Micah A. Jacobs

Identification and Prognostic Significance of an Epithelial-Mesenchymal Transition Expression Profile in Human Bladder Tumors

Purpose: Epithelial to mesenchymal transition (EMT) is reportedly an important transition in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. In this study, we examined the expression pattern of EMT markers in vivo and determined the occurrence and clinical significance of these events in a series of bladder carcinomas. Experimental Design: Eight hundred and twenty-five tumor samples from 572 bladder cancer patients were assembled in 10 tissue microarrays. Paraffin sections from each tissue microarray were subjected to antigen retrieval and processed by immunohistochemistry for the expression of E-cadherin, plakoglobin, β-catenin, N-cadherin, and vimentin. Results: Pathologic expression of E-cadherin, β-catenin, plakoglobin, and vimentin were associated with the clinicopathologic variables of grade and stage with only the cytoplasmic localization of plakoglobin found associated with lymph node status. Associations between the aforementioned markers were found significant as determined by the Spearman correlation coefficient with N-cadherin showing no associations in this analysis. In univariate survival analysis involving patients who underwent cystectomy, the reduction or loss of plakoglobin significantly influenced overall survival (P = 0.02) in which the median time to death was 2 years compared with 4 years when a normal level of plakoglobin was recorded. When the analysis was done for cancer-specific survival, low levels of both plakoglobin (P = 0.02) and β-catenin (P = 0.02) significantly influenced survival. Conclusion: The putative markers of EMT defined within a panel of bladder carcinoma cell lines were recorded in vivo, frequently associated with tumors of high grade and stage. Although multivariate analysis showed no significant influence of the EMT biomarkers on survival, alterations associated with plakoglobin were identified as significant prognostic features in these tumors.

Long-Term Outcomes of Bladder Neck Reconstruction without Augmentation Cystoplasty in Children

PURPOSE Bladder outlet procedures without augmentation cystoplasty remain controversial. We hypothesized that bladder outlet procedures without augmentation cystoplasty may lead to unfavorable bladder dynamics, upper tract changes and/or continued incontinence. We reviewed long-term urodynamic, upper tract and continence outcomes following bladder outlet procedures without augmentation cystoplasty. MATERIALS AND METHODS We retrospectively reviewed all patients who underwent bladder neck reconstruction/closure/sling without augmentation cystoplasty between 2000 and 2014. Because of variation in length of followup, we calculated the cumulative incidence and proportion of cases of upper tract and urodynamic changes, augmentation cystoplasty and subsequent continence procedures. Preoperative factors were compared between patients with and without adverse outcomes. RESULTS A total of 109 patients underwent bladder outlet procedures without augmentation cystoplasty at a mean age of 8.5 years. At a mean of 4.9 years of followup 59 patients (54%) had undergone additional continence surgery, 20 (18%) had undergone augmentation cystoplasty, 50 (46%) manifested vesicoureteral reflux or hydronephrosis and 23 (21%) had newly diagnosed or worsening renal scarring. At augmentation cystoplasty 13 of 18 patients (72%) had upper tract changes, 15 (83%) had continued incontinence and 11 (61%) had an end fill pressure of greater than 40 cm H2O. All patients had resolution of these changes after augmentation cystoplasty. Patients who had previously undergone vesicostomy or surgery for vesicoureteral reflux were significantly more likely to undergo a subsequent augmentation cystoplasty or to show upper tract changes. CONCLUSIONS Following bladder outlet procedures without augmentation cystoplasty the estimated 10-year cumulative incidence of augmentation cystoplasty is 30%, continence procedures 70%, upper tract changes greater than 50% and chronic kidney disease 20%. Because of these risks, careful patient selection and close followup are essential if considering a bladder outlet procedure without augmentation cystoplasty.

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.

Conservative management vs early surgery for high grade pediatric renal trauma - Do nephrectomy rates differ?

PURPOSE Guidelines for management of pediatric high grade renal injuries are currently based on limited pediatric data and algorithms from adults, for whom initial nonoperative management is associated with decreased nephrectomy risk. Using a national database, we compared nephrectomy rates between children with high grade renal injury managed conservatively and those undergoing early surgical intervention. MATERIALS AND METHODS All children with high grade renal injuries were identified in the National Trauma Data Bank®. High grade renal injuries were defined as American Association for the Surgery of Trauma grade IV or V renal injuries. After excluding fatalities within 24 hours of hospitalization, 419 pediatric patients comprised our study cohort. A total of 81 patients underwent early (within 24 hours of hospitalization) surgical intervention, while 338 were initially treated conservatively. Using stratified analysis with adjustment for relevant covariates, we compared nephrectomy rates between these groups. RESULTS Nephrectomy was performed less often in patients treated conservatively (RR 0.24, 95% CI 0.16 to 0.36, adjusted for age, renal injury grade and injury mechanism). The decreased risk of nephrectomy was more marked among children with grade IV vs grade V renal injuries (adjusted RR 0.16, 95% CI 0.08 to 0.23). Multiple procedures were more common in patients initially observed. Of pediatric patients with grade IV and V renal injuries 11% still underwent nephrectomy. CONCLUSIONS Conservative management of high grade renal injuries is common in children. Although mechanism of injury and renal injury grade impact initial clinical management decisions, the risk of nephrectomy was consistently decreased in children with high grade renal trauma managed conservatively regardless of injury characteristics.

Diagnosing Testicular Torsion before Urological Consultation and Imaging: Validation of the TWIST Score

PURPOSE The TWIST (Testicular Workup for Ischemia and Suspected Torsion) score uses urological history and physical examination to assess risk of testis torsion. Parameters include testis swelling (2 points), hard testis (2), absent cremasteric reflex (1), nausea/vomiting (1) and high riding testis (1). While TWIST has been validated when scored by urologists, its diagnostic accuracy among nonurological providers is unknown. We assessed the usefulness of the TWIST score when determined by nonurological nonphysician providers, mirroring emergency room evaluation of acute scrotal pain. MATERIALS AND METHODS Children with unilateral acute scrotum were prospectively enrolled in a National Institutes of Health clinical trial. After undergoing basic history and physical examination training, emergency medical technicians calculated TWIST score and determined Tanner stage per pictorial diagram. Clinical torsion was confirmed by surgical exploration. All data were captured into REDCap™ and ROC curves were used to evaluate the diagnostic usefulness of TWIST. RESULTS Of 128 patients (mean age 11.3 years) 44 (13.0 years) had torsion. TWIST score cutoff values of 0 and 6 derived from ROC analysis identified 31 high, 57 intermediate and 40 low risk cases (positive predictive value 93.5%, negative predictive value 100%). CONCLUSIONS TWIST score assessed by nonurologists, such as emergency medical technicians, is accurate. Low risk patients do not require ultrasound to rule out torsion. High risk patients can proceed directly to surgery, with more than 50% avoiding ultrasound. In the future emergency medical technicians and/or emergency room triage personnel may be able to calculate TWIST score to guide radiological evaluation and immediate surgical intervention at initial assessment long before urological consultation.

Prognostic significance of altered p120ctn expression in bladder cancer

To identify the frequency of change in the expression and localization of p120ctn in bladder tumours and its association with clinical outcomes, and to investigate the potential role of p120ctn in the migratory and invasive behaviour of bladder carcinoma cells.

Comparison of Complications of Robot-Assisted Laparoscopic and Open Appendicovesicostomy in Children

PURPOSE Robot-assisted laparoscopic appendicovesicostomy in children has become increasingly popular. However, the literature on this technique mainly consists of small case series with only 1 small comparison to an open cohort. We compared the number of complications and surgical revisions required with open and robotic surgery in children undergoing appendicovesicostomy at our institution. MATERIALS AND METHODS We retrospectively reviewed the charts of all patients who underwent appendicovesicostomy by 3 surgeons between July 2002 and September 2013. Acute complications and surgical revisions were recorded and compared between groups with t-tests for continuous variables and Fisher exact test for categorical variables. RESULTS A total of 28 open and 39 robotic appendicovesicostomies were included. At a mean followup of 2.7 years there was no difference in number of complications or reoperations (p = 0.788 and p = 0.791, respectively) between groups. Time to first reoperation was shorter in the robotic group. However, there was no significant difference between groups regarding number of patients who underwent reoperation within the first 12 months postoperatively (p = 0.346). CONCLUSIONS Comparison of robotic and open appendicovesicostomy revealed no significant difference in the number of acute complications or reoperations between groups. However, the nature and timing of complications differed between groups.

Demographics of pediatric renal trauma

PURPOSE There is a lack of national data describing the demographics and nature of pediatric renal trauma. We used the National Trauma Data Bank to analyze mechanisms and grades of injury, demographics and treatment characteristics of pediatric renal trauma cases. MATERIALS AND METHODS Renal injuries were identified by Abbreviated Injury Scale codes and converted to American Association for the Surgery of Trauma renal injury grades. Patients were stratified by age (0 to 1, 2 to 4, 5 to 14 and 15 to 18 years) for more specific analyses of mechanisms and grades of injury. Data reviewed included mechanisms and grades of renal injury, demographics, and setting and type of treatment. RESULTS A total of 2,213 pediatric renal injuries were converted to American Association for the Surgery of Trauma grade. Mean ± SD age at injury was 13.7 ± 4.4 years, with 2,089 patients (94%) being 5 to 18 years old. Of the injuries 79% were grade I, II or III. Penetrating injury accounted for less than 10% of all pediatric renal injuries. A majority of patients (57%) were admitted to university hospitals with a dedicated trauma service (73%) and only 12% of patients were admitted to a pediatric hospital. A total of 122 nephrectomies (5.5%) were performed. CONCLUSIONS Most renal trauma in children is low grade, is blunt in nature and occurs after age 5 years. The majority of these cases are managed at adult hospitals. Although most patients are treated conservatively, the rate of nephrectomy is 3 times higher at adult hospitals than at pediatric centers.

Pediatric Priapism Secondary to Psychotherapeutic Medications.

With the increased application of many different drug classes for the treatment of psychiatric conditions in children, the incidence of priapism has also increased. Priapism of pharmacotherapeutic etiology in the pediatric population is a complex and poorly understood entity that continues to present new management challenges for clinicians. We present 2 cases of pediatric priapism thought to be secondary to the use of pharmacotherapeutic agents. In the first case, sertraline, an antidepressant, and in the second case, atomoxetine, a nonstimulant medication, are implicated as the most likely causative agents. Both medications have a growing association with priapism in the literature.

New hydronephrosis and/or vesicoureteral reflux after bladder outlet surgery without augmentation in 75 children with neurogenic bladder.

OBJECTIVE We report new upper tract changes in children after bladder neck (BN) surgery without augmentation for neurogenic incontinence. MATERIALS AND METHODS Consecutive children with neurogenic sphincteric incompetency had BN surgery without augmentation. Postoperative renal sonography and fluoroscopic urodynamics were done at 6 months, 12 months, and then annually. RESULTS There were 75 patients with mean follow-up of 48 months. Of these, 17 (23%) developed new hydronephrosis (HN) or vesicoureteral reflux (VUR). All HN resolved with medical management, as did 25% of VUR cases. Persistent VUR was treated by dextranomer/hyaluronic acid injection, or re-implantation in two patients undergoing re-operative BN surgery. There was no association between these upper tract changes and end filling pressures (<40 cm vs. >40 cm) or continence status (dry vs. wet). CONCLUSIONS Upper tract changes developed in 25% of patients with neurogenic bladders after BN surgery without augmentation during a follow-up of 48 months. All new HN and most new VUR resolved with medical management or minimally invasive intervention. No patient developed upper tract changes requiring augmentation.