Hiroshi Furuse

Resistive Index: A Newly Identified Predictor of Outcome of Transurethral Prostatectomy in Patients With Benign Prostatic Hyperplasia

OBJECTIVE To examine the usefulness of several preoperative parameters obtained through transrectal ultrasonography in predicting the outcome of transurethral resection of the prostate (TURP). METHODS A total of 572 men aged 51-85 years scheduled to undergo TURP for benign prostatic hyperplasia were prospectively enrolled, and 560 were ultimately evaluated. We preoperatively assessed International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum urinary flow rate (Q(max)), and postvoid residual urine volume (PVR), and measured total prostate volume (TPV), transition zone (TZ) index, and resistive index (RI) using transrectal ultrasonography. To compare the usefulness of the latter 3 indices, we calculated the area under the receiver operating characteristic (ROC) curve for each index and for IPSS. RESULTS IPSS (total, postmicturition symptoms, storage symptoms, voiding symptoms), QOL score, Q(max), and PVR were significantly improved after TURP. Significant differences between the effective and noneffective groups were observed with regard to age, IPSS (total, postmicturition symptoms, storage symptoms, voiding symptoms), QOL score, TPV, TZ index, RI, Q(max), and PVR. The area under the ROC curve was 0.663 for IPSS, 0.691 for TPV, 0.719 for the TZ index, and 0.845 for the RI. CONCLUSIONS The RI is a useful predictor of an effective outcome after TURP in patients with benign prostatic hyperplasia and may be useful for determining suitability for surgical intervention.

Primary signet ring cell carcinoma of the urinary bladder successfully treated with intra-arterial chemotherapy alone.

A 65-year-old man presented with the complaint of gross hematuria. Cystoscopy revealed a sessile tumor on the left bladder wall. It was diagnosed as primary signet ring cell carcinoma of the bladder (T3bN0M0). The patient did not want surgical treatment. Therefore, three courses of arterial infusion of carboplatin were administered at 3-week intervals. Complete remission was obtained and has been maintained for 44 months. Our case appears to be the first report of successful treatment with chemotherapy alone of an infiltrating signet ring cell carcinoma of the bladder.

Comparative Assessment of Efficacies Between 2 Alternative Therapeutic Sequences With Novel Androgen Receptor-Axis-Targeted Agents in Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer

Background The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor‐axis‐targeted (ARAT) agents in patients with docetaxel‐naïve metastatic castration‐resistant prostate cancer (mCRPC). Patients and Methods This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate‐specific antigen (PSA) progression‐free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively. Results Of these patients, 49 and 59 received ARAT therapy with the AA‐to‐Enz sequence (AA‐to‐Enz group) and with the reverse sequence (Enz‐to‐AA group), respectively. No significant differences in the baseline characteristics were noted between the 2 groups. In the overall patient population, the PSA response rate to the second‐line ARAT agent (21.3%) was significantly lower than that of the first‐line ARAT agent (58.3%). The combined PSA PFS in the AA‐to‐Enz group (median, 18.4 months) was significantly superior to that of the Enz‐to‐AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (ie, AA‐to‐Enz vs. Enz‐to‐AA group) in addition to performance status as an independent predictor of combined PSA PFS in these patients. However, there was no significant difference in overall survival (OS) between the 2 groups. Conclusions Although cross‐resistance between ARAT agents is a common phenomenon in docetaxel‐naïve patients with mCRPC, different efficacies were observed favoring the AA‐to‐Enz rather than Enz‐to‐AA sequence in this series with respect to combined PSA PFS but not OS. Micro‐Abstract The investigation of the efficacy of sequential therapies with novel androgen receptor‐axis‐targeted (ARAT) agents for docetaxel‐naïve patients with metastatic castration‐resistant prostate cancer revealed the superiority of the abiraterone‐to‐enzalutamide sequence over the reverse sequence regarding combined prostate‐specific antigen progression‐free survival, but not overall survival. Therefore, despite the occurrence of cross‐resistance with either sequence, ARAT therapy with the abiraterone‐to‐enzalutamide sequence might be preferable.

Holmium: YAG Laser Resection of the Prostate Versus Visual Laser Ablation of the Prostate and Transurethral Ultrasound‐Guided Laser Induced Prostatectomy: A Retrospective Comparative Study

Background:

Oral 5-aminolevulinic acid mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A randomized, double-blind, multicentre phase II/III study.

BACKGROUND Photodynamic diagnosis (PDD) of non-muscle-invasive bladder cancer (NMIBC) following transurethral administration of a hexalated form of 5-aminolevulinic acid (5-ALA), 5-ALA hexyl ester, is widely performed in Western countries. In this study, effectiveness and safety of the oral administration of 5-ALA is assessed in a phase II/III study of PDD for NMIBC in comparison to those of conventional white-light endoscopic diagnosis. METHODS Patients with NMIBC were allocated to two groups that were orally administered 10 and 20 mg/kg of 5-ALA under the double-blind condition. Effectiveness was evaluated by setting the primary endpoint to sensitivity. Safety was also analyzed. Moreover, clinically recommended doses of 5-ALA was also investigated as an investigator-initiated multicenter cooperative clinical trial in which five medical institutions participated. RESULTS All 62 enrolled patients completed the clinical trial. The sensitivities of PDD were higher (84.4 and 75.8% in the 10 and 20 m g/kg-groups, respectively) than those of conventional endoscopic diagnosis (67.5 and 47.6%, respectively) (p = 0.014 and p < 0.001, respectively). Five episodes of serious adverse events developed in four patients; whereas a causal relationship with the investigational agent was ruled out in all episodes. CONCLUSION This investigator-initiated clinical trial confirmed the effectiveness and safety of PDD for NMIBC following oral administration of 5-ALA. Both doses of 5-ALA may be clinically applicable; however, the rate of detecting tumors only by PDD was higher in the 20 mg/kg-group suggesting that this dose would be more useful.

Plasma Soluble (Pro)renin Receptor Reflects Renal Damage.

Background (Pro)renin receptor [(P)RR], a specific receptor for renin and prorenin, was identified as a member of the renin-angiotensin system (RAS). (P)RR is cleaved by furin, and soluble (P)RR [s(P)RR] is secreted into the extracellular space. Previous reports have indicated that plasma s(P)RR levels show a significant positive relationship with urinary protein levels, which represent renal damage. However, it is not fully known whether plasma s(P)RR reflects renal damage. Methods We recruited 25 patients who were admitted to our hospital to undergo heminephrectomy. Plasma s(P)RR levels were examined from blood samples drawn before nephrectomy. The extent of renal damage was evaluated by the levels of tubulointerstitial fibrosis. Immunohistochemical analysis of intrarenal (P)RR and cell surface markers (cluster of differentiation [CD]3, CD19, and CD68) was performed on samples taken from the removed kidney. Moreover, double staining of (P)RR and cell surface markers was also performed. Results There were significant positive relationships between plasma s(P)RR and tubulointerstitial fibrosis in all the patients and those not receiving RAS blocker therapy. Significant positive relationships were found between plasma s(P)RR levels and the extent of tubulointerstitial fibrosis after adjustment for age, sex, body weight, blood pressure, and plasma angiotensin II, in all the patients and those not receiving RAS blockers. Moreover, (P)RR expression was elevated in infiltrated mononuclear cells but not connecting tubules or collecting ducts and vessels. Infiltrated cells positive for (P)RR consisted of CD3 and CD68 but not CD19. Conclusions These data suggest that plasma s(P)RR levels may reflect (P)RR expression levels in infiltrated mononuclear cells, which can be a surrogate marker of renal damage.

Transurethral resection of the bladder tumour (TURBT) for non-muscle invasive bladder cancer: basic skills.

Transurethral resection of the bladder tumour (TURBT) is the standard surgical procedure for non‐muscle invasive bladder cancer. We believe that all urologists should be trained in this procedure. This DVD provides an overview of TURBT with particular focus on basic skills, including basic surgical techniques such as the obturator nerve block.

Arteriosclerosis Related Factors Had No Clinical Significant Correlation With Resistive Index in Symptomatic Benign Prostatic Hyperplasia

OBJECTIVE To investigate whether the resistive index (RI) in symptomatic benign prostatic hyperplasia (BPH) could be used as a surrogate index of the severity of lower urinary tract symptoms (LUTS) due to BPH, and whether arteriosclerosis-related factors were associated with the RI in LUTS due to BPH. METHODS From January 2005 to April 2008, a total of 625 men with LUTS due to BPH were prospectively enrolled. Patients with heart failure, liver cirrhosis, prostatic cancer, neurogenic bladder, acute prostatitis, acute urinary retention, urethral stenosis, history of transurethral resection or any drug treatment for BPH, or currently under drug treatment for type 2 diabetes mellitus or dyslipidemia were excluded. Variables analyzed included estimated smoking status, blood pressure, body mass index (BMI), serum fasting glucose (FBS), lipid profile (low-density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglyceride), serum prostate-specific antigen, International Prostatic Symptom Score (IPSS), quality of life score, maximum urinary flow rate (Q(max.)), and postvoid residual urine volume (PVR). We also measured total prostate volume, transition zone (TZ) index, and RI using transrectal ultrasonography. Correlations among parameters were statistically examined. RESULTS RI was significantly correlated with IPSS, Q(max.), and PVR, but not with blood pressure, BMI, or FBS. On multiple regression analysis, RI was a significant independent variable of IPSS, TZ index, and PVR. CONCLUSIONS These findings suggest that RI might represent a surrogate index of the severity of LUTS due to BPH, and that RI might have no clinically significant relationship with arteriosclerosis-related factors.

Successful treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with laparoscopic adrenalectomy: a case series

IntroductionAdrenocorticotropic hormone-independent macronodular adrenal hyperplasia, characterized by bilateral macronodular adrenal hypertrophy and autonomous cortisol production, is a rare cause of Cushing’s syndrome. Bilateral adrenalectomy is considered the standard treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia but obliges the patient to receive lifetime steroid replacement therapy subsequently, and may increase the patient’s risk of adrenal insufficiency. These circumstances require surgeons to carefully consider operative strategies on an individual basis.Case presentationWe performed successful laparoscopic adrenalectomy on four patients with adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. Computed tomography scans showed bilateral adrenal enlargement in all patients. Case 1: a 56-year-old Japanese woman presented with obvious Cushing’s symptoms during treatment for diabetes mellitus and hypertension. Case 2: a 37-year-old Japanese man also presented with Cushing’s symptoms during treatment for diabetes mellitus and hypertension. These patients were diagnosed as Cushing’s syndrome caused by adrenocorticotropic hormone-independent macronodular adrenal hyperplasia based on endocrinologic testing, and underwent bilateral laparoscopic adrenalectomy. Case 3: an 80-year-old Japanese woman was hospitalized due to unusual weight gain and heightened general fatigue, and was diagnosed as Cushing’s syndrome caused by adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. She underwent unilateral laparoscopic adrenalectomy due to high operative risk. Case 4: a 66-year-old Japanese man was discovered to have bilateral adrenal tumors on medical examination. He did not have Cushing’s symptoms and was diagnosed as subclinical Cushing’s syndrome due to suppressed adrenocorticotropic hormone serum levels and loss of cortisol circadian rhythm without abnormal levels of serum cortisol. He underwent unilateral laparoscopic adrenalectomy. During follow-up, serum cortisol levels were within the normal range in all cases, and serum adrenocorticotropic hormone levels were not suppressed. Further, cases with Cushing’s syndrome experienced clinical improvement.ConclusionsWe were able to effectively treat adrenocorticotropic hormone-independent macronodular adrenal hyperplasia in patients with obvious Cushing’s symptoms by laparoscopic bilateral adrenalectomy, which promptly improved symptoms. Further, unilateral adrenalectomy was effective for treating an older patient at high operative risk and a patient with subclinical Cushing’s syndrome.

Reduced expression of the DNA glycosylase gene MUTYH is associated with an increased number of somatic mutations via a reduction in the DNA repair capacity in prostate adenocarcinoma

8‐Hydroxyguanine (8OHG), a major oxidative DNA lesion, is known to accumulate in prostate cancer; however, the status of one of its repair enzymes, MUTYH, in prostate cancer remains to be elucidated. In this study, we showed that the expression levels of MUTYH mRNA and protein were significantly lower in prostate cancer than in non‐cancerous prostatic tissue by examining two independent, publicly available databases and by performing an immunohistochemical analysis of prostate cancer specimens obtained at our hospital, respectively. About two‐thirds of the prostate cancers exhibited a reduced MUTYH expression. When the effect of reduced MUTYH expression in prostate adenocarcinoma on the somatic mutation load was examined using data from the Cancer Genome Atlas (TCGA) database, the numbers of total somatic mutations and somatic G:C to T:A mutations were significantly higher in the reduced MUTYH expression group than in the other group (P < 0.0001 and P = 0.0013, respectively). To determine the reason why reduced MUTYH expression leads to somatic mutation loads in prostate adenocarcinoma, we compared the DNA repair capacities between PC‐3 prostatic cell line derived clones with different MUTYH expression levels. Both the capacities to cleave DNA containing adenine:8OHG mispairs and to suppress mutations caused by 8OHG were significantly lower in prostatic cell lines with lower MUTYH expression than in prostatic cell lines with higher MUTYH expression. These results suggested that reduced MUTYH expression is associated with somatic mutation loads via a reduction in DNA repair capacity in prostate adenocarcinoma.