RESUMO
Pancreatic cancer (PaCa) is the third leading cause of cancer-related deaths in the United States. There is an unmet need to develop strategies to detect PaCa at an early, operable stage and prevent its progression. Intraductal papillary mucinous neoplasms (IPMNs) are cystic PaCa precursors that comprise nearly 50% of pancreatic cysts detected incidentally via cross-sectional imaging. Since IPMNs can progress from low- and moderate-grade dysplasia to high-grade dysplasia and invasion, the study of these lesions offers a prime opportunity to develop early detection and prevention strategies. Organoids are an ideal preclinical platform to study IPMNs, and the objective of the current investigation was to establish a living biobank of patient-derived organoids (PDO) from IPMNs. IPMN tumors and adjacent normal pancreatic tissues were successfully harvested from 15 patients with IPMNs undergoing pancreatic surgical resection at Moffitt Cancer Center & Research Institute (Tampa, FL) between May of 2017 and March of 2019. Organoid cultures were also generated from cryopreserved tissues. Organoid count and size were determined over time by both Image-Pro Premier 3D Version 9.1 digital platform and Matlab application of a Circular Hough Transform algorithm, and histologic and genomic characterization of a subset of the organoids was performed using immunohistochemistry and targeted sequencing, respectively. The success rates for organoid generation from IPMN tumor and adjacent normal pancreatic tissues were 81% and 87%, respectively. IPMN organoids derived from different epithelial subtypes showed different morphologies in vitro, and organoids recapitulated histologic and genomic characteristics of the parental IPMN tumor. In summary, this preclinical model has the potential to provide new opportunities to unveil mechanisms of IPMN progression to invasion and to shed insight into novel biomarkers for early detection and targets for chemoprevention.
Assuntos
Bancos de Espécimes Biológicos , Organoides/patologia , Pâncreas/patologia , Neoplasias Intraductais Pancreáticas/patologia , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Técnicas de Cultura de Células , Feminino , Histocitoquímica , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Organoides/citologia , Pâncreas/citologia , Técnicas de Cultura de TecidosRESUMO
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.
Assuntos
Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Endossonografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/diagnóstico por imagem , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/patologia , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios XRESUMO
Serological assays have been used in seroprevalence studies to inform the dynamics of COVID-19. Lateral flow immunoassay (LFIA) tests are a very practical technology to use for this objective; however, one of their challenges may be variable diagnostic performance. Given the numerous available LFIA tests, evaluation of their accuracy is critical before real-world implementation. We performed a retrospective diagnostic evaluation study to independently determine the diagnostic accuracy of 4 different antibody-detection LFIA tests: Now Check (Bionote), CareStart (Access bio), Covid-19 BSS (Biosynex) and OnSite (CTK Biotech). The sample panel was comprised of specimens collected and stored in biobanks; specifically, specimens that were RT-PCR positive for SARS-CoV-2 collected at various times throughout the COVID-19 disease course and those that were collected before the pandemic, during 2018 or earlier, from individuals with upper respiratory symptoms but were negative for tuberculosis. Clinical performance (sensitivity and specificity) was analyzed overall, and subset across individual antibody isotypes, and days from symptoms onset. A very high specificity (98% - 100%) was found for all four tests. Overall sensitivity was variable, ranging from 29% [95% CI: 21%-39%] to 64% [95% CI: 54%-73%]. When considering detection of IgM only, the highest sensitivity was 42% [95% CI: 32%-52%], compared to 57% [95% CI: 47%-66%] for IgG only. When the analysis was restricted to at least 15 days since symptom onset, across any isotype, the sensitivity reached 90% for all four brands. All four LFIA tests proved effective for identifying COVID-19 antibodies when two conditions were met: 1) at least 15 days have elapsed since symptom onset and 2) a sample is considered positive when either IgM or IgG is present. With these considerations, the use of this assays could help in seroprevalence studies or further exploration of its potential uses.
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BACKGROUND: Given the growing interest in using microRNAs (miRNAs) as biomarkers of early disease, establishment of robust protocols and platforms for miRNA quantification in biological fluids is critical. OBJECTIVE: The goal of this multi-center pilot study was to evaluate the reproducibility of NanoString nCounter™ technology when analyzing the abundance of miRNAs in plasma and cystic fluid from patients with pancreatic lesions. METHODS: Using sample triplicates analyzed across three study sites, we assessed potential sources of variability (RNA isolation, sample processing/ligation, hybridization, and lot-to-lot variability) that may contribute to suboptimal reproducibility of miRNA abundance when using nCounter™, and evaluated expression of positive and negative controls, housekeeping genes, spike-in genes, and miRNAs. RESULTS: Positive controls showed a high correlation across samples from each site (median correlation coefficient, r> 0.9). Most negative control probes had expression levels below background. Housekeeping and spike-in genes each showed a similar distribution of expression and comparable pairwise correlation coefficients of replicate samples across sites. A total of 804 miRNAs showed a similar distribution of pairwise correlation coefficients between replicate samples (p= 0.93). After normalization and selecting miRNAs with expression levels above zero in 80% of samples, 55 miRNAs were identified; heatmap and principal component analysis revealed similar expression patterns and clustering in replicate samples. CONCLUSIONS: Findings from this pilot investigation suggest the nCounter platform can yield reproducible results across study sites. This study underscores the importance of implementing quality control procedures when designing multi-center evaluations of miRNA abundance.
Assuntos
MicroRNA Circulante , MicroRNAs , Benchmarking , MicroRNA Circulante/genética , Perfilação da Expressão Gênica/métodos , Humanos , MicroRNAs/genética , Projetos Piloto , Controle de Qualidade , Reprodutibilidade dos TestesRESUMO
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.
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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.
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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.
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Caquexia/epidemiologia , Caquexia/etiologia , Disparidades nos Níveis de Saúde , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/epidemiologia , Caquexia/mortalidade , Feminino , Florida/epidemiologia , Florida/etnologia , Geografia Médica , Humanos , Incidência , Masculino , Mortalidade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Sistema de Registros , Programa de SEER , Fatores Socioeconômicos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND OBJECTIVES: Residency training is a pivotal time to establish skills for career-long practices, particularly for challenging skills such as human papillomavirus (HPV) vaccine recommendation. Training experience and preferences related to delivering HPV vaccine recommendations were examined for family medicine (FM) residents and faculty. METHODS: Residents (n=28) and faculty (n=19) were identified through a national FM residency directory and recruited from training programs in Florida. Participants completed a phone interview assessing key aspects of HPV vaccine recommendation training. Interviews were audio recorded, transcribed verbatim, and analyzed using content analysis. A brief follow-up survey assessing training, practices, and demographics was emailed after the interview. RESULTS: Residents' training experience with HPV vaccine recommendation varied from none to extensive, and was often self-directed. Variation in training was seen between and within programs. Faculty often noted HPV vaccination training was not standardized and residents lacked instruction about effective communication. Most programs relied on preceptors for training residents but training from preceptors varied widely and was often not standardized within the program. CONCLUSIONS: This study identified a lack of consistent and standardized training for delivering HPV vaccine recommendations. A training curriculum that uses multiple modalities and reflects resident and faculty preferences is needed.
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Docentes de Medicina/educação , Medicina de Família e Comunidade/educação , Internato e Residência , Vacinas contra Papillomavirus/administração & dosagem , Vacinação/métodos , Currículo , Feminino , Humanos , Entrevistas como Assunto , Masculino , Infecções por Papillomavirus/prevenção & controleRESUMO
A physician's recommendation for human papillomavirus (HPV) vaccine is a key predictor of vaccine uptake; however, little is known about how physicians communicate about HPV vaccine with male patients. We sought to describe physicians' HPV vaccine communication practices with males who are of vaccine-eligible age (9-26 years). We surveyed representative samples of pediatric and family medicine physicians in Florida, and assessed whether physicians present HPV vaccine as optional or routine, and as a vaccine that prevents cancer. We also assessed the type of visit during which physicians discuss HPV vaccine with adolescent males and whether other healthcare providers in the practice discuss HPV vaccine or make the initial recommendation. We received 367 completed surveys (50.7% response rate). Few physicians (29.9%) reported they typically present HPV vaccine as routine to males ages 11-12 years, who constitute the target group for routine vaccination. When discussing HPV vaccination, many physicians reported somewhat or strongly emphasizing cancer prevention (80.0%). Physicians most often discussed HPV vaccine when they saw patients for well-child visits (93.0%) and least often at acute care visits (15.3%). Over half reported that at least one other healthcare professional in their practice discusses (56.1%) or makes the initial recommendation for (54.9%) HPV vaccination. Many physicians in our sample are presenting HPV vaccine as optional rather than routine and are missing opportunities to communicate with males about the vaccine. Our findings identify areas for future interventions to improve physicians' HPV vaccine communication and, ultimately, increase the use of this cancer-preventing vaccine.
Assuntos
Comunicação em Saúde , Neoplasias/prevenção & controle , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Médicos , Adolescente , Adulto , Criança , Florida , Humanos , Masculino , Pessoa de Meia-Idade , Pediatras , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Rates of routine human papillomavirus (HPV) vaccination of adolescent males in the United States are low. Leading health organizations advocate consistent and strong physician recommendations to improve HPV vaccine dissemination. This study describes the prevalence and correlates of consistent and strong physician recommendations for HPV vaccination of adolescent males. METHODS: We surveyed pediatric and family medicine physicians in Florida about their HPV vaccine recommendations for male vaccine-eligible age groups (11-12, 13-17, 18-21 years). Descriptive statistics compared consistency and strength of HPV recommendations across age groups. Multivariable logistic regression examined factors associated with consistent and strong recommendations for 11- to 12-year-olds. RESULTS: We received 367 completed surveys (51% response rate). Physicians most often consistently and strongly recommended HPV vaccine to males ages 13 to 17 (39%) compared with ages 11 to 12 (31%) and 18 to 21 (31%). Consistent and strong recommendation for 11- to 12-year-old males was more likely to be delivered by Vaccine for Children providers and less likely among physicians who reported more personal barriers to vaccination, particularly concerns about vaccine safety, concerns about adding vaccines to the vaccine schedule, and difficulty in remembering to discuss HPV vaccination. CONCLUSIONS: Physicians' current consistency and strength of HPV vaccine recommendations do not align with national recommendations. Interventions to improve HPV vaccine recommendations must also consider the influence of physicians' personal barriers to HPV vaccine delivery. IMPACT: As one of the first studies to examine both consistency and strength of physicians' HPV vaccine recommendations for males, our findings can inform future interventions focused on facilitating physicians' recommendations. Cancer Epidemiol Biomarkers Prev; 25(10); 1435-46. ©2016 AACR.