Localized PD-1 Blockade in a Mouse Model of Renal Cell Carcinoma.

Herein we report the impact of localized delivery of an anti-mouse PD-1-specific monoclonal antibody (aPD1) on Renca tumors in the resulting T cell responses and changes in broader immune gene expression profiles. Renca is a BALB/c mice syngeneic tumor that has been used to model human renal cell carcinoma In this study, T cell subsets were examined in tumors and draining lymph nodes of mice treated with localized PD-1 with and without the addition of adenosine deaminase (ADA), an enzyme that catabolizes adenosine (ADO), identified as an immune checkpoint in several types of human cancers. The biologics, aPD1, or aPD1 with adenosine deaminase (aPD1/ADA), were formulated with the self-assembling peptides Z15_EAK to enhance retention near the tumor inoculation site. We found that both aPD1 and aPD1/ADA skewed the local immune milieu towards an immune stimulatory phenotype by reducing Tregs, increasing CD8 T cell infiltration, and upregulating IFNÉ£. Analysis of tumor specimens using bulk RNA-Seq confirmed the impact of the localized aPD1 treatment and revealed differential gene expressions elicited by the loco-regional treatment. The effects of ADA and Z15_EAK were limited to tumor growth delay and lymph node enlargement. These results support the notion of expanding the use of locoregional PD-1 blockade in solid tumors.

Emerging role of cytoreductive prostatectomy in patients with metastatic disease.

Traditionally, systemic androgen deprivation therapy (ADT) has been the primary treatment modality in metastatic prostate cancer (mPCa) while treatment of the primary tumor has been reserved for patients with clinically localized disease. Emerging data suggests that treating the primary tumor in patients with metastatic disease may provide a survival benefit. However, these studies are fraught with selection bias towards patients with favorable disease characteristics. Despite these limitations, clinicians are becoming increasingly interested in consolidative treatment of the primary tumor in this setting. Many translational models and observational studies of cytoreduction in mPCa have yielded compelling results, suggesting a potential biological and clinical benefit. While there are no published randomized control trials on cytoreduction in mPCa, the literature regarding safety, feasibility, and potential symptomatic benefit of cytoreductive prostatectomy (CRP) in mPCa supports further investigation. Thus, MEDLINE and PubMed electronic databases were queried for English language articles related to patients with mPCa who underwent radical prostatectomy. Keywords used include: cytoreductive prostatectomy, radical prostatectomy, oligometastatic, mPCa, and oligometastasis. In this review we examine the literature regarding the feasibility of CRP as well as the reported oncologic outcomes, limitations of the literature, and future directions. Since there is currently no level one evidence to support its use, CRP should not be applied outside a clinical trial. A better understanding of the biology driving mPCa, in conjunction with standardization of clinical trials, will help expedite actionable data acquisition that may improve clinical outcomes.

Surgery and hormonal treatment for prostate cancer and sexual function.

Prostate cancer (PC) is one of the most common cancers effecting men today. With earlier detection and improvements in available treatment modalities, there still remains significant morbidity associated with the treatment of PC. Male sexual health and erectile function are greatly impacted by these therapies and remain a concern to PC survivors. This article reviews the current literature on male sexual health following radical prostatectomy (RP) or androgen ablation therapy for PC. Each treatment modality affects male sexual function to an appreciable level, although certain patients have better outcomes if they have preoperative potency, are younger, or have nerve-sparing surgery. There is a delayed recovery up to 2 years seen in erectile function following RP. With androgen deprivation therapy (ADT), attempts can be made at different administration strategies and exercise may possibly play a role in maintaining erectile function. Penile rehabilitation protocols attempt to protect erectile function immediately following therapy through different modalities, although no one approach has been agreed upon.

Feigning acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant genetic defect in heme synthesis. Patients with this illness can have episodic life-threatening attacks characterized by abdominal pain, neurological deficits, and psychiatric symptoms. Feigning this illness has not been reported in the English language literature to date. Here, we report on a patient who presented to the hospital with an acute attack of porphyria requesting opiates. Diligent assessment of extensive prior treatment records revealed thirteen negative tests for AIP.