Urinary microRNA-10a levels in diagnosis and prognosis of urinary bladder cancer.

Background: Urinary bladder cancer (UBC) is a disease quite common in developed countries; however, its incidence is increasing in developing countries as well. The diagnosis of UBC is generally based on a number of methods, of which urinary cytology is a very commonly used one. But it is not very reliable. Therefore many new markers and methods are being investigated to make non-invasive diagnosis of UBC easy and reliable. Objective: This study was carried out to find the usefulness of microRNA (miRNA)-10a as a diagnostic and prognostic marker in non-muscle-invasive urinary bladder carcinoma. Material and Method: Twenty patients with UBC were taken as cases with 20 controls. Urine cytological examination was done, as well as histopathological examination of tumor tissue of cases. Urinary miRNA-10a estimation of both the cases and controls were done. Result and Conclusion: It was found that miRNA-10a is significantly high in urine of patients with UBC. Its value also significantly correlated with the grade and stage of the tumor. Hence it can be concluded that urinary miRNA-10a is a potential candidate in the diagnosis and prognosis of UBC.

Evaluation of prostate cancer tissue metabolomics: would clinics utilise it for diagnosis?

The difficulty of diagnosing prostate cancer (PC) with the available biomarkers frequently leads to over-diagnosis and overtreatment of PC, underscoring the need for novel molecular signatures. The purpose of this review is to provide a summary of the currently available cellular metabolomics for PC molecular signatures. A comprehensive search on PubMed was conducted to find studies published between January 2004 and August 2022 that reported biomarkers for PC detection, development, aggressiveness, recurrence and treatment response. Although potential studies have reported the presence of distinguishing molecules that can distinguish between benign and cancerous prostate tissue. However, there are few studies looking into signature molecules linked to disease development, therapy response or tumour recurrence. The majority of these studies use high-dimensional datasets, and the number of potential metabolites investigated frequently exceeds the size of the available samples. In light of this, pre-analytical, statistical, methodological and confounding factors such as antiandrogen therapy (NAT) may also be linked to the identified chemometric multivariate differences between PC and relevant control samples in the datasets. Despite the methodological and procedural challenges, a range of methodological groups and processes have consistently identified a number of signature metabolites and pathways that appear to imply a substantial involvement in the cellular metabolomics of PC for tumour formation and recurrence.

Management of Metastatic Renal Cell Carcinoma in a Tertiary Care Hospital.

Background The behavior of metastatic renal cell carcinoma (mRCC) is unpredictable and elusive. International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scores, histological subtypes, and targeted therapy predict survival and prognosis. However, there is a paucity of literature from the Indian subcontinent on mRCC outcomes. Therefore, this prospective study reports overall survival outcomes and complications due to targeted therapy of mRCC from a single tertiary care center. Methodology Between 2015 and 2020, 110 patients were included in the study. The treatment was based on the IMDC. Cytoreductive nephrectomy was done in 30 patients, and renal mass biopsy was done in 80 patients. Six were lost to follow-up after histopathological diagnosis, and targeted therapy was administered to 104 patients (sunitinib in 41, sorafenib in 33, and pazopanib in 30). During targeted therapy, six died within 30 days of treatment. The overall survival outcomes and complications due to targeted therapy were analyzed. Results The mean overall survival was 21.52 months with a 95% confidence interval of 17.04-25.98 months. Six variables significantly correlated with inferior survival in univariable Cox regression analysis. Weight loss, hemoglobin, platelet count, lung metastasis, and ≥2 visceral metastases were associated with poor outcomes. Performance status >2 and lung metastasis predicted poor outcomes in multivariate analysis. Overall survival was 24.52 months in clear cell carcinoma versus 21.39 months (13.32-29.45 months) in papillary cell carcinoma, which was not significant. Conclusions IMDC groups show significant differences in overall survival. The histological subtypes and types of targeted therapy did not differ in overall survival, and the presence of sarcomatoid differentiation correlated with poor prognosis concerning IMDC.

Oct-4: a prognostic biomarker of urinary bladder cancer in North India.

BACKGROUND: The objective of this study was to evaluate Octamer-binding transcription factor 4 (Oct-4), neutrophil to lymphocyte ratio (NLR) and body mass index (BMI) as independent prognostic biomarkers for prediction of urinary bladder cancer (UBC) outcomes. With the advancement in prognostic biomarker discovery, tumor recurrence is difficult to accurately predict in UBC. UBC is costly to treat due to the requirement of frequent invasive follow-up sessions. Therefore, it is of utmost importance to evaluate good prognostic biomarkers for UBC surveillance. METHODS: We studied 39 UBC tissue samples. Oct-4 protein expression was evaluated semiquantitatively by immunohistochemistry (IHC). Complete blood count data and body weight as well as the height of the patients were retrieved and recorded before the date of the first transurethral resection of bladder tumor (TURBT). The follow-up period was 48 months for recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). RESULTS: Oct-4 expression profile was found to be significantly associated with gender (p = 0.028), tumor grade (p = 0.038), tumor stage (p = 0.003), lymph node status (p = 0.029), recurrence (p = 0.004), progression (p = 0.011), and treatment modality (p = 0.016). Tumor grade and progression were found significant with NLR values (tumor grade, p = 0.006; progression, p = 0.038) and BMI (tumor grade, p = 0.036; progression, p = 0.014). Moreover, BMI was also significantly associated with UBC recurrence (p = 0.014). Kaplan-Meier survival analysis showed poor prognosis with both high Oct-4 expression (RFS, p = 0.001; PFS, p = 0.004; OS, p = 0.014) and high NLR values (RFS, p = 0.049; PFS, p = 0.004; OS, p = 0.005). Patients with high BMI too had poor RFS (p = 0.025) and poor PFS (p = 0.032). Furthermore, multivariate Cox regression analysis, indicated Oct-4 as an independent prognostic biomarker for RFS (HR = 0.240, 95% CI, 0.072-0.804, p = 0.021). CONCLUSIONS: We conclude that the expression profile of Oct-4 will be beneficial in prediction of UBC recurrence, and could have profound implications on the development of new therapeutic targets for UBC treatment.

Does 24bp Duplication of Human CHIT1 Gene (Chitotriosidase1) Predispose to Filarial Chyluria? A Case-Control Study.

INTRODUCTION: Chyluria which is endemic in many parts of the world is mainly caused by Wuchereria bancrofti. CHIT1 (chitotriosidase) is produced by macrophages and plays an important role in the defense against chitin containing pathogen such as filarial parasite. Variation in the coding region with 24 bp duplication allele results in reduced CHIT1 activity that enhance the survival of parasite which may play a role in the occurrence of disease. AIM: To examine the role of 24bp duplication of CHIT1 gene in patients of filarial chyluria (FC). MATERIALS AND METHODS: A case-control study was carried out where 155 confirmed FC patients and equal number of age-, sex- and residence-matched controls without any symptoms or signs of lymphatic filariasis, confirmed by negative immunochromatographic card test (ICT) and IgG/IgM combo rapid antibody test, from a hospital-based population were enrolled. Filarial aetiology was confirmed on the basis of DEC-provocative test (Giemsa staining), ICT and IgG/IgM- antifiarial antibody test. The patients positive by either of these tests were enrolled as FC cases. 24bp duplication in CHIT1 gene in FC was detected by the product size 99bp of amplified gene using polymerase chain reaction. RESULTS: The mean ages of patients and controls were 38.25±12.09 and 35.45±12.53 years, respectively while male: female ratio was 2.4:1. The mean duration of illness in chyluria patients was 62.81±60.83 months and mean number of episodes was 2.54±1.11. Homozygous wild type, heterozygous and homozygous mutant frequencies were 10.3%, 81.3% and 8.4% in FC patients and 18.7%, 75.5%, and 5.8% in controls, respectively. The 24bp duplication in CHIT1 gene showed a significant association in Heterozygous (HT) genotype with Odd Ratio (OR) of 1.95, 95% Confidence Interval (CI) (1.01-3.77); p=0.04. However, the homozygous mutant genotype (TT) was found to be non-significant with OR of 2.61, 95% CI (0.91-7.45); p=0.07. The combination of both HT+TT was also found to be significant with OR of 2.00, 95% CI (1.03-3.85); p=0.03. CONCLUSION: In this study from Northern India, CHIT1 gene polymorphism showed an influence as a possible risk factor for susceptibility to FC. Further studies need to be done on a larger number of FC patients in different regions of the country.

2-Methyl-4/5-nitroimidazole derivatives potentiated against sexually transmitted Trichomonas: Design, synthesis, biology and 3D-QSAR study.

Trichomoniasis is the most prevalent, non-viral sexually transmitted diseases (STD) caused by amitochondriate protozoan Trichomonas vaginalis. Increased resistance of T. vaginalis to the marketed drug Metronidazole necessitates the development of newer chemical entities. A library of sixty 2-methyl-4/5-nitroimidazole derivatives was synthesized via nucleophilic ring opening reaction of epoxide and the efficacies against drug-susceptible and -resistant Trichomonas vaginalis were evaluated. All the molecules except two were found to be active against both susceptible and resistant strains with MICs ranging 8.55-336.70 µM and 28.80-1445.08 µM, respectively. Most of the compounds were remarkably more effective than the standard Metronidazole. This study analyzes the in vitro and in vivo activities of the new 5-nitroimidazoles, which were found to be safe against human cervical HeLa cells with good selectivity index. The exploration of SAR by the synthesis of four different prototypes and 3D-QSAR study has shown the importance of prototype 1 over other prototypes.

Ammonium salts of carbamodithioic acid as potent vaginal trichomonacides and fungicides.

Chemical attenuation of the reactive oxygen species (ROS)-sensitive anaerobes Trichomonas vaginalis, which is the most prevalent non-viral sexually transmitted infection, and two often coexisting vaginal infections, namely Candida albicans and Staphylococcus aureus, which are opportunistic reproductive tract infections, was attempted with novel ammonium salts of carbamodithioic acid through inhibition of free thiols. In vitro and in vivo efficacies of the designed compounds were evaluated as topical vaginal microbicides. Five compounds showed exceptional activity against drug-resistant and -susceptible strains with negligible toxicity to host (HeLa) cells in vitro in comparison with the standard vaginal microbicide nonoxynol-9 (N-9), without disturbing the normal vaginal flora (i.e. Lactobacillus). The compounds significantly inhibited the cytopathic effects of Trichomonas on HeLa cells in vitro with efficacies comparable with metronidazole (MTZ); however, their efficacy to rescue host cells from co-infection (protozoal and fungal) was greater than that of MTZ. The compounds inhibited ß-haemolysis of red blood cells caused by Trichomonas and were found to be active in vivo in the mouse subcutaneous abscess assay. Some compounds rapidly immobilized human sperm. A mechanism involving inhibition of free thiols and consequently the cysteine proteases of T. vaginalis by the new compounds has been proposed. Thus, a unique scaffold of antimicrobial agents has been discovered that warrants further investigation for development as contraceptive vaginal microbicides.

Innovative Disulfide Esters of Dithiocarbamic Acid as Women-Controlled Contraceptive Microbicides: A Bioisosterism Approach.

In an ongoing effort to discover an effective, topical, dual-function, non-surfactant contraceptive vaginal microbicide, a novel series of 2,2'-disulfanediylbis(3-(substituted-1-yl)propane-2,1-diyl) disubstituted-1-carbodithioates were designed by using a bioisosterism approach. Thirty-three compounds were synthesized, and interestingly, most demonstrated multiple activities: they were found to be spermicidal at a minimal effective concentration of 1-0.001 %, trichomonacidal against drug-susceptible and resistant Trichomonas strains at minimal inhibitory concentration (MIC) ranges of 10.81-377.64 and 10.81-754.14 µM, respectively, and fungicidal at MIC 7.93-86.50 µM. These compounds were also found to be non-cytotoxic to human cervical (HeLa) epithelial cells and vaginal microflora (Lactobacilli) in vitro. The most promising compound, 2,2'-disulfanediylbis(3-(pyrrolidin-1-yl)propane-2,1-diyl)dipyrrolidine-1-carbodithioate (5), exhibited spermicidal activity 15-fold higher than that of the marketed spermicide Nonoxynol-9 (N-9) and also demonstrated microbicidal potency. To identify common structural features required for spermicidal activity, a 3D-QSAR analysis was carried out, as well as in vivo efficacy studies and fluorescent labeling studies to determine the biological targets of compound 5.

N-Alkyl/aryl-4-(3-substituted-3-phenylpropyl)piperazine-1-carbothioamide as dual-action vaginal microbicides with reverse transcriptase inhibition.

The growing population and health-care burden (due to STIs and HIV) imposes a particular economic crisis over resource-poor countries. Thus a novel approach as vaginal microbicides emerges as integrated tool to control both population and anti-STIs/HIV. Our continued efforts in this field led to the synthesis of fifteen N-alkyl/aryl-4-(3-substituted-3-phenylpropyl) piperazine-1-carbothioamide (12-26) derivatives as topical vaginal microbicides which were evaluated for anti-Trichomonas, spermicidal, antifungal and reverse transcriptase (RT) inhibitory activities. All compounds were also tested for preliminary safety through cytotoxicity assays against human cervical cell line (HeLa) and the vaginal flora, Lactobacillus. Docking studies were performed to gain an insight into the binding mode and interactions of the most promising compound 12 [oxo derivative], comprising of reverse transcriptase (RT) inhibitory (72.30%), spermicidal (MEC 0.01%), anti-Trichomonas (MIC 46.72 µM) and antifungal (MIC 9.34-74.8 µM) activities, along with its hydroxyl (17) and O-alkylated 4-trifluoromethylphenoxy (22) derivative, with similar activities. The stability of compound 12 in simulated vaginal fluid (SVF) and its preliminary in vivo pharmacokinetics performed in female NZ-rabbits signifies its clinical safety in comparison to marketed spermicide Nonoxynol-9.

Congenital anterior urethral valve with or without diverticulum: a single-centre experience.

INTRODUCTION: Congenital anterior urethral valves (AUV) are rare and can occur as an isolated entity or in association with proximal diverticula. Diagnosis may be overlooked and ideal treatment is not standardized when both the valve and diverticulum are simultaneously present. We present our experience of congenital AUV. MATERIAL & METHODS: From January 2007 to June 2012 a retrospective review of the medical records of 7 cases of AUV was performed. RESULTS: Three patients were diagnosed as isolated AUV while four presented with associated diverticula. The age of presentation ranged from 10 months to 6 years. Weak voiding stream and dribbling were the most common symptoms. Renal function was found to be deranged in two patients (28%). Hydro-ureteronephrosis was present in three boys (42%) and reflux was present in one patient. Post-void residual volume was >20 ml (mean 55 ml) in all children. Transurethral holmium laser fulguration was carried out on isolated AUV or AUV with small diverticula. Open resection and reconstruction or plication was performed in patients with AUV and proximal large (>3 cm) diverticula. Surgical outcome was successful in all patients except for occurrence of urethrocutaneous fistula in one patient. CONCLUSIONS: In isolated AUV or valve with associated small diverticulum, transurethral holmium:YAG laser ablation is the treatment of choice. Primary excision and repair or plication are preferred if a large diverticula has formed. Eventual outcomes of AUV are good if irreversible changes have not been established.

Use of holmium:YAG laser in posterior urethral valves: another method of fulguration.

OBJECTIVE: To evaluate the use of holmium:YAG laser for posterior urethral valve (PUV) fulguration and compare with electro-fulguration. METHODS: Forty boys underwent primary fulguration of PUV using 20-25 W holmium laser (Group 1) from January 2009 to December 2011. Data of last 40 boys (retrospective cohort: January 2005 to December 2008) who underwent electro-fulguration (Group 2) for PUV were compared with group 1. Ultrasonography was done at 2 weeks and 3 months and voiding cystourethrography at 3 and 6 months respectively after fulguration and as needed thereafter. DTPA scan and urodynamic study were performed during follow-up in select patients, as required. RESULTS: Pre-operative parameters were comparable between groups. Improvement in voiding occurred in 38 and 34 boys in group 1 and 2, respectively. Hydroureteronephrosis and vesico-ureteric reflux resolved in 53% and 60% in group 1 and 51% and 53% in group 2, respectively. Boys in group 1 had statistically significant greater success in voiding after catheter removal (40 vs 32), shorter period of catheterization (1 vs 1.8 days), lower mean operative time (15 vs 20 min), needed re-fulguration less commonly (2 vs 6), and were less likely to develop urethral stricture (0 vs 2) and urinary incontinence (0 vs 1). CONCLUSION: PUV fulguration using holmium:YAG laser is a feasible, safe and effective alternative for endoscopic transurethral ablation with similar success, and appears to have fewer complications than electro-fulguration.

Grading complications after transurethral resection of prostate using modified Clavien classification system and predicting complications using the Charlson comorbidity index.

PURPOSE: To retrospectively report and grade the peri-operative complications of transurethral resection of the prostate (TURP) using the modified Clavien classification system (MCCS) and validate whether Charlson comorbidity index (CCI) predicts the complications after TURP. MATERIALS AND METHODS: Between September 2006 and 2012, data of 722 patients who underwent TURP were analyzed after excluding patients with incomplete data (n = 40). Data recorded included the age, prostate volume, operative time, mean prostatic tissue removed and duration of hospitalization while complications were recorded using the MCCS. Preexisting comorbidities were evaluated using the CCI, and patients were classified into 3 CCI score categories (0, 1, ≥ 2). RESULTS: Two hundred and forty-four complications were seen in 145 (20 %) patients. CCI score was "0" for 480 patients (66.5 %), "1" for 184 patients (25.5 %) and "≥ 2" for 58 patients (8 %). Significant difference was observed between patient groups with CCI score 0, 1 and ≥ 2 for mean age, prostatic weight, operative time, weight of prostatic chips and duration of hospitalization. Similarly, a significant difference in occurrence of various MCCS grades of complication among patients groups with different CCI score was observed. CONCLUSION: Grades I, II and III complications constituted the main bulk (90 %) while grade IV were less common (<8 %) and grade V was rare (1 %) after TURP. Men with higher CCI score had a significantly higher rate of morbidity than those with a lower score. The present study is the first to validate that CCI can predict complications of TURP recorded according to the MCCS.

Anterior vesical hitch--a step to enhance safety of percutaneous access to bladder.

PURPOSE: To describe the novel technique of anterior vesical hitch to enhance the efficacy and safety of percutaneous bladder surgery. MATERIALS AND METHODS: The anterior bladder wall is anchored to the anterior abdominal wall with the help of a prolene suture passed slightly lateral to the midline midway between the pubic symphysis and umbilicus. Percutaneous cystolitholapaxy and antegrade posterior urethral valve ablation were performed after anterior vesical hitch in five pediatric male patients. Data collected included operative parameters and complications related to the technique. RESULTS: Mean patient age was 2.9 years (range 1.5-6 years). Three patients had bladder stones and two had posterior urethral valves. Mean time to achieve bilateral parietal fixation of the bladder was 7 min 20 s. There was no intraoperative slippage of Amplatz sheath or suture cut through. No bleeding from the puncture site was encountered. No postoperative complication related to the percutaneous access tract was noted in any patient. CONCLUSIONS: The anterior vesical hitch procedure is safe and easy. It prevents slippage of Amplatz sheath during percutaneous access to the bladder lumen.

Auto-Penectomy: A Devastating Complication of Advanced, Neglected Penile Carcinoma: Autopenectomy due to penile carcinoma.

Auto-penectomy is a rare consequence of penile carcinoma (PC). Two men, 65 and 74 years of age, presented with total penile loss secondary to PC. Due to poor hygiene and negligence, the ulcer was infected with maggots. The management was by local debridement and suprapubic cystostomy. No further treatment was done as the patients did not come for follow-up.

Preventing Inadvertent Placement of Foley Catheter into Prostatic Urethra During Suprapubic Trocar Cystostomy: A Simple Face-saver Trick.

During suprapubic cystostomy using standard technique, there always remains a chance of accidental migration of foley catheter through bladder neck into prostatic urethra. We herein present a point of technique in which by keeping the direction of cannula slot toward umbilicus and making it vertical or slightly tilting its tip toward umbilicus during foley placement, prevents the inadvertent migration of catheter into prostatic urethra and further complications.

Prospective Randomized Comparison of Open versus Transperitoneal Laparoscopic Ureterolithotomy: Experience of a Single Center from Northern India.

AIM: Prospective randomized study on transperitoneal laparoscopic ureterolithotomy (TPLU) versus open ureterolithotomy (OU) for treatment of large impacted ureteric stones (≥ 1.5 cm) and assessment of overall results. MATERIAL & METHODS: In a prospective study between 2010 to 2012, 30 patients underwent TPLU and 30 OU based on 1:1 randomization. The operation was indicated primarily in 44 cases or after failed shock-wave lithotripsy/ureteroscopy in 16 cases. Two groups were compared for operative time, success rate, visual pain score, analgesic requirement, hospital stay, and postoperative complications. Statistical analysis was performed with SPSS® version 16.0 using Fisher exact or Mann-Whitney U tests with p < 0.05 considered statistically significant. RESULTS: The difference in visual pain score (6.2 in TPLU group vs 3.1 in OU group on day 1; 4.8 vs. 2.4 on day 2) and tramadol requirements (184.32 mg in TPLU group vs. 150.87 mg in OU group on day 1; 97.34 mg vs. 65.56 mg on day 2) were statistically significant and more in OU. Hospital stay and convalescence were significantly lower in the TPLU. However, stone removal in one attempt was similar in both the groups. CONCLUSION: Although successful stone removal rates are equal in both groups, TPLU is associated significantly with less postoperative pain, less analgesic requirement, shorter hospital stay and short convalescence in comparison to OU.

The twin amplatz sheath method: a modified technique of percutaneous cystolithotripsy for large bladder stones in female patients.

To minimize the operative time and to avoid open cystolithotomy in women with large bladder stone (>5 cm), we present here a modification of percutaneous cystolithotomy, a well-described standard procedure for urinary bladder stones. With this technique, suprapubic percutaneous access was achieved under cystoscopic guidance. The suprapubic tract was dilated and an Amplatz sheath of 30 Fr was placed. Simultaneously, the urethra was sequentially dilated with fascial dilators and a 28 Fr Amplatz sheath was guided into the bladder and the foot end of the table lowered to 20° to facilitate high-speed outflow of irrigant and stone particles. A 26.5 Fr nephroscope was passed through the suprapubic Amplatz sheath and the stone was fragmented by intracorporeal pneumatic device keeping the stone close to the proximal end of the urethral Amplatz. These maneuvers help in washing out stone fragments periurethrally and keeping the endoscopic vision clear while breaking the stone.

Anastomotic urethroplasty in female urethral stricture guided by cystoscopy - a point of technique.

PURPOSE: During anastomotic urethroplasty for stricture urethra with false passage using standard technique, there remains a chance of anastomosis of normal distal urethra to proximal false lumen. Herein, we present a point of technique in which by using antegrade cystoscope, one cannot just identify and dissect normal anatomical proximal urethral lumen, but also perform some of the steps for anastomosis under direct vision. This will avoid making anastomosis to false lumen and thus leading to further complications. MATERIALS AND METHODS: We report a case of 35-years-female who was presented to us with total mid-urethral stricture with false passage following multiple urethral dilatation attempts. We used antegrade cystoscopy during anastomotic urethroplasty to identify and dissect the proximal end of urethra thereby avoiding anastomosis to false tract. RESULTS: We successfully performed anastomotic urethroplasty avoiding false passage. Post-operative Uroflow showed Q max of 18 ml/sec. Voiding cystourethrogram post-operatively showed anastomosis between normal anatomical lumens. CONCLUSION: This modification of using antegrade cystoscopy helps to identify proximal urethral end which in turn helps in avoiding anastomosis to false tract and ensures anastomosis between normal lumens.