RESUMEN
OBJECTIVES: To produce a best practice consensus guideline for the conduct of scrotal exploration for suspected testicular torsion using formal consensus methodology. MATERIALS AND METHODS: A panel of 16 expert urologists, representing adult, paediatric, general, and andrological urology used the RAND/UCLA Appropriateness Consensus Methodology to score a 184 statement pre-meeting questionnaire on the conduct of scrotal exploration for suspected testicular torsion. The collated responses were presented at a face-to-face online meeting and each item was rescored anonymously after a group discussion, facilitated by an independent chair with expertise in consensus methodology. Items were scored for agreement and consensus and the items scored with consensus were used to derive a set of best practice guidelines. RESULTS: Statements scored as with consensus increased from Round 1 (122/184, 66.3%) to Round 2 (149/200, 74.5%). Recommendations were generated in ten categories: consent, assessment under anaesthetic, initial incision, intraoperative decision making, fixation, medical photography, closure, operation note, logistics and follow-up after scrotal exploration. Our statements assume that the decision to operate has already been made. Key recommendations in the consent process included the discussion of the possibility of orchidectomy and the possibility of subsequent infection of the affected testis or wound requiring antibiotic therapy. If after the examination under anaesthesia, the index of suspicion of testicular torsion is lower than previously thought, then the surgeon should still proceed to scrotal exploration as planned. A flow chart guiding decision making dependent on intraoperative findings has been designed. If no torsion is present on exploration and the bell clapper deformity is absent, the testis should not be fixed. When fixing a testis using sutures, 3 or 4-point is acceptable and non-absorbable sutures are preferred. CONCLUSIONS: We have produced consensus recommendations to inform best practice in the conduct of scrotal exploration for suspected testicular torsion.
RESUMEN
Importance: Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. Objective: To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC. Design, Setting, and Participants: This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required. Interventions: Oral selenium (200 µg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo. Main Outcome and Measures: Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022). Results: The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment. Conclusions and Relevance: In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required. Trial Registration: isrctn.org Identifier: ISRCTN13889738.
Asunto(s)
Neoplasias Vesicales sin Invasión Muscular , Selenio , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Anciano , Vitamina E/uso terapéutico , Selenio/uso terapéutico , Estudios Prospectivos , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/prevención & control , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
The tumour immune microenvironment is considered to influence cancer behaviour and outcome. Using a panel of markers for innate and adaptive immune cells we set out to characterise and understand the bladder tumour microenvironment of 114 patients from a prospective multicentre cohort of newly-diagnosed bladder cancer patients, followed-up for 4.33±1.71 years. We found IL-17-positive cells were significantly increased in primary and concomitant carcinoma in situ (CIS), p<0.0001, a highly malignant lesion which is the most significant single risk factor for disease progression. Further characterisation of the tumour immunophenotype identified IL-17+ cells as predominantly mast cells rather than T-cells, in contrast to most other tumour types. Expression of the IL-17-receptor in bladder tumours, and functional effects and gene expression changes induced by IL-17 in bladder tumour cells in vitro suggest a role in tumour behaviour. Finally, we assessed the effects of IL-17 in the context of patient outcome, following intravesical BCG immunotherapy which is the standard of care; higher numbers of IL-17+ cells were associated with improved event-free survival (p = 0.0449, HR 0.2918, 95% CI 0.08762-0.9721) in patients with primary and concomitant CIS (n = 41), we propose a model of IL-17+ Mast cells mechanism of action. Thus, in the context of bladder CIS, IL-17+ mast cells predict favourable outcome following BCG immunotherapy indicative of a novel mechanism of BCG immunotherapy in UBC and could form the basis of a stratified approach to treatment.
Asunto(s)
Vacuna BCG/uso terapéutico , Carcinoma in Situ/inmunología , Inmunoterapia , Interleucina-17/farmacología , Mastocitos/metabolismo , Microambiente Tumoral/inmunología , Neoplasias de la Vejiga Urinaria/inmunología , Carcinoma in Situ/tratamiento farmacológico , Carcinoma in Situ/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Humanos , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Estudios Prospectivos , Células Tumorales Cultivadas , Microambiente Tumoral/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
PURPOSE: Orchalgia is a common problem with varicoceles however the association between varicocele embolisation for the treatment of varicocele related pain has not been widely investigated. We aim to investigate the effectiveness of varicocele embolisation for the treatment of orchalgia secondary to varicoceles; and to see if pre-embolisation pain scores can be used to predict treatment outcomes. METHODS: A prospectively collected database of patients undergoing varicocele embolisation for pain was analysed over a 10-year period. Pain scores were assessed with a 10-point visual analogue score. Analgesia requirements and satisfaction scores were assessed with questionnaires. RESULTS: Total of 96 cases. Median age was 34 years old. Median pain scores reduced significantly following embolisation (p < 0.001). 74% had reduced pain (30% of these had resolution of pain), 24% had no change in symptoms and 1% had worsening pain. Those with moderate or severe pain had a reduction of pain in 81 and 79% of cases respectively, however 64% of cases with mild pain did not experience any benefit. We also noted a reduction in analgesia requirements and a median satisfaction score of 8/10. CONCLUSION: Primary varicocele embolisation can successfully reduce varicocele related orchalgia. It works best in those with moderate or severe pain. The majority of patients with mild pain may not experience any benefit so should be counseled appropriately. The classification of patients into those with mild, moderate or severe symptoms prior to embolisation should be done, so robust consenting can be performed.
RESUMEN
[This corrects the article DOI: 10.1186/s40064-015-1177-2.].