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Survival outcomes of conversion surgery for metastatic pancreatic ductal adenocarcinoma after neoadjuvant therapy

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Journal of pancreatology 2023年第3期6卷 110-118页

作者： Lingyu Zhu Suizhi Gao Xinqian Wu Bo Li Xiaohan Shi Xiaoyi Yin Huan Wang Meilong Shi Penghao Li Yikai Li Chaoliang Zhong Chuanqi Teng Jiawei Han Yiwei Ren Jian Wang Zhendong Fua Xinyu Liu Kailian Zheng Shiwei Guo Gang Jin department of Pancreatic Hepatobiliary Surgery Changhai HospitalNaval Medical UniversityYangpu DistrictShanghaiChina

Objective:To evaluate the survival outcomes of patients who underwent conversion surgery for metastatic pancreatic ductal adenocarcinoma(mPDAC)after neoadjuvant therapy(NAT)and to identify potential candidates that may benefit from this treat-ment ***:The role and eligibility population of conversion surgery for mPDAC remains controversial in the era of ***:A consecutive cohort of patients diagnosed with mPDAC and treated with NAT followed by conversion surgery be-tween 2019 and 2021 were confirmed from a prospective database maintained by the department of Pancreatic Hepatobiliary Surgery of Changhai *** accordance with residual metastases and technical resectability after NAT,patients were classi-fied as the complete pathological response of metastases(ypM0)resection group,residual metastases(ypM1)resection group,and exploration *** overall survival(mOS)was calculated using the Kaplan-Meier method,uni-and multivariable cox regression was performed to identify clinicopathological predictors of ***:A total of 244 patients with mPDAC were identified from the prospective database,with 19(7.8%)patients who un-derwent ypM0 resection,22(9.0%)underwent ypM1 resection,and 23(9.4%)underwent explorative *** mOS was 32.6 months for ypM0 resected patients,15.1 months for ypM1 resected patients,and 13.4 months for those who underwent explorative laparotomy(P<.001).Univariable and multivariable Cox regression analyses confirmed that ypM0 resection,normal-ization of preoperative CA19-9 levels,and continued adjuvant therapy were independent prognostic factors of conversion surgery for mPDAC after *** analyses revealed that oligometastases and continued adjuvant therapy were associated with improved prognosis in the ypM1 resection ***:In patients with mPDAC who underwent NAT followed by conversion surgery,the complete pathological response of metastases,normalization of preoperative CA19-9 levels,and c

关键词： Conversion surgery Metastatic pancreatic ductal adenocarcinoma Neoadjuvant therapy Survival

The Achilles’ Heel of Pancreatic Cancer: Targeting pancreatic cancer’s unique immunologic characteristics and metabolic dependencies in clinical trials

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Journal of pancreatology 2020年第3期3卷 121-131页

作者： Despina Siolas Christy Morrissey Paul E.Oberstein department of Medicine Perlmutter Comprehensive Cancer CenterNYU Langone HealthNew YorkNYUSA

Pancreatic ductal adenocarcinoma(PDAC)has a high mortality rate and is notoriously refractory to multiple cancer *** recent years,cancer therapy has expanded beyond traditional cytotoxic chemotherapy to targeted agents and immunotherapy which have been successfully implemented in many *** robust pre-clinical research,these novel therapies have only had a small impact on ***,there have been successes with emerging clinical data supporting a potential role for checkpoint inhibitor therapy and targeted therapy with poly(ADP-ribose)polymerase inhibitors for select subsets of PDAC *** this clinical review,we discuss recent pre-clinical evidence for targeting metabolic pathways as well as prevalent intratumoral immune subsets,and focus on clinical trials designed to test novel agents in *** challenge of translating pre-clinical findings to patients remains substantial and many clinical trials yield negative results,but collaborative efforts and renewed focus on novel clinical trials have led to optimism that we will identify additional options for PDAC patients and change outcomes for this deadly disease.

关键词： BRCA mutation Clinical trials Immunotherapy Pancreatic cancer Targeted therapy Tumor-associated macrophages

Notch signaling inhibitor and anti-PD-L1 antibody combination therapies decelerate tumor progression in pancreatic cancer

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Journal of pancreatology 2021年第2期4卷 106-114页

作者： Hongmei Dai Xiafei Hong Dan Huang Huanwen Wu Xianze Wang Hao Chen Rui Jiang Wenyan Chen Yupei Zhao Wenming Wu department of General Surgery School of MedicineTsinghua UniversityBeijingChina Medical Research Center School of MedicineTsinghua UniversityBeijingChina department of Pathology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeSchool of MedicineTsinghua UniversityBeijingChina department of Basic Medical Sciences School of MedicineTsinghua UniversityBeijingChina

Objective:Pancreatic cancer(PC)is a highly lethal malignancy with an immunosuppressive ***,current immune checkpoint inhibitor monotherapies have shown limited efficacy in PC,prompting the need for combination ***,we hypothesized that combinations of Notch signaling inhibitor and anti-ligand programmed death-ligand 1(PD-L1)antibody immunotherapy would show synergistic ***: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 *** an in vitro study,MIA PaCa2 and SW1990 were used to explore the mechanism between Notch signaling and *** 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 *** 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 ***-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 *** effector HES1 knockdown produced PD-L1 upregulation in both MIA PaCa2 and SW1990 *** 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 *** cytometry analysis revealed significantly increased CD8+T cell infiltration in tumors of the combination group compared with those of the monotherapy ***:Notch signaling blockade might enhance the antitumor effect of anti-PD-L1 therapy in PC.

关键词： DAPT Notch signaling blockade Pancreatic cancer PD-L1 immune checkpoint PD-L1 upregulation

Design and analysis of high-risk medical device clinical trials for diabetes monitoring and treatment: a review

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Journal of pancreatology 2019年第4期2卷 123-130页

作者： Zhang Bo Shankara Sravya B. Ye Shangyuan Zhang Hui department of Neurology and ICCTR Biostatistics and Research Design Center Boston Children’s HospitalHarvard Medical SchoolBoston Program in Health:Science Societyand PolicyBrandeis UniversityWaltham department of Population Medicine Harvard Pilgrim Health Care and Harvard Medical SchoolBostonMA Division of Biostatistics Department of Preventive MedicineFeinberg School of MedicineNorthwestern UniversityChicagoILUSA

Class III medical devices are those devices that support or sustain human life or prevent impairment of human health but,when used,pose high risks to the *** were 15 class III medical devices that were approved by the US Food and Drug Administration from September 1,2005 to December 31,2018 for glucose monitoring and diabetes *** this article,we reviewed the study design and statistical analysis in clinical trials that were conducted to provide evidences for safety and effectiveness of these medical *** exemplars of clinical trials for"Eversense continuous glucose monitoring system"and"t:slim X2 Insulin Pump with Basal-IQ Technology"are discussed in details.

关键词： Analysis Clinical trials Diabetes treatment Glucose monitoring Medical device Study design

Consensus on the clinical diagnosis and treatment of grade 3 pancreatic neuroendocrine tumors

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Journal of pancreatology 2024年第2期7卷 97-105页

作者： Jie Chen Wenming Wu Chunmei Bai Yihebali Chi Li Huo Liming Jiang Yuan Ji Jie Luo Jie Li Jingnan Li Wenhui Lou Chenghao Shao Lin Shen Feng Wang Yu Wang Ling Xue Jin Xu Chunhui Yuan Xianjun Yu Xiaoyu Yin Hong Zhao Xiongzeng Zhu Yupei Zhao Centre for Neuroendocrine Tumors Fudan University Shanghai Cancer CenterShanghai 200032China department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China department of Medical Oncology Peking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China department of Nuclear Medicine State Key Laboratory of Complex Severe and Rare DiseasesBeijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear MedicinePeking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China department of Diagnostic Radiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China department of Pathology Zhongshan HospitalFudan UniversityShanghai 200032China department of Pathology China-Japan Friendship HospitalBeijing 100029China department of Gastroenterological Oncology Beijing Cancer HospitalPeking University Cancer Hospital&InstituteBeijing 100142China department of Gastroenterology Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China department of Pancreatic Surgery Zhongshan HospitalFudan UniversityShanghai 200032China department of Pancreatic-Biliary Surgery Second Affiliated Hospital of Naval Medical UniversityShanghai 200003China department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer Hospital&InstituteBeijing 100142China department of Nuclear Medicine Nanjing First HospitalNanj

The World Health Organization(WHO)2017 classifications for neuroendocrine neoplasms(NENs)subdivided grade 3 pancreatic neuroendocrine neoplasms(pNENs)into G3 well-differentiated pancreatic neuroendocrine tumors(G3 pNETs)and poorly differentiated pancreatic neuroendocrine carcinomas(pNECs),according to the mitotic count,Ki-67 index,and cell *** a new category,G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical ***,the Chinese Pancreatic Surgery Association,Chinese Society of Surgery,Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

关键词： Clinical diagnosis Grade 3 Pancreatic neuroendocrine tumors Treatment

Application of interventional therapy via hepatic artery in pancreatic neuroendocrine neoplasms liver metastases

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Journal of pancreatology 2024年第2期7卷 141-144页

作者： Haikuan Liu Hang Yu Dequan Yang Wang Yao Yu Wang department of Interventional Oncology the First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

Pancreatic neuroendocrine neoplasm(PNEN)is the second most common malignant tumor of the *** has the characteristic of high metastases rate,and the liver is the most common site for *** affects prognosis and survival seriously.A number of earlier studies have shown that the interventional therapy via hepatic artery could reduce hepatic tumor burden and hormone secretion safely and rapidly,significantly improve objective response rate(ORR),and enhance the efficacy and prolong the survival time when combined with system *** interventional therapy via hepatic artery plays an important role in the treatment of PNEN liver *** therapy via hepatic artery could possibly increase ORR,prolong progression-free survival,and even overall survival for appropriate patients.

关键词： Interventional therapy Liver metastases Neuroendocrine neoplasm Pancreas

The wrath of pancreatic enzymes:a rare case of hematuria

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Journal of pancreatology 2019年第3期2卷 113-115页

作者： Twohig Patrick A. Rivington Jaclyn R. Soma David Becker Jeffery department of Medicine Case Western Reserve UniversityMetroHealth HospitalClevelandOH 44109USA

Acute pancreatitis(AP)is an inflammatory disease of the *** is one of the most common diseases of the gastrointestinal tract,with an annual incidence of 4.9 to 73.4 cases per 100,000 worldwide.[1]AP is the most common gastroenterology hospital discharge diagnosis.[1]The most common cause of AP is gallstones impacting the distal common bile-pancreatic duct(38%)and alcoholism(36%).[2]It is associated with many local complications including peripancreatic fluid collections,pseudocysts,and necrosis(Fig.1).Many of these complications occur secondary to proteolytic damage and systemic inflammatory response syndrome,which significantly increase the morbidity and mortality risk of AP.[2]We present an unusual complication of AP:the first documented case of destruction of the ureter from pancreatic enzymes.

关键词： Acute pancreatitis Case report Hematuria Ureteral damage

DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancer

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Journal of pancreatology 2020年第3期3卷 154-160页

作者： Yangchun Xie Feimei Kuang Jiao Liu Daolin Tang Rui Kang department of Oncology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410008China The Third Affiliated Hospital Guangzhou Medical UniversityGuangdong 510600China department of Surgery UT Southwestern Medical CenterDallasTX 75390USA

Ferroptosis is a oxidative damage-dependent form of regulated cell death that has become an emerging target for disease prevention and ***,we show that dual-specificity phosphatase 1(DUSP1),a phosphatase playing multiple roles in stress-signaling pathways,is a new repressor of ferroptosis in human pancreatic cancer *** classical ferroptosis activators(eg,erastin and RSL3)induce the expression of DUSP1,but not other members of DUSP,which depends on extracellular signal-regulated protein kinases 1 and 2(ERK1/2).Moreover,shRNA-mediated DUSP1 knockdown increases the anticancer activity of ferroptosis activators in pancreatic cancer cells through activating lipid peroxidation in vitro and in ***,DUSP1-mediated autophagy is responsible for lipid peroxidation-mediated ferroptotic cell ***,the DUSP1-related ferroptotic pathway may represent a potential target for therapeutic intervention in pancreatic cancer.

关键词： Dual-specificity phosphatase 1 Ferroptosis Pancreatic cancer

Correlative factor of death in patients with infected pancreatic necrosis after surgical intervention

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Journal of pancreatology 2022年第4期5卷 141-145页

作者： Yuhui Chen Zhiwei Liu Shouwang Cai department of General Surgery the First Medical CenterChinese PLA General HospitalHaidian DistrictBeijingChina department of Hepatobiliary and Pancreatic Surgery First Medical CenterChinese PLA General HospitalHaidian DistrictBeijingChina

Background:Acute pancreatitis(AP)was a potentially fatal disease with a variation in *** pancreatic necrosis was a common complication in AP which needed surgical *** present study was to study the correlative factors of death in patients with infected pancreatic necrosis after surgical ***:From January 2016 to October 2019,a total of 186 patients with infected pancreatic necrosis after surgical intervention in the First Medical Center,Chinese PLA General Hospital were retrospectively enrolled in this *** the 186 patients,22 who died in the hospital were defined as a mortality group and the others as a survival *** clinical characteristic of the 2 groups was compared and the relative risk of mortality in patients with infected pancreatic necrosis after the surgical intervention was ***:Acute fluid collection,acute kidney injury,acute lung injury,acute liver injury,multiple organ dysfunction syndromes,abdominal bleeding,abdominal Acinetobacter baumannii infection,pulmonary infection,pulmonary A baumannii infection,positive blood culture,A baumannii of blood culture,severe acute pancreatitis according to Atlanta 2012,the use of continuous renal replacement therapy,mechanical ventilation and minimally invasive retroperitoneal pancreatic necrosectomy was associated with death in *** age,longer acute kidney injury lasting time,longer acute lung injury lasting time,longer acute liver injury lasting time,and longer multiple organ dysfunction syndromes lasting time in predicting mortality in patients with infected pancreatic necrosis after surgical intervention were(0.635[95%confidence interval(CI):0.512-0.758],P=.040),(0.877[95%CI:0.788-0.965],P=.000),(0.932[95%CI:0.897-0.968],P=.000),(0.822[95%CI:0.708-0.935],P=.000),and(0.943[95%CI:0.887-0.998],P=.000).Due to the small number of death cases,the results of the multivariate analyses were not ***:In this single-center retrospectiv

关键词： Infected pancreatic necrosis Mortality Risk factors Surgical intervention