Occupational and Environmental Exposure Influences the Inflammatory (Pro-and Anti-) Status in Benign Prostate Hyperplasia and Prostate Carcinoma Patients: A Retrospective Analysis.

Multiple diseases and disorders are connected with occupational and environmental exposure risk. It is also well-established that chemicals and chemical mixtures have an influence on the immune cells of humans. This is an important field of research that has been pursued extensively in relation to autoimmune illnesses, allergy/asthma, and lung cancer, but Prostate Carcinoma has received rare reports. Chronic chemical exposure is known to produce inflammation, which is one of the most prominent characteristics of all malignancies. Changes in the ratio of pro-inflammatory to anti-inflammatory molecules are thought to be a key factor in the emergence of inflammation. Prostate gland cells express the pro-inflammatory cytokine interleukin-18 (IL-18), which is a major facilitator of immunological responses. Conversely, interleukin-10 (IL-10) is an anti-inflammatory cytokine that is linked to immune responses and inhibits the development of an inflammatory environment. Our goal is to investigate the inflammatory status of IL-18 (pro-) and IL-10 (anti-) in a variety of occupationally exposed populations in patients with Benign Prostate Hyperplasia (BPH) and patients with Prostate Carcinoma. The present study was conducted with 664 subjects, comprising 285 Prostate Carcinoma patients, 94 BPH patients and 285 controls. The subjects of BPH and Prostate Carcinoma were screened and confirmed on the basis of Prostate Serum Antigen (PSA) and pathological biopsy. All subjects were categorized as per their occupational exposure into various groups. The pro-inflammatory and anti-inflammatory Interleukins (IL-18 and IL-10) and serum PSA levels were analysed by using corresponding quantitative ELISA kits. The results showed that as compared to control participants, the serum PSA levels were higher in the Prostate Carcinoma and BPH groups. When mean levels of IL-18 were compared between various occupational groups, Tanners (tanning industry), Agriculture, and Ordnance workers had significantly higher levels (P < 0.05) of IL-18 than sedentary workers. The pro-inflammatory cytokine (IL-18) levels were also found to be aggravated in Prostate Carcinoma compared to BPH and controls. According to the findings of the current study, the levels of inflammatory cytokines (IL-18 and IL-10) in various occupational groups of BPH, Prostate Carcinoma, and controls were altered. Long-term occupational exposure may have a negative influence on inflammation levels and the immune system; therefore, preventative measures should be explored for improved health.

Immunohistochemical expressions of EMT markers in pan-RAS-pERK1/2-positive tumors improve diagnosis and prognosis assessment of non-muscle invasive bladder cancer and muscle invasive bladder cancer patients.

Mutation or overexpression renders pan-RAS (rat sarcoma) proteins insensitive to inactivation. Activated pan-RAS communicates signal from the cell surface receptor to activate RAS-MAPK/ERK (RAS-mitogen-activated protein kinases/extracellular signal regulated kinases) signaling and orchestrates epithelial-to-mesenchymal transition-activating transcription factors (EMT-ATFs) reprogramming to induce EMT. Owing to limited studies available in bladder cancer, the present study is taken up to examine the expressions of the EMT-associated markers in pan-RAS-pERK1/2 (pan-RAS-phosphoERK1/2)-positive well-characterized cohort of forty-two non-muscle invasive bladder cancer (NMIBC) and forty-five muscle invasive bladder cancer (MIBC) patients. Immunohistochemical staining was performed on paraffin embedded tissue sections to determine the immunolevels and cellular localization of marker proteins. Semi-quantitative expressions of pan-RAS, pERK1/2, and EMT markers (E-cadherin, Vimentin, N-cadherin, Snail, Slug Twist, and Zeb1) were statistically examined with clinicohistopathological profile of the patients using SPSS, version 20.0 software. The study documents the diagnostic relevance of immunohistochemical expressions of pan-RAS-pERK1/2/EMT-associated markers in order to stratify NMIBC and MIBC patients. Follow-up studies supported the role of altered EMT phenotype in pan-RAS-pERK1/2-activated positive tumors with disease aggressiveness. To the best of our knowledge, our study is the first concluding the impact of altered EMT phenotype via pan-RAS-pERK1/2 axis on the short survival outcome [short overall survival (OS) (p = 0.04), short progression-free survival (PFS) (p = 0.02) and short cancer-specific survival (CSS) (p = 0.03)] of muscle invasive bladder cancer patients.

Diagnostic and therapeutic cystoscopy in bladder pain syndrome/interstitial cystitis: systematic review of literature and consensus on methodology.

INTRODUCTION AND HYPOTHESIS: Cystoscopy has been routinely performed in patients suspected to be suffering from bladder pain syndrome/interstitial cystitis (BPS/IC) across the globe. The methodology reported by various guidelines appears to have differences in the techniques and hence there is a need for a review of all those techniques in order to arrive at a consensus. The aim was to review the literature describing the prevalent techniques of cystoscopy for patients of BPS/IC and try to evolve a consensus. METHODS: The group the Global Interstitial Cystitis, Bladder Pain Society (GIBS) has worked collectively to systematically review the literature using the key words, "Cystoscopy in Hunner's lesions, bladder pain syndrome, painful bladder syndrome and interstitial cystitis" in the PubMed, COCHRANE, and SCOPUS databases. A total of 3,857 abstracts were studied and 96 articles referring to some part of technique of cystoscopy were short-listed for review as full-length articles. Finally, six articles with a description of a technique of cystoscopy were included for final tabulation and comparison. The group went on to arrive at a consensus for a stepwise technique of diagnostic and therapeutic cystoscopy in cases of BPS/IC. This technique has been compared with the previously described techniques and may serve to be a useful practical guide for treating physicians. CONCLUSION: It is important to have a uniform standardized technique for performing a diagnostic and therapeutic cystoscopy in patients with BPS/IC. Consensus on one such a technique has been arrived at and described in the present article.

Promoter hypomethylation as potential confounder of Ras gene overexpression and their clinical significance in subsets of urothelial carcinoma of bladder.

Overexpression of normal Ras and its aberrant CpG island methylation in the promoter regions have been shown to direct cells for uncontrolled abnormal growth and bladder tumor formation and therefore, fetched recent attention as a marker of diagnosis and prognosis to predict the biological behavior of urothelial carcinoma of bladder (UCB). Methylation pattern at CpG islands of the promoter regions of rat sarcoma (Ras) gene homologues namely Kristen-Ras (K-Ras), Harvey (H-Ras), and Neuroblastoma (N-Ras) were examined by methylation specific polymerase chain reaction (MSP). Real time-quantitative polymerase chain reaction (RT-qPCR) was done to determine transcriptomic expressions of these Ras isoforms in the prospective series of 42 NMIBC (non-muscle invasive bladder cancer) and 45 MIBC (muscle invasive bladder cancer) biopsies. CpG loci in H-Ras and K-Ras were observed to be more hypomethylated in MIBC, whereas more hypomethylation in N-Ras was noted in NMIBC. Strong association of hypomethylation index with tumor stage, grade, type and size validate them it as marker of diagnosis in UCB patients. Differential overexpression of H-Ras, N-Ras and K-Ras genes in NMIBC and MIBC and their association with patients' demographics identify them as important diagnostic markers in pathogenesis of UCB. Given the reported ability of promoter hypomethylation to activate Ras expression, correlation studies examined positive significant association between hypomethylation index and expression. Study concludes that promoter hypomethylation of N-Ras and K-Ras could be a potential confounder of their increased expression in NMIBC. Biological significance of simultaneous presence of higher expression and promoter hypomethylation of Ras gene isoforms in MIBC is difficult to resolve in a given cohort of patients.

Transvaginal Repair of Vesico Vaginal Fistula: A 10-Year Experience with Analysis of Factors Affecting Outcomes.

OBJECTIVES: To highlight the transvaginal route as an excellent approach for repair of a simple trigonal, supra-trigonal vesico-vaginal and urethrovaginal fistulae without compromising on the successful patient outcomes. We also determine factors affecting outcomes in such patients. MATERIALS AND METHODS: A retrospective analysis was carried out on 58 patients with simple trigonal, supra trigonal and urethrovaginal fistula who underwent transvaginal repair in the last 10 years. Simple fistulas were defined as fistula less than 3 cm in size or recurrent fistulae less than 1.5-2 cm in size and located either supra-trigonally (above the bar of mercier) or sub-trigonally (below the bar of mercier) as determined by cystoscopy. RESULTS: Obstetric cause, due to obstructed labour, was the most common cause of fistula formation (68.96%), while remaining (29.31%) were attributed to hysterectomy. Primary fistulae were found in 68.9% of patients and recurrent fiistulae in 31.1% patients. The mean age of patients was 33.4 years. Average fistula size was 1.5 cm. The success rate of primary operation was 84.12% (50/58). On using a multivariate regression model, the underlying aetiology (OR 2.2), fistula location (OR 2.5) and history of previous repair (OR 2.4) were found to be significant factors affecting outcome. CONCLUSION: The transvaginal approach is less invasive and achieves comparable success rates as compared to other methods of vesico-vaginal fistula repair. This surgery with Foley catheter has a high success rate with reduced morbidity. We postulate that vaginal approach should be preferred over abdominal approach for repair of all vaginally accessible vesico vaginal fistulae, both of obstetrical and gynaecological origin.

A prospective study assessing feasibility of performing percutaneous nephrolithotomy in chronic kidney disease patients - What factors affect the outcome?

OBJECTIVES: To primarily evaluate the functional outcomes of PCNL for bilateral renal calculi/calculi in solitary functioning kidney with Chronic Kidney Disease(CKD). To identify factors affecting the renal replacement therapy following PCNL. MATERIALS AND METHODS: Patients with bilateral renal calculi/calculi in solitary kidney and CKD (eGFR<60/s.creatinine>2) and Good Performance Status [Eastern Cooperative Oncology Group (ECOG): 0-2] were included in the study. RESULTS: A total of 60 patients with CKD who had bilateral renal calculi/calculi in solitary functioning kidney underwent PCNL. At 6 months, eGFR improved or stabilized in 45 (75%) patients, while in 15 (25%) patients eGFR deteriorated. A total of 5 (14.28%) and 2 (25%) patients of CKD stage 4 and 5 respectively had improvement in eGFR as well as CKD stage. Fourteen (82.35%), 21 (60%), 3 (37.5%) patients of CKD stage 3, 4, 5 had improvement in eGFR but not signifi cant enough to cause stage migration. Again 3 (17.65%), 9 ( 40%) and 3 (37.5%) patients of CKD stage 3, 4, 5 had reduction in eGFR but not signifi cant enough to cause stage migration. None of the patients had worsening of CKD stage. Preoperative CKD stage and eGFR were compared with measurements made at the fi nal follow up visit (6 months). CONCLUSION: Our results indicate that most patients of renal calculi with CKD show improvement or stabilization of renal function with aggressive stone removal. Improvement is more in patients who have mild to moderate CKD. Aggressive management of comorbidities, peri-operative UTI and complications may delay or avoid progression of CKD status in such patients.

Identification of essential surgical competencies to be imparted in urological residency: A survey-based study.

INTRODUCTION: There are variations in surgical procedures included in urology residency curricula across various programs. We conducted a survey of practicing urologists to determine which procedures are considered essential to a core urology residency curriculum. MATERIALS AND METHODS: A web-based survey was conducted between October 2016 and February 2017 using SurveyMonkey. The questionnaire, comprising a set of 5-questions, was sent to the members of the Urological Society of India. Respondents were requested to grade 37 of the most common urological procedures (competencies) into three groups. Group A, were those that the respondent believed were vital for the trainee to learn (must know). Group B, were those that the respondent thought were essential to acquire (good to know). Group C procedures were labeled as desirable to know by respondents. RESULTS: A total of 485 (15.75%) responses were received out of 3018 members contacted. 67% respondents were working in the private-sector. Out of the 37 listed procedures, 20 procedures received a median weightage of 1 indicating vital clinical competency for urology curriculum, 15 were identified as "essential to know" while two procedures were identified as "desirable to know." CONCLUSIONS: Twenty surgical procedures were identified as'must-know' for a urology trainee. The choice of procedures was not affected by the region of the responder or his practice type, suggesting a wide consensus.

Diseases and Molecular Diagnostics: A Step Closer to Precision Medicine.

The current advent of molecular technologies together with a multidisciplinary interplay of several fields led to the development of genomics, which concentrates on the detection of pathogenic events at the genome level. The structural and functional genomics approaches have now pinpointed the technical challenge in the exploration of disease-related genes and the recognition of their structural alterations or elucidation of gene function. Various promising technologies and diagnostic applications of structural genomics are currently preparing a large database of disease-genes, genetic alterations etc., by mutation scanning and DNA chip technology. Further the functional genomics also exploring the expression genetics (hybridization-, PCR- and sequence-based technologies), two-hybrid technology, next generation sequencing with Bioinformatics and computational biology. Advances in microarray "chip" technology as microarrays have allowed the parallel analysis of gene expression patterns of thousands of genes simultaneously. Sequence information collected from the genomes of many individuals is leading to the rapid discovery of single nucleotide polymorphisms or SNPs. Further advances of genetic engineering have also revolutionized immunoassay biotechnology via engineering of antibody-encoding genes and the phage display technology. The Biotechnology plays an important role in the development of diagnostic assays in response to an outbreak or critical disease response need. However, there is also need to pinpoint various obstacles and issues related to the commercialization and widespread dispersal of genetic knowledge derived from the exploitation of the biotechnology industry and the development and marketing of diagnostic services. Implementation of genetic criteria for patient selection and individual assessment of the risks and benefits of treatment emerges as a major challenge to the pharmaceutical industry. Thus this field is revolutionizing current era and further it may open new vistas in the field of disease management.

Are there any factors affecting the outcome of endoscopic sclerotherapy in filarial chyluria? A prospective study.

INTRODUCTION: Filarial chyluria is a frequent problem in India. While endoscopic therapy is the mainstay of treatment, it is not always successful. We aimed to determine parameters that affect outcomes of endoscopic sclerotherapy for filarial chyluria (FC). METHODS: Prospectively maintained data of FC patients who received endoscopic sclerotherapy between June 2011 and March 2015 were analyzed. Sclerotherapy included either povidone-iodine (0.1%) or silver nitrate (1%). The parameters recorded included clinical evaluation, urinary triglyceride (TG)/cholesterol, sclerotherapy treatment, and follow-up. RESULTS: One hundred and fifty-seven patients (male: female, 104:53) with a mean age (± standard deviation [SD]) 41.12 ± 13.68 years underwent endoscopic sclerotherapy. Grade II (68.88%) chyluria was a most common presentation followed by Grade III (25.69%). One hundred and forty-four patients responded whereas six patients failed to respond; another seven were lost to follow up, and twenty patients had recurrence. Overall success rate was 86.11%. Baseline urinary TG (mean ± SD) between success and recurrence group was 195.51 ± 164.73 mg/dl and 652.65 ± 62.55 mg/dl and cholesterol (mean ± SD) was 16.99 ± 10.08 mg/dl and 89.07 ± 39.87 mg/dl, respectively. Patient with urinary TGs >300 mg/dl and urinary cholesterol >30 mg/dl had 3.2 and 1.3 times higher chance to have recurrence after endoscopic sclerotherapy, respectively. Choice of sclerosing agent (silver nitrate 1% versus povidone-iodine 0.1%) had no difference in success rate, but silver nitrate had slightly higher complications rate (25% vs. 20%). A higher number of instillations (>3) was associated with better success rate. Majority of the complications were either Clavien Grade 1 or 2. CONCLUSIONS: The factors predicting recurrence were higher clinical grade, higher number of pretreatment courses, and high urinary TG and cholesterol.

Functional polymorphisms in the IL6 gene promoter and the risk of urinary bladder cancer in India.

BACKGROUND: Interleukin-6 is a multifunctional cytokine, which plays a key role in tumor proliferation and differentiation. Variations in its gene (IL6) sequence may affect the risk of developing various cancers, including urinary bladder cancer. The present study was done to find the association of functional polymorphisms in the IL6 promoter with urinary bladder cancer. MATERIALS AND METHODS: Single nucleotide polymorphisms were genotyped in histologically confirmed 232 cases of urinary bladder cancer and 250 healthy controls. The controls subjects were matched to the cases by age, sex, and ethnicity. Genotyping of the polymorphisms (-174G>C; -572G>C, -596A>G) was undertaken by direct DNA sequencing. The level of association between the genotypes and urinary bladder cancer risk was estimated by odds ratios and 95% confidence intervals generated by applying the chi-square test. Linkage disequilibrium (LD) between SNPs and haplotype analysis were performed using Haploview software. RESULT: Significantly higher number of smokers (p=0.047), tobacco chewers (p=<0.001) and those with non-vegetarian food habits (p=0.016) were seen in the case group. The distribution of genotypes at -174G>C locus differed significantly between cases and controls and the variant genotypes GC+CC were significantly rarer in the cases (p=0.00073; OR=0.52 95% CI 0.35-0.75). Variant genotypes (GC+CC) were more common in grade I than grade III tumors (p=0.032), further suggesting a protective effect. No LD was found between the SNPs; however, the frequency of haplotype AGC was significantly lesser in the cases than controls (p=0.0103), suggesting a protective effect. Genotype distribution at the other two loci (-572G>C and -596A>G) did not show association with bladder cancer. CONCLUSIONS: IL6 (-174G>C) substitution confers significant protection against the risk of urinary bladder cancer in the study population, while other substitutions in this gene (-572G>C and -596A>G) do not affect the risk. In general, there is a lack of studies on the cytokine gene polymorphisms in urinary bladder cancer.

Meatal Occlusive Disease in Adult Males: Are There Any Clinical Variations?

OBJECTIVE: The study aimed to document the types of meatal occlusive disease (MOD) in adult males in terms of its clinical presentation, management and prognosis. MATERIAL AND METHODS: Eighty-six adult males with MOD were assessed during the study period. The patients were divided into Group 1, having meatal opening that was occluded by flimsy adhesions (meatal synechia/adhesive type MOD), and Group 2 that included patients who had circumferential constriction of the meatus (meatal stenosis/constrictive type MOD). All patients underwent meatal dilatation up to 18 Fr followed by self-dilatation for 3 months with topical clobetasol for 4 weeks. Degree of discomfort during self-dilation, improvement in flow rate, International Prostate Symptom Score (IPSS score) and recurrences were recorded at pre-determined intervals. RESULTS: Twenty-eight patients had meatal synechia (Group 1) and 48 had meatal stenosis (Group 2). Discomfort during self-dilatation in Group 1 patients was significantly less; there was improvement in IPSS and peak flow rate (mean follow-up 26.8 months) as compared to Group 2. With dilation alone, no recurrence was noted in Group 1; however, Group 2 showed 62.8% recurrence indicating poor outcome in this subset of patients. CONCLUSION: MOD in adult males consists of 2 separate clinical entities with different therapeutic outcomes.

Status and Interrelationship of Zinc, Copper, Iron, Calcium and Selenium in Prostate Cancer.

Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer. Unpaired two tailed t test/Mann-Whitney U test and Pearson correlation coefficient were used to compare the level of trace elements, elemental ratios and their interrelations. As compared to benign prostatic tissue, malignant prostatic tissue had significantly lower selenium (p = 0.038) and zinc (p = 0.043) concentrations, a lower zinc/iron ratio (p = 0.04) and positive correlation of selenium with zinc (r = 0.71, p = 0.02) and iron (r = 0.76, p = 0.009). Considerably divergent interrelationship of elements and elemental ratios in prostate cancer versus benign prostatic hyperplasia was noted. Understanding of differential elemental changes and their interdependence may be useful in defining the complex metabolic alterations in prostate carcinogenesis with potential for development of element based newer diagnostic, preventive and therapeutic strategies. Further studies may be needed to elucidate this complex relationship between trace elements and prostate carcinogenesis.

Primary emphysematous adrenal hydatid: Unusual site for presentation with rare pathology.

Hydatid disease of the adrenal gland is uncommon. We present images and description a case of emphysematous hydatid cyst of the adrenal gland that had an unfavourable intraoperative outcome.

Grading of complications of transurethral resection of bladder tumor using Clavien-Dindo classification system.

INTRODUCTION: Clavien-Dindo classification system is used for grading complications of various oncological, renal, and endourological procedures. We applied this system for grading the severity of perioperative complications in patients undergoing transurethral resection of bladder tumor (TURBT) and identify parameters predicting these complications. MATERIALS AND METHODS: Data of 984 patients who underwent TURBT from 2006 to 2014 were included in this study. All data was retrospectively collected and analyzed for complications occurring within the first postoperative month. All complications were classified according to the five grades of modified CCS (.Clavien classification system). RESULTS: A total of 172 complications were observed in 138 patients. Majority were low grade complications (Grade 1 [77.3%] and Grade 2 [12.7%]). Higher grade complications were rare (Grade 3 [6.4%] and Grade 4 [3.0%]). There was one death (Grade 5 0.6%), with an overall mortality rate of 0.1%. The incidence of complications was significantly greater for age >60 years, baseline serum creatinine >1.4 mg/dl, size of tumor >4 cm, tumor located at dome, resection time >60 min, incomplete resection and if surgery performed by a resident urologist. CONCLUSIONS: Clavien-Dindo classification system can be easily applied to grade the complications of TURBT, and it is easily reproducible. We observed that TURBT was a safe procedure. Majority of complications were Grade 1-2 (90%) and Grade 3-5 were rare (10%). Postoperative bleeding is the most common complication. A greater rate of complications of TURBT was associated with patient age, size of tumor, location of tumor, surgeon experience, resection time, and completion of tumor resection.