Adjuvant Intravesical Chemohyperthermia Versus Passive Chemotherapy in Patients with Intermediate-risk Non-muscle-invasive Bladder Cancer (HIVEC-II): A Phase 2, Open-label, Randomised Controlled Trial.

BACKGROUND: Adjuvant intravesical chemotherapy following tumour resection is recommended for intermediate-risk non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To assess the efficacy and safety of adjuvant intravesical chemohyperthermia (CHT) for intermediate-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: HIVEC-II is an open-label, phase 2 randomised controlled trial of CHT versus chemotherapy alone in patients with intermediate-risk NMIBC recruited at 15 centres between May 2014 and December 2017 (ISRCTN 23639415). Randomisation was stratified by treating hospital. INTERVENTIONS: Patients were randomly assigned (1:1) to adjuvant CHT with mitomycin C at 43°C or to room-temperature mitomycin C (control). Both treatment arms received six weekly instillations of 40 mg of mitomycin C lasting for 60 min. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 24-mo disease-free survival as determined via cystoscopy and urinary cytology. Analysis was by intention to treat. RESULTS: A total of 259 patients (131 CHT vs 128 control) were randomised. At 24 mo, 42 patients (32%) in the CHT group and 49 (38%) in the control group had experienced recurrence. Disease-free survival at 24 mo was 61% (95% confidence interval [CI] 51-69%) in the CHT arm and 60% (95% CI 50-68%) in the control arm (hazard ratio [HR] 0.92, 95% CI 0.62-1.37; log-rank p = 0.8). Progression-free survival was higher in the control arm (HR 3.44, 95% CI 1.09-10.82; log-rank p = 0.02) on intention-to-treat analysis but was not significantly higher on per-protocol analysis (HR 2.87, 95% CI 0.83-9.98; log-rank p = 0.06). Overall survival was similar (HR 2.55, 95% CI 0.77-8.40; log-rank p = 0.09). Patients undergoing CHT were less likely to complete their treatment (n =75, 59% vs n = 111, 89%). Adverse events were reported by 164 patients (87 CHT vs 77 control). Major (grade III) adverse events were rare (13 CHT vs 7 control). CONCLUSIONS: CHT cannot be recommended over chemotherapy alone for intermediate-risk NMIBC. Adverse events following CHT were of low grade and short-lived, although patients were less likely to complete their treatment. PATIENT SUMMARY: The HIVEC-II trial investigated the role of heated chemotherapy instillations in the bladder for treatment of intermediate-risk non-muscle-invasive bladder cancer. We found no cancer control benefit from heated chemotherapy instillations over room-temperature chemotherapy. Adverse events following heated chemotherapy were low grade and short-lived, although these patients were less likely to complete their treatment.

Malignancies of suprapubic catheter (SPC) tracts in spinal cord injury patients: a case series and review of literature.

Introduction: Spinal cord injury (SCI) patients are at increased risk of bladder cancer. A rare variation of this is a malignancy arising or including the suprapubic catheter (SPC) tract. Case series: We present the first case series of malignancy of the SPC tract in SCI patients, including a case of mucinous adenocarcinoma, squamous cell carcinoma and sarcoma. Presentation of patients ranged from bleeding at the site of the SPC to a rapidly growing mass. All three patients were thoroughly investigated, and management was bespoke to the extent of disease and their physiological state at the time of diagnosis. This ranged from extensive surgical intervention including cystectomy, partial sigmoidectomy, excision of the abdominal wall with reconstruction and ileal conduit formation to palliation. Discussion: SCI patients represent 50% of all known published cases of malignancy of the SPC tract. Presentation and diagnosis can be challenging; however, prompt investigation and intervention are essential given the high degree of morbidity and mortality. Routine check of the SPC site may be indicated in those patients in whom the SPC has been present for more than 5 years.

Clinical and Patient-reported Outcome Measures in Men Referred for Consideration of Surgery to Treat Lower Urinary Tract Symptoms: Baseline Results and Diagnostic Findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM).

BACKGROUND: Clinical evaluation of male lower urinary tract symptoms (MLUTS) in secondary care uses a range of assessments. It is unknown how MLUTS evaluation influences outcome of therapy recommendations and choice, notably urodynamics (UDS; filling cystometry and pressure flow studies). OBJECTIVE: To report participants' sociodemographic and clinical characteristics, and initial diagnostic findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM). UPSTREAM is a randomised controlled trial evaluating whether symptoms are noninferior and surgery rates are lower if UDS is included. DESIGN, SETTING, AND PARTICIPANTS: A total of 820 men (≥18 yr of age) seeking treatment for bothersome LUTS were recruited from 26 National Health Service hospital urology departments. INTERVENTION: Care pathway based on routine, noninvasive tests (control) or routine care plus UDS (intervention arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome is International Prostate Symptom Score (IPSS) and the key secondary outcome is surgery rates 18 mo after randomisation. International Consultation on Incontinence Questionnaires were captured for MLUTS, sexual function, and UDS satisfaction. Baseline clinical and patient-reported outcome measures (PROMs), and UDS findings were informally compared between arms. Trends across age groups for urinary and sexual PROMs were evaluated with a Cuzick's test, and questionnaire items were compared using Pearson's correlation coefficient. RESULTS AND LIMITATIONS: Storage LUTS, notably nocturia, and impaired sexual function are prominent in men being assessed for surgery. Sociodemographic and clinical evaluations were similar between arms. Overall mean IPSS and quality of life scores were 18.94 and 4.13, respectively. Trends were found across age groups, with older men suffering from higher rates of incontinence, nocturia, and erectile dysfunction, and younger men suffering from increased daytime frequency and voiding symptoms. Men undergoing UDS testing expressed high satisfaction with the procedure. CONCLUSIONS: Men being considered for surgery have additional clinical features that may affect treatment decision making and outcomes, notably storage LUTS and impaired sexual function. PATIENT SUMMARY: We describe initial assessment findings from a large clinical study of the treatment pathway for men suffering with bothersome urinary symptoms who were referred to hospital for further treatment, potentially including surgery. We report the patient characteristics and diagnostic test results, including symptom questionnaires, bladder diaries, flow rate tests, and urodynamics.

Does urinary cytology have a role in haematuria investigations?

OBJECTIVES: To determine the diagnostic accuracy of urinary cytology to diagnose bladder cancer and upper tract urothelial cancer (UTUC) as well as the outcome of patients with a positive urine cytology and normal haematuria investigations in patients in a multicentre prospective observational study of patients investigated for haematuria. PATIENT AND METHODS: The DETECT I study (clinicaltrials.gov NCT02676180) recruited patients presenting with haematuria following referral to secondary case at 40 hospitals. All patients had a cystoscopy and upper tract imaging (renal bladder ultrasound [RBUS] and/ or CT urogram [CTU]). Patients, where urine cytology were performed, were sub-analysed. The reference standard for the diagnosis of bladder cancer and UTUC was histological confirmation of cancer. A positive urine cytology was defined as a urine cytology suspicious for neoplastic cells or atypical cells. RESULTS: Of the 3 556 patients recruited, urine cytology was performed in 567 (15.9%) patients from nine hospitals. Median time between positive urine cytology and endoscopic tumour resection was 27 (IQR: 21.3-33.8) days. Bladder cancer was diagnosed in 39 (6.9%) patients and UTUC in 8 (1.4%) patients. The accuracy of urinary cytology for the diagnosis of bladder cancer and UTUC was: sensitivity 43.5%, specificity 95.7%, positive predictive value (PPV) 47.6% and negative predictive value (NPV) 94.9%. A total of 21 bladder cancers and 5 UTUC were missed. Bladder cancers missed according to grade and stage were as follows: 4 (19%) were ≥ pT2, 2 (9.5%) were G3 pT1, 10 (47.6%) were G3/2 pTa and 5 (23.8%) were G1 pTa. High-risk cancer was confirmed in 8 (38%) patients. There was a marginal improvement in sensitivity (57.7%) for high-risk cancers. When urine cytology was combined with imaging, the diagnostic performance improved with CTU (sensitivity 90.2%, specificity 94.9%) superior to RBUS (sensitivity 66.7%, specificity 96.7%). False positive cytology results were confirmed in 22 patients, of which 12 (54.5%) had further invasive tests and 5 (22.7%) had a repeat cytology. No cancer was identified in these patients during follow-up. CONCLUSIONS: Urine cytology will miss a significant number of muscle-invasive bladder cancer and high-risk disease. Our results suggest that urine cytology should not be routinely performed as part of haematuria investigations. The role of urine cytology in select cases should be considered in the context of the impact of a false positive result leading to further potentially invasive tests conducted under general anaesthesia.

Management of stress urinary incontinence in spinal cord injured female patients with a mid-urethral tape - a single center experience.

Context/Objective Stress urinary incontinence (SUI) affects the quality of life of females with spinal cord injury (SCI), has a negative impact on functional independence and disturbs their psychosocial interaction. Our aim was to assess the efficacy of mid-urethral tapes (MUT) in managing stress urinary incontinence in this population. Design Retrospective cohort study. Participants SCI females with upper motor neuron lesion and urodynamically proven stress or mixed urinary incontinence that was treated with a mid-urethral tape and followed up for at least 12 months. Interventions Mid-urethral tapes such TVT, TOT and mini-Arc. Patient reported outcomes based on the daily use of pads and ICIQ modular questionnaire scores. Outcome measures The primary endpoint was defined as the success rate of MUT surgery in managing stress incontinence at 12. The secondary endpoints included the improvement rate at 12 months, the complication rates and the need for additional treatments. Results 38 females were studied. At 12 months the overall patient reported success rate was 52.6%. 16% reported significant improvement. 68.4% felt the quality of life to improve. Nine patients develop tape related complications (five de novo urgency, one vaginal extrusion, one frequent dysreflexia and one worsening of incontinence). Conclusion Mid-urethral tapes are effective in the management of stress urinary incontinence in female patients with spinal cord injury. There are demonstrable improvements in both continence and quality of life.

Keratinizing desquamative squamous metaplasia in the kidney of a patient with complex spinal cord injury.

CONTEXT: Keratinizing desquamative squamous metaplasia (KDSM) of the upper urinary tract was previously thought, but never proven, to represent a premalignant condition. However, no clear guidelines exist regarding the long-term management and follow up once this rare diagnosis has been made. FINDINGS: Patients with spinal cord injury often develop a range of risk factors for malignancy of the urinary tract. We present the first reported case of KDSM in the kidney of a 44-year-old man with spinal cord injury whose complex urological history includes previous augmentation cystoplasty, recurrent calculi, infections and indwelling catheters. CLINICAL RELEVANCE: Recent literature has suggested a move away from the previous mainstay of treatment with radical surgery towards nephron-sparing endoscopic and radiological surveillance. This case highlights the complexity of preserving renal function in a spinal cord injured patient with KDSM of the kidney.

Expression profiling of CD133+ and CD133- epithelial cells from human prostate.

BACKGROUND: Recent evidence suggests that prostate stem cells in benign and tumor tissue express the cell surface marker CD133, but these cells have not been well characterized. The aim of our study was to gene expression profile CD133-expressing cells. METHODS: We analyzed CD133-positive (CD133+) and -negative (CD133-) sub-populations of high-integrin expressing epithelial cells isolated from benign human prostate tissue and hormone-refractory prostate cancer (HRPC). RESULTS: CD133+ cells freshly isolated from benign prostate tissue exhibited an expression profile characteristic of a putative stem/progenitor cell population, with transcripts involved in biological processes ranging from development and ion homeostasis to cell communication. The profile of CD133- cells was consistent with that of a transit amplifying population, suggesting up-regulated proliferation and metabolism. Comparison of benign populations to those from HRPC showed some similarities between CD133+ profiles but also revealed significant differences that provide a tumor-specific pattern, which included evidence of increased metabolic activity and active proliferation. Subsequently, we demonstrated protein expression of a number of candidate genes in these cell populations and in benign tissue. In a novel observation we also found expression of some of these markers in prostate tumors, including the oligodendrocyte lineage transcription factor OLIG1. CONCLUSIONS: This study provides a unique genome-wide molecular signature of CD133+ and CD133- human prostate epithelial cells. This will provide a valuable resource for prostate stem cell biology research and the identification of novel therapeutic targets for the treatment of prostate cancer.

Vaginoplasty.

PURPOSE OF REVIEW: This review summarizes the most recent advances in the field of vaginoplasty. New surgical techniques and recent modifications to existing techniques are included as well as up-to-date outcome data when available. RECENT FINDINGS: It is increasingly clear that vaginal dilation treatment is a successful method of vaginal creation and avoids the risks of surgery. When vaginal dilation is unsuitable or unsuccessful, however, vaginal reconstruction surgery is needed. Most of the novel advances in vaginal reconstruction have been related to the advances made in laparoscopic techniques. It is anticipated that as surgeons become more adept at such procedures, maximally invasive procedures such as intestinal neovagina may be necessary only in a small minority of patients. Autologous vaginal tissue transplantation may also transform this field. Long-term sexual function outcome data are essential for full evaluation and comparison of surgical techniques and the recent literature has begun to include this information. SUMMARY: Vaginal dilation treatment should be the first choice of treatment. If unsuccessful, laparoscopic techniques offer good outcomes and quick recovery. Additional research into the long-term outcomes of sexual satisfaction, orgasm and patient body image is essential, however, to allow a comparison of newer and traditional procedures.

Laparoscopic management of cervical agenesis.

OBJECTIVE: To assess the possibility of laparoscopic management of cervical agenesis. DESIGN: Case report. SETTING: Patient recruited from a tertiary referral hospital. PATIENT(S): Adult female with diagnosis of cervical agenesis. INTERVENTION(S): Laparoscopic uterovaginal anastomosis. MAIN OUTCOME MEASURE(S): The patency of the anastomosis site was assessed with hysteroscopy. RESULT(S): Patient was menstruating normally and had been sexually active at 6 months after the procedure. CONCLUSION(S): Laparoscopic treatment of these cases is feasible and should be considered as a first-line treatment option.

Congenital adrenal hyperplasia and lower urinary tract symptoms.

OBJECTIVES: To assess urinary symptoms in adult women with congenital adrenal hyperplasia (CAH), as feminizing surgery in infancy is current standard practice for CAH and one of the indications for surgery is to reduce urinary symptoms. PATIENTS, SUBJECTS AND METHODS: In a case-control study, 19 women with CAH, of whom 16 had had childhood feminizing genital surgery, and age-matched women with no CAH, were evaluated. Subjects and controls completed the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaire. RESULTS: Urge incontinence was reported in 13 (68%) patients and three (16%) controls (P = 0.003); stress incontinence was present in 47% and 26%, respectively (P = 0.31). Results from the controls were comparable with those documented in larger studies on normal populations. Nine of the patients felt that their urinary symptoms had an adverse effect on their lives, compared with only one of the controls (P = 0.008). CONCLUSION: Patients with a diagnosis of CAH are more likely to have significant urinary symptoms than normal controls. At present it is not clear whether this is a result of surgery or an effect of CAH. In at least two-thirds of patients surgery did not achieve the objective of reducing urinary symptoms.

The pitfalls of vaginal construction.

OBJECTIVE: To evaluate a group of young women undergoing complex vaginoplasty, which may be defined as where there has already been previous complex pelvic surgery and the patient is unsuitable for conservative treatment or minor surgical revision. PATIENTS AND METHODS: All patients who had undergone a complex vaginoplasty between 1997 and 2004 were reviewed retrospectively. Information was recorded on the underlying condition, previous surgery and preoperative assessment. The operative technique and complications were noted, and the outcome in terms of menstruation and sexual activity. In all, 15 patients fulfilled the criteria (mean age 22.2 years, range 17-36) and the mean follow-up was 4.75 (0.75-7) years. RESULTS: Fourteen patients had complex congenital anomalies of the lower genital tract and 11 of these had associated anomalies of the urinary and gastrointestinal system; four were XY females. The 15 patients had had 31 vaginal procedures, including ileal vaginoplasty, mobilization of perineal skin flaps and split-skin grafting. Three patients required osteotomies to increase pelvic outlet diameter. The commonest complications were stenosis (six patients) and fistula formation (four). Eight patients are now sexually active; the remaining seven have not attempted sexual intercourse. CONCLUSIONS: Complications are common and can be major; most patients require many repeat operations to achieve a patent vagina. Unfortunately at present, this is the only option for this group of young women to achieve a functional vagina. Patients with complex congenital anomalies of the reproductive and genital tracts are increasingly surviving into adulthood, and the numbers of these patients is likely to increase in the future.

Long-term outcomes of anorectal malformations.

Anorectal malformations (ARMs) and cloacal anomalies are rare and complex malformations of the lower gastrointestinal and genitourinary tracts. They affect approximately 1 in 3,500 live births. The treatment of these patients has traditionally focused on achieving urinary and faecal continence, with preservation of renal function. With improved surgical techniques and paediatric intensive care facilities, these patients now live relatively normal lives, with a near-normal life expectancy. Comparing results reported by different surgeons is difficult because a wide range of terminology is employed to describe the anomalies encountered. This paper attempts to simplify some of the reported outcomes of bowel function to allow a more direct comparison between groups. Urinary outcomes were not so easily comparable due to the disparity in assessing patient outcomes. Therefore, before a global analysis of all groups can take place, a standardised terminology will be necessary. At present there is a gap in the published literature of comprehensive follow-up in this group of patients, particularly regarding reproductive and sexual functioning. More detailed information on long-term outcomes is needed in these patients to facilitate informed decision-making by the primary physician (usually the paediatric surgeon) and the parents on behalf of their child.