Urinary Symptom Nonresponse ("LUTS Failure") after Urethroplasty: Incidence and Associations.

PURPOSE: An ill-defined proportion of patients undergoing urethroplasty fail to experience improvement in lower urinary tract symptoms (LUTS) despite being stricture-free. We aim to identify the incidence, associations and causes of "LUTS failure" after urethroplasty. MATERIALS AND METHODS: Patients undergoing urethroplasty over a 6-year period were offered enrollment in a prospective study examining urinary function after urethroplasty. Patients were assessed preoperatively and 6 months postoperatively using the International Prostate Symptom Score (IPSS) and cystoscopy. "LUTS failure" was defined as ≤3-point improvement in IPSS despite an anatomically successful urethroplasty. Multivariable logistic regression was utilized to evaluate the association between patient factors and "LUTS failure." RESULTS: Of 365 patients meeting inclusion criteria, mean postoperative IPSS (20.3 vs. 5.4, p <0.0001) and median urinary quality of life (UQOL; 5 vs. 1; p <0.0001) were significantly improved. Despite being stricture-free, 7.7% of patients reported "LUTS failure" and 10.1% reported UQOL nonresponse. On multivariable logistic regression, increasing age (OR 1.04, 95% CI 1.01-1.06; p=0.006) and hypospadias (OR 18.2, 95% CI 2.1-156.0; p=0.008) were associated with "LUTS failure," while stricture location (p=0.76), length (p=0.14), previous urethroplasty (p=0.96), failed endoscopic treatment (p=0.17), type of urethroplasty (p=0.93) and other etiologies were not. Qualitatively, the most likely causes of "LUTS failure" were detrusor underactivity (39.3%), overactivity (21.4%), pelvic floor dysfunction (21.4%) or benign prostatic hyperplasia (14.3%). Only increasing age was associated with UQOL nonresponse (OR 1.03, 95% CI 1.01-1.07; p=0.02). CONCLUSIONS: While many patients experience improved voiding function after urethroplasty, 7.7% experience "LUTS failure" and 10.1% report UQOL nonresponse. Both occurrences are independently associated with increasing patient age and most commonly related to detrusor underactivity.

Nontransecting Techniques Reduce Sexual Dysfunction after Anastomotic Bulbar Urethroplasty: Results of a Multi-Institutional Comparative Analysis.

PURPOSE: The purpose of this multi-institutional study was to compare outcomes of transecting and nontransecting anastomotic bulbar urethroplasty. MATERIALS AND METHODS: We performed a retrospective, multi-institutional review of the records of 352 patients who underwent transecting or nontransecting anastomotic bulbar urethroplasty performed by 1 of 4 reconstructive urologists from September 2003 to March 2017. Study outcomes were urethroplasty success, defined as urethral patency greater than 16Fr on cystoscopy; de novo sexual dysfunction assessed at 6 months, defined as a 5-point or greater change in the SHIM (Sexual Health Inventory for Men) or a patient reported adverse change; and 90-day complications, defined as Clavien 2 or greater. When appropriate, comparisons were made between the transecting and nontransecting cohorts using the Mantel-Cox test, the t-test or the chi-square test. RESULTS: Of the 352 patients with a mean stricture length of 1.7 cm (range 0.5 to 5) 258 and 94 underwent transecting and nontransecting anastomotic bulbar urethroplasty, respectively. The overall success rate was 94.9% at a mean followup of 64.2 months (range 6 to 170). Of the patients 7.1% experienced a 90-day complication and 11.6% reported sexual dysfunction. When comparing transecting and nontransecting techniques, there was no difference in success (93.8% vs 97.9%, Mantel-Cox test p = 0.18) or postoperative complications (8.1% vs 4.3%, p = 0.25). Patients treated with transecting anastomotic urethroplasty were more likely to report an adverse change in sexual function (14.3% vs 4.3%, p = 0.008). On multivariate analysis only transecting urethroplasty was associated with sexual dysfunction (p = 0.01) while age (p = 0.29), stricture length (p = 0.42), etiology (p = 0.99) and surgeon (p = 0.88) were not. CONCLUSIONS: Anastomotic urethroplasty is a highly effective surgery with relatively minimal associated morbidity. Nontransecting anastomotic urethroplasty compares quite favorably to the transecting technique and likely reduces the risk of associated sexual dysfunction.

Incidence and Predictors of Complications due to Urethral Stricture in Patients Awaiting Urethroplasty.

PURPOSE: We examined the incidence and predictors of complications due to urethral stricture in patients awaiting urethroplasty. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients who underwent urethroplasty from 2009 to 2013. The primary outcome was complications, defined as any unplanned interaction with the health care system due to urethral stricture during the period between the decision to perform surgery and urethroplasty. RESULTS: A total of 276 patients were identified for analysis. Median stricture length was 4.0 cm and 67.4% of strictures were in the bulbar urethra. The most common stricture etiologies were idiopathic in 47.8% of cases and traumatic in 15.9%. Overall 15.9% of patients presented with a complication with a median time to complication of 43 days. Median surgical wait time was 151 days. Complications included urinary tract infections in 56.8% of patients, acute urinary retention in 20.5%, genitourinary pain in 5.8% and catheter related issues in 15.9%. Univariate analysis suggested that catheter dependent status, number of prior endoscopic treatments, a hypospadias and/or trauma etiology, and prior urethroplasty were potential significant predictors of complications. Multivariate analysis yielded only catheter dependent status (HR 5.2, 95% CI 2.4-11.3, p <0.0001) and prior failed urethroplasty (HR 1.6, 95% CI 1.1-2.3, p = 0.03) as significantly associated with complications. CONCLUSIONS: To our knowledge our study is the first to examine and quantify the morbidity of urethroplasty wait time. Approximately 16% of patients experienced a complication while awaiting urethroplasty. The optimal wait time should be less than 43 days. Patients with prior urethroplasty and catheters at the time of the surgical decision should be prioritized as they may be more likely to experience complications.

Long-Term outcomes of cecostomy tube insertion for patients with bowel dysfunction: A retrospective review.

BACKGROUND: Constipation is common in the pediatric population and in severe forms it can lead to debilitating fecal incontinence which has a significant impact on quality of life. Cecostomy tube insertion is a procedural option for cases refractory to medical management, however there is limited data investigating the long-term success and complication rate. METHODS: A retrospective review was performed evaluating patients at our centre undergoing cecostomy tube (CT) insertion between 2002 and 2018. The primary outcomes of the study were the rate of fecal continence at 1-year, and the incidence of unplanned exchanges prior to annual scheduled exchange. Secondary outcomes include the frequency of anaesthetic requirements and length of hospital stay. Descriptive statistics, t-test, and chi-square analysis was performed where appropriate using SPSS v25. RESULTS: Of 41 patients, the average age at the time of initial insertion was 9.9 years with the average length of stay in hospital being 3.47 days. The most common etiology of bowel dysfunction was spina bifida, which was present in 48.8% (n = 20) of patients. Fecal continence was achieved in 90% (n = 37) of patients at 1 year and the average rate of cecostomy tube exchange was 1.3/year with an average of 3.6 general anaesthetics being required by patients and the average age of no longer requiring one being 14.9 years. DISCUSSION: Analysis of patients undergoing cecostomy tube insertion at our centre has further supported the use of cecostomy tubes as a safe and effective option for management of fecal incontinence refractory to medical management. However, a number of limitations exist in this study including its retrospective design and failure to investigate changes in quality of life using validated questionnaires. Additionally, while our research provides greater insight to practitioners and patients what degree of care and types of complications or issues they may encounter with an indwelling tube over the long-term, our single-cohort design limits any conclusions that could be made regarding optimal management strategies for overflow fecal incontinence through direct comparison with other management strategies. CONCLUSIONS: CT insertion is a safe and effective method for managing fecal incontinence due to constipation in the pediatric population, however, unplanned exchange of tube due to malfunction, mechanical breakage, or dislodgment occurs frequently and may impact quality of life and independence. LEVEL OF EVIDENCE: IV.

Clinical outcomes of glansectomy with split-thickness skin graft reconstruction for localized penile cancer.

INTRODUCTION: Penectomy as the traditional surgical treatment of penile cancer has substantial adverse functional and psychological impact. Glansectomy with split-thickness skin graft (STSG) reconstruction aims to provide curative resection while maximizing functional outcomes and minimizing psychological harm. We describe our outcomes of glansectomy with STSG reconstruction for penile cancer in a Canadian setting. METHODS: We identified patients undergoing glansectomy with STSG genital reconstruction for squamous cell carcinoma of the penis from July 2006 to July 2019 at a single center. Patients undergoing glansectomy for reasons other than penile cancer were excluded. We collected clinical and pathological data, including patient demographics, 90-day complications, positive margin rate, local recurrence rate, disease-specific survival, and functional outcomes. Descriptive statistics were used to characterize our cohort and to examine outcomes. RESULTS: Twelve men met study criteria with a median age of 62 years. Seven patients had failed prior treatment. The 90-day complication rate (Clavien >2) was 0% and graft take was excellent in all cases. The positive margins rate was 16.7% (n=2). Local recurrence occurred in two patients (16.7%), one of whom underwent a repeat organ-sparing surgery for salvage, while the other underwent radical penectomy for high-risk pathological features. Disease-free survival at a median followup of 14 months was 91.7% (11/12). Standing voiding and erectile function, as well as satisfactory cosmesis, were preserved in all patients. CONCLUSIONS: Glansectomy with STSG reconstruction is a safe and effective treatment for men with localized penile cancer with simultaneous preservation of cosmesis, as well as urinary and sexual function.

Better defining the optimal management of penile urethral strictures: A retrospective comparison of single-stage vs. two-stage urethroplasty.

INTRODUCTION: We aimed to compare single-stage and two-stage urethroplasty techniques for the treatment of penile urethral strictures. METHODS: We performed a retrospective review of all penile urethroplasties performed at a single centre between 2003 and 2017. The primary outcome was urethral patency, defined as the ability to easily pass a 16 Fr flexible cystoscope at six and 18 months of followup, and development of 90-day complications. RESULTS: Overall, 101 single-stage procedures (48 buccal mucosal graft [BMG] and 53 penile fasciocutaneous flap [PFF]) and 53 two-stage procedures were performed. There was no difference in median stricture length between groups (p=0.25). Cox regression analysis did not identify stricture etiology, length, age, obesity, prior reconstruction, or urethroplasty technique to be associated with failure. Log-rank testing did not demonstrate a difference in success rates between surgical techniques (91% [48/53] PFF vs. 83% [40/48] BMG vs. 87% two-stage [46/53]). Thirty-nine percent (60/154) of patients experienced a complication (51% [27/53] PFF vs. 29% [14/48] BMG vs. 36% [19/53] two-stage). Multivariate analysis found urethroplasty technique to be the only factor associated with development of complication (p=0.02); odds ratio relative to BMG was 3.1 (p=0.009) for PFF and 1.4 (p=0.43) for two-stage. CONCLUSIONS: There appears to be little difference in success between penile urethroplasty techniques. The shift in technique to a single-stage BMG, when appropriate, appears to be founded on the basis of fewer operations for the patient, relative to a two-stage repair, and a lower complication profile, relative to single-stage PFF, without compromising success rates.

Monitoring photodynamic therapy with photoacoustic microscopy.

Abstract. We present our work on examining the feasibility of monitoring photodynamic therapy (PDT)-induced vasculature change with acoustic-resolution photoacoustic microscopy (PAM). Verteporfin, an FDA-approved photosensitizer for clinical PDT, was utilized. With a 60-µm-resolution PAM system, we demonstrated the capability of PAM to monitor PDT-induced vasculature variations in a chick chorioallantoic membrane model with topical application and in a rat ear with intravenous injection of the photosensitizer. We also showed oxygen saturation change in target blood vessels due to PDT. Success of the present approach may potentially lead to the application of PAM imaging in evaluating PDT efficacy, guiding treatment, and predicting responders from nonresponders.

Detecting functional changes with [(18)F]FAZA in a renal cell carcinoma mouse model following sunitinib therapy.

BACKGROUND: The multitargeting tyrosine kinase inhibitor (TKI) sunitinib is currently the first-line drug therapy for metastasizing renal cell carcinoma (RCC). TKIs have profound effects on tumor angiogenesis, leading to modifications of the tumor microenvironment. The goal of this study was to determine whether these treatment-induced changes can be detected with [(18)F]FAZA. METHODS: The present study utilized positron emission tomography (PET) to analyze tumor oxygenation status during and after sunitinib therapy in the murine Caki-1 RCC tumor model. Dynamic and static scans were performed, as well as ex vivo biodistributions at 3 h post injection (p.i.). Immunohistochemical analysis of tumor tissue was carried out for the quantification of pimonidazole binding and the hypoxia-associated factors CD-31, Ki-67, and Von Willebrand factor (VWF). In addition, in vitro cellular uptake studies were done to analyze the direct effects of sunitinib on the Caki-1 cells. RESULTS: During therapy with sunitinib (40 mg/kg/day), uptake of [(18)F]FAZA into Caki-1 mice decreased by 46 ± 5% (n = 4; 5 days) at 3 h post injection (p.i.) during the first study and 22 ± 5% (n = 8; 9 days) during the long-term study, indicating a decrease in the tumor's hypoxia level. However, when drug therapy was stopped, this effect was reversed completely, and the tumor [(18)F]FAZA uptake increased to 126 ± 6% (n = 6) of the control tumor uptake, indicative of an even higher level of tumor hypoxia compared to the therapy starting point. Sunitinib had no direct effect on [(18)F]FAZA uptake into Caki-1 cells in vitro. CONCLUSION: [(18)F]FAZA PET could be used to monitor drug response during sunitinib therapy in RCC and may guide combination therapies based on the tumor's hypoxia status.

One Health: Lessons Learned from East Africa.

Africa is faced with many of the most daunting challenges of our time. It comprises roughly 15% of the world's human population, and most of its countries are perpetually ranked "Low" on the United Nations' Human Development Index. On the other hand, Africa has arguably the largest proportion of intact natural ecosystems, biodiversity, and sociocultural capital and the lowest impact on global warming of any continent. Thus, African leaders are faced with competing demands and values among a multitude of complex issues, such as high human population growth, extreme poverty, food insecurity, land use policy, climate change, and biodiversity conservation. In this context, building sustainable national systems for human and/or animal health is one of the grand challenges of this generation. Today's complex global health and development challenges require long-term commitment and a range of approaches that are too broad for any one discipline, institution, or country to implement on its own. The One Health concept recognizes the interconnectedness of global health issues and, as such, promotes the importance of and need for international, interdisciplinary, and cross-sectoral communication and collaboration at local, national, and international levels. By taking advantage of natural cultural tendencies for shared leadership, resource allocation, and community values, African leaders are currently proactively demonstrating the principles of One Health, and thus becoming a model for this global vision. And by focusing on partnerships rather than donor-recipient relationships, they are fostering the development of shared priorities and are increasingly driving their own health agenda to fulfill their own needs.

Encapsulated islet transplantation: strategies and clinical trials.

Encapsulation of tissue has been an area of intense research with a myriad number of therapeutic applications as diverse as cancer, tissue regeneration, and diabetes. In the case of diabetes, transplantation of pancreatic islets of Langerhans containing insulin-producing beta cells has shown promise toward a cure. However, anti-rejection therapy that is needed to sustain the transplanted tissue has numerous adverse effects, and the islets might still be damaged by immune processes. Furthermore, the profound scarcity of healthy human donor organs restricts the availability of islets for transplant. Islet encapsulation allows the protection of this tissue without the use of toxic medications, while also expanding the donor pool to include animal sources. Before the widespread application of this therapy, there are still issues that need to be resolved. There are many materials that can be used, differing shapes and sizes of capsules, and varied sources of islets to name a few variables that need to be considered. In this review, the current options for capsule generation, past animal and human studies, and future directions in this area of research are discussed.

Synthesis, characterisation and evaluation of a novel copper-64 complex with selective uptake in EMT-6 cells under hypoxic conditions.

The radiometal (64)Cu is now widely used in the development of diagnostic imaging agents for positron emission tomography (PET). The present study has led to the development and evaluation of a novel chelating agent for (64)Cu: the new monothiourea tripodal ligand 1-benzoyl-3-{6-[(bis-pyridin-2-ylmethyl-amino)-methyl]-pyridin-2-yl}-thiourea (MTUBo). X-ray crystallographic analysis has shown this ligand forms a mononuclear complex with copper(II) and co-ordinates via a trigonal bipyramidal N4S array of donor atoms. Promisingly, cell uptake studies revealed that (64)Cu-MTUBo selectively accumulates in EMT-6 cells incubated under hypoxic conditions which may result from its relatively high Cu(II/I) redox potential. Small-animal PET imaging and ex vivo biodistribution studies in EMT-6 tumor bearing BALB/c mice revealed significant tumor uptake after 1 h p.i., yielding tumor-to-muscle (T/M) and tumor-to-blood (T/B) ratios of 8.1 and 1.1, respectively. However, injection of (64)Cu-acetate resulted in similar uptake indicating that the observed uptake was most likely non-specific. Despite showing high in vitro stability, it is likely that in vivo the complex undergoes transchelation to proteins within the blood in a relatively short timeframe. For comparison, the hypoxia imaging agent (64)Cu-ATSM was also evaluated in the same murine tumor model and showed about 60% higher tumor uptake than (64)Cu-MTUBo.

Adverse renal outcomes in subjects undergoing nephrectomy for renal tumors: a population-based analysis.

BACKGROUND: There has been increasing interest in determining renal outcomes after nephrectomy for renal tumors. Previous studies have not assessed all relevant risk factors, including proteinuria. OBJECTIVE: We sought to determine the risk and predictors for the development of adverse renal outcomes in a population-based cohort of subjects undergoing partial or complete nephrectomy. DESIGN, SETTING, AND PARTICIPANTS: A large population-based data set was used to identify all subjects undergoing nephrectomy in Alberta, Canada, from 2002 to 2007 using administrative codes. Comorbid conditions were determined using validated algorithms, and baseline estimated glomerular filtration rate (eGFR) and proteinuria status were determined. MEASUREMENTS: Postsurgical outcomes of end-stage renal disease, acute dialysis, chronic kidney disease (CKD) (eGFR <30 ml/min per 1.73 m(2)), and rapidly progressive CKD (eGFR <60 ml/min per 1.73 m(2) and eGFR loss ≥4 ml/min per 1.73 m(2) per year) were assessed. The risk and risk factors for developing the composite renal outcome were determined using a multivariable Cox proportional hazards model. RESULTS AND LIMITATIONS: Of 1151 subjects, 10.5% developed an adverse renal outcome over a mean of 32 mo. Complete (vs partial) nephrectomy was associated with a hazard ratio (HR) of 1.75 (95% confidence interval [CI], 1.02-2.99) for the primary outcome, as was lower baseline eGFR. Subjects with proteinuria were more likely to experience the primary outcome (42% vs 9%), conferring an adjusted HR of 2.40 (95% CI, 1.47-3.88). CONCLUSIONS: Clinically important adverse renal outcomes are common in patients undergoing nephrectomy for renal tumors. In addition to baseline eGFR and the extent of the renal mass removed, proteinuria is a strong independent risk factor. Assessment of proteinuria, in addition to other risk factors, should be performed to inform prognosis and the optimal treatment strategy.