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author:("Nakai, sushi")
1.  Review by urological pathologists improves the accuracy of Gleason grading by general pathologists 
BMC Urology  2015;15:70.
Urologists use biopsy Gleason scores for patient counseling, prognosis prediction, and decision making. The accuracy of Gleason grading is very important. However, the variability of Gleason grading between general pathologists cannot be overlooked. Here we evaluate the discrepancy in the Gleason grading between 2 urologic pathologists and general pathologists as well as improvement in the accuracy of Gleason grading by general pathologists as a result of review by urologic pathologists.
The subjects enrolled in the study were 755 patients who underwent prostate needle biopsy at affiliate hospitals of Nara Medical University over a period of 2 years. The biopsy samples were diagnosed by general pathologists. All biopsy samples were sent to Nara Medical University where they were diagnosed by 2 urologic pathologists. The results were then returned to the general pathologists. We compared the diagnostic accuracy of the general pathologists with that of the urologic pathologists for the parameters of no malignancy, atypical small acinar proliferation, high grade prostatic intraepithelial neoplasia and Gleason score (6, 3 + 4, 4 + 3 and 8–10). We then evaluated the concordance rate between the general and urologic pathologists for each of four consecutive 6-month periods.
The overall concordance rate of urologic pathologists and general pathologists in the first, second, third and last 6-month periods was 71.8 % (140/198), 79.8 % (168/225), 89.7 % (166/185) and 89.9 % (133/148), respectively. The concordance rate of the Gleason score between urologic pathologists and general pathologists in the first, second, third and last 6-month periods was 47.5 %(38/80), 62.6 %(57/91),76.9 %(50/65) and 78.7 %(48/61), respectively, and the kappa value was 0.55, 0.68, 0.81 and 0.84, respectively. The concordance rate improved significantly over the course of each period (P = 0.04).
The concordance rate of the Gleason grading between the general pathologists and the urologic pathologists was 47.5 %. However, improvement of the concordance rate as a result of review by the urological pathologist could be seen.
PMCID: PMC4511985  PMID: 26201393
Gleason score; Prostate biopsy; General pathologist; Urological pathologist
2.  External beam radiation plus concurrent intra-arterial chemotherapy with low dose cisplatin for muscle invasive bladder cancer 
We aimed to investigate the long-term outcome of trimodality therapy consisting of transurethral resection of bladder tumor, external beam radiation therapy, and concurrent intra-arterial low dose cisplatin for patients with muscle invasive bladder cancer.
Materials and Methods:
We retrospectively reviewed the medical records of 37 consecutive patients (28 men and 9 women) who underwent trimodality therapy for T2-3N0M0 bladder cancer at our hospital between 1996 and 2011. A total of 60Gy of external beam radiation therapy was administered. A daily low dose of cisplatin was administered intra-arterially through a subcutaneously placed reservoir on the days of radiation therapy. Complete response was defined as no residual cancer in transurethral resection specimens and negative cytology. When a complete response could not be achieved, patients underwent additional intra-arterial chemotherapy.
Five-year cause specific, disease free, and overall survival rates were 86.4%, 69.7%, and 69.6%, respectively, with a mean follow-up period of 56.5 ± 6.1 months. Five-year cause specific survivals of the complete response group after the trimodality therapy, the complete response group after additional intra-arterial chemotherapy and the non-complete response group were 100% (n = 21), 85.9% (n = 9) and 0% (n = 7), respectively. Five-year overall survivals of the complete response group after the trimodality therapy, the complete response group after additional intra-arterial chemotherapy and the non-complete response group were 82.8%, 85.3% and 0%, respectively.
This trimodality therapy for muscle invasive bladder cancer could achieve favorable survival rates with bladder preservation and minimal adverse events. This trimodality therapy can be one of the useful treatment options.
PMCID: PMC4300573  PMID: 25624577
Bladder preservation; intra-arterial chemotherapy; muscle invasive bladder cancer; radiotherapy
3.  Photodynamic diagnosis of shed prostate cancer cells in voided urine treated with 5-aminolevulinic acid 
BMC Urology  2014;14:59.
Past attempts at detecting prostate cancer (PCa) cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities. To improve the sensitivities, we evaluate the feasibility and clinical utility of photodynamic diagnosis (PDD) of prostate cancer by using 5-aminolevulinic acid (5-ALA) to examine shed prostate cancer cells in voided urine samples.
One hundred thirty-eight patients with an abnormal digital rectal exam (DRE) and/or abnormal prostate-specific antigen (PSA) levels were recruited between April 2009 and December 2010. Voided urine specimens were collected before prostate biopsy. Urine specimens were treated with 5-ALA and imaged by fluorescence microscopy and reported as protoporphyrin IX (PPIX) positive (presence of cells demonstrating simultaneous PPIX fluorescence) or PPIX negative (lack of cells demonstrating fluorescence).
Of the 138 patients, PCa was detected on needle biopsy in 81 patients (58.7%); of these 81 patients with PCa, 60 were PPIX-positive (sensitivity: 74.1%). Although 57 patients did not harbor PCa by conventional diagnostic procedures, 17 of these at-risk patients were found to be PPIX-positive (specificity: 70.2%). PPIX–PDD was more sensitive compared with DRE and transrectal ultrasound and more specific compared with PSA and PSA density. The incidence of PPIX–PDD positivity did not increase with increasing total PSA levels, tumor stage or Gleason score.
To our knowledge, this is the first successful demonstration of PPIX in urine sediments treated with 5-ALA used to detect PCa in a noninvasive yet highly sensitive manner. However, further studies are warranted to determine the role of PPIX–PPD for PCa detection.
PMCID: PMC4130698  PMID: 25086448
5-aminolevulinic acid; Prostate cancer; Photodynamic diagnosis; Urine cytology
4.  Diagnostic approach for cancer cells in urine sediments by 5-aminolevulinic acid-based photodynamic detection in bladder cancer 
Cancer Science  2014;105(5):616-622.
Bladder urothelial carcinoma is diagnosed and followed up after transurethral resection using a combination of cystoscopy, urine cytology and urine biomarkers at regular intervals. However, cystoscopy can overlook flat lesions like carcinoma in situ, and the sensitivity of urinary tests is poor in low-grade tumors. There is an emergent need for an objective and easy urinary diagnostic test for the management of bladder cancer. In this study, three different modalities for 5-aminolevulinic acid (ALA)-based photodynamic diagnostic tests were used. We developed a compact-size, desktop-type device quantifying red fluorescence in cell suspensions, named “Cellular Fluorescence Analysis Unit” (CFAU). Urine samples from 58 patients with bladder cancer were centrifuged, and urine sediments were then treated with ALA. ALA-treated sediments were subjected to three fluorescence detection assays, including the CFAU assay. The overall sensitivities of conventional cytology, BTA, NMP22, fluorescence cytology, fluorescent spectrophotometric assay and CFAU assay were 48%, 33%, 40%, 86%, 86% and 87%, respectively. Three different ALA-based assays showed high sensitivity and specificity. The ALA-based assay detected low-grade and low-stage bladder urothelial cells at shigher rate (68–80% sensitivity) than conventional urine cytology, BTA and NMP22 (8–20% sensitivity). Our findings demonstrate that the ALA-based fluorescence detection assay is promising tool for the management of bladder cancer. Development of a rapid and automated device for ALA-based photodynamic assay is necessary to avoid the variability induced by troublesome steps and low stability of specimens.
PMCID: PMC4317833  PMID: 24602011
5-Aminolevulinic acid; bladder cancer; fluorescence; urine biomarker; urine cytology
5.  Calculated Tumor Volume Is an Independent Predictor of Biochemical Recurrence in Patients Who Underwent Retropubic Radical Prostatectomy 
Advances in Urology  2012;2012:204215.
Purpose. The purpose of this study is to investigate whether the clinicopathological biopsy findings can predict the oncological outcome in patients who undergo radical prostatectomy. Materials and Methods. Between January 1997 and March 2006, 255 patients with clinically localized adenocarcinoma of the prostate (clinical T1-3N0M0) who had undergone retropubic radical prostatectomy were enrolled in this study. None of the patients received neoadjuvant or adjuvant therapy. Clinicopathological parameters were assessed to determine a predictive parameter of biochemical recurrence. Results. Of the total 255 patients, 77 showed biochemical recurrence during the follow-up period. The estimated 5-year overall survival, 5-year cause-specific survival, and 5-year biochemical recurrence-free survival rates were 97.7%, 99.5%, and 67.3%, respectively. Multivariate analysis using the Cox proportional hazards model showed that calculated cancer volume was an independent predictor among the preoperative clinicopathological parameters (P < 0.05). SVI and PSM were independent predictors among the postoperative parameters (SVI; P < 0.001, PSM; P = 0.049). Among the significant preoperative and postoperative parameters, calculated cancer volume remained an independent predictive parameter in multivariate analysis (P < 0.01). Conclusions. Tumor volume, as calculated by preoperative parameters, is an independent predictor of biochemical recurrence in patients who had undergone radical prostatectomy.
PMCID: PMC3359669  PMID: 22654901
6.  5-fluorouracil enhances the antitumor effect of sorafenib and sunitinib in a xenograft model of human renal cell carcinoma 
Oncology Letters  2012;3(6):1195-1202.
Sorafenib and sunitinib are multi-kinase inhibitors with antitumor activity in patients with advanced renal cell carcinoma (RCC). Several studies have evaluated the effect of sorafenib/sunitinib in combination with chemotherapeutic agents in different types of tumor. However, few studies have addressed the activity of fluorinated pyrimidine in combination with sorafenib/sunitinib. In this study, we examined the potential of combination therapy with 5FU and sorafenib/sunitinib in human RCC cell lines. Three human RCC cell lines, ACHN, Caki-1 and Caki-2, were used to assess sensitivity to 5-fluorouracil (5FU), sorafenib and sunitinib alone or in combination using an in vitro cell survival assay. Caki-2 cells demonstrated significantly higher resistance to 5FU and sorafenib as compared to ACHN and Caki-1. Additive antitumor effects of the combination therapy were observed in the in vitro study. There was a tendency for a positive correlation between the sensitivity to sunitinib and platelet-derived growth factor β (PDGFR-β) expression levels, which were examined by reverse transcription polymerase chain reaction. Caki-1 xenograft models were prepared by inoculating cells subcutaneously into nude mice, which were divided randomly into six groups: control, 5FU (8 mg/kg/day, intraperitoneally), sorafenib (15 mg/kg/day, orally), sunitinib (20 mg/kg/day, orally), and 5FU with sorafenib or sunitinib. The treatments were administered on 5 days each week, and tumor growth was monitored for 42 days following inoculation of cells. Synergistic antitumor effects of the combination therapy were observed in an in vivo study. The resected tumors were evaluated using the Ki-67 labeling index and microvessel density. Both the Ki-67 labeling index and microvessel density were decreased in tumors treated with the combination therapy compared to those treated with sorafenib/sunitinib alone. These findings suggest that the combination therapy of 5FU with sorafenib/sunitinib may be an effective therapeutic modality for advanced RCC patients.
PMCID: PMC3392575  PMID: 22783417
renal cell carcinoma; 5-fluorouracil; sorafenib; sunitinib; angiogenesis

Results 1-6 (6)