简介：Treatmentofpancreaticcancerismultimodalandsurgeryisanessentialpart,mandatoryforcurativepotential.Alsochemotherapyisessential,andseriouspostoperativecomplicationsorrapiddiseaseprogressionmayprecludecompletionofmultimodaltreatment.Thesequenceoftreatmentinterventionshasthereforebecomeanimportantconcern,andnumerousongoingrandomizedcontrolledtrialscompareclinicaloutcomeafterupfrontsurgeryandneoadjuvanttreatmentwithsubsequentresection.Inpreviousyears,borderlineresectableandlocallyadvancedpancreaticcancerwasmostoftenconsideredunresectable.Moreeffectivechemotherapytogetherwiththelatestimprovementsinsurgicalexpertisehasresultedinextendedoperations,pushingthebordersofresectability.Multivisceralresectionswithorwithoutresectionofmajormesen-tericvesselsarenowperformedinnumerouspatients,resultinginbetteroutcome,recordedasoverallsurvivaland/orpatientreportedoutcome.Butpostoperativemorbidityincreasesconcurrently,andclinicalbenefitmustbecarefullyevaluatedagainstriskofpotentialharm,associatedwithnewcomprehensivemultimodaltreatmentsequences.Eventhoughcost/utilityanalysesaredeficient,extendedsurgeryhasresultedinsignifi-cantlylongerandbetterlifeformanypatientswithnoothertreatmentalternative.Improvedselectionofpatientstosurgeryand/orchemotherapywillinthenearfuturebepossible,basedonbettertumorbiologyinsight.Clinicallyavailablebiomarkersenablingpersonalizedtreatmentareforthcoming,buttheseoptionsarestilllimited.Theimportanceofsurgicalresectionforeachpatient’sprognosisispresentlyincreasing,justifyingsustainedexpansionofthesurgicaltreatmentmodality.

简介：胰腺的癌症继续是有仍然高的死亡和差的幸存的致命的恶意。尽管有重要进展，很少进步在理解，诊断，和常规、新奇的治疗的存取在先进胰腺的癌症的治疗上被取得了。损害的分子的病理是我们位于这癌症的发展下面的机制的理解的钥匙并且将可能在更早的诊断和更好治疗学的结果帮助我们。新治疗策略和创新治疗的更小心的评估清楚地为这疾病被需要。鉴于许多调查结果，胰腺的癌症应该被认为是全身的疾病，并且在最后几年，调查者获得了导致恶意的发展的分子的生物学和事件的更好的理解。我们这里在在胰腺的癌症的为通常变异的基因的全身的探索考察新奇开发。

简介：AbstractPancreatic ductal adenocarcinoma (PDAC) is a lethal, aggressive, and incurable disease. The patients with PDAC are often diagnosed at the advanced stage, leading to poor overall survival because of no current effective treatment. Further exploration of the mechanism is needed urgently to provide insights on the prevention, detection, or intervention of pancreatic cancer. Oncogenic KRAS and mutated tumor suppressor genes serve essential roles in PDAC tumorigenesis. Different groups of scientists indicated that yes-associated protein and transcriptional coactivator with PDZ-binding motif, which are the main effectors of the Hippo pathway, are the center in the development of PDAC. Here, we will focus on the recent advances of the molecular mechanisms of core components in the Hippo kinases cascade and discuss their clinical implications.

简介：AbstractPancreatic cancer is one of the most aggressive malignancies. The poor prognosis of pancreatic cancer patients is mainly attributed to low diagnostic rate at the early stage, highly aggressive nature coupled with the inadequate efficacy of current chemotherapeutic regimens. Novel therapeutic strategies are urgently needed for pancreatic cancer. MicroRNAs (miRNAs) play an important regulatory role in key processes of cancer development. The aberrant expression of miRNAs is often involved in the initiation, progression, and metastasis of pancreatic cancer. The discovery of tumor suppressor miRNAs provides prospects for the development of a novel treatment strategy for pancreatic cancer. We reviewed recent progress on the understanding of the role of miRNAs in pancreatic cancer, highlighted the efficient application of miRNAs-based therapies for pancreatic cancer in animal models and clinical trials, and proposed future prospects. This review focuses on the promise of integrating miRNAs into the treatment of pancreatic cancer and provides guidance for the development of precision medicine for pancreatic cancer.

简介：作为高度恶意的癌症和在世界上的癌症相关的死亡的第四个原因，胰腺的癌症被忧郁的预后描绘，由于到化疗的快速的疾病前进，高度侵略的瘤显型，和抵抗。尽管有在疾病的治疗的重要进展在过去的十年期间，幸存率几乎没被改进。到差的结果的一个贡献因素是为早诊断的适当敏感、特定的biomarkers的缺乏。而且，为指向，指导并且估计治疗学的干预，以及为剩余或周期性的癌症的察觉的biomarkers也被需要。因此，在胰腺的癌症的足够的biomarkers的鉴定具有极端重要性。最近，伴随proteomic技术和设备的发展，越来越潜在的biomarkers出现了并且被报导。在这评论，我们在胰腺的癌症提供基于proteome的biomarkers的角色的概述，包括织物，浆液，果汁，尿和房间线。我们以后也讨论可能的机制和前景。那个信息可能希望对这块地里的进一步的研究有用。

简介：AbstractPancreatic ductal adenocarcinoma is the main cause of cancer-related mortality, with a lack of effective treatments and overall survival rates far lower than other solid cancers. This clinical challenge is related to late diagnosis as well as primary or acquired resistance to therapy-induced apoptosis. Targeting nonapoptotic cell death pathways may provide alternative therapeutic strategies to overcome drug resistance. In particular, recent studies have suggested that ferroptosis, a type of iron-dependent nonapoptotic cell death, is a promising target for pancreatic ductal adenocarcinoma. Ferroptosis can be triggered by inhibiting or activating the redox or iron metabolism-related pathways, mediated by extrinsic/membrane transports (e.g., solute carrier family 7 member 11) or intrinsic/enzymes (e.g., glutathione peroxidase 4). Although the exact effector molecule remains obscure, reactive oxygen species-induced lipid peroxidation and subsequent plasma membrane damage appears to play a central role in mediating ferroptotic death. While treatment-induced ferroptosis is beneficial to suppress tumor growth, inflammation-related immunosuppression caused by ferroptotic damage may promote the occurrence of pancreatic ductal adenocarcinoma. In this review, we outline the latest knowledge about the regulation and function of ferroptosis in pancreatic tumorigenesis and therapy.

简介：AbstractThe incidence of pancreatic cancer has been rising worldwide, and its clinical diagnosis and treatment remain a great challenge. To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years, Chinese Pancreatic Association, the Chinese Society of Surgery, Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China (2014) after reviewing evidence-based and problem-oriented literature published during 2015-2021, mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer, conversion strategies for locally advanced pancreatic cancer, treatment of pancreatic cancer with oligo metastasis, adjuvant and neoadjuvant therapy, standardized processing of surgical specimens and evaluation of surgical margin status, systemic treatment for unresectable pancreatic cancer, genetic testing, as well as postoperative follow up of patients with pancreatic cancer. Forty recommendation items were finally proposed based on the above issues, and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation, Assessment, Development, and Evaluation system. This guideline aims to standardize the clinical diagnosis and therapy, especially surgical treatment of pancreatic cancer in China, and further improve the prognosis of patients with pancreatic cancer.

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简介：AbstractPancreatic ductal adenocarcinoma (PDAC) is an extremely malignant disease, which has an extremely low survival rate of <9% in the United States. As a new hallmark of cancer, metabolism reprogramming exerts crucial impacts on PDAC development and progression. Notably, arginine metabolism is altered in PDAC cells and participates in vital signaling pathways. In addition, arginine and its metabolites including polyamine, creatine, agmatine, and nitric oxide regulate the proliferation, growth, autophagy, apoptosis, and metastasis of cancer cells. Due to the loss of argininosuccinate synthetase 1 (ASS1) expression, the key enzyme in arginine biosynthesis, arginine deprivation is regarded as a potential strategy for PDAC therapy. However, drug resistance develops during arginine depletion treatment, along with the re-expression of ASS1, metabolic dysfunction, and the appearance of anti-drug antibody. Additionally, arginase 1 exerts crucial roles in myeloid-derived suppressor cells, indicating its potential targeting by cancer immunotherapy. In this review, we introduce arginine metabolism and its impacts on PDAC cells. Also, we discuss the role of arginine metabolism in arginine deprivation therapy and immunotherapy for cancer.

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简介：在细胞的增长和内长的脉管的endothelial生长因素(VEGF)上调查melatonin的效果的目的在胰腺的癌房间(PANC-1)的表示。方法PANC-1房间为这研究是有教养的。在文化媒介的分泌VEGF集中用ELISA方法被决定，在肿瘤房间的VEGF生产被immunocytochemistry，和VEGFmRNA表示检测被RT-PCR决定。更高结果melatonin集中显著地禁止了细胞的增长，与展出最高禁止的效果的1mmol/L集中(P<0.01)。在房间文化上层清液和intra小房的VEGF集中都显著地在melatonin(1mmol/L)以后被减少孵化(P<0.05)。VEGFmRNA表示在观察时期期间以一种时间依赖者方式显著地减少了(P<0.05)。结论高melatonin集中显著地禁止了胰腺的癌房间的增长。内长的VEGF表示被melatonin孵化也压制。

简介：AIMTocompareKAI1incancerofpapillaofVaterandpancreastoevaluatewhethertherearedifferencesinbiologicbehaviorwhichmightaccountforprognosis.METHODSWecomparedtheexpressionin24papillayand29pancreaticcancersusingNorthernblotanalysis,immunochemicalassayandinsituhybridization,andinvestigatedwhetherearlydiagnosisormoleculardifferencespredicttheoutcomeinthesetumorentities.RESULTSByNorthernblotanalysisthereisnostatisticaldifferenceofKAI1levelsinnormalandcancerouspapilla.NoassociationbetweenKAI1mRNAexpressionandtumorstageortumordifferentiationwasfoundinthetumors.Byimmunohistochemicalassay,KAI1stainingincytoplasmofpapillarycancercellswassimilartothatofnormalpapillarycells.Byinsituhybridization,theresultsofKAI1mRNAexpressioninnormalandcancerouspapillaweresimilartothosewithimmunohistochemicalassay.Thenormalandcancerouspancreastissueswerealsoanalyzedbythemethodsusedinpapillarysamples.CONCLUSIONAlthoughthebiologicrolesofKAI1havenotbeenclarified,ourresultssuggestthatKAI1mayrestricttheprogressionofmalignantpapillarycancer,butitsexpressionmightnothaveanyeffectonthecharacteristicsofpapillarytumor,whereasbytheanalysisofKAl1gene,itsreducedexpressioniscloselyrelatedtotheprogressionandmetastasesofpancreaticcancer.

简介：Objective:Humanpancreaticcancerisoneofthemostcommonclinicalmalignancies.Theeffectofcomprehensivetreatmentbasedonsurgeryisgeneral.Theeffectsofchemotherapywerenotobviousmainlybecauseoflackoftargetingandchemoresistanceinpancreaticcancer.Thisstudyaimedtoinvestigatetheeffectsoffolatereceptor(FR)-mediatedgemcitabineFA-Chi-Gemnanoparticleswithacore-shellstructurebyelectrostaticsprayonpancreaticcancer.Methods:Inthisstudy,thelevelsofexpressionofFRinsixhumanpancreaticcancercelllineswerestudiedbyimmunohistochemicalanalysis.Theuptakerateofisothiocyanate-labeledFA-ChinanoparticlesinFRhighexpressioncelllineCOLO357wasassessedbyfluorescencemicroscopeandtheinhibitionrateofFAChi-GemnanoparticlesonCOLO357cellswasevaluatedbyMTTassay.Moreover,thebiodistributionofPEG-FA-ICGDER02-Chiintheorthotopicpancreatictumormodelwasobservedusingnear-infraredimagingandthehumanpancreaticcancerorthotopicxenograftsweretreatedwithdifferentnanoparticlesandnormalsalinecontrol.Results:TheexpressionofFRinCOLO357wasthehighestamongthesixpancreaticcancercelllines.TheFRmainlydistributedoncellmembraneandfewerinthecytoplasminpancreaticcancer.Moreover,theabsorptionrateoftheFA-Chi-GemnanoparticleswasmorethantheChinanoparticleswithoutFAmodified.TheproliferationofCOLO357wassignificantlyinhibitedbyFA-Chi-Gemnanoparticles.ThePEG-FAICGDER02-Chinanoparticleswereenrichedintumortissueinhumanpancreaticcancerxenografts,whilenon-targetednanoparticlesweremainlyinnormallivertissue.PEG-FA-Gem-Chisignificantlyinhibitedthegrowthofhumanpancreaticcancerxenografts(PEG-FA-Gem-Chivs.Gem,t=22.950,P=0.000).Conclusions:PEG-FA-FITC-ChinanoparticlesmightbeaneffectivetargeteddrugfortreatinghumanFR-positivepancreaticcancer.

简介：AbstractObjectives:To establish Nomogram to predict the overall survival (OS) rate of pancreatic cancer patients with lung metastasis by utilizing the database of the Surveillance, Epidemiology, and End Results (SEER) Program.Methods:We obtained the data of 363 pancreatic cancer patients with lung metastasis who were diagnosed between 2010 and 2016 from the SEER database. These patients were randomly divided into training (n=255) and validation (n=108) cohorts. The Cox proportional hazards regression model was performed to evaluate the prognostic effects of multiple clinicopathologic factors on OS. Significant prognostic factors were combined to build Nomogram. The predictive performance of Nomogram was evaluated via internal (training cohort data) and external validation (validation cohort data) by calculating index of concordance (C-index) and plotting area under curve (AUC) and calibration curves. All data from SEER database have been fully de-identified and may be used without further independent ethics committee approval.Results:In the training cohort, the results of Cox proportional hazards regression model showed that, tumor location, surgery, chemotherapy and other organ of metastasis were significantly associated with the survival prognosis (P <.05). These factors were used to establish Nomogram. The Nomogram showed good accuracy in predicting OS rate, with C-index of 0.727 [95%CI was (0.689, 0.764)] in internal validation and C-index of 0.738 [95%CI was (0.679, 0.796)] in external validation. All calibration curves showed excellent consistency between prediction by Nomogram and actual observation.Conclusion:Novel Nomogram for pancreatic cancer patients with lung metastasis was established to predict OS in our study. It has good prognostic significance. And it could provide the clinicians with more accurate and practical predictive tools which can quickly and accurately assess the patients’ survival prognosis individually, and make clinical suggestion for doctors in the follow-up treatment of patients.

简介：Gastrointestinaltoxicities(GIT),includingoralmucositis,nauseaandvomiting,anddiarrhea,arecommonsideeffectsofchemotherapyandtargetedagentsinpatientswithadvancedcolorectalcancerandpancreaticcancer.Beingoftenunderreported,itisstilldifficulttopreciselyestablishtheirburdenintermsofbothpatient’squalityoflifeandcancercarecosts.Moreover,withtheuseofmoreintensiveupfrontcombinationregimens,thefrequencyofthesetoxicitiesisrapidlygrowingwithapotentialnegativeeffectalsoonpatient’soutcome,asaresultofdosereductions,delaysorevendiscontinuationofactivetreatments.Thus,identifyingpatientsathigherriskofdevelopingGITaswellasanoptimalmanagementareparamountinordertoimprovepatient’scomplianceandoutcome.Afterthedescriptionofthemaintreatment-inducedGIT,wediscussthecurrentknowledgeonthepathophysiologyofthesesideeffectsandcommentthescalescommonlyusedtoassessandgradethem.WethenprovideacriticalupdateonGITincidencebasedontheresultsofkeyrandomizedtrialsconductedinpatientswithmetastaticcolorectalcancerandadvancedpancreaticcancer.

简介：Objective:Earlymetastasisisamajorbiologicalfeatureofpancreaticcancer.ThecurrentstudyexaminedwhethersilencingSlc38a1,ageneinvolvedinenergymetabolism,usingshorthairpinRNA(shRNA)couldinhibitthegrowth,migration,andinvasivenessofpancreaticcancercells.Methods:AseriesofSlc38a1shRNAsweredesignedandclonedintothepGPU6/GFP/Neovectors.AnshRNAwiththemostefficaciousinhibitoryactiononSCL38A1expression(65%inhibition)uponscreeninginDH5αbacteriawasusedtotransfectSW1990humanpancreaticcancercells.Cellgrowth,migration,andinvasivenesswereexaminedusingcellcountingkit-8,BoydenchamberwithoutandwithMatrigel,respectively.Results:TransfectionofSW1990cellswiththeSLCs38A1shRNAsignificantlydecreasedtheproliferation(P<0.0001)andmigratorypotential(by46.7%,P=0.0399)ofthecancercells.Invasiveness,however,wasnotaffected.Conclusions:InhibitingSlc38a1usingshRNAtechnologycoulddecreasethegrowthandmigrationofrepresentativepancreaticcancercells.However,thefactthatinvasivenesswasnotaffectedsuggestedthatSLC38A1isunlikelytoberesponsibleforearlymetastasis.

简介：AbstractObjective:Pancreatic cancer (PC) is a highly lethal malignancy with an immunosuppressive environment. Yet, current immune checkpoint inhibitor monotherapies have shown limited efficacy in PC, prompting the need for combination therapies. Herein, we hypothesized that combinations of Notch signaling inhibitor and anti-ligand programmed death-ligand 1 (PD-L1) antibody immunotherapy would show synergistic efficacy.Methods:The baseline expression of PD-L1 and HES1 was measured in PC cell lines, single-cell RNA-seq data of PC (GSA: CRA001160), and cBioPortal databases. In an in vitro study, MIA PaCa2 and SW1990 were used to explore the mechanism between Notch signaling and PD-L1. To study the effects in vivo, a subcutaneous tumor model was established using Pan02 cells treated with either anti-PD-L1 monoclonal antibody and/or Notch inhibitor DAPT. The study performed involving human samples was approved by the Ethics Committee of Peking Union Medical College Hospital (approval No. S-K460, approval date: April 23, 2018). Animal studies were approved by the Animal Research Ethics Committee of Peking Union Medical College Hospital (approval No. XHDW-2019-049, approval date: November 28, 2019).Results:The Notch signaling inhibitor upregulated PD-L1 expression in PC tumor cells both in vitro and in vivo. Notch effector HES1 knockdown produced PD-L1 upregulation in both MIA PaCa2 and SW1990 cells. Combined DAPT and anti-PD-L1 antibody treatment of Pan02 subcutaneous tumor model resulted in significantly reduced tumor weights compared to that with monotherapy, as well as significantly reduced Ki67 than that in the monotherapy group and control group. Flow cytometry analysis revealed significantly increased CD8+ T cell infiltration in tumors of the combination group compared with those of the monotherapy group.Conclusion:Notch signaling blockade might enhance the antitumor effect of anti-PD-L1 therapy in PC.

简介：AbstractObjective:Irreversible electroporation (IRE) is emerging as a new therapy for locally advanced pancreatic cancer (LAPC). We aimed to conduct survival and safety analyses in LAPC patients after treatment with IRE combined with chemotherapy.Methods:A total of 64 patients with LAPC who had received IRE and chemotherapy were retrospectively collected from August 2015 to March 2019 at Sun Yat-sen University Cancer Center. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier method and compared by the log-rank test. A multivariate Cox regression model was used to determine the prognostic factors of survival. The perioperative complications of IRE were also evaluated. The study was approved by the Institutional Review Board of Sun Yat-sen University Cancer Center (approval No. C2021-003).Results:The median survival of all included patients were 24.63 (95% confidence interval: 21.78-27.49) for overall survival and 13.00 (95% confidence interval: 8.81-17.19) months for progression-free survival, with 96.8%, 51.9%, 18.3%; and 52.3%, 21.5%, 7.9% as the 1-, 2-and 3-year OS and PFS rates, respectively. Tumor size [OS, hazard ratio (HR)=1.768, P= 0.048; PFS, HR= 0.304, P= 0.010], neoadjuvant chemotherapy (OS, HR= 0.338, P= 0.030; PFS, HR= 0.358, P= 0.034), carbohydrate antigen 19-9 variation after IRE (OS, HR= 19.320, P= 0.003; PFS, HR= 14.591, P= 0.021) and tumor response after neoadjuvant chemotherapy (OS, HR= 8.779, P= 0.033; PFS, HR= 5.562, P= 0.008) were predictive factors of survival in patients with LAPC after IRE. Complications were observed in 20.3% of patients. Grade B pancreatic fistula was the most common complication. The complication rates of the late treatment group (6.1%) were significantly lower than those of the first 15 patients after IRE treatment (66.7%). The median length of hospital stay of late treatment group was 8.6 days, which was also shorter than that of the early treatment group (10.0 days).Conclusions:IRE combined with chemotherapy could improve survival of LAPC patients with acceptable complication rates. Therefore, it may be a suitable method for LAPC but should be validated in prospective randomized trials.

简介：AbstractObjective:In 2015, the Chinese Pancreatic Association of the Chinese Society of Surgery of the Chinese Medical Association launched a national multicenter online system for registration of surgical treatment of pancreatic cancer in China, called China Pancreas Data Center (CPDC). With continued effort, the CPDC has developed over time. Herein, we report the general results of the CPDC from January 2016 to January 2020 to present the real-world situation of surgical treatment of pancreatic cancer in China.Methods:The data of the CPDC from January 2016 to January 2020 were retrieved and analyzed in this real-world study, including the data on patient demographics, comorbidities, diagnostic modalities, neoadjuvant treatment, surgical procedures, postoperative complications and treatment, pathological examinations, postoperative adjuvant treatment, survival, and risk factors.Results:A total of 13,595 cases from 70 centers in 28 provinces were retrieved for analysis. This study reported the largest cohort of patients who underwent surgical treatment for pancreatic cancer in China to date. More cases were derived from the Eastern regions, among which Shanghai, Beijing, and Zhejiang ranked in the top three. The peak age of the patients ranged from 60 to 69 years. The ratio of males to females was 1.5:1. Overall, 64.3% of the tumors were located in the head and neck of the pancreas, and 35.7% in the body and tail of the pancreas. Of the patients, 23.0% underwent positron-emission tomography-computed tomography, 21.6% underwent endoscopic ultrasound, and 4.8% underwent preoperative biopsy. Two percent of the patients underwent neoadjuvant treatment, while 68.9% underwent R0 surgical resection (margin free of tumor cells). Of the latter, 78.6% of the operations were open procedures, 12.6% were laparoscopic procedures, 2.9% were robotic procedures, and 3.7% were converted to open procedures. The in-hospital mortality rate after surgery was 0.4%. The incidence of grade 2 and grade 3 postoperative pancreatic fistulas was 25.5% and 2.5%, respectively. The incidence of complications based on the Clavien-Dindo classification was 17.9% of grade II, 4.3% of grade IIIa, 1% of grade IIIb, and 0.6% of grade IV. Of the patients, 28.9% underwent postoperative adjuvant chemotherapy. The 1-year, 2-year, and 3-year overall survival of these patients were 77%, 51%, and 38%, respectively. In the 8542 patients who underwent R0 resection, the 1-year, 2-year, and 3-year overall survival and disease-free survival were 77% , 54%, and 43%, and 68%, 49%, and 41%, respectively. The factors related to the prognosis of these patients were also identified after uni-and multi-variate analyses.Conclusion:The surgical quality, safety, and long-term survival of the patients in CPDC are similar to those of international high-volume pancreatic centers. However, neoadjuvant and postoperative adjuvant chemotherapy should be improved.

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.