Persistent or recurrent ventral curvature after failed proximal hypospadias repair.

PURPOSE: Persistent or recurrent ventral curvature (VC) in patients with complications after proximal hypospadias repair is reported. METHODS: Records of patients undergoing re-operation for complications after proximal repair performed elsewhere were reviewed, including earlier operative reports when available. Original extent of VC, means used for straightening, and presenting complaints and findings at re-operation were tabulated. Ventral curvature at re-operation was objectively measured by goniometry and classified as due to short ventral skin and/or scarring of skin/dartos, short neourethra, or short ventral corpora (corporal disproportion). The finding of corporal disproportion at re-operation was considered to be failure of initial straightening. RESULTS: There were 73 patients with an average of 2.7 [1-5] prior operations for proximal shaft to perineal hypospadias; of which, 83% had VC at re-operation averaging 50° (30-90). This was due to short skin/scarring in 7% patients, a short neourethra in 23%, and corporal disproportion in 70%. Initial straightening was performed by chordee excision in 18 patients, dorsal plication in 23, and ventral lengthening in 15. Persistent or recurrent corporal disproportion was significantly more likely after chordee excision or dorsal plication than after ventral lengthening (p = 0.005). Of patients with VC, 93% also had urethroplasty complications, including recurrent fistulas and wound dehiscences that appeared related to the curvature. DISCUSSION: The VC that was encountered during proximal hypospadias re-operations was important for several reasons. First, all patients with VC who had completed urethroplasty had complications that included recurrent fistulas and wound dehiscences (Figure). Even if they had healed without complications, this VC exceeded 30° in all cases, which is associated with sexual dysfunction in adults. This VC was not reported by 37% of caregivers and sometimes not apparent on pre-operative physical examination. It is possible there is selection bias in this series, although nearly all patients were self-referred for complications, and nearly 40% of them were not aware their son had VC. Furthermore, the finding that most initially had dorsal plication agrees with an earlier survey of pediatric urologists' preferences for straightening penile curvature. CONCLUSIONS: The most common complication in this series was persistent or recurrent VC, and nearly all these patients also had urethroplasty complications. This VC was more likely when the urethral plate was preserved during straightening and when chordee excision or dorsal plication rather than ventral lengthening was performed. These data suggest that surgeons should objectively measure VC and consider ventral lengthening rather than chordee excision or dorsal plication when it is ≥ 30°. Re-operations for urethroplasty complications should include artificial erection.

Pre-incision urethral plate width does not impact short-term Tubularized Incised Plate urethroplasty outcomes.

INTRODUCTION: Two reports have found that urethral plate (UP) widths <8 mm before tubularized incised plate (TIP) incision increased urethroplasty complications. The present study measured pre-incision UP width in consecutive boys undergoing TIP to determine if it affected outcomes. METHODS: The present study followed the method previously used by Holland and Smith, and Sarhan et al. to measure UP width before creating glans wings or performing midline plate incision in consecutive patients with primary hypospadias and ventral curvature <30°, who all underwent TIP repair (Summary Fig.). Glans width at its widest point was also measured. Multiple logistic regression assessed urethroplasty complications (fistula, glans dehiscence, meatal stenosis/urethral stricture, diverticulum) based on pre-incision UP width, glans width, patient age, and meatal location. RESULTS: The UP widths were determined in 224 consecutive primary TIP repairs during 2012-2015: 200 distal, 11 midshaft, and 13 proximal. The UP width was <8 mm in 192/224 (86%) patients. Mean pre-incision width was 6.1 mm (SD 1.5, range 2-11), without difference in UP widths according to meatal location (P = 0.06). Mean post-incision UP width was 12 mm (SD 2.2, range 10-16). Mean change in width after incision (delta/original UP width) was 116% (SD 63, range 20-250). There was follow-up in 186 patients for a mean of 6 months. Urethroplasty complications (five fistulas, six glans dehiscence) were diagnosed in 11 (6%): 9/165 distal, 1/9 midshaft, and 1/12 proximal repairs. There was no difference in those <8 vs ≥8 mm (11/160 vs 0/26, P = 0.17). Similarly, UP width was not different between patients with and without urethroplasty complications. Multiple logistic regression in these 186 patients - including meatal location, UP width, glans width, and age - found only glans width <14 mm was associated with increased odds of urethroplasty complications (OR 19.2, 95% CI 3.5-106, AUC = 0.799). DISCUSSION: The data show that pre-incision UP width is not an independent risk factor for urethroplasty complications. However, it is possible that technical factors, such as how deeply the dorsal incision is made or size of the urethral stent, might contribute to this finding by other authors. After watching the TIP repair, Smith stated that the plate incision was deeper than he made. Sarhan et al. reported a mean change of 57% in UP width after incision, whereas the present one was double at 116% (i.e. from 6 mm pre-incision to 12 mm post incision), and they used an 8-Fr catheter. While they stated that they incised the plate deeply, the lower percentage increase in width suggests that it was not as deep as was recommended. CONCLUSIONS: The UP width before incision did not increase urethroplasty complications. Surgeons do not need to measure or categorize the UP to determine suitability for TIP repair, as long as the plate incision is made deeply to the corpora.

Re-operative urethroplasty after failed hypospadias repair: how prior surgery impacts risk for additional complications.

PURPOSE: The primary aim of this report was to compare urethroplasty complications for primary distal and proximal repairs with those after 1, 2, 3, and 4 or more re-operations. METHODS: Prospectively collected data on consecutive hypospadias repairs (tubularized incised plate (TIP), inlay, two-stage graft) from 2000 to 2015 were reviewed. Isolated fistula closures were excluded. Extracted information included patient age, meatal location, repair type, primary vs. re-operative surgery, number of prior operations, any testosterone use, glans width, and urethroplasty complications. Pre-operative testosterone stimulation was used during the study period until 2012. Initially, it was given for a subjectively small-appearing glans, but from 2008 to 2012 use was determined by glans width <14 mm. Patients initially managed elsewhere were queried for any testosterone treatment. The number of prior operations was determined by patient history and confirmed by review of records. Calibrations, dilations, cystoscopies, and/or isolated skin revisions were not considered as prior urethroplasty operations. Multiple logistic regression was performed for all patients, and for the subset of patients undergoing re-operation, using stepwise regression for the following potential risk factors: meatal location (distal vs. midshaft/proximal), number of prior surgeries (0, 1, 2, 3, ≥4), pre-operative testosterone use (yes/no), small glans (<14 vs. ≥14), surgery type (TIP, inlay and two-stage graft), and age (continuous in months), with P-values <0.05 considered statistically significant. RESULTS: In contrast to the 135/1085 (12%) complication rate in patients undergoing primary distal and proximal TIP repair, re-operative urethroplasty complications occurred in 61/191 (32%) TIP, 16/46 (35%) inlay, and 49/124 (40%) two-stage repairs, P<0.0001. Data regarding testosterone use was available for 1490 (96%) patients. A total of 139 received therapy, of which 65 (46%) had urethroplasty complications vs. 229 of 1351 (16%) without treatment, P = 0.0001. Logistic regression in 1536 patients demonstrated that each prior surgery increased the odds of subsequent urethroplasty complications 1.5-fold (OR 1.51, 95% CI 1.25-1.83), along with small glans <14 mm (OR 2.40, 95% CI 1.48-3.87), mid/proximal meatal location (OR 2.54, 95% CI 1.65-3.92), and use of pre-operative testosterone (OR 2.57, 95% CI 1.53-4.31); age and surgery type did not increase odds (AUC = 0.739). DISCUSSION: Urethroplasty complications doubled in people undergoing a second hypospadias urethroplasty compared with those undergoing primary repair. This risk increased to 40% with three or more re-operations. Logistic regression demonstrates that each surgery increases the odds for additional complications 1.5-fold. Mid/proximal meatal location, small glans <14 mm, and use of pre-operative testosterone also significantly increase odds for complications. These observations support the theory that previously operated tissues have less robust vascularity than assumed in a primary repair, and suggest additional adjunctive therapies are needed to improve wound healing in re-operations. The finding that even a single re-operative urethroplasty has twice the risk for additional complications vs. a primary repair emphasizes the need for hypospadias surgeons to 'get it right the first time'. The fact that 40% of the re-operative urethroplasties in this series followed distal repairs emphasizes that there is no 'minor' hypospadias. CONCLUSIONS: A single re-operative hypospadias urethroplasty has twice the risk for additional complications vs. the primary repair, which increases to 40% with three or more re-operations. These results support a theory that vascularity of penile tissues decreases with successive operations, and suggest the need for treatments to improve vascularity. The higher risk for complications during re-operative urethroplasties also emphasizes the need to get the initial repair correct.

Results of distal hypospadias repair after pediatric urology fellowship training: A comparison of junior surgeons with their mentor.

BACKGROUND: Teaching and learning hypospadias repair is a major component of pediatric urology fellowship training. Educators must transfer skills to fellows, without increasing patient complications. Nevertheless, few studies report results of surgeons during their first years of independent practice. PURPOSE: To review outcomes of distal hypospadias repairs performed during the same 2-year period by consecutive, recently matriculated, surgeons in independent practice, and to compare them to results by their mentor (with >20 years of experience). MATERIALS: Exposure to hypospadias surgery during fellowship was determined from case logs of five consecutive fellows completing training from 2007-2011. TIP was the only technique used to repair distal hypospadias. No fellow operated independently or performed complete repairs under supervision. Instead, the first 3 months were spent assisting their mentor, observing surgical methodology and decision-making. Then, each performed selected portions under direct supervision, including: degloving, penile straightening, developing glans wings, incising and tubularizing the urethral plate, creating a barrier layer, sewing the glansplasty, and skin closure. Overall fellow participation in each case was <50%. In 2011-2012, urethroplasty complications (fistula, glans dehiscence, meatal stenosis, urethral stricture, diverticulum) were recorded for consecutive patients undergoing primary distal repair by these recent graduates in their independent practices. The fellow graduating in 2011 provided 1 year of data. All patients undergoing repair during the study period were included in the analysis, except those lost to follow-up after catheter removal. Composite urethroplasty complications were compared between junior surgeons, and between junior surgeons and their mentor, with Fisher's exact contingency test. RESULTS: Training logs indicated fellow participation ranged from 76-134 hypospadias repairs, including distal, proximal and reoperative surgeries. Post-graduation case volumes ranged from 25-68 by junior surgeons versus 136 by the mentor. With similar mean follow-up, urethroplasty complication rates were statistically the same between the former fellows, and between them versus the mentor, ranging from 5-13%. Nearly all were fistulas or glans dehiscence. Junior surgeons reported they performed TIP as learned during fellowship, with one exception who used 7-0 polydioxanone rather than polyglactin for urethroplasty. DISCUSSION: This is the first study directly comparing hypospadias surgical outcomes by recently graduated fellows in independent practice with those of their mentor. We found junior surgeons achieved similar results for distal TIP hypospadias repair. Although their participation during training largely comprised observation and surgical assistance, with discrete performance of key steps, skills sufficient to duplicate the mentor's results were transferred. These data suggest there should be no learning curve for distal hypospadias after training. This report raises several considerations for surgical educators. First, mentors should review their own results, to be certain that they are correctly performing and teaching procedures. Second, programs need to determine key steps for procedures they teach, and then emphasize their optimal performance. Finally, mentors should expect former fellows to report back their initial results of hypospadias repair to be certain lessons taught were learned. Otherwise, preventable complications resulting from technical errors will be multiplied in the children operated by their trainees as they enter independent practice.

Non-absorbable sutures are associated with lower recurrence rates in laparoscopic percutaneous inguinal hernia ligation.

INTRODUCTION: Laparoscopic hernia repair with percutaneous ligation of the patent processes vaginalis is a minimally invasive alternative to open inguinal herniorrhaphy in children. With the camera port concealed at the umbilicus, this technique offers an excellent cosmetic result. It is also faster than the traditional laparoscopic repair with no differences in complication rates or hospital stay. The goal of this study was to describe a series of consecutive patients, emphasizing the impact of suture materials (absorbable vs. non-absorbable) on hernia recurrences. METHODS: A retrospective review was performed of consecutive transperitoneal laparoscopic subcutaneous ligations of a symptomatic hernia and/or communicating hydrocele by 4 surgeons. Patients > Tanner 2 or with prior hernia repair were excluded. The success of the procedure and number of sutures used was compared between cases performed with absorbable vs. non-absorbable suture. Risk factors for surgical failure (age, weight, number of sutures used, suture type) were assessed with logistic regression. RESULTS: 94 patients underwent laparoscopic percutaneous hernia ligation at a mean age of 4.9 years. Outcomes in 85 (90%) patients with 97 hernia repairs at a mean of 8 months after surgery revealed 26% polyglactin vs 4% polyester recurrences (p = 0.004) which occurred at mean of 3.6 months after surgery, Table 1. Repairs performed with non-absorbable suture required only 1 suture more often than those performed with absorbable suture (76% vs 60%, p = 0.163). Logistic regression revealed suture type was an independent predictor for failure (p = 0.017). Weight (p = 0.249), age (p = 0.055), and number of sutures (p = 0.469) were not significantly associated with recurrent hernia. DISCUSSION: Our review of consecutive hernia repairs using the single port percutaneous ligation revealed a significantly higher recurrent hernia rate with absorbable (26%) versus non-absorbable (4%) suture. This finding remained significant in a logistic regression model irregardless of number of sutures placed, age, and weight. Though the authors acknowledge the drawback of the potential for learning curve to confound our data, we still feel these findings are clinically important as this analysis of outcomes has changed our surgical practice as now all providers involved perform this procedure with exclusively non-absorbable suture. We thus suggest that surgeons who perform this technique, especially those newly adopting it, use non-absorbable suture for optimal patient outcomes. CONCLUSIONS: Recurrent hernia after laparoscopic percutaneous hernia ligation was significantly lower in repairs performed with non-absorbable suture. Based on this data, we recommend the use of non-absorbable suture during laparoscopic ligation of inguinal hernias in children.

Renal damage detected by DMSA, despite normal renal ultrasound, in children with febrile UTI.

OBJECTIVES: 2011 American Academy of Pediatrics guidelines recommended renal-bladder ultrasound (RBUS) as the only evaluation after febrile urinary tract infection (FUTI) in infants aged 2-24 months. We determined the sensitivity, specificity, and false negative rate of RBUS to identify DMSA-detected renal damage in this age group as well as in older children. METHODS: Consecutive patients referred to pediatric urology with a history of FUTI underwent DMSA ≥ 3 months after FUTI. Abnormal RBUS was defined as: Society of Fetal Urology hydronephrosis grades I-IV; hydroureter ≥ 7 mm; renal scar defined as focal parenchymal thinning; and/or size discrepancy ≥ 1 cm between kidneys. Abnormal DMSA was presence of any focal uptake defects and/or split renal function < 44%. We calculated sensitivity, specificity, positive and negative predictive values, and false negative rates of RBUS compared to DMSA. RESULTS: 618 patients (79% female), median age 3.4 years, were referred for FUTIs. Of the 512 (83%) with normal RBUS, 99 (19%) had abnormal DMSA. Children with normal RBUS after their first FUTI had abnormal DMSA in 15/151 (10%) aged ≤ 24 months and 23/119 (19%) aged > 24 months. RBUS had poor sensitivity (34%) and low positive predictive value (47%) to identify patients with renal damage. 99/149 (66%) children with renal damage on DMSA had normal RBUS. CONCLUSION: After FUTI, 66% of children with reduced renal function and/or renal cortical defects found by DMSA scintigraphy had a normal RBUS. Since abnormal DMSA may correlate with increased risk for VUR, recurrent FUTI and renal damage, our data suggest RBUS alone will fail to detect a significant proportion of patients at risk. The data suggest that imaging after FUTI should include acute RBUS and delayed DMSA, reserving VCUG for patients with abnormal DMSA and/or recurrent FUTI.

Adipose tissue fatty acid storage factors: effects of depot, sex and fat cell size.

BACKGROUND/OBJECTIVES: Patterns of postabsorptive adipose tissue fatty acid storage correlate with sex-specific body fat distribution. Some proteins and enzymes participating in this pathway include CD36 (facilitated transport), acyl-CoA synthetase (ACS; the first step in fat metabolism) and diacylglycerol acetyltransferase (DGAT; the final step of triglyceride synthesis). Our aim was to better define CD36, ACS and DGAT in relation to sex, subcutaneous fat depots and adipocyte size. SUBJECTS/METHODS: Data were collected from studies conducted at Mayo Clinic between 2004 and 2012. Abdominal and femoral subcutaneous fat biopsy samples must have been collected in the postabsorptive state from healthy males and premenopausal females. Body composition was measured with dual-energy X-ray absorptiometry and abdominal computerized tomography scans. Adipocyte size (microscopy), CD36 protein content (enzyme-linked immunosorbent assay) and ACS and DGAT enzyme activities were measured. Data are presented as medians and 25th, 75th quartiles. RESULTS: Males (n=60) and females (n=78) did not differ by age (37; 28, 46 years), body mass index (28.4; 24.6, 32.1 kg m(-)(2)) or abdominal (0.60; 0.45, 0.83 µg lipid per cell) and femoral adipocyte size (0.76; 0.60, 0.94 µg lipid per cell). Femoral ACS and DGAT were greater in females than males when expressed per mg lipid (ACS: 73 vs. 55 pmol/mg lipid/min; DGAT: 5.5 vs. 4.0 pmol/mg lipid/min; P<0.0001 for both) and per 1000 adipocytes (ACS: 59 vs. 39 pmol per min per 1000 adipocytes; DGAT: 4.3 vs 3.1 pmol per min per 1000 adipocytes; P⩽0.0003 for both). There were no differences in abdominal fat storage factors between sexes. ACS and DGAT decreased as a function of adipocyte size (P<0.0001 for both). The decrease in ACS was greater in males and abdominal subcutaneous fat. There were no sex differences in CD36 in either fat depot, nor did it vary across adipocyte size. CONCLUSIONS: Facilitated transport of fatty acids by CD36 under postabsorptive conditions would not be different in those with large vs small adipocytes in either depot of both sexes. However, intracellular trafficking of fatty acids to triglyceride storage by ACS and DGAT may be less efficient in larger adipocytes.

Gut hormone activity of children born to women with and without gestational diabetes.

UNLABELLED: What is already known about this subject Children born to women with gestational diabetes have greater risk for obesity. Obesity in adults and children is associated with blunted postprandial gut hormone responses. What this study adds Children of women with gestational diabetes have a blunted postprandial response of GLP-1. Children of women with gestational diabetes have high fasting PYY concentrations. BACKGROUND: Intrauterine exposure to gestational diabetes mellitus (GDM) increases risk for obesity. Obesity is associated with a blunted postprandial gut hormone response, which may impair satiety and thereby contribute to weight gain. The postprandial response of gut hormones among children of women with GDM has not previously been investigated. OBJECTIVE: To examine whether children of women with GDM have suppressed peptide-tyrosine-tyrosine (PYY) and glucagon-like-peptide-1 (GLP-1), and higher concentrations of ghrelin, following a meal challenge. A secondary objective was to investigate associations of these hormones with children's free-living energy intake. METHODS: Children (n = 42) aged 5-10 years were stratified into two groups: offspring of GDM mothers (OGD) and of non-diabetic mothers (CTRL). Body composition was measured by dual-energy X-ray absorptiometry, and circulating PYY, GLP-1 and total ghrelin were measured during a liquid meal challenge. Energy intake was assessed by three 24-h diet recalls. RESULTS: Between-groups analyses of fasting and incremental area under the curve (AUC) found no differences in ghrelin. Incremental AUC for GLP-1 was greater among the CTRL vs. OGD (P < 0.05), and fasting PYY, but not incremental AUC, was higher among OGD vs. CTRL (P < 0.01). Associations of fasting and incremental AUC for each gut hormone with children's usual energy intake did not differ significantly by group. CONCLUSIONS: Further research is needed to more fully examine the potential role of postprandial GLP-1 suppression and high-fasting PYY concentrations on the feeding behaviour and risk for obesity among children exposed to GDM in utero.

Overweight status and intrauterine exposure to gestational diabetes are associated with children's metabolic health.

BACKGROUND: Offspring of women with gestational diabetes (OGD) have greater risk for obesity and impaired metabolic health. Whether impaired metabolic health occurs in the absence of obesity is not clear. OBJECTIVE: The purpose of this study was to investigate the independent and interactive effects of intrauterine exposure to gestational diabetes and of children's current weight status on their metabolic health. METHODS: Children aged 5­10 years (n = 51) with and without intrauterine exposure to gestational diabetes (OGD vs. offspring of non-diabetic women [CTRL]) were grouped into normal weight (body mass index [BMI] < 85th %) and overweight (BMI > 85th %) according to Centers for Disease Control growth curves. Lipid profile was obtained by fasting blood draw, insulin sensitivity (SI) and secretion by liquid meal tolerance test, and body composition by dual-energy X-ray absorptiometry. RESULTS: Despite similar average BMI percentiles among normal weight OGD versus CTRL, and overweight OGD vs. CTRL, OGD had greater total %fat and trunk fat adjusted for leg fat compared with CTRL (P < 0.05). Overweight children had lower SI (P < 0.05) and greater basal, static, and total insulin secretion independent of SI (P < 0.05). OGD was independently associated with greater static insulin secretion (P < 0.05) and the interaction between OGD and overweight was associated with greater basal insulin secretion independent of SI (P < 0.01). OGD and overweight were each associated with lower high-density lipoprotein-cholesterol (HDL-C) (P < 0.05). CONCLUSION: Intrauterine exposure to gestational diabetes was associated with greater central adiposity and insulin secretion, and lower HDL-C, irrespective of current weight status. Future research should examine respective contributions of the intrauterine environment and of underlying genotype on children's metabolic health.

Properties of yeast cells depleted of the OSCP subunit of mitochondrial ATP synthase by regulated expression of the ATP5 gene.

OSCP is a subunit of the FA stalk sector of yeast mitochondrial ATP synthase complex. Cells of a null mutant for OSCP, constructed by disruption of the chromosomal ATP5 gene of Saccharomyces cerevisiae, exhibited a high level of genetic instability (petite formation). Study of the effects of ablation of OSCP required the development of a progressive depletion strategy. Introduction of a vector bearing an ATP5 gene cassette under GAL1 transcriptional control into null mutant cells gave rise to a stable yeast strain from which OSCP could be depleted in a controlled manner by manipulation of the level of galactose in the growth medium. Cells progressively depleted of OSCP exhibited properties of cellular respiration indicative of a decline in the functional coupling of the catalytic F1 sector to the proton channel F0 sector (normally linked by FA). Cells depleted of OSCP also exhibited a physical uncoupling of F1 from other subunits of the complex such that other FA subunits and F0 subunit 6 were not recovered in immunoprecipitates of ATP synthase complexes. Thus, OSCP plays a role in the assembly as well as function of the enzyme complex.