Divya Ajay

Convection Enhanced Delivery of Macromolecules for Brain Tumors

The blood brain barrier (BBB) poses a significant challenge for drug delivery of macromolecules into the brain. Convection-enhanced delivery (CED) circumvents the BBB through direct intracerebral infusion using a hydrostatic pressure gradient to transfer therapeutic compounds. The efficacy of CED is dependent on the distribution of the therapeutic agent to the targeted region. Here we present a review of convection enhanced delivery of macromolecules, emphasizing the role of tracers in enabling effective delivery anddiscuss current challenges in the field.

The Artificial Urinary Sphincter is Superior to a Secondary Transobturator Male Sling in Cases of a Primary Sling Failure

PURPOSE We compared continence outcomes in patients with post-prostatectomy stress urinary incontinence treated with a salvage artificial urinary sphincter vs a secondary transobturator sling. MATERIALS AND METHODS We retrospectively reviewed the records of patients undergoing salvage procedures after sling failure from 2006 to 2012. Postoperative success was defined as the use of 0 or 1 pad, a negative stress test and pad weight less than 8 gm per day. We performed the Wilcoxon test and used a Cox regression model and Kaplan-Meier survival analysis. RESULTS A total of 61 men presenting with sling failure were included in study, of whom 32 went directly to an artificial urinary sphincter and 29 received a secondary sling. Of the artificial urinary sphincter cohort 47% underwent prior external beam radiation therapy vs 17% of the secondary sling cohort (p = 0.01). Average preoperative 24 hour pad weight and pad number were higher in the artificial urinary sphincter cohort. Median followup in artificial urinary sphincter and secondary sling cases was 4.5 (IQR 4-12) and 4 months (IQR 1-5), respectively. Overall treatment failure was seen in 55% of patients (16 of 29) with a secondary sling vs 6% (2 of 32) with an artificial urinary sphincter (unadjusted HR 7, 95% CI 2-32 and adjusted HR 6, 95% CI 1-31). CONCLUSION In this cohort of patients with post-prostatectomy stress urinary incontinence and a failed primary sling those who underwent a secondary sling procedure were up to 6 times more likely to have persistent incontinence vs those who underwent artificial urinary sphincter placement. These data are useful for counseling patients and planning surgery. We currently recommend placement of an artificial urinary sphincter for patients in whom an initial sling has failed.

The Ohmmeter Identifies the Site of Fluid Leakage during Artificial Urinary Sphincter Revision Surgery

PURPOSE While the AMS 800 artificial urinary sphincter improves continence in up to 90% of patients, revision surgery may be needed in up to 50%. We determined whether an ohmmeter could accurately assess the site of fluid leak from individual components of the artificial urinary sphincter at the time of revision surgery. MATERIALS AND METHODS We retrospectively reviewed the records of patients who underwent artificial urinary sphincter revision surgery between 1996 and 2013. Patients in whom fluid loss was identified preoperatively by plain film radiography and who subsequently underwent revision surgery using the ohmmeter were assessed for outcomes. RESULTS The ohmmeter was used intraoperatively in a total of 20 surgeries in 19 patients and it correctly identified the location of fluid loss in 18 of 20 (90%). Fluid leakage was found from the pressure regulating balloon in 13 cases, from the cuff in 4 and from the tubing to the pressure regulating balloon in 1. None had fluid loss from the pump. In the 17 cases in which only the malfunctioning component was replaced a satisfactory postoperative outcome with a fully functional device was documented in all. Repeat surgery was performed in 5 of 17 cases (29.4%) at a median of 17 months (range 2 to 39). No patient underwent repeat surgery due to failure to accurately diagnose a component leak. CONCLUSIONS In cases of suspected fluid loss as a cause of artificial urinary sphincter malfunction an ohmmeter can identify the site of fluid loss during component revision surgery.

Immunotherapy with Tumor Vaccines for the Treatment of Malignant Gliomas

With an average life expectancy of 14 months, Glioblastoma multiforme (GBM), is the most aggressive primary brain tumor. Our growing understanding of the immune system and its role in oncogenesis has helped develop cancer vaccines as a promising treatment modality against this disease. What follows is a comprehensive discussion on the history of immunotherapy and the various vaccine based therapies being developed and utilized for the treatment of malignant gliomas.

Evaluation and Management of Neurogenic Stress Urinary Incontinence

Neurogenic bladder is a broad term that encompasses many different types of neurologic diseases and a wide spectrum of dysfunction of the lower urinary tract. Patient with neurogenic stress urinary incontinence (SUI) have poor urine store storage due to outlet dysfunction. Office examination, cystoscopy, video urodynamics (UDS), and renal imaging all play an important role in evaluating these patients (Wyndaele et al. Neurourol Urodyn. 2009;29:662-669 [27]). Based on patients’ overall function, bladder capacity and compliance, and ability to void or perform clean intermittent catheterizations, outlet procedures such as slings and artificial urinary sphincters may be offered safely (Arun Sahai et al. Curr Urol Rep. 2011;12:404-412 [28••]). Other options for partial or complete urinary diversion exist for patients with limited residual function or low capacity bladders. Improving continence in this population can positively impact quality of life and help with issues such as skin break down and chronic infection from incontinence (Ku. BJU Int. 2006;98:739-745 [26]).

Lower Urinary Tract Symptoms and Incontinence in Children with Pompe Disease

BACKGROUND Pompe disease (PD) is a disorder of lysosomal glycogen storage. The introduction of enzyme replacement therapy (ERT) has shifted the focus of care from survival to quality of life. The presence of lower urinary tract symptoms (LUTS) and incontinence has not been previously described in children with PD. METHODS Children with PD followed in the Duke Lysosomal Storage Disease Clinic completed a validated bladder control symptom score (BCSS) and additional questions regarding urinary tract infections (UTIs), giggle, and stress incontinence. Descriptive statistics were used to discriminate urinary symptoms between gender, age, and different types of PD. RESULTS Sixteen of 23 children (aged 4-14 years) seen in our clinic participated. Seven were girls; ten had classic infantile PD, two atypical infantile PD, and four childhood presentation late-onset PD (LOPD). When stratified by PD subtype, median BCSS was worst for the classic PD subtype followed by atypical PD and LOPD. Daytime urinary incontinence accompanied by constipation was noted in six. Eight reported urinary incontinence with laughing: giggle incontinence in six and stress incontinence in two. Four girls reported a history of UTI. Longitudinal follow-up in 11 patients showed stable BCSS in six, improvement in three, and worsening in two. Worsening corresponded with changes in bowel function and improvement with increase in ERT dose or treatment of constipation. CONCLUSIONS LUTS and incontinence are common in children with PD with greater symptoms noted with infantile-type PD. Improved bowel function and increase in ERT dose may lead to improvements in BCSS.

Wilms Tumor after Orthotopic Liver Transplant in a Patient with Alagille Syndrome .

We present a case of Wilms Tumor in a patient with Alagille syndrome 10 months after liver transplant. We explore a suggested genetic connection between these 2 diseases. In children with Wilms Tumor, we propose a pathoembryologic explanation for not just the tumor, but also for the cause of associated benign ureteral and renal parenchymal aberrancies that are commonly seen in the Alagille population. We also discuss the diagnostic and therapeutic challenges that can arise in a liver transplant patient with Alagille syndrome who subsequently develops a renal mass.