Morphologic and molecular correlates of EZH2 as a predictor of platinum resistance in high-grade ovarian serous carcinoma.

BACKGROUND: Enhancer of zesta homologue 2 (EZH2) is an essential component of polycomb repressive complex 2 (PRC2) that contributes to tumor progression and chemo-resistance. The aim of this study was to comprehensively assess the prognostic value of EZH2 across the morphologic and molecular spectra of high-grade serous ovarian carcinoma (HGSOC) by utilizing both immunohistochemistry (IHC) and proteogenomic technologies. METHODS: IHC of EZH2 was performed using a tissue microarray of 79 HGSOC scored (+/-) for lymphovascular invasion (LVI), tumor-infiltrating lymphocytic aggregates ≥1 mm (TIL) and architectural growth patterns. The association of EZH2 H-score with response to therapy and overall survival was evaluated by tumor features. We also evaluated EZH2 transcriptional (RNA sequencing) and protein (mass spectrometry) expression from bulk tumor samples from 336 HGSOC from The Cancer Genome Atlas (TCGA). EZH2 expression and co-expression networks were compared by clinical outcomes. RESULTS: For HGSOC without TIL (58%), EZH2 expression was almost 2-fold higher in platinum resistant tumors (P = 0.01). Conversely, EZH2 was not associated with platinum resistance among TIL+ HGSOC (P = 0.41). EZH2 expression was associated with reduced survival for tumors with LVI (P = 0.04). Analysis of TCGA found higher EZH2 expression in immunoreactive and proliferative tumors (P = 6.7 × 10- 5) although protein levels were similar across molecular subtypes (P = 0.52). Both mRNA and protein levels of EZH2 were lower in platinum resistant tumors although they were not associated with survival. Co-expression analysis revealed EZH2 networks totaling 1049 mRNA and 448 proteins that were exclusive to platinum sensitive or resistant tumors. The EZH2 network in resistant HGSOC included CARM1 which was positively correlated with EZH2 at both mRNA (r = 0.33, p = 0.003) and protein (r = 0.14, P = 0.01) levels. Further, EZH2 co-expression with CARM1 corresponded to a decreased prognostic significance of EZH2 expression in resistant tumors. CONCLUSIONS: Our findings demonstrate that EZH2 expression varies based on its interactions with immunologic pathways and tumor microenvironment, impacting the prognostic interpretation. The association between high EZH2 expression and platinum resistance in TIL- HGSOC warrants further study of the implications for therapeutic strategies.

Comparison of imaging modalities for measuring the diameter of intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic cysts detected by imaging. Cyst size is one of many features evaluated on computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic ultrasonography (EUS) to help guide IPMN management. Our objective was to determine which imaging modality best predicts pathological cyst size. METHODS: We analyzed records for 57 IPMN cases surgically treated at Moffitt Cancer Center from 2008 to 2016 for whom pre-operative CT, MRI, and EUS IPMN cyst size and post-operative pathological cyst size values were available. Long axis cyst diameter measurements were compared to each other and corresponding pathological cyst measurements using within-subjects ANOVA, Bland-Altman analysis, and linear regression. Consensus measurements were also performed on CT and MRI images. RESULTS: Cyst size measured via CT and MRI overestimated pathological size by 0.33 cm and 0.27 cm, respectively, whereas EUS underestimated pathological size by 0.05 cm and had the narrowest 95% limit of agreement (LOA). Among pathologically-confirmed cysts <3 cm, MRI overestimated pathological size by 0.30 cm (P = 0.049) and had the widest LOA, followed by EUS and CT. Among cysts ≥3 cm, EUS underestimated pathological size by 0.35 cm (P = 0.059) and MRI and CT overestimated pathological size by 0.23 cm and 0.51 cm, respectively. CONCLUSIONS: In this small retrospective study, EUS cyst size measurements correlated best with pathologic specimens compared to CT and MRI, especially for cysts < 3 cm. Larger prospective studies are needed to determine which imaging modalities are best to risk-stratify IPMNs and guide surgical versus. Non-surgical management.

Baseline markers of inflammation, lipids, glucose, and Dietary Inflammatory Index scores do not differ between adults willing to participate in an intensive inflammation reduction intervention and those who do not.

BACKGROUND:: Chronic inflammation is associated with numerous chronic diseases and can be managed with diet. AIM:: The purpose of this study was to examine differences in baseline characteristics and plasma inflammation levels between two groups of participants that participated in an intensive, lifestyle intervention or a remotely delivered intervention. This work also assessed the association between Dietary Inflammatory Index (DII)® scores and participants' inflammatory and metabolic biomarkers at baseline. METHOD:: Ninety-five participants (61 intervention, 34 control) chose to enroll in either a 12-month intervention consisting of a face-to-face nutrition, physical activity, and stress management intervention or a remotely-delivered intervention (control group) focusing on general cancer prevention. The intervention group met at the University of South Carolina for classes and the control group had materials emailed to them. A quantile regression was used to compare participants' high-sensitivity C-reactive protein and interleukin-6 levels. Multiple linear regression was used to determine the association between DII scores and biomarkers. RESULTS:: There were significant differences in age, body mass index, body fat percentage, and blood pressure between groups, but there were no differences in levels of inflammatory biomarkers. Values of interleukin-6 at the 90th percentile of its distribution were 8.31 pg/ml higher among those in DII quartile 4 compared with quartile 1 ( p = 0.02). All other outcomes were not significant. CONCLUSION:: Given similar levels of inflammatory biomarkers, participants opting for the control group would also have benefited from a more intensive lifestyle intervention focusing on reducing inflammation.

Mentoring, Training, and Scholarly Productivity Experiences of Cancer-Related Health Disparities Research Trainees: Do Outcomes Differ for Underrepresented Scientists?

The study aims to explore variation in scholarly productivity outcomes by underrepresented status among a diverse sample of researchers in a community-engaged training program. We identified 141 trainees from a web-based survey of researchers in the National Cancer Institute-funded, Community Networks Program Centers (CNPCs) (2011-2016). We conducted a series of multiple logistic regression models to estimate the effect of National Institutes of Health (NIH)-defined underrepresented status on four, self-reported, scholarly productivity outcomes in the previous 5 years: number of publications (first-authored and total) and funded grants (NIH and any agency). Sixty-five percent (n = 92) indicated NIH underrepresented status. In final adjusted models, non-NIH underrepresented (vs. underrepresented) trainees reported an increased odds of having more than the median number of total publications (> 9) (OR = 3.14, 95% CI 1.21-8.65) and any grant funding (OR = 5.10, 95% CI 1.77-14.65). Reporting ≥ 1 mentors (vs. none) was also positively associated (p < 0.05) with these outcomes. The CNPC underrepresented trainees had similar success in first-authored publications and NIH funding as non-underrepresented trainees, but not total publications and grants. Examining trainees' mentoring experiences over time in relation to scholarly productivity outcomes is needed.

The Impact of Obesity on Surgical Outcome in Endometrial Cancer Patients: A Systematic Review.

Background: Obesity is a significant public health problem in the United States, and many studies have established obesity as a significant risk factor for endometrial cancer. Surgery is the standard of care in staging and treatment of endometrial cancer, and obesity may influence surgical outcomes because of its attendant comorbid conditions. Therefore, assessment of the impact of obesity on surgical outcome is important for decreasing morbidity and improving survival in patients with endometrial cancer. Objective: The aims of this research were to evaluate and review epidemiologic data systematically on the impact of obesity on surgical outcomes and to assess safety and feasibility of newer surgical techniques in obese patients. Materials and Methods: A systematic search of PubMed was conducted to identify articles between 2004 and 2013 that focused on the impact of obesity on surgical outcome. Reference lists of retrieved articles were also used to identify other relevant articles. Thirteen relevant articles were reviewed. Results: Evidence from epidemiologic studies showed that obesity impacts surgical outcome adversely. On average, obese patients have worse surgical outcomes than their nonobese counterparts. In addition, surgical outcome worsens as level of obesity increases. However, surgical procedure also influences this association. Minimally invasive surgeries are more useful and are accompanied with fewer complications than conventional laparotomy and can be performed safely in obese patients. Conclusions: Obesity is a significant risk in the etiology, treatment, and surgical outcomes of patients with endometrial cancer. Future research will need more randomized controlled trials and prospective studies to identify the best procedures for maximal outcomes. (J GYNECOL SURG 32:149).

Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-naïve patients with pancreatic ductal adenocarcinoma.

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management. Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS). Materials and methods: A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations. Results: CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS. Conclusions: Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

Comparison of Radiomic Features in a Diverse Cohort of Patients With Pancreatic Ductal Adenocarcinomas.

BACKGROUND: Significant racial disparities in pancreatic cancer incidence and mortality rates exist, with the highest rates in African Americans compared to Non-Hispanic Whites and Hispanic/Latinx populations. Computer-derived quantitative imaging or "radiomic" features may serve as non-invasive surrogates for underlying biological factors and heterogeneity that characterize pancreatic tumors from African Americans, yet studies are lacking in this area. The objective of this pilot study was to determine if the radiomic tumor profile extracted from pretreatment computed tomography (CT) images differs between African Americans, Non-Hispanic Whites, and Hispanic/Latinx with pancreatic cancer. METHODS: We evaluated a retrospective cohort of 71 pancreatic cancer cases (23 African American, 33 Non-Hispanic White, and 15 Hispanic/Latinx) who underwent pretreatment CT imaging at Moffitt Cancer Center and Research Institute. Whole lesion semi-automated segmentation was performed on each slice of the lesion on all pretreatment venous phase CT exams using Healthmyne Software (Healthmyne, Madison, WI, USA) to generate a volume of interest. To reduce feature dimensionality, 135 highly relevant non-texture and texture features were extracted from each segmented lesion and analyzed for each volume of interest. RESULTS: Thirty features were identified and significantly associated with race/ethnicity based on Kruskal-Wallis test. Ten of the radiomic features were highly associated with race/ethnicity independent of tumor grade, including sphericity, volumetric mean Hounsfield units (HU), minimum HU, coefficient of variation HU, four gray level texture features, and two wavelet texture features. A radiomic signature summarized by the first principal component partially differentiated African American from non-African American tumors (area underneath the curve = 0.80). Poorer survival among African Americans compared to Non-African Americans was observed for tumors with lower volumetric mean CT [HR: 3.90 (95% CI:1.19-12.78), p=0.024], lower GLCM Avg Column Mean [HR:4.75 (95% CI: 1.44,15.37), p=0.010], and higher GLCM Cluster Tendency [HR:3.36 (95% CI: 1.06-10.68), p=0.040], and associations persisted in volumetric mean CT and GLCM Avg Column after adjustment for key clinicopathologic factors. CONCLUSIONS: This pilot study identified several textural radiomics features associated with poor overall survival among African Americans with PDAC, independent of other prognostic factors such as grade. Our findings suggest that CT radiomic features may serve as surrogates for underlying biological factors and add value in predicting clinical outcomes when integrated with other parameters in ongoing and future studies of cancer health disparities.

The Florida Pancreas Collaborative Next-Generation Biobank: Infrastructure to Reduce Disparities and Improve Survival for a Diverse Cohort of Patients with Pancreatic Cancer.

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders; study eligibility and design; recruitment strategies; standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data; our cloud-based data management platform; and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

Impact of a 3-Month Anti-inflammatory Dietary Intervention Focusing on Watermelon on Body Habitus, Inflammation, and Metabolic Markers: A Pilot Study.

An anti-inflammatory dietary intervention called the Inflammation Management Intervention (IMAGINE) was adapted to emphasize watermelon due to its anti-inflammatory properties. This pilot study (n = 23) tested the effect of a watermelon-enhanced IMAGINE intervention (n = 15) on body habitus and markers of inflammation and metabolism. This 3-month self-selection trial, consisting of weekly in-person classes and online education for 12 weeks, focused on incorporating watermelon into an already anti-inflammatory diet. Controls (n = 8) received basic health education via email and blogs. Measurements, including diet, anthropometrics, actigraphy, and a blood draw, were made at baseline and immediately postintervention. Linear regression analyses were conducted using intervention status as the main exposure. Post hoc analyses then ignored intervention assignment and grouped participants based on their change in their energy-adjusted Dietary Inflammatory Index (E-DIITM) score. There were no group-by-time interactions for any of the studied outcomes. However, some intervention participants' diets became more proinflammatory, and several control participants' diets became more anti-inflammatory. Those participants below the median of E-DII change (ie, more anti-inflammatory changes) showed reductions in body fat percent (-1.27% vs +0.90%, respectively, P = .01), body mass index (-0.66 vs +0.38 kg/m2, respectively, P = .06) and body weight (-0.99 vs +0.54 kg, respectively, P = .08) compared to those above the median of E-DII change. This study demonstrates that individuals who adopt a more anti-inflammatory diet containing watermelon will have improvements in body anthropometrics. Future studies should focus on increasing adherence and compliance to intervention prescriptions, exploring options to extend interventions to evaluate long-term changes, and further examining changes in inflammatory biomarkers. Clinical Trials Registration: NCT03158740.

Polyphenol-Rich Foods and Osteoporosis.

BACKGROUND: Osteoporosis is a metabolic disease affecting the bone mineral density and thus compromise the strength of the bones. Disease prevention through diet is the objective of the study and discussion. Among the several nutrients investigated, the intake of phenols seems to influence bone mineral density by acting as free radical scavengers, preventing oxidation-induced damage to bone cells. In addition, the growing understanding of the bone remodelling process supports the theory that inflammation significantly contributes to the etiopathogenesis of osteoporosis. METHODS: To provide an overview of current evidence on polyphenol-rich foods and osteoporosis prevention we made a comprehensive review of the literature focusing on the state of art of the topic. RESULTS: Some polyphenol-rich foods, including olive oil, fruit and vegetable, tea and soy, seem to be beneficial for preventing osteoporosis disease and its progression. The mechanism is still partly unknown and may involve different pathways which include inflammation and other disease reactions. CONCLUSIONS: However, further research is needed to better understand the mechanisms regulating the molecular interaction between osteoporosis incidence and progression and polyphenol-rich foods. The current evidence suggests that dietary intervention with polyphenol rich foods may be useful to prevent incidence and progression of this condition.

Characteristics and Clinical Outcomes of Individuals at High Risk for Pancreatic Cancer: A Descriptive Analysis from a Comprehensive Cancer Center.

Pancreatic cancer (PC), a leading cause of cancer-related deaths in the United States, is typically diagnosed at an advanced stage. To improve survival, there is an unmet need to detect pre-malignant lesions and early invasive disease. Prime populations to study for early detection efforts include cohorts of high risk individuals (HRI): those with increased risk to develop pre-malignant pancreatic cysts and PC because of a familial or hereditary predisposition to the disease and those in the general population of sporadic cases who are incidentally found to harbor a pre-malignant pancreatic cyst. The objective of this study was to describe the characteristics and clinical outcomes of cohorts of HRI identified at Moffitt Cancer Center. We set out to determine the uptake of screening, the prevalence and characteristics of solid and cystic pancreatic lesions detected via screening or as incidental findings, and the age at which lesions were detected. Of a total of 329 HRI, roughly one-third were found to have pancreatic lesions, most of which constituted pre-malignant cysts known as intraductal papillary mucinous neoplasms. Individuals with the highest genetic risk for PC were found to have smaller cysts at a much earlier age than sporadic cases with incidental findings; however, many individuals at high genetic risk did not have abdominal imaging reports on file. We also identified a subset of HRI at moderate genetic risk for PC that were found to have cystic and solid pancreatic lesions as part of a diagnostic work-up rather than a screening protocol. These findings suggest the pancreatic research community should consider expanding criteria for who should be offered screening. We also emphasize the importance of continuity of care between cancer genetics and gastrointestinal oncology clinics so that HRI are made aware of the opportunities related to genetic counseling, genetic testing, and screening.

Racial and ethnic disparities in a state-wide registry of patients with pancreatic cancer and an exploratory investigation of cancer cachexia as a contributor to observed inequities.

Pancreatic cancer (PC) is characterized by racial/ethnic disparities and the debilitating muscle-wasting condition, cancer cachexia. Florida ranks second in the number of PC deaths and has a large and understudied minority population. We examined the primary hypothesis that PC incidence and mortality rates may be highest among Black Floridians and the secondary hypothesis that biological correlates of cancer cachexia may underlie disparities. PC incidence and mortality rates were estimated by race/ethnicity, gender, and county using publicly available state-wide cancer registry data that included approximately 2700 Black, 25 200 Non-Hispanic White (NHW), and 3300 Hispanic/Latino (H/L) Floridians diagnosed between 2004 and 2014. Blacks within Florida experienced a significantly (P < 0.05) higher incidence (12.5/100 000) and mortality (10.97/100 000) compared to NHW (incidence = 11.2/100 000; mortality = 10.3/100 000) and H/L (incidence = 9.6/100 000; mortality = 8.7/100 000), especially in rural counties. To investigate radiologic and blood-based correlates of cachexia, we leveraged data from a subset of patients evaluated at two geographically distinct Florida Cancer Centers. In Blacks compared to NHW matched on stage, markers of PC-induced cachexia were more frequent and included greater decreases in core musculature compared to corresponding healthy control patients (25.0% vs 10.1% lower), greater decreases in psoas musculature over time (10.5% vs 4.8% loss), lower baseline serum albumin levels (3.8 vs 4.0 gm/dL), and higher platelet counts (332.8 vs 268.7 k/UL). Together, these findings suggest for the first time that PC and cachexia may affect Blacks disproportionately. Given its nearly universal contribution to illness and PC-related deaths, the early diagnosis and treatment of cachexia may represent an avenue to improve health equity, quality of life, and survival.

Understanding the Importance of Gene and Environment in the Etiology and Prevention of Type 2 Diabetes Mellitus in High-Risk Populations.

Current literature focuses on the complications and treatment of Type 2 Diabetes Mellitus (T2DM) while clustering environmental and genetic factors to explain the disease. Interventions proposed to reduce diabetes prevalence should focus predominantly on initiating active rapports of family members and promoting a more communication-oriented preventative approach between diabetics and non-diabetics. Due to varying risks in T2DM by race and ethnicity, these populations should follow race-appropriate guidelines to prevent further T2DM occurrence and complications. The review consists of information related to the genetic component of T2DM to help identify high-risk groups and focuses on the environmental aspect of the disease to help consider appropriate techniques to reduce disease burden. Genetic factors play important roles in the pathogenesis of diabetes and thus are an essential element of understanding the cause of the disease and possible methods of prevention. Focusing on high-risk groups with T2DM could have profound effects on the current health care situation. In this review, we discuss the epidemiology of diabetes in the United States and propose methods of preventing and delaying the development of T2DM in high-risk individuals.