Updates in the management of cancer therapy-related hypertension.

PURPOSE OF REVIEW: To provide a comprehensive review of hypertension among patients with cancer. Several cancer therapies cause hypertension which has resulted in a growing and vulnerable population of patients with difficult to control hypertension which has significant downstream effects. RECENT FINDINGS: Hypertension affects up to 50% of cancer patients and higher comorbidity when compared to the general population. Many anticancer therapies can cause hypertension through their treatment effect. Antihypertensive treatment is crucial given cardiovascular mortality is a leading cause of death among cancer patients. It is already known that hypertension is poorly controlled in the general population, and there are additional challenges in management among patients with cancer. Patients with cancer suffer from multimorbidity, are on multiple medications creating concern for drug interactions, and often have blood pressure lability, which can worsen clinical inertia among patients and their providers. It is crucial to effectively treat hypertension in cancer patients to mitigate downstream adverse cardiovascular events. SUMMARY: In recent years, there have been significant changes in management guidelines of hypertension and simultaneously as influx of new cancer therapeutics. We provide an update on hypertension treatment among patients with cancer on different chemotherapeutic agents.

Anomalous right coronary artery from the main pulmonary artery (ARCAPA): Incidental finding in an asymptomatic septuagenarian.

Anomalous right coronary artery (RCA) from the main pulmonary artery (ARCAPA) is a rare finding. Clinical presentations range from asymptomatic to sudden death. We present the case of ARCAPA in a septuagenarian initially suspected on a screening chest computed tomography (CT) and later confirmed on cardiac CT. A summary of important points related to this entity is also discussed.

Involvement of Rho-Associated Coiled-Coil Containing Kinase (ROCK) in BCR-ABL1 Tyrosine Kinase Inhibitor Cardiovascular Toxicity.

Background: Second- and third-generation BCR-ABL1 tyrosine kinase inhibitors (TKIs) are associated with cardiovascular adverse events (CVAEs) in patients with Philadelphia chromosome-positive (Ph+) leukemia. Objectives: We hypothesized that second- and third-generation BCR-ABL1 TKIs may cause CVAEs through the activation of Rho-associated coiled-coil containing kinase (ROCK). Methods: Peripheral blood mononuclear cells from 53 Ph+ patients on TKIs and 15 control patients without Ph+ leukemia were assessed for ROCK activity through capillary electrophoresis (median follow-up = 26 months [Q1-Q3: 5-37 months]). We also investigated the effects of TKIs and ROCK on endothelial dysfunction in vitro, which could contribute to CVAEs. Results: Patients receiving second- and third-generation TKIs had 1.6-fold greater ROCK activity compared with patients receiving imatinib and control patients. Elevated ROCK activity was associated with an increased incidence of CVAEs in Ph+ leukemia patients. In endothelial cells in vitro, we found that dasatinib and ponatinib treatment led to changes in actin intensity and endothelial permeability, which can be reversed by pharmacologic inhibition of ROCK. Ponatinib led to decreased cell proliferation, but this was not accompanied by senescence. Dasatinib and ponatinib treatment led to phosphor-inhibition of endothelial nitric oxide synthase and decreased nitric oxide production. ROCK inhibition reversed endothelial permeability and endothelial nitric oxide synthase-related endothelial dysfunction. Imatinib and nilotinib induce phosphorylation of p190RhoGAP. Conclusions: Our findings suggest ROCK activity may be a prognostic indicator of CVAEs in patients receiving BCR-ABL1 TKIs. With further study, ROCK inhibition may be a promising approach to reduce the incidence of CVAEs associated with second- and third-generation BCR-ABL1 TKIs.

Imaging Cardiac Masses in Patients with Cancer.

BACKGROUND: Cardiac tumors are rare and the majority are from a primary source outside of the heart. Most are found, incidentally, with echocardiography but often additional cardiac imaging is needed to refine the differential diagnosis. For this purpose, cardiac magnetic resonance imaging (MRI) and to a lesser extent cardiac computed tomography (CT) or 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) are useful imaging modalities to better characterize a cardiac tumor and determine the likelihood of a neoplastic versus non-neoplastic origin. Cardiac CT may be useful to evaluate the effect of treatment while using 18F-FDG PET/CT to evaluate cardiac masses is under-studied but may be useful in patients who are already having a scan performed for oncologic reasons. It is through understanding the clinical context of a newly discovered cardiac mass, knowledge of the typical locations of various cardiac tumor types, combined with imaging techniques that avoid ionizing radiation that yield the greatest confidence in the noninvasive diagnosis of a cardiac mass.

Statin use and risk of prostate cancer biochemical recurrence after radical prostatectomy.

BACKGROUND: Multiple studies have investigated the role of statins in prostate cancer (CaP), the leading cause of cancer related death in men. Retrospective cohort studies investigating the correlation between statin use and biochemical recurrence free (BCRF) survival in men with CaP have been inconclusive. OBJECTIVES: In the largest reported surgical cohort to date, we investigated the effect of statin therapy on BCRF and overall survival in patients with CaP who have undergone radical prostatectomy (RP). PATIENTS AND METHODS: We performed a retrospective analysis of men (n = 3,088) participating in the NCI funded Specialized Program of Research Excellence (SPORE) in CaP at Northwestern University (NM) in Chicago, Illinois. Patients were treated with RP between 2002 and 2015. Patients in the statin users group received treatment within 2 years prior to or subsequent to RP. Wilcoxon rank-sum and Fisher's exact tests were used to compare age, race, Gleason score, clinical staging, and pathological stage between statin users and nonstatin users. RESULTS: The analysis identified 1,222 statin users and 1,865 nonusers (mean age 71 years, 92% Caucasian). After a median follow-up time of 49.0 months, the 5-year BCRF survival rate was 93.3% (95% confidence interval [CI]: 91.9-94.8%) among statin users and 88.6% (95% CI: 87.1%-90%) among nonusers (log-rank P< 0.001). After 10 years, the progression-free survival (PFS) was 91.7% (95% CI: 90.1%-93.3%) among statin users and 86.5% (95% CI: 84.4%-88.2%) among nonusers (log-rank P< 0.001). CONCLUSIONS: Extended follow-up data in this large surgical cohort show statin use improves BCRF but not overall survival in RP patients.

Influence of breast reconstruction on technical aspects of echocardiographic image acquisition compared with physician-assessed image quality.

INTRODUCTION: Assessment of cardiac function after treatment for breast cancer relies on interval evaluation of ventricular function through echocardiography. Women who undergo mastectomy more frequently choose to undergo breast reconstruction with implant. This could impede assessment of cardiac function in those with left-sided implant. We aimed to examine whether left-sided breast reconstruction with tissue expanders (TE) affect echo image acquisition and quality, possibly affecting clinical decision-making. METHODS: A retrospective case-control study was conducted in 190 female breast cancer patients who had undergone breast reconstruction with TE at an urban academic center. Echocardiographic technical assessment and image quality were respectively classified as excellent/good or adequate/technically difficult by technicians; and excellent/good or adequate/poor by 2 board-certified cardiologist readers. Likelihood ratio was used to test multivariate associations between image quality and left-sided TE. RESULTS: We identified 32 women (81.3% white; mean age 48 years) with left-sided/bilateral TE, and 158 right-sided/no TE (76.6% white, mean age 57 years). In multivariable analyses, we found a statistically significant difference in technician-assessed difficulty in image acquisition between cases and controls (p = 0.01); but no differences in physician-assessed image quality between cases and controls (p = 0.09, Pearson's r = 0.467). CONCLUSIONS: Left-sided breast TE appears to affect the technical difficulty of echo image acquisition, but not physician-assessed echo image quality. This likely means that echo technicians absorb most of the impediments associated with imaging patients with breast TE such that the presence of TE has no bearing on downstream clinical decision-making associated with echo image quality.

Characterizing Sphingosine Kinases and Sphingosine 1-Phosphate Receptors in the Mammalian Eye and Retina.

Sphingosine 1-phosphate (S1P) signaling regulates numerous biological processes including neurogenesis, inflammation and neovascularization. However, little is known about the role of S1P signaling in the eye. In this study, we characterize two sphingosine kinases (SPHK1 and SPHK2), which phosphorylate sphingosine to S1P, and three S1P receptors (S1PR1, S1PR2 and S1PR3) in mouse and rat eyes. We evaluated sphingosine kinase and S1P receptor gene expression at the mRNA level in various rat tissues and rat retinas exposed to light-damage, whole mouse eyes, specific eye structures, and in developing retinas. Furthermore, we determined the localization of sphingosine kinases and S1P receptors in whole rat eyes by immunohistochemistry. Our results unveiled unique expression profiles for both sphingosine kinases and each receptor in ocular tissues. Furthermore, these kinases and S1P receptors are expressed in mammalian retinal cells and the expression of SPHK1, S1PR2 and S1PR3 increased immediately after light damage, which suggests a function in apoptosis and/or light stress responses in the eye. These findings have numerous implications for understanding the role of S1P signaling in the mechanisms of ocular diseases such as retinal inflammatory and degenerative diseases, neovascular eye diseases, glaucoma and corneal diseases.