Sarel Halachmi

Intravesical mitomycin C combined with hyperthermia for patients with T1G3 transitional cell carcinoma of the bladder

OBJECTIVES Non-muscle invasive bladder cancer (NMIBC) classified as T1G3 represents one of the most challenging issues in urologic oncology. Although it is still considered a lesion amenable for conservative management, the risk for recurrence and progression remains high. The aim of this study was to define both recurrence and progression rate in patients with T1G3 UCC treated by complete transurethral resection (TURT) and adjuvant thermochemotherapy approach. MATERIALS AND METHODS We retrospectively evaluated the clinical data of patients with T1G3 NMIBC who underwent TURT followed by thermochemotherapy (TCT) treatment. Data recorded included age, gender, previous resections, previous intravesical treatment, time to tumor recurrence, and progression. TCT was given once weekly for 6 consecutive weeks, followed by 6 maintenance sessions at 4 to 6 weeks intervals. During each treatment session, 40 mg of mitomycin C (MMC) was instilled into the bladder in combination with bladder wall hyperthermia of 42 ± 2 °C for 60 minutes. Follow-up cystoscopy and urinary cytology were performed every 3 months for the first 2 years and than biannually. RESULTS A total of 56 T1G3 patients were treated with adjuvant TCT treatment at 7 urologic centers. Mean age was 68 years (range 35-91), 10 were females and 46 were males. Twenty-six patients failed on at least 1 previous intravesical treatment. Five patients who dropped out due to adverse events before reaching the first outcome evaluation cystoscopy were referred to another intravesical therapy, and were therefore excluded from the current analysis. A total 51 patients were available for analysis. Median follow-up time of tumor-free patients was 18 months (average 20, range 2-49 months). Seventeen patients (33.3%) had tumor recurrence and 4 of them progressed to muscle invasive disease. The median time to recurrence was 9 months (average 11, range 2-31 months). The Kaplan-Meier estimated recurrence rate for this group is: 42.9% at 2 years, 51.0% at 4 years. CONCLUSIONS TCT can be an effective adjuvant treatment option after TURT to prevent recurrence in patients with T1G3 NMIBC. Progression rate after this treatment was low (7.9%). TCT treatment was documented to be effective also in those who failed previous intravesical BCG. Treatment was confirmed to be safe and well tolerated.

ETView tracheoscopic ventilation tube for surveillance after tube position in patients undergoing percutaneous nephrolithotomy

BACKGROUND Tracheal tube (TT) displacement during general anaesthesia may result in life-threatening complications and continuous direct vision of the position of the tube may enable safer management. The ETView tracheoscopic ventilation tube (TVT) is a single-use TT incorporating a video camera and a light source in its tip. The view from the tip appears continuously on a portable monitor in the anaesthetists vicinity. This study was designed to test the ETView TVT in monitoring the TT position during general anaesthesia. METHODS In this prospective study, the ETView TVT was used to ventilate the lungs of 30 adult patients undergoing percutaneous nephrolithotomy (PCNL), which required changing patient position three times. During surgery, the anaesthetist followed the carinal view on the ETView TVT portable monitor. Tube movement within 1 cm was recorded, as was the need for repositioning of the tube when the carina was not seen on the camera monitor. RESULTS During anaesthesia, tiny movements synchronous with heart beats and lung ventilation were observed. Tube movement of 1 cm was detected in eight (26%) patients. In two (7%) patients, the carina was no longer viewed after moving to the lithotomy position and the tube was repositioned. None of the events was associated with changes in oxygen saturation, end-tidal CO(2), or airway pressure. CONCLUSIONS We found that the ETView TVT facilitated surveillance of tube position by providing a clear high-quality view of the carina, throughout PCNL with several changes of patient position.

Congenital urological anomalies diagnosed in adulthood – Management considerations

OBJECTIVE Despite worldwide availability of prenatal ultrasound, many patients are diagnosed in adult life with congenital anomalies such as ureteropelvic junction obstruction (UPJO), undescended testicle (UDT), ureterocele, hypospadias, vesicoureteral reflux (VUR) and primary obstructing megaureter (POM). The aim of this review was to describe these clinical conditions and their suggested management based on the available medical literature. REVIEW Adult UPJO is not a rare condition; symptomatic patients should be treated rather than observed. Treatment options are nephrectomy for non-functioning kidneys and reconstructive surgery for functioning renal units. The adult UDT has low fertility potential and increased cancer risk; hence most of the data in the literature indicate performing an orchiectomy. Adult ureteroceles are usually related to single systems and they are intravesical and less obstructive. For symptomatic patients endoscopic incision showed high efficacy for symptom elimination with minimal side effects. Primary hypospadias correction in the adult patient is feasible, but success rates are low compared to the pediatric age group. Secondary correction, whether primary correction was performed in childhood or adulthood, is a challenging task with a high complication rate. Treatment decisions regarding adult patients with VUR are difficult to make as the available data are inconsistent; there is no strict evidence that reflux in an adult is directly related to renal growth impairment, ascending pyelonephritis, and/or embryo loss in a pregnant woman. In contrast to the pediatric age group, adult POM is usually a symptomatic condition and related to a high complication rate including infections, stone formation and renal failure. Spontaneous resolution is rare and hence active surgical management is advocated. CONCLUSION Congenital urological anomalies identified in adulthood are not rare and pose a management challenge to the urologist. For most of the reviewed diseases, evidence-based management direction is difficult due to a lack of randomized trials and long-term follow up.

Improving Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer by adding interleukin 2 (IL-2): a mathematical model

One of the treatments offered to non-invasive bladder cancer patients is BCG instillations, using a well-established, time-honoured protocol. Some of the patients, however, do not respond to this protocol. To examine possible changes in the protocol, we provide a platform for in silico testing of alternative protocols for BCG instillations and combinations with IL-2, to be used by urologists in planning new treatment strategies for subpopulations of bladder cancer patients who may benefit from a personalized protocol. We use a systems biology approach to describe the BCG-tumour-immune interplay and translate it into a set of mathematical differential equations. The variables of the equation set are the number of tumour cells, bacteria cells, immune cells, and cytokines participating in the tumour-immune response. Relevant parameters that describe the systems dynamics are taken from a variety of independent literature, unrelated to the clinical trial results assessed by the model predictions. Model simulations use a clinically relevant range of initial tumour sizes (tumour volume) and tumour growth rates (tumour grade), representative of a virtual population of fifty patients. Our model successfully retrieved previous clinical results for BCG induction treatment and BCG maintenance therapy with a complete response (CR) rate of 82%. Furthermore, we designed alternative maintenance protocols, using IL-2 combinations with BCG, which improved success rates up to 86% and 100% of the patients, albeit without considering possible side effects. We have shown our simulation platform to be reliable by demonstrating its ability to retrieve published clinical trial results. We used this platform to predict the outcome of treatment combinations. Our results suggest that the subpopulation of non-responsive patients may benefit from an intensified combined BCG IL-2 maintenance treatment.

The molecular pathways behind bladder stretch injury

Stretch injury is a non-reversible process that changes the cellular and extracellular characteristics of the bladder wall, leading to bladder dysfunction. Posterior urethral valve and neurogenic bladder are examples of disorders that may lead to stretch injury. There is a lack of understanding of the molecular processes leading to stretch injury. The current literature is reviewed in this paper, with the aim of giving some insight into the molecular and genetic pathways of bladder stretch injury.

Functional and oncological outcomes of open nephron-sparing surgery for complex renal masses.

OBJECTIVE To present our long-term functional and oncological outcomes in open nephron-sparing surgery for complex renal masses. PATIENTS AND METHODS We enrolled 584 patients who underwent open partial nephrectomy between January 1995 and May 2014 at our institution; 108 (18.4%) patients had hilar or completely intraparenchymal tumors or both. We compared change in renal function, perioperative complications, and survival outcomes between complex and noncomplex renal masses. RESULTS Mean tumor diameter was 4.3 and 3.5cm in patients with hilar and completely intraparenchymal lesions, respectively. R.E.N.A.L. nephrometry scores were significantly higher in patients with complex tumors as compared with patients with exophytic tumors. There was no significant difference between mean estimated glomerular filtration rate at last follow-up compared with preoperative mean estimated glomerular filtration rate in any of the groups. The incidence of perioperative complications was similar across all patients groups. Estimated 10-year cancer-specific survival probabilities were 100% in patients with hilar and intraparenchymal tumors. The 10-year recurrence-free survival probabilities were 96% and 95% in patients with hilar and intraparenchymal tumors, respectively. The main limitations include retrospective design and the lack of kidney-specific functional scan. CONCLUSION Open nephron-sparing surgery should be considered for complex renal masses yielding excellent functional and oncological outcomes without higher incidence of complications.

A Review on Hematuria in Children

Asymptomatic hematuria is very common in pediatric and adolescent patients. In contrast to painless hematuria in adults, the differential diagnosis and investigative modalities in the pediatric population is vastly different. This article presents the major diseases that may cause hematuria in children and suggests an evaluation algorithm for the pediatric urologist.

Three-Dimensional Imaging Using Spiral Computerized Tomography prior to Tumor Enucleation in a Patient with a Solitary Kidney

The authors present a case of renal cell carcinoma in a man with a solitary kidney. Three-dimensional computerized tomography instead a selective renal angiography was used preoperatively as a noninvasive technique for visualization of the renal tumor and renal vascularization.

The role of hyperthermia as a treatment for non-muscle invasive bladder cancer.

ABSTRACT Non-muscle invasive bladder cancer (NMIBC) has a high tendency for recurrence and progression. Currently, all known intravesical agents are associated with adverse effects (AEs) and limited efficacy. The combination of hyperthermia (HT) with intravesical Mitomycin C (MMC) chemotherapy has been shown to improve outcomes. The added efficacy of HT to MMC was first shown in preclinical studies. The reports on patients with NMIBC have indicated that the treatment is safe and well tolerated. Several clinical studies reported the efficacy of radiofrequency-induced chemotherapy effect (RITE) in the treatment of patients with NMIBC. This modality was shown to be superior to MMC alone. RITE was effective also in patients with high-risk NMIBC, including those who failed Bacillus Calmette-Guérin (BCG). This study provides an updated review of literature regarding the use of RITE in patients with NMIBC.

Congenital Anomalies in Adults: Diagnosis and Management Considerations

Diagnosis of a congenital urological anomaly in an adult is not a rare event. Management considerations in the adult patient are sometimes different compared to the pediatric age group. In adults, more emphasis is given to symptoms, patient age and additional co-morbidities. The adult age group may benefit from a wider choice of surgical techniques that cannot be applied in children such as endoscopic procedures. Despite utilizing similar operational skills and techniques, surgical outcome in adults may be different from that in children. In general, there is a relatively large arsenal of available therapeutic solutions to offer to adult patients with congenital urological anomalies.