Frequent expression of a novel cancer testis antigen, protein kinase human monopolar spindle 1 (hMps1/TTK) in human urinary bladder transitional cell carcinoma.

Urothelial bladder cancer (UBC) is a frequently occurring malignancy of the urinary tract. The present study was undertaken to evaluate the mRNA and immunohistochemical (IHC) expression of protein kinase human monopolar spindle 1 (hMps1/TTK) gene in transitional cell carcinoma (TCC) of the bladder and correlate its expression with the clinicopathological characteristics of patients. In the present study, quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate TTK mRNA expression in TCC. IHC analysis of TTK was also evaluated. Independent Student's t, ANOVA and chi-square (χ2) tests were used to analyze the data statistically. The frequency of TTK mRNA over expression was detected in 50% of UBC (38/76) by qRT-PCR. Relative mean fold expression of TTK mRNA was found significantly (p < 0.05) higher in muscle-invasive bladder cancer (MIBC) as compared to non-muscle-invasive bladder cancer (NMIBC) patients (8.96 ± 4.51 vs. 5.64 ± 3.53, p = 0.03). Moreover, IHC reveals heterogenous immunostaining pattern of TTK in TCC tissues. The frequency of TTK protein over expression was detected in 56.9% (37 of 65) UBC patients. No significant IHC expression of TTK was detected among adjacent noncancerous tissues (ANCTs) and benign prostatic hyperplasia (BPH) used as control. Collectively our study observations conclude that TTK is a novel cancer/testis antigen (CTA) as a diagnostic marker for early diagnosis of UBC.

CASC5 is a potential cancer-testis gene in human urinary bladder transitional cell carcinoma.

Urinary Bladder cancer (UBC) is a diversified disease with an array of clinicopathological attributes. Several studies have shown that cancer susceptibility candidate 5 (CASC5) plays important roles in various types of malignancies; however its expression and clinical significance in human UBC remain largely unknown. This research study was intended to explore mRNA/protein expression pattern of CASC5 as a member of the cancer-testis (CT) gene family and assess its clinical utility in diagnostic management of patients with UBC. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) was employed to appraise the detailed expression profile of CASC5 in patients with UBC. The mRNA over expression of CASC5 was detected in testis tissue and relatively high frequency 59.2% (45 of 76) of CASC5 mRNA was detected in UBC tissues. CASC5 mRNA relative mean fold expression was also significantly (p < 0.01) higher in the muscle-invasive tumor tissues compared to non-muscle-invasive tumor tissues (12.26 ± 9.53 vs. 4.64 ± 2.50, p = 0.005). Heterogeneous staining pattern of CASC5 protein was exclusively detected using IHC. The frequency of CASC5 protein over expression was detected in 67.7% (44 of 65) UBC patients and negative in benign prostatic hyperplasia (BPH). Further, CASC5 protein expression was significantly (p < 0.001) associated with cigarette smoking habit in UBC patients. Our study findings testified that CASC5 over expression among patients with UBC as compared to controls and concludes that CASC5 is a potential CT gene in UBC.

Prospective evaluation of definitive chemoradiotherapy with volumetric modulated arc therapy in patients with muscle invasive carcinoma of urinary bladder.

INTRODUCTION: Concurrent chemoradiotherapy (CTRT) remains one of the treatment options in patients with muscle invasive bladder cancer (MIBC) unwilling/unsuitable for radical surgery. We evaluated the role of volumetric modulated arc therapy (VMAT) in MIBC patients treated with definitive CTRT. MATERIAL AND METHODS: 25 patients of histologically proven transitional cell MIBC (T2-T4a, N0, M0) unwilling/unsuitable for radical surgery (after maximal transurethral resection of bladder tumour) were recruited in this prospective study. Primary clinical target volume (CTV) consisted of the gross tumour and whole bladder. Primary planning target volume (PTV) and nodal PTV were prescribed 60 Gy and 54 Gy (both in 30 fractions). Concurrent chemotherapy was cisplatin (40 mg/m2) weekly. Acute toxicities were assessed as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Survival estimates were done from the date of registration using the Kaplan-Meier method. RESULTS: Median age was 70 years (37-80 years). Median overall treatment time was 45 days (44-51). Median number of chemotherapy cycles was 5 (range 3-6). 5 (20%) and 4 (16%) patients respectively suffered from acute grade ≥ 2 gastrointestinal and grade ≥ 2 genitourinary toxicities during treatment. One patient each had grade 3 anaemia and neutropenia. At a median follow-up of 34 months (10-45 months), 3-year progression-free survival and overall survival were 65.6% and 81.2% respectively. 3-year distant metastasis-free survival was 90.5%. Bladder preservation rate at 3 years was 68%. CONCLUSIONS: Definitive CTRT with VMAT is well tolerated in patients with MIBC unsuitable for surgery and yields decent survival and bladder preservation outcome.

W-V flap: a new technique for reconstruction of female distal urethral stricture using vestibular mucosa.

A premenopausal woman having a totally occlusive distal urethral stricture, with suprapubic catheter (SPC) in situ, was referred to us for a definitive procedure. On discussion of the treatment options, the patient refused for a buccal or vaginal flap procedure. Thus, a local W-V flap was fashioned from the periurethral vestibular mucosa with seemingly excellent results, both in terms of resolution of her symptoms and a forwardly directed stream of urine without incontinence.

Preventing intra-urethral migration of a guidewire during antegrade placement of a JJ stent: a technical modification.

A JJ stent is usually inserted in antegrade fashion after percutaneous renal surgery. We describe a new technical modification for antegrade stent insertion that prevents intraoperative intra-urethral migration of the guidewire and saves operative time and cost.

Evaluation of factors predicting clinical pleural injury during percutaneous nephrolithotomy: a prospective study.

The purpose of this study is to prospectively identify factors that predict the chance of pleural injury (detected clinically or on postoperative X-ray chest) during percutaneous nephrolithotomy (PCNL). All patients with renal/upper ureteric stones, undergoing PCNL between January 2013 and June 2014, were evaluated for pleural injury. An erect chest X-ray on inspiration was done within 6 h of PCNL. The patients were divided into Groups A and B depending on whether they developed or did not develop pleural injury. Patient-, stone-, renal-, and procedure-related factors were compared between the two groups. 332 patients with mean age 36.76 ± 15.01 years (range 4-80) and M:F of 172:160 fulfilled the inclusion criteria. Pleural complications occurred in 10 patients (3 %). Of 141 patients with supracostal punctures (59 had additional infracostal punctures), 4.2 % (n = 6) had pleural injury. Of 191 patients with only infracostal punctures, 4 developed pleural injuries (2 %). Patients in group A had significantly lower age (27.00 ± 11.18 vs. 37.06 ± 15.03, p = 0.03) and lower BMI (18.0 ± 1.90 vs. 21.12 ± 2.24 p = 0.002). Incidence of pleural injury was significantly higher (p = 0.001) on right side [4.0 % (7/172) vs. 1.8 %, 3/160)]. Incidence of pleural injury had no association with staghorn calculi, stone surface area (590.51 ± 313.88 for Group A vs. 593.02 ± 387.10 for Group B; p = 0.11), degree of hydronephrosis, and operative time (65.13 ± 19.45 for Group A vs. 72.21 ± 19.56 for Group B; p = 0.06). On multivariate analysis, only low BMI and mean age <27 years were associated with higher risk of pleural injury. Higher incidence of pleural injury was noted in patients with low BMI and younger age.

Mechanical suction for clot evacuation: experience with "suction bridge" for safe and effective clot removal.

OBJECTIVES: To present the experience with the use of a "suction bridge" for removal of bladder clots. METHODS: In all patients presenting with bladder clots, mechanical suction was done using a "suction bridge". This bridge has a luer lock that is fixed to the cystoscope sheath, and the other end is connected to suction tube. The suction pressure was started at 250 mmHg and was increased up to 400 mmHg if needed. RESULTS: Twenty patients with a mean age of 59.4 years were included. The etiologies of bladder clots included bladder tumor in nine, benign prostate hyperplasia (BPH) in two, BPH with bladder stone in one, hematochyluria in three, and post-transurethral prostate resection in 10. Eighteen patients presented in clot retention. The estimated clot size ranged from 50 mL to more than 1 L. The mean duration for clot removal was 15 min (range 5-60). The procedure was successful in all patients. There was no bladder injury. The limitations include the small number of recruits, the non-randomized nature of study, and no control group for comparison. CONCLUSION: Mechanical suction is another safe, fast, and effective option of clot removal from the urinary bladder. The suction bridge is useful while using this method.

Labda-8(17),12,14-trien-19-oic acid contained in fruits of Cupressus sempervirens suppresses benign prostatic hyperplasia in rat and in vitro human models through inhibition of androgen and STAT-3 signaling.

Fruit extract of Cupressus sempervirens (CS), which is used traditionally to treat Benign Prostatic Hyperplasia (BPH)-like urinary symptoms in patients, was scientifically validated for anti-BPH activity. The ethanolic fruit extract of CS inhibited proliferation of human BPH-stromal cells and the activity was localized to its chloroform-soluble, diterpene-rich fraction. Eight major diterpenes isolated from this fraction exhibited moderate to potent activity and the most active diterpene (labda-8(17),12,14-trien-19-oic acid) exhibited an IC50 of 37.5 µM (antiproliferative activity against human BPH-stromal cells). It significantly inhibited activation (phosphorylation) of Stat-3 in BPH-stromal cells and prevented transactivation of androgen sensitive KLK3/PSA and TMPRSS2 genes in LNCaP cells. Labda-8(17),12,14-trien-19-oic acid-rich CS fraction prevented prostatic hyperplasia in rat model and caused TUNEL labeling of stromal cells with lower expressions of IGF-I, TGF-ß and PCNA, and bcl-2/bax ratio. Human BPH tissues exhibited precise lowering of stromal component after incubation in labda-8(17),12,14-trien-19-oic acid, ex vivo. We conclude that labda-8(17),12,14-trien-19-oic acid contained in CS exhibits anti-BPH activity through inhibition of stromal proliferation and suppression of androgen action in the prostate, presenting a unique lead structure for further optimization of anti-BPH activity.

Prevalence and risk factors of urinary incontinence in Indian women: A hospital-based survey.

BACKGROUND AND OBJECTIVES: Urinary incontinence is a problem that creates both physical and psychological nuisance to a woman. This problem needs to be studied in detail in Indian population because of lack of precise data. The objectives of this study were to study the prevalence and risk factors of urinary incontinence in Indian women. MATERIALS AND METHODS: This hospital-based cross-sectional study conducted from August 2005 to June 2007 included women attending gynecology OPD (consulters) and hospital employees (nonconsulters). Subjects who were incontinent were asked a standard set of questions. Incontinence was classified as urge, stress, or mixed based on symptoms. A univariate followed by multivariate analysis was done to look for risk factors. RESULTS: Of 3000 women enrolled, 21.8% (656/3000) women were incontinent. There was no significant difference in incontinence rate between consulters and nonconsulters [618/2804 (22.1%) vs. 38/196 (19.4%); P value = 0.6). Of the total women having incontinence, highest numbers were found to have stress incontinence [73.8% (484/656)] followed by mixed [16.8% (110/656)] and urge incontinence [9.5% (62/656)]. Age more than 40 years; multiparity; postmenopausal status; body mass index more than 25; history of diabetes and asthma; and habit of taking tea, tobacco, pan, and betel are risk factors found to be associated with increased prevalence of urinary incontinence in univariate analysis. On multivariate analysis, age more than 40 years, multiparity, vaginal delivery, hysterectomy, menopause, tea and tobacco intake, and asthma were found to be significantly associated with overall incontinence. Stress incontinence was separately not associated with menopause. Urge incontinence was not associated with vaginal delivery. CONCLUSION: Urinary incontinence is a bothersome problem for women. Simple questionnaire can help to detect this problem and diagnose associated risk factors, so that necessary steps can be taken in its prevention and treatment.

Excluded calyx following percutaneous nephrolithotomy: a rare complication.

Radiological images in a case of excluded calyx are shown that resulted from percutaneous nephrolithotomy for a stag horn stone that was approached through the superior calyx.

Selective estrogen receptor modulators regulate stromal proliferation in human benign prostatic hyperplasia by multiple beneficial mechanisms--action of two new agents.

The existing drugs for benign prostatic hyperplasia (BPH) are partially effective with undesirable side-effects; hence new agents acting by different mechanism(s) are required as supplements. Modulation of estrogen receptor signaling using selective estrogen receptor modulators (SERMs) offers an alternative approach for BPH management. Using human BPH-derived stromal cells and tissue explants in culture we evaluated two SERMs, DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2 H-1-benzopyran (BP) and Ormeloxifene (Orm) in comparison to Tamoxifen (Tam) and 4-hydroxytamoxifen (OHT). BP, OHT and Tam were more effective than Orm in reducing stromal cell proliferation of human BPH. BP was either equipotent or more effective than OHT and Tam in increasing estrogen receptor(ER)-ß, TGFß1, Fas and FasL, and in decreasing ER-α, AR, EGF-R and IGF-I expressions in BPH stromal cells. BP, Tam and Orm (1.0 mg/Kg) reduced rat prostate weights by almost same extent as Finasteride (Fin, 5.0 mg/Kg); however combination treatment (SERM+Fin) was more effective. BP was exceptionally efficient in reducing IGF-1 and cleaving PARP while combination treatments more effectively increased bax:bcl-2 ratio. Fin reduced acinar diameter and prostatic DHT level but increased testosterone, estradiol (E(2)) and E(2)/T+DHT ratio. SERMs, especially BP, reduced epithelial cell height drastically without significantly altering steroid hormone levels and E(2)/T+DHT ratio. Combination treatment reduced both acinar diameter and epithelial cell height with modest increase in E(2), T and E(2)/T+DHT. The study reveals the potential of SERMs per se for BPH management, and more effectively in combination with a 5α-reductase inhibitor. BP appears promising for further evaluation as a drug candidate for BPH and prostate cancer.

Arylpiperazines for management of benign prostatic hyperplasia: design, synthesis, quantitative structure-activity relationships, and pharmacokinetic studies.

A series of 27 aryl/heteroaryl/aralkyl/aroyl piperazines were synthesized, and most of these compounds reduced prostate weight of mature rats by 15-47%. Three compounds, 10, 12, and 18, had better activity profile (reduced prostate weight by 47%, 43%, and 39%, respectively) than the standard drug flutamide (24% reduction). QSAR suggested structures with more cyclic and branched moieties, increased topological separation of O and N therein, and reduced solvation connectivity index for better activity. Pharmacokinetic study with compound 10 at an oral dose of 10.0 mg/kg indicated good absorption, negligible extrahepatic elimination, and rapid distribution to the target organ (prostate) but restricted entry through the blood-brain barrier. A 10-fold decrease in PSA and 15-fold increase in ER-ß gene expressions of human prostate cancer cells (LNCaP) by compound 10 in vitro indicated AR and ER-ß mediated actions. The findings may stimulate further explorations of identified lead for the management of benign prostatic hyperplasia.

Gritty sensation on catheter: a new clinical sign for self-diagnosis of stone formation in the continent urinary pouch.

With more experience and better management, the incidence of complications like stone formation after continent urinary diversion is uncommon today. We report a case of large stone bulk in a patient who underwent this surgery 10 years back and who suggested the formation of stones in the pouch herself by sounding them. Proper counseling, regular pouch irrigation and follow-up are essential in any kind of diversion.

Taurine - a possible fingerprint biomarker in non-muscle invasive bladder cancer: A pilot study by 1H NMR spectroscopy.

Urinary bladder cancer is a major epidemiological problem that continues to grow each year. It opens avenues for investigative research for the identification of new disease markers and diagnostic techniques. In this pilot study, utility of non-invasive (1)H NMR spectroscopy has been evaluated for probing the metabolic perturbations occurring in non-muscle invasive urinary bladder cancer. (1)H NMR spectra of urine of bladder cancer patients and controls (healthy and urinary tract infection/bladder stone) (n = 103) were acquired at 400MHz. The non-overlapping resonances of citrate, dimethylamine, phenylalanine, taurine and hippurate were first identified and then quantitated by (1)H NMR spectra, with respect to an external reference sodium-3-trimethylsilylpropionate (TSP). The concentrations of these metabolites were then statistically analyzed. The cancer patients showed significant (p < 0.05) variations in concentration of hippurate and citrate as compared with healthy controls and benign controls. The significant elevation in concentration of taurine was observed in urine of bladder cancer patients, which was below the sensitivity limit of 400MHz in control cases. However, stages Ta, T1 and carcinoma in situ (CIS) cannot be differentiated on the basis of altered metabolite indices but their composition may reflect the biochemical alterations in metabolism of cancer cells.

Meatoplasty using double buccal mucosal graft technique.

OBJECTIVE: Glanular urethral/meatal stricture is associated with severe narrowing of the urethral lumen and treatment is sometimes associated with recurrence. We describe our technique and results of double buccal mucosa graft placement for the treatment of these strictures. METHODS: After penile degloving, the strictured urethra was opened ventrally and glanular wings were raised. A dorsal urethrotomy incision then creates a dorsal bed where an appropriately sized buccal mucosal graft was stitched. In the glanular portion, a ventral graft was also placed, which is secured ventrally by the glans wings created before. Thus the glans wings provide a vascular bed to the ventral graft. RESULTS: Ten adult patients were treated with this technique. The stricture etiologies were lichen sclerosus (n = 7) and post-catheterization (n = 3). At mean follow-up duration of 13.5 months, all patients had a satisfactory clinical outcome as assessed by symptoms and uroflow results with acceptable cosmetic outcome. CONCLUSIONS: Our double graft technique for treatment of meatal/glanular strictures has shown promise and can be a treatment option for such strictures in adults.