2023
A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer
Baretti M, Murphy A, Zahurak M, Gianino N, Parkinson R, Walker R, Lopez-Vidal T, Zheng L, Rosner G, Ahuja N, Kurt S, Azad N. A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer. Clinical Epigenetics 2023, 15: 74. PMID: 37120591, PMCID: PMC10149019, DOI: 10.1186/s13148-023-01485-x.Peer-Reviewed Original ResearchConceptsColorectal cancer patientsAdvanced colorectal cancer patientsImmune checkpoint inhibitor therapyMedian progression-free survivalDurable partial responseHematological adverse eventsMMR-proficient tumorsCheckpoint inhibitor therapyAdvanced colorectal cancerProgression-free survivalImmune cell infiltrationHistone deacetylasesImmunologic shiftCheckpoint inhibitorsRECIST criteriaAdverse eventsCheckpoint therapyOverall survivalPartial responseInhibitor therapyMedian ageColorectal cancerFurther mechanistic investigationsCancer patientsCell infiltration
2022
A randomized, phase II trial of oral azacitidine (CC-486) in patients with resected pancreatic adenocarcinoma at high risk for recurrence
Heumann T, Baretti M, Sugar E, Durham J, Linden S, Lopez-Vidal T, Leatherman J, Cope L, Sharma A, Weekes C, O’Dwyer P, Reiss K, Monga D, Ahuja N, Azad N. A randomized, phase II trial of oral azacitidine (CC-486) in patients with resected pancreatic adenocarcinoma at high risk for recurrence. Clinical Epigenetics 2022, 14: 166. PMID: 36463226, PMCID: PMC9719150, DOI: 10.1186/s13148-022-01367-8.Peer-Reviewed Original ResearchConceptsResectable pancreatic ductal adenocarcinomaCC-486OBS patientsMetastatic settingAdjuvant therapyTreatment-related grade 3Randomized phase II studyMedian age 66Next-line therapyResultsForty-nine patientsMedian treatment durationPhase II studyEvidence of diseaseHigh-risk featuresPhase II trialProgression-free survivalStandard adjuvant therapyPancreatic ductal adenocarcinomaCancer recursEvaluable patientsMedian OSMedian PFSOral azacitidineR1 resectionSubsequent chemotherapyEvaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery
Bakkila BF, Kerekes D, Nunez-Smith M, Billingsley KG, Ahuja N, Wang K, Oladele C, Johnson CH, Khan SA. Evaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery. JAMA Network Open 2022, 5: e225664. PMID: 35377425, PMCID: PMC8980937, DOI: 10.1001/jamanetworkopen.2022.5664.Peer-Reviewed Original ResearchConceptsGastrointestinal tract cancerNegative resection marginsTract cancerNegative surgical marginsBlack patientsAdequate lymphadenectomyWhite patientsQuality of careRacial disparitiesSurgical resectionResection marginsSurgical marginsSurgical careNational Cancer DatabaseRetrospective cohort studySite of cancerLonger median survivalHealth careStandard of careCommon age rangeSignificant racial disparitiesAdjuvant chemotherapyBiliary resectionAdjuvant therapyAdult patients
2020
Understanding the Barriers to Reporting Sexual Harassment in Surgical Training
Freedman-Weiss MR, Chiu AS, Heller DR, Cutler AS, Longo WE, Ahuja N, Yoo PS. Understanding the Barriers to Reporting Sexual Harassment in Surgical Training. Annals Of Surgery 2020, Publish Ahead of Print: &na;. PMID: 30946072, DOI: 10.1097/sla.0000000000003295.Peer-Reviewed Original Research
2019
A phase 1 trial of the oral DNA methyltransferase inhibitor CC‐486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors
Gaillard SL, Zahurak M, Sharma A, Durham J, Reiss K, Sartorius‐Mergenthaler S, Downs M, Anders N, Ahuja N, Rudek M, Azad N. A phase 1 trial of the oral DNA methyltransferase inhibitor CC‐486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors. Cancer 2019, 125: 2837-2845. PMID: 31012962, PMCID: PMC6663621, DOI: 10.1002/cncr.32138.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overAnorexiaAntineoplastic Combined Chemotherapy ProtocolsAzacitidineDepsipeptidesDNA Modification MethylasesDrug Administration ScheduleFemaleHistone Deacetylase InhibitorsHumansLong Interspersed Nucleotide ElementsMaleMaximum Tolerated DoseMethyltransferasesMiddle AgedNauseaNeoplasmsConceptsHistone deacetylase inhibitor romidepsinDisease control rateAdvanced solid tumorsPhase 1 studyCC-486Solid tumorsDose-escalation portionPhase 2 doseDose-limiting toxicityPossible clinical benefitPhase 1 trialDose-escalation designElement-1 methylationLINE-1 methylationStable diseaseCommon toxicitiesDose expansionExpansion cohortPrimary outcomeClinical benefitControl rateDrug exposureBlood samplesDay 1Dose levelsOperative Mortality Prediction for Primary Rectal Cancer: Age Matters
Li Z, Coleman J, D'Adamo CR, Wolf J, Katlic M, Ahuja N, Blumberg D, Ahuja V. Operative Mortality Prediction for Primary Rectal Cancer: Age Matters. Journal Of The American College Of Surgeons 2019, 228: 627-633. PMID: 30630082, DOI: 10.1016/j.jamcollsurg.2018.12.014.Peer-Reviewed Original ResearchConceptsPrimary rectal cancerRectal cancerLogistic regression modelsActual mortalityOlder patientsRisk calculatorAmerican CollegeCovariate-adjusted logistic regression modelsCurrent risk calculatorsICD-9/10 codesColorectal cancer increasesSurgeons NSQIP databaseYears age groupAge categoriesMortality risk estimatesOperative mortalityNSQIP databaseRegression modelsPrognostic valueFunctional statusCancer increasesCare discussionsMortality predictionCPT codesAge groups
2018
A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan
Lee V, Wang J, Zahurak M, Gootjes E, Verheul H, Parkinson R, Kerner Z, Sharma A, Rosner G, De Jesus-Acosta A, Laheru D, Le DT, Oganesian A, Lilly E, Brown T, Jones P, Baylin S, Ahuja N, Azad N. A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan. Clinical Cancer Research 2018, 24: 6160-6167. PMID: 30097434, DOI: 10.1158/1078-0432.ccr-18-0421.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerNeutropenic feverMetastatic colorectal cancer patientsDurable partial responseMost common toxicitiesDose-escalation studyColorectal cancer patientsInjection site reactionsOngoing phase IIPhase I trialInitial disease progressionCycles of treatmentCommon toxicitiesDrain infectionEvaluable patientsStable diseaseColonic obstructionPartial responseI trialMulticenter trialColorectal cancerGastrointestinal cancerSite reactionsCancer patientsDisease progressionTrends in Outcomes After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy
Gani F, Conca-Cheng AM, Nettles B, Ahuja N, Johnston FM. Trends in Outcomes After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy. Journal Of Surgical Research 2018, 234: 240-248. PMID: 30527480, DOI: 10.1016/j.jss.2018.09.032.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCarcinomaChemotherapy, Cancer, Regional PerfusionCombined Modality TherapyCytoreduction Surgical ProceduresDatabases, FactualFemaleHumansHyperthermia, InducedLogistic ModelsMaleMiddle AgedPatient SelectionPeritoneal NeoplasmsPostoperative ComplicationsRisk FactorsTreatment OutcomeConceptsCRS/HIPECHyperthermic intraperitoneal chemotherapyMedian operative timeLength of stayPostoperative morbidityCytoreductive surgeryOperative timeIntraperitoneal chemotherapySelect patientsClinical outcomesSurgeons National Surgical Quality Improvement Program databaseNational Surgical Quality Improvement Program databaseCommon primary tumor siteQuality Improvement Program databaseMultivariable logistic regression analysisLow preoperative hematocritImprovement Program databasePreoperative serum albuminCareful patient selectionPrimary tumor siteLogistic regression analysisPostoperative complicationsPostoperative deathsPreoperative hematocritPeritoneal carcinomatosisExtraskeletal versus Skeletal Ewing Sarcoma in the adult population: Controversies in care
Lynch AD, Gani F, Meyer CF, Morris CD, Ahuja N, Johnston FM. Extraskeletal versus Skeletal Ewing Sarcoma in the adult population: Controversies in care. Surgical Oncology 2018, 27: 373-379. PMID: 30217290, DOI: 10.1016/j.suronc.2018.05.016.Peer-Reviewed Original ResearchConceptsExtraskeletal Ewing's sarcomaCharlson-Deyo scoreOverall survivalTriple therapyCombination therapyLocal therapyEwing's sarcomaProportional hazards regression analysisHazards regression analysisSkeletal Ewing sarcomaEwing's sarcoma patientsAdult patientsIndependent predictorsEE patientsSarcoma patientsRisk factorsTreatment characteristicsSmall tumorsOutcome differencesPatientsTherapyAdult populationLack of consensusChemotherapyRegression analysisAutomated diagnosis of colon cancer using hyperspectral sensing
Beaulieu RJ, Goldstein SD, Singh J, Safar B, Banerjee A, Ahuja N. Automated diagnosis of colon cancer using hyperspectral sensing. International Journal Of Medical Robotics And Computer Assisted Surgery 2018, 14: e1897. PMID: 29479794, DOI: 10.1002/rcs.1897.Peer-Reviewed Original ResearchConceptsColorectal cancerPossible metastatic diseaseColorectal cancer detectionColorectal cancer reliesMultiple tumor typesMetastatic diseaseOperative resectionSurgical resectionPathologic evaluationSurgical managementCancer reliesTumor specimensColon specimensColon cancerTumor typesPatient specimensCancerResectionPatientsDiagnostic methodsTumorsCancer detectionDiagnostic technologiesContrast agents
2017
Circulating Epithelial Cells in Intraductal Papillary Mucinous Neoplasms and Cystic Pancreatic Lesions
Poruk KE, Valero V, He J, Ahuja N, Cameron JL, Weiss MJ, Lennon AM, Goggins M, Wood LD, Wolfgang CL. Circulating Epithelial Cells in Intraductal Papillary Mucinous Neoplasms and Cystic Pancreatic Lesions. Pancreas 2017, 46: 943-947. PMID: 28697136, DOI: 10.1097/mpa.0000000000000869.Peer-Reviewed Original ResearchConceptsIntraductal papillary mucinous neoplasmHigh-grade dysplasiaPapillary mucinous neoplasmBlood of patientsEpithelial cellsMucinous neoplasmsPancreatic lesionsAbsence of malignancyBenign pancreatic lesionsCystic pancreatic lesionsNineteen patientsPancreatic resectionPeripheral bloodPancreatic cystsISET methodPatientsPancreas-specific markersResectionMalignancyDysplasiaBloodNeoplasmsPancreatic sourceLow gradeLesionsLong‐term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer
Shrestha B, Sun Y, Faisal F, Kim V, Soares K, Blair A, Herman JM, Narang A, Dholakia AS, Rosati L, Hacker‐Prietz A, Chen L, Laheru DA, De Jesus‐Acosta A, Le DT, Donehower R, Azad N, Diaz LA, Murphy A, Lee V, Fishman EK, Hruban RH, Liang T, Cameron JL, Makary M, Weiss MJ, Ahuja N, He J, Wolfgang CL, Huang C, Zheng L. Long‐term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer. Cancer Medicine 2017, 6: 1552-1562. PMID: 28639410, PMCID: PMC5504321, DOI: 10.1002/cam4.1104.Peer-Reviewed Original ResearchConceptsMedian overall survivalUpfront chemotherapyNeoadjuvant chemotherapyNeoadjuvant therapySurgical resectionOverall survivalUpfront chemoradiationBorderline resectable pancreatic adenocarcinomaLong-term survival benefitBorderline resectable pancreatic cancerCurative surgical resectionResectable pancreatic cancerUpfront neoadjuvant chemotherapyResectable pancreatic adenocarcinomaSubpopulation of patientsJohns Hopkins HospitalLong-term survivalCurative intentNeoadjuvant chemoradiationConsecutive patientsSurvival benefitPancreatic cancerPancreatic adenocarcinomaRetrospective analysisChemoradiationCombination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study
Connolly RM, Li H, Jankowitz RC, Zhang Z, Rudek MA, Jeter SC, Slater SA, Powers P, Wolff AC, Fetting JH, Brufsky A, Piekarz R, Ahuja N, Laird PW, Shen H, Weisenberger DJ, Cope L, Herman JG, Somlo G, Garcia AA, Jones PA, Baylin SB, Davidson NE, Zahnow CA, Stearns V. Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study. Clinical Cancer Research 2017, 23: 2691-2701. PMID: 27979916, PMCID: PMC5457329, DOI: 10.1158/1078-0432.ccr-16-1729.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerObjective response rateCombination epigenetic therapyEstrogen receptorEndocrine therapyPrimary endpointPartial responseMulticenter phase II studyEpigenetic therapyAdditional partial responsesHormone-resistant diseasePhase II studyTime of progressionBreast cancer modelClin Cancer ResHistone deacetylase inhibitorsImportant therapeutic targetPosttreatment biopsiesTNBC cohortII studyBreast cancerDNA methyltransferase inhibitorTherapeutic targetResponse rateCancer modelA Four-Gene Promoter Methylation Marker Panel Consisting of GREM1, NEURL, LAD1, and NEFH Predicts Survival of Clear Cell Renal Cell Cancer Patients
van Vlodrop IJH, Joosten SC, De Meyer T, Smits KM, Van Neste L, Melotte V, Baldewijns MMLL, Schouten LJ, van den Brandt PA, Jeschke J, Yi JM, Schuebel KE, Ahuja N, Herman JG, Aarts MJ, Bosman FT, Van Criekinge W, van Engeland M. A Four-Gene Promoter Methylation Marker Panel Consisting of GREM1, NEURL, LAD1, and NEFH Predicts Survival of Clear Cell Renal Cell Cancer Patients. Clinical Cancer Research 2017, 23: 2006-2018. PMID: 27756787, DOI: 10.1158/1078-0432.ccr-16-1236.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAutoantigensBiomarkers, TumorCarcinoma, Renal CellDisease-Free SurvivalDNA MethylationFemaleHigh-Throughput Nucleotide SequencingHumansIntercellular Signaling Peptides and ProteinsKaplan-Meier EstimateKidney NeoplasmsMaleMiddle AgedNeurofilament ProteinsNon-Fibrillar CollagensOligonucleotide Array Sequence AnalysisPrognosisPromoter Regions, GeneticProportional Hazards ModelsUbiquitin-Protein LigasesConceptsClear cell renal cell carcinomaPrognostic modelNonmetastatic clear cell renal cell carcinomaMethylation markersCox proportional hazards modelPrimary clear cell renal cell carcinomaIndependent patient seriesCause-specific survivalOutcomes of patientsCell renal cell carcinomaPrognosis of patientsKaplan-Meier curvesLog-rank testConfidence intervalsCurrent prognostic modelsRenal cell carcinomaProportional hazards modelClin Cancer ResCcRCC cell linesCancer Genome AtlasClinicopathologic featuresPatient seriesCell carcinomaMethylation-specific PCRPoor survivalCombination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat; a phase 2 consortium/stand Up 2 cancer study
Azad NS, el-Khoueiry A, Yin J, Oberg AL, Flynn P, Adkins D, Sharma A, Weisenberger DJ, Brown T, Medvari P, Jones PA, Easwaran H, Kamel I, Bahary N, Kim G, Picus J, Pitot HC, Erlichman C, Donehower R, Shen H, Laird PW, Piekarz R, Baylin S, Ahuja N. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat; a phase 2 consortium/stand Up 2 cancer study. Oncotarget 2017, 5: 35326-35338. PMID: 28186961, PMCID: PMC5471058, DOI: 10.18632/oncotarget.15108.Peer-Reviewed Original ResearchConceptsCombination epigenetic therapyMetastatic colorectal cancerRECIST responseCRC patientsMedian progression-free survivalCycles of therapySignificant clinical activityMetastatic CRC patientsProgression-free survivalSubset of patientsM2 days 1Serial tumor biopsiesMulti-institutional studyHistone deacetylase inhibitor entinostatEpigenetic therapyColorectal cell linesSubcutaneous azacitidinePrimary endpointPrior therapyLiver involvementOverall survivalTolerable therapySerial biopsiesColorectal cancerClinical activity
2016
Locally advanced primary recto-sigmoid cancers: Improved survival with multivisceral resection
Laurence G, Ahuja V, Bell T, Grim R, Ahuja N. Locally advanced primary recto-sigmoid cancers: Improved survival with multivisceral resection. The American Journal Of Surgery 2016, 214: 432-436. PMID: 28082009, DOI: 10.1016/j.amjsurg.2016.12.018.Peer-Reviewed Original ResearchConceptsMultivisceral resectionAdvanced colorectal cancerColorectal cancerCancer patientsYear survivalNon-metastatic colorectal cancerRadiation treatmentRecto-sigmoid cancerFive-year survivalSignificant associated morbidityKaplan-Meier analysisExtensive surgical proceduresGreatest survival advantageEligible patientsAssociated morbiditySelect patientsMeier analysisStandard surgeryRadical operationSEER dataAdjacent organsSurgical proceduresSurvival advantagePatientsSurgical specialistsCirculating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma
Poruk KE, Valero V, Saunders T, Blackford AL, Griffin JF, Poling J, Hruban RH, Anders RA, Herman J, Zheng L, Rasheed ZA, Laheru DA, Ahuja N, Weiss MJ, Cameron JL, Goggins M, Iacobuzio-Donahue CA, Wood LD, Wolfgang CL. Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma. Annals Of Surgery 2016, 264: 1073-1081. PMID: 26756760, PMCID: PMC4936958, DOI: 10.1097/sla.0000000000001600.Peer-Reviewed Original ResearchConceptsCytokeratin-positive CTCsPancreatic adenocarcinomaMesenchymal markersVimentin-positive CTCsEpithelial tumor cells (ISET) methodFourth leading causeBetter treatment stratificationPortal blood samplesSignificant independent predictorsPotential prognostic biomarkerBiology of metastasisDetection of CTCsSurgical resectionIndependent predictorsPrognostic factorsMedian timeMultivariable analysisPDAC patientsPrognostic utilityCancer deathPatient prognosisLeading causeTreatment stratificationCancer recurrencePoor survivalTumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients
Fu T, Liu Y, Li K, Wan W, Pappou EP, Iacobuzio-Donahue CA, Kerner Z, Baylin SB, Wolfgang CL, Ahuja N. Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients. Oncotarget 2016, 5: 86480-86489. PMID: 27880934, PMCID: PMC5349928, DOI: 10.18632/oncotarget.13441.Peer-Reviewed Original ResearchConceptsDisease-free survivalStage II colorectal cancer patientsStage II CRC patientsCpG island methylator phenotypeMLH1 methylation statusColorectal cancer patientsOverall survivalLymphovascular invasionCRC patientsCancer patientsMucin productionMethylator phenotypeKaplan-Meier analysisPoor clinical outcomeMethylation statusDuodenal adenocarcinomaClinical outcomesAggressive featuresPoor prognosisPrognostic valuePatient subgroupsTumor locationMultivariate analysisPatientsM groupA Contemporary Evaluation of the Cause of Death and Long‐Term Quality of Life After Total Pancreatectomy
Wu W, Dodson R, Makary MA, Weiss MJ, Hirose K, Cameron JL, Ahuja N, Pawlik TM, Wolfgang CL, He J. A Contemporary Evaluation of the Cause of Death and Long‐Term Quality of Life After Total Pancreatectomy. World Journal Of Surgery 2016, 40: 2513-2518. PMID: 27177647, DOI: 10.1007/s00268-016-3552-8.Peer-Reviewed Original ResearchConceptsCause of deathTotal pancreatectomyInsulin-dependent diabetesDiabetes-dependent QoLSF-36 surveyShort Form-36Majority of deathsLong-term qualityTotal hospitalizationsForm-36Preoperative stateDiabetes complicationsPreoperative assessmentWorse QoLDiabetic complicationsQOL surveyDiffuse diseasePatientsPancreatic enzymesQoLEuropean OrganizationHealth changesLife implicationsDeathPancreatectomyLong‐term outcomes in treatment of retroperitoneal sarcomas: A 15 year single‐institution evaluation of prognostic features
Abdelfatah E, Guzzetta AA, Nagarajan N, Wolfgang CL, Pawlik TM, Choti MA, Schulick R, Montgomery EA, Meyer C, Thornton K, Herman J, Terezakis S, Frassica D, Ahuja N. Long‐term outcomes in treatment of retroperitoneal sarcomas: A 15 year single‐institution evaluation of prognostic features. Journal Of Surgical Oncology 2016, 114: 56-64. PMID: 27076350, PMCID: PMC4917421, DOI: 10.1002/jso.24256.Peer-Reviewed Original ResearchConceptsCompartmental resectionRPS patientsSurgical resectionPrognostic factorsR0/R1 marginsR0/R1 resectionEn bloc surgical resectionBloc surgical resectionCornerstone of therapyMainstay of treatmentFive-year survivalRetrospective chart reviewPresence of metastasesEn bloc resectionExtent of resectionConnective tissue tumorsJohns Hopkins HospitalWarrants further investigationR1 resectionRetroperitoneal sarcomaChart reviewMedian survivalR1 marginsDistal recurrenceLocal recurrence