Low-grade Disease Research Articles

Abstract 4530: An independent validation of a screening test using mass spectrometry for detection of hepatocellular carcinoma

Abstract Background: Early detection is critical to improve outcome in hepatocellular carcinoma (HCC). Despite inadequate sensitivity (SS) and specificity (SP), abdominal ultrasound and alpha-fetoprotein (AFP) are considered methods of choice for HCC surveillance. As less than 30% of patients (pts) are diagnosed early enough for resection or transplantation, a test with improved SS and SP is needed. A test to detect HCC in a high-risk population from 10 uL serum, combining MALDI mass spectrometry and AFP data was developed using a dropout-regularized hierarchical machine learning approach designed to minimize overfitting in small development sets. It was previously validated in 293 high risk pts (158 HCC, 135 non-HCC) with SS/SP of 83%/84% in development and 81%/79% in validation across various etiologies and Child-Pugh classification [1]. Methods: The test was applied to an independent validation cohort of 156 pts (97 HCC, 59 non-HCC healthy controls), blinded to clinical data, the performance was assessed by SS, SP. Sub-group analyses were performed by grade and stage. Performance was compared with that of AFP by area under the curve (AUC), using the test output prior to the predefined thresholding which yields the final binary cancer/benign test result. Results: Table 1.HCC patient demographics in the independent validation setClinical characteristicsIndependent validationPatients with HCC (N=97)Median age (range), years62 (38 - 89)Median AFP (range), ng/mL4.0 (less than 1.5 - 10,000)Gender, male / female85% / 16%Hepatitis B / C / No virus / not available (NA)3% / 27% / 20% / 51%Grade I / II / III / NA17% / 22% / 12% / 50%Stage I / II / III / IV / NA12% / 14% / 33% / 26% / 14%Previous liver directed or systemic therapy yes/no44% / 54%ECOG PS 0 / 1 / 2 / 3 / NA13% / 20% / 11% / 5% / 51% In independent validation, AUC for the test output prior to thresholding was 0.979, significantly better than AFP AUC 0.915 (P<0.001). SS and SP were 88% and 100%. SS in grade I, II, and III was 75%, 76%, and 92% and in stage I, II, III, and IV was 75%, 86%, 94%, and 92%. Conclusion: Results in the independent cohort confirm performance of the test, with better SS and SP than AFP and historical ultrasound. The SS was also high in low grade and early stage disease, indicating the test’s potential to improve early detection of HCC when curative approaches are feasible. Data and samples from Data Bank and BioRepository, Roswell Park; funding by the NCI grant P30CA016056 [1] D Mahalingam et al. Hepatology 62(S1): 1135A (2015) Citation Format: Sunyoung S. Lee, Kristopher Attwood, Heinrich Roder, Senait Asmellash, Krista Meyer, Stylianos Kakolyris, Carlos Oliveira, Joanna Roder, Julia Grigorieva, Leonidas Chelis, Renuka Iyer, Devalingam Mahalingam. An independent validation of a screening test using mass spectrometry for detection of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4530.

Noninvasive Detection of Bladder Cancer by Shallow-Depth Genome-Wide Bisulfite Sequencing of Urinary Cell-Free DNA for Methylation and Copy Number Profiling.

The current diagnosis and monitoring of bladder cancer are heavily reliant on cystoscopy, an invasive and costly procedure. Previous efforts in urine-based detection of bladder cancer focused on targeted approaches that are predicated on the tumor expressing specific aberrations. We aimed to noninvasively detect bladder cancer by the genome-wide assessment of methylomic and copy number aberrations (CNAs). We also investigated the size of tumor cell-free (cf)DNA fragments. Shallow-depth paired-end genome-wide bisulfite sequencing of urinary cfDNA was done for 46 bladder cancer patients and 39 cancer-free controls with hematuria. We assessed (a) proportional contribution from different tissues by methylation deconvolution, (b) global hypomethylation, (c) CNA, and (d) cfDNA size profile. Methylomic and copy number approaches were synergistically combined to detect bladder cancer with a sensitivity of 93.5% (84.2% for low-grade nonmuscle-invasive disease) and a specificity of 95.8%. The prevalence of methylomic and CNAs reflected disease stage and tumor size. Sampling over multiple time points could assess residual disease and changes in tumor load. Muscle-invasive bladder cancer was associated with a higher proportion of long cfDNA, as well as longer cfDNA fragments originating from genomic regions enriched for tumor DNA. Bladder cancer can be detected noninvasively in urinary cfDNA by methylomic and copy number analysis without previous knowledge or assumptions of specific aberrations. Such analysis could be used as a liquid biopsy to aid diagnosis and for potential longitudinal monitoring of tumor load. Further understanding of the differential size and fragmentation of cfDNA could improve the detection of bladder cancer.

Subchondral insufficiency fracture of the knee: grading, risk factors, and outcome.

To propose an magnetic resonance imaging (MRI) grading system for subchondral insufficiency fracture of the knee (SIFK) to predict outcome and assess risk factors. A total of 50 SIFK patients were retrospectively reviewed utilizing two MRI examinations approximately a year apart and compared them with 51 control subjects. A grading system was introduced that classifies lesions as low- vs high-grade. Lesion location 3D dimensions, extent of bone marrow edema (BME), location of meniscal tears and associated extrusion, degree of chondrosis and among other parameters were stratified according to lesion grade and compared with follow-up examinations. Statistical analyses were performed (Pearson's correlation, binary logistic regression, and Chi-squared analysis). The majority of SIFK lesions were low-grade (LG; 78%) and most of them (70%) were observed in the medial femoral condyle. Predictor variables comparing low-grade and high-grade SIFK lesions included meniscal tear (p = 0.01), degree of extrusion (p < 0.003), chondrosis (p = 0.01), medial chondrosis grade (p = 0.001), medial femoral condyle (p = 0.01), surface collapse (p < 0.0001), marrow edema improvement (p < 0.0001), first MRI anteroposterior dimension (p = 0.001), transverse dimension (p < 0.001), and ellipsoid volume (p = 0.02). Predictor variables found to be significantly different between controls and patients were meniscal tear (p = 0.024), location of the medial meniscal tear (p < 0.0001), degree of extrusion (p < 0.0001), chondrosis (p < 0.0001), joint effusion (p < 0.0001), Baker's cyst (p < 0.0001), knee lock (p = 0.03) and buckle (p = 0.01), and history of trauma (p = 0.01). A SIFK grading system for MRI is introduced. Surrogate markers of high-grade lesions include medial meniscus posterior root tears with associated moderate to severe extrusion, high-grade chondrosis, larger lesion sizes (anteroposterior/transverse), and articular surface collapse. Improvement of BME on follow-up was highly predictive of low-grade disease.

The endoscopic endonasal approach for sinonasal and nasopharyngeal adenoid cystic carcinoma.

To determine factors affecting outcomes for patients with sinonasal and nasopharyngeal adenoid cystic carcinoma (SNACC) treated using the endoscopic endonasal approach (EEA) with preservation of key structures followed by adjuvant radiotherapy (RT). Retrospective case series of 30 patients treated at the University of Pittsburgh between 2000 and 2014. Hospital records were reviewed for clinical and pathologic data. Outcome measures included overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates. The majority of patients had T4a and T4b disease (23.3%, and 63.3%). Microscopically positive margins were present in 21 patients (63.6%). Positive margins were present in nine patients (30.0%). The mean and median follow-up were 3.97 and 3.29 years. Five-year OS, DFS, LRFS, and DMFS were 62.66%, 58.45%, 87.54%, and 65.26%. High-/intermediate-grade tumors had worse DFS (P = .023), and LRFS (P = .026) (HR = 4.837, 95% CI, 1.181-19.812). No factors were associated with significantly worse DMFS. No patient suffered CSF leak, optic nerve, or internal carotid injury. The mean and median length of hospital stay was 4.1 days and 2.0 days (range: 0-32 days). Organ-preserving EEA with adjuvant RT for low-grade SNACC offers 5-year survival similar to that reported by other studies, which include radical, open skull base surgery. Patients with high-grade disease do poorly and may benefit from novel treatment strategies. For low-grade disease, organ-preserving EEA with RT may be the best option, offering a balance of survival, quality of life, and decreased morbidity for patients with this difficult-to-cure disease. 4 Laryngoscope, 130:1414-1421, 2020.

Salvage Radiotherapy for Recurrent Prostate Cancer: Can the Prognostic Grade Group System Inform Treatment Timing?

In order to better time salvage radiotherapy (SRT) for post-radical prostatectomy biochemical failure, we examined the association between pre-SRT prostate-specific antigen (PSA) and PSA control as a function of the new prognostic grade group (PGG) system. Using the Shared Equal Access Regional Cancer Hospital database, we identified men after radical prostatectomy with PSA > 0.2 ng/mL and without cancer involvement of lymph nodes who underwent SRT alone. SRT failure was defined as post-SRT PSA nadir+ 0.2 ng/mL or receipt of post-SRT hormone therapy. Men were stratified by pre-SRT PSA (0.2-0.49, 0.5-0.99, and≥ 1.0 ng/mL). Multivariable Cox models were used to test the association between pre-SRT PSA and SRT failure, stratified by PGG. A total of 358 men met the inclusion criteria and comprised our study cohort. Median post-SRT follow-up was 78 months. A total of 174 men (49%) had pre-SRT PSA 0.2-0.49 ng/mL, 97 (27%) PSA 0.5-0.99 ng/mL, and 87 (24%) PSA≥ 1.0 ng/mL. On multivariable analysis among men with PGG 1-2, pre-SRT PSA 0.2-0.49 ng/mL had similar outcomes as PSA 0.5-0.99 ng/mL; those with PSA≥ 1.0 ng/mL had higher recurrence risks (hazard ratio= 2.78, P< .001). Among PGG 3-5, PSA 0.5-0.99 ng/mL or≥ 1.0 ng/mL had a higher recurrence risk (hazard ratio= 2.15, P= .021; and hazard ratio= 2.49, P= .010, respectively) versus PSA 0.2-0.49 ng/mL. In men with higher-grade prostate cancer (PGG 3-5), SRT should be provided earlier (PSA< 0.5 ng/mL), while among men with lower-grade disease (PGG 1-2), SRT results in equal PSA control up to PSA 1.0 ng/mL.

Current Status of MRI and PET in the NCCN Guidelines for Prostate Cancer.

Prostate cancer (PCa) represents a significant source of morbidity and mortality for men in the United States, with approximately 1 in 9 being diagnosed with PCa in their lifetime. The role of imaging in the evaluation of men with PCa has evolved and currently plays a central role in diagnosis, treatment planning, and evaluation of recurrence. Appropriate use of multiparametric MRI (mpMRI) and MRI-guided transrectal ultrasound (MR-TRUS) biopsy increases the detection of clinically significant PCa while decreasing the detection of clinically insignificant PCa. This process may help patients with clinically insignificant PCa avoid the adverse effects of unnecessary therapy. In the setting of a known PCa, patients with low-grade disease can be observed using active surveillance, which often includes a combination of prostate-specific antigen (PSA) testing, serial mpMRI, and, if indicated, follow-up systematic and targeted TRUS-guided tissue sampling. mpMRI can provide important information in the posttreatment setting, but PET/CT is creating a paradigm shift in imaging standards for patients with locally recurrent and metastatic PCa. This article examines the strengths and limitations of mpMRI for initial PCa diagnosis, active surveillance, recurrent disease evaluation, and image-guided biopsies, and the use of PET/CT imaging in men with recurrent PCa. The goal of this review is to provide a rational basis for current NCCN Clinical Practice Guidelines in Oncology for PCa as they pertain to the use of these advanced imaging modalities.

Can MRI be used to diagnose histologic grade in T1a (&lt; 4 cm) clear cell renal cell carcinomas?

To assess whether MRI can differentiate low-grade from high-grade T1a cc-RCC. With IRB approval, 49 consecutive solid < 4cm cc-RCC (low grade [Grade 1 or 2] N = 38, high grade [Grade 3] N = 11) with pre-operative MRI before nephrectomy were identified between 2013 and 2018. Tumor size, apparent diffusion coefficient (ADC) histogram analysis, enhancement wash-in and wash-out rates, and chemical shift signal intensity index (SI index) were assessed by a blinded radiologist. Subjectively, two blinded Radiologists also assessed for (1) microscopic fat, (2) homogeneity (5-point Likert scale), and (3) ADC signal (relative to renal cortex); discrepancies were resolved by consensus. Outcomes were studied using Chi square, multivariate analysis, logistic regression modeling, and ROC. Inter-observer agreement was assessed using Cohen's kappa. Tumor size was 24 ± 7 (13-39)mm with no association to grade (p = 0.45). Among quantitative features studied, corticomedullary phase wash-in index (p = 0.015), SI index (p = 0.137), and tenth-centile ADC (p = 0.049) were higher in low-grade tumors. 36.8% (14/38) low-grade tumors versus zero high-grade tumors demonstrated microscopic fat (p = 0.015; Kappa = 0.67). Microscopic fat was specific for low-grade disease (100.0% [71.5-100.0]) with low sensitivity (36.8% [21.8-54.6]). Other subjective features did not differ between groups (p > 0.05). A logistic regression model combining microscopic fat + wash-in index + tenth-centile-ADC yielded area under ROC curve 0.98 (Confidence Intervals 0.94-1.0) with sensitivity/specificity 87.5%/100%. The combination of microscopic fat, higher corticomedullary phase wash-in and higher tenth-centile ADC is highly accurate for diagnosis of low-grade disease among T1a clear cell RCC.

Impact of bariatric surgery on type 2 diabetes: contribution of inflammation and gut microbiome?

Obesity is a chronic low-grade inflammatory disease (both at the systemic and adipose tissue level) that continues to rise worldwide. It is associated with an abundance of comorbidities, including type 2 diabetes (T2D). Bariatric surgery, which induces modifications of the intestinal tract, is to date the most successful treatment for obesity. Its use has dramatically increased in number as it enables both weight reduction and metabolic improvements, with 60% of patients even achieving diabetes remission. Several mechanisms are actually demonstrated to be involved in those clinical improvements. Importantly, both obesity and T2D share many phenotypic characteristics, including increased systemic and adipose tissue inflammation, as well as gut microbiota dysbiosis. These characteristics are deeply modulated after bariatric surgery. This review will address the host metabolic changes observed after bariatric surgery, focusing on the induced gut architectural changes, as well as on the modifications of the inflammatory tone and the gut microbiota.

Clinical Advances in Immunonutrition and Atherosclerosis: A Review.

Atherosclerosis is a chronic low-grade inflammatory disease that affects large and medium-sized arteries and is considered to be a major underlying cause of cardiovascular disease (CVD). The high risk of mortality by atherosclerosis has led to the development of new strategies for disease prevention and management, including immunonutrition. Plant-based dietary patterns, functional foods, dietary supplements, and bioactive compounds such as the Mediterranean Diet, berries, polyunsaturated fatty acids, ω-3 and ω-6, vitamins E, A, C, and D, coenzyme Q10, as well as phytochemicals including isoflavones, stilbenes, and sterols have been associated with improvement in atheroma plaque at an inflammatory level. However, many of these correlations have been obtained in vitro and in experimental animals' models. On one hand, the present review focuses on the evidence obtained from epidemiological, dietary intervention and supplementation studies in humans supporting the role of immunonutrient supplementation and its effect on anti-inflammatory response in atherosclerotic disease. On the other hand, this review also analyzes the possible molecular mechanisms underlying the protective action of these supplements, which may lead a novel therapeutic approach to prevent or attenuate diet-related disease, such as atherosclerosis.

Automatic stratification of prostate tumour aggressiveness using multiparametric MRI: a horizontal comparison of texture features

Background: Previous studies have identified apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can stratify prostate cancer into high- and low-grade disease (HG and LG, respectively). In this study, we consider the improvement of incorporating texture features (TFs) from T2-weighted (T2w) multiparametric magnetic resonance imaging (mpMRI) relative to mpMRI alone to predict HG and LG disease.Material and methods: In vivo mpMRI was acquired from 30 patients prior to radical prostatectomy. Sequences included T2w imaging, DWI and dynamic contrast enhanced (DCE) MRI. In vivo mpMRI data were co-registered with ‘ground truth’ histology. Tumours were delineated on the histology with Gleason scores (GSs) and classed as HG if GS ≥ 4 + 3, or LG if GS ≤ 3 + 4. Texture features based on three statistical families, namely the grey-level co-occurrence matrix (GLCM), grey-level run length matrix (GLRLM) and the grey-level size zone matrix (GLSZM), were computed from T2w images. Logistic regression models were trained using different feature subsets to classify each lesion as either HG or LG. To avoid overfitting, fivefold cross validation was applied on feature selection, model training and performance evaluation. Performance of all models generated was evaluated using the area under the curve (AUC) method.Results: Consistent with previous studies, ADC was found to discriminate between HG and LG with an AUC of 0.76. Of the three statistical TF families, GLCM (plus select mpMRI features including ADC) scored the highest AUC (0.84) with GLRLM plus mpMRI similarly performing well (AUC = 0.82). When all TFs were considered in combination, an AUC of 0.91 (95% confidence interval 0.87–0.95) was achieved.Conclusions: Incorporating T2w TFs significantly improved model performance for classifying prostate tumour aggressiveness. This result, however, requires further validation in a larger patient cohort.

Nutrition as Adjunct Therapy in Periodontal Disease Management

Periodontal disease and its associated systemic diseases have gained public attention due to their increasing global prevalence. Still, the gold standard for the management of periodontitis is scaling and root planing (SRP). However, bacterial recolonization is considered a limitation of this approach. Further, the efficacy of adjunctive agents such as antibiotics, antimicrobials, and probiotics has been investigated extensively. Nowadays, drug resistance development due to antibiotics and antimicrobials abuse has become a global problem and our concern. In order to reduce the spread of drug resistance development, many investigations have been focused on the use of nutritional compounds rather than synthetic drugs for treating periodontitis, a relatively low-grade inflammatory disease. Moreover, if periodontitis is understood as a bacterial dysbiosis-induced inflammatory disease, then its treatment could be designed not only to eliminate periodontopathogens, but also to modify the host immune response. Therefore, this review will highlight the effectiveness of some pertinent nutrients towards periodontal condition. Nutrients are known to possess anti-inflammatory, antioxidant, and antimicrobial properties that maintain homeostasis. In vivo and in vitro studies have demonstrated the positive effects of nutrient intake on the maintenance and restoration of periodontal health. Vitamins, fatty acids, and probiotics are increasingly being found to have remarkable benefits and valuable properties. Further, considering the oral-systemic connection, nutritional supplementation is encouraged as a possible adjunct therapy for the improvement of both oral and systemic health.

OR29-3 Targeted Assessment of G0S2 Methylation Identifies a Rapidly Recurrent, Routinely Fatal Molecular Subtype of Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy with frequently dismal prognosis and few therapies. Patients with locoregional ACC routinely receive surgery and adjuvant mitotane, but >50% recur with metastases even after complete resection. Histological grade (Ki67>10% or >20 mitoses/50 HPF) is the strongest clinical predictor of recurrence, but time to recurrence in patients with high grade disease is variable and patients with low grade disease frequently recur. Recent molecular profiling studies suggest risk stratification by DNA methylation may better identify patients with homogenously dismal outcomes; in The Cancer Genome Atlas study on ACC (ACC-TCGA), we similarly identified that patients with tumors bearing CpG island hypermethylation (CIMP-high) exhibit rapid recurrence and early death. However, clinical translation of this complex molecular signature remains challenging. Here, we reanalyzed ACC-TCGA data and show that CIMP-high ACC is characterized by upregulation of cell cycle and DNA damage response programs, and identify that hypermethylation and silencing of G0S2 distinguishes this subgroup. We evaluated G0S2 methylation in a multi-institutional retrospective cohort of treatment-naive primary ACC (n=80) and adrenocortical adenomas (n=22) using a straightforward, overnight restriction digest/qPCR-based assay, validated by targeted bisulfite sequencing. We identified that G0S2 hypermethylation is exclusive to a subset of ACC (40%). G0S2 hypermethylation is associated with decreased disease-free survival (median DFS=14 mo., HR=6.91, p<0.0001; Cox regression) and overall survival (median OS=17 mo., HR=2.65, p<0.005; Cox regression). These observations remain significant in multivariate analyses, demonstrating that G0S2 hypermethylation independently predicts rapidly recurrent and fatal ACC. Our data suggests that prospective targeted assessment of G0S2 methylation may enable clinicians to identify patients with CIMP-high ACC, unlikely to exhibit durable response to standard of care. Ultimately, we hope that improved identification of this subgroup will facilitate the evaluation of more aggressive adjuvant therapies for these patients, and increase patient survival in the face of this devastating disease.

Is Parkinson's disease a chronic low-grade inflammatory bowel disease?

While the pathogenesis of Parkinson's disease is not fully understood, there is increasing evidence that inflammatory responses in the brain are implicated in both disease initiation and progression. The inflammatory process in Parkinson's disease is, however, not limited to the brain but also involves the gastrointestinal tract. High amounts of cytokines and inflammatory markers are found in the colon of Parkinson's disease patients and there is now strong epidemiological and genetical evidence linking Parkinson's disease to inflammatory bowel diseases. Recent findings obtained in both experimental inflammatory bowel diseases and Parkinson's disease further support a bidirectional link between gastrointestinal inflammation and brain neurodegeneration. Altogether, these observations suggest a role for gastrointestinal inflammation in the initiation and progression of Parkinson's disease.

Tratamiento conservador de la osteoartrosis de cadera con toxina botulínica tipo A

Osteoarthritis (OA) of the hip is a low-grade inflammatory disease of multiple etiology that has a limited conservative management and insufficiently explored. The application of botulinum toxin type A (BoNT-A) produces in the applied muscle a temporary, delimitable and reversible flaccid paralysis, which applicated in a strategic way achives to reduce mechanical stress and pain. To evaluate the effect on pain perception, functionality and rigidity and changes in flexibility, internal and external rotation, before and 90 days after the application of BoNT-A. Clinical, experimental, longitudinal, open study, with a total of 35 patients and 45 hips treated. BoNT-A of 500 U was applied in iliac, adductor brevis and longus muscles. The Wilcoxon test was used to compare the evaluation scores on days 0-90, observing the decrease in referred pain (p < 0.0001), rigidity (p < 0.002), improved perceived function (p < 0.001) and mobility arcs: flexion, internal and external rotation (p < 0.0001). The treatment with BoNT-A provides a conservative and safe option for the management of symptoms and physical restraint caused by hip OA.

J-108 Role of DNA methylation in prediction of human papillomavirus persistence and carcinogenesis

J-108 Role of DNA methylation in prediction of human papillomavirus persistence and carcinogenesis

Association between Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios and Coronary Artery Calcification Score among Asymptomatic Patients: Data from a Cross-Sectional Study.

Introduction Atherosclerosis is a low-grade inflammatory disease. Among markers of inflammation, importance has been given to the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). The objective of this study was to examine the association between these hematological indices of inflammation and coronary atherosclerotic calcification in clinically asymptomatic patients. Methods This study had clinical and laboratorial data collected from consecutive asymptomatic patients that underwent computed tomography coronary artery calcium (CAC) scoring. Risk factors, NLR, and PLR were evaluated at different categories of CAC scoring. Statistical tests included chi-square, linear regression, and logistic regression. Patients (N = 247; age 60.4 ± 8.0 years and 60.7% men) were allocated into four categories according to the CAC score. Results Respective age, sex (male), NLR, and PLR distribution within groups were as follows: CAC = 0 (n = 98; 52.5 ± 13.6 years, 55%, 2.0 ± 1.0, and 121.5 ± 41.5), CAC 1-100 (N = 64; 61.3 ± 11.0 years, 60%, 2.2 ± 1.2, and 125.6 ± 45.6), CAC 101-400 (N = 37; 64.2 ± 11.6 years, 67%, 2.6 ± 1.3, and 125.4 ± 55.9), and CAC > 400 (N = 48; 69.3 ± 11.1 years, 66%, 3.3 ± 2.0, and 430.1 ± 1787.4). The association between risk factors and CAC score was assessed. Hypertension status and smoking status were similar within groups, while the presence of diabetes (P = 0.02) and older age (P ≤ 0.001) was more prevalent in the CAC > 400 group. LDL cholesterol was greater in the higher CAC score groups (P = 0.002). Multivariate logistic regression of the quartile analysis showed that age and NLR were independently associated with CAC > 100 (OR (CI), P value): 2.06 (1.55-2.73, P = 0.00001) and 1.82 (1.33-2.49, P = 0.0002), respectively. Conclusion Within asymptomatic patients, NLR provides additional risk stratification, as an independent association between NLR extent and CAD extent was identified. Moreover, PLR was not an inflammation marker for CAD severity.

HPV infection and pre-term birth: a data-linkage study using Scottish Health Data.

Background: We aimed to investigate whether infection with high-risk (HR) types of human papilloma virus (HPV) or HPV-associated cervical disease were associated with preterm birth (<37 weeks gestation). In a sub-group of younger women who were eligible for the HPV vaccine, we aimed to determine whether prior vaccination against the specific HPV-types, HPV-16 and -18 modified preterm birth risk. Methods: This was a data-linkage study, which linked HPV-associated viral and pathological information (from the Scottish HPV Archive) from women aged 16-45 years to routinely collected NHS maternity- and hospital-admission records from 1999-2015. Pregnancy outcomes from 5,598 women with term live birth (≥37 weeks gestation, n=4,942), preterm birth (<37 weeks gestation, n=386) or early miscarriage (<13 weeks gestation, n=270). Of these, data from HPV vaccine-eligible women (n=3,611, aged 16-25 years) were available, of whom 588 had been vaccinated. HPV-associated disease status was defined as: HR HPV-positive no disease, low-grade abnormalities or high-grade disease. Results: High-grade HPV-associated cervical disease was associated with preterm birth (odds ratio=1.843 [95% confidence interval 1.101-3.083], p=0.020) in adjusted binary logistic regression analysis, in all women, but there were no associations with HR HPV-infection alone or with low-grade abnormalities. No associations between any HPV parameter and preterm birth were seen in vaccine-eligible women, nor was there any effect of prior vaccination. Conclusions: HPV-associated high-grade cervical disease was associated with preterm birth, but there were no associations with HR HPV-infection or low-grade cervical disease. Thus HPV-infection alone (in the absence of cervical disease) does not appear to be an independent risk factor for preterm birth. For women who have undergone treatment for CIN and become pregnant, these results demonstrate the need to monitor for signs of preterm birth.

Performance of a validated urine exosome gene expression test (EPI) in men within the USPSTF suggested age-group of 55 to 69 years at initial biopsy with a PSA 2-10 ng/mL.

53 Background: Prostate-specific antigen (PSA) plays a key-role in prostate cancer (PCa) risk stratification but leads to over-diagnosis of low grade PCa. Recently, the USPSTF recommended that the decision to undergo PSA-based screening for men aged 55 to 69 years should be an individual one. We have developed and validated a non-invasive diagnostic test (ExoDx Prostate(IntelliScore), EPI) as a decision aid to guide the initial prostate biopsy decision process for men in the PSA gray zone of 2-10 ng/mL. The EPI test is a urine exosome gene expression assay to discriminate high-grade (GG 2) from low-grade (GG 1) and benign disease, thereby reducing the number of unnecessary biopsies. Methods: Patient data from two clinical trials were merged and constrained by age (55-69) according to the USPSTF suggested age-group resulting in a cohort of 701 patients with PSA 2-10 ng/mL, scheduled for initial prostate needle biopsy. EPI test results as well as PCPT2.0 risk calculator, ERSPC risk calculator and PSA results are compared with biopsy outcomes. Performances are reported using the area under the receiver operating characteristic curve (AUC), Negative predictive value (NPV), Positive predictive value (PPV), Sensitivity, and Specificity for discriminating ≥GG2 from GG1 and benign disease. Results: EPI showed a superior AUC of 0.70 compared to PSA (AUC: 0.57), PCPT2.0 (AUC: 0.60) and ERSPC (AUC: 0.58) (all p-values &lt; 0.001) for discriminating ≥GG2 PCa from benign and GG1. The previously validated EPI cut-point of 15.6 would avoid 22% of all prostate biopsies and 29% of unnecessary biopsies, with an NPV of 93% and miss only 5.4% of ≥GG2, respectively. Conclusions: EPI is a non-invasive, easy to use urine exosome RNA expression assay to discriminate high-grade (GG2) from low-grade (GG1) PCa and benign disease. EPI significantly outperformed the other standard of care parameters tested and applying the EPI test for risk stratification of patients in the USPSTF suggested age group, should reduce the number of unnecessary biopsies.

Radiotherapy for parotid malignancies: patterns of care and impact on overall survival

Parotid tumors are rare, and no clinical trial data exists to guide postoperative radiation therapy (PORT) usage. We sought to determine the impact of PORT on the overall survival (OS) of patients with parotid malignancies. Patient data was queried from the National Cancer Database. Patients with surgical resection of parotid gland carcinomas from 2004 to 2012 were analyzed. Kaplan-Meier and Cox proportional hazards were used to assess OS among those receiving PORT or not. Additionally, variables affecting OS and use of PORT were evaluated. A total of 12,439 patients were identified for analysis. Increasing T stage, N stage, tumor grade, and positive margin status were predictive of PORT. Survival for patients receiving PORT versus surgery only at 5 and 10 years was 65.5% and 50.3% versus 74.4% and 61.2% for surgery only (p ≤ 0.001). After multivariable adjustment, PORT improved OS (adjusted hazard ratio 0.79, 95% confidence interval 0.70–0.89). In subgroup analysis, PORT provided benefit for certain histologic subtypes and all other patient groups except those with T1 tumors and undifferentiated/anaplastic tumor grades. Our data suggests that PORT was associated with improved survival. Additionally, some subgroups may receive additional benefit and patients with small (T1), low-grade disease may be able to forgo PORT.

Impact of intravesical therapy for non-muscle invasive bladder cancer on the accuracy of urine cytology.

Urine cytology remains an essential diagnostic tool in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC). The correlation of urine cytology with biopsy specimens to determine its accuracy following induction intravesical therapy has not been investigated. A retrospective review was performed of patients who underwent intravesical therapy for biopsy-proven non-muscle invasive disease between 2013 and 2016 at our institution. All patients uniformly underwent cytology and systematic bladder biopsies in the operating room within 12weeks following intravesical therapy. The accuracy of urinary cytology in predicting high-grade disease recurrence following intravesical therapy was confirmed by correlating cytology results to post-treatment systematic biopsies, regardless of endoscopic findings. Only patients with complete information regarding urine cytology and pathologic biopsy results, both pre- and post-intravesical therapy, were included. 90 cytology samples following intravesical therapy were analyzed from 76 patients who met inclusion criteria. 72 (80.0%) and 18 (20.0%) of the samples were collected from patients initially treated for high- and low-grade disease, respectively. Fifty-six (62.2%) specimens were obtained from patients following induction of bacillus Calmette-Guerin (BCG) therapy; the remainder were from patients treated with intravesical gemcitabine/docetaxel, mitomycin, or BCG/interferon. For patients treated with BCG, cytology was positive for high-grade disease in 8/15 patients with high-grade pathology on follow-up biopsy, thus demonstrating a sensitivity of 53% (95% CI 27-79%), specificity of 95% (95% CI 84-99%), positive predictive value of 80% (95% CI 44-98%), and negative predictive value of 85% (95% CI 71-94%). If cytologic interpretation was broadened to include high-grade and "suspicious for high-grade" findings, sensitivity increased to 67% (95% CI 38-88%) and specificity decreased to 88% (95% CI 74-96%). While urinary cytology maintains a high specificity following intravesical therapy, it demonstrates a low sensitivity for potentially aggressive high-grade urothelial carcinoma. Further evaluation of more effective, clinic-based enhanced cystoscopy techniques and biomarkers is warranted to better identify patients at risk for disease recurrence following BCG therapy.