Outcomes of Preoperative Medical Therapy for Thyroidectomy in Autoimmune Thyroid Disease.

INTRODUCTION: Thyroidectomy provides definitive treatment for autoimmune thyroid disease (AITD) often resulting in improved quality of life. Historically, patients with AITD undergoing thyroidectomy have increased rates of postoperative hypoparathyroidism and recurrent laryngeal nerve palsy. We investigated the outcomes of preoperative medications in patients with AITD undergoing thyroidectomy. METHODS: We performed a retrospective analysis of patients who underwent thyroidectomy for AITD at a single institution from 2015 to 2021. Surgical outcomes and perioperative laboratory values were analyzed by type of AITD and type of preoperative medical treatment: none, saturated solution of potassium iodide (SSKI), corticosteroids, or both SSKI and corticosteroids. RESULTS: A total of 123 patients underwent thyroidectomy for AITD and were included in analysis: 50 received no preoperative medications, 40 received SSKI, 20 received corticosteroids, and 13 received both. Seventy-six patients had Graves' disease and 47 had Hashimoto's thyroiditis. There were no significant differences in blood loss, operative time, wound complications, hematoma, or recurrent laryngeal nerve injury for patients treated with preoperative corticosteroids compared to those who were not. Patients who received corticosteroids and patients with Graves' disease more commonly had at least one instance of hypocalcemia postoperatively (P < 0.01, P = 0.01), although only on postoperative day 1 was mean calcium < 8.5 mg/dL. There was no difference in rate of transient or permanent hypoparathyroidism. CONCLUSIONS: Patients who received corticosteroids preoperatively had no increased risk of complications. They did have mildly lower calcium levels in the early postoperative period, although no difference in hypoparathyroidism. Further exploration is warranted to investigate the impact of preoperative corticosteroids on operative difficulty, quality of life, and autoantibody clearance.

Patients' perspectives on weight recurrence after bariatric surgery: a single-center survey.

BACKGROUND: Weight recurrence (WR) affects nearly 20% of patients after bariatric surgery and may decrease its benefits, affecting patients' quality of life negatively. Patient perspectives on WR are not well known. OBJECTIVES: Assess patient needs, goals, and preferences regarding WR treatment. SETTING: Single MBSAQIP-accredited academic center, and online recruitment. METHODS: An 18-item, web-based survey was distributed to adults seeking treatment for WR after a primary bariatric surgery (PBS), in addition to online recruitment, between 2021 and 2023. Survey items included somatometric data, questions about the importance of factors for successful weight loss, procedure decision-making, and treatment expectations. RESULTS: Fifty-six patients with > 10% increase from their nadir weight were included in the study. Patients had initially undergone Roux-en-Y gastric bypass (62.5%), sleeve gastrectomy (28.6%), adjustable gastric banding (3.6%), or other procedures (5.3%). When assessing their satisfaction with PBS, 57.1% were somewhat/extremely satisfied, 33.9% somewhat/extremely dissatisfied, while 8.9% were ambivalent. Patients considered the expected benefits (for example, weight loss) as the most important factor when choosing a treatment option for WR. Patient goals included "feeling good about myself" (96.4% very/extremely important), "being able to resume activities I could not do before" (91% very/extremely important), and "improved quality of life" and "-life expectancy" (> 90% very/extremely important). Finally, RBS, lifestyle modification with peer support, and anti-obesity medication were ranked as first treatment options for WR by 40%, 38.8%, and 29.8% of the respondents, respectively. CONCLUSIONS: Patients considered weight loss as the most important factor when choosing treatment modality for WR, with RBS and lifestyle changes being preferred over weight-loss medications. Large prospective randomized trials are needed to counsel this patient population better.

TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria.

BACKGROUND: Excess tumor necrosis factor (TNF) is implicated in the pathogenesis of hyperinflammatory experimental cerebral malaria (eCM), including gliosis, increased levels of fibrin(ogen) in the brain, behavioral changes, and mortality. However, the role of TNF in eCM within the brain parenchyma, particularly directly on neurons, remains underdefined. Here, we investigate electrophysiological consequences of eCM on neuronal excitability and cell signaling mechanisms that contribute to observed phenotypes. METHODS: The split-luciferase complementation assay (LCA) was used to investigate cell signaling mechanisms downstream of tumor necrosis factor receptor 1 (TNFR1) that could contribute to changes in neuronal excitability in eCM. Whole-cell patch-clamp electrophysiology was performed in brain slices from eCM mice to elucidate consequences of infection on CA1 pyramidal neuron excitability and cell signaling mechanisms that contribute to observed phenotypes. Involvement of identified signaling molecules in mediating behavioral changes and sickness behavior observed in eCM were investigated in vivo using genetic silencing. RESULTS: Exploring signaling mechanisms that underlie TNF-induced effects on neuronal excitability, we found that the complex assembly of fibroblast growth factor 14 (FGF14) and the voltage-gated Na+ (Nav) channel 1.6 (Nav1.6) is increased upon tumor necrosis factor receptor 1 (TNFR1) stimulation via Janus Kinase 2 (JAK2). On account of the dependency of hyperinflammatory experimental cerebral malaria (eCM) on TNF, we performed patch-clamp studies in slices from eCM mice and showed that Plasmodium chabaudi infection augments Nav1.6 channel conductance of CA1 pyramidal neurons through the TNFR1-JAK2-FGF14-Nav1.6 signaling network, which leads to hyperexcitability. Hyperexcitability of CA1 pyramidal neurons caused by infection was mitigated via an anti-TNF antibody and genetic silencing of FGF14 in CA1. Furthermore, knockdown of FGF14 in CA1 reduced sickness behavior caused by infection. CONCLUSIONS: FGF14 may represent a therapeutic target for mitigating consequences of TNF-mediated neuroinflammation.

What is the ideal timing of cholecystectomy after percutaneous cholecystostomy for acute cholecystitis?

BACKGROUND: Acute cholecystitis (AC) is one of the most prevalent diseases in clinical practice. Poor surgical candidates may benefit from early percutaneous cholecystostomy (PC) drainage followed by interval cholecystectomy (IC), which is the definitive treatment. The optimal timing between the PC drainage and the IC has not been identified. This study aimed to investigate how the duration between PC and IC affects perioperative outcomes and identify the optimal IC timing to minimize complications. METHODS: This retrospective cohort study included all adult patients diagnosed with AC who underwent PC followed by IC at a single institution center between 2014 and 2022. Patients with a history of hepatobiliary surgery, stones in the common bile duct, cirrhosis, active malignancy, or prolonged immunosuppression were excluded. The analysis did not include cases with major concurrent procedures during cholecystectomy, previously aborted cholecystectomies, or failure of the PC drain to control the inflammation. Linear and logistic regression models were used to analyze the impact of the interval between PC and IC on intra- and perioperative outcomes. RESULTS: One hundred thirty-two patients (62.1% male) with a mean age of 64.4 ± 15 (mean ± SD) years were diagnosed with AC (25% mild, 47.7% moderate, 27.3% severe). All patients underwent PC followed by IC after a median of 64 [48-91] days. Longer ICU stay was associated with longer time intervals between PC and IC (Coef 105.98, p < 0.001). No significant variations were detected in the intraoperative and perioperative outcomes between patients undergoing IC within versus after 8 weeks from PC placement. However, a higher percentage of patients with delayed IC (after 8 weeks) were discharged home (96.4% vs. 83.7%; p = 0.019). CONCLUSIONS: Patients may benefit from undergoing IC after the 8-week cutoff after PC. However, very long periods between PC and IC procedures may increase the risk of longer ICU stay.

Resolution and recurrence of anemia following repair of paraesophageal hernias.

BACKGROUND: Iron deficiency anemia is a common paraesophageal hernia (PEH) symptom and may improve after repair. When present, anemia has also been proposed to be associated with an increase in length of hospital stay, morbidity, and mortality after PEH repair. This study aimed to determine anemia-related factors in patients with PEH, the rate of anemia resolution after PEH repair, and the risk of anemia recurrence when repair failed. METHODS: We included patients who received a PEH repair between June 2019 and June 2020 and had 24 months of postoperative follow-up. Demographics and comorbidities were recorded. Anemia was defined as pre-operative hemoglobin values < 12.0 for females and < 13.0 for males, or if patients were receiving iron supplementation. Anemia resolution was determined at 6 months post-op. Length of hospital stay, morbidity, and mortality was recorded. Logistic regression and ANCOVA were used for binary and continuous outcomes respectively. RESULTS: Of 394 patients who underwent PEH repair during the study period, 101 (25.6%) had anemia before surgery. Patients with pre-operative anemia had larger hernia sizes (6.55 cm ± 2.77 vs. 4.34 cm ± 2.50; p < 0.001). Of 68 patients with available data by 6 months after surgery, anemia resolved in 36 (52.9%). Hernia recurred in 6 patients (16.7%), 4 of whom also had anemia recurrence (66.7%). Preoperative anemia was associated with a higher length of hospital stay (3.31 days ± 0.54 vs 2.33 days ± 0.19 p = 0.046) and an increased risk of post-operative all-cause mortality (OR 2.7 CI 1.08-6.57 p = 0.05). Fundoplication type (p = 0.166), gastropexy, or mesh was not associated with an increased likelihood of resolution (OR 0.855 CI 0.326-2.243; p = 0.05) (OR 0.440 CI 0.150-1.287; p = 0.05). CONCLUSIONS: Anemia occurs in 1 out of 4 patients with PEH and is more frequent in patients with larger hernias. Anemia is associated with a longer hospital stay and all-cause mortality after surgery. Anemia recurrence coincided with hernia recurrence in roughly two-thirds of patients.

Pharmacologically Targeting the Fibroblast Growth Factor 14 Interaction Site on the Voltage-Gated Na+ Channel 1.6 Enables Isoform-Selective Modulation.

Voltage-gated Na+ (Nav) channels are the primary molecular determinant of the action potential. Among the nine isoforms of the Nav channel α subunit that have been described (Nav1.1-Nav1.9), Nav1.1, Nav1.2, and Nav1.6 are the primary isoforms expressed in the central nervous system (CNS). Crucially, these three CNS Nav channel isoforms display differential expression across neuronal cell types and diverge with respect to their subcellular distributions. Considering these differences in terms of their localization, the CNS Nav channel isoforms could represent promising targets for the development of targeted neuromodulators. However, current therapeutics that target Nav channels lack selectivity, which results in deleterious side effects due to modulation of off-target Nav channel isoforms. Among the structural components of the Nav channel α subunit that could be pharmacologically targeted to achieve isoform selectivity, the C-terminal domains (CTD) of Nav channels represent promising candidates on account of displaying appreciable amino acid sequence divergence that enables functionally unique protein-protein interactions (PPIs) with Nav channel auxiliary proteins. In medium spiny neurons (MSNs) of the nucleus accumbens (NAc), a critical brain region of the mesocorticolimbic circuit, the PPI between the CTD of the Nav1.6 channel and its auxiliary protein fibroblast growth factor 14 (FGF14) is central to the generation of electrical outputs, underscoring its potential value as a site for targeted neuromodulation. Focusing on this PPI, we previously developed a peptidomimetic derived from residues of FGF14 that have an interaction site on the CTD of the Nav1.6 channel. In this work, we show that whereas the compound displays dose-dependent effects on the activity of Nav1.6 channels in heterologous cells, the compound does not affect Nav1.1 or Nav1.2 channels at comparable concentrations. In addition, we show that the compound correspondingly modulates the action potential discharge and the transient Na+ of MSNs of the NAc. Overall, these results demonstrate that pharmacologically targeting the FGF14 interaction site on the CTD of the Nav1.6 channel is a strategy to achieve isoform-selective modulation, and, more broadly, that sites on the CTDs of Nav channels interacted with by auxiliary proteins could represent candidates for the development of targeted therapeutics.

Long-term sexual health outcomes in men with classic bladder exstrophy.

OBJECTIVES: To identify the long-term sexual health outcomes and relationships in men born with classic bladder exstrophy (CBE). MATERIALS AND METHODS: A prospectively maintained institutional database comprising 1248 patients with exstrophy-epispadias was used. Men aged ≥18 years with CBE were included in the study. A 42-question survey was designed using a combination of demographic information and previously validated questionnaires. RESULTS: A total of 215 men met the inclusion criteria, of whom 113 (53%) completed the questionnaire. The mean age of the respondents was 32 years. Ninety-six (85%) of the respondents had been sexually active in their lifetime, and 66 of these (58%) were moderately to very satisfied with their sex life. The average Sexual Health Inventory for Men score was 19.8. All aspects of assessment using the Penile Perception Score questionnaire were on average between 'very dissatisfied' and 'satisfied'. Thirty-two respondents (28%) had attempted to conceive with their partner. Twenty-three (20%) were successful in conceiving, while 31 (27%) reported a confirmed fertility problem. A total of 31 respondents (27%) reported undergoing a semen analysis or post-ejaculatory urine analysis. Of these, only four respondents reported azoospermia. CONCLUSION: Patients with CBE have many of the same sexual and relationship successes and concerns as the general population. This is invaluable information to give to both the parents of boys with CBE, and to the boys themselves as they transition to adulthood.

Cost and radiation exposure in the workup of febrile pediatric urinary tract infections.

BACKGROUND: Technetium-99m dimercaptosuccinic acid (DMSA) scans are often used in the evaluation of pediatric patients with febrile urinary tract infections (UTIs). Given the prevalence of febrile UTIs, we sought to quantify the cost, radiation exposure, and clinical utility of DMSA scans when compared with dedicated pediatric renal ultrasounds (RUSs). MATERIALS AND METHODS: An institutional review board approved retrospective study of children under the age of 18 years evaluated at our institution for febrile UTIs between the years 2004-2013 was conducted. The patients had to meet all of the following inclusion criteria: a diagnosis of vesicoureteral reflux, a fever >38°C, a positive urine culture, and evaluation with a DMSA scan and RUS. A chart review was used to construct a cost analysis of technical and professional fees, radiographic results, and radiation dose equivalents. RESULTS: Overall, 104 children met the inclusion criteria. A total of 122 RUS and 135 DMSA scans were performed. The technical costs of a DMSA scan incurred a 35% cost premium as compared to an RUS. The average effective radiation dose of a single DMSA scan was 2.84 mSv. New radiographic findings were only identified on 7% of those patients who underwent greater than 1 DMSA scan. CONCLUSIONS: The utility of the unique information acquired from a DMSA scan as compared to a RUS in the evaluation of febrile UTI must be evaluated on an individual case-by-case basis given the increased direct costs and radiation exposure to the patient.

Non-erosive urethral perforation between tandem artificial urinary sphincter cuffs.

Tandem cuff artificial urinary sphincter (AUS) is a well-accepted treatment modality for refractory urinary incontinence following prostatectomy. We present a unique case of a 60-year-old male who experienced spontaneous urethral perforation between tandem AUS cuffs following a strong valsalva maneuver. The patient was treated with immediate AUS explant and transcorporal single cuff placement several months later.

Fluoroscopy time during uncomplicated unilateral ureteroscopy for urolithiasis decreases with urology resident experience.

PURPOSE: To determine predictors of fluoroscopy time during uncomplicated, unilateral ureteroscopy for urolithiasis performed by urology residents during the first 2 years of residency. METHODS: The patient charts and computed tomography scans of consecutive, unilateral, uncomplicated ureteroscopy cases for urolithiasis were retrospectively reviewed. The cases were performed by beginning urology residents over the course of their first 2 years of urology residency training. RESULTS: A total of 200 ureteroscopy cases were reviewed. The mean stone diameter was 7.1 (±3.2) mm. Forty-three percent of cases were performed for renal stones and 58 % for ureteral stones. The mean operative time was 80.2 (±36.9) min. The mean fluoroscopy time was 69.1 (±38.2) s. No significant differences existed between cases performed by each of the two residents, and no statistical differences in case difficulty were observed throughout the study period. Linear regression analysis revealed the strongest association with lower fluoroscopy time to be increasing resident experience (p < 0.001). By the end of the 2-year review, fluoroscopy time decreased by 79 % from 135 to 29 s per case. Other significant factors associated with increasing fluoroscopy time were placement of a postoperative stent under fluoroscopic guidance (p < 0.001), utilization of a flexible ureteroscope as opposed to a semirigid ureteroscope (p < 0.001), and balloon dilation of the ureteral orifice (p < 0.001). CONCLUSIONS: Fluoroscopy time during uncomplicated, unilateral ureteroscopy for urolithiasis decreases with increasing urology resident operative experience. Other technical options during ureteroscopy were also found to influence fluoroscopy time.

Voltage-Gated Na+ Channels in Alzheimer's Disease: Physiological Roles and Therapeutic Potential.

Alzheimer's disease (AD) is the most common cause of dementia and is classically characterized by two major histopathological abnormalities: extracellular plaques composed of amyloid beta (Aß) and intracellular hyperphosphorylated tau. Due to the progressive nature of the disease, it is of the utmost importance to develop disease-modifying therapeutics that tackle AD pathology in its early stages. Attenuation of hippocampal hyperactivity, one of the earliest neuronal abnormalities observed in AD brains, has emerged as a promising strategy to ameliorate cognitive deficits and abate the spread of neurotoxic species. This aberrant hyperactivity has been attributed in part to the dysfunction of voltage-gated Na+ (Nav) channels, which are central mediators of neuronal excitability. Therefore, targeting Nav channels is a promising strategy for developing disease-modifying therapeutics that can correct aberrant neuronal phenotypes in early-stage AD. This review will explore the role of Nav channels in neuronal function, their connections to AD pathology, and their potential as therapeutic targets.

Cholecystectomy After Percutaneous Cholecystostomy for Acute Cholecystitis: Experience and Outcomes in an Academic Practice.

Percutaneous cholecystostomy (PC) tube insertion has been shown to be an effective treatment of acute cholecystitis (AC) as a temporary step to subsequent laparoscopic cholecystectomy (LC). However, the optimal time gap between PC implantation and LC has not been identified. Adult patients who underwent PC followed by LC for the treatment of AC between 2016 and 2020 were retrospectively reviewed and analyzed. One hundred twelve patients, consisting of 59.8% males, were included and received LC after a median of 65 [48 - 96.5] days following the PC placement. No deaths or reoperations occurred within 30 days, but 16 (14.3%) patients were readmitted, and 16 (14.3%) required subsequent reintervention. Although a longer interval between PC and LC had no effect on perioperative outcomes, it was associated with considerably longer intensive care unit (ICU) stay. According to these findings, patients may benefit from early LC following PC for the treatment of AC.

Patient perspectives on the usefulness of the MBSAQIP Bariatric Surgical Risk/Benefit Calculator: a randomized controlled trial.

BACKGROUND: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Bariatric Surgical Risk/Benefit Calculator uses procedure-specific prediction models to generate individualized surgical risk/outcome estimates. This tool helps guide informed consent and operative selection. We hypothesized that calculator use would influence patient procedure choice. OBJECTIVE: To assess patient perspectives on the bariatric surgical calculator. SETTING: A randomized controlled trial at an MBSAQIP-accredited center. METHODS: During the preoperative bariatric surgical office consultation, patients were randomized into 2 groups: the control group received conventional surgeon-led counseling, whereas surgeons used the risk/benefit calculator to guide decision making for the calculator group. Surveys were completed by patients following consultations to evaluate satisfaction and perceived impact of the risk/benefit calculator on operative selection. RESULTS: Between 2020 and 2022, 61 patients were randomized to the calculator group and 68 patients to the control group. The percentage of patients whose procedure of choice changed following consultation was similar in the calculator versus control group (44.3% versus 41.2%; P = .723). However, calculator group patients were less likely to perceive surgeon counseling as very important for their decision making (43.3% versus 76.5%; P < .001). Eighty-five percent of calculator group patients rated the calculator as useful or very useful, and only 1.7% found it not very important. The reasons patients changed procedure choice were similar between the groups (P = .091); the most common cause was to improve their anticipated outcome (48.7% versus 54.8%). CONCLUSIONS: While the risk/benefit calculator was perceived as a helpful tool by most patients, its use did not influence their procedure choice. However, the patient-reported usefulness and importance of the calculator during surgeon counseling suggest that the information provided has weight in patient decision making.

Pharmacological Inhibition of Wee1 Kinase Selectively Modulates the Voltage-Gated Na+ Channel 1.2 Macromolecular Complex.

Voltage-gated Na+ (Nav) channels are a primary molecular determinant of the action potential (AP). Despite the canonical role of the pore-forming α subunit in conferring this function, protein-protein interactions (PPI) between the Nav channel α subunit and its auxiliary proteins are necessary to reconstitute the full physiological activity of the channel and to fine-tune neuronal excitability. In the brain, the Nav channel isoforms 1.2 (Nav1.2) and 1.6 (Nav1.6) are enriched, and their activities are differentially regulated by the Nav channel auxiliary protein fibroblast growth factor 14 (FGF14). Despite the known regulation of neuronal Nav channel activity by FGF14, less is known about cellular signaling molecules that might modulate these regulatory effects of FGF14. To that end, and building upon our previous investigations suggesting that neuronal Nav channel activity is regulated by a kinase network involving GSK3, AKT, and Wee1, we interrogate in our current investigation how pharmacological inhibition of Wee1 kinase, a serine/threonine and tyrosine kinase that is a crucial component of the G2-M cell cycle checkpoint, affects the Nav1.2 and Nav1.6 channel macromolecular complexes. Our results show that the highly selective inhibitor of Wee1 kinase, called Wee1 inhibitor II, modulates FGF14:Nav1.2 complex assembly, but does not significantly affect FGF14:Nav1.6 complex assembly. These results are functionally recapitulated, as Wee1 inhibitor II entirely alters FGF14-mediated regulation of the Nav1.2 channel, but displays no effects on the Nav1.6 channel. At the molecular level, these effects of Wee1 inhibitor II on FGF14:Nav1.2 complex assembly and FGF14-mediated regulation of Nav1.2-mediated Na+ currents are shown to be dependent upon the presence of Y158 of FGF14, a residue known to be a prominent site for phosphorylation-mediated regulation of the protein. Overall, our data suggest that pharmacological inhibition of Wee1 confers selective modulatory effects on Nav1.2 channel activity, which has important implications for unraveling cellular signaling pathways that fine-tune neuronal excitability.

Predictors of a successful primary bladder closure in cloacal exstrophy: A multivariable analysis.

PURPOSE: To investigate the factors affecting primary bladder closure in cloacal exstrophy (CE). A successful primary closure is important for optimizing reconstructive outcomes, and it is a critical first-step in the reconstruction of CE. The authors' hypothesize that a smaller diastasis and use of an osteotomy are independent predictors of a successful closure. METHODS: A prospectively maintained database of 1332 exstrophy-epispadias complex (EEC) patients was reviewed for CE patients closed between 1975 and 2015. Univariate and multivariable analyses were performed to identify significant factors associated with CE primary bladder closure. RESULTS: Of 143 CE patients identified, 99 patients met inclusion criteria. Median follow-up time was 8.82 [IQR 5.43-14.26] years. In the multivariable model, the odds of having a successful closure are about 4 times greater for the staged cloacal approach compared to the 1-stage approach (OR, 3.7; 95% CI 1.2-11.5; p-value = 0.023). Also, having an osteotomy increases the chance of a successful closure by almost six-fold (OR, 5.8; 95% CI 1.7-19.6; p-value = 0.004). CONCLUSIONS: Using the staged approach with a pelvic osteotomy is paramount to a successful primary closure in CE. The authors strongly recommend using the staged approach and osteotomy as these factors independently increase the chance for a successful primary bladder closure. STUDY TYPE: Therapeutic study. LEVEL OF EVIDENCE: Level III, Retrospective comparative study.

Achieving urinary continence in cloacal exstrophy: The surgical cost.

INTRODUCTION: Cloacal exstrophy (CE) is a severe midline congenital abnormality that requires numerous surgical corrections to achieve an acceptable quality of life. Candidates for urinary continence undergo multiple procedures, most often continent bladder diversions, to become socially dry. Here, the authors investigate the number of genitourinary interventions that patients with CE undergo to attain urinary continence. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database of 1311 exstrophy epispadias complex patients was performed. Patients with CE who have had at least one continence procedure were included. A continence procedure was defined as bladder neck reconstruction with or without augmentation, bladder neck transection with continent urinary diversion, augmentation cystoplasty, or use of injectable bulking agents. Continence was defined as a dry interval greater than 3 hours without leakage at night. RESULTS: In total, 140 CE and CE variant patients have been managed at the authors' institution. Of the 116 CE patients, 59 received at least one continence procedure, 14 were excluded for incontinent diversion or cystectomy, and the remaining 43 patients are awaiting a continence procedure. At the time of analysis, 42 (71%) patients who underwent a continence procedure were dry. The median number of total urologic procedures to reach urinary continence was 4 (range 2-10). This included 1 bladder closure (range 1-3), 2 urinary continence procedures (range 1-4), and 1 (range 0-4) "other" genitourinary procedures. The median time to urinary continence was 11.0 years (95% CI [9.2-14.2]). CONCLUSIONS: A majority of CE patients who undergo a diversion procedure can achieve urinary continence. However multiple continence procedures are likely necessary. Of patients who are candidates for a continence procedure, half will be continent by the age of 11. LEVEL OF EVIDENCE: Level IV, Case series with no comparison group.

Bladder Re-augmentation in Classic Bladder Exstrophy: Risk Factors and Prevention.

OBJECTIVE: To characterize the causes of re-augmentation in patients with classic bladder exstrophy (CBE). METHODS: A prospectively maintained institutional database of 1327 exstrophy-epispadias complex patients was reviewed for patients with CBE who underwent more than 1 augmentation cystoplasty (AC) procedure. Data regarding bladder capacities, complications following AC, and reasons for re-augmentation were evaluated. RESULTS: A total of 166 patients with CBE underwent AC. Of these, 67 (40.4%) were included in the control group and 17 (10%) patients underwent a re-augmentation. There were several indications for re-augmentation including continued small bladder capacity (17 of 17), inadequate bladder necks (8 of 17), failed rattail augmentation (2 of 17), stomal incontinence (1 of 17), a urethrocutaneous fistula (1 of 17), and an hourglass augmentation (1 of 17). Of note, 5 of the 17 patients (29%) had a re-augmentation procedure with a ureteral reimplantation. The sigmoid colon was the most commonly used bowel segment in the failed initial AC (8 patients), whereas the ileum was the most commonly used segment during re-augmentation (12 patients). In the re-augmentation cohort, the mean amount of bowel used during the first AC procedure was 12 cm (standard deviation [SD] 3.6) compared with 19 cm (SD 5.0) during re-augmentation. The mean amount of bowel used for control group augmentations was 20.8 cm (SD 4). The mean re-augmentation preoperative bladder capacity of 100 mL (SD 60) immediately increased after re-augmentation to 180.8 mL (SD 56.4) (P = .0001). CONCLUSION: Bladder re-augmentation is most commonly required in the setting of a small bladder capacity after an initial AC, when an insufficient amount of bowel is used during the first AC procedure.

Combined Bladder Neck Reconstruction and Continent Stoma Creation as a Suitable Alternative for Continence in Bladder Exstrophy: A Preliminary Report.

OBJECTIVE: To explore the use of concomitant bladder neck reconstruction (BNR) and creation of a continent stoma (CS) in patients who are not quite eligible for BNR but still strongly desire volitional voiding. METHODS: The authors retrospectively reviewed an institutional database of patients with exstrophy-epispadias complex who underwent BNR-CS between 2000 and 2015. Indications for a BNR-CS, perioperative outcomes, and continence status were evaluated. Method of voiding and continence status were analyzed for patients with greater than 6 months of follow-up after the BNR-CS. RESULTS: A total of 24 patients with exstrophy-epispadias complex (15 male and 9 female) underwent BNR-CS at a median age of 8.9 years (range 5.4-17.4). This included 18 patients with classic bladder exstrophy, 5 with epispadias, and 1 with a cloacal exstrophy variant. There were 5 surgical complications (20.1%) following the BNR-CS, including 3 febrile urinary tract infections, 1 superficial wound infection, and 1 urethrocutaneous fistula. The median follow-up time from the time of BNR-CS was 1.1 years (range 0.1-14.1). Seventeen of 24 patients (71%) had a follow-up greater than 6 months and were evaluated for continence. Twelve patients (71%) were completely dry for intervals greater than 3 hours following BNR-CS. Five (29%) did not achieve continence with BNR-CS. Of those 5 patients, 3 (60%) underwent subsequent bladder neck transection. CONCLUSION: Combined BNR and CS is a suitable alternative to achieve urinary continence in patients who are not ideal candidates for BNR alone. This approach can offer a select group of patients the opportunity for volitional voiding.

Cystectomy in the Pediatric Exstrophy Population: Indications and Outcomes.

OBJECTIVE: To explore the long-term outcomes and indications for cystectomy in patients with bladder exstrophy. Although rare, cystectomy is the final surgical alternative to bladder repair among these patients with a poor quality bladder template. METHODS: A prospectively maintained database of 1298 patients with exstrophy-epispadias complex was reviewed for patients who underwent cystectomy between 1970 and 2015 at the authors' institution. Demographic data, indication for cystectomy, surgical history, postoperative outcomes, and continence status were collected. RESULTS: Eighteen (6 male; 12 female) patients with exstrophy (15 classic bladder exstrophy; 2 bladder exstrophy variants; 1 cloacal exstrophy) underwent cystectomy at a median age of 3.8 years. Six patients (33.3%) underwent primary cystectomy without attempted bladder closure. Eight patients (44.4%) had a history of failed primary closure with loss of capacity or inadequate growth after closure. Four patients (22.2%) had successful primary closure but underwent cystectomy secondary to poor bladder compliance with declining renal function or poor bladder growth or quality. Urinary diversion included 6 cutaneous ureterostomies, 4 bowel conduits (1 ileal; 3 colon), 6 continent urinary diversions with ileosigmoid reservoir, and 1 ureterosigmoidostomy. Of 8 patients who underwent a continence procedure, all were dry at a median of 25.3 months after cystectomy. CONCLUSION: Cystectomy was most commonly indicated in intrinsically diseased bladder templates that remained too small despite permitting time for interval growth. These bladders often were of poor quality and compliance and did not reduce into the pelvis on examination. It was, however, possible to achieve urinary continence in these patients with cystectomy and urinary diversion.

Pelvic and lower extremity immobilization for cloacal exstrophy bladder and abdominal closure in neonates and older children.

INTRODUCTION: Successful bladder closure in cloacal exstrophy (CE) is best accomplished through a multidisciplinary team and attention to pre- and postoperative technique. This study from a high volume exstrophy center investigates outcomes and complications of primary and reoperative bladder closures in patients immobilized with spica cast or patients with external fixation (EF) and skin traction. METHODS: The authors reviewed an institutionally approved and daily updated database of 1311 patients with exstrophy-epispadias complex and identified patients with cloacal exstrophy born between 1975 and 2015 who had undergone primary or reoperative bladder closures. Only the closures that used spica casting or external fixation were included for analysis. Demographic, operative, and outcomes data were compared between patients with spica cast only and patients with external fixation and skin traction. RESULTS: Out of 140 patients with CE or a CE variant, a total of 71 patients with 94 bladder closures (66 primary and 28 reoperative) met inclusion criteria. Median follow-up time was 8.8 years (range 1.5-29.1). There were 37 closures performed at the authors' institution and 58 from outside hospitals. Pelvic osteotomy was undertaken in 66 (70.2%) of all closures, and in 36 (97.3%) of closures at the authors' institution. Postoperative immobilization was achieved with spica cast alone in 46 (48.9%) closures, external fixation and skin traction in 43 (45.7%), and spica cast and external fixation in 5 (5.3%) closures. For all closures, there were 33 failures (71.7%) among those immobilized with spica cast alone versus 4 failures (9.3%) for those immobilized with external fixation and skin traction (p<0.001). When restricted to closures performed with osteotomy, the failure rates were 50.0% and 9.3% respectively (p=0.002). There was minimal differences in complication rates between spica and external fixation groups (8.7% versus 23.3%, p=0.059). CONCLUSION: Failure of CE closure can occur with any form of pelvic and lower extremity immobilization. This study, however, provides continued evidence that external fixation with skin traction is an optimal, secure technique (3.8% failure rate) for postoperative management in an older child (1-2 years). LEVEL OF EVIDENCE: Level III, Retrospective comparative study STUDY TYPE: Therapeutic study.