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.

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.

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

ABSTRACT 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 significant 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 significant 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 final 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.

Clinicohistopathological implications of phosphoserine 9 glycogen synthase kinase-3ß/ ß-catenin in urinary bladder cancer patients.

BACKGROUND: Aberrant activation of phosphorylated form of glycogen synthase kinase-3ß [pS9GSK-3ß (Serine 9 phosphorylation)] is known to trigger Wnt/ß-catenin signal cascade but its clinicohistopathological implications in bladder carcinogenesis remain unknown. AIM: To investigate the diagnostic and prognostic relevance of expressions of pS9GSK-3ß, ß-catenin and its target genes in the pathobiology of bladder cancer. METHODS: Bladder tumor tissues from ninety patients were analyzed for quantitative expression and cellular localization of pS9GSK-3ß by immunohistochemical (IHC) staining. Real time-quantitative polymerase chain reaction and IHC were done to check the expression of ß-catenin, Cyclin D1, Snail and Slug at transcriptome and protein level respectively. Clinicohistopathological variables were obtained from histology reports, follow up and OPD visits of patients. Expressions of the markers were statistically correlated with these variables to determine their significance in clinical setting. Results were analysed using SPSS 20.0 software. RESULTS: Aberrant (low or no membranous/high nuclear/high cytoplasmic) expression of pS9GSK-3ß was noted in 51% patients and found to be significantly associated with tumor stage and tumor grade (P = 0.01 and 0.04; Mann Whitney U test). Thirty one percent tumors exhibited aberrant co-expression of pS9GSK-3ß and ß-catenin proteins and showed strong statistical association with tumor stage, tumor type, smoking/tobacco chewing status (P = 0.01, 0.02 and 0.04, Mann-Whitney U test) and shorter overall survival probabilities of patients (P = 0.02; Kaplan Meier test). Nuclear immunostaining of Cyclin D1 in tumors with altered pS9GSK-3ß/ß-catenin showed relevance with tumor stage, grade and type. CONCLUSION: ß-catenin and pS9GSK-3ß proteins are identified as markers of diagnostic/prognostic significance in disease pathogenesis. Observed histopathological association of Cyclin D1 identifies it as marker of potential relevance in tumors with altered pS9GSK-3ß/ß-catenin.

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.

Laparoscopic transperitoneal heminephrectomy for treatment of the nonfunctioning moiety of duplex kidney in adults: A case series.

Purpose: We report the results and experience of a tertiary care center in laparoscopic transperitoneal heminephrectomy for the treatment of a non-functioning upper pole moiety of duplex kidney in adults. Materials and Methods: The key point of the technique included the placement of a 6-Fr ureteric catheter in the healthy ureter at the beginning of the procedure under fluoroscopic guidance cystoscopically. A standard laparoscopic 3- to 4-port placement was done after placing the patient in a 45 to 90 degrees lateral decubitus position. The upper pole was mobilized transperitoneally and transected using a harmonic scalpel. Results: A total of 17 patients aged 19 to 44 years underwent laparoscopic upper pole heminephrectomy. All patients had a complete duplicated renal collecting system on the ipsilateral side. Three patients were found to have ureterocele. The average blood loss was minimal (50-150 mL) with a mean of 95 ml. None of the patients required any blood transfusions. The mean operative time was 220 minutes (range, 160-315 minutes). The average length of hospital stay was 3 days (range, 2-4 days). Only 2 patients had Clavien-Dindo grade 3a complications, which were managed by double J stenting and percutaneous aspiration, respectively. Conclusions: Laparoscopic heminephrectomy is playing a cornerstone role in the treatment of the non-functioning moiety of duplex kidneys. The procedure is safe, efficient and offers the typical preoperative and postoperative benefits of laparoscopic surgery. The rate of complications in adults is acceptable and is similar to that reported in pediatric 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.

Evaluation of resistive index of the prostate and bladder sonomorphologic parameters as replacements for urodynamics to predict bladder outlet obstruction in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: This study investigated whether the resistive index (RI) of prostate and bladder sonomorphologic parameters (total prostate volume [TPV], detrusor wall thickness [DWT], intraprostatic protrusion [IPP]) can be used instead of urodynamic studies (UDS) to predict bladder outlet obstruction (BOO) in benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). METHODS: Men aged ≥50 years with clinical BPH/LUTS were prospectively enrolled included. Basic evaluations, measurement of sonomorphologic parameters, and UDS were performed in accordance with the International Continence Society's Good Urodynamics Practices protocol. RESULTS: Data of 240 patients were divided into two groups based on the BOO index(BOOI). Group 1 consisted of patients negative for BOO (BOOI <40), whereas Group 2 consisted of patients positive for BOO (BOOI > 40). Patient age, International Prostate Symptom Score (IPSS), quality of life score and post-void residual volume were comparable between the two groups, whereas significant differences were evident in peak flow rate, TPV, DWT, RI, and IPP (P < 0.01 for all). Pearson correlation analysis revealed a significant correlation between BOOI and DWT (r = 0.198, P = 0.002), IPP (r = 0.450, P = 0.000), and RI (r = 0.334, P = 0.000). Multiple regression analysis revealed a significant correlation between BOOI and IPP (ß = 0.382, P = 0.000) and RI (ß = 0.226, P = 0.000). Receiver operating characteristic analysis showed that the area under curve was 0.785 for RI (95% confidence interval [CI] 0.703-0.867, P < 0.001) and 0.905 for IPP (95% CI 0.850-0.961, P < 0.001). At a cut-off value of 7.5 mm for IPP, the sensitivity was 86.9%, specificity was 83.3% and positive predictive value was 92.41%. CONCLUSION: IPP and RI may be the best non-invasive predictors for BOO in selected patients with LUTS/BPH.

A prospective study evaluating impact on renal function following percutaneous nephrolithotomy using Tc99m ethylenedicysteine renal scan: Does multiplicity of access tracts play a role?

PURPOSE: A prospective study evaluating impact of percutaneous nephrolithotomy (PCNL) on renal function following PCNL using ethylenedicysteine (EC) renal scan. Does multiplicity of access tracts play a role? MATERIALS AND METHODS: A prospective observational study was done and patients undergoing PCNL for renal calculi at our urology department were selected. Renal Tc99m EC scan was done pre-surgery and at 3 months follow-up. An assessment was done on decline in glomerular filtration rate (GFR) in postoperative period based on number of access tracts required. RESULTS: A total of 110 patients were enrolled in the study. The total number of punctures was 170 with 141 being supra-costal puncture and 29 infra-costal. The total number of single punctures were 60 and classified as Group I whereas patients with double puncture and triple puncture (40 and 10 patients, respectively) were classified as Group II. Mean postoperative split renal function (in Tc99m EC scans) of patients of Group I (40.93±19.62%) was found to be higher than that of Group II (32.82±16.98%). Mean change (decline) in GFR for single, double and triple tracts were 2.68 mL/min, 3.80 mL/min, and 4.2 mL/min, respectively. CONCLUSIONS: PCNL used for stone removal can improve renal function by eradicating obstruction; however, this procedure may itself negatively impact the functions of the targeted kidney. Our study showed post PCNL decrease in GFR which worsens with an increasing number of accesses.

Epigenetic Silencing of miRNA-338-5p and miRNA-421 Drives SPINK1-Positive Prostate Cancer.

PURPOSE: Serine peptidase inhibitor, Kazal type-1 (SPINK1) overexpression defines the second most recurrent and aggressive prostate cancer subtype. However, the underlying molecular mechanism and pathobiology of SPINK1 in prostate cancer remains largely unknown. EXPERIMENTAL DESIGN: miRNA prediction tools were employed to examine the SPINK1-3'UTR for miRNA binding. Luciferase reporter assays were performed to confirm the SPINK1-3'UTR binding of shortlisted miR-338-5p/miR-421. Furthermore, miR-338-5p/-421-overexpressing cancer cells (SPINK1-positive) were evaluated for oncogenic properties using cell-based functional assays and a mouse xenograft model. Global gene expression profiling was performed to unravel the biological pathways altered by miR-338-5p/-421. IHC and RNA in situ hybridization were carried out on prostate cancer patients' tissue microarray for SPINK1 and EZH2 expression, respectively. Chromatin immunoprecipitation assay was performed to examine EZH2 occupancy on the miR-338-5p/-421-regulatory regions. Bisulfite sequencing and methylated DNA immunoprecipitation were performed on prostate cancer cell lines and patients' specimens. RESULTS: We established a critical role of miRNA-338-5p/-421 in posttranscriptional regulation of SPINK1. Ectopic expression of miRNA-338-5p/-421 in SPINK1-positive cells abrogates oncogenic properties including cell-cycle progression, stemness, and drug resistance, and shows reduced tumor burden and distant metastases in a mouse model. Importantly, we show that patients with SPINK1-positive prostate cancer exhibit increased EZH2 expression, suggesting its role in epigenetic silencing of miRNA-338-5p/-421. Furthermore, presence of CpG dinucleotide DNA methylation marks on the regulatory regions of miR-338-5p/-421 in SPINK1-positive prostate cancer cells and patients' specimens confirms epigenetic silencing. CONCLUSIONS: Our findings revealed that miRNA-338-5p/-421 are epigenetically silenced in SPINK1-positive prostate cancer, although restoring the expression of these miRNAs using epigenetic drugs or synthetic mimics could abrogate SPINK1-mediated oncogenesis.See related commentary by Bjartell, p. 2679.

Giant vesicle calculi leading to spontaneous bladder rupture and acute renal failure: an unusual presentation.

Spontaneous rupture of the urinary bladder is extremely rare. We report a case of a 70-year-old man with spontaneous bladder rupture secondary to neglected giant vesicle calculi who presented as acute renal failure. The patient was stabilised with per-urethral catheterisation and extravesical drain placement. About 700 mL pus mixed with urine was drained through the per-urethral catheter and approximately 2000 mL of pus was drained through the extravesical drain. Cystolithotomy showed two large calculi which were removed.