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Find video protocols related to scientific articles indexed in Pubmed.
Effective communication between ENT and primary care - a survey and analysis of outpatient correspondence structure.
Clin Otolaryngol
PUBLISHED: 10-28-2014
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To improve the quality of outpatient clinic communication between Otolaryngology and primary care doctors.
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Extracellular lumican inhibits pancreatic cancer cell growth and is associated with prolonged survival after surgery.
Clin. Cancer Res.
PUBLISHED: 10-23-2014
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Purpose:To evaluate the relevance between lumican expression patterns and the clinical course of PDAC patients, and to investigate the role of lumican in PDAC progression. Experimental Design:131 patient tumors were chosen for tissue microarray staining and Cox regression analysis was used to test the associations between lumican expression and clinical, pathologic, and oncologic outcomes in all patients. Primary PDAC cells and recombinant human lumican protein were used to establish a working model to mimic the in vivo interactions between stromal lumican and PDAC cells. Using this model, we tested the effects of lumican on EGFR signaling via Akt and HIF-1? and its subsequent influence on glucose consumption, lactate production, intracellular ATP, and apoptotic cell death. Results:Lumican was present in the stroma surrounding PDAC cells in roughly one-half of primary tumors and the direct xenografts. Patients with stromal lumican were associated with a profound reduction in metastatic recurrence after surgery and three-fold longer survival than patients without stromal lumican. In PDAC cells, extracellular lumican reduced EGFR expression and phosphorylation through enhanced dimerization and internalization of EGFR and the resultant inhibition of Akt kinase activity. Lumican also reduced HIF-1? expression and activity via Akt. PDAC cells with enhanced HIF-1? activity were resistant to lumican-induced inhibition of glucose consumption, lactate production, intracellular ATP, and apoptosis. Conclusions:There is a positive association between stromal lumican in primary PDAC tumors and prolonged survival after tumor resection. Lumican plays a restrictive role in EGFR-expressing pancreatic cancer progression.
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Genistein potentiates the antitumor effect of 5-Fluorouracil by inducing apoptosis and autophagy in human pancreatic cancer cells.
Anticancer Res.
PUBLISHED: 09-10-2014
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Although 5-fluorouracil (5-FU)-based combination chemotherapy (i.e. FOLFIRINOX) has demonstrated effectiveness against pancreatic cancer, novel therapeutic strategies must be developed to increase the therapeutic window of these cytotoxic agents. Genistein is a soy-derived isoflavone with pleiotropic biological effects that can enhance the antitumor effect of chemotherapeutic agents.
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Hepatobiliary/Pancreas Pathology: SY11-3 PANCREATIC DUCTAL ADENOCARCINOMA: NEOADJUVANT THERAPIES AND PATHOLOGY.
Pathology
PUBLISHED: 09-05-2014
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies with less than 5% five-year survival rate. Despite significant improvements in medical and surgical oncology and postoperative mortality rate, the overall survival for patients with pancreatic cancer has not changed significantly in the last four decades. Neoadjuvant chemoradiation therapy (NCT) is increasingly used to treat patients with potentially resectable PDAC, especially for patients with borderline resectable disease. However, analysis of prognostic factors is limited for patients with PDAC treated with NCT and pancreaticoduodenectomy. We systemically examined the pancreaticoduodenectomy specimens from 240 consecutive patients with PDAC who received NCT and pancreaticoduodenectomy between 1999 and 2007 at our institution. We found that posttreatment pathologic stage, pathologic tumor response grading, tumor involvement of the superior mesenteric/portal vein, tumor invasion into the muscular vessels, and perineural invasion are significant prognostic factors in our patient population. Therefore careful pathologic evaluation of the pancreatectomy specimens plays a key role in predicting prognosis of patients with PDAC who received NCT and pancreaticoduodenectomy.
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The Canary in the Coal Mine: The Growth of Patient-Derived Tumorgrafts in Mice Predicts Clinical Recurrence after Surgical Resection of Pancreatic Ductal Adenocarcinoma.
Ann. Surg. Oncol.
PUBLISHED: 08-19-2014
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Recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) is common, thus postoperative surveillance is critical for detection and treatment of recurrent disease. The development of biologically based techniques for early recurrence detection may enable more timely and effective treatment of such recurrences.
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Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function.
Nature
PUBLISHED: 08-10-2014
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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in western countries, with a median survival of 6 months and an extremely low percentage of long-term surviving patients. KRAS mutations are known to be a driver event of PDAC, but targeting mutant KRAS has proved challenging. Targeting oncogene-driven signalling pathways is a clinically validated approach for several devastating diseases. Still, despite marked tumour shrinkage, the frequency of relapse indicates that a fraction of tumour cells survives shut down of oncogenic signalling. Here we explore the role of mutant KRAS in PDAC maintenance using a recently developed inducible mouse model of mutated Kras (Kras(G12D), herein KRas) in a p53(LoxP/WT) background. We demonstrate that a subpopulation of dormant tumour cells surviving oncogene ablation (surviving cells) and responsible for tumour relapse has features of cancer stem cells and relies on oxidative phosphorylation for survival. Transcriptomic and metabolic analyses of surviving cells reveal prominent expression of genes governing mitochondrial function, autophagy and lysosome activity, as well as a strong reliance on mitochondrial respiration and a decreased dependence on glycolysis for cellular energetics. Accordingly, surviving cells show high sensitivity to oxidative phosphorylation inhibitors, which can inhibit tumour recurrence. Our integrated analyses illuminate a therapeutic strategy of combined targeting of the KRAS pathway and mitochondrial respiration to manage pancreatic cancer.
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Squamoid cystosis of pancreatic ducts: a variant of a newly-described cystic lesion, with evidence for an obstructive etiology.
Rare Tumors
PUBLISHED: 07-30-2014
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We describe a 40-year-old man who was found to have a cystic mass in the pancreatic tail during workup for weight loss and abdominal discomfort. Although computed tomography scan showed a single cyst associated with dilatation of the main pancreatic duct, gross and histologic examination of the distal pancreatectomy specimen actually revealed a central cyst that was surrounded by multiple smaller cystic spaces. This distinctive appearance was formed from extensive cystic dilatation and squamous metaplasia of the native pancreatic duct system. Further, a traumatic neuroma was discovered near the junction between normal and abnormal parenchyma. We believe that this case represents a variant of the newly-described squamoid cyst of pancreatic ducts which we term squamoid cystosis of pancreatic ducts. The presence of chronic pancreatitis and a traumatic neuroma supports the hypothesis that squamoid cysts are non-neoplastic lesions arising from prior duct obstruction.
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Selective efficacy of zoledronic acid on metastasis in a patient-derived orthotopic xenograph (PDOX) nude-mouse model of human pancreatic cancer.
J Surg Oncol
PUBLISHED: 07-13-2014
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Patient-derived orthotopic xenograft (PDOX) nude-mouse models replicate the behavior of clinical cancer, including metastasis. The objective of the study was to determine the efficacy of zoledronic acid (ZA) on metastasis of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of pancreatic cancer.
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Neoadjuvant Therapy is Associated with a Reduced Lymph Node Ratio in Patients with Potentially Resectable Pancreatic Cancer.
Ann. Surg. Oncol.
PUBLISHED: 06-19-2014
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The use of neoadjuvant therapy (NAC) for the treatment of potentially resectable pancreatic cancer remains controversial. In this study, we sought to evaluate cancer-specific endpoints in patients undergoing a NAC versus a surgery-first (SF) approach with specific emphasis on lymph node metastases.
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Diagnostic yield of endoscopic retrograde cholangiopancreatography-based cytology for distinguishing malignant and benign intraductal papillary mucinous neoplasm: systematic review and meta-analysis.
Dig Endosc
PUBLISHED: 01-22-2014
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Published studies have revealed the diagnostic yield of cytology obtained from endoscopic retrograde cholangiopancreatography (ERCP) in distinguishing malignant and benign intraductal papillary mucinous neoplasm (IPMN). However as a result of small sample sizes, the overall magnitude of benefit is unknown. Additionally, the optimal endoscopic procedure for cytology acquisition is also unclear. The aim of the present study was to evaluate the diagnostic yield of ERCP-based cytology in patients with IPMN and clarify the optimal sampling technique.
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Oral feeding following laryngectomy: Early or delayed?
Int J Surg
PUBLISHED: 01-20-2014
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A best evidence topic in otolaryngology was written according to a structured protocol. The question addressed was: In patients having undergone laryngectomy, does the timing of oral feeding lead to a higher post-operative complication rate? 172 papers were found using the described protocol. Five of these papers were chosen to describe the best evidence to address the question. The authors, date and country of publication, study type, patient group, outcomes and key results of these papers have been represented in a table. All of these studies demonstrate that initiation of early feeding in patients post-laryngectomy provides no increased risk of development of pharyngocutaneous fistulas than delayed initiation of feeding. One study demonstrated a statistically significant reduction in hospitalisation of patients after early post-operative feeding. Therefore despite problems with study design, the literature concludes that early feeding is as safe as delayed feeding and may reduce the hospitalisation period. Further powered studies are required before recommendations on explicit inclusion criteria and feeding regimen details can be made.
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Aberrant expression of p53, p21, cyclin D1, and Bcl2 and their clinicopathological correlation in ampullary adenocarcinoma.
Hum. Pathol.
PUBLISHED: 01-17-2014
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Previous studies on the molecular alterations in ampullary adenocarcinoma (AA) are limited, and little is known about their clinical implications. The objective of this study is to examine the expression of p53, p21, cyclin D1, and Bcl2 and their clinical significance in patients with AA. Tissue microarrays were constructed using archival tissue from 92 patients with AA who underwent pancreaticoduodenectomy at our institution. Each tumor was sampled in triplicate with a 1.0-mm punch from representative areas. The expression of p53, p21, cyclin D1, and Bcl2 was evaluated by immunohistochemistry, and the staining results were correlated with clinicopathological features and survival. Among 92 cases studied, overexpression of p53, p21, cyclin D1, and Bcl2 was observed in 58.7%, 39.2%, 71.7%, and 5.4% of tumors, respectively. Patients whose tumor showed high level of cyclin D1 expression had higher risk of disease recurrence (P = .02) and worse recurrence-free and overall survivals after pancreaticoduodenectomy than did those with no or low cyclin D1 expression (P = .027 and P = .02, respectively). In multivariate analysis, cyclin D1 expression was an independent prognostic factor for both recurrence-free and overall survival (P < .05). However, there was no significant correlation between p53, p21, or Bcl2 expression and survival (P > .05). Our study showed that p53, p21, and cyclin D1, but not Bcl2, are frequently overexpressed in AAs. Cyclin D1 overexpression is associated with increased risk of disease recurrence and worse survival in patients with AA after resection.
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Solid pseudopapillary neoplasm of the pancreas: clinicopathologic and survival analyses of 64 cases from a single institution.
Am. J. Surg. Pathol.
PUBLISHED: 01-15-2014
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Although solid pseudopapillary neoplasms (SPNs) are considered tumors of low malignant potential, patients may present with aggressive disease (ie, liver metastasis/invasion into adjacent organs) and, rarely, die from disease. Although the clinicopathologic features associated with aggressive SPNs have been reported, important prognostic factors of survival remain unclear. We systematically reviewed 64 cases of SPN resected at our institution for tumor size, extent of invasion, margin status, presence of lymphovascular, muscular vessel, and perineural invasion, and lymph node and distant metastases. Clinicopathologic characteristics were correlated with the presence of metastasis/recurrence and disease-specific survival. Five (8%) patients presented with stage IV disease. During follow-up, 5 (13%) of 39 patients with stage I-II disease had recurrences. Patients with metastatic/recurrent SPNs had significantly larger tumor size (P<0.001) and more frequent tumor invasion into muscular vessels (P=0.02). In a median follow-up of 76 months, only 2 died of disease (1 who presented with extensive peritoneal tumor involvement who died 2.5 mo after surgery, and 1 unusual case who presented with multiple liver metastasis and peritoneal seeding who died 19 mo after surgery), and 5 were alive with disease. The 10-year disease-specific survival rate was 96%. Muscular vessel invasion (P=0.001), tumor (T) stage by European Neuroendocrine Tumors Society (ENETS) classification (P<0.001), ENETS stage grouping (P<0.001), and stage grouping by the American Joint Committee on Cancer (AJCC stage, P<0.001) were important predictors of disease-specific survival in patients with SPN. Our study highlights the importance of pathologic evaluation in risk assessment in patients with SPNs.
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SOX9: a useful marker for pancreatic ductal lineage of pancreatic neoplasms.
Hum. Pathol.
PUBLISHED: 01-15-2014
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Previous studies showed that SOX9 plays a critical role in pancreatic ductal development. The aim of this study was to evaluate SOX9 as a marker for pancreatic ductal lineage. SOX9 expression was evaluated by immunohistochemistry in 146 benign pancreas (BP), 136 pancreatic ductal adenocarcinomas, 47 pancreatic intraepithelial neoplasia (PanIN), 21 intraductal papillary mucinous neoplasms (IPMNs), 14 mucinous cystic neoplasms, 10 serous cystadenomas, 39 pancreatic neuroendocrine tumors, 9 acinar cell carcinomas, and 23 solid pseudopapillary neoplasms. Nuclear expression of SOX9 was detected in the centroacinar cells and ductal cells, but not in acinar or endocrine cells in 100% BP. Focal or diffuse SOX9 expression was detected in 100% PanINs, 100% IPMNs, 100% mucinous cystic neoplasms, 100% serous cystadenomas, 89.0% pancreatic ductal adenocarcinomas, 2.6% pancreatic neuroendocrine tumors, 11.1% acinar cell carcinomas, and 0% solid pseudopapillary neoplasms. SOX9 expression was lower in PanIN2 and PanIN3 than in PanIN1 lesions (P < .01). Compared with BP, IPMN had lower SOX9 expression (P < .05). No correlation between SOX9 expression and other clinicopathologic parameters was identified. Our study showed that SOX9 is expressed in centroacinar and ductal epithelial cells of BP and is a useful marker for pancreatic ductal lineage of pancreatic neoplasms.
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Efficacy of Salmonella typhimurium A1-R versus chemotherapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX).
J. Cell. Biochem.
PUBLISHED: 01-13-2014
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The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on pancreatic cancer patient-derived orthotopic xenografts (PDOX). The PDOX model was originally established from a pancreatic cancer patient in SCID-NOD mice. The pancreatic cancer PDOX was subsequently transplanted by surgical orthotopic implantation (SOI) in transgenic nude red fluorescent protein (RFP) mice in order that the PDOX stably acquired red fluorescent protein (RFP)-expressing stroma for the purpose of imaging the tumor after passage to non-transgenic nude mice in order to visualize tumor growth and drug efficacy. The nude mice with human pancreatic PDOX were treated with A1-R or standard chemotherapy, including gemcitabine (GEM), which is first-line therapy for pancreatic cancer, for comparison of efficacy. A1-R treatment significantly reduced tumor weight, as well as tumor fluorescence area, compared to untreated control (P?=?0.011), with comparable efficacy of GEM, CDDP, and 5-FU. Histopathological response to treatment was defined according to Evans's criteria and A1-R had increased efficacy compared to standard chemotherapy. The present report is the first to show that A1-R is effective against a very low-passage patient tumor, in this case, pancreatic cancer. The data of the present report suggest A1-1 will have clinical activity in pancreatic cancer, a highly lethal and treatment-resistant disease and may be most effectively used in combination with other agents.
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Role of neoadjuvant therapy in the multimodality treatment of older patients with pancreatic cancer.
J. Am. Coll. Surg.
PUBLISHED: 01-03-2014
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A well-defined treatment strategy for elderly patients with resectable pancreatic cancer is lacking. Multiple reports have described highly selected older cancer patients who have successfully undergone pancreatectomy. However, multimodality therapy is essential for long-term survival, and elderly patients are at high risk for not receiving adjuvant therapy postoperatively. We sought to describe the treatment patterns and outcomes of a series of elderly patients with pancreatic cancer who were treated with a multimodality strategy that liberally used neoadjuvant therapy.
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Transport properties of pancreatic cancer describe gemcitabine delivery and response.
J. Clin. Invest.
PUBLISHED: 01-03-2014
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The therapeutic resistance of pancreatic ductal adenocarcinoma (PDAC) is partly ascribed to ineffective delivery of chemotherapy to cancer cells. We hypothesized that physical properties at vascular, extracellular, and cellular scales influence delivery of and response to gemcitabine-based therapy.
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SMAD4 regulates cell motility through transcription of N-cadherin in human pancreatic ductal epithelium.
PLoS ONE
PUBLISHED: 01-01-2014
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Expression of the cellular adhesion protein N-cadherin is a critical event during epithelial-mesenchymal transition (EMT). The SMAD4 protein has been identified as a mediator of transforming growth factor-? (TGF-?) superfamily signaling, which regulates EMT, but the mechanisms linking TGF-? signaling to N-cadherin expression remain unclear. When the TGF-? pathway is activated, SMAD proteins, including the common mediator SMAD4, are subsequently translocated into the nucleus, where they influence gene transcription via SMAD binding elements (SBEs). Here we describe a mechanism for control of CDH2, the gene encoding N-cadherin, through the canonical TGF?-SMAD4 pathway. We first identified four previously undescribed SBEs within the CDH2 promoter. Using telomerase immortalized human pancreatic ductal epithelium, we found that TGF-? stimulation prompted specific SMAD4 binding to all four SBEs. Luciferase reporter and SMAD4-knockdown experiments demonstrated that specific SMAD4 binding to the SBE located at -3790 bp to -3795 bp within the promoter region of CDH2 was necessary for TGF-?-stimulated transcription. Expression of N-cadherin on the surface of epithelial cells facilitates motility and invasion, and we demonstrated that knockdown of SMAD4 causes decreased N-cadherin expression, which results in diminished migration and invasion of human pancreatic ductal epithelial cells. Similar reduction of cell motility was produced after CDH2 knockdown. Together, these findings suggest that SMAD4 is critical for the TGF-?-driven upregulation of N-cadherin and the resultant invasive phenotype of human pancreatic ductal epithelial cells during EMT.
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Cooperativity of oncogenic K-ras and downregulated p16/INK4A in human pancreatic tumorigenesis.
PLoS ONE
PUBLISHED: 01-01-2014
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Activation of K-ras and inactivation of p16 are the most frequently identified genetic alterations in human pancreatic epithelial adenocarcinoma (PDAC). Mouse models engineered with mutant K-ras and deleted p16 recapitulate key pathological features of PDAC. However, a human cell culture transformation model that recapitulates the human pancreatic molecular carcinogenesis is lacking. In this study, we investigated the role of p16 in hTERT-immortalized human pancreatic epithelial nestin-expressing (HPNE) cells expressing mutant K-ras (K-rasG12V). We found that expression of p16 was induced by oncogenic K-ras in these HPNE cells and that silencing of this induced p16 expression resulted in tumorigenic transformation and development of metastatic PDAC in an orthotopic xenograft mouse model. Our results revealed that PI3K/Akt, ERK1/2 pathways and TGF? signaling were activated by K-ras and involved in the malignant transformation of human pancreatic cells. Also, p38/MAPK pathway was involved in p16 up-regulation. Thus, our findings establish an experimental cell-based model for dissecting signaling pathways in the development of human PDAC. This model provides an important tool for studying the molecular basis of PDAC development and gaining insight into signaling mechanisms and potential new therapeutic targets for altered oncogenic signaling pathways in PDAC.
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The expression of PTEN is associated with improved prognosis in patients with ampullary adenocarcinoma after pancreaticoduodenectomy.
Arch. Pathol. Lab. Med.
PUBLISHED: 10-31-2013
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Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Somatic mutations of PTEN occur in many tumors including those of the gastrointestinal and hepatobiliary tracts. Loss of PTEN expression is associated with poor prognosis in patients with metastatic colonic adenocarcinoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma, and pancreatic ductal adenocarcinoma.
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Pancreatic neuroendocrine neoplasms: diagnosis and management.
Abdom Imaging
PUBLISHED: 09-04-2013
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Pancreatic neuroendocrine neoplasms are uncommon but rising in incidence. There have been recent changes in the WHO nomenclature and a newly proposed American Joint Committee on Cancer TNM staging, which complement each other. These neoplasms are of great medical and radiological interest because of their diverse presenting features and imaging appearances. There is an increased role for both anatomic and functional imaging in the assessment of these neoplasms. A review of the nomenclature, staging, and imaging is presented in this paper.
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Complications of Whipple surgery: imaging analysis.
Abdom Imaging
PUBLISHED: 09-04-2013
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The purpose of this article is to describe and illustrate anatomic findings after the Whipple procedure, and the appearance of its complications, on imaging.
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Radiographic Tumor-Vein Interface as a Predictor of Intraoperative, Pathologic, and Oncologic Outcomes in Resectable and Borderline Resectable Pancreatic Cancer.
J. Gastrointest. Surg.
PUBLISHED: 07-25-2013
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Venous resection may be required to achieve complete resection of pancreatic cancers. We assessed the ability of radiographic criteria to predict the need for superior mesenteric-portal vein (SMV-PV) resection and the presence of histologic vein invasion.
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Feasibility study of EUS-NOTES as a novel approach for pancreatic cancer staging and therapy: an international collaborative study.
Hepatogastroenterology
PUBLISHED: 07-24-2013
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EUS guided Natural Orifice Transluminal Endoscopic Surgery (NOTES) could be a potentially viable approach for pancreatic surgery. EUS-guided access through the stomach wall may prove to be a safe and effective method for accessing the pancreas. The aim of the study was to assess the EUS-guided diagnostic and therapeutic procedures during NOTES for both anterior and posterior approach of the pancreas.
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Treatment Sequencing for Resectable Pancreatic Cancer: Influence of Early Metastases and Surgical Complications on Multimodality Therapy Completion and Survival.
J. Gastrointest. Surg.
PUBLISHED: 07-17-2013
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Barriers to multimodality therapy (MMT) completion among patients with resectable pancreatic adenocarcinoma include early cancer progression and postoperative major complications (PMC). We sought to evaluate the influence of these factors on MMT completion rates of patients treated with neoadjuvant therapy (NT) and surgery-first (SF) approaches. We evaluated all operable patients treated for clinically resectable pancreatic head adenocarcinoma at our institution from 2002 to 2007. Rates of MMT completion, 90-day PMC, and overall survival (OS) were evaluated. Ninety-five of 115 (83 %) NT and 29/50 (58 %) SF patients completed MMT. Patients who completed MMT lived longer than those who did not (36 vs. 11 months, p?
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Clinicopathologic features and prognosis of duodenal adenocarcinoma and comparison with ampullary and pancreatic ductal adenocarcinoma.
Hum. Pathol.
PUBLISHED: 06-05-2013
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Because of the rarity of duodenal adenocarcinoma (DAC), the clinicopathologic features and prognostication data for DAC are limited. There are no published studies directly comparing the prognosis of DAC to that of ampullary adenocarcinoma (AA) and of pancreatic ductal adenocarcinoma (PDA) after resection. In this study, we examined the clinicopathologic features of 68 patients with DAC, 92 patients with AA, and 126 patients with PDA who underwent resection. Patient clinicopathologic and survival information were extracted from medical records. Statistical analysis was performed using Statistical Package for the Social Sciences with 2-sided significance level of .05. Patients with DAC had higher American Joint Committee on Cancer (AJCC) stage than AA patients (P = .001). Lymph node metastasis (P = .013) and AJCC stage (P = .02) correlated with overall survival in DAC patients. Patients with DAC or AA had lower frequencies of lymph node metastasis and positive margin and better survival than those with PDA (P < .05). However, no differences in nodal metastasis, margin status, or survival were observed between DAC patients and those with AA. Our study showed that lymph node metastasis and AJCC stage are important prognostic factors for overall survival in DAC patients. Patients with DAC had less frequent nodal metastasis and better prognosis than those with PDA. There was no significant difference in prognosis between DAC and AA.
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Morbidity and Mortality after Pancreaticoduodenectomy in Patients with Borderline Resectable Type C Clinical Classification.
J. Gastrointest. Surg.
PUBLISHED: 06-04-2013
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We previously described the clinical classification of patients with resectable pancreatic tumor anatomy but marginal performance status (PS) or reversible comorbidities as "borderline resectable type C" (BR-C). This study was designed to analyze the incidence and risk factors for post-pancreaticoduodenectomy (PD) morbidity/mortality in a multi-institutional cohort of BR-C patients.
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Resection of at-risk mesenteric lymph nodes is associated with improved survival in patients with small bowel neuroendocrine tumors.
World J Surg
PUBLISHED: 05-10-2013
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Neuroendocrine tumors of the small intestine commonly metastasize to regional lymph nodes (LNs). Single-institution reports suggest that removal of LNs improves outcome, but comprehensive data are lacking. We hypothesized that the extent of lymphadenectomy reported in a large administrative database would be associated with overall survival for jejunal and ileal neuroendocrine tumors.
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Pancreatic intraepithelial neoplasia and histological changes in non-neoplastic pancreas associated with neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma.
Histopathology
PUBLISHED: 04-16-2013
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To study the histological changes in non-neoplastic pancreas and the effects on pancreatic intraepithelial neoplasia (PanIN) after neoadjuvant chemoradiation therapy (NCRT) for pancreatic ductal adenocarcinoma (PDAC).
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Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer.
HPB (Oxford)
PUBLISHED: 04-02-2013
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The purpose of this study was to determine the relationship between carbohydrate antigen (CA) 19-9 levels and outcome in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy (NT).
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A focused curriculum in surgical oncology for the third-year medical students.
J. Surg. Res.
PUBLISHED: 04-02-2013
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Educating medical students in surgical subspecialty fields can be challenging, and the optimal timing and curriculum remain unknown. Despite advocacy for earlier exposure, competing core clerkship rotations often leave little time for subspecialty fields. We report our experience with a novel, short, and focused curriculum in surgical oncology for the third-year medical students.
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Race does not impact pancreatic cancer treatment and survival in an equal access federal health care system.
Ann. Surg. Oncol.
PUBLISHED: 03-27-2013
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Black patients with pancreatic adenocarcinoma (PDAC) have been reported to undergo surgical resection less frequently and to have a shorter overall survival duration than white patients. We sought to determine whether disparities in clinical management and overall survival exist between black and white patients with PDAC treated in an equal access health care system.
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Predicting the risks of venous thromboembolism versus post-pancreatectomy haemorrhage: analysis of 13?771 NSQIP patients.
HPB (Oxford)
PUBLISHED: 03-20-2013
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The fear of an early post-pancreatectomy haemorrhage (PPH) may prevent surgeons from prescribing post-operative venous thromboembolism (VTE) chemoprophylaxis. The primary hypothesis of this study was that the national post-pancreatectomy early PPH rate was lower than the rate of VTE. The secondary hypothesis was that patients at high risk for post-discharge VTE could be identified, potentially facilitating the selective use of extended chemoprophylaxis.
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Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.
Nature
PUBLISHED: 02-21-2013
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Cancer cells have metabolic dependencies that distinguish them from their normal counterparts. Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes. Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into ?-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours.
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Frequency and intensity of postoperative surveillance after curative treatment of pancreatic cancer: a cost-effectiveness analysis.
Ann. Surg. Oncol.
PUBLISHED: 02-14-2013
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Few data exist to guide oncologic surveillance following curative treatment of pancreatic cancer. We sought to identify a rational, cost-effective postoperative surveillance strategy.
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The Cost-Effectiveness of Neoadjuvant Chemoradiation is Superior to a Surgery-First Approach in the Treatment of Pancreatic Head Adenocarcinoma.
Ann. Surg. Oncol.
PUBLISHED: 02-10-2013
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In treating pancreatic cancer, there is no clearly defined optimal sequence of chemotherapy, radiation therapy and surgery. Therefore, cost-effectiveness should be considered. The objective of this study was to compare cost and outcomes between a surgery-first approach versus neoadjuvant chemoradiation followed by surgery for resectable pancreatic head cancer.
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Use of EUS-FNA in diagnosing pancreatic neoplasm without a definitive mass on CT.
Gastrointest. Endosc.
PUBLISHED: 01-29-2013
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Diagnosis of pancreatic neoplasm is challenging in patients with inconclusive findings on pancreatic multidetector row CT (MDCT).
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A High-Fat Diet Activates Oncogenic Kras and COX2 to Induce Development of Pancreatic Ductal Adenocarcinoma in Mice.
Gastroenterology
PUBLISHED: 01-25-2013
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Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis. The oncogenic form of KRAS is expressed during early stages of PDAC development and is detected in almost all of these tumors. However, there is evidence that mutant KRAS requires an additional stimulus to activate its full oncogenic activity and that this stimulus involves the inflammatory response. We investigated whether the inflammation induced by a high-fat diet, and the accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity during pancreatic carcinogenesis in mice.
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Deciphering the mechanisms of tumorigenesis in human pancreatic ductal epithelial cells.
Clin. Cancer Res.
PUBLISHED: 01-22-2013
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The most common genetic lesions in pancreatic ductal adenocarcinoma (PDAC) have been identified. However, significant gaps still exist in our understanding of how such genetic alterations act in concert to induce PDAC development. In this study, we investigated the mechanism of tumorigenic transformation in the immortalized human pancreatic ductal epithelial (HPDE) cell line by sequentially introducing PDAC signature alterations into this cell line.
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Endoscopic management of duodenal adenomas in familial adenomatous polyposis--a single-center experience.
Dig. Dis. Sci.
PUBLISHED: 07-09-2011
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Duodenal lesions (DLS) are common in patients with familial adenomatosis polyposis (FAP), and screening for duodenal adenocarcinoma (DA) is currently recommended. Endoscopic treatment of DLS is controversial.
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Pathologic complete response to neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma is associated with a better prognosis.
Ann Diagn Pathol
PUBLISHED: 07-03-2011
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In patients with pancreatic ductal adenocarcinoma (PDA) who received neoadjuvant therapy and pancreatectomy, pathologic complete response (pCR) is rarely observed and the prognostic significance of pCR is not clear. In this study, we identified 11 patients with pCR (2.5%) from 442 patients with PDA who received neoadjuvant treatment and pancreatectomy from 1995 to 2010. There were 6 men and 5 women, with a median age of 61 years. Four patients had either synchronous or history of extrapancreatic cancer. Five patients received neoadjuvant chemotherapy followed by chemoradiation, and 6 received chemoradiation alone. Ten patients had pancreaticoduodenectomy, and 1 had distal pancreatectomy. Scar and chronic pancreatitis consistent with therapy effect were present in all cases (100%). Pancreatic intraepithelial neoplasia (PanIN) 3/carcinoma in situ was present in 5 cases, and PanIN1 and PanIN2 in 5 cases. However, no residual invasive carcinoma or lymph node metastasis was identified in all cases. Follow-up information was available in 10 patients. Follow-up time ranges from 6 to 194 months (median, 63 months). During the follow-up, 3 patients died of other causes, and 1 developed a second primary PDA in the tail of the pancreas at 84 months after the initial pancreaticoduodenectomy and died at 105 months after the initial diagnosis of PDA. The other 6 patients were alive with no evidence of disease. Patients with pCR had a better survival than did those who had posttherapy stage I or IIA disease (P < .001). Patients with PDA who received neoadjuvant therapy and had pCR in pancreatectomy are rare but have a better prognosis.
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Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression.
J. Clin. Oncol.
PUBLISHED: 06-27-2011
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This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC).
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Histologic grading of the extent of residual carcinoma following neoadjuvant chemoradiation in pancreatic ductal adenocarcinoma: a predictor for patient outcome.
Cancer
PUBLISHED: 06-11-2011
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Several grading schemes for the extent of residual tumor in posttreatment pancreaticoduodenectomy (PD) specimens have been proposed. However, the prognostic significance of these grading schemes is unknown.
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ALDH activity selectively defines an enhanced tumor-initiating cell population relative to CD133 expression in human pancreatic adenocarcinoma.
PLoS ONE
PUBLISHED: 05-06-2011
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Multiple studies in recent years have identified highly tumorigenic populations of cells that drive tumor formation. These cancer stem cells (CSCs), or tumor-initiating cells (TICs), exhibit properties of normal stem cells and are associated with resistance to current therapies. As pancreatic adenocarcinoma is among the most resistant human cancers to chemo-radiation therapy, we sought to evaluate the presence of cell populations with tumor-initiating capacities in human pancreatic tumors. Understanding which pancreatic cancer cell populations possess tumor-initiating capabilities is critical to characterizing and understanding the biology of pancreatic CSCs towards therapeutic ends.
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Histologic tumor involvement of superior mesenteric vein/portal vein predicts poor prognosis in patients with stage II pancreatic adenocarcinoma treated with neoadjuvant chemoradiation.
Cancer
PUBLISHED: 04-25-2011
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Studies have shown that superior mesenteric vein (SMV)/portal vein (PV) resection with pancreaticoduodenectomy (PD) is safe and feasible for patient with pancreatic adenocarcinoma (PAC). However, the prognostic significance of tumor involvement of the resected vein in patients who received neoadjuvant therapy is unclear.
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Effect of neoadjuvant chemoradiation and surgical technique on recurrence of localized pancreatic cancer.
J. Gastrointest. Surg.
PUBLISHED: 04-23-2011
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To determine the influence of neoadjuvant chemoradiation and standardized dissection of the superior mesenteric artery upon the oncologic outcome of patients with localized pancreatic adenocarcinoma.
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Self-expanding metal stents for biliary drainage in patients with resectable pancreatic cancer: single-center experience with 79 cases.
Dig. Dis. Sci.
PUBLISHED: 04-05-2011
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To study pre-operative and peri-operative course and outcome on follow up after pancreaticoduodenenctomy (PD) for resectable pancreatic cancer amongst patients receiving self-expanding metal stents (SEMS).
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Identification of cancer stem cells in human gastrointestinal carcinoid and neuroendocrine tumors.
Gastroenterology
PUBLISHED: 03-04-2011
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Metastatic gastrointestinal neuroendocrine tumors (NETs) frequently are refractory to chemotherapy. Chemoresistance in various malignancies has been attributed to cancer stem cells (CSCs). We sought to identify gastrointestinal neuroendocrine CSCs (N-CSCs) in surgical specimens and a NET cell line and to characterize novel N-CSC therapeutic targets.
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Combined esophagectomy and pancreaticoduodenectomy: expanded indication for supercharged jejunal interposition.
J. Gastrointest. Surg.
PUBLISHED: 02-23-2011
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Combined pancreaticoduodenectomy and esophagectomy poses a challenge for reconstruction.
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Survival and quality of life of patients with resected pancreatic adenocarcinoma treated with adjuvant interferon-based chemoradiation: a phase II trial.
Ann. Surg. Oncol.
PUBLISHED: 02-22-2011
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We conducted a phase II trial to assess the survival duration and quality of life of patients who received adjuvant interferon-based chemoradiation for pancreatic adenocarcinoma after pancreaticoduodenectomy.
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Molecular profiling of direct xenograft tumors established from human pancreatic adenocarcinoma after neoadjuvant therapy.
Ann. Surg. Oncol.
PUBLISHED: 02-11-2011
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Pancreatic adenocarcinoma is among the most resistant of human cancers, yet specific mechanisms of treatment resistance remain poorly understood. Models to study pancreatic cancer resistance remain limited and should reflect in vivo changes that occur within patient tumors. We sought to identify consistent, differentially expressed genes between treatment of naive pancreatic tumors and those exposed to neoadjuvant therapy using a strict, in vivo direct xenograft model system.
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Post-therapy pathologic stage and survival in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiation.
Cancer
PUBLISHED: 01-07-2011
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Neoadjuvant chemoradiation before surgery is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC). However, analysis of prognostic factors is limited for patients with PDAC treated with neoadjuvant chemoradiation and pancreaticoduodenectomy (PD).
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Current status of adjuvant therapy for pancreatic cancer.
Oncologist
PUBLISHED: 11-02-2010
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In this article, we review the rationale for and outcomes associated with the use of adjuvant and neoadjuvant therapy for resectable and borderline resectable cancer of the pancreatic head and uncinate process. Localized pancreatic cancer is a systemic disease that requires nonoperative therapies to minimize the local and systemic recurrences that almost invariably occur in the absence of such therapy, even following complete surgical resection. A well-defined role exists for the systemic administration of gemcitabine or 5-fluorouracil in the postoperative setting. Although the survival benefit associated with adjuvant chemoradiation has not been as rigorously defined, its use is supported by extensive historic experience; chemoradiation should be considered particularly for patients at high risk for local recurrence. Delivery of chemotherapy and/or chemoradiation prior to surgery has multiple potential advantages, although the superiority of neoadjuvant therapy over standard postoperative therapy has yet to be demonstrated. Neoadjuvant therapy may be particularly beneficial among patients with borderline resectable cancers. Although the existing literature is confusing, and indeed controversial, available evidence suggests that systemic chemotherapy and/or chemoradiation should be offered to all patients with pancreatic cancer who undergo potentially curative resection. Well-designed prospective trials are needed to define the optimal adjuvant or neoadjuvant therapy strategy for these patients.
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High levels of expression of human stromal cell-derived factor-1 are associated with worse prognosis in patients with stage II pancreatic ductal adenocarcinoma.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-23-2010
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Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, have been shown to mediate invasiveness and metastatic behavior in a number of cancers, including ovarian, prostate, bladder, breast, and pancreatic cancers. The expression and significance of SDF-1 in pancreatic ductal adenocarcinoma (PDA) have not been systematically studied.
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Defective feedback regulation of NF-kappaB underlies Sjogrens syndrome in mice with mutated kappaB enhancers of the IkappaBalpha promoter.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-09-2010
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Feedback regulation of transcription factor NF-kappaB by its inhibitor IkappaBalpha plays an essential role in control of NF-kappaB activity. To understand the biological significance of IkappaBalpha-mediated feedback regulation of NF-kappaB, we generated mice harboring mutated kappaB enhancers in the promoter of the IkappaBalpha gene (IkappaBalpha(M/M)) to inhibit NF-kappaB-regulated IkappaBalpha expression. Here, we report that these mutant mice are defective in NF-kappaB-induced expression of IkappaBalpha. This defective feedback regulation of NF-kappaB by IkappaBalpha not only altered activity of NF-kappaB, but also the expression of NF-kappaB-regulated genes. As a result, IkappaBalpha(M/M), the homozygous knock-in mice with mutated kappaB enhancers in the IkappaBalpha promoter, acquire shorten life span, hypersensitivity to septic shock, abnormal T-cell development and activation, and Sjögrens Syndrome. These findings therefore demonstrate that the IkappaBalpha-mediated feedback regulation of NF-kappaB has an essential role in controlling T-cell development and functions, provide mechanistic insight into the development of Sjögrens Syndrome, and suggest the potential of NF-kappaB signaling as a therapeutic target for Sjögrens Syndrome and other autoimmune diseases.
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High levels of nucleolar expression of nucleolin are associated with better prognosis in patients with stage II pancreatic ductal adenocarcinoma.
Clin. Cancer Res.
PUBLISHED: 07-13-2010
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Nucleolin is a major nucleolar protein that has been shown to be overexpressed in rapidly dividing cells and plays an essential role in cell proliferation and survival. However, the expression and significance of nucleolin in pancreatic ductal adenocarcinoma (PDA) have not been studied.
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Intravenous delivery of the plasma fraction of stored packed erythrocytes promotes pancreatic cancer growth in immunocompetent mice.
Cancer
PUBLISHED: 06-22-2010
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Perioperative blood transfusion in pancreatic cancer patients has been linked to decreased survival; however, a causal mechanism has not been determined. During the processing and storage of packed erythrocytes, biologically active molecules accumulated in the acellular plasma fraction; therefore, the authors hypothesized that the plasma fraction of stored packed erythrocytes promoted tumor progression.
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Overexpression of receptor tyrosine kinase Axl promotes tumor cell invasion and survival in pancreatic ductal adenocarcinoma.
Cancer
PUBLISHED: 04-07-2010
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The receptor tyrosine kinase Axl has been reported to be overexpressed in a variety of human cancers. Although previous studies have identified the role of Axl in the transformation, proliferation, survival, and invasion in cancers, the expression and functions of Axl in pancreatic cancer have not been studied in detail.
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Serum CA 19-9 as a marker of resectability and survival in patients with potentially resectable pancreatic cancer treated with neoadjuvant chemoradiation.
Ann. Surg. Oncol.
PUBLISHED: 02-17-2010
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The role of carbohydrate antigen (CA) 19-9 in the evaluation of patients with resectable pancreatic cancer treated with neoadjuvant therapy prior to planned surgical resection is unknown. We evaluated CA 19-9 as a marker of therapeutic response, completion of therapy, and survival in patients enrolled on two recently reported clinical trials.
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Role of EUS-FNA-based cytology in the diagnosis of mucinous pancreatic cystic lesions: a systematic review and meta-analysis.
Dig. Dis. Sci.
PUBLISHED: 02-12-2010
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Preoperative diagnosis of malignancy in pancreatic cystic lesions (PCLs) remains challenging. Most non-mucinous cystic lesions (NMCLs) are benign, but mucinous cystic lesions (MCLs) are more likely to be premalignant or malignant.
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Metastatic adult granulosa cell tumor mimicking a benign pancreatic cyst.
Ann Diagn Pathol
PUBLISHED: 02-11-2010
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We report an unusual case of metastatic adult granulosa cell tumor in the head of pancreas mimicking a benign pancreatic cyst in a 43-year-old female. Clinically, it was considered a benign cyst of the pancreas based on its appearance by imaging and that repeated fine-needle aspiration and cytologic examination of cystic fluid failed to identify malignant cells. The cyst in her pancreas grew slowly during the 15 months of close follow-up. Subsequent drainage and open biopsy of the cyst wall established the diagnosis of metastatic adult granulosa cell tumor that was confirmed in pancreaticoduodenectomy specimen. Immunohistochemical study and clinical history were critical to make the correct diagnosis and to differentiate this tumor from other more commonly encountered cystic neoplasms of the pancreas.
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Multidisciplinary management strategy for incidental cystic lesions of the pancreas.
J. Am. Coll. Surg.
PUBLISHED: 01-21-2010
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At our institution, incidental pancreatic cysts are frequently identified in asymptomatic patients undergoing routine imaging for staging of nonpancreatic malignancies. Management of these patients is unclear because a small but significant number of incidental pancreatic cysts are malignant.
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Generation of orthotopic and heterotopic human pancreatic cancer xenografts in immunodeficient mice.
Nat Protoc
PUBLISHED: 10-29-2009
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For decades, xenografts using well-established human tumor cell lines have been the most commonly used models to study human cancers in mice. More recently, human tumors implanted directly into immunodeficient mice have become increasingly popular as evidence accrues that they more accurately recapitulate features of patient tumors. Here we describe our protocols for the orthotopic and heterotopic implantation of pancreatic cancer cell lines and freshly isolated patient tumors into immunodeficient mice. We also describe procedures for the digestion of tumors into single-cell suspensions for the isolation of subpopulations of tumor cells. Orthotopic or heterotopic implantation of established cell lines requires 1-2 h, with 1-cm tumors arising after 2-5 weeks. Engraftment of patient tumor samples takes approximately 2 h and growth of palpable tumor requires approximately 14 weeks. Once established, direct xenograft tumors require 2 and 5 h for heterotopic and orthotopic implantation, respectively, and 5-6 weeks for palpable tumor growth.
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TrkBT1 induces liver metastasis of pancreatic cancer cells by sequestering Rho GDP dissociation inhibitor and promoting RhoA activation.
Cancer Res.
PUBLISHED: 09-22-2009
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Many genetic and molecular alterations, such as K-ras mutation and NF-kappaB activation, have been identified in pancreatic cancer. However, the mechanisms by which pancreatic cancer metastasizes still remain to be determined. Although we previously showed that the tropomyosin-related kinase B (TrkB) was significantly correlated with the development of liver metastasis, its function in pancreatic cancer metastasis remained unresolved. In the present study, we showed that overexpressed TrkB is an alternatively spliced transcript variant of TrkB (TrkBT1) with a unique COOH-terminal 12-amino acid sequence and is mainly localized in the cytoplasm. Our results showed that overexpression of Flag-tagged TrkBT1 but not a Flag-tagged TrkBT1 COOH-terminal deletion mutant (Flag-TrkBT1DeltaC) in nonmetastatic pancreatic cancer cells enhanced cell proliferation, promoted formation of colonies in soft agar, stimulated tumor cell invasion, and induced liver metastasis in an orthotopic xenograft mouse model of pancreatic cancer. TrkBT1 interacted with Rho GDP dissociation inhibitor (GDI) in vivo, but Flag-TrkBT1DeltaC did not. Furthermore, overexpression of Flag-TrkBT1 and knockdown of RhoGDI expression by RhoGDI short hairpin RNAs promoted RhoA activation, but Flag-TrkBT1DeltaC overexpression did not. Therefore, our results showed that TrkBT1 overexpression induces liver metastasis of pancreatic cancer and uncovered a unique signaling mechanism by which TrkBT1 sequesters GDI and activates RhoA signaling.
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K-Ras promotes angiogenesis mediated by immortalized human pancreatic epithelial cells through mitogen-activated protein kinase signaling pathways.
Mol. Cancer Res.
PUBLISHED: 06-09-2009
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Activating point mutations in the K-Ras oncogene are among the most common genetic alterations in pancreatic cancer, occurring early in the progression of the disease. However, the function of mutant K-Ras activity in tumor angiogenesis remains poorly understood. Using human pancreatic duct epithelial (HPDE) and K-Ras4B(G12V)-transformed HPDE (HPDE-KRas) cells, we show that activated K-Ras significantly enhanced the production of angiogenic factors including CXC chemokines and vascular endothelial growth factor (VEGF). Western blot analysis revealed that K-Ras activation promoted the phosphorylation of Raf/mitogen-activated protein kinase kinase-1/2 (MEK1/2) and expression of c-Jun. MEK1/2 inhibitors, U0126 and PD98059, significantly inhibited the secretion of both CXC chemokines and VEGF, whereas the c-Jun NH(2)-terminal kinase inhibitor SP600125 abrogated only CXC chemokine production. To further elucidate the biological functions of oncogenic K-Ras in promoting angiogenesis, we did in vitro invasion and tube formation assays using human umbilical vein endothelial cells (HUVEC). HUVEC cocultured with HPDE-KRas showed significantly enhanced invasiveness and tube formation as compared with either control (without coculture) or coculture with HPDE. Moreover, SB225002 (a CXCR2 inhibitor) and 2C3 (an anti-VEGF monoclonal antibody) either alone or in a cooperative manner significantly reduced the degree of both Ras-dependent HUVEC invasiveness and tube formation. Similar results were obtained using another pair of immortalized human pancreatic duct-derived cells, E6/E7/st and its oncogenic K-Ras variant, E6/E7/Ras/st. Taken together, our results suggest that angiogenesis is initiated by paracrine epithelial secretion of CXC chemokines and VEGF downstream of activated oncogenic K-Ras, and that this vascular maturation is in part dependent on MEK1/2 and c-Jun signaling.
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The recognition and surgical management of heritable lesions of the pancreas.
Surg. Oncol. Clin. N. Am.
PUBLISHED: 03-19-2009
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Our knowledge regarding the inherited factors that lead to the development of lesions within the pancreas is clearly incomplete. This article addresses clinical issues in patients at moderate-to-high risk for pancreatic malignancy, with special emphasis on the recognition and diagnosis of known genetic syndromes. Using the current available information, the authors attempt to equip the practicing surgeon with critical information to increase clinical suspicion for heritable syndromes and inform specific surgical management. Additionally, this article is meant to encourage the practicing surgeon to participate in the genetic testing/screening, cancer surveillance, and prevention activities of patients who have heritable cancer syndromes and associated pancreatic lesions that require surgery.
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Influence of obesity on cancer-related outcomes after pancreatectomy to treat pancreatic adenocarcinoma.
Arch Surg
PUBLISHED: 03-18-2009
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To examine the influence of obesity, as measured by body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), on clinicopathologic factors and survival after pancreatectomy to treat adenocarcinoma.
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Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma.
Ann. Surg. Oncol.
PUBLISHED: 02-05-2009
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Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.
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The fallen one: the inferior parathyroid gland that descends into the mediastinum.
J. Am. Coll. Surg.
PUBLISHED: 01-21-2009
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Inferior parathyroid glands are located along the embryologic migration path of the thymus and can rest in the thyrothymic ligament or anterior mediastinum. Our nomenclature system designates these glands as "fallen" (type F) glands. This study reviews our experience with type F parathyroid glands to determine which can be retrieved successfully through a cervical incision.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.