简介：AbstractPancreatic cancer is an aggressive malignancy with a high recurrence rate even after curative-intent resection. Improvements in survival have not been achieved in the last 25 years thus highlighting the need for effective multimodal treatment strategies. The role of radiation therapy for pancreatic cancer remains ill-defined due to historical lack of a standard definition of resectability, and the use of antiquated radiation delivery techniques and chemotherapy regimens. Current level I data regarding neoadjuvant chemoradiotherapy for resectable and borderline resectable pancreatic adenocarcinoma (PDAC) are limited to 2 randomized controlled trials and several retrospective studies and suggest that it may lead to an increased likelihood of a margin-negative resection and certainly allows for improved patient selection for pancreaticoduodenectomy when compared to upfront surgery. In the adjuvant setting, data are similarly lacking but suggest that chemoradiotherapy may be beneficial for patients at high risk of locoregional recurrence. Here we review existing data regarding the role of radiation in PDAC.

简介：AbstractThe management of pancreatic cancer has dramatically changed since the first major randomized trial published in 2001 by the European Study Group for Pancreatic Cancer (ESPAC) stimulated the development of multimodality oncosurgical therapies. ESPAC-1 demonstrated a survival improvement from upfront surgery of only 8%, increasing to 21% 5-year survival for 5-fluorouracil/folinic acid but only 10.8% for chemoradiotherapy. ESPAC-4 has shown a 5-year survival rate of 30% for all patients without restriction of 30% using a combination of gemcitabine and capecitabine, rising to 40% in those with an R0 resection margin, or nearly 50% in those with N0 lymph node status. In selected patients with favorable prognostic features mFOLFIRINOX can produce a 50% 5-year survival rate but with added toxicity. While a positive resection margin is associated with an increased likelihood of local recurrence, this of itself is not the contributor to reduced survival, but rather reflects the increased probability of systemic disease. Thus, strategies aimed at local control, may reduce subsequent local progression, but will not improve overall survival. Neoadjuvant chemotherapy is increasingly utilized in cases of borderline resectable or locally advanced pancreatic cancer, but there is still a lack of proof of concept studies. High-quality evidence from randomized controlled trials to identify the indications and benefits of neoadjuvant therapy in pancreatic cancer are required. The use of patient-derived tumor organoids may predict response to chemotherapy which could open a new opportunity in pancreatic cancer treatment, stratifying patients into treatment groups based on their response to these therapies in the laboratory.

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简介：AbstractThe tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.

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简介：AIM:Toinvestigatethelifetimeriskofdevelopmentofesophagealadenocarcinomaand/orhigh-gradedysplasiainpatientsdiagnosedwithBarrett’sesophagus.METHODS:DatawereextractedfromtheUnitedKingdomNationalBarrett’sOesophagusRegistryondateofdiagnosis,patientageandgenderof7877patientsfromwhohadbeenregisteredfrom35UnitedKingdomcenters.LifeexpectancywasevaluatedfromUnitedKingdomNationalStatisticsdatabasedupongenderandageatyearatdiagnosis.Thesedatawerethenusedwithpublishedestimatesofannualadenocarcinomaandhigh-gradedysplasiaincidencesfrommetaanalysesandlargepopulation-basedstudiestoestimateoveralllifetimeriskofdevelopmentofthesestudyendpoints.RESULTS:ThemeanageatdiagnosisofBarrett’sesophaguswas61.6yearsinmalesand67.3yearsinfemales.Themeanlifeexpectancyatdiagnosiswas23.1yearsinmales,20.7yearsinfemalesand22.2yearsoverall.Usingdatafrompublishedmeta-analyses,thelifetimeriskofdevelopmentofadenocarcinomawasbetween1in8and1in14andthelifetimeriskofhigh-gradedysplasiaoradenocarcinomawas1in5to1in6.Usingdatafrom3largerecentpopulation-basedcohortstudiesthelifetimeriskofadenocarcinomawasbetween1in10and1in37andofthecombinedendpointofhigh-gradedysplasiaandadenocarcinomawasbetween1in8and1in20.AgeatBarrett’sesophagusdiagnosisisreducingandlifeexpectancyisincreasing,whichwillpartiallycounter-balancelowerannualcancerincidence.CONCLUSION:Thereisasignificantlifetimeriskofdevelopmentofhigh-gradedysplasiaandadenocarcinomainBarrett’sesophagus.

简介：AbstractIntroduction:Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that disproportionately affects geriatric patients. Combination therapy with surgery and chemotherapy is associated with longer survival than medical treatment or supportive care. Preoperative selection of patients for surgical treatment, based on patient-specific factors such as sarcopenia, may help risk-stratify patients and improve outcomes. This paper aims to review the current literature on the impact of sarcopenia and sarcopenic obesity on patients undergoing treatment for PDAC.Outcomes:The impact of sarcopenia and sarcopenia obesity on perioperative and long-term outcomes after treatment for PDAC is variable. Sarcopenia has been associated with high-grade complications, longer length of hospital, and intensive care unit stays, more frequent discharge to skilled nursing facilities and decreased utilization of adjuvant therapy in patients treated with curative intent surgery. Sarcopenic obesity has been associated with more complications, high-grade complications, and hematologic toxicities. Patients with sarcopenic obesity may have even lower overall survival than sarcopenic patients.Discussion:The effect of a pre-treatment diagnosis of sarcopenia or sarcopenic obesity on outcomes for patients undergoing treatment for PDAC remains unknown, in part due to the heterogeneity of studies and definitions. Prehabilitation programs including resistance exercise and nutritional supplementation have shown benefit in sarcopenic patients.Conclusion:PDAC remains a deadly disease and patient-specific factors such as sarcopenia and sarcopenic obesity identified at the time of cancer diagnosis offer potential as risk stratification measures and points of intervention. Currently, a paucity of standardized measurement tools, definitions, and prehabilitation regimens limits the clinical implementation of such knowledge.

简介：DearEditor,Adenocarcinomaofthenonpigmentedciliaryepithelium(NPCE)isararemalignanttumorwhichisnoteasytobefoundintheearlystage~([1]).Herein,wereportacaseofadenocarcinomaoftheNPCEinaChineseboyanddiscussits

简介：UsingFX-4000strainunit,theprolierationinhumanlungadenocarcinomaA549cellsthatunderwentmechanicalstrainofdifferentwaveform、frequencyanddurationwerestudied.Imageanalysisrevealedthatcellularproliferationrate(PR)reducedsignificantlyaftercellsweresubjectedtosquarewavewith0～20%elongationatfrequency30,40,50and60cycles/minfor2h.ThePRhadnodistinctdifferenceatheartwave,trianglewaveandsinewavegroupcomparedwithcontrol.ItisconcludedthatsquarewaveandhigherfrequencyplayanimportantroleininhibitingA549cellsproliferation.

简介：Objective:Toclonemultidrugresistance(MDR)relatedgenesinlungadenocarcinomacelllines.Methods:ThedifferentiallyexpressedcDNAfragmentsbetweenA549andA549DDPcellswereanalyzedbymRNAdifferentialdisplayPCR(DDRT-PCR).ThefragmentsthusobtainedwerefurtheranalyzedbyDNAsequencingandNorthernblotting.Results:ThreedifferentiallyexpressedcDNAfragmentswereobtainedandconfirmedbyNorthernblot.Sequenceanalysisrevealedthattwoofthemwerenovelandonewas100%identicalwithICEgene.Conclusion:AnalyzingdifferentiallyexpressedfragmentbetweenA549andA549DDPcellsmaybehelpfulforfindingnewMDRrelatedgenes.ThedrugresistanceofA549DDPcellsmayberelatedtotheinhibitionordown-regulationofICEgene.

简介：AIM:Toclarifythecorrelationwithphenotypicexpression,clinicopathologicalfeatures,geneticalterationandmicrosatellite-instabilitystatusinsmallintestinaladenocarcinoma(SIA).METHODS:Thecasesof47patientsdiagnosedwithprimarySIAsthatweresurgicallyresectedatourinstitutionin1975-2005werestudied.Wereviewedclinicopathologicalfindings(age,gender,tumorsize,grossappearance,histologicalmorphologictype,invasiondepth,lymphaticpermeation,venousinvasion,andlymphnodemetastasis),andtheimmunohistochemicalexpressionofMUC5AC,MUC6,MUC2,CD10,andmismatch-repair(MMR)proteins(MLH1andMSH2).WeanalyzedKRASandBRAFgenemutations,andthemicrosatelliteinstability(MSI)status.TheimmunohistochemicalstainingofCD10,MUC2,MUC5ACandMUC6wasconsideredpositivewhendistinctstainingin>5%oftheadenocarcinomacellswasrecorded.ToevaluateofMMRproteinexpression,weusedadjacentnormaltissueincludinglymphoidfollicles,inflammatorycells,andstromalcellsasaninternalpositivecontrol.SectionswithoutnuclearstaininginthetumorcellswereconsideredtohavelosttheexpressionoftherespectiveMMRprotein.RESULTS:Therewere29malesand18femalespatients(meanage59.9years,range:23-87years).Tumorswerelocatedintheduodenumin14cases(30%),thejejunumin21cases(45%),andtheileumin12cases(25%).Aphenotypicexpressionanalysisrevealed20MUC2-positivetumors(42.6%),11MUC5AC-positive(23.4%),4MUC6-positive(8.5%),and7CD10-positive(14.9%).ThetumorsizesoftheMUC2(+)tumorsweresignificantlylargerthanthoseoftheMUC2(-)tumors(mean,5.7±1.4cmvs4.7±2.1cm,P<0.05).AllthreetumorswithadenomatouscomponentwerepositiveforMUC2(P<0.05).PolypoidappearancewasseensignificantlymorefrequentlyintheCD10(+)groupthanintheCD10(-)group(P<0.05).ThetumorsizewassignificantlylargerintheCD10(+)groupthanintheCD10(-)group(mean,5.9±1.4cmvs5.0±2.1cm,P<0.05).Of34SIAswithsuccessfullyobtainedMSIdata,4wereMSI-high.O

简介：Apocrinecarcinomaisararemalignantadnexalneoplasm.Thedifferentialdiagnosisbetweenapocrinecarcinomaandcutaneousmetastasisisoftendifficult.Here,wereportacaseoflocallyrecurrentpenileapocrinecarcinomainitiallydiagnosedasmetastaticadenocarcinomaofthecolon.A75-year-oldmanwithahistoryofsurgicalresectionduetosigmoidcoloncancerandpenilemetastasistwoyearspriortothisstudypresentedwithanoduleattheleftpenilebase.Heunderwentawidelocalresectionofthepenilemassunderasuggestedpreoperativediagnosisofextra-mammaryPaget’sdisease(EMPD)associatedwithprevioussigmoidcoloncancer.However,thepreviouslyandcurrentlyresectedpenilemasseswereidentifiedasprimaryapocrinecarcinomauponhematoxylinandeosin(H&E)stainingandimmunohistochemicalstaining.Althoughtheincidenceisextremelyrare,bothcliniciansandpathologistsshouldbealerttothepossibilityofsynchronousdoubleprimaryapocrinecarcinomaincancerpatientswithmalignantcutaneouslesions.

简介：AbstractPancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive malignancies, and the majority of patients with PDAC present with metastatic disease, mainly in the liver, at the time of diagnosis. Surgical resection is the only treatment that can offer prolonged survival and possible cure. However, the indications for surgery for patients with PDAC metastases remain extremely limited to highly selected patients with localized disease, and metastatic disease is generally regarded as a contraindication to surgery. Recently, however, the advent of more effective chemotherapy has changed the treatment strategy for metastatic PDAC. In fact, cases in which resection of synchronous or metachronous PDAC liver metastases lead to prolonged survival in highly selected patients have been reported. In this review, we provide current data regarding survival outcomes after surgery, and discuss the role of surgical resection and selection criteria for patients with PDAC liver metastases in the modern era.

简介：AbstractBackground:Recent studies have demonstrated that microRNAs (miRNAs) in the blood circulation can serve as promising diagnostic markers for cancers. This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma (LA) diagnosis.Methods:The study was carried out between 2016 and 2017. The Exiqon miRNA qPCR panel (3 LA vs. 1 normal control [NC] pooled serum samples) was used for initial screening to acquire miRNA profiles. Thirty-five dysregulated miRNAs were further evaluated in the training (24 LA vs. 24 NCs) and testing stages (110 LA vs. 110 NCs) using quantitative real-time polymerase chain reaction assays.Results:Four serum miRNAs (miR-133a-3p, miR-584-5p, miR-10b-5p, and miR-221-3p) were significantly overexpressed in LA patients compared with NCs. The diagnostic value of the four-miRNA panel was validated by an external cohort (36 LA vs. 36 NCs). The areas under the receiver operating characteristic curve of the four-miRNA panel in the training, testing, and external validation stages were 0.734, 0.803, and 0.894 respectively. Meanwhile, the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues (19 LA vs. 19 NCs). The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples (18 LA vs. 18 NCs). The expression of miR-133a-3p, miR-584-5p, and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs.Conclusion:The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.

简介：AbstractDiabetes mellitus and pancreatic ductal adenocarcinoma are two common diseases worldwidely which are both derived from different components of pancreas. The pancreatic and duodenal homeobox-1 (PDX1) is an essential transcription factor for the early development of pancreas that is required for the differentiation of all pancreatic cell lineages. Current evidence suggests an important role of PDX1 in both the origin and progression of pancreatic diseases. In this review, we discussed recent studies of PDX1 in diabetes mellitus and pancreatic cancer, and the therapeutic strategies derived from this transcription factor.

简介：ＥＸＰＲＥＳＳＩＯＮＯＦｃｅｒｂＢ２ＡＮＤＰＣＮＡＩＮＣＥＲＶＩＣＡＬＡＤＥＮＯＣＡＲＣＩＮＯＭＡＡＮＤＩＴＳＳＩＧＮＩＦＩＣＡＴＩＯＮＨｕａｎｇＹｏｎｇ黄勇ＣａｉＳｈｕｍｏ蔡树模ＹｕＳｈａｏｙｉｎ俞绍音ＳｈｉＤａｒｅｎ施达仁ＣａｎｃｅｒＨｏｓｐ...

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简介：Objective:Gastriccancer(GC)isoneoftheleadingcausesofdeathinChinaandotherAsiancountries.Recently,gastricendoscopyhasbecomethemainapproachforGCscreening,buttheidentificationofhigh-riskindividualsremainsachallengeinGCscreeningprograms.Methods:Therewere7,302patientswithchronicgastritisinvolvedinthisstudy.Endoscopicexaminationswereperformed,andtheirdemographiccharacteristicsandlifestyledatawerecollected.EachpossibleassociatedfactorofGC/premalignantandprecursorlesionswasevaluatedbyunivariateandmultivariatelogisticregressions.Nomogramswereusedforvisualizationofthosemodels,andreceiveroperatingcharacteristic(ROC)curveanalysiswasusedtopresentthepredictiveaccuracy.Results:Wedetected8(0.11%)gastricadenocarcinomas,17(0.23%)dysplasiacases,14(0.19%)hyperplasiacases,52(0.71%)intestinalmetaplasiacases,217(2.97%)inflammatorylesions,141(1.93%)gastriculcers,10(0.14%)atrophicgastritiscases,1,365(18.69%)erosivegastritiscases,and5,957(81.58%)superficialgastritiscasesin7,302patients.Theage(P<0.001),gender(P=0.086),laborintensity(P=0.018)andleekfoodintake(P=0.143)wereidentifiedasindependentpredictivefactorsofGC/premalignantlesionspossibility.Thecorrespondingnomogramexhibitedanareaunderthecurve(AUC)[95%confidenceinterval(95%CI)]of0.82(0.74–0.89)forthemodelinggroupand0.80(0.75–0.85)forthevalidationgroup.Theage(P=0.002),gender(P=0.024),smoking(P=0.002)andleekfoodintake(P=0.039)wereindependentpredictivefactorsofprecursorlesionspossibility.ThecorrespondingnomogramexhibitedanAUC(95%CI)of0.62(0.60–0.65)forthemodelinggroupand0.61(0.59–0.63)forthevalidationgroup.Conclusions:WeidentifiedseveralpotentialassociatedfactorsandprovidedapreclinicalnomogramwiththepotentialtopredictthepossibilityofGC/premalignantandprecursorlesions.

简介：AbstractPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival. Local control through surgical resection paired with radiotherapy and chemotherapy comprise the primary tenets of treatment. Debate exists regarding the timing of treatment and ordering of systemic therapy and resection in the management of early stage disease. The goal of this study was to review the literature and describe the contemporary evidence basis for the role of neoadjuvant therapy (NAT) in the setting of upfront resectable (UP-R) PDAC. Five databases were searched in parallel to identify relevant original articles investigating neoadjuvant therapy where at least 1 study arm contained UP-R PDAC; studies with only borderline resectable or locally advanced disease were excluded. Due to the diversity in NAT regimens and study design between trials, qualitative analyses were performed to investigate patient selection, impact on perioperative and survival outcomes, safety, and cost effectiveness. Thirty-five studies met inclusion criteria, of which 24 unique trials are discussed here in detail. These studies included those trials using single agents as well as more recent trials comparing modern multiagent therapies, and several large database analyses. Overall the data suggest that NAT is safe, may confer survival benefit for appropriately selected patients, is cost effective, and is an appropriate approach for UP-R PDAC. Nevertheless, the risk for disease progression during upfront medical therapy, requires appropriate patient identification and close monitoring, and emphasizes the need for further discovery of more effective chemotherapeutics, useful biomarkers or molecular profiles, and additional prospective comparative studies.

简介：Inthepresentstudy,thechemosensitivityofMGc80-3humangastricadenocarcinomacellswasdeterminedbymeansofcolony-formingassayandtheinvitroactivitiesof10anticancerdrugswereexaminedonthebasisoftheclinicallyachievablepeakplasmadrugconcentration.TheresultsshowedthatMGc80-3cellsweremostsensitivetomitomyc’nC,adriamycinand5-fluorouracil,beingconsistentwiththeresponsenotedinclinicalgastriccancer.Thiscelllinemayretainitsoriginaldrugsensitivityandmaybeusefulinscreeningfornewcompoundswithactivityagainstthisdisease.