SUMMARY Some species thrive in captivity but others exhibit extensive psychological and physiological deficits, which can be a challenge to animal husbandry and conservation as well as wild immunology. Here, we investigated whether captivity duration impacted the regulation of a key innate immune response, inflammation, of a common wild bird species, the house sparrow (Passer domesticus). Inflammation is one of the most commonly induced and fast-acting immune responses animals mount upon exposure to a parasite. However, attenuation and resolution of inflammatory responses are partly coordinated by glucocorticoid hormones, hormones that can be disregulated in captivity. Here, we tested whether captivity duration alters corticosterone regulation and hence the inflammatory response by comparing the following responses to lipopolysaccharide (LPS; a Gram-negative bacteria component that induces inflammation) of birds caught wild and injected immediately versus those held for 2 or 4 weeks in standard conditions: (1) the magnitude of leukocyte immune gene expression [the cytokines, interleukin 1β and interleukin 6, and Toll-like receptor 4 (TLR4)], (2) the rate of clearance of endotoxin, and (3) the release of corticosterone (CORT) in response to endotoxin (LPS). We predicted that captivity duration would increase baseline CORT and thus suppress gene expression and endotoxin clearance rate. However, our predictions were not supported: TLR4 expression increased with time in captivity irrespective of LPS, and cytokine expression to LPS was stronger the longer birds remained captive. Baseline CORT was not affected by captivity duration, but CORT release post-LPS occurred only in wild birds. Lastly, sparrows held captive for 4 weeks maintained significantly higher levels of circulating endotoxin than other groups, perhaps due to leakage of microbes from the gut, but exogenous LPS did not increase circulating levels over the time scale samples were collected. Altogether, captivity appears to have induced a hyper-inflammatory state in house sparrows, perhaps due to disregulation of glucocorticoids, natural microflora or both.

Penile cancer is a rare disease in the United States, but rates are increasing, causing concern. Several risk factors have been associated with the disease, including human papillomavirus (HPV) infection. Knowledge of HPV pathogenesis has led to the development of a vaccine, which has proven instrumental in reducing the incidence of female HPV-related cancers, but results in men have yet to be elucidated. Fortunately, rates of vaccination are up-trending in both males and females in the past several years. In addition, targeted therapies are the focus of several ongoing research efforts. Some of these therapeutics are currently in use, while several are in trials. With continued patient education and research, both treatment and prevention of HPV-related pre-malignant lesions and penile cancer will likely diminish.

Purpose:Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) has an incidence of approximately 20%–50%. Studies to date have been composed of mixed treatment cohorts—open, laparoscopic and robotic. The objective of this study is to assess clinicopathological risk factors for intravesical recurrence after RNU for UTUC in a completely minimally invasive cohort.Materials and Methods:We performed a multicenter, retrospective analysis of 485 patients with UTUC without prior or concurrent bladder cancer who underwent robotic or laparoscopic RNU. Patients were selected from an international cohort of 17 institutions across the United States, Europe and Asia. Univariate and multiple Cox regression models were used to identify risk factors for bladder recurrence.Results:A total of 485 (396 robotic, 89 laparoscopic) patients were included in analysis. Overall, 110 (22.7%) of patients developed IVR. The average time to recurrence was 15.2 months (SD 15.5 months). Hypertension was a significant risk factor on multiple regression (HR 1.99, CI 1.06; 3.71, p=0.030). Diagnostic ureteroscopic biopsy incurred a 50% higher chance of developing IVR (HR 1.49, CI 1.00; 2.20, p=0.048). Treatment specific risk factors included positive surgical margins (HR 3.36, CI 1.36; 8.33, p=0.009) and transurethral resection for bladder cuff management (HR 2.73, CI 1.10; 6.76, p=0.031).Conclusions:IVR after minimally invasive RNU for UTUC is a relatively common event. Risk factors include a ureteroscopic biopsy, transurethral resection of the bladder cuff, and positive surgical margins. When possible, avoidance of transurethral resection of the bladder cuff and alternative strategies for obtaining biopsy tissue sample should be considered.

Penile cancer (PeCa) is a rare malignancy with potentially devastating effects. Squamous cell carcinoma is the most common variant with distinct precancerous lesions before development into invasive disease. Involvement of the inguinal lymph nodes is the most important prognostic factor in PeCa, and once disease is present outside the groin, prognosis is poor. Metastatic PeCa is challenging to treat and often requires multidisciplinary approaches in management. Due to its rarity, molecular understanding of the disease continues to be limited with most studies based on small, single center series. Thus far, it appears PeCa has diverse mechanisms of carcinogenesis affecting similar molecular pathways. In this review, we evaluate the current landscape of the molecular carcinogenesis of PeCa and explore ongoing research on potential actionable targets of therapy. The emergence of anti-epidermal growth factor receptor (EGFR) and other immunotherapeutic strategies may improve outcomes for PeCa patients.

No abstract