Risk for intravesical recurrence of bladder cancer stratified by the results on two consecutive UroVysion fluorescence in situ hybridization tests: a prospective follow-up study in Japan.

BACKGROUND: A previous comparative study in Japan has demonstrated that the two consecutive UroVysion tests are useful tools to detect the presence of bladder cancer during follow-up after transurethral resection, but they also presented their high rates of false-positive results. Here, we aimed to evaluate the relationship between the UroVysion tests and subsequent intravesical recurrence. METHODS: In the previous study, patients without bladder cancer during the first analysis showed the same examination set repeated 3 months later as the second analysis. In this follow-up study, 326 patients showed negative findings confirmed on cystoscopy during the second UroVysion test. Recurrence-free survival was assessed using a median follow-up of 27 months. RESULTS: In the two consecutive UroVysion tests, 214 patients (65.6%) showed negative UroVysion results in both tests, whereas 91 presented a positive result on either tests and 21 patients presented positive results in both tests. During the follow-up, 40 patients (12.3%) had an intravesical recurrence with non-muscle-invasive bladder cancer. The recurrence rates in patients with negative results in both tests, those with one positive result in either tests, and those with positive results in both tests were 8.4%, 16.5%, and 33.3%, respectively. The multivariate analysis indicated that the history of bladder cancer and the consecutive UroVysion test pattern were independent risk factors for recurrence. CONCLUSIONS: Our data confirmed the effectiveness of two consecutive UroVysion tests in predicting intravesical recurrence after TURBT. Further prospective studies would help determine an appropriate interval for cystoscopy follow-up.

Clinical evaluation of two consecutive UroVysion fluorescence in situ hybridization tests to detect intravesical recurrence of bladder cancer: a prospective blinded comparative study in Japan.

BACKGROUND: We evaluated the use of UroVysion fluorescence in situ hybridization tests to detect the intravesical recurrence of bladder cancer during follow-up after a transurethral resection of bladder tumor (TURBT). METHODS: In this prospective, blinded, comparative study, 486 patients treated by TURBT within the prior 2 years were registered at 12 centers. Urine cytology and UroVysion tests were performed once or twice at a central testing laboratory. For the patients with no suspicious findings of bladder cancer in the first analysis, the same examination set was repeated 3 months later as the second analysis. Totals of 468 and 399 patients were eligible for the first and second analyses, respectively. We determined the sensitivity and specificity of two consecutive UroVysion tests. RESULTS: Bladder cancers were identified in 44 patients at the first analysis. The UroVysion test had 50.0% (95% CI 35.2-64.8%) sensitivity and 72.4% (68.3-76.8%). Urine cytology had 4.5% (0.0-10.7%) sensitivity and 99.8% (99.3-100.0%) specificity. The concordant rate of the first and second UroVysion test results was 72% (kappa coefficient 0.157). Interestingly, the patients with two consecutive positive UroVysion test results had the highest cancer detection rate (14.8%), which is greater than those of the patients with a positive result in either (7.2%) or neither (1.2%) of the two tests at the 3-month follow-up. CONCLUSIONS: The UroVysion test provided higher sensitivity than urine cytology to detect bladder cancer during post-TURBT follow-up. Two consecutive UroVysion tests might be a better indicator to predict intravesical recurrence.

Randomized Controlled Study of the Efficacy, Safety and Quality of Life with Low Dose bacillus Calmette-Guérin Instillation Therapy for Nonmuscle Invasive Bladder Cancer.

PURPOSE: The optimal dose of intravesical bacillus Calmette-Guérin for the treatment of nonmuscle invasive bladder cancer is controversial. We investigated if induction therapy with low dose bacillus Calmette-Guérin could achieve a complete response rate similar to that of standard dose bacillus Calmette-Guérin, with less toxicity and higher quality of life. MATERIALS AND METHODS: After transurethral resection, patients with unresectable multiple nonmuscle invasive bladder cancer and/or carcinoma in situ were randomized to receive standard (80 mg) or low dose (40 mg) bacillus Calmette-Guérin instillation induction therapy (weekly, 8 times). The primary end point was noninferiority of low dose bacillus Calmette-Guérin with a null hypothesis of a 15% decrease in complete response rate. Secondary end points were recurrence-free survival, progression-free survival, overall survival, patient compliance, adverse events and quality of life using the EORTC QLQ-C30. RESULTS: In an intent to treat analysis of 166 patients the complete response rates for low dose and standard dose bacillus Calmette-Guérin were 79% (95% CI 0.70-0.88) and 85% (95% CI 0.77-0.92), respectively. Dunnett-Gent analysis revealed that the null hypothesis of inferiority of low dose bacillus Calmette-Guérin in terms of complete response could not be rejected (p = 0.119). However, there were no significant differences between the groups in terms of recurrence, progression and overall survival. Low dose bacillus Calmette-Guérin was associated with significantly less fever (p = 0.001) and micturition pain (p = 0.047), and significantly higher quality of life scores for global quality of life, role functioning and functional impairment. CONCLUSIONS: The noninferiority of low dose bacillus Calmette-Guérin was not proven. However, low dose bacillus Calmette-Guérin was associated with lower toxicity and higher quality of life compared to standard dose bacillus Calmette-Guérin in patients with nonmuscle invasive bladder cancer.

Serum exosomal P-glycoprotein is a potential marker to diagnose docetaxel resistance and select a taxoid for patients with prostate cancer.

OBJECTIVES: Docetaxel is used as the first-line chemotherapy for castration-resistant prostate cancer (CRPC), but docetaxel resistance occurs in part owing to induction of P-glycoprotein (P-gp) encoded by multidrug resistance protein 1 (MDR1) gene. A recently developed taxane-cabazitaxel-has poor affinity for P-gp and is thereby effective in docetaxel-resistant CRPC. It has been recently demonstrated that exosomes in the body fluids could serve as a diagnostic marker because they contain proteins and RNAs specific to the cells from which they are derived. In this study, we aimed to investigate if P-gp in blood exosomes could be a marker to diagnose docetaxel resistance and select a taxoid for patients with CRPC. METHODS AND MATERIALS: Exosomes were isolated by differential centrifugation from docetaxel-resistant prostate cancer (PC-3) cells (PC-3R) and their parental PC-3 cells and from the serum of patients. Silencing of P-gp was performed by small interfering RNA transfection. Protein expression was examined by Western blot analysis. Viability of cells treated with docetaxel or cabazitaxel was determined by water soluble tetrazolium salt (WST) assay. RESULTS: The level of P-gp was higher in exosomes as well as cell lysates from PC-3R cells than in those from PC-3 cells. Cabazitaxel effectively killed PC-3R cells, and MDR1 knockdown improved the sensitivity of PC-3R cells to docetaxel but not to cabazitaxel. The P-gp level in blood exosomes was relatively higher in clinically docetaxel-resistant patients than in therapy-naïve patients. CONCLUSIONS: Our results suggest that detection of P-gp in blood exosomes, which is involved in resistance to docetaxel but not to cabazitaxel, could be useful to diagnose docetaxel resistance and select an appropriate taxoid for patients with CRPC-docetaxel or cabazitaxel.

CCR1/CCL5 interaction promotes invasion of taxane-resistant PC3 prostate cancer cells by increasing secretion of MMPs 2/9 and by activating ERK and Rac signaling.

Castration-refractory prostate cancer (CRPC) is treated with taxane-based chemotherapy, but eventually becomes drug resistant. It is thus essential to identify novel therapeutic targets for taxane resistance in CRPC patients. We investigated the role of the chemokine (C-C motif) receptor 1 (CCR1) and its ligand, chemokine (C-C motif) ligand 5 (CCL5), in taxane-resistant CRPC using paclitaxel-resistant prostate cancer cells (PC3PR) established from PC3 cells. We found that the expression levels of CCR1 mRNA and protein were up-regulated in PC3PR cells compared to PC3 cells. In order to investigate the role of increased CCR1 in PC3PR cells, we stimulated cells with CCL5, one of the chemokine ligands of CCR1. In CCL5-stimulated PC3PR cells, siRNA-mediated knockdown of CCR1 expression reduced phosphorylation of ERK1/2 and Rac1/cdc42. Furthermore, CCR1 knockdown and MEK1/2 inhibition decreased CCL5-stimulated secretion of MMPs 2 and 9, which play important roles in cancer cell invasion and metastasis. In the Matrigel invasion assay, knockdown of CCR1 and inhibition of the ERK and Rac signaling pathways significantly decreased the number of invading cells. Finally, the serum CCL5 protein level as measured by ELISA was not different among the three groups of patients: those with negative prostate biopsy, those at initial diagnosis of prostate cancer, and those with taxane-resistant prostate cancer. These results demonstrated for the first time that the interaction of CCR1 with CCL5 caused by increased expression of CCR1 promotes invasion of PC3PR cells by increasing secretion of MMPs 2 and 9 and by activating ERK and Rac signaling. Our findings suggest that CCR1 could be a novel therapeutic target for taxane-resistant CRPC.

Rapid progression of a urinary bladder leiomyosarcoma: report of a case.

The case we report shows rapid progression and a very poor prognosis only for a month that differs from the clinical course reported in the literature. An 83-year-old man was referred to our hospital for macroscopic hematuria. Computed tomography (CT) revealed a large bladder tumor measuring 4 cm × 3 cm and magnetic resonance imaging revealed extravesical invasion and pelvic wall invasion of the tumors. Chest CT and bone scintigraphy revealed no evidence of distant visceral metastases, and a clinical diagnosis of T4N0M0 was made. Transurethral resection of the bladder tumor (TUR-BT) was performed for histopathological diagnosis 18 days after admission, and no further adjuvant treatment was given. At 15 days after TUR-BT, the patient's clinical status worsened with symptoms of exertional dyspnea. CT showed multiple metastatic lesions in the lung, liver, and retroperitoneal lymphadenopathy. The patient died 2 days later and underwent autopsy. A final histopathological diagnosis of leiomyosarcoma was made based on immunohistochemical staining.

[Segmental testicular infarction--a case report].

A 31-year-old male visited our hospital with a complaint of left scrotal pain that began suddenly one week before the visit. The results of scrotal examination, blood cell count and biochemical examination were normal. Enhanced magnetic resonance imaging (MRI) showed a well-defined avascular lesion of the left testis with rim enhancement. With the suspicion of a segmental testicular infarction, left testicular biopsy and bilateral orchiopexy were performed. Pathological examination demonstrated a testicular infarction. One month after surgery, enhanced MRI showed normal testis.

[Discrepancy between Gleason score of needle biopsies and radical prostatectomy specimens--current situation of general pathologists].

We retrospectively reviewed the discrepancy in Gleason score between needle biopsy and radical prostatectomy specimens. Specimens from 153 patients who underwent radical retropubic prostatectomy at Gifu University Hospital and 9 community-based institutions between January 2001 and December 2005, were studied. Gleason score was determined by the general pathologist at each institution. The coincidence rate of Gleason score between biopsy and prostatectomy specimens was 49.7%. In contrast, 37.4% of biopsy specimens were undergraded. In biopsy specimens given a Gleason score of 5 or less, the Gleason score was coincident or undergraded compared with prostatectomy specimens. In biopsy specimens given a Gleason score of 6, the coincidence rate was 39.6%. In 56% in biopsy specimens of cancers with a Gleason score of 6 the Gleason score was undergraded compared with the prostatectomy specimen. In this group, extra-prostatic extention was found significantly more often than in other groups (p = 0.04). In patients, who underwent extended biopsy, or had a more positive biopsy core (> or = 25%), the coincidence rate was significantly greater (p = 0.03). We should be aware of the limitations of Gleason scores based on biopsy specimens, and give treatment opinions careful consideration.

[Laparoscopic examination of the nonpalpable testis].

We evaluated the results and advantages of laparoscopic examination in 28 patients with 32 nonpalpable testes. Between April 1991 and May 2006, 28 patients, 12 months to 12 years old, with 32 nonpalpable testes underwent diagnostic laparoscopy under general anesthesia before surgical management of the testes. If the blind end of the vas deferens and/or spermatic vessels was observed, the diagnosis of vanishing testis was made, and no further examination or treatment was performed. If intra-abdominal testis was observed, laparoscopic orchiectomy or open orchiopexy was performed. If the internal spermatic vessels and vas deferens entered into the internal inguinal ring, the diagnosis of intra-canalicular testis was made so that the inguinal canal was opened for surgical interventions. Of the 32 nonpalpable testes 10 were on the right side and 22 were on the left side (4 patients had bilateral undescended testes). There were 7 (21.8%) vanishing, 5 (15.6%) intra-abdominal and 20 (62.5%) intra-canalicular testes. There were no complications related to laparoscopy. Laparoscopy can be safely performed to assess the location of the non-palpable testes. Another advantage of the laparoscopic examination is that orchiopexy or orchiectomy can be immediately performed after the examination to avoid a second surgery.

[Renal adenoma treated with partial nephrectomy: a case report].

We report a case of renal adenoma which was diagnosed as renal cell carcinoma preoperatively. A 78-year-old man, who had been under observation for bladder cancer for 4 years, was incidentally found to have a small right renal tumor at follow-up computed tomography (CT). Enhanced CT demonstrated a tumor which was hypervascular, 10 x 10 mm size, at the lower pole of the right kidney. There was no evidence of distant metastasis. The preoperative diagnosis was renal cell carcinoma, cT1aN0M0, and we performed right partial nephrectomy. The histopathorogical finding was renal adenoma. Renal adenomas are benign tumors and not uncommon in autopsy cases. However, when they are detected clinically, it is difficult to distinguish them from renal cell carcinoma preoperatively.

[Clinical evaluation of our first 50 laparoscopic adrenalectomies].

We performed 50 laparoscopic adrenalectomies during the period from 1998 through 2003. We report our experience and the outcomes of this procedure, which has become a standard surgery for adrenal tumors. In most cases, the transperitoneal approach was used. In 48 cases, laparoscopic adrenalectomy was performed successfully. However, in two cases, the operation was converted to an open procedure because of bleeding. As our experience with laparoscopic adrenalectomy increased, operation time decreased. Laparoscopic adrenalectomy should be used more widely in the future.

[A case of delayed infection of a pelvic lymphocele following radical prostatectomy 4 months after operation].

Symptomatic lymphocele presented after pelvic lymphadenectomy for localized carcinoma of the prostate is a relatively rare complication. We treated a case of infected lymphocele presenting 4 months after a limited staging pelvic lymphadenectomy and a radical prostatectomy for adenocarcinoma of the prostate. The patient was a 70-year-old Japanese man having the chief complaint of fever, right lower abdominal pain, nausea and vomiting. Pelvic computed tomography showed a 14 cm cystic mass with a thick capsule on the right iliopsoas muscle. It was suspected to be an infected lymphocele. After percutaneous drainage, sclerotherapy (povidone iodine, minocycline and ethanol) and antibiotic drugs, the infected lymphocele was resolved.

Microscopic pulmonary tumor embolism secondary to adenocarcinoma of the prostate.

We report a case of pulmonary tumor embolism involving multiple emboli from an unusual site, an adenocarcinoma of the prostate. A 78-year-old Japanese man was diagnosed with stage IV (1997 version of the TNM classification) moderately differentiated adenocarcinoma of the prostate in December 1997. He underwent bilateral orchiectomy and hormonal therapy with flutamide was started. The patient suffered from relapse in April 1998, and estramustine phosphate was administered as treatment for hormone-refractory prostate cancer. He noticed a dry cough in May 1998, and on June 13, he developed acute progressive dyspnea and was admitted to our hospital. Radiological findings, blood gas analysis, and clinical symptoms suggested pulmonary thrombosis. Despite anticoagulation and oxygen therapy, he remained severely dyspnoeic. He died of respiratory failure 4 days after admission. Autopsy confirmed dissemination of poorly differentiated adenocarcinoma of the prostate to the majority of the pulmonary muscular arteries.

[Comparison of laparoscopic versus open surgery for adrenal tumor].

We performed 25 laparoscopic adrenalectomies for adrenal tumor between January 1998 and December 2000. In 23 cases, adrenal tumors were successfully removed laparoscopically, but in 2, the laparoscopic procedure was converted to open surgery because of liver injury and endoscopically uncontrolled bleeding at the renal hilum. Postoperative complications, involving retroperitoneal hematoma, hypercapnia, and wound infections, could be managed without surgical treatment. We compared laparoscopic adrenalectomy with conventional open surgery, which had been performed for 24 adrenal tumors in our clinic. The mean operative time for the laparoscopic adrenalectomy (228.8 +/- 65.5 minutes) was significantly longer than those for the open surgery (156.0 +/- 43.8 minutes). The estimated blood loss (82.3 +/- 125.4 g) was significantly less than those for the open surgery (210.8 +/- 167.7 g), and the laparoscopic adrenalectomy had significant advantages in lessening postoperative analgesic requirements, shortening postoperative recovery period, and preserving good physical appearance. Therefore, we conclude that the laparoscopic adrenalectomy is a less invasive surgery, and is acceptable as a standard operation for adrenal tumors.