2024
Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments
Rüschoff J, Kumar G, Badve S, Jasani B, Krause E, Rioux-Leclercq N, Rojo F, Martini M, Cheng L, Tretiakova M, Mitchell C, Anders R, Robert M, Fahy D, Pyle M, Le Q, Yu L, Glass B, Baxi V, Babadjanova Z, Pratt J, Brutus S, Karasarides M, Hartmann A. Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments. Virchows Archiv 2024, 484: 597-608. PMID: 38570364, DOI: 10.1007/s00428-024-03795-8.Peer-Reviewed Original ResearchConceptsPD-L1 expressionImmune checkpoint inhibitorsPD-L1Tumor cellsAssess programmed death ligand 1Assessment of PD-L1 expressionScoring of PD-L1 expressionInternational multi-institutional studyPD-L1 expression analysisFood and Drug Administration-approvedPD-L1 stainingDeath-ligand 1Drug Administration-approvedMulti-institutional studyCheckpoint inhibitorsUrothelial carcinomaPathological assessmentBiomarker expressionInterobserver variabilityLigand 1Cancer treatmentExpert pathologistsClinical settingMultinational studyPositive rate
2023
Guidelines for best practices in monitoring established coeliac disease in adult patients
Elli L, Leffler D, Cellier C, Lebwohl B, Ciacci C, Schumann M, Lundin K, Chetcuti Zammit S, Sidhu R, Roncoroni L, Bai J, Lee A, Dennis M, Robert M, Rostami K, Khater S, Comino I, Cebolla A, Branchi F, Verdu E, Stefanolo J, Wolf R, Bergman-Golden S, Trott N, Scudeller L, Zingone F, Scaramella L, Sanders D. Guidelines for best practices in monitoring established coeliac disease in adult patients. Nature Reviews Gastroenterology & Hepatology 2023, 21: 198-215. PMID: 38110546, DOI: 10.1038/s41575-023-00872-2.Peer-Reviewed Original ResearchConceptsCoeliac diseaseLevel of evidenceLife-long gluten-free dietGluten-free dietMucosal atrophyAdult patientsCirculating autoantibodiesFollow-upGenetic predispositionImmunological diseasesRecommendations AssessmentMonitoring patientsClinical guidelinesEvidence levelPatientsConsumption of glutenDiagnosisDiseaseGuidelinesScientific societiesCeDAutoantibodiesGastroenterologistsAtrophyWATS3D: An Interobserver Study of Barrett's Esophagus–Associated Dysplasia Among Gastrointestinal Pathologists
Patil D, Goldblum J, Lauwers G, Lewis J, Robert M, Singer M, Odze R. WATS3D: An Interobserver Study of Barrett's Esophagus–Associated Dysplasia Among Gastrointestinal Pathologists. Clinical And Translational Gastroenterology 2023, 15: e00661. PMID: 38088399, PMCID: PMC10887448, DOI: 10.14309/ctg.0000000000000661.Peer-Reviewed Original ResearchConceptsBarrett's esophagusGI pathologistsCell blocksWide-area transepithelial samplingDetection rate of dysplasiaBE-associated dysplasiaRate of dysplasiaKappa valuesDetection of neoplasiaGastrointestinal (GILiquid cytologyEvaluate digital imagesSmear specimensGastrointestinal pathologistsInterobserver variabilityIndividual diagnostic categoriesStudy pathologistsInterobserver studyDysplasiaPathologistsCellular fociComputer-assisted analysisDiagnostic categoriesDetection rateTraining sessionsStandardizing Randomized Controlled Trials in Celiac Disease: An International Multidisciplinary Appropriateness Study
Lebwohl B, Ma C, Lagana S, Pai R, Baker K, Zayadi A, Hogan M, Bouma G, Cellier C, Goldsmith J, Lundin K, Pinto-Sanchez M, Robert M, Rubio-Tapia A, Sanders D, Schaeffer D, Semrad C, Silvester J, Verdú E, Verma R, Wu T, Feagan B, Crowley E, Jairath V, Murray J. Standardizing Randomized Controlled Trials in Celiac Disease: An International Multidisciplinary Appropriateness Study. Gastroenterology 2023, 166: 88-102. PMID: 37704112, DOI: 10.1053/j.gastro.2023.08.051.Peer-Reviewed Original ResearchConceptsRandomized controlled trialsSecondary patient-reported outcome measuresOutcome measuresRandomized controlled trial designPatient-reported outcome measuresControlled trialsGluten challengeStandard Randomized Controlled TrialPatient-reported outcomesGluten-free dietReversal of histological changesMethods studyCeliac diseaseEligibility criteriaHistological end pointsPrevention of relapseEffective pharmacological optionsAppropriate studiesTrial outcomesExclusion criteriaClinical trial designTrial designTreatment of celiac diseasePediatric patientsPharmacological optionsScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis
Mann J, Lucca L, Austin M, Merkin R, Robert M, Al Bawardy B, Raddassi K, Aizenbud L, Joshi N, Hafler D, Abraham C, Herold K, Kluger H. ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis. Journal For ImmunoTherapy Of Cancer 2023, 11: e007358. PMID: 37586769, PMCID: PMC10432652, DOI: 10.1136/jitc-2023-007358.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsT cell subsetsCheckpoint inhibitorsImmune environmentImmune checkpoint inhibitor-induced colitisCheckpoint inhibitor-induced colitisPeripheral immune environmentsStages of colitisTreatment of colitisMerkel cell carcinomaT cell populationsPeripheral blood samplesCourse of progressionT cell receptorMultiple tumor typesAlternative cancer therapyCommon toxicitiesICI colitisTreatment discontinuationAdverse eventsBiologic therapyImmune suppressionCell carcinomaColitisBlood samplesCholangiocarcinoma: Pathologic and Molecular Classification in the Era of Precision Medicine.
Gopal P, Robert M, Zhang X. Cholangiocarcinoma: Pathologic and Molecular Classification in the Era of Precision Medicine. Archives Of Pathology & Laboratory Medicine 2023, 148: 359-370. PMID: 37327187, DOI: 10.5858/arpa.2022-0537-ra.Peer-Reviewed Original ResearchConceptsDiagnosis of cholangiocarcinomaImmune checkpoint inhibitorsAdvanced tumor stageHeterogeneous tumor groupTumor growth patternEra of precision medicineTherapeutic decision-makingEvaluation of cholangiocarcinomaExtrahepatic biliary treeGenetic testing methodologiesSite of originCheckpoint inhibitorsTumor inaccessibilityMetastatic adenocarcinomaPeriductal infiltrationTumor stageIntraductal tumorClinical presentationDifferentiate cholangiocarcinomaImmunohistochemical profileTumor groupExtrahepatic cholangiocarcinomaTargeted therapyPathological diagnosisIntrahepatic cholangiocarcinomaIdiopathic myointimal hyperplasia of the mesenteric veins: A systematic review and individual patient data regression analysis
Rozner R, Gisriel S, Damianos J, Grimshaw A, Rizwan R, Nawaz A, Chan K, Wan D, Pantel H, Bhutta A, Fenster M, Brandt L, Barbieri A, Robert M, Feuerstadt P, Li D. Idiopathic myointimal hyperplasia of the mesenteric veins: A systematic review and individual patient data regression analysis. Journal Of Gastroenterology And Hepatology 2023, 38: 1040-1046. PMID: 37086041, DOI: 10.1111/jgh.16193.Peer-Reviewed Original ResearchConceptsIdiopathic myointimal hyperplasiaColonic ischemiaMesenteric veinRectal bleedingRectal involvementMyointimal hyperplasiaSystematic reviewYounger ageMultivariate logistic regression analysisCurative surgical resectionInferior mesenteric veinPre-surgical identificationLogistic regression analysisRegression analysisIschemic colitisAbdominal painMucosal ulcerationEndoscopic findingsSelect patientsSurgical resectionUncommon causeDiagnostic delaySurgical treatmentClinical featuresHospital recordsHigh Interobserver Variability Among Pathologists Using Combined Positive Score to Evaluate PD-L1 Expression in Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma
Robert M, Rüschoff J, Jasani B, Graham R, Badve S, Rodriguez-Justo M, Kodach L, Srivastava A, Wang H, Tang L, Troncone G, Rojo F, Van Treeck B, Pratt J, Shnitsa I, Kumar G, Karasarides M, Anders R. High Interobserver Variability Among Pathologists Using Combined Positive Score to Evaluate PD-L1 Expression in Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma. Modern Pathology 2023, 36: 100154. PMID: 36925069, DOI: 10.1016/j.modpat.2023.100154.Peer-Reviewed Original ResearchConceptsCombined positive scorePD-L1 expressionCheckpoint inhibitor therapyPD-L1Tumor cellsImmune cellsIntraclass correlation coefficientInhibitor therapyInterpretation of PD-L1 expressionPD-L1 combined positive scoreInterobserver variabilityBiopsy samplesEvaluate PD-L1 expressionImmune checkpoint inhibitor therapyInterpathologist agreementProgrammed death-ligand 1PD-L1 immunohistochemistryDeath-ligand 1Variable intensity of stainingIntensity of stainingPositive scoresRetrospective histologic reviewPretreatment biopsiesTumor stainingHistologic reviewPrecision Medicine for Pancreas Cancer Treatment: A Multidisciplinary Challenge or Opportunity?
Farrell J, Robert M, Lacy J. Precision Medicine for Pancreas Cancer Treatment: A Multidisciplinary Challenge or Opportunity? Clinical Gastroenterology And Hepatology 2023, 21: 2740-2742. PMID: 36640803, DOI: 10.1016/j.cgh.2022.12.033.Peer-Reviewed Original Research
2022
Mitochondrial fitness and cancer risk
Kossenkov AV, Milcarek A, Notta F, Jang GH, Wilson JM, Gallinger S, Zhou DC, Ding L, Ghosh JC, Perego M, Morotti A, Locatelli M, Robert ME, Vaira V, Altieri DC. Mitochondrial fitness and cancer risk. PLOS ONE 2022, 17: e0273520. PMID: 36223343, PMCID: PMC9555630, DOI: 10.1371/journal.pone.0273520.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaSenescence-Associated Secretory PhenotypeIndependent patient cohortsPoor patient outcomesAggressive disease variantFolfirinox failureLocal inflammationPatient cohortDuctal adenocarcinomaPatient outcomesPatient riskMultiple malignanciesCancer riskMitochondrial fitnessSecretory phenotypeGene signatureHallmarks of cancerMetastatic propensityNormal tissuesHuman tumorsInterferon SignalingTumorsInner membrane mitochondrial proteinMalignancyMolecular signaturesImmune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes
Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC. Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes. JCI Insight 2022, 7: e156330. PMID: 35925682, PMCID: PMC9536276, DOI: 10.1172/jci.insight.156330.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitorsΒ-cellsPD-1/PD-L1 pathwayT-lymphocyte antigen-4PD-1 blockadePD-L1 pathwayDeath ligand 1NOD mouse modelDevelopment of diabetesHuman β-cellsAutoimmune complicationsNOD miceΒ-cell populationDeath-1Diabetes mellitusImmune infiltratesInflammatory mediatorsPancreatic inflammationPD-L1Induced diabetesLymphocytic infiltrationInflammatory cytokinesAntigen-4Immune cellsT cellsComprehensive molecular profiling of pancreatic ductal adenocarcinoma in FNA, biopsy, and resection specimens
Razzano D, Bouza SJ, Hernandez PV, Wang M, Robert ME, Walther Z, Cai G. Comprehensive molecular profiling of pancreatic ductal adenocarcinoma in FNA, biopsy, and resection specimens. Cancer Cytopathology 2022, 130: 726-734. PMID: 35511415, DOI: 10.1002/cncy.22589.Peer-Reviewed Original ResearchConceptsFine-needle aspirationFine-needle biopsyPancreatic ductal adenocarcinomaOncomine Comprehensive AssayResection specimensMolecular alterationsMolecular testingFNB samplesDuctal adenocarcinomaTherapeutic implicationsSuccess rateComprehensive molecular analysisComprehensive molecular testingComprehensive molecular profilingPotential therapeutic implicationsSimilar success ratesResection casesKRAS mutationsFNB specimensFNA materialFNA specimensAmplification analysisMolecular profilingFusion assessmentGene mutationsCytoskeletal dynamics regulates stromal invasion behavior of distinct liver cancer subtypes
Nguyen RY, Xiao H, Gong X, Arroyo A, Cabral AT, Fischer TT, Flores KM, Zhang X, Robert ME, Ehrlich BE, Mak M. Cytoskeletal dynamics regulates stromal invasion behavior of distinct liver cancer subtypes. Communications Biology 2022, 5: 202. PMID: 35241781, PMCID: PMC8894393, DOI: 10.1038/s42003-022-03121-5.Peer-Reviewed Original ResearchGhost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability
Ghosh JC, Perego M, Agarwal E, Bertolini I, Wang Y, Goldman AR, Tang HY, Kossenkov AV, Landis CJ, Languino LR, Plow EF, Morotti A, Ottobrini L, Locatelli M, Speicher DW, Caino MC, Cassel J, Salvino JM, Robert ME, Vaira V, Altieri DC. Ghost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2115624119. PMID: 35177476, PMCID: PMC8872753, DOI: 10.1073/pnas.2115624119.Peer-Reviewed Original ResearchMeSH KeywordsCell DeathCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionHumansMitochondriaMitochondrial DynamicsMitochondrial ProteinsMuscle ProteinsNeoplasm InvasivenessNeoplasm MetastasisNeoplasmsNeoplastic ProcessesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesSignal TransductionConceptsEpithelial-mesenchymal transitionGene expression programsTherapeutic vulnerabilitiesTumor cell movementCytokine/chemokine signalingExpression programsTherapeutic targetCell movementMitochondrial dynamicsEssential scaffoldMitochondrial structureSurvival signalingMitochondrial integrityCancer metabolismStress responseActionable therapeutic targetsCell deathChemokine signalingMitochondriaSmall-molecule drug screensCell proliferationOxidative damageInnate immunityMetastatic disseminationHuman tumors
2021
Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma
Gao Y, Wang M, Guo X, Hu J, Chen TM, Finn S, Lacy J, Kunstman JW, H. C, Bellin MD, Robert ME, Desir GV, Gorelick FS. Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma. PLOS ONE 2021, 16: e0250539. PMID: 34587190, PMCID: PMC8480607, DOI: 10.1371/journal.pone.0250539.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Pancreatic DuctalCase-Control StudiesFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedMonoamine OxidaseNeoplasm GradingPancreatic NeoplasmsPrognosisProspective StudiesRetrospective StudiesSurvival AnalysisUp-RegulationYoung AdultConceptsPlasma renalase levelsBorderline resectable PDACRenalase levelsPDAC precursor lesionsOverall survivalPDAC tissuesTumor characteristicsResectable PDACChronic pancreatitisPrecursor lesionsNormal pancreasPancreatic ductal adenocarcinoma growthAdvanced tumor characteristicsVaried clinical stagesWorse tumor characteristicsNode-positive diseasePancreatic ductal adenocarcinomaNormal pancreatic headSpindle-shaped cellsPlasma renalaseRenalase expressionUnderwent resectionAbdominal traumaPancreatic headPositive diseaseTrefoil factor 2 secreted from damaged hepatocytes activates hepatic stellate cells to induce fibrogenesis
Zhang B, Lapenta K, Wang Q, Nam JH, Chung D, Robert ME, Nathanson MH, Yang X. Trefoil factor 2 secreted from damaged hepatocytes activates hepatic stellate cells to induce fibrogenesis. Journal Of Biological Chemistry 2021, 297: 100887. PMID: 34146542, PMCID: PMC8267550, DOI: 10.1016/j.jbc.2021.100887.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsTrefoil factor 2Liver injuryStellate cellsActivation of HSCsPrimary hepatic stellate cellsPlatelet-derived growth factor receptor betaChronic liver diseaseGrowth factor receptor betaProcess of fibrogenesisLiver-specific deletionFactor 2Spontaneous fibrosisLiver diseaseLiver fibrosisFibrogenic processReceptor betaFibrogenesisWT hepatocytesProtein expressionFibrosisHepatocytesInjuryNovel factorActivationInternational consensus to standardise histopathological scoring for small bowel strictures in Crohn’s disease
Gordon I, Bettenworth D, Bokemeyer A, Srivastava A, Rosty C, de Hertogh G, Robert M, Valasek M, Mao R, Li J, Harpaz N, Borralho P, Pai R, Odze R, Feakins R, Parker C, Guizzetti L, Nguyen T, Shackelton L, Sandborn W, Jairath V, Baker M, Bruining D, Fletcher J, Feagan B, Pai R, Rieder F. International consensus to standardise histopathological scoring for small bowel strictures in Crohn’s disease. Gut 2021, 71: 479-486. PMID: 33952604, PMCID: PMC8903083, DOI: 10.1136/gutjnl-2021-324374.Peer-Reviewed Original ResearchConceptsSmall bowel stricturesMucosal inflammatory diseasesBowel stricturesCrohn's diseaseHistopathological scoring systemScoring systemInflammatory diseasesIncreased bowel wall thicknessCrypt architectural distortionIntact surface epitheliumSurgically resected specimensPyloric gland metaplasiaSmall bowel Crohn's diseaseEffective medical therapyLos Angeles methodologyPaneth cell hyperplasiaBowel wall thicknessBasal lymphoplasmacytosisAnastomotic strictureMedical therapyStricture diseaseCell hyperplasiaClinical trial efficiencyNeutrophilic inflammationLymphoid aggregatesCheckpoint Inhibitor Colitis Shows Drug-Specific Differences in Immune Cell Reaction That Overlap With Inflammatory Bowel Disease and Predict Response to Colitis Therapy
Lo YC, Price C, Blenman K, Patil P, Zhang X, Robert ME. Checkpoint Inhibitor Colitis Shows Drug-Specific Differences in Immune Cell Reaction That Overlap With Inflammatory Bowel Disease and Predict Response to Colitis Therapy. American Journal Of Clinical Pathology 2021, 156: 214-228. PMID: 33555016, DOI: 10.1093/ajcp/aqaa217.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseCD8/FOXP3 ratioBiopsy specimensCPI patientsPD-1CD68 scoreFOXP3 ratioBowel diseasePD-L1Antibody-treated patientsCheckpoint inhibitor colitisPD-L1 groupInitial biopsy specimensPD-L1 expressionImmune cell reactionsColonic biopsy specimensDrug-specific differencesIBD groupCheckpoint inhibitorsChronicity scoreActivity scoreImmune phenotypeTherapeutic responseColitisShared pathophysiology
2020
Frontiers in Celiac Disease
Patel N, Robert ME. Frontiers in Celiac Disease. The American Journal Of Surgical Pathology 2020, 46: e43-e54. PMID: 33739793, DOI: 10.1097/pas.0000000000001639.Peer-Reviewed Original ResearchConceptsCeliac diseaseType II refractory celiac diseaseMonoclonal T-cell populationChildhood viral infectionsDuodenal mucosal histologyImportant autoimmune diseasesRefractory celiac diseaseCommon autoimmune disorderT cell populationsCeliac disease patientsCeliac disease pathogenesisEvaluation of responseCeliac disease manifestationsGluten toleranceDietary glutenGluten exposureMechanisms of diseaseAutoimmune conditionsHLA-DQ2Mucosal histologySymptomatic diseaseInflammatory cascadeInitial diagnosisPatient's symptomsAutoimmune disordersNeutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis
Takeuchi M, Vidigal PT, Guerra MT, Hundt MA, Robert ME, Olave-Martinez M, Aoki S, Khamphaya T, Kersten R, Kruglov E, de la Rosa Rodriguez R, Banales JM, Nathanson MH, Weerachayaphorn J. Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis. Gut 2020, 70: 342-356. PMID: 33214166, PMCID: PMC7906004, DOI: 10.1136/gutjnl-2020-322540.Peer-Reviewed Original ResearchConceptsBile ductCholestatic changesLimited treatment optionsPresence of cholestasisAbility of neutrophilsLife-threatening diseaseNew therapeutic targetsHuman bile ductIntracellular calcium channelsAlcoholic hepatitisLiver biopsyControl neutrophilsPathological findingsHepatocellular damageHistological findingsTreatment optionsCell adhesion moleculeHistological parametersDisease altersITPR3 expressionTherapeutic targetAnimal modelsCalcium channelsNeutrophilsPatients