Mohammad Shamim Khan

Characterization of Salmonella enterica Derivatives Harboring Defined aroC and Salmonella Pathogenicity Island 2 Type III Secretion System (ssaV) Mutations by Immunization of Healthy Volunteers

ABSTRACT The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica serovar Typhi (Ty2 ΔaroC ΔssaV, designated ZH9) and S. enterica serovar Typhimurium (TML ΔaroC ΔssaV, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 107, 108, or 109 CFU. ZH9 was well tolerated, not detected in blood, nor persistently excreted in stool. Six of nine volunteers elicited anti-serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting cell (ASC) responses, with three of three vaccinees receiving 108 and two of three receiving 109 CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 108 and 109 CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 109 CFU of WT05 mounted detectable serovar Typhimurium LPS-specific ASC responses and serum antibody responses were variable. These data indicate that mutations in type III secretion systems may provide a route to the development of live vaccines in humans and highlight significant differences in the potential use of serovars Typhimurium and Typhi.

Recent advances in the diagnosis and treatment of bladder cancer

Bladder cancer is the commonest malignancy of the urinary tract. In this review, we look at the latest developments in the diagnosis and management of this condition. Cystoscopy and urine cytology are the most important tools in the diagnosis and follow-up of bladder cancer. Various alternatives have been investigated, either to reduce the frequency of cystoscopy, or improve its sensitivity for detection of tumors. These include urine-based markers and point-of-care tests. Narrow-band imaging and photodynamic diagnosis/blue-light cystoscopy have shown promise in improving detection and reducing recurrence of bladder tumors, by improving the completion of bladder resection when compared with standard resection in white light. The majority of patients with a new diagnosis of bladder cancer have non-muscle-invasive bladder cancer, which requires adjuvant intravesical chemotherapy and/or immunotherapy. Recent developments in post-resection intravesical regimens are discussed. For patients with muscle-invasive bladder cancer, both laparoscopic radical cystectomy and robot-assisted radical cystectomy have been shown to reduce peri-operative morbidity, while being oncologically equivalent to open radical cystectomy in the medium term. Bladder-preserving strategies entail resection and chemoradiation, and in selected patients give equivalent results to surgery. The development, advantages, and disadvantages of these newer approaches are also discussed.

Repeated Botulinum Toxin Type A Injections for Refractory Overactive Bladder: Medium-Term Outcomes, Safety Profile, and Discontinuation Rates

BACKGROUND Efficacy and safety of botulinum toxin type A (BoNTA) injection is supported by level 1 evidence, but data regarding repeated injections are limited in patients with refractory overactive bladder (OAB) and idiopathic detrusor overactivity (IDO). OBJECTIVES Describe medium-term outcomes and discontinuation rates for patients adopting repeated BoNTA as a management strategy for IDO. DESIGN, SETTING, AND PARTICIPANTS Prospective data from a single centre were collected from the first 100 patients. INTERVENTION Bladder injection of BoNTA (predominantly 200 U onabotulinumtoxinA; Allergan Ltd., Marlow, Buckinghamshire, UK) in an outpatient setting. MEASUREMENTS OAB symptoms, quality of life, discontinuation rates, interinjection interval, and adverse events were recorded. Data comparisons were performed using a generalised linear model or a chi-square test where appropriate. RESULTS AND LIMITATIONS Two hundred seven injections were performed in 100 patients. All patients had 1 injection, 53 had a total of 2, 20 had 3, 13 had 4, 10 had 5, 5 had 6, 3 had 7, 1 had 8, 1 had 9, and 1 had 10 injections. Statistics were applied up to five repeated injections. A statistically significant reduction in frequency, urgency, and urge urinary incontinence were seen following the first BoNTA injection compared to baseline. This improvement was maintained after repeated injections and was not statistically different when comparing differences between injections. Thirty-seven patients stopped treatment after the first two injections; thereafter, dropouts were rare. The most common reasons for discontinuing treatment were poor efficacy (13%) and clean intermittent self-catheterisation (CISC)-related issues (11%). The incidence of CISC after the first injection was 35%. Bacteriuria was detected in 21% of patients. The mean interinjection interval was 322 d. Limitations included the concurrent use of antimuscarinic drugs in some patients. CONCLUSIONS BoNTA can provide a safe and effective medium-term management option for patients with refractory IDO. The most common reasons cited for stopping treatment were poor efficacy and CISC-related issues.

Assessing the cost effectiveness of robotics in urological surgery - a systematic review

Study Type – Therapy (systematic review)

Analysis of Early Complications of Robotic-assisted Radical Cystectomy Using a Standardized Reporting System

OBJECTIVE To analyze the early complications of robotic-assisted laparoscopic radical cystectomy (RARC) with extracorporeal ileal conduit or orthotopic (Studer) bladder reconstruction using the Clavien Classification, the management of these complications, and possible preventive measures. MATERIALS AND METHODS Detailed data on all patients undergoing RARC were recorded prospectively on an encrypted database, including intraoperative or postoperative complications within 90 days of surgery. Outcome data during follow-up of up to 4 years was also collected prospectively. RESULTS A total of 50 patients (M:F 44:6) underwent RARC and extracorporeal ileal conduit urinary diversion (n = 45) or orthotopic bladder reconstruction (n = 5) between 2004 and 2008. The overall perioperative complication rate was 17 of 50 (34%), including 3 (6%) Clavien I, 9 (18%) Clavien II, and 5 (10%) Clavien III. Final histology showed 9 (18%) patients had no residual disease pT0, 7 (14%) pTa, 11 (22%) pT1, 9 (18%) pT2, 11 (22%) pT3, and 3 (6%) pT4. CONCLUSION Radical cystectomy remains a complex and morbid procedure with significant complication rate regardless of surgical approach. Using the Clavien reporting system, we identified early complications in 34% of patients, of which five required a significant intervention. Use of this standardized reporting system has allowed us to stratify complications after RARC, allowing easy comparison to other techniques and targeting further reductions in the future.

Effectiveness of Procedural Simulation in Urology: A Systematic Review

PURPOSE We analyzed studies validating the effectiveness and deficiencies of simulation for training and assessment in urology. We documented simulation types (synthetic, virtual reality and animal models), participant experience level and tasks performed. The feasibility, validity, cost-effectiveness, reliability and educational impact of the simulators were also evaluated. MATERIALS AND METHODS The MEDLINE®, EMBASE™ and PsycINFO® databases were systematically searched until September 2010. References from retrieved articles were reviewed to broaden the search. RESULTS The study included case reports, case series and empirical studies of training and assessment in urology using procedural simulation. The model name, training tasks, participant level, training duration and evaluation scoring were extracted from each study. We also extracted data on face, content and construct validity. Most studies suitably addressed content, construct and face validation as well as the feasibility, educational impact and cost-effectiveness of simulation models. Synthetic, animal and virtual reality models were demonstrated to be effective training and assessment tools for junior trainees. Few investigators looked at the transferability of skills from simulation to real patients. CONCLUSIONS Current simulation models are valid and reliable for the initial phase of training and assessment. For advanced and specialist level skill acquisition animal models can be used but availability is limited due to supply shortages and ethical restrictions. More research is needed to validate simulated environments for senior trainees and specialists.

Current status of robotic assisted pelvic surgery and future developments.

AIMS The aim of this review is to assess the role of robotics in pelvic surgery in terms of outcomes. We have also highlighted the issues related to training and future development of robotic systems. MATERIALS AND METHODS We searched MEDLINE, EMBASE and the Cochrane Databases from 1980 to 2009 for systematic reviews of randomised controlled trials, prospective observational studies, retrospective studies and case reports assessing robotic surgery. RESULTS During the last decade, there has been a tremendous rise in the use of robotic surgical systems for all forms of precision operations including pelvic surgery. The short-term results of robotic pelvic surgery in the fields of urology, colorectal surgery and gynaecology have been shown to be comparable to the laparoscopic and open surgery. Robotic surgery offers an opportunity where many of these obstacles encountered during open and laparoscopic surgery can be overcome. CONCLUSIONS Robotic surgery is a continually advancing technology, which has opened new horizons for performing pelvic surgery with precision and accuracy. Although its use is rapidly expanding in all surgical disciplines, particularly in pelvic surgery, further comparative studies are needed to provide robust guidance about the most appropriate application of this technology within the surgical armamentarium.

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

The search for a biomarker in overactive bladder syndrome (OAB) is an emerging field of interest, as bladder dysfunction is a common complaint that causes significant morbidity. A biomarker may give us insight as a diagnostic tool, and also inform us about how severe the condition is, how it may progress and how it may best be treated. The protein of interest here is nerve growth factor (NGF) and it has been shown to be a dynamic molecule in the bladder of patients with OAB. Urinary levels have been seen to rise in patients with OAB and fall in those who respond to treatment. However, there have also been many studies that examine this trend in numerous other conditions, e.g. interstitial cystitis, bladder outflow obstruction, renal stone disease and patients with neurological impairment after stroke. As a result the specificity of this as a potential urinary biomarker for OAB is questioned.

Cystine calculi: challenging group of stones.

Cystinuria is an autosomal recessive disorder in renal tubular and intestinal transport of dibasic amino acids, which results in increased urinary excretion of cystine, ornithine, lysine and arginine. It affects 1 in 20 000 people and is caused by a defect in the rBAT gene on chromosome 2. Development of urinary tract cystine calculi is the only clinical manifestation of this disease. Owing to recurrent episodes of stone formation, these patients require a multi-modal approach to management. The role of medical management and minimally invasive surgery was reviewed for the treatment of cystinuria.

Embolization of a Bleeding Renal Angiomyolipoma in Pregnancy: Case Report and Review

A case is described of a woman 10 weeks pregnant who had severe bleeding, secondary to a renal angiomyolipoma (AML), that was treated with embolization. Subsequent pregnancy was uneventful and she delivered a normal female infant 28 weeks after the procedure. One month after delivery, liquefaction of the AML occurred, which eventually required surgical drainage. We review and discuss AML during pregnancy, its management and post-embolization complications.