Database : MEDLINE
Search on : Pancreatic and Neoplasms [Words]
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[PMID]: 29510135
[Au] Autor:Anand G; Youssef F; Gupta S
[Ad] Address:Veterans Affairs San Diego Healthcare System, Division of Gastroenterology, Department of Internal Medicine, University of California San Diego, San Diego, California.
[Ti] Title:Overall Mortality and Pancreatic Cancer Mortality Among Patients With Pancreatic Cystic Neoplasms.
[So] Source:Gastroenterology;, 2018 Mar 03.
[Is] ISSN:1528-0012
[Cp] Country of publication:United States
[La] Language:eng
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 76168 MEDLINE  
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[PMID]: 29211796
[Au] Autor:Saison-Ridinger M; DelGiorno KE; Zhang T; Kraus A; French R; Jaquish D; Tsui C; Erikson G; Spike BT; Shokhirev MN; Liddle C; Yu RT; Downes M; Evans RM; Saghatelian A; Lowy AM; Wahl GM
[Ad] Address:Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America.
[Ti] Title:Reprogramming pancreatic stellate cells via p53 activation: A putative target for pancreatic cancer therapy.
[So] Source:PLoS One;12(12):e0189051, 2017.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely dense fibrotic stroma, which contributes to tumor growth, metastasis, and drug resistance. During tumorigenesis, quiescent pancreatic stellate cells (PSCs) are activated and become major contributors to fibrosis, by increasing growth factor signaling and extracellular matrix deposition. The p53 tumor suppressor is known to restrict tumor initiation and progression through cell autonomous mechanisms including apoptosis, cell cycle arrest, and senescence. There is growing evidence that stromal p53 also exerts anti-tumor activity by paracrine mechanisms, though a role for stromal p53 in PDAC has not yet been described. Here, we demonstrate that activation of stromal p53 exerts anti-tumor effects in PDAC. We show that primary cancer-associated PSCs (caPSCs) isolated from human PDAC express wild-type p53, which can be activated by the Mdm2 antagonist Nutlin-3a. Our work reveals that p53 acts as a major regulator of PSC activation and as a modulator of PDAC fibrosis. In vitro, p53 activation by Nutlin-3a induces profound transcriptional changes, which reprogram activated PSCs to quiescence. Using immunofluorescence and lipidomics, we have also found that p53 activation induces lipid droplet accumulation in both normal and tumor-associated fibroblasts, revealing a previously undescribed role for p53 in lipid storage. In vivo, treatment of tumor-bearing mice with the clinical form of Nutlin-3a induces stromal p53 activation, reverses caPSCs activation, and decreases fibrosis. All together our work uncovers new functions for stromal p53 in PDAC.
[Mh] MeSH terms primary: Carcinoma, Pancreatic Ductal/therapy
Cellular Reprogramming
Genes, p53
Pancreatic Neoplasms/therapy
Pancreatic Stellate Cells/metabolism
[Mh] MeSH terms secundary: Animals
Carcinoma, Pancreatic Ductal/metabolism
Carcinoma, Pancreatic Ductal/pathology
Cholesterol Esters/metabolism
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pancreatic Neoplasms/metabolism
Pancreatic Neoplasms/pathology
Transcription, Genetic
Triglycerides/metabolism
Tumor Cells, Cultured
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Cholesterol Esters); 0 (Triglycerides)
[Em] Entry month:1712
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[Js] Journal subset:IM
[Da] Date of entry for processing:171207
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189051

  3 / 76168 MEDLINE  
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[PMID]: 29450630
[Au] Autor:Shibasaki S; Suda K; Nakauchi M; Nakamura T; Kadoya S; Kikuchi K; Inaba K; Uyama I
[Ad] Address:Department of Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan.
[Ti] Title:Outermost layer-oriented medial approach for infrapyloric nodal dissection in laparoscopic distal gastrectomy.
[So] Source:Surg Endosc;32(4):2137-2148, 2018 Apr.
[Is] ISSN:1432-2218
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:BACKGROUND: Based on our experience of suprapancreatic nodal dissection in laparoscopic gastrectomy, we developed an outermost layer-oriented medial approach for infrapyloric nodal dissection. The objective of this single-institution retrospective study was to determine the feasibility, safety, and reproducibility of this novel and unique dissection procedure. METHODS: This approach can be performed in the same manner as suprapancreatic nodal dissection but by replacing the left gastric artery with the right gastroepiploic artery (RGEA), the common hepatic artery with the anterior superior pancreaticoduodenal artery (ASPDA), and the splenic artery with the gastroduodenal artery. It comprises five steps: (1) mobilization of the transverse mesocolon along the prepancreatic membrane, (2) medial dissection along the dissectable layer between the pancreatic head and the dorsal side of the right gastroepiploic vein (RGEV), (3) division of the RGEV and determination of the lateral and cranial borders, (4) dissection along the outermost layer of the RGEA and ASPDA and transection of the infrapyloric artery and RGEA, and (5) transection of the duodenal bulb. RESULTS: This novel method was applied in 112 patients who underwent laparoscopic distal gastrectomy from 2014 to 2015. The anatomical landmarks that we determined to appropriately identify the outermost layer were highly reproducible, and our novel procedure based on these landmarks was successfully completed in all cases, without any intraoperative complications. Furthermore, in all cases, no. 6 lymph nodes were fully and adequately dissected within the infrapyloric area anatomically defined in the Japanese Classification of Gastric Carcinoma ver. 14. Pancreatic fistula occurred only in 1.8% cases. CONCLUSIONS: This novel outermost layer-oriented medial approach is a robust procedure that may help laparoscopic surgeons in performing safe and reproducible infrapyloric nodal dissection.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Data-Review
[do] DOI:10.1007/s00464-018-6111-6

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[PMID]: 29351303
[Au] Autor:Mihaylov IB; Mellon EA; Yechieli R; Portelance L
[Ad] Address:Department of Radiation Oncology, University of Miami,Miami, FL, United States of America.
[Ti] Title:Automated inverse optimization facilitates lower doses to normal tissue in pancreatic stereotactic body radiotherapy.
[So] Source:PLoS One;13(1):e0191036, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: Inverse planning is trial-and-error iterative process. This work introduces a fully automated inverse optimization approach, where the treatment plan is closely tailored to the unique patient anatomy. The auto-optimization is applied to pancreatic stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: The automation is based on stepwise reduction of dose-volume histograms (DVHs). Five uniformly spaced points, from 1% to 70% of the organ at risk (OAR) volumes, are used. Doses to those DVH points are iteratively decreased through multiple optimization runs. With each optimization run the doses to the OARs are decreased, while the dose homogeneity over the target is increased. The iterative process is terminated when a pre-specified dose heterogeneity over the target is reached. Twelve pancreatic cases were retrospectively studied. Doses to the target, maximum doses to duodenum, bowel, stomach, and spinal cord were evaluated. In addition, mean doses to liver and kidneys were tallied. The auto-optimized plans were compared to the actual treatment plans, which are based on national protocols. RESULTS: The prescription dose to 95% of the planning target volume (PTV) is the same for the treatment and the auto-optimized plans. The average difference for maximum doses to duodenum, bowel, stomach, and spinal cord are -4.6 Gy, -1.8 Gy, -1.6 Gy, and -2.4 Gy respectively. The negative sign indicates lower doses with the auto-optimization. The average differences in the mean doses to liver and kidneys are -0.6 Gy, and -1.1 Gy to -1.5 Gy respectively. CONCLUSIONS: Automated inverse optimization holds great potential for personalization and tailoring of radiotherapy to particular patient anatomies. It can be utilized for normal tissue sparing or for an isotoxic dose escalation.
[Mh] MeSH terms primary: Automation
Radiotherapy Dosage
[Mh] MeSH terms secundary: Humans
Pancreas/radiation effects
Pancreatic Neoplasms/radiotherapy
Retrospective Studies
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180120
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191036

  5 / 76168 MEDLINE  
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[PMID]: 29521942
[Au] Autor:Gausman V; Kandel P; Van Riet PA; Moris M; Kayal M; Do C; Poneros JM; Sethi A; Gress FG; Schrope BA; Luk L; Hecht E; Jovani M; Bruno MJ; Cahen DL; Wallace MB; Gonda TA
[Ti] Title:Predictors of Progression Among Low-Risk Intraductal Papillary Mucinous Neoplasms in a Multicenter Surveillance Cohort.
[So] Source:Pancreas;47(4):471-476, 2018 Apr.
[Is] ISSN:1536-4828
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVES: Our aim was to identify baseline characteristics associated with disease progression and malignant transformation in low-risk suspected intraductal papillary mucinous neoplasms (IPMNs). METHODS: This is a retrospective cohort study of prospectively maintained databases of pancreatic cysts at 3 international, academic institutions. Five hundred fifty-nine adult patients with clinically suspected asymptomatic IPMN evaluated by radiologic studies or endoscopic ultrasound between 2003 and 2013 without worrisome features and under surveillance for 12 months or longer were included. We evaluated the relationship of baseline demographics and cyst features to disease progression (size increase, development of worrisome features, or high-grade dysplasia/cancer). RESULTS: After a median of 44 months follow-up, 269 (48%) patients experienced cyst size increase, 68 (12%) developed worrisome features, and 11 (2%) developed high-grade dysplasia/cancer. In multivariable Cox-regression analysis, no baseline characteristics were associated with size increase. An initial cyst size of 2 cm or greater, multifocality, history of prostate cancer, and smoking were the strongest predictors of development of new worrisome features. Univariable analysis found male sex, diabetes, and recent weight loss associated with development of high-grade dysplasia/cancer. CONCLUSIONS: Our study demonstrates that low-risk suspected IPMNs carry a small but clinically relevant risk of disease progression and provides data on baseline characteristics that may help in risk stratification.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1097/MPA.0000000000001027

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[PMID]: 29520563
[Au] Autor:Uccella S; La Rosa S; Volante M; Papotti M
[Ad] Address:Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
[Ti] Title:Immunohistochemical Biomarkers of Gastrointestinal, Pancreatic, Pulmonary, and Thymic Neuroendocrine Neoplasms.
[So] Source:Endocr Pathol;, 2018 Mar 09.
[Is] ISSN:1559-0097
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Neuroendocrine neoplasms (NENs) are a heterogeneous group of epithelial neoplastic proliferations that irrespective of their primary site share features of neural and endocrine differentiation including the presence of secretory granules, synaptic-like vesicles, and the ability to produce amine and/or peptide hormones. NENs encompass a wide spectrum of neoplasms ranging from well-differentiated indolent tumors to highly aggressive poorly differentiated neuroendocrine carcinomas. Most cases arise in the digestive system and in thoracic organs, i.e., the lung and thymus. A correct diagnostic approach is crucial for the management of patients with both digestive and thoracic NENs, because their high clinical and biological heterogeneity is related to their prognosis and response to therapy. In this context, immunohistochemistry represents an indispensable diagnostic tool that pathologists need to use for the correct diagnosis and classification of such neoplasms. In addition, immunohistochemistry is also useful in identifying prognostic and theranostic markers. In the present article, the authors will review the role of immunohistochemistry in the routine workup of digestive and thoracic NENs.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1007/s12022-018-9522-y

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[PMID]: 29518779
[Au] Autor:Pellat A; Dreyer C; Couffignal C; Walter T; Lombard-Bohas C; Niccoli P; Seitz JF; Hentic O; André T; Coriat R; Faivre S; Zappa M; Ruszniewski P; Pote N; Couvelard A; Raymond E
[Ad] Address:Medical Oncology, Hôpital Saint Antoine, AP-HP, Paris, France.
[Ti] Title:Clinical and Biomarker Evaluations of Sunitinib in Patients with Grade 3 Digestive Neuroendocrine Neoplasms.
[So] Source:Neuroendocrinology;, 2018 Mar 08.
[Is] ISSN:1423-0194
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:BACKGROUND/AIMS: Angiogenesis is extensively developed in well-differentiated pancreatic neuroendocrine tumours (PanNET) where sunitinib was shown to prolong progression-free survival, leading to nationwide approval. However, clinical experience in patients with grade 3 gastroenteropancreatic neuroendocrine neoplasms (GEPNEN-G3) remains limited. This prospective phase II trial evaluated potential predictive biomarkers of sunitinib activity in patients with advanced GEPNEN-G3. METHODS: Sunitinib was given at a dose of 37.5 mg/day as a continuous daily dosing until progression or unacceptable toxicity. Evaluation of activity was based on RECIST1.1. Safety was evaluated according to NCI-CTCAE v4. Pharmacokinetics of sunitinib and its main active metabolite SU12662 were evaluated. All tumour samples were reviewed histologically for tumour differentiation. PDGFRß, carbonic anhydrase 9, Ki-67, VEGFR2, and p-AKT were quantified using immunohistochemistry and their expression correlated with response by RECIST1.1. RESULTS: Thirty-one patients were included and 26 had available histological tissue. Six and 20 patients presented well-differentiated tumours (NET-G3) and neuroendocrine carcinoma (NEC), respectively. Eighteen patients responded to sunitinib (4 experienced partial responses and 14 tumour stabilization). A high p-AKT expression correlated with lower response to sunitinib (OR 0.94, 95% CI 0.89-0.99, p = 0.04). Safety and PK exposure to sunitinib and SU12662 in these patients were consistent with that reported in PanNET. CONCLUSION: Sunitinib showed evidence of activity in patients with GEPNEN-G3 with expected toxicity profile. In the NET-G3 and NEC groups, 4/6 and 11/20 patients were responders, respectively. High p-AKT expression predicted a lower response to sunitinib. Our study allowed the identification of a potential biomarker of resistance/sensitivity to sunitinib in aggressive GEPNEN-G3.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1159/000487237

  8 / 76168 MEDLINE  
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[PMID]: 29452147
[Au] Autor:Lin YK; Fang Z; Jiang TY; Wan ZH; Pan YF; Ma YH; Shi YY; Tan YX; Dong LW; Zhang YJ; Wang HY
[Ad] Address:International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, PR China.
[Ti] Title:Combination of Kras activation and PTEN deletion contributes to murine hepatopancreatic ductal malignancy.
[So] Source:Cancer Lett;421:161-169, 2018 Feb 13.
[Is] ISSN:1872-7980
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:Kras mutations are among the most common genetic abnormalities in human neoplasms, including cholangiocarcinomas, pancreatic cancer and colon cancer. PTEN has previously been associated with cholangiocarcinoma development in murine models. Here, we have established novel mouse models of neoplasms by liver-specific and biliary-pancreatic Kras activation and PTEN deletion. By liver-specific disruption of PTEN and activation of Kras in mice caused rapid development of intrahepatic biliary epithelial proliferative lesions (Intrahepatic cholangiocarcinoma, ICC), which progress through dysplasia to invasive carcinoma. In contrast, Kras activation in combination with heterozygous PTEN deletion induced mixed carcinomas of liver (both ICC and hepatocellular carcinoma, HCC), whereas Kras activation alone did not induce biliary tract neoplasm. Use of Sox9-Cre-LoxP-based approach to coordinately delete PTEN and activate Kras in the adult mouse resulted in not only development of low-grade biliary lesions (ICC and extrahepatic bile duct carcinoma, ECC) but also pancreatic carcinomas. Our data provide a functional link between PTEN gene status, hepatobiliary cell fate, and HCC, biliary carcinoma, pancreatic cancer pathogenesis, and present novel genetically engineered mouse models of PTEN loss-driven malignancy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher

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[PMID]: 29299757
[Au] Autor:Beger HG
[Ad] Address:Department of General and Visceral Surgery, University of Ulm, c/o Universitätsklinikum Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany. hans@beger-ulm.de.
[Ti] Title:Benign Tumors of the Pancreas-Radical Surgery Versus Parenchyma-Sparing Local Resection-the Challenge Facing Surgeons.
[So] Source:J Gastrointest Surg;22(3):562-566, 2018 Mar.
[Is] ISSN:1873-4626
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Pancreaticoduodenectomy and left-sided pancreatectomy are the surgical treatment standards for tumors of the pancreas. Surgeons, who are requested to treat patients with benign tumors, using standard oncological resections, face the challenge of sacrificing pancreatic and extra-pancreatic tissue. Tumor enucleation, pancreatic middle segment resection and local, duodenum-preserving pancreatic head resections are surgical procedures increasingly used as alternative treatment modalities compared to classical pancreatic resections. Use of local resection procedures for cystic neoplasms and neuro-endocrine tumors of the pancreas (panNETs) is associated with an improvement of procedure-related morbidity, when compared to classical Whipple OP (PD) and left-sided pancreatectomy (LP). The procedure-related advantages are a 90-day mortality below 1% and a low level of POPF B+C rates. Most importantly, the long-term benefits of the use of local surgical procedures are the preservation of the endocrine and exocrine pancreatic functions. PD performed for benign tumors on preoperative normo-glycemic patients is followed by the postoperative development of new onset of diabetes mellitus (NODM) in 4 to 24% of patients, measured by fasting blood glucose and/or oral/intravenous glucose tolerance test, according to the criteria of the international consensus guidelines. Persistence of new diabetes mellitus during the long-term follow-up after PD for benign tumors is observed in 14.5% of cases and after surgery for malignant tumors in 15.5%. Pancreatic exocrine insufficiency after PD is found in the long-term follow-up for benign tumors in 25% and for malignant tumors in 49%. Following LP, 14-31% of patients experience postoperatively NODM; many of the patients subsequently change to insulin-dependent diabetes mellitus (IDDM). The decision-making for cystic neoplasms and panNETs of the pancreas should be guided by the low surgical risk and the preservation of pancreatic metabolic functions when undergoing a limited, local, tissue-sparing procedure.
[Pt] Publication type:EDITORIAL
[Em] Entry month:1801
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1007/s11605-017-3644-2

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[PMID]: 29288362
[Au] Autor:Goonesekere NCW; Andersen W; Smith A; Wang X
[Ad] Address:Department of Chemistry and Biochemistry, University of Northern Iowa, 1227 W. 27th Street, Cedar Falls, IA, 50613-0423, USA. nalin.goonesekere@uni.edu.
[Ti] Title:Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets.
[So] Source:J Cancer Res Clin Oncol;144(2):309-320, 2018 Feb.
[Is] ISSN:1432-1335
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:PURPOSE: The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease. METHODS: In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets. We have used qRT-PCR to confirm the downregulation of selected genes in a panel of PC cell lines. RESULTS: This study has yielded several novel candidate tumor-suppressor genes (TSGs) including GNMT, CEL, PLA2G1B and SERPINI2. We highlight the role of GNMT, a methyl transferase associated with the methylation potential of the cell, and CEL, a lipase, as potential therapeutic targets. We have uncovered genetic links to risk factors associated with PC such as smoking and obesity. Genes important for patient survival and prognosis are also discussed, and we confirm the dysregulation of metabolic pathways previously observed in PC. CONCLUSIONS: While many of the genes downregulated in our dataset are associated with protein products normally produced by the pancreas for excretion, we have uncovered some genes whose downregulation appear to play a more causal role in PC. These genes will assist in providing a better understanding of the disease etiology of PC, and in the search for new therapeutic targets and biomarkers.
[Mh] MeSH terms primary: Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Pancreatic Neoplasms/genetics
[Mh] MeSH terms secundary: Cell Line, Tumor
Datasets as Topic
Down-Regulation
Humans
Molecular Targeted Therapy
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
[Pt] Publication type:JOURNAL ARTICLE; META-ANALYSIS
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:171231
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2558-4


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