High-precision Bladder Cancer Irradiation in the Elderly: Clinical Results for a Plan-of-the-day Integrated Boost Technique with Image Guidance Using Lipiodol Markers.

BACKGROUND: For most elderly patients with muscle-invasive bladder cancer (MIBC), surgery is not an option because of patient frailty. Conventional radiotherapy, with its high-dose irradiation of surrounding healthy tissues, remains the only curative treatment for this patient population. OBJECTIVE: To determine whether targeted radiotherapy with Lipiodol demarcation and plan-of-the-day integrated boost technique (LPOD) is a viable curative treatment for elderly patients with MIBC. DESIGN, SETTING, AND PARTICIPANTS: Between September 2008 and September 2016 all MIBC patients in our hospital were screened for eligibility. We included patients with localised, unifocal T2-T4N0M0 grade 2-3 MIBC. Patients with a tumour volume >50% of the bladder wall surface, previous pelvic radiotherapy, and unilateral or bilateral hip prostheses were excluded. INTERVENTION: Targeted radiotherapy using LPOD. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival, urothelial cell cancer-specific survival (UCCSS), disease recurrence, and Radiation Therapy Oncology Group (RTOG) toxicity were measured. Statistical analyses included independent-sample t tests, χ2 tests, and Mann-Whitney U tests. RESULTS AND LIMITATIONS: A total of 44 patients (median age 80 yr) were included. Over median follow-up of 38 mo, one patient ceased treatment and 23 patients died. LPOD resulted in a 11.4% chance of local recurrence, high 3-yr UCCSS of 77%, RTOG grade >3 toxicity of 2.3-12.9%, and 3-yr overall survival of 49%. CONCLUSIONS: LPOD is a feasible first-line treatment option for older patients with limited-volume T2-T4N0M0 grade 2-3 MIBC. PATIENT SUMMARY: We looked at outcomes after targeted radiotherapy in elderly patients with muscle-invasive bladder cancer. We found that this treatment results in a low chance of disease recurrence with few toxicity complaints. We conclude that this treatment is a viable first-line treatment option for elderly patients.

Minimal Device Encrustation on Vesair Intravesical Balloons in the Treatment of Stress Urinary Incontinence: Analysis of Balloons Removed from Women in the SOLECT Trial.

INTRODUCTION: Encrustation of urinary biomaterials is common; however, the incidence of surface deposition on the Vesair® intravesical pressure-attenuation balloon has not been previously reported. The purpose of this analysis is to determine the incidence and potential risk factors for encrustation of the Vesair intravesical balloon. METHODS: The SOLECT trial is a prospective randomized controlled trial conducted at several European centers to evaluate the safety and efficacy of the Vesair balloon for the treatment of female stress urinary incontinence (SUI). Women included in the study demonstrated SUI symptoms for more than 12 months without complicating factors, such as history of recurrent urinary tract infections or nephrolithiasis. All balloons removed from women enrolled in the SOLECT trial were analyzed for surface characteristics and encrustation. Surface deposition severity was quantified and composition analyzed with infrared spectroscopy and scanning electron microscopy. Incidence of surface deposition was tabulated and risk factors analyzed. RESULTS: One hundred and five balloons removed from 75 women were included in this analysis. Measurable stone deposition of less than 1.5 mm was found on four balloons (3.8%), surface granules were noted on 42 (40.0%), surface film on 11 (10.5%), and both granules and film on two (1.9%). Analysis identified calcium oxalate both in measurable encrustation deposits as well as those with surface granulation. Pooled analysis found that dwell time was a risk factor for calcium deposition. CONCLUSION: The rate of encrustation on the Vesair intravesical balloon is low and does not appear to increase the rate of adverse outcomes or reduce clinical efficacy. FUNDING: Solace Therapeutics, Inc.

A randomized, controlled clinical trial of an intravesical pressure-attenuation balloon system for the treatment of stress urinary incontinence in females.

AIMS: Evaluate the efficacy, safety, and tolerability of a novel pressure-attenuation balloon for the treatment of female stress urinary incontinence (SUI) using a prospective, randomized, single-blind, multi-center design, evaluated at 3 months. METHODS: Sixty-three females with SUI were randomized 2:1 to treatment with a balloon (N = 41) or sham procedure (N = 22). The sham (control) entailed the same procedure without the deployment of a balloon. Endpoints were evaluated at 3 months and included a composite endpoint that required both ≥10 point increase in the 22-item Incontinence Quality of Life Survey (I-QOL) and ≥50% decrease in provocative pad weight. Additional endpoints included incontinence episode frequency, and PGII assessment. RESULTS: In an ITT analysis, 63% of women in the treatment group achieved the composite endpoint, compared to 31% in the Control Group (P = 0.0200). In a per protocol analysis, 81% of women in the treatment arm had a 50% decrease in pad weight test vs. 45% in the Control Group (P = 0.0143); 41.6% of the treatment patients were dry on pad weight test (≤1gram) vs. 0% in the Control Group (P < 0.001), and 58% of treated patients reported improvement on a PGII assessment versus 25% of women in the Control Group (P = 0.025). Adverse events in the treatment group included dysuria (14.6%), gross hematuria (9.8%), and UTI (7.3%). CONCLUSIONS: This minimally invasive treatment for female SUI with an intravesical pressure-attenuation balloon was safe and effective. The concept of pressure attenuation as a therapy for SUI is valid and feasible for those patients that can tolerate the balloon.

TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer.

OBJECTIVES: To evaluate the optimal treatment conditions and effects of TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD(®) Soluble VTP treatment in patients with localised prostate cancer. PATIENTS AND METHODS: Men (aged >18 years) diagnosed with localised prostate cancer, who were suitable for active surveillance, were invited to take part in the study. Patients who had received prior or current treatment for their cancer were excluded. There were two parts to the study: in part one, patients were assigned to one of two treatment groups based on the size of their prostates (patients with prostate size <60 mL would receive 4 mg/kg TOOKAD(®) Soluble and patients with prostate size ≥60 mL would receive 6 mg/kg TOOKAD(®) Soluble both activated with 200 J/cm light). In part two, patients were assigned to one of two treatment groups based on predefined criteria and received either 4 or 6 mg/kg TOOKAD(®) Soluble and 200 or 300 J/cm light. VTP was conducted under general anaesthesia using TOOKAD(®) Soluble administered intravenously and activated by light-diffusing fibres within the prostate via the perineum. Follow-up was conducted for 6 months. Magnetic resonance imaging (MRI) carried out at 1 week after VTP and transrectal prostate biopsy at 6 months were the key endpoints. Adverse event (AE) recording and patient-reported outcome measures were collected. RESULTS: In all, 86 patients were enrolled in the study and 85 patients received treatment. Of the 85 treated patients, one patient discontinued (due to withdrawal of consent). At 6 months, 61/83 (74%) patients who underwent prostate biopsy had histopathology that was negative for prostate cancer (95% confidence interval (CI) 62.7-82.6%). Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), which are considered optimal treatment parameters, 38/46 (83%) patients had histopathology from the biopsies that was negative for prostate cancer at 6 months (95% CI 68.6-92.2%; P < 0.001). The mean percentage of necrosis of the targeted prostate tissue at 7 days after VTP was 78% overall (83 patients) with extraprostatic necrosis reported in 76% (63/83) of patients. Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), the mean 7-day necrosis percentage was 88% (46 patients) with extraprostatic necrosis reported in 72% (33/46) of patients. All occurrences of extraprostatic necrosis were considered clinically acceptable and none were associated with any clinical sequelae. The mean percentage prostate necrosis at 7 days was statistically significantly higher (P < 0.001) in patients treated with a therapeutic light density index (LDI) of ≥1 than those treated with a LDI of <1. The percentage of patients with negative biopsies at 6 months was also higher in patients treated with a therapeutic LDI of ≥1 than those treated with a LDI of <1 (78.6% and 63.0%, respectively). In all, 87% (75/86) of patients reported at least one treatment-emergent AE during the study. Most AEs were mild or moderate in intensity and considered related to the technical procedures of the study. No treated patients had hypotension or discontinued due to AEs. Eight patients (9.3%) had serious AEs; none resulted in discontinuation from the study. CONCLUSIONS: Biopsy data, post-treatment dynamic contrast-enhancement MRI at 1 week after VTP and analysis of the safety data have shown that 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light are the optimal treatment conditions for the VTP procedure resulting in >80% of patients treated with this regimen having a negative biopsy at 6 months. Overall, the treatment was well tolerated and exhibited early signs of efficacy for minimally invasive focal treatment of localised prostate cancer.

High precision bladder cancer irradiation by integrating a library planning procedure of 6 prospectively generated SIB IMRT plans with image guidance using lipiodol markers.

PURPOSE: To increase local control and decrease side effects for urinary bladder cancer patients by integrating a library planning procedure with image guidance using lipiodol markers. METHODS AND MATERIALS: Twenty patients with T2-T4N0M0 grade 2-3 invasive bladder carcinoma were treated according to an online adaptive protocol. Initially, the gross tumour volume (GTV) was demarcated during cystoscopy by injecting several drops of lipiodol in the submucosa around the tumour. Subsequently two CT scans were acquired with a full bladder and a voided bladder. On both scans, the boost volume (GTV) and the low-risk bladder volume were delineated. Using an interpolation tool, six concomitant boost IMRT plans with increasing bladder volumes were generated. For each fraction the procedure at the treatment unit was as follows: Firstly, a ConeBeam-CT was acquired and based on the amount of bladder filling the best fitting bladder contours and corresponding GTV and IMRT plans were selected. Secondly, the lipiodol markers were registered using the corresponding GTV contours and it was verified that the corresponding 95%-isodose surface covered the entire bladder. Finally, an online setup correction was applied based on this registration and the corresponding treatment plan was irradiated. RESULTS: The lipiodol markers were very useful in outlining the GTV at the planning CT and for daily setup correction. While the patients strived for a full bladder filling at time of the treatment, this was seldom accomplished. Due to our protocol an appropriate plan with adequate coverage of the PTV and without excessive dose to healthy tissue was delivered every day. The treatment was very well tolerated by all patients. At the end of the treatment no grade 3 urinary or gastro-intestinal toxicity was observed. After a median follow-up of 28 months two local relapses occurred. CONCLUSION: Using the library planning approach combined with online image guidance using lipiodol markers, we were able to deliver a highly conformal dose distribution to all bladder cancer patients achieving promising clinical results.

[Transverse testicular ectopia confirmed by ultrasonography]. / Transverse testisectopie vastgesteld door echografie.

Two newborn boys aged 2 and 3 months with unilateral inguinal hernia and a contralateral impalpable, non-scrotal testis, and a third boy aged 2.5 years with an impalpable non-scrotal testis were found to have transverse testicular ectopia. This is an uncommon abnormality in which both gonads migrate toward the same hemiscrotum. We illustrate that unilateral cryptorchidism and a contralateral inguinal hernia may indicate the presence of a rare type of male pseudohermaphroditism: persistent müllerian duct syndrome (PMDS). This syndrome is characterized by the presence of a uterus and fallopian tubes associated with abdominal testes and frequently inguinal hernia in a phenotypically and genotypically normal male. This syndrome is often discovered during repair of inguinal hernia or non-descended testes (cryptorchidism). Pre-operative ultrasonography in children with impalpable non-scrotal testis and a contralateral inguinal hernia (patent processus vaginalis) may enable an early diagnosis of transverse testicular ectopia and proper surgical planning. Surgical orchidopexy was carried out and in the first two patients resection of the müllerian duct remnant (utriculus masculinus).

Vaginal stones in a 5-year-old girl: a novel approach of removal.

BACKGROUND: Primary vaginal stones in children are extremely rare and removal can be difficult. We describe a procedure for safe extraction of vaginal stones. CASE: A 5-year-old, wheelchair-bound girl was referred to the urologic department with recurrent febrile urinary tract infection. Diagnostics of the kidneys showed no abnormalities. The bladder appeared to contain two stones. On urethro-cystoscopy no stones were seen. Vaginoscopy identified vaginal stones. After 4 weeks of estrogen treatment, a second procedure via vaginal introduction of a nephroscope in combination with an ultrasonic device, effectively disintegrated the stones. SUMMARY AND CONCLUSION: We recommend the use of a nephroscope in visualizing the vagina and cervix and facilitating instrumentation in prepubertal girls.

Transurethral microwave thermotherapy: the gold standard for minimally invasive therapies for patients with benign prostatic hyperplasia?

From all available minimally invasive methods for the treatment of symptomatic benign prostatic hyperplasia (BPH), transurethral microwave thermotherapy (TUMT) has gained a firm position as the most attractive option. Recent research has produced innovations in high-energy TUMT, including new treatment protocols, refined selection criteria, and monitoring of intraprostatic temperature. Furthermore, long-term results from randomized studies comparing TUMT with transurethral resection of the prostate (TURP) or medical treatment are now available. All these data indicate that more durable clinical outcomes and less morbidity can be achieved with TUMT, strengthening its position as a standard treatment for BPH. This paper describes the status of TUMT in the treatment of lower urinary tract symptoms related to BPH, focusing on variations in the outcomes with different devices, the durability of treatment outcomes, morbidity, selection criteria, and cost. The relation of TUMT to medical management and TURP also is addressed.

Computerised assessment of maximum urinary flow: an efficient, consistent and valid approach.

OBJECTIVES: To evaluate the relative accuracy of a computerised method to quantitatively assess maximum urinary flow. METHODS: A total of 1147 uroflows were evaluated by the computerised method and by three experts from different European countries. The sample consisted of uroflows from the respective visits by a 20% sample of randomly chosen patients (n = 223) with lower urinary tract symptoms with participation in two clinical trials in which the efficacy and safety of Permixon was evaluated. The proportions of automated maximum flow values included in the 10% extended range of experts (and their 95% confidence intervals) were assessed, as well as the concordance coefficients between experts and the computerised method and the paired Student's t-test for the average differences between experts and computer. RESULTS: The rate of agreement between experts and computer varied between about 95 and 100% over factor levels for visit, type of machine and country. Concordance coefficients indicated good agreement between experts and the automated method. When looking at average differences between experts and the computer, the smallest differences were observed between experts 2, 3 and the computer (differences not statistically significant). Statistically significant average differences were observed between expert 1 and the other experts as well as between expert 1 and the computer. CONCLUSIONS: The computerised assessment decreases the fraction of variability of maximum urinary flow caused by artifacts as well as intra- and inter-expert variation. The computerised assessment of maximum urinary flow is an efficient, consistent and valid approach to quantitatively assess maximum urinary flow in clinical trials.