Edward M. Gong

Comparison of Laparoscopic and Open Partial Nephrectomy in Clinical T1a Renal Tumors

PURPOSE Partial nephrectomy has been established as a standard of care for T(1a) renal tumors. Laparoscopic partial nephrectomy (LPN) has been described as more difficult to perform than open partial nephrectomy (OPN). We compare our series of LPN and OPN. PATIENTS AND METHODS From October 2002 to January 2006, 76 LPNs were performed for patients with clinical T(1a) tumors. These patients were matched with a cohort of patients who underwent OPN for solitary tumors of 4 cm or smaller in diameter. The cohorts were compared with regard to demographics, perioperative data, and outcomes. RESULTS The patient populations were demographically similar. Although mean tumor size was smaller in the laparoscopic cohort (2.5 v 2.9 cm, P=0.002), the OPN cohort demonstrated shorter operative (193 v 225 min, P=0.004) and ischemia times (20.5 v 32.8 min). LPN was associated with less blood loss (212 v 385 mL, P<0.001) and shorter hospital stay (2.5 v 5.6 days, P<0.001), however. One positive margin occurred in each of the LPN and OPN cohorts. Intraoperative complications were similar, although LPN was associated with fewer postoperative complications. Of note, two LPN (2.6%) patients had emergent reoperation and complete nephrectomy because of postoperative hemorrhage. CONCLUSIONS Despite increased operative and ischemia times, LPN patients demonstrated quicker recovery and fewer postoperative complications. Two patients in the LPN group, however, had emergent complete nephrectomy because of hemorrhage. We conclude that LPN is still an evolving alternative to OPN in patients with small renal tumors.

Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation.

Currently, gastrointestinal segments are considered the gold standard for bladder reconstructive procedures. However, significant complications including chronic urinary tract infection, metabolic abnormalities, urinary stone formation, bowel dysfunction, and secondary malignancies are associated with this approach. Biomaterials derived from silk fibroin may represent a superior alternative due their robust mechanical properties, biodegradable features, and processing plasticity. In the present study, we evaluated the efficacy of a gel spun silk-based matrix for bladder augmentation in a murine model. Over the course of 70 d implantation period, H&E and Massons trichrome (MTS) analysis revealed that silk matrices were capable of supporting both urothelial and smooth muscle regeneration at the defect site. Prominent uroplakin and contractile protein expression (α-actin, calponin, and SM22α) was evident by immunohistochemical analysis demonstrating maturation of the reconstituted bladder wall compartments. Gel spun silk matrices also elicited a minimal acute inflammatory reaction following 70 d of bladder integration, in contrast to parallel assessments of small intestinal submucosa (SIS) and poly-glycolic acid (PGA) matrices which routinely promoted evidence of fibrosis and chronic inflammatory responses. Voided stain on paper analysis revealed that silk augmented animals displayed similar voiding patterns in comparison to non surgical controls by 42 d of implantation. In addition, cystometric evaluations of augmented bladders at 70 d post-op demonstrated that silk scaffolds supported significant increases in bladder capacity and voided volume while maintaining similar degrees of compliance relative to the control group. These results provide evidence for the utility of gel spun silk-based matrices for functional bladder tissue engineering applications.

Artery-Only Occlusion May Provide Superior Renal Preservation During Laparoscopic Partial Nephrectomy

OBJECTIVES Artery-only occlusion (AO) has been used during nephron-sparing surgery to reduce ischemic damage. However, this has not been demonstrated in laparoscopic partial nephrectomy (LPN). We compared our experience with AO and both artery and vein occlusion (AV) in LPN to optimize the method of ischemia. METHODS This retrospective case-control study identified 25 patients who underwent AO during LPN and matched them to a cohort of 53 patients who underwent LPN with AV. The groups were compared for ischemia time, blood loss, transfusion rate, and renal function. RESULTS The 2 cohorts were comparable on demographic data. Blood loss was similar, with AO and AV demonstrating equivalent transfusion rates. The 2 cohorts had similar warm ischemia times. Positive margin rate was not affected by venous backflow in the AO cohort (0% AO vs 1.9% AV, P = .679). No significant postoperative change in creatinine (Cr) or creatinine clearance (CrCl) was seen for AO; however, a significant change in Cr and CrCl was seen in AV. CONCLUSIONS AO during LPN does not lead to a greater blood loss or an increased warm ischemia time. The benefit of AO on renal function is significant and requires further investigation.

Inhibition of TNF-α Improves the Bladder Dysfunction That Is Associated With Type 2 Diabetes

Diabetic bladder dysfunction (DBD) is common and affects 80% of diabetic patients. However, the molecular mechanisms underlying DBD remain elusive because of a lack of appropriate animal models. We demonstrate DBD in a mouse model that harbors hepatic-specific insulin receptor substrate 1 and 2 deletions (double knockout [DKO]), which develops type 2 diabetes. Bladders of DKO animals exhibited detrusor overactivity at an early stage: increased frequency of nonvoiding contractions during bladder filling, decreased voided volume, and dispersed urine spot patterns. In contrast, older animals with diabetes exhibited detrusor hypoactivity, findings consistent with clinical features of diabetes in humans. The tumor necrosis factor (TNF) superfamily genes were upregulated in DKO bladders. In particular, TNF-α was upregulated in serum and in bladder smooth muscle tissue. TNF-α augmented the contraction of primary cultured bladder smooth muscle cells through upregulating Rho kinase activity and phosphorylating myosin light chain. Systemic treatment of DKO animals with soluble TNF receptor 1 (TNFRI) prevented upregulation of Rho A signaling and reversed the bladder dysfunction, without affecting hyperglycemia. TNFRI combined with the antidiabetic agent, metformin, improved DBD beyond that achieved with metformin alone, suggesting that therapies targeting TNF-α may have utility in reversing the secondary urologic complications of type 2 diabetes.

Contemporary national comparison of open, laparoscopic, and robotic-assisted laparoscopic pediatric pyeloplasty.

OBJECTIVE We sought to determine current and longitudinal trends in the usage of open (OP), laparoscopic (LP), and robotic pyeloplasties. (RALP) Furthermore, we aimed to describe patient and hospital level characteristics associated with the use of minimally invasive pyeloplasties (MIP) and to compare basic utilization metrics for each approach. MATERIALS/METHODS The 2000, 2003, 2006, and 2009 Kids Inpatient Databases (KID) were used to determine current and longitudinal trends. As a result of a specific billing code for robotic surgery introduced in 2008, the 2009 KID database was used for analysis of RALP. Patient and hospital characteristics examined included: age, gender, race, insurance status, hospital location, and academic status. Utilization metrics of length of stay (LOS) and cost were determined from each modality. RESULTS In 2009, there were 3354 pediatric pyeloplasties performed in the USA (85% OP, 3% LP, 12% RP). Compared with 2000, this represents an 11.7% decrease in the overall number of pyeloplasties but a progressive increase in MIP from 0.34% in 2000 to 11.7%. Mean patient age was 3.7 years for OP, 9.3 years for LP and 9.9 years for RALP. MIP was more commonly performed in females, Caucasians, patients with private insurance, at urban hospitals and at teaching hospitals. Although length of stay (LOS) in days was statistically lower for MIP (3.46 OP, 2.86 LP, 1.96 RP, p < 0.001), total cost between the groups was not statistically different. On multivariable logistic regression analysis, age (OR 1.17, p < 0.001) increased the odds of MIP whereas lack of private insurance decreased the odds of MIP (OR 0.62, p = 0.002). CONCLUSION Although utilization of MIP is increasing in the USA, especially in older children, OP remains predominant. MIP was associated with a decrease in LOS. The odds of MIP were higher in older children, whereas the lack of private insurance decreased the odds of MIP.

An Akt- and Fra-1-Dependent Pathway Mediates Platelet-Derived Growth Factor-Induced Expression of Thrombomodulin, a Novel Regulator of Smooth Muscle Cell Migration

Overdistension of hollow organs evokes pathological changes characterized by smooth muscle remodeling. Mechanical stimuli induce smooth muscle cell (SMC) growth through acute activation of signaling cascades and by increased expression of soluble mitogens. Physical forces have also been implicated in ligand-independent activation of receptor tyrosine kinases, including the platelet-derived growth factor (PDGF) receptor, although the extent to which this occurs in intact tissue is unknown. Previously, we implicated Akt and activator protein-1 (AP-1) as mediators of growth and gene expression in SMC exposed to cyclic stretch or PDGF. Here we show that bladder wall distension leads to PDGFR activation and identify thrombomodulin (TM) as an Akt and AP-1 target in SMC. We demonstrate that TM, also induced by bladder stretch injury, is regulated at the transcriptional level by the AP-1 components c-jun and Fra1. Mutation of an AP-1 motif at -2010/-2004 abolished both AP-1 binding and PDGF responsiveness of the TM promoter. Fra1 silencing diminished PDGF-induced TM expression and SMC cell cycle transit. In contrast, TM knockdown did not affect cell growth but attenuated PDGF-stimulated SMC migration. Taken together, these results reveal new facets of TM regulation in SMC and provide the first demonstration of a role for endogenous TM in PDGF-induced cell migration. Moreover, TM induction on bladder injury suggests that it may be a biomarker for pathological smooth muscle remodeling.

FosB Regulates Stretch-Induced Expression of Extracellular Matrix Proteins in Smooth Muscle

Fibroproliferative remodeling in smooth muscle-rich hollow organs is associated with aberrant extracellular matrix (ECM) production. Although mechanical stimuli regulate ECM protein expression, the transcriptional mediators of this process remain poorly defined. Previously, we implicated AP-1 as a mediator of smooth muscle cell (SMC) mechanotransduction; however, its role in stretch-induced ECM regulation has not been explored. Herein, we identify a novel role for the AP-1 subunit FosB in stretch-induced ECM expression in SMCs. The DNA-binding activity of AP-1 increased after stretch stimulation of SMCs in vitro. In contrast to c-Jun and c-fos, which are also activated by the SMC mitogen platelet-derived growth factor, FosB was only activated by stretch. FosB silencing attenuated the expression of the profibrotic factors tenascin C (TNC) and connective tissue growth factor (CTGF), whereas forced expression of Jun~FosB stimulated TNC and CTGF promoter activity. Chromatin immunoprecipitation revealed enrichment of AP-1 at the TNC and CTGF promoters. Bladder distension in vivo enhanced nuclear localization of c-jun and FosB. Finally, the distension-induced expression of TNC and CTGF in the detrusor smooth muscle of bladders from wild-type mice was significantly attenuated in FosB-null mice. Together, these findings identify FosB as a mechanosensitive regulator of ECM production in smooth muscle.

Saw palmetto and benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a common health issue that affects 8% of all men at the age of 40, 60% of men in their 70s, and 90% of those greater than 80 years of age. One-fourth of these men will develop moderate to severe lower urinary tract symptoms that greatly affect their quality of life. Recent evidence suggests that the use of saw palmetto leads to improvements in urinary function for those suffering from BPH. The favorable comparison of saw palmetto with tamsulosin, a well-known first line agent in the treatment of urinary tract symptoms, demonstrates promise towards a beneficial effect of this herbal agent, with very few, if any, adverse effects. However, what degree of this beneficial activity is due to placebo effects is yet to be determined. In addition, the precise mechanism of action of saw palmetto in men with BPH remains unclear.

Diagnosis and Management of Periurethral Cysts

Background/Aims: Periurethral cysts are a rare entity that may be confused with urethral diverticula. The protocol for diagnosis and management of these lesions is still unclear. We present our experience with six patients presenting with periurethral cysts. Methods: From 2001 to 2005 we evaluated six patients with a paraurethral mass. History, physical examination, laboratory and radiographic findings were analyzed to determine factors helpful in mass diagnosis. Cyst excision was performed via trans-vaginal approach in all patients and outcomes of this approach were assessed. Results: Six female patients, average age of 29.7 years, presented with the complaint of a paraurethral mass. Transvaginal sonography was performed in two patients to confirm the presence of a periurethral cyst. Cystourethroscopy in all patients revealed no communication between the cyst and the urethra or presence of other lesions. Pathology revealed a benign cyst in all patients. No cyst recurrence has been seen in any patient. Conclusion: Most periurethral cysts can be diagnosed by physical examination. The diagnosis may be confirmed with transvaginal sonography. Cystourethroscopy should be performed to rule out other pathology, but may be done in the same setting as surgical excision. Complete surgical excision is effective and is associated with minimal risk of recurrence during short-term follow-up.

Pediatric urology and the internet--does an uncommon topic decrease content quality?

PURPOSE The Internet has become a widely used resource for patients and families to obtain medical information but the quality of information available is highly variable. We sought to determine if Web pages addressing common and uncommon pediatric urology topics differ in terms of quality or characteristics. MATERIALS AND METHODS We performed an Internet search using 5 common conditions (vesicoureteral reflux, hypospadias, prenatal hydronephrosis, cryptorchidism, enuresis) and 5 uncommon conditions (exstrophy, prune belly, posterior urethral valves, Wilms tumor, ureterocele). We recorded total hits, presence of sponsored links, page owner and author type, last update, content quality, readability, accreditation and advertising. Content quality was graded on a 5-point scale for accuracy and completeness of natural history, diagnosis and treatment. RESULTS We evaluated 100 sites on 10 topics. Common topics had more hits (980,000 vs 194,000) and were more likely to have sponsored advertisements (40% vs 0%) than uncommon topics. No difference was seen between topics in time from last update, owner/author type, financial disclosure, accreditation or advertising. Median quality grade was 4.0. Common topics had higher quality grades for disease natural history and diagnosis. Reading grade level was high and was similar between the groups. CONCLUSIONS Web sites devoted to common pediatric urology topics have higher quality information for disease diagnosis and natural history. Otherwise, the quality of pediatric urology information on the Internet is high for common and uncommon topics. A high reading level is required to use these resources.