Relationship between genomic risk scores (GRS) and coronary artery calcium (CAC) score: A pilot study.

BACKGROUND: Coronary artery disease (CAD) genomic risk scores (GRS), as FDR202, GRS46K, 1.7M, and MetaGRS, help in assessing cardiovascular related morbidity and mortality. Interventions to adhere to a healthy lifestyle as a means of prevention based on the GRS have a potential to greatly reduce incident CAD event rates. We performed a prospective observational study to see the relationship between GRS and coronary artery calcium (CAC) scoring in individuals who are at risk. METHODS: 104 subjects with mean age 55.1 ± 8.8 years were enrolled and consented and all the participants underwent CAC scoring. 55 (53%) were male. CAC score was measured using the Agatston method. Spearman correlation analysis assessed relationships between GRS scores and CAC scores, in the entire sample and in subjects with CAC score greater than zero. Multivariable linear regression analyzed associations while adjusting potential confounding variables. RESULTS: Mean ± SD CAC score of the study population was 49.0 ± 130. A significant negative correlation was noted between FDR202 Prevalence and total CAC Score in 39 subjects with CAC >0, r = -0.35, p = 0.02. Multivariable analysis shows a significant association between FDR202 prevalence and log adjusted CAC score in subjects with CAC >0 while adjusting age, gender, hypertension and hyperlipidemia (ß = -0.2, SE = 0.1, p = 0.04). No significant correlations were found between GRS46K, 1.7M, and MetaGRS with CAC score. CONCLUSION: Additional research is necessary in a larger population to evaluate the potential role of GRS for the detection of CAD. This allows the individuals to adopt a healthy lifestyle modification to minimize the cardiovascular risk and delays the onset of most diseases of old age to prolong the life.

Management of regorafenib-related toxicities: a review.

Regorafenib (Stivarga, BAY 73-4506; Bayer Pharma AG, Berlin, Germany) is an oral multikinase inhibitor that targets the angiogenic tumor microenvironment and oncogenic kinases including vascular endothelial growth factor receptor 2 (VEGFR2), VEGFR1, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), RAF, KIT, RET and BRAF. Its antiangiogenic effect is greater than that of its related drug, sorafenib. Regorafenib has been approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer (mCRC) in patients who have failed treatment with fluoropyrimidine, oxaliplatin and irinotecan based chemotherapy, an anti-VEGF therapy and, if KRAS wild type, an anti-EGFR therapy. The FDA based this approval on data from the CORRECT trial, which showed the efficacy of regorafenib compared with placebo. The most common grade 3-4 adverse reactions with the drug are hand foot skin reactions (HFSR), diarrhea, hypertension and fatigue. This review discusses the efficacy data, and the incidence and management of regorafenib's toxicities.

Elevated CA19-9 Is Associated With Increased Mortality In A Prospective Cohort Of Hepatocellular Carcinoma Patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. CA19-9 is a glycoprotein that predicts poor prognosis in pancreatic and biliary malignancies. We evaluated it as a prognostic biomarker for patients with HCC. METHODS: We prospectively enrolled 145 patients with HCC, diagnosed using American Association for Study of Liver Diseases criteria, between October 2008 and November 2012. We examined whether baseline serum CA19-9 levels predicted overall survival. We also examined immunostains of hepatic resections and explants of patients with elevated and normal serum CA19-9. RESULTS: In a cohort of predominantly hepatitis C and B patients, CA19-9 ≥100 U/ml was associated with a 2.7-fold increased mortality (hazard ratio (HR): 2.72; 95% confidence interval (CI): 1.52-4.88, P<0.001). It remained a significant predictor (HR: 2.58; 95% CI: 1.41-4.72, P=0.002) in a multivariable model adjusted for Child-Pugh score, alpha-fetoprotein, Barcelona Clinic Liver Cancer stage, and Model for End-Stage Liver Disease. CA19-9 immunohistochemistry performed on a subset of liver resection and explant specimens showed increased CA19-9 immunostaining of non-tumor liver parenchyma in patients with elevated serum CA19-9. It also showed staining of native and reactive bile ducts, and of progenitor-like cells at the periphery of cirrhotic nodules. CONCLUSIONS: Elevated serum CA19-9 ≥100 U/ml is an independent predictor of poor overall survival in this hypothesis-generating study. The unfavorable prognosis seen with elevated serum levels may be related to progenitor-like cells in the non-tumor liver.

Value of non-contrast sequences in magnetic resonance angiography of hepatic arterial vasculature.

OBJECTIVE: To evaluate value of adding non-contrast MR angiographic sequence (In-Flow Inversion Recovery [IFIR]) to standard fat-suppressed T1-weighted postcontrast sequence (3D spoiled gradient echo [3D-GRE]) for evaluating hepatic arterial anatomy. METHODS: Retrospective evaluation of 30 consecutive patients undergoing multiphase liver MRI. Individual vessels for IFIR/3D-GRE sequences were evaluated by two blinded readers using a four-point scale. Statistical analysis was performed using the Wilcoxon signed-rank test for vessel conspicuity between IFIR/3D-GRE sequences. RESULTS: IFIR alone diagnostically imaged 8.1% of vessels, 3D-GRE alone 25.8%, 55.8% by both 3D-GRE/IFIR, and 10.3% of vessels by neither. Two patients with variant vascular anatomy were visualized with both sequences. Addition of IFIR to 3D-GRE resulted in statistically significant increase in arterial visualization (p<0.001), 10% relative increase in identified vessels, and 3-5 mi increase in acquisition time for total scan time of 30-35 min. CONCLUSIONS: IFIR may be a useful adjunct to 3D-GRE in hepatic angiography without adding considerably to scan time. 10% more hepatic arteries were seen when combining information from IFIR/3D-GRE vs. 3D-GRE alone.

Imaging approaches with advanced prostate cancer: techniques and timing.

INTRODUCTION: In conjunction with biomarkers, imaging is an important component of the diagnostic work up and subsequent management of men with prostate cancer. MATERIALS AND METHODS: The relevant literature was retrieved from a search of MEDLINE with appropriate key words. RESULTS: Osseous metastases develop in close to 90% of patients with metastatic prostate cancer, thus making bone scans (single photon, using Tc-99m labeled phosphonates) the mainstay of imaging in advanced prostate cancer. Bone scans are limited by their lack of specificity and an unclear relationship between bone scan changes and disease progression or response to therapy. In addition to Tc-99m bone scans, other technologies that accurately identify of sites of active disease would considerably aid castration resistant prostate cancer (CRPC) management. Accordingly, metabolic imaging, cell surface receptor targeting, and magnetic resonance imaging (MRI) are being studied for their role in evaluating metastatic disease. Due to the increasing availability of advanced imaging modalities, the optimal modality and appropriate clinical time point for its use remains unclear. CONCLUSION: A number of imaging modalities are currently or imminently available for use in advanced prostate cancer. Future research will focus on the appropriate incorporation of these modalities in prostate cancer management.

Positron emission tomography imaging of pancreatic cancer.

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is increasingly used for the staging of solid malignancies, including lung and esophagus. However, controversy still exists in relation to the application of PET in pancreatic cancer. The authors review seven studies (Abstracts #183, #189, #190, #254, #357, #375, #378) presented at the 2014 ASCO Gastrointestinal Cancers Symposium and discuss on the role of PET in this disease. As the limitations of the Response Evaluation Criteria In Solid Tumors (RECIST) continue to become evident, FDG-PET may identify changes in the metabolic activity within pancreatic adenocarcinoma, and can provide both diagnostic and prognostic information.

Highlights on novel imaging methods of pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer deaths. Since the majority of patients present with incurable metastatic disease, novel imaging methods are needed to identify pancreatic cancer and assess response to therapy. Research presented at the 2013 American Society of Oncology (ASCO) Annual Meeting provided insight into potential imaging methods. We discuss Abstracts #4049, #TPS4144, #TPS4146, and #E15069 in this paper.

Quantitative X-ray computed tomography peritoneography in malignant peritoneal mesothelioma patients receiving intraperitoneal chemotherapy.

BACKGROUND: Intraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients. METHODS: Thirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR. RESULTS: Decreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167). DISCUSSION: Computed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment's surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.

Primary peritoneal carcinoma in complete remission: a case report.

Primary peritoneal carcinoma (PPCa) is a relatively uncommonly diagnosed tumor. It has a similar presentation to ovarian cancer. PPCa has a poor prognosis with survival ranging from 12-18 months. PPCa spreads mainly transperitoneally, but lymphatic and hematological metastases have also been reported. It is a diagnosis of exclusion made after pathological report. Here, a case of a 71-year-old female who presented with early satiety, fatigue, weight loss and left cervical lymphadenopathy and was diagnosed with metastatic PPCa, is reported. The patient was treated with chemotherapy and achieved a complete remission. The management of this rare tumor is discussed herein.

Imaging pelvic floor disorders: trend toward comprehensive MRI.

OBJECTIVE: The purpose of this article is to review the relevant anatomy and sonographic, fluoroscopic, and MRI options for evaluating patients with pelvic floor disorders. CONCLUSION: Disorders of the pelvic floor are a heterogeneous and complex group of problems. Imaging can help elucidate the presence and extent of pelvic floor abnormalities. MRI is particularly well suited for global pelvic floor assessment including pelvic organ prolapse, defecatory function, and pelvic floor support structure integrity.

Decreased incidence of NSF in patients on dialysis after changing gadolinium contrast-enhanced MRI protocols.

PURPOSE: To retrospectively determine the incidence of nephrogenic systemic fibrosis (NSF) in patients on dialysis administered either a lower dose high-relaxivity linear gadolinium-chelate, gadobenate dimeglumine (MultiHance, MH), compared to a standard dose linear gadolinium chelate, gadodiamide (Omniscan, OM). MATERIALS AND METHODS: This study was Health Insurance Portability and Accountability Act (HIPAA)-compliant and Institutional Review Board (IRB)-approved. As per institution standardized contrast-enhanced magnetic resonance imaging (MRI) protocols, patients on dialysis were imaged using either MH, between 2/2007 to 9/2008, or OM between 10/2003 and 1/2007. Rates of NSF were compared using 95% score-based confidence intervals (CI). The Wilcoxon rank sum test was used to test similarity/difference between contrast doses given to each patient group. RESULTS: Overall, 312 patients on dialysis received OM and eight (2.6%) developed NSF (95% CI: 1.30%-4.98%). In all, 784 patients on dialysis received MH at a mean cumulative dose of 0.11 mmol/kg (0.05-0.75 mmol/kg) and no cases of NSF were identified (upper 95% confidence bound of 0.45%). The mean cumulative dose of OM was 0.16 mmol/kg (0.1-0.9 mmol/kg) for all patients and 0.28 mmol/kg (0.1-0.8 mmol/kg) for the patients with NSF. The median OM dose was greater in patients who developed NSF (P = 0.03), and was greater than the median MH dose (P < 0.005). CONCLUSION: NSF incidence in at-risk patients receiving contrast-enhanced MRI can be reduced after changing contrast administration protocols that includes changing the type and dose of contrast agent.

On improving temporal and spatial resolution of 3D contrast-enhanced body MR angiography with parallel imaging.

Use of a parallel imaging technique to improve temporal and spatial resolution at three-dimensional contrast-enhanced magnetic resonance (MR) angiography was investigated. Thirty experiments were performed in five groups of healthy subjects. In groups 1-3, the technique was used to improve imaging speed by a factor of two or four while maintaining spatial resolution. Contrast agent concentration was two to four times higher than at standard MR angiography, to take advantage of the faster imaging speed. In groups 4 and 5, the technique was used to double spatial resolution in the phase-encoding direction while maintaining imaging speed and contrast agent concentration. At a two to four times faster imaging speed, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) almost equaled those at standard MR angiography, likely a result of increased contrast agent concentration. The use of parallel imaging to achieve higher spatial resolution was also proved feasible, but with substantial reduction in SNR and CNR.

Low-density pheochromocytoma on CT: a mimicker of adrenal adenoma.

OBJECTIVE: Attenuation values on CT of less than 10 H are considered characteristic of adrenal adenomas. Adrenal pheochromocytomas can infrequently contain fat that could result in low attenuation on CT. The purpose of our study was to determine if pheochromocytomas could be confused with adenomas by virtue of their attenuation values on unenhanced CT. MATERIALS AND METHODS: CT attenuation and size of nine adrenal nodules producing pheochromocytoma syndrome were measured on unenhanced CT in nine patients. For five patients who received IV contrast material, washout profiles were also calculated. RESULTS: Two of the nine patients had adrenal lesions with attenuation values of less than 10 H; one had a pheochromocytoma with an attentuation of 9.0 H, and the other had a medullary hyperplasia with an attenuation of 1.8 H. These two nodules showed evidence of microscopic fat at histologic examination. No macroscopic fat was seen on the CT scans. The remaining seven patients had lesions with attenuation values exceeding 10 H (mean value, 25.6 H; range, 1.8-41 H). Mean diameter of the nine tumors (including the hyperplastic nodule) was 3.2 cm (range, 0.8-6.7 cm; SD, +/- 2.3 cm). The two low-attenuation lesions also mimicked adenomas by displaying more than 60% contrast washout on 10-min-delayed contrast-enhanced scans, unlike the other three pheochromocytomas for which we had washout data. CONCLUSION: On CT, pheochromocytomas may have attenuation values less than 10 H and also may display more than 60% washout of contrast agents on delayed scanning. Adrenal pheochromocytomas should be included with adenomas in the differential diagnosis both for masses with low attenuation on unenhanced CT and for lesions exhibiting a high percentage of contrast washout.