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pancreatic adenocarcinoma: A review of recent paradigms and advances in epidemiology, clinical diagnosis and management

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World Journal of Gastroenterology 2021年第23期27卷 3158-3181页

作者： Nikhil Gupta Raghav Yelamanchi Department of Surgery Atal Bihari Vajpayee Institute of Medical Sciences and Dr.Ram Manohar Lohia HospitalDelhi 110001India

pancreatic cancer is one of the dreaded malignancies for both the patient and the *** five-year survival rate of pancreatic adenocarcinoma(PDA)is as low as 2%despite multimodality treatment even in the best *** per the Global Cancer Observatory of the International Agency for Research in Cancer estimates of pancreatic cancer,by 2040,a 61.7%increase is expected in the total number of cases *** the widespread availability of next-generation sequencing,the entire genome of the tumors is being sequenced regularly,providing insight into their *** invasive PDA arises from pancreatic intraepithelial neoplasia and mucinous neoplasm and intraductal papillary neoplasm,screening for them can be beneficial as the disease is curable with resection at an early *** preoperative biliary drainage has no role in patients suffering from PDA with obstructive *** performed,metallic stents are preferred over plastic *** invasive procedures are preferred to open procedures as they have less *** duct-to-mucosa technique for pancreaticojejunostomy is presently widely *** role of intraperitoneal drains after surgery for PDA is *** chemoradiotherapy has been proven to have a significant role both in locally advanced as well as in resectable *** new regimens and drugs have been added in the arsenal of chemoradiotherapy for metastatic *** roles of immunotherapy and gene therapy in PDA are being *** review article is intended to improve the understanding of the readers with respect to the latest updates of PDA,which may help to trigger new research ideas and make better management decisions.

关键词： pancreatic adenocarcinoma pancreatic cancer Chemotherapy Chemoradiotherapy pancreaticoduodenectomy Distal pancreatectomy

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pancreatic adenocarcinoma:Beyond first line,where are we?

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World Journal of Gastroenterology 2021年第17期27卷 1847-1863页

作者： Sara Cherri Silvia Noventa Alberto Zaniboni Department of Oncology Fondazione PoliambulanzaBrescia 25124Italy

pancreatic cancer is considered one of the most aggressive cancers,with an increasing incidence in recent *** date,chemotherapy is still the standard of care for advanced metastatic disease,unfortunately providing only a slight advantage in terms of *** molecular and cellular characteristics of pancreatic cancer cells,as well as the cells that characterize the pancreatic tumour microenvironment,are the basis of the mechanisms of resistance to *** progression during first-line treatment,few patients are eligible for secondline treatment due to the loss of performance *** date,a clear survival advantage has not yet been demonstrated for second-line *** medicine could be the key to increasing responses to cancer treatment and finally impacting survival in this difficult-to-treat *** this review,we analyze current recommendations in the second-line setting and potential future prospects.

关键词： pancreatic adenocarcinoma Second-line Chemotherapy Targeted therapy Immunotherapy

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KLF16 promotes pancreatic adenocarcinoma cell proliferation and migration by positively regulating SMAD6

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World Journal of Gastrointestinal Oncology 2022年第11期14卷 2157-2169页

作者： Wei Mi Zhi Zheng Jiong-Di Lu Shu-Quan Duan Jie Zhang Hai-Qiao Zhang Yi-Xuan Ding Jie Yin Feng Cao Jun Zhang Fei Li Department of General Surgery Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of General Surgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Digestive Minimally Invasive Surgery The Second Affiliated Hospital of Baotou Medical CollegeBaotou 014030Inner Mongolia Autonomous RegionChina Department of Radiology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China

BACKGROUND pancreatic adenocarcinoma(PAAD)is a cancerous tumor with an extremely poor 5-year survival *** exploration of biomarkers for the diagnosis and treatment of PAAD is crucial in clinical ***üppel-like factors(KLFs)are involved in a variety of biological functions in *** to multiple studies,KLF16 behave as an oncogene in prostate,breast and gastric ***,no research has been done on the significance of KLF16 in *** To explore the molecular mechanisms of KLF16 in *** KLF16 was identified in the tumor specimens and normal tissues by GEPIA database and verified by quantitative real-time PCR(qRT-PCR).Knockdown or exogenous expression of KLF16,combined with in vitro and in vivo assays,was performed to show the functional significance of *** molecular mechanism of KLF16 was demonstrated by qRT-PCR,western blotting,immunoprecipitation assay and flow *** We showed that KLF16 was highly expressed in PAAD patients based on the GEPIA ***16 silencing suppressed while KLF16 overexpression promoted the malignant function of PAAD *** on RNA sequencing,we discovered that KLF16 potentiated the expression of SMAD6 in PAAD ***6 transcript abundance was increased and positively correlated with KLF16 expression in PAAD *** addition,inhibiting SMAD6 was able to mitigate the effects of KLF16 overexpression on PAAD cell processes,suggesting the importance of SMAD6 in the development of KLF16-triggered *** KLF16/SMAD6 axis might be explored as a therapeutic target for PAAD therapy.

关键词： KLF16 pancreatic adenocarcinoma SMAD6 Tumorigenesis Therapeutic target

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Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma

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Cancer Biology & Medicine 2022年第7期19卷 1029-1046页

作者： Duo Zuo Yongzi Chen Xinwei Zhang Zhuozhi Wang Wenna Jiang Fan Tang Runfen Cheng Yi Sun Lu Sun Li Ren Rui Liu Department of Clinical Laboratory Department of Tumor Cell Biology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China School of Biomedical Engineering Tianjin Medical UniversityTianjin 300070China Department of Pathology Tianjin Huanhu HospitalTianjin 300350China Department of Pathology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China School of Pharmacy Tianjin Medical UniversityTianjin 300070China Department of Gastrointestinal Medical Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Objective:The main reasons for the poor prognoses of pancreatic adenocarcinoma(PA)patients are rapid early-stage progression,advanced stage metastasis,and chemotherapy *** of novel diagnostic and prognostic biomarkers of PA is therefore urgently ***:Three mRNA microarray datasets were obtained from the Gene Expression Omnibus database to select differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for hub genes were performed using *** between expression levels of hub genes and cancer-infiltrating immune cells were investigated by *** proportional hazard regression analyses were also *** hub genes were screened using the HPA platform and verified for diagnostic value using ***:We identified 59 hub genes among 752 *** analysis indicated that these 59 hub genes were mainly involved in the defense response to viruses and the type I interferon signaling *** also discovered that RSAD2 and SMC4 were associated with immune cell infiltration in the PA ***,DLGAP5 mRNA might be used as an independent risk factor for the prognoses of PA ***,the protein encoded by ISG15,which exists in peripheral blood,was validated as a potential diagnostic biomarker that distinguished PA patients from healthy controls(area under the curve:0.902,95%confidence interval:0.819–0.961).Conclusions:Our study suggested that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment,while DLGAP5 mRNA expression might be an independent risk factor for the survival prognoses of PA ***,ELISAs indicated that serum ISG15 could be a potential novel diagnostic biomarker for PA.

关键词： RSAD2 SMC4 DLGAP5 ISG15 pancreatic adenocarcinoma

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Stereotactic body radiotherapy in pancreatic adenocarcinoma

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Hepatobiliary & pancreatic Diseases International 2024年第1期23卷 14-19页

作者： Carolina de la Pinta Radiation Oncology Department Ramón y Cajal University HospitalIRYCISAlcaláUniversity28034 MadridSpain

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding *** review aimed at the SBRT application in the treatment of pancreatic *** sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December *** used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were *** articles were assessed for validity and relevant ***:Optimal doses and fractionation have not yet been ***,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to ***,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic ***:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease *** opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

关键词： Chemoradiotherapy pancreatic adenocarcinoma Radiotherapy Stereotactic body radiotherapy Stereotactic ablative radiotherapy

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pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1554-1567页

作者： Yau-tuen Chan Hor-yue Tan Yuanjun Lu Cheng Zhang Chien-shan Cheng Junyu Wu Ning Wang Yibin Feng School of Chinese Medicine the University of Hong KongHong KongChina Centre for Chinese Herbal Medicine Drug Development School of Chinese MedicineHong Kong Baptist UniversityHong KongChina Department of Traditional Chinese Medicine Shanghai Jiaotong UniversitySchool of Medicine Affiliated Ruijin HospitalShanghai 200025China

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma(PAAD)*** regulation could improve *** is an endogenous hormone that delivers multiple *** we showed that pancreatic melatonin level is associated with patients'*** PAAD mice models,melatonin supplementation suppressed tumor growth,while blockade of melatonin pathway exacerbated tumor *** anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils(TANs),and TANs depletion reversed effects of *** induced TANs infiltration and activation,therefore induced cell apoptosis of PAAD *** arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor *** of Cxcl2 in tumor cells abolished neutrophil migration and ***-induced neutrophils presented an N1-like anti-tumor phenotype,with increased neutrophil extracellular traps(NETs)causing tumor cell apoptosis through cell-to-cell *** analysis revealed that this reactive oxygen species(ROS)-mediated inhibition was fueled by fatty acid oxidation(FAO)in neutrophils,while FAO inhibitor abolished the anti-tumor *** of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil ***2,or TANs,combined with NET marker,can better predict patients'***,we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

关键词： pancreatic adenocarcinoma Melatonin Anti-tumor immunity Tumor-associated neutrophils Tumor microenvironment CXCL2 Neutrophil extracellular traps NETosis

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Artificial intelligence for early detection of pancreatic adenocarcinoma: The future is promising

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World Journal of Gastroenterology 2021年第13期27卷 1283-1295页

作者： Antonio Mendoza Ladd David L Diehl Department of Internal Medicine Division of GastroenterologyTexas Tech University Health Sciences Center El PasoEl PasoTX 79905United States Department of Gastroenterology and Nutrition Geisinger Medical CenterDanvillePA 17822United States

pancreatic ductal adenocarcinoma(PDAC) is a worldwide public health concern. Despite extensive research efforts toward improving diagnosis and treatment, the 5-year survival rate at best is approximately 15%. This dismal figure can be attributed to a variety of factors including lack of adequate screening methods, late symptom onset, and treatment resistance. pancreatic ductal adenocarcinoma remains a grim diagnosis with a high mortality rate and a significant psychological burden for patients and their families. In recent years artificial intelligence(AI) has permeated the medical field at an accelerated pace, bringing potential new tools that carry the promise of improving diagnosis and treatment of a variety of diseases. In this review we will summarize the landscape of AI in diagnosis and treatment of PDAC.

关键词： pancreatic adenocarcinoma Artificial intelligence Neural network Future perspectives Early diagnosis Improved performance

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Endoscopic ultrasound-guided fine-needle aspiration pancreatic adenocarcinoma samples yield adequate DNA for next-generation sequencing:A cohort analysis

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World Journal of Gastroenterology 2023年第18期29卷 2864-2874页

作者： Stefania Bunduc Bianca Varzaru Razvan Andrei Iacob Andrei Sorop Ioana Manea Andreea Spiridon Raluca Chelaru Adina Emilia Croitoru Gabriel Becheanu Mona Dumbrava Simona Dima Irinel Popescu Cristian Gheorghe Faculty of Medicine Carol Davila University of Medicine and PharmacyBucharest 020021Romania Digestive Diseases and Liver Transplantation Center Fundeni Clinical InstituteBucharest 022328Romania Center of Excellence in Translational Medicine Fundeni Clinical InstituteBucharest 022328Romania

BACKGROUND Genetic tests are increasingly performed for the management of unresectable pancreatic *** genotyping aimed samples current guidelines recommend using core specimens,although based on moderate quality ***,in clinical practice among the endoscopic ultrasound(EUS) guided tissue acquisition methods,fine needle aspiration(FNA) is the most widely *** To assess the adequacy for next generation sequencing(NGS) of the DNA yielded from EUS-FNA pancreatic adenocarcinoma(PDAC) *** Between November 2018 and December 2021,105 patients with PDAC confirmed by EUS-FNA were included in the study at our tertiary gastroenterology *** 22 gauge(G) or 19G FNA needles were *** pass was dedicated to DNA *** concentration and purity(A260/280,A260/230) were assessed by *** assessed the differences in DNA parameters according to needle size and tumor characteristics(size,location) and the adequacy of the extracted DNA for NGS(defined as A260/280 ≥ 1.7,and DNA yield:≥ 10 ng for amplicon based NGS,≥ 50 ng for whole exome sequencing [WES],≥ 100 ng for whole genome sequencing [WGS]) by analysis of variance and ttest ***,we compared DNA purity parameters across the different DNA yield *** Our cohort included 49% male patients,aged 67.02 ± 8.38 *** 22G needle was used in 71%of the *** DNA parameters across our samples varied as follows:DNA yield:1289 ng(inter quartile range:534.75-3101),A260/280 = 1.85(1.79-1.86),A260/230 = 2.2(1.72-2.36).DNA yield was > 10 ng in all samples and > 100 ng in 93% of them(one sample < 50 ng).There were no significant differences in the concentration and A260/280 between samples by needle *** size was the only independent predictor of A260/230 which was higher in the 22G samples(P =0.038).NGS adequacy rate was 90% for 19G samples regardless of NGS type,and for 22G samples it reached 89% for WGS adequacy and 91% for WES and

关键词： pancreatic adenocarcinoma Endoscopic ultrasound guided fine needle aspiration Next generation sequencing DNA yield Needle size Genetic testing

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Computed tomography perfusion imaging evaluation of angiogenesis in patients with pancreatic adenocarcinoma

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World Journal of Clinical Cases 2022年第8期10卷 2393-2403页

作者： Wen Liu Bo Yin Zong-Hui Liang Yang Yu Na Lu Department of Radiology Jinshan HospitalFudan UniversityShanghai 201508China Department of Radiology Huashan HospitalFudan UniversityShanghai 200000China Department of Radiology Huashan Hospital NorthFudan UniversityShanghai 200000China Department of Radiology Shanghai Jing’an District Central HospitalHuashan Hospital Jing’an BranchFudan UniversityShanghai 200000China

BACKGROUND pancreatic adenocarcinoma is one of the most common malignant tumors of the digestive *** than 80%of patients with pancreatic adenocarcinoma are not diagnosed until late stage and have distant or local *** To investigate the value of computed tomography(CT)perfusion imaging in the evaluation of angiogenesis in pancreatic adenocarcinoma *** This is a retrospective cohort *** with pancreatic adenocarcinoma and volunteers without pancreatic diseases underwent CT perfusion imaging from December 2014 to August 2017 in Huashan Hospital,Fudan University Shanghai,*** A total number of 35 pancreatic adenocarcinoma patients and 33 volunteers were *** relative blood flow(r BF),and relative blood volume(r BV)were significantly lower in patients with pancreatic adenocarcinoma than in the control group(Ppancreatic adenocarcinoma was significantly higher than that in controls(Ppancreatic adenocarcinoma than in gradeⅠ-Ⅱpancreatic adenocarcinoma(Ppancreatic adenocarcinoma than in gradeⅠ-Ⅱpancreatic adenocarcinoma(Ppancreatic adenocarcinoma.

关键词： pancreatic adenocarcinoma Perfusion computed tomography Angiogenesis Evaluation Imaging Quantitative assessment

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Current controversies and advances in the management of pancreatic adenocarcinoma

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World Journal of Gastrointestinal Oncology 2021年第6期13卷 472-494页

作者： Muhammad Shehroz Zeeshan Zeeshan Ramzan Gastrointestinal Section Department of MedicineTexas Health Harris Methodist HospitalFort WorthTX 76104United States

pancreatic adenocarcinoma is a lethal disease with a mortality rate that has not significantly improved over *** is likely due to several challenges unique to pancreatic *** patients with pancreatic cancer are diagnosed at a late stage of disease due to the lack of specific symptoms prompting an early investigation.A small subset of patients who are diagnosed at an early stage have a better chance at survival with curative surgical resection,but most patients still succumb to the disease in a few *** dismal overall prognosis is due to suspected micro-metastasis at an early *** to this reason,there is a recent interest in treating all patients with pancreatic cancers with systemic therapy upfront(including the ones that are surgically resectable).This approach is still not the standard of care due to the lack of robust prospective data *** advancements in treatment regimens of chemotherapy,radiation and immunotherapy have improved the overall short-term survival but the long-term survival still remains *** approaches in diagnosis and treatment have shown promise in clinical studies but long-term clinical data is *** following manuscript presents an overview of the epidemiology,diagnosis,staging,recent advances,novel approaches and controversies in the management of pancreatic adenocarcinoma.

关键词： pancreatic adenocarcinoma Advances in management Imaging Novel approaches Chemotherapy Controversies

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