Development of nomogram to non-steroidal antiandrogen sequential alternation in prostate cancer for predictive model.

OBJECTIVES: To clarify clinical predictors for a prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy and to develop a nomogram to predict the prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy in patients with advanced prostate cancer that relapsed after initial combined androgen blockade. We previously reported that combined androgen blockade with an alternative non-steroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial combined androgen blockade. METHODS: We enrolled 161 patients from 14 medical institutions with histologically confirmed prostate cancer who had been treated with combination therapy and in whom cancer progressed after first-line combined androgen blockade therapy. A nomogram for the prostate-specific antigen decrease ≥50% from baseline prostate-specific antigen in response to alternative non-steroidal antiandrogen therapy was developed based on the final logistic regression model. RESULTS: Overall prostate-specific antigen decreased ≥50% in 75 of 161 patients (46.6%) in response to alternative non-steroidal antiandrogen therapy. Using five independent risk factors (initial serum level of prostate-specific antigen, hemoglobin, C-reactive protein, prostate-specific antigen nadir to second hormone therapy and Gleason sum), a nomogram was developed for the prediction of prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy. The receiver operating characteristic curve showed that the accuracy of the predicted probability was 72.5% for the model. CONCLUSIONS: This predictive nomogram could predict the prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy and might be of benefit to determine the sequential treatment strategy in patients with relapse after first combined androgen blockade.

Retroperitoneal biloma-A rare differential diagnosis of perirenal fluid accumulation.

Introduction: Nontraumatic biliary rupture and retroperitoneal biloma infrequently occur. Here, we report a case of retroperitoneal biloma due to spontaneous left hepatic duct perforation, which was difficult to differentiate from a perirenal abscess. Case presentation: A 94-year-old female patient was hospitalized with symptoms of fatigue and right back pain that lasted for 5 days. Computed tomography revealed fluid accumulation in the retroperitoneum, and urinary extravasation and right perinephric abscess were suspected. Antimicrobial treatment and drainage with ureteral stents and urethral catheters demonstrated no symptom improvement. Ultrasound-guided puncture of the abscess revealed the presence of bile. Pigtail catheter drainage improved symptoms and inflammatory response. After diagnosis, endoscopic retrograde cholangiopancreatography revealed bile leakage, and a bile duct stent was inserted. Conclusion: Biloma can cause perirenal fluid accumulation, and they should be considered an origin of perirenal fluid accumulation when urinary tract lesions are excluded.

Bladder cancer with urinary diversion by a sigmoid colon conduit after transverse colon stoma.

Introduction: Sigmoid conduit is one of the methods for achieving urinary diversion, but it is performed less frequently than ileal conduit and ureterostomy. Herein, we report a case in which a sigmoid colon conduit was performed after nephrostomy and transverse colostomy. Case presentation: A 70-year-old man was referred to our hospital because of a bladder tumor. Computed tomography and transurethral biopsy revealed advanced bladder cancer with ureteral and rectal invasion. Despite drug therapy, the tumor progressed. Thus, nephrostomy and transverse colostomy were performed for urinary and fecal diversion, respectively. Subsequently, chemotherapy was administered for 8 months. As nephrostomy-related complications occurred frequently during chemotherapy, a sigmoid colon conduit was performed instead of nephrostomy for urinary diversion to improve the patient's quality of life. Conclusion: In patients with advanced bladder cancer requiring a double stoma of the urinary and fecal tracts, sigmoid colon conduit may be selected as a urinary diversion method.

Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade.

PURPOSE: Large meta-analyses have documented that maximum androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer confers survival benefits, although it remains controversial. Also, we and others have reported the effectiveness of second line hormonal therapy for prostate cancer that relapses after initial hormone therapy. However, there is little clinical evidence of the effectiveness of the latter treatment strategy. Therefore, in this multicenter trial in Japan we analyzed clinical outcomes following alternative changing from 1 nonsteroidal antiandrogen to another, ie bicalutamide to flutamide and flutamide to bicalutamide, for advanced prostate cancer that relapsed after initial maximum androgen blockade. MATERIALS AND METHODS: The study included 232 patients with advanced prostate cancer who were initially treated with maximum androgen blockade, including surgical or medical castration combined with nonsteroidal antiandrogens. If a patient relapsed while on first line therapy, we discontinued antiandrogen and evaluated the patient for antiandrogen withdrawal syndrome. We then administered an alternative antiandrogen and evaluated its effect. RESULTS: The incidence of antiandrogen withdrawal syndrome after initial maximum androgen blockade was 15.5% for bicalutamide and 12.8% for flutamide. A prostate specific antigen decrease after antiandrogen withdrawal was a prognostic factor. Nonsteroidal antiandrogens as alternative therapy in patients with relapse after the initial maximum androgen blockade were effective (prostate specific antigen decrease greater than 50%) as second line maximum androgen blockade. Of 232 patients 142 (61.2%) showed a prostate specific antigen decrease in response to an alternative antiandrogen. These responders had significantly better survival than nonresponders, suggesting that responsiveness to second line therapy predicts increased survival. CONCLUSIONS: Following maximum androgen blockade with an alternative nonsteroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial maximum androgen blockade. Even a partial response to second line maximum androgen blockade was associated with improved survival. Our data support the notion that responders to second line regimens are androgen independent but still hormonally sensitive.

Differential impact of lower urinary tract symptoms on generic and disease-specific quality of life in men and women.

INTRODUCTION: We investigated how generic and disease-specific measures differ in estimating the quality of life (QoL) impact of lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 172 men and 67 women >or=40 years old who attended the public lectures completed the questionnaire comprising the International Prostate Symptom Score, benign prostatic hyperplasia impact index and SF-36 Health Survey. The multiple regression analysis was performed to evaluate the QoL impact of LUTS. RESULTS: Both storage and voiding symptoms showed significant correlations with disease-specific QoL. Among men, voiding symptom correlated more closely with disease-specific QoL than storage symptom did, and this finding was reversed among women. Storage but not voiding symptoms showed a significant correlation with generic QoL. Among men, storage symptom correlated more closely with mental health than physical health, and the reversed finding was obtained among women. Generic QoL, especially physical health, was significantly influenced by some comorbid diseases, but disease-specific QoL was not. CONCLUSIONS: The QoL impact of LUTS was differentially estimated by disease-specific and generic measures with sex differences.

Endovascular treatment of ureteroarterial fistulas with stent-grafts.

Ureteroarterial fistula is a rare condition with life-threatening hematuria that should be diagnosed and treated immediately. We reported two patients of ureteroarterial fistula who underwent successful endovascular treatment by stent-grafts. They had undergone pelvic surgery followed by placement of an indwelling ureteral stent for stricture of the ureter before sudden hematuria occurred. Routine contrast-enhanced computed tomography did not reveal extravasation or a pseudo-aneurysm. Angiograms with multiple oblique views demonstrated small pseudoaneurysms of the iliac artery overriding the ipsilateral ureter. The endovascular treatment of ureteroarterial fistula using stent-grafts was successful, and the hematuria disappeared immediately after stent-graft deployment. The hematuria did not recur up to the last follow-up visits of 3 and 19 months, respectively.

Retroperitoneoscopic nephron-sparing surgery of renal tumor using a microwave tissue coagulator without renal ischemia: comparison with open procedure.

PURPOSE: It is ideal to use not a transperitoneal but a retroperitoneal approach for both open and endoscopic partial nephrectomy. We compared the results of retroperitoneoscopic nephron-sparing surgery for small renal tumors using a microwave tissue coagulator without renal pedicle clamping with those of a retroperitoneal open procedure. PATIENTS AND METHODS: Between 1996 and 2002, eight patients with small renal tumors underwent retroperitoneoscopic partial nephrectomy without renal ischemia, and nine patients with small renal tumors underwent open partial nephrectomy via a retroperitoneal approach. Both groups were operated on using a microwave tissue coagulator. RESULTS: Retroperitoneoscopic partial nephrectomy without renal ischemia was performed without any major or minor complications in any patient. The mean operation time for retroperitoneoscopic surgery was significantly longer than that for open partial nephrectomy (221.9 minutes v 145.9 minutes; P = 0.0004). However, the mean estimated blood loss for retroperitoneoscopic surgery was less than that for open partial nephrectomy (137.5 mL v 334.8 mL; P = 0.012). In addition, the retroperitoneoscopic group seemed to recover more rapidly than the open surgery group. CONCLUSIONS: Retroperitoneoscopic nephron-sparing surgery of small renal tumors using a microwave tissue coagulator without renal ischemia is feasible as minimally invasive procedure. It results in saving renal function, minimal blood loss, and rapid recovery.

[Pharmacokinetics of paclitaxel and carboplatin in a hemodialysis patient with metastatic urothelial carcinoma--a case report].

A 69-year-old-man undergoing hemodialysis for 8 years developed metastatic urothelial carcinoma and received combination chemotherapy with paclitaxel and carboplatin. Paclitaxel 175 mg/m2 was given as a 3-hour intravenous infusion, and carboplatin was dosed to the area under the plasma concentration-time curve (AUC) of 5 mg.min/ml calculated according to the Calvert formula as a 30-minute intravenous infusion immediately after paclitaxel. Hemodialysis was started 1 hour after carboplatin, then their pharmacokinetics was determined in the patient. The AUC of paclitaxel and carboplatin were 15.2 and 64.56 micrograms.h/ml, respectively. The metastatic tumor size was reduced by more than 20% after 3 courses of this chemotherapy. Grade 3 neutropenia and grade 1 thrombopenia were observed. This is the first report that the combination of paclitaxel and carboplatin is feasible in a patient with metastatic urothelial carcinoma undergoing hemodialysis, with low toxicity and safety.

Real-time quantitative analysis for human telomerase reverse transcriptase mRNA and human telomerase RNA component mRNA expressions as markers for clinicopathologic parameters in urinary bladder cancer.

AIM: The expression of the telomerase subunits such as human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTR) may be associated with tumor development and progression. We evaluated the relationship between mRNA quantification of both hTERT and hTR and clinicopathologic parameters in bladder cancer. METHODS: We examined the mRNA expression of hTERT and hTR in 29 specimens with bladder cancer (Grade: Grade I, 9 cases; Grade II, 13 cases and Grade III, 7 cases. Stage: pTa-pT1, 18 cases; pT2-T4, 11 cases). We immediately froze all of specimens obtained during TUR-Bt and isolated the total RNA from each specimen. We measured the quantity of hTERT, hTR and GAPDH mRNA by a real-time reverse transcription-polymerase chain reaction method based on TaqMan technology. RESULTS: The hTERT/GAPDH mRNA ratio and hTERT mRNA/total RNA in superficial bladder tumor was significantly lower than in invasive bladder tumor. The hTR/GAPDH mRNA ratio and hTR mRNA/total RNA in superficial tumor were significantly lower than in invasive bladder tumor. The hTERT mRNA expression significantly correlated with tumor grade, but the hTR mRNA expression did not correlate with tumor grade. There was no significant difference in the hTERT/GAPDH mRNA ratio and hTR mRNA/total RNA according to multiplicity of bladder tumor. CONCLUSIONS: Our results demonstrated that the expression of hTERT mRNA correlated with the progression of stage and grade in bladder cancer. The quantitative analysis of hTERT and hTR mRNA might be a marker for clinicopathologic parameters in bladder cancer.

Decreased expression of G protein-coupled receptor kinases in the detrusor smooth muscle of human urinary bladder with outlet obstruction.

AIM: We examine the expression of mRNA of G protein-coupled receptor kinase (GRK) subtypes and muscarinic acetylcholine receptor (M) subtypes in the detrusor smooth muscle of the human urinary bladder. Furthermore, we confirm the presence and the localization of GRK proteins in the detrusor smooth muscle of the obstructed bladder in comparison with the control bladder. METHODS: Detrusor smooth muscle tissues of the human urinary bladder were obtained from 12 male patients; 6 patients did not have bladder outlet obstruction, and the other 6 patients had bladder outlet obstruction. Portions of the dome or anterior wall of the urinary bladder were used for the present study. Reverse transcription/polymerase chain reaction for GRK2, M2 and M3 was performed using total RNA extracted from human urinary bladder detrusor. Antibodies to GRK2, GRK3 and GRK4 were used to confirm the presence of the protein product in the human urinary bladder using immunohistochemical staining and the western blotting technique. RESULTS: All complementary DNA (cDNA) transcribed from three different mRNA (M2, M3 and GRK2) were successfully amplified and size-fractionated. The expression of GRK2 protein was strong in the human bladder detrusor, but was significantly weakened by western blotting in obstructed bladder in comparison with control bladder. CONCLUSIONS: Failure in desensitization mechanisms of muscarinic acetylcholine receptors might be related to storage symptom elicited by overactivity in obstructed bladder with benign prostatic hyperplasia.

Modified endoscopic live donor nephrectomy: retroperitoneoscopy followed by hand-assistance.

We have developed a novel modification of previous approaches to donor nephrectomy and herein review our original operative procedure. First, the posterior aspect of the kidney was dissected retroperitoneoscopically and dissection of the renal artery, ureter and gonadal vein was almost completed. Second, the anterior aspect of the kidney was dissected with transperitoneal hand-assistance, and dissection of the renal pedicle from the anterior surface was accomplished easily and safely. This operative procedure was successfully performed for two donors with no intraoperative or postoperative complications. Our modified endoscopic donor nephrectomy is feasible as a minimally invasive procedure because of its safety, and its ability to preserve renal function and establish an excellent operative field for both posterior and anterior aspects of the kidney.

Lower urinary tract symptoms in men and women without underlying disease causing micturition disorder: a cross-sectional study assessing the natural history of bladder function.

PURPOSE: We examined the influence of aging on bladder function in men and women. MATERIALS AND METHODS: Using the International Prostate Symptom Score questionnaire with an additional question on urinary incontinence lower urinary tract symptoms were evaluated in all outpatients who first visited our urological department from June 2001 to December 2002. In 550 of the 1,201 patients who completed the questionnaire any pathological conditions that might cause micturition disorder could not be detected with urological examinations. Symptom scores of these patients without underlying disease causing micturition disorder were the basis of this study. RESULTS: In men and women total and storage symptom scores but not the voiding symptom score increased significantly with age. In each age group total, storage and voiding symp-tom scores were not significantly different between men and women. Women 50 to 69 years old had significant higher incontinence scores than men of the same age, whereas a significant increase in the incontinence score with age was found only in men. The quality of life score increased with age in men but not in women. However, the 2 sexes did not significantly differ in quality of life score. CONCLUSIONS: Lower urinary tract symptoms, especially storage symptoms, showed age related alterations in the 2 sexes without any underlying disease causing micturition disorder. The prevalence of urinary symptoms was not different between men and women. Therefore, bladder function in each sex might be subject to a gender independent aging process.

Diagnosis and treatment of voiding symptoms.

Lower urinary tract symptoms (LUTS) are associated with lower urinary tract dysfunction. Symptoms are the subjective indicator of a disease or change in condition as perceived by the patient, caregiver, or partner and may lead the individual to seek help from health care professionals. LUTS are usually qualitative and, therefore, cannot usually be used to make a definitive diagnosis. LUTS also can indicate pathologies other than lower urinary tract dysfunction, such as urinary infection. LUTS are divided into 7 groups: storage, voiding (obstructive), postmicturition symptoms and 4 others. Voiding symptoms, which are caused by lower urinary tract obstruction, include slow stream, splitting or spraying, intermittency, hesitancy, straining, and terminal dribble. Postmicturition symptoms, which are experienced immediately after micturition, consist of the feeling of incomplete emptying and postmicturition dribble. Postmicturition dribble describes the involuntary loss of urine immediately after the individual has finished passing urine; in men, usually after leaving the toilet and in women, after rising from the toilet. Hence, postmicturition dribble is elicited by different situations or is considered as having different implications. For example, although postmicturition dribble usually implies incomplete emptying (voiding symptoms) in elderly men with benign prostatic hyperplasia, postmicturition dribble is often considered as urinary incontinence (a storage symptom) in many patients, even with bladder outlet obstruction. In such cases, detailed history taking and further evaluation, such as urinary flowmetry, postvoid residual volume, and comprehensive urodynamic evaluation, should be performed as appropriate. If no urodynamic abnormalities of either the detrusor or the outlet can be detected despite significant LUTS, factors unrelated to the lower urinary tract may be responsible for the voiding symptoms.