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Manabu Miki,
Norihito Soga,
Satoru Masui, Yasuhide Hori,
Yuuko Yoshio,
Yoshihiro Hasegawa,
Hideki Kanda,
Yasushi Yamada,
Hideaki Kise,
Kiminobu Arima,
Yoshiki Sugimura
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ABSTRACT: The patient was a 74-year-old man. Computed tomography (CT) detected a right renal tumor with paraaortic lymph node swelling. Radical nephrectomy and left lymphadenectomy were performed in September 2008. Interferon-alpha (6 million international units three times per week) was administered as adjuvant therapy. Due to the development of side effects, including fatigue, the patient's immunotherapy was discontinued after 6 months. Radiofrequency ablation for pulmonary metastasis was performed 9 months after surgery. A nodular pedunculated tumor was detected on the posterior wall of the urinary bladder by CT, and transurethral resection was performed 18 months after nephrectomy/lymphadenectomy. Since the pathological diagnosis of the bladder tumor was clear cell carcinoma, that tumor was thought to have originated from the renal cell carcinoma. We have summarized 43 cases of bladder metastasis of renal cell carcinoma in Japanese patients, including ours.
Hinyokika kiyo. Acta urologica Japonica 05/2012; 58(5):231-5.
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ABSTRACT: To evaluate long-term clinical outcomes in cT1c-T3a prostate cancer patients following delayed-combined androgen blockade therapy.
From January 2001 to December 2004, 92 cT1c-T3a prostate cancer cases were enrolled. Medical castration and anti-androgen treatment were used sequentially as delayed-combined androgen blockade therapy. Time to prostate-specific antigen biochemical failure was estimated, and risk factors for prostate-specific antigen biochemical failure were evaluated.
The average patient age was 76.4 years (range, 59-91 years), the median observation period was 52.8 months (range, 26-106.6 months) and the median pre-treatment prostate-specific antigen level was 14 ng/ml (range, 3.68-492 ng/ml). The TNM classification distribution was as follows: T1c, n= 27; T2a, n = 39; T2b, n = 20; and T3a, n = 6. In the multivariate analysis, Gleason's score ≥8 (P < 0.05; hazard ratio, 3.02), prostate-specific antigen nadir >1.4 ng/ml (P = 0.001; hazard ratio, 8.76) and a half-life of the prostate-specific antigen level >1.2 months (P < 0.005; hazard ratio, 6.3) during the initial 6 months of luteinizing hormone-releasing hormone agonist monotherapy were significant independent risk factors for prostate-specific antigen biochemical failure with luteinizing hormone-releasing hormone agonist monotherapy. The high-risk group, which had at least one of these three risk factors, had a shorter time to prostate-specific antigen biochemical failure than the low-risk group, during luteinizing hormone-releasing hormone agonist monotherapy (P < 0.0001). For the total delayed-combined androgen blockade therapy observation period, the free-prostate-specific antigen biochemical failure rate was 88.3% at 5 years. Only a maintenance period following luteinizing hormone-releasing hormone agonist monotherapy (P < 0.005; hazard ratio, 16.8) was revealed to be a significant independent risk factor for prostate-specific antigen biochemical failure with total delayed-combined androgen blockade.
The free-prostate-specific antigen biochemical failure rate of delayed-combined androgen blockade therapy in our study was as valuable as those in other androgen deprivation therapy of previous reports.
Japanese Journal of Clinical Oncology 03/2012; 42(6):534-40. · 1.78 Impact Factor
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ABSTRACT: In the tumor microenvironment, carcinoma-associated fibroblasts (CAFs) are considered to play a critical role in the promotion of tumorigenesis. However, the mechanisms that generate CAFs are not well elucidated. To understand how CAFs are generated during primary cancer progression, we investigated the biochemical characteristics of normal human prostate stromal cells (PrSC) co-cultured with human prostate cancer (PCa) cells in vitro. In primary cultures of human PCa-derived stromal cells (PCaSC-8 and PCaSC-9), expression of TNC, ACTA2, EGF, FGF7, and IGF1 mRNA was generally higher than PrSC but gene expression patterns were not uniform between PCaSC-8 and PCaSC-9 cells. Transforming growth factor β (TGFβ) and vascular endothelial growth factor (VEGF) protein levels in both PCaSC-8 and PCaSC-9 cells were generally higher than PrSC but levels of both secreted proteins were not same. When PrSCs were co-cultured with androgen-sensitive LNCaP cells or its sublines, androgen-low-sensitive E9 cells and androgen-insensitive AIDL cells, mRNA expression of IGF1 was significantly increased in all combinations. In contrast, expression of COL1A1, TNC, and ACTA2 mRNA was significantly increased only in LNCaP + PrSC and E9 + PrSC co-cultures. Protein production of VEGF was significantly increased only in LNCaP + PrSC and E9 + PrSC co-cultures. Increase of TGFβ protein was observed only in E9 + PrSC co-cultures. These biochemical characteristics of PrSC were partially recapitulated in TGFβ-treated PrSC. We have demonstrated that normal fibroblasts co-cultured with cancer cells become activated and exhibit biochemical characteristics of CAFs in a heterogenous manner. Our results suggest that heterogenous induction of CAF-like differentiation might be strongly dependent on biochemical characteristics of adjacent cancer cells.
Journal of Cellular Biochemistry 08/2011; 112(12):3604-11. · 2.87 Impact Factor
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Kouhei Nishikawa,
Norihito Soga,
Kenichiro Ishii,
Manabu Kato,
Yoichi Iwamoto, Yasuhide Hori,
Michiru Etoh,
Takeshi Ohkawara,
Tomomi Yamada,
Katsunori Uchida,
Hideaki Kise,
Kiminobu Arima,
Masaaki Narita,
Taizo Shiraishi,
Yoshiki Sugimura
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ABSTRACT: OBJECTIVES: To investigate the presence of manserin in human prostate cancers and to correlate manserin expression with pathologic outcomes and progression-free survival. METHODS: Eighty-seven patients with recent prostate cancer were classified into 4 groups based on Gleason score, and manserin immunohistochemistry was correlated with Gleason sum grade. To investigate the validity of manserin as a prognostic factor, the Cox proportional hazards regression model was performed on 48 patients in our cohort with T3 or T4 prostate cancer who were initially treated with androgen deprivation therapy. RESULTS: The manserin-positive rates of patients with Gleason sums of 6, 7, 8, and ≥9 were 0%, 20.0%, 35.0%, and 48.1%, respectively. Manserin-positive rates were positively correlated with Gleason sums (P = 0.0001). Median times to cancer progression in groups with (n = 8) and without (n = 40) manserin expression were 8 months and 28 months, respectively (P = 0.01). Univariate Cox analysis revealed that manserin expression, clinical stage T4, and high Gleason sum were significantly associated with progression. Multivariate analysis revealed that only 2 factors, manserin expression (hazard ratio (HR) 4.99, P = 0.01) and clinical stage T4 (HR 4.77, P = 0.03), were independent risk factors for progression. CONCLUSIONS: This is the first report of manserin expression in human prostate cancers. Manserin may serve as a marker of prostate cancer progression.
Urologic Oncology 07/2011; · 3.22 Impact Factor
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ABSTRACT: In prostate cancer, tumor-stroma interactions play a critical role in the promotion of tumorigenesis, and thus the prevention of those interactions is a promising target to suppress tumor growth. Several studies demonstrated that alpha(1)-adrenoceptor (α(1)-AR) antagonists, therapeutic drugs for benign prostatic hyperplasia, have growth inhibitory effects on human prostate cancer (PCa) cells through induction of apoptosis or G(1) cell-cycle arrest. However, their direct actions on stromal cells surrounding cancer cells have not yet been elucidated. In this study, we investigated the effects of subtype-selective α(1)-AR antagonists (naftopidil, tamsulosin, and silodosin) on prostate tumor growth with a focus on the role of stroma, using commercially available fibroblast cells (PrSC). Tumorigenic studies in vivo showed significant reductions in tumor growth when E9 cells (an androgen low-sensitive LNCaP subline) grafted with PrSC were treated with naftopidil. In in vitro analyses, naftopidil and silodosin showed antiproliferative effects on PCa cells regardless of androgen sensitivity and α(1)-AR subtype expression. In PrSC, a strong growth inhibitory effect was observed with naftopidil but not silodosin. Flow cytometric analysis revealed that naftopidil, but not silodosin, induced G(1) cell-cycle arrest in both PCa cells and PrSC. In naftopidil-treated PrSC, total interleukin-6 protein was significantly reduced with increased suppression of cell proliferation. Silodosin induced weak early apoptosis only in PCa cells. These findings demonstrated that naftopidil strongly suppressed cell proliferation of stromal cells, resulting in decreased tumorigenic soluble factor, suggesting that naftopidil might be effective in preventing stromal support of tumor cells.
Cancer Prevention Research 01/2011; 4(1):87-96. · 4.91 Impact Factor
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ABSTRACT: We report a case of a large vesicourethral stone resulting from a long-term indwelling urethral catheter. A 66-year-old man visited our hospital emergency room on October 24, 2006 with a chief complaint of difficult urination. Although a urethral catheter was inserted temporarily based on the diagnosis of the doctor on duty, the patient did not return to our hospital for follow-up examination. On July 10, 2008, he was wheeled into our hospital with symptoms of general fatigue, urinary retention and post-renal failure due to urethral catheter obstruction. The catheter was undisturbed, and computed tomography revealed a large bladder stone that extended along the lines of the catheter. A cystostomy was established, and after renal function had recovered, the bladder stone was completely removed via laparotomy following the transurethral approach. The stone consisted of magnesium ammonium phosphate and calcium phosphate. It was concluded that the stone was closely related to a urinary tract infection caused by a Proteus strain. We discuss this unusual case, which is characterized by the stone size and the clinical course.
Hinyokika kiyo. Acta urologica Japonica 05/2010; 56(5):273-5.
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ABSTRACT: Alpha1-adrenoceptor antagonists (alpha1-blockers) are currently used as first-line drugs for the treatment of benign prostatic hyperplasia (BPH). However, cases of BPH are often encountered in which the efficacy of alpha1-blockers decreases and switching to surgical treatment is required. One factor responsible for this resistance includes structural changes in prostatic tissue architecture following repeated oral administration of alpha1-blockers. Forty patients suspected of having prostate cancer, but without evidence of malignancy on prostatic biopsy were divided into two groups: an untreated group (n = 17) and an oral alpha1-blocker-treated group (n = 23). Twenty-one patients exhibiting resistance to oral alpha1-blocker therapy who underwent surgery were assigned into the surgically treated group. Each tissue sample was subjected to Masson's trichrome staining to distinguish collagen fibers from smooth muscle constituting prostatic stroma. The mean collagen fiber share was 62.2 +/- 10.4% in the untreated group, 72.1 +/- 9.1% in the oral alpha1-blocker-treated group, and 72.2 +/- 15.7% in the surgically treated group. Focusing on cases exhibiting high-collagen fiber share (70% or more), the distribution in each of the two alpha1-blocker-treated groups (16 of the 23 cases from the oral alpha1-blocker-treated group and 10 of the 21 cases from the surgically treated group) differed significantly from that in the untreated group (2 of the 17 cases). Our findings suggest that the accumulation of collagen fibers in prostatic stroma could be one of the factors responsible for alpha1-blocker treatment.
Clinical and Experimental Medicine 10/2009; 10(2):99-106. · 1.58 Impact Factor
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ABSTRACT: We present one year observations on Photoselective Vaporization of the Prostate (PVP) of 101 men with benign prostatic hyperplasia (BPH) to investigate its safety and efficacy.
101 patients underwent Photoselective Vaporization of the Prostate (PVP) using 80 W Potassium-titanyl-phosphate (KTP) laser 17 patients were being treated with oral anticoagulant therapy, and anticoagulants were stopped before operation. Baseline characteristics, perioperative data, adverse events and postoperative outcome were evaluated immediate postoperatively, and at 2 weeks and 1, 3, 6 and 12 months postoperatively were recorded.
With all 101 patients KTP laser vaporization was performed successfully. There was minimal blood loss and none of patients need blood transfusion. No major complication occurred intraoperatively or postoperatively. At 1, 3, 6, and 12 months mean International Prostate Symptom Score index (IPSS) decreased from 20.3 preoperatively to 8.9, 6.9, 6.2 and 7.2. Mean QQL score decreased from 5.1 to 2.3, 1.7, 1.5 and 1.6. Mean urinary peak flow increased from 7.5 ml per second to 15.6, 16.7 16.7 and 16.7 respectively. Complication was mild, included transient dysuria (8.9%).
Photoselective vaporization of the prostate (PVP) using 80W Potassium-titanyl-phosphate (KTP) laser for benign prostatic hyperplasia (BPH) proved to be an effective and safe procedure for our patients including those treated with oral anticoagulants.
International Journal of Urology 12/2008; 15(12):1067-71. · 1.75 Impact Factor
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ABSTRACT: We investigated the safety and efficacy of photoselective vaporization of the prostate (PVP) in 318 men who had lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia with or without oral anticoagulant therapy (OAT). PVP was done using an 80 W potassium titanyl phosphate (KTP) laser under general or spinal anesthesia. We evaluated perioperative parameters, functional outcome (international prostate symptom score, quality of life score, maximum flow rate, postvoid residual urine volume), and adverse events up to 3 months postoperatively. The results in 51 patients under OAT (the group includes 6 men ongoing oral anticoagulants during the procedure) were compared with those obtained in 267 men who underwent PVP for the same indication but who were not under OAT (control). KTP laser vaporization was successfully performed on all patients. There was minimal blood loss, thus none of the patients needed a blood transfusion. No major complications occurred intraoperatively or postoperatively. In patients under OAT, the international prostate symptom score, quality of life score, maximum flow rate and postvoid residual urine volume were significantly improved from preoperative data (p < 0.05), and were comparable with the control. Although postoperative gross hematuria increased with resumption of OAT, PVP using 80 W KTP laser proved to be safe and effective for men who were taking oral anticoagulant medication.
Hinyokika kiyo. Acta urologica Japonica 11/2008; 54(10):651-6.
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ABSTRACT: We report herein a case of ureteral obstruction associated with pelvic inflammatory disease in a long-term intrauterine contraceptive device (IUD) user. A 62-year-old woman presented with a 2-week history of left flank pain and high fever, but no abdominal pain. She had forgotten the use of an IUD. Retrograde pyelography showed a stricture in the lower third of the left ureter. Magnetic resonance showed swelling of the uterus wall and left parametria, but did not reveal the presence of an IUD. Subtotal hysterectomy, bilateral salpingo-oophorectomy and left nephronureterectomy was performed. The IUD was then found in the uterine cavity. The results of pathological and bacteriological findings for Actinomyces infection were negative. Therefore we diagnosed this case as ureteral obstruction associated with pelvic inflammatory disease. Ureteral obstruction associated with pelvic inflammatory disease in a long-term IUD user is extremely rare.
International Journal of Urology 04/2006; 13(3):315-7. · 1.75 Impact Factor
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Koichiro Yamakado,
Atsuhiro Nakatsuka,
Shigeki Kobayashi,
Masao Akeboshi,
Haruyuki Takaki,
Zentaro Kariya,
Hiroyuki Kinbara,
Kiminobu Arima,
Makoto Yanagawa, Yasuhide Hori,
Hiromi Kato,
Yoshiki Sugimura,
Kan Takeda
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ABSTRACT: The purpose of the study was to evaluate the feasibility, safety, and therapeutic effects of the combination of renal arterial embolization and radiofrequency (RF) ablation to reinforce the anticancer effect on renal cell carcinomas (RCCs) measuring 3.5 cm or larger. This study was undertaken to evaluate this combined therapy on large RCCs-based tumor geometry. Eleven patients with 12 RCCs 3.5 cm or larger in diameter (3.5-9.0 cm) underwent combined therapy. Two were exophytic tumors, and the remaining 10 tumors had components extending into the renal sinus fat. Tumor vessels were selectively embolized in nine patients and the renal artery was completely embolized in two patients with polyvinyl alcohol or ethanol mixed with iodized oil. RF ablation was percutaneously done under the computed tomographic (CT)-fluoroscopic guidance. Response to treatment was evaluated by dynamic contrast-enhanced CT and magnetic resonance (MR) imaging. Tumor enhancement was eliminated after a single RF session in nine tumors (75%), after two sessions in two tumors (17%), and after four sessions in one tumor (8%). Both exophytic tumors (100%) and 7 of 10 tumors having components in the renal sinus fat (70%) were completely ablated with a single RF session. All tumors remained controlled during a mean follow-up period of 13 months and showed significant reduction in tumor sizes (5.2 +/- 1.7 cm to 3.6 +/- 1.4 cm, p < 0.001). A delayed abscess developed in the ablated lesion in a patient, which was percutaneously drainaged. Combined therapy as described in this report is a feasible, relatively safe, and promising treatment method for large RCCs regardless of tumor geometry.
CardioVascular and Interventional Radiology 29(3):389-94. · 2.09 Impact Factor
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ABSTRACT: Transforming growth factor-α (TGFα) promotes cell proliferation by binding to the epidermal growth factor receptor (EGFR). TGFα and EGFR overexpression have been reported in various human cancers. However, whether TGFα induces cancer by itself is unknown in urogenital organs. To investigate whether TGFα overexpression induces carcinogenesis in urogenital organs, we analyzed the phenotypes of urogenital organs in male TGFα transgenic (TG) mice of the CD1 strain. Urogenital organs including the kidney, bladder, prostate, seminal vesicles, testes, and epididymis were isolated from 4- to 48-week-old TGFα TG and wild-type (WT) CD1 mice. Prostates were separated into anterior prostate (AP), dorsolateral prostate (DLP), and ventral prostate (VP). Neither tumor formation nor epithelial hyperplasia was observed in the TGFα TG mouse urogenital organs that we have investigated. Histopathologically, in prostate, we found an increased number of p63-positive basal epithelial cells in the TGFα TG mice AP and DLP. There was no morphological change in the stromal component, such as hypercellular stroma or fibrosis. However, bladder weight was greater in TGFα TG mice than that in WT mice, and distended bladders were observed macroscopically in 19 of 20 TGFα TG mice over 20 weeks of age. Ki67 labeling index was increased significantly in the TGFα TG mouse urethral epithelium, whereas neither epithelial hyperplasia nor hypertrophy was observed. In conclusion, our results suggest that TGFα overexpression in mouse urogenital organs alone may not be responsible for tumor formation and epithelial hyperplasia, but is involved in bladder outlet obstruction.
Differentiation 80(2-3):82-8. · 2.81 Impact Factor
