Publications by authors named "Motokiyo Komiyama"

35 Publications

Prognostic implication of staging of seminal vesicle invasion in patients with prostatic adenocarcinoma after prostatectomy.

Int J Urol 2021 Jul 21. Epub 2021 Jul 21.

Department of, Pathology, National Cancer Center Hospital, Tokyo, Japan.

Objectives: To evaluate whether the extent of seminal vesicle invasion of prostatic adenocarcinoma can stratify the risk of biochemical recurrence after radical prostatectomy.

Methods: We carried out radical prostatectomy for 1309 patients with prostatic adenocarcinoma between 2006 and 2019; 135 (10.3%) patients had seminal vesicle invasion. After excluding patients with neo-/adjuvant therapy, we reviewed 105 patients. We analyzed the correlation of the extent of seminal vesicle invasion and biochemical recurrence-free survival after prostatectomy and adjusted by various clinicopathological factors in multivariate analyses. Seminal vesicle invasion was stratified into three groups; the proximal part from the base was defined as level 1, followed by level 2 and the distal part as level 3.

Results: Among the 105 patients, 30 (29%), 54 (51%) and 21 patients (20%) had seminal vesicle invasion at levels 1, 2 and 3, respectively. Median times to biochemical recurrence were 110, 67 and 12 months in patients with levels 1, 2 and 3, respectively (P = 0.002). The extent of seminal vesicle invasion was the independent risk factor for biochemical recurrence in univariate (level 3 vs 1, P = 0.001; level 3 vs 2, P = 0.015) and multivariate analyses (level 3 vs 1, P = 0.025; level 3 vs 2, P = 0.030).

Conclusions: The extent of seminal vesicle invasion might be a significant predictor of biochemical recurrence in prostate cancer patients undergoing radical prostatectomy.
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http://dx.doi.org/10.1111/iju.14643DOI Listing
July 2021

Patient-reported outcomes following neoadjuvant endocrine therapy, external beam radiation, and adjuvant continuous/intermittent endocrine therapy for locally advanced prostate cancer: A randomized phase III trial.

Cancer Med 2021 05 1;10(10):3240-3248. Epub 2021 May 1.

Kotake Clinic, Osaka, Japan.

Background: We evaluated patient-reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca).

Methods: A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT-P questionnaires and EPIC urinary, bowel, and sexual bother subscales.

Results: The FACT-P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well-being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05).

Conclusion: The PRO was significantly favorable in IADT on FACT-P total score at 20 M and 38 M, PWB and functional scores at 38 M.
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http://dx.doi.org/10.1002/cam4.3895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124125PMC
May 2021

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer.

J Radiat Res 2021 May;62(3):511-516

Department of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.
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http://dx.doi.org/10.1093/jrr/rraa056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127693PMC
May 2021

External validation of the albumin, C-reactive protein and lactate dehydrogenase model in patients with metastatic renal cell carcinoma receiving second-line axitinib therapy in a Japanese multi-center cohort.

Jpn J Clin Oncol 2021 Apr;51(5):810-818

Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Purpose: To externally validate the utility of the albumin, C-reactive protein and lactate dehydrogenase model to predict the overall survival of previously treated metastatic renal cell carcinoma patients.

Patients And Methods: The ability of the albumin, C-reactive protein and lactate dehydrogenase model to predict overall survival was validated and compared with those of other prognostication models using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib therapy at 36 hospitals belonging to the Japan Urologic Oncology Group.

Results: The following factors in this cohort were independently associated with poor overall survival in a multivariate analysis: a low Karnofsky performance status, <1 year from diagnosis to targeted therapy, a high neutrophil count, and low albumin, elevated C-reactive protein, and elevated lactate dehydrogenase, and the Japan Urologic Oncology Group model was newly developed based on the presence/absence of these independent factors. In this cohort, 151 (35.9%), 125 (27.7%) and 145 (34.4%) patients were classified into the favorable, intermediate and poor risk groups, respectively, according to the albumin, C-reactive protein and lactate dehydrogenase model; however, the proportions of patients in the intermediate risk group stratified by the Japan Urologic Oncology Group, Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models were >50%. The superiority of the albumin, C-reactive protein and lactate dehydrogenase model to the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models, but not the Japan Urologic Oncology Group model, was demonstrated by multiple statistical analyses.

Conclusions: The utility of the albumin, C-reactive protein and lactate dehydrogenase model as a simple and objective prognostication tool was successfully validated using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib.
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http://dx.doi.org/10.1093/jjco/hyaa264DOI Listing
April 2021

The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report.

BMC Urol 2020 Dec 14;20(1):196. Epub 2020 Dec 14.

Department of Radiation Therapy, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, Japan.

Background: In definitive radiation therapy for prostate cancer, the SpaceOAR® System, a hydrogel spacer, is widely used to decrease the irradiated dose and toxicity of rectum. On the other hand, periprostatic abscesses formation and rectal perforation are known as rare adverse effects of SpaceOAR. Nevertheless, there is a lack of reports clarifying the association between aggravation of abscesses and radiation therapy, and hyperbaric oxygen therapy (HBOT) is effective for a peri-SpaceOAR abscess and rectal perforation.

Case Presentation: We report a case of a 78-year-old high-risk prostate cancer patient. After SpaceOAR insertion into the correct space, he started to receive external beam radiation therapy (EBRT). He developed a fever, perineal pain and frequent urination after the completion of EBRT, and the magnetic resonance imaging (MRI) revealed a peri-SpaceOAR abscess. Scheduled brachytherapy was postponed, administration of antibiotics and opioid via intravenous drip was commenced, and transperineal drainage was performed. After the alleviation of the abscess, additional EBRT instead of brachytherapy was performed with MRI-guided radiation therapy (MRgRT). On the last day of the MRgRT, perineal pain reoccurred, and MRI and colonoscopy detected the rectal perforation. He received an intravenous antibiotics drip and HBOT, and fully recovered from the rectal perforation.

Conclusions: Our report indicates that EBRT can lead to a severe rectum complication by causing inflammation for patients with a peri-SpaceOAR abscess. Furthermore, HBOT was effective for the peri-SpaceOAR abscess and rectal perforation associated with EBRT.
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http://dx.doi.org/10.1186/s12894-020-00767-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737272PMC
December 2020

Clinical outcomes of definitive whole pelvic radiotherapy for clinical lymph node metastatic prostate cancer.

Cancer Med 2020 09 4;9(18):6629-6637. Epub 2020 Aug 4.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Background: In this study, we aim to present the clinical outcomes of radiotherapy (RT) in clinical pelvic lymph node-positive prostate cancer (cN1) patients. We also analyze the prognostic factors with focus on RT dose escalation to metastatic lymph nodes (LN).

Methods: We retrospectively analyzed the data from cN1 patients who were treated with definitive RT and androgen deprivation therapy (ADT) between June 2004 and February 2016. All patients received localized irradiation to the prostate region and whole pelvis irradiation. Some patients received intensity-modulated radiation therapy with RT dose escalation to metastatic LN. Univariate analyses using log-rank test were performed to find prognostic factors between patient subgroups.

Results: Fifty-one consecutive patients were identified. The median follow-up period for all patients was 88 (range 20-157) months. Primary Gleason pattern and LN RT dose were statistically significant prognostic factors for relapse-free survival (RFS) and distant metastasis-free survival (DMFS). Especially, RT dose escalation (60 Gy or more) to metastatic LN significantly improved RFS and DMFS compared with standard dose RT (4-year RFS 90.6% vs 82.1%, 7-year RFS 90.6% vs 58.0%, P = .015; 4-year DMFS 90.6% vs 82.1%, 7-year DMFS 90.6% vs 62.8%, P = .023). The following factors were all statistically significant for biochemical relapse-free survival (BRFS): T stage, LN RT dose, local RT dose, and ADT duration period. Any significantly different toxicity was not seen for each LN or local RT dose except for the incident rate of grade 2 or more acute urinary retention, which was significantly higher in the higher LN RT dose (60 Gy or more) group by the Chi-square test.

Conclusions: RT dose escalation to metastatic LN in cN1 patients improves BRFS, RFS, and DMFS at 4 and 7 years, without increasing severe adverse events.
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http://dx.doi.org/10.1002/cam4.2985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520291PMC
September 2020

Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial.

Cancer 2020 09 23;126(17):3961-3971. Epub 2020 Jun 23.

Kotake Clinic, Osaka, Japan.

Background: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT).

Methods: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death.

Results: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722).

Conclusions: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.
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http://dx.doi.org/10.1002/cncr.33034DOI Listing
September 2020

Oncological outcomes of a multicenter cohort treated with axitinib for metastatic renal cell carcinoma.

Cancer Sci 2020 Jul 12;111(7):2460-2471. Epub 2020 Jun 12.

Department of Urology, Ibaraki Prefectural Central Hospital, Ibaraki Cancer Center, Kasama, Japan.

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.
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http://dx.doi.org/10.1111/cas.14449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385391PMC
July 2020

Integrated exome and RNA sequencing of dedifferentiated liposarcoma.

Nat Commun 2019 12 12;10(1):5683. Epub 2019 Dec 12.

Laboratory of DNA Information Analysis, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.

The genomic characteristics of dedifferentiated liposarcoma (DDLPS) that are associated with clinical features remain to be identified. Here, we conduct integrated whole exome and RNA sequencing analysis in 115 DDLPS tumors and perform comparative genomic analysis of well-differentiated and dedifferentiated components from eight DDLPS samples. Several somatic copy-number alterations (SCNAs), including the gain of 12q15, are identified as frequent genomic alterations. CTDSP1/2-DNM3OS fusion genes are identified in a subset of DDLPS tumors. Based on the association of SCNAs with clinical features, the DDLPS tumors are clustered into three groups. This clustering can predict the clinical outcome independently. The comparative analysis between well-differentiated and dedifferentiated components identify two categories of genomic alterations: shared alterations, associated with tumorigenesis, and dedifferentiated-specific alterations, associated with malignant transformation. This large-scale genomic analysis reveals the mechanisms underlying the development and progression of DDLPS and provides insights that could contribute to the refinement of DDLPS management.
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http://dx.doi.org/10.1038/s41467-019-13286-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908635PMC
December 2019

Expanding the clinicopathologic and molecular spectrum of BCOR-associated sarcomas in adults.

Histopathology 2020 Mar 21;76(4):509-520. Epub 2020 Feb 21.

Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.

Aims: BCOR gene alteration is a genetic signature of rare subsets of sarcomas. Most BCOR-associated sarcomas thus far reported are in the pediatric population, except for uterine sarcomas. We studied seven cases of BCOR-associated non-uterine sarcomas in adult patients.

Methods And Results: The patients were four men and three women ranging from 26 to 71 years in age. Three tumors, two of which primarily affected the kidney, showed BCOR-CCNB3. One tumor with a ZC3H7B-BCOR occurred in the chest wall, and a tumor with a novel CIITA-BCOR was found in the sinonasal tract. Two tumors in the lung and breast harbored exon 15 internal tandem duplications of BCOR, a highly unexpected observation in this age group. All seven sarcomas consisted of dense proliferations of uniform round to spindle cells with fine chromatin within vascular stroma. BCOR-CCNB3 sarcomas showed swirling fascicular growth. The tumor with the ZC3H7B-BCOR fusion showed a multinodular growth of spindle cells, and the tumors with the CIITA-BCOR fusion showed palisading of oval cells. Both tumors with BCOR internal tandem duplication demonstrated nested to palisading growth of round cells within sclerotic non-myxoid stroma. All seven sarcomas diffusely expressed BCOR and SATB2 immunohistochemically, with all three BCOR-CCNB3 sarcomas being immunopositive for CCNB3. BCOR alterations were confirmed by RNA sequencing, polymerase chain reaction, Sanger sequencing, and/or fluorescence in situ hybridization.

Conclusions: This study expands the clinicopathologic and molecular spectrum of BCOR-associated sarcomas, and emphasizes the importance of being aware of this entity in the differential diagnosis of adult non-uterine sarcomas.
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http://dx.doi.org/10.1111/his.14023DOI Listing
March 2020

Nodule Size After Chemotherapy and Primary-Tumor Teratoma Components Predict Malignancy of Residual Pulmonary Nodules in Metastatic Nonseminomatous Germ Cell Tumor.

Ann Surg Oncol 2018 Nov 6;25(12):3668-3675. Epub 2018 Sep 6.

Urology Division, National Cancer Center Hospital, Tokyo, Japan.

Background: The treatment goal for visceral metastatic nonseminomatous germ cell tumor (NSGCT) is to remove any residual teratoma or viable NSGCT after chemotherapy. However, this provides no therapeutic benefit to patients whose metastases necrotize on their own. This study therefore analyzed NSGCTs with pulmonary metastases to determine preoperative factors that predict necrosis and could help identify patients who might be treated with monitoring rather than surgery.

Methods: The study retrospectively analyzed 41 patients (135 metastatic pulmonary nodules) treated from 1997 to 2016 for NSGCT who showed tumor marker normalization after chemotherapy. Relationships between clinicopathologic characteristics and necrosis in resected pulmonary specimens were analyzed.

Results: Receiver operating characteristic analysis of the pulmonary nodules showed 9 mm to be the optimal cutoff length for predicting necrosis. The logistic regression model showed that absence of teratoma components in the primary tumor and all pulmonary nodules shorter than 10 mm after chemotherapy both were independent predictors of pathologic necrosis in pulmonary specimens. No patients experienced late recurrence (i.e., > 2 years afterward).

Conclusions: The presence of teratoma components in primary tumors and nodular size after chemotherapy predict the pathology of residual pulmonary nodules. Patients whose residual nodules all are shorter than 10 mm and who have no primary-tumor teratoma components might be candidates for careful monitoring before pulmonary resection.
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http://dx.doi.org/10.1245/s10434-018-6742-9DOI Listing
November 2018

Tolerability and Efficacy of Neoadjuvant Chemotherapy with a Tri-Weekly Interval Methotrexate, Doxorubicin, Vinblastine, and Cisplatin Regimen for Patients with Locally Advanced Bladder Cancer.

Case Rep Oncol 2018 May-Aug;11(2):450-460. Epub 2018 Jul 5.

Department of Pharmacy, National Cancer Center Hospital, Tokyo, Japan.

Objective: Compared with standard treatment, a modified tri-weekly MVAC (methotrexate, doxorubicin, vinblastine, and cisplatin) treatment regimen with a high cisplatin dose intensity shows good efficacy and lower toxicity. Thus, we retrospectively investigated the tolerability and efficacy of a modified tri-weekly MVAC neoadjuvant regimen.

Methods: We analyzed 25 patients with locally advanced bladder cancer medicated by a modified tri-weekly MVAC neoadjuvant regimen that omits treatment on days 15 and 22. The efficacy and tolerability were assessed retrospectively.

Results: The numbers of patients in clinical stages 2, 3, and 4 were 13 (52.0%), 1 (4.0%), and 11 (44.0%), respectively. Surgery could be performed on all patients. Five patients (20.0%) had no cancer remaining in their surgical specimens. Remaining non-muscle-invasive cancer without metastasis was observed in 7 patients (28.0%), and the total downstaging rate was 44.0%. The 5-year overall and relapse-free survival rates were 79.0 and 75.0%, respectively. The overall relative dose intensity was 0.90. Serious hematologic toxicities rated grade 3 or greater were leukopenia in 6 patients (24.0%) and anemia in 1 patient (4.0%).

Conclusions: Sufficient efficacy and tolerability of a modified tri-weekly MVAC neoadjuvant regimen were suggested. Thus, tri-weekly modified MVAC may be an option for neoadjuvant chemotherapy of advanced bladder cancer.
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http://dx.doi.org/10.1159/000490458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071437PMC
July 2018

Neoadjuvant crizotinib in ALK-rearranged inflammatory myofibroblastic tumor of the urinary bladder: A case report.

Int J Surg Case Rep 2018 1;48:1-4. Epub 2018 May 1.

Department of Urology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0054, Japan.

Introduction: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that involves various organs, but has a predilection for the urinary bladder in the genitourinary tract. Given that approximately half of all IMT cases have anaplastic lymphoma kinase (ALK) rearrangements, the ALK inhibitor crizotinib is suggested as a promising treatment for unresectable cases. No reports on neoadjuvant crizotinib therapy for locally advanced IMT of the bladder are available.

Presentation Of Case: We report a case of a 17-year-old Japanese boy referred to our institution for painful urination and increased urinary frequency. He was diagnosed with ALK-positive IMT via transurethral resection of the bladder tumor. Computed tomography (CT) revealed a 5-cm mass and extramural invasion at the bladder dome. The diagnosis was locally advanced IMT of the bladder. We decided that partial cystectomy can be performed if neoadjuvant crizotinib therapy reduced the tumor size. After 2 months of administration, CT showed that the longest tumor diameter was reduced by 48%. Thus, we performed partial cystectomy, and the surgical margin was negative. No recurrence developed for over 1 year.

Discussion: IMT has intermediate malignant potential because its clinical course is relatively indolent with low risk of distant metastasis. As this patient is young and IMT of the bladder has good prognosis after surgical resection, bladder-preserving surgery is the most preferred approach.

Conclusion: Neoadjuvant crizotinib therapy may be effective for large, locally advanced, and difficult to resect tumors.
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http://dx.doi.org/10.1016/j.ijscr.2018.04.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019858PMC
May 2018

Novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application.

Cancer Sci 2018 May 17;109(5):1690-1700. Epub 2018 Apr 17.

Department of Pathology, Keio University School of Medicine, Tokyo, Japan.

The aim of this study was to develop a new methodology that is suitable for DNA methylation diagnostics and to demonstrate its clinical applicability. We developed a new anion-exchange column for high-performance liquid chromatography (HPLC) with electrostatic and hydrophobic properties. Both cytosine and thymine, corresponding to methylated and unmethylated cytosine after bisulfite modification, respectively, are captured by electrostatic interaction and then discriminated from each other by their hydrophobic interactions. The DNA methylation levels of synthetic DNA were quantified accurately and reproducibly within 10 minutes without time-consuming pretreatment of PCR products, and the measured values were unaffected by the distribution of methylated CpG within the synthetic DNA fragments. When the DNA methylation status of the FAM150A gene, a marker of the CpG island methylator phenotype specific to clear cell renal cell carcinoma (ccRCC), was examined in 98 patients with ccRCC, bulk specimens of tumorous tissue including cancer cells showing DNA methylation of the FAM150A gene were easily identifiable by simply viewing the differentiated chromatograms, even when the cancer cell content was low. Sixteen ccRCC showing DNA methylation more frequently exhibited clinicopathological parameters reflecting tumor aggressiveness (ie, a larger diameter, higher histological grade, vascular involvement, renal vein tumor thrombi, infiltrating growth, tumor necrosis, renal pelvis invasion and higher pathological TNM stage), and had significantly lower recurrence-free and overall survival rates. These data indicate that HPLC analysis using this newly developed anion-exchange column could be a powerful tool for DNA methylation diagnostics, including prognostication of patients with cancers, in a clinical setting.
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http://dx.doi.org/10.1111/cas.13566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980336PMC
May 2018

Clarifying the Distinction Between Malignant Peripheral Nerve Sheath Tumor and Dedifferentiated Liposarcoma: A Critical Reappraisal of the Diagnostic Utility of MDM2 and H3K27me3 Status.

Am J Surg Pathol 2018 05;42(5):656-664

Departments of Pathology and Clinical Laboratories.

Malignant peripheral nerve sheath tumor (MPNST) and dedifferentiated liposarcoma (DDLPS) are 2 major types of pleomorphic spindle cell sarcoma. The differentiation of MPNST and DDLPS by histomorphology alone can be problematic. Although MDM2 amplification and PRC2 alteration leading to H3K27me3 deficiency are genetic hallmarks of DDLPS and MPNST, respectively, a small number of MDM2-amplified MPNSTs and H3K27me3-deficient DDLPSs have been reported in the literature. We systematically compared MDM2 and H3K27me3 status in 68 MPNSTs and 47 DDLPSs. Of the 62 MPNSTs, 22 were immunopositive for MDM2, mostly in a weak and/or focal manner. Of the 21 MDM2-positive MPNSTs successfully tested by fluorescence in situ hybridization, high-level MDM2 amplification was observed in 1 case. In contrast, MDM2 staining and high-level MDM2 amplification were positive in all the DDLPS tested (28/28 and 20/20). Of the 68 MPNSTs, 42 cases (62%) exhibited complete loss of H3K27me3. All the 13 MPNSTs that showed heterologous differentiation were deficient in H3K27me3. Of the 47 DDLPSs, 3 cases (6%) had complete loss of H3K27me3, all of which exhibited heterologous differentiation. One case of H3K27me3-deficient DDLPS exhibited homozygous loss of EED according to targeted next-generation sequencing, whereas there were no alterations in NF1 and CDKN2A. In conclusion, high-level MDM2 amplification strongly suggests DDLPS over MPNST. Although a good marker for MPNST, H3K27me3 deficiency also uncommonly occurs in DDLPS in association with PRC2 mutational inactivation. Because both markers are imperfectly specific, rare sarcomas with dual features could be encountered, and their classification should integrate other parameters.
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http://dx.doi.org/10.1097/PAS.0000000000001014DOI Listing
May 2018

Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features.

Am J Surg Pathol 2017 Nov;41(11):1523-1531

Departments of *Pathology and Clinical Laboratories §Urology ∥Musculoskeletal Oncology ¶Medical Oncology, National Cancer Center Hospital ‡Rare Cancer Center, National Cancer Center Hospital †Department of Pathology, the University of Tokyo, Tokyo, Japan.

Dedifferentiated liposarcoma (DDLPS) demonstrates a variety of growth patterns, and their histologic resemblance to other spindle cell mesenchymal tumors has been widely recognized. However, epithelioid morphology in DDLPS has only rarely been documented. Here, we report 6 cases of DDLPS with striking epithelioid/epithelial features. The patients were 5 men and 1 woman with a median age of 61 years. All tumors were located in the internal trunk. During follow-up of 1 to 41 months, local recurrence, distant metastases, and tumor-related death occurred in 4, 2, and 4 patients, respectively. Beside well-differentiated liposarcoma component and conventional high-grade spindle cell morphology, all tumors focally exhibited growth comprising small or large epithelioid cells in diffuse or sheet-like proliferation. Rhabdoid cells were present in 2 cases. All 5 tumors tested harbored MDM2 amplification. Cytokeratin and/or epithelial membrane antigen were at least focally positive in all 5 tumors tested. One case contained a small focus of novel heterologous epithelial differentiation with acinar structures, wherein cytokeratin, MOC31, and claudin-4 were diffusely expressed and H3K27me3 expression was lost. DDLPS with epithelioid/epithelial features may lead to misdiagnosis of carcinoma or mesothelioma, and their diagnosis should be based on correlation with clinicopathologic and molecular findings. The epithelioid morphology in DDLPS may suggest an aggressive behavior based on this small series. In addition, we document 2 cases of MDM2-amplified undifferentiated neoplasm with epithelioid features in the internal trunk that lacked association with well-differentiated liposarcoma histology and showed rapid clinical course. Whether these latter tumors belong to DDLPS with epithelioid features requires further study.
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http://dx.doi.org/10.1097/PAS.0000000000000910DOI Listing
November 2017

Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma.

Oncotarget 2017 Feb;8(8):12941-12952

Department of Clinical Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.

Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are closely related tumors commonly characterized by MDM2/CDK4 gene amplification, and lack clinically effective treatment options when inoperable. To identify novel therapeutic targets, we performed targeted genomic sequencing analysis of 19 WDLPS and 37 DDLPS tumor samples using a panel of 104 cancer-related genes (NCC oncopanel v3) developed specifically for genomic testing to select suitable molecular targeted therapies. The results of this analysis indicated that these sarcomas had very few gene mutations and a high frequency of amplifications of not only MDM2 and CDK4 but also other genes. Potential driver mutations were found in only six (11%) samples; however, gene amplification events (other than MDM2 and CDK4 amplification) were identified in 30 (54%) samples. Receptor tyrosine kinase (RTK) genes in particular were amplified in 18 (32%) samples. In addition, growth of a WDLPS cell line with IGF1R amplification was suppressed by simultaneous inhibition of CDK4 and IGF1R, using palbociclib and NVP-AEW541, respectively. Combination therapy with CDK4 and RTK inhibitors may be an effective therapeutic option for WDLPS/DDLPS patients with RTK gene amplification.
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http://dx.doi.org/10.18632/oncotarget.14652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355068PMC
February 2017

Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas.

Int J Cancer 2015 Dec 30;137(11):2589-606. Epub 2015 Jun 30.

Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.

CpG-island methylator phenotype (CIMP)-positive clear cell renal cell carcinomas (RCCs) are characterized by accumulation of DNA hypermethylation of CpG islands, clinicopathological aggressiveness and poor patient outcome. The aim of this study was to clarify the molecular pathways participating in CIMP-positive renal carcinogenesis. Genome (whole-exome and copy number), transcriptome and proteome (two-dimensional image converted analysis of liquid chromatography-mass spectrometry) analyses were performed using tissue specimens of 87 CIMP-negative and 14 CIMP-positive clear cell RCCs and corresponding specimens of non-cancerous renal cortex. Genes encoding microtubule-associated proteins, such as DNAH2, DNAH5, DNAH10, RP1 and HAUS8, showed a 10% or higher incidence of genetic aberrations (non-synonymous single-nucleotide mutations and insertions/deletions) in CIMP-positive RCCs, whereas CIMP-negative RCCs lacked distinct genetic characteristics. MetaCore pathway analysis of CIMP-positive RCCs revealed that alterations of mRNA or protein expression were significantly accumulated in six pathways, all participating in the spindle checkpoint, including the "The metaphase checkpoint (p = 1.427 × 10(-6))," "Role of Anaphase Promoting Complex in cell cycle regulation (p = 7.444 × 10(-6))" and "Spindle assembly and chromosome separation (p = 9.260 × 10(-6))" pathways. Quantitative RT-PCR analysis revealed that mRNA expression levels for genes included in such pathways, i.e., AURKA, AURKB, BIRC5, BUB1, CDC20, NEK2 and SPC25, were significantly higher in CIMP-positive than in CIMP-negative RCCs. All CIMP-positive RCCs showed overexpression of Aurora kinases, AURKA and AURKB, and this overexpression was mainly attributable to increased copy number. These data suggest that abnormalities of the spindle checkpoint pathway participate in CIMP-positive renal carcinogenesis, and that AURKA and AURKB may be potential therapeutic targets in more aggressive CIMP-positive RCCs.
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http://dx.doi.org/10.1002/ijc.29630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755138PMC
December 2015

Tumour multifocality and grade predict intravesical recurrence after nephroureterectomy in patients with upper urinary tract urothelial carcinoma without a history of bladder cancer.

Jpn J Clin Oncol 2015 May 12;45(5):488-93. Epub 2015 Feb 12.

Urology Division, National Cancer Center Hospital, Tokyo.

Objective: Patients with upper urinary tract urothelial carcinoma (UUT-UC) without a history of bladder cancer have a different natural history of intravesical recurrence after nephroureterectomy compared with those with a history of bladder cancer. The aim of this study was to identify predictive factors for post-operative intravesical recurrence in patients with non-metastatic upper urinary tract-localized urothelial carcinoma without a history of bladder cancer and who were not taking medication during the perioperative period.

Methods: This retrospective study included 133 patients who were treated between 1995 and 2012. Univariate and multivariate analyses were used to evaluate the clinical and pathological factors associated with the cumulative incidence of bladder cancer.

Results: Of the 133 patients, 51 (38.3%) developed intravesical recurrence during a median follow-up of 71 months (range, 0.8-210.8). In the multivariate analysis, multifocality (P = 0.03) and high tumour grade (P = 0.007) were significantly associated with the cumulative incidence of bladder cancer. We constructed a prediction classification model on the basis of the total number of risk factors. The 2-year cumulative incidence rates were 5.6, 34.8 and 50.0% in individuals with no, one and two risk factors, respectively. There was a significant difference between patients with no risk factors and those with two risk factors (P = 0.01).

Conclusions: Although this retrospective study had several limitations, tumour multifocality and tumour grade were found to be potential risk factors for intravesical recurrence in our cases.
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http://dx.doi.org/10.1093/jjco/hyv019DOI Listing
May 2015

Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes.

BMC Cancer 2014 Oct 20;14:772. Epub 2014 Oct 20.

Division of Molecular Pathology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Background: The CpG island methylator phenotype (CIMP) of clear cell renal cell carcinomas (ccRCCs) is characterized by accumulation of DNA methylation at CpG islands and poorer patient outcome. The aim of this study was to establish criteria for prognostication of patients with ccRCCs using the ccRCC-specific CIMP marker genes.

Methods: DNA methylation levels at 299 CpG sites in the 14 CIMP marker genes were evaluated quantitatively in tissue specimens of 88 CIMP-negative and 14 CIMP-positive ccRCCs in a learning cohort using the MassARRAY system. An additional 100 ccRCCs were also analyzed as a validation cohort.

Results: Receiver operating characteristic curve analysis showed that area under the curve values for the 23 CpG units including the 32 CpG sites in the 7 CIMP-marker genes, i.e. FAM150A, ZNF540, ZNF671, ZNF154, PRAC, TRH and SLC13A5, for discrimination of CIMP-positive from CIMP-negative ccRCCs were larger than 0.95. Criteria combining the 23 CpG units discriminated CIMP-positive from CIMP-negative ccRCCs with 100% sensitivity and specificity in the learning cohort. Cancer-free and overall survival rates of patients with CIMP-positive ccRCCs diagnosed using the criteria combining the 23 CpG units in a validation cohort were significantly lower than those of patients with CIMP-negative ccRCCs (P = 1.41 × 10-5 and 2.43 × 10-13, respectively). Patients with CIMP-positive ccRCCs in the validation cohort had a higher likelihood of disease-related death (hazard ratio, 75.8; 95% confidence interval, 7.81 to 735; P = 1.89 × 10-4) than those with CIMP-negative ccRCCs.

Conclusions: The established criteria are able to reproducibly diagnose CIMP-positive ccRCCs and may be useful for personalized medicine for patients with ccRCCs.
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http://dx.doi.org/10.1186/1471-2407-14-772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216836PMC
October 2014

Ability of preoperative 3.0-Tesla magnetic resonance imaging to predict the absence of side-specific extracapsular extension of prostate cancer.

Int J Urol 2013 Oct 29;20(10):993-9. Epub 2013 Jan 29.

Urology Division, National Cancer Center Hospital, Tokyo, Japan.

Objective: Recent studies have shown an improvement in prostate cancer diagnosis with the use of 3.0-Tesla magnetic resonance imaging. We retrospectively assessed the ability of this imaging technique to predict side-specific extracapsular extension of prostate cancer.

Methods: From October 2007 to August 2011, prostatectomy was carried out in 396 patients after preoperative 3.0-Tesla magnetic resonance imaging. Among these, 132 (primary sample) and 134 patients (validation sample) underwent 12-core prostate biopsy at the National Cancer Center Hospital of Tokyo, Japan, and at other institutions, respectively. In the primary dataset, univariate and multivariate analyses were carried out to predict side-specific extracapsular extension using variables determined preoperatively, including 3.0-Tesla magnetic resonance imaging findings (T2-weighted and diffusion-weighted imaging). A prediction model was then constructed and applied to the validation study sample.

Results: Multivariate analysis identified four significant independent predictors (P < 0.05), including a biopsy Gleason score of ≥8, positive 3.0-Tesla diffusion-weighted magnetic resonance imaging findings, ≥2 positive biopsy cores on each side and a maximum percentage of positive cores ≥31% on each side. The negative predictive value was 93.9% in the combination model with these four predictors, meanwhile the positive predictive value was 33.8%. Good reproducibility of these four significant predictors and the combination model was observed in the validation study sample.

Conclusions: The side-specific extracapsular extension prediction by the biopsy Gleason score and factors associated with tumor location, including a positive 3.0-Tesla diffusion-weighted magnetic resonance imaging finding, have a high negative predictive value, but a low positive predictive value.
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http://dx.doi.org/10.1111/iju.12091DOI Listing
October 2013

Prognostic risk stratification of patients with urothelial carcinoma of the bladder with recurrence after radical cystectomy.

J Urol 2013 Apr 30;189(4):1275-81. Epub 2012 Oct 30.

Department of Urology, National Cancer Center Hospital and Division of Molecular Pathology, National Cancer Center Research Institute (EA, YK), Tokyo, Japan.

Purpose: We identify clinicopathological variables predicting overall survival in patients with recurrent bladder urothelial carcinoma after radical cystectomy.

Materials And Methods: We retrospectively collected data on 114 patients treated with radical cystectomy for bladder urothelial carcinoma who subsequently had remote metastasis and/or local recurrence. The Kaplan-Meier method with the log rank test and multivariate Cox regression models were used to address overall survival after recurrence.

Results: During followup 99 of the 114 patients died. Median survival in the 114 patients was 11.2 months. One and 3-year overall survival rates were 48.0% and 12.1%, respectively. On multivariate analysis independent predictors of poorer overall survival included less than 1 year to recurrence, symptoms at recurrence, 2 or more metastatic organs at recurrence, high serum C-reactive protein, high lactate dehydrogenase, no post-recurrence platinum based chemotherapy and no metastasectomy. Based on the 4 variables (time to recurrence, symptoms, number of metastatic organs and C-reactive protein), we constructed a risk model predicting post-recurrence overall survival that classified patients into 3 groups with significantly different overall survival (p <0.0001).

Conclusions: Our data confirm that recurrent urothelial carcinoma after radical cystectomy is a highly aggressive, lethal disease. Seven clinicopathological factors were identified that predicted post-recurrence overall survival. Our risk model based on the 4 variables could be useful to provide relevant prognostic information to patients and physicians, and better stratify patients in clinical trials.
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http://dx.doi.org/10.1016/j.juro.2012.10.065DOI Listing
April 2013

Characteristics of lymph node metastases defining the outcome after radical cystectomy of urothelial bladder carcinoma.

Jpn J Clin Oncol 2012 Nov 22;42(11):1066-72. Epub 2012 Aug 22.

Department of Urology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Objective: The aim of this study was to identify clinicopathological variables associated with the clinical outcomes of patients with lymph node metastasis-positive urothelial bladder carcinoma after radical cystectomy.

Methods: Forty-six patients who underwent radical cystectomy without preoperative chemotherapy and had histologically proven nodal metastasis were included in the study. The status of lymph nodes and primary lesion was analyzed in terms of disease-specific survival and recurrence-free survival.

Results: The 5-year disease-specific survival and recurrence-free survival for the 46 patients overall were 41.3 and 32.2%, respectively. Univariate analysis showed that pN status, the total number of involved lymph nodes, lymph node density and extranodal invasion were statistically significant variables predictive of disease-specific survival. Multivariate analysis revealed that the total number of involved lymph nodes, extranodal invasion and diameter of the metastatic lesion were statistically significant variables predictive of disease-specific survival. Interestingly, the diameter of metastatic lesions was inversely correlated with poorer survival. Patients with large (≥10 mm) metastatic lesions and no extranodal invasion (expansive growth) had significantly better disease-specific survival than those with multiple small (<10 mm) metastatic lesions and no extranodal invasion (highly spreading) (P=0.0156) or those with extranodal invasion (infiltrative growth) (P=0.0181).

Conclusions: Our data indicate that the clinical outcome of node-positive patients is not only stratified according to the tumor burden reflected in the total number of involved lymph nodes, but also affected by tumor biology including invasiveness and potential for metastasis, which is reflected in pathological characteristics such as extranodal invasion and the diameter of metastatic lesions.
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http://dx.doi.org/10.1093/jjco/hys136DOI Listing
November 2012

A case of left renal cell carcinoma with massive tumor thrombus extending into the inferior vena cava.

Jpn J Clin Oncol 2012 Jul;42(7):658

National Cancer Center Hospital, Tokyo, Japan.

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http://dx.doi.org/10.1093/jjco/hys095DOI Listing
July 2012

The incidence and management of metachronous testicular germ cell tumors in patients with extragonadal germ cell tumors.

Urol Oncol 2012 May-Jun;30(3):319-24. Epub 2010 May 14.

Breast and Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.

Objectives: The optimal management of extragonadal germ cell tumor (EGGCT) and metachronous testicular germ cell tumor (MTGCT) has not been determined.

Patients And Methods: Fifty-one consecutive patients with EGGCT were identified. Testicular palpation or ultrasonography to rule out a primary testicular tumor was performed. Pretreatment testicular biopsies were not performed. The incidence and outcome of MTGCT, and the prognosis of EGGCT were evaluated.

Results: Twenty-five and 26 patients, respectively, had mediastinal and retroperitoneal EGGCT. Fourteen and 37 patients, respectively, had seminoma and nonseminoma. Five patients developed MTGCT in patients with retroperitoneal EGGCT. The median interval from the primary treatment for EGGCT to MTGCT diagnosis was 64 months (range 15-120). The cumulative risk of developing MTGCT was 8.3% at 6 y. Five patients underwent an orchiectomy and have survived in the 16-months median follow-up period (range 4-30). Among the patients with seminomatous and nonseminomatous EGGCT, the 5-year survival rate was 84.6% and 78.3%, respectively. Among the patients with retroperitoneal and mediastinal nonseminomatous EGGCT, the 5-year survival rate was 94.7% and 58.8%, respectively.

Conclusions: The prognosis of EGGCT without testicular biopsies was sufficient. EGGCT patients, especially retroperitoneal EGGCT, need long-term follow-up for MTGCT.
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http://dx.doi.org/10.1016/j.urolonc.2010.02.008DOI Listing
September 2012

Characteristics of prostate cancers found in specimens removed by radical cystoprostatectomy for bladder cancer and their relationship with serum prostate-specific antigen level.

Cancer Sci 2009 Oct 1;100(10):1880-4. Epub 2009 Jul 1.

Urology Division, National Cancer Center Hospital, National Cancer Center Research Institute, Tokyo, Japan.

Prostate cancer mass screening using serum prostate-specific antigen (PSA) has been conducted widely in the world. However, little is known about the true prevalence of prostate cancer in the 'normal' PSA range (4.0 ng/mL or less). The aim of the present study was to elucidate the clinicopathological features of prostate cancer occurring in men with a wide range of PSA levels. The study comprised 349 male patients who underwent radical cystoprostatectomy for bladder cancer. Patients who had had treatment for known prostate cancer were excluded. Tissue specimens were reviewed microscopically. Ninety-one patients (26.1%) were found to have prostate cancer, and 68 (74.7%) of these 91 cancers were considered to be clinically significant. Both increasing patient age and PSA level were significantly correlated with an increased incidence of both all and significant prostate cancers. Sixty-five (21.9%) among 297 patients with PSA < 4.0 ng/mL had prostate cancer, and 45 (69.2%) of the 65 cancers were significant cancers. Eighteen patients had prostate cancers 0.5 mL or more in volume. Among the 18 patients, the PSA level was 4 ng/mL or more in 11, and 3 ng/mL or more in 15. Our study shows that prostate cancer is a common finding in radical cystoprostatectomy specimens excised because of bladder cancers, and a significant proportion of these cancers are clinically significant. PSA still appears to be a useful screening tool for detecting prostate cancers with significant volume.
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http://dx.doi.org/10.1111/j.1349-7006.2009.01267.xDOI Listing
October 2009

Weekly paclitaxel and carboplatin against advanced transitional cell cancer after failure of a platinum-based regimen.

Eur Urol 2007 Oct 5;52(4):1115-22. Epub 2007 Apr 5.

Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.

Objective: Weekly administration of paclitaxel plus carboplatin is hypothesized to be an effective second-line treatment for advanced transitional cell cancer after failure of platinum-based regimen. In this phase 2 trial, we tested this hypothesis.

Patients And Methods: Patients with advanced transitional cell cancer who showed evidence of progressive or recurrent disease after methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy were eligible for this study. Weekly paclitaxel (80mg/m(2)) and carboplatin (AUC 2) were administered on days 1, 8, 15, 22, 29, and 36; the cycle was repeated every 7 wk until disease progression or intolerable toxicity (maximum 18 doses).

Results: Thirty-five patients entered this study. Among the 31 patients who were assessable, 10 had an objective response (overall response rate: 32.3%, 95% confidence interval, 15.8-48.7%). The median progression-free survival (PFS) and median survival times were 3.7 and 7.9 mo, respectively. Among the 22 patients who received prior MVAC therapy for metastatic disease, 36% had an objective response; their median PFS and median survival times were 4.3 and 7.9 mo, respectively; neither survival time significantly differed from the survival time of those who received prior MVAC as adjuvant setting. Toxicities were mild except one toxic death due to neutropenic sepsis.

Conclusions: Weekly paclitaxel plus carboplatin was a manageable, active second-line treatment for advanced transitional cell cancer after failure of platinum-based therapy.
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http://dx.doi.org/10.1016/j.eururo.2007.03.078DOI Listing
October 2007

Primary adenocarcinoma of the rete testis with preceding diagnosis of pulmonary metastases.

Int J Urol 2006 Dec;13(12):1532-5

Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.

We report a case of primary adenocarcinoma of the rete testis in a 55-year-old man with pulmonary metastases that were detected 11 months prior to the diagnosis of the primary lesion. Primary adenocarcinoma of the rete testis is an extremely rare malignant tumor with a poor outcome. The most common primary symptom is a scrotal mass, often accompanied by hydrocele and chronic epididymitis. The diagnosis is often delayed because of non-specific clinical presentation and symptoms. We cannot forget that rete testis is a possible primary site for a primary, unknown metastatic adenocarcinoma.
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http://dx.doi.org/10.1111/j.1442-2042.2006.01580.xDOI Listing
December 2006