Risk-stratified surveillance protocol improves cost-effectiveness after radical nephroureterectomy in patients with upper tract urothelial carcinoma.

OBJECTIVES: To develop a surveillance protocol with improved cost-effectiveness after radical nephroureterectomy (RNU), as the cost-effectiveness of oncological surveillance after RNU remains unclear. RESULTS: Of 426 patients, 109 (26%) and 113 (27%) experienced visceral and intravesical recurrences, respectively. The pathology-based protocol found significant differences in recurrence-free survival in the visceral recurrence but not in the intravesical recurrence. The medical costs per visceral recurrence detected were high, especially in normal-risk (≤ pT2N0, LVI-, SM-) patients. We developed a risk score associated with visceral recurrence using Cox regression analysis. The risk score-based protocol was significantly more cost-effective than the pathology-based protocol. Estimated cost differences reached $747,929 per recurrence detected, a suggested 55% reduction. MATERIALS AND METHODS: We retrospectively evaluated 426 patients with RNU for upper tract urothelial carcinoma (UTUC) without distant metastasis at 4 hospitals. Patients with routine oncological follow-up were stratified into normal-, high- and very high-risk groups according to a pathology-based protocol utilizing pathological stage, lymphovascular invasion (LVI) and surgical margin (SM). Cost-effectiveness of the pathology-based protocol was evaluated, and a risk score-based protocol was developed to optimize cost-effectiveness. Risk scores were calculated by summing up risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate- and high-risk score. Estimated cost per recurrence detected by pathology-based and risk score-based protocols was compared. CONCLUSIONS: A risk score-stratified surveillance protocol has the potential to reduce over investigation during follow-up, making surveillance more cost-effective.

Oncologic outcomes for open and laparoscopic radical nephroureterectomy in patients with upper tract urothelial carcinoma.

BACKGROUND: Oncologic benefits of laparoscopic radical nephroureterectomy (LNU) are unclear. We aimed to evaluate the impact of surgical approach for radical nephroureterectomy on oncologic outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). METHODS: Of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017, we retrospectively investigated oncological outcomes in 229 with locally advanced UTUC (stages cT3-4 and/or cN+). The surgical approach was classified as open nephroureterectomy (ONU) or LNU, and oncologic outcomes, including intravesical recurrence-free survival (RFS), visceral RFS, cancer-specific survival (CSS), and overall survival (OS), were compared between the groups. The inverse probability of treatment weighting (IPTW)-adjusted Cox-regression analyses was performed to evaluate the impact of LNU on the prognosis. RESULTS: Of the 229 patients, 48 (21%) underwent LNU. There were significant differences in patient backgrounds, including preoperative renal function, lymph-node involvement, lymphovascular invasion, and surgical margins, between the groups. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS were significantly inferior in the ONU group than in the LNU group. However, in the IPTW-adjusted Cox-regression analysis, no significant differences were observed in intravesical RFS (hazard ratio [HR], 0.65; P = 0.476), visceral RFS (HR, 0.46; P = 0.109), CSS (HR, 0.48; P = 0.233), and OS (HR, 0.40; P = 0.147). CONCLUSION: Surgical approaches were not independently associated with prognosis in patients with locally advanced UTUC.

The utility of neoadjuvant gemcitabine plus carboplatin followed by immediate radical cystectomy in patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy.

BACKGROUND: There are currently no data supporting carboplatin-based regimens in muscle-invasive bladder cancer patients who are unsuitable for neoadjuvant cisplatin treatment. The aim of this study was to investigate the potential benefit of carboplatin-based regimens in patients with muscle-invasive bladder cancer who were unsuitable for cisplatin. METHODS: We focused on 171 patients ineligible for cisplatin, including 98 patients who received neoadjuvant gemcitabine and carboplatin (GCarbo) followed by immediate radical cystectomy (GCarbo cohort) and 73 patients who underwent radical cystectomy (RC alone cohort) at Hiroaki University or Aomori Prefectural Hospital. In the neoadjuvant GCarbo cohort, patients underwent two 21-day cycles of GCarbo the two courses of neoadjuvant chemotherapy were followed by radical cystectomy at an interval of 1 month. RESULTS: Of the enrolled patients, 165 (95.3 %) had renal impairment. The median age of the enrolled patients was 71 years, and the median follow-up period was 63 months. The 5-year overall survival rates for the GCarbo and the RC-alone cohorts were 79.5 and 53.8 %, respectively (P < 0.001), while the 5-year disease-free survival rates were 75.5 and 55.4 %, respectively (P = 0.013). Surgical specimens of 16 (16.3 %) patients in the GCarbo cohort indicated stage pT0 disease. The rate of positive surgical margins in the RC-alone cohort was significantly higher than that in the GCarbo cohort (P < 0.001). CONCLUSIONS: In this study, the oncological outcomes were significantly improved in cisplatin-unfit patients with muscle-invasive bladder cancer who received neoadjuvant GCarbo chemotherapy, compared with those in patients who underwent RC alone. The standard of care for muscle-invasive bladder cancer, especially for patients who are unfit for cisplatin, may include neoadjuvant carboplatin chemotherapy followed by radical cystectomy.

Primary leiomyosarcoma of a horseshoe kidney in a woman with Turner syndrome: a case report.

BACKGROUND: Turner syndrome is characterized by complete or partial X-chromosome monosomy and has various clinical features, including horseshoe kidney. Leiomyosarcoma is an extremely rare tumor that accounts for only 0.1% of all invasive renal tumors. CASE PRESENTATION: A 50-year-old Japanese woman presented at a community hospital with a chief complaint of abdominal pain. Computed tomography revealed a horseshoe kidney with a hypovascular tumor (size, 9 × 7 cm) showing calcification in the upper pole of the right kidney. Open right heminephrectomy and division of the isthmus were performed. Histological examination revealed alternating fascicles of spindle cells with blunt ended non-tapering nuclei and eosinophilic cytoplasm. The tumor had high mitotic activity with a mitotic count of 8 mitoses/10 high-power fields. On the basis of these findings, we diagnosed the patient as having leiomyosarcoma. CONCLUSION: Primary leiomyosarcoma of the horseshoe kidney in a patient with Turner syndrome is a very rare occurrence.

[Significance of a simple assay of urine telomerase activity for the detection of bladder cancer].

We developed a simple urine telomerase activity assay by a modification of the TeloTAGGG telomerase polymerase chain reaction (PCR) enzyme-linked immunosorbent assay kit. We conjugated digoxygenin (DIG) with the CX primer of omitting hybridization of PCR products and DIG-labeled probe. The sensitivity and specificity of bladder cancer diagnosis on 100 patients with bladder cancer and 25 healthy volunteers using the simple urine telomerase activity measurement were 81% and 92%, respectively. The positive rate for bladder cancer by the present assay system was affected by neither tumor grade nor invasiveness. The diagnostic potential of the present method is superior to the conventional urine telomerase assay kit and urine nuclear matrix protein-22 (NMP22). The present method is simple, and can be used for mass screening of bladder cancer.

[Chemo-endocrine therapy with low-dose cisplatin, UFT, and dexamethasone for hormone-refractory prostate cancer patients].

Since September 2005, twenty-two patients with hormone-refractory prostate cancer (aged 55-81 years) were treated with LH-RH agonist and low-dose cisplatin, UFT, and dexamethasone after proving resistant to estramustine phosphate therapy. The regimen of this therapy consists of 5 mg/body of cisplatin intravenously once a week, 300 mg/day of UFT and 1 mg/day of dexamethasone orally, every day. All patients suffered from clinical progression such as local recurrence in 11 patients who had already received radiation therapy, lymph node metastasis in 7 patients, and bone metastasis in 15 patients. Initial PSA value ranged from 1.7 ng/mL to 215.1 ng/mL. The PSA response rate, which decreased more than 50% in PSA values was 72. 7% (16/22). The follow-up term ranged from 2 to 43 months, and nine patients died of cancer progression. The median time to progression was 11 months, and median overall survival was 19 months. There were no severe adverse effects, and stoppages of the therapy for 13 patients were all due to disease progression. Following this therapy, 9 patients received best supportive care and 4 patients received docetaxel chemotherapy. We considered this therapy to be effective for patients with hormone-refractory prostate cancer because it maintained their good QOL.

Cauda equina symptoms are closely related to male lower urinary tract symptoms.

INTRODUCTION: To determine the impact of cauda equina symptoms on male lower urinary tract function, we investigated the related risk factors in healthy Japanese men. METHODS: Subjects included 345 healthy males (average age 56 years; range 26-83) who participated in the Iwaki Health Promotion Project in 2006. They were residents of Iwaki district, Hirosaki City, northern Japan. Using a self-administered, self-reported questionnaire for lumbar spinal stenosis and International Prostate Symptom Score (IPSS), we investigated the prevalence of cauda equina symptoms. We also measured body mass index; blood pressure; and triglyceride, cholesterol, glucohemoglobin, and prostate-specific antigen levels. RESULTS: Nineteen participants (5.5%) were positive for cauda equina symptoms; 270 participants (78.3%) scored 0-7 points on the total IPSS survey, 65 (18.8%) scored 8-19, and 10 (2.9%) scored 20-35. The total IPSS, and storage and voiding symptom scores of participants negative for cauda equina symptoms were significantly lower than those who were positive. Multiple logistic regression analysis revealed that age and cauda equina symptoms were independent significant risk factors for total IPSS and storage symptoms. CONCLUSIONS: Cauda equina symptoms are closely related to lower urinary tract symptoms in healthy Japanese men.

[Relationship between tumor volume and PSA recurrence after radical prostatectomy].

We examined whether the tumor volume (TV) is a good predictor of PSA recurrence after radical prostatectomy. Data were collected for 158 patients with clinically localized prostate cancer undergoing radical prostatectomy without neoadjuvant hormonal therapy in our hospital since April 2005 to September 2007. Along with the routine pathological assessment, TV was assessed in all prostatectomy specimens. PSA recurrence was defined as PSA levels of greater than 0.2 ng/ml. The TVs were 1.81+/-1.66 ml (mean +/-SD) ranging from 0.02 to 8.20 ml. The TV in cT1c was 1.77+/-1.64, and 1.89+/-1.72 ml in cT2 (not significant). Significant differences were observed between TV and pT. The TVs in pT2a, pT2b and pT3/4 were 0.54+/-0.54, 1.63+/-1.47 and 2.67+/-1.80 ml, respectively. The median follow-up period was 32.3 months (range from 15 to 45) after radical prostatectomy, and PSA recurrence was observed in 32 cases. Patients with smaller TV (TV <1.3 ml) had a higher PSA-free survival rate (89.5%) than those with a larger TV (TV > or = 1.3 ml, 66.7%) with a significant difference atp <0.001 (log-rank test). A multivariate analysis was performed for PSA, TV, pT, Gleason Score (GS), and surgical margins. Significant differences were observed for GS, and surgical margins, but not for TV. Clinically organ-confined disease in Japanese patients with prostate cancer included various cancers from clinically insignificant to locally advanced ones. In our series, TV was not regarded as a predictor of PSA recurrence after radical prostatectomy.

Risk factors for erectile dysfunction in healthy Japanese men.

The aim of this study was to identify risk factors for erectile dysfunction (ED) in healthy men. A comprehensive risk factor investigation was carried out in a Japanese community. The subjects were 280 healthy male volunteers with an average age of 56 years (range: 20-83 years) who participated in the Iwaki Health Promotion Project in 2006. They were residents of Iwaki district, Hirosaki City, in northern Japan. The participants completed the five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (I-PSS) surveys at the site of examination. We measured blood pressure and brachial-ankle pulse wave velocity (baPWV). We also measured risk factors for metabolic syndrome and sex hormones. We compared these risk factors with the IIEF-5 scores. Ninety-five participants (34%) scored 11 points or fewer on the IIEF-5 survey (severe/moderate ED), 154 (55%) scored 12-21 points (mild ED) and 31 (11%) scored 22 points or more (no ED). The prevalence of ED in the Japanese rural community was 89% (249/280). The severe/moderate ED group had significantly higher total I-PSS scores (p = 0.001), baPWV values (p < 0.001) and systolic blood pressure (p < 0.001) than the mild/no ED group. The same group had significantly lower free testosterone (p < 0.001) and dehydroepiandrosterone sulphate (p < 0.001) than the mild/no ED group. Logistic regression analysis revealed significant differences in baPWV (p = 0.003), total I-PSS (p = 0.015) and free testosterone (p = 0.003). Lower urinary tract symptoms, baPWV and free testosterone are independent risk factors for ED in healthy Japanese men.

[Solitary fibrous tumor of the kidney: a case report].

Solitary fibrous tumor (SFT) of the kidney is rare. A 76-year-old woman was referred to our hospital with a complaint of an incidentaloma of the right kidney. Computed tomography revealed an ovoid, hypervascular tumor in the right kidney. Magnetic resonance imaging showed a low intensity tumor occupying the upper calyx of the right kidney (T2 weighted image). Laparoscopic right radical nephrectomy was performed. An immunohistochemical study using a monoclonal antibody directed against the human hematopoietic progenitor cell antigen (CD34) stain confirmed SFT. The follow up at 48 months after surgery showed no recurrence or distant metastasis.

[Risk factors for surgical site infection in radical cystectomy: efficacy of buried suture by absorbable thread for skin closure].

We assessed the incidence, risk factors and causative organism for surgical site infection (SSI). We reviewed the clinical charts of the consecutive 100 patients who underwent radical cystectomy from December 2003 to April 2008. All patients received intravenous prophylactic antimicrobial agent, 1 gram of cefotium hydrochloride before surgery followed by the same agent twice a day through postoperative day 3. Skin closures were carried out by interrupted sutures employing a 3-0 nylon for the first 50 patients (interrupted group), and by buried suture employing 3-0 or 4-0 braided polyglactin for the last 50 patients (buried group). SSI occurred in 13 cases (26%) with interrupted group including 8 patients with ureterocutaneoustomy and 5 patients with orthotopic ileal neobladder reconstruction. On the other hand, SSI was found in 1 patient (2%) in the buried group for whom ileal neobladder reconstruction was carried out (P= 0.021). Superficial inflectional SSI was found in 6 patients (5 patients in the interrupted group, patient in the buried group) and deep incisional SSI occurred in 5 patients in the interrupted group only. The most frequently isolated organism was Enterococcus faecalis. Univariate analysis revealed that body mass index (BMI) and the skin closure methods were significant risk factors for SSI (P<0.001, P=0.021, respectively). These 2 risk factors for SSI were also significant in multivariate analysis (P=0.003, P=0.037, respectively). These results suggested that BMI and the skin closure methods are independent risk factors in radical cystectomy. Furthermore, it may be possible to reduce the incidence of SSI by performing the buried suture for the skin closure.

[Multiple inflammatory pseudotumor of the paranephric fat].

A 57-year-old man was referred to our hospital because of a paranephric tumor detected by preoperative computed tomography (CT) for the ascending colon carcinoma. Since the paranephric tumor was small, surgical treatment was performed only for the colon carcinoma. The follow-up CT showed increase in size and number of paranephric tumor masses. It was suspected to be a soft tissue malignant tumor. Left radical nephrectomy was performed. Pathological findings revealed inflammatory pseudotumor of the paranephric fat. To our knowledge, this is the 4th case with inflammatory pseudotumor of the paranephric fat.

Protein profiling of post-prostatic massage urine specimens by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to discriminate between prostate cancer and benign lesions.

Post-prostatic massage urine specimens (PMUS) are expected to be rich in proteins originating from the prostatic acini. In this study, we created a PMUS bank consisting of 57 samples obtained from patients with biopsy-proven prostate cancer (PC) and 56 samples from subjects with biopsy-proven benign lesions to analyze protein profiles of PMUS by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Strong anion-exchange (Q10), weak cation-exchange (CM10) and immobilized metal affinity capture (IMAC30) ProteinChip Arrays were used for protein profiling. In PC samples, single-marker analysis detected 49 mass peaks that were significantly up-regulated and 23 peaks that were significantly down-regulated, compared with peaks obtained from benign lesion samples. To confirm reproducibility we performed additional three rounds of assay using CM10 chip with pH 4.0 binding buffer. Among these significant peaks, a peak of m/z 10788 was significant throughout all 4 rounds of assays. For hierarchical clustering analysis (HCA), we used the 72 peaks which revealed significant differences in single-marker analysis. The heat map discriminated PC from benign lesions with a sensitivity of 91.7% and a specificity of 83.3%. Therefore, SELDI-TOF MS profiling of PMUS can be applied to differentiate patients with PC from cancer-free subjects. However, further investigation is required to verify the usefulness of this method in clinical practice.

Low-dose instillation therapy with bacille Calmette-Guérin Tokyo 172 strain after transurethral resection: historical cohort study.

OBJECTIVES: To evaluate the effectiveness and side effects of prophylactic low-dose bacille Calmette-Guérin (BCG) Tokyo 172 strain. METHODS: We conducted a historical cohort study to compare the clinical usefulness of standard-dose versus low-dose BCG Tokyo 172 strain. A total of 156 patients with superficial bladder cancer (Stage Ta-T1) were historically allocated to either 40 or 80 mg of BCG after transurethral resection. Of the 156 patients, 89 had received standard-dose (80 mg) BCG from 1988 to 2000 and 67 had received low-dose (40 mg) BCG from 1996 to 2005. BCG was instilled into the bladder once a week for 6 consecutive weeks. We excluded 6 patients who did not complete the BCG treatment course. The median follow-up period was 66.9 months (range 2 to 176). RESULTS: Tumor recurrence developed in 21 (32.3%) of 65 patients in the 40-mg group and 29 (34.5%) of 85 patients in the 80-mg group. No significant difference was found in the incidence of tumor recurrence between the two groups (P = 0.6377). Tumor progression was found in 4 (6.2%) of 65 patients in 40-mg group and 9 (10.6%) of 85 patients in the 80-mg group. No significant difference was found in tumor progression between the two groups (P = 0.5010). The overall incidence of side effects and severity of pollakisuria were significantly lower in the 40-mg group than in the 80-mg group (P = 0.012 and P = 0.013, respectively). CONCLUSIONS: The low-dose BCG Tokyo 172 strain achieved identical recurrence-free and progression-free survival as the standard dose with reduced toxicity.

[Persistent Müllerian duct syndrome diagnosed by laparoscopic examination: a case report].

A 2-year-old boy presented for the evaluation of left nonpalpable testis. Laparoscopic examination revealed right migratory testis without any abnormal appearance and a uterine-like structure with an immature gonad in rectovesical fossa. Right spermatic duct merged into the uterine-like structure on the right side. The immature gonad was removed by laparoscopic procedure, while the uterine-like structure was not removed to preserve the right spermatic duct. Right orchidopexy was also performed. Histopathologic diagnosis for the removed gonad was hypoplastic testis. After the chromosomal analysis, 46 XY karyotype, we diagnosed this case as persistent Müllerian duct syndrome. Persistent Müllerian duct syndrome diagnosed by laparoscopic examination is very rare. To the best of our knowledge, this is the third case in Japan.

[Short-term outcome of neoadjuvant gemcitabine-carboplatin therapy for muscle-invasive bladder cancer].

Twenty-three patients with muscle-invasive bladder cancer were treated with combination chemotherapy of gemcitabine and carboplatin. Gemcitabine at a dose of 800 mg/m2 by intravenous infusion for 30 minutes on Days 1, 8 and 15. Carboplatin at an AUC of 4, according to the Calvert formula, was administered by intravenous infusion for 3 hours on Day 2. The treatment was repeated every 21 days without drug-free-weeks for a total of 2 cycles. Six patients achieved a complete response(CR)and 8 patients achieved a partial response(PR). Overall response rate(CR+PR) was 60.8%. In addition, 7 patients achieved stable disease(SD), whereas 2 were found to have progressive disease (PD). Although Grade 3 or 4 leukocytopenia was seen in 10 patients(43.4%), low-grade toxicities of anemia, thrombocytopenia and nausea were seen in several patients, so it was possible to complete the treatment on schedule in all patients. Five SD patients died(4 by cancer and 1 by another cause), 2 PD patients were found to have disease progression, and 16 patients were alive without recurrence with a mean follow-up period of 12.6 months(range: 8-19).

[Adenocarcinoma of the ileal segment 40 years after ileocystoplasty: a case report].

We reported a case of ileal segment adenocarcinoma arising in the augmented bladder 40 years after the operation. The patient was a 57-year-old man who underwent ileocystoplasty (Goodwin method) for contracted bladder due to tubercurosis in 1962. He was referred to our clinic for examination of gross hematuria. Cystoscopy revealed a tumor on the ileal segment of the augmented bladder. He underwent resection of the ileal segment and ureterocutaneostomy. The pathological diagnosis was poorly differentiated adenocarcinoma in the ileal segment. He died of the disease 6 months after the operation.