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.

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.

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：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：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：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：AbstractObjective:It remains unclear whether adjuvant chemoradiotherapy (CRT) improves survival outcome of pancreatic ductal adenocarcinoma (PDAC) patients after surgery. This study aimed to investigate the efficacy and safety of tegafur/gimeracil/oteracil (S-1)-based adjuvant concurrent chemoradiotherapy in resected PDAC patients with defined high-risk pathological features.Methods:We conducted a single-arm, prospective, and interventional study at Zhongshan Hospital Fudan University from December 2012 to December 2019 and the last follow-up was conducted in December 2021. This study was approved by the Ethics Committee of Zhongshan Hospital Fudan University on December 27, 2012 (approval No. B2012-139). Resected PDAC patients with high-risk pathological features, including positive resection margin, pathological T3-4N1-2M0 disease, peripancreatic fat invasion, microvascular invasion, and perineural invasion, were recruited. Primary endpoint was overall survival and secondary endpoints were disease-free survival, treatment toxicity, and 2-, 5-year survival rates.Results:A total of 54 patients were recruited. Mean age was 63.6 years old (±7.2). The distribution of T and N stages were 24.1% for T1, 46.3% for T2, 27.8% for T3, 1.9% for T4, 33.3% for N1, and 11.1% for N2. Seven patients had R1 resection. The median overall survival and disease-free survival were 27.1 and 13.7 months, respectively, while no fatal adverse events were recorded. Subgroup analyses showed differences in survival outcomes among patients with microvascular invasion, different N stages, and preoperative CA 19-9 levels. Further, a Cox proportional hazard model demonstrated associations of lymph node metastases, CA 19-9 level, and microvascular invasion with overall survival and disease-free survival.Conclusion:S-1 -based adjuvant CRT showed promising efficacy and manageable toxicity in resected PDAC patients with highrisk pathological features.

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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：AbstractObjective:This study conducted inverse probability of treatment weighting (IPTW) survival analysis to examine survival in pancreatic adenocarcinoma patients.Methods:In this population-based study, data from the Surveillance, Epidemiology, and End Results program of the United States were analyzed to identify patients diagnosed with adenocarcinoma of the pancreas 2004 to 2014. Differences in survival rates were examined among patients who underwent pancreatectomy alone, radiotherapy alone, and those who had pancreatectomy plus adjuvant radiotherapy. Kaplan-Meier estimates and Cox proportional hazards models with the IPTW were performed to determine the effect of different treatments on overall and cancer-specific survival. This study was approved by the Ethics Review Board of Weifang Medical University.Results:A total of 8191 patients were included, with 3409 taking pancreatectomy only, 2865 taking radiotherapy only, and 1917 taking pancreatectomy plus adjuvant radiotherapy. Patients who received surgery plus adjuvant radiotherapy had statistically a higher survival rate than those who received the other 2 treatments. Survival analysis with the IPTW for the 3 different groups showed that the difference in median overall survival time among these patient groups was significant.Conclusion:Using IPTW survival analysis, the present study shows that surgery with adjuvant radiotherapy is significantly associated with improved overall and cancer-specific survival among patients with pancreatic adenocarcinoma.

简介：客观：学习在胸方法的ductalcarcinomainsitu的作为一个预示的因素的组织学的分级的意义：根据凡·奈鈥檚分类，胸的ductalcarcinomainsitu(DCIS)的32个盒子被划分成三个组。结果：低等级(很好区分的、低等级DCIS)12个病人(37.5%)；中间的等级，9个病人(28.1%)；高等级(糟糕区分的DCIS)11个病人(34.4%)。在高等级DCIS之中，histologic子类型是粉刺(9个病人)，micropapillary(1个病人)和固体(1个病人)。在高等级DCIS的积极表示ofc-erbB-2，p53和MIB-1在中间、低的等级DCIS比那高。高等级和低等级DCIS之间的差别是重要的(P<0.05)。表示嗯在高等级，DCIS在中间、低的等级DCIS是比那低的。结论：胸ductalcarcinomainsitu的组织学的分级可以是一个好预示的因素。

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.

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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：AbstractEndoscopic drainage of pancreatic fluid collections (PFCs) with fewer complications and less trauma has gradually replaced surgery or percutaneous drainage to become the first-line treatment for PFCs. In recent years, the differential efficacy of various stent techniques to drain different types of PFCs has been controversial. This review summarizes the clinical applications of endoscopic ultrasound-guided stent placement for PFCs drainage.

简介：TherevisedAtlantaclassificationofacutepancreatitiswasadoptedbyinternationalconsensus,andisbasedonactuallocalandsystemicdeterminantsofdiseaseseverity.Thelocaldeterminantispancreaticnecrosis(sterileorinfected),andthesystemicdeterminantisorganfailure.Localcomplicationsofpancreatitiscanincludeacuteperi-pancreaticfluidcollection,acutenecroticcollection,pseudocystformation,andwalledoffnecrosis.Interventionalendoscopicultrasound(EUS)hasbeenincreasingutilizedinmanagingtheselocalcomplications.AfterperformingaPubMedsearch,theauthorsmanuallyappliedpre-definedinclusioncriteriaorafiltertoidentifypublicationsrelevanttoEUSandpancreaticcollections(PFCs).Theauthorsthenreviewedtheutility,efficacy,andrisksassociatedwithusingtherapeuticEUSandinvolvedEUSdevicesintreatingPFCs.Duetothedevelopmentandregulatoryapprovalofimprovedandnovelendoscopicdevicesspecificallydesignedfortransmuraldrainageoffluidandnecroticdebris(accessandpatencydevices),theauthorspredictcontinuingevolutioninthemanagementofPFCs.WebelievethatEUSwillbecomeanindispensablepartofproceduresusedtodiagnosePFCsandperformimage-guidedinterventions.AfterdrainingaPFC,theamountoftissuenecrosisisthemostimportantpredictorofasuccessfuloutcome.Hence,itseemslogicaltoclassifythesecollectionsbasedontheirpercentageofnecroticcomponentordebrispresentwhenviewedbyimagingmethodsorEUS.Finally,theauthorsproposeanalgorithmformanagingfluidcollectionsbasedontheirsize,location,associatedsymptoms,internalechogenicpatterns,andcontent.

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。