A multi-institutional critical assessment of dorsal onlay urethroplasty for post-radiation urethral stenosis.

PURPOSE: To critically evaluate a multi-institutional patient cohort undergoing Dorsal-Onlay Buccal Mucosal Graft Urethroplasty (D-BMGU) for recurrent post-radiation posterior urethral stenosis. METHODS: Retrospective multi-institutional review of patients with posterior urethral stenosis from 10 institutions between 2010-2019 was performed. Patients with at least 1-year follow-up were assessed. Patient demographics, stenosis characteristics, peri-operative outcomes, and post-operative clinical and patient-reported outcomes were analyzed. The primary outcomes were stenosis recurrence and de-novo stress urinary incontinence (SUI). Secondary outcomes were changes in voiding, sexual function, and patient-reported satisfaction. RESULTS: Seventy-nine men with post-radiation urethral stenosis treated with D-BMGU met inclusion criteria. Median age and stenosis length were 72 years, (IQR 66-75), and 3.0 cm (IQR 2.5-4 cm), respectively. Radiation modalities included: 36 (45.6%) external beam radiotherapy (EBRT), 13 (16.5%) brachytherapy (BT), 10 (12.7%) combination EBRT/BT, and 20 (25.3%) EBRT/radical prostatectomy. At a median follow-up of 21 months (IQR 13-40), 14 patients (17.7%) had stenosis recurrence. Among 37 preoperatively-continent patients, 3 men (8.1%) developed de-novo SUI following dorsal onlay urethroplasty. Of 29 patients with preoperative SUI all but one remained incontinent post-operatively (96.6%). Following repair, patients experienced significant improvement in PVR (92.5 to 26 cc, p = 0.001) and Uroflow (4.6 to 15.9 cc/s, p = 0.001), and high overall satisfaction, with 91.9% reporting a GRA of + 2 or better). CONCLUSION: Dorsal onlay buccal mucosa graft urethroplasty is a safe and feasible technique in patients with post-radiation posterior urethral stenosis. This non-transecting approach may confer low rates of de-novo SUI. Further research is needed to compare this technique with excisional urethroplasty.

Advancements in transurethral management of urethral stricture disease.

PURPOSE OF REVIEW: To explore and report the recent evolution of transurethral management of urethral stricture disease. RECENT FINDINGS: In recent years, new promising techniques in the transurethral management of urethral stricture disease have emerged including adjuvant therapies to direct vision internal urethrotomy, regenerative therapy with buccal mucosa cells and minimally invasive transurethral urethroplasty procedures that avoid skin incisions. SUMMARY: Although further work is needed, the expanding field of transurethral therapies for urethral stricture disease demonstrates early promising results through a variety of modalities.

Transurethral ventral buccal mucosa graft inlay for treatment of distal urethral strictures: international multi-institutional experience.

PURPOSE: To critically evaluate a multi-institutional patient cohort undergoing single-stage distal urethral repair using a novel transurethral buccal mucosa graft inlay urethroplasty technique (TBMGI). METHODS: A retrospective multi-institutional review of consecutive patients with fossa navicularis (FN) strictures treated with a single-stage TBMGI technique at 12 institutions from March 2014-March 2018 was performed. Patient demographics, stricture characteristics, clinical and patient-reported outcomes were analyzed. The primary outcomes were stricture recurrence and complications. Secondary outcomes were change in maximum urinary flow rate (Qmax), PVR, and changes in IPSS, SHIM and global response assessment (GRA) questionnaire responses. Descriptive statistical analysis was used for evaluation of outcomes. RESULTS: Sixty-eight men met inclusion criteria. Median age and stricture length were 60 years (IQR 48-69) and 2 cm (IQR 2-3), respectively. Most common stricture etiology was lichen sclerosus (34%). Median operative time and EBL were 72 min (IQR 50-120) and 20 mL (IQR 10-43), respectively. Fifty-seven men completed ≥ 12-month follow-up. At a median follow-up of 17 months (IQR 13-22), 54 patients (95%) remained stricture-free. Median Qmax improved from 5 to 18 mL/s (p < 0.0001), PVR 76-21 mL (p < 0.0001), and IPSS 15-5 (p < 0.0001); IPSS-QOL score: 5-1 (p < 0.0001). SHIM score did not significantly change following repair (median 22-21 p = 0.85). On GRA assessment, a majority of men reported "marked" (64%) or "moderate" (28%) overall improvement. No patient developed fistula, glanular dehiscence, graft necrosis or chordee. CONCLUSIONS: This novel minimally invasive transurethral urethroplasty technique is feasible and has demonstrated generalizable outcomes in a multi-institutional cohort with varying etiologies.

Dorsal Onlay Urethroplasty for Membranous Urethral Strictures: Urinary and Erectile Functional Outcomes.

PURPOSE: We evaluated urinary and erectile functional outcomes after dorsal onlay urethroplasty for bulbomembranous urethral strictures. Our aim was to understand the functional implications of dissection of the posterior urethra. MATERIALS AND METHODS: We report on men who underwent membranous urethral stricture repair by buccal mucosal graft dorsal onlay substitution urethroplasty. Continence and erectile function were assessed preoperatively and postoperatively. Tissue routinely excised from the intercrural space during dissection of the dorsal aspect of the membranous urethra was evaluated for scar, striated muscle and nerves. RESULTS: A total of 16 consecutive men with a mean age of 48.3 years (range 26 to 72) who had strictures with a mean length of 56 mm (range 15 to 170) involving the membranous urethra were included in analysis. Of the 16 men 15 were continent preoperatively and remained continent postoperatively. Three of 10 men (30%) with a preoperative SHIM (Sexual Health Inventory for Men) score of 17 to 25 had a decrease after urethroplasty. All 16 men had an improved maximum urinary flow rate with a mean improvement of 22 ml per second. I-PSS (International Prostate Symptom Score) improved from a median of 23 to 4 postoperatively with a median bother score improvement of 5 to 0. Histopathological assessment identified striated muscle and nerves in 6 (46%) and 9 (69%) of 13 specimens. Overall nerves and muscle comprised an average of less than 15% of the specimen. CONCLUSIONS: The dorsal onlay technique with a buccal mucosal graft for membranous urethral stricture repair does not compromise continence or erectile function in most patients. Dissection at the level of the membranous urethra should be limited because striated muscle and cavernous nerves are present.

Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER Database.

PURPOSE: The renal cell cancer incidence is relatively low in younger patients, encompassing 3% to 7% of all renal cell cancers. While young patients may have renal tumors due to hereditary syndromes, in some of them sporadic renal cancers develop without any family history or known genetic mutations. Our recent observations from clinical practice have led us to hypothesize that there is a difference in histological distribution in younger patients compared to the older cohort. MATERIALS AND METHODS: We queried the SEER (Surveillance, Epidemiology and End Results) 18-registry database for all patients 20 years old or older who were surgically treated for renal cell carcinoma between 2001 and 2008. Patients with unknown race, grade, stage or histology and those with multiple tumors were excluded from study. Four cohorts were created by dividing patients by gender, including 1,202 females and 1,715 males younger than 40 years old, and 18,353 females and 30,891 males 40 years old or older. Chi-square analysis was used to compare histological distributions between the cohorts. RESULTS: While clear cell carcinoma was still the most common renal cell cancer subtype across all genders and ages, chromophobe renal cell cancer was the most predominant type of nonclear renal cell cancer histology in young females, representing 62.3% of all nonclear cell renal cell cancers (p <0.0001). In all other groups papillary renal cell cancer remained the most common type of nonclear renal cell cancer. CONCLUSIONS: It is possible that hormonal factors or specific pathway dysregulations predispose chromophobe renal cell cancer to develop in younger women. We hope that this work provides some new observations that could lead to further studies of gender and histology specific renal tumorigenesis.

Employers, workers, and the future of employment-based health benefits.

EBRI'S BIANNUAL POLICY FORUM: This Issue Brief summarizes presentations at EBRI's 65th biannual policy forum, held in Washington, DC, on Dec. 10, 2009, on the topic, "Employers, Workers, and the Future of Employment-Based Health Benefits." The forum brought together a wide range of economic, benefits, management, and labor experts to share their expertise at a time when major health reform legislation was being debated in Congress. The focus: How might this affect the way that the vast majority of Americans currently get their health insurance coverage? THE EMPLOYMENT-BASED HEALTH INSURANCE SYSTEM: Most people who have health insurance coverage in the United States get it through their job: In 2008, about 61 percent of the nonelderly population had employment-based health benefits, 19 percent were covered by public programs, 6 percent had individual coverage, and 17 percent were uninsured. DIFFERENCES, AGREEMENTS: Not surprisingly, given the deep conflicts that exist over President Obama's health reform plan and the different bills that have passed the House and Senate, benefits experts also do not agree on what "health reform" will mean for either workers or employers. Views ranged from "Will anyone notice?" to predictions of great upheaval for workers and their employers, patients and health care providers, and the entire U.S. health care system. One point of consensus among both labor and management representatives: Imposing a tax on health benefits is likely to cause major cuts in health benefits and might result in structural changes in the employment-based benefits system. A common disappointment voiced at the forum was that the initial effort to reform the delivery and cost of health care in America gradually became focused on just financing and coverage of health insurance. RECENT TRENDS: The ever-rising cost of health insurance affects different employers and workers in different ways--with small employers and low-wage workers being the most disadvantaged. With health premiums having risen almost five times as much as the overall rate of inflation since 2000, employers face unsustainable cost increases in health benefits. For a minimum-wage worker, the cost of family coverage (averaging about $13,700 a year in a small firm) exceeds their total annual income (about $11,500 a year). Small employers, if they offer health benefits at all, pay proportionately more than large employers for the same health coverage. PUBLIC OPINION: As reflected by the debate in Congress, the American public has conflicted opinions on both the U.S. health care system and on reform: Surveys find that people tend to be satisfied with the quality of their own care but not with costs and access, and a majority rates the system as fair or poor. Opinions divide sharply along partisan lines. PERSPECTIVES: While large employers tend to express continued commitment to health benefits, small employers see themselves strongly disadvantaged by the current system. Consultants report many employers privately want to drop benefits to control costs, but realize there are risks to doing so and none wants to be first. Employers express strong interest in wellness and disease management programs as a way to control costs, even though some experts say there is no evidence these work. Consumer-driven health plans are expected to continue their slow rate of growth.

Clinical and Patient-reported Outcomes of 1-sided Anterior Urethroplasty for Long-segment or Panurethral Strictures.

OBJECTIVE: To evaluate clinical and patient-reported urinary and sexual outcomes after a long-segment stricture repair using the 1-sided urethral dissection, penile invagination, and dorsal buccal mucosa graft onlay technique described by Kulkarni et al. METHODS: Patients from 4 institutions after single-stage repairs for long-segment urethral strictures (>8 cm) from January 2002 to April 2016 were reviewed. Technique described by Kulkarni et al was used in all cases. Clinical outcomes included uroflowmetry (Qmax) and post-void residuals. Patient-reported outcome measures included International Prostate Symptom Score survey, Sexual Health Inventory for Men, Male Sexual Health Questionnaire, and Global Response Assessment questionnaire to measure voiding, sexual, ejaculatory symptoms, and overall improvement, respectively. RESULTS: Seventy-three patients with a minimum of 12 months' follow-up were included. The mean age and stricture length were 56 (21-80) years and 13.6 (8-21) cm, respectively. At a mean follow-up of 44 (12-162) months, 9 of 73 (12%) strictures recurred. The mean baseline International Prostate Symptom Score of 23 (7-24) decreased to 10 (1-17) on follow-up (P <.001). Eight of 42 patients (21.4%) reported an increase, and 6 of 42 patients (14.3%) decreased in Sexual Health Inventory for Men following urethroplasty. Ejaculatory function on Male Sexual Health Questionnaire improved after urethroplasty from 8 preoperatively to 11 postoperatively (P <.004). All patients reported improvement after urethroplasty on Global Response Assessment questionnaire. Post-void dribbling and chordee occurred in 45% and 25% of patients, respectively. CONCLUSION: Durable patency in most patients is demonstrated in this study. PROMs indicate an improvement in urinary function and moderate effect on sexual function. Transient penile chordee was evident in 25% of patients.

Hypoandrogenism is Prevalent in Males With Urethral Stricture Disease and is Associated with Longer Strictures.

OBJECTIVE: To assess the association of hypoandrogenism (HA) with urethral stricture disease in a series of patients undergoing urethroplasty at 2 institutions. HA has recently been associated with increased urethral atrophy in artificial sphincter failures and decreased androgen receptors and periurethral vascularity. HA might be an etiologic factor in urethral stricture disease. METHODS: We reviewed the charts in 202 men with anterior urethral strictures between 2011 and 2017. We excluded patients with radiation-induced stricture, previous prostatectomy, previous urethroplasty, pelvic fracture-related strictures, or those on testosterone replacement. We defined HA by a total testosterone of less than 300 ng/dL. We used as age-matched cohort from a national database (National Health and Nutrition Examination Survey), as a reference. Stricture characteristics, such as length, location, and etiology were compared in HA and eugonadal groups. RESULTS: Of 202 men with anterior urethral strictures, we excluded 45. Of the remaining 157 patients, 115 (73%) had preoperative testosterone measurements. Overall, hypoandrogenism (HA) was found in 65 of 115 (57%) men in the urethral stricture group compared with 28% of age-matched men in the national database. Mean stricture length in HA and eugonadal men was 7.2 cm and 4.8 cm, respectively (P = .02). CONCLUSION: HA may be more prevalent and associated with increased disease severity in men with anterior urethral strictures. The relationship between HA and stricture formation and its potential impact on therapeutic outcomes merit further prospective investigation.

Primary non-transecting bulbar urethroplasty long-term success rates are similar to transecting urethroplasty.

OBJECTIVES: To review the long-term outcomes of transecting versus non-transecting urethroplasty to repair bulbar urethral strictures. METHODS: A retrospective review was conducted of 342 patients who underwent anterior urethroplasty performed by a single surgeon from 2003 to 2014. Patients were excluded from further analysis if there had been prior urethroplasty, stricture location outside the bulbous urethra, or age <18 years. In the transecting group, surgical techniques used included excision and primary anastomosis and augmented anastomotic urethroplasty. In the non-transecting group, surgical techniques used included non-transecting anastomotic urethroplasty and dorsal and/or ventral buccal grafting. The primary endpoint was stricture resolution in transecting vs. non-transecting bulbar urethroplasty. Success was defined as freedom from secondary procedures including dilation, urethrotomy, or repeat urethroplasty. RESULTS: One hundred and fifty-two patients met inclusion criteria. At a mean follow-up of 65 months (range: 10-138 months), stricture-free recurrence in the transecting and non-transecting groups was similar, 83% (n = 85/102) and 82% (n = 41/50), respectively (p = 0.84). Surgical technique (p = 0.91), stricture length (p = 0.8), and etiology (p = 0.6) did not affect stricture recurrence rate on multivariate analysis. There was no difference detected in time to stricture recurrence (p = 0.21). CONCLUSIONS: In this retrospective series, transecting and non-transecting primary bulbar urethroplasty resulted in similar long-term stricture resolution rate. Prospective studies are needed to determine what differences may present in outcomes related to sexual function and long-term success.

Surgical Repair of Bulbar Urethral Strictures: Advantages of Ventral, Dorsal, and Lateral Approaches and When to Choose Them.

Objectives. To review the available literature describing the three most common approaches for buccal mucosal graft (BMG) augmentation during reconstruction of bulbar urethral strictures. Due to its excellent histological properties, buccal mucosa graft is now routinely used in urethral reconstruction. The best approach for the placement of such a graft remains controversial. Methods. PubMed search was conducted for available English literature describing outcomes of bulbar urethroplasty augmentation techniques using dorsal, ventral, and lateral approaches. Prospective and retrospective studies as well as meta-analyses and latest systematic reviews were included. Results. Most of the studies reviewed are of retrospective nature and majority described dorsal or ventral approaches. Medium- and long-term outcomes of all three approaches were comparable ranging between 80 and 88%. Conclusion. Various techniques of BMG augmentation urethroplasty have been described for repairs of bulbar urethral strictures. In this review, we describe and compare the three most common "competing" approaches for bulbar urethroplasty with utilization of BMG.

Preoperative cross-sectional imaging allows for avoidance of unnecessary adrenalectomy during RCC surgery.

OBJECTIVES: To assess the frequency of adrenal involvement and the reliability of preoperative imaging to predict adrenal involvement in patients treated for cortical renal masses at a single institution. METHODS: Using a retrospective pathology database, we identified 117 consecutive patients who underwent radical nephrectomy and concomitant ipsilateral adrenalectomy at our institution over the course of 2 decades. Patient demographics, tumor characteristics, and radiographic results were obtained for analysis. RESULTS: Of 117 patients, only 6 (5.1%) were identified as having adrenal involvement. The average age of the patient was 58.3 years, and the average tumor size was 7.13 cm. The mean tumor size in patients without adrenal involvement was 6.79 cm, whereas in those with adrenal involvement, it was 9.62 cm (P = 0.057). Of 6 patients with adrenal involvement, 5 had imaging studies available for review, and all 5 demonstrated suspicion for adrenal involvement preoperatively. Among 111 patients without adrenal involvement, 53 (47.7%) had imaging available for review, with only 3 (5.7%) demonstrating suspicion for adrenal involvement. The negative predictive value was 100%, whereas the sensitivity and specificity were 100% and 94.3%, respectively. CONCLUSIONS: Ipsilateral adrenal involvement in renal cell carcinoma is uncommon and reliably predicted by preoperative cross-sectional imaging. Among all adrenalectomies in this series, nearly 95% were performed unnecessarily. With careful review, preoperative imaging can help avoid unnecessary adrenalectomy during radical nephrectomy in patients with renal cortical tumors.

Open reconstruction of recurrent vesicourethral anastomotic stricture after radical prostatectomy.

OBJECTIVES: To determine the outcomes of open vesicourethral anastomotic reconstruction (VUAR) for outlet stenosis following radical prostatectomy (RP). METHODS: Review of all cases of VUAR within an IRB-approved database was performed. Preoperative factors assessed included cancer treatment modality, duration of symptoms, prior treatments, and length of defect. Outcomes reviewed included length-of-stay (LOS), complications, maintenance of patency, continence, and need for additional procedures. RESULTS: Twelve cases of VUAR performed by a single surgeon (BJF) from 2004 to 2012 were identified. Surgical approaches were either abdominal (7), perineal (3), or abdominoperineal (2). All patients underwent prior RP, with 25 % having subsequent radiotherapy. Among patients with stenosis, 43 % were completely obliterated. Two cases had prior anastomotic disruption in the early postoperative period after RP. The median length of stenosis was 2.5 cm (range 1-5 cm) and median LOS was 3.0 days (range 1-7 days). At a median follow-up of 75.5 months (range 14-120 months), 92 % of men retained patency; only 25 % were continent. CONCLUSION: In experienced hands, VUAR can restore durable patency for men afflicted with outlet stenosis after RP. Despite anatomic restoration, incontinence is likely.

The eIF1A C-terminal domain promotes initiation complex assembly, scanning and AUG selection in vivo.

Translation initiation factor 1A stimulates 40S-binding of the eukaryotic initiation factor 2 (eIF2)/GTP/Met-tRNA(iMet) ternary complex (TC) and promotes scanning in vitro. eIF1A contains an OB-fold present in bacterial IF1 plus N- and C-terminal extensions. Truncating the C-terminus (deltaC) or mutating OB-fold residues (66-70) of eIF1A reduced general translation in vivo but increased GCN4 translation (Gcd- phenotype) in a manner suppressed by overexpressing TC. Consistent with this, both mutations diminished 40S-bound TC, eIF5 and eIF3 in vivo, and deltaC impaired TC recruitment in vitro. The assembly defects of the OB-fold mutation can be attributed to reduced 40S-binding of eIF1A, whereas deltaC impairs eIF1A function on the ribosome. A substitution in the C-terminal helix (98-101) also reduced 43S assembly in vivo. Rather than producing a Gcd- phenotype, however, 98-101 impairs GCN4 derepression in a manner consistent with defective scanning by reinitiating ribosomes. Indeed, 98-101 allows formation of aberrant 48S complexes in vitro and increases utilization of non-AUG codons in vivo. Thus, the OB-fold is crucial for ribosome-binding and the C-terminal domain of eIF1A has eukaryotic-specific functions in TC recruitment and scanning.