Kiminobu Arima

Adjuvant methotrexate, vinblastine, adriamycin, and cisplatin chemotherapy has potential to prevent recurrence of bladder tumors after surgical removal of upper urinary tract transitional cell carcinoma

Objectives:  To evaluate the efficacy of adjuvant platinum based chemotherapy in upper urinary tract urothelial cancer following surgical resection in terms of survival benefit and inhibition of bladder cancer recurrence.

Midterm results of radiofrequency ablation versus nephrectomy for T1a renal cell carcinoma.

PurposeThe aim of this study was to retrospectively evaluate midterm results of renal radiofrequency (RF) ablation compared to the results after nephrectomy in patients with T1a renal cell carcinoma (RCC).Materials and methodsA total of 115 patients with a single RCC measuring ≤4 cm (T1a) were included; 51 patients underwent RF ablation, 54 patients radical nephrectomy, and 10 patients partial nephrectomy. The survival and the percent decreases in glomerular filtration rate (GFR) were compared among the three treatments.ResultsAlthough overall survival after RF ablation (75.0% at 5 years) was lower than those after radical and partial nephrectomy, the RCC-related survival (100% at 5 years) was comparable to those following radical nephrectomy (100% at 5 years) and partial nephrectomy (100% at 3 years). The disease-free survival (DFS) after RF ablation (98.0% at 5 years) was also comparable to those after radical nephrectomy (95.0% at 5 years) (P = 0.72) and partial nephrectomy (75.0% at 3 years) (P = 0.13). The percent decrease in the GFR at last follow-up in the RF ablation group (median 7.9%) was significantly lower than that in the radical nephrectomy group (median 29.0%) (P < 0.001) and comparable to that in the partial nephrectomy group (median 11.5%) (P = 0.73).ConclusionRF ablation provides RCC-related and DFS comparable to that found after nephrectomy with little loss of renal function.

Percutaneous radiofrequency ablation with transarterial embolization is useful for treatment of stage 1 renal cell carcinoma with surgical risk: results at 2-year mean follow up.

Objectives:  Despite laparoscopic partial nephrectomy and laparoscopic cryotherapy being performed lately, an even less invasive treatment would be desirable in high‐risk patients. Under local anesthesia with i.v. sedation, we were able to perform percutaneous radiofrequency ablation (RFA) combined with renal arterial embolization for unresectable stage 1 (T1NoMo) renal cell carcinoma (RCC). We evaluated the feasibility, safety and therapeutic effects of this technique after a 2‐year mean follow up.

Radiofrequency Ablation Combined with Renal Arterial Embolization for the Treatment of Unresectable Renal Cell Carcinoma Larger Than 3.5 cm: Initial Experience

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.

Endocrine Disrupter Bisphenol A Increases In Situ Estrogen Production in the Mouse Urogenital Sinus

The balance between androgens and estrogens is very important in the development of the prostate, and even small changes in estrogen levels, including those of estrogen-mimicking chemicals, can lead to serious changes. Bisphenol A (BPA), an endocrine-disrupting chemical, is a well-known, ubiquitous, estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we examined alterations of the in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS). In the BPA-treated UGS, estradiol (E2) levels and CYP19A1 (cytochrome P450 aromatase) activity were significantly increased compared with those of the untreated and diethylstilbestrol (DES)-treated UGS. The mRNAs of steroidogenic enzymes, Cyp19a1 and Cyp11a1, and the sex-determining gene, Nr5a1, were up-regulated specifically in the BPA-treated group. The up-regulation of mRNAs was observed in the mesenchymal component of the UGS as well as in the cerebellum, heart, kidney, and ovary but not in the testis. The number of aromatase-expressing mesenchymal cells in the BPA-treated UGS was approximately twice that in the untreated and DES-treated UGS. The up-regulation of Esrrg mRNA was observed in organs for which mRNAs of steroidogenic enzymes were also up-regulated. We demonstrate here that fetal exposure to low-dose BPA has the unique action of increasing in situ E2 levels and CYP19A1 (aromatase) activity in the mouse UGS. Our data suggest that BPA might interact with in situ steroidogenesis by altering tissue components, such as the accumulation of aromatase-expressing mesenchymal cells, in particular organs.

Naftopidil, a selective α-1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest

α‐1 adrenoceptor antagonists are generally prescribed for benign prostate hyperplasia with lower urinary tract symptoms. Naftopidil, a selective α‐1 adrenoceptor antagonist, is frequently used in Japan because it has fewer side effects. Here we demonstrate for the first time that naftopidil has growth inhibitory effect in androgen‐sensitive and ‐insensitive human prostate cancer cell lines. The concentrations causing 50% inhibition (IC50) of cancer cell growth were 22.2 ± 4.0 μM in androgen‐sensitive LNCaP cells and 33.2 ± 1.1 μM in androgen‐insensitive PC‐3 cells. FACS analysis revealed that cell growth inhibition by naftopidil was due to the arrest of the G1 cell cycle. Expressions of p27kip1 and p21cip1 were significantly increased in LNCaP cells treated with naftopidil. In PC‐3 cells, naftopidil induced p21cip1 but not p27kip1. In vivo, oral administration of naftopidil to nude mice inhibited the growth of PC‐3 tumors as compared to vehicle‐treated controls. These results suggest that naftopidil may be useful in the chemoprevention of prostate cancer and the intervention of hormone refractory prostate cancer.

Percutaneous radiofrequency ablation for unresectable pulmonary metastases from renal cell carcinoma

To evaluate the clinical utility of lung radiofrequency ablation (RFA) in patients with unresectable pulmonary metastasis from renal cell carcinoma (RCC).

Radiofrequency Ablation versus Radical Nephrectomy: Clinical Outcomes for Stage T1b Renal Cell Carcinoma

PURPOSE To compare clinical outcomes of radiofrequency (RF) ablation retrospectively with those after radical nephrectomy in patients with stage T1b renal cell carcinoma (RCC). MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and the requirement to obtain written informed consent was waived. From June 2002 to March 2012, 60 patients (mean age, 65.2 years; age range, 39-86 years) with a single RCC measuring 4.1-7.0 cm (stage T1b) underwent RF ablation (n = 21) or radical nephrectomy (n = 39). Selective renal artery embolization was performed before RF ablation in eight patients. The overall, RCC-related, and disease-free survival rates, the percentage decrease in the glomerular filtration rate (GFR), and safety were compared by using the log-rank (survival), paired and Student t (GFR), and Fisher exact (safety) tests. RESULTS The overall survival rate was significantly lower in the RF ablation group than in the radical nephrectomy group (48% vs 97% at 10 years, respectively; 95% confidence interval [CI]: 12.4%, 76.7% vs 78.2%, 99.5%; P < .009). The RCC-related survival rate (94% [95% CI: 62.6%, 99.1%] with RF ablation vs 100% with radical nephrectomy at 10 years) and the disease-free survival rate (88% [95% CI: 59.2%, 96.9%] with RF ablation vs 84% [95% CI: 60.6%, 94.3%] with radical nephrectomy at 10 years, P = .99) were comparable between the two groups. No treatment-related deaths occurred. Although major complication rates were similar between the two patient groups (8.0% [two of 25 patients] vs 5.1% [two of 39 patients], P = .61), the percentage decrease in the GFR was significantly lower in the RF ablation group than in the radical nephrectomy group at the last follow-up (12.5% ± 23.4 vs 32.3% ± 20.8, respectively; P < .003). CONCLUSION RF ablation is a safe procedure for patients at substantial surgical risk for radical nephrectomy, providing comparable RCC-related and disease-free survival and preserving renal function.

Werner’s Syndrome Associated with Malignancies:Five Case Reports with a Survey of Case Histories in Japan

We present 5 cases of Werners syndrome associated with malignancies and a survey of 26 cases in the Japanese literature. Though tumors of mesenchymal origin have been reported in Werners syndrome, 14 of the 31 cases cited in this paper developed carcinomas. Carcinoma of the thyroid gland was relatively high in frequency. The significance of carcinomas in Werners syndrome should be further investigated.

Naftopidil, a Selective α1-Adrenoceptor Antagonist, Suppresses Human Prostate Tumor Growth by Altering Interactions between Tumor Cells and Stroma

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 alpha1-adrenoceptor (α1-AR) antagonists, therapeutic drugs for benign prostatic hyperplasia, have growth inhibitory effects on human prostate cancer (PCa) cells through induction of apoptosis or G1 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 α1-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 α1-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 G1 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 Prev Res; 4(1); 87–96. ©2011 AACR.