简介：AbstractThere has been a rising trend in the incidence and prevalence of non-functioning pancreatic neuroendocrine tumors (NFPanNETs). While a significant number of the newly diagnosed NFPanNETs are asymptomatic, a majority of patients will present with liver metastasis (LM) at the time of diagnosis. Surgical resection remains the only curative treatment, especially for localized NFPanNETs. While a majority of small NFPanNETs are indolent, some are not. This heterogeneity in tumor biology presents the surgeon with the unique challenge of determining which patient will benefit from surgery, given the morbidity of pancreatic surgery. There has been a recent push for a more aggressive approach to the care of these patients, given the emergence of data supporting such measures. However, the risk of over or under treatment has generated immense debate amongst experts in the field. The heterogeneity of current practice guidelines and institutional practices around the world is a reflection of the disparate opinion on the management of NFPanNET. In this review, we set out to examine the evidence regarding some of the most controversial and challenging aspects of the surgical treatment of NFPanNET. We evaluate the following questions; should patients with small NFPanNETs ≤ 2 cm in size be resected; should patients with metastatic NFPanNETs undergo surgical debulking, and should there be resection of the primary tumor in the setting of non-resectable metastatic disease?Although there are currently no Level 1 data to answer these questions conclusively, we believe that the current literature supports a more aggressive approach to the management of NFPanNET.

简介：AbstractPancreatic neuroendocrine tumors (PNETs) are a rare group of neoplasms originating from the endocrine pancreas. PNETs are classified as functional or non-functional tumors. PNETs are more often diagnosed at a higher stage with distant metastases or advanced locoregional disease. The majority of individuals with hepatic metastases will ultimately die of liver failure; therefore, the treatment of liver tumor burden is critical to providing a survival impact. While surgical resection remains the only chance of cure for disease confined to the pancreas or for locoregional disease, the treatment of advanced or metastatic PNETs is more complex and often requires a multimodal approach. This review focuses on treatment options for well and moderately differentiated PNETs with metastatic disease to the liver. These include surgery, liver-directed therapies including ablative and intra-arterial therapies, and systemic therapies such as somatostatin analogues, targeted therapies, chemotherapy, and peptide receptor radionuclide therapy. Developing an individualized treatment strategy requires careful assessment of liver tumor burden and predicted biological behavior. Aggressive surgical resection of hepatic metastases secondary to PNET primary tumors is associated with improved survival in multiple retrospective studies. General goals of treatment for metastatic disease include prolonging overall survival and progression free survival, improving quality of life, and control of symptoms.

简介：AbstractPancreatic neuroendocrine tumors (pNET) are heterogenous tumors originated from the diffuse neuroendocrine cells of pancreas, which show the function of synthesis, storage and secretion of peptide hormones and biomimetic amines. Biomarkers play a crucial role in the diagnosing, evaluating prognosis and predicting treatment response for pNET patients. Traditional NET markers such as chromogranin A and Neuron Specific Enolase, as a diagnostic biomarker, have relatively low sensitivity and specificity in pNET patients. The emergence of new types of biomarkers provides more reliable indicators for diagnosis and prognosis evaluation. Among them, NETest score is a promising biomarker with the highest diagnostic sensitivity (80%) and specificity (94%). In addition, this molecule can be also used as a prognostic biomarker, which can predict disease progression and shorter overall survival. Biomarkers related to therapeutic targets, such as vascular endothelial growth factor, vascular endothelial growth factor receptor, and key molecules of mTOR signaling pathway, have capability to predict response of treatment. With the development of next-generation sequencing, chip array, and digital droplet PCR, novel biomarkers such as circulating tumor cells, tumor-derived exosomes, and circulating tumor DNA and mRNA are expected to provide more accurate diagnosis, prognostic information, and prospective therapeutic targets. In this paper, biomarkers of pancreatic neuroendocrine tumor and their role in diagnosis, prognosis, diagnosis, treatment and monitoring are systematically introduced. Our conclusions can provide new basis for clinicians in the diagnosis and treatment process.

简介：AbstractPancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

简介：A64-year-oldmanwasadmittedtotheSunYat-SenUniversityCancerCenterwithchiefcomplaintsofrecurrentabdominalpainanddiarrheaforabout3yearsandwithahistoryofsurgicalrepairforintestinalperforationowingtostressulcer.Positronemissiontomography(PET)/computedtomography(CT)demonstratedaprimarytumoronthepancreatictailwithmultifocallivermetastases.Pathologicalandimmunohistochemistrystainingrevealedthelesiontobeapancreaticneuroendocrinetumor(pNET).AccordingtothelatestWorldHealthOrganization(WHO,2013)classification,thetumorwasclassifiedasstageIVfunctionalG1pNET.Afterreferraltothemultidisciplinarytreatmentboard(MDT),thepatientwasstartedonperiodicdoseofomeprazole,somatostatinanaloguesandInterferonα(IFNα)andhadscanningfollow-ups.Basedupontheimagingresults,CT-guidedradioactiveiodine-125(125I)seedsimplantationtherapy,radiofrequencyablationtherapy(RFA)ormicrowaveablationtechniquewerechosenforthetreatmentoftheprimarytumor.Transarterialchemoembolization(TACE),RFAandmicrowaveablationtechniquesweredecideduponforlivermetastases.Thepatientshowedbeneficialresponsetothetreatmentwithclinicallymanageablelow-gradesideeffectsandattainedpartialremission(RECISTcriteria)withagoodqualityoflife.

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简介：由于市场的快速的变化和比赛的压力，生产公司被强迫改编他们的生产方法支持顾客需要的差异和新产品开发的增加。因为生物有机体相当能够适应环境变化和刺激，启发简历的概念被认出了对适应生产合适系统控制。因此，这份报纸建议启发NeuroEndocrine的生产系统(NEIMS)的一个新奇概念。建议NEIMS控制体系结构与neuro控制和荷尔蒙规定原则基于类比。它有能力明确地包括控制点，材料，信息流动路径和逻辑操作指定生产控制计划，并且活泼地在商店地板水平处理意外骚乱的经常的出现。从控制论观点，NEIMS的控制模型由于外部环境在产品要求显示适应行为到变化并且作为内部环境生产房间失灵。最后，一个原型系统被设置了启用NEIMS模拟。

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.

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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：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：这个领域里的快速的发展在过去的十年眼用光技术为癌症诊断表明一个潜力。这评论加亮使用光技术的原则和优点，并且在临床的使用在肿瘤诊断和他们的限制集中于他们的申请。这些光技术是快速的方法，它能从常规方法提供很多不同信息，当时，它仍然要求临床的试用学习为临床的癌症开发并且保证这些光技术的适用性诊断。

简介：Gradingprocedureinroutineseacucumberhatcheryproductionisthoughttoaffectjuvenileseacucumberimmunologicalresponse.Thepresentstudyinvestigatedtheimpactofa3-minmechanicalperturbationmimickingthegradingprocedureonneuroendocrineandimmuneparametersoftheseacucumberApostichopusjaponicus.Duringtheapplicationofstress,concentrationsofnoradrenalineanddopamineincoelomicfluidincreasedsignificantly,indicatingthatthemechanicalperturbationresultedinatransientstateofstressinseacucumbers.Coelomocytesconcentrationincoelomicfluidincreasedtransientlyafterthebeginningofstressing,andreachedthemaximumin1h.Whereas,coelomocytesphagocytosisat3min,superoxideanionproductionfrom3minto0.5h,acidphosphataseactivityat0.5h,andphenoloxidaseactivityfrom3minto0.5hwereallsignificantlydown-regulated.Alloftheimmuneparametersrecoveredtobaselinelevelsaftertheexperimentwasconductedfor8h,andanimmunostimulationoccurredafterthestressconsideringthephagocytosisandacidphosphataseactivity.Theresultssuggestedthat,asinothermarineinvertebrates,neuroendocrine/immuneconnectionsexistinseacucumberA.japonicus.Mechanicalstresscanelicitaprofoundinfluenceonseacucumberneuroendocrinesystem.Neuroendocrinemessengersactinturntomodulatetheimmunityfunctions.Therefore,theseeffectsshouldbeconsideredfordevelopingbetterhusbandryprocedures.

简介：Neuroendocrinetumors(NET)areaheterogeneousgroupofcancers,withindolentbehavior.Themostcommonprimaryoriginisthegastro-intestinaltractbutcanalsoappearinthelungs,kidneys,adrenals,ovariesandotherorgans.Ingeneral,NETisusuallydiscoveredinthemetastaticphase(40%-80%).Theliveristhemostcommonorganinvolvedwhenmetastasesoccur(40%-93%),followedbybone(12%-20%)andlung(8%-10%).Anumberofdifferenttherapeuticoptionsareavailableforthetreatmentofhepaticmetastasesincludingsurgicalresection,transplantation,ablation,trans-arterialchemoembolization,chemotherapyandsomatostatinanalogues.Recently,moleculartargetedtherapieshavebeenused,usuallyincombinationwithothertreatmentoptions,toimproveoutcomesinpatientswithmetastases.ThisarticleemphasizesontheroleofsurgeryinthetreatmentoflivermetastasesfromNET.

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：AbstractImportance:The diversity of pediatric genitourinary malignancies requires a timely resource detailing tumor characteristics and survival.Objective:To determine the incidence, demographics, and outcomes of all pediatric genitourinary tumors within the United States.Methods:A population-based search for patients diagnosed with genitourinary cancers under age 15 was performed using the National Cancer Institute’s Surveillance, Epidemiology, and End Results 18 registry. Information on primary tumor location, histologic type, patient age, sex, year of diagnosis, race, treatment, cause of death, and survival months was extracted. Descriptive epidemiological and survival statistics were calculated for all variables.Results:A total of 4576 cases from 1973 through 2015 were identified. The most common primary tumor sites were the kidney (80.3%), testis (12.3%), bladder (2.8%), and vagina (1.5%). Nephroblastoma (87.9%) and sarcoma (3.4%) were the most common renal malignancies. Rhabdomyosarcoma was common in the vagina, bladder, and testis at rates of 66.2%, 61.2%, and 24.6%, respectively. Germ cell tumors (71.0%) were the most common primary tumor of the testis. Ten-year overall survival (OS) for renal nephroblastoma and sarcoma was 88% and 82%, respectively. Ten-year OS for RMS of the testis was 91%, the bladder was 79%, the vagina was 79%, and the prostate was 56%. Germ cell tumor 10-year OS were 96% in the testis and 100% in the vagina.Interpretation:A better understanding of the overall distribution and outcomes associated with pediatric genitourinary cancers allows physicians to best understand the patient’s disease in the context of current frequency in a genitourinary setting and reported outcomes.

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简介：背景：测试的HIV-1genotypic和phenotypic危险性(通用终端)优化antiretroviral选择，但是它幸存上的效果是未知的。客观：评估在通用终端和幸存之间的协会。设计：队学习。设定：10个美国HIV诊所。病人：为通过2005从1999看见的通用终端(血浆HIVRNA水平>1000copies/mL)合格的2699个感染HIV的病人。大小：人口统计的特征，临床的因素，通用终端使用，所有原因死亡，和为有幸存的通用终端的协会的粗略、调整的危险比率(HR)。结果：病人们被跟随为一3.3年中部；(34%)915有通用终端。把通用终端有的病人比那些降低死亡率(2.0对2.7死亡每100人年)。在标准考克斯模型，通用终端与改进幸存被联系(调整HR，0.69[95%CI，0.51～0.94]；P=0.017)在为临床的后续的人口统计的特征，CD4⁺房间计数，HIVRNA水平，和紧张控制以后。在亚群分析，通用终端与改进幸存被联系因为2107高度活跃的antiretroviral治疗(HAART)经历了病人(2.2对3.2死亡每为有没有通用终端的通用终端对那些的病人的100人年；调整HR，0.60[CI，0.43～0.82]；P=0.002)并且为921个三倍的antiretroviral班富有经验病人(2.1对3.1死亡每100人年；调整HR，0.61[CI0.40到0.93]；P=0.022)。边缘的结构的模型支持了在通用终端之间的协会并且在全面的队改进了幸存(调整HR，0.54；P=0.001)并且在HAART富有经验的组(调整HR，0.56；P=0.003)。限制：通用终端的使用没被使随机化。剩余惊讶可以存在。结论：通用终端的使用独立地在HAART富有经验的病人之中与改进幸存被联系。

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