Shigeto Ishidoya

Prospective Randomized Phase II Trial of a Single Early Intravesical Instillation of Pirarubicin (THP) in the Prevention of Bladder Recurrence After Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: The THP Monotherapy Study Group Trial

PURPOSE We evaluated the efficacy of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS From December 2005 to November 2008, 77 patients clinically diagnosed with UUT-UC from 11 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were preoperatively enrolled in this study. Patients were randomly assigned to receive or not receive a single instillation of THP (30 mg in 30 mL of saline) into the bladder within 48 hours after nephroureterectomy. Cystoscopy and urinary cytology were repeated every 3 months for 2 years or until the occurrence of first bladder recurrence. RESULTS Seventy-two patients were evaluable for efficacy analysis, 21 of whom had a subsequent bladder recurrence. Significantly fewer patients who received THP had a recurrence compared with the control group (16.9% at 1 year and 16.9% at 2 years in the THP group v 31.8% at 1 year and 42.2% at 2 years in the control group; log-rank P = .025). No remarkable adverse events were observed in the THP-treated group. Based on multivariate analysis, THP instillation (hazard rate [HR], 0.26; 95% CI, 0.07 to 0.91; P = .035) and open surgery (HR, 0.28; 95% CI, 0.09 to 0.84; P = .024) were independently predictive of a reduced incidence of bladder recurrence. CONCLUSION In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations.

Localization of Aldosterone-Producing Adrenocortical Adenomas: Significance of Adrenal Venous Sampling

Accurate localization of aldosterone-producing adenoma (APA) is essential for the treatment of primary aldosteronism (PA). In order to confirm the clinical usefulness of adrenal venous sampling (AVS), we retrospectively studied 87 cases of PA in whom AVS was conducted. We collected right and left adrenal venous effluents simultaneously before and after adrenocorticotropic hormone (ACTH) stimulation for measurements of aldosterone concentration (A) and cortisol concentration (C). Based on AVS results, we judged 66 cases as having unilateral aldosterone hypersecretion and the remaining 21 cases as having no apparent laterality. Of the above 66 subjects, 61 underwent laparoscopic removal of the adrenal gland through a retroperitoneal approach. The presence of APA was histopathologically confirmed, and blood pressure decreased significantly with normalization of plasma aldosterone concentration (PAC) in all cases. The receiver operator characteristics (ROC) curve analysis between the operated and no–apparent-laterality groups revealed that the ratio of A/C on the higher side to A/C on the lower side (A/C ratio) after ACTH stimulation is a useful index, with a cutoff value of 2.6, a sensitivity of 0.98 and a specificity of 1.0. The ROC curve analysis between the APA side and contralateral side within the operated patients revealed that the cutoff value of A was 1,340 ng/dL, with a sensitivity of 0.92 and a specificity of 1.00. Our results indicate the usefulness of simultaneous AVS and ACTH stimulation for localizing APA.

Quality of life after radical prostatectomy in Japanese men: a 5-Year follow up study.

Objectives:  To measure health‐related quality of life (HRQOL) after radical prostatectomy (RP) in Japanese men with localized prostate cancer.

Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan

BackgroundSeveral studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT) using intra-prostate fiducial markers for clinically localized prostate cancer.MethodsIn total, 141 patients with localized prostate cancer treated with image-guided IMRT (76 Gy in 13 patients and 80 Gy in 128 patients) between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88%) for a median of 11 months (range: 2–88 months). Prostate-specific antigen (PSA) relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call). The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5-year cause-specific survival (CSS), the 5-year overall survival (OS) outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months.ResultsThe 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score (<8 vs. ≥8) was significant for the 5-year PSA relapse-free survival on multivariate analysis (p = 0.044). There was no grade 3 or 4 acute toxicity. The incidence of grade 2 acute gastrointestinal (GI) and genitourinary (GU) toxicities were 1.4% and 8.5%, respectively. The 5-year actuarial likelihood of late grade 2–3 GI and GU toxicities were 6% and 6.3%, respectively. No grade 4 GI or GU late toxicity was observed.ConclusionsThese medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further follow-up is needed to confirm the long-term treatment outcomes.

Single-center Outcome of Laparoscopic Unilateral Adrenalectomy for Patients With Primary Aldosteronism: Lateralizing Disease Using Results of Adrenal Venous Sampling

OBJECTIVES To assess the clinical effect of the universal use of adrenal venous sampling and to investigate the characteristics of patients with primary aldosteronism undergoing laparoscopic adrenalectomy at a single tertiary care center. METHODS After the screening examination, confirmatory test, and computed tomography (CT) scans were completed, all patients with biochemically diagnosed hyperaldosteronism underwent adrenal venous sampling to differentiate unilateral disease from bilateral idiopathic hyperaldosteronism. A total of 174 consecutive patients with unilateral aldosterone excess underwent unilateral laparoscopic adrenalectomy. RESULTS The surgically treated cohort was divided into 3 groups according to the CT findings. A total of 129 patients (74.1%) had findings associated with CT-positive macroadenoma (type 1A) and 42 (24.1%) with CT-negative microadenoma (type 2A). Only 3 patients (1.8%) had adrenocortical hyperplasia (type 3). The aldosterone level was normalized in all but 2 patients (98.9%), and the number of antihypertensive agents was significantly reduced within 1 month after adrenalectomy. Of the 174 patients, 155 (89.1%) showed resolution or improvement of hypertension. CONCLUSIONS The routine use of adrenal venous sampling could adequately detect lateralization in patients with unilateral aldosterone excess, which led to satisfactory short-term outcomes after surgery. The results of the present study showed that nearly one fourth of patients with the unilateral form had a CT-negative aldosterone-producing microadenoma.

Haptoglobin-β chain defined by monoclonal antibody RM2 as a novel serum marker for prostate cancer

In our previous study, monoclonal antibody RM2, established toward the glycosyl epitope, reflected grade of malignancy of prostate cancer cells whereas RM2 reactivity to benign glands was negative or weak. RM2 reactivity was also detected in stroma, suggesting the glycoprotein RM2 recognizes could be released into the bloodstream. Then, we explored RM2 reactivity to sera of early prostate cancer. We compared RM2 reactivity to sera between 62 patients with early prostate cancer and 43 subjects with benign prostatic disease, and examined RM2 reactivity before and after radical prostatectomy in 15 patients by Western blotting. We also examined RM2 reactivity to sera of the other urogenital cancers. RM2 reactivity was significantly enhanced on a serum glycoprotein with molecular mass ∼40 kDa, hereby termed GPX, in the patients with early prostate cancer when compared with those with benign prostatic disease (p < 0.0001). Setting an appropriate cutoff level, RM2 reactivity to GPX for detection of prostate cancer had sensitivity of 87% and specificity of 84%, respectively. Furthermore, the level of RM2 reactivity significantly decreased after radical prostatectomy (p = 0.006). However, increased RM2 reactivity to GPX was also observed in the other urogenital cancers. The proteomics approach identified GPX as haptoglobin‐β chain and RM2 showed preferential reactivity toward haptoglobin‐β chain derived from prostate cancer when compared with polyclonal anti‐haptoglobin antibody. Haptoglobin‐β chain defined by RM2 is a novel serum marker that may be useful for detection of early prostate cancer when coupled with prostate‐specific antigen because it is not specific to prostate cancer.

Significance of simultaneous determination of serum human chorionic gonadotropin (hCG) and hCG-beta in testicular tumor patients.

Background : Simultaneous determinations of human chorionic gonadotropin hormone (hCG) and hCG‐β frequently produce discrepancies, that is when hCG or hCG‐β is normal, the other is elevated. Accordingly, we examined the significance of simultaneous determination of serum hCG and hCG‐β in testicular tumors.

Is there a role for segmental adrenal venous sampling and adrenal sparing surgery in patients with primary aldosteronism

OBJECTIVE AND DESIGN Adrenal venous sampling (AVS) is critical to determine the subtype of primary aldosteronism (PA). Central AVS (C-AVS)--that is, the collection of effluents from bilateral adrenal central veins (CV)--sometimes does not allow differentiation between bilateral aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism. To establish the best treatment course, we have developed segmental AVS (S-AVS); that is, we collect effluents from the tributaries of CV to determine the intra-adrenal sources of aldosterone overproduction. We then evaluated the clinical utility of this novel approach in the diagnosis and treatment of PA. METHODS We performed C-AVS and/or S-AVS in 297 PA patients and assessed the accuracy of diagnosis based on the results of C-AVS (n=138, 46.5%) and S-AVS (n=159, 53.5%) by comparison with those of clinicopathological evaluation of resected specimens. RESULTS S-AVS demonstrated both elevated and attenuated secretion of aldosterone from APA and non-tumorous segments, respectively, in patients with bilateral APA and recurrent APA. These findings were completely confirmed by detailed histopathological examination after surgery. S-AVS, but not C-AVS, also served to identify APA located distal from the CV. CONCLUSIONS Compared to C-AVS, S-AVS served to identify APA in some patients, and its use should expand the pool of patients eligible for adrenal sparing surgery through the identification of unaffected segments, despite the fact that S-AVS requires more expertise and time. Especially, this new technique could enormously benefit patients with bilateral or recurrent APA because of the preservation of non-tumorous glandular tissue.

Five-year Follow-up of Health-related Quality of Life after Intensity-modulated Radiation Therapy for Prostate Cancer

OBJECTIVE We evaluated health-related quality of life (HRQOL) in patients with localized prostate cancer who underwent intensity-modulated radiation therapy (IMRT) or three-field conformal radiotherapy (3DCRT). METHODS A total of 97 patients underwent 3DCRT and 36 underwent IMRT for localized prostate cancer between 2002 and 2004. We measured the general and disease-specific HRQOL with the Medical Outcomes Study 36-Item Health Survey and University of California, Los Angeles Prostate Cancer Index, respectively. RESULTS There were no significant differences in the pre-operative characteristics of the two groups. The patients in the 3DCRT group were more likely to receive hormonal therapy compared with the IMRT group before and after radiation therapy (P < 0.001 and P = 0.011, respectively). With regard to general HRQOL domains, both the 3DCRT and IMRT group scores showed no significant difference between baseline and any of the observation periods. At 60 months after treatment, the 3DCRT group had significantly worse bowel function and bother scores than baseline (both P < 0.001). On the other hand, there were no significant differences between the baseline and any of the post-treatment time periods in the IMRT group. In the 3DCRT group, sexual function remained substantially lower than the baseline level (P = 0.023). The IMRT group tended to show a decrease in sexual function, which was not statistically significant (P = 0.11). CONCLUSIONS IMRT can provide the possibility to deliver a high irradiation dose to the prostate with satisfactory functional outcomes for long-term periods.

Risk factors in past histories and familial episodes related to development of testicular germ cell tumor.

Abstract  Background:  A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus.