Endocrine,Sexual Function,and Infertility Side Effects of Immune Checkpoint Inhibitor Therapy for Genitourinary Cancers

Purpose of Review

Immune checkpoint therapy has grown in prominence in the last few decades and is being increasingly utilized in treatment of advanced cancers. Although information on toxicities of these drugs is forthcoming, not much is known regarding the toxicity profile of these drugs from a sexual function standpoint. We undertook the current review to appraise the literature for endocrine/sexual side effects of anti-PD-1/PD-L1 and anti-CTLA-4 therapy.

Recent Findings

Our review included 32 articles and focused primarily on the programmed death (PD) pathway. We found that endocrine side effects after anti-PD-1/PD-L1 therapy are relatively rare, with hypothyroidism (range <?1 to 40%) and hypophysitis (range <?1 to 10%) being the two most common. None of the studies specifically commented on the infertility or sexual side effects of these drugs. However, two studies evaluating biochemical profiles of patients undergoing therapy with ipilimumab (a CTLA-4 inhibitor) or combination therapy (CTLA-4 + PD-1/PD-L1 inhibitors) noted that about <?1 to ~?60% of the patients developed hypogonadotropic hypogonadism. None of the studies provided information regarding clinically meaningful sexual health endpoints such as libido, erectile function assessments, or sexual function-related quality of life.

Summary

Endocrine side effects, although uncommon, are important and unique side effects of immune checkpoint therapy because they are often complex and can be life threatening. While side effects on sexual health may not be life threatening, they are lifestyle limiting. Thus, long-term follow-up, post-marketing surveillance, and future studies will need to elucidate the true rates of endocrine/sexual side effects and the mechanisms underlying them. This will aid in better counseling of the patients, as more of them undergo these novel immune checkpoint inhibitor therapies.

     

The expression profile of p14, p53 and p21 in tumour cells is associated with disease-specific survival and the outcome of postoperative chemotherapy treatment in muscle-invasive bladder cancer

Purpose: We investigated the effects of alterations in the biological markers p14, p53, p21, and p16 in relation to tumour cell proliferation, T-category, N- category, lymphovascular invasion, and the ability to predict prognosis in patients with muscle-invasive bladder cancer (MIBC) treated with cystectomy and, if applicable, chemotherapy.Materials and methods: We prospectively studied patients with urinary bladder cancer pathological stage pT1 to pT4 treated with cystectomy, pelvic lymph node dissection and postoperative chemotherapy. Tissue microarrays from paraffin-embedded cystectomy tumour samples were examined for expression of immunostaining of p14, p53, p21, p16 and Ki-67 in relation to other clinical and pathological factors as well as cancer-specific survival.Results: The median age of the 110 patients was 70 years (range 51-87 years), and 85 (77%) were male. Pathological staging was pT1 to pT2 (organ-confined) in 28 (25%) patients and pT3 to pT4 (non-organ-confined) in 82 (75%) patients. Lymph node metastases were found in 47 patients (43%). P14 expression was more common in tumours with higher T-stages (P?=?0.05). The expression of p14 in p53 negative tumours was associated with a significantly shorter survival time (P=0.003). Independently of p53 expression, p14 expression was associated with an impaired response to chemotherapy (P=0.001). The expression of p21 in p53 negative tumours was associated with significantly decrease levels of tumour cell proliferation detected as Ki-67 expression (P=0.03).Conclusions: The simultaneous expression of the senescence markers involved in the p53-pathway shows a more relevant correlation to the pathological outcome of MIBC than each protein separately. P14 expression in tumours with non-altered (p53-) tumours is associated with poor prognosis. P14 expression is associated with impaired response to chemotherapy. P21 expression is related to decreased tumour cell proliferation.     

Efficacy of Local Treatment in Prostate Cancer Patients with Clinically Pelvic Lymph Node-positive Disease at Initial Diagnosis

Background

There is limited evidence supporting the use of local treatment (LT) for prostate cancer (PCa) patients with clinically pelvic lymph node-positive (cN1) disease.

Alginate-Based Hydrogels and Tubes,as Biological Macromolecule-Based Platforms for Peripheral Nerve Tissue Engineering: A Review

Annals of Biomedical Engineering - Unlike the central nervous system, the peripheral nervous system (PNS) has an inherent capacity to regenerate following injury. However, in the case of large...     

Taurine deficiency damages photoreceptors and retinal ganglion cells in vigabatrin-treated neonatal rats

The anti-epileptic drug vigabatrin induces an irreversible constriction of the visual field, but is still widely used to treat infantile spasms and some forms of epilepsy. We recently reported that vigabatrin-induced cone damage is due to a taurine deficiency. However, optic atrophy and thus retinal ganglion cell degeneration was also reported in children treated for infantile spasms. We here show in neonatal rats treated from postnatal days 4 to 29 that the vigabatrin treatment triggers not only cone photoreceptor damage, disorganisation of the photoreceptor layer and gliosis but also retinal ganglion cell loss. Furthermore, we demonstrate in these neonatal rats that taurine supplementation partially prevents these retinal lesions and in particular the retinal ganglion cell loss. These results provide the first evidence of retinal ganglion cell neuroprotection by taurine. They further confirm that taurine supplementation should be administered with the vigabatrin treatment for infantile spasms or epilepsy.     

The SRI24 multichannel atlas of normal adult human brain structure

This article describes the SRI24 atlas, a new standard reference system of normal human brain anatomy, that was created using template‐free population registration of high‐resolution magnetic resonance images acquired at 3T in a group of 24 normal control subjects. The atlas comprises anatomical channels (T1, T2, and proton density weighted), diffusion‐related channels (fractional anisotropy, mean diffusivity, longitudinal diffusivity, mean diffusion‐weighted image), tissue channels (CSF probability, gray matter probability, white matter probability, tissue labels), and two cortical parcellation maps. The SRI24 atlas enables multichannel atlas‐to‐subject image registration. It is uniquely versatile in that it is equally suited for the two fundamentally different atlas applications: label propagation and spatial normalization. Label propagation, herein demonstrated using diffusion tensor image fiber tracking, is enabled by the increased sharpness of the SRI24 atlas compared with other available atlases. Spatial normalization, herein demonstrated using data from a young–old group comparison study, is enabled by its unbiased average population shape property. For both propagation and normalization, we also report the results of quantitative comparisons with seven other published atlases: Colin27, MNI152, ICBM452 (warp5 and air12), and LPBA40 (SPM5, FLIRT, AIR). Our results suggest that the SRI24 atlas, although based on 3T MR data, allows equally accurate spatial normalization of data acquired at 1.5T as the comparison atlases, all of which are based on 1.5T data. Furthermore, the SRI24 atlas is as suitable for label propagation as the comparison atlases and detailed enough to allow delineation of anatomical structures for this purpose directly in the atlas. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Primary extensive pyomyositis in an immunocompetent patient: case report and literature review

Pyomyositis is a suppurative infection of the skeletal muscle; it mainly occurs in immunocompromised patients or, exceptionally, in immunocompetent patients in tropical or other areas. We present a 24-year-old immunocompetent lady with bilateral thigh myalgia and fever. Upon investigation, extensive multifocal bilateral fluid collections involving the extensor muscles of both thighs were demonstrated. Pus aspirate from the involved muscles proved the presence of Staphylococcus aureus. Incision and drainage of the involved muscles were performed with successful and complete recovery.     

Inhibitory effect of live-attenuated Listeria Monocytogenes-based vaccines expressing MIA gene on malignant melanoma

Listeria monocytogenes(LM),a Gram-positive facultative intracellular bacterium,can be used as an effective exogenous antigen expression vector in tumor-target therapy.But for successful clinical application,it is necessary to construct attenuated LM stain that is safe yet retains the potency of LM based on the full virulent pathogen.In this study,attenuated LM and recombinants of LM expressing melanoma inhibitory activity(MIA) were constructed successfully.The median lethal dose(LD 50) and invasion efficiency of attenuated LM strains were detected.The recombinants were utilized for immunotherapy of animal model of B16F10 melanoma.The level of MIA mRNA expression in tumor tissue was detected by using real-time polymerase chain reaction(PCR) with specific sequence,meanwhile the anti-tumor immune response was assayed by flow cytometric analysis and enzyme-linked immunosorbent spot(ELISPOT) assay.The results showed the toxicity and invasiveness of attenuated LM were decreased as compared with LM,and attenuated LM expressing MIA,especially the double-genes attenuated LM recombinant,could significantly induce anti-tumor immune response and inhibit tumor growth.This study implicates attenuated LM may be a safer and more effective vector for immunotherapy of melanoma.