Penile Strangulation: Analysis of Postextrication Follow-Up, Sequelae, and a Review of Literature.

Numerous case reports exist on penile strangulation injuries and extrication methods; however, the care and long-term consequences of penile strangulation injuries have been under-reported. Our aim is to investigate the long-term outcomes and sequalae following penile strangulation injuries. The PubMed Medline database was searched using the keyword string "penile strangulation," "penis strangulation," and "constriction" for all studies reporting outcomes of published penile strangulation injuries. Articles were evaluated for follow-up after strangulation injury, strangulating agent, extricating agent, and sequelae of injury. Fifty-six studies resulted with reports of 100 cases of penile strangulation and extrication from January 2000 to December 2019. The mean patient age was 41 (range: 3-86) years. Twenty-four (24/100) cases reported sequalae following extrication. Follow-up ranged from 2 weeks to 7 years with median follow-up time in the 7- to 12-month grouping. Metal rings comprised 36% (36/100) of strangulation agents and 50% of reported incidents were attributed to sexual activity. To our knowledge, this is the only study focusing on long-term outcomes after penile strangulation. This review provides a summary of 56 studies that document penile strangulation injuries over the last 20 years. Although a wide array of penile strangulation injuries have been documented in the literature, reports lack secondary management and long-term outcomes after removal of the strangulation device. We recommend that providers report long-term penile strangulation outcomes for future urologic evaluations after extrication.

Pilot Study of the Effects of Paced Breathing on Measures of Convergent and Divergent Thinking.

BACKGROUND: The ability of the autonomic nervous system's stress response to impair aspects of cognitive flexibility is known. However, the ability to modulate the sympathetic response and improve these cognitive impairments via nonpharmacological intervention, such as paced breathing (PB), requires further investigation. OBJECTIVE: To better elucidate the effects of PB on cognition. METHOD: We employed a PB protocol in a total of 52 healthy men and women and measured performance on convergent and divergent cognitive tasks, perceived stress, and physiological measures (eg, blood pressure, heart rate). Participants attended two experimental sessions consisting of either PB or normal breathing followed by cognitive assessments including convergent (compound remote associate, anagram) and divergent (alternate use, fluency) tasks. Experiment 2 consisted of more difficult versions of cognitive tasks compared with Experiment 1. RESULTS: In Experiment 1, PB significantly reduced the female participants' systolic and diastolic blood pressure immediately after the breathing protocol without affecting their cognition. In Experiment 2, PB significantly reduced perceived stress immediately after the breathing protocol, regardless of sex. There was no effect on cognition in Experiment 2, but a correlation was observed between perceived stress change and anagram number solved change. CONCLUSION: While PB modulates sympathetic activity in females, there was a lack of improvement in cognitive flexibility performance. At least for a single trial of PB, cognitive flexibility did not improve.

Detection of PD-L1-Expressing Myeloid Cell Clusters in the Hyaluronan-Enriched Stroma in Tumor Tissue and Tumor-Draining Lymph Nodes.

Expression of the transmembrane protein PD-L1 is frequently upregulated in cancer. Because PD-L1-expressing cells can induce apoptosis or anergy of T lymphocytes through binding to the PD1 receptor, the PD-L1-mediated inhibition of activated PD1+ T cells is considered a major pathway for tumor immune escape. However, the mechanisms that regulate the expression of PD-L1 in the tumor microenvironment are not fully understood. Analysis of organotypic tumor tissue slice cultures, obtained from mice with implanted syngeneic tumors (MBT2 bladder tumors in C3H mice, Renca kidney, and CT26 colon tumors in BALB/c mice), as well as from patients with cancer, revealed that tumor-associated hyaluronan (HA) supports the development of immunosuppressive PD-L1+ macrophages. Using genetically modified tumor cells, we identified epithelial tumor cells and cancer-associated mesenchymal fibroblast-like cells as a major source of HA in the tumor microenvironment. These HA-producing tumor cells, and particularly the vimentin-positive fibroblast-like cells of bone marrow origin, directly interact with tumor-recruited myeloid cells to form large stromal congregates/clusters that are highly enriched for both HA and PD-L1. Furthermore, similar cell clusters composed of HA-producing fibroblast-like cells and PD-L1+ macrophages were detected in tumor-draining, but not in distant, lymph nodes. Collectively, our findings indicate that the formation of multiple large HA-enriched stromal clusters that support the development of PD-L1-expressing APCs in the tumor microenvironment and draining lymph nodes could contribute to the immune escape and resistance to immunotherapy in cancer.

Impact of hospital transfer on testicular torsion outcomes: A systematic review and meta-analysis.

INTRODUCTION: Testicular torsion is an emergent condition requiring prompt treatment. Previous studies have suggested transfer of pediatric testicular torsion cases may be detrimental to patient outcomes. Findings have not reached statistical significance. No study has quantitatively analyzed all literature reporting outcomes for transferred torsion patients. The aim of this study was to elucidate the impact of hospital transfer on pediatric testicular torsion outcomes through a systematic review and meta-analysis. METHODS: A predefined study protocol registered with PROSPERO was developed according to PRISMA. A comprehensive literature review of articles investigating outcomes for pediatric testicular torsion for transferred and non-transferred (treated "directly" at presentation institution) patients with orchiectomy as the primary outcome was conducted by systematically searching PubMed and Embase. Potential studies were screened against a predefined study protocol. Meta-analysis using a random effects model with transferred status as the "intervention" was performed using Review Manager 5.3. RESULTS: Of 18 eligible studies, 9 retrospective studies comprised of 2564 patients (532 transferred and 2032 direct) were suitable for quantitative analysis. Main analysis showed transfer status does not have a significant effect on torsion outcomes (RR 0.96 [95% CI 0.78-1.17]; I2 = 44%). Subgroup analysis for torsion patients presenting within 24 h of symptom onset shows patients who are transferred to another facility for management are more likely to undergo orchiectomy than those treated at their presenting institution (RR 0.35 [95% CI 0.24-0.51]; I2 = 4%). CONCLUSIONS: In this meta-analysis, hospital transfer does not affect orchiectomy rate in pediatric patients with testicular torsion when pooling data from all presentation timeframes. Subgroup analysis of patients presenting with testicular torsion in an acute setting (<24 h of symptom onset) suggests the delay associated with hospital transfer has a deleterious effect on testicular viability.

Hyal2 Expression in Tumor-Associated Myeloid Cells Mediates Cancer-Related Inflammation in Bladder Cancer.

The increased presence of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) in tumor tissue has been extensively reported. However, their role in the regulation of hyaluronan (HA) metabolism in the tumor microenvironment has not been established. Here we describe a novel function of tumor-associated myeloid cells related to the enhanced breakdown of extracellular HA in human bladder cancer tissue, leading to the accumulation of small HA fragments with molecular weight (MW) <20 kDa. Increased fragmentation of extracellular HA and accumulation of low molecular weight HA (LMW-HA) in tumor tissue was associated with elevated production of multiple inflammatory cytokines, chemokines, and angiogenic factors. The fragmentation of HA by myeloid cells was mediated by the membrane-bound enzyme hyaluronidase 2 (Hyal2). Increased numbers of Hyal2+CD11b+ myeloid cells were detected in the tumor tissue as well as in the peripheral blood of patients with bladder cancer. Coexpression of CD33 suggested that these cells belong to monocytic myeloid-derived suppressor cells. The HA-degrading function of Hyal2-expressing MDSCs could be enhanced by exposure to tumor-conditioned medium, and IL1ß was identified as one of the factors involved in the stimulation of Hyal2 activity. CD44-mediated signaling played an important role in the regulation of HA-degrading activity of Hyal2-expressing myeloid cells, as the engagement of CD44 receptor with specific mAb triggered translocation of Hyal2 enzyme to the cellular surface and stimulated secretion of IL1ß. Taken together, this work identifies Hyal2-expressing tumor-associated myeloid cells as key players in the accumulation of LMW-HA in the tumor microenvironment and cancer-related inflammation and angiogenesis. SIGNIFICANCE: This study identifies Hyal2-expressing tumor-associated myeloid cells of monocyte-macrophage lineage as contributors to hyaluronan degradation in bladder cancer tissue, leading to accumulation of inflammatory and proangiogenic low molecular weight hyaluronan fragments.

Robot-Assisted Laparoscopic Resection of the Mesonephric Duct Remnant in a Patient with Zinner Syndrome.

Introduction: A 17-year-old male with Zinner syndrome, a right seminal vesicle cyst, and a solitary left kidney presented with chronic pelvic pain. Previous surgeons had attempted robot-assisted laparoscopic seminal vesicle cyst aspiration and transurethral resection of the ejaculatory duct. Neither surgery provided sustained symptom relief. Abdominal and pelvic MRI showed a cystic structure lodged between the prostate and bladder. The right seminal vesicle, kidney, and ureter were not observed. Materials and Methods: A robot-assisted laparoscopic seminal vesiculectomy was planned. Dissection distal to the right vas deferens and between the bladder neck and prostate revealed a cystic seminal vesicle-like structure. Attached to this was a tubular structure coursing deep to the vas deferens from the right renal fossa. This was presumed to be a dysplastic ureter. The dysplastic ureter was transected from the seminal vesicle and the seminal vesicle was marsupialized to the deep pelvis. Proximally, the dysplastic ureter was transected and left open. Results: Histologic assessment of the specimen revealed an ∼12.1 cm tubular mesonephric remnant. The postoperative course was uncomplicated. At 6 months follow-up, the patient remains free of symptoms with preserved ejaculatory volume. Conclusions: Mesonephric duct abnormalities and symptoms present on a spectrum. We present a safe and effective resection of a mesonephric duct remnant from a 17-year-old male with Zinner syndrome. A robotic approach localized to the right allowed for excellent observation without compromising left-sided genitourinary anatomy. In males presenting with renal agenesis and pelvic symptoms, clinicians should be suspicious of Zinner syndrome and other mesonephric abnormalities.

Lessons from rodent gastric bypass model of enteric hyperoxaluria.

PURPOSE OF REVIEW: The aim of the article is to review studies on bone health and oxalate metabolism/therapeutics in the obese rodent model of Roux-en-Y gastric bypass (RYGB) and examine pathways to decrease procedural morbidity. RECENT FINDINGS: Compared with controls, RYGB rodents have up to 40-fold more fat in their stool (steatorrhea) which positively correlates to increased urinary oxalate. These unabsorbed intestinal fatty acids bind calcium and prevent gut calcium oxalate formation, increasing soluble luminal oxalate availability and absorption (enteric hyperoxaluria). When intraluminal fecal fat exceeded about 175 mg/24 h in our model, more paracellular and transcellular oxalate transport across the distal colon occurred. Increasing dietary calcium and colonization with Oxalobacter formigenes reduced hyperoxaluria, whereas vitamin B6 supplementation did not. RYGB animals, when severely calcium deficient, had bone mineral density loss that could not be rescued with vitamin D supplementation. SUMMARY: The findings of hyperoxaluria, steatorrhea, and decreased bone mineral density are seen in both human and rodent RYGB. Our model suggests that a low-fat, low-oxalate diet combined with calcium supplementation can decrease urinary oxalate and improve skeletal bone health. Our model is a useful tool to study renal and bone RYGB effects. Studies of longer duration are required to further evaluate mechanisms of disease and durability of therapeutics.

Immunotherapy for stone disease.

PURPOSE OF REVIEW: In addition to traditional risk factors such as low urine volume or hypercalciuria, emerging data suggest that calcium oxalate (CaOx), one of the most common mineral complexes in the urine, elicits a strong immunologic response. This review highlights those studies and projects how future therapies may be directed for kidney stone prevention. RECENT FINDINGS: Over the last 2 years, several groups have studied the response of the immune system to CaOx crystals using cell culture and animal models. Dominguez et al. found that CaOx crystals were recognized by monocytes through an lipopolysaccharide-mediated mechanism, leading to M1 'inflammatory' macrophage phenotype. Patel et al. proposed excessive oxalate-mediated reactive oxygen species within macrophage mitochondria may impair their ability to properly clear stones. Two other groups developed mouse models (an androgen receptor knock-out and an overexpression of Sirtuin 3 protein) and demonstrated increased renal anti-inflammatory macrophage differentiation and decreased CaOx deposition in experimental compared with controls. Anders et al. fed hyperoxaluric mice 1,3-butanediol, which blocks an inflammatory form of cell death called NLRP3 inflammasome and found less intrarenal oxidative damage and higher anti-inflammatory renal infiltrates in experimentals. Finally, monocytes exposed to CaOx crystals followed by hydroxyapatite had reduced inflammatory cytokine and chemokine production compared with those without hydroxyapatite, suggesting that Randall's plaque may play a role in dampening M1-mediatiated CaOx inflammation. SUMMARY: By modulating the immune response, immunotherapy could provide the means to prevent stone recurrences in certain individuals. The promotion of M2 over M1 macrophages and inhibition of inflammation could prevent the cascade that leads to CaOx nucleation. Future therapies may target the ability of macrophages to degrade CaOx crystals to prevent stones.

Pediatric Robot-Assisted Laparoscopic and Ureteroscopic Ureterolithotomy and Ureteroplasty.

Background: Pediatric urolithiasis may coexist with congenital urinary tract abnormalities, complicating conventional methods of stone treatment. Here, we present an effective case of robot-assisted laparoscopy and simultaneous ureteropyeloscopy for the definitive management of pediatric urolithiasis complicated by a congenital ureteral stricture. Case Presentation: A 3-year-old girl presented to clinic with an outside noncontrast CT scan showing two 6-7 mm nonobstructing calculi in a mildly distended upper pole moiety of a duplex left kidney. Ureteral duplication status was unclear. The patient had suffered multiple febrile urinary tract infections throughout her life. Retrograde ureteropyelogram showed a stenotic waist in the upper pole ureter just proximal to the duplex ureteral convergence, and flexible ureteroscopy confirmed a congenital ureteral stricture. Simultaneous robot-assisted laparoscopic and ureteroscopic ureterolithotomy and ureteroplasty were offered and performed using a 3-armed robotic approach. The precise location of the stricture was identified robotically with simultaneous left ureteroscopy. A medial 1.5 cm longitudinal ureterotomy was made through the ureteral stricture to facilitate upper moiety ureterorenoscopy. The calculi were visualized in the upper moiety and retrieved in whole using a stone basket. The calculi were passed via the ureterotomy to the robotic instruments intraperitoneally. The longitudinal ureterotomy was closed transversely. A ureteral stent was placed, and indocyanine green was administered intravenously to confirm good perfusion of the ureteroplasty segment via fluorescence imaging. The stent was removed at 4 weeks. Retrograde ureterography and flexible ureteroscopy revealed complete patency of the anastomosis. At 11 months, the upper pole moiety remained decompressed on ultrasonography. The patient has remained off antibiotic prophylaxis without further infection. Conclusion: Robot-assisted approaches can be primary or adjunct tools in the definitive treatment of pediatric urolithiasis with concomitant urinary tract abnormalities.