Refraining from Smoking for 15 Years or More Reduced the Risk of Tumor Recurrence in Non-muscle Invasive Bladder Cancer Patients.

PURPOSE: We investigated whether smoking cessation could have preventative effects against tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). METHODS: Our study population comprised 634 patients with initially diagnosed NMIBC at Keio University Hospital, Saiseikai Central Hospital, and Saitama Medical University Hospital between 1995 and 2012. We analyzed the relationships between tumor recurrence in NMIBC and patient clinicopathological parameters, including smoking status. RESULTS: Overall, 181 patients (28.5 %) were classified as current smokers, 154 (24.3 %) as former smokers, and 299 (47.2 %) as non-smokers. Kaplan-Meier curve analysis revealed that the tumor recurrence rate was significantly lower in the non-smoker group than in the current- and former-smoker groups (p < 0.001 and p < 0.001, respectively). In the 154 former smokers, Kaplan-Meier curve analysis revealed that smoking intensity and duration was not associated with tumor recurrence rate; however, patients with a smoking cessation period of 15 years or more had a significantly lower tumor recurrence rate than their counterparts (p < 0.001). A multivariate analysis identified a smoking cessation period of <15 years (hazard ratio [HR] 2.20; p = 0.003) and T1 tumors (HR 1.99; p = 0.013) as independent risk factors for tumor recurrence in the former-smokers subgroup. CONCLUSIONS: A positive smoking history was identified as one of the independent risk factors for bladder tumor recurrence after transurethral resection of the bladder tumor. Furthermore, refraining from smoking for 15 years or more reduced the risk of tumor recurrence in former smokers with NMIBC regardless of the intensity or duration of smoking. Therefore, smoking cessation may reduce the risk of tumor recurrence in patients with NMIBC.

The Preoperative Neutrophil-to-lymphocyte Ratio is a Novel Biomarker for Predicting Worse Clinical Outcomes in Non-muscle Invasive Bladder Cancer Patients with a Previous History of Smoking.

PURPOSE: We speculated that a heterogeneous population of non-muscle invasive bladder cancer (NMIBC) patients with a previous history of smoking may be more precisely stratified by a biomarker associated with tumor aggressiveness and then focused on the preoperative neutrophil-to-lymphocyte ratio (pre-NLR), which is a simple index of systemic inflammation. METHODS: Our study population comprised 605 patients initially diagnosed with NMIBC at our 3 institutions between 1995 and 2013. We analyzed the relationships between pre-NLR levels and clinical outcomes in NMIBC. A pre-NLR level of ≥2.2 was defined as elevated according to a calculation by a receiver-operating curve analysis. RESULTS: In overall, a total of 296 patients (48.9 %) had pre-NLR ≥ 2.2, and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. Among 344 patients with a previous history of smoking, 184 (53.5 %) had pre-NLR ≥ 2.2 and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. The 5-year recurrence-free survival and progression-free survival rates in patients with pre-NLR < 2.2 were 66.3 and 97.5 %, respectively, which were significantly higher than those in their counterparts (31.7 and 90.4 %, p < 0.001). In either subgroup of patients who were current smokers (N = 175) or former smokers (N = 169), the pre-NLR level was the only independent risk factor for tumor recurrence. The pre-NLR level was not associated with tumor recurrence or stage progression in 261 nonsmoking patients. CONCLUSIONS: Pre-NLR levels may be a useful marker for identifying worse clinical outcomes in NMIBC patients, particularly those with a previous history of smoking.

A prospective longitudinal survey of erectile function status in symptomatic benign prostatic hyperplasia patients treated with dutasteride.

We prospectively evaluated erectile function (EF) using the Sexual Health Inventory for Men (SHIM) and the erectile hardness score (EHS) as well as urinary statuses using the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) before and 3, 6, and 12 months after a daily treatment with 0.5 mg dutasteride (DUT). Significant improvements were observed in IPSS and OABSS in 98 patients with the DUT treatment, and the effects were similar between 28 patients with potency with baseline SHIM of 8 or greater and 70 severe erectile dysfunction (ED) patients at baseline. In the 28 patients with potency, significant decreases were observed in SHIM and EHS after 3, 6, and 12 months of the DUT treatment, with the severity of ED according to SHIM deteriorating in half of these patients after 12 months of the DUT treatment. Eighteen out of 28 patients (64.3%) with potency at baseline had awareness of the occurrence of ED before the DUT treatment, were younger, and had higher SHIM and EHS just before the DUT treatment than their counterparts. Regular assessments of EF may be needed, especially in younger patients and those with higher levels of EF before the administration of DUT.

Do metastatic upper tract urothelial carcinoma and bladder carcinoma have similar clinical responses to systemic chemotherapy? A Japanese multi-institutional experience.

OBJECTIVE: There has been no clear evidence supporting similar chemo-responses for upper and lower urothelial carcinomas. METHODS: We conducted a multicenter retrospective cohort study to analyze urothelial carcinoma patients who underwent systemic chemotherapy at 17 centers from 2004 to 2010. A total of 298 patients with either urothelial carcinoma of the bladder (N = 151) or upper tract urothelial carcinoma (N = 147) were included. Differences in tumor location (urothelial carcinoma of the bladder vs. upper tract urothelial carcinoma) were evaluated in relation to the patient backgrounds and clinical responses to systemic chemotherapy. RESULTS: Overall 216 patients were treated with cisplatin-based chemo-regimens (gemcitabine and cisplatin in 92, or methotrexate, vinblastine, adriamycin and cisplatin/methotrexate, epirubicin and cisplatin in 124). Among 186 initially metastatic patients, the incidences of lung metastasis and liver metastasis were 39.2 and 34.1%, respectively, in upper tract urothelial carcinoma patients, and were significantly higher than those with urothelial carcinoma of the bladder (22.4% for lung; 8.4% for liver metastasis). Among 112 post-surgical recurrent/metastatic patients, age was significantly higher and estimated glomerular filtration rate at baseline was significantly lower in upper tract urothelial carcinoma patients than those with urothelial carcinoma of the bladder. No significant differences were observed in overall clinical response rates for systemic chemotherapy between urothelial carcinoma of the bladder (45.8%) and upper tract urothelial carcinoma (38%) in initially metastatic patients or between urothelial carcinoma of the bladder (43.2%) and upper tract urothelial carcinoma (44.1%) in post-surgical recurrent/metastatic patients. Tumor location was not independently associated with cancer-specific survival in either initially metastatic or post-surgical recurrent/metastatic urothelial carcinoma patients. CONCLUSIONS: No significant difference was observed in response rates of urothelial carcinoma of the bladder and upper tract urothelial carcinoma to systemic chemotherapy, suggesting that a similar chemo-regimen can be applied to metastatic urothelial carcinoma patients regardless of tumor location (upper vs. lower).

Visceral obesity is associated with better recurrence-free survival after curative surgery for Japanese patients with localized clear cell renal cell carcinoma.

OBJECTIVE: To investigate the prognostic significance of visceral obesity to predict recurrence after curative surgery for Japanese patients with localized renal cell carcinoma. METHODS: The data of 285 patients who underwent curative surgery for localized renal cell carcinoma were retrospectively reviewed. Median follow-up was 36.7 months. The association between visceral obesity and recurrence-free survival rate was evaluated using the Kaplan-Meier method and Cox regression models. Visceral fat area at the level of the umbilicus measured using pre-operative computed tomography was used as an index of visceral obesity. RESULTS: Twenty-nine patients (10.2%) experienced recurrence. Five-year recurrence-free survival rates were 91.3% in high visceral fat area group (≥ 120 cm(2)) and 76.9% in low visceral fat area group (<120 cm(2)) (P = 0.037); however, visceral fat area was not an independent predictor of recurrence-free survival in multivariate analysis. In the patients with clear cell renal cell carcinoma, 28 patients (11.6%) experienced recurrence. Five-year recurrence-free survival rates were 88.7% in high visceral fat area group and 71.0% in low visceral fat area group (P = 0.043), and visceral fat area was an independent predictor of recurrence-free survival (hazard ratio: 1.974, P = 0.042) as well as C-reactive protein, Fuhrman nuclear grade, tumor size and microvascular invasion. In patients with organ confined clear cell renal cell carcinoma in particular, visceral fat area was also a useful and independent predictor of recurrence-free survival (hazard ratio: 2.807, P = 0.038). Body mass index was not useful in either cohort. CONCLUSIONS: High visceral fat area was a positive predictive biomarker for better recurrence-free survival after curative surgeries for localized clear cell renal cell carcinomas; however, body mass index was not a predictor.

How does visceral obesity affect surgical performance in laparoscopic radical nephrectomy?

OBJECTIVE: In a previous study, we described the relationship between operating time and obesity, particularly visceral obesity, in laparoscopic surgery. Operating time in laparoscopic surgery is affected by the experience and technique of the surgeon. Here, we investigated whether a difference in the surgeon's experience affects the operating time for laparoscopic radical nephrectomy in patients with visceral obesity. METHODS: From January 2006 to February 2012, 167 laparoscopic radical nephrectomies were performed at our institution. Visceral fat area was measured at the level of the umbilicus using computed tomography. A visceral fat area ≥ 100 cm(2) was used as the definition of visceral obesity. All laparoscopic radical nephrectomies were performed by six surgeons. Two of the six surgeons perform 50 cases or more laparoscopic surgeries every year and they were defined as the expert group. We analyzed the relationships between clinical findings, methods, surgeon experience, body mass index or visceral fat area and operating time. RESULTS: The expert and non-expert surgeons performed 77 and 90 laparoscopic radical nephrectomies, respectively, and the median operating time was 167.0 ± 44.0 and 227.5 ± 60.6 min. Twenty-five patients underwent laparoendoscopic single-site nephrectomy by the expert surgeons. For all surgeons, visceral obesity was a significant factor for prolonged operating time. Multivariate analysis showed that visceral obesity and clinical T stage were independent risk factors for prolonged operating time for the non-expert surgeons [P = 0.004, hazard ratio (HR): 5.15, P = 0.037, HR:10.41]. However, for the expert surgeons, clinical T stage was the only independent risk factor for prolonged operating time (P = 0.039, HR: 4.33). CONCLUSION: Visceral obesity was a factor of prolonged operating time in laparoscopic radical nephrectomy. The non-expert surgeons were particularly affected by visceral obesity.

What is the predictor of prolonged operative time during laparoscopic radical prostatectomy?

OBJECTIVES: To study the impact of high body mass index and large prostate weight on operative time of laparoscopic radical prostatectomy. METHODS: A retrospective analysis of medical records from patients who had undergone extraperitoneal laparoscopic radical prostatectomy by a single surgeon at our institution between September 2008 and April 2011 was carried out. For each case, the following parameters were recorded: age, body mass index, prostate weight, cross-section area of the Retzius space, and history of previous lower abdominal surgery, repeated prostate biopsy and neoadjuvant hormone therapy. The laparoscopic radical prostatectomy procedure was divided into seven surgical steps: (i) port insertion and lymph node dissection; (ii) endopelvic fascia incision; (iii) dorsal vein complex ligation; (iv) prostate dissection from bladder neck; (v) dissection of seminal vesicles and vas deferens; (vi) prostate dissection from rectum; and (vii) vesicourethral anastomosis. The overall operative time and the duration of each surgical step were retrieved. Potential predictors of prolonged total operative time and prolonged duration of a step were assessed by multivariate logistic regression analysis. RESULTS: A total of 152 patients were analyzed. High body mass index (≥25.0 kg/m(2) ) and prostate weight were independent predictors of prolonged total operative time. High body mass index was an independent predictor of prolonged step 1, 3, 4, 5 and 6. Prostate weight was an independent predictor of prolonged step 2, 5 and 6. A history of previous lower abdominal surgery was a predictor of prolonged step 1. CONCLUSIONS: High body mass index and high prostate weight are independent predictors of prolonged total operative time in extraperitoneal laparoscopic radical prostatectomy. Although high body mass index seems to affect most of the surgical steps of the procedure, prostate weight mainly impacts the dissection close to the prostate, as enlarged prostate results in a narrower working space.

Prognostic value of renin-angiotensin system blockade in non-muscle-invasive bladder cancer.

BACKGROUND: To determine whether the administration of renin-angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), affect disease outcome in non-muscle-invasive bladder cancer (NMIBC). METHODS: A total of 330 patients with initially diagnosed NMIBC were identified. We retrospectively investigated the clinical outcomes after transurethral resection of bladder tumor (TUR-BT) in patients who did or did not receive RAS inhibitors. The median follow-up period was 4.1 years. RESULTS: A total of 128 patients (38.8 %) experienced subsequent tumor recurrence, and stage progression was observed in 17 patients (5.2 %) during follow-up. Fifty-one patients (15.5 %) had received ACEI or ARB administration at transurethral resection. Multivariate analysis demonstrated that tumor multiplicity, absence of bacillus Calmette-Guérin instillation, and no administration of ACEI or ARB (P = 0.010, hazard ratio 2.26) were independent risk factors for subsequent tumor recurrence. The 5-year recurrence-free survival rate was 78.4 % in patients administered ACEIs or ARBs, and 53.3 % in their counterparts (P = 0.011). CONCLUSIONS: The absence of RAS inhibitor administration was an independent risk factor for subsequent tumor recurrence in patients with initially diagnosed NMIBC. Our data support further investigation of the role of RAS inhibitors as a potential therapy to decrease tumor recurrence in NMIBC.

Extrapancreatic solid pseudopapillary tumor: case report and review of the literature.

A 22-year-old woman complained of abdominal discomfort. Ultrasonography, computed tomography, and an endocrinologic work-up revealed a 7-cm nonfunctional tumor at the left adrenal lesion. A transumbilical laparo-endoscopic single-site adrenalectomy was successfully completed in 166 min. The postoperative period was uneventful. The pathologic examination confirmed the solid pseudopapillary tumor occurred in the retroperitoneum. There are only five previous reports of extrapancreatic solid pseudopapillary tumors. In this case, the tumor was separated from the pancreas and no ectopic pancreas was histologically observed. To the best of our knowledge, this case is the first report of a solid pseudopapillary tumor of the retroperitoneum.

Multiple metastases of androgen indifferent prostate cancer in the urinary tract: two case reports and a literature review.

BACKGROUND: Prostate cancer (PC) is mainly known to metastasize to bone, lung and liver, but isolated metastases of prostate cancer, including ductal carcinoma, in the urinary tract are very rare. We describe two patients with nodular masses in the urinary tract (the anterior urethra or the urinary bladder) that were found on cystoscopy during treatment of castration-resistant prostate cancer. CASE PRESENTATION: In both cases, the pathological diagnosis from transurethral tumor resection showed that they were androgen indifferent prostate cancer (AIPC), including aggressive variant prostate cancer (AVPC) in Case 1 and treatment-induced neuroendocrine differentiation prostate cancer (NEPC) in Case 2. In Case 1, Loss of genetic heterozygosity (LOH) of BRCA2 and gene amplification of KRAS was identified from the urethra polyps. In Case 2, homozygous deletion was observed in PTEN, and LOH without mutation was observed in RB1. CONCLUSION: These are the first reports of two cases of urinary tract metastasis of AIPC.

Could patient age influence tumor recurrence rate in non-muscle-invasive bladder cancer patients treated with BCG immunotherapy?

OBJECTIVE: The effect of local immunotherapy with bacille Calmette-Guérin in elderly patients with non-muscle-invasive bladder cancer has not yet been fully evaluated. The aim of the present study was to evaluate whether patients' age influences the response to bacille Calmette-Guérin treatment for the prevention of tumor recurrence and whether the side effects were tolerable. METHODS: We reviewed 1252 cases with non-muscle-invasive bladder cancer treated with transurethral bladder tumor resection, and 447 cases who underwent bacille Calmette-Guérin immunotherapy were included. The associations between patient age or pathological findings and tumor recurrence were determined. Side effects were classified as minor or major and were analyzed on the basis of their incidences in each age group. RESULTS: The patients were divided into four age categories: younger than 55 (n= 86), 55-64 (n = 143), 65-74 (n = 132) and equal or older than 75 years (n = 86). The Kaplan-Meier curves of recurrence-free survival rates demonstrated that patients aged 55-64 had been continuously tumor-free than the equal or older than 75 group. The presence of previous bladder cancer and Grade 3 were independent predictors for tumor recurrence; however, patients' age was not selected. The incidence of fever was slightly higher and that of cystitis was lower in the younger group. CONCLUSIONS: Age does not certainly affect recurrence in patients with bladder cancer treated with bacille Calmette-Guérin therapy. The related side effects in the elderly patients were almost equal to those in the younger. With careful monitoring, bacille Calmette-Guérin therapy is safe even in elderly patients.

Initial experience of transumbilical laparoendoscopic single-site surgery of partial adrenalectomy in patient with aldosterone-producing adenoma.

BACKGROUND: Laparoscopic single-site surgery has recently emerged in the field of urology and this minimally-invasive surgery has resulted in a further reduction in morbidity compared with traditional laparoscopy. We present our initial experience with laparoendoscopic single-site surgery of partial adrenalectomy (LESS-PA) to treat aldosterone-producing adenomas. CASE PRESENTATION: A 60-year-old woman was diagnosed with aldosterone-producing macroadenomas in the left adrenal and aldosterone-producing microadenomas in the right adrenal. A two-step operation was planned. The first step involved transumbilical LESS-PA for the left adrenal tumors. A multichannel port was inserted through the center of the umbilicus and the left adrenal gland was approached using bent instruments according to standard traditional laparoscopic procedures. The tumors were resected using an ultrasonic scalpel, and the resected site was coagulated using a vessel sealing instrument and then sealed with fibrin glue. Operative time was 123 minutes and blood loss was minimal. The patient was discharged from hospital within 72 hours. Her right adrenal microadenomas will be treated in the next several months. CONCLUSIONS: Although our experience is limited, LESS-PA appears to be safe and feasible for treating aldosterone-producing adenomas. More cases and comparisons with the multiport technique are needed before drawing any definite conclusions concerning the technique.

Nicotine Induces Tumor Growth and Chemoresistance through Activation of the PI3K/Akt/mTOR Pathway in Bladder Cancer.

Continued smoking is highly associated with not only a higher incidence but also greater risk of tumor recurrence, progression, and acquired chemoresistance of urothelial carcinoma. We investigated whether nicotine affects urothelial carcinoma, and the detailed mechanism by which nicotine could induce tumor growth and any associated chemoresistance. Cell viability was evaluated in the human bladder cancer cell line T24 exposed to nicotine with or without cisplatin (CDDP) and NVP-BEZ235 as a PI3K/mTOR dual inhibitor by the WST-1 assay. Protein expression of the PI3K/Akt/mTOR pathway was investigated by Western blotting or immunohistochemical analysis. The influence of nicotine on tumor growth was also evaluated with or without CDDP and/or NVP-BEZ235 in a subcutaneous bladder tumor model. The result demonstrated that cell proliferation was increased in T24 cells after exposure to nicotine. Phospho-specific Akt (pAkt) and phospho-specific p70 S6 kinase (pS6) were significantly upregulated by nicotine exposure. Tumor growth in vivo was significantly induced by nicotine exposure in accordance with increased pS6 expression. Nicotine attenuated inhibition of T24 cell growth by CDDP and further upregulated pS6 expression in vitro and in vivo. NVP-BZE235 inhibited T24 cell proliferation and pAkt and pS6 expression induced after exposure to nicotine and/or CDDP. In conclusion, nicotine increases tumor growth and induces acquired chemoresistance through activation of the PI3K/Akt/mTOR pathway in bladder cancer.

Periprostatic fat area is an independent factor that prolonged operative time in laparoscopic radical prostatectomy.

OBJECTIVE: To evaluate the effect of visceral obesity on surgical outcomes in laparoscopic radical prostatectomy (LRP). METHODS: Visceral fat area (VFA) and periprostatic fat area (PPFA) were used as index of visceral obesity. In addition to VFA and PPFA, age, body mass index (BMI), prostate weight, cross-section area of Retzius space, history of previous abdominal surgery, repeated transrectal needle biopsy, and neoadjuvant hormone therapy were recorded. LRP was separated into 7 steps (1: port insertion and lymph node dissection, 2: endopelvic fascia incision, 3: dorsal vein complex ligation, 4: prostate dissection from bladder neck, 5: dissection of seminal vesicle and vas deferens, 6: prostate dissection from rectum, and 7: vesicourethral anastomosis). Potential factors that prolonged total operative time (OT), pneumoperitoneum time, and duration of each step were assessed by multivariate logistic regression analysis. The association between visceral obesity and other surgical outcomes was also evaluated. RESULTS: One hundred sixteen LRPs were performed by a single experienced surgeon. High PPFA and prostate weight were independent factors that prolonged total OT and pneumoperitoneum time. High BMI was not a factor. PPFA affected steps 1, 4, 5, and 6, and prostate weight affected prolonged steps 5 and 6. Estimated blood loss, duration of urethral catheterization, postoperative hospital stay, perioperative complications, and margin status were not affected by visceral obesity. CONCLUSION: PPFA was more useful to accurately predict prolonged OT than VFA or BMI. Safety and margin status were not compromised even in high PPFA group when operations were performed by an experienced surgeon.

Discontinuance of bacille Calmette-Guérin instillation therapy for nonmuscle-invasive bladder cancer has negative effect on tumor recurrence.

OBJECTIVES: To investigate whether the occurrence of side effects or discontinuance of bacille Calmette-Guérin (BCG) therapy because of side effects is associated with its therapeutic efficacy. METHODS: We analyzed the data from 145 patients who had had nonmuscle-invasive bladder cancer (Stage pTa, pT1, or pTis) and had undergone an initial course of adjuvant BCG therapy after transurethral resection of bladder tumor from 1996 and 2006 at Keio University Hospital. Side effects were classified as minor and major, and the association between the occurrence of side effects or discontinuance of BCG therapy because of side effects and tumor recurrence or progression was analyzed. RESULTS: Side effects occurred in 106 patients (73.1%) during BCG instillation. Of these 106 patients, 38 had major side effects and 95 had minor; 27 patients had both. BCG therapy was discontinued in 19 patients (13.1%) because of severe hematuria in 2, high fever in 8, and severe lower urinary tract symptoms in 9. Multivariate analyses demonstrated that discontinuance of BCG therapy (P = .018) was an independent predictor for tumor recurrence, in addition to multiplicity (P = .043). However, the occurrence of side effects was not an independent predictor for tumor recurrence (P = .935). Multivariate analyses also demonstrated that neither discontinuance of BCG therapy (P = .308) nor the occurrence of side effects (P = .333) was an independent predictor for tumor progression. CONCLUSIONS: Discontinuation of BCG therapy has a significantly deleterious effect on reducing the incidence of tumor recurrence. When major side effects occur, it might be preferable to attempt to mitigate the major side effects to maintain the BCG therapy on schedule.