Predicting recurrence and progression in non-muscle-invasive bladder cancer using European organization of research and treatment of cancer risk tables.

Introduction:We determined the recurrence and progression at 1 year in Patients with non-muscle-invasive urothelial carcinoma who underwent transurethral resection of bladder tumor (TURBT) and compared those with the calculated risk according to the European Organization of Research and Treatment of Cancer (EORTC). Materials and Methods: Follow-up data of 92 Patients with non-muscle-invasive bladder cancer who underwent TURBT were reviewed, and their 1st year recurrence and progression were recorded. The risk of recurrence and progression were calculated for 1 year according to the EORTC scoring system, using tumors\u27 stage, grade, size, and multiplicity, and the presence of carcinoma in situ and previous recurrence episodes. The outcomes were compared with the EORTC\u27s predictive scores. Results: The Patients were 75 men and 17 women with an age range of 31 to 91 years. Sixteen Patients (17.4%) had a recurrent disease, 41 (44.6%) had a tumor larger than 3 cm in diameter, 35 (38.0%) had multiple lesions, 2 (2.2%) had carcinoma in situ, 73 (79.3%) had stage T1 lesions, and 8 (8.7%) had a high-grade disease. Recurrence was found in 34 Patients (37.0%). The recurrence rates were 20.0%, 28.2%, 40.5%, and 83.3% in groups with the predicted EORTC risks of 15%, 24%, 38%, and 61%, respectively. There were 2 Patients (2.2%) with progression of the diseases. Conclusions: A significant concordance was noted between the EORTC\u27s calculated risk and the recurrence rate of stage Ta T1 bladder cancer at 1 year. Progression was less than that predicted, probably due to our small sample size

The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates

Prostate cancer (PC) displays a strong familial link and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions, and, ultimately, carcinogenesis. The most widely studied epigenetic event in PC is aberrant DNA methylation (hypo- and hypermethylation); besides this, chromatin remodeling and micro RNA (miRNA) are other studied alterations in PC. These all lead to genomic instability and inappropriate gene expression. Causative dysfunction of histone modifying enzymes results in generic and locus-specific changes in chromatin remodeling. miRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen-receptor signaling and apoptosis. These epigenetic alterations have the potential to act as biomarkers for PC for screening and diagnosis as well as prognosis and follow-up. The variable biological potential for a newly diagnosed PC is one of the biggest challenges. The other major clinical problem is in the management of castration-resistant PC. Neuroendocrine (NE) differentiation is one of the putative explanations for the development of castration-resistant disease. Most advanced and poorly differentiated cancer does not produce prostate-specific antigen (PSA) in response to disease progression. Circulating and tissue biomarkers like chromogranin A (CgA) thus become important tools. There is the potential to use various genetic and epigenetic alterations and NE differentiation as therapeutic targets in the management of PC. However, we are still some distance from developing clinically effective tools. Valuable insights into the nature of NE differentiation in PC have been gained in the last decades, but additional understanding of its pathogenetic mechanisms is needed. This will help in devising novel therapeutic strategies to develop targeted therapies. CgA has the potential to become an important marker of advanced castration-resistant PC in cases where prostate-specific antigen can no longer be relied upon. Aberrant androgen-receptor signaling at various levels provides evidence of the importance of this pathway for the development of castration-resistant PC. Many epigenetic influences - in particular, the role of changing miRNA expression - provide valuable insights. Currently, massive sequencing efforts are underway to define important somatic genetic alterations (amplifications, deletions, point mutations, translocations) in PC, and these alterations hold great promise as prognostic markers and for predicting response to therapy

Urology training in the developing world: The trainers\u27 perspective

Context: Despite producing some of the leading urologists in the world, urological training in the developing world is marred by inconsistency, and a lack of structure and focus on evidence-based practice. In this review we address these issues from the trainers\u27 perspective. Introduction: Teaching the art and science of urological practice is a demanding task. It not only involves helping the resident to develop the depth of cognitive knowledge, but also to have an appropriate surgical judgement, and an ability to act quickly but thoughtfully and, when necessary, decisively. Discussion: The surgeon must have compassion, communication skills, be perceptive and dedicated. Most importantly, however, he or she should have the ability to cut and suture. Not all of these can be inculcated in the training programme, even with the best of efforts. The selection of an appropriate candidate therefore becomes an issue of pivotal importance. The changing focus of urological training incorporates research and evidence-based practice as essential components. It is particularly important in the developing world, as there is a dearth of standardised practice models across the healthcare system. Encouraging female residents can be done by improving and tailoring the working conditions. The \u27brain drain\u27 is a major problem in the developing world, and bureaucracy and government need to take appropriate measures to provide high-quality healthcare facilities with room for professional growth. Conclusions: The future of urology will depend on improved education and training, leading to high-quality urological care, and to developing a service that is patient focused

New and contemporary markers of prognosis in nonmuscle invasive urothelial cancer

Abstract Nonmuscle invasive (NMI) urothelial cancer (UC) is associated with varied biological potential. It is characterized by frequent recurrence and progression, which thus worsens the oncological outcome. Nearly three-quarters of NMI UCs recur within 5 years, whereas half can progress during follow-up. Progression is particularly seen in T1 and carcinoma in situ (CIS). Undoubtedly, NMI UC is one of the most expensive cancers to manage. The European Organisation for Research and Treatment of Cancer (EORTC) risk calculator is a commonly used tool for assessing the recurrence and progression potential of a newly diagnosed cancer. The parameters used in the assessment are tumor size and number, pathological stage and grade of the cancer, presence of CIS, and prior recurrence rate. The main advantages of the EORTC tool are its ease of use and the lack of need to run expensive molecular tests. However, reproducibility of pathologic stage and grade is modest, which is a concern to clinicians. Molecular markers have potential for predicting the clinical outcome of NMI UC, given that clinico-pathologic variables are not sufficient for prediction of prognosis in an individual. Significant work has been done in the past 2 decades in understanding the molecular biology of bladder cancer; however, the translational value of this knowledge remains poor. The role for molecular markers in predicting recurrence seems limited because multifocal disease and incomplete treatment are probably more important for recurrence than the molecular features of a resected tumor. Urinary markers have very limited value in prognostication of bladder cancer and are used (mainly as an adjunct to cytology) for detection and surveillance of urothelial cell cancer recurrence. Prediction of progression with molecular markers holds considerable promise. Nevertheless, the contemporary value of molecular markers over clinico-pathologic indexes is limited

Assessment of Urinary Incontinence (UI) in Adult Patients

The diagnosis and assessment of urinary incontinence (UI) are variable. In general, diagnosis is made in primary care using clinical evaluation (a good history and physical examination), bladder diary and validated symptom scales. Condition-specific diagnosis is made in secondary care, and it often involves interventional tools such as urodynamic studies. The evidence available on the accuracy and acceptability of the assessment of UI is inconsistent and variable. A structured data collection tool was used for initial assessment of UI. Some key questions are required for initial assessment of UI in order to diagnose the type of UI. This chapter includes a gender-specific evaluation based on history and clinical examination. Pelvic organ prolapse (POP) in female patients is associated with UI and POP diagnosis, and staging is made by clinical examination only, while male patients are examined for prostate obstructive urinary symptoms. Basic evaluation includes bladder diary in cases of overactive bladder and stress test, for stress urinary incontinence. Other diagnostic tests include urine analysis, uroflowmetry and measurement of post-void residual volume in cases of neurogenic bladder and benign prostate hypertrophy. Patients referred to specialist require further assessment of UI using urodynamic testing, electrophysiological test and imaging

Current management of advanced and metastatic renal cell carcinoma.

Introduction:Unresectable renal cell carcinoma (RCC) is a technically incurable condition. Historically, RCC is resistant to chemotherapy and radiotherapy. Cytokine therapy was until recently considered the mainstay of treatment. However, responses are modest. Improvement in the understanding of the biology of RCC, particularly the hereditary types, is providing the basis for novel therapeutic targets. Our aim was to review the clinical utility of various systemic agents and surgery in the management of advanced RCC and suggest practice guidelines in the light of current literature. Materials and Methods: Evidence was collected by review of current literature, guidelines of the American and European associations and the national comprehensive cancer network. Results: Treatment of advanced RCC has recently undergone a major change with the development of targeted agents and potent angiogenesis inhibitors. Small-molecule multikinase inhibitors that target vascular endothelial growth factor receptors have a favorable toxicity profile and can prolong time to progression and preserve quality of life when used in newly diagnosed or previously treated Patients, bevacizumab enhances the response rate and prolongs disease control when added to interferon-alpha. Temsirolimus, a mammalian target of rapamycin inhibitor, prolongs the survival duration of Patients with poor-risk disease. All currently available agents have variable toxicity profile and they, at best, improve survival by a few months. Surgery still has a significant role in the management of stage IV RCC. Conclusions: Supportive care and surgery remain the mainstay of treatment even in the management of advanced and metastatic RCC. Systemic therapeutic agents are showing promising results

Extent of lymphadenectomy in radical cystectomy for bladder cancer

BACKGROUND: The benefit of pelvic lymphadenectomy in patients with cancer of the urinary bladder remains controversial. Though the inclusion of lymph node dissection in conjunction with radical cystectomy for patients with clinically negative nodes is well accepted, however, the extent of the nodal dissection remains contentious, particularly in patients with gross disease and T(1)G(3 )cancer. The extent of the primary bladder tumor, number of lymph nodes removed and the lymph node tumor burden are important prognostic variables in patients undergoing cystectomy. We analyzed the impact of the extent of lymphadenectomy during radical cystectomy on survival in the contemporary literature. METHODS: A Pubmed search was carried out for the literature published over the last 15 years using bladder cancer, radical cystectomy, survival, lymphadenectomy and complications as the key words. We have discussed the extent of lymphadenectomy on survival and its anatomical basis to determine the optimal number of lymph nodes to be removed and the concept of node density. RESULTS: Evidence from contemporary literature indicate significantly increased survival rates after cystectomy in patients with bladder cancer diagnosed with stages III or IV disease who have had relatively more lymph nodes examined, suggesting that even some patients with higher stage disease may benefit from extended pelvic lymphadenectomy at the time of cystectomy. Studies also indicate that more extensive lymphadenectomy significantly improved the prognosis of patients with bladder cancer, not only by providing prognostic information but perhaps it is also due to its inherent therapeutic value. CONCLUSION: Extended lymph node dissection improves local control and survival. However, in the absence of controlled randomized trial this remains a dubitable issue

Single instillation of mitomycin C reduces 1st year recurrence following transurethral resection of non-muscle invasive bladder cancer

Objective: To study the impact of single instillation of 40 mg Mitomycin C (MMC-40) within first hour of transurethral resection (TUR), on first year recurrence of non-muscle invasive bladder cancer. Methods: In this study of two groups of patients with similar demographics and tumour profile were compared to assess first year tumour recurrence pattern. Group A received MMC-40 within 30 minutes of TUR. Group B patients only had TUR of bladder tumour. Patients\u27 charts were reviewed for demographic profile, preoperative diagnosis and imaging used, cytological work up, tumour profile both during cystoscopy and imaging used, patients records were also reviewed for all subsequent check cystoscopies for recurrence. Any adjuvant treatments like intravesical chemo/immunotherapy etc. were also noted. The results were analysed using a commercially available statistical package, SPSS. The level of significance was \u3c or = 0.05.Results: There were 29 and 46 patients in group A and B respectively. The demographic profile in terms of age, gender distribution, tumour characteristics (size, site, multiplicity) and pathological evaluation including, tumour grade and presence of carcinoma in situ were similar (p \u3c 0.4 and p \u3c 0.5) respectively. The first year recurrence rate in group A was 15% whereas it was 37.4% in group B (p \u3c 0.04).Conclusions: The first year recurrence rate is significantly decreased if MMC-40 is instilled following TUR. MMC-40 is safe and cost effective. Most low grade, low volume tumours would not require any further treatment if MMC-40 is given immediately following TUR