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 chemotherapy
2019
Next-generation Sequencing in the Management of Gastric and Esophageal Cancers
Rubinstein JC, Nicolson NG, Ahuja N. Next-generation Sequencing in the Management of Gastric and Esophageal Cancers. Surgical Clinics Of North America 2019, 99: 511-527. PMID: 31047039, DOI: 10.1016/j.suc.2019.02.005.Peer-Reviewed Original ResearchConceptsNext-generation sequencingHigh-throughput sequencing technologyAvailable genomic dataSingle-nucleotide resolutionGenome-wide molecular profilingSpecific oncogenic pathwaysSequencing technologiesGenomic dataOncogenic pathwaysGenomic profilesMolecular profilingSequencingPathwayDifficult disease processManagement of gastricIndividual tumorsOrgan-specific treatmentTumorigenesisAbundanceProfilingCancer careEsophageal malignancyEsophageal cancerImmense potentialDisease processAging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and Braf V600E-Induced Tumorigenesis
Tao Y, Kang B, Petkovich DA, Bhandari YR, In J, Stein-O'Brien G, Kong X, Xie W, Zachos N, Maegawa S, Vaidya H, Brown S, Yen R, Shao X, Thakor J, Lu Z, Cai Y, Zhang Y, Mallona I, Peinado MA, Zahnow CA, Ahuja N, Fertig E, Issa JP, Baylin SB, Easwaran H. Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and Braf V600E-Induced Tumorigenesis. Cancer Cell 2019, 35: 315-328.e6. PMID: 30753828, PMCID: PMC6636642, DOI: 10.1016/j.ccell.2019.01.005.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAge FactorsAgingAnimalsCell Transformation, NeoplasticColonic NeoplasmsDNA MethylationGene Expression Regulation, NeoplasticGene SilencingGenetic Predisposition to DiseaseHumansMice, Inbred NODMice, Mutant StrainsMice, SCIDMutationPhenotypeProto-Oncogene Proteins B-rafStem CellsTime FactorsTissue Culture TechniquesWnt Signaling PathwayConceptsCell fate changesPromoter DNA hypermethylationStem-like stateAging-like phenotypesCpG island methylationFate changesDifferentiation defectsEpigenetic abnormalitiesDNA hypermethylationSimultaneous inactivationWnt pathwayWnt activationPromoter hypermethylationTumorigenesisGenesHypermethylationMethylator phenotypeColon tumorigenesisPhenotypeOrganoidsPrecursor roleCRISPRMethylationSupStemness
2018
Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria
Hanada Y, Choi AY, Hwang JH, Draganov PV, Khanna L, Sethi A, Bartel MJ, Goel N, Abe S, De Latour RA, Park K, Melis M, Newman E, Hatzaras I, Reddy SS, Farma JM, Liu X, Schlachterman A, Kresak J, Trapp G, Ansari N, Schrope B, Lee JY, Dhall D, Lo S, Jamil LH, Burch M, Gaddam S, Gong Y, Del Portillo A, Tomizawa Y, Truong CD, Brewer Gutierrez OI, Montgomery E, Johnston FM, Duncan M, Canto M, Ahuja N, Lennon AM, Ngamruengphong S. Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria. Clinical Gastroenterology And Hepatology 2018, 17: 1763-1769. PMID: 30471457, DOI: 10.1016/j.cgh.2018.11.031.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAged, 80 and overCarcinoma, Signet Ring CellEndoscopic Mucosal ResectionFemaleGastrectomyHumansJapanLymph NodesLymphatic MetastasisMaleMiddle AgedNeoplasm GradingNeoplasm InvasivenessNeoplasm StagingPractice Guidelines as TopicRetrospective StudiesStomach NeoplasmsTumor BurdenUnited StatesConceptsFrequency of lymphEarly gastric cancerEndoscopic resectionLymph node metastasisLymph nodesGastric cancerLymphovascular invasionNode metastasisGastric adenocarcinomaEarly gastric cancer lesionsEarly-stage gastric cancerEndoscopic resection criteriaLymph node dissectionTertiary care centerRisk of lymphRisk of metastasisGastric cancer lesionsDefinitive therapyNode dissectionResection criteriaSurgical resectionAsian patientsRetrospective studySubmucosal invasionRisk factors
2016
Circulating 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 survivalMethylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma
Fu T, Sharmab A, Xie F, Liu Y, Li K, Wan W, Baylin SB, Wolfgang CL, Ahuja N. Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma. PLOS ONE 2016, 11: e0162929. PMID: 27643594, PMCID: PMC5028050, DOI: 10.1371/journal.pone.0162929.Peer-Reviewed Original ResearchConceptsDisease-free survivalCpG island methylator phenotypeDuodenal adenocarcinomaOverall survivalMethylation of MGMTMGMT methylationMicrosatellite instabilityPoor prognosisKRAS mutationsCox proportional hazards modelMGMT unmethylated groupTumor molecular featuresChemotherapy/radiotherapyIndependent prognostic factorO6-methylguanine-DNA methyltransferase methylation statusWorse overall survivalPossible prognostic valueProportional hazards modelMGMT methylation statusPrognostic factorsClinicopathological characteristicsTumor characteristicsMethylation statusPrognostic valueTumor differentiationPatterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma
Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, Yang S, Duncan M, Ahuja N, Taube JM, Anders RA, Kelly RJ. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut 2016, 66: 794. PMID: 26801886, PMCID: PMC4958028, DOI: 10.1136/gutjnl-2015-310839.Peer-Reviewed Original ResearchConceptsPD-L1 expressionProgression-free survivalEpstein-Barr virusT-cell densityImmune stromaOverall survivalPD-L1T cellsAdaptive immune resistance mechanismHigh PD-L1 expressionMembranous PD-L1 expressionStromal PD-L1 expressionCD8 T cell infiltrationWorse progression-free survivalImmune resistance mechanismsImmune checkpoint inhibitorsPD-L1 positivityPD-L1 statusGastro-oesophageal junctionImmune-based therapiesT cell infiltrationPercentage of tumorsTumor-stromal interfaceCD8 densityCD8 infiltration
2015
Time to Chemotherapy After Abdominoperineal Resection: Comparison Between Primary Closure and Perineal Flap Reconstruction
Althumairi AA, Canner JK, Ahuja N, Sacks JM, Safar B, Efron JE. Time to Chemotherapy After Abdominoperineal Resection: Comparison Between Primary Closure and Perineal Flap Reconstruction. World Journal Of Surgery 2015, 40: 225-230. PMID: 26336877, DOI: 10.1007/s00268-015-3224-0.Peer-Reviewed Original ResearchConceptsFlap reconstruction groupAdjuvant chemotherapyFlap reconstructionPrimary closureAbdominoperineal resectionWound complicationsRectal adenocarcinomaReconstruction groupWound healingPerineal flap reconstructionPerineal wound complicationsPrimary closure groupPerineal wound closureLength of healingRetrospective reviewClosure groupChemotherapyPatientsPerineal defectsWound closureHealingResectionComplicationsAdenocarcinomaLength of timeAGA Guidelines for the Management of Pancreatic Cysts
Lennon AM, Ahuja N, Wolfgang CL. AGA Guidelines for the Management of Pancreatic Cysts. Gastroenterology 2015, 149: 825. PMID: 26231607, DOI: 10.1053/j.gastro.2015.05.062.Peer-Reviewed Original Research
2014
The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma
Wu W, He J, Cameron JL, Makary M, Soares K, Ahuja N, Rezaee N, Herman J, Zheng L, Laheru D, Choti MA, Hruban RH, Pawlik TM, Wolfgang CL, Weiss MJ. The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma. Annals Of Surgical Oncology 2014, 21: 2873-2881. PMID: 24770680, PMCID: PMC4454347, DOI: 10.1245/s10434-014-3722-6.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsChemotherapy, AdjuvantCombined Modality TherapyFemaleFollow-Up StudiesHumansMaleMiddle AgedNeoplasm StagingPancreatic NeoplasmsPancreaticoduodenectomyPostoperative ComplicationsPrognosisRadiotherapy, AdjuvantRetrospective StudiesSurvival RateConceptsAdjuvant therapyPostoperative complicationsMedian survivalMultivariate analysisClavien-Dindo complication gradeTherapy warrants further investigationMultimodality adjuvant therapyOverall complication rateMethodsA retrospective reviewGrade of complicationsLonger median survivalLength of stayWarrants further investigationAdjuvant chemotherapyMedian TTANeoadjuvant approachComplication gradeComplication rateSevere complicationsRetrospective reviewClinicopathological dataResultsA totalPancreaticoduodenectomyRadiation therapyComplications
2013
2564 resected periampullary adenocarcinomas at a single institution: trends over three decades
He J, Ahuja N, Makary MA, Cameron JL, Eckhauser FE, Choti MA, Hruban RH, Pawlik TM, Wolfgang CL. 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades. Hepato Pancreato Biliary 2013, 16: 83-90. PMID: 23472829, PMCID: PMC3892319, DOI: 10.1111/hpb.12078.Peer-Reviewed Original ResearchConceptsPeriampullary adenocarcinomaBile ductSingle institutionPancreatic cancerIntraductal papillary mucinous neoplasmNumber of patientsPapillary mucinous neoplasmRelative survival ratesCurative intentWorse survivalLongterm outcomesMucinous neoplasmsSafe resectionLongterm survivalPathological diagnosisPrimary siteSurvival ratePancreaticoduodenectomyAdenocarcinomaPatientsSurvivalResectionSignificant differencesCancerDiagnosisKRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma
Fu T, Guzzetta AA, Jeschke J, Vatapalli R, Dave P, Hooker CM, Morgan R, Iacobuzio‐Donahue C, Liu B, Ahuja N. KRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma. International Journal Of Cancer 2013, 132: 2502-2509. PMID: 23065691, PMCID: PMC3579006, DOI: 10.1002/ijc.27910.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBiomarkers, TumorCell DifferentiationDNA, NeoplasmDuodenal NeoplasmsFemaleHumansMaleMicrosatellite RepeatsMiddle AgedMutationNeoplasm Recurrence, LocalNeoplasm StagingPolymerase Chain ReactionPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsSurvival RateConceptsPoor tumor differentiationKRAS GPositive lymph nodesDuodenal adenocarcinomaKRAS mutationsTumor differentiationMutation carriersDistant relapseLymph nodesMultivariate logistic regression analysisShorter relapse-free survivalFuture staging systemsRelapse-free survivalShorter overall survivalPossible prognostic roleLogistic regression analysisCurative resectionPoor OSOverall survivalPrognostic roleTumor characteristicsClinical outcomesClinicopathological characteristicsPoor prognosisPrognostic significance
2012
CpG Island Methylator Phenotype–Positive Tumors in the Absence of MLH1 Methylation Constitute a Distinct Subset of Duodenal Adenocarcinomas and Are Associated with Poor Prognosis
Fu T, Pappou EP, Guzzetta AA, Jeschke J, Kwak R, Dave P, Hooker CM, Morgan R, Baylin SB, Iacobuzio-Donahue CA, Wolfgang CL, Ahuja N. CpG Island Methylator Phenotype–Positive Tumors in the Absence of MLH1 Methylation Constitute a Distinct Subset of Duodenal Adenocarcinomas and Are Associated with Poor Prognosis. Clinical Cancer Research 2012, 18: 4743-4752. PMID: 22825585, PMCID: PMC3482463, DOI: 10.1158/1078-0432.ccr-12-0707.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdenocarcinomaAgedCpG IslandsDNA MethylationDuodenal NeoplasmsFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMicrosatellite InstabilityMiddle AgedMutL Protein Homolog 1Nuclear ProteinsPrognosisProportional Hazards ModelsProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Ras ProteinsConceptsMLH1 methylation statusDuodenal adenocarcinomaMicrosatellite instabilityPoor prognosisBRAF mutationsMLH1 methylationCox proportional hazards modelDuodenal adenocarcinoma patientsKaplan-Meier analysisSignificant prognostic valueCpG island methylator phenotype (CIMP) statusProportional hazards modelBRAF V600E mutationMethylation statusWorse OSOverall survivalClinicopathologic featuresTumor characteristicsAdenocarcinoma patientsPrognostic valueKRAS mutationsMSI statusHazards modelAdenocarcinomaV600E mutation
2011
Duodenal Adenocarcinoma: Clinicopathologic Analysis and Implications for Treatment
Poultsides GA, Huang LC, Cameron JL, Tuli R, Lan L, Hruban RH, Pawlik TM, Herman JM, Edil BH, Ahuja N, Choti MA, Wolfgang CL, Schulick RD. Duodenal Adenocarcinoma: Clinicopathologic Analysis and Implications for Treatment. Annals Of Surgical Oncology 2011, 19: 1928-1935. PMID: 22167476, PMCID: PMC3663711, DOI: 10.1245/s10434-011-2168-3.Peer-Reviewed Original ResearchConceptsDuodenal adenocarcinomaOverall survivalLymph nodesMultivariate analysisInvolved lymph nodesSmall bowel adenocarcinomaEffective systemic therapyFive-year survivalOnly independent predictorProlongs overall survivalAmpulla of VaterConclusionsThe prognostic significanceAdjuvant chemoradiationBowel adenocarcinomaUnderwent pancreaticoduodenectomySystemic therapyAdequate lymphadenectomyIndependent predictorsLocal recurrenceNodal metastasisClinicopathologic analysisPrognostic significanceClinicopathologic variablesRare cancersAdenocarcinoma
2010
Is the Debate Finally Over?: Comment on “Survival Effects of Adjuvant Chemoradiation Following Chemoradiotherapy After Resection for Pancreatic Carcinoma”
Ahuja N. Is the Debate Finally Over?: Comment on “Survival Effects of Adjuvant Chemoradiation Following Chemoradiotherapy After Resection for Pancreatic Carcinoma”. JAMA Surgery 2010, 145: 56-56. PMID: 20088100, DOI: 10.1001/archsurg.2009.241.Peer-Reviewed Original Research
2008
Is There a Difference in Survival Between Right- Versus Left-Sided Colon Cancers?
Meguid RA, Slidell MB, Wolfgang CL, Chang DC, Ahuja N. Is There a Difference in Survival Between Right- Versus Left-Sided Colon Cancers? Annals Of Surgical Oncology 2008, 15: 2388. PMID: 18622647, PMCID: PMC3072702, DOI: 10.1245/s10434-008-0015-y.Peer-Reviewed Original ResearchConceptsRight-sided colon cancerLeft-sided colon cancerProportional hazards regression analysisHazards regression analysisColon cancerMedian survivalCox proportional hazards regression analysisLongitudinal population-based databaseLong-term survival outcomesEnd Results Program databaseInvasive colon adenocarcinomaRight-sided cancersOverall median survivalLeft-sided cancersYear of diagnosisPopulation-based databaseRetrospective survival analysisSubset of subjectsRegression analysisSEER databaseSurgical resectionLymph nodesWorse prognosisSurvival outcomesTumor size
1999
Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification.
Toyota M, Ho C, Ahuja N, Jair KW, Li Q, Ohe-Toyota M, Baylin SB, Issa JP. Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Research 1999, 59: 2307-12. PMID: 10344734.Peer-Reviewed Original Research5-MethylcytosineAdenocarcinomaChondroitin Sulfate ProteoglycansCloning, MolecularColorectal NeoplasmsCpG IslandsCytosineDNA MethylationDNA-Binding ProteinsDNA, NeoplasmDNA, RibosomalExonsEye ProteinsGenes, p16Homeobox Protein Nkx-2.5Homeodomain ProteinsHumansLectins, C-TypePaired Box Transcription FactorsPAX6 Transcription FactorPolymerase Chain ReactionRepressor ProteinsRNA, RibosomalSubtraction TechniqueTranscription FactorsTubulinVersicans