Clinical utility of mesenchymal stem/stromal cells in regenerative medicine and cellular therapy.

Mesenchymal stem/stromal cells (MSCs) have been carefully examined to have tremendous potential in regenerative medicine. With their immunomodulatory and regenerative properties, MSCs have numerous applications within the clinical sector. MSCs have the properties of multilineage differentiation, paracrine signaling, and can be isolated from various tissues, which makes them a key candidate for applications in numerous organ systems. To accentuate the importance of MSC therapy for a range of clinical indications, this review highlights MSC-specific studies on the musculoskeletal, nervous, cardiovascular, and immune systems where most trials are reported. Furthermore, an updated list of the different types of MSCs used in clinical trials, as well as the key characteristics of each type of MSCs are included. Many of the studies mentioned revolve around the properties of MSC, such as exosome usage and MSC co-cultures with other cell types. It is worth noting that MSC clinical usage is not limited to these four systems, and MSCs continue to be tested to repair, regenerate, or modulate other diseased or injured organ systems. This review provides an updated compilation of MSCs in clinical trials that paves the way for improvement in the field of MSC therapy.

Robotic Radical Cystectomy Outcomes after Intervention for Prostate Cancer.

Introduction and Objectives: We evaluated patients who underwent treatment for prostate cancer and then subsequent robot-assisted radical cystectomy (RARC). Our objective was to understand clinical, pathologic, and survival outcomes in these patients. Materials and Methods: A total of 333 male patients underwent RARC with standard intracorporeal urinary diversion from 2009 to 2019. We evaluated patients who underwent a radical prostatectomy (RP) and either external beam radiation or brachytherapy (XRT) before RARC. These patients were compared with patients who underwent RARC without any prior intervention for or history of prostate cancer (radical cystectomy [RC]). Results: Patients in the RP and XRT groups were found to be older than the RC group (p = 0.0108) and also have a greater Charlson comorbidity index (p < 0.001). There was no difference in estimated blood loss, operative time, and length of stay across all three groups. The RP group had a higher rate of positive margins 31.58% compared with RC and XRT at 8.22% and 10.00%, respectively (p = 0.0036). There was also a higher rate of extravesical disease on final pathology report for the XRT group at 60.00% compared with 37.5% and 36.85% for RC and RP, respectively (p = 0.0056). Overall survival was lowest in the XRT group compared with RP and RC (p > 0.001) with no difference in recurrence-free survival. Conclusion: Patients in the RP group have higher rates of positive margin, whereas patients in the XRT group have higher rates of extravesical disease and overall survival after undergoing a RARC. Careful counseling and attention to these parameters is required in these patient populations.

Ureteral Reimplantation via Robotic Nontransecting Side-to-Side Anastomosis for Distal Ureteral Stricture.

Objective: To describe a novel technique of ureteral reimplantation through robotic nontransecting side-to-side anastomosis. Although the standard approach to ureteroneocystostomy has a high rate of success, it involves transection of the ureter that may impair vascularity and contribute to recurrent strictures. Our method seeks to maximally preserve distal ureteral blood flow that may reduce this risk. Materials and Methods: We retrospectively reviewed a multi-institutional ureteral reconstruction database to identify patients who underwent this operation between 2014 and 2018, analyzing perioperative and postoperative outcomes. Results: Our technique was utilized in 16 patients across three U.S. academic institutions. Median operative time and estimated blood loss were 178 minutes (interquartile range [IQR] 150-204) and 50 mL (IQR 38-100), respectively. The median length of stay was 1 day (IQR 1-2). No intraoperative complications or postoperative complications with Clavien score ≥3 were reported. Postoperatively, 15 of 16 (93.8%) patients reported clinical improvement in flank pain, and all patients who underwent follow-up imaging had radiographic improvement with decrease in hydronephrosis at a median follow-up of 12.5 months. Conclusions: Ureteral reimplantation through a robotic nontransecting side-to-side anastomosis is a feasible and effective operation for distal ureteral stricture that may have advantages over the standard of care transecting ureteroneocystostomy.

The Two-Point Technique for Fluoroscopic-Guided Endoscopic Procedures in Urology: A Validation Study.

Introduction: The widespread use of diagnostic and therapeutic ionizing radiation raises concerns regarding excessive occupational and patient exposure. In this study, we test a novel fluoroscopic technique that has the potential to minimize radiation dose during urologic procedures. Materials and Methods: A prospective evaluation of all patients undergoing endoscopic urologic procedures in our institution was conducted. A "two-point technique (TPT)" is described in which the fluoroscope image intensifier (c-arm) is shifted between caudal and cephalad set points of the operative field. We wished to determine whether patient radiation exposure was lower with TPT than with a non-structured conventional technique, referred to as the cognitive fluoroscopic technique (CFT), in which the manipulation of the c-arm was at the discretion of the user. We obtained all clinical, radiographic, and fluoroscopic data of patients in the study period and used unpaired nonparametric statistical analysis of univariates entered stepwise into a logistic regression model. Results: A total of 106 endoscopic urologic procedures from January 2016 to November 2018 were reviewed. Forty-four (41.5%) cases were performed using TPT and 62 (58.5%) using CFT. The mean fluoroscopy time of TPT vs CFT was 71.1 (±60.8) seconds vs 104.5 (±91.6) seconds, respectively (p = 0.04), and the mean radiation dose on TPT vs CFT was 11.6 (±10.6) mGy vs 20.3 (±24.3) mGy, respectively (p = 0.03). TPT was an independent predictor of reduced operative room (OR) time and fluoro time (p < 0.05), while body mass index, age, and operator were not. Conclusion: The "TPT" helps reducing radiation dose and fluoroscopic time during endoscopic urologic procedures. The TPT is useful to lower radiation exposure to patients and OR staff.

Contemporary Trends in Percutaneous Nephrolithomy Across New York State: A Review of the Statewide Planning and Research Cooperative System.

Introduction and Objectives: Percutaneous nephrolithotomy (PCNL) is a complex multistep surgery that has shown a steady increase in use for the past decade in the United States. We sought to evaluate the trends and factors associated with PCNL usage across New York State (NYS). Our goal was to characterize patient demographics and socioeconomic factors across high-, medium-, and low-volume institutions. Materials and Methods: We searched the NYS, Statewide Planning and Research Cooperative System (SPARCS) database from 2006 to 2014 using ICD-9 Procedure Codes 55.04 (percutaneous nephrostomy with fragmentation) for all hospital discharges. Patient demographics including age, gender, race, insurance status, and length of hospital stay were obtained. We characterized each hospital as a low-, medium-, or high-volume center by year. Patient and hospital demographics were compared and reported using chi-square analysis and Student's t-test for categorical and continuous variables, respectively, with statistical significance as a p-value of <0.05. Results: We identified a total of 4576 procedures performed from 2006 to 2014 at a total of 77 hospitals in NYS (Table 1). Total PCNL volume performed across all NYS hospitals increased in the past decade, with the greatest number of procedures performed in 2012 to 2013. Low-volume institutions were more likely to provide care to minority populations (21.4% vs 17.3%, p < 0.001) and those with Medicaid (25.5% vs 21.5%, p < 0.001). High-volume institutions provided care to patients with private insurance (42.1% vs 34.0%, p < 0.001) and had a shorter length of stay (3.3 days vs 4.1 days, p < 0.001). Conclusion: Our data provide insight into the patient demographics of those treated at high-, medium-, and low-volume hospitals for PCNL across NYS. Significant differences in race, insurance status, and length of stay were noted between low- and high-volume institutions, indicating that racial and socioeconomic factors play a role in access to care at high-volume centers.

Conservative Management of a Pyelovenous Fistula After a Renal Gunshot Wound.

Background: We report the diagnosis and management of a pyelovenous fistula that was detected 5 days after a renal gunshot wound (GSW). Case Presentation: A 16-year-old boy presented to the trauma center with a single GSW to the right flank. CT scan revealed a shattered right kidney with active contrast extravasation and ureteral discontinuity, metal fragments in the L1 vertebra, and a bullet lodged in the upper pole of the left kidney. The patient was taken for emergent exploratory laparotomy. A right nephrectomy was performed. A left retrograde pyelogram demonstrated an intact collecting system. A left Double-J stent was placed to protect against delayed thermal injury. Repeat pyelogram on postoperative day 5 revealed a pyelovenous fistula and a stent was left in place. At 6 weeks, interval pyelogram showed complete resolution of the pyelovenous fistula and the stent was removed. At 6 months the patient was asymptomatic and normotensive with an unremarkable left kidney on ultrasonography. Conclusion: Pyelovenous fistula is a rare complication of a retained bullet in the kidney. Conservative management with ureteral stenting was effective in resolving the fistula.

Metastatic Colorectal Adenocarcinoma in a Bifid Ureter.

Background: Secondary malignancies of the ureter are uncommon. We report the diagnosis and management of metastatic colon cancer to the bifurcation of a bifid ureter. Case Presentation: A 59-year-old man presented with diffuse metastasis with right hydronephrosis in both renal moieties of a partially duplicated system and an enhancing lesion within the proximal common ureter. Ureteral biopsy was positive for colorectal adenocarcinoma. The patient was subsequently started on palliative chemoradiation. Conclusion: The ureter is a rare location for hematogenous/lymphatic metastases. When a ureteral mass is present on imaging, ureteroscopy should be performed to characterize the extent of tumor and to rule out secondary malignancy.

Device Malfunctions and Complications Associated with Benign Prostatic Hyperplasia Surgery: Review of the Manufacturer and User Facility Device Experience Database.

Introduction and Objectives: Multiple surgical therapies for benign prostatic hyperplasia (BPH) have been developed to decrease complications and increase provider efficiency. We investigated contemporary BPH treatment device-related adverse events by searching a publicly available database. Materials and Methods: The Manufacturer and User Facility Device Experience (MAUDE) database was queried for contemporary BPH treatments. All devices were evaluated for malfunction, patient complications, and manufacturer review. The MAUDE adverse event classification system was used to standardize complications. Univariate analysis was performed to identify associations between BPH devices and adverse events. Results: A total of 2567 reports were identified: transurethral resection of the prostate (TURP) 197 (7.67%), holmium laser enucleation of the prostate (HoLEP) 39 (1.52%), GreenLight™ 2315 (90.2%), and UroLift® 16 (0.62%). The most common deviations for each modality included cutting loop detachment during TURP 116 (58.9%), morcellator dysfunction for HoLEP 23 (58.9%), tip fracture/detachment for GreenLight (68.8%), and failure to deploy during UroLift 10 (62.5%). Only 18 (0.7%) patients required medical/surgical management (MAUDE II-IV) due to a device complication. No significant relationship was seen between each modality and complications; however, morcellator use (27.8%) was observed in higher grade complications. Manufacturer review occurred in 61.7% of cases, with 41.3% of reviewed cases finding the operator the cause of the malfunction. Conclusion: Each BPH modality investigated had minimal patient harm with over 99% of patients experiencing no complication after device malfunction. Of note, great care should be taken with morcellator use during HoLEP as it had the greatest number of MAUDE II to IV complications among all devices. Manufacturer review revealed that over 40% of cases were due to misuse by the user. Therefore, urologists should select the modalities they are most familiar with to decrease patient harm and prevent device malfunctions.

Detection of lymph node metastases in penile cancer.

Penile cancer (PC) is a relatively rare malignancy in the United States (US) but a greater concern in developing nations. Lymph node imaging remains critical to the staging and treatment of this disease as metastases develop in a predictable, anatomic fashion. Early surgical intervention remains a mainstay in treatment and imaging often aids in decision making. This review highlights the indications for imaging in both low-stage and advanced disease. Furthermore, we discuss the benefits and limitations of currently available imaging for staging of inguinal and pelvic lymph nodes in PC and novel modalities in development.

Penile and Scrotal Strangulation due to Metal Rings: Case Reports and a Review of the Literature.

Penile and scrotal entrapment from a metal ring placed at the base of the penis is a rare, but important clinical dilemma encountered in urology. Emergent presentation to the urologist, after ring placement far longer than safely practiced, risks ischemic and permanent injury to penile, scrotal, and intrascrotal structures. Treating urologists should be aware of the prevalence of metal ring use, their potential complications, and the surgical approach to their safe removal. We present two patients who were identified at our institution with strangulating injuries of retained penile rings. The first patient was a healthy, 43-year-old male with a metal ring retained for 24 hours that was safely removed with industrial bolt cutters. The second patient, a 74-year-old male, died as a result of sepsis from injuries secondary to penoscrotal ischemia after >48 hour ring retention despite prompt removal at emergent presentation. Although rare, sexual practices may include the use of penoscrotal rings. When retained, ischemic injury and edema may lead to strangulation. Emergent removal may require industrial equipment that is not within the confines of normal operating room tools. Tissue injury may be severe and sepsis life-threatening, even after ring removal.

Prostate Cancer Screening Trends After United States Preventative Services Task Force Guidelines in an Underserved Population.

Purpose: Prostate cancer screening is a controversial topic. We examined trends in Prostate Specific Antigen (PSA) testing in an underserved population before and after the United States Preventative Services Task Force (USPSTF) recommendation against screening. Methods: Data were collected on all PSA and cholesterol screening tests from 2008 to 2014. We examined the trend of these tests and prostate biopsies while comparing this data to lipid panel data to adjust for changes in patient population. Results: A decrease in PSA screening was observed from 2010 through 2014, with the greatest decline in 2012. The age group most affected was patients aged 55-69 years. The amount of prostate biopsies during this period decreased as well. Conclusions: Decreased rates of PSA screening were observed in our urban hospital population that preceded the publication of the USPSTF guidelines. The incidence of prostate biopsies decreased in this timeframe. It now remains to be demonstrated whether decreased PSA screening rates impact the diagnosis of and ultimately the survival from prostate cancer.

Percutaneous and Endoscopic Management of Nephrolithiasis in a Patient with Five Native Ureters (Trifid Right and Bifid Left Collecting System).

Triplication of the ureter is a rare urologic finding that has been well described in the literature. Patients can present with urinary tract infections, incontinence, and calculi. We present the case of a patient with extensive stone burden with right trifid and left bifid collecting systems. Stone management was performed with a multimodal approach using a combination of endoscopic and percutaneous approaches. Our systematic and staged approach highlights a method for efficacious stone treatment in a complex endourologic case.

Device-Related Adverse Events During Percutaneous Nephrolithotomy: Review of the Manufacturer and User Facility Device Experience Database.

INTRODUCTION AND OBJECTIVES: Percutaneous nephrolithotomy (PCNL) is an established technique for removal of large stones from the upper urinary tract. It is a complex multistep procedure requiring several classes of instruments that are subject to operator misuse and device malfunction. We report device-related adverse events during PCNL from the Manufacturer and User Facility Device Experience (MAUDE) database using a recently developed standardized classification system. MATERIALS AND METHODS: The MAUDE database was queried for "percutaneous nephrolithotomy" from 2006 to 2016. The circumstances and patient complications associated with classes of devices used during PCNL were identified. We then utilized a novel MAUDE classification system to categorize clinical events. Logistic regression analysis was performed to identify associations between device classes and severe adverse events. RESULTS: A total of 218 device-related events were reported. The most common classes included: lithotripter 53 (24.3%), wires 43 (19.7%), balloon dilators 30 (13.8%), and occlusion balloons 28 (12.8%). Reported patient complications included need for a second procedure 12 (28.6%), bleeding 8 (19.0%), retained fragments 7 (16.7%), prolonged procedure 4 (9.5%), ureteral injury 2 (4.8%), and conversion to an open procedure 3 (7.1%). Using a MAUDE classification system, 176 complications (81%) were Level I (mild/none), 26 (12%) were Level II (moderate), 15 (7%) were Level III (severe), and 1 (0.5%) was Level IV (life threatening). On univariate analysis, balloon dilators had the highest risk of Level II-IV complications compared with the other device classes [odds ratio: 4.33, confidence interval: 1.978, 9.493, p < 0.001]. The device was evaluated by the manufacturer in 93 (42.7%) cases, with 54.8% of reviewed cases listing the source of malfunction as misuse by the operator. CONCLUSIONS: PCNL is subject to a wide range of device-related adverse events. A MAUDE classification system is useful for standardized, clinically-relevant reporting of events. Our findings highlight the importance of proper surgeon training with devices to maximize efficiency and decrease harm.

Hyper IgE Syndrome and Renal Cell Carcinoma.

Hyper IgE Syndrome (HIES) is an immunodeficiency disorder characterized by increased serum levels of IgE, eczema, and recurrent cutaneous and pulmonary infections. In this report, we present, to our knowledge, the first documented case of renal cell carcinoma (RCC) found in a patient with HIES. The patient received infectious disease clearance prior to obtaining a partial nephrectomy which revealed clear cell histology. Both HIES and RCC have an immunological basis for their pathophysiology and may involve common pathways. Further studies may provide insight into any possible link and clinicians should be mindful of immunocompromised patients who present with risk factors for genitourinary malignancy.

Comparative Analysis of Smoking as a Risk Factor among Renal Cell Carcinoma Histological Subtypes.

PURPOSE: Smoking is the best established modifiable risk factor for renal cell carcinoma. However, the risks of individual renal cell carcinoma histological subtypes are unknown. Therefore, we investigated the relationship between smoking and renal cell carcinoma subtype. MATERIALS AND METHODS: Cigarette smoking data were prospectively collected from 816 consecutive patients with nonfamilial renal cell carcinoma (705) or benign pathology (111) undergoing nephrectomy at a single National Comprehensive Cancer Network® cancer center, and were retrospectively tested for an association with histological diagnosis on univariable and propensity adjusted analyses. RESULTS: Smoking was reported by 51% of patients, including 21% active smokers and 30% former smokers. Active smoking was more common with clear cell (23%) or papillary (26%) renal cell carcinoma than benign histology (14%, p <0.05 each), yet strikingly less common with chromophobe renal cell carcinoma (6%, p <0.05 vs clear cell or papillary). Any smoking history (active or former) was also relatively uncommon with chromophobe (26%) vs clear cell (53%, p = 0.003) or papillary (58%, p = 0.001) histology. Smoking extent based on mean pack-years was significantly greater with clear cell (15.3 mean pack-years) or papillary (15.2 mean pack-years) renal cell carcinoma but not chromophobe renal cell carcinoma (9.4 mean pack-years) compared to benign histology (9.4 mean pack-years, p ≤0.05, p <0.05, p = 1.0, respectively). On propensity analyses adjusting for multiple variables, clear cell (OR 2.2, p <0.05) and papillary (OR 2.4, p <0.05) histologies but not chromophobe histology remained independently associated with active smoking. CONCLUSIONS: Traditional understanding of smoking as a renal cell carcinoma risk factor applies to clear cell and papillary renal cell carcinoma but not the chromophobe subtype. These findings underscore distinct carcinogenic mechanisms underlying the various renal cell carcinoma subtypes.

Localization and quantification of intact, undamaged right-handed double-stranded B-DNA, and denatured single-stranded DNA in normal human epidermis and its effects on apoptosis and terminal differentiation (denucleation).

Quantification of two types of nucleic acids [double-stranded (ds-) and single-stranded (ss-) DNA] was performed to understand the distribution of DNA within the epidermal strata and to examine the effects of DNA structure on gene expression, viz., apoptosis and terminal differentiation. In addition, we examined the precise starting point of cell death within the epidermis (suprabasal layer); examined how DNA structure affects gene expression of melanocytes; and characterized the "transitional cells" located between the stratum granulosum and stratum corneum, viz., epidermal phase transition zone (EPTZ). Ultrasensitive anti-DNA antibody probes (ds-DNA, ss-DNA), the Feulgen reaction, histological stains (morphological characterization) and the terminal deoxyribonucleotidyl transferase (TUNEL) assay (apoptosis) were used to characterize cell death in normal human epidermis. This study characterized, for the first time, the deterioration of right-handed ds-B-DNA and the increase in denatured ss-DNA during epidermal maturation. For the first time, this approach also allowed for the quantitative and qualitative characterization of DNA content and structure in all epidermal strata, using anti-ds-B-DNA and anti-ss-DNA antibodies. In order to improve the retention and quality of DNA, a novel histotechnological processing procedure was used. The results indicate that the largest decline in DNA occurred within the stratum granulosum, followed by the EPTZ, and the stratum spinosum. Not all epidermal nuclei lost DNA, indicating two differentiating keratinocyte pathways, viz., apoptotic and non-apoptotic. Both pathways united in the stratum granulosum. These results suggest that keratinocyte terminal differentiation and apoptosis are distinct cellular events, cell death begins earlier than expected, and molecular epidermal events take place in a gradual and orderly manner within keratinocytes. During maturation, ds-B-DNA decreases as ss-DNA increases. Therefore, during differentiation of keratinocytes, both DNA content and DNA structure are altered.