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Photoacoustic detection of circulating melanoma cells in late stage patients

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Journal of Innovative Optical Health Sciences 2020年第6期3卷 47-54页

作者： John A.Viator Marc Hazur Andrea Sajewski Ahmad Tarhini Martin E.Sanders Robert H.Edgar Department of Engineering Duquesne University 600 Forbes Avenue PittsburghPennsylvania 15282USA Department of Bioengineering University of Pittsburgh 3700 O'Hara Street PittsburghPA 15260USA moffitt comprehensive cancer center and research institute 10920 mckinley drive TampaFlorida 33612USA Acousys Biodevices Inc 1777 Highland Drive Ann ArborMichigan 48108USA

Melanoma is the deadliest skin cancer and is responsible for over 7000 deaths in the US *** spread of cancer,or metastasis,is responsible for these deaths,as secondary tumors interrupt normal organ *** tumor cells,or those cells that spread throughout the body from the primary tumor,are thought to be responsible for *** developed an optical method,photoacoustic flow cytometry,in order to detect and enumerate circulating melanoma cells(CMCs)from blood samples of *** tested the blood of StageⅣmelanoma patients to show the ability of the photoacoustic flow cytometer to detect these rare cells in *** then tested the system on archived blood samples from StageⅢmelanoma patients with known outcomes to determine if detection of CMCs can predict future *** detected between 0 and 66 CMCs in StageⅣ*** the StageⅢstudy,we found that of those samples with CMCs,two remained disease free and five developed *** those without CMCs,six remained disease free and one developed *** believe that photoacoustic detection of CMCs provides valuable information for the prediction of metastasis and we postulate a system for more accurate prognosis.

关键词： Diagnosis metastasis optoacoustics

Multiphase computed tomography radiomics of pancreatic intraductal papillary mucinous neoplasms to predict malignancy

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World Journal of Gastroenterology 2020年第24期26卷 3458-3471页

作者： Stuart L Polk Jung W Choi Melissa J McGettigan Trevor Rose Abraham Ahmed Jongphil Kim Kun Jiang Yoganand Balagurunathan Jin Qi Paola T Farah Alisha Rathi Jennifer B Permuth Daniel Jeong University of South Florida College of Medicine TampaFL 33612United States Department of Diagnostic and Interventional Radiology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612United States Department of Biostatistics and Bioinformatics H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612United States Department of Anatomic Pathology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612United States Department of cancer Physiology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612United States Department of Clinical Science H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612United States Department of Radiology University of FloridaGainesvilleFL 32610United States Department of cancer Epidemiology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612United States

BACKGROUND Intraductal papillary mucinous neoplasms(IPMNs)are non-invasive pancreatic precursor lesions that can potentially develop into invasive pancreatic ductal ***,the International Consensus Guidelines(ICG)for IPMNs provides the basis for evaluating suspected IPMNs on computed tomography(CT)*** using the ICG,it remains challenging to accurately predict whether IPMNs harbor high grade or invasive disease which would warrant surgical resection.A supplementary quantitative radiological tool,radiomics,may improve diagnostic accuracy of radiological evaluation of *** hypothesized that using CT whole lesion radiomics features in conjunction with the ICG could improve the diagnostic accuracy of predicting IPMN *** To evaluate whole lesion CT radiomic analysis of IPMNs for predicting malignant histology compared to International Consensus *** Fifty-one subjects who had pancreatic surgical resection at our institution with histology demonstrating IPMN and available preoperative CT imaging were included in this retrospective *** lesion semi-automated segmentation was performed on each preoperative CT using Healthmyne software(Healthmyne,Madison,WI).Thirty-nine relevant radiomic features were extracted from each lesion on each available contrast *** analysis of the 39 radiomics features was performed for each contrast phase and values were compared between malignant and benign IPMN groups using logistic *** quantitative and qualitative CT measurements were also compared between groups,viaχ2(categorical)and Mann Whitney U(continuous)*** Twenty-nine subjects(15 males,age 71±9 years)with high grade or invasive tumor histology comprised the"malignant"cohort,while 22 subjects(11 males,age 70±7 years)with low grade tumor histology were included in the"benign"*** analysis showed 18/39 precontrast,19/39 arterial phase,and 21/39 venous phase features

关键词： Radiomics Intraductal papillary mucinous neoplasm Multiphase computed tomography Pancreas Oncology Pancreatic cancer

A pilot study of radiologic measures of abdominal adiposity:weighty contributors to early pancreatic carcinogenesis worth evaluating?

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cancer Biology & Medicine 2017年第1期14卷 66-73页

作者： Jennifer B.Permuth Jung W.Choi Dung-Tsa Chen Kun Jiang Gina DeNicola Jian-Nong Li Domenico Coppola Barbara A.Centeno Anthony Magliocco Yoganand Balagurunathan Nipun Merchant Jose G.Trevino Daniel Jeong Departments of cancer Epidemiology Gastrointestinal Oncology Diagnostic Imaging and Interventional Radiology Biostatistics and Bioinformatics Anatomic Pathology cancer Imaging and Metabolism Moffitt Cancer Center and Research InstituteTamPa 33612FLUSA Department of Surgery Sylvester Comprehensive Cancer Center at the University of Miami Miller School of MedicineMiami 33136FLUSA Department of Surgery Division of General SurgeryUniversity of Florida Health Sciences CenterGainesville 32611FLUSA

Objective:Intra-abdominal fat is a risk factor for pancreatic cancer(PC),but little is known about its contribution to PC precursors known as intraductal papillary mucinous neoplasms(IPMNs).Our goal was to evaluate quantitative radiologic measures of abdominal/visceral obesity as possible diagnostic markers of IPMN severity/***:In a cohort of 34 surgically-resected,pathologically-confirmed IPMNs(17 benign;17 malignant) with preoperative abdominal computed tomography(CT) images,we calculated body mass index(BMI) and four radiologic measures of obesity:total abdominal fat(TAF) area,visceral fat area(VFA),subcutaneous fat area(SFA),and visceral to subcutaneous fat ratio(V/S).Measures were compared between groups using Wilcoxon two-sample exact tests and other ***:Mean BMI for individuals with malignant IPMNs(28.9 kg/m^2) was higher than mean BMI for those with benign IPMNs(25.8 kg/m^2)(P=0.045).Mean VFA was higher for patients with malignant IPMNs(199.3 cm^2) compared to benign IPMNs(120.4cm^2),P=0.092.V/S was significantly higher(P=0.013) for patients with malignant versus benign IPMNs(1.25 vs.0.69 cm^2),especially among *** accuracy,sensitivity,specificity,and positive and negative predictive value of V/S in predicting malignant IPMN pathology were 74%,71%,76%,75%,and 72%,***:Preliminary findings suggest measures of visceral fat from routine medical images may help predict IPMN pathology,acting as potential noninvasive diagnostic adjuncts for management and targets for intervention that may be more biologically-relevant than *** investigation of gender-specific associations in larger,prospective IPMN cohorts is warranted to validate and expand upon these observations.

关键词： Abdominal obesity pre-malignant lesions pancreatic cancer computed tomography

Manifestations of gastrointestinal plasmablastic lymphoma: A case series with literature review

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World Journal of Gastroenterology 2014年第33期20卷 11894-11903页

作者： Lynette Luria Johnny Nguyen Jun Zhou Michael Jaglal Jane L Messina Domenico Coppola Lubomir Sokol Ling Zhang Department of Pathology University of South Florida Morsani College of Medicine Tampa FL 33612 United States. Department of Pathology Wayne State University School of Medicine Detroit MI 48202 United States Department of Malignant Hematology H. Lee Moffitt Cancer Center and Research Institute Tampa FL 33612 United States Department of Surgical Pathology H. Lee Moffitt Cancer Center and Research Institute Tampa FL 33612 United States Department of Hematopathology and Laboratory Medicine H. Lee Moffitt Cancer Center and Research Institute Tampa FL 33612 United States

Plasmablastic lymphoma (PBL) rarely occurs in the gastrointestinal (GI) tract with limited studies reported. We reviewed the clinical histories and pathology of four patients with GI PBL at our institute and similar case reports published in peer-reviewed journals. In our first case, a 40 year-old human immunodeficiency virus positive male presented with a hemorrhoid-like sensation, and was diagnosed with PBL via biopsy of a rectal mass. The second case involves a 65 year-old healthy male with bloody diarrhea who was found to have PBL in a resected sigmoid mass. The third patient was a 41 year-old male with a history of Crohn’s disease who presented with abdominal pain, diarrhea, and weight loss. A small intestinal mass (PBL) was removed. The fourth patient was a 65-year-old male who was found PBL after surgical resection of bowel for his florid Crohn’s disease. He later developed secondary acute myeloid leukemia. Clinical outcome was very poor in 3 out of 4 patients as reported in the literature. One patient survived chemotherapy followed by autologous transplant. The prototypical clinical presentation and variations of PBL can help create a more comprehensive differential diagnosis for GI tumors and establish an appropriate therapeutic guideline.

关键词： Plasmablastic lymphoma Undifferentiated carcinoma Non-Hodgkin lymphoma Diverse clinical manifestation and treatment

Novel strategy for disease risk prediction incorporating predicted gene expression and DNA methylation data:a multi-phased study of prostate cancer

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cancer Communications 2021年第12期41卷 1387-1397页

作者： Chong Wu Jingjing Zhu Austin King Xiaoran Tong Qing Lu Jong Y.Park Liang Wang Guimin Gao Hong-Wen Deng Yaohua Yang Karen E.Knudsen Timothy R.Rebbeck Jirong Long Wei Zheng Wei Pan David V.Conti Christopher A Haiman Lang Wu Department of Statistics Florida State UniversityTallahasseeFL 32304USA cancer Epidemiology Division Population Sciences in the Pacific ProgramUniversity of Hawaii Cancer CenterUniversity of Hawaii at ManoaHonoluluHI 96813USA Department of Epidemiology and Biostatistics Michigan State UniversityEast LansingMI 48824USA Department of Biostatistics University of FloridaGainesvilleFL 32603USA Department of cancer Epidemiology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612USA Department of Tumor Biology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612USA Department of Public Health Sciences University of ChicagoChicagoIL 60637USA center of Bioinformatics and Genomics Department of Global Biostatistics and Data ScienceTulane UniversityNew OrleansLA 70112USA Division of Epidemiology Department of MedicineVanderbilt Epidemiology CenterVanderbilt-Ingram Cancer CenterVanderbilt University Medical CenterNashvilleTN 37203USA Department of cancer Biology Sidney Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaPA 19107USA Department of Medical Oncology Dana-Farber Cancer InstituteBostonMA 02215USA Department of Epidemiology Harvard TH Chan School of Public HealthBostonMA 02115USA Division of Biostatistics University of MinnesotaMinneapolisMN 55455USA Department of Preventive Medicine Keck School of MedicineUniversity of Southern California/Norris Comprehensive Cancer CenterLos AngelesCA 90033USA

Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores(PRSs).Here,we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation,and other genomic information using an integrative ***:Using data from the PRACTICAL consortium,we derived multiple sets of genetic scores,including those based on available single-nucleotide polymorphisms through widely used methods of pruning and thresholding,LDpred,LDpred-funt,AnnoPred,and EBPRS,as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding *** the tuning step,using the UK Biobank data(1458 prevalent cases and 1467 controls),we selected PRSs with the best *** an independent set of data from the UK Biobank,we developed an integrative PRS combining information from individual ***,in the testing step,we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and ***:Our constructed PRS had improved performance(C statistics:76.1%)over PRSs constructed by individual benchmark methods(from 69.6%to 74.7%).Furthermore,our new PRS had much higher risk assessment power than family *** overall net reclassification improvement was 69.0%by adding PRS to the baseline model compared with 12.5%by adding family ***:We developed and validated a new PRS which may improve the utility in predicting the risk of developing *** innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes.

关键词： risk prediction polygenic risk scores predicted gene expression predicted DNA methylation integrative models prostate cancer

Advancing the field of rare genitourinary tumors:Challenges and opportunities

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Asian Journal of Urology 2022年第4期9卷 347-348,F0002页

作者： Philippe E.Spiess Andrea Necchi Department of Genitourinary Oncology and Tumor Biology Moffitt Cancer CenterTampaUSA Vita Salute San Raffaele University and Urological research institute IRCCS San Raffaele Hospital and Scientific InstituteMilanItaly

Firstly,I would like to congratulate the editorial team of the Asion Journol of Urology for dedicating a speclial isue of the joumal to this important *** recent advances in our fundamental understanding of the pathop... 详细信息

关键词： urinary tumors rare

comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

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Frontiers of Medicine 2021年第2期15卷 275-291页

作者： Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive Medicine Center for Global HealthNanjing Medical UniversityNanjing 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China China International Cooperation center for Environment and Human Health School of Public HealthNanjing Medical UniversityNanjing 211166China Division of cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892-9304USA Department of Integrative Oncology British Columbia Cancer AgencyVancouverBC V5Z 1L3Canada Faculty of Medicine University of Oviedo and CIBERESPOviedo 33006Spain Program in Epidemiology Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleWA 98109-1024USA Public Health Sciences Division Swedish Cancer InstituteSeattleWA 98026USA Department of Clinical Biochemistry Copenhagen University HospitalCopenhagen DK-1017Denmark National cancer institute BethesdaMD 20892-9304USA Genetic Epidemiology Group International Agency for Research on CancerLyon 69372France cancer center Cluster Salzburg at PLUS Department of Molecular BiologyUniversity of SalzburgHeidelberg 5020Austria institute of Medical Informatics Biometry and EpidemiologyChair of EpidemiologyLudwig Maximilians UniversityMunichBavaria 80539Germany Department of Genetic Epidemiology University Medical Center GoettingenGoettingen 37075Germany Technion Faculty of Medicine Carmel Medical CenterHaifa 3448516Israel Markey cancer center University of KentuckyLexingtonKY 40506-0054USA Department of Molecular and Clinical cancer Medicine Roy Castle Lung Cancer Research ProgrammeThe University of Liverpool Institute of Translational MedicineLiverpool L697Z

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely *** integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility *** identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive *** factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was *** annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency *** results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

关键词： lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity

Genitourinary manifestations of Lynch syndrome in the urological practice

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Asian Journal of Urology 2022年第4期9卷 443-450页

作者： Chiara Lonati Claudio Simeone Nazareno Suardi Philippe ESpiess Andrea Necchi Marco Moschini Urology Unit ASST Spedali Civili di BresciaDepartment of Medical and Surgical SpecialtiesRadiological Science and Public HealthUniversity of BresciaBresciaItaly Department of Urology Luzerner KantonsspitalLucerneSwitzerland Department of Genitourinary Oncology H.Lee Moffitt Cancer Center and Research InstituteTamplaFLUSA University Vita-Salute San Raffaele MilanItaly Department of Medical Oncology IRCCS San Raffaele Hospital and Scientific InstituteMilanItaly Division of Experimental Oncology/Unit of Urology Urological Research InstituteIRCCS Ospedale San RaffaeleMilanItaly

Objective:Lynch syndrome(LS)is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in EPCAM *** a clinical perspective,LS patients exhibit an increased predisposition to multiple primary malignancies and early age of onset compared to general *** aimed to provide a comprehensive overview of all the genitourinary manifestations of LS,focusing on incidence,diagnosis,clinical features,therapeutic strategies,and screening ***:Previous literature was assessed through Medline,Scopus,and Google Scholar data-bases.A narrative review of the most relevant articles from January 1996 to June 2021 on urological manifestations of LS was ***:In the LS tumor spectrum,upper tract urothelial carcinoma(UTUC)represents the third most frequent malignancy,and the first most common cancer in the urological field,with an approximately 14-fold increased risk of developing UTUC compared to general *** diagnosis among patients experiencing UTUC as first malignancy is a step-by-step process,including(i)clinical criteria,(ii)molecular testing,and(iii)genetic testing to confirm the hereditary *** current European Association of Urology(EAU)guidelines recommend to perform molecular testing among UTUC patients under 65 years old,or UTUC patients with personal history of LS-related tumor,or UTUC patients with one first-degree relative under the age of 50 years with LS-related tumor,or UTUC patients with two first-degree relatives with LS-related tumor regardless of age of *** diagnosed LS patients should be referred to a multidisci-plinary management,including gastroenterologists and ***,considering the increased risk of metachronous recurrence,treatments other than radical nephroureterectomy may be a valuable therapeutic *** urological malignancies other than UTUC should be included in the LS tumor spectrum is still cont

关键词： Hereditary disease Hereditary nonpolyposis colorectal cancer Lynch syndrome Mismatch repair Upper tract urothelial carcinoma

Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors

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World Journal of Gastroenterology 2015年第8期21卷 2450-2459页

作者： Jonathan R Strosberg George A Fisher Al B Benson Lowell B Anthony Bulent Arslan John F Gibbs Edward Greeno Renuka V Iyer Michelle K Kim William J Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder Department of Gastrointestinal Oncology H. Lee Moffitt Cancer Center and Research Institute Department of Medicine Division of Oncology Stanford University Medical Center Stanford Robert H. Lurie comprehensive cancer center of Northwestern University Department of Internal Medicine Division of Medical Oncology University of Kentucky Markey Cancer Center Rush University Medical center Department of Surgery University at Buffalo - State University of New York Department of Medicine Division of Hematology Oncology and Transplantation University of Minnesota Department of Medical Oncology Roswell Park Cancer Institute Department of Medicine Gastroenterology Mount Sinai School of Medicine Mission Health System Asheville Department of Oncology Karmanos Cancer Institute Partnership for Health Analytic research LLC

AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment ***:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic *** this time,there is little data to guide treatment selection and *** therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment *** appropriateness ratings were collected using the RAND/UCLA modified Delphi *** studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 *** were done both before and after an extended discussion of the *** measurements of agreement were made and consensus statements developed from the second round ***:Specialties represented were medical and surgical oncology,interventional radiology,and *** had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)*** the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were *** statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be *** patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated u

关键词： Unresectable Neuroendocrine carcinomas Neuroendocr