Flaps and Grafts in Robotic Reconstructive Surgery.

PURPOSE OF REVIEW: The robotic approach is increasingly popular in reconstructive urology. Reconstructive surgeons have commonly used flaps and grafts for obliterating dead space including tissue interposition or as an alternative to mesh in addressing lower urinary tract dysfunction. Advantages of the robotic approach are less incisional pain, excellent visualization in the deep pelvis, and improved surgeon ergonomics. In this literature review, we describe flaps and grafts used in lower urinary tract robotic reconstructive urology, serving as an almanac for these techniques. RECENT FINDINGS: Omental, peritoneal, vertical rectus abdominis musculocutaneous (VRAM), sigmoid epiploica, gracilis flaps, and Alloderm™ have been reported for tissue interposition during fistula repair. Fascia lata has been described as a mesh alternative for robotic sacrocolpopexy. Besides providing interposition, flaps support native tissue healing and blood supply. Grafts are easy to use with low patient morbidity, but rely on the blood supply at the recipient site. Robotic reconstruction is an emerging field, and more studies are needed to define the best uses for each flap and graft as well as strategies to maximize outcomes and minimize morbidity.

Evaluation of toxicities for intravesical drugs in phase 1 bladder cancer trials.

BACKGROUND: Improving clinical trial design is important for optimizing approval of safe and effective drugs. Phase 1 clinical trials seek to determine phase 2 doses by investigating predefined dose-limiting toxicities. Traditional definitions of dose-limiting toxicity may not be applicable to intravesical therapies for bladder cancer. This study compared the frequency of dose-limiting toxicities and serious adverse events in bladder cancer trials for intravesical therapies to other routes of administration. METHODS: Studies were abstracted from ClinicalTrials.gov and reconciled with a PubMed search. Primary and secondary end points were predefined before data abstraction, and the primary end point was subject-level dose-limiting toxicity rate. Fisher exact tests were performed with p < .05 designated as significant. RESULTS: Eighteen intravesical studies and 24 studies with other routes of administration (the per os/intravenous/intramuscular [PO/IV/IM] group) were identified. Dose-limiting toxicities were reported in 38.9% of intravesical studies, affecting 3.29% of subjects, compared with 30.0% of PO/IV/IM studies representing 4.19% of subjects (p = .52 for study-level and p = .60 for subject-level comparisons). Serious adverse events occurred in 53.9% of intravesical studies in 10.3% of subjects versus 91.0% of studies reporting serious adverse events affecting 41.4% of subjects in the PO/IV/IM group (p = .03 for subject-level and p < .0001 for study-level comparisons). CONCLUSIONS: There was no difference in subject-level dose-limiting toxicity rate between intravesical and PO/IV/IM bladder cancer trials. The serious adverse event rate was lower in the intravesical group. Heterogeneity of dose-limiting toxicity definition may affect interpretation of toxicity in phase 1 bladder cancer clinical trials studying different routes of administration. LAY SUMMARY: Bladder cancer is a common cancer type that may be treated with therapies that are instilled into the bladder and act locally, called intravesical therapies. This study used publicly available regulatory data from early phase clinical trials to determine whether measures of tolerability used in clinical trials are applicable to intravesical therapies for bladder cancer.

Feasibility and clinical outcomes of ureteral stenting in the office procedural suite.

INTRODUCTION: Stent placement is a common procedure for addressing obstructive uropathy. However, lack of operating room (OR) availability can substantially delay this procedure. In this study, we sought to assess the feasibility, safety, and efficacy of this procedure in a clinical setting using nitrous oxide (N2O) and local anesthesia. MATERIALS AND METHODS: Patients included in this study included those who were determined to need management of urinary obstruction with a JJ ("double J") stent and had their procedure performed in the clinic procedure suite with N2O anesthesia. RESULTS: We present a case series of 565 patients undergoing ureteral stent placements in a clinic operative suite with N2O. In this cohort, complications occurred after 4.1% of procedures and unplanned admissions to the hospital occurred after 2.5% of procedures. Stent placements failed in 1.0% of procedures. Failures occurred due to pain in 2/565 patients. No anesthetic complications were encountered. CONCLUSION: We report the feasibility and clinical outcomes of ureteral stent placements for ureteral obstruction in a clinic setting with the use of local anesthetic or N2O anesthesia, with excellent results. A majority of patients tolerated the procedure well and only 2 of 565 had their procedures stopped due to discomfort. To our knowledge, this is the first report of the use of N2O anesthetic for conscious sedation for the placement of ureteral stents.

Cardiac myosin-binding protein-C is a critical mediator of diastolic function.

Diastolic dysfunction prominently contributes to heart failure with preserved ejection fraction (HFpEF). Owing partly to inadequate understanding, HFpEF does not have any effective treatments. Cardiac myosin-binding protein-C (cMyBP-C), a component of the thick filament of heart muscle that can modulate cross-bridge attachment/detachment cycling process by its phosphorylation status, appears to be involved in the diastolic dysfunction associated with HFpEF. In patients, cMyBP-C mutations are associated with diastolic dysfunction even in the absence of hypertrophy. cMyBP-C deletion mouse models recapitulate diastolic dysfunction despite in vitro evidence of uninhibited cross-bridge cycling. Reduced phosphorylation of cMyBP-C is also associated with diastolic dysfunction in patients. Mouse models of reduced cMyBP-C phosphorylation exhibit diastolic dysfunction while cMyBP-C phosphorylation mimetic mouse models show enhanced diastolic function. Thus, cMyBP-C phosphorylation mediates diastolic function. Experimental results of both cMyBP-C deletion and reduced cMyBP-C phosphorylation causing diastolic dysfunction suggest that cMyBP-C phosphorylation level modulates cross-bridge detachment rate in relation to ongoing attachment rate to mediate relaxation. Consequently, alteration in cMyBP-C regulation of cross-bridge detachment is a key mechanism that causes diastolic dysfunction. Regardless of the exact molecular mechanism, ample clinical and experimental data show that cMyBP-C is a critical mediator of diastolic function. Furthermore, targeting cMyBP-C phosphorylation holds potential as a future treatment for diastolic dysfunction.

Narrative review of flaps and grafts in robotic reconstructive urologic surgery.

Background and Objective: Flaps and grafts are used for filling dead space, ureteral substitution, and as mesh alternatives. The surgical robot is invaluable in urologic reconstructive surgery due to the ability of the robot to reach the deep pelvis, its minimally invasive access, the ability to use indocyanine green to identify structures and assess tissue perfusion and viability, and ergonomics for the surgeon. Robotic reconstruction can involve tissue transfer in the form of flaps and grafts to provide form and function to organs that have been damaged by iatrogenic injuries, trauma, infections, cancer, radiation injury, or congenital abnormalities. Common flaps and grafts can be readily adapted to the robotic approach. In this literature review, we examine the robotic use of flaps and grafts in reconstructive urology. Methods: A thorough literature review was conducted via a PubMed search for predefined terms. Key Content and Findings: Flaps and grafts in reconstructive urology are used for interposition, ureteral substitution, and as mesh alternatives. Omental flaps are used for tissue interposition, or to provide structure and nutrients, and are easily employed with the robot. Various robotic applications of peritoneal flaps have been described. Vascular rectus abdominis musculocutaneous flaps are well-vascularized flaps that occupy dead space and provide structural support, which can be harvested readily with the robot. Sigmoid epiploica are an excellent flap for pelvic reconstruction. Gracilis flaps and fascia lata grafts are well-tolerated and provide space occupying tissue. Boari flaps aid in robotic ureteral reconstruction, especially in the setting of long defects. Oral mucosa is excellent for ureteral or bladder neck reconstruction. Rectal mucosa is well-tolerated and easy to harvest robotically for a variety of urinary tract reconstructive applications. The appendix or ileum can be interposed for repair of damaged ureters. Conclusions: Various flaps and grafts have been adapted for robotic reconstructive urology. As the field develops, refinement of techniques and innovation in flaps and employment of the robot will propel this field forward. More studies, especially comparative studies, are needed to elucidate the flaps and grafts that are most likely to be successful with the least morbidity for each use case.

Neighborhood Social Vulnerability Impacts Quality of Life in Kidney Stone Patients.

INTRODUCTION: This study aimed to investigate the association between social vulnerability, as measured by the Centers for Disease Control and Prevention's Social Vulnerability Index (SVI), and the quality of life (QoL) of kidney stone patients using the validated Wisconsin Stone Quality of Life Questionnaire (WISQOL). METHODS: A retrospective analysis was conducted on medical records of new urolithiasis patients who completed the WISQOL at the University of Rochester Medical Center kidney stone clinic. The primary outcome was WISQOL score, which was measured across multiple domains. SVI was used to assess social vulnerability. Neighborhoods with high SVI were defined by a threshold greater than or equal to the 75th percentile nationally. Demographic and clinical data were collected. Statistical analyses, including univariate tests and multivariate linear regression, were performed to evaluate the relationships between social vulnerability and disease-specific QoL. RESULTS: A total of 1718 patients were included in the study. One hundred five subjects (6.1%) were from neighborhoods of high social vulnerability. Patients residing in neighborhoods with high social vulnerability (SVI quartile) reported significantly lower QoL scores (69.1 vs 77.2; P = .001) and this persisted across all domains, including social impact (32.6 vs 35.1; P = .002), emotional impact (25.2 vs 27.5; P = .006), disease impact (28.5 vs 31.4; P = .001), and vitality (10.3 vs 11.2; P = .015). Younger age, female sex, and higher number of comorbidities were identified as independent predictors of lower QoL scores. However, non-White race and Latinx ethnicity did not exhibit a significant association with QoL scores. CONCLUSIONS: These findings highlight the negative impact of high social vulnerability on QoL, emphasizing the importance of considering socioeconomic factors in patient care. These results emphasize the need for targeted interventions to support vulnerable populations. While this study offers initial insights, further research is essential to corroborate these outcomes across larger and more diverse populations.

Getting hot in here! Comparison of Holmium vs. thulium laser in an anatomic hydrogel kidney model.

As laser technology has advanced, high-power lasers have become increasingly common. The Holmium: yttrium-aluminum-garnet (Ho:YAG) laser has long been accepted as the standard for laser lithotripsy. The thulium fiber laser (TFL) has recently been established as a viable option. The aim of this study is to evaluate thermal dose and temperature for the Ho:YAG laser to the TFL at four different laser settings while varying energy, frequency, operator duty cycle (ODC). Utilizing high-fidelity, 3D-printed hydrogel models of a pelvicalyceal collecting system (PCS) with a synthetic BegoStone implanted in the renal pelvis, laser lithotripsy was performed with the Ho:YAG laser or TFL. At a standard power (40W) and irrigation (17.9 ml/min), we evaluated four different laser settings with ODC variations with different time-on intervals. Temperature was measured at two separate locations. In general, the TFL yielded greater cumulative thermal doses than the Ho:YAG laser. Thermal dose and temperature were typically greater at the stone when compared away from the stone. Regarding the TFL, there was no general trend if fragmentation or dusting settings yielded greater thermal doses or temperatures. The TFL generated greater temperatures and thermal doses in general than the Ho:YAG laser with Moses technology. Temperatures and thermal doses were greater closer to the laser fiber tip. It is inconclusive as to whether fragmentation or dusting settings elicit greater thermal loads for the TFL. Energy, frequency, ODC, and laser-on time significantly impact thermal loads during ureteroscopic laser lithotripsy, independent of power.

Redefining Clinically Significant Hematuria After Holmium Enucleation of the Prostate.

Introduction and Objective: Holmium laser enucleation of the prostate (HoLEP) is often offered for symptomatic prostatic enlargement at high risk for bleeding. However, prior studies define clinically significant hematuria (CSH) narrowly as the need for blood transfusion or significant decrease in hemoglobin. We sought to evaluate risk factors contributing to a broader definition of CSH, which may contribute to alteration of clinical course. Methods: We analyzed 164 patients in a prospectively maintained database who underwent HoLEP at a single institution across two surgeons from November 2020 to April 2023. HoLEP was performed using Moses 2.0 (Boston Scientific) laser and the Piranha enucleation system (Richard Wolf). We defined CSH broadly as follows: clot retention, return to operating room, perioperative management variation due to hematuria, or continued gross hematuria past 1 month postoperatively. Univariable and multivariable ANOVAs were used. Multivariable analysis of CSH risk based on the use of antiplatelet (AP) agents or anticoagulants included correction for age, enucleation time (surrogate for case difficulty), and prostate volume. Results: 17.7% (29/164) of our patients developed CSH after HoLEP. Longer enucleation time was a mild risk factor for developing CSH (multivariate odds ratio [OR] 1.01, p = 0.02). The strongest predictor of CSH was the use of anticoagulation or AP agents (OR 2.71 p < 0.02 on univariable analysis, OR 2.34 p < 0.02 on multivariable analysis), even when aspirin 81 mg was excluded. Conclusion: With a broadened definition, 18% of patients developed CSH following HoLEP, which impacted the clinical course. Our data suggest that the current definition of significant hematuria is too narrow and does not capture many patients whose clinical course is affected by hematuria. While safe, anticoagulants and APs significantly predicted an increased CSH risk, and patients should be counseled accordingly.

Predictors of postoperative urinary tract infection following holmium laser enucleation of the prostate.

INTRODUCTION: Storage urinary symptoms and urinary tract infection (UTI) are among the most common complications following holmium laser enucleation of the prostate (HoLEP). We aimed to study the incidence and risk factors for storage urinary symptoms and early UTI following HoLEP. METHODS: A prospectively maintained database was reviewed for patients who underwent HoLEP over a five-year period at a single tertiary center. Patient demographics, preoperative, operative, and postoperative characteristics, as well as infection rates, were obtained and analyzed using the appropriate statistical methods. RESULTS: Of a total 514 patients who underwent HoLEP, 473 patients with complete followup data were included. Mean (± standard deviation) age and median (interquartile range) prostate volume were 72±9.1 years and 89 (68-126) g, respectively. Preoperative positive urine culture and urine retention were seen in 28.5% (n=135) and 23.46 % (n=111) of patients, respectively. At six-week followup, irritative urinary symptoms were seen in 32.3% (n=153) of patients, while 13.5% (n= 64) of patients had positive urine culture. Bivariate and multivariate analysis showed that factors associated with significant higher rate of postoperative UTI at six weeks were high body mass index (BMI) (p= 0.023), weak grip strength within preoperative frailty assessment (p=0.042), positive preoperative urine culture (p=0.025), and postoperative incontinence (p=0.002). CONCLUSIONS: Storage urinary symptoms are common complaints post-HoLEP; however, it may be caused by an inflammatory rather than infective process in a significant percentage of patients. Possible predictors of UTI after HoLEP are high BMI, preoperative positive urine culture, higher frailty scale, and postoperative urinary incontinence.

The contribution of the immune system to genitourinary fibrosis.

Fibrotic diseases of the genitourinary tract are devastating and incompletely understood pathologies. These diseases include urethral and ureteral strictures, retroperitoneal fibrosis, and Peyronie's disease. They can contribute to obstructive uropathy and sexual dysfunction. Poor understanding of the pathophysiology of these diseases severely limits our ability to prevent and treat them. Genitourinary fibrotic diseases likely represent related pathologies that share common underlying mechanisms involving wound healing in response to injury. These diseases share the common feature of extracellular matrix abnormalities-such as collagen deposition, transforming growth factor-ß accumulation, and dysregulation of collagen maturation-leading to abnormal tissue stiffness. Given the association of many of these diseases with autoimmunity, a systemic pro-inflammatory state likely contributes to their associated fibrogenesis. Herein, we explore the immunologic contribution to fibrogenesis in several fibrotic diseases of the genitourinary system. Better understanding how the immune system contributes to fibrosis in these diseases may improve prevention and therapeutic strategies and elucidate the functions of immunologic contributors to fibrosis in general.

Is parenteral antibiotic prophylaxis associated with fewer infectious complications in stented, distal hypospadias repair?

INTRODUCTION: Judicious use of antibiotics for surgical prophylaxis is important for reducing antimicrobial resistance while preventing infectious surgical complications. In the setting of pediatric distal hypospadias repairs, it is unclear if antibiotic surgical prophylaxis is beneficial. OBJECTIVE: The purpose of this study was to compare rates of infectious complications in pediatric subjects undergoing distal hypospadias repair who received any peri-operative antibiotics to those who did not. STUDY DESIGN: This was a review of a retrospective cohort from a database of individuals undergoing hypospadias repairs evaluating whether they received peri-operative or post-operative antibiotic prophylaxis and determining the rate of infectious complications in those who did compared to those who did not receive antibiotic prophylaxis. Infectious complications were defined as surgical site infection (SSI) or urinary tract infection (UTI). RESULTS: There was no significant difference in infectious complication rates between individuals who received peri-operative parenteral antibiotic prophylaxis and those who did not. All subjects with infectious complications received post-operative oral antibiotic prophylaxis. There was one instance of C. difficile infection in a subject who received peri-operative parenteral antibiotics. DISCUSSION: Reducing antibiotic utilization without increasing infectious surgical complications is important in safely reducing antimicrobial resistance. In this study of pediatric distal hypospadias repair, peri-operative antibiotics did not demonstrate a clear benefit and post-operative oral antibiotics demonstrated no benefit in preventing infectious complications. Other studies evaluating peri- and post-operative antibiotics for pediatric hypospadias repair have also failed to demonstrate a benefit for antibiotics in preventing infections. Practitioners should reconsider the use of antibiotics in this setting. CONCLUSION: Routine antibiotic prophylaxis does not appear beneficial for preventing infectious complications following uncomplicated, stented pediatric distal hypospadias repairs.

A Comparison of Clinical Outcomes of Operating Room Versus Office-based Ureteral Stenting With the Novel Use of Nitrous Oxide Sedation.

OBJECTIVES: To examine the safety and effectiveness of placing ureteral stents in an office-based setting vs in the operating room (OR). METHODS: A retrospective chart review was performed to examine outcomes, specifically complication rate, unanticipated hospitalizations, and stent failures, when patients received JJ stents in the clinic procedure suite, using local analgesia and/or nitrous oxide gas analgesia, compared to patients who had ureteral stents placed in the OR, typically with general anesthesia. Additionally, multivariable analysis was performed to determine predictors of complications. RESULTS: Around 565 procedures were performed in the clinic and 179 were performed in the OR. The complication rate for the clinic group was 4.1%, compared to 7.8% in the OR group. Unplanned admissions to the hospital occurred after 3.0% of clinic procedures and 9.5% of OR procedures. Stent placements failed in 1.1% of clinic procedures and 0.56% of OR procedures. Clinic procedure time was 10 minutes vs 12 minutes in the OR (P <0.01). Clinic vs OR setting was not predictive of complications (P = 0.99). We did not identify factors that impacted complication rate in ureteral stent placement in the clinic vs OR setting. Notably, the procedure time for a clinic stent placement was significantly shorter than the OR stent placement. CONCLUSIONS: This study demonstrates excellent outcomes with a novel approach to a standard procedure, with shorter procedure time and no difference in complication rates.

The use of a string with a stent for self-removal following ureteroscopy: A safe practice to remain.

ABSTRACT OBJECTIVES: To examine the safety and effectiveness of the use of a stent with a string attached after ureteroscopy (URS) for self-removal of the stent by the patient. PATIENTS AND METHODS: After Institutional Review Board approval, a retrospective chart review was performed concerning patients who underwent URS and received an indwelling stent with or without a string attached to the stent (94 vs 349, respectively). Amongst the string group patients received a single- or a double-arm-stringed stent (31 vs 63, respectively). Statistical analyses included chi-squared and Student's t-tests. RESULTS: The string group consisted of 94 procedures, in which 59.6% of the patients were male with a mean (SD) age of 50.0 (16.5) years. In the no-string group, 51.3% of the 349 procedures were performed in males and the mean (SD) age was 54.9 (18.1) years. Complication rates were 12.8% in the string group and 14.0% in the no-string group (P = 0.867). In the string group, 17.0% of the patients returned to the Emergency Department, whilst 15.8% of the no-string patients returned (P = 0.753). The complication rate in the single- and double-arm groups were 12.9% and 12.7%, respectively (P > 0.910). Self-removal of stents was successful in 94.7% of patients (89/94). CONCLUSIONS: The use of a stent with a string after URS appears safe and effective. Few patients had difficulty removing their stents and complication rates were similar in the groups with and without a string attached to their stents. Single- and double-arm-stringed stents have similar complication rates.

Comparison of utilization of pressurized automated versus manual hand irrigation during ureteroscopy in the absence of ureteral access sheath.

This study compared patient outcomes following irrigation applied using an automated pressure system (AP) to hand irrigation utilizing a syringe (HI) during ureteroscopy. Retrospective chart review was performed to evaluate ureteroscopy procedures without a ureteral access sheath. Procedures in which irrigation was applied by AP were compared to those with HI. Statistical analyses included chi-squared tests and Student's t tests. The AP group contained 206 procedures and the HI group, 25. The AP and HI groups were 54.9% and 36% male, respectively. Mean ages were 53.7 ± 18.9 years in the AP group and 44.0 ± 18.5 years in the HI group. Complication rates were 11.2% in the AP and 8.3% in the HI group (P > 0.99). One stone retrieval failure and one stone recurrence occurred in the HI group; one patient had residual stone in the AP group. No urinary tract infections occurred in the HI group; in the AP group, urinary tract infections occurred in 1.9% of cases. The postoperative pain incidence was equivalent (P = 0.498). The AP group had one subcapsular hematoma; no calyceal ruptures occurred in either group. In conclusion, irrigation applied by an automated setup appears safe, with similar outcomes to irrigation applied with a handheld syringe.

Intraabdominal pressure in women during CrossFit exercises and the effect of age and parity.

To determine intraabdominal pressure (IAP) in women during CrossFit and to determine whether parity, age, or CrossFit experience affects IAP during CrossFit exercises, we evaluated 10 women: 5 experienced and active CrossFitters and 5 who were not regularly engaged in CrossFit. A Laborie urodynamics abdominal pressure probe with the Goby wireless system measured IAP during 10 repetitions of 13 different CrossFit exercises. Women had a mean age of 36 years. A significant difference was found between mean peak IAP of the 5 parous vs the 5 nulliparous women (P = 0.009). Experience with CrossFit did not affect mean peak IAP achieved with exercise. In some exercises, there was a significant change in IAP as participants progressed through repetitions (P = 0.003 for back squats and 0.04 for sit-ups). Participants achieved IAP values that were markedly higher than those previously published.

Burn Injury-Associated MHCII+ Immune Cell Accumulation Around Lymphatic Vessels of the Mesentery and Increased Lymphatic Endothelial Permeability Are Blocked by Doxycycline Treatment.

It is theorized that toxic agents are transported from the hyperpermeable gut of burn victims through the lymph, to the systemic circulation, causing global injury. We believe that immune cells respond to leakage of "toxic lymph" following trauma causing the attraction of these cells to the perilymphatic space. To test this, we utilized a model of burn on rats to examine changes in a single immune cell population associated with mesenteric lymphatic dysfunction. We examined the ability of serum from these animals to increase permeability in lymphatic endothelial monolayers and disrupt cellular junctions. We also treated burn animals with doxycycline, an inhibitor of microvascular permeability, and observed the effects on immune cell populations, morphometry, and lymphatic endothelial permeability. Burn injury increased the number of MHCII+ immune cells along the vessel (>50%). The size and shape of these cells also changed significantly following burn injury. Serum from burn animals increased lymphatic endothelial permeability (∼1.5-fold) and induced breaks in VE-cadherin staining. Doxycycline treatment blocked the accumulation of immune cells along the vessel, whereas serum from doxycycline-treated animals failed to increase lymphatic endothelial permeability. The size of cells along the vessel in doxycycline-treated burn animals was not affected, suggesting that the cells already present on the lymphatic vessels still respond to substances in the lymph. These findings suggest that factors produced during burn can induce lymphatic endothelial barrier disruption and lymph produced during traumatic injury can influence the attraction and morphology of immune cell populations along the vessel.

Targeting newly identified ERß/TGF-ß1/SMAD3 signals with the FDA-approved anti-estrogen Faslodex or an ERß selective antagonist in renal cell carcinoma.

Renal cell carcinoma (RCC) has the third highest mortality rate among urological tumors, and 20-30% of RCC patients present with metastatic RCC at the time of diagnosis. Although recent studies have indicated that estrogen receptor ß (ERß) could play promoting roles in RCC progression, the detailed mechanisms remain to be clarified. In the present study, we found that expression of ERß, but not ERα, increases with tumor stage and grade, and also observed that modification of ERß signals using estrogens/anti-estrogens, shRNA knockdown of ERß and overexpression of ERß using ectopic cDNA affects RCC cell proliferation, migration and invasion. Mechanism analysis revealed that ERß can promote RCC cell invasion via an increase in transforming growth factor ß1 (TGF-ß1)/SMAD3 signals, and interrupting TGF-ß1/SMAD3 signals with a TGFßR1 inhibitor can reverse/block ERß-increased RCC cell migration. Importantly, preclinical analyses using in vivo mouse models of RCC revealed that targeting of this newly identified ERß/TGF-ß1/SMAD3 pathway with either the FDA-approved anti-estrogen ICI182,780 (Faslodex) or a selective ERß antagonist 4-[2-phenyl-5,7 bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol can significantly reduce RCC tumor growth and invasion, which may be suitable as the basis for novel therapies to more effectively suppress metastatic RCC.

The impact of quercetin on wound healing relates to changes in αV and ß1 integrin expression.

Overly fibrotic wound healing can lead to excess scar formation, causing functional impairment and undesirable cosmetic results. However, there are few successful treatments available to prevent or remediate scars. This study sought to explore the molecular mechanisms by which quercetin, a naturally-occurring antifibrotic agent, diminishes scar formation. Using both mice and fibroblast cells, we examined quercetin's impact on fibrosis and the wound healing rate, and potential molecular mechanisms underlying the quercetin-mediated reduction of fibrosis. While cultured fibroblasts demonstrated normal growth in response to quercetin, quercetin increased surface αV integrin and decreased ß1 integrin. These changes in surface integrin expression may impact factors that contribute to fibrosis including cell migration, proliferation, and extracellular matrix production. In both quercetin-treated and control mice, wounds healed in about 14 days. Masson's trichrome stain revealed diminished fibrosis at the wound site in quercetin-treated animals despite the normal healing rate, indicating the potential for better cosmetic results without delaying healing. An in vitro scratch wound model using cells plated on an artificial extracellular matrix demonstrated delayed closure following quercetin treatment. The extracellular matrix also ameliorated quercetin's effect on αV integrin. Thus, αV integrin recruitment in response to quercetin treatment may promote the quercetin-mediated decrease extracellular matrix because cells require less extracellular matrix to migrate into a wound. With added extracellular matrix, ß1 integrin remained diminished in response to quercetin, indicating that quercetin's effect on ß1 integrin expression is independent of extracellular matrix -mediated signaling and is likely driven by inhibition of the intracellular mechanisms driving ß1 expression. These findings suggest that quercetin could alter the cells' interactions with the extracellular matrix through the regulation of integrin expression to promote a decrease in fibrosis. Furthermore, this work demonstrates that this naturally occurring and commercially available supplement could be used to improve wound healing by impacting integrin expression, leading to a lower extracellular matrix requirement to achieve healing. Impact statement Scar formation during wound healing can be problematic for patients but there are limited therapies available to treat or prevent excess fibrosis at wound sites. This work examines the impact of quercetin, a flavonoid that decreases fibrosis, on wound healing, and relates quercetin's effects to changes in integrin expression on the surface of fibroblast cells. To our knowledge, this is the first report that quercetin alters integrin expression or that this impact may be part of the mechanism by which quercetin prevents fibrosis. This work demonstrates that quercetin can be used to modulate integrin expression and that this effect may in turn reduce fibrosis during wound healing. Furthermore, this paper identifies the modulation of integrin expression as a possible therapeutic target in preventing scars. This information could be used to improve therapeutics to aid in the cosmetic and functional results following wound healing.

The contribution of interleukin-2 to effective wound healing.

Ineffective skin wound healing is a significant source of morbidity and mortality. Roughly 6.5 million Americans experience chronically open wounds and the cost of treating these wounds numbers in the billions of dollars annually. In contrast, robust wound healing can lead to the development of either hypertrophic scarring or keloidosis, both of which can cause discomfort and can be cosmetically undesirable. Appropriate wound healing requires the interplay of a variety of factors, including the skin, the local microenvironment, the immune system, and the external environment. When these interactions are perturbed, wounds can be a nidus for infection, which can cause them to remain open an extended period of time, or can scar excessively. Interleukin-2, a cytokine that directs T-cell expansion and phenotypic development, appears to play an important role in wound healing. The best-studied role for Interleukin-2 is in influencing T-cell development. However, other cell types, including fibroblasts, the skin cells responsible for closing wounds, express the Interleukin-2 receptor, and therefore may respond to Interleukin-2. Studies have shown that treatment with Interleukin-2 can improve the strength of healed skin, which implicates Interleukin-2 in the wound healing process. Furthermore, diseases that involve impaired wound healing, such as diabetes and systemic lupus erythematosus, have been linked to deficiencies in Interleukin-2 or defects Interleukin-2-receptor signaling. The focus of this review is to summarize the current understanding of the role of Interleukin-2 in wound healing, to highlight diseases in which Interleukin-2 and its receptor may contribute to impaired wound healing, and to assess Interleukin-2-modulating approaches as potential therapies to improve wound healing.

Case series: Bladder clot evacuation using a prostate morcellation device.

INTRODUCTION: We sought to provide a technical update on the use of a prostate morcellator device (PMD) to manage organized blood clots of the bladder following laser prostatectomy. METHODS: Herein, we describe our experience in using the Wolf Piranha morcellator in managing organized bladder blood clots supplemented with a retrospective chart review of the patients in whom this procedure was performed. RESULTS: Six patients, all male with a mean age of 75 ± 8.9 years, had organized bladder clots following either holmium laser enucleation or photoselective vaporization of the prostate managed with a PMD. Clots were recognized based on hematuria or urinary retention a median of 3.5 days following the aforementioned procedures. Initial management was attempted with more conservative measures, including a three-way Foley catheter, followed by cystoscopy with an Ellik evacuator, or a glass Tommey syringe. Morcellation times were a mean of 10.2 ± 6.15 minutes (range 2-18). This technique was able to manage clots that were an average of 173.3 ± 115.9 cc in size. The procedure was well-tolerated. No patients experienced intraoperative or morcellator-related complications. CONCLUSIONS: Benign prostatic hypertrophy frequently requires surgical endoscopic management and can be complicated by hematuria and bladder blood clot formation. When these clots become organized, this can lead to urinary retention and the required management, evacuation, may be difficult. The use of a Wolf Piranha PMD is a safe, well-tolerated, and effective in evacuating organized blood clots of the bladder.