in Japanese patients enrolled in the randomized Phase III trial of axitinib versus sorafenib after failure of one prior systemic therapy for metastatic renal cell carcinoma. RESULTS: Twenty-five (of 361) and 29 (of 362) patients randomized to the axitinib and sorafenib arms, respectively, were Japanese and included in this analysis. Median progression-free survival in Japanese patients was 12.1 months (95% confidence interval 8.6 to not estimable) for axitinib and 4.9 months (95% confidence interval 2.8-6.6) for sorafenib (hazard ratio 0.390; 95% confidence interval 0.130-1.173; stratified one-sided P = 0.0401). The objective response rate was 52.0% for axitinib and 3.4% for sorafenib (P = 0.0001). The common all-causality adverse events (all grades) in Japanese patients were dysphonia (68%), hypertension (64%), hand-foot syndrome (64%) and diarrhea (56%) for axitinib, and hand-foot syndrome (86%), hypertension (62%) and diarrhea (52%) for sorafenib. The safety profiles of axitinib and sorafenib in Japanese patients were generally similar to those observed in the overall population, with the exceptions of higher incidences of hypertension, dysphonia, hand-foot syndrome, hypothyroidism and stomatitis. CONCLUSIONS: Axitinib is efficacious and well tolerated in Japanese patients with previously treated metastatic renal cell carcinoma, consistent with the results in the overall population, providing a new targeted therapy for these Japanese patients.
Japanese Journal of Clinical Oncology 04/2013; · 1.78 Impact Factor
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Sachiyo Nishida,
Yoshihiko Hirohashi,
Toshihiko Torigoe,
Ryuta Inoue,
Hiroshi Kitamura,
Toshiaki Tanaka,
Akari Takahashi,
Hiroko Asanuma,
Naoya Masumori, Taiji Tsukamoto,
Noriyuki Sato
Cancer Science 04/2013; 104(4):Aprilcover. · 3.33 Impact Factor
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ABSTRACT: Radical cystectomy followed by urinary diversion or reconstruction (RC) is a standard treatment for patients with muscle-invasive bladder cancer. In these operations, a high frequency of complications, especially postoperative infection, has been reported. However, there have only been a few studies about postoperative anaerobic bacterial infection. To clarify the significance and role of anaerobic bacteria in postoperative infection, we retrospectively analyzed cases in which postoperative infection by these organisms developed. A total of 126 patients who underwent RC from 2006 to 2010 were included in this study. Various types of postoperative infection occurred in 66 patients. Anaerobic bacterial infections were detected with cultures for urine and blood in one case, for blood in two cases, and for surgical wound pus in four. The frequency of postoperative anaerobic bacterial infection in RC was less than that of colon surgery. However, this study revealed the possible development of a nonnegligible number of postoperative anaerobic bacterial infections. Therefore, we should consider anaerobic bacteria as possible pathogens in postoperative infection after RC.
Journal of Infection and Chemotherapy 03/2013; · 1.80 Impact Factor
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Yuki Kyoda,
Ko Kobayashi,
Megumi Hirobe,
Tetsuya Shindo,
Fumimasa Fukuta,
Kohei Hashimoto,
Toshiaki Tanaka,
Akiko Tonooka,
Hiroshi Kitamura,
Satoshi Takahashi,
Naoya Masumori,
Tadashi Hasegawa, Taiji Tsukamoto
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ABSTRACT: OBJECTIVE: We evaluated the outcome of renal cell carcinoma (RCC) after surgery in a long-term follow-up study to elucidate the specific biological behaviors of RCC, such as late recurrence and late cancer-specific death. MATERIALS AND METHODS: We retrospectively reviewed the clinical and pathological features of 625 patients who were diagnosed as having renal cell carcinoma at our institution from 1975 to 2006. We analyzed the parameters and outcomes for the patients who had received radical or partial nephrectomy. Pathological staging was reviewed again by two pathologists. RESULTS: The median age of the patients was 61 years (range 16-87). The median follow-up was 7.0 years (range 0.1-30.3). Of the 516 patients with localized or locally advanced RCC, 124 (24.0 %) had recurrence after surgery. Lung metastasis was observed most frequently. The 10-year cancer-specific survival rates were 92.4, 91.0, 64.1 and 11.8 % for stages I, II, III and IV, respectively. The late recurrence rates in patients with localized and locally advanced RCC 5 and 10 years after initial surgery were 8.5 and 3.7 %, respectively. Cancer death more than 10 years after initial treatment of the disease occurred in 16 patients. Of the 16 patients, 9 had localized disease at the time of the initial surgery. Specific findings that characterized them were not identified in these patients. CONCLUSIONS: Late recurrence of RCC is not rare. Cancer-specific death more than 10 years after the initial treatment was observed in 16 patients with localized or advanced disease. No specific findings were identified to characterize these patients with late cancer death.
International Journal of Clinical Oncology 02/2013; · 1.41 Impact Factor
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ABSTRACT: A 56-year-old man visited a local hospital after experiencing urinary frequency for five years. A digital rectal examination revealed a markedly enlarged prostate and his serum prostate specific antigen (PSA) was 9.0 ng/ml. Although the first transrectal biopsy could not determine the final diagnosis due to insufficient sampling, the additional biopsy revealed prostatic stromal tumor of uncertain malignant potential. Magnetic resonance imaging and computed tomography showed an organ-confined huge prostate tumor. We performed radical prostatectomy uneventfully and the specimen weighed 141 g. One year after the operation, the patient had no urinary symptoms and no evidence of disease recurrence.
Hinyokika kiyo. Acta urologica Japonica 02/2013; 59(2):137-40.
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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Small, organ-confined renal cell carcinoma (RCC) generally has favourable pathological characteristics and a good prognosis. However, late recurrence is a known characteristic of the biological behaviour of RCC and no consensus has been established for surveillance protocols from 5 years after radical or partial nephrectomy. In the present study with long-term follow-up of patients with small RCCs, 18 of 172 patients (10.5%) with pT1a RCC developed recurrence and eight of these (4.7%) died from cancer. Patients with microvascular invasion had a higher risk for cancer death than those without (P < 0.001, Log-rank test). Therefore long-term follow-up is required after surgery, particularly when the disease has microvascular invasion. OBJECTIVES: To identify the long-term clinical course of small, organ-confined renal cell carcinoma (RCC). To detect the risk factors of recurrence and of cancer death in small RCC. PATIENTS AND METHODS: Retrospectively reviewed 172 patients who were pathologically diagnosed as having pT1a RCC without metastasis at our institution from 1980 to 2005. All pathology slides were re-reviewed by a single experienced pathologist. Associations of microvascular invasion (MVI), development of metastasis, and cancer death were evaluated using Cox proportional hazards analysis. RESULTS: During a median (range) follow-up of 104.5 (8-308) months, 18 patients (10.5%) developed progression and eight patients (4.7%) died from cancer. Kaplan-Meier curves showed higher cancer-specific survival (CSS) in patients without MVI (P < 0.001). In multivariate analysis, MVI was the only factor that reached statistical significance (P = 0.006). The 10-year CSS rates were 85.1% and 96.5% in patients with and without MVI, respectively. CONCLUSIONS: Patients with MVI have worse survival than those without MVI. This suggests that long-term follow-up of patients with small RCCs is needed because of the risk of recurrence and cancer death even 10 years after surgery, particularly when the disease has apparent MVI.
BJU International 01/2013; · 2.84 Impact Factor
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Sachiyo Nishida,
Yoshihiko Hirohashi,
Toshihiko Torigoe,
Ryuta Inoue,
Hiroshi Kitamura,
Toshiaki Tanaka,
Akari Takahashi,
Hiroko Asanuma,
Naoya Masumori, Taiji Tsukamoto,
Noriyuki Sato
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ABSTRACT: Prostate cancer cells include a small population of cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) that have roles in initiation and progression of the cancer. Recently, we isolated prostate CSCs/CICs as aldehyde dehydrogenase 1-highh (ALDH1(high) ) cells using the ALDEFLUOR assay; however, the molecular mechanisms of prostate CSCs/CICs are still elusive. Prostate CSCs/CICs were isolated as ALDH1(high) cells using the ALDEFLUOR assay, and the gene expression profiles were analyzed using a cDNA microarray and RT-PCR. We found that prostate CSCs/CICs expressed higher levels of growth factors including hepatocyte growth factor (HGF). HGF protein expression was confirmed by ELISA and Western blotting. On the other hand, c-MET HGF receptor was expressed in both CSCs/CICs and non-CSCs/CICs at similar levels. HGF and the supernatant of myofibloblasts derived from the prostate augmented prostasphere formation in vitro, and prostasphere formation was inhibited by an anti-HGF antibody. Furthermore, c-MET gene knockdown by siRNA inhibited the prostasphere-forming ability in vitro and tumor-initiating ability in vivo. Taken together, the results indicate that HGF secreted by prostate CSCs/CICs and prostate myofibroblasts has a role in the maintenance of prostate CSCs/CICs in an autocrine and paracrine fashion.
Cancer Science 01/2013; · 3.33 Impact Factor
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Yukiko Sugiyama,
Naoya Masumori,
Fumimasa Fukuta,
Akihiro Yoneta,
Tokimasa Hida,
Toshiharu Yamashita,
Machiko Minatoya,
Yoshie Nagata,
Mitsuru Mori,
Hirokazu Tsuji,
Hideyuki Akaza, Taiji Tsukamoto
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ABSTRACT: Background: The age-adjusted incidence rate of prostate cancer (PCa) has been reported to be lower among Asians than Western populations. A traditional Japanese meal, high in soybean products or isoflavones, may be associated with a decreased risk of PCa. Equol, which is converted from daidzein by human intestinal flora, is biologically more active than any other isoflavone aglycone. Materials and Methods: We reviewed not only recent epidemiological studies on association of isoflavones with PCa risk, but also recent research on human intestinal bacteria responsible for converting daidzein into equol. Studies were systematically searched from the database published within the last 5 years of from 2008-2012. Results: Five out of 6 articles showed significant association of isoflavones with a decreased risk of PCa, and two of them consistently showed that equol-producers carry a significantly reduced risk of PCa. Furthermore, 5 human intestinal bacteria that can convert daidzein into equol were identified in the last 5 years. Conclusions: If equol can reduce risk of PCa, a possible strategy for reducing the risk of PCa may be to increase the proportion of equol-producers by changing the intestinal flora to carrying an equol-producing bacterium with dietary alteration or probiotic technology.
Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(1):1-4. · 0.66 Impact Factor
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ABSTRACT: A 60-year-old woman with interstitial cystitis (IC), who had previously received hydrodistention surgery, intravesical instillation of resiniferatoxin and medication, was being followed. Although urinary cytology was regularly tested with no positive findings, computed tomography carried out for screening of recurrent colon cancer showed muscle-invasive squamous cell carcinoma (SCC) of the bladder (cT3bN0M0). Cystectomy was performed, but she died due to rapid disease progression at 3 months postoperatively. Chronic inflammation can be the cause of development of SCC. It is dubious whether the specific treatments for IC affected her disease. In cases of IC with persistent pyuria, the development of SCC should be kept in mind, and affirmative examination including cystoscopy should be done regularly for early detection of the disease.
Hinyokika kiyo. Acta urologica Japonica 01/2013; 59(1):31-3.
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ABSTRACT: BACKGROUND: To evaluate the clinical outcomes of urothelial carcinoma of the prostate (UCP). MATERIALS AND METHODS: This retrospective study included a total of 46 patients with UCP detected in radical cystectomy specimens from 1990 to 2006. All patients were stratified by patterns for extension of UC from the bladder and invasion of the prostatic stroma. The overall survival rates of patients were determined by pathological variables of radical cystectomy specimens. RESULTS: Of the 46 patients with UCP, 34 (74 %) and 12 (26 %) had prostatic stromal and no stromal involvement, respectively. Of 34 patients with UC having prostatic stromal involvement, 22 had contiguous involvement from bladder cancer. Twenty-four patients (52.1 %) had non-contiguous UCP, and of these, 12 (50 %) had UC of the prostatic stroma. UCP patients with prostatic stromal invasion showed a significantly worse prognosis than those without stromal invasion (P = 0.0108). There was no significant difference in survival between patients with contiguous and non-contiguous involvement (P = 0.0877). Patients with non-contiguous UCP (prostatic urethral cancer) showed poor prognosis if the UC invaded into the prostatic stroma and lymph node metastasis was present. Multivariate analysis revealed that these 2 variables were factors that significantly affected the clinical outcome of these patients. CONCLUSIONS: Patients having UCP with stromal invasion of the prostatic urethra showed much worse prognosis than those without stromal invasion regardless of extension patterns from UC of the bladder. In prostatic urethral cancer, prostatic stromal invasion and lymph node metastasis were significant prognostic factors.
International Journal of Clinical Oncology 12/2012; · 1.41 Impact Factor
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Takashi Shimizu,
Hiromu Suzuki,
Masanori Nojima,
Hiroshi Kitamura,
Eiichiro Yamamoto,
Reo Maruyama,
Masami Ashida,
Tomo Hatahira,
Masahiro Kai,
Naoya Masumori,
Takashi Tokino,
Kohzoh Imai, Taiji Tsukamoto,
Minoru Toyota
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ABSTRACT: BACKGROUND: Dysregulation of microRNAs (miRNAs) has been implicated in bladder cancer (BCa), although the mechanism is not fully understood. OBJECTIVE: We aimed to explore the involvement of epigenetic alteration of miRNA expression in BCa. DESIGN, SETTING, AND PARTICIPANTS: Two BCa cell lines (T24 and UM-UC-3) were treated with 5-aza-2'-deoxycytidine (5-aza-dC) and 4-phenylbutyric acid (PBA), after which their miRNA expression profiles were analyzed using a TaqMan array (Life Technologies, Carlsbad, CA, USA). Bisulfite pyrosequencing was used to assess miRNA gene methylation in 5 cancer cell lines, 83 primary tumors, and 120 preoperative and 47 postoperative urine samples. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of the miRNA gene panel. RESULTS AND LIMITATIONS: Of 664 miRNAs examined, 146 were upregulated by 5-aza-dC plus PBA. CpG islands were identified in the proximal upstream of 23 miRNA genes, and 12 of those were hypermethylated in cell lines. Among them, miR-137, miR-124-2, miR-124-3, and miR-9-3 were frequently and tumor-specifically methylated in primary cancers (miR-137: 68.7%; miR-124-2: 50.6%; miR-124-3: 65.1%; miR-9-3: 45.8%). Methylation of the same four miRNAs in urine specimens enabled BCa detection with 81% sensitivity and 89% specificity; the area under the ROC curve was 0.916. Ectopic expression of silenced miRNAs in BCa cells suppressed growth and cell invasion. CONCLUSIONS: Our results indicate that epigenetic silencing of miRNA genes may be involved in the development of BCa and that methylation of miRNA genes could be a useful biomarker for cancer detection.
European urology 11/2012; · 7.67 Impact Factor
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ABSTRACT: Survivin, a member of the inhibitor of apoptosis protein gene family, inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localization of survivin could predict survival of patients with upper urinary tract urothelial carcinoma (UUTUC). Immunohistochemical staining for survivin was carried out on archival specimens from 125 consecutive patients with UUTUC who underwent radical nephroureterectomy. Nuclear and cytoplasmic staining of survivin was scored and compared with clinicopathologic features and cancer-specific survival (CSS). Nuclear expression of survivin was significantly correlated with tumor grade (p < 0.001), lymphovascular invasion (p = 0.022) and poor survival with an estimated 5-year CSS probability of 54 % for tumors with nuclear expression of survivin vs. 73 % for those without nuclear expression of survivin (hazard ratio = 2.19; 95 % confidence interval = 1.02-4.70; p = 0.043). The 5-year cancer-specific survival rates of patients with cytoplasmic survivin-negative and -positive tumors were 66 and 67 %, respectively. There was no difference in survival between patients with cytoplasmic survivin-negative tumors and those with cytoplasmic survivin-positive tumors. Using univariate analysis, nuclear survivin expression, tumor grade, pathological T stage, pathological N stage, and lymphovascular invasion were the predictive variables for CSS. In contrast, cytoplasmic survivin expression had no prognostic relevance. These data suggest that nuclear accumulation of survivin represents biologic aggressiveness and that nuclear survivin is a negative prognostic marker in patients with resected UUTUC.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 11/2012; · 2.49 Impact Factor
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ABSTRACT: Objective: Sorafenib is an oral multi-kinase inhibitor of Raf-1, VEGF and PDGF receptors and others, resulting in tumor regression and anti-angiogenesis. We studied serum pancreatic enzyme increase associated with sorafenib treatment. Patients and methods: In a phase II study of Japanese patients with metastatic renal cell carcinoma, a total of 131 patients received sorafenib 400 mg twice per day. Serum levels of lipase and amylase were measured on day 7 and every 3-4 weeks thereafter during treatment period. When grade 3 or 4 enzyme abnormalities were observed, ultrasound or computed tomography scan was performed to detect pancreatitis. Results: The incidence of all-grades lipase and amylase increases were 55. 7% and 38. 2%, respectively, while those of grade 3 or 4 were 30. 5% and 5. 3%, respectively. The majority of these events were observed in the first 3 weeks of sorafenib treatment. Grade 3 or 4 lipase increase was detected in 32 patients (24. 4%)on day 7 measurement. These abnormal elevations spontaneously resolved in all patients. Regarding grade 3 lipase increase, the median time to recovery to grade 2 and 1 were 7 and 14 days, respectively. Three patients required interruption of the treatment. No patient showed any clinical manifestation or abnormal imaging finding suggesting pancreatitis. Conclusion: Pancreatic enzyme increases observed frequently under sorafenib treatment were transient and asymptomatic. They were not related to symptomatic pancreatitis.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2012; 39(11):1651-1656.
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ABSTRACT: OBJECTIVES: To determine the incidence of and the risk factors for treatment in Japanese men with benign prostatic hyperplasia/lower urinary tract symptoms enrolled into a longitudinal community-based study. METHODS: A total of 267 of 319 men aged 40-79 years were eligible for this study, with nearly 15 years of follow up. Their medical records were checked to look for any medical treatment for benign prostatic hyperplasia/lower urinary tract symptoms. The risk of treatment for benign prostatic hyperplasia/lower urinary tract symptoms was determined by calculating the hazard ratio using the Cox proportional hazards model. Five baseline parameters were considered: the International Prostate Symptom Score, the peak urinary flow rate, the prostate volume, the serum prostate-specific antigen and the internal prostatic architecture on transrectal ultrasonography. RESULTS: Data were successfully collected for 171 men (64%; 121 survivors and 50 deceased). During approximately 1900 person-years of follow up, the overall incidence of treatment for benign prostatic hyperplasia/lower urinary tract symptoms was 15.4/1000 person-years. All five parameters were statistically significant predictors of future treatment for benign prostatic hyperplasia/lower urinary tract symptoms: International Prostate Symptom Score greater than 7 (hazard ratio 6.2, P < 0.001), prostate volume greater than 30 mL (hazard ratio 4.3, P = 0.002), peak urinary flow rate less than 12 mL/s (hazard ratio 4.4, P < 0.001), prostate-specific antigen greater than 1.4 ng/mL (hazard ratio 4.0, P < 0.001) and internal prostatic architecture group 3 (hazard ratio 3.2, P = 0.002). CONCLUSIONS: Severity of lower urinary tract symptoms, decreased peak urinary flow rate, enlarged prostate volume, high prostate-specific antigen value and internal prostatic architecture at baseline are independent risk factors for treatment in Japanese men presenting with benign prostatic hyperplasia/lower urinary tract symptoms.
International Journal of Urology 10/2012; · 1.75 Impact Factor
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ABSTRACT: OBJECTIVE: There are few reports investigating the potential benefits of preoperative systemic chemotherapy for patients with node-positive upper tract urothelial carcinoma. The purpose of this study was to examine the impact of preoperative systemic chemotherapy on the clinical outcomes of patients with node-positive upper tract urothelial carcinoma treated by radical nephroureterectomy. METHODS: Data were collected on 195 consecutive patients with upper tract urothelial carcinoma treated by radical nephroureterectomy between 1995 and 2010 at a single institute. Of these, 29 patients with node-positive disease but no visceral metastasis were retrospectively evaluated. In patients who underwent preoperative systemic chemotherapy, tumor response, post-therapy pathological downstaging to either residual disease at radical nephroureterectomy or no residual lymph node metastasis (pN0) and toxicity were the endpoints of interest. Overall survival was compared between two groups: those with and without preoperative chemotherapy. RESULTS: All patients underwent regional lymphadenectomy. Overall, 15 patients (52%) underwent preoperative systemic chemotherapy. Pathological downstaging was achieved in 47%, including pN0, but there was no pathological complete response. Eighty-six percent of the patients with pathological downstaging had no evidence of recurrence. The median overall survivals were 38 and 9 months for patients with and without preoperative systemic chemotherapy, respectively (hazard ratio: 0.26, P = 0.015, log-rank test). There was no significant difference in operative morbidity between the two groups, and no operations were delayed because of preoperative chemotherapy. CONCLUSIONS: The survival of patients who undergo preoperative systemic chemotherapy following radical nephroureterectomy seems to be superior to that of those undergoing radical nephroureterectomy alone. However, to confirm this, prospective randomized studies are needed.
Japanese Journal of Clinical Oncology 10/2012; · 1.78 Impact Factor
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ABSTRACT: BACKGROUND: We retrospectively investigated short-term functional and oncological outcomes of partial nephrectomy (PN) for the anatomically or functionally solitary kidney in patients with renal cell carcinoma. METHODS: Between 1993 and 2011, 193 partial nephrectomies were performed and 16 (8.3 %) had an imperative indication in our institution. The patients' characteristics, peri- and postoperative complications, surgical margin status and postoperative changes in estimated glomerular filtration rates (eGFR) were assessed. RESULTS: The median follow-up period was 31.2 months and median age was 69.5 years. Open and laparoscopic PN were performed for 13 and 2 patients, respectively. One patient received ex-vivo PN followed by autotransplantation. There was no case with a positive surgical margin. All patients survived at the final day of observation. Median preoperative eGFR was 48.67 mL/min/1.73 m(2) and the reduction rate of eGFR at 3 months after operation was 20.9 % (0-50.2). Three patients (18.8 %) required temporary hemodialysis after operation and all these patients had stage 4 chronic kidney disease (CKD) before operation. Only one patient needed chronic hemodialysis at 8 months after operation. CONCLUSIONS: PN can be performed safely and provides feasible functional and oncological outcomes. Preoperative CKD stage 4 patients may have a risk of temporary hemodialysis in the perioperative period.
International Journal of Clinical Oncology 10/2012; · 1.41 Impact Factor
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Masatoshi Eto,
Tomomi Kamba,
Hideaki Miyake,
Masato Fujisawa,
Takao Kamai,
Hirotsugu Uemura, Taiji Tsukamoto,
Haruhito Azuma,
Akio Matsubara,
Kazuo Nishimura,
Tsuyoshi Nakamura,
Osamu Ogawa,
Seiji Naito
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ABSTRACT: BACKGROUND: In our 2007 retrospective study, we reported that single nucleotide polymorphisms (SNPs) in the signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3) gene were significantly associated with better response to interferon (IFN)-α in patients with metastatic renal cell carcinoma (mRCC). OBJECTIVE: To prospectively confirm those results, the Japan Immunotherapy SNPs-Study Group for Kidney Cancer conducted this trial. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, prospective study, 203 eligible patients were enrolled. We evaluated the correlation between the antitumor effects of IFN-α and 11 SNPs (STAT3-2, STAT3-0, SOCS3-1, IL4R-34, PTGS1-3, PTGS1-4, PTGS1-5, PTGS2-12, IRF2-67, ICSBP-38, and TAP2-5) in eight genes in 180 patients who received IFN-α for >12 wk. INTERVENTIONS: Patients were treated with three doses per week of IFN-α 5 million IU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analyzed the association of response to IFN-α and overall survival (OS) with genetic polymorphisms using a chi-square test and a logistic regression model. RESULTS AND LIMITATIONS: The response rate of IFN-α was 13.8% (28 of 203 patients; 9 complete responses [CRs], 19 partial responses [PRs]). The CR rate of 4.4% was higher than we expected. Response to IFN-α was not associated with any of the 11 SNPs examined. However, when we assessed patients with CR, PR, and stable disease >24 wk as a group representing those with clinical response, a significant association was observed between STAT3-2 (rs1905341) and the clinical response of IFN-α (p=0.039). Namely, C/C genotype of STAT3-2 was significantly associated with the clinical response of IFN-α and OS. These results were generated in Japanese patients and should be studied in other ethnic groups. CONCLUSIONS: This is the first prospective study demonstrating that a STAT3 polymorphism can be a predictive marker for treatment with IFN-α for patients with mRCC.
European urology 09/2012; · 7.67 Impact Factor
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ABSTRACT: The adherence of uropathogenic Escherichia coli (UPEC) to the host urothelial surface is the first step for establishing UPEC infection. Uroplakin Ia (UPIa), a glycoprotein expressed on bladder urothelium, serves as a receptor for FimH, a lectin located at bacterial pili, and their interaction initiates UPEC infection. Surfactant protein D (SP-D) is known to be expressed on mucosal surfaces in various tissues besides the lung. However, the functions of SP-D in the non-pulmonary tissues are poorly understood. The purposes of this study were to investigate the possible function of SP-D expressed in the bladder urothelium and the mechanisms by which SP-D functions. SP-D was expressed in human bladder mucosa and its mRNA was increased in the bladder of the UPEC infection model in mice. SP-D directly bound to UPEC and strongly agglutinated them in a Ca2+-dependent manner. Co-incubation of SP-D with UPEC decreased the bacterial adherence to 5637 cells, the human bladder cell line, and the UPEC-induced cytotoxicity. In addition, pre-incubation of SP-D with 5637 cells resulted in the decreased adherence of UPEC to the cells and in the reduced number of the cells injured by UPEC. SP-D directly bound to UPIa and competed with FimH for UPIa binding. Consistent with the in vitro data, the exogenous administration of SP-D inhibited UPEC adherence to the bladder and dampened UPEC-induced inflammation in mice. These results support the conclusion that SP-D can protect the bladder urothelium against UPEC infection, and suggest a possible function of SP-D in urinary tract.
Journal of Biological Chemistry 09/2012; · 4.77 Impact Factor
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ABSTRACT: BACKGROUND: Since neuroendocrine (NE) cells play an important role in the development of castration-resistant prostate cancer (CRPC), target therapy to NE cells should be considered for treating CRPC. We investigated the effects zoledronic acid (ZOL) and two somatostatin analogs (octreotide: SMS, and pasireotide: SOM) on an NE allograft (NE-10) and its cell line (NE-CS), which were established from the prostate of the LPB-Tag 12T-10 transgenic mouse. METHODS: We examined the in vivo effects of ZOL, SMS and SOM as single agents and their combinations on subcutaneously inoculated NE-10 allografts and the in vitro effects on NE-CS cells. Apoptosis and cell cycle activity were assessed by immunohistochemistry using TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and a Ki-67 antibody, respectively. RESULTS: In vivo growth of NE-10 tumors treated with ZOL, ZOL plus SMS, or ZOL plus SOM was significantly inhibited compared to the control as a consequence of induction of apoptosis and cell cycle arrest. ZOL induced time- and dose-dependent inhibition of in vitro proliferation of NE-CS cells, but the somatostatin analogs (SMS and SOM) did not. ZOL also inhibited migration of NE-CS cells. These effects were caused by inhibition of Erk1/2 phosphorylation via impairment of prenylation of Ras. CONCLUSIONS: ZOL, but not SMS or SOM, induced apoptosis and inhibition of proliferation and migration through impaired prenylation of Ras in NE carcinoma models. Our findings support the possibility that ZOL could be used in the early phase for controlling NE cells, which may trigger progression to CRPC. Prostate © 2012 Wiley Periodicals, Inc.
The Prostate 09/2012; · 3.48 Impact Factor
