Benign Status Research Articles

A Tumor-Activatable Liposomal Nanoprobe for Selective Visualization of Metastatic Lymph Nodes.

The precise identification of sentinel lymph nodes (SLNs) during surgery and assessment of their benign status is crucial for accurate tumor staging and optimal treatment strategizing. Currently, a deficiency exists in non-invasive in vivo diagnostic techniques that can accurately pinpoint SLNs during surgery while simultaneously evaluating their benign status. Here, a tumor-activatable liposomal nanoprobe (nTAL) is developed, remotely loaded with clinically approved photosensitizer, methyl aminolevulinate (MAL), to noninvasively visualize the tumor metastasis lymph nodes (LNs) with precision. Benefited from the highly efficient LNsdraining of nanosized liposome and tumor cell-specific transformation of the non-fluorescent MAL to fluorescent protoporphyrin IX (PPIX), nTAL succeeded in targeting the SLNs and differentiated the metastatic from the benign ones with a positive correlation between PPIX generation and tumor cell infiltration in LNs. Moreover, the nTAL technology is capable of probing the early metastatic stage with a primary tumor size of 50 mm3. This study provides a new strategy for intraoperative visualization of real-time sentinel node dissection.

Endobronchial ultrasound sonographic characteristics of mediastinal lymph node in the evaluation of lung cancer.

Endobronchial ultrasound (EBUS) and contrast-enhanced computed tomography (CECT) are essential components of lung cancer evaluation. Features of mediastinal lymph nodes on EBUS and CECT can help in predicting metastatic disease. Clinical, radiological, and EBUS data of patients with clinico-radiological suspicion of lung cancer who have undergone EBUS with no transbronchial needle aspiration (TBNA) or nonyielding EBUS-TBNA were retrospectively collected from medical records. EBUS features of lymph nodes for metastatic disease [size >1 cm, round shape, heterogeneous echotexture, indistinct margin, coagulation necrosis (CN), absence of central hilar structures (CHS), and grade II-III vascularity] were noted. CECT findings were noted from CECT films and reports to analyze and compare with EBUS findings. Scoring criteria of EBUS sonographic characteristics from previous studies for discriminating benign and malignant lymph nodes were also assessed for possible prediction. 31 patients [male: 18 (58.1%), female: 13 (41.9); age (mean ± standard deviation): 52.9±15.7 years] with CECT findings suggesting lung cancer were studied. EBUS showed mediastinal lymphadenopathy at 82 lymph node stations in 29 patients. Size >1 cm, round shape, heterogeneous echotexture, distinct margin, CN, absence of CHS and grade II-III vascularity at 33 (40%), 28 (34%), 31 (38%), 55 (67%), 3 (4%), 77 (94%), and 6 (7.3%) lymph nodes, respectively, were found. The malignant or benign status assigned to lymph nodes using different scoring criteria was highly discordant. Compared to EBUS, CECT revealed abnormal mediastinal lymph nodes in significantly fewer patients [21 (67.7%) versus 29 (93.5%), p=0.01] involving a lower number of lymph node stations (37 versus 82, p<0.001). Lymphadenopathy frequency at different LNS on EBUS and CECT showed a weak positive but significant correlation (r=0.356; p=0.0426). EBUS characteristics and related scores have limited accuracy in differentiating benign and malignant nodes. CECT underestimates lymphadenopathy in comparison to EBUS. A larger prospective study of EBUS features with cyto/histopathology correlation may elicit its clinical significance and help to create better and more composite scoring criteria.

Detecting early stage breast cancer using low-depth cell-free DNA fragmentomics: A multi-center cohort study.

3075 Background: Breast cancer (BC) has contributed to the most cancer-related mortalities among females in 2020. Early detection using breast imaging methods, such as mammography and ultrasound, has significantly improved patients' survival. However, these early-screening methods suffer from high false-positive rates, resulting in many unnecessary biopsies which add to patients' discomfort. Cell-free DNA (cfDNA) fragmentomics assays have recently illustrated prominent abilities for detecting various cancer. In this multi-center prospective cohort study, we aim to develop a non-invasive liquid biopsy assay utilizing cfDNA fragmentomics and machine learning for detecting early-stage BC patients. Methods: We recruited 402 female patients (234 with BC and 168 with benign nodules [BN]) from the Yantai Yuhuangding Hospital (training cohort, N = 193, 91 BC and 102 BN) and the Cancer Hospital of the Chinese Academy of Medical Sciences (independent validation cohort, N = 209, 143 BC and 66 BN). Surgical or core needle biopsies were performed for all 402 patients following positive breast imaging results by mammography and ultrasound. Each patient's malignant or benign status was then pathologically confirmed using the tissue specimen. Women with negative biopsy results were excluded from breast cancer through a 6-month follow-up. The fragmentomics profiles, which were generated using plasma cfDNA WGS data (~5X), were used by our machine-learning algorithm. An automated machine learning approach was deployed to optimize base models before being ensembled into the final predictive model. Results: Our predictive model showed excellent performance in discriminating BCs from BNs, reaching an Area Under the Curve (AUC) of 0.816 and 0.811 in the training cohort (5-fold cross-validation) and the independent validation cohort, respectively. It achieved 74.1% sensitivity (95% CI: 66.1-81.1%) at 81.8% specificity (95% CI: 70.4-90.2%) in the validation cohort. In a potential clinical setting, our model could detect 53.0% (95% CI: 40.3-65.4%) false positives from the breast imaging methods at a targeted 90% sensitivity (89.5%, 95% CI:83.3–94.0%), which could theistically reduce more than half of the unnecessary biopsies. Moreover, our model illustrated great predictive power (AUC = 0.830) among small nodules (≤ 1cm), which were difficult to distinguish by the traditional imaging methods (AUC = 0.690). Finally, our model maintained its predictive power during a down-sampling process, even using 2X WGS data in the independent validation cohort (mean AUC: 0.789, 0.781-0.798). Conclusions: Our non-invasive liquid biopsy assay, which utilized low-depth cfDNA fragmentomics profiling and machine learning, can distinguish malignant nodules from benign nodules. The highlight of our model is its ability to prevent unnecessary biopsies among patients with false positive breast imaging results.

PO-01-240 UTILITY OF IN VITRO FUNCTIONAL CHARACTERIZATION IN THE PROMOTION OR DEMOTION OF CLINICALLY ENCOUNTERED VARIANTS OF UNCERTAIN SIGNIFICANCE IN THE THREE MOST COMMON LONG QT SYNDROME-CAUSATIVE GENES: KCNQ1, KCNH2, AND SCN5A

Genetic testing for cardiac channelopathies such as long QT syndrome (LQTS) and Brugada syndrome (BrS) is standard of care. Although the American College of Medical Genetics (ACMG) guidelines for variant interpretation have provided a framework for distinguishing pathogenic variants from benign, many rare genetic variants remain classified as a variant of uncertain significance (VUS) due to lack of epidemiologic or functional data to either promote or demote the variant to pathogenic or benign status, respectively. To functionally characterize clinically encountered VUSs in the three most common LQTS-causative genes: KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3 and BrS1) in vitro by patch clamp technique to provide additional evidence for variant promotion/demotion. A total of 89 rare nonsynonymous VUS (15 KCNQ1, 19 KCNH2, and 55 SCN5A) were engineered by site directed mutagenesis and expressed in either HEK293 cells or TSA201 cells. Whole cell patch-clamp technique was used to functionally characterize these 89 variants to determine gain-of-function (GOF), loss-of-function (LOF), or normal channel function. Overall, the majority of VUS (50/89; 56.2%) studied displayed a wild-type-like electrophysiological phenotype and enabled demotion to likely benign status. The remaining VUS (39/89; 43.8%) were promoted to likely pathogenic status based on either a GOF or LOF electrophysiological signature following patch-clamp analysis. Among 15 KCNQ1 variants, 11 (73.3%) had normal channel function, 3 (20.0%) LOF, and 1 (6.7%) GOF. Of the 19 KCNH2 variants, 11 (57.9%) displayed normal channel function, 5 (26.3%) LOF, and 3 (15.8%) GOF. Finally, among the 55 SCN5A variants, 28 (50.9%) exhibited normal channel function, 19 (34.5%) LOF, and 8 (14.5%) GOF. Here, we provide functional characterization of 89 nonsynonymous VUSs identified during the course of clinically indicated genetic testing. Consistent with the clinical index of suspicion in the VUS-positive subject, 44% of the VUS were promoted to a likely pathogenic variant while 56% were demoted to a likely benign variant. Whether genetic test companies will incorporate this functionally characterized compendium of VUS and issue amended genetic test reports awaits their review and incorporation into their internal framework for variant annotation.

The Importance of Superb Microvascular Imaging for the Differentiation of Malignant Breast Lesions from Benign Lesions.

In this prospective study, the diagnostic performance of the new version of superb microvascular imaging (SMI) in differentiating malignant from benign lesions was evaluated. Ninety breast lesions were included. During color SMI examination, both free-hand region of interest (ROI) and box ROI were used. Vascular index (VI) values were obtained from the lesion using both types of ROI and from normal breast tissue via box ROI. VI values, monochrome SMI grading and histopathological results were compared. The efficacy of color SMI and monochrome SMI was investigated in differentiating between benign and malignant breast lesions. The cut-off value, in the differentiation of benign and malignant lesions with color SMI was 0.50 for box ROI, while it was 0.30 for free-hand ROI. The specificity of VI values obtained with box ROI was higher than that of free-hand ROI when differentiating malignant lesions from benign. Comparison of VI values from a lesion and from normal breast tissue showed that VI values in malignant lesions were significantly higher (p<0.05). The VI values of benign lesions and VI values of normal breast tissue were similar. There was a statistically significant relationship between monochrome SMI grading and the malignancy or benign status of the lesion (p<0.001). Drawing the lesion circumference free-hand using a free-shape ROI did not enhance the sensitivity and specificity. Contrary to popular belief, a more easy and practical measurement method may be more suitable for SMI examination. It is hoped that this will be one of the earliest studies to assess the clinical performance of the latest version of SMI.

Abstract 10579: Prevalence and Morphology of Premature Ventricular Contractions on Routine Athletic Electrocardiogram Screening

Introduction: The clinical implications of incidental premature ventricular contractions (PVCs) are poorly understood. Though controversial, athletes often receive electrocardiograms (ECGs) during pre-participation exams. The prevalence and morphologies of PVCs in this cohort have not been widely reported. Recent studies have defined benign PVC morphologic patterns in athlete populations that may guide clinical evaluations. Methods: Digital ECGs were obtained from 10,728 screened athletes aged 14 to 35 at school and professional team screenings in California. Captured PVCs were analyzed using simultaneous frontal and horizontal plane leads, displaying each standard ECG lead in full-length, allowing for morphologic categorization. PVCs were coded for morphology and benign status using recommended criteria outlined in Figure 1. Results: Twenty-six of 10,728 athletes (0.24%) had at least one PVC (Figure 1); 7 of those (27%) had bigeminy and 3 of those (12%) had trigeminy. Overall, participants were 43% female, 62% White, 12% Black, 9% Asian, and 8% Hispanic. Of those with PVCs, 50% were female, 65% were White, 23% were Black, 8% were Asian, and 4% were Hispanic. Twenty-four ECGs (92%) had PVCs with benign patterns, including 17 with right ventricular outflow tract, 5 with left anterior fascicle, and 2 with left posterior fascicle morphology. Two ECGs had non-benign PVCs with left bundle branch patterns and superior axes. Both of these athletes had normal echocardiograms and exercise testing and are being followed closely. Conclusions: We found a low prevalence of PVCs on routine ECG screening of young athletes, although evaluation of PVC prevalence and frequency are limited by the short duration of an ECG. Most incidental PVCs among young athletes had benign patterns. This study also demonstrates the value of digital ECG recorders to display simultaneous frontal and horizontal plane leads for the morphologic categorization of PVCs which may guide further workup.

CALCIFICATION CLUSTERS AND LESIONS ANALYSIS IN MAMMOGRAM USING MULTI-ARCHITECTURE DEEP LEARNING ALGORITHMS

Today, radiologists observe a mammogram to determine whether breast tissue is normal. However, calcifications on the mammogram are so small that sometimes radiologists cannot locate them without a magnified observation to make a judgment. If clusters formed by malignant calcifications are found, the patient should undergo a needle localization surgical biopsy to determine whether the calcification cluster is benign or malignant. However, a needle localization surgical biopsy is an invasive examination. This invasive examination leaves scars, causes pain, and makes the patient feel uncomfortable and unwilling to receive an immediate biopsy, resulting in a delay in treatment time. The researcher cooperated with a medical radiologist to analyze calcification clusters and lesions, employing a mammogram using a multi-architecture deep learning algorithm to solve these problems. The features of the location of the cluster and its benign or malignant status are collected from the needle localization surgical biopsy images and medical order and are used as the target training data in this study. This study adopts the steps of a radiologist examination. First, VGG16 is used to locate calcification clusters on the mammogram, and then the Mask R-CNN model is used to find micro-calcifications in the cluster to remove background interference. Finally, an Inception V3 model is used to analyze whether the calcification cluster is benign or malignant. The prediction precision rates of VGG16, Mask R-CNN, and Inception V3 in this study are 93.63%, 99.76%, and 88.89%, respectively, proving that they can effectively assist radiologists and help patients avoid undergoing a needle localization surgical biopsy.

Hepatic CPT1A Facilitates Liver-Adipose Cross-Talk via Induction of FGF21 in Mice.

Hepatosteatosis, defined as excessive intrahepatic lipid accumulation, represents the first step of NAFLD. When combined with additional cellular stress, this benign status progresses to local and systemic pathological conditions such as NASH and insulin resistance. However, the molecular events directly caused by hepatic lipid build-up, in terms of its impact on liver biology and peripheral organs, remain unclear. Carnitine palmitoyltransferase 1A (CPT1A) is the rate limiting enzyme for long chain fatty acid beta-oxidation in the liver. Here we utilise hepatocyte-specific Cpt1a knockout (LKO) mice to investigate the physiological consequences of abolishing hepatic long chain fatty acid metabolism. Compared to the wild-type (WT) littermates, high fat diet (HFD)-fed LKO mice displayed more severe hepatosteatosis but were otherwise protected against diet-induced weight gain, insulin resistance, hepatic ER stress, inflammation and damage. Interestingly, increased energy expenditure was observed in LKO mice, accompanied by enhanced adipose tissue browning. RNAseq analysis revealed that the peroxisome proliferator activator alpha (PPARα)- fibroblast growth factor 21 (FGF21) axis was activated in liver of LKO mice. Importantly, antibody-mediated neutralization of FGF21 abolished the healthier metabolic phenotype and adipose browning in LKO mice, indicating that the elevation of FGF21 contributes to the improved liver pathology and adipose browning in HFD-treated LKO mice. Liver with deficient CPT1A expression adopts a healthy steatotic status that protects against HFD-evoked liver damage and potentiates adipose browning in an FGF21-dependent manner. Inhibition of hepatic CPT1A may serve as a viable strategy for the treatment of obesity and NAFLD.

Laparoscopic Technique for Extraction of Large Abdominopelvic Masses

<h3>Study Objective</h3> To review preoperative evaluation of a patient presenting with an abdominopelvic mass. To discuss methods of drainage and spill prevention during surgical management of large abdominopelvic masses and to demonstrate an efficient laparoscopic method for extraction of large adnexal masses. <h3>Design</h3> N/A <h3>Setting</h3> In the operating room with patient in dorsal lithotomy position with both arms tucked. Five-millimeter ports were placed in the umbilicus, the right lower quadrant and the left mid-abdomen. The specimen was extracted through an 8 mm port in the left lower quadrant. <h3>Patients or Participants</h3> 27-year-old female with a 15 × 13 cm abdominopelvic mass who presented with right lower quadrant and low back pain and mild right hydronephrosis. She had a benign appearing cyst on ultrasound and her tumor markers were negative. <h3>Interventions</h3> We employ a morcellation method we refer to as apple-peeling to cut the cyst into a long strip of 1 inch width to allow easy removal through an 8 mm laparoscopic port without spill or struggle. <h3>Measurements and Main Results</h3> N/A <h3>Conclusion</h3> Large abdominopelvic masses can be managed via laparoscopic approach with proper pre-operative work-up to ensure benign status. The apple-peeling morcellation technique demonstrated in this video allows efficient extraction of abominopelvic masses > 10 cm through small laparoscopic ports (8mm)

Are the anatomical, clinical, and ultrasound characteristics of thyroid nodules with Bethesda III or IV cytology and ACR TI-RADS 3, 4, or 5 able to refine the indications for molecular diagnostic tests?

To analyze the association of clinical, anatomical, and ultrasound (US) characteristics of malignancies in Bethesda III or IV (III-B or IV-B) thyroid nodules. The association between malignancies and the following variables were analyzed: III-B or IV-B, age < 55 years and ≥ 55 years, sex, family history of thyroid cancer, history of irradiation, nodule size, and ACR TI-RADS classification in 62 participants who underwent thyroidectomy. Of the 62 participants, 87.1% (54/62) were women, 74.2% were < 55 years old, 95.2% had no family history of thyroid cancer, 56.5% had nodules < 2 cm in size, 62.9% were IV-B, and 69.4% were ACR TI-RADS 4. Thirty-two patients had thyroid carcinoma, and 30 had benign histology. Among all factors associated with malignancy, only ACR TI-RADS 5 classification on US was found to be statistically significant (p = 0.014), while III-B with architectural atypia cytological classification was the only one significantly associated with benign status (p = 0.004). Only a high risk of malignancy as assessed using US was able to refine the indication for molecular tests in a group of patients with indeterminate nodules. We found 85% (53/62) of III-B or IV-B thyroid nodules would benefit from available molecular diagnostic tests.

Long-term analysis of patients with benign multiple sclerosis: new insights about the disability course.

To describe the course of disability in patients with benign multiple sclerosis-i.e., with an expanded disability status scale score < 3 10years after disease onset-for up to 30years after disease onset. We evaluated the proportion of patients remaining in the benign state on the long term and the factor associated with this favorable outcome and determined the pattern of disability course after the loss of the benign status. Patients were selected from the ReLSEP, a French population-based registry. We studied the probability (Kaplan-Meier method) and predictors (multivariate Cox model) of remaining < 3 after year 10, and the course of disability after score 3 according to the duration of the benign phase in patients with ≥ 30years of follow-up (graphs of the course of the mean expanded disability status scale scores in subgroups of patients). 2295/3440 patients had benign multiple sclerosis (66.7%). The probability of remaining benign at year 30 was 0.26 (95% CI 0.26-0.32). A young age at disease onset and a good recovery after the first relapse were associated with remaining benign. Graphs illustrate that those who lost their benign status between years 10 and 30 follow a two-stage course. Beyond score 3, disability accumulation is similar in all but lower disability scores at advanced age are associated with longer benign periods. The longer a patient remains in the benign state, the lower the final EDSS at advanced age.

Convolutional Neural Networks Accurately Predict Benign versus Malignant Status Among Peripheral Nerve Sheath Tumors

Convolutional Neural Networks Accurately Predict Benign versus Malignant Status Among Peripheral Nerve Sheath Tumors

Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Healthful and unhealthful plant-based dietary patterns and their role on 10-year transition to metabolically unhealthy status in obese participants of the ATTICA prospective (2002–2012) study

Abstract Background/Introduction Plant-based diets have been widely promoted for their protective role on cardiometabolic health. However, in the recent literature it is highly suggested that the quality of plant-based diets varies. Purpose The association between plant-based diet indices and 10-year transition to metabolically unhealthy status in metabolically healthy obese (MHO) individuals was assessed. Methods A prospective study was conducted during 2001–2012 studying n=1,514 males and n=1,528 females (aged &amp;gt;18 years old) free of CVD. Healthy metabolic status was defines as absence of all NCEP ATP III (2005) metabolic syndrome components (excluding waist circumference). Follow-up CVD assessment (2011–2012) was achieved in n=2,020 participants (n=317 cases). Overall, healthful and unhealthful plant-based dietary indices (PDI, hPDI and uPDI) were created through a standard procedure; hPDI was principally characterized by increased consumption of fruits/vegetables, whole grains, nuts, legumes, oils, tea/coffee while uPDI was related with increased intake of juices, sweetened beverages, refined grains, potatoes and sweets. Results MHO prevalence reached 4.8% (n=146) (4.9% in men and 4.7% in women, p=0.198). 28.2% of obese participants presented a metabolically benign status. Within the decade, almost half of MHO participants resulted as metabolically unhealthy obese (45% in men and 54% in women, p=0.04). Ranking from 1st to 3rd PDI tertile, transition to metabolically unhealthy status was for men, 63%, 48% and 22% (p&amp;lt;0.001) and for women 67%, 58% and 34% (p&amp;lt;0.001). Multiadjusted analysis revealed significant inverse associations between PDI and 10-year transition to metabolically unhealthy status for men [Hazard Ratio (HR) (3rd vs. 1st tertile)=0.63 95% Confidence Interval (95% CI) (0.41, 0.95)] yet –borderline significantly– for women [HR (3rd vs. 1st PDI tertile) = 0.82 95% CI (0.67, 1.09)]. When the indices for quality of plant-based patterns were used (hPDI and uPDI), only participants assigned to the higher level of adherence to healthful plant-based pattern retained their metabolically healthy profile with this relation being stronger in women; [HR (3rd vs. 1st hPDI tertile) = 0.55 95% CI (0.37, 0.84), for women] and [HR (3rd vs. 1st hPDI tertile) = 0.79 95% CI (0.64, 1.03), for men]. Similarly, the aggravating effect of high adherence to less healthful plant-based food choices was higher for women [HR (3rd vs. 1st uPDI tertile) = 1.68 95% CI (1.23, 1.99)]. Conclusions Higher adherence to plant-based diet was associated with substantially higher likelihood for an obese individual to long-term retain its healthy metabolic status. Most importantly, the healthy or unhealthy food choices within this pattern seemed to determine cardiometabolic status with stronger remarks in women. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].

Association of acute pyelonephritis with double-J ureteral stenting: a nationwide population-based case control study

Objective Urinary Tract Infections (UTIs) due to ureteral catheters has been frequently seen. The risk factors of this include both timing and those of the female gender. However, the association of Acute Pyelonephritis (APN) with use of ureteral DJ stents has rarely been investigated. Materials and Methods: This study enrolled a total of 6,459 patients who were being treated with a ureteral catheter over a 10 year period from the nationwide database of Taiwan’s National Health Insurance Bureau. From these subjects, episodes of APN were found in a total of 500 patients. Additionally, 2,000 patients without APN were randomly enrolled as a control group in order to analyze the associated factors. Results The results indicate that the percentage of those with regards gender, age, duration of implantation, ureteral stent type, hypertension, T2DM, presence of urinary tract infection, benign prostate hyperplasia and pregnancy status were significantly statistically higher in APN patients than non-APN patients. APN did not associate with the use of antibiotics, urolithiasis, chronic kidney disease, malignancy, or uric acid stone in patients with a ureteral catheter. Conclusion: In conclusion, patients with a ureteral catheter associated with APN should be given close attention with regards to the above risk factors. Early removal of the catheter is the best policy for the prevention of APN.

Corrigendum: Machine Learning and Feature Selection Methods for Disease Classification With Application to Lung Cancer Screening Image Data

[This corrects the article DOI: 10.3389/fonc.2019.01393.].

Dietary anti-inflammatory index, metabolic syndrome and transition in metabolic status; a gender-specific analysis of ATTICA prospective study

AimsTo examine the association between dietary anti-inflammatory index (D-AII) and metabolic syndrome (MetS)prevalence, 10-year (2002–2012) diabetes, hypertension, hypercholesterolaemia incidence and 10-year transition from healthy (absence of all MetS traits, excluding waist circumference) to unhealthy metabolic status. MethodsIn 2001–2002, n = 1514 men and n = 1528 women (>18 years old) in Athens, Greece, free of cardiovascular disease were recruited. MetS was defined according to the revised NCEP ATP III (2005) or the IDF criteria or the harmonized criteria. The validated D-AII was calculated using a standardized procedure (range 10–77). ResultsInverse associations were observed between D-AII and transition from healthy to unhealthy metabolic status (Odds Ratio (OR)3rd vs. 1st tertile = 0.88 95% Confidence Interval (95%CI)(0.73, 0.98)) and diabetes (OR3rd vs. 1st tertile = 0.55, 95%CI(0.29, 0.77)). In women, D-AII was inversely associated with transition from healthy to unhealthy metabolic status (OR3rd vs. 1st tertile = 0.55, 95%CI(0.26, 0.90), diabetes (OR3rd vs. 1st tertile = 0.41, 95%CI(0.18, 0.64) and hypertension (OR3rd vs. 1st tertile = 0.75, 95%CI(0.20, 0.95), yet only with diabetes incidence in men (OR3rd vs. 1st tertile = 0.62, 95%CI(0.38, 0.93). ConclusionsDiet with high anti-inflammatory load seems an effective preventive measure to retain a metabolically benign status, principally in terms of glycemic control.

Near-Infrared Labeling of EGFR+ Cells Can Allow Differentiation between Benign and Metastatic Lymph Nodes.

HomeRadiology: Imaging CancerVol. 2, No. 1 PreviousNext Research HighlightsFree AccessNear-Infrared Labeling of EGFR+ Cells Can Allow Differentiation between Benign and Metastatic Lymph NodesAdeline N. BoettcherAdeline N. BoettcherAdeline N. BoettcherPublished Online:Jan 31 2020https://doi.org/10.1148/rycan.2020194014MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major focus: Improving ex vivo identification of benign and metastatic lymph nodes for solid tumor staging.■ Key result: Panitumumab-IRDye800CW (anti-EGFR) imaging of resected lymph nodes from patients with solid tumors enhanced ex vivo classification of benign and metastatic lymph nodes.■ Impact: This imaging methodology can increase efficiency and accuracy of lymph node characterization and can be further developed for in vivo imaging during resection surgeries to easily visualize metastatic lymph nodes.Standard staging of head and neck squamous cell carcinomas is performed by histopathologic assessment of resected lymph nodes from the neck. Metastatic or benign status of resected lymph nodes can be used in the tumor, node, metastasis (TNM) staging system to stage patient tumors. Proper staging of tumors is critical for determining the optimal treatment plan. Current practice requires assessing as many as possible collected lymph nodes for staging. Lymph nodes are typically analyzed by hematoxylin-eosin (H-E) staining to detect differences in tissue architecture for benign or metastatic classification, which can be a time-consuming and subjective process. Nishio et al describe the use of panitumumab-IRDye800CW (anti–epidermal growth factor receptor [EGFR]) as a near-infrared fluorescently labeled agent to selectively label metastatic lymph nodes during ex vivo evaluation.In this single-center, nonrandomized, phase I study, 22 patients underwent surgical resection of primary tumors, as well as either a unilateral or bilateral neck dissection. Panitumumab-IRDye800CW was infused into patients 1–5 days prior to surgery with an average dose of 0.67 mg/kg (range, 0.26–1.05 mg/kg). Resected lymph nodes were subjected to closed-field fluorescence imaging, as well as standard H-E staining, to determine the sensitivity and specificity of fluorescent EGFR labeling. Nishio et al quantified two imaging parameters: (a) mean fluorescence intensity (MFI) and (b) signal-to-background (SBR) and compared these results to histopathologic findings of the lymph nodes. Metastatic lymph nodes had significantly higher MFI and SBR than benign lymph nodes. Taking both MFI and SBR into account, metastatic lymph nodes could be identified with high sensitivity (84.6%), specificity (94.0%), negative predictive value (99.3%), and an acceptable positive predictive value (36.2%).In all, using panitumumab-IRDye800CW to label metastatic lymph nodes could reduce the total number of lymph nodes required for histologic determination of benign or metastatic status. Additionally, regular implementation of the described anti-EGFR labeling approach could help to increase standardization and efficacy of lymph node identification.Highlighted ArticleNishio, N, van den Berg NS, van Keulen S, et al. Optical molecular imaging can differentiate metastatic benign lymph nodes in head and neck cancer. Nat Commun 2019;10:5044. doi: https://doi.org/10.1038/s41467-019-13076-7Highlighted ArticleNishio, N, van den Berg NS, van Keulen S, et al. Optical molecular imaging can differentiate metastatic benign lymph nodes in head and neck cancer. Nat Commun 2019;10:5044. doi: https://doi.org/10.1038/s41467-019-13076-7 Crossref, Medline, Google ScholarArticle HistoryPublished online: Jan 31 2020 FiguresReferencesRelatedDetailsRecommended Articles USPIO-enhanced MRI for Nodal Staging in Patients with Head and Neck CancerRadiology: Imaging Cancer2022Volume: 4Issue: 5Advances in Diagnosis and Multidisciplinary Management of Oropharyngeal Squamous Cell Carcinoma: State of the ArtRadioGraphics2019Volume: 39Issue: 7pp. 2055-2068Application of N Descriptors Proposed by the International Association for the Study of Lung Cancer in Clinical StagingRadiology2021Volume: 300Issue: 2pp. 450-457CT-based Radiomic Signatures for Predicting Histopathologic Features in Head and Neck Squamous Cell CarcinomaRadiology: Imaging Cancer2020Volume: 2Issue: 3Impact of 18F-DCFPyL PET on Staging and Treatment of Unfavorable Intermediate or High-Risk Prostate CancerRadiology2022Volume: 304Issue: 3pp. 600-608See More RSNA Education Exhibits AJCC 2018 Head and Neck Cancer Staging Manual: Get Prepared for the ENT Tumor BoardDigital Posters2018Cystic Cervical Lymph Nodes: A Systematic Approach and Useful Imaging Features for their DifferentiationDigital Posters2020Esophageal Cancer: Role of Imaging in Primary Staging and Assessment of Response to Neoadjuvant TherapyDigital Posters2018 RSNA Case Collection Synovial sarcoma of neckRSNA Case Collection2020Multiple Endocrine Neoplasia Type 1 SyndromeRSNA Case Collection2021Horner syndrome in neuroblastomaRSNA Case Collection2020 Vol. 2, No. 1 Metrics Altmetric Score PDF download

Machine Learning and Feature Selection Methods for Disease Classification With Application to Lung Cancer Screening Image Data.

As awareness of the habits and risks associated with lung cancer has increased, so has the interest in promoting and improving upon lung cancer screening procedures. Recent research demonstrates the benefits of lung cancer screening; the National Lung Screening Trial (NLST) found as its primary result that preventative screening significantly decreases the death rate for patients battling lung cancer. However, it was also noted that the false positive rate was very high (>94%).In this work, we investigated the ability of various machine learning classifiers to accurately predict lung cancer nodule status while also considering the associated false positive rate. We utilized 416 quantitative imaging biomarkers taken from CT scans of lung nodules from 200 patients, where the nodules had been verified as cancerous or benign. These imaging biomarkers were created from both nodule and parenchymal tissue. A variety of linear, nonlinear, and ensemble predictive classifying models, along with several feature selection methods, were used to classify the binary outcome of malignant or benign status. Elastic net and support vector machine, combined with either a linear combination or correlation feature selection method, were some of the best-performing classifiers (average cross-validation AUC near 0.72 for these models), while random forest and bagged trees were the worst performing classifiers (AUC near 0.60). For the best performing models, the false positive rate was near 30%, notably lower than that reported in the NLST.The use of radiomic biomarkers with machine learning methods are a promising diagnostic tool for tumor classification. The have the potential to provide good classification and simultaneously reduce the false positive rate.

P5295Stable and temporal metabolically benign obesity and cardiovascular disease onset in males and females: the missing link with adiponectin

Abstract Background/Introduction Metabolically healthy obesity (MHO) status has been recently conferred to be a transient condition with cohorts revealing that a considerable proportion, from 33% to 52%, lose their status over time. Purpose To evaluate the stability of MHO, its effect on 10-year first fatal/non fatal CVD onset and the mediating effect of adiponectin. Methods A prospective study was conducted during 2001–2012 studying n=1,514 males and n=1,528 females (aged &gt;18 years old) free of CVD. Follow-up CVD assessment (2011–2012) was achieved in n=2,020 participants; of them, n=317 incident cases were identified. Obesity was defined as body mass index≥30kg/m2 and healthy metabolic status as absence of all NCEP ATP III (2005) metabolic syndrome components (excluding waist circumference). Circulating adiponectin level was measured at baseline (4.0 (2.0) μg/mL). Results MHO prevalence reached 4.8% (n=146) (4.9% in males and 4.7% in females, p=0.198). 28.2% of obese participants presented a metabolically benign status at baseline. In the 5-year follow-up period, transition to metabolically unhealthy status was observed for 33% of MHO participants. Within the decade, almost half of MHO participants resulted as metabolically unhealthy obese. Unadjusted analysis revealed that stable vs. temporal MHO subjects had better lifestyle (i.e. higher adherence to Mediterranean diet and better physical activity status) at the recruitment (all ps&lt;0.05). Temporal MHO subjects presented lower adiponectin values (2.8 (1.1) μg/mL) compared with their stable MHO counterparts (4.1 (1.9) μg/mL) (p&lt;0.05). Multivariate Cox regression analysis revealed no significant discrepancies on 10-year CVD risk between MHO and metabolically healthy non-obese subjects (Hazard Ratio (HR)=0.95, 95% Confidence Interval (95% CI) 0.37, 2.08, p=0.32). Only the subset of temporal MHO subjects reached the level of significance (HR=1.43, 95% CI 1.02, 2.01, p=0.04). Stable MHO status was not independently associated with 10-year CVD risk (p&gt;0.05). Low vs. high adiponectin level was associated with ∼1.3 times higher 10-year risk to move from MHO to metabolically unhealthy obesity status (HR=1.33 95% CI 1.10, 4.02). Sensitivity analyses revealed that adiponectin had a significant interacting effect on the examined associations (p for interaction=0.01); stratified analysis using the mean value of adiponectin to define the strata revealed that MHO (stable or temporal) status was positively associated with 10-year CVD event only in participants with low adiponectin levels i.e. below the mean value of 4.1 μg/mL (HR=1.45 95% CI 1.19, 3.68). Conclusions Weight management is needed to prevent cardiometabolic features even in participants with increased weight status with healthy metabolic status. It is noteworthy that adiponectin may be an underlying path of the stability and CVD risk corresponding to this intermediate condition probably related with insulin resistance and other relevant paths. Acknowledgement/Funding The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].