Prognostic model with alkaline phosphatase, lactate dehydrogenase and presence of Gleason pattern 5 for worse overall survival in low-risk metastatic hormone-sensitive prostate cancer.

BACKGROUND: Randomized trials showed the survival benefits of the combined use of androgen receptor axis-targeted agents with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer (mHSPC), regardless of the risk. However, treating patients with low-risk mHSPC with such intensive treatment is still debatable. METHODS: This retrospective study included 155 low-risk patients among 467 mHSPC patients treated in our affiliated institutions. The association between predictive factors and treatment outcomes was estimated using the Kaplan-Meier method and log-rank test. Predictive factors for castration resistant prostate cancer (CRPC)-free survival were investigated using Cox regression analyses. RESULTS: During the median follow-up of 39 months, 38.7% of patients developed CRPC and 14.2% died. In the multivariate analyses, a presence of Gleason pattern 5 (hazard ratio [HR] 2.04), high alkaline phosphatase (HR 1.007) and high lactate dehydrogenase (HR 1.009) were significant predictive factors for shorter CRPC-free survival. Finally, 155 patients were stratified into favorable- and unfavorable-risk groups based on the numbers of the predictive factors. The overall survival (OS) in the unfavorable-risk group (total scores: 2-3) was significantly worse than that of the favorable-risk group (total score: 0-1) (P = 0.02). This prognostic model was assessed with 50 low-risk mHSPC patients from the external validation dataset and found both the time to CRPC, and the OS in the unfavorable-risk group was significantly worse than that of the favorable-risk group (P < 0.01). CONCLUSIONS: The combination of Gleason pattern 5, high alkaline phosphatase and lactate dehydrogenase can predict those with worse OS in low-risk mHSPC patients.

High pressure balloon dilation for vesicourethral anastomotic strictures after radical prostatectomy.

BACKGROUND: Vesicourethral anastomotic stricture (VAS) is a rare but serious complication following radical prostatectomy (RP), and various types of managements for VAS have been proposed. We investigated the efficacy of transurethral balloon dilation in the management of VAS after RP. METHODS: A total of 128 consecutive patients underwent open RP at our hospital between 2008 and 2013; of these, 10 patients (7.8%) developed VAS. Transurethral balloon dilation was performed in all 10 patients, using a high pressure balloon catheter under fluoroscopic and endoscopic guidance. Follow-up endoscopy was performed, and patients in whom the stricture had recurred underwent repeat dilation. We retrospectively evaluated the management of VAS and short-term efficacy of high pressure balloon dilation. RESULTS: The mean time from RP to diagnosis of VAS was 9 months (2-40 months); eight patients (80%) were diagnosed within 6 months of RP. Balloon dilation of VAS was technically successful in all patients, and no perioperative complications were recorded. The median follow-up after balloon dilation was 24 months (7-67 months). There was no recurrence of VAS in eight patients (80%) after the first balloon dilation, and all patients were controlled within the twice. CONCLUSION: High pressure balloon dilation is a highly effective and minimally invasive procedure for treating VAS.

[Clinical Evaluation of Primary Aldosteronism with Subclinical Cushing's Syndrome].

Primary aldosteronism characterized by the overproduction of aldosterone by the adrenal glands, is sometimes accompanied by autonomous cortisol secretion. In this study, we retrospectively analyzed 8 cases of primary aldosteronism (PA) with subclinical Cushing's syndrome (SCS). A total of 71 patients with PA underwent surgery at Jikei University Hospital from 2004 to 2013, and 8 of them were diagnosed with coexistent SCS. Four patients were male and four were female. The mean patient age was 56.9 years. One of the patients also had pheochromocytoma in the adrenal gland on the ipsilateral side. All patients had hypertension, 6 had hypokalemia, 5 had diabetes mellitus, and 3 had hyperlipidemia. All patients had autonomous cortisol secretion as shown in 1 mg- or 8 mg-dexamethasone suppression tests even though baseline cortisol levels were normal. Adrenal venous blood sampling with adrenocorticotropic hormone (ACTH) stimulation was performed on 5 patients, but the localization of PA could not be detected in 1 patient. Adrenocortical scintigraphy revealed suppression of the contra-lateral adrenal uptake in all 7 patients. Six patients including one patient who showed complete suppression of the contra-lateral adrenal uptake in adrenocortical scintigraphy, and 2 patients, whose ACTH levels were less than the detection limit, received postoperative steroid hormone replacement. In the literature, SCS co-existed in approximately 8. 6% of the patients with PA. In our study, SCS co-existed in approximately 11.3%. The degree of the autonomous secretion of cortisol varied with the patient, and some cases are accompanied by Cushing's syndrome. Therefore, it is important to analyze the autonomous cortisol secretion even in patients with PA.

Cross-sensitization mechanisms between colon and bladder via transient receptor potential A1 stimulation in rats.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to analyze the mechanism underlying cross-sensitization between the colon and the bladder via activation of transient receptor potential A1 (TRPA1) channels. METHODS: Using female Sprague-Dawley rats, polyethylene catheters were inserted into the colon between two ligations at the levels of 40 and 60 mm rostral to the anus and into the bladder. (1) We examined changes in colon and bladder activity after the application of allyl isothiocyanate (AI, 50 mM, 300 µl), a TRPA1 activator, into the colon or the bladder in an awake condition. Inhibitory effects of the pretreatment with HC-030031 (HC, 3 mg/kg), a TRPA1 inhibitor, on colon-to-bladder cross-sensitization induced by AI instilled in the colon were also investigated. (2) We examined Evans blue (EB) dye extravasation after TRPA1 stimulation in the colon or the bladder to evaluate vascular permeability due to tissue inflammation. RESULTS: (1) Intercontraction intervals during continuous saline infusion into the bladder (0.04 ml/min) were significantly decreased after the intracolonic AI application, which significantly increased mean intracolonic pressure, indicative of colon-to-bladder cross-sensitization. The AI-induced colon-to-bladder cross-sensitization was completely prevented by the pretreatment with intravenous application of HC. On the other hand, mean intracolonic pressure was significantly decreased after the intravesical AI application, which significantly increased mean intravesical pressure. (2) EB dye extravasation was significantly increased in the AI-treated inflamed organs and also in the bladder following intracolonic AI treatment. CONCLUSIONS: Colon-to-bladder cross-sensitization is mediated via TRPA1 stimulation in the colon, although TRPA1 expressed in the bladder does not seem to participate in bladder-to-colon cross-sensitization.

[Six cases of renal collecting duct carcinoma].

We treated 6 patients with renal collecting duct carcinoma (CDC) in our hospital from December 2004 to December 2011. We compared clinico-pathological findings among all patients. The median age was 58 years (range, 37-77 years). Hematuria, back pain, and fatigue were observed in 5 patients with CDC. Five patients were pathologically diagnosed by radical nephrectomy while a patient was diagnosed by percutaneous renal biopsy without radical nephrectomy. Lymph node metastasis and distant metastasis were observed at diagnosis in 3 and 2 patients, respectively. Five of the 6 patients received systemic therapy after surgery, cytokine therapy in 2 patients, systemic chemotherapy in a patient, and molecular-targeting therapy in 2 patients, respectively. The median overall survival was 15 months (range, 1-44 months). Overall, the 1- and 3-year survival rates were 67 and 33%, respectively. Most of the patients had symptomatic advanced disease at diagnosis. Even though nephrectomy was performed, systemic treatment was not effective in such patients.

[Giant subcutaneous hematoma with hemorrhagic shock induced by goserelin acetate injection for prostate cancer : report of a case].

A 87-year-old man was diagnosed with prostate cancer (cT2aN0M0 Gleason score 4＋4 with initial prostate specific antigen of 23.4 ng/ml). Prostate cancer was treated with combined androgen blockade (goserelin acetate plus flutamide). He was administered goserelin acetate depot injection without any complications as an outpatient. However, 5 hours after he left the hospital, he came back to the hospital, complaining of lower abdominal pain. Abdominal computed tomography revealed a giant subcutaneous hematoma in the lower abdomen. Hemoglobin was 6.9 g/dl and blood pressure was lower than 80 mmHg. He was admitted and given a blood transfusion. Because of pre-disseminated intravascular coagulation score 6, it was hard to antagonize warfarin by Vitamin K (he had taken warfarin because of atrial fibrillation). Arteriography was performed and injury to a branch of the lower epigastric artery was found. Transcatheter arterial embolization was performed at the same time. Injecting goserelin acetate may cause severe arterial injury.

Pathophysiology of urinary incontinence in murine models.

Urethral closure mechanisms under stress conditions consist of passive urethral closure involving connective tissues, fascia and/or ligaments in the pelvis and active urethral closure mediated by hypogastric, pelvic and pudendal nerves. Furthermore, we have previously reported that the active urethral closure mechanism might be divided into two categories: (i) the central nervous control passing onto Onuf's nucleus under sneezing or coughing; and (ii) the bladder-to-urethral spinal reflex under Valsalva-like stress conditions, such as laughing, exercise or lifting heavy objects. There are over 200 million people worldwide with urinary incontinence, a condition that is associated with a significant social impact and reduced quality of life. Therefore, basic research for urinary continence mechanisms in response to different stress conditions can play an essential role in developing treatments for stress urinary incontinence. It has been clinically shown that the etiology of stress urinary incontinence is divided into urethral hypermobility and intrinsic sphincter deficiency, which could respectively correspond to passive and active urethral closure dysfunction. In this review, we summarize the representative stress urinary incontinence animal models and the methods to measure leak point pressures under stress conditions, and then highlight stress-induced urinary continence mechanisms mediated by active urethral closure mechanisms, as well as future pharmacological treatments of stress urinary incontinence. In addition, we introduce our previous reports including sex differences in urethral closure mechanisms under stress conditions and urethral compensatory mechanisms to maintain urinary continence after pudendal nerve injury in female rats.

[The prevalence of hypertension after adrenalectomy in patients with primary aldosteronism].

The cure rate of hypertension after surgery for primary aldosteronism (PA) was assessed in a single institution. In the present study, we studied the risk factors on the cure rate of hypertension after surgery in patients with PA. Thirty-five patients who underwent surgery for PA between January 2004 and December 2009, with a follow-up time of 1 year or longer were studied. The mean age at surgery was 50.7 years old. The male to female ratio was 24 : 11. Factors confounding the cure rate of hypertension after surgery were analyzed using the univariate and the multivariate analysis. Nineteen (54%) of the 35 patients were completely cured after surgery. In most cases, a complete cure was seen within 1 month after surgery. At 1 year after surgery, the dose of medication for hypertension could be decreased in 11 (13%) of the 16 non cured patients. Although hypertension in patients with PA may be curable by surgery, the cure rate of hypertension after surgery has been reported to be from 16 to 67%. In the present study, age, gender, preoperative serum creatinine, the period of hypertension, the number of medications for hypertension, and family history for hypertension were significant in the univariate analysis for the cure rate of hypertension (persistent hypertension) after surgery. Multivariate analysis showed that the age of 55 years old or older was a significant predictor for non-curable hypertension after surgery. Our result suggests that earlier surgery may contribute to a better outcome on the cure rate of postoperative hypertension in patients with PA.

Time-dependent changes in bladder function and plantar sensitivity in a rat model of fibromyalgia syndrome induced by hydrochloric acid injection into the gluteus.

OBJECTIVE: To examine the correlation between muscular pain and bladder hypersensitivity in order to clarify the pathogenesis of comorbidity of bladder pain syndrome/interstitial cystitis with other chronic pain conditions such as fibromyalgia syndrome (FMS). MATERIALS AND METHODS: Under isoflurane anaesthesia, 0.2 mL of hydrochloric acid (HCl) solution (pH 4.0) was injected into the bilateral gluteus muscles of female Sprague-Dawley rats to produce an FMS model, as the gluteus is one of the specific tender points in patients with FMS. Control rats received saline injection (0.2 mL). The mechanical sensitivity of the plantar was evaluated using the mean number of bilateral hindlimb withdrawals in response to tactile stimulation with a 2.0-g von Frey filament at 1, 2 and 3 weeks after the HCl injection. In a separate rat group, cystometry was performed with the rats awake during saline infusion (0.06 mL/min) into the bladder before and after 1% lidocaine injection (0.2 mL) into the bilateral gluteus 1, 2 and 3 weeks after the HCl injection. RESULTS: The mean number of hindlimb withdrawals was significantly higher in FMS rats than in controls at 1 and 2 weeks. Using cystometry, we found that the intercontraction interval (ICI) and voided volume (VV) were significantly lower in FMS rats than in controls at 1 and 2 weeks. In addition, the voiding threshold pressure, ICI and VV were significantly higher after lidocaine injection in FMS rats, but not in controls, at 1 and 2 weeks. CONCLUSIONS: HCl injection (pH 4.0) into the gluteus can induce plantar hypersensitivity and urinary frequency for up to 2 weeks after the injection, suggesting that somatic (gluteus)-to-visceral (bladder) cross-sensitization might underlie bladder hypersensitivity in patients with FMS. Moreover, intervention at specific tender points outside the bladder could be effective in treating urinary frequency because lidocaine injection into the gluteus normalized bladder function in FMS rats for up to 2 weeks.

[Evaluation of supplemental administration of Eviprostat in patients with benign prostatic hyperplasia with persistent symptoms following treatment with alpha1-adrenoceptor blocker].

We examined the effectiveness of supplemental administration of Eviprostat in patients with benign prostatic hyperplasia (BPH) whose lower urinary tract symptoms (LUTS) caused by BPH were not adequately relieved by an alpha1-adrenoceptor blocker. Twenty-nine patients with insufficient improvement in the International Prostate Symptom Score (IPSS) and quality of life (QOL) score after administration of 50 mg naftopidil for 4 weeks or more received 6 tablets of Eviprostat in addition to naftopidil for another 2 weeks or more. With supplemental administration of Eviprostat, significant improvement was observed in the symptoms of incomplete emptying, daytime frequency, intermittency, weak stream, total IPSS, sum of the IPSS subscores for voiding symptoms (intermittency, weak stream and straining), sum of the IPSS subscores for storage symptoms (daytime frequency, urgency and nocturia), and QOL score. Supplemental administration of Eviprostat is therefore effective for the improvement of LUTS and QOL in BPH patients resistant to an alpha1-adrenoceptor blocker.

[A case of adrenocortical carcinoma with masculinization, obtaining long prognosis with surgical treatment alone].

A 28 year-old woman presented right upper abdominal pain. She had been pointed out her masculinization and amenorrhea. CT scan and magnetic resonance imaging showed right adrenal tumor. In the endocrinological study, the serum cortisol and testosterone was elevated. Transabdominal right adrenalectomy and nephrectomy was carried out and histopathological diagnosis was adrenocortical carcinoma. The masculine symptom had disappeared after the operation and she has been without recurrence for five years.

[Mucinous adenocarcinoma of the prostate: a case report and review of 32 cases on immunohistochemical study of both PSA and CEA].

Mucinous adenocarcinoma of the prostate is extremely rare and its biological behavior is not well known. We report a case of mucinous adenocarcinoma of the prostate which stained positively for prostate specific antigen (PSA) and negatively for carcinoembryonic antigen (CEA) on immunohistochemical study. Our case contained conventional adenocarcinomas and no signet-ring cells. Thirty two cases of mucinous adenocarcinoma of the prostate which performed on immunohistochemical study of both PSA and CEA, including our case, were reviewed. 17 of the 23 cases of immunoreactive to PSA contained conventional adenocarcinomas, and 3 of the 10 cases of immunoreactive to CEA contained them, respectively. The 6 cases of immunoreactive to CEA only contained signet-ring cells. It indicated that there seemed to be the two types of mucinous adenocarcinoma of the prostate, the one which stained positively for PSA was the subtype of conventional adenocarcinomas, and the other which stained positively for CEA and negatively for PSA was derived from the intestinal metaplasia with atypia of the prostatic urethra.

[Clinical studies on TUR-P using clinical path: report of 50 cases and review of literature].

PURPOSE: This study was undertaken to clarify the usefulness and problems involved in the clinical path of transurethral prostatectomy (TUR-P) in hospital. PATIENTS AND METHODS: The subjects consisted of 50 patients, for whom the Department of Urology, Jikei Medical University Hospital introduced its own clinical path and performed TUR-P during a period of 9 months from July 1999 to March 2000. The mean length of hospital stay, rate of postoperative complications, and the medical insurance claims made by these patients were clarified and compared with those of 73 patients before introduction of the clinical path. RESULTS: With the introduction of the clinical path, the length of hospital stay decreased by an average of 3.4 days and the total medical insurance claims decreased by an average of 18.5%. The rate of postoperative complications before and after introduction was almost equal. CONCLUSION: Our clinical path for TUR-P was well accepted by both patients and comedicals. However, the present medical treatment system in Japan is not as yet prepared to promote the introduction of this clinical path, and it will take some time before this clinical path is introduced on a full scale.

Clinical studies on inverted papilloma of the urinary tract: report of 48 cases and review of the literature.

PURPOSE: We report on 48 clinicopathologic cases of inverted papilloma and present the clinical significance attributed to these lesions in terms of the current literature. MATERIALS AND METHODS: From 1976 to 2002 we had experience with 48 cases of inverted papilloma in urinary tract. We present the clinical features of these cases and report the results of prognosis research. RESULTS: Patient age ranged from 24 to 82 years (mean 56). Coexistence of transitional cell carcinoma occurred in a different location in the bladder in 3 cases and within a single neoplasm in the ureter in 2. Followup data were available in 42 of the 48 cases. Followup ranged from 8 months to 23 years 6 months (mean 8 years 1 month). Of the 42 cases 3 (7%) had a recurrence and range from initial resection at 5 months, 1 year 4 months and 2 years 6 months, respectively. CONCLUSIONS: Our study suggests that there are 2 types of urinary inverted papilloma. The lesions in 1 type behave in a benign fashion and in another they have malignant potential. At this time we have no strategy with which to distinguish the 2 types of urinary inverted papilloma. Our results indicate that we must follow all cases for at least more than 2 years after initial treatment.