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.

Assessing Residents in the Department of Surgery at a Tertiary Care Centre Using Mini-Clinical Evaluation Exercise (Mini-CEX).

OBJECTIVE: This study aimed to introduce, sensitize, and train our postgraduate students and faculty of the department of general surgery with the use of mini-Clinical Evaluation Exercise (mini­CEX) and to assess the perception of students and faculty towards it. MATERIAL AND METHODS: A cross­sectional observational study was conducted over a period of four months. Ten surgery residents in the department were asked to volunteer to participate and five professors conducted the session. Five sessions of mini­CEX (nine points) were conducted for each resident in different settings of the out­patient department (OPD) and in­patient department (IPD). A total of five skills were tested. Feedback from faculty and residents regarding the perception of mini­CEX was also taken. RESULTS: A statistically significant difference in mean scores of all domains was observed comparing the first and last assessment (p<0.05). Hundred percent of the residents scored superior category (7-9) in the final assessment in all domains, whereas the maximum was in a satisfactory scoring grade in 1st assessment. The time taken for the assessment significantly reduced from 1st assessment to the last assessment in OPD and IPD settings (p=0.001). The mini-CEX assessment tool got 100% feedback from faculty in terms of skill improvement, method, attitude of residents, and ability to identify gaps in knowledge. However, one assessor thought that "time given for assessment" was inadequate and more effort was required than the usual traditional assessment methods. The most identified problem faced by residents was that the "time given during assessment" was less (50%); however, overall residents also found it valid, effective, and helpful in identifying knowledge gaps and improving clinical and communication skills. CONCLUSION: Mini­CEX improves the learning environment in residency and also leads to improvement in medical interviewing skills, physical examination skills, humanistic qualities/professionalism, and counseling skills. So, it can be used for residency training in clinical departments.

Utilising anterolateral bladder flap to create a continent cutaneous diversion in a patient with pelvic fracture urethral injury.

A male child in the first decade of life presented to us with a history of a pelvic fracture and urethral injury resulting from a road traffic accident 4 months prior. He had previously undergone an exploratory laparotomy and suprapubic cystostomy at another medical centre. He was circumcised and exhibited a substantial urethral defect on the retrograde urethrogram, as well as on the micturating cystourethrogram. Following a careful assessment of the patient's and caregivers' expectations, a continent cutaneous catheterisable channel was planned. This procedure involved the use of an anterolateral bladder flap, and continence was achieved through the creation of a Nissen-type seromuscular invagination. Three months postoperatively, the child remains continent, can easily catheterise the stoma and has resumed his education.

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.

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.

Effect of Clinical, Biochemical, and Genetic Variations on Medical Management in Filarial Chyluria: A Prospective Study at a Tertiary Care Centre in North India.

Objective To analyze the effect of clinical, biochemical factors, and Mannose Binding Lectin 2 (MBL2) gene variations on medical management in filarial chyluria (FC) patients. Material and methods We conducted a study between March 2013 and April 2016. MBL2polymorphisms were genotyped in confirmed 101 medically-treated cases of FC. Demographic, clinical, and biochemical variables were compared between remission and failure groups. Genotyping of MBL2 codon 54 and promoter -221 were undertaken by polymerase chain reaction. Genotype frequencies were compared with clinical and biochemical variables and medical treatment outcomes (remission/failure). The association between genotypes and treatment response was estimated by OR and 95% CI and generated by the chi-square test. Results The mean age was 36.9±10.28-years and the male-female ratio was 3:1.2. Sixty-six patients had remission (Group-A) while 35 had recurrence (Group-B) at a mean follow-up of 21 months. The success rate for medical therapy was 65.35%. There was no statistical difference observed in the demographic profile of the two groups. On multivariate analysis, patients in Group-B had a higher grade of chyluria (p=0.005), had experienced greater number of disease attacks in the past (p=0.022), and had higher urinary triglyceride levels (TG) (p<0.001) as compared to Group-A patients. A significant association of MBL2 codon 54 genotypes was observed with the recurrent presentation of chyluria (p=0.044), grade of chyluria (p=0.028), and urinary TGs (p=0.001). However, genotype distribution at -221 did not show association with clinical and biochemical parameters of FC patients. The distribution of genotypes at codon 54 differed significantly between remission and failure/recurrence group; the variant genotype BB was significantly higher in the recurrence or failure group (OR:6.00; 95%CI, 1.00-35.91; p=0.050). However, frequencies of variant genotype YX and recessive group YX+XX of MBL2 -221 promoter was higher in remission group (OR:2.97;95%CI, 1.23-7.13; p=0.018 and OR:2.76; 95%CI, 1.80-6.50; p=0.020), respectively, showing that genetic variant may be associated with response to medical therapy. Conclusion Higher grade of chyluria, a higher number of disease attacks in the past, and higher urinary TGs levels were clinical predictors of poor response to medical treatment. Our results showed that the variants of MBL2 genes have an impact on treatment outcomes in FC patients. These observations may be limited by sample size.

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.

Mutational analysis of Ras hotspots in patients with urothelial carcinoma of the bladder.

BACKGROUND: Mutational activation of Ras genes is established as a prognostic factor for the genesis of a constitutively active RAS-mitogen activated protein kinase pathway that leads to cancer. Heterogeneity among the distribution of the most frequent mutations in Ras isoforms is reported in different patient populations with urothelial carcinoma of the bladder (UCB). AIM: To determine the presence/absence of mutations in Ras isoforms in patients with UCB in order to predict disease outcome. METHODS: This study was performed to determine the mutational spectrum at the hotspot regions of H-Ras, K-Ras and N-Ras genes by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing followed by their clinical impact (if any) by examining the relationship of mutational spectrum with clinical histopathological variables in 87 UCB patients. RESULTS: None of the 87 UCB patients showed point mutations in codon 12 of H-Ras gene; codon 61 of N-Ras gene and codons 12, 13 of K-Ras gene by PCR-RFLP. Direct DNA sequencing of tumor and normal control bladder mucosal specimens followed by Blastn alignment with the reference wild-type sequences failed to identify even one nucleotide difference in the coding exons 1 and 2 of H-Ras, N-Ras and K-Ras genes in the tumor and control bladder mucosal specimens. CONCLUSION: Our findings on the lack of mutations in H-Ras, K-Ras and N-Ras genes could be explained on the basis of different etiological mechanisms involved in tumor development/progression, inherent genetic susceptibility, tissue specificity or alternative Ras dysfunction such as gene amplification and/or overexpression in a given cohort of patients.

Utility of trans-vaginal ultrasound in diagnosis and follow-up of non-pregnant sexually active females with lower ureteric calculi.

OBJECTIVE: To assess the utility of trans-vaginal ultrasonography in evaluation of non-pregnant sexually active female patients with lower ureteric calculi. METHODS: A prospective study was done from January 2015 to December 2017 including non-pregnant sexually active females with suspected ureteric calculus. Trans-abdominal ultrasound was initially done in all patients. In those patients in whom trans-abdominal ultrasound was inconclusive or there was indirect evidence of lower ureteric calculus in form of ureteral dilation but no calculus was evident, trans-vaginal ultrasound was done. The patients with ureteric calculi detected on trans-vaginal ultrasound and kept on conservative management were also followed up with trans-vaginal ultrasound. Non-contrast computed tomography was done in patients with inconclusive trans-vaginal ultrasound. RESULTS: As per the study protocol, 156 out of the total 468 patients evaluated by trans-abdominal ultrasound were eligible for trans-vaginal ultrasound. Trans-vaginal ultrasound was done in 149 patients, as seven patients did not give consent. Seventy-nine patients were detected with a lower ureteric calculus on trans-vaginal ultrasound and 27 patients had gynecologic or other cause for their symptoms. Forty-three patients had an inconclusive trans-vaginal ultrasound of which 36 underwent non-contrast computed tomography, among them only one patient had a lower ureteric calculus. Stone free status could be easily demonstrated on follow-up trans-vaginal ultrasound. CONCLUSION: Trans-vaginal ultrasound in addition to trans-abdominal ultrasound is a very useful tool in evaluation of sexually active females with suspected lower ureteric calculus.

Duplication mutation in CHIT1 gene is associated with poor response to medical therapy in patients affected with filarial chyluria.

We explore the impact of CHIT1 gene mutation on clinical, biochemical parameters and response to outcome (remission/failure) of medical treatment in North Indian filarial chyluria (FC) patients. Data of 101 subjects of FC treated medically between March 2013 and April 2016 in whom CHIT1 gene polymorphism was determined were analyzed. Filarial etiology was confirmed by DEC-provocative test, immuno-chromatographic test and IgG/IgM-combo rapid antibody test. CHIT1 gene polymorphism was genotyped by polymerase chain reaction. Of 101 patients (mean age, 36.9±10.28 years; male: female, 3:1.2), 66 experienced remission (Group-A) while 35 experienced relapse or failed to respond (Group-B). A significant association was observed between CHIT1 genotypes and higher grade of disease (p= 0.001). Wild-type, heterozygous and homozygous mutant frequencies of CHIT1 genotypes were 78.6%, 72.5% and 27.8% in remission and 21.4%, 27.5% and 72.2%, in recurrence/failure, respectively. Our results showed that patients with mutant genotype (TT) of CHIT1 gene showed significantly higher rate of recurrence or failure to medical therapy than wild type (HH) genotypes [OR (95% CI) = 9.53 (1.84-49.21), p=0.011]. This preliminary study showed the impact of CHIT1 gene variants on treatment outcome in FC patients. This observation needs to be confirmed using studies with larger numbers of FC patients.