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Pancreatic cancer: Advances in treatment

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World Journal of Gastroenterology 2014年第28期20卷 9354-9360页

作者： Somala Mohammed George Van Buren Ⅱ William E Fisher the elkins pancreas center Michael E DeBakey Department of Surgeryand Dan L Duncan Cancer CenterBaylor College of Medicine

Pancreatic cancer is a leading cause of cancer mortality and the incidence of this disease is expected to continue *** patients with pancreatic cancer have traditionally faced a dismal prognosis,over the past several years various advances in diagnosis and treatment have begun to positively impact this *** of effective combinations of existing chemotherapeutic agents,such as the FOLFIRINOX and the gemcitabine+nab-paclitaxel regimen,has improved survival for selected patients although concerns regarding their toxicity profiles remain.A better understanding of pancreatic carcinogenesis has identified several pre-malignant precursor lesions,such as pancreatic intraepithelial neoplasias,intraductal papillary mucinous neoplasms,and cystic *** technology has also evolved dramatically so as to allow early detection of these lesions and thereby facilitate earlier *** remains a cornerstone of treatment for patients with resectable pancreatic tumors,and advances in surgical technique have allowed patients to undergo resection with decreasing perioperative morbidity and *** has also become feasible in selected patients with borderline resectable tumors as a result of neoadjuvant ***,pancreatectomy involving vascular reconstruction and pancreatectomy with minimally invasive techniques have demonstrated safety without significantly compromising oncologic ***,a deeper understanding of molecular aberrations contributing to the development of pancreatic cancer shows promise for future development of more targeted and safe therapeutic agents.

关键词： Pancreatic cancer Pancreaticoduodenectomy Treatment advances Pancreatic oncology Chemotherapy FOLFIRINOX Pancreatic resection

Association of Mosaic Chromosomal Alterations and Genetic Factors with the Risk of Cirrhosis

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Journal of Clinical and Translational Hepatology 2024年第6期12卷 562-570页

作者： Xinyuan Ge Lu Zhang Maojie Liu Xiao Wang Xin Xu Yuqian Yan Chan Tian Juan Yang Yang Ding Chengxiao Yu Jing Lu Longfeng Jiang Qiang Wang Qun Zhang Ci Song Department of Epidemiology China International Cooperation Center on Environment and Human HealthCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsuChina The Dumont-UCLA Transplant center Division of Liver and Pancreas TransplantationDepartment of SurgeryDavid Geffen School of Medicine at UCLALos AngelesCAUSA Department of Health Promotion center Jiangsu Province Hospital and Nanjing Medical University First Affiliated HospitalNanjingJiangsuChina Department of Infectious Disease The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChina Department of Clinical Science Intervention and Technology(CLINTEC)Karolinska InstitutetStockholmSweden Changzhou Medical center Nanjing Medical UniversityNanjingJiangsuChina Research Units of Cohort Study on Cardiovascular Diseases and Cancers Chinese Academy of Medical SciencesBeijingChina Collaborative Innovation center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsuChina

Background and Aims:Age-related mosaic chromosomal alterations(mCAs)detected from genotyping of blood-de-rived DNA are structural somatic variants that indicate clonal *** study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score(PRS)on cirrhosis risk ***:mCA call sets of individuals with European ancestry were obtained from the UK *** PRS was constructed based on 12 susceptible single-nucleotide poly-morphisms for *** proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis ***:Among 448,645 individuals with a median follow-up of 12.5 years,we identified 2,681 cas-es of cirrhosis,1,775 cases of compensated cirrhosis,and 1,706 cases of decompensated *** to non-carriers,individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis(hazard ratio(HR)1.42,95%confidence interval(CI)1.12-1.81).This risk was higher in patients with expanded cell fractions of mCAs(cell fractions≥10%*** fractions<10%),especially for the risk of decompensated cirrhosis(HR 2.03[95%CI 1.09-3.78]vs.1.14[0.80-1.64]).In comparison to non-carriers of mCAs with low genetic risk,individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk(HR5.39[95%CI 2.41-12.07]).Conclusions:The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.

关键词： UK Biobank Cirrhosis Mosaic chromosomal alterations Polygenic risk score Genetic susceptibility Interaction effect

Delayed gastric emptying following pancreaticoduodenectomy:Incidence,risk factors,and healthcare utilization

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World Journal of Gastrointestinal Surgery 2017年第3期9卷 73-81页

作者： Somala Mohammed George Van Buren II Amy Mc Elhany Eric J Silberfein William E Fisher elkins pancreas center Michael E DeBakey Department of SurgeryBaylor College of MedicineHoustonTX 77030United States

AIM To characterize incidence and risk factors for delayed gastric emptying(DGE) following pancreaticoduodenectomy and examine its implications on healthcare utilization. METHODS A prospectively-maintained database was reviewed. DGE was classified using International Study Group of Pancreatic Surgery criteria. Patients who developed DGE and those who did not were compared. RESULTS Two hundred and seventy-six patients underwent pancreaticoduodenectomy(PD)(> 80% pyloruspreserving, antecolic-reconstruction). DGE developed in 49 patients(17.8%): 5.1% grade B, 3.6% grade C. Demographic, clinical, and operative variables were similar between patients with DGE and those without. DGE patients were more likely to present multiplecomplications(32.6% vs 4.4%, ≥ 3 complications, P < 0.001), including postoperative pancreatic fistula(POPF)(42.9% vs 18.9%, P = 0.001) and intra-abdominal abscess(IAA)(16.3% vs 4.0%, P = 0.012). Patients with DGE had longer hospital stay(median, 12 d vs 7 d, P < 0.001) and were more likely to require transitional care upon discharge(24.5% vs 6.6%, P < 0.001). On multivariate analysis, predictors for DGE included POPF [OR = 3.39(1.35-8.52), P = 0.009] and IAA [OR = 1.51(1.03-2.22), P = 0.035].CONCLUSION Although DGE occurred in < 20% of patients after PD, it was associated with increased healthcare utilization. Patients with POPF and IAA were at risk for DGE. Anticipating DGE can help individualize care and allocate resources to high-risk patients.

关键词： Delayed gastric emptying Pancreaticoduodenectomy Post-operative pancreatic fistula

Autoimmune pancreatitis not otherwise specified(NOS): Clinical features and outcomes of the forgotten type

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Hepatobiliary & Pancreatic Diseases International 2019年第6期18卷 576-579页

作者： Nicolò de Pretis Filippo Vieceli Alessandro Brandolese Lorenzo Brozzi Antonio Amodio Luca Frulloni Gastroenterology Unit Pancreas Center University of Verona

Background:Autoimmune pancreatitis(AIP)is a well-recognized fibroinflammatory disease of the *** the significant number of studies published on AIP type 1 and 2,no studies have been focused on AIP type not otherwise specified(NOS)and therefore very little is known about clinical features and long-term outcomes of these *** aim of this study was to investigate clinical and radiological features of AIP type ***:Patients classified as AIP type NOS at clinical onset included in our database prospectively maintained since 1995 were ***,clinical data were collected and ***:Forty-six patients were included in the *** clinical onset was mainly characterized by weight loss,jaundice and acute *** patients(17.4%)were reclassified as AIP type 2 during follow-up because of the development of ulcerative *** patients(15.2%)experienced relapse after steroid treatment but only one(2.2%)needed immunosuppressive drugs because of recurrent ***:AIP type NOS shares clinical features similar to AIP type 2 and a relevant proportion of patients was reclassified as AIP type 2 during follow-up because of the development of ulcerative *** risk of relapse is low but not irrelevant.

关键词： Autoimmune pancreatitis Not otherwise specified Outcome Follow-up Therapy

Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees Department of Surgery Vanderbilt University Medical CenterNashvilleTN 37232United States Department of Pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States Division of Surgical Oncology and Endocrine Surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic *** disease is typically associated with increased tumor diameter,multifocality,and vascular *** report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic *** SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid *** CT evaluations demonstrated steatosis,but no cirrhosis or liver *** ultrasound demonstrated a normal-appearing pancreas,biliary tree,and *** needle aspiration yielded atypical *** differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal *** review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated *** resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 *** fetoprotein was 23.3 ng/*** patient was diagnosed with HCC with portocaval nodal ***:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic *** identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic *** Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

Radiomic features on contrast-enhanced images of the remnant liver predict the prognosis of hepatocellular carcinoma after partial hepatectomy

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iLIVER 2024年第1期3卷 15-29页

作者： Meilong Wu Liping Liu Xiaojuan Wang Ying Xiao Shizhong Yang Jiahong Dong Division of Hepatobiliary and pancreas Surgery Department of General SurgeryShenzhen People's HospitalShenzhen 518020China The Second Clinical Medical College Jinan UniversityShenzhen 518020China The First Affiliated Hospital Southern University of Science and TechnologyShenzhen 518020China Hepato-pancreato-biliary center Beijing Tsinghua Changgung HospitalBeijing 102218China Key Laboratory of Digital Intelligence Hepatology Chinese Ministry of EducationBeijing 102218China School of Clinical Medicine Tsinghua UniversityBeijing 100084China Research Unit of Precision Hepatobiliary Surgery Paradigm Chinese Academy of Medical SciencesBeijing 102218China Department of Pathology Beijing Tsinghua Changgung HospitalBeijing 102218China

Background and aims:Radiomic features extracted from preoperative contrast-enhanced computed tomography(CT)images have been shown to predict the prognosis of hepatocellular carcinoma(HCC).However,the prognostic role of radiomic features obtained from postoperative contrast-enhanced CT images of the remnant liver remains *** study explored the prognostic value of radiomic features extracted from postoperative contrast-enhanced CT images in patients with ***:Robust radiomic features were obtained from postoperative contrast-enhanced CT images for 78 patients with primary HCC and used to construct a radiomics score.A clinical model and a combined model that integrated clinicopathological indicators and the radiomics score were *** predictive performance of the model was assessed using the concordance index and net reclassification ***:The postoperative radiomics score for the remnant liver was an independent prognostic factor for diseasefree survival(DFS)and overall survival(OS).The combined model was not inferior to the clinical model in predicting DFS but was superior in predicting *** net reclassification index confirmed that the combined model was more accurate and efficient in predicting OS and *** radiomics score for DFS was significantly associated with tumor thrombus in the portal vein and the postoperative neutrophil-lymphocyte *** radiomics score for OS was associated with multiple tumors,microvascular invasion,and tumor thrombus in the portal ***:Postoperative contrast-enhanced CT radiomic features of the remnant liver were valuable prognostic indicators that could potentially reflect tumor burden and postoperative inflammatory status and provide more information for clinical decision-making.

关键词： Hepatocellular carcinoma Computed tomography Radiomics Postoperative Survival Remnant

Double-layer probiotic encapsulation for enhanced bacteriotherapy against inflammatory bowel disease

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Nano Research 2024年第10期17卷 9103-9110页

作者： Yixin Wang Jun Liu Sichen Yuan Yawen You Quanyin Hu Pharmaceutical Sciences Division School of PharmacyUniversity of Wisconsin-MadisonMadisonWI 53705USA Carbone Cancer center School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonWI 53705USA Wisconsin center for NanoBioSystems School of PharmacyUniversity of Wisconsin-MadisonMadisonWI 53705USA

Inflammatory bowel disease(IBD)is inflammatory intestinal disorders associated with dysregulated gut *** that leverages bacteria as therapeutics has shown tremendous promise in resolving gut dysbiosis and reducing inflammatory mediators to treat *** delivered probiotics,such as Escherichia coli Nissle 1917(EcN),can produce beneficial ingredients,competitively inhibit the proliferation of pathogens,and promote the restoration of gut microbiome ***,environmental stresses(such as gastric acids)in the gastrointestinal(GI)tract pose an enormous challenge to the probiotics following oral administration,leading to decreases in viability and activity of ***,the inferior mucoadhesive capability of probiotics results in low colonization efficacy,further compromising their therapeutic *** probiotics with functional biomaterials may protect them from elimination and prolong their retention in the GI ***,we developed a facile double-layer electrostatic assembly technique to encapsulate EcN bacteria in protective layers of mucoadhesive chitosan(CS)and immunomodulatory hyaluronic acid(HA)to generate *** biomaterials confer the coated EcN resistance to environmental assault and enhanced mucoadhesion in the GI *** probiotics equipped with the multifunctional shield can thus suppress inflammation and reshape the intestinal microenvironment to enhance therapeutic efficacy for the prevention and treatment of ***,this study presents a novel probiotic coating strategy to augment the outcome of bacteriotherapy to combat IBD.

关键词： probiotics biomaterial coating inflammatory bowel disease mucoadhesion oral administration

Mesenchymal stromal cells modulate unfolded protein response and preserve β-cell mass in type 1 diabetes

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BIOCELL 2024年第7期48卷 1115-1126页

作者： SIYUAN LIU YUAN ZHAO YU YU DOU YE QIAN WANG ZHAOYAN WANG ZUO LUAN Department of Pediatrics The Sixth Medical CenterChinese PLA General HospitalBeijing100037China

Introduction:Transplantation of mesenchymal stromal cells(MSCs)is a promising therapy for type 1 diabetes(T1D).However,whether the infused MSCs affect the endoplasmic reticulum stress or subsequent unfolded protein response inβcells remains ***:To investigate this,we induced early-onset T1D in non-obese diabetic mice using ***,T1D mice were randomly assigned to receive either MSCs or phosphate-buffered *** observed the in vivo homing of MSCs and assessed their effectiveness by analyzing blood glucose levels,body weight,histopathology,pancreatic protein expression,and serum levels of cytokines,proinsulin,and ***:Infused MSCs were found in the lungs,liver,spleen,and pancreas of T1D *** exhibited various effects,including reducing blood glucose levels,regulating immunity,inhibiting inﬂammation,increasingβ-cell areas,and reducing the expression of key proteins in the unfolded protein response *** serum proinsulin and C-peptide levels were signiﬁcantly higher in the MSCs treatment group than in the T1D model ***,there was no signiﬁcant difference in the biomarker ofβ-cell endoplasmic reticulum stress,the ratio of fasting serum proinsulin to C-peptide,between the two ***:Ourﬁndings reveal that MSCs infusion does not alleviate endoplasmic reticulum stress inβcells directly but modulates the unfolded protein response pathway to preserveβ-cell mass and function in T1D mice.

关键词： Type 1 diabetes Mesenchymal stromal cells Endoplasmic reticulum stress Unfolded protein response Non-obese diabetic mice

Liver-brain axis with alcohol:Role of fibroblast growth factor 21(FGF21)

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Genes & Diseases 2024年第2期11卷 509-511页

作者： Ke Zhang Elena Blokhina Evgeny Krupitsky Marina Vetrova Ti-Fei Yuan Hua Wang Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Pavlov University Valdman Institute of PharmacologySt.Petersburg 197022Russia Bekhterev National Medical Research center for Psychiatry and Neurology St.Petersburg 192019Russia Co-innovation center of Neuroregeneration Nantong UniversityNantongJiangsu 226007China Department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230032China

Fibroblast growth factor21(FGF21)is a hormone that can balance nutrient fluctuations,control metabolic processes,and maintain energy *** FGF21 is produced by a variety of cell types,including hepatocytes,adipocytes,bone cells,myocardial cells,and pancreas cells,and act on various effector tissues such as brain,adipose tissue,liver,heart,and skeletal muscle.1 The target that FGF21 interacts with is the cell-surface receptor composed of FGF receptors in complex with the single-pass transmembrane proteinβ-*** receptors are abundantly expressed,both in peripheral tissues and some regions of the CNS,such as the hypothalamus and amygdala and the locus coeruleus(LC).2 Physiologically,FGF21 can be induced by various metabolic stresses,including hunger,protein deficiency,monosaccharides,and alcohol,by acting onβ-Klotho receptor in corresponding tissues,ultimately exerting regulatory effects(Fig.1)

关键词： Klotho homeostasis alcohol