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Sample records for human pancreatic duct

  1. Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

    OpenAIRE

    Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

    2017-01-01

    Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring...

  2. Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport

    DEFF Research Database (Denmark)

    Novak, Ivana; Hede, Susanne; Hansen, Mette

    2007-01-01

    , it was found that 58% of PANC-1 cells responded to adenosine, whereas only 9% of CFPAC-1 cells responded. Adenosine elicited Ca(2+) signals only in a few rat and human duct cells, which did not seem to correlate with Cl(-) signals. A(2A) receptors were localized in the luminal membranes of rat pancreatic ducts......, plasma membrane of many PANC-1 cells, but only a few CFPAC-1 cells. Taken together, our data indicate that A(2A) receptors open Cl(-) channels in pancreatic ducts cells with functional CFTR. We propose that adenosine can stimulate pancreatic secretion and, thereby, is an active player in the acini...

  3. Ion Transport in Human Pancreatic Duct Epithelium, Capan-1 Cells, Is Regulated by Secretin, VIP, Acetylcholine, and Purinergic Receptors

    DEFF Research Database (Denmark)

    Wang, Jing; Novak, Ivana

    2013-01-01

    OBJECTIVES: The objective of the study was to establish a solid model of polarized epithelium for human pancreatic ducts, where electrical parameters could be measured as indicators of ion transport. Further, we aimed to determine functional expression of several receptors, in particular, puriner...... transport in human pancreatic duct epithelium, Capan-1 cells, is regulated by secretin, VIP, acetylcholine, adenosine, and purinergic P2 receptors; and this human model has a good potential for studies of physiology and pathophysiology of pancreatic duct ion transport....

  4. Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming.

    Directory of Open Access Journals (Sweden)

    Nathalie Swales

    Full Text Available AIMS/HYPOTHESIS: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3. In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it. METHODS: The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was measured employing genome wide mRNA profiling. By modulation of the Delta-Notch signaling or addition of pancreatic endocrine transcription factors Myt1, MafA and Pdx1 we intended to improve the reprogramming. RESULTS: Ngn3 stimulates duct cells to express a focused set of genes that are characteristic for islet endocrine cells and/or neural tissues. This neuro-endocrine shift however, is incomplete with less than 10% of full duct-to-endocrine reprogramming achieved. Transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto-activation of this gene. Furthermore, pancreatic endocrine reprogramming of human duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1. CONCLUSIONS/INTERPRETATION: The results provide further insight into the plasticity of adult human duct cells and suggest measurable routes to enhance Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy in diabetes.

  5. Establishment of three-dimensional cultures of human pancreatic duct epithelial cells

    International Nuclear Information System (INIS)

    Gutierrez-Barrera, Angelica M.; Menter, David G.; Abbruzzese, James L.; Reddy, Shrikanth A.G.

    2007-01-01

    Three-dimensional (3D) cultures of epithelial cells offer singular advantages for studies of morphogenesis or the role of cancer genes in oncogenesis. In this study, as part of establishing a 3D culture system of pancreatic duct epithelial cells, we compared human pancreatic duct epithelial cells (HPDE-E6E7) with pancreatic cancer cell lines. Our results show, that in contrast to cancer cells, HPDE-E6E7 organized into spheroids with what appeared to be apical and basal membranes and a luminal space. Immunostaining experiments indicated that protein kinase Akt was phosphorylated (Ser473) and CTMP, a negative Akt regulator, was expressed in both HPDE-E6E7 and cancer cells. However, a nuclear pool of CTMP was detectable in HPDE-E6E7 cells that showed a dynamic concentrated expression pattern, a feature that further distinguished HPDE-E637 cells from cancer cells. Collectively, these data suggest that 3D cultures of HPDE-E6E7 cells are useful for investigating signaling and morphological abnormalities in pancreatic cancer cells

  6. Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

    DEFF Research Database (Denmark)

    Nielsen, Sonja K; Møllgård, Kjeld; Clement, Christian A

    2008-01-01

    Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct...... adenocarcinoma cell lines, PANC-1 and CFPAC-1. We show that the onset of Hh signaling from human embryogenesis to fetal development is associated with accumulation of Hh signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3 in the duct epithelium. Smo, Ptc, and Gli2 localized to primary...... cilia of PANC-1 and CFPAC-1 cells, which may maintain high levels of nonstimulated Hh pathway activity. These findings indicate that primary cilia are involved in pancreatic development and postnatal tissue homeostasis....

  7. ATP release, generation and hydrolysis in exocrine pancreatic duct cells

    DEFF Research Database (Denmark)

    Kowal, Justyna Magdalena; Yegutkin, G.G.; Novak, Ivana

    2015-01-01

    Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, ou...... may be important in pancreas physiology and potentially in pancreas pathophysiology....... aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan...

  8. In vitro modeling of human pancreatic duct epithelial cell transformation defines gene expression changes induced by K-ras oncogenic activation in pancreatic carcinogenesis.

    Science.gov (United States)

    Qian, Jiaying; Niu, Jiangong; Li, Ming; Chiao, Paul J; Tsao, Ming-Sound

    2005-06-15

    Genetic analysis of pancreatic ductal adenocarcinomas and their putative precursor lesions, pancreatic intraepithelial neoplasias (PanIN), has shown a multistep molecular paradigm for duct cell carcinogenesis. Mutational activation or inactivation of the K-ras, p16(INK4A), Smad4, and p53 genes occur at progressive and high frequencies in these lesions. Oncogenic activation of the K-ras gene occurs in >90% of pancreatic ductal carcinoma and is found early in the PanIN-carcinoma sequence, but its functional roles remain poorly understood. We show here that the expression of K-ras(G12V) oncogene in a near diploid HPV16-E6E7 gene immortalized human pancreatic duct epithelial cell line originally derived from normal pancreas induced the formation of carcinoma in 50% of severe combined immunodeficient mice implanted with these cells. A tumor cell line established from one of these tumors formed ductal cancer when implanted orthotopically. These cells also showed increased activation of the mitogen-activated protein kinase, AKT, and nuclear factor-kappaB pathways. Microarray expression profiling studies identified 584 genes whose expression seemed specifically up-regulated by the K-ras oncogene expression. Forty-two of these genes have been reported previously as differentially overexpressed in pancreatic cancer cell lines or primary tumors. Real-time PCR confirmed the overexpression of a large number of these genes. Immunohistochemistry done on tissue microarrays constructed from PanIN and pancreatic cancer samples showed laminin beta3 overexpression starting in high-grade PanINs and occurring in >90% of pancreatic ductal carcinoma. The in vitro modeling of human pancreatic duct epithelial cell transformation may provide mechanistic insights on gene expression changes that occur during multistage pancreatic duct cell carcinogenesis.

  9. The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells

    DEFF Research Database (Denmark)

    Hayashi, M.; Inagaki, A.; Novak, Ivana

    2016-01-01

    Adenosine modulates a wide variety of biological processes via adenosine receptors. In the exocrine pancreas, adenosine regulates transepithelial anion secretion in duct cells and is considered to play a role in acini-to-duct signaling. To identify the functional adenosine receptors and Cl......− channels important for anion secretion, we herein performed experiments on Capan-1, a human pancreatic duct cell line, using open-circuit Ussing chamber and gramicidin-perforated patch-clamp techniques. The luminal addition of adenosine increased the negative transepithelial potential difference (Vte......) in Capan-1 monolayers with a half-maximal effective concentration value of approximately 10 μM, which corresponded to the value obtained on whole-cell Cl− currents in Capan-1 single cells. The effects of adenosine on Vte, an equivalent short-circuit current (Isc), and whole-cell Cl− currents were inhibited...

  10. Purinergic receptors and calcium signalling in human pancreatic duct cell lines

    DEFF Research Database (Denmark)

    Hansen, Mette R; Krabbe, Simon; Novak, Ivana

    2008-01-01

    pancreatic duct cell lines PANC-1 and CFPAC-1. Expression of P2 receptors was examined using RT-PCR and immunocytochemistry. Both cell lines, and also Capan-1 cells, express RNA transcripts for the following receptors: P2Y1, P2Y2, P2Y4, P2Y6, P2Y11-14 and P2X1, P2X2, P2X4, P2X5, P2X6 and P2X7. Using Fura-2...... and single-cell imaging we tested effects of various nucleotide analogues on intracellular Ca(2+) signals in PANC-1 and CFPAC-1 cells. The cell lines responded to all nucleotides with the following efficiency: UTP >or= ATP = ATPgammaS > BzATP. ATP, UTP and ATPgammaS elicited oscillatory responses. Bz...

  11. Metabolism of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene in cultured human bronchus and pancreatic duct

    DEFF Research Database (Denmark)

    Harris, Curtis C.; Autrup, Herman; Stoner, Gary

    1977-01-01

    The metabolism of two carcinogenic polynuclear aro matic hydrocarbons, benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene, was studied in expiants of human pancreatic duct and bronchus cultured in a chemically defined medium. In cultured human bronchial mucosa, activity of aryl hydrocarbon hy...

  12. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis

    NARCIS (Netherlands)

    Cahen, Djuna L.; Gouma, Dirk J.; Nio, Yung; Rauws, Erik A. J.; Boermeester, Marja A.; Busch, Olivier R.; Stoker, Jaap; Lameris, Johan S.; Dijkgraaf, Marcel G. W.; Huibregtse, Kees; Bruno, Marco J.

    2007-01-01

    BACKGROUND: For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS: All symptomatic patients with chronic pancreatitis and a distal

  13. Neogenesis and proliferation of β-cells induced by human betacellulin gene transduction via retrograde pancreatic duct injection of an adenovirus vector

    International Nuclear Information System (INIS)

    Tokui, Yae; Kozawa, Junji; Yamagata, Kazuya; Zhang, Jun; Ohmoto, Hiroshi; Tochino, Yoshihiro; Okita, Kohei; Iwahashi, Hiromi; Namba, Mitsuyoshi; Shimomura, Iichiro; Miyagawa, Jun-ichiro

    2006-01-01

    Betacellulin (BTC) has been shown to have a role in the differentiation and proliferation of β-cells both in vitro and in vivo. We administered a human betacellulin (hBTC) adenovirus vector to male ICR mice via retrograde pancreatic duct injection. As a control, we administered a β-galactosidase adenovirus vector. In the mice, hBTC protein was mainly overexpressed by pancreatic duct cells. On immunohistochemical analysis, we observed features of β-cell neogenesis as newly formed insulin-positive cells in the duct cell lining or islet-like cell clusters (ICCs) closely associated with the ducts. The BrdU labeling index of β-cells was also increased by the betacellulin vector compared with that of control mice. These results indicate that hBTC gene transduction into adult pancreatic duct cells promoted β-cell differentiation (mainly from duct cells) and proliferation of pre-existing β-cells, resulting in an increase of the β-cell mass that improved glucose tolerance in diabetic mice

  14. Calcium influx pathways in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Hug, M J; Pahl, C; Novak, I

    1996-01-01

    A number of agonists increase intracellular Ca2+ activity, [Ca2+]i, in pancreatic ducts, but the influx/efflux pathways and intracellular Ca2+ stores in this epithelium are unknown. The aim of the present study was to characterise the Ca2+ influx pathways, especially their pH sensitivity, in nati...

  15. Morphological study of pancreatic duct in red jungle fowl | Kadhim ...

    African Journals Online (AJOL)

    Neither goblet cells nor ductal glands were found in the pancreatic ducts. Secretion of both neutral and sulfated materials by the epithelial lining the pancreatic ducts, suggesting that they are acting not only to facilitate the transport of the pancreatic juice, but also as a protective barrier to protect the gland from autodigestion.

  16. Pancreatic duct stones in patients with chronic pancreatitis: surgical outcomes.

    Science.gov (United States)

    Liu, Bo-Nan; Zhang, Tai-Ping; Zhao, Yu-Pei; Liao, Quan; Dai, Meng-Hua; Zhan, Han-Xiang

    2010-08-01

    Pancreatic duct stone (PDS) is a common complication of chronic pancreatitis. Surgery is a common therapeutic option for PDS. In this study we assessed the surgical procedures for PDS in patients with chronic pancreatitis at our hospital. Between January 2004 and September 2009, medical records from 35 patients diagnosed with PDS associated with chronic pancreatitis were retrospectively reviewed and the patients were followed up for up to 67 months. The 35 patients underwent ultrasonography, computed tomography, or both, with an overall accuracy rate of 85.7%. Of these patients, 31 underwent the modified Puestow procedure, 2 underwent the Whipple procedure, 1 underwent simple stone removal by duct incision, and 1 underwent pancreatic abscess drainage. Of the 35 patients, 28 were followed up for 4-67 months. There was no postoperative death before discharge or during follow-up. After the modified Puestow procedure, abdominal pain was reduced in patients with complete or incomplete stone clearance (P>0.05). Steatorrhea and diabetes mellitus developed in several patients during a long-term follow-up. Surgery, especially the modified Puestow procedure, is effective and safe for patients with PDS associated with chronic pancreatitis. Decompression of intraductal pressure rather than complete clearance of all stones predicts postoperative outcome.

  17. Molecular basis of potassium channels in pancreatic duct epithelial cells

    DEFF Research Database (Denmark)

    Hayashi, M.; Novak, Ivana

    2013-01-01

    Potassium channels regulate excitability, epithelial ion transport, proliferation, and apoptosis. In pancreatic ducts, K channels hyperpolarize the membrane potential and provide the driving force for anion secretion. This review focuses on the molecular candidates of functional K channels...... and pancreatic pathologies, including pancreatitis, cystic fibrosis, and cancer, in which the dysregulation or altered expression of K channels may be of importance....

  18. Reference values of MRI measurements of the common bile duct and pancreatic duct in children

    Energy Technology Data Exchange (ETDEWEB)

    Gwal, Kriti; Bedoya, Maria A.; Patel, Neal; Darge, Kassa; Anupindi, Sudha A. [University of Pennsylvania Perelman School of Medicine, Department of Radiology, The Children' s Hospital of Philadelphia, Philadelphia, PA (United States); Rambhatla, Siri J. [Beth Israel Medical Center, Department of Pediatrics, Newark, NJ (United States); Sreedharan, Ram R. [University of Pennsylvania, Departments of Gastroenterology, Hepatology and Nutrition, The Children' s Hospital of Philadelphia, Perelman School of Medicine, Philadelphia, PA (United States)

    2015-08-15

    Magnetic resonance imaging/cholangiopancreatography (MRI/MRCP) is now an essential imaging modality for the evaluation of biliary and pancreatic pathology in children, but there are no data depicting the normal diameters of the common bile duct (CBD) and pancreatic duct. Recognition of abnormal duct size is important and the increasing use of MRCP necessitates normal MRI measurements. To present normal MRI measurements for the common bile duct and pancreatic duct in children. In this retrospective study we searched all children ages birth to 10 years in our MR urography (MRU) database from 2006 until 2013. We excluded children with a history of hepatobiliary or pancreatic surgery. We stratified 204 children into five age groups and retrospectively measured the CBD and the pancreatic duct on 2-D axial and 3-D coronal T2-weighted sequences. We performed statistical analysis, using logistic and linear regressions to detect the age association of the visibility and size of the duct measurements. We used non-parametric tests to detect gender and imaging plane differences. Our study included 204 children, 106 (52%) boys and 98 (48%) girls, with a median age of 33 months (range 0-119 months). The children were distributed into five age groups. The common bile duct was visible in all children in all age groups. The pancreatic duct was significantly less visible in the youngest children, group 1 (54/67, 80.5%; P = 0.003) than in the oldest children, group 5 (22/22, 100%). In group 2 the pancreatic duct was seen in 19/21 (90.4%), in group 3 52/55 (94.5%), and in group 4 39/39 (100%). All duct measurements increased with age (P < 0.001; r-value > 0.423), and the incremental differences between ages were significant. The measurement variations between the axial and coronal planes were statistically significant (P < 0.001); however these differences were fractions of millimeters. For example, in group 1 the mean coronal measurement of the CBD was 2.1 mm and the axial

  19. Reference values of MRI measurements of the common bile duct and pancreatic duct in children

    International Nuclear Information System (INIS)

    Gwal, Kriti; Bedoya, Maria A.; Patel, Neal; Darge, Kassa; Anupindi, Sudha A.; Rambhatla, Siri J.; Sreedharan, Ram R.

    2015-01-01

    Magnetic resonance imaging/cholangiopancreatography (MRI/MRCP) is now an essential imaging modality for the evaluation of biliary and pancreatic pathology in children, but there are no data depicting the normal diameters of the common bile duct (CBD) and pancreatic duct. Recognition of abnormal duct size is important and the increasing use of MRCP necessitates normal MRI measurements. To present normal MRI measurements for the common bile duct and pancreatic duct in children. In this retrospective study we searched all children ages birth to 10 years in our MR urography (MRU) database from 2006 until 2013. We excluded children with a history of hepatobiliary or pancreatic surgery. We stratified 204 children into five age groups and retrospectively measured the CBD and the pancreatic duct on 2-D axial and 3-D coronal T2-weighted sequences. We performed statistical analysis, using logistic and linear regressions to detect the age association of the visibility and size of the duct measurements. We used non-parametric tests to detect gender and imaging plane differences. Our study included 204 children, 106 (52%) boys and 98 (48%) girls, with a median age of 33 months (range 0-119 months). The children were distributed into five age groups. The common bile duct was visible in all children in all age groups. The pancreatic duct was significantly less visible in the youngest children, group 1 (54/67, 80.5%; P = 0.003) than in the oldest children, group 5 (22/22, 100%). In group 2 the pancreatic duct was seen in 19/21 (90.4%), in group 3 52/55 (94.5%), and in group 4 39/39 (100%). All duct measurements increased with age (P < 0.001; r-value > 0.423), and the incremental differences between ages were significant. The measurement variations between the axial and coronal planes were statistically significant (P < 0.001); however these differences were fractions of millimeters. For example, in group 1 the mean coronal measurement of the CBD was 2.1 mm and the axial

  20. Ultrasound imaging of the mouse pancreatic duct using lipid microbubbles

    Science.gov (United States)

    Banerjee, B.; McKeown, K. R.; Skovan, B.; Ogram, E.; Ingram, P.; Ignatenko, N.; Paine-Murrieta, G.; Witte, R.; Matsunaga, T. O.

    2012-03-01

    Research requiring the murine pancreatic duct to be imaged is often challenging due to the difficulty in selectively cannulating the pancreatic duct. We have successfully catheterized the pancreatic duct through the common bile duct in severe combined immune deficient (SCID) mice and imaged the pancreatic duct with gas filled lipid microbubbles that increase ultrasound imaging sensitivity due to exquisite scattering at the gas/liquid interface. A SCID mouse was euthanized by CO2, a midline abdominal incision made, the common bile duct cut at its midpoint, a 2 cm, 32 gauge tip catheter was inserted about 1 mm into the duct and tied with suture. The duodenum and pancreas were excised, removed in toto, embedded in agar and an infusion pump was used to instill normal saline or lipid-coated microbubbles (10 million / ml) into the duct. B-mode images before and after infusion of the duct with microbubbles imaged the entire pancreatic duct (~ 1 cm) with high contrast. The microbubbles were cavitated by high mechanical index (HMI) ultrasound for imaging to be repeated. Our technique of catheterization and using lipid microbubbles as a contrast agent may provide an effective, affordable technique of imaging the murine pancreatic duct; cavitation with HMI ultrasound would enable repeated imaging to be performed and clustering of targeted microbubbles to receptors on ductal cells would allow pathology to be localized accurately. This research was supported by the Experimental Mouse Shared Service of the AZ Cancer Center (Grant Number P30CA023074, NIH/NCI and the GI SPORE (NIH/NCI P50 CA95060).

  1. FGF-2b and h-PL Transform Duct and Non-Endocrine Human Pancreatic Cells into Endocrine Insulin Secreting Cells by Modulating Differentiating Genes

    Directory of Open Access Journals (Sweden)

    Giulia Donadel

    2017-10-01

    Full Text Available Background: Diabetes mellitus (DM is a multifactorial disease orphan of a cure. Regenerative medicine has been proposed as novel strategy for DM therapy. Human fibroblast growth factor (FGF-2b controls β-cell clusters via autocrine action, and human placental lactogen (hPL-A increases functional β-cells. We hypothesized whether FGF-2b/hPL-A treatment induces β-cell differentiation from ductal/non-endocrine precursor(s by modulating specific genes expression. Methods: Human pancreatic ductal-cells (PANC-1 and non-endocrine pancreatic cells were treated with FGF-2b plus hPL-A at 500 ng/mL. Cytofluorimetry and Immunofluorescence have been performed to detect expression of endocrine, ductal and acinar markers. Bromodeoxyuridine incorporation and annexin-V quantified cells proliferation and apoptosis. Insulin secretion was assessed by RIA kit, and electron microscopy analyzed islet-like clusters. Results: Increase in PANC-1 duct cells de-differentiation into islet-like aggregates was observed after FGF-2b/hPL-A treatment showing ultrastructure typical of islets-aggregates. These clusters, after stimulation with FGF-2b/hPL-A, had significant (p < 0.05 increase in insulin, C-peptide, pancreatic and duodenal homeobox 1 (PDX-1, Nkx2.2, Nkx6.1, somatostatin, glucagon, and glucose transporter 2 (Glut-2, compared with control cells. Markers of PANC-1 (Cytokeratin-19, MUC-1, CA19-9 were decreased (p < 0.05. These aggregates after treatment with FGF-2b/hPL-A significantly reduced levels of apoptosis. Conclusions: FGF-2b and hPL-A are promising candidates for regenerative therapy in DM by inducing de-differentiation of stem cells modulating pivotal endocrine genes.

  2. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis.

    Science.gov (United States)

    Cahen, Djuna L; Gouma, Dirk J; Nio, Yung; Rauws, Erik A J; Boermeester, Marja A; Busch, Olivier R; Stoker, Jaap; Laméris, Johan S; Dijkgraaf, Marcel G W; Huibregtse, Kees; Bruno, Marco J

    2007-02-15

    For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, Psurgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, PSurgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-trials.com].). Copyright 2007 Massachusetts Medical Society.

  3. Optimizing the Treatment of Acute Duct-Destructive Pancreatitis

    Science.gov (United States)

    Zhakiev, Bazylbek S.; Karsakbayev, Uteugali G.; Kelimberdiev, Mersaid S.; ?uhamedgalieva, Bodagoz M.; K?nonenko, Aleksander F.

    2016-01-01

    The search for new methods for treating duct-destructive pancreatitis is a relevant problem. Endogenous intoxication and oxidative stress that accompany acute pancreatitis often progress even after surgery, which forces one to search for additional possibilities of preventing these severe consequences. This research studied the effect of small…

  4. Sonographic and radiologic diagnosis of a pancreatic duct stone

    International Nuclear Information System (INIS)

    Habscheid, W.; Kulke, H.; Heidbreder, E.

    1986-01-01

    A case is reported in which asymptomatic chronic pancreatitis of initially unknown etiology was detected as result of a routine follow-up examination of a patient with membraneproliferative glomerulonephritis. Ultrasound and endoscopic cholangio-pancreatography detected a stone in the major pancreatic duct. The stone was of such size and irregular form that endoscopic extraction was impossible. (orig.) [de

  5. Sonographic and radiologic diagnosis of a pancreatic duct stone

    Energy Technology Data Exchange (ETDEWEB)

    Habscheid, W.; Kulke, H.; Heidbreder, E.

    1986-09-01

    A case is reported in which asymptomatic chronic pancreatitis of initially unknown etiology was detected as result of a routine follow-up examination of a patient with membraneproliferative glomerulonephritis. Ultrasound and endoscopic cholangio-pancreatography detected a stone in the major pancreatic duct. The stone was of such size and irregular form that endoscopic extraction was impossible.

  6. Bile Duct Obstruction Secondary to Chronic Pancreatitis in Seven Dogs

    Science.gov (United States)

    Cribb, Alastair E.; Burgener, David C.; Reimann, Keith A.

    1988-01-01

    Seven icteric dogs were determined to have bile duct obstruction secondary to chronic pancreatitis. All dogs had histories of intermittent vomiting and diarrhea. Alkaline phosphatase and alanine aminotransferase activities and total bilirubin concentrations were markedly elevated. Diagnosis was based on exploratory laparotomy and histological examination. Each dog had a 3 to 10 cm mass in the body of the pancreas and obstruction of the common bile duct. Three dogs treated with pancreatectomy, gastrojejunostomy, and cholecystojejunostomy died within five weeks. Three dogs treated with conservative surgical procedures were alive at 8, 16, and 26 months postoperatively. One dog was euthanized because of suspected neoplasia. Hepatic enzyme activity and bilirubin levels decreased markedly in the surviving dogs. Histological examination of the pancreatic masses indicated chronic pancreatitis. Hepatic biopsies revealed evidence of cholestasis. Chronic pancreatitis should be included in the differential diagnoses of icterus, bile duct obstruction, and masses in the pancreas. PMID:17423102

  7. Risk of pancreatitis after pancreatic duct guidewire placement during endoscopic retrograde cholangiopancreatography.

    Directory of Open Access Journals (Sweden)

    Yuki Ishikawa-Kakiya

    Full Text Available Advanced techniques have been developed to overcome difficult cannulation cases in endoscopic retrograde cholangiopancreatography (ERCP. Pancreatic duct guidewire placement method (PGW is performed in difficult cannulation cases; it is possible that it places patients at risk of post-ERCP pancreatitis (PEP. The mechanism of PEP is still unclear, but pancreatic duct pressure and injury of pancreatic duct are known causes of PEP. Therefore, we hypothesized a relationship between pancreatic duct diameter and PEP and predicted that PGW would increase the risk of PEP in patients with non-dilated pancreatic ducts. This study aimed to investigate whether PGW increased the risk of PEP in patients with pancreatic duct diameter ≤ 3 mm.We analyzed 332 patients with pancreatic duct ≤ 3 mm who performed first time ERCP session. The primary endpoint was the rate of adverse event of PEP. We evaluated the risk of PEP in patients who had undergone PGW compared to those who had not, using the inverse probability of treatment weighting (IPTW analysis.PGW was found to be an independent risk factor for PEP by univariate analysis (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.12-5.38; p = 0.03 after IPTW in patients with pancreatic duct diameter ≤ 3 mm. Adjusted for all covariates, PGW remained an independent risk factor for PEP (OR, 3.12; 95% CI, 1.33-7.33; p = 0.01.Our results indicate that PGW in patients with pancreatic duct diameter ≤ 3 mm increases the risk of PEP.

  8. Indications and results of pancreatic stump duct occlusion after duodenopancreatectomy.

    Science.gov (United States)

    Alfieri, Sergio; Quero, Giuseppe; Rosa, Fausto; Di Miceli, Dario; Tortorelli, Antonio Pio; Doglietto, Giovanni Battista

    2016-09-01

    Severe post-operative complications after pancreaticoduodenectomy (PD) are largely due to pancreatic fistula onset. The occlusion of the main pancreatic duct using synthetic glue may prevent these complications. Aim of this study is to describe this technique and to report short- and long-term results as well as the post-operative endocrine and exocrine insufficiency. Two hundred and four patients who underwent PD with occlusion of the main pancreatic duct in a period of 15 years were retrospectively analyzed. Post-operative complications and their management were the main aim of the study with particular focus on pancreatic fistula incidence and its treatment. At 1-year follow-up endocrine and exocrine functions were analyzed. We observed a 54 % pancreatic fistula incidence, most of which (77/204 patients) were a grade A fistula with little change in medical management. Twenty-eight patients developed a grade B fistula while only 2 % of patients (5/204) developed a grade C fistula. Nine patients required re-operation, 5 of whom had a post-operative grade C fistula. Post-operative mortality was 3.4 %. At 1-year follow-up, 31 % of patients developed a post-operative diabetes while exocrine insufficiency was encountered in 88 % of patients. The occlusion of the main pancreatic duct after PD can be considered a relatively safe and easy-to-perform procedure. It should be reserved to selected patients, especially in case of soft pancreatic texture and small pancreatic duct and in elderly patients with comorbidities, in whom pancreatic fistula-related complications could be life threatening.

  9. Bile Duct Obstruction Secondary to Chronic Pancreatitis in Seven Dogs

    OpenAIRE

    Cribb, Alastair E.; Burgener, David C.; Reimann, Keith A.

    1988-01-01

    Seven icteric dogs were determined to have bile duct obstruction secondary to chronic pancreatitis. All dogs had histories of intermittent vomiting and diarrhea. Alkaline phosphatase and alanine aminotransferase activities and total bilirubin concentrations were markedly elevated. Diagnosis was based on exploratory laparotomy and histological examination. Each dog had a 3 to 10 cm mass in the body of the pancreas and obstruction of the common bile duct. Three dogs treated with pancreatectomy,...

  10. The diameter of main pancreatic duct on endoscopic retrograde pancreatography and the appearance of main pancreatic duct on computed tomography

    International Nuclear Information System (INIS)

    Tanno, Naoaki; Yamazaki, Hideo; Toyota, Takayoshi; Nakanome, Chiyuki; Sasaki, Masayoshi; Sato, Waichi; Komatsu, Kanji.

    1990-01-01

    We have carried out a comparative study of the diameter of main pancreatic duct (MPD) on endoscopic retrograde pancreatography (ERP) with the fequency of detection of MPD by computed tomography (CT) in order to clarify the importance of MPD appearance on CT in the pancreatic and biliary diseases. The normal MPD on ERP was demonstrated by CT in a low frequency. MPD was most frequently observed in the pancreatic body on CT. The dilatation of MPD on ERP was found in both moderate and advanced pancreatitis group. However, the significant demonstration of MPD by CT was found in advanced group alone. We observed that CT finding of dilated duct correlated with that on ERP in advanced group alone. (author)

  11. ß-adrenergic regulation of ion transport in pancreatic ducts: Patch-clamp study of isolated rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I

    1998-01-01

    BACKGROUND & AIMS: In the intact pancreas, bicarbonate secretion is thought to be controlled by a number of regulators, including adrenergic agonists. The aim of this study was to investigate the effects of adrenergic agonists on pancreatic ducts, which are the site of bicarbonate secretion....... METHODS: Small intralobular ducts were isolated from rat pancreas and studied in vitro by the whole-cell patch clamp technique. Cell membrane voltages and currents were indicators of cellular ion transport. In some ducts, intracellular Ca2+ activity was measured by fluorescence optical methods. RESULTS...

  12. Autoimmune pancreatitis: Assessment of the enhanced duct sign on multiphase contrast-enhanced computed tomography

    International Nuclear Information System (INIS)

    Kawai, Yuichi; Suzuki, Kojiro; Itoh, Shigeki; Takada, Akira; Mori, Yoshine; Naganawa, Shinji

    2012-01-01

    Purpose: To assess the usefulness of the computed tomography (CT) finding of main pancreatic duct (MPD) wall enhancement, termed the “enhanced duct sign”, for diagnosis of autoimmune pancreatitis (AIP) in comparison with diagnosis of pancreatic carcinoma and chronic pancreatitis. Materials and methods: Two radiologists independently evaluated the presence or absence of the enhanced duct sign on multiphase contrast-enhanced CT in patients with AIP (n = 55), pancreatic carcinoma (n = 50), and chronic pancreatitis (n = 50). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of AIP were calculated. In patients demonstrating the enhanced duct sign, additional findings were evaluated by consensus. Results: The enhanced duct sign was more frequently observed in patients with AIP (37/55, 67%) than in patients with pancreatic carcinoma (5/50, 10%) or chronic pancreatitis (0/50, 0%) (P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the finding were 0.67, 0.95, 0.85, 0.88, and 0.84, respectively. In AIP, the lumen within the enhanced duct was completely or partially invisible in 29 of 37 (78%) patients, and the enhanced duct was observed within the affected pancreatic parenchyma in 35 of 37 (95%) patients. In pancreatic carcinoma, the lumen within the enhanced duct was visible in all patients (5/5, 100%), and the enhanced duct was observed downstream of the tumor (5/5, 100%). Conclusion: The enhanced duct sign is highly specific of AIP.

  13. Autoimmune pancreatitis: Assessment of the enhanced duct sign on multiphase contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Yuichi, E-mail: kawai.yuichi@a.mbox.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Suzuki, Kojiro, E-mail: kojiro@med.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Itoh, Shigeki, E-mail: shigeito@nagoya-1st.jrc.or.jp [Department of Diagnostic Radiology, Japan Red Cross Nagoya Daiichi Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya 453-8511 (Japan); Takada, Akira, E-mail: takadaa@med.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Mori, Yoshine, E-mail: yoshine@med.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Naganawa, Shinji, E-mail: naganawa@med.nagoya-u.ac.jp [Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

    2012-11-15

    Purpose: To assess the usefulness of the computed tomography (CT) finding of main pancreatic duct (MPD) wall enhancement, termed the 'enhanced duct sign', for diagnosis of autoimmune pancreatitis (AIP) in comparison with diagnosis of pancreatic carcinoma and chronic pancreatitis. Materials and methods: Two radiologists independently evaluated the presence or absence of the enhanced duct sign on multiphase contrast-enhanced CT in patients with AIP (n = 55), pancreatic carcinoma (n = 50), and chronic pancreatitis (n = 50). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of AIP were calculated. In patients demonstrating the enhanced duct sign, additional findings were evaluated by consensus. Results: The enhanced duct sign was more frequently observed in patients with AIP (37/55, 67%) than in patients with pancreatic carcinoma (5/50, 10%) or chronic pancreatitis (0/50, 0%) (P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the finding were 0.67, 0.95, 0.85, 0.88, and 0.84, respectively. In AIP, the lumen within the enhanced duct was completely or partially invisible in 29 of 37 (78%) patients, and the enhanced duct was observed within the affected pancreatic parenchyma in 35 of 37 (95%) patients. In pancreatic carcinoma, the lumen within the enhanced duct was visible in all patients (5/5, 100%), and the enhanced duct was observed downstream of the tumor (5/5, 100%). Conclusion: The enhanced duct sign is highly specific of AIP.

  14. Intracellular pH in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I; Hug, M; Greger, R

    1997-01-01

    In order to study the mechanism of H+ and HCO3- transport in a HCO3- secreting epithelium, pancreatic ducts, we have measured the intracellular pH (pHi) in this tissue using the pH sensitive probe BCECF. We found that exposures of ducts to solutions containing acetate/acetic acid or NH4+/NH3...... buffers (20 mmol/l) led to pHi changes in accordance with entry of lipid-soluble forms of the buffers, followed by back-regulation of pHi by duct cells. In another type of experiment, changes in extracellular pH of solutions containing HEPES or HCO3-/CO2 buffers led to significant changes in pHi that did....... Under some conditions, these exchangers can be invoked to regulate cell pH....

  15. Computed tomography after modified Whipple procedure with pancreatic duct occlusion

    International Nuclear Information System (INIS)

    Abildgaard, A.; Kolmannskog, F.; Mathisen, O.; Bergan, A.; Rikshospitalet, Oslo

    1990-01-01

    Eighty-two CT examinations performed on 28 patients who had undergone a modified Whipple procedure including pancreatic duct occlusion were reviewed. Reduction of the antero-posterior diameter of the body and tail of the pancreatic remnant was observed on consecutive scans in 8 patients (29%). Decreasing liver attenuation was seen in 4 patients (14%) postoperatively, and pseudocysts in the pancreatic remnant in 6 (21%). In 10 examinations performed because of suspected intraabdominal abscess postoperatively, abscess was diagnosed in 2 patients. In 62 routine follow-up CT examinations, significant positive findings were diagnosed in 5 patients: tumor recurrence or metastases in 4, and a large pseuodocyst in one. CT is of value in the early postoperative phase to reveal postoperative complications and in the follow-up of patients with specific symptoms indicating tumor recurrence or metastases. (orig.)

  16. External pancreatic duct stent reduces pancreatic fistula: a meta-analysis and systematic review.

    Science.gov (United States)

    Patel, Krishen; Teta, Anthony; Sukharamwala, Prashant; Thoens, Jonathan; Szuchmacher, Mauricio; DeVito, Peter

    2014-01-01

    Postoperative pancreatic fistula formation (POPF) remains one of the most common and detrimental complications following pancreaticojejunostomy (PJ). The aim of this meta-analysis is to analyze the efficacy of external pancreatic duct stent placement in preventing POPF formation following PJ. The primary end-point was the incidence of POPF formation following pancreaticoduodenectomy (PD) in the presence and absence of external stent placement. Secondary outcomes examined were the incidence of perioperative mortality, delayed gastric emptying, postoperative wound infection, operative time, blood loss, and length of hospital stay. Four trials were included comprising 416 patients. External pancreatic duct stenting was found to reduce the incidence of both any grade POPF formation (OR 0.37, 95% CI = 0.23 to 0.58, p = 0.0001) and clinically significant (grade B or C) POPF formation (OR 0.50, 95% CI = 0.30 to 0.84, p = 0.0009) following PD. The use of an external stent was also found to significantly lessen length of hospital stay (SMD -0.39, 95% CI = -0.63 to -0.15, p = 0.001). This analysis has shown that external pancreatic duct stenting is indeed efficacious in the incidence of both any grade as well as clinically significant POPF formation following PD. Length of hospital stay was also found to be significantly less by external duct stenting. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  17. Targeted transgastric drainage of isolated pancreatic duct segments to cure persistent pancreaticocutaneous fistulas from pancreatitis.

    Science.gov (United States)

    Boas, F Edward; Kadivar, Fatemeh; Kelly, Peter D; Drebin, Jeffrey A; Vollmer, Charles M; Shlansky-Goldberg, Richard D

    2015-02-01

    Chronic pancreaticocutaneous fistulas can be difficult to treat. This article presents a snare-target technique for draining a nondilated pancreatic duct into the stomach, diverting pancreatic fluid away from the pancreaticocutaneous fistula to allow it to heal. Internal or internal/external transgastric pancreatic duct or fistula drains were placed in six patients. After an average of 4 months of drainage, all six patients experienced resolution of the cutaneous fistula. Two patients developed a pseudocyst but no recurrent fistula after drain removal, and the other four patients had no pseudocyst or fistula after an average 27-month follow-up (range, 6-74 mo). Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

  18. Modified duval procedure for small-duct chronic pancreatitis without head dominance.

    Science.gov (United States)

    Oida, Takatsugu; Aramaki, Osamu; Kano, Hisao; Mimatsu, Kenji; Kawasaki, Atsushi; Kuboi, Youichi; Fukino, Nobutada; Kida, Kazutoshi; Amano, Sadao

    2011-01-01

    In the case of small-duct chronic pancreatitis, surgery for pain relief is broadly divided into resection and drainage procedures. These procedures should be selected according to the location of dominant lesion, diameter of the pancreatic duct and extent of the disease. The appropriate procedure for the treatment of small-duct chronic pancreatitis, especially small-duct chronic pancreatitis without head dominance, remains controversial. We developed the modified Duval procedure for the treatment of small-duct chronic pancreatitis without head dominance and determined the efficacy of this procedure. We retrospectively studied 14 patients who underwent surgical drainage with or without pancreatic resection for chronic pancreatitis with small pancreatic duct (Puestow procedure group and the modified Duval procedure group. No complications occurred in the modified Duval group. In the modified Puestow procedure group, complete and partial pain relief were observed in 62.5%, and 37.5% of patients respectively. In contrast, complete pain relief was observed in all the patients in the modified Duval procedure group. Our modified Duval procedure is useful and should be considered the appropriate surgical technique for the treatment of small-duct chronic pancreatitis without head dominance.

  19. Endoscopic Ultrasonography-Guided Techniques for Accessing and Draining the Biliary System and the Pancreatic Duct.

    Science.gov (United States)

    Rimbaş, Mihai; Larghi, Alberto

    2017-10-01

    When endoscopic retrograde cholangiopancreatography (ERCP) fails to decompress the biliary system or the pancreatic duct, endoscopic ultrasonography (EUS)-guided biliary or pancreatic access and drainage can be used. Data show a high success rate and acceptable adverse event rate for EUS-guided biliary drainage. The outcomes of EUS-guided biliary drainage seem equivalent to percutaneous drainage and ERCP, whereas only retrospective studies are available for pancreatic duct drainage. In this article, revision of the technical and clinical status and the current evidence of interventional EUS-guided biliary and pancreatic duct access and drainage are presented. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Enterovirus strain and type-specific differences in growth kinetics and virus-induced cell destruction in human pancreatic duct epithelial HPDE cells.

    Science.gov (United States)

    Smura, Teemu; Natri, Olli; Ylipaasto, Petri; Hellman, Marika; Al-Hello, Haider; Piemonti, Lorenzo; Roivainen, Merja

    2015-12-02

    Enterovirus infections have been suspected to be involved in the development of type 1 diabetes. However, the pathogenetic mechanism of enterovirus-induced type 1 diabetes is not known. Pancreatic ductal cells are closely associated with pancreatic islets. Therefore, enterovirus infections in ductal cells may also affect beta-cells and be involved in the induction of type 1 diabetes. The aim of this study was to assess the ability of different enterovirus strains to infect, replicate and produce cytopathic effect in human pancreatic ductal cells. Furthermore, the viral factors that affect these capabilities were studied. The pancreatic ductal cells were highly susceptible to enterovirus infections. Both viral growth and cytolysis were detected for several enterovirus serotypes. However, the viral growth and capability to induce cytopathic effect (cpe) did not correlate completely. Some of the virus strains replicated in ductal cells without apparent cpe. Furthermore, there were strain-specific differences in the growth kinetics and the ability to cause cpe within some serotypes. Viral adaptation experiments were carried out to study the potential genetic determinants behind these phenotypic differences. The blind-passage of non-lytic CV-B6-Schmitt strain in HPDE-cells resulted in lytic phenotype and increased progeny production. This was associated with the substitution of a single amino acid (K257E) in the virus capsid protein VP1 and the viral ability to use decay accelerating factor (DAF) as a receptor. This study demonstrates considerable plasticity in the cell tropism, receptor usage and cytolytic properties of enteroviruses and underlines the strong effect of single or few amino acid substitutions in cell tropism and lytic capabilities of a given enterovirus. Since ductal cells are anatomically close to pancreatic islets, the capability of enteroviruses to infect and destroy pancreatic ductal cells may also implicate in respect to enterovirus induced type 1

  1. Purinergic receptors stimulate Na+/Ca2+ exchange in pancreatic duct cells: possible role of proteins handling and transporting Ca2+

    DEFF Research Database (Denmark)

    Hansen, Mette R; Krabbe, Simon; Ankorina-Stark, Ieva

    2009-01-01

    ). Since NCX can also be connected with epithelial Ca(2+) transport, we also investigated expression of some Ca(2+)-handling/transporting proteins. Expression analysis revealed that pancreatic ducts of rat and human duct cell line CFPAC-1 (also PANC-1 and Capan-1) express the Na(+)/Ca(2+) exchanger (splice...

  2. [Retrograde pancreatic duct imaging and surgical tactics in hemorrhagic necrotizing pancreatitis. Preliminary report].

    Science.gov (United States)

    Gebhardt, C; Gall, F P; Lux, G; Riemann, J; Link, W

    1983-12-01

    In patients with haemorrhagic necrotizing pancreatitis who are scheduled for surgery we have been carrying out a preoperative retrograde investigation of the pancreatic duct system for the past months. The results in, to date, ten patients revealed four different morphological findings of importance for the surgical tactic: 1. A normal pancreatic duct system with no signs of fistulae: only peripancreatic necrosectomy is required. - 2. Contrast medium leaks via a ductal fistula: left resection including the removal of the fistulous area must be done. - 3. Normal duct system with complete segmental parenchymal staining, representing total necrosis in this region: left resection of the pancreas. - 4. Duodenoscopically demonstrable perforation into the duodenum of a necrotic cavity in the head of the pancreas: conservative management only, no surgery, since this lesion resulting in drainage of the necrotic cavity into the bowel permits self-healing, while the site of the perforation within the necrotic wall cannot be dealt with by surgery. - The experience gained so far indicates that the surgical tactic can be determined with greater selectivity by the use of ERP.

  3. Long-term assessments after pancreaticoduodenectomy with pancreatic duct invagination anastomosis

    International Nuclear Information System (INIS)

    Fujino, Yasuhiro; Matsumoto, Ippei; Sakai, Tetsuya; Ajiki, Tetsuo; Ueda, Takashi; Kuroda, Yoshikazu; Suzuki, Yasuyuki

    2007-01-01

    The purpose of this cohort was to evaluate the long-term patency of the anastomosis and the remnant pancreatic functions. Fifty-six consecutive patients undergoing a pancreaticoduodenectomy with pancreatic duct invagination anastomosis were enrolled in this study. During the follow-up, changes in the remnant pancreatic duct size, pancreatic exocrine and endocrine functions, and nutritional status were monitored. No seriously activated pancreatic fistula, no hemorrhagic complications, no reoperations, and no in-hospital deaths were observed after surgery. A dilatation of remnant pancreatic duct was detected a total of 37 times (51%) during annual computed tomography (CT) evaluations. Pancreatic dysfunctions were observed in a considerable number of patients (exocrine 4/12, 9/14, and 8/16, endocrine 9/35, 8/27, and 4/16 at 1, 2, and 3 postoperative years, respectively). Functional declines in the remnant pancreas, duct dilatation, and a decrease in the body mass index were observed from the first year. However, these data did not progressively deteriorate thereafter, at least during the first 3 postoperative years. This study demonstrated a significant correlation between the duct dilatation and endocrine dysfunction. Our pancreatic duct invagination anastomosis resulted in somewhat limited long-term outcomes, although it did prevent serious complications in the short-term. (author)

  4. Pancreatic duct drainage using EUS-guided rendezvous technique for stenotic pancreaticojejunostomy.

    Science.gov (United States)

    Takikawa, Tetsuya; Kanno, Atsushi; Masamune, Atsushi; Hamada, Shin; Nakano, Eriko; Miura, Shin; Ariga, Hiroyuki; Unno, Jun; Kume, Kiyoshi; Kikuta, Kazuhiro; Hirota, Morihisa; Yoshida, Hiroshi; Katayose, Yu; Unno, Michiaki; Shimosegawa, Tooru

    2013-08-21

    The patient was a 30-year-old female who had undergone excision of the extrahepatic bile duct and Roux-en-Y hepaticojejunostomy for congenital biliary dilatation at the age of 7. Thereafter, she suffered from recurrent acute pancreatitis due to pancreaticobiliary maljunction and received subtotal stomach-preserving pancreaticoduodenectomy. She developed a pancreatic fistula and an intra-abdominal abscess after the operation. These complications were improved by percutaneous abscess drainage and antibiotic therapy. However, upper abdominal discomfort and the elevation of serum pancreatic enzymes persisted due to stenosis from the pancreaticojejunostomy. Because we could not accomplish dilation of the stenosis by endoscopic retrograde cholangiopancreatography, we tried an endoscopic ultrasonography (EUS) guided rendezvous technique for pancreatic duct drainage. After transgastric puncture of the pancreatic duct using an EUS-fine needle aspiration needle, the guidewire was inserted into the pancreatic duct and finally reached to the jejunum through the stenotic anastomosis. We changed the echoendoscope to an oblique-viewing endoscope, then grasped the guidewire and withdrew it through the scope. The stenosis of the pancreaticojejunostomy was dilated up to 4 mm, and a pancreatic stent was put in place. Though the pancreatic stent was removed after three months, the patient remained symptom-free. Pancreatic duct drainage using an EUS-guided rendezvous technique was useful for the treatment of a stenotic pancreaticojejunostomy after pancreaticoduodenectomy.

  5. Evidence for a Na+-Ca2+ exchanger in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Hug, M; Pahl, C; Novak, I

    1996-01-01

    Only recently has it been recognized that intracellular Ca2+ is an important cellular mediator in pancreatic ducts. The aim of the present study was to characterize the Ca2+ efflux pathway in ducts freshly prepared from rat pancreas. Lowering of extracellular Na+ concentration resulted in a signi......Only recently has it been recognized that intracellular Ca2+ is an important cellular mediator in pancreatic ducts. The aim of the present study was to characterize the Ca2+ efflux pathway in ducts freshly prepared from rat pancreas. Lowering of extracellular Na+ concentration resulted...

  6. Prediction of common bile duct stones in the earliest stages of acute biliary pancreatitis

    NARCIS (Netherlands)

    Santvoort, H.C. van; Bakker, O.J.; Besselink, M.G.; Bollen, T.L.; Fischer, K.; Nieuwenhuijs, V.B.; Gooszen, H.G.; Erpecum, K.J. van

    2011-01-01

    BACKGROUND AND STUDY AIMS: Accurate prediction of common bile duct (CBD) stones in acute biliary pancreatitis is warranted to select patients for early therapeutic endoscopic retrograde cholangiopancreatography (ERCP). We evaluated commonly used biochemical and radiological predictors of CBD stones

  7. Prediction of common bile duct stones in the earliest stages of acute biliary pancreatitis

    NARCIS (Netherlands)

    van Santvoort, H. C.; Bakker, O. J.; Besselink, M. G.; Bollen, T. L.; Fischer, K.; Nieuwenhuijs, V. B.; Gooszen, H. G.; Erpecum, K. J.

    Background and study aims: Accurate prediction of common bile duct (CBD) stones in acute biliary pancreatitis is warranted to select patients for early therapeutic endoscopic retrograde cholangiopancreatography (ERCP). We evaluated commonly used biochemical and radiological predictors of CBD stones

  8. Retrograde cholangiopancreatography in the diagnosis of biliary and pancreatic duct diseases

    International Nuclear Information System (INIS)

    Vasil'ev, Yu.D.; Sedletskaya, T.N.

    1980-01-01

    Results of retrograde cannulation with the aid of flexible fibroduodenoscopes with subsequent introduction of a contrast substance into biliary and pancreatic ducts are presented. The investigation is carried out on 120 patients with different diseases of hepatopancreatoduodenal zone. The standard technique of X-ray examination has been applied permitting to obtain the most exhaustive information. Using retrograde cholangiopancreatography revealed have been choledocholithiasis, deformation of biliary ducts after surgical intervention, pancreatic cyst, tumor of the main pancreatic duct etc. Results of investigation of biliary and pancreatic ducts using retrograde cannulation are reaffirmed with the data of operations on biliary tract in 72 patients. Intraoperational cholangiography has been carried out on 36 of them during operation. An attempt to cannulate big duodenal papilla in 12 patients proved to be ineffective. No complications have been observed during examination

  9. Occlusion of the pancreatic duct versus pancreaticojejunostomy: a prospective randomized trial.

    NARCIS (Netherlands)

    K.T. Tran; C.H.J. van Eijck (Casper); V. di Carlo (Valerio); W.C.J. Hop (Wim); A. Zerbi (Alessandro); G. Balzano (Gianpaolo); J. Jeekel (Hans)

    2002-01-01

    textabstractOBJECTIVE: Using a prospective randomized study to assess postoperative morbidity and pancreatic function after pancreaticoduodenectomy with pancreaticojejunostomy and duct occlusion without pancreaticojejunostomy. SUMMARY BACKGROUND DATA: Postoperative complications

  10. Effect of vasoactive intestinal peptide, carbachol and other agonists on the membrane voltage of pancreatic duct cells

    DEFF Research Database (Denmark)

    Pahl, C; Novak, I

    1993-01-01

    pancreatic ducts and, as a physiological response, we measured the basolateral membrane voltage of the duct cells (Vbl) with microelectrodes. Pancreatic ducts were dissected from pancreas of normal rats and bathed in a HCO(3-)(-containing solution. Under control conditions, the average Vbl was between -50...

  11. Factors associated with post-ERCP pancreatitis and the effect of pancreatic duct stenting in a pediatric population.

    Science.gov (United States)

    Troendle, David M; Abraham, Omana; Huang, Rong; Barth, Bradley A

    2015-01-01

    Risk factors for the development of post-ERCP pancreatitis (PEP) have not been identified in the pediatric population. It remains unclear what constitutes appropriate prophylaxis in this patient population. To assess the prevalence and severity of PEP in the pediatric population and identify factors associated with developing PEP and to evaluate the effect of prophylactic pancreatic duct stenting in high-risk patients. Retrospective analysis of an ERCP database at a single large pediatric center. Academic center. A total of 432 ERCPs performed on 313 patients younger than 19 years of age from January 2004 to October 2013. ERCP for any indication. Rates and severity of PEP, preprocedural and procedural risk factors for the development of PEP, and the effect of pancreatic stents on preventing PEP in high-risk patients. PEP occurred after 47 procedures (prevalence, 10.9%). Thirty-four cases were mild, 9 were moderate, and 4 were severe. There was no mortality. On multiple logistic analysis, pancreatic duct injection (Ppancreatic sphincterotomy (Passociated with PEP. A history of chronic pancreatitis was negatively associated with PEP (Ppancreatic stent was associated with significantly increased rates of PEP in patients with pancreatic duct injection compared with those who had no attempt at stent placement (Ppancreatitis had prophylactic pancreatic stents in place. Retrospective investigation. In the pediatric population, pancreatic duct injection and pancreatic sphincterotomy are associated with significantly increased rates of PEP, whereas a history of chronic pancreatitis is negatively associated. Prophylactic pancreatic stenting is associated with higher rates of PEP in high-risk patients and does not eliminate severe PEP. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  12. Pancreatic Serous Cystadenoma with Compression of the Main Pancreatic Duct: An Unusual Entity

    Directory of Open Access Journals (Sweden)

    Stéphanie Truant

    2011-01-01

    Full Text Available Serous cystadenoma is a common benign neoplasm that can be managed without surgery in asymptomatic patients provided that the diagnosis is certain. We describe a patient, whose pancreatic cyst exhibited a radiological appearance distinct from that of typical serous cystadenoma, resulting in diagnostic difficulties. CT and MRI showed a 10 cm-polycystic tumor with upstream dilatation of the main pancreatic duct (MPD, suggestive of intraductal papillary mucinous tumor (IPMT. Ultrasonographic aspect and EUS-guided fine-needle aspiration gave arguments for serous cystadenoma. ERCP showed a communication between cysts and the dilated MPD, compatible with IPMT. The patient underwent left pancreatectomy with splenectomy. Pathological examination concluded in a serous cystadenoma, with only a ductal obstruction causing proximal dilatation.

  13. Different purinergic receptors lead to intracellular calcium increases in pancreatic ducts

    DEFF Research Database (Denmark)

    Christoffersen, B C; Hug, M J; Novak, I

    1998-01-01

    that might play a role in the regulation of pancreatic bicarbonate transport. Native intralobular ducts were obtained from rat pancreas and [Ca2+]i in 10-20 cells was measured using the fura-2 method. ATP (10(-4) mol/l) evoked a characteristic biphasic Ca2+ transient in duct cells. Nucleotides, used...

  14. Effect of portal hypertension and duct ligature on pancreatic fluid pressures in cats

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Heyeraas, K J

    1990-01-01

    measured before and after acutely induced portal hypertension; in the other group of cats the pressures were measured after an overnight ligature of the pancreatic main duct. At rest the needle pressure was equal to duct pressure but significantly lower than interstitial fluid pressure and portal pressure...

  15. Pancreatic duct abnormalities in focal autoimmune pancreatitis: MR/MRCP imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Negrelli, Riccardo; Manfredi, Riccardo; Pedrinolla, Beatrice; Boninsegna, Enrico; Ventriglia, Anna; Mehrabi, Sara; Pozzi Mucelli, Roberto [G.B. Rossi University Hospital, University of Verona, Department of Radiology, Verona (Italy); Frulloni, Luca [Universita di Verona, Department of Gastroenterology, Policlinico G.B. Rossi, Verona (Italy)

    2014-08-09

    To evaluate the magnetic resonance (MR) imaging-MR cholangiopancreatographic (MRCP) findings of focal forms of autoimmune pancreatitis (AIP) to describe ductal involvement at diagnosis. MR examinations of 123 patients affected by AIP were analysed. We included 26 patients who satisfied International Consensus Diagnostic Criteria and were suffering from focal AIP. Image analysis included: site of parenchymal enlargement, main pancreatic duct (MPD) diameter, MPD stenosis, stricture length, presence of upstream dilation within the stricture, signal intensity, and pancreatic enhancement. Signal intensity abnormalities were localized in the head in 10/26 (38.5 %) and in the body-tail in 16/26 (61.5 %) patients. MRCP showed a single MPD stenosis in 12/26 (46.1 %) and multiple MPD stenosis in 14/26 (53.8 %) patients, without a dilation of the upstream MPD (mean: 3.83 mm). Lesions showed hypointensity on T1-weighted images in all patients, and hyperintensity on T2-weighted images in 22/26 (84.6 %) patients. The affected parenchyma was hypovascular during the arterial phase in 25/26 (96.2 %) patients with contrast retention. MR-MRCP are effective techniques for the diagnosis of AIP showing the loss of the physiological lobulation and the typical contrastographic appearance. The presence of multiple, long stenoses without an upstream MPD dilation at MRCP suggests the diagnosis of AIP, and can be useful in differential diagnosis of pancreatic adenocarcinoma. (orig.)

  16. Regulation of the Na+/Ca2+ exchanger in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Ankorina-Stark, I; Amstrup, J; Novak, I

    2002-01-01

    by hormones/agonists affecting pancreatic secretion. Whole pancreas, pure pancreatic acini and ducts were obtained from rats and used for RT-PCR and Western blot analysis, immunohistochemistry and intracellular Ca2+ measurements using Fura-2. RT-PCR analysis indicated Na+/Ca2+-exchanger isoforms NCX1.......3 and NCX1.7 in acini and pancreas. Western blot with NCX1 antibody identified bands of 70, 120 and 150 kDa in isolated ducts, acini and pancreas. Immunofluorescence experiments showed the Na+/Ca2+ exchanger on the basolateral membrane of acini and small intercalated/intralobular ducts, but in larger...

  17. Assessment of the form and patency of the pancreatic duct by magnetic resonance cholangiopancreatography (MRCP)

    International Nuclear Information System (INIS)

    Kitamura, Masaya; Takahashi, Tuyoshi; Yoshida, Muneki; Shimada, Ken; Kakita, Akira; Isobe, Yoshinori

    1999-01-01

    There have been no reliable methods for the assessment of the patency of an end-to-side style pancreaticojejunal anastomosis in Whipple procedure. We evaluated the ability of MR-Cholangiopancreatography (MRCP) to assess the form and patency of the pancreatic duct in 181 patients. The pancreatic duct was displayed on MRCP in 70.9% of the patients. The domostrative rate of the pancreatic duct on MRCP and the PFD test were well correlated (p=0.031). Further, we assessed the patency of pancreaticojejunal anastomosis in Whipple procedure by MRCP following a secretin load. It was considered that the pancreatic duct to be patent when pancreatic excretion into the jejunum had increased and/or the ability to display the pancreatic duct had improved on MRCP following an i.v. load of secretin. A secretin-loading MRCP was suggested to be of much help in the assessment of the patency of pancreaticojejunostomy in patients undergoing Whipple procedure for a long-term follow up. (author)

  18. Assessment of the form and patency of the pancreatic duct by magnetic resonance cholangiopancreatography (MRCP)

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Masaya; Takahashi, Tuyoshi; Yoshida, Muneki; Shimada, Ken; Kakita, Akira; Isobe, Yoshinori [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine

    1999-02-01

    There have been no reliable methods for the assessment of the patency of an end-to-side style pancreaticojejunal anastomosis in Whipple procedure. We evaluated the ability of MR-Cholangiopancreatography (MRCP) to assess the form and patency of the pancreatic duct in 181 patients. The pancreatic duct was displayed on MRCP in 70.9% of the patients. The domostrative rate of the pancreatic duct on MRCP and the PFD test were well correlated (p=0.031). Further, we assessed the patency of pancreaticojejunal anastomosis in Whipple procedure by MRCP following a secretin load. It was considered that the pancreatic duct to be patent when pancreatic excretion into the jejunum had increased and/or the ability to display the pancreatic duct had improved on MRCP following an i.v. load of secretin. A secretin-loading MRCP was suggested to be of much help in the assessment of the patency of pancreaticojejunostomy in patients undergoing Whipple procedure for a long-term follow up. (author)

  19. Laparoscopic Longitudinal Pancreaticojejunostomy Using Barbed Sutures: an Efficient and Secure Solution for Pancreatic Duct Obstructions in Patients with Chronic Pancreatitis.

    Science.gov (United States)

    Kim, Eun Young; Hong, Tae Ho

    2016-04-01

    We describe our laparoscopic longitudinal pancreaticojejunostomy (LPJ) technique using barbed sutures to manage a pancreatic duct obstruction. We performed laparoscopic longitudinal anterior pancreaticojejunostomy using barbed sutures (3-0 absorbable wound closure device, V-Loc, Covidien, Minneapolis, MN, USA) in 11 patients who presented with signs of a pancreas ductal obstruction and chronic pancreatitis. The surgical outcomes and follow-up records at the outpatient department were reviewed, and the effectiveness and feasibility of this method were analyzed. Mean patient age was 54.4 ± 9.5 years, and pancreatic duct stones were removed from all patients without conversion to laparotomy. Overall operative time was 200.7 ± 56.4 min, and estimated blood loss was 42.2 ± 11.2 ml. No pancreatic anastomosis leakage or postoperative bleeding was detected. Mean length of hospital stay was 6.5 ± 0.8 days, and mean time to start a soft diet was 4.8 ± 0.7 days. No patient complained of postoperative abdominal pain, and all patients recovered without significant complications or relapse of pancreatitis. The follow-up period was 4-21 months. Our new laparoscopic longitudinal anterior pancreaticojejunostomy technique (Puestow procedure) using barbed sutures is a potentially efficient and minimally invasive procedure for patients who suffer from pancreatic duct obstruction and chronic pancreatitis.

  20. Pancreatic-duct-lavage cytology in candidates for surgical resection of branch-duct intraductal papillary mucinous neoplasm of the pancreas: should the International Consensus Guidelines be revised?

    Science.gov (United States)

    Sai, Jin Kan; Suyama, Masafumi; Kubokawa, Yoshihiro; Watanabe, Sumio; Maehara, Tadayuki

    2009-03-01

    The International Consensus Guidelines are helpful for the management of branch-duct intraductal papillary mucinous neoplasms (IPMNs), because they allow us to exclude malignancy. However, it is not possible to predict malignancy with certainty, and further preoperative differentiation between benign and malignant IPMNs is required to avoid the false-positive results. To examine the usefulness of pancreatic-duct-lavage cytology by using an originally designed double-lumen catheter for discriminating benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines. Pancreatic-duct-lavage cytology was investigated in 24 patients with branch-duct IPMNs who underwent surgical resection based on the International Consensus Guidelines, namely, they either had intramural nodules or the ectatic branch duct was >30 mm in diameter. Single-center retrospective study. Academic medical center. The sensitivity and specificity of pancreatic-duct-lavage cytology for discriminating benign from malignant IPMNs. More than 30 mL of pancreatic-duct-lavage fluid was obtained from each patient, and there were no patients with noninformative results. The sensitivity, specificity, positive predictive value, and negative predictive value of the cytologic diagnosis were 78%, 93%, 88%, and 88%, respectively. Single-center and small number of patients. Pancreatic-duct-lavage cytology can improve differentiation between benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines.

  1. The potent activation of Ca(2+)-activated K(+) current by NVP-AUY922 in the human pancreatic duct cell line (PANC-1) possibly independent of heat shock protein 90 inhibition.

    Science.gov (United States)

    Chiang, Nai-Jung; Wu, Sheng-Nan; Chen, Li-Tzong

    2015-04-01

    NVP-AUY922 (AUY) is a potent inhibitor of heat shock protein 90 (HSP90). Whether this compound can exert additional effects on membrane ion channels remains elusive. We investigated the effect of AUY on ion currents in human pancreatic duct epithelial cells (PDECs), including PANC-1 and MIA PaCa-2. AUY increased the amplitude of the K(+) current (IK) in PANC-1 cells shown by whole-cell configuration. Single-channel recordings revealed a large-conductance Ca(2+)-activated K(+) (BKCa) channel in PANC-1, but not in MIA PaCa-2. In cell-attached mode, AUY increased the probability of BKCa channel opening and also potentiated the activity of stretch-induced channels. However, other HSP inhibitors, 17-AAG or BIIB021 only slightly increased the activity of BKCa channels. In inside-out recordings, sodium hydrosulphide or caffeic acid phenethyl ester increased the activity of BKCa channels, but AUY did not. We further evaluated whether conductance of Ca(2+)-activated K(+) channels (IK(Ca)) influenced secretion of HCO3(-) and fluid in PDECs by using a modified Whitcomb-Ermentrout model. Simulation studies showed that an increase in IK(Ca) resulted in additional secretion of HCO3(-) and fluid by mimicking the effect of AUY in PDECs. Collectively, AUY can interact with the BKCa channel to largely increase IK(Ca) in PDECs. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  2. Morphological study of pancreatic duct in red jungle fowl

    African Journals Online (AJOL)

    Jane

    2010-10-18

    Oct 18, 2010 ... African Journal of Biotechnology Vol. 9(42), pp. 7209-7215 ... pancreatic tissues, while the endocrine units were observed frequently in the third and splenic lobes. A ... histological and histochemical features of the pancreatic.

  3. Direct measurement of acid efflux from isolated guinea pig pancreatic ducts.

    Science.gov (United States)

    Hootman, Seth R; Hobbs, Errett C; Luckie, Douglas B

    2005-05-01

    The current studies used the technique of microphysiometry to directly determine the effects of stimulators and inhibitors of pancreatic duct secretion on acid efflux from isolated pancreatic ducts. Main and interlobular ducts were isolated from guinea pig pancreata by collagenase digestion and manual selection. Segments were placed in the chambers of a microphysiometer, which uses a silicon chip-based, light-addressable potentiometric sensor to determine the proton concentration in the superfusing solution. Isolated ducts were superfused with a low buffer capacity Ringer's solution at 37 degrees C and the extracellular acidification rate (EAR) was determined by computer-directed protocols. A survey of potential agonists demonstrated that both secretin and the cholinomimetic, carbachol, dramatically increased EAR, with EC50 of 3 nmol/L and 0.6 mumol/L, respectively. The changes in EAR induced by both secretagogues were rapid, peaking within 4-6 minutes, and then declining to a level below the peak but above basal EAR. The enhanced EAR was maintained for at least 30 minutes in the presence of either secretagogue. More modest increases in EAR were evoked by bombesin, substance P, and vasoactive intestinal peptide (VIP). Cholecystokinin and isoproterenol caused no significant change in pancreatic duct EAR. A combination of amiloride and bafilomycin A1, inhibitors, respectively, of Na/H exchange and of vacuolar type H-ATPase activity, caused a dramatic drop in EAR but did not fully inhibit the increase in EAR elicited by carbachol, suggesting that other mechanisms may contribute to agonist-stimulated EAR of pancreatic ducts. Thus, the results support the use of microphysiometry as a tool to study pancreatic duct physiology and in particular a method to measure acid efflux from the serosal surface.

  4. Squamoid cystosis of pancreatic ducts: a variant of a newly-described cystic lesion, with evidence for an obstructive etiology

    Directory of Open Access Journals (Sweden)

    Wai Chin Foo

    2014-09-01

    Full Text Available 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 panreatic 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.

  5. Spiral (Helical) computed tomographic imaging for the diagnosis of bile duct cancer. Vascular and pancreatic invasions

    International Nuclear Information System (INIS)

    Kon, Masanori

    1997-01-01

    The development of several imaging techniques for diagnosing bile duct cancer have improved, however, its diagnosis at the early stage is still difficult. We discuss the significance of the spiral (helical) computed tomography (SCT) imaging for the diagnosis of bile duct cancer at an early stage. We performed, as a preoperative examination, SCT under intravenous angiography (IV-SCT) for all cases, which included 233 cases of benign bile duct diseases, 42 cases of gallbladder cancer and 22 cases of bile duct cancer. The accuracy rate of diagnosis ability of 42 cases of gallbladder cancer by IV-SCT was 91%, and that of portal vein invasion was 91%. In the cases of bile duct cancer, IV-SCT showed destructive images of the bile duct wall and the tumor images invaded into the pancreatic parenchyma, in the cases of invasion at the splenic vein and confluence site of the portal vein, IV-SCT gave clearer 3D images than conventional angiography. The accuracy rate of diagnosing pancreatic invasion in bile duct cancer by IV-SCT was 80%. However, it is still difficult to determine completely the layer structures of the bile duct and the invasion into the walls along the long axis. As the future development of SCT for the diagnosis of bile duct cancer, we expect further progression of diagnosis ability of bile duct cancer and the invasion level by the applying high resolution thin-section CT images or endoscopical images of the luminal organs in examining the bile duct. (K.H.)

  6. Covered Metal Stenting for Malignant Lower Biliary Stricture with Pancreatic Duct Obstruction: Is Endoscopic Sphincterotomy Needed?

    Directory of Open Access Journals (Sweden)

    Kazunari Nakahara

    2013-01-01

    Full Text Available Aims. To evaluate the need for endoscopic sphincterotomy (EST before covered self-expandable metal stent (CSEMS deployment for malignant lower biliary stricture with pancreatic duct obstruction. Methods. This study included 79 patients who underwent CSEMS deployment for unresectable malignant lower biliary stricture with pancreatic duct obstruction. Treatment outcomes and complications were compared between 38 patients with EST before CSEMS deployment (EST group and 41 without EST (non-EST group. Results. The technical success rates were 100% in both the EST and the non-EST group. The incidence of pancreatitis was 2.6% in the EST, and 2.4% in the non-EST group (. The incidences of overall complications were 18.4% and 14.6%, respectively, (. Within the non-EST groups, the incidence of pancreatitis was 0% in patients with fully covered stent deployment and 3.6% in those with partially covered stent deployment (. In the multivariate analysis, younger age (, OR 12 and nonpancreatic cancer (, OR 24 were significant risk factors for overall complications after CSEMS deployment. EST was not identified as a risk factor. Conclusions. EST did not reduce the incidence of pancreatitis after CSEMS deployment in patients of unresectable distal malignant obstruction with pancreatic duct obstruction.

  7. Clinical response to dorsal duct drainage via the minor papilla in refractory obstructing chronic calcific pancreatitis

    Science.gov (United States)

    Kwon, Chang-Il; Gromski, Mark A.; Sherman, Stuart; El Hajj, Ihab I.; Easler, Jeffrey J.; Watkins, James; McHenry, Lee; Lehman, Glen A.; Fogel, Evan L.

    2017-01-01

    Background and study aims Complete stone removal from the main pancreatic duct might not be achieved in all patients with obstructive chronic calcific pancreatitis. We report our results for endoscopic dorsal pancreatic duct (DPD) bypass of obstructing stones in the ventral pancreatic duct (VPD). Patients and methods 16 patients with obstructive chronic calcific pancreatitis were treated with a DPD bypass. Clinical success was defined as significant pain relief and no hospital admissions for pain management during the ongoing treatment period. Results Among 16 patients meeting entry criteria, 10 (62.5%) had a history of unsuccessful endoscopic therapy, and 8 had failed extracorporeal shockwave lithotripsy (ESWL). Clinical success was achieved in 12 patients (75 %). Among these responders, 10 patients (83.3 %) had markedly improved or complete pain relief after the first stent placement, which persisted throughout the follow-up period; 11 patients (91.7 %) were able to discontinue their daily analgesics. Conclusions In selected patients with obstructive chronic calcific pancreatitis, the DPD bypass may be considered as a rescue endoscopic therapy, potentially obviating the need for surgery when standard endoscopic methods and ESWL fail. PMID:28201840

  8. Experience in surgical treatment of 19 patients with pancreatic duct stones

    Directory of Open Access Journals (Sweden)

    ZHANG Yahui

    2015-05-01

    Full Text Available ObjectiveTo summarize the experience in the diagnosis and surgical treatment selection of pancreatic duct stones (PDS. MethodsThe medical records of 19 patients with PDS in Rongchang Hospital of Traditional Chinese Medicine from January 2006 to September 20l4 were analyzed retrospectively in terms of clinical characteristics, diagnosis, and treatment. All 19 patients were diagnosed with PDS by imaging examinations such as B-ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography. Besides all cases diagnosed with chronic pancreatitis, 3 cases were accompanied by diabetes, 2 cases by jaundice, 1 case by biliary tract hemorrhage, and 1 case by carcinoma of the pancreatic head. ResultsAll patients received surgeries including 9 cases of pancreatic duodenal resection, 5 cases of both pancreatolithotomy and pancreatic duct jejunum anastomosis, 2 cases of simple resection of pancreatic body and tail, and 2 cases of duodenum-preserving pancreatic head resection. ConclusionSurgery is the most commonly used, curative method for PDS patients. Based on fully analyzing the actual situation of patients, personalized operation treatment can ensure operation success rate and improve patients′ quality of life.

  9. Pancreatic duct stenosis: Differential diagnosis between malignant and benign conditions at secretin-enhanced MRCP.

    Science.gov (United States)

    Boninsegna, Enrico; Manfredi, Riccardo; Negrelli, Riccardo; Avesani, Giacomo; Mehrabi, Sara; Pozzi Mucelli, Roberto

    To define imaging criteria of benign and malignant nature in patients with main pancreatic duct (MPD) stenosis. S-MRCPs of 35 patients with pancreatitis and 14 with adenocarcinoma were evaluated. Adenocarcinoma caused higher prevalence of complete stenosis (14/14-100% vs 17/35-49%), dilated side-branches (14/14-100% vs 18/35-51%) and lower prevalence of duct-penetrating sign (0/14-0% vs 31/35-89%). The number of stenoses was higher in benign conditions (mean 1.4 Vs 1). Upstream MPD diameter was higher in cancer-induced stenoses (4.5 vs 2.9mm). Single complete stenosis with dilated side branches, increased MPD caliber and absent duct-penetrating sign are suggestive of malignancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Noninvasive study of anatomic variations of the bile and pancreatic duct using magnetic resonance cholangiopancreatography

    International Nuclear Information System (INIS)

    Fernandez, E.; Falco, J.; Campo, R.; Martin, J.; Brullet, E.; Espinos, J.

    1999-01-01

    To identify anatomic variations of the bile duct and pancreatic duct and papillary anomalies by means of magnetic resonance cholangiopancreatography (MRCP) and determine their correlation with endoscopic retrograde cholangiopancreatography (ERCP) findings. Eighty-five patients were selected by means of a prospective study comparing MRCP and ERCP. Coronal and axial HASTE images and coronal and oblique coronal RARE images were acquired in all the patients. Four of the studies (6%) were excluded because of poor technical quality. Anatomic variations were observed in 26 cases (30.5%), including trifurcation (n=7; 27%), right hepatic duct draining into left hepatic duct (n=2, 7.7%), right hepatic duct draining into common bile duct (n=4; 15.4%), extrahepatic confluence (n=2; 7.7%), medial cystic duct (n=2; 7.7%), parallel cystic duct (n=3; 11.5%), juxtapapillary duodenal diverticulum (n=3; 11.5%) and pancreas divisum (n=3; 11.5%). A good correlation was observed between the MRCP and ERCP findings. The introduction of MRCP into the noninvasive study of biliary disease may be useful in the detection of anatomic variations relevant to laparoscopic surgery and other endoscopic and interventional techniques. (Author) 11 refs

  11. Characterization of Insulin-Immunoreactive Cells and Endocrine Cells Within the Duct System of the Adult Human Pancreas.

    Science.gov (United States)

    Li, Rong; Zhang, Xiaoxi; Yu, Lan; Zou, Xia; Zhao, Hailu

    2016-01-01

    The adult pancreatic duct system accommodates endocrine cells that have the potential to produce insulin. Here we report the characterization and distribution of insulin-immunoreactive cells and endocrine cells within the ductal units of adult human pancreas. Sequential pancreas sections from 12 nondiabetic adults were stained with biomarkers of ductal epithelial cells (cytokeratin 19), acinar cells (amylase), endocrine cells (chromogranin A; neuron-specific enolase), islet hormones (insulin, glucagon, somatostatin, pancreatic polypeptide), cell proliferation (Ki-67), and neogenesis (CD29). The number of islet hormone-immunoreactive cells increased from large ducts to the terminal branches. The insulin-producing cells outnumbered endocrine cells reactive for glucagon, somatostatin, or pancreatic polypeptide. The proportions of insulin-immunoreactive count compared with local islets (100% as a baseline) were 1.5% for the main ducts, 7.2% for interlobular ducts, 24.8% for intralobular ducts, 67.9% for intercalated ducts, and 348.9% for centroacinar cells. Both Ki-67- and CD29-labeled cells were predominantly localized in the terminal branches around the islets. The terminal branches also showed cells coexpressing islet hormones and cytokeratin 19. The adult human pancreatic ducts showed islet hormone-producing cells. The insulin-reactive cells predominantly localized in terminal branches where they may retain potential capability for β-cell neogenesis.

  12. The Impact of Bile Duct Cultures on Surgical Site Infections in Pancreatic Surgery.

    Science.gov (United States)

    Herzog, Torsten; Belyaev, Orlin; Akkuzu, Rehsan; Hölling, Janine; Uhl, Waldemar; Chromik, Ansgar M

    2015-08-01

    In pancreatic surgery pre-operative biliary drainage (PBD) is associated with bacteribilia, which increases the risk for surgical site infections (SSIs). This study is a retrospective observational cohort design that compared micro-organisms of intra-operative bile duct cultures with micro-organisms of SSIs after pancreaticoduodenectomy. From January 2004 until December 2010, 887 patients underwent pancreaticoduodenectomy or hepaticojejunostomy for benign and malignant peri-ampullary lesions. Surgical site infections occurred in 10% (87/887). Cultures of SSIs with corresponding intra-operative bile duct cultures were available for 59 patients. Sixty-four percent (38/59) had undergone PBD. Pre-operative biliary drainage was associated with positive intra-operative bile duct cultures in 95% (36/38), versus 48% (10/21; p≤0.001). The correlation of SSIs with intra-operative bile duct cultures was 59% (35/59). There was a significant association between the micro-organisms cultured from SSIs and the corresponding bile duct cultures for Enterococcus spp., Escherichia coli, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), Enterobacteriaceae with extended spectrum ß-lactamase (ESBL), and Candida spp. After pancreaticoduodenectomy, SSIs are often caused by the same micro-organisms that are present on intra-operative bile duct cultures, especially after PBD. Therefore, intra-operative bile duct cultures should be performed routinely to adjust the antibiotic prophylaxis according to the local hospital surveillance data.

  13. Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis.

    Science.gov (United States)

    Cahen, Djuna L; Gouma, Dirk J; Laramée, Philippe; Nio, Yung; Rauws, Erik A J; Boermeester, Marja A; Busch, Olivier R; Fockens, Paul; Kuipers, Ernst J; Pereira, Stephen P; Wonderling, David; Dijkgraaf, Marcel G W; Bruno, Marco J

    2011-11-01

    A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis.

    Science.gov (United States)

    Łaski, Dariusz; Hać, Stanisław; Marek, Iwona; Kobiela, Jarosław; Kostro, Justyna; Adrych, Krystian; Śledziński, Zbigniew

    2018-03-01

    Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland - NFZ) and the national insurance system (Poland - ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung's duct within the Polish health care system. In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months.

  15. Can pancreatic duct-derived progenitors be a source of islet regeneration?

    International Nuclear Information System (INIS)

    Xia, Bing; Zhan, Xiao-Rong; Yi, Ran; Yang, Baofeng

    2009-01-01

    The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing β-cells. The functional mass of β-cells is decreased in type 1 diabetes, so replacing missing β-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the β-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding β-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet β-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal cells as an in vivo progenitor for

  16. Can pancreatic duct-derived progenitors be a source of islet regeneration?

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Bing [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Zhan, Xiao-Rong, E-mail: xiaorongzhan@sina.com [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Yi, Ran [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Yang, Baofeng [Department of Pharmacology, State Key Laboratory of Biomedicine and Pharmacology, Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China)

    2009-06-12

    The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing {beta}-cells. The functional mass of {beta}-cells is decreased in type 1 diabetes, so replacing missing {beta}-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the {beta}-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding {beta}-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet {beta}-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal

  17. Evaluation of pancreatic exocrine insufficiency by cine-dynamic MRCP using spatially selective inversion-recovery (IR) pulse: Correlation with severity of chronic pancreatitis based on morphological changes of pancreatic duct.

    Science.gov (United States)

    Yasokawa, Kazuya; Ito, Katsuyoshi; Kanki, Akihiko; Yamamoto, Akira; Torigoe, Teruyuki; Sato, Tomohiro; Tamada, Tsutomu

    2018-05-01

    To evaluate the correlation between the pancreatic exocrine insufficiency estimated by cine-dynamic MRCP using spatially selective IR pulse and the severity stages (modified Cambridge classification) based on morphological changes of the pancreatic duct in patients with suspected chronic pancreatitis. Thirty-nine patients with suspected chronic pancreatitis underwent cine-dynamic MRCP with a spatially selective IR pulse. The secretion grading score (5-point scale) based on the moving distance of pancreatic juice inflow on cine-dynamic MRCP was assessed, and compared with the stage of the severity of chronic pancreatitis based on morphological changes of pancreatic duct. The stage of the severity of chronic pancreatitis based on morphological changes had significant negative correlations with the secretion grade (r=-0.698, P0.70 in 2 (33%) of 6 patients showing normal pancreatic exocrine function. It should be noted that the degree of morphological changes of pancreatic duct does not necessarily reflect the severity of pancreatic exocrine insufficiency at cine-dynamic MRCP in stage 2-3 chronic pancreatitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer

    Science.gov (United States)

    2018-04-27

    Extrahepatic Bile Duct Adenocarcinoma, Biliary Type; Gallbladder Adenocarcinoma, Biliary Type; Metastatic Pancreatic Adenocarcinoma; Recurrent Cholangiocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Intrahepatic Cholangiocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Gallbladder Cancer AJCC V7; Stage III Hepatocellular Carcinoma AJCC v7; Stage III Intrahepatic Cholangiocarcinoma AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7; Stage IVB Gallbladder Cancer AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Carcinoma

  19. Extracorporeal shock wave lithotripsy for pancreatic and large common bile duct stones

    Science.gov (United States)

    Tandan, Manu; Reddy, D Nageshwar

    2011-01-01

    Extraction of large pancreatic and common bile duct (CBD) calculi has always challenged the therapeutic endoscopist. Extracorporeal shockwave lithotripsy (ESWL) is an excellent tool for patients with large pancreatic and CBD calculi that are not amenable to routine endotherapy. Pancreatic calculi in the head and body are targeted by ESWL, with an aim to fragment them to ESWL with 5000 shocks being delivered at each session. The use of epidural anesthesia helped in reducing patient movement. This, together with the better focus achieved with newer third-generation lithotripters, prevents collateral tissue damage and minimizes the complications. Complications in our experience with nearly 1300 patients were minimal, and no extension of hospital stay was required. Similar rates of clearance of pancreatic and biliary calculi with minimal adverse effects have been reported from the centers where ESWL is performed regularly. In view of its high efficiency, non-invasive nature and low complication rates, ESWL can be offered as the first-line therapy for selected patients with large pancreatic and CBD calculi. PMID:22110261

  20. IMMEDIATE AND DISTANT EFFECTS OF THE PANCREATIC DUCT OCCLUSION BY THE FIBRIN ADHESIVE

    Directory of Open Access Journals (Sweden)

    Vojin Savić

    2002-05-01

    Full Text Available The paper represent an experimental study whose aim was to determine immediate consequences of the pancreatic duct occlusion by the fibrin adhesive upon the pancreas parenchyma as well as distant negative effects upon the exocrine and endocrine pancreatic secretion.The experiment was carried out on the dogs divided into two groups of twenty animals, namely, into the experimental group of those animals that were subdued to the pancreas resection with the PJA formation and the anastomosis protection by means of the pancreatic duct occlusion with the fibrin adhesive (Tissucol - Immuno AG and the control group that was, under the same conditions, subdued to the pancreas resection and the PJA with no anastomosis protection. In the post-operative course the animals cere monitored for five months and during that time they were subjected to the clinic, biochemical, pathohistological, histochemical, immunocito-chemical and scanning electronic-microscopic examination.The fibrin cork lyse was noticed since the fifth post-operative day while it was fully completed on the thirteenth post-operative day. The statistical analysis of the biochemical parameters as well as pathohistological and scanning-electronic exami-nations have revealed the signs of easier, sub-clinic forms of edematose pancreatitis with a short-term increase of the amylase level. The examinations after 150 days have shown the preserved morphology and the functional integrity of the exocrine and en-docrine pancreas.The authors conclude that the fibrin adhesive application in preventing the loosening up of the pancreatic jejuna anastomosis represents a simple and efficient procedure with no negative effects upon the exocrine and endocrine function and the pancreas morphology.

  1. Resolving external pancreatic fistulas in patients with disconnected pancreatic duct syndrome: using rendezvous techniques to avoid surgery (with video).

    Science.gov (United States)

    Irani, Shayan; Gluck, Michael; Ross, Andrew; Gan, S Ian; Crane, Robert; Brandabur, John J; Hauptmann, Ellen; Fotoohi, Mehran; Kozarek, Richard A

    2012-09-01

    An external pancreatic fistula (EPF) generally results from an iatrogenic manipulation of a pancreatic fluid collection (PFC), such as walled-off pancreatic necrosis (WOPN). Severe necrotizing pancreatitis can lead to complete duct disruption, causing disconnected pancreatic duct syndrome (DPDS) with viable upstream pancreas draining out of a low-pressure fistula created surgically or by a percutaneous catheter. The EPF can persist for months to years, and distal pancreatectomy, often the only permanent solution, carries a high morbidity and defined mortality. To describe 3 endoscopic and percutaneous rendezvous techniques to completely resolve EPFs in the setting of DPDS. A retrospective review of a prospective database of 15 patients who underwent rendezvous internalization of EPFs. Tertiary-care pancreatic referral center. Fifteen patients between October 2002 and October 2011 with EPFs in the setting of DPDS and resolved WOPN. Three rendezvous techniques that combined endoscopic and percutaneous procedures to internalize EPFs by transgastric, transduodenal, or transpapillary methods. EPF resolution and morbidity. Fifteen patients (12 men) with a median age of 51 years (range 24-65 years) with EPFs and DPDS (cutoff/blowout of pancreatic duct, with inability to demonstrate upstream body/tail of pancreas on pancreatogram) resulting from severe necrotizing pancreatitis underwent 1 of 3 rendezvous procedures to eliminate the EPFs. All patients were either poor surgical candidates or refused surgery. At the time of the rendezvous procedure, WOPN had fully resolved, DPDS was confirmed on pancreatography, and the EPF had persisted for a median of 5 months (range 1-48 months), producing a median output of 200 mL/day (range 50-700 mL/day). The rendezvous technique in 10 patients used the existing percutaneous drainage fistula to puncture into the stomach/duodenum to deliver wires that were captured endoscopically. The transenteric fistula was dilated and two

  2. Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression. A longitudinal prospective analysis of the modified puestow procedure.

    Science.gov (United States)

    Nealon, W H; Thompson, J C

    1993-05-01

    This study evaluated the effect of operative drainage of the main pancreatic duct (MPD) on functional derangements associated with chronic pancreatitis (CP). The author previously reported delayed functional impairment in an evaluation of the impact of operative drainage in patients with CP. The author now reports on a prospective study of 143 patients with this diagnosis. Each patient underwent 1) ERCP, 2) the Bentiromide PABA, 3) 72-hour fecal fat test, 4) oral glucose tolerance test (OGTT) and 5) fat meal (LIPOMUL)--stimulated pancreatic polypeptide release (PP). All patients were stratified as mild/moderate (M/M) or severe CP on the basis of a 5-point system that was developed by the author. Patients were studied at 16-month intervals. All 143 patients underwent initial and follow-up evaluations in a mean follow-up of 47.3 months; 83 of 143 patients had M/M grade at initial evaluation. Eighty-seven patients underwent (MPD) decompression to relieve abdominal pain. In a separate prospective 17 patients with a diagnosis of CP, a grade of M/M and non-disabling abdominal pain were randomized to operative or non-operative treatment; 9 of these randomized patients were operated upon and 8 were not. No patient improved their grade during follow-up; 47 of 83 M/M patients had operative drainage and 36 did not. This grade was preserved in 41 of 47 (87%) operated patients but in only 8 of the 36 non-operated patients (22%). In the randomized trial, seven of nine operated patients retained their functional status in follow-up, whereas only two of eight patients (25%) randomized to non-operation preserved their functional grade. These data in this large study as well as among a previous randomized sample, support a policy of early operative drainage before the development of irreversible functional impairment in patients with chronic pancreatitis and associated dilation of the main pancreatic duct.

  3. The Main Anatomical Variations of the Pancreatic Duct System: Review of the Literature and Its Importance in Surgical Practice.

    Science.gov (United States)

    Dimitriou, Ioannis; Katsourakis, Anastasios; Nikolaidou, Eirini; Noussios, George

    2018-05-01

    Anatomical variations or anomalies of the pancreatic ducts are important in the planning and performance of endoscopic retrograde cholangiopancreatography (ERCP) and surgical procedures of the pancreas. Normal pancreatic duct anatomy occurs in approximately 94.3% of cases, and multiple variations have been described for the remaining 5.7%. The purpose of this study was to review the literature on the pancreatic duct anatomy and to underline its importance in daily invasive endoscopic and surgical practice. Two main databases were searched for suitable articles published from 2000 to 2017, and results concerning more than 8,200 patients were included in the review. The most common anatomical variation was that of pancreas divisum, which appeared in approximately 4.5% of cases.

  4. Chloride and potassium conductances of cultured human sweat ducts

    DEFF Research Database (Denmark)

    Novak, I; Pedersen, P S; Larsen, Erik Hviid

    1992-01-01

    The purpose of this study was to characterize the ion conductances, in particular those for Cl- and K+, of human sweat duct cells grown in primary culture. Sweat duct cells from healthy individuals were grown to confluence on a dialysis membrane, which was then mounted in a mini-Ussing chamber an...

  5. Primary cystic pancreatic neoplasms and tumor-like conditions. MR cholangiopancreatographic evaluation of lesions and Wirsung's duct

    International Nuclear Information System (INIS)

    Garcia, Adriana; Spina, Juan C. h; Rogondino, Jose; Chacon, Carolina; Gutierrez, Silvia

    2003-01-01

    Objective: To evaluate the contribution of single shot fast spin echo (SSFSE) in the diagnosis of cystic lesions in the pancreas, and their relation to Wirsung's duct. Material and methods: In 66 patients (33 women and 33 men; mean age: 66 years) cystic pancreatic lesions were retrospectively analyzed. The SSFSE technique was used, including an evaluation of Wirsung's duct. Conventional pancreatic sequences were added. The following lesion features were assessed: location, number, size, relation to Wirsung's duct, nature of the cystic image and signal intensity of the neoplasm or tumor-like condition. Surgical and anatomopathological correlation was obtained in 31/66 cases (47%). Results: The cystic lesions were divided in 2 groups: A) cystic lesions related to Wirsung's duct, 30 patients: all lesions measured less than 30 mm in size. Seven patients underwent surgical treatment; in 22 cases surgery was not indicated. One patient refused surgery. A mucinous papilliferous intraductal tumor was diagnosed in 3 cases, ampullar carcinoma in 1 case, pancreatic carcinoma, 1 case, autoimmune pancreatitis, 1 case, and cystic duct dilatation due to benign fibrous stenosis, 1 case. B) Cystic lesions not related to Wirsung's duct (36 patients): 7 serous cystadenomas, 7 adenocarcinomas with a cystic component, 1 mucinous cystadenoma, 1 duodenal diverticulum, 7 pseudocysts and 1 neuroendocrine tumor. In 12 patients surgery was not carried out due to clinical contraindication or patient's refusal. Conclusion: SSFSE allowed a clear differentiation between cystic lesions related (Group A) and non-related (Group B) to Wirsung's duct. The diagnosis could not be achieved by usual MRI sequences. However, benign and malignant lesions were observed in both groups. In all cases SSFSE afforded useful data either for surgical treatment or clinical follow-up. (author)

  6. Isolated Main Pancreatic Duct Dilatation: CT Differentiation Between Benign and Malignant Causes.

    Science.gov (United States)

    Kim, Se Woo; Kim, Se Hyung; Lee, Dong Ho; Lee, Sang Min; Kim, Yeon Soo; Jang, Jin Young; Han, Joon Koo

    2017-11-01

    The purpose of this study is to retrospectively evaluate the differential CT features of isolated benign and malignant main pancreatic duct (MPD) dilatation and to investigate whether the diagnostic performance of radiologists can be improved with knowledge of these differential CT features. Forty-one patients who had isolated MPD dilatation without any visible mass on CT from January 2000 to October 2016 were retrospectively enrolled in the study. Two radiologists reviewed CT images in consensus for the location, shape (smooth vs abrupt), length of transition, dilated pancreatic duct (PD) diameter, presence of duct penetrating sign, parenchymal atrophy, attenuation difference, associated pancreatitis, calcification, PD or common bile duct (CBD) enhancement, and perilesional cyst. The chi-square test, Fisher exact test, and t test were used to find the differential CT features of benign and malignant MPD dilatation. Two successive review sessions for differentiation between the two disease entities were then independently performed by three other reviewers with differing expertise, with the use of a 5-point confidence scale. The first session provided no information for differentiation; however, reviewers were aware of the results of univariate analyses in the second session. The diagnostic performance of the radiologists was evaluated using a pairwise comparison of ROC curves. A total of 19 benign and 22 malignant MPD dilatations were identified. In patients with benign MPD dilatation, transition areas were frequently located in the head (57.9% [11/19] vs 13.6% [3/22], p = 0.003) and showed significantly shorter (< 6.1 mm) (78.9% [15/19] vs 9.1% [2/22], p < 0.0001) and smooth transition (89.5% [17/19] vs 9.1% [2/22], p < 0.0001). Duct penetrating sign was exclusively observed in patients with benign MPD dilatation (73.7% [14/19] vs 0% [0/22], p < 0.0001). In contrast, malignant MPD dilatation frequently was accompanied by attenuation difference (63.6% [14/22] vs

  7. Rapid Evolution from the First Episode of Acute Pancreatitis to Chronic Pancreatitis in Human Subjects

    OpenAIRE

    Elie Aoun; Adam Slivka; Dionysios J Papachristou; David C Whitcomb; Ferga C Gleeson; Georgios I Papachristou

    2007-01-01

    Context Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. Objective To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. Setting The Severity of Acute Pancreatit...

  8. The Crosstalk between Nrf2 and TGF-β1 in the Epithelial-Mesenchymal Transition of Pancreatic Duct Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Sarah Arfmann-Knübel

    Full Text Available Nrf2 and TGF-β1 both affect tumorigenesis in a dual fashion, either by preventing carcinogen induced carcinogenesis and suppressing tumor growth, respectively, or by conferring cytoprotection and invasiveness to tumor cells during malignant transformation. Given the involvement of Nrf2 and TGF-β1 in the adaptation of epithelial cells to persistent inflammatory stress, e.g. of the pancreatic duct epithelium during chronic pancreatitis, a crosstalk between Nrf2 and TGF-β1 can be envisaged. By using premalignant human pancreatic duct cells (HPDE and the pancreatic ductal adenocarcinoma cell line Colo357, we could show that Nrf2 and TGF-β1 independently but additively conferred an invasive phenotype to HPDE cells, whereas acting synergistically in Colo357 cells. This was accompanied by differential regulation of EMT markers like vimentin, Slug, L1CAM and E-cadherin. Nrf2 activation suppressed E-cadherin expression through an as yet unidentified ARE related site in the E-cadherin promoter, attenuated TGF-β1 induced Smad2/3-activity and enhanced JNK-signaling. In Colo357 cells, TGF-β1 itself was capable of inducing Nrf2 whereas in HPDE cells TGF-β1 per-se did not affect Nrf2 activity, but enhanced Nrf2 induction by tBHQ. In Colo357, but not in HPDE cells, the effects of TGF-β1 on invasion were sensitive to Nrf2 knock-down. In both cell lines, E-cadherin re-expression inhibited the proinvasive effect of Nrf2. Thus, the increased invasion of both cell lines relates to the Nrf2-dependent downregulation of E-cadherin expression. In line, immunohistochemistry analysis of human pancreatic intraepithelial neoplasias in pancreatic tissues from chronic pancreatitis patients revealed strong Nrf2 activity already in premalignant epithelial duct cells, accompanied by partial loss of E-cadherin expression. Our findings indicate that Nrf2 and TGF-β1 both contribute to malignant transformation through distinct EMT related mechanisms accounting for an

  9. Ex vivo human bile duct radiofrequency ablation with a bipolar catheter.

    Science.gov (United States)

    Atar, Mustafa; Kadayifci, Abdurrahman; Daglilar, Ebubekir; Hagen, Catherine; Fernandez-Del Castillo, Carlos; Brugge, William R

    2018-06-01

    Management of the primary and secondary tumors of the bile ducts still remains as a major clinical challenge. Radiofrequency (RF) ablation (RFA) of these tumors is feasible but the effect of RF energy on the human common bile duct (CBD) and surrounding tissues has not been investigated. This pilot study aimed to determine the relationship between RF energy and the depth of ablation in the normal human CBD. The study was performed on fresh ex vivo human biliary-pancreatic tissue which had been resected for a pancreatic cyst or mass. The study was conducted within 15 min after resection. A bipolar Habib RFA catheter was placed into the middle of the intact CBD, and three different (5, 7, 10 W) power settings were applied over a 90-s period by an RF generator. Gross and histological examinations were performed. The depth of coagulation necrosis in CBD and the effect of RFA on CBD wall and surrounding pancreas tissue were determined by microscopic examination. The study included eight tissue samples. 5 W power was applied to three sites and RFA caused only focal epithelial necrosis limited to the CBD mucosa. 7 and 10 W were applied to five sites and coagulation necrosis occurred in all cases. Microscopically, necrosis was transmural, involved accessory bile duct glands, and extended to the surrounding pancreatic tissue in four of these cases. Macroscopically, RFA resulted in circumferential white-yellowish color change extending approximately 2 cm of the CBD. Bipolar RF energy application with 5 W resulted in limited ablation on CBD wall. However, 7 and 10 W generated tissue necrosis which extended through the CBD wall and into surrounding pancreas tissue. Endoscopic biliary RFA is an effective technique for local biliary tissue ablation but the use of high energy may injure surrounding tissue.

  10. Electrophysiological study of transport systems in isolated perfused pancreatic ducts: properties of the basolateral membrane

    DEFF Research Database (Denmark)

    Novak, I; Greger, R

    1988-01-01

    - concentration from 0 to 25 mmol/l produced fast and sustained depolarization of PDbl by 8.5 +/- 1.0 mV (n = 149). It was investigated whether the effect of HCO3- was due to a Na+-dependent transport mechanism on the basolateral membrane, where the ion complex transferred into the cell would be positively...... was monitored by electrophysiological techniques. In this report some properties of the basolateral membrane of pancreatic duct cells are described. The transepithelial potential difference (PDte) in ducts bathed in HCO3(-)-free and HCO3(-)-containing solution was -0.8 and -2.6 mV, respectively. The equivalent...... short circuit current (Isc) under similar conditions was 26 and 50 microA . cm-2. The specific transepithelial resistance (Rte) was 88 omega cm2. In control solutions the PD across the basolateral membrane (PDbl) was -63 +/- 1 mV (n = 314). Ouabain (3 mmol/l) depolarized PDbl by 4.8 +/- 1.1 mV (n = 6...

  11. Hilar cholangiocarcinoma is pathologically similar to pancreatic duct adenocarcinoma: suggestions of similar background and development.

    Science.gov (United States)

    Nakanuma, Yasuni; Sato, Yasunori

    2014-07-01

    Routine experiences suggest that cholangiocarcinomas (CCAs) show different clinicopathological behaviors along the biliary tree, and hilar CCA apparently resembles pancreatic duct adenocarcinoma (PDAC). Herein, the backgrounds for these similarities were reviewed. While all cases of PDAC, hilar CCA, intrahepatic CCA (ICCA) and CCA components of combined hepatocellular-cholangiocarcinoma (cHC-CCA) were adenocarcinomas, micropapillary patterns and columnar carcinoma cells were common in PDAC and hilar CCA, and trabecular components and cuboidal carcinoma cells were common in ICCA and CCA components of cHC-CCA. Anterior gradient protein-2 and S100P were frequently expressed in perihilar CCA and PDAC, while neural cell adhesion molecule and luminal epithelial membrane antigen were common in CCA components of c-HC-CCA. Pdx1 and Hes1 were frequently and markedly expressed aberrantly in PDAC and perihilar CCA, although their expression was rare and mild in CCA components in cHC-CCA and ICCA. Hilar CCA showed a similar postoperative prognosis to PDAC but differed from ICCA and cHC-CCA. Taken together, hilar CCA may differ from ICCA and CCA components of cHC-CCA but have a similar development to PDAC. These similarities may be explained by the unique anatomical, embryological and reactive nature of the pancreatobiliary tract. Further studies of these intractable malignancies are warranted. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  12. Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression

    Directory of Open Access Journals (Sweden)

    Rute M.M. Ferreira

    2017-10-01

    Full Text Available The cell of origin of pancreatic ductal adenocarcinoma (PDAC has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs, duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions. Using orthotopic transplantation and chimera experiments, we demonstrate that PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy tissues, explaining the co-existence of mucinous and non-mucinous lesions and highlighting the need to distinguish between true precursor PanINs and PanIN-like bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according to cell of origin, highlight that not all PanIN-like lesions are precursors of PDAC, and add an alternative progression route to the current model of PDAC development.

  13. Noninvasive Quantification of Pancreatic Fat in Humans

    OpenAIRE

    Lingvay, Ildiko; Esser, Victoria; Legendre, Jaime L.; Price, Angela L.; Wertz, Kristen M.; Adams-Huet, Beverley; Zhang, Song; Unger, Roger H.; Szczepaniak, Lidia S.

    2009-01-01

    Objective: To validate magnetic resonance spectroscopy (MRS) as a tool for non-invasive quantification of pancreatic triglyceride (TG) content and to measure the pancreatic TG content in a diverse human population with a wide range of body mass index (BMI) and glucose control.

  14. Postprandial changes in secretory flow of pancreatic juice in the main pancreatic duct: evaluation with cine-dynamic MRCP with a spatially selective inversion-recovery (IR) pulse

    International Nuclear Information System (INIS)

    Yasokawa, Kazuya; Ito, Katsuyoshi; Tamada, Tsutomu; Yamamoto, Akira; Hayashida, Minoru; Torigoe, Teruyuki; Tanimoto, Daigo; Higaki, Atsushi; Noda, Yasufumi; Kido, Ayumu

    2016-01-01

    To evaluate the influence of oral ingestion on the secretory flow dynamics of physiological pancreatic juice within the main pancreatic duct in healthy subjects by using cine-dynamic MRCP with spatially-selective inversion-recovery (IR) pulse non-invasively. Thirty-eight healthy subjects were investigated. MRCP with spatially-selective IR pulse was repeated every 15 s for 5 min to acquire a total of 20 images (cine-dynamic MRCP). A set of 20 MRCP images was repeatedly obtained before and after liquid oral ingestion every 7 min (including 2-min interval) for 40 min (a total of seven sets). Secretion grade of pancreatic juice on cine-dynamic MRCP was compared before and after oral ingestion using the nonparametric Wilcoxon signed-rank test. Median secretion grades of pancreatic juice at 5 min (score = 2.15), 12 min (score = 1.95) and 19 min (score = 2.05) after ingestion were significantly higher than that before ingestion (score = 1.40) (P = 0.004, P = 0.032, P = 0.045, respectively). Secretion grade of pancreatic juice showed a maximum peak of 2.15 at 5 min after ingestion. Thereafter, the secretion grade of pancreatic juice tended to gradually decline. Non-invasive cine-dynamic MRCP using spatially-selective IR pulse showed potential for evaluating postprandial changes in the secretory flow dynamics of pancreatic juice as a physiological reaction. (orig.)

  15. Postprandial changes in secretory flow of pancreatic juice in the main pancreatic duct: evaluation with cine-dynamic MRCP with a spatially selective inversion-recovery (IR) pulse

    Energy Technology Data Exchange (ETDEWEB)

    Yasokawa, Kazuya; Ito, Katsuyoshi; Tamada, Tsutomu; Yamamoto, Akira; Hayashida, Minoru; Torigoe, Teruyuki; Tanimoto, Daigo; Higaki, Atsushi; Noda, Yasufumi; Kido, Ayumu [Kawasaki Medical School, Department of Diagnostic Radiology, Kurashiki, Okayama (Japan)

    2016-12-15

    To evaluate the influence of oral ingestion on the secretory flow dynamics of physiological pancreatic juice within the main pancreatic duct in healthy subjects by using cine-dynamic MRCP with spatially-selective inversion-recovery (IR) pulse non-invasively. Thirty-eight healthy subjects were investigated. MRCP with spatially-selective IR pulse was repeated every 15 s for 5 min to acquire a total of 20 images (cine-dynamic MRCP). A set of 20 MRCP images was repeatedly obtained before and after liquid oral ingestion every 7 min (including 2-min interval) for 40 min (a total of seven sets). Secretion grade of pancreatic juice on cine-dynamic MRCP was compared before and after oral ingestion using the nonparametric Wilcoxon signed-rank test. Median secretion grades of pancreatic juice at 5 min (score = 2.15), 12 min (score = 1.95) and 19 min (score = 2.05) after ingestion were significantly higher than that before ingestion (score = 1.40) (P = 0.004, P = 0.032, P = 0.045, respectively). Secretion grade of pancreatic juice showed a maximum peak of 2.15 at 5 min after ingestion. Thereafter, the secretion grade of pancreatic juice tended to gradually decline. Non-invasive cine-dynamic MRCP using spatially-selective IR pulse showed potential for evaluating postprandial changes in the secretory flow dynamics of pancreatic juice as a physiological reaction. (orig.)

  16. Postprandial changes in secretory flow of pancreatic juice in the main pancreatic duct: evaluation with cine-dynamic MRCP with a spatially selective inversion-recovery (IR) pulse.

    Science.gov (United States)

    Yasokawa, Kazuya; Ito, Katsuyoshi; Tamada, Tsutomu; Yamamoto, Akira; Hayashida, Minoru; Torigoe, Teruyuki; Tanimoto, Daigo; Higaki, Atsushi; Noda, Yasufumi; Kido, Ayumu

    2016-12-01

    To evaluate the influence of oral ingestion on the secretory flow dynamics of physiological pancreatic juice within the main pancreatic duct in healthy subjects by using cine-dynamic MRCP with spatially-selective inversion-recovery (IR) pulse non-invasively. Thirty-eight healthy subjects were investigated. MRCP with spatially-selective IR pulse was repeated every 15 s for 5 min to acquire a total of 20 images (cine-dynamic MRCP). A set of 20 MRCP images was repeatedly obtained before and after liquid oral ingestion every 7 min (including 2-min interval) for 40 min (a total of seven sets). Secretion grade of pancreatic juice on cine-dynamic MRCP was compared before and after oral ingestion using the nonparametric Wilcoxon signed-rank test. Median secretion grades of pancreatic juice at 5 min (score = 2.15), 12 min (score = 1.95) and 19 min (score = 2.05) after ingestion were significantly higher than that before ingestion (score = 1.40) (P = 0.004, P = 0.032, P = 0.045, respectively). Secretion grade of pancreatic juice showed a maximum peak of 2.15 at 5 min after ingestion. Thereafter, the secretion grade of pancreatic juice tended to gradually decline. Non-invasive cine-dynamic MRCP using spatially-selective IR pulse showed potential for evaluating postprandial changes in the secretory flow dynamics of pancreatic juice as a physiological reaction. • Secretion grade of pancreatic juice at cine-dynamic MRCP after ingestion was evaluated. • Secretion grade was significantly increased within 19 min after liquid meal ingestion. • Secretion grade showed maximum peak of 2.15 at 5 min after ingestion. • Postprandial changes in pancreatic juice flow can be assessed by cine-dynamic MRCP.

  17. Locally advanced pancreatic duct adenocarcinoma: pancreatectomy with planned arterial resection based on axial arterial encasement.

    Science.gov (United States)

    Perinel, J; Nappo, G; El Bechwaty, M; Walter, T; Hervieu, V; Valette, P J; Feugier, P; Adham, M

    2016-12-01

    Pancreatectomy with arterial resection for locally advanced pancreatic duct adenocarcinoma (PDA) is associated with high morbidity and is thus considered as a contraindication. The aim of our study was to report our experience of pancreatectomy with planned arterial resection for locally advanced PDA based on specific selection criteria. All patients receiving pancreatectomy for PDA between October 2008 and July 2014 were reviewed. The patients were classified into group 1, pancreatectomy without vascular resection (66 patients); group 2, pancreatectomy with isolated venous resection (31 patients), and group 3, pancreatectomy with arterial resection for locally advanced PDA (14 patients). The primary selection criteria for arterial resection was the possibility of achieving a complete resection based on the extent of axial encasement, the absence of tumor invasion at the origin of celiac trunk (CT) and superior mesenteric artery (SMA), and a free distal arterial segment allowing reconstruction. Patient outcomes and survival were analyzed. Six SMA, two CT, four common hepatic artery, and two replaced right hepatic artery resections were undertaken. The preferred arterial reconstruction was splenic artery transposition. Group 3 had a higher preoperative weight loss, a longer operative time, and a higher incidence of intraoperative blood transfusion. Ninety-day mortality occurred in three patients in groups 1 and 2. There were no statistically significant differences in the incidence, grade, and type of complications in the three groups. Postoperative pancreatic fistula and postpancreatectomy hemorrhage were also comparable. In group 3, none had arterial wall invasion and nine patients had recurrence (seven metastatic and two loco-regional). Survival and disease-free survival were comparable between groups. Planned arterial resection for PDA can be performed safely with a good outcome in highly selected patients. Key elements for defining the resectability is based on

  18. Anatomic variants of the pancreatic duct and their clinical relevance: an MR-guided study in the general population

    International Nuclear Information System (INIS)

    Buelow, Robin; Thiel, Robert; Thamm, Patrick; Messner, Philip; Hosten, Norbert; Kuehn, Jens-Peter; Simon, Peter; Lerch, Markus M.; Mayerle, Julia; Voelzke, Henry

    2014-01-01

    To investigate the frequency of pancreatic duct (PD) variants and their effect on pancreatic exocrine function in a population-based study using non-invasive secretin-stimulated magnetic resonance cholangiopancreatography (sMRCP). Nine hundred and ninety-five volunteers, 457 women and 538 men, aged 51.9 ± 13.4 years, underwent navigator-triggered, T2-weighted, 3D turbo spin echo MRCP on a 1.5 T system after 1 unit/kg secretin administration. Two readers evaluated images for PD variants. Pancreatic exocrine function and morphological signs of chronic pancreatitis such as abnormalities of the main PD, side branch dilatation, and pancreatic cysts were evaluated and related to PD variants using a Kruskal-Wallis test and post hoc analysis. Of all sMRCP, 93.2 % were of diagnostic quality. Interobserver reliability for detection of PD variants was found to be kappa 0.752 (95 %CI, 0.733 - 0.771). Normal PD variants were observed in 90.4 % (n = 838/927). Variants of pancreas divisum was identified in 9.6 % (n = 89/927). Abnormalities of the main PD, side branch dilatation, and pancreatic cysts were observed in 2.4 %, 16.6 %, and 27.7 %, respectively, and were not significantly different between pancreas divisum and non-divisum group (P = 0.122; P = 0.152; P = 0.741). There was no association between PD variants and pancreatic exocrine function (P = 0.367). PD variants including pancreas divisum are not associated with morphological signs of chronic pancreatitis or restriction of pancreatic exocrine function. (orig.)

  19. Anatomic variants of the pancreatic duct and their clinical relevance: an MR-guided study in the general population

    Energy Technology Data Exchange (ETDEWEB)

    Buelow, Robin; Thiel, Robert; Thamm, Patrick; Messner, Philip; Hosten, Norbert; Kuehn, Jens-Peter [University Medicine, Ernst Moritz Arndt University Greifswald, Department of Radiology and Neuroradiology, Greifswald (Germany); Simon, Peter; Lerch, Markus M.; Mayerle, Julia [University Medicine, Ernst Moritz Arndt University Greifswald, Division of Gastroenterology and Department of Medicine A, Greifswald (Germany); Voelzke, Henry [University Medicine, Ernst Moritz Arndt University Greifswald, Institute for Community Medicine, Greifswald (Germany)

    2014-12-15

    To investigate the frequency of pancreatic duct (PD) variants and their effect on pancreatic exocrine function in a population-based study using non-invasive secretin-stimulated magnetic resonance cholangiopancreatography (sMRCP). Nine hundred and ninety-five volunteers, 457 women and 538 men, aged 51.9 ± 13.4 years, underwent navigator-triggered, T2-weighted, 3D turbo spin echo MRCP on a 1.5 T system after 1 unit/kg secretin administration. Two readers evaluated images for PD variants. Pancreatic exocrine function and morphological signs of chronic pancreatitis such as abnormalities of the main PD, side branch dilatation, and pancreatic cysts were evaluated and related to PD variants using a Kruskal-Wallis test and post hoc analysis. Of all sMRCP, 93.2 % were of diagnostic quality. Interobserver reliability for detection of PD variants was found to be kappa 0.752 (95 %CI, 0.733 - 0.771). Normal PD variants were observed in 90.4 % (n = 838/927). Variants of pancreas divisum was identified in 9.6 % (n = 89/927). Abnormalities of the main PD, side branch dilatation, and pancreatic cysts were observed in 2.4 %, 16.6 %, and 27.7 %, respectively, and were not significantly different between pancreas divisum and non-divisum group (P = 0.122; P = 0.152; P = 0.741). There was no association between PD variants and pancreatic exocrine function (P = 0.367). PD variants including pancreas divisum are not associated with morphological signs of chronic pancreatitis or restriction of pancreatic exocrine function. (orig.)

  20. Congenital varitans and anomalies of the pancreas and pancreatic duct: Imaging by magnetic resonance cholangiopancreaticography and multidetector computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Tuerkvatan, Aysel; Yener, Ouzlem [Dept. of Radiology, Tuerkiye Yueksek Ihtisas Hospital, Ankara (Turkmenistan); Erden, Aysel [Dept. of Radiology, Ankara University School of Medicine, Antalya (Turkmenistan); Tuerkoglu, Mehmet Akif [Dept. of General Surgery, Antalya University School of Medicine, Antalya (Turkmenistan)

    2013-12-15

    Though congenital anomalies of the pancreas and pancreatic duct are relatively uncommon and they are often discovered as an incidental finding in asymptomatic patients, some of these anomalies may lead to various clinical symptoms such as recurrent abdominal pain, nausea and vomiting. Recognition of these anomalies is important because these anomalies may be a surgically correctable cause of recurrent pancreatitis or the cause of gastric outlet obstruction. An awareness of these anomalies may help in surgical planning and prevent inadvertent ductal injury. The purpose of this article is to review normal pancreatic embryology, the appearance of ductal anatomic variants and developmental anomalies of the pancreas, with emphasis on magnetic resonance cholangiopancreaticography and multidetector computed tomography.

  1. Intraluminal wallstent +/- HDR brachytherapy in palliation of obstructive pancreatic and bile duct cancers: first report

    International Nuclear Information System (INIS)

    Bonetta, A.; Ricci, E.; Mortilla, M.G.; Conigliaro, R.; Zingoni, A.; Armaroli, L.

    1996-01-01

    Purpose: To report the first data of the Reggio Emilia Trial on tolerance and effectiveness of the High Dose Rate brachytherapy in the palliative treatment of extrahepatic bile ducts obstructions. The endpoints of this study are to assess if the endoluminal irradiation can delay the biliary tract re-occlusion and prolong the survival. Material and methods: All patients were treated positioning the Wallstent prosthesis by endoscopic route in the stenotic biliary tract; then they were randomised between observation and endoluminal brachytherapy. From 6/1994, 11 patients with bilio-pancreatic locally advanced cancer (8 pancreas, 3 biliary tract) were admitted to this study: 6 in the control arm and 5 in the brachytherapy group. The radiotherapy was performed by naso-biliary route, in the same day of the stenting, using a High Dose Rate Unit (Iridium 192 source) and prescribing the dose (14 Gy) at 1 cm from the catheter axis. The treatment was always performed in only one day, in 2 fractions with 8 hours split. Clinical data and haematological tests were recorded at 1 st , 7 th , 30 th days and every 3 months. Results: All patients had a complete regression of the jaundice; haematological tests (on 7 th and 30 th day) showed bilirubin, alkaline phosphatase, transaminases (SGOT, SGPT), and leukocytosis normalisation. Pancreatic or hepatic acute side effects, cholangitis (due to the endoscopy), actinic erosive gastroduodenitis, radiotherapy local necrosis, peritoneal reactions or naso-biliary tube intolerance were not observed. The average follow up is 144 days (30-476). So far, 8 patients are alive without symptoms and 3 patients died at 476,104, 87 days; 1 for cancer and 2 for other causes. Re-obstructions of the biliary tract did not occur. Conclusions: Wallstent prosthesis is highly efficient in jaundice palliation. The brachytherapy does not increase the toxicity of the disobstrucive treatments. So far, the overall and symptoms free survivals are not significantly

  2. Endoscopic ultrasonography-guided pancreatic duct access: techniques and literature review of pancreatography, transmural drainage and rendezvous techniques.

    Science.gov (United States)

    Itoi, Takao; Kasuya, Kazuhiko; Sofuni, Atsushi; Itokawa, Fumihide; Kurihara, Toshio; Yasuda, Ichiro; Nakai, Yousuke; Isayama, Hiroyuki; Moriyasu, Fuminori

    2013-05-01

    Endoscopic ultrasonography-guided (EUS)-guided pancreatic interventions have gained increasing attention. Here we review EUS-guided pancreatic duct (PD) access techniques and outcomes. EUS-guided PD intervention is divided into two types, antegrade and rendezvous techniques, following EUS-guided pancreatography. In the antegrade technique, pancreaticoenterostomy is carried out by stent placement between the PD and the stomach, duodenum, or jejunum. Transenteric antegrade PD stenting is conducted by stent placement, advancing anteriorly into the PD through the pancreatic tract. The rendezvous technique is carried out by using a guidewire through the papilla or anastomotic site for retrograde stent insertion. In terms of EUS-guided PD stenting, 11 case reports totaling 75 patients (35 normal anatomy, 40 altered anatomy) have been published. The technical success rate was greater than 70%. Early adverse events, including severe hematoma and severe pancreatitis,occurred in seven (63.6%) of 11 reports. Regarding the rendezvous technique, 12 case reports totaling 52 patients (22 normal anatomy, 30 altered anatomy) have been published. The technical success rate ranged from 25% to 100%. It was 48% in one report that involved more than 20 cases. Once stents were placed, all patients became free of symptoms. Early mild adverse events occurred in four (36.4%) of 11 reports. In conclusion, although it can be risky because of possible serious or even fatal adverse events, including pancreatic juice leakage, perforation and severe acute pancreatitis, EUS-PD access seems to be promising for treating symptomatic pancreatic diseases caused by PD stricture and pancreaticoenterostomy stricture. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

  3. CT and MRI assessment of symptomatic organized pancreatic fluid collections and pancreatic duct disruption: an interreader variability study using the revised Atlanta classification 2012.

    Science.gov (United States)

    Kamal, Ayesha; Singh, Vikesh K; Akshintala, Venkata S; Kawamoto, Satomi; Tsai, Salina; Haider, Maera; Fishman, Elliot K; Kamel, Ihab R; Zaheer, Atif

    2015-08-01

    Compare CT and MRI for fluid/debris component estimate and pancreatic duct (PD) communication with organized pancreatic fluid collections in acute pancreatitis. Evaluate fat density globules on CT as marker for debris. 29 Patients with 46 collections with CECT and MRI performed ≥4 weeks of symptom onset assessed for necrotizing pancreatitis, estimated percentage of fluid volume and PD involvement by two radiologists on separate occasions. T2WI used as standard for estimated percentage of fluid volume. Presence of fat globules and fluid attenuation on CT was recorded. Spearman rank correlation and kappa statistics were used to assess the correlation between imaging techniques and interreader agreement, respectively. Necrotizing pancreatitis seen on CT in 27 (93%, κ 0.119) vs. 20 (69%, κ 0.748) patients on MRI. CT identified 42 WON and 4 pseudocysts vs. 34 WON, and 12 pseudocysts on MRI. Higher interreader agreement for percentage fluid volume on MRI (κ = 0.55) vs. CT (κ = 0.196). Accuracy of CT in evaluation of percentage fluid volume was 65% using T2WI MRI used as standard. Fat globules identified on CT in 13(65%) out of 20 collections containing collections containing >75% fluid (p = 0.0001). PD involvement confidently excluded on CT in 68% collections vs. 93% on MRI. MRI demonstrates higher reproducibility for fluid to debris component estimation. Fat globules on CT were frequently seen in organized pancreatic fluid collections with large amount of debris. PD disruption more confidently excluded on MRI. This information may be helpful for pre-procedure planning.

  4. Duodenal duplication cyst (DDC) communicating with the pancreatobiliary duct--a rare cause of recurrent acute pancreatitis in adults.

    Science.gov (United States)

    Bong, Jan Jin; Spalding, Duncan

    2010-01-01

    Duodenal duplication cysts (DDC) are rare congenital anomalies that usually present in infancy and childhood. Acute presentation in adults is even rarer. We report a case of a 34-year-old man who presented with recurrent acute pancreatitis and was found to have a cystic lesion in the second part of his duodenum. Further investigations revealed communication between the cystic lesion and the distal common bile duct. We describe the details of the operative approach taken to resect the DDC. We describe the differential diagnoses and the criteria for diagnosing DDC. Management options for DDC are discussed along with our recommendations.

  5. Quantification of pancreatic exocrine function with secretin-enhanced magnetic resonance cholangiopancreatography: normal values and short-term effects of pancreatic duct drainage procedures in chronic pancreatitis. Initial results

    International Nuclear Information System (INIS)

    Bali, M.A.; Sztantics, A.; Metens, T.; Matos, C.; Arvanitakis, M.; Delhaye, M.; Deviere, J.

    2005-01-01

    The aim of this study was to quantify pancreatic exocrine function in normal subjects and in patients with chronic pancreatitis (CP) before and after pancreatic duct drainage procedures (PDDP) with dynamic secretin-enhanced magnetic resonance (MR) cholangiopancreatography (S-MRCP). Pancreatic exocrine secretions [quantified by pancreatic flow output (PFO) and total excreted volume (TEV)] were quantified twice in ten healthy volunteers and before and after treatment in 20 CP patients (18 classified as severe, one as moderate, and one as mild according to the Cambridge classification). PFO and TEV were derived from a linear regression between MR-calculated volumes and time. In all subjects, pancreatic exocrine fluid volume initially increased linearly with time during secretin stimulation. In controls, the mean PFO and TEV were 6.8 ml/min and 97 ml; intra-individual deviations were 0.8 ml/min and 16 ml. In 10/20 patients with impaired exocrine secretions before treatment, a significant increase of PFO and TEV was observed after treatment (P<0.05); 3/20 patients presented post-procedural acute pancreatitis and a reduced PFO. The S-MRCP quantification method used in the present study is reproducible and provides normal values for PFO and TEV in the range of those obtained from previous published intubation studies. The initial results in CP patients have demonstrated non-invasively a significant short-term improvement of PFO and TEV after PDDP. (orig.)

  6. Duct-ectatic type of mucin producing tumor of the pancreas--new concept of pancreatic neoplasia.

    Science.gov (United States)

    Kimura, W; Sasahira, N; Yoshikawa, T; Muto, T; Makuuchi, M

    1996-01-01

    Although there have been recent reports of mucin-producing tumor of the pancreas, there has been no thorough clinicopathological analysis of a large number of cases. Two hundred forty four cases of mucin-producing tumor of the pancreas from Japanese, European and American reports, together with 15 cases of our own, were analyzed clinicopathologically. Mucin-producing tumor of the pancreas was found in 177 males and 82 females (M:F = 2.2:1). The mean age was 65.5 years. Jaundice, diabetes mellitus and a past history of pancreatitis were found in 15%-19% of the cases. The tumor was most frequently (62%) found in the head of the pancreas. Pathologically, hyperplasia or adenoma was found in 58 cases, and adenocarcinoma in 160 cases. Five-year-survival rate by the Kaplan-Meier method was 82.6% in all of the cases and postoperative survival curve was much better in cases with this type of carcinoma than in cases with ordinary pancreatic duct cell carcinoma (5-year-survival rate: 82.6% vs 17.3%). Serum tumor markers such as CEA or CA 19-9 were not effective in differentiating between benign and malignant, or in determining the degree of cancerous spread, while cytology of the pancreatic juice and biopsy of the tumor could contribute to the diagnosis. Mucin-producing tumor has unique clinicopathological characteristics, such as the dilated main pancreatic duct or branches, dilatation of the orifice of the papilla of Vater, or good prognosis. Since a diagnosis for benign or malignant is very difficult in some cases, methods for distinguishing benign from malignant lesions or for determining cancerous spread, such as molecular biological techniques, should be established.

  7. Frey procedure for the treatment of chronic pancreatitis associated with common bile duct stricture.

    Science.gov (United States)

    Rebibo, Lionel; Yzet, Thierry; Cosse, Cyril; Delcenserie, Richard; Bartoli, Eric; Regimbeau, Jean-Marc

    2013-12-01

    The Frey procedure (FP) is the treatment of choice for symptomatic chronic pancreatitis (CP). In cases of biliary stricture, biliary derivation can be performed by choledochoduodenostomy, Roux-en-Y choledochojejunostomy or, more recently, reinsertion of the common bile duct (CBD) into the resection cavity. The objective of the present study was to evaluate the outcomes associated with each of these three types of biliary derivation. We retrospectively analyzed demographic, CP-related, surgical and follow-up data for patients having undergone FP for CP with biliary derivation between 2004 and 2012 in our university medical center. The primary efficacy endpoint was the rate of CBD stricture recurrence. The secondary endpoints were surgical parameters, postoperative complications, postoperative follow-up and the presence of risk factors for secondary CBD stricture. Eighty patients underwent surgery for CP during the study period. Of these, 15 patients received biliary derivation with the FP. Eight of the FPs (53.3%) were combined with choledochoduodenostomy, 4 (26.7%) with choledochojejunostomy and 3 (20.0%) with reinsertion of the CBD into the resection cavity. The mean operating time was 390 minutes. Eleven complications (73.3%) were recorded, including one major complication (6.7%) that necessitated radiologically-guided drainage of an abdominal collection. The mean (range) length of stay was 17 days (8-28) and the median (range) follow-up time was 35.2 months (7.2-95.4). Two patients presented stricture after CBD reinsertion into the resection cavity; one was treated with radiologically-guided dilatation and the other underwent revisional Roux-en-Y choledochojejunostomy. Three patients presented alkaline reflux gastritis (37.5%), one (12.5%) cholangitis and one CBD stricture after FP with choledochoduodenostomy. No risk factors for secondary CBD stricture were identified. As part of a biliary derivation, the FP gave good results. We did not observe any

  8. Endoscopic stenting for common bile duct stenoses in chronic pancreatitis: results and impact on long-term outcome.

    Science.gov (United States)

    Eickhoff, A; Jakobs, R; Leonhardt, A; Eickhoff, J C; Riemann, J F

    2001-10-01

    The overall incidence of common bile duct strictures due to chronic pancreatitis is reported to be approximately 10-30%. It remains a challenging problem for gastroenterologists and surgeons. The exact role of endoscopic stenting has not yet been clearly defined. Thirty-nine patients with chronic pancreatitis and symptomatic common bile duct stenoses underwent endoscopic stenting and were studied retrospectively. We were particularly interested in how many patients would achieve resolution of the stricture and tolerate removal of the stents in the long term. Indications for endoscopic stenting were symptomatic cholestasis, jaundice or cholangitis. The initial serum bilirubin was 8.3 mg/dl and the diameter of the common bile duct was 14.2 mm before stenting. Within 3-7 days of stenting, all patients presented improvement of jaundice and cholestasis. After a median stenting time of 9 months (range 1-144 months), 46% of the patients demonstrated regression of the stricture and clinical improvement, 26% required further stenting, and 28% were referred to surgery. Five patients received a self-expandable metal Wallstent. Thirty-one per cent demonstrated complete clinical recovery of the stricture as well as 10.2% a complete, radiologically verified stricture regression in a median follow-up of 58 months. There seems to be a therapeutic benefit for short-term endoscopic treatment but medium-term and long-term outcome remains questionable. Endoscopic stenting should be applied as an initial therapy before surgery, but it can be the definitive approach for older and morbid patients or cases with complete stricture regression after stent removal. Overall, it should not be considered as a routine procedure for symptomatic cases.

  9. Effect of L-cysteine on remote organ injury in rats with severe acute pancreatitis induced by bile-pancreatic duct obstruction.

    Science.gov (United States)

    Yang, Li-Juan; Wan, Rong; Shen, Jia-Qing; Shen, Jie; Wang, Xing-Peng

    2013-08-01

    Remote organ failure occurs in cases of acute pancreatitis (AP); however, the reports on AP induced by pancreatic duct obstruction are rare. In this study we determined the effect of L-cysteine on pancreaticobiliary inflammation and remote organ damage in rats after pancreaticobiliary duct ligation (PBDL). AP was induced by PBDL in rats with 5/0 silk. Sixty rats were randomly divided into 4 groups. Groups A and B were sham-operated groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). Groups C and D were PBDL groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). The tissue samples of the pancreas and remote organs such as the lung, liver, intestine and kidney were subsequently examined for pathological changes under a light microscope. The samples were also stored for the determination of malondialdehyde and glutathione levels. Blood urea nitrogen (BUN), plasma amylase, ALT and AST levels were determined spectrophotometrically using an automated analyzer. Also, we evaluated the effect of L-cysteine on remote organ injury in rats with AP induced by retrograde infusion of 3.5% sodium taurocholate (NaTc) into the bile-pancreatic duct. Varying degrees of injury in the pancreas, lung, liver, intestine and kidney were observed in the rats 24 hours after PBDL. The severity of injury to the lung, liver and intestine was attenuated, while injury status was not changed significantly in the pancreas and kidney after L-cysteine treatment. Oxidative stress was also affected by L-cysteine in PBDL-treated rats. The concentration of tissue malondialdehyde decreased in the pancreas and remote organs of PBDL and L-cysteine administrated rats, and the concentration of glutathione increased more significantly than that of the model control group. However, L-cysteine administration reduced the severity of injury in remote organs but not in the pancreas in rats with Na

  10. Removable fully covered self-expandable metal stents in the treatment of common bile duct strictures due to chronic pancreatitis: a case series

    NARCIS (Netherlands)

    Cahen, D. L.; Rauws, E. A.; Gouma, D. J.; Fockens, P.; Bruno, M. J.

    2008-01-01

    The aim of this study was to test the removability of fully covered self-expandable metal stents (FCSEMS) in patients with a benign common bile duct (CBD) stricture. A FCSEMS was inserted in six patients with a CBD stricture due to chronic pancreatitis who were considered to be unfit for surgery,

  11. Complete pancreatic heterotopia of gallbladder with hypertrophic duct simulating an adenomyoma

    Science.gov (United States)

    Pilloni, Luca; Cois, Alessandro; Uccheddu, Alessandro; Ambu, Rossano; Coni, Pierpaolo; Faa, Gavino

    2006-01-01

    The gallbladder is an unusual location of pancreatic heterotopia, defined as the presence of pancreatic tissue lacking anatomical and vascular continuity with the main body of the gland. A 28-year-old man presented with anorexia, nausea and pain in the right upper abdomen. On physical examination, the abdomen was tender to palpation and Murphy sign was positive. The patient underwent a cholecystecomy. This case, in our opinion, is very interesting since it permits to consider a controversial issue in the pathology of the gallbladder. The histological appearance of ductal structure in pancreatic heterotopia resembles the histological picture of both Aschoff-Rokitansky (AR) sinuses and adenomyomas. This finding suggests that these lesions are linked by a common histogenetic origin. We suggest that the finding of an adenomyoma in the gallbladder should prompt an extensive sampling of the organ in order to verify the coexistence of pancreatic rests. PMID:16586554

  12. IL-8 Expression in Granulocytic Epithelial Lesions of Idiopathic Duct-centric Pancreatitis (Type 2 Autoimmune Pancreatitis).

    Science.gov (United States)

    Ku, Yuna; Hong, Seung-Mo; Fujikura, Kohei; Kim, Sung Joo; Akita, Masayuki; Abe-Suzuki, Shiho; Shiomi, Hideyuki; Masuda, Atsuhiro; Itoh, Tomoo; Azuma, Takeshi; Kim, Myung-Hwan; Zen, Yoh

    2017-08-01

    Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (Ppancreatitis adjacent to pancreatic cancers (peritumoral pancreatitis) exhibited IL-8 expression in the epithelium (3/12; 25%) and inflammatory cells (10/12; 83%), expression levels were significantly lower than those in type 2 AIP (Ppancreatitis with 92% sensitivity and 92% to 100% specificity. Furthermore, CD3/IL-8-coexpressing lymphocytes were almost restricted to type 2 AIP. Interestingly, a similar pattern of IL-8 expression was also observed in colonic biopsies of ulcerative colitis. In conclusion, the overexpression of IL-8 may underlie the development of GELs in type 2 AIP, and IL-8 immunostaining or IL-8/CD3 double staining may become an ancillary method for its diagnosis. The similar expression pattern of IL-8 in ulcerative colitis also suggests a pathogenetic link between the 2 conditions.

  13. Oral Supplementation with a Special Additive of Retinyl Palmitate and Alpha Tocopherol Reduces Growth Retardation in Young Pancreatic Duct Ligated Pigs Used as a Model for Children Suffering from Exocrine Pancreatic Insufficiency

    Directory of Open Access Journals (Sweden)

    Anne Mößeler

    2016-09-01

    Full Text Available Pancreatic exocrine insufficiency (PEI is a disease of diverse aetiology—e.g., majority of patients suffering from cystic fibrosis (CF show PEI congenitally. Malnutrition and malabsorption of nutrients impair growth and nutritional status. As reduced fat digestion leads to a deficiency of fat-soluble vitamins the supplementation is standard, but absorption is a critical point in PEI-patients. The pancreatic duct ligated (PL pig is an established model for PEI in humans and has been proven to be a suitable model to compare different vitamin additives for supplementation. In a former study, PEI caused distinct growth retardation in young piglets, but did not affect growth in older ones. Our study hypothesised that this age-dependent effect is caused by exhausted body reserves of fat-soluble vitamins and, therefore, extra supply reduces growth retardation. PEI was induced by PL at the age of seven (PL-7 or 16 weeks (PL-16. Controls (C underwent a sham surgery. Some PL-7 pigs (PL-7 + Vit were fed a special vitamin additive. PEI reduced the mean final body weight (kg at 26 weeks of age significantly with lower effect in PL-16-pigs (C:117; PL-7:49.5; PL-7 + Vit:77.1; PL-16:96.4. Extra vitamin supply resulted in an increased growth and normalised serum concentration of alpha-tocopherol, underlining the importance of special supplementation in PEI-patients.

  14. Pancreatic Duct in Autoimmune Pancreatitis: Intraindividual Comparison of Magnetic Resonance Pancreatography at 1.5 T and 3.0 T.

    Science.gov (United States)

    Kim, Jin Hee; Byun, Jae Ho; Kim, Myung-Hwan; Lee, Sung Koo; Kim, Song Cheol; Kim, Hyoung Jung; Lee, Seung Soo; Kim, So Yeon; Lee, Moon-Gyu

    2017-08-01

    The aim of this study was to intraindividually compare magnetic resonance pancreatography (MRP) image quality at 1.5 T and 3.0 T when demonstrating main pancreatic duct (MPD) abnormalities in patients with autoimmune pancreatitis (AIP). Thirty prospectively enrolled patients with AIP underwent MRP at both 1.5 T and 3.0 T followed by endoscopic retrograde pancreatography before treatment. Two readers independently analyzed the MRP images and graded the visualization of MPD strictures and full-length MPD, using endoscopic retrograde pancreatography as the reference standard, as well as overall image artifacts on a 4-point scale. The contrast between the MPD and periductal area was calculated using a region-of-interest measurement. Visualization scores of MPD strictures and full-length MPD, and summed scores of each qualitative analysis, were significantly greater at 3.0-T MRP than at 1.5-T MRP for both readers (P ≤ 0.02). There were less image artifacts at 3.0 T compared with 1.5 T (P ≤ 0.052). The contrast between the MPD and periductal area was significantly greater at 3.0-T MRP than at 1.5-T MRP (P 3.0 T was superior to 1.5-T MRP for demonstrating MPD abnormalities in AIP, with better image contrast and fewer image artifacts. Consequently, 3.0-T MRP may be useful for the diagnosis and management of patients with AIP.

  15. Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells.

    Science.gov (United States)

    Kojima, Takashi; Takasawa, Akira; Kyuno, Daisuke; Ito, Tatsuya; Yamaguchi, Hiroshi; Hirata, Koichi; Tsujiwaki, Mitsuhiro; Murata, Masaki; Tanaka, Satoshi; Sawada, Norimasa

    2011-10-01

    The novel tight junction protein marvelD3 contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain like occludin and tricellulin. However, little is yet known about the detailed role and regulation of marvelD3 in normal epithelial cells and cancer cells, including pancreatic cancer. In the present study, we investigated marvelD3 expression in well and poorly differentiated human pancreatic cancer cell lines and normal pancreatic duct epithelial cells in which the hTERT gene was introduced into human pancreatic duct epithelial cells in primary culture, and the changes of marvelD3 during Snail-induced epithelial-mesenchymal transition (EMT) under hypoxia, TGF-β treatment and knockdown of FOXA2 in well differentiated pancreatic cancer HPAC cells. MarvelD3 was transcriptionally downregulated in poorly differentiated pancreatic cancer cells and during Snail-induced EMT of pancreatic cancer cells in which Snail was highly expressed and the fence function downregulated, whereas it was maintained in well differentiated human pancreatic cancer cells and normal pancreatic duct epithelial cells. Depletion of marvelD3 by siRNAs in HPAC cells resulted in downregulation of barrier functions indicated as a decrease in transepithelial electric resistance and an increase of permeability to fluorescent dextran tracers, whereas it did not affect fence function of tight junctions. In conclusion, marvelD3 is transcriptionally downregulated in Snail-induced EMT during the progression for the pancreatic cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Effect of bicarbonate on potassium conductance of isolated perfused rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I; Greger, R

    1991-01-01

    dissected from rat pancreas. The basolateral membrane potential PDbl of unstimulated duct cells was between -60 mV and -70 mV, and the cells had a relatively large K+ conductance in the basolateral membrane as demonstrated by (a) 20-22 mV depolarization of PDbl in response to increase in bath K...

  17. Operative drainage of the pancreatic duct delays functional impairment in patients with chronic pancreatitis. A prospective analysis.

    Science.gov (United States)

    Nealon, W H; Townsend, C M; Thompson, J C

    1988-01-01

    In a prospective study, 85 patients with chronic pancreatitis have been subjected to evaluation by morphologic analysis (endoscopic retrograde cholangiopancreatography), by exocrine function tests (bentiromide PABA and 72-hour fecal fat testing), and by endocrine function tests (oral glucose tolerance test and fat-stimulated release of pancreatic polypeptide). All patients were graded on a five-point system, with 1 point assessed for an abnormal result in each of the five tests performed. Zero score denoted mild disease; 1-2 points signaled moderate disease; and 3-5 points indicated severe disease. In 68 patients, both an initial and late (mean follow-up period of 14 months) evaluation were performed. Forty-one patients underwent modified Puestow side-to-side Roux-en-Y pancreaticojejunostomy. The Puestow procedure alone was performed in 18 patients. Eight patients also had drainage of pseudocysts, seven also had a biliary bypass, and eight had pseudocyst drainage plus bypass, in addition to the Puestow. There were no deaths. Of the 68 patients who were studied twice, 30 had operations and 38 did not. None of the patients with severe disease improved their grade during follow-up. Of 24 patients who did not undergo operation, 17 (71%) who were graded mild/moderate progressed to a severe grade at follow-up. By contrast, only three of the 19 patients operated on (16%) and who were initially graded as mild/moderate progressed to severe disease at follow-up testing. More than 75% of all of the patients had a history of weight loss. Twenty-six of 30 patients operated on (87%) (all of whom had lost weight before surgery) gained a mean 4.2 kg (range 1.4-2.7 kg) after surgery, compared with no significant weight change (range -3.6-2.7 kg) among patients not operated on. These findings support a policy of early operation for chronic pancreatitis, perhaps even in the absence of disabling abdominal pain. PMID:3421756

  18. Safety and Efficacy of Radiofrequency Ablation in the Management of Unresectable Bile Duct and Pancreatic Cancer: A Novel Palliation Technique

    Directory of Open Access Journals (Sweden)

    Paola Figueroa-Barojas

    2013-01-01

    Full Text Available Objectives. Radiofrequency ablation (RFA has replaced photodynamic therapy for premalignant and malignant lesions of the esophagus. However, there is limited experience in the bile duct. The objective of this pilot study was to assess the safety and efficacy of RFA in malignant biliary strictures. Methods: Twenty patients with unresectable malignant biliary strictures underwent RFA with stenting between June 2010 and July 2012. Diameters of the stricture before and after RFA, immediate and 30 day complications and stent patency were recorded prospectively. Results. A total of 25 strictures were treated. Mean stricture length treated was 15.2 mm (SD = 8.7 mm, Range = 3.5–33 mm. Mean stricture diameter before RFA was 1.7 mm (SD = 0.9 mm, Range = 0.5–3.4 mm while the mean diameter after RFA was 5.2 mm (SD = 2 mm, Range = 2.6–9 mm. There was a significant increase of 3.5 mm (t = 10.8, DF = 24, P value = <.0001 in the bile duct diameter post RFA. Five patients presented with pain after the procedure, but only one developed mild post-ERCP pancreatitis and cholecystitis. Conclusions: Radiofrequency ablation can be a safe palliation option for unresectable malignant biliary strictures. A multicenter randomized controlled trial is required to confirm the long term benefits of RFA and stenting compared to stenting alone.

  19. Comprehensive proteomic analysis of human pancreatic juice

    DEFF Research Database (Denmark)

    Grønborg, Mads; Bunkenborg, Jakob; Kristiansen, Troels Zakarias

    2004-01-01

    Proteomic technologies provide an excellent means for analysis of body fluids for cataloging protein constituents and identifying biomarkers for early detection of cancers. The biomarkers currently available for pancreatic cancer, such as CA19-9, lack adequate sensitivity and specificity...... contributing to late diagnosis of this deadly disease. In this study, we carried out a comprehensive characterization of the "pancreatic juice proteome" in patients with pancreatic adenocarcinoma. Pancreatic juice was first fractionated by 1-dimensional gel electrophoresis and subsequently analyzed by liquid...... in this study could be directly assessed for their potential as biomarkers for pancreatic cancer by quantitative proteomics methods or immunoassays....

  20. In Patients with a Soft Pancreas, a Thick Parenchyma, a Small Duct, and Fatty Infiltration Are Significant Risks for Pancreatic Fistula After Pancreaticoduodenectomy.

    Science.gov (United States)

    Sugimoto, Motokazu; Takahashi, Shinichiro; Kojima, Motohiro; Kobayashi, Tatsushi; Gotohda, Naoto; Konishi, Masaru

    2017-05-01

    This study sought to characterize soft and hard pancreatic textures radiologically and histologically, and to identify specific risks in a soft pancreas associated with postoperative pancreatic fistula (POPF) formation after pancreaticoduodenectomy (PD). Consecutive 145 patients who underwent PD at a single institution between January 2010 and May 2013 were studied. Pancreatic consistency was intraoperatively judged as soft or hard. Pancreatic configuration was assessed using preoperative CT. Histologic components of the pancreatic stump were evaluated using a morphometric analysis. Clinicopathologic parameters were then analyzed for the risk of clinically relevant POPF. Compared with patients with a hard pancreas (n = 66), those with a soft pancreas (n = 79) had a smaller main pancreatic duct (MPD) diameter and a larger parenchymal thickness on CT, had a smaller fibrosis ratio and a larger lobular ratio histologically, and developed clinically relevant POPF more frequently (P pancreas, an MPD diameter pancreas, a thick parenchyma, a small MPD, and fatty infiltration were strongly associated with clinically relevant POPF after PD.

  1. Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.

    Science.gov (United States)

    Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-Ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

    2013-11-19

    Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

  2. Assessment of a Revised Management Strategy for Patients With Intraductal Papillary Mucinous Neoplasms Involving the Main Pancreatic Duct.

    Science.gov (United States)

    Sugimoto, Motokazu; Elliott, Irmina A; Nguyen, Andrew H; Kim, Stephen; Muthusamy, V Raman; Watson, Rabindra; Hines, O Joe; Dawson, David W; Reber, Howard A; Donahue, Timothy R

    2017-01-18

    According to the 2012 International Consensus Guidelines, the diagnostic criterion of intraductal papillary mucinous neoplasms (IPMNs) involving the main duct (MD IPMNs) or the main and branch ducts (mixed IPMNs) of the pancreatic system is a main pancreatic duct (MPD) diameter of 5.0 mm or greater on computed tomography (CT) or magnetic resonance imaging (MRI). However, surgical resection is recommended for patients with an MPD diameter of 10.0 mm or greater, which is characterized as a high-risk stigma. An MPD diameter of 5.0 to 9.0 mm is not an indication for immediate resection. To determine an appropriate cutoff (ie, one with high sensitivity and negative predictive value) of the MPD diameter on CT or MRI as a prognostic factor for malignant disease and to propose a new management algorithm for patients with MD or mixed IPMNs. This retrospective cohort study included 103 patients who underwent surgical resection for a preoperative diagnosis of MD or mixed IPMN and in whom IPMN was confirmed by surgical pathologic findings at a single institution from July 1, 1996, to December 31, 2015. Malignant disease was defined as high-grade dysplasia or invasive adenocarcinoma on results of surgical pathologic evaluation. An appropriate MPD diameter on preoperative CT or MRI to predict malignant disease was determined using a receiver operating characteristic curve analysis. The prognostic value of the new management algorithm that incorporated the new MPD diameter cutoff was evaluated. Among the 103 patients undergoing resection for an MD or mixed IPMN (59 men [57.3%]; 44 women [42.7%]; median [range] age, 71 [48-86] years), 64 (62.1%) had malignant disease. Diagnostic accuracy for malignant neoplasms was highest at an MPD diameter cutoff of 7.2 mm (area under the receiver operating characteristic curve, 0.70; 95% CI, 0.59-0.81). An MPD diameter of 7.2 mm or greater was also an independent prognostic factor for malignant neoplasms (odds ratio, 12.76; 95% CI, 2

  3. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    Science.gov (United States)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

  4. Restoration of CFTR Activity in Ducts Rescues Acinar Cell Function and Reduces Inflammation in Pancreatic and Salivary Glands of Mice.

    Science.gov (United States)

    Zeng, Mei; Szymczak, Mitchell; Ahuja, Malini; Zheng, Changyu; Yin, Hongen; Swaim, William; Chiorini, John A; Bridges, Robert J; Muallem, Shmuel

    2017-10-01

    Sjögren's syndrome and autoimmune pancreatitis are disorders with decreased function of salivary, lacrimal glands, and the exocrine pancreas. Nonobese diabetic/ShiLTJ mice and mice transduced with the cytokine BMP6 develop Sjögren's syndrome and chronic pancreatitis and MRL/Mp mice are models of autoimmune pancreatitis. Cystic fibrosis transmembrane conductance regulator (CFTR) is a ductal Cl -  channel essential for ductal fluid and HCO 3 - secretion. We used these models to ask the following questions: is CFTR expression altered in these diseases, does correction of CFTR correct gland function, and most notably, does correcting ductal function correct acinar function? We treated the mice models with the CFTR corrector C18 and the potentiator VX770. Glandular, ductal, and acinar cells damage, infiltration, immune cells and function were measured in vivo and in isolated duct/acini. In the disease models, CFTR expression is markedly reduced. The salivary glands and pancreas are inflamed with increased fibrosis and tissue damage. Treatment with VX770 and, in particular, C18 restored salivation, rescued CFTR expression and localization, and nearly eliminated the inflammation and tissue damage. Transgenic overexpression of CFTR exclusively in the duct had similar effects. Most notably, the markedly reduced acinar cell Ca 2+ signaling, Orai1, inositol triphosphate receptors, Aquaporin 5 expression, and fluid secretion were restored by rescuing ductal CFTR. Our findings reveal that correcting ductal function is sufficient to rescue acinar cell function and suggests that CFTR correctors are strong candidates for the treatment of Sjögren's syndrome and pancreatitis. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. Epidermal growth factor and its receptors in human pancreatic carcinoma

    International Nuclear Information System (INIS)

    Chen, Y.F.; Pan, G.Z.; Hou, X.; Liu, T.H.; Chen, J.; Yanaihara, C.; Yanaihara, N.

    1990-01-01

    The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells

  6. Pancreatic trauma.

    Science.gov (United States)

    Lahiri, R; Bhattacharya, S

    2013-05-01

    Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: 'pancreatic trauma', 'pancreatic duct injury', 'radiology AND pancreas injury', 'diagnosis of pancreatic trauma', and 'management AND surgery'. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important prognostic factor is pancreatic duct disruption and in these cases

  7. Pancreatitis

    Science.gov (United States)

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  8. Comparison of Fasting Human Pancreatic Polypeptide Levels Among Patients With Pancreatic Ductal Adenocarcinoma, Chronic Pancreatitis, and Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Nagpal, Sajan Jiv Singh; Bamlet, William R; Kudva, Yogish C; Chari, Suresh T

    2018-05-17

    Human pancreatic polypeptide (HPP) is a hormone secreted by the ventral pancreas. While postprandial HPP levels have been studied in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC), there are limited data on fasting HPP in these diseases. Fasting serum HPP was measured in the following groups of patients: CP with diabetes mellitus (DM) (n = 16), CP without DM (n = 34), PDAC with new-onset DM (n = 50), PDAC without DM (n = 49), new-onset type 2 DM (n = 50), and controls without DM (n = 49). Sixty-six had type 3c DM (CP with DM, n = 16; PDAC with new-onset DM, n = 50). Median fasting HPP levels (in picograms per milliliter) were similar among all groups. Median (interquartile range) HPP levels in new-onset type 2 DM (n = 50; 288.3 [80.1-1072.1]) were similar to those in type 3c DM (n = 66; 242.3 [64.9-890.9]) (P = 0.71). In PDAC (n = 99), HPP values were similar in pancreatic head (n = 75) versus body/tail (n = 24) tumors (245.3 [64.3-1091.3] vs 334.7 [136.1-841.5]; P = 0.95), regardless of DM. Fasting HPP levels are similar in CP, PDAC, and controls regardless of glycemic status.

  9. Properties of the luminal membrane of isolated perfused rat pancreatic ducts. Effect of cyclic AMP and blockers of chloride transport

    DEFF Research Database (Denmark)

    Novak, I; Greger, R

    1988-01-01

    - and interlobular ducts of rat pancreas was used. Responses of the epithelium to inhibitors and agonists were monitored by electrophysiological techniques. Addition of HCO-3/CO2 to the bath side of nonstimulated ducts depolarized the PD across the basolateral membrane (PDbl) by about 9 mV, as also observed...

  10. Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver

    DEFF Research Database (Denmark)

    Vestentoft, Peter S; Jelnes, Peter; Hopkinson, Branden M

    2011-01-01

    BACKGROUND: During liver development, intrahepatic bile ducts are thought to arise by a unique asymmetric mode of cholangiocyte tubulogenesis characterized by a series of remodeling stages. Moreover, in liver diseases, cells lining the Canals of Hering can proliferate and generate new hepatic...... in normal liver and in the extensive ductular reactions originating from intrahepatic bile ducts and branching into the parenchyma of the acetaminophen intoxicated liver. In the developing human liver, three-dimensional reconstructions using multiple marker proteins confirmed that the human intrahepatic...

  11. Pancreatic elastase in human serum. Determination by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Geokas, M.C. (Univ. of California, Davis); Brodrick, J.W.; Johnson, J.H.; Largman, C.

    1977-01-10

    This study demonstrates that a serine endopeptidase of pancreatic origin (elastase 2) circulates in human blood. A specific and highly sensitive radioimmunoassay has been developed for pancreatic elastase 2 in human serum. The inactivation of elastase 2 employed as radioiodinated tracer with an active site-specific reagent (phenylmethanesulfonyl fluoride) was necessary to prevent its binding by serum ..cap alpha../sub 1/-antitrypsin and ..cap alpha../sub 2/-macroglobulin while maintaining its immunoreactivity. The assay is based upon competition of standard human pancreatic elastase 2 with /sup 125/I-labeled phenylmethanesulfonyl elastase 2 for specific antibody binding sites, after which a second antibody precipitation step is used to separate bound from free /sup 125/I-labeled phenylmethanesulfonyl elastase 2. The minimum detectable concentration of elastase 2 was 0.9 ng/ml. The average normal fasting serum level determined was 71 ng/ml, approximately 80-fold greater than the minimum detectable amount.

  12. CXCL12 chemokine expression suppresses human pancreatic cancer growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ishan Roy

    Full Text Available Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites.

  13. A Suspicious Pancreatic Mass in Chronic Pancreatitis: Pancreatic Actinomycosis

    Directory of Open Access Journals (Sweden)

    F. de Clerck

    2015-01-01

    Full Text Available Introduction. Pancreatic actinomycosis is a chronic infection of the pancreas caused by the suppurative Gram-positive bacterium Actinomyces. It has mostly been described in patients following repeated main pancreatic duct stenting in the context of chronic pancreatitis or following pancreatic surgery. This type of pancreatitis is often erroneously interpreted as pancreatic malignancy due to the specific invasive characteristics of Actinomyces. Case. A 64-year-old male with a history of chronic pancreatitis and repeated main pancreatic duct stenting presented with weight loss, fever, night sweats, and abdominal pain. CT imaging revealed a mass in the pancreatic tail, invading the surrounding tissue and resulting in splenic vein thrombosis. Resectable pancreatic cancer was suspected, and pancreatic tail resection was performed. Postoperative findings revealed pancreatic actinomycosis instead of neoplasia. Conclusion. Pancreatic actinomycosis is a rare type of infectious pancreatitis that should be included in the differential diagnosis when a pancreatic mass is discovered in a patient with chronic pancreatitis and prior main pancreatic duct stenting. Our case emphasizes the importance of pursuing a histomorphological confirmation.

  14. Histological study of human sublingual gland with special emphasis on intercalated and striated ducts

    International Nuclear Information System (INIS)

    Rana, R.; Minhas, L.A.; Mubarik, A.

    2012-01-01

    Objective: To study the histomorphological characteristics of human sublingual gland, specially of intercalated and striated ducts. Study design: Descriptive study Place and duration of study: Army Medical College from Jan 2002 to Dec 2002 Materials and methods: Fifteen sublingual glands (right and left) from postmortem cases were obtained from District Headquarter Hospital Rawalpindi, within twelve hours of death. Five micrometer thick sections were made and stained with Haematoxylin and Eosin (H and E). Morphology of intercalated and striated ducts was studied and their number was counted. Results: The mean number of intercalated ducts in the right gland 'a'and 'b' parts, and in the left gland 'a' and 'b' parts was 1.45+-0.14, 1.39+-.009, 1.31+-0.11 and 1.18+-0.10 respectively. The mean diameter of intercalated ducts in the same parts was 19.76+-0.44 micro m, 20.6+-0.53 micro m, 20.34+-0.49 micro m and 19.84+-0.98 micro m respectively. The mean number of striated ducts in the right gland ''a'' and ''b'' parts, and in the left gland ''a'' and ''b'' parts was 0.55+-.008, 0.57+-.008, 0.80+-0.14 and 0.80+-0.14 while mean diameter of striated ducts in the right gland ''a'' and ''b'' parts, and in the left gland ''a'' and ''b'' parts was 49.90+-4.70 micro m, 53.23+-2.50 micro m, 61.68+-3.93 micro m and 57.73+-2.85 micro m respectively. Conclusion: The difference between the mean number and diameter of the ducts of right and left glands was statistically insignificant. (author)

  15. Isolated Roux-en-Y anastomosis of the pancreatic stump in a duct-to-mucosa fashion in patients with distal pancreatectomy with en-bloc celiac axis resection.

    Science.gov (United States)

    Okada, Ken-Ichi; Kawai, Manabu; Tani, Masaji; Hirono, Seiko; Miyazawa, Motoki; Shimizu, Atsushi; Kitahata, Yuji; Yamaue, Hiroki

    2014-03-01

    A pancreatic fistula is one of the most serious complications in distal pancreatectomy with en bloc celiac axis resection (DP-CAR), because the pancreatic transection is performed on the right side of the portal vein, which results in a large cross-section surface, and because post-pancreatectomy hemorrhage is hard to treat by interventional radiology. Therefore, a procedure to decrease the incidence of postoperative pancreatic fistula is urgently needed. Twenty-six consecutive patients who underwent DP-CAR between April 2008 and August 2012 were reviewed retrospectively. The first 13 consecutive patients underwent DP-CAR with no anastomosis, and the subsequent 13 consecutive patients were treated with Roux-en-Y pancreaticojejunostomy (PJ) in a duct-to-mucosa fashion. Extremely high amylase levels (>4000 IU/l) of all drainage fluid specimens on postoperative day (POD) 1, 3 and 4 were detected more frequently in cases with no anastomosis (n = 7) compared to those with PJ (n = 1) (P = 0.056). The incidence of grade B/C pancreatic fistulas was 15.4% in cases with isolated Roux-en-Y anastomosis of the pancreatic stump performed in a duct-to-mucosa fashion, and we are currently examining whether this anastomosis method reduces the pancreatic fistula rate in a multicenter, randomized controlled trial for distal pancreatectomy patients (ClinicalTrials.gov NCT01384617). © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  16. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

    NARCIS (Netherlands)

    Geuken, Erwin; Visser, Dorien; Kuipers, Folkert; Blokzijl, Hans; Leuvenink, Henri G. D.; de Jong, Koert P.; Peeters, Paul M. J. G.; Jansen, Peter L. M.; Slooff, Maarten J. H.; Gouw, Annette S. H.; Porte, Robert J.

    2004-01-01

    BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily

  17. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

    NARCIS (Netherlands)

    Geuken, E; Visser, D; Kuipers, F; Blokzijl, H; Leuvenink, HGD; de Jong, KP; Peeters, PMJG; Jansen, PLM; Slooff, MJH; Gouw, ASH; Porte, RJ

    2004-01-01

    Background/Aims: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. Methods: In 28 liver transplant recipients, bile samples were collected daily

  18. Noninvasive study of anatomic variations of the bile and pancreatic duct using magnetic resonance cholangiopancreatography; Estudio no invasivo de variantes anatomicas de la via biliar y pancreatica mediante colangiopancreatografia por resonancia magnetica (CPRM)

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, E.; Falco, J.; Campo, R.; Martin, J.; Brullet, E. [SDI-UDIAT Corporacio Sanitaria Parc Tauli. Sabadell (Spain); Espinos, J. [Hospital Mutua de Tarrasa (Spain)

    1999-07-01

    To identify anatomic variations of the bile duct and pancreatic duct and papillary anomalies by means of magnetic resonance cholangiopancreatography (MRCP) and determine their correlation with endoscopic retrograde cholangiopancreatography (ERCP) findings. Eighty-five patients were selected by means of a prospective study comparing MRCP and ERCP. Coronal and axial HASTE images and coronal and oblique coronal RARE images were acquired in all the patients. Four of the studies (6%) were excluded because of poor technical quality. Anatomic variations were observed in 26 cases (30.5%), including trifurcation (n=7; 27%), right hepatic duct draining into left hepatic duct (n=2, 7.7%), right hepatic duct draining into common bile duct (n=4; 15.4%), extrahepatic confluence (n=2; 7.7%), medial cystic duct (n=2; 7.7%), parallel cystic duct (n=3; 11.5%), juxtapapillary duodenal diverticulum (n=3; 11.5%) and pancreas divisum (n=3; 11.5%). A good correlation was observed between the MRCP and ERCP findings. The introduction of MRCP into the noninvasive study of biliary disease may be useful in the detection of anatomic variations relevant to laparoscopic surgery and other endoscopic and interventional techniques. (Author) 11 refs.

  19. Blunt trauma pancreatic duct injury managed by non-operative technique, a case study and literature review

    Directory of Open Access Journals (Sweden)

    A. Zala

    2015-02-01

    Full Text Available We describe the case of a 15 year old boy who presented with generalised abdominal pain following a seemingly minor collision at weekend soccer. Investigation revealed a grade IV pancreatic injury that was subsequently managed with pancreatic stent insertion by endoscopic retrograde cholangiopancreatography (ERCP and total parenteral nutrition (TPN prior to recommencing low fat diet 10 days post-injury. Keywords: Trauma, Blunt injury, Pancreas, Non-operative

  20. [External pancreatic fistulas management].

    Science.gov (United States)

    Stepan, E V; Ermolov, A S; Rogal', M L; Teterin, Yu S

    The main principles of treatment of external postoperative pancreatic fistulas are viewed in the article. Pancreatic trauma was the reason of pancreatic fistula in 38.7% of the cases, operations because of acute pancreatitis - in 25.8%, and pancreatic pseudocyst drainage - in 35.5%. 93 patients recovered after the treatment. Complex conservative treatment of EPF allowed to close fistulas in 74.2% of the patients with normal patency of the main pancreatic duct (MPD). The usage of octreotide 600-900 mcg daily for at least 5 days to decrease pancreatic secretion was an important part of the conservative treatment. Endoscopic papillotomy was performed in patients with major duodenal papilla obstruction and interruption of transporting of pancreatic secretion to duodenum. Stent of the main pancreatic duct was indicated in patients with extended pancreatic duct stenosis to normalize transport of pancreatic secretion to duodenum. Surgical formation of anastomosis between distal part of the main pancreatic duct and gastro-intestinal tract was carried out when it was impossible to fulfill endoscopic stenting of pancreatic duct either because of its interruption and diastasis between its ends, or in the cases of unsuccessful conservative treatment of external pancreatic fistula caused by drainage of pseudocyst.

  1. Estudio por ecoendoscopia de la vía biliar extrahepática en pacientes con pancreatitis aguda biliar Endoscopic ultrasonographic examination of the common bile duct in patients with acute biliary pancreatitis

    Directory of Open Access Journals (Sweden)

    A. Repiso

    2008-06-01

    Full Text Available Objetivo: el objetivo de nuestro estudio fue valorar la utilidad de la ecoendoscopia en el estudio de la vía biliar extrahepática en los pacientes diagnosticados de pancreatitis aguda biliar y determinar los factores clínicos y analíticos relacionados con el resultado de la técnica. Material y métodos: se incluyeron en el estudio de modo consecutivo 73 pacientes (31 varones, 42 mujeres; media de edad 64 ± 15 años con pancreatitis aguda biliar remitidos a nuestro servicio para la realización de ecoendoscopia biliopancreática. En todos los pacientes se realizó la técnica seguida de CPRE con esfinterotomía y técnica endoscópica para la extracción de cálculos cuando se identificó por ecoendoscopia la existencia de coledocolitiasis. Se compararon las características clínico-evolutivas de estos pacientes con respecto al resultado obtenido con la ecoendoscopia. Resultados: la media de tiempo transcurrido desde el ingreso hasta la realización de la ecoendoscopia fue de 7 ± 6 días. En 18 pacientes (24% se observó en la ecoendoscopia la existencia de coledocolitiasis y en 17 de ellos se realizó esfinterotomía endoscópica. La presencia de coledocolitiasis fue más frecuente en aquellos pacientes con dilatación de la vía biliar extrahepática (55 vs. 14%; p 0,05. Tampoco se observó esta diferencia en el subgrupo de pacientes con pancreatitis aguda severa (45 vs. 55%; p > 0,05. Conclusiones: la ecoendoscopia es una técnica útil en la selección de los pacientes con pancreatitis aguda biliar que se beneficiarán de la realización de una esfinterotomía endoscópica.Objective: the objective of our study was to evaluate the usefulness of endoscopic ultrasonography (EUS for the study of the common bile duct in patients diagnosed with acute biliary pancreatitis, and to establish clinical and laboratory factors related to this technique. Materials and methods: seventy-three consecutive patients with acute biliary pancreatitis were

  2. Focal pancreatic enlargement: differentiation between pancreatic adenocarcinoma and focal pancreatitis on CT and ERCP

    International Nuclear Information System (INIS)

    Kim, Eun Kyung; Kim, Ki Whang; Lee, Jong Tae; Kim, Hee Soo; Yoo, Hyung Sik; Yu, Jeong Sik; Yoon, Sang Wook

    1995-01-01

    To differentiate the pancreatic adenocarcinoma from focal pancreatitis on CT and ERCP in cases of focal pancreatic enlargement. We analysed CT findings of 66 patients of pancreatic adenocarcinoma (n = 45) or focal pancreatitis (n = 21) with respect to size, density, calcification, pancreatic or biliary duct dilatation, fat plane obliteration around the vessels, direction of retroperitoneal extension, lymphadenopathy, pseudocyst formation and atrophy of pancreas. ERCP available in 48 patients were analysed in respect to morphologic appearance of CBD and pancreatic duct, and distance between the two ducts. The patients in focal pancreatitis were younger with more common history of alcohol drinking. There was no statistical difference in calcifications of the mass (18% in the adenocarcinoma, 33% in the focal pancreatitis), but a tendency of denser, larger number of calcifications was noted in focal pancreatitis. The finding of fat plane obliteration around the vessels were more common in pancreatic adenocarcinoma, and fascial thickenings were more prominent in focal pancreatitis, although not statistically significant. On ERCP, there were no differential points of CBD, pancreatic duct morphology, but distance between the two ducts at the lesion center was more wider in focal pancreatitis. Differentiating focal pancreatitis from pancreatic adenocarcinoma is difficult. However, we should consider the possibility of focal pancreatitis in cases of patients with young age, having alcoholic history in association with CT findings of large numbers of and dense calcifications, and ERCP findings of prominent separation of two duct at the lesion center

  3. Differential diagnosis of sclerosing cholangitis with autoimmune pancreatitis and periductal infiltrating cancer in the common bile duct at dynamic CT, endoscopic retrograde cholangiography and MR cholangiography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Hee; Byun, Jae Ho; Lee, So Jung; Park, Seong Ho; Kim, Hyoung Jung; Lee, Seung Soo; Lee, Moon-Gyu [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Asanbyeongwon-gil 86, Songpa-Gu, Seoul (Korea, Republic of); Kim, Myung-Hwan [University of Ulsan College of Medicine, Asan Medical Center, Department of Internal Medicine, Asanbyeongwon-gil 86, Songpa-Gu, Seoul (Korea, Republic of); Kim, Jihun [University of Ulsan College of Medicine, Asan Medical Center, Department of Diagnostic Pathology, Asanbyeongwon-gil 86, Songpa-Gu, Seoul (Korea, Republic of)

    2012-11-15

    To compare findings at dynamic computed tomography (CT), endoscopic retrograde cholangiography (ERC) and magnetic resonance cholangiography (MRC) in patients with sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and periductal infiltrating cancer in the common bile duct (CBD), and to evaluate the diagnostic performance of ERC and MRC in differentiating between the two diseases. Bile duct changes at dynamic CT, ERC and MRC were compared in 58 patients with SC-AIP and CBD involvement and 93 patients with periductal infiltrating CBD cancer. Two radiologists rated their confidence in differentiating between the two diseases and the diagnostic performances of ERC and MRC were compared. At CT, SC-AIP was more frequently associated with intrapancreatic CBD involvement, thinner CBD walls, concentric wall thickening, smooth outer margins, and lower degrees of upstream ductal dilatation and contrast enhancement (P {<=} 0.05) than CBD cancer. At ERC and MRC, SC-AIP was more frequently associated with smooth margins, gradual and symmetric narrowing, multifocal involvement and hourglass appearance (P {<=} 0.027) than CBD cancer. MRC showed good diagnostic performance comparable to ERC. Dynamic CT, ERC and MRC can be helpful in distinguishing SC-AIP from periductal infiltrating CBD cancer. MRC may be a useful diagnostic alternative to ERC in differentiating between the two diseases. (orig.)

  4. Differential diagnosis of sclerosing cholangitis with autoimmune pancreatitis and periductal infiltrating cancer in the common bile duct at dynamic CT, endoscopic retrograde cholangiography and MR cholangiography

    International Nuclear Information System (INIS)

    Kim, Jin Hee; Byun, Jae Ho; Lee, So Jung; Park, Seong Ho; Kim, Hyoung Jung; Lee, Seung Soo; Lee, Moon-Gyu; Kim, Myung-Hwan; Kim, Jihun

    2012-01-01

    To compare findings at dynamic computed tomography (CT), endoscopic retrograde cholangiography (ERC) and magnetic resonance cholangiography (MRC) in patients with sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and periductal infiltrating cancer in the common bile duct (CBD), and to evaluate the diagnostic performance of ERC and MRC in differentiating between the two diseases. Bile duct changes at dynamic CT, ERC and MRC were compared in 58 patients with SC-AIP and CBD involvement and 93 patients with periductal infiltrating CBD cancer. Two radiologists rated their confidence in differentiating between the two diseases and the diagnostic performances of ERC and MRC were compared. At CT, SC-AIP was more frequently associated with intrapancreatic CBD involvement, thinner CBD walls, concentric wall thickening, smooth outer margins, and lower degrees of upstream ductal dilatation and contrast enhancement (P ≤ 0.05) than CBD cancer. At ERC and MRC, SC-AIP was more frequently associated with smooth margins, gradual and symmetric narrowing, multifocal involvement and hourglass appearance (P ≤ 0.027) than CBD cancer. MRC showed good diagnostic performance comparable to ERC. Dynamic CT, ERC and MRC can be helpful in distinguishing SC-AIP from periductal infiltrating CBD cancer. MRC may be a useful diagnostic alternative to ERC in differentiating between the two diseases. (orig.)

  5. Antiproliferation and apoptosis induced by tamoxifen in human bile duct carcinoma QBC939 cells via upregulated p53 expression

    International Nuclear Information System (INIS)

    Han, Peng; Kang, Jin-He; Li, Hua-Liang; Hu, Su-Xian; Lian, Hui-Hui; Qiu, Ping-Ping; Zhang, Jian; Li, Wen-Gang; Chen, Qing-Xi

    2009-01-01

    Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been used in the treatment of breast cancer for over 30 years. Recently, it was shown that TAM also has efficacy on gastrointestinal neoplasms such as hepatocarcinoma and pancreatic carcinoma, and that the chemopreventive activities of TAM might be due to its abilities to inhibit cell growth and induce apoptosis. In the present study, we investigated the effects of tamoxifen on growth and apoptosis in the human bile duct carcinoma (BDC) cell line QBC939 using MTT assay, inverted microscopy, fluorescence microscopy, transmission electron microscopy, classic DNA fragmentation agarose gel electrophoresis assay, PI single- and FITC/PI double-staining flow cytometry, and Western blotting. Our data revealed that TAM could significantly inhibit growth and induce apoptosis in QBC939 cells. Increased expression of p53 was observed in TAM-treated cells, indicating that p53 might play an important role in TAM-induced apoptosis in QBC939 cells. These results provide significant insight into the anticarcinogenic action of TAM on BDC.

  6. Antiproliferation and apoptosis induced by tamoxifen in human bile duct carcinoma QBC939 cells via upregulated p53 expression

    Energy Technology Data Exchange (ETDEWEB)

    Han, Peng; Kang, Jin-He; Li, Hua-Liang [Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Hu, Su-Xian [First Hospital Attached to Fujian Medical University, Xiamen 361004 (China); Lian, Hui-Hui; Qiu, Ping-Ping; Zhang, Jian [Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Li, Wen-Gang [First Hospital Attached to Fujian Medical University, Xiamen 361004 (China); Chen, Qing-Xi [Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen 361005 (China)

    2009-07-24

    Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been used in the treatment of breast cancer for over 30 years. Recently, it was shown that TAM also has efficacy on gastrointestinal neoplasms such as hepatocarcinoma and pancreatic carcinoma, and that the chemopreventive activities of TAM might be due to its abilities to inhibit cell growth and induce apoptosis. In the present study, we investigated the effects of tamoxifen on growth and apoptosis in the human bile duct carcinoma (BDC) cell line QBC939 using MTT assay, inverted microscopy, fluorescence microscopy, transmission electron microscopy, classic DNA fragmentation agarose gel electrophoresis assay, PI single- and FITC/PI double-staining flow cytometry, and Western blotting. Our data revealed that TAM could significantly inhibit growth and induce apoptosis in QBC939 cells. Increased expression of p53 was observed in TAM-treated cells, indicating that p53 might play an important role in TAM-induced apoptosis in QBC939 cells. These results provide significant insight into the anticarcinogenic action of TAM on BDC.

  7. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy

    NARCIS (Netherlands)

    T.C. Tran; G. van 't Hof; G. Kazemier (Geert); W.C.J. Hop (Wim); C.J. Pek (Chulja); A.W. van Toorenenbergen (Albert); H. van Dekken (Herman); C.H.J. van Eijck (Casper)

    2008-01-01

    textabstractBackground: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and

  8. Effect of ATP on intracellular pH in pancreatic ducts involves P2X7 receptors

    DEFF Research Database (Denmark)

    Henriksen, Katerine L; Novak, Ivana

    2003-01-01

    which P2 receptors might be involved. Ducts were obtained from rat pancreas, and the pH sensitive fluorophore BCECF was used to measure pHi and recovery rates from cellular acidosis induced by ammonium pre-pulses. In order to reveal Na+/H+ exchange, Cl-/HCO3- exchange or a Na+-HCO3- cotransport...

  9. Serial Cases of Combining ESWL and ERCP Procedures in Management Chronic Pancreatitis and Difficult Bile Duct Stones

    OpenAIRE

    Fauzi, Achmad; Rasyid, Nur; Syam, Ari Fahrial; Abdullah, Murdani; Makmun, Dadang; Simadibrata, Marcellus; Manan, Chudahman; Rani, Abdul Aziz; Daldiyono, Daldiyono

    2009-01-01

    Extracorporeal shock wave lithotripsy (ESWL) has an established role in the management of pancreaticductalcalculiandasfurthertreatmentmodalityforlargeordifficultcomplicatedcommon bile duct(CBD)stones. Combinedwithminimally invasive endoscopic procedure suchasendoscopic retrogradecholangio-pancreatography(ERCP),it has replaced open surgeryas theinitial form of therapy. ESWL has also proved to bean effective therapyin treating intrahepaticstones that are refractory toroutine endoscopic extracti...

  10. An international multicenter study comparing EUS-guided pancreatic duct drainage with enteroscopy-assisted endoscopic retrograde pancreatography after Whipple surgery.

    Science.gov (United States)

    Chen, Yen-I; Levy, Michael J; Moreels, Tom G; Hajijeva, Gulara; Will, Uwe; Artifon, Everson L; Hara, Kazuo; Kitano, Masayuki; Topazian, Mark; Abu Dayyeh, Barham; Reichel, Andreas; Vilela, Tiago; Ngamruengphong, Saowanee; Haito-Chavez, Yamile; Bukhari, Majidah; Okolo, Patrick; Kumbhari, Vivek; Ismail, Amr; Khashab, Mouen A

    2017-01-01

    Endoscopic management of post-Whipple pancreatic adverse events (AEs) with enteroscopy-assisted endoscopic retrograde pancreatography (e-ERP) is associated with high failure rates. EUS-guided pancreatic duct drainage (EUS-PDD) has shown promising results; however, no comparative data have been done for these 2 modalities. The goal of this study is to compare EUS-PDD with e-ERP in terms of technical success (PDD through dilation/stent), clinical success (improvement/resolution of pancreatic-type symptoms), and AE rates in patients with post-Whipple anatomy. This is an international multicenter comparative retrospective study at 7 tertiary centers (2 United States, 2 European, 2 Asian, and 1 South American). All consecutive patients who underwent EUS-PDD or e-ERP between January 2010 and August 2015 were included. In total, 66 patients (mean age, 57 years; 48% women) and 75 procedures were identified with 40 in EUS-PDD and 35 in e-ERP. Technical success was achieved in 92.5% of procedures in the EUS-PDD group compared with 20% of procedures in the e-ERP group (OR, 49.3; P procedures in the EUS-PDD group compared with 23.1% in the e-ERP group (OR, 23.3; P Procedure time and length of stay were not significantly different between the 2 groups. EUS-PDD is superior to e-ERP in post-Whipple anatomy in terms of efficacy with acceptable safety. As such, EUS-PDD should be considered as a potential first-line treatment in post-pancreaticoduodenectomy anatomy when necessary expertise is available. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  11. In vitro expansion and differentiation of rat pancreatic duct-derived stem cells into insulin secreting cells using a dynamicthree-dimensional cell culture system.

    Science.gov (United States)

    Chen, X C; Liu, H; Li, H; Cheng, Y; Yang, L; Liu, Y F

    2016-06-27

    In this study, a dynamic three-dimensional cell culture technology was used to expand and differentiate rat pancreatic duct-derived stem cells (PDSCs) into islet-like cell clusters that can secrete insulin. PDSCs were isolated from rat pancreatic tissues by in situ collagenase digestion and density gradient centrifugation. Using a dynamic three-dimensional culture technique, the cells were expanded and differentiated into functional islet-like cell clusters, which were characterized by morphological and phenotype analyses. After maintaining 1 x 108 isolated rat PDSCs in a dynamic three-dimensional cell culture for 7 days, 1.5 x 109 cells could be harvested. Passaged PDSCs expressed markers of pancreatic endocrine progenitors, including CD29 (86.17%), CD73 (90.73%), CD90 (84.13%), CD105 (78.28%), and Pdx-1. Following 14 additional days of culture in serum-free medium with nicotinamide, keratinocyte growth factor (KGF), and b fibroblast growth factor (FGF), the cells were differentiated into islet-like cell clusters (ICCs). The ICC morphology reflected that of fused cell clusters. During the late stage of differentiation, representative clusters were non-adherent and expressed insulin indicated by dithizone (DTZ)-positive staining. Insulin was detected in the extracellular fluid and cytoplasm of ICCs after 14 days of differentiation. Additionally, insulin levels were significantly higher at this time compared with the levels exhibited by PDSCs before differentiation (P cell culture system, PDSCs can be expanded in vitro and can differentiate into functional islet-like cell clusters.

  12. The human thoracic duct is functionally innervated by adrenergic nerves

    DEFF Research Database (Denmark)

    Telinius, Niklas; Baandrup, Ulrik; Rumessen, Jüri Johs.

    2013-01-01

    ) that is predominantly adrenergic. TDs harvested from 51 patients undergoing esophageal and cardia cancer surgery were either fixed for structural investigations or maintained in vitro for the functional assessment of innervation by isometric force measurements and electrical field stimulation (EFS). Electron microscopy......, and methacholine was demonstrated by exogenous application to human TD ring segments. Norepinephrine provided the most consistent responses, whereas responses to the other agonists varied. We conclude that the human TD is functionally innervated with both cholinergic and adrenergic components, with the latter...

  13. Single Cell Dissection of Human Pancreatic Islet Dysfunction in Diabetes

    Science.gov (United States)

    2017-06-01

    of memory T cells , innate cells and the differentiation potential of naive T cells during ME/CFS; and 3) To determine the T cell and innate cell ...apoptosis and the innate immune response in human pancreatic β- cells . Diabetes 64: 3808–3817. Marselli L, Thorne J, Dahiya S, Sgroi DC, Sharma A, Bonner-Weir...interactive nature of CellView aids in cell doublet identification. In the PBMC data, ‘Subcluster-analysis’ reveals a mixture of lymphoid and myeloid

  14. A pylorus-retaining pancreatic head-duodenectomy for cancers of the duodenal papilla and the lower bile duct.

    Science.gov (United States)

    Iwamoto, M; Sasahara, H; Kawabata, S; Hoshiko, M; Yasumoto, K; Imamura, K; Takagi, K; Morimatsu, M; Fujii, T; Shirouzu, K

    1996-01-01

    With the development of diagnostic technology, the surgical methods of cancer therapy have been expanded, and operations have been performed using a procedure corresponding to the stage of cancer to improve the postoperative QOL. A 79-year-old man with cancer of the duodenal papilla and obstructive jaundice, and a 63-year-old woman with cholangiocarcinoma in the lower region complicated by cholangitis caused by Candida underwent resections of the pancreatic head and duodenum, and pancreaticogastrostomies retaining the pylorus. Satisfactory results were obtained in both cases. The merits of the procedure were that there were few complaints, sufficient food could be ingested and the QCL was maintained. The benefits of pancreaticogastrostomy are that the anastomosis procedure is simple, the gastric wall is thicker than the jejunum and blood flow is plentiful. The dorsal gastric wall is located close to the pancreatic cut-end, therefore tension is not created, and the pancreatic enzymes are not activated because the anastomosis site does not contact the intestinal fluid. These characteristics should decrease the rate of anastomosis failure which can be a fetal complication. A safer operation is desirable, particularly for elderly patients or patients who have complications.

  15. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Davorin Dajčman

    2007-05-01

    Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

  16. Effect of secretin and inhibitors of HCO3-/H+ transport on the membrane voltage of rat pancreatic duct cells

    DEFF Research Database (Denmark)

    Novak, I; Pahl, C

    1993-01-01

    depolarized the basolateral membrane voltage, Vbl, by up to 35 mV (n = 37); a half-maximal response was obtained at 3 x 10(-11) mol/l. In unstimulated ducts a decrease in the luminal Cl- concentration (120 to 37 mmol/l) had a marginal effect on Vbl, but after maximal secretin stimulation it evoked a 14 +/- 2......), respectively. The fractional resistance of the basolateral membrane (FRbl) doubled, and the depolarizing responses to changes in bath K+ concentrations (5 to 20 mmol/l) decreased from 22 +/- 1 to 11 +/- 2 mV.(ABSTRACT TRUNCATED AT 250 WORDS)...

  17. Animal models for investigating chronic pancreatitis

    Science.gov (United States)

    2011-01-01

    Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

  18. Chronic pancreatitis.

    Science.gov (United States)

    Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

    2017-09-07

    Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

  19. Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker.

    Science.gov (United States)

    Ray, Partha; Rialon-Guevara, Kristy L; Veras, Emanuela; Sullenger, Bruce A; White, Rebekah R

    2012-05-01

    Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition-based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer.

  20. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

    Science.gov (United States)

    Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

    2008-01-01

    Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

  1. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  2. Protective effect of human umbilical cord-derived mesenchymal stem cells against severe acute pancreatitis in rats

    Directory of Open Access Journals (Sweden)

    Dong-ye WU

    2017-06-01

    Full Text Available Objective To study the protective effects of human umbilical cord-derived mesenchymal stem cells (ucMSCs against severe acute pancreatitis (SAP in rats. Methods A total of 135 Sprague-Dawley male rats were randomly divided into Sham group, SAP group and SAP+ucMSCs group (45 each. SAP+ucMSCs group: Severe acute pancreatitis was induced by injecting 5% sodium taurocholate (0.1ml/100g into the common biliopancreatic duct and then CM-DiI-labeled ucMSCs at 1×107cells/kg were injected via the tail vein. All the rats were sacrificed 12, 24 and 72 hours after SAP. The 72h death rate was counted. Pathological changes in the pancrease were detected by HE staining and pathological score was graded. ucMSCs colonization was observed by fluorescence microscopy. The serum levels of amylase, lipase, TNF-α, IL-1β, IL-4 and IL-10 were determined by ELISA. Results ucMSCs colonize the injured area of pancreatic tissue, the 72h death rate was reduced, and the serum amylase and lipase were also reduced significantly. Moreover, ucMSCs significantly reduced the pathological score of the pancrea and the level of proinflammatory cytokines (TNF-α and IL-1β, but the levels of anti-inflammatory cytokines were increased (IL-4 and IL-10. Conclusion Transplantation of ucMSCs can reduce the severity of pancreatic injury and inflammation in SAP rats. DOI: 10.11855/j.issn.0577-7402.2017.05.03

  3. Comparison of regional pancreatic tissue fluid pressure and endoscopic retrograde pancreatographic morphology in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    The relation between pancreatic tissue fluid pressure measured by the needle method and pancreatic duct morphology was studied in 16 patients with chronic pancreatitis. After preoperative endoscopic retrograde pancreatography (ERP) the patients were submitted to a drainage operation. The predrain......The relation between pancreatic tissue fluid pressure measured by the needle method and pancreatic duct morphology was studied in 16 patients with chronic pancreatitis. After preoperative endoscopic retrograde pancreatography (ERP) the patients were submitted to a drainage operation...

  4. Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.

    Science.gov (United States)

    Delitto, Daniel; Judge, Sarah M; Delitto, Andrea E; Nosacka, Rachel L; Rocha, Fernanda G; DiVita, Bayli B; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Wallet, Shannon M; Judge, Andrew R; Trevino, Jose G

    2017-01-03

    Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

  5. Autologous Pancreatic Islet Transplantation in Human Bone Marrow

    Science.gov (United States)

    Maffi, Paola; Balzano, Gianpaolo; Ponzoni, Maurilio; Nano, Rita; Sordi, Valeria; Melzi, Raffaella; Mercalli, Alessia; Scavini, Marina; Esposito, Antonio; Peccatori, Jacopo; Cantarelli, Elisa; Messina, Carlo; Bernardi, Massimo; Del Maschio, Alessandro; Staudacher, Carlo; Doglioni, Claudio; Ciceri, Fabio; Secchi, Antonio; Piemonti, Lorenzo

    2013-01-01

    The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. We recently have shown in mice that the bone marrow (BM) may be a valid alternative to the liver, and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Because the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients, islets engrafted successfully as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples analyzed during follow-up. Thus far, we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained for the maximum follow-up of 944 days. The encouraging results of this pilot study provide new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of endocrine tissue in the BM in humans. PMID:23733196

  6. Secretin stimulates HCO3(-) and acetate efflux but not Na+/HCO3(-) uptake in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I; Christoffersen, B C

    2001-01-01

    to be important in HCO3(-) -transporting epithelia. pHi was measured with BCECF in freshly isolated intralobular ducts. A reduction in extracellular Na+ concentration or application of HOE 694 (1 microM) decreased pHi by 0.1 to 0.6 pH units, demonstrating Na+/H+ exchanger activity. A reduction in extracellular Cl......- concentration or addition of H2DIDS (10 microM) increased pHi by 0.1 to 0.5 pH units, demonstrating Cl-/ HCO(3)- (OH ) exchanger activity. In experimental acidosis, extracellular HCO3(-)/CO2 buffer did not increase the rate of pHi recovery, indicating that provision of HCO3(-) by the Na+/HCO3(-) cotransporter...... was not apparent. Most importantly, Na+/HCO3(-) cotransport was not stimulated by secretin (1 nM). In contrast, in experimental alkalosis the pHi recovery was increased in HCO3(-)/CO2 buffer, possibly due to Na+/HCO3(-) cotransport in the efflux mode. Secretin (1 nM) and carbachol (1 microM) stimulated HCO3...

  7. Identification of Interstitial Cajal-like cells in the Human Thoracic Duct

    DEFF Research Database (Denmark)

    Bødtkjer, Donna Marie Briggs; Rumessen, Jüri; Baandrup, Ulrik

    2013-01-01

    were used to identify ICLCs in live tissue. Methylene blue stained cells with morphology suggestive of ICLCs in the TD. Immunoreactivity localized the ICLC protein markers c-kit, CD34 and vimentin to many cells and processes associated with smooth muscle cells (SMCs): coexpression of c......-kit with vimentin or CD34 was observed in some cells. Electron microscopy analysis confirmed ICLCs as a major cell type of the human TD. Lymphatic ICLCs possess caveolae, dense bands, a patchy basal lamina, intermediate filaments and specific junctions to SMCs. ICLCs were ultrastructurally differentiable from other......Interstitial Cajal-like cells (ICLCs) are speculated to be pacemakers in smooth muscle tissues. While the human thoracic duct (TD) is spontaneously active, the origin of this activity is unknown. We hypothesized that ICLCs could be present in the TD and using histological techniques...

  8. Reconstructing human pancreatic differentiation by mapping specific cell populations during development

    DEFF Research Database (Denmark)

    Ramond, Cyrille; Glaser, Nicolas; Berthault, Claire

    2017-01-01

    . Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic......Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate...... cell types and how such lineage decisions are regulated....

  9. Chronic Pancreatitis

    International Nuclear Information System (INIS)

    Betancur, Jorge

    2002-01-01

    It is presented a case of a man with alcoholic chronic pancreatitis, whose marked dilatation of the ducts reasoned the issue. The severe untreatable pain was the surgery indication, which was practiced without complications either during or after the surgery. By the way, a shallow revision of the literature is made, by mentioning classification, physiopatholoy, clinical square, medical, surgical and endoscopic treatment

  10. Characterization of human mesothelin transcripts in ovarian and pancreatic cancer

    International Nuclear Information System (INIS)

    Muminova, Zhanat E; Strong, Theresa V; Shaw, Denise R

    2004-01-01

    Mesothelin is an attractive target for cancer immunotherapy due to its restricted expression in normal tissues and high level expression in several tumor types including ovarian and pancreatic adenocarcinomas. Three mesothelin transcript variants have been reported, but their relative expression in normal tissues and tumors has been poorly characterized. The goal of the present study was to clarify which mesothelin transcript variants are commonly expressed in human tumors. Human genomic and EST nucleotide sequences in the public databases were used to evaluate sequences reported for the three mesothelin transcript variants in silico. Subsequently, RNA samples from normal ovary, ovarian and pancreatic carcinoma cell lines, and primary ovarian tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing to directly identify expressed transcripts. In silico comparisons of genomic DNA sequences with available EST sequences supported expression of mesothelin transcript variants 1 and 3, but there were no sequence matches for transcript variant 2. Newly-derived nucleotide sequences of RT-PCR products from tissues and cell lines corresponded to mesothelin transcript variant 1. Mesothelin transcript variant 2 was not detected. Transcript variant 3 was observed as a small percentage of total mesothelin amplification products from all studied cell lines and tissues. Fractionation of nuclear and cytoplasmic RNA indicated that variant 3 was present primarily in the nuclear fraction. Thus, mesothelin transcript variant 3 may represent incompletely processed hnRNA. Mesothelin transcript variant 1 represents the predominant mature mRNA species expressed by both normal and tumor cells. This conclusion should be important for future development of cancer immunotherapies, diagnostic tests, and gene microarray studies targeting mesothelin

  11. Early versus late surgical drainage for obstructive pancreatitis in an experimental model

    NARCIS (Netherlands)

    Lamme, B.; Boermeester, M. A.; Straatsburg, I. H.; van Buijtenen, J. M.; Boerma, D.; Offerhaus, G. J. A.; Gouma, D. J.; van Gulik, T. M.

    2007-01-01

    BACKGROUND: Chronic pancreatitis (CP) is characterized by intractable abdominal pain, and pancreatic exocrine and endocrine dysfunction. This study investigated whether early surgical drainage of pancreatic duct obstruction leads to improved recovery of pancreatic function compared with late

  12. Autoimmune pancreatitis can develop into chronic pancreatitis

    Science.gov (United States)

    2014-01-01

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

  13. Autoimmune pancreatitis can develop into chronic pancreatitis.

    Science.gov (United States)

    Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Kawa, Shigeyuki

    2014-05-21

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.

  14. Targeting Trypsin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model

    Science.gov (United States)

    2016-10-01

    foster mothers , confirming genotype of new pups using standard genotyping techniques, and weaning and delivering of SPF R122H mice to the Principal...present The activities in this part of the project involve the use of freshly isolated pancreatic acini (clusters of acinar cells ) obtained from wild...acinar cells . However, when use experimentally at supra-physiological concentrations, CCK induces acinar cell damage and pancreatitis responses

  15. Targeting Trysin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model

    Science.gov (United States)

    2017-10-01

    including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing...relatively small portion of patients with alcohol abuse and smoking develop pancreatitis, it is very likely that there are genetic underlying predisposing...factors that have not been discovered that explain why certain individuals develop pancreatitis. A genetic defect in the trypsinogen gene (PRSS1

  16. Endoscopic or surgical intervention for painful obstructive chronic pancreatitis

    NARCIS (Netherlands)

    Ali, U. Ahmed; Pahlplatz, J.M.; Nealon, W.H.; Goor, H. van; Gooszen, H.G.; Boermeester, M.A.

    2015-01-01

    BACKGROUND: Endoscopy and surgery are the treatment modalities of choice for patients with chronic pancreatitis and dilated pancreatic duct (obstructive chronic pancreatitis). Physicians face, without clear consensus, the choice between endoscopy or surgery for this group of patients. OBJECTIVES: To

  17. Acute pancreatitis in children: an experience with 50 cases

    African Journals Online (AJOL)

    pancreatitis admitted to the Pediatric Surgery Unit at the. Al-Azhar ... treatment. The most common long-term morbidity was recurrent pancreatitis [7]. The objective of this ... duct abnormalities in four patients (8%), familial chronic pancreatitis in ...

  18. Inhibition of human pancreatic and biliary output but not intestinal motility by physiological intraileal lipid loads

    DEFF Research Database (Denmark)

    Keller, Jutta; Holst, Jens Juul; Layer, Peter

    2005-01-01

    Lipid perfusion into the distal ileal lumen at supraphysiological loads inhibits pancreatic exocrine secretion and gastrointestinal motility in humans. In the present study, we sought to determine the effects of physiological postprandial intraileal lipid concentrations on endogenously stimulated...

  19. Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

    Directory of Open Access Journals (Sweden)

    Cindy J.M. Loomans

    2018-03-01

    Full Text Available Summary: Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi, express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC, and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+ cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. : In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate. Keywords: pancreas, organoid, human, ALDH, endocrine differentiation, beta cells, insulin, progenitor, fetal, diabetes

  20. [Pancreatic trauma].

    Science.gov (United States)

    Arvieux, C; Guillon, F; Létoublon, Ch; Oughriss, M

    2003-10-01

    Early diagnosis of pancreatic trauma has always been challenging because of the lack of correlation between the initial clinical symptomatology, radiologic and laboratory findings, and the severity of the injury. Thanks to the improved performance of spiral CT scanning and magnetic resonance pancreatography, it is now often possible to make an early diagnosis of pancreatic contusion, to localize the site of the injury, and (most importantly) to identify injury to the main pancreatic duct which has major implications for the management of the case. When the trauma victim is unstable, radiologic work-up may be impossible and urgent laparotomy is required. Control of hemorrhage is the primary concern here and a damage control approach with packing may be appropriate; if the pancreatic head has been destroyed, a pancreaticoduodenectomy with delayed reconstruction may be required. If the trauma victim is stable, the treatment strategy will be governed by a variety of parameters--age, clinical condition, associated local anatomic findings (pancreatitis, injury to the duodenum or biliary tract), involvement of the pancreatic duct, and localization of the injury within the gland (to right or left of the mesenteric vessels).

  1. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    NARCIS (Netherlands)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  2. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells.

    Science.gov (United States)

    D'Amour, Kevin A; Bang, Anne G; Eliazer, Susan; Kelly, Olivia G; Agulnick, Alan D; Smart, Nora G; Moorman, Mark A; Kroon, Evert; Carpenter, Melissa K; Baetge, Emmanuel E

    2006-11-01

    Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synthesizing the pancreatic hormones insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm, gut-tube endoderm, pancreatic endoderm and endocrine precursor--en route to cells that express endocrine hormones. The hES cell-derived insulin-expressing cells have an insulin content approaching that of adult islets. Similar to fetal beta-cells, they release C-peptide in response to multiple secretory stimuli, but only minimally to glucose. Production of these hES cell-derived endocrine cells may represent a critical step in the development of a renewable source of cells for diabetes cell therapy.

  3. Generation of polyhormonal and multipotent pancreatic progenitor lineages from human pluripotent stem cells.

    Science.gov (United States)

    Korytnikov, Roman; Nostro, Maria Cristina

    2016-05-15

    Generation of pancreatic β-cells from human pluripotent stem cells (hPSCs) has enormous importance in type 1 diabetes (T1D), as it is fundamental to a treatment strategy based on cellular therapeutics. Being able to generate β-cells, as well as other mature pancreatic cells, from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) will also enable the development of platforms that can be used for disease modeling and drug testing for a variety of pancreas-associated diseases, including cystic fibrosis. For this to occur, it is crucial to develop differentiation strategies that are robust and reproducible across cell lines and laboratories. In this article we describe two serum-free differentiation protocols designed to generate specific pancreatic lineages from hPSCs. Our approach employs a variety of cytokines and small molecules to mimic developmental pathways active during pancreatic organogenesis and allows for the in vitro generation of distinct pancreatic populations. The first protocol is designed to give rise to polyhormonal cells that have the potential to differentiate into glucagon-producing cells. The second protocol is geared to generate multipotent pancreatic progenitor cells, which harbor the potential to generate all pancreatic lineages including: monohormonal endocrine cells, acinar, and ductal cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Effect of cyclophilin A on gene expression in human pancreatic cancer cells.

    Science.gov (United States)

    Li, Min; Wang, Hao; Li, Fei; Fisher, William E; Chen, Changyi; Yao, Qizhi

    2005-11-01

    We previously found that cyclophilin A (CypA) is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147. In this study, we further investigated the effect of CypA on gene expression of several key molecules that are involved in pancreatic cancer cell proliferation. Human pancreatic cancer cell lines (Panc-1, MIA PaCa-2, and BxPC-3) and human pancreatic ductal epithelial (HPDE) cells were used. The messenger RNA (mRNA) levels of CypA, CypB, CD147, neuropilins (NRPs), vascular endothelial growth factor (VEGF), and VEGF receptors upon the treatment of exogenous recombinant human CypA were determined by real-time reverse-transcription polymerase chain reaction. Exogenous human recombinant CypA reduced the mRNA levels of NRP-1 and VEGF, but not endogenous CypA, CypB, and CD147, in Panc-1, MIA PaCa-2, and BxPC-3 cells. In contrast, HPDE cells showed a decrease of endogenous CypA and CD147 mRNA, but not detectable changes of CypB, NRPs, and VEGF mRNA levels upon exogenous CypA treatment. These data show that exogenous CypA downregulates NRP-1 and VEGF expression in pancreatic cancer cells. This effect is different in normal HPDE cells. Thus, soluble CypA may affect cell growth of pancreatic cancer.

  5. Altered central pain processing after pancreatic surgery for chronic pancreatitis

    NARCIS (Netherlands)

    Bouwense, S. A.; Ahmed Ali, U.; ten Broek, R. P.; Issa, Y.; van Eijck, C. H.; Wilder-Smith, O. H.; van Goor, H.

    2013-01-01

    Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered central pain processing. This study evaluated the relationship between pain processing and pain outcome after pancreatic duct decompression and/or pancreatic resection in patients with CP. Patients with CP

  6. Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis.

    Directory of Open Access Journals (Sweden)

    Hiromitsu Ito

    Full Text Available Patients with pancreatic cancer typically develop tumor invasion and metastasis in the early stage. These malignant behaviors might be originated from cancer stem cells (CSCs, but the responsible target is less known about invisible CSCs especially for invasion and metastasis. We previously examined the proteasome activity of CSCs and constructed a real-time visualization system for human pancreatic CSCs. In the present study, we found that CSCs were highly metastatic and dominantly localized at the invading tumor margins in a liver metastasis model. Microarray and siRNA screening assays showed that doublecortin-like kinase 1 (DCLK1 was predominantly expressed with histone modification in pancreatic CSCs with invasive and metastatic potential. Overexpression of DCLK1 led to amoeboid morphology, which promotes the migration of pancreatic cancer cells. Knockdown of DCLK1 profoundly suppressed in vivo liver metastasis of pancreatic CSCs. Clinically, DCLK1 was overexpressed in the metastatic tumors in patients with pancreatic cancer. Our studies revealed that DCLK1 is essential for the invasive and metastatic properties of CSCs and may be a promising epigenetic and therapeutic target in human pancreatic cancer.

  7. CT diagnosis of pancreatic carcinoma and chronic pancreatitis

    International Nuclear Information System (INIS)

    Luan Baoqing; Jin Erhu; Zhang Lizhen; Jiang Haibin

    1997-01-01

    To improve the diagnostic accuracy of pancreatic carcinoma and chronic pancreatitis. The CT findings of 154 cases with pancreatic carcinoma, chronic pancreatitis and mis-diagnosed other pancreatic diseases proven clinically and pathologically were analysed. Slice thickness of 8 mm and slice interval of 8 mm were used and thin-section scan and enhancement study were performed in some cases. The main signs in degassing and differential diagnosis between pancreatic carcinoma and chronic pancreatitis included: (1) focal or diffuse enlargement and density abnormality of pancreas; (2) dilated common bile duct was suddenly obstructed, peripancreatic blood vessels were invaded and cancerous thrombus was revealed, enlargement of abdominal lymph nodes and metastasis in the liver were discovered; (3) calcium deposit in the pancreatic duct area and dilated pancreatic duct which passed through the lesion or not; (4) presence and location of pancreatic cyst and its relationship to pancreatic contour. CT is the imaging modality of choice in the diagnosis of pancreatic carcinoma and chronic pancreatitis at present. The diagnostic accuracy of CT was over 90% in this series

  8. The "flying" bile duct: avulsion of the common bile duct in a plane crash survivor.

    LENUS (Irish Health Repository)

    Mohan, H

    2012-02-01

    Blunt trauma is an unusual cause of extrahepatic bile duct injury. This is a case of a 51-year-old gentleman who sustained a significant seatbelt injury in a plane crash. Laparotomy, performed due to persistent abdominal pain, revealed that the common bile duct (CBD) was completely avulsed from the duodenum. Following insertion of drains and transfer to a hepatobiliary centre, the devascularised CBD was excised and replaced with a roux-en-y hepaticojejunostomy. Necrotic tissue was debrided from the pancreatic head. A persistent bile leak developed from the sub-hepatic drain. Repeat laparotomy revealed a bile leak from small ducts on the liver surface. Ligation of the ducts and bioglue sealing of the area were successfully performed. Subsequent to this a pancreatic fistula developed from the main pancreatic duct, which has since resolved. This unusual case illustrates the need for prompt recognition and early repair to optimise outcomes in traumatic CBD injury.

  9. An Interstitial Network of Podoplanin-Expressing Cells in the Human Endolymphatic Duct

    Science.gov (United States)

    Mayerl, Christina; Rubin, Kristofer; Wick, Georg; Rask-Andersen, Helge

    2006-01-01

    The human endolymphatic duct (ED) with encompassing interstitial connective tissue (CT) is believed to be important for endolymph resorption and fluid pressure regulation of the inner ear. The periductal CT cells are interconnected via numerous cellular extensions, but do not form vessel structures. Here we report that the periductal CT is populated by two distinct cell phenotypes; one expressing podoplanin, a protein otherwise found on lymph endothelia and on epithelia involved in fluid fluxes, and a second expressing a fibroblast marker. A majority of the interstitial cells expressed podoplanin but not the lymphatic endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial growth factor receptor-3 (VEGFR-3). The fibroblast marker positive cells were found close to the ED epithelium. In the mid- and distal parts of the ED, these cells were enriched under folded epithelia. Furthermore, subepithelial CT cells were found to express activated platelet derived growth factor (PDGF)-β receptors. Cultured CT cells from human inner ear periductal and perisaccular explant tissues were identified as fibroblasts. These cells compacted a three-dimensional collagen lattice by a process that could be promoted by PDGF-BB, a factor involved in interstitial fluid pressure regulation. Our results are compatible with the notion that the periductal CT cells are involved in the regulation of inner ear fluid pressure. By active compaction of the periductal CT and by the formation of villous structures, the CT cells could modulate fluid fluxes over the ED epithelium as well as the longitudinal flow of endolymph in the ED. PMID:16408168

  10. Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models

    Science.gov (United States)

    Wen, Li; Voronina, Svetlana; Javed, Muhammad A.; Awais, Muhammad; Szatmary, Peter; Latawiec, Diane; Chvanov, Michael; Collier, David; Huang, Wei; Barrett, John; Begg, Malcolm; Stauderman, Ken; Roos, Jack; Grigoryev, Sergey; Ramos, Stephanie; Rogers, Evan; Whitten, Jeff; Velicelebi, Gonul; Dunn, Michael; Tepikin, Alexei V.; Criddle, David N.; Sutton, Robert

    2015-01-01

    Background & Aims Sustained activation of the cytosolic calcium concentration induces injury to pancreatic acinar cells and necrosis. The calcium release–activated calcium modulator ORAI1 is the most abundant Ca2+ entry channel in pancreatic acinar cells; it sustains calcium overload in mice exposed to toxins that induce pancreatitis. We investigated the roles of ORAI1 in pancreatic acinar cell injury and the development of acute pancreatitis in mice. Methods Mouse and human acinar cells, as well as HEK 293 cells transfected to express human ORAI1 with human stromal interaction molecule 1, were hyperstimulated or incubated with human bile acid, thapsigargin, or cyclopiazonic acid to induce calcium entry. GSK-7975A or CM_128 were added to some cells, which were analyzed by confocal and video microscopy and patch clamp recordings. Acute pancreatitis was induced in C57BL/6J mice by ductal injection of taurolithocholic acid 3-sulfate or intravenous' administration of cerulein or ethanol and palmitoleic acid. Some mice then were given GSK-7975A or CM_128, which inhibit ORAI1, at different time points to assess local and systemic effects. Results GSK-7975A and CM_128 each separately inhibited toxin-induced activation of ORAI1 and/or activation of Ca2+ currents after Ca2+ release, in a concentration-dependent manner, in mouse and human pancreatic acinar cells (inhibition >90% of the levels observed in control cells). The ORAI1 inhibitors also prevented activation of the necrotic cell death pathway in mouse and human pancreatic acinar cells. GSK-7975A and CM_128 each inhibited all local and systemic features of acute pancreatitis in all 3 models, in dose- and time-dependent manners. The agents were significantly more effective, in a range of parameters, when given at 1 vs 6 hours after induction of pancreatitis. Conclusions Cytosolic calcium overload, mediated via ORAI1, contributes to the pathogenesis of acute pancreatitis. ORAI1 inhibitors might be developed

  11. Particle deposition in ventilation ducts

    Energy Technology Data Exchange (ETDEWEB)

    Sippola, Mark Raymond [Univ. of California, Berkeley, CA (United States)

    2002-09-01

    Exposure to airborne particles is detrimental to human health and indoor exposures dominate total exposures for most people. The accidental or intentional release of aerosolized chemical and biological agents within or near a building can lead to exposures of building occupants to hazardous agents and costly building remediation. Particle deposition in heating, ventilation and air-conditioning (HVAC) systems may significantly influence exposures to particles indoors, diminish HVAC performance and lead to secondary pollutant release within buildings. This dissertation advances the understanding of particle behavior in HVAC systems and the fates of indoor particles by means of experiments and modeling. Laboratory experiments were conducted to quantify particle deposition rates in horizontal ventilation ducts using real HVAC materials. Particle deposition experiments were conducted in steel and internally insulated ducts at air speeds typically found in ventilation ducts, 2-9 m/s. Behaviors of monodisperse particles with diameters in the size range 1-16 μm were investigated. Deposition rates were measured in straight ducts with a fully developed turbulent flow profile, straight ducts with a developing turbulent flow profile, in duct bends and at S-connector pieces located at duct junctions. In straight ducts with fully developed turbulence, experiments showed deposition rates to be highest at duct floors, intermediate at duct walls, and lowest at duct ceilings. Deposition rates to a given surface increased with an increase in particle size or air speed. Deposition was much higher in internally insulated ducts than in uninsulated steel ducts. In most cases, deposition in straight ducts with developing turbulence, in duct bends and at S-connectors at duct junctions was higher than in straight ducts with fully developed turbulence. Measured deposition rates were generally higher than predicted by published models. A model incorporating empirical equations based on the

  12. Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans

    Science.gov (United States)

    Ochi, Atsuo; Graffeo, Christopher S.; Zambirinis, Constantinos P.; Rehman, Adeel; Hackman, Michael; Fallon, Nina; Barilla, Rocky M.; Henning, Justin R.; Jamal, Mohsin; Rao, Raghavendra; Greco, Stephanie; Deutsch, Michael; Medina-Zea, Marco V.; Saeed, Usama Bin; Ego-Osuala, Melvin O.; Hajdu, Cristina; Miller, George

    2012-01-01

    Pancreatic ductal adenocarcinoma is an aggressive cancer that interacts with stromal cells to produce a highly inflammatory tumor microenvironment that promotes tumor growth and invasiveness. The precise interplay between tumor and stroma remains poorly understood. TLRs mediate interactions between environmental stimuli and innate immunity and trigger proinflammatory signaling cascades. Our finding that TLR7 expression is upregulated in both epithelial and stromal compartments in human and murine pancreatic cancer led us to postulate that carcinogenesis is dependent on TLR7 signaling. In a mouse model of pancreatic cancer, TLR7 ligation vigorously accelerated tumor progression and induced loss of expression of PTEN, p16, and cyclin D1 and upregulation of p21, p27, p53, c-Myc, SHPTP1, TGF-β, PPARγ, and cyclin B1. Furthermore, TLR7 ligation induced STAT3 activation and interfaced with Notch as well as canonical NF-κB and MAP kinase pathways, but downregulated expression of Notch target genes. Moreover, blockade of TLR7 protected against carcinogenesis. Since pancreatic tumorigenesis requires stromal expansion, we proposed that TLR7 ligation modulates pancreatic cancer by driving stromal inflammation. Accordingly, we found that mice lacking TLR7 exclusively within their inflammatory cells were protected from neoplasia. These data suggest that targeting TLR7 holds promise for treatment of human pancreatic cancer. PMID:23023703

  13. Gene expression patterns in pancreatic tumors, cells and tissues.

    Directory of Open Access Journals (Sweden)

    Anson W Lowe

    2007-03-01

    Full Text Available Cancers of the pancreas originate from both the endocrine and exocrine elements of the organ, and represent a major cause of cancer-related death. This study provides a comprehensive assessment of gene expression for pancreatic tumors, the normal pancreas, and nonneoplastic pancreatic disease.DNA microarrays were used to assess the gene expression for surgically derived pancreatic adenocarcinomas, islet cell tumors, and mesenchymal tumors. The addition of normal pancreata, isolated islets, isolated pancreatic ducts, and pancreatic adenocarcinoma cell lines enhanced subsequent analysis by increasing the diversity in gene expression profiles obtained. Exocrine, endocrine, and mesenchymal tumors displayed unique gene expression profiles. Similarities in gene expression support the pancreatic duct as the origin of adenocarcinomas. In addition, genes highly expressed in other cancers and associated with specific signal transduction pathways were also found in pancreatic tumors.The scope of the present work was enhanced by the inclusion of publicly available datasets that encompass a wide spectrum of human tissues and enabled the identification of candidate genes that may serve diagnostic and therapeutic goals.

  14. LTB4 stimulates growth of human pancreatic cancer cells via MAPK and PI-3 kinase pathways

    International Nuclear Information System (INIS)

    Tong, W.-G.; Ding, X.-Z.; Talamonti, Mark S.; Bell, Richard H.; Adrian, Thomas E.

    2005-01-01

    We have previously shown the importance of LTB4 in human pancreatic cancer. LTB4 receptor antagonists block growth and induce apoptosis in pancreatic cancer cells both in vitro and in vivo. Therefore, we investigated the effect of LTB4 on proliferation of human pancreatic cancer cells and the mechanisms involved. LTB4 stimulated DNA synthesis and proliferation of both PANC-1 and AsPC-1 human pancreatic cancer cells, as measured by thymidine incorporation and cell number. LTB4 stimulated rapid and transient activation of MEK and ERK1/2 kinases. The MEK inhibitors, PD98059 and U0126, blocked LTB4-stimulated ERK1/2 activation and cell proliferation. LTB4 also stimulated phosphorylation of p38 MAPK; however, the p38 MAPK inhibitor, SB203580, failed to block LTB4-stimulated growth. The activity of JNK/SAPK was not affected by LTB4 treatment. Phosphorylation of Akt was also induced by LTB4 and this effect was blocked by the PI-3 kinase inhibitor wortmannin, which also partially blocked LTB4-stimulated cell proliferation. In conclusion, LTB4 stimulates proliferation of human pancreatic cancer cells through MEK/ERK and PI-3 kinase/Akt pathways, while p38 MPAK and JNK/SAPK are not involved

  15. Ductal Mucus Obstruction and Reduced Fluid Secretion Are Early Defects in Chronic Pancreatitis

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    Anita Balázs

    2018-05-01

    Full Text Available Objective: Defective mucus production in the pancreas may be an important factor in the initiation and progression of chronic pancreatitis (CP, therefore we aimed to (i investigate the qualitative and quantitative changes of mucus both in human CP and in an experimental pancreatitis model and (ii to correlate the mucus phenotype with epithelial ion transport function.Design: Utilizing human tissue samples and a murine model of cerulein induced CP we measured pancreatic ductal mucus content by morphometric analysis and the relative expression of different mucins in health and disease. Pancreatic fluid secretion in CP model was measured in vivo by magnetic resonance cholangiopancreatography (MRCP and in vitro on cultured pancreatic ducts. Time-changes of ductal secretory function were correlated to those of the mucin production.Results: We demonstrate increased mucus content in the small pancreatic ducts in CP. Secretory mucins MUC6 and MUC5B were upregulated in human, Muc6 in mouse CP. In vivo and in vitro fluid secretion was decreased in cerulein-induced CP. Analysis of time-course changes showed that impaired ductal ion transport is paralleled by increased Muc6 expression.Conclusion: Mucus accumulation in the small ducts is a combined effect of mucus hypersecretion and epithelial fluid secretion defect, which may lead to ductal obstruction. These results suggest that imbalance of mucus homeostasis may have an important role in the early-phase development of CP, which may have novel diagnostic and therapeutic implications.

  16. Demonstration of pepsinogen C in human pancreatic islets

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1987-01-01

    Pancreatic tissue from 16 post mortem kidney donors have been examined for the content of pepsinogens. A zymogen with electrophoretic mobility, isoelectric point and molecular weight equal to that of pepsinogen C of gastric origin was found in all specimens. A comparison between pepsinogen C extr...

  17. Knockdown of ZFR suppresses cell proliferation and invasion of human pancreatic cancer

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    Xiaolan Zhao

    Full Text Available BACKGROUND: Zinc finger RNA binding protein (ZFR is involved in the regulation of growth and cancer development. However, little is known about ZFR function in pancreatic cancer. METHODS: Herein, to investigate whether ZFR is involved in tumor growth, Oncomine microarray data was firstly used to evaluate ZFR gene expression in human pancreatic tumors. Then short hairpin RNA (shRNA targeting ZFR was designed and delivered into PANC-1 pancreatic cancer cells to knock down ZFR expression. Cell viability, cell proliferation and cell cycle analysis after ZFR knockdown were determined by MTT, colony forming and FACS, respectively. In addition, cell migration and invasion were assessed using the Transwell system. RESULTS: The expression of ZFR was significantly higher in pancreatic tumors than normal pancreas tissues by Oncomine database analysis. Knockdown of ZFR by shRNA-expressing lentivirus significantly decreased the viability and invasion ability of pancreatic cancer cells. Moreover, FACS analysis showed that knockdown of ZFR in PANC-1 cells caused a significant cell cycle arrest at G0/G1 phase. Furthermore, knockdown of ZFR decreased the levels of CDK2, CDK4, CyclinA and CyclinD1 and enhanced the expression of p27, which has evidenced by qRT-PCR and Western blot analysis. CONCLUSIONS: Knockdown of ZFR might provide a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation.

  18. Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells

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    Jamie Trott

    2017-06-01

    Full Text Available Pluripotent stem cells have been proposed as an unlimited source of pancreatic β cells for studying and treating diabetes. However, the long, multi-step differentiation protocols used to generate functional β cells inevitably exhibit considerable variability, particularly when applied to pluripotent cells from diverse genetic backgrounds. We have developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas. These cultured pancreatic progenitor (cPP cells express key pancreatic transcription factors, including PDX1 and SOX9, and exhibit transcriptomes closely related to their in vivo counterparts. Upon exposure to differentiation cues, cPP cells give rise to pancreatic endocrine, acinar, and ductal lineages, indicating multilineage potency. Furthermore, cPP cells generate insulin+ β-like cells in vitro and in vivo, suggesting that they offer a convenient alternative to pluripotent cells as a source of adult cell types for modeling pancreatic development and diabetes.

  19. A Novel Ras Inhibitor (MDC-1016 Reduces Human Pancreatic Tumor Growth in Mice

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    Gerardo G Mackenzie

    2013-10-01

    Full Text Available Pancreatic cancer has one of the poorest prognoses among all cancers partly because of its persistent resistance to chemotherapy. The currently limited treatment options for pancreatic cancer underscore the need for more efficient agents. Because activating Kras mutations initiate and maintain pancreatic cancer, inhibition of this pathway should have a major therapeutic impact. We synthesized phospho-farnesylthiosalicylic acid (PFTS; MDC-1016 and evaluated its efficacy, safety, and metabolism in preclinical models of pancreatic cancer. PFTS inhibited the growth of human pancreatic cancer cells in culture in a concentration- and time-dependent manner. In an MIA PaCa-2 xenograft mouse model, PFTS at a dose of 50 and 100 mg/kg significantly reduced tumor growth by 62% and 65% (P < .05 vs vehicle control. Furthermore, PFTS prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. PFTS appeared to be safe, with the animals showing no signs of toxicity during treatment. Following oral administration, PFTS was rapidly absorbed, metabolized to FTS and FTS glucuronide, and distributed through the blood to body organs. Mechanistically, PFTS inhibited Ras-GTP, the active form of Ras, both in vitro and in vivo, leading to the inhibition of downstream effector pathways c-RAF/mitogen-activated protein-extracellular signal-regulated kinase (ERK kinase (MEK/ERK1/2 kinase and phosphatidylinositol 3-kinase/AKT. In addition, PFTS proved to be a strong combination partner with phospho-valproic acid, a novel signal transducer and activator of transcription 3 (STAT3 inhibitor, displaying synergy in the inhibition of pancreatic cancer growth. In conclusion, PFTS, a direct Ras inhibitor, is an efficacious agent for the treatment of pancreatic cancer in preclinical models, deserving further evaluation.

  20. Autoimmune Pancreatitis.

    Science.gov (United States)

    Majumder, Shounak; Takahashi, Naoki; Chari, Suresh T

    2017-07-01

    Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP. Histologically, lymphoplasmacytic acinar inflammation and storiform fibrosis are seen in both. In addition, the histologic hallmark of IDCP is the granulocyte epithelial lesion: intraluminal and intraepithelial neutrophils in medium-sized and small ducts with or without granulocytic acinar inflammation often associated with destruction of ductal architecture. Initial treatment of both AIP and IDCP is with oral corticosteroids for duration of 4 weeks followed by a gradual taper. Relapses are common in AIP and relatively uncommon in IDCP, a relatively rare disease for which the natural history is not well understood. For patients with relapsing AIP, treatment with immunomodulators and more recently rituximab has been recommended. Although rare instances of pancreaticobiliary malignancy has been reported in patients with AIP, overall the lifetime risk of developing pancreatic cancer does not appear to be elevated.

  1. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

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    Hitoshi Nakagama

    2011-02-01

    Full Text Available Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropylamine (BOP into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5’ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

  2. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    International Nuclear Information System (INIS)

    Takahashi, Mami; Hori, Mika; Mutoh, Michihiro; Wakabayashi, Keiji; Nakagama, Hitoshi

    2011-01-01

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention

  3. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Mami, E-mail: mtakahas@ncc.go.jp; Hori, Mika; Mutoh, Michihiro [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Wakabayashi, Keiji [Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526 (Japan); Nakagama, Hitoshi [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan)

    2011-02-09

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

  4. The tobacco carcinogen NNK is stereoselectively reduced by human pancreatic microsomes and cytosols.

    Science.gov (United States)

    Trushin, Neil; Leder, Gerhard; El-Bayoumy, Karam; Hoffmann, Dietrich; Beger, Hans G; Henne-Bruns, Doris; Ramadani, Marco; Prokopczyk, Bogdan

    2008-07-01

    Cigarette smoking increases the risk of cancer of the pancreas. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the only known environmental compound that induces pancreatic cancer in laboratory animals. Concentrations of NNK are significantly higher in the pancreatic juice of smokers than in that of nonsmokers. The chiral NNK metabolite, (R,S)-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is itself a potent pancreatic carcinogen in rats. The carcinogenicity of NNAL is related to its stereochemistry; (S)-NNAL is a more potent lung tumorigen in the A/J mouse than is (R)-NNAL. In this study, we determined the potential of the human pancreas to convert NNK into NNAL. Human pancreatic microsomes and cytosols were incubated with [5-(3)H]NNK, and the metabolic products were determined by high-performance liquid chromatography (HPLC). (S)-NNAL was the predominant isomer formed in all cytosolic incubations. In ten microsomal samples, NNAL was formed at an average rate of 3.8 +/- 1.6 pmol/mg/min; (R)-NNAL was the predominant isomer in this group. The average rate of NNAL formation in 18 other microsomal samples was significantly lower, 0.13 +/- 0.12 pmol/mg/min (p < 0.001); (S)-NNAL was the predominant isomer formed in this group. In human pancreatic tissues, there is intraindividual variability regarding the capacity for, and stereoselectivity of, carbonyl reduction of NNK.

  5. The novel cytokine interleukin-33 activates acinar cell proinflammatory pathways and induces acute pancreatic inflammation in mice.

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    Duraisamy Kempuraj

    Full Text Available Acute pancreatitis is potentially fatal but treatment options are limited as disease pathogenesis is poorly understood. IL-33, a novel IL-1 cytokine family member, plays a role in various inflammatory conditions but its role in acute pancreatitis is not well understood. Specifically, whether pancreatic acinar cells produce IL-33 when stressed or respond to IL-33 stimulation, and whether IL-33 exacerbates acute pancreatic inflammation is unknown.In duct ligation-induced acute pancreatitis in mice and rats, we found that (a IL-33 concentration was increased in the pancreas; (b mast cells, which secrete and also respond to IL-33, showed degranulation in the pancreas and lung; (c plasma histamine and pancreatic substance P concentrations were increased; and (d pancreatic and pulmonary proinflammatory cytokine concentrations were increased. In isolated mouse pancreatic acinar cells, TNF-α stimulation increased IL-33 release while IL-33 stimulation increased proinflammatory cytokine release, both involving the ERK MAP kinase pathway; the flavonoid luteolin inhibited IL-33-stimulated IL-6 and CCL2/MCP-1 release. In mice without duct ligation, exogenous IL-33 administration induced pancreatic inflammation without mast cell degranulation or jejunal inflammation; pancreatic changes included multifocal edema and perivascular infiltration by neutrophils and some macrophages. ERK MAP kinase (but not p38 or JNK and NF-kB subunit p65 were activated in the pancreas of mice receiving exogenous IL-33, and acinar cells isolated from the pancreas of these mice showed increased spontaneous cytokine release (IL-6, CXCL2/MIP-2α. Also, IL-33 activated ERK in human pancreatic tissue.As exogenous IL-33 does not induce jejunal inflammation in the same mice in which it induces pancreatic inflammation, we have discovered a potential role for an IL-33/acinar cell axis in the recruitment of neutrophils and macrophages and the exacerbation of acute pancreatic inflammation

  6. Pseudocyst in the pancreatic tail associated with chronic pancreatitis successfully treated by transpapillary cyst drainage.

    Science.gov (United States)

    Naitoh, Itaru; Ohara, Hirotaka; Okayama, Yasutaka; Nakazawa, Takahiro; Ando, Tomoaki; Hayashi, Kazuki; Okumura, Fumihiro; Kitajima, Yasuhiro; Ban, Tessin; Miyabe, Katsuyuki; Ueno, Koichiro; Joh, Takashi; Sano, Hitoshi

    2008-09-01

    We report a 50-year-old male with pseudocysts in the pancreatic tail associated with chronic pancreatitis successfully treated by transpapillary cyst drainage. He had previously undergone ultrasonography-guided percutaneous cyst drainage for a pancreatic pseudocyst in our hospital. He was readmitted due to abdominal pain and fever. Computed tomography showed recurrence of a pseudocyst in the pancreatic tail measuring 5 cm in diameter. Since conservative treatment failed, endoscopic retrograde pancreatography was performed. There was communication between the pseudocyst and the main pancreatic duct, and pancreatic duct stenosis proximal to the pseudocyst. First, transpapillary pancreatic duct drainage was performed using a plastic stent, but the pseudocyst did not decrease in size and became infected. After removal of the stent, a pigtail type nasocystic catheter was placed in the pseudocyst via the pancreatic duct. The pseudocyst infection immediately disappeared, and the pseudocyst gradually decreased and disappeared. After removal of the nasocystic catheter, no recurrence was observed. As transpapillary drainage of pancreatic pseudocyst, cyst drainage and pancreatic duct drainage have been reported. In our patient with pseudocyst in the pancreatic tail, duct drainage was ineffective and the pseudocyst was infected, whereas cyst drainage was very effective. We considered that cyst drainage by a nasocystic catheter was the first-line therapy as the transpapillary drainage of the pancreatic pseudocyst.

  7. Pseudocyst in the Pancreatic Tail Associated with Chronic Pancreatitis Successfully Treated by Transpapillary Cyst Drainage

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    Itaru Naitoh

    2008-11-01

    Full Text Available We report a 50-year-old male with pseudocysts in the pancreatic tail associated with chronic pancreatitis successfully treated by transpapillary cyst drainage. He had previously undergone ultrasonography-guided percutaneous cyst drainage for a pancreatic pseudocyst in our hospital. He was readmitted due to abdominal pain and fever. Computed tomography showed recurrence of a pseudocyst in the pancreatic tail measuring 5 cm in diameter. Since conservative treatment failed, endoscopic retrograde pancreatography was performed. There was communication between the pseudocyst and the main pancreatic duct, and pancreatic duct stenosis proximal to the pseudocyst. First, transpapillary pancreatic duct drainage was performed using a plastic stent, but the pseudocyst did not decrease in size and became infected. After removal of the stent, a pigtail type nasocystic catheter was placed in the pseudocyst via the pancreatic duct. The pseudocyst infection immediately disappeared, and the pseudocyst gradually decreased and disappeared. After removal of the nasocystic catheter, no recurrence was observed. As transpapillary drainage of pancreatic pseudocyst, cyst drainage and pancreatic duct drainage have been reported. In our patient with pseudocyst in the pancreatic tail, duct drainage was ineffective and the pseudocyst was infected, whereas cyst drainage was very effective. We considered that cyst drainage by a nasocystic catheter was the first-line therapy as the transpapillary drainage of the pancreatic pseudocyst.

  8. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    Science.gov (United States)

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

  9. Solitary main pancreatic ductal calculus of possible biliary origin causing acute pancreatitis.

    Science.gov (United States)

    Chaparala, Ramakrishna Prasad Chowdary; Patel, Rafiuddin; Guthrie, James Ahsley; Davies, Mervyn Huw; Guillou, Pierre J; Menon, Krishna V

    2005-09-10

    Pancreatic ductal calculi are most often associated with chronic pancreatitis. Radiological features of chronic pancreatitis are readily evident in the presence of these calculi. However, acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. A 59-year-old man presented with a first episode of acute pancreatitis. Contrast enhanced computerized tomography (CT) scan and endoscopic retrograde cholangiopancreatography (ERCP) revealed a calculus in the main pancreatic duct in the head of the pancreas causing acute pancreatitis. There were no features suggestive of chronic pancreatitis on CT scanning. The episode acute pancreatitis was managed conservatively. ERCP extraction of the calculus failed as the stone was impacted in the main pancreatic duct resulting in severe acute pancreatitis. Once this resolved, a transduodenal exploration and extraction of the pancreatic ductal calculus was performed successfully. Crystallographic analysis revealed the composition of the calculus was different to that seen in chronic pancreatitis, but more in keeping with a calculus of biliary origin. This could be explained by migration of the biliary calculus via the common channel into the main pancreatic duct. Following the operation the patient made an uneventful recovery and was well at two-year follow up. Acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. Failing endoscopic extraction, transduodenal exploration and extraction is a safe option after resolution of acute pancreatitis.

  10. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

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    Sala Abdalla

    2016-01-01

    Full Text Available Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions.

  11. Litotricia por ondas de choque extracorpóreas como tratamiento de los cálculos del conducto pancreático principal Extracorporeal shock- wave lithotripsy as a treatment of the calculi of the main pancreatic duct

    Directory of Open Access Journals (Sweden)

    Domingo Pérez González

    2004-12-01

    Full Text Available Las ondas de choque extracorpóreas se utilizan desde hace varios años con buenos resultados en la fragmentación de cálculos vesiculares y de las vías biliares en pacientes seleccionados. Cuando los cálculos del conducto pancreático principal no pueden extraerse endoscópicamente está indicada esta variante no quirúrgica. Se presentan 4 pacientes del sexo masculino, entre 41 y 55 años de edad, con antecedentes de alcoholismo y el diagnóstico de pancreatitis crónica con litiasis en el conducto principal, 3 de ellos con más de 1 cálculo, que recibieron ondas de choque generadas por el principio electromagnético. Todos fragmentaron. El paciente con cálculo único eliminó los fragmentos espontáneamente, mientras que en los 3 restantes fue necesario asociar la endoscopia para obtener la limpieza total de Wirsung . Durante el seguimiento de más de 5 años se constató la regresión de los síntomas, fundamentalmente del dolor, sin recidivasThe extracorporeal shock waves have been used for several years with good results in the fragmentation of calculi of the gallbladder and of the biliary tract in selected patients. When the calculi of the main pancreatic duct cannot be endoscopically removed, this non-surgical variant is indicated. 4 male patients aged 41-55 with alcoholism history and the diagnosis of chronic pancreatitis with lithiasis in the main duct are presented. 3 of them with more than a calculus received shock waves generated by electromagnetic principle. All the calculi were fragmented. The patient with only one calculus eliminated the fragments spontaneously, whereas in the other 3 it was necessary to associate endoscopy to obtain Wirsung's total cleaning. During the follow-up of more than 5 years it was proved the regression of the symptoms, mainly pain, without relapses

  12. Cloning and functional expression of a human pancreatic islet glucose-transporter cDNA

    International Nuclear Information System (INIS)

    Permutt, M.A.; Koranyi, L.; Keller, K.; Lacy, P.E.; Scharp, D.W.; Mueckler, M.

    1989-01-01

    Previous studies have suggested that pancreatic islet glucose transport is mediated by a high-K m , low-affinity facilitated transporter similar to that expressed in liver. To determine the relationship between islet and liver glucose transporters, liver-type glucose-transporter cDNA clones were isolated from a human liver cDNA library. The liver-type glucose-transporter cDNA clone hybridized to mRNA transcripts of the same size in human liver and pancreatic islet RNA. A cDNA library was prepared from purified human pancreatic islet tissue and screened with human liver-type glucose-transporter cDNA. The authors isolated two overlapping cDNA clones encompassing 2600 base pairs, which encode a pancreatic islet protein identical in sequence to that of the putative liver-type glucose-transporter protein. Xenopus oocytes injected with synthetic mRNA transcribed from a full-length cDNA construct exhibited increased uptake of 2-deoxyglucose, confirming the functional identity of the clone. These cDNA clones can now be used to study regulation of expression of the gene and to assess the role of inherited defects in this gene as a candidate for inherited susceptibility to non-insulin-dependent diabetes mellitus

  13. Glycolysis in Panc-1 human pancreatic cancer cells is inhibited by everolimus.

    Science.gov (United States)

    Liu, Ling; Gong, Liansheng; Zhang, Yangde; Li, Nianfeng

    2013-01-01

    The aim of this study was to evaluate the effects and molecular mechanisms of everolimus on Panc-1 human pancreatic cancer cells. Panc-1 human pancreatic cancer cells were treated with everolimus (10 μg/ml) at selected time points (6, 12 and 24 h). Cell proliferation and apoptosis were evaluated by MTT and flow cytometric analyses. The glycolytic activity was determined by measuring the activity of the key enzyme lactate dehydrogenase (LDH) and lactate production. The activity of mammalian target of rapamycin (mTOR) signaling was measured by western blotting. The expression of genes, including hexokinase 2 (HK2) and microRNA-143 (miR-143), was evaluated by real-time polymerase chain reaction (PCR). The administration of everolimus time-dependently inhibited proliferation and glycolysis and induced apoptosis in the Panc-1 human pancreatic cancer cells. As the time of treatment with everolimus increased, the mTOR signaling activity decreased, indicated by lower phosphorylation levels of S6 kinase; however, the phosphorylation levels of mTOR barely changed. Moreover, our data showed an everolimus-induced increase in miR-143 and decrease in HK2 in Panc-1 cells in a time-dependent manner. In conclusion, the current study indicates a novel role of everolimus in its antitumor effect as an inhibitor of glycolysis in Panc-1 human pancreatic cancer cells. Furthermore, our data highlights the significance of exploring the mechanisms of everolimus and miR-143 in malignant tumors.

  14. Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer

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    Nelson S. Yee

    2012-02-01

    Histone deacetylases (HDACs and RNA polymerase III (POLR3 play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis in zebrafish. We aim to test the hypothesis that Hdacs and Polr3 cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A and an inhibitor of Polr3 (ML-60218 synergistically prohibited the expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA and ML-60218 produced augmented suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive upregulation of the pro-apoptotic regulator BAX and the cyclin-dependent kinase inhibitor p21CDKN1A. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators of exocrine pancreas can be translated into an approach with potential impact on therapeutic response in pancreatic cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.

  15. MUC1 selectively targets human pancreatic cancer in orthotopic nude mouse models.

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    Jeong Youp Park

    Full Text Available The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2 antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MUC1 antibody demonstrated fluorescent areas on the membrane of Panc-1 cancer cells. After injecting the conjugated anti-MUC1 antibodies via the tail vein, subcutaneously transplanted Panc-1 and BxPC-3 tumors emitted strong fluorescent signals. In the subcutaneous tumor models, the fluorescent signal from the conjugated anti-MUC1 antibody was noted around the margin of the tumor and space between the cells. The conjugated anti-MUC1 antibody bound the tumor in orthotopically-transplanted Panc-1 and BxPC-3 models enabling the tumors to be imaged. This study showed that fluorophore conjugated anti-MUC1 antibodies could visualize pancreatic tumors in vitro and in vivo and may help to improve the diagnosis and treatment of pancreatic cancer.

  16. Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

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    Shengzhang Lin

    2013-01-01

    Full Text Available Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990 with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153, a marker of the endoplasmic-reticulum-stress- (ERS- mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78, phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK, and phosphoeukaryotic initiation factor-2α (phospho-eIF2α, activating transcription factor 4 (ATF4 and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

  17. Curcumin Inhibits Tumor Growth and Angiogenesis in an Orthotopic Mouse Model of Human Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2013-01-01

    Full Text Available Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The best chemotherapeutic agent used to treat pancreatic cancer is the gemcitabine. However, gemcitabine treatment is associated with many side effects. Thus novel strategies involving less toxic agents for treatment of pancreatic cancer are necessary. Curcumin is one such agent that inhibits the proliferation and angiogenesis of a wide variety of tumor cells, through the modulation of many cell signalling pathways. In this study, we investigated whether curcumin plays antitumor effects in MIA PaCa-2 cells. In vitro studies showed that curcumin inhibits the proliferation and enhances apoptosis of MIA PaCa-2 cells. To test whether the antitumor activity of curcumin is also observed in vivo, we generated an orthotopic mouse model of pancreatic cancer by injection of MIA PaCa-2 cells in nude mice. We placed mice on diet containing curcumin at 0.6% for 6 weeks. In these treated mice tumors were smaller with respect to controls and showed a downregulation of the transcription nuclear factor NF-κB and NF-κB-regulated gene products. Overall, our data indicate that curcumin has a great potential in treatment of human pancreatic cancer through the modulation of NF-κB pathway.

  18. uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human pancreatic tumors.

    Science.gov (United States)

    Sobrevals, Luciano; Mato-Berciano, Ana; Urtasun, Nerea; Mazo, Adela; Fillat, Cristina

    2014-01-01

    Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The identification of therapies that can eliminate this population of cells might provide with more effective treatments. In the current work we evaluated the potential of oncolytic adenoviruses to act against pancreatic cancer stem cells (PCSC). PCSC from two patient-derived xenograft models were isolated from orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic agent gemcitabine. An enrichment in the number of PCSC expressing the cell surface marker CD133 and a marked enhancement on tumorsphere formation was observed in gemcitabine treated tumors. No significant increase in the CD44, CD24, and epithelial-specific antigen (ESA) positive cells was observed. Neoplastic sphere-forming cells were susceptible to adenoviral infection and exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous administration of a single dose of AduPARE1A in human-derived pancreatic xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine AduPARE1A treatment did not result in PCSC enrichment. No enrichment on tumorspheres neither on the CD133(+) population was detected. Therefore our data provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for the elimination of pancreatic cancer stem cells. © 2013.

  19. CT findings of the mucin producing pancreatic cancer

    International Nuclear Information System (INIS)

    Ri, Kyoushichi; Hashimoto, Toushi; Munechika, Hirotsugu

    1992-01-01

    Mucin-producing pancreatic cancers (MPPC), which include mucinous adenocarcinoma, papillary adenocarcinoma and cystadenocarcinoma, are radiographically characterized by diffuse or localized dilatation of the main pancreatic duct due to excessive mucin production. Therefore, MPPC are occasionally difficult to distinguish from chronic pancreatitis on CT unless the primary pancreatic lesion is visualized. We compared five cases of MPPC with five cases of chronic pancreatitis with marked duct dilatation to determine differences in CT images between the two diseases. There was no significant difference between the two diseases in the nature of duct dilatation (size, extent, contour) or parenchymal changes (atrophy, enlargement, calcification, cystic lesion). However, dilatation of the intramural duct was characteristically observed in MPPC but not in chronic pancreatitis. Papillary masses in the pancreatic duct, when observed, were another finding specific to MPPC. (author)

  20. In vitro cytotoxicity of alpha conjugates for human pancreatic cancer cell lines

    International Nuclear Information System (INIS)

    Qu, C.; Li, Y.; Rizvi, M.A.; Allen, B.; Samra, J.; Smith, R.

    2003-01-01

    Targeted Alpha therapy (TAT) can inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The aim of this study is to demonstrate the cytotoxicity of different alpha conjugates in vitro to human metastatic pancreatic cancer cell lines (CAPAN-1, CFPAN-1 and PANC-1). We are labeling the C595 and J591 (non-specific controls) monoclonal antibodies (Mabs) with 213 Bi were performed according to the standard methods in our laboratory. 213 Bi-C595 is specifically cytotoxic to CAPAN-1, CFPAN-1 and PANC-1cell lines in a concentration-dependent fashion. While non-specific alpha conjugates only killed very small fractions of pancreatic cancer cells. These alpha conjugates might be useful agents for the treatment of micro-metastases in pancreatic cancer patients with over-expression of the targeted receptors

  1. Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin βE subunit

    International Nuclear Information System (INIS)

    Hashimoto, Osamu; Ushiro, Yuuki; Sekiyama, Kazunari; Yamaguchi, Osamu; Yoshioka, Kazuki; Mutoh, Ken-Ichiro; Hasegawa, Yoshihisa

    2006-01-01

    Activins, TGF-β superfamily members, have multiple functions in a variety of cells and tissues. Recently, additional activin β subunit genes, βC and βE, have been identified. To explore the role of activin E, we created transgenic mice overexpressing human activin βE subunit. There were pronounced differences in the pancreata of the transgenic animals as compared with their wild-type counterparts. Pancreatic weight, expressed relative to total body weight, was significantly reduced. Histologically, adipose replacement of acini in the exocrine pancreas was observed. There was a significant decrease in the number of PCNA-positive cells in the acinar cells, indicating reduced proliferation in the exocrine pancreas of the transgenic mice. However, quantitative pancreatic morphometry showed that the total number and mass of the islets of the transgenic mice were comparable with those of the nontransgenic control mice. Our findings suggest a role for activin E in regulating the proliferation of pancreatic exocrine cells

  2. A Dimeric Mutant of Human Pancreatic Ribonuclease with Selective Cytotoxicity toward Malignant Cells

    Science.gov (United States)

    Piccoli, Renata; di Gaetano, Sonia; de Lorenzo, Claudia; Grauso, Michela; Monaco, Carmen; Spalletti-Cernia, Daniela; Laccetti, Paolo; Cinatl, Jaroslav; Matousek, Josef; D'Alessio, Giuseppe

    1999-07-01

    Monomeric human pancreatic RNase, devoid of any biological activity other than its RNA degrading ability, was engineered into a dimeric protein with a cytotoxic action on mouse and human tumor cells, but lacking any appreciable toxicity on mouse and human normal cells. This dimeric variant of human pancreas RNase selectively sensitizes to apoptotic death cells derived from a human thyroid tumor. Because of its selectivity for tumor cells, and because of its human origin, this protein represents a potentially very attractive, novel tool for anticancer therapy.

  3. Nanotopography Promotes Pancreatic Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Kim, Jong Hyun; Kim, Hyung Woo; Cha, Kyoung Je; Han, Jiyou; Jang, Yu Jin; Kim, Dong Sung; Kim, Jong-Hoon

    2016-03-22

    Although previous studies suggest that nanotopographical features influence properties and behaviors of stem cells, only a few studies have attempted to derive clinically useful somatic cells from human pluripotent stem cells using nanopatterned surfaces. In the present study, we report that polystyrene nanopore-patterned surfaces significantly promote the pancreatic differentiation of human embryonic and induced pluripotent stem cells. We compared different diameters of nanopores and showed that 200 nm nanopore-patterned surfaces highly upregulated the expression of PDX1, a critical transcription factor for pancreatic development, leading to an approximately 3-fold increase in the percentage of differentiating PDX1(+) pancreatic progenitors compared with control flat surfaces. Furthermore, in the presence of biochemical factors, 200 nm nanopore-patterned surfaces profoundly enhanced the derivation of pancreatic endocrine cells producing insulin, glucagon, or somatostatin. We also demonstrate that nanopore-patterned surface-induced upregulation of PDX1 is associated with downregulation of TAZ, suggesting the potential role of TAZ in nanopore-patterned surface-mediated mechanotransduction. Our study suggests that appropriate cytokine treatments combined with nanotopographical stimulation could be a powerful tool for deriving a high purity of desired cells from human pluripotent stem cells.

  4. Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells.

    Science.gov (United States)

    Rostovskaya, Maria; Bredenkamp, Nicholas; Smith, Austin

    2015-10-19

    Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta cells. Several protocols have been reported for generating pancreatic progenitors by in vitro differentiation of human pluripotent stem cells. Here we first assessed one of these protocols on a panel of pluripotent stem cell lines for capacity to engender glucose sensitive insulin-producing cells after engraftment in immunocompromised mice. We observed variable outcomes with only one cell line showing a low level of glucose response. We, therefore, undertook a systematic comparison of different methods for inducing definitive endoderm and subsequently pancreatic differentiation. Of several protocols tested, we identified a combined approach that robustly generated pancreatic progenitors in vitro from both embryo-derived and induced pluripotent stem cells. These findings suggest that, although there are intrinsic differences in lineage specification propensity between pluripotent stem cell lines, optimal differentiation procedures may consistently direct a substantial fraction of cells into pancreatic specification. © 2015 The Authors.

  5. Identification of markers for quiescent pancreatic stellate cells in the normal human pancreas.

    Science.gov (United States)

    Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Detlefsen, Sönke

    2017-10-01

    Pancreatic stellate cells (PSCs) play a central role as source of fibrogenic cells in pancreatic cancer and chronic pancreatitis. In contrast to quiescent hepatic stellate cells (qHSCs), a specific marker for quiescent PSCs (qPSCs) that can be used in formalin-fixed and paraffin embedded (FFPE) normal human pancreatic tissue has not been identified. The aim of this study was to identify a marker enabling the identification of qPSCs in normal human FFPE pancreatic tissue. Immunohistochemical (IHC), double-IHC, immunofluorescence (IF) and double-IF analyses were carried out using a tissue microarray consisting of cores with normal human pancreatic tissue. Cores with normal human liver served as control. Antibodies directed against adipophilin, α-SMA, CD146, CRBP-1, cytoglobin, desmin, GFAP, nestin, S100A4 and vinculin were examined, with special emphasis on their expression in periacinar cells in the normal human pancreas and perisinusoidal cells in the normal human liver. The immunolabelling capacity was evaluated according to a semiquantitative scoring system. Double-IF of the markers of interest together with markers for other periacinar cells was performed. Moreover, the utility of histochemical stains for the identification of human qPSCs was examined, and their ultrastructure was revisited by electron microscopy. Adipophilin, CRBP-1, cytoglobin and vinculin were expressed in qHSCs in the liver, whereas cytoglobin and adipophilin were expressed in qPSCs in the pancreas. Adipophilin immunohistochemistry was highly dependent on the preanalytical time interval (PATI) from removal of the tissue to formalin fixation. Cytoglobin, S100A4 and vinculin were expressed in periacinar fibroblasts (FBs). The other examined markers were negative in human qPSCs. Our data indicate that cytoglobin and adipophilin are markers of qPSCs in the normal human pancreas. However, the use of adipophilin as a qPSC marker may be limited due to its high dependence on optimal PATI

  6. Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination

    Directory of Open Access Journals (Sweden)

    Takao Itoi

    2017-04-01

    Full Text Available This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC from malignant diseases, such as biliary tract cancer (BTC, intraductal papillary mucinous carcinoma (IPMC, and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41 of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140. Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel–Dwass test. Four multiple logistic regression models (MLR were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC of 0.970 (95% confidential interval (CI, 0.946–0.994, p < 0.0001. Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650–1.01, p = 0.0020 with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, pancreatic cancer-associated antigen (DUPAN2 and s-pancreas-1 antigen (SPAN1. Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

  7. Pathogenic mechanisms of pancreatitis

    Science.gov (United States)

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-01-01

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  8. The management of complex pancreatic injuries

    African Journals Online (AJOL)

    Nicky

    pancreatic injuries. Leakage of pancreatic exocrine secre- ... gland damage and the likelihood of duct injury is usually sufficient to ..... creatic function. The decision to resort to pancreaticoduo- denectomy is based upon the extent of the pancreatic injury, the size and vascular status of any duodenal injury, the integrity of the ...

  9. Usefulness of three-dimensional CT pancreatography (3D-CTP) after the balloon-ERP for pancreatic diseases

    International Nuclear Information System (INIS)

    Ueki, Toshiharu; Oishi, Yayoi; Sakaguchi, Seigo; Sakurai, Toshihiro; Yao, Tsuneyoshi; Ichimaru, Yoshihiko; Koga, Yuki; Ikeda, Seiyo

    1998-01-01

    The clinical usefulness of 3D-CTP combined with the balloon-ERP and helical-CT was discussed. Authors diagnosed 42 patients with pancreatic diseases, including 5 of pancreatic carcinoma, 3 of serous cystadenoma, 6 of muciparous pancreatic cyst, 28 of chronic pancreatitis (including 8 cases of complicated pseudocyst). The images could reconstruct three-dimensionally the tapering constriction in the main pancreatic duct for all 5 cases of pancreatic carcinoma, the exclusion in the main pancreatic duct for 3 cases of serous cystadenoma and 1 case of muciparous pancreatic cyst, the parietal irregularity for 14 cases and the smooth constriction for 9 cases in main pancreatic duct of chronic pancreatitis, the morphology of the cyst and the spatial relationship between the cyst and the pancreatic duct in 5 of 6 cases of muciparous pancreatic cyst and 7 of 8 cases of complicated pseudocyst. Furthermore, the 3D-CTP could demonstrate the branched pancreatic duct at the constriction site which was not detected by the balloon-ERP in 2 cases of chronic pancreatitis with the constriction at the main pancreatic duct, and the joining manner of cyst to the pancreatic duct which was indistinct by the balloon-ERP in 6 cases of pancreatic cyst. These results show that 3D-CTP is useful for the qualitative diagnosis and applicable for the understanding of pancreatic diseases and for the simulation of surgery. (K.H.)

  10. A Review of Double Common Bile Duct and Its Sequelae.

    Science.gov (United States)

    Kolli, Sindhura; Etienne, Denzil; Reddy, Madhavi; Shahzad, Ghulamullah

    2018-02-01

    A double or accessory common bile duct (ACBD) is a rare congenital anomaly. We report the case of a 60-year-old American Asian male, who was found to have a double or duplicated common bile duct after being admitted for evaluation of a pancreatic mass. A duplicated bile duct has the same mucosa histologically as a single bile duct. However, the opening of a duplicated bile duct lacks a sphincter allowing retrograde flow of gut contents which results in a higher probability of intraductal calculus formation. On rare occasions, it can predispose to liver abscesses, pancreatitis, pancreatic cancer, gallbladder cancer, gastric cancer, and ampullary cancer depending on the location of the opening of the ACBD. We present an integrative review of the limited cases of ACBD with correlation to the current case and discussion regarding the aspects of diagnosis and management.

  11. Clinical application of duodenum-preserving pancreatic head resection

    OpenAIRE

    ZHOU Songqiang

    2018-01-01

    Objective To investigate the indications and therapeutic effect of duodenum-preserving pancreatic head resection (DPPHR). Methods A retrospective analysis was performed for the clinical data of 17 patients who underwent DPPHR in Fujian Provincial Hospital from January 2013 to February 2017. Among these patients, 6 had chronic pancreatitis with pancreatic duct stones, 2 had chronic pancreatitis with pancreatic pseudocyst, 3 had solid pseudopapillary tumor of the pancreatic head, 3 had intraduc...

  12. Profile of MMP and TIMP Expression in Human Pancreatic Stellate Cells: Regulation by IL-1α and TGFβ and Implications for Migration of Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Vegard Tjomsland

    2016-07-01

    Full Text Available Pancreatic ductal adenocarcinoma is characterized by a prominent fibroinflammatory stroma with both tumor-promoting and tumor-suppressive functions. The pancreatic stellate cell (PSC is the major cellular stromal component and the main producer of extracellular matrix proteins, including collagens, which are degraded by metalloproteinases (MMPs. PSCs interact with cancer cells through various factors, including transforming growth factor (TGFβ and interleukin (IL-1α. The role of TGFβ in the dual nature of tumor stroma, i.e., protumorigenic or tumor suppressive, is not clear. We aimed to investigate the roles of TGFβ and IL-1α in the regulation of MMP profiles in PSCs and the subsequent effects on cancer cell migration. Human PSCs isolated from surgically resected specimens were cultured in the presence of pancreatic cancer cell lines, as well as IL-1α or TGFβ. MMP production and activities in PSCs were quantified by gene array transcripts, mRNA measurements, fluorescence resonance energy transfer–based activity assay, and zymography. PSC-conditioned media and pancreatic cancer cells were included in a collagen matrix cell migration model. We found that production of IL-1α by pancreatic cancer cells induced alterations in MMP and tissue inhibitors of matrix metalloproteinase (TIMP profiles and activities in PSCs, upregulated expression and activation of MMP1 and MMP3, and enhanced migration of pancreatic cancer cells in the collagen matrix model. TGFβ counteracted the effects of IL-1α on PSCs, reestablished PSC MMP and TIMP profiles and activities, and inhibited migration of cancer cells. This suggests that tumor TGFβ has a role as a suppressor of stromal promotion of tumor progression through alterations in PSC MMP profiles with subsequent inhibition of pancreatic cancer cell migration.

  13. Two avirulent, lentogenic strains of Newcastle disease virus are cytotoxic for some human pancreatic tumor lines in vitro.

    Science.gov (United States)

    Walter, Robert J; Attar, Bashar M; Rafiq, Asad; Delimata, Megan; Tejaswi, Sooraj

    2012-09-10

    Pancreatic cancer is the fourth leading cause of cancer death in the U.S. Highly infectious Newcastle disease virus (NDV) strains are known to be very cytotoxic for an array of human tumor cell types in vitro and in vivo but the effects of these and avirulent NDV strains on pancreatic neoplasms are little known. Here, the direct cytolytic effects of the avirulent Hitchner-B1 (B1) and Ulster (U) NDV strains on 7 human pancreatic tumor cell lines and 4 normal human cell lines were studied. Cytotoxicity assays used serially diluted NDV to determine minimum cytotoxic plaque forming unit (PFU) doses. For NDV-B1, normal human cells were killed only by relatively high doses (range: 471-3,724 PFU) whereas NDV-U killed these cells at low PFU (range: 0.32-1.60 PFU). Most pancreatic cancer cell types were killed by much lower NDV-B1 doses (range: 0.40-2.60 PFU) while NDV-U killed Capan-1 and SU.86.86 cultures at very low doses (0.00041 PFU and 0.0034 PFU, respectively). On average, 1,555 times more NDV-B1 was needed to kill normal cells than most pancreatic tumor cells and 558 times more NDV-U to kill the two most sensitive pancreatic cancer lines. These innately-targeted lentogenic viruses may have meaningful potential in treating pancreatic cancer.

  14. FGF7 and cell density are required for final differentiation of pancreatic amylase-positive cells from human ES cells.

    Science.gov (United States)

    Takizawa-Shirasawa, Sakiko; Yoshie, Susumu; Yue, Fengming; Mogi, Akimi; Yokoyama, Tadayuki; Tomotsune, Daihachiro; Sasaki, Katsunori

    2013-12-01

    The major molecular signals of pancreatic exocrine development are largely unknown. We examine the role of fibroblast growth factor 7 (FGF7) in the final induction of pancreatic amylase-containing exocrine cells from induced-pancreatic progenitor cells derived from human embryonic stem (hES) cells. Our protocol consisted in three steps: Step I, differentiation of definitive endoderm (DE) by activin A treatment of hES cell colonies; Step II, differentiation of pancreatic progenitor cells by re-plating of the cells of Step I onto 24-well plates at high density and stimulation with all-trans retinoic acid; Step III, differentiation of pancreatic exocrine cells with a combination of FGF7, glucagon-like peptide 1 and nicotinamide. The expression levels of pancreatic endodermal markers such as Foxa2, Sox17 and gut tube endoderm marker HNF1β were up-regulated in both Step I and II. Moreover, in Step III, the induced cells expressed pancreatic markers such as amylase, carboxypeptidase A and chymotrypsinogen B, which were similar to those in normal human pancreas. From day 8 in Step III, cells immunohistochemically positive for amylase and for carboxypeptidase A, a pancreatic exocrine cell product, were induced by FGF7. Pancreatic progenitor Pdx1-positive cells were localized in proximity to the amylase-positive cells. In the absence of FGF7, few amylase-positive cells were identified. Thus, our three-step culture protocol for human ES cells effectively induces the differentiation of amylase- and carboxypeptidase-A-containing pancreatic exocrine cells.

  15. Distinct Internalization Pathways of Human Amylin Monomers and Its Cytotoxic Oligomers in Pancreatic Cells

    Science.gov (United States)

    Trikha, Saurabh; Jeremic, Aleksandar M.

    2013-01-01

    Toxic human amylin oligomers and aggregates are implicated in the pathogenesis of type 2 diabetes mellitus (TTDM). Although recent studies have shown that pancreatic cells can recycle amylin monomers and toxic oligomers, the exact uptake mechanism and trafficking routes of these molecular forms and their significance for amylin toxicity are yet to be determined. Using pancreatic rat insulinoma (RIN-m5F) beta (β)-cells and human islets as model systems we show that monomers and oligomers cross the plasma membrane (PM) through both endocytotic and non-endocytotic (translocation) mechanisms, the predominance of which is dependent on amylin concentrations and incubation times. At low (≤100 nM) concentrations, internalization of amylin monomers in pancreatic cells is completely blocked by the selective amylin-receptor (AM-R) antagonist, AC-187, indicating an AM-R dependent mechanism. In contrast at cytotoxic (µM) concentrations monomers initially (1 hour) enter pancreatic cells by two distinct mechanisms: translocation and macropinocytosis. However, during the late stage (24 hours) monomers internalize by a clathrin-dependent but AM-R and macropinocytotic independent pathway. Like monomers a small fraction of the oligomers initially enter cells by a non-endocytotic mechanism. In contrast a majority of the oligomers at both early (1 hour) and late times (24 hours) traffic with a fluid-phase marker, dextran, to the same endocytotic compartments, the uptake of which is blocked by potent macropinocytotic inhibitors. This led to a significant increase in extra-cellular PM accumulation, in turn potentiating amylin toxicity in pancreatic cells. Our studies suggest that macropinocytosis is a major but not the only clearance mechanism for both amylin’s molecular forms, thereby serving a cyto-protective role in these cells. PMID:24019897

  16. Bilio-pancreatic common channel (BPCC) in children

    International Nuclear Information System (INIS)

    Suarez, F.; Bernard, O.; Gauthier, F.; Valayer, J.; Brunelle, F.

    1987-01-01

    Twelve patients (11 girls and 1 boy) with dilated bile ducts and anomalous junction between the common bile duct and pancreatic duct are reported. All patients underwent preoperative opacification of the bile ducts either by transhepatic cholangiography or percutaneous cholecystography. Abdominal pain and jaundice were the main clinical symptoms. Reflux of pancreatic enzymes in the bile duct was proven by measuring amylase and lipase activity in the biliary system after IV injection of 1 IU/kg of cholecystokinin. All patients were operated upon. Bile duct size returned to normal in all patients who are clinical well with a follow-up from 6 to 1 years. (orig.)

  17. Alcohol and the pancreas. II. Pancreatic morphology of advanced alcoholic pancreatitis.

    Science.gov (United States)

    Noronha, M; Bordalo, O; Dreiling, D A

    1981-08-01

    The histopathology of advanced chronic alcoholic pancreatitis is dominated by cellular degeneration, atrophy and fibrosis. Sequential changes in the histopathology of alcoholic pancreatic disease has been defined and traced from initial injury to end-stage disease. These sequential histopathologies have been correlated with clinical syndrome and secretory patterns. The data are more consistent with a toxic-metabolic pathogenesis of alcoholic pancreatitis than the previous Big Duct and Small Duct hypotheses.

  18. Bile Duct Exploration

    Science.gov (United States)

    ... Home / Health Library / Diagnostics & Testing / Bile Duct Exploration Bile Duct Exploration Common bile duct exploration is a ... Test Details Results and Follow-Up What is bile, and what is bile duct exploration? Bile is ...

  19. Expression of human cationic trypsinogen (PRSS1) in murine acinar cells promotes pancreatitis and apoptotic cell death

    Science.gov (United States)

    Athwal, T; Huang, W; Mukherjee, R; Latawiec, D; Chvanov, M; Clarke, R; Smith, K; Campbell, F; Merriman, C; Criddle, D; Sutton, R; Neoptolemos, J; Vlatković, N

    2014-01-01

    Hereditary pancreatitis (HP) is an autosomal dominant disease that displays the features of both acute and chronic pancreatitis. Mutations in human cationic trypsinogen (PRSS1) are associated with HP and have provided some insight into the pathogenesis of pancreatitis, but mechanisms responsible for the initiation of pancreatitis have not been elucidated and the role of apoptosis and necrosis has been much debated. However, it has been generally accepted that trypsinogen, prematurely activated within the pancreatic acinar cell, has a major role in the initiation process. Functional studies of HP have been limited by the absence of an experimental system that authentically mimics disease development. We therefore developed a novel transgenic murine model system using wild-type (WT) human PRSS1 or two HP-associated mutants (R122H and N29I) to determine whether expression of human cationic trypsinogen in murine acinar cells promotes pancreatitis. The rat elastase promoter was used to target transgene expression to pancreatic acinar cells in three transgenic strains that were generated: Tg(Ela-PRSS1)NV, Tg(Ela-PRSS1*R122H)NV and Tg(Ela-PRSS1*N29I)NV. Mice were analysed histologically, immunohistochemically and biochemically. We found that transgene expression is restricted to pancreatic acinar cells and transgenic PRSS1 proteins are targeted to the pancreatic secretory pathway. Animals from all transgenic strains developed pancreatitis characterised by acinar cell vacuolisation, inflammatory infiltrates and fibrosis. Transgenic animals also developed more severe pancreatitis upon treatment with low-dose cerulein than controls, displaying significantly higher scores for oedema, inflammation and overall histopathology. Expression of PRSS1, WT or mutant, in acinar cells increased apoptosis in pancreatic tissues and isolated acinar cells. Moreover, studies of isolated acinar cells demonstrated that transgene expression promotes apoptosis rather than necrosis. We therefore

  20. Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue

    International Nuclear Information System (INIS)

    Lechner, Andreas; Nolan, Anna L.; Blacken, Robyn A.; Habener, Joel F.

    2005-01-01

    Cellular replacement therapy holds promise for the treatment of diabetes mellitus but donor tissue is severely limited. Therefore, we investigated whether insulin-secreting cells could be differentiated in vitro from a monolayer of cells expanded from human donor pancreatic islets. We describe a three-step culture protocol that allows for the efficient generation of insulin-producing cell clusters from in vitro expanded, hormone-negative cells. These clusters express insulin at levels of up to 34% that of average freshly isolated human islets and secrete C-peptide upon membrane depolarization. They also contain cells expressing the other major islet hormones (glucagon, somatostatin, and pancreatic polypeptide). The source of the newly differentiated endocrine cells could either be indigenous stem/progenitor cells or the proliferation-associated dedifferentiation and subsequent redifferentiation of mature endocrine cells. The in vitro generated cell clusters may be efficacious in providing islet-like tissue for transplantation into diabetic recipients

  1. Human pancreatic islet-derived extracellular vesicles modulate insulin expression in 3D-differentiating iPSC clusters.

    Directory of Open Access Journals (Sweden)

    Diana Ribeiro

    Full Text Available It has been suggested that extracellular vesicles (EVs can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of pancreatic EVs on stem cell differentiation into pancreatic lineages remains unknown. Herein, human islet-derived EVs (h-Islet-EVs were isolated, characterized and subsequently added to human induced pluripotent stem cell (iPSC clusters during pancreatic differentiation. The h-islet-EVs had a mean size of 117±7 nm and showed positive expression of CD63 and CD81 EV markers as measured by ELISA. The presence of key pancreatic transcription factor mRNA, such as NGN3, MAFA and PDX1, and pancreatic hormone proteins such as C-peptide and glucagon, were confirmed in h-Islet-EVs. iPSC clusters were differentiated in suspension and at the end stages of the differentiation protocol, the mRNA expression of the main pancreatic transcription factors and pancreatic hormones was increased. H-Islet-EVs were supplemented to the iPSC clusters in the later stages of differentiation. It was observed that h-Islet-EVs were able to up-regulate the intracellular levels of C-peptide in iPSC clusters in a concentration-dependent manner. The effect of h-Islet-EVs on the differentiation of iPSC clusters cultured in 3D-collagen hydrogels was also assessed. Although increased mRNA expression for pancreatic markers was observed when culturing the iPSC clusters in 3D-collagen hydrogels, delivery of EVs did not affect the insulin or C-peptide intracellular content. Our results provide new information on the role of h-Islet-EVs in the regulation of insulin expression in differentiating iPSC clusters, and are highly relevant for pancreatic tissue engineering applications.

  2. CT of the pancreatic body and tail in cancer of the head

    International Nuclear Information System (INIS)

    Ono, Minoru; Muranaka, Tooru; Nishitani, Hiromu; Onitsuka, Hideo; Kawanami, Takashi; Matsuura, Keiichi

    1983-01-01

    In comparison with chronic pancreatitis (27 cases), CT images of secondary changes in the pancreatic body and tail in cancer of the pancreatic head were studied in 17 cases. In cancer cases, the pancreatic duct was dilated in a rosary or linear form, and a fairly large portion of the duct was visualized in continuation in one slice. The parenchyma was uniformly atrophic. Chronic pancreatitis demonstrated various CT images. In the localized-mass-forming type, the pancreatic body and tail showed findings similar to those of cancer in some cases, but unevenness of the pancreatic parenchyma and flexion, tortuosity and discontinuity of the pancreatic duct were observed only in chronic pancreatitis. As well as improvement in CT images, the spatial relationship between the pancreatic duct and parenchyma should be studied in more detail. (Chiba, N.)

  3. Efficient generation of functional pancreatic β-cells from human induced pluripotent stem cells.

    Science.gov (United States)

    Yabe, Shigeharu G; Fukuda, Satsuki; Takeda, Fujie; Nashiro, Kiyoko; Shimoda, Masayuki; Okochi, Hitoshi

    2017-02-01

    Insulin-secreting cells have been generated from human embryonic or induced pluripotent stem cells (iPSCs) by mimicking developmental processes. However, these cells do not always secrete glucose-responsive insulin, one of the most important characteristics of pancreatic β-cells. We focused on the importance of endodermal differentiation from human iPSCs in order to obtain functional pancreatic β-cells. A six-stage protocol was established for the differentiation of human iPSCs to pancreatic β-cells using defined culture media without feeders or serum. The effects of CHIR99021, a selective glycogen synthase kinase-3β inhibitor, were examined in the presence of fibroblast growth factor 2, activin, and bone morphogenetic protein 4 (FAB) during definitive endodermal induction by immunostaining for SRY (sex determining region Y)-box 17 (SOX17) and Forkhead box protein A2 (FOXA2). Insulin secretion was compared between the last stage of monolayer culture and spheroid culture conditions. Cultured cells were transplanted under kidney capsules of streptozotocin-diabetic non-obese diabetic-severe combined immunodeficiency mice, and blood glucose levels were measured once a week. Immunohistochemical analyses were performed 4 and 12 weeks after transplantation. Addition of CHIR99021 (3 μmol/L) in the presence of FAB for 2 days improved endodermal cell viability, maintaining the high SOX17-positive rate. Spheroid formation after the endocrine progenitor stage showed more efficient insulin secretion than did monolayer culture. After cell transplantation, diabetic mice had lower blood glucose levels, and islet-like structures were detected in vivo. Functional pancreatic β-cells were generated from human iPSCs. Induction of definitive endoderm and spheroid formation may be key steps for producing these cells. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  4. Genetic Modification of Human Pancreatic Progenitor Cells Through Modified mRNA.

    Science.gov (United States)

    Lu, Song; Chow, Christie C; Zhou, Junwei; Leung, Po Sing; Tsui, Stephen K; Lui, Kathy O

    2016-01-01

    In this chapter, we describe a highly efficient genetic modification strategy for human pancreatic progenitor cells using modified mRNA-encoding GFP and Neurogenin-3. The properties of modified mRNA offer an invaluable platform to drive protein expression, which has broad applicability in pathway regulation, directed differentiation, and lineage specification. This approach can also be used to regulate expression of other pivotal transcription factors during pancreas development and might have potential therapeutic values in regenerative medicine.

  5. Idiopathic fibrosing pancreatitis: a rare cause of chronic obstructive jaundice in childhood

    International Nuclear Information System (INIS)

    Park, Hye Seong; Kim, Hyun Sook; Kim, Hack Hee; Kim, Ok Hwa; Kim, Choon Yul; Bahk, Yong Whee

    1992-01-01

    We report a 14-months-old infant who had obstructive jaundice caused by idiopathic fibrosing pancreatitis. Ultrasonography and abdominal computed tomography showed dilatation of the intrahepatic ducts, common bile duct, and the pancreatic duct. Diffuse swelling of the pancreas was also noted on CT. At laparotomy, the head portion of the pancreas revealed a stony hard consistency, and proliferation of fibrotic tissue was confirmed pathologically. Idiopathic fibrosing pancreatitis is a very rare disease entity in childhood, but should be considered in the differential diagnosis of obstructive jaundice in children who demonstrate bile duct and pancreatic duct dilatation and/or diffuse pancreas swelling

  6. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  7. Hereditary chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Mössner Joachim

    2007-01-01

    Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

  8. Gemcitabine inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells.

    Science.gov (United States)

    Yong-Xian, Gui; Xiao-Huan, Li; Fan, Zhang; Guo-Fang, Tian

    2016-10-01

    The aim of the study is to investigate the underlying molecular mechanisms by which gemcitabine (gem) inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells in vitro. After PANC-1 cells had been treated by indicated concentration (0, 5, and 25 mg/L) of gem for 48 h, cell proliferation was evaluated by 3'-(4, 5 dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay; cell morphology was observed by transmission electron microscopy; Expression of c-IAP2 and Bcl-2 proteins was analyzed by Western blot; the activity of caspase-3 and -9 was detected by spectrophotometry. Gem significantly inhibited cell proliferation and could induce apoptosis of human pancreatic cancer PANC-1 cells, with a dose-dependent manner. Western blot analysis showed that gem significantly reduced c-IAP2 and Bcl-2 proteins expression level (P PANC-1 cells. Gem could induce apoptosis of human pancreatic cancer PANC-1 cells, probably through downregulating c-IAP2 and Bcl-2 expression levels, and at the same time activating caspase-3 and -9.

  9. Effect of Wasabi Component 6-(Methylsulfinylhexyl Isothiocyanate and Derivatives on Human Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chen

    2014-01-01

    Full Text Available The naturally occurring compound 6-(methylsulfinylhexyl isothiocyanate (6-MITC was isolated from Wasabia japonica (Wasabi, a pungent spice used in Japanese food worldwide. The synthetic derivatives 6-(methylsulfenylhexyl isothiocyanate (I7447 and 6-(methylsulfonylhexyl isothiocyanate (I7557 are small molecule compounds derived from 6-MITC. This study aimed to evaluate the effect of these compounds on human pancreatic cancer cells. Human pancreatic cancer cell lines PANC-1 and BxPC-3 were used to perform an MTT assay for cell viability and Liu’s stain for morphological observation. The cell cycle was analyzed by DNA histogram. Aldehyde dehydrogenase (ALDH activity was used as a marker for cancer stem cells (CSC. Western blotting was performed for the expression of proteins related to CSC signaling. The results showed that compounds 6-MITC and I7557, but not I7447, inhibited viability of both PANC-1 and BxPC-3 cells. Morphological observation showed mitotic arrest and apoptosis in 6-MITC- and I7557-treated cells. These two compounds induced G2/M phase arrest and hypoploid population. Percentages of ALDH-positive PANC-1 cells were markedly reduced by 6-MITC and I7557 treatment. The expression of CSC signaling molecule SOX2, but not NOTCH1, ABCG2, Sonic hedgehog, or OCT4, was inhibited by 6-MITC and I7557. In conclusion, wasabi compounds 6-MITC and I7557 may possess activity against the growth and CSC phenotypes of human pancreatic cancer cells.

  10. A scalable system for production of functional pancreatic progenitors from human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Thomas C Schulz

    Full Text Available Development of a human embryonic stem cell (hESC-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50-100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry.

  11. Considerations for the grade IIIb pancreatic trauma

    International Nuclear Information System (INIS)

    Ito, Katsuhiko; Ishii, Takayuki; Ootawa, Satoru; Shimizu, Yoshiaki; Kondo, Eisuke; Nishiya, Kei; Yokoyama, Kouya; Shimizu, Kimio; Ogawa, Kiyoshi

    2011-01-01

    Pancreatic duct disruption accompanied by pancreatic trauma is very severe. Endoscopic retrograde pancreatography (ERP) is considered the main diagnostic modality. However, it is invasive and can be associated with significant complications. We diagnosed pancreatic trauma based on only Computed tomography (CT) scan data. We operated based on specific signs of pancreatic injuries on CT scans, such as edema or hematoma of the pancreatic parenchyma, fractures or lacerations of the pancreas, active hemorrhage and, in all cases, there were main pancreatic duct injuries. Certain drainage of the pancreatic juice is necessary for pancreatic duct disruption. The operation method was selected according to the location of the damage. If it is at all possible pancreas preserving surgery should be performed. It is necessary to select the operation according to the patient's age and general condition, the cause of the injury, the range of the injury, and the experience of the surgeon. When the main duct injury was not certain, ERP during the operation was very useful. We report on a method of endoscopically treating a pseudocyst, which has adhered to the stomach, secondary to pancreatic main duct disruption. Transgastric placement of a stent into the pseudocyst is possible in restricted cases. (author)

  12. Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer

    International Nuclear Information System (INIS)

    Loos, Martin; Hedderich, Dennis M; Ottenhausen, Malte; Giese, Nathalia A; Laschinger, Melanie; Esposito, Irene; Kleeff, Jörg; Friess, Helmut

    2009-01-01

    Costimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer. B7-H3 expression was evaluated by immunohistochemistry in 68 patients with pancreatic cancer who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells. B7-H3 expression was significantly upregulated in pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with high tumor B7-H3 levels had a significantly better postoperative prognosis than patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3 expression significantly correlated with the number of tumor-infiltrating CD8+ T cells (p = 0.018). We demonstrate for the first time that B7-H3 is abundantly expressed in pancreatic cancer and that tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival. Our findings suggest that B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer

  13. Proton pump inhibitors inhibit pancreatic secretion

    DEFF Research Database (Denmark)

    Wang, Jing; Barbuskaite, Dagne; Tozzi, Marco

    2015-01-01

    +/K+-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H+/K+-ATPases are expressed in human pancreatic cells. Pumps have similar...... of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO3-, pancreas also secretes K+. In conclusion, this study calls for a revision of the basic model for HCO3- secretion. We propose that proton transport is driving secretion, and that in addition...

  14. Autoimmune pancreatitis in an 11-year-old boy

    International Nuclear Information System (INIS)

    Refaat, Rania; Harth, Marc; Proschek, Petra; Lindemayr, Sebastian; Vogl, Thomas J.

    2009-01-01

    We report a case of histopathologically proven autoimmune pancreatitis in an 11-year-old boy. Abdominal US and MRI showed a focal swelling of the pancreatic head, the latter also showing delayed contrast enhancement. There was diffuse irregular pancreatic duct narrowing, compression of the intrapancreatic common bile duct, and mild proximal biliary dilatation on MR cholangiopancreatography. Laboratory results revealed normal serum IgG and subclass 4 with negative autoimmune antibodies, and slightly elevated carbohydrate antigen 19-9. This highlights the differentiation of autoimmune pancreatitis from pancreatic head cancer and, to a lesser extent, other forms of pancreatitis in children. (orig.)

  15. Autoimmune pancreatitis in an 11-year-old boy

    Energy Technology Data Exchange (ETDEWEB)

    Refaat, Rania [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany); Ain Shams University, Department of Diagnostic and Interventional Radiology, Cairo (Egypt); Harth, Marc; Proschek, Petra; Lindemayr, Sebastian; Vogl, Thomas J. [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany)

    2009-04-15

    We report a case of histopathologically proven autoimmune pancreatitis in an 11-year-old boy. Abdominal US and MRI showed a focal swelling of the pancreatic head, the latter also showing delayed contrast enhancement. There was diffuse irregular pancreatic duct narrowing, compression of the intrapancreatic common bile duct, and mild proximal biliary dilatation on MR cholangiopancreatography. Laboratory results revealed normal serum IgG and subclass 4 with negative autoimmune antibodies, and slightly elevated carbohydrate antigen 19-9. This highlights the differentiation of autoimmune pancreatitis from pancreatic head cancer and, to a lesser extent, other forms of pancreatitis in children. (orig.)

  16. Identificação trans-operatória do óstio do Wirsung após a papilo-esfincterotomia Intra-operatory identification of the ostium of Wirsung's pancreatic duct after sphincterotomy

    Directory of Open Access Journals (Sweden)

    A.L. da Silva

    1999-04-01

    Full Text Available OBJETIVO: Contribuir para o achado do óstio de Wirsung durante a técnica da papilo-esfincteroplastia, prevenindo a pancreatite aguda pós-operatória. CASUÍSTICA E MÉTODO: Foram estudados 27 pacientes submetidos a papilo-esfincteroplastia por coledocolitíase com ou sem odite. Após a papilo-esfincterotomia (PET terapêutica, por via duodenal, realizou-se estudo da localização do óstio do ducto de Wirsung. A PET transforma a ampola de Vater em um triângulo isósceles, cujas medidas foram obtidas através de compasso. Utilizando-as, o óstio do Wirsung poderá ser facilmente identificado e cateterizado no trans-operatório, antes de se fazer a sutura muco-mucosa da papila seccionada. RESULTADOS: O óstio geralmente é encontrado medialmente na metade esquerda do triângulo e a uma distância média de 0,19cm a 0,25cm acima da base do triângulo, considerando-se a ausência ou presença de inflamação, respectivamente. CONCLUSÃO: A determinação transoperatória das distâncias padronizadas neste estudo, permite a detecção e cateterização segura do óstio do Wirsung na presença ou não de odite.PURPOSE: The aim of this study is to suggest a feasible method to find the ostium of the Wirsung's duct during sphincteroplasty of the Vater's papilla, in order to avoid post-operative complications such as acute pancreatitis. PATIENTS AND METHODS: A total of 27 patients were submitted to sphincteroplasty for choledocolithiasis with or without Odditis. After therapeutic papillotomy and sphincterotomy through the duodenun, the location of the ostium of the Wirsung's duct was determined and studied. After papillotomy, the Vater's papilla becomes an isosceles triangle and its measurements were made with a compass. Thereby the ostium of Wirsung's duct was easily detected and a catheter was inserted before the suture of the mucosa of the papilla. RESULTS: The ostium was generally found medially, on the left side of the triangle, 0.19cm to 0.25cm

  17. Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes.

    Science.gov (United States)

    Mocan, Lucian; Tabaran, Flaviu A; Mocan, Teodora; Bele, Constantin; Orza, Anamaria Ioana; Lucan, Ciprian; Stiufiuc, Rares; Manaila, Ioana; Iulia, Ferencz; Dana, Iancu; Zaharie, Florin; Osian, Gelu; Vlad, Liviu; Iancu, Cornel

    2011-01-01

    The process of laser-mediated ablation of cancer cells marked with biofunctionalized carbon nanotubes is frequently called "nanophotothermolysis". We herein present a method of selective nanophotothermolisys of pancreatic cancer (PC) using multiwalled carbon nanotubes (MWCNTs) functionalized with human serum albumin (HSA). With the purpose of testing the therapeutic value of these nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically resected specimens from patients with PC were preserved in a cold medium and kept alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra-arterially administered in the greater pancreatic artery under ultrasound guidance. Confocal and transmission electron microscopy combined with immunohistochemical staining have confirmed the selective accumulation of HSA-MWCNTs inside the human PC tissue. The external laser irradiation of the specimen has significantly produced extensive necrosis of the malign tissue after the intra-arterial administration of HSA-MWCNTs, without any harmful effects on the surrounding healthy parenchyma. We have obtained a selective photothermal ablation of the malign tissue based on the selective internalization of MWCNTs with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra-arterial perfusion.

  18. Genome-wide analysis of PDX1 target genes in human pancreatic progenitors

    Directory of Open Access Journals (Sweden)

    Xianming Wang

    2018-03-01

    Full Text Available Objective: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4. Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing β-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult β-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. Methods: In this study, we have generated a novel induced pluripotent stem cell (iPSC line that efficiently differentiates into human pancreatic progenitors (PPs. Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. Results: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation

  19. Embelin suppresses growth of human pancreatic cancer xenografts, and pancreatic cancer cells isolated from KrasG12D mice by inhibiting Akt and Sonic hedgehog pathways.

    Directory of Open Access Journals (Sweden)

    Minzhao Huang

    Full Text Available Pancreatic cancer is a deadly disease, and therefore effective treatment and/or prevention strategies are urgently needed. The objectives of this study were to examine the molecular mechanisms by which embelin inhibited human pancreatic cancer cell growth in vitro, and xenografts in Balb C nude mice, and pancreatic cancer cell growth isolated from KrasG12D transgenic mice. XTT assays were performed to measure cell viability. AsPC-1 cells were injected subcutaneously into Balb c nude mice and treated with embelin. Cell proliferation and apoptosis were measured by Ki67 and TUNEL staining, respectively. The expression of Akt, and Sonic Hedgehog (Shh and their target gene products were measured by the immunohistochemistry, and Western blot analysis. The effects of embelin on pancreatic cancer cells isolated from 10-months old KrasG12D mice were also examined. Embelin inhibited cell viability in pancreatic cancer AsPC-1, PANC-1, MIA PaCa-2 and Hs 766T cell lines, and these inhibitory effects were blocked either by constitutively active Akt or Shh protein. Embelin-treated mice showed significant inhibition in tumor growth which was associated with reduced expression of markers of cell proliferation (Ki67, PCNA and Bcl-2 and cell cycle (cyclin D1, CDK2, and CDK6, and induction of apoptosis (activation of caspase-3 and cleavage of PARP, and increased expression of Bax. In addition, embelin inhibited the expression of markers of angiogenesis (COX-2, VEGF, VEGFR, and IL-8, and metastasis (MMP-2 and MMP-9 in tumor tissues. Antitumor activity of embelin was associated with inhibition of Akt and Shh pathways in xenografts, and pancreatic cancer cells isolated from KrasG12D mice. Furthermore, embelin also inhibited epithelial-to-mesenchymal transition (EMT by up-regulating E-cadherin and inhibiting the expression of Snail, Slug, and ZEB1. These data suggest that embelin can inhibit pancreatic cancer growth, angiogenesis and metastasis by suppressing Akt and

  20. Management of pancreatic trauma.

    Science.gov (United States)

    Girard, E; Abba, J; Arvieux, C; Trilling, B; Sage, P Y; Mougin, N; Perou, S; Lavagne, P; Létoublon, C

    2016-08-01

    Pancreatic trauma (PT) is associated with high morbidity and mortality; the therapeutic options remain debated. Retrospective study of PT treated in the University Hospital of Grenoble over a 22-year span. The decision for initial laparotomy depended on hemodynamic status as well as on associated lesions. Main pancreatic duct lesions were always searched for. PT lesions were graded according to the AAST classification. Of a total of 46 PT, 34 were grades II or I. Hemodynamic instability led to immediate laparotomy in 18 patients, for whom treatment was always drainage of the pancreatic bed; morbidity was 30%. Eight patients had grade III injuries, six of whom underwent immediate operation: three underwent splenopancreatectomy without any major complications while the other three who had simple drainage required re-operation for peritonitis, with one death related to pancreatic complications. Four patients had grades IV or V PT: two pancreatoduodenectomies were performed, with no major complication, while one patient underwent duodenal reconstruction with pancreatic drainage, complicated by pancreatic and duodenal fistula requiring a hospital stay of two months. The post-trauma course was complicated for all patients with main pancreatic duct involvement. Our outcomes were similar to those found in the literature. In patients with distal PT and main pancreatic duct involvement, simple drainage is associated with high morbidity and mortality. For proximal PT, the therapeutic options of drainage versus pancreatoduodenectomy must be weighed; pancreatoduodenectomy may be unavoidable when the duodenum is injured as well. Two-stage (resection first, reconstruction later) could be an effective alternative in the emergency setting when there are other associated traumatic lesions. Copyright © 2016. Published by Elsevier Masson SAS.

  1. Knowledge Gaps in Rodent Pancreas Biology: Taking Human Pluripotent Stem Cell-Derived Pancreatic Beta Cells into Our Own Hands.

    Science.gov (United States)

    Santosa, Munirah Mohamad; Low, Blaise Su Jun; Pek, Nicole Min Qian; Teo, Adrian Kee Keong

    2015-01-01

    In the field of stem cell biology and diabetes, we and others seek to derive mature and functional human pancreatic β cells for disease modeling and cell replacement therapy. Traditionally, knowledge gathered from rodents is extended to human pancreas developmental biology research involving human pluripotent stem cells (hPSCs). While much has been learnt from rodent pancreas biology in the early steps toward Pdx1(+) pancreatic progenitors, much less is known about the transition toward Ngn3(+) pancreatic endocrine progenitors. Essentially, the later steps of pancreatic β cell development and maturation remain elusive to date. As a result, the most recent advances in the stem cell and diabetes field have relied upon combinatorial testing of numerous growth factors and chemical compounds in an arbitrary trial-and-error fashion to derive mature and functional human pancreatic β cells from hPSCs. Although this hit-or-miss approach appears to have made some headway in maturing human pancreatic β cells in vitro, its underlying biology is vaguely understood. Therefore, in this mini-review, we discuss some of these late-stage signaling pathways that are involved in human pancreatic β cell differentiation and highlight our current understanding of their relevance in rodent pancreas biology. Our efforts here unravel several novel signaling pathways that can be further studied to shed light on unexplored aspects of rodent pancreas biology. New investigations into these signaling pathways are expected to advance our knowledge in human pancreas developmental biology and to aid in the translation of stem cell biology in the context of diabetes treatments.

  2. Three-dimensional computer-assisted dissection of pancreatic lymphatic anatomy on human fetuses: a step toward automatic image alignment.

    Science.gov (United States)

    Bardol, T; Subsol, G; Perez, M-J; Genevieve, D; Lamouroux, A; Antoine, B; Captier, G; Prudhomme, M; Bertrand, M M

    2018-05-01

    Pancreatic cancer is the fourth cause of death by cancer worldwide. Lymph node (LN) involvement is known to be the main prognostic factor. However, lymphatic anatomy is complex and only partially characterized. The aim of the study was to study the pancreatic lymphatic system using computer-assisted anatomic dissection (CAAD) technique and also to update CAAD technique by automatizing slice alignment. We dissected three human fetuses aged from 18 to 34 WA. 5-µm serial sections of duodeno-pancreas and spleen blocks were stained (hematoxylin-eosin, hematoxylin of Mayer and Masson trichrome), scanned, aligned and modeled in three dimensions. We observed a rich, diffuse but not systematized lymphatic network in the peri-pancreatic region. There was an equal distribution of LNs between the cephalic and body-tail portions. The lymphatic vascularization appeared in continuity from the celiac trunk to the distal ends of its hepatic and splenic arterial branches parallel to the nerve ramifications of the celiac plexus. We also observed a continuity between the drainage of the pancreatic head and the para-aortic region posteriorly. In view of the wealth of peri-pancreatic LNs, the number of LNs to harvest could be increased to improve nodal staging and prognostic evaluation. Pancreatic anatomy as described does not seem to be compatible with the sentinel LN procedure in pancreatic surgery. Finally, we are now able to offer an alternative to manual alignment with a semi-automated alignment.

  3. Role of staging laparoscopy in the management of Pancreatic Duct Carcinoma (PDAC): Single-center experience from a tertiary hospital in Brazil.

    Science.gov (United States)

    de Jesus, Victor Hugo Fonseca; da Costa Junior, Wilson Luiz; de Miranda Marques, Tomás Mansur Duarte; Diniz, Alessandro Landskron; de Castro Ribeiro, Héber Salvador; de Godoy, André Luis; de Farias, Igor Correia; Coimbra, Felipe José Fernandez

    2018-03-06

    Proper staging is critical to the management of pancreatic ductal carcinoma (PDAC). Laparoscopy has been used to stage patients without gross metastatic disease with variable success. We aimed to identify the frequency of patients diagnosed by laparoscopy with occult metastatic disease. Also, we looked for variables related to a higher chance of occult metastasis. Patients with PDAC submitted to staging laparoscopy either immediately before pancreatectomy or as a separate procedure between January 2010 and December 2016 were included. None presented gross metastatic disease at initial staging. We used logistic regression to search for variables associated with metastatic disease. The study population consisted of 63 patients. Among all patients, nine (16.7%) had occult metastases at laparoscopy. Unresectable tumor (Odds ratio = 18.0, P = 0.03), increasing tumor size (Odds ratio = 1.36, P = 0.01), and abdominal pain (Odds ratio = 5.6, P = 0.04) significantly predicted the risk of occult metastases in univariate analysis. In multivariate analysis, only tumor size predicted the risk of occult metastases. Laparoscopy remains a valuable tool in PDAC staging. Patients with either large or unresectable tumors, or presenting with abdominal pain present the highest risk for occult intra-abdominal metastases. © 2018 Wiley Periodicals, Inc.

  4. MR pancreatography (MRP) for mucin-producing pancreatic tumors

    International Nuclear Information System (INIS)

    Usuki, Noriaki; Nishimoto, Masaoki; Shima, Tomoko; Hirokawa, Keiko; Tashiro, Takahiko; Saiwai, Shigeo; Miyamoto, Takeshi; Okabe, Sumihiro

    1997-01-01

    MR pancreatography was performed in 11 patients with mucin-producing pancreatic tumor (main duct type: four and branch duct type: seven) using HASTE with a body phased array coil on a 1.5-T unit. The results of MR pancreatography were compared with imaging of endoscopic retrograde pancreatography (ERP). In all cases, MR pancreatography demonstrated all dilated pancreatic ducts and cysts. ERP did not completely demonstrate dilated ducts and cysts because of mucinous materials. Conspicuity of an intraductal tumor was more excellent by ER pancreatography than MR pancreatography. Therefore MR pancreatography and ER pancreatography are complementary methods in diagnosis for mucin-producing pancreatic tumors. (author)

  5. Acinar cell-specific knockout of the PTHrP gene decreases the proinflammatory and profibrotic responses in pancreatitis.

    Science.gov (United States)

    Bhatia, Vandanajay; Rastellini, Cristiana; Han, Song; Aronson, Judith F; Greeley, George H; Falzon, Miriam

    2014-09-01

    Pancreatitis is a necroinflammatory disease with acute and chronic manifestations. Accumulated damage incurred during repeated bouts of acute pancreatitis (AP) can lead to chronic pancreatitis (CP). Pancreatic parathyroid hormone-related protein (PTHrP) levels are elevated in a mouse model of cerulein-induced AP. Here, we show elevated PTHrP levels in mouse models of pancreatitis induced by chronic cerulein administration and pancreatic duct ligation. Because acinar cells play a major role in the pathophysiology of pancreatitis, mice with acinar cell-specific targeted disruption of the Pthrp gene (PTHrP(Δacinar)) were generated to assess the role of acinar cell-secreted PTHrP in pancreatitis. These mice were generated using Cre-LoxP technology and the acinar cell-specific elastase promoter. PTHrP(Δacinar) exerted protective effects in cerulein and pancreatic duct ligation models, evident as decreased edema, histological damage, amylase secretion, pancreatic stellate cell (PSC) activation, and extracellular matrix deposition. Treating acinar cells in vitro with cerulein increased IL-6 expression and NF-κB activity; these effects were attenuated in PTHrP(Δacinar) cells, as were the cerulein- and carbachol-induced elevations in amylase secretion. The cerulein-induced upregulation of procollagen I expression was lost in PSCs from PTHrP(Δacinar) mice. PTHrP immunostaining was elevated in human CP sections. The cerulein-induced upregulation of IL-6 and ICAM-1 (human acinar cells) and procollagen I (human PSCs) was suppressed by pretreatment with the PTH1R antagonist, PTHrP (7-34). These findings establish PTHrP as a novel mediator of inflammation and fibrosis associated with CP. Acinar cell-secreted PTHrP modulates acinar cell function via its effects on proinflammatory cytokine release and functions via a paracrine pathway to activate PSCs. Copyright © 2014 the American Physiological Society.

  6. Abdominal ultrasonogram of autoimmune pancreatitis: Five cases of pancreatic lesions accompanied by Sjögren syndrome.

    Science.gov (United States)

    Yoshizaki, Hideo; Takeuchi, Kazuo; Okuda, Chikao; Honjyo, Hajime; Yamamoto, Takatugu; Kora, Tetuo; Takamori, Yoriyuki

    2002-09-01

    The concept of autoimmune pancreatitis has recently been established, and ultrasonographic findings we obtained from five cases consistent with autoimmune pancreatitis are reported here. Case 1, a 77-year-old man, was admitted complaining of loss of body weight. Serum hepatobiliary enzymes and γ-globulin levels were elevated, and antinuclear antibody was positive, Abdominal ultrasonography showed dilatation of the intrahepatic bile duct, wall thickening of the common bile duct and hypoechoic swelling of the pancreatic head and body. ERCP revealed multiple stenosis of the intra-and extra-hepatic bile ducts, and diffuse irregular narrowing of the main pancreatic duct. The patient complained of thirst, and the minor salivary gland was examined histologically. Our diagnosis was Sjögren syndrome accompanied by sclerosing cholangitis and a pancreatic lesion. Obstructive jaundice also developed, and PTCD was therefore performed. Both the pancreatic swelling and multiple stenosis of the bile duct improved after steroids were administered. Case 2, a 71-year-old man, was admitted with jaundice. Abdominal ultrasonography showed hypoechoic swelling of the pancreas. ERCP showed stenosis of the common bile duct in the pancreatic head region and diffuse irregular narrowing of the main pancreatic duct. Histological examination of the minor salivary gland suggested Sjögren syndrome. Steroids were therefore administered because the presence of both hyper-γ-globulinemia and positive antinuclear antibody suggested involvement of the autoimmune mechanism. Steroid therapy improved the jaundice as well as the findings from the cholangiograms and pancreatograms. We also encountered three similar cases, all consistent with the concept of autoimmune pancreatitis. The ultrasonographic findings of the pancreatic lesion (1) showed them as homogeneous and markedly hypoechoic areas and, (2) visualized the main pancreatic duct in the lesion, which facilitated a differential diagnosis of the

  7. Orlistat Reduces Proliferation and Enhances Apoptosis in Human Pancreatic Cancer Cells (PANC-1).

    Science.gov (United States)

    Sokolowska, Ewa; Presler, Malgorzata; Goyke, Elzbieta; Milczarek, Ryszard; Swierczynski, Julian; Sledzinski, Tomasz

    2017-11-01

    Pancreatic cancer is a disease with very poor prognosis, and none of currently available pharmacotherapies have proven to be efficient in this indication. The aim of this study was to analyze the expression of fatty acid synthase (FASN) gene as a potential therapeutic target in proliferating human pancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as an anti-obesity drug, inhibits PANC-1 proliferation. The effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis was studied in PANC-1 cell culture. Expression of FASN increased during proliferation of PANC-1. Inhibition of FASN by orlistat resulted in a significant reduction of PANC-1 proliferation and enhanced apoptosis of these cells. This study showed, to our knowledge for the first time, that orlistat exhibits significant antitumor activity against PANC-1 cells. This implies that orlistat analogs with good oral bioavailability may find application in pharmacotherapy of pancreatic cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Serum deprivation induces glucose response and intercellular coupling in human pancreatic adenocarcinoma PANC-1 cells.

    Science.gov (United States)

    Hiram-Bab, Sahar; Shapira, Yuval; Gershengorn, Marvin C; Oron, Yoram

    2012-03-01

    This study aimed to investigate whether the previously described differentiating islet-like aggregates of human pancreatic adenocarcinoma cells (PANC-1) develop glucose response and exhibit intercellular communication. Fura 2-loaded PANC-1 cells in serum-free medium were assayed for changes in cytosolic free calcium ([Ca]i) induced by depolarization, tolbutamide inhibition of K(ATP) channels, or glucose. Dye transfer, assayed by confocal microscopy or by FACS, was used to detect intercellular communication. Changes in messenger RNA (mRNA) expression of genes of interest were assessed by quantitative real-time polymerase chain reaction. Proliferation was assayed by the MTT method. Serum-deprived PANC-1 cell aggregates developed [Ca]i response to KCl, tolbutamide, or glucose. These responses were accompanied by 5-fold increase in glucokinase mRNA level and, to a lesser extent, of mRNAs for K(ATP) and L-type calcium channels, as well as increase in mRNA levels of glucagon and somatostatin. Trypsin, a proteinase-activated receptor 2 agonist previously shown to enhance aggregation, modestly improved [Ca]i response to glucose. Glucose-induced coordinated [Ca]i oscillations and dye transfer demonstrated the emergence of intercellular communication. These findings suggest that PANC-1 cells, a pancreatic adenocarcinoma cell line, can be induced to express a differentiated phenotype in which cells exhibit response to glucose and form a functional syncytium similar to those observed in pancreatic islets.

  9. Applied Developmental Biology: Making Human Pancreatic Beta Cells for Diabetics.

    Science.gov (United States)

    Melton, Douglas A

    2016-01-01

    Understanding the genes and signaling pathways that determine the differentiation and fate of a cell is a central goal of developmental biology. Using that information to gain mastery over the fates of cells presents new approaches to cell transplantation and drug discovery for human diseases including diabetes. © 2016 Elsevier Inc. All rights reserved.

  10. Interdependence of Gemcitabine Treatment, Transporter Expression, and Resistance in Human Pancreatic Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Wolfgang Hagmann

    2010-09-01

    Full Text Available Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment of pancreatic cancer. Our previous experimental chemotherapy studies have shown that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU alters the cellular transporter expression profile and that modulation of the expression of multidrug resistance protein 5 (MRP5; ABCC5 influences the chemoresistance of these tumor cells. Here, we studied the influence of acute and chronic gemcitabine treatment on the expression of relevant uptake and export transporters in pancreatic carcinoma cells by reverse transcription-polymerase chain reaction (RT-PCR, quantitative RT-PCR, and immunoblot analyses. The specific role of MRP5 in cellular gemcitabine sensitivity was studied by cytotoxicity assays using MRP5-overexpressing and MRP5-silenced cells. Exposure to gemcitabine (12 nM for 3 days did not alter the messenger RNA (mRNA expression of MRP1, MRP3, MRP5, and equilibrative nucleoside transporter 1 (ENT1, whereas high dosages of the drug (20 µM for 1 hour elicited up-regulation of these transporters in most cell lines studied. In cells with acquired gemcitabine resistance (up to 160 nM gemcitabine, the mRNA or protein expression of the gemcitabine transporters MRP5 and ENT1 was upregulated in several cell lines. Combined treatment with 5-FU and gemcitabine caused a 5- to 40-fold increase in MRP5 and ENT1 expressions. Cytotoxicity assays using either MRP5-overexpressing (HEK and PANC-1 or MRP5-silenced (PANC1/shMRP5 cells indicated that MRP5 contributes to gemcitabine resistance. Thus, our novel data not only on drug-induced alterations of transporter expression relevant for gemcitabine uptake and export but also on the link between gemcitabine sensitivity and MRP5 expression may lead to improved strategies of future chemotherapy regimens using gemcitabine in pancreatic carcinoma patients.

  11. Pancreatic Stones: Treat or Ignore?

    Directory of Open Access Journals (Sweden)

    DA Howell

    1999-01-01

    Full Text Available Painful, chronic pancreatitis is of complex etiology, but increasing clinical experience suggests that removal of pancreatic duct stones in many cases significantly improves patients’ symptoms. The development and refinement of therapeutic endoscopic retrograde choledochopancreatography have permitted improved access to the pancreatic duct, which makes the development of new techniques of stone fragmentation and fragment removal a much more successful nonsurgical intervention. A major step forward has been the understanding of the safety and efficacy of pancreatic sphincterotomy, which is necessary for the removal of these difficult stones. The recognition that extracorporeal shock wave lithotripsy can be delivered safely with good efficacy has revolutionized the nonsurgical management of pancreatic duct stones. Nevertheless, advanced and sophisticated therapeutic endoscopy is necessary to achieve clearance of the duct, which can generally be accomplished in the majority of selected patients. State-of-the-art treatments are described, and some new approaches using pancreatoscopy and electrohydrolic lithotripsy are discussed. Newly recognized long term complications are reviewed. Finally, it must be recognized that chronic pancreatitis is an ongoing disease that does not have a simple treatment or cure, and frequently represents a process of remissions and relapses requiring interventions and problem solving.

  12. miR-146a Suppresses Invasion of Pancreatic Cancer Cells

    Science.gov (United States)

    Li, Yiwei; VandenBoom, Timothy G.; Wang, Zhiwei; Kong, Dejuan; Ali, Shadan; Philip, Philip A.; Sarkar, Fazlul H.

    2010-01-01

    The aggressive course of pancreatic cancer is believed to reflect its unusually invasive and metastatic nature, which is associated with epidermal growth factor receptor (EGFR) overexpression and NF-κB activation. MicroRNAs (miRNA) have been implicated in the regulation of various pathobiological processes in cancer, including metastasis in pancreatic cancer and in other human malignancies. In this study, we report lower expression of miR-146a in pancreatic cancer cells compared with normal human pancreatic duct epithelial cells. Reexpression of miR-146a inhibited the invasive capacity of pancreatic cancer cells with concomitant downregulation of EGFR and the NF-κB regulatory kinase interleukin 1 receptor–associated kinase 1 (IRAK-1). Cellular mechanism studies revealed crosstalk between EGFR, IRAK-1, IκBα, NF-κB, and MTA-2, a transcription factor that regulates metastasis. Treatment of pancreatic cancer cells with the natural products 3,3′-diinodolylmethane (DIM) or isoflavone, which increased miR-146a expression, caused a downregulation of EGFR, MTA-2, IRAK-1, and NF-κB, resulting in an inhibition of pancreatic cancer cell invasion. Our findings reveal DIM and isoflavone as nontoxic activators of a miRNA that can block pancreatic cancer cell invasion and metastasis, offering starting points to design novel anticancer agents. PMID:20124483

  13. Type 1 autoimmune pancreatitis.

    Science.gov (United States)

    Zen, Yoh; Bogdanos, Dimitrios P; Kawa, Shigeyuki

    2011-12-07

    Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed

  14. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh

    2011-12-01

    Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of

  15. Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers

    International Nuclear Information System (INIS)

    Li, Zhaomin; Dong, Zizheng; Myer, David; Yip-Schneider, Michele; Liu, Jianguo; Cui, Ping; Schmidt, C Max; Zhang, Jian-Ting

    2010-01-01

    Pancreatic cancer is the fourth leading cause of death in the US. Unlike other solid tumors such as testicular cancer which are now curable, more than 90% of pancreatic cancer patients die due to lack of response to therapy. Recently, the level of 14-3-3σ mRNA was found to be increased in pancreatic cancers and this increased expression may contribute to the failure in treatment of pancreatic cancers. In the present study, we tested this hypothesis. Western blot analysis was used to determine 14-3-3σ protein level in fresh frozen tissues and was correlated to clinical outcome. A stable cell line expressing 14-3-3σ was established and the effect of 14-3-3σ over-expression on cellular response to radiation and anticancer drugs were tested using SRB assay and clonogenic assays. Cell cycle distribution and apoptosis analyses were performed using propidium iodide staining and PARP cleavage assays. We found that 14-3-3σ protein level was increased significantly in about 71% (17 of 24) of human pancreatic cancer tissues and that the 14-3-3σ protein level in cancers correlated with lymph node metastasis and poor prognosis. Furthermore, we demonstrated that over-expression of 14-3-3σ in a pancreatic cancer cell line caused resistance to γ-irradiation as well as anticancer drugs by causing resistance to treatment-induced apoptosis and G2/M arrest. The increased level of 14-3-3σ protein likely contributes to the poor clinical outcome of human pancreatic cancers by causing resistance to radiation and anticancer drugs. Thus, 14-3-3σ may serve as a prognosis marker predicting survival of pancreatic cancer patients and guide the clinical treatment of these patients

  16. Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process

    Science.gov (United States)

    Ghosal, Abhisek; Sekar, Thillai V.

    2014-01-01

    Biotin is essential for the normal function of pancreatic beta cells. These cells obtain biotin from their surroundings via transport across their cell membrane. Little is known about the uptake mechanism involved, how it is regulated, and how it is affected by internal and external factors. We addressed these issues using the mouse-derived pancreatic beta-TC-6 cells and freshly isolated mouse and human primary pancreatic beta cells as models. The results showed biotin uptake by pancreatic beta-TC-6 cells occurs via a Na+-dependent, carrier-mediated process, that is sensitive to desthiobiotin, as well as to pantothenic acid and lipoate; the process is also saturable as a function of concentration (apparent Km = 22.24 ± 5.5 μM). These cells express the sodium-dependent multivitamin transporter (SMVT), whose knockdown (with doxycycline-inducible shRNA) led to a sever inhibition in biotin uptake. Similarly, uptake of biotin by mouse and human primary pancreatic islets is Na+-dependent and carrier-mediated, and both cell types express SMVT. Biotin uptake by pancreatic beta-TC-6 cells is also adaptively regulated (via transcriptional mechanism) by extracellular substrate level. Chronic treatment of pancreatic beta-TC-6 cells with bacterial lipopolysaccharides (LPS) leads to inhibition in biotin uptake. This inhibition is mediated via a Toll-Like receptor 4-mediated process and involves a decrease in membrane expression of SMVT. These findings show, for the first time, that pancreatic beta cells/islets take up biotin via a specific and regulated carrier-mediated process, and that the process is sensitive to the effect of LPS. PMID:24904078

  17. Pancreatitis - discharge

    Science.gov (United States)

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... You were in the hospital because you have pancreatitis. This is a swelling of the pancreas. You ...

  18. Pancreatic Enzymes

    Science.gov (United States)

    ... Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

  19. Characterization of the distal promoter of the human pyruvate carboxylase gene in pancreatic beta cells.

    Directory of Open Access Journals (Sweden)

    Ansaya Thonpho

    Full Text Available Pyruvate carboxylase (PC is an enzyme that plays a crucial role in many biosynthetic pathways in various tissues including glucose-stimulated insulin secretion. In the present study, we identify promoter usage of the human PC gene in pancreatic beta cells. The data show that in the human, two alternative promoters, proximal and distal, are responsible for the production of multiple mRNA isoforms as in the rat and mouse. RT-PCR analysis performed with cDNA prepared from human liver and islets showed that the distal promoter, but not the proximal promoter, of the human PC gene is active in pancreatic beta cells. A 1108 bp fragment of the human PC distal promoter was cloned and analyzed. It contains no TATA box but possesses two CCAAT boxes, and other putative transcription factor binding sites, similar to those of the distal promoter of rat PC gene. To localize the positive regulatory region in the human PC distal promoter, 5'-truncated and the 25-bp and 15-bp internal deletion mutants of the human PC distal promoter were generated and used in transient transfections in INS-1 832/13 insulinoma and HEK293T (kidney cell lines. The results indicated that positions -340 to -315 of the human PC distal promoter serve as (an activator element(s for cell-specific transcription factor, while the CCAAT box at -71/-67, a binding site for nuclear factor Y (NF-Y, as well as a GC box at -54/-39 of the human PC distal promoter act as activator sequences for basal transcription.

  20. SMAD4 regulates cell motility through transcription of N-cadherin in human pancreatic ductal epithelium.

    Directory of Open Access Journals (Sweden)

    Ya'an Kang

    Full Text Available 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-β (TGF-β superfamily signaling, which regulates EMT, but the mechanisms linking TGF-β signaling to N-cadherin expression remain unclear. When the TGF-β 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 TGFβ-SMAD4 pathway. We first identified four previously undescribed SBEs within the CDH2 promoter. Using telomerase immortalized human pancreatic ductal epithelium, we found that TGF-β 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-β-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-β-driven upregulation of N-cadherin and the resultant invasive phenotype of human pancreatic ductal epithelial cells during EMT.

  1. Impact of global Fxr deficiency on experimental acute pancreatitis and genetic variation in the FXR locus in human acute pancreatitis

    NARCIS (Netherlands)

    Nijmeijer, Rian M.; Schaap, Frank G.; Smits, Alexander J. J.; Kremer, Andreas E.; Akkermans, Louis M. A.; Kroese, Alfons B. A.; Rijkers, Ger T.; Schipper, Marguerite E. I.; Verheem, André; Wijmenga, Cisca; Gooszen, Hein G.; van Erpecum, Karel J.

    2014-01-01

    Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs including the

  2. Bile Duct Cancer (Cholangiocarcinoma)

    Science.gov (United States)

    ... Home > Types of Cancer > Bile Duct Cancer (Cholangiocarcinoma) Bile Duct Cancer (Cholangiocarcinoma) This is Cancer.Net’s Guide to Bile Duct Cancer (Cholangiocarcinoma). Use the menu below to ...

  3. β-Cell regeneration through the transdifferentiation of pancreatic cells: Pancreatic progenitor cells in the pancreas.

    Science.gov (United States)

    Kim, Hyo-Sup; Lee, Moon-Kyu

    2016-05-01

    Pancreatic progenitor cell research has been in the spotlight, as these cells have the potential to replace pancreatic β-cells for the treatment of type 1 and 2 diabetic patients with the absence or reduction of pancreatic β-cells. During the past few decades, the successful treatment of diabetes through transplantation of the whole pancreas or isolated islets has nearly been achieved. However, novel sources of pancreatic islets or insulin-producing cells are required to provide sufficient amounts of donor tissues. To overcome this limitation, the use of pancreatic progenitor cells is gaining more attention. In particular, pancreatic exocrine cells, such as duct epithelial cells and acinar cells, are attractive candidates for β-cell regeneration because of their differentiation potential and pancreatic lineage characteristics. It has been assumed that β-cell neogenesis from pancreatic progenitor cells could occur in pancreatic ducts in the postnatal stage. Several studies have shown that insulin-producing cells can arise in the duct tissue of the adult pancreas. Acinar cells also might have the potential to differentiate into insulin-producing cells. The present review summarizes recent progress in research on the transdifferentiation of pancreatic exocrine cells into insulin-producing cells, especially duct and acinar cells.

  4. Pancreatic bicarbonate secretion involves two proton pumps.

    Science.gov (United States)

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L; Haanes, Kristian A; Krabbe, Simon; Nitschke, Roland; Hede, Susanne E

    2011-01-07

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H(+)/HCO(3)(-) transporters, which depend on gradients created by the Na(+)/K(+)-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H(+)-K(+)-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H(+)-K(+) pump inhibitors and ion substitutions. Gastric and non-gastric H(+)-K(+) pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H(+)/HCO(3)(-) and fluid transport shows that the H(+)-K(+) pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H(+)-K(+) pumps in pathophysiology.

  5. Secretion of N-ERC/mesothelin and expression of C-ERC/mesothelin in human pancreatic ductal carcinoma.

    Science.gov (United States)

    Inami, Koichi; Kajino, Kazunori; Abe, Masaaki; Hagiwara, Yoshiaki; Maeda, Masahiro; Suyama, Masafumi; Watanabe, Sumio; Hino, Okio

    2008-12-01

    ERC/mesothelin gene (MSLN) encodes a precursor protein, which is cleaved by proteases to generate N-ERC/mesothelin and C-ERC/mesothelin. N-ERC/mesothelin is a soluble protein, also known as megakaryocyte-potentiating factor, which is released into extracellular space. N-ERC/mesothelin is known to be a serum marker of mesothelioma. We have previously developed an enzyme-linked immunosorbent assay system for N-ERC/mesothelin, which can detect mesothelioma. C-ERC/mesothelin is expressed in normal mesothelial cell, pancreatic cancers, ovarian cancers, mesotheliomas and some other cancers. Pancreatic ductal carcinoma remains a fatal disease because its diagnosis often occurs very late. In this study, we examined ERC/mesothelin expression in human pancreatic cancer cell lines (MIA-PaCa2, PK-1, KP-3, TCC-PAN2, PK-59 and PK-45H) by reverse transcription-polymerase chain reaction and immunoblotting and N-ERC/mesothelin concentration in the supernatant of cultured cancer cells by the ELISA system. We also investigated C-ERC/mesothlein expression in human pancreatic ductal carcinoma tissues by immunostaining using 5B2 anti-mesothelin monoclonal antibody and N-ERC/mesothelin concentration in sera obtained from patients with pancreatic ductal carcinoma via ELISA. In vitro, N-ERC/mesothelin concentration in cell culture medium nearly correlated with the expression level of C-ERC/mesothelin. Although C-ERC/mesothelin was frequently expressed in human pancreatic ductal carcinoma, serum N-ERC/mesothelin concentration of cancer patients was equivalent to healthy controls. N-ERC/mesothelin was not useful as a serum marker of pancreatic ductal carcinoma, but because of frequent expression, C-ERC/mesothelin might be useful as a target of molecular imaging and immunotherapy.

  6. Effect of alcohol on insulin secretion and viability of human pancreatic islets

    Directory of Open Access Journals (Sweden)

    Nikolić Dragan

    2017-01-01

    Full Text Available Introduction/Objective. There are controversial data in the literature on the topic of effects of alcohol on insulin secretion, apoptosis, and necrosis of the endocrine and exocrine pancreas. The goal of this research was to determine how alcohol affects the insulin secretion and viability of human adult pancreatic islets in vitro during a seven-day incubation. Methods. Human pancreatic tissue was digested with Collagenase XI, using a non-automated method. Cultures were incubated in Roswell Park Memorial Institute (RPMI medium containing alcohol (10 μl of alcohol in 100 ml of medium. Insulin stimulation index (SI and viability of the islets were determined on the first, third, and seventh day of cultivation. Results. Analysis of the viability of the islets showed that there wasn’t significant difference between the control and the test group. In the test group, viability of the cultures declined with the time of incubation. SI of the test group was higher compared to the control group, by 50% and 25% on the first and third day of cultivation, respectively. On the seventh day, insulin secretion was reduced by 25%. The difference was not statistically significant (p > 0.05. In the test group, significant decline in insulin secretion was found on the third and seventh day of incubation (p ≤ 0.05. Conclusion. Alcohol can increase or decrease insulin secretion of islets cultures, which may result in an inadequate response of pancreatic β-cells to blood glucose, leading to insulin resistance, and increased risk of developing type 2 diabetes. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 41002

  7. Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes

    Directory of Open Access Journals (Sweden)

    Mocan L

    2011-04-01

    Full Text Available Lucian Mocan1, Flaviu A Tabaran2, Teodora Mocan1, Constantin Bele3, Anamaria Ioana Orza1, Ciprian Lucan4, Rares Stiufiuc1, Ioana Manaila1, Ferencz Iulia1, Iancu Dana1, Florin Zaharie1, Gelu Osian1, Liviu Vlad1, Cornel Iancu11Department of Nanomedicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Department of Pathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania; 3Department of Biochemistry, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania; 4Clinical Institute of Urology and Renal Transplantation, Cluj-Napoca, RomaniaAbstract: The process of laser-mediated ablation of cancer cells marked with biofunctionalized carbon nanotubes is frequently called “nanophotothermolysis”. We herein present a method of selective nanophotothermolisys of pancreatic cancer (PC using multiwalled carbon nanotubes (MWCNTs functionalized with human serum albumin (HSA. With the purpose of testing the therapeutic value of these nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically resected specimens from patients with PC were preserved in a cold medium and kept alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra-arterially administered in the greater pancreatic artery under ultrasound guidance. Confocal and transmission electron microscopy combined with immunohistochemical staining have confirmed the selective accumulation of HSA-MWCNTs inside the human PC tissue. The external laser irradiation of the specimen has significantly produced extensive necrosis of the malign tissue after the intra-arterial administration of HSA-MWCNTs, without any harmful effects on the surrounding healthy parenchyma. We have obtained a selective photothermal ablation of the malign tissue based on the selective internalization of MWCNTs with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra

  8. Possibilities of radiologic diagnosis of pancreatic calcinosis and chronic calculous pancreatics

    International Nuclear Information System (INIS)

    Loginov, A.S.; Sivash, Eh.S.; Kudryavtseva, G.V.

    1982-01-01

    X-ray diagnosis of the pancreatic gland calculous damage as well as chronic pancreatitis have been studied in 23 patients. A methodologic approach to examination of this group of patients was defined. Posteroanterior radiography has been shown to be of decisive importance in diagnosis of the calcified pancreatic gland. Duodenography and choleduodenography both considerably promote recognition of chronic pancreatitis. The radiologic method also allows one to reveal a series of complications: the common bile duct compression, duodenal stenosis, pancreatic tumor in the presence of chronic pancreatitis, malabsorption syndrome

  9. Pancreatic bicarbonate secretion involves two proton pumps

    DEFF Research Database (Denmark)

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L.

    2011-01-01

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium expres...

  10. Differential diagnosis of groove pancreatic carcinomas vs. groove pancreatitis: Usefulness of the portal venous phase

    International Nuclear Information System (INIS)

    Ishigami, Kousei; Tajima, Tsuyoshi; Nishie, Akihiro; Kakihara, Daisuke; Fujita, Nobuhiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Irie, Hiroyuki; Nakamura, Masafumi; Takahata, Shunichi; Ito, Tetsuhide; Honda, Hiroshi

    2010-01-01

    Purpose: To clarify if the portal venous phase is helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis. Materials and methods: MDCT and MRI of groove pancreatic carcinomas (n = 7) and groove pancreatitis (n = 15) were retrospectively reviewed by two radiologists independently. The signal intensity on T2-weighted images was subjectively assessed. The presence or absence of common bile duct (CBD) and main pancreatic duct (MPD) strictures, calcifications, and cystic lesions was evaluated. Additionally, the appearance of groove pancreatic carcinoma and that of groove pancreatitis in the portal venous phase on dynamic MDCT and MRI were compared. Results: There were no significant differences in the signal intensity on T2-weighted images and in the presence or absence of CBD and MPD strictures, calcifications, and cystic lesions between groove pancreatic carcinomas and groove pancreatitis. However, patchy focal enhancement in the portal venous phase was more commonly observed in groove pancreatitis than groove pancreatic carcinoma (Reviewers 1 and 2: 14/15 [93.3%] vs. 1/7 [14.3%], P < 0.0001). In addition, peripheral enhancement was only seen in groove pancreatic carcinomas (Reviewer 1: 4/7 [57.1%] vs. 0/15 [0%], P < 0.005, and Reviewer 2: 3/7 [42.9%] vs. 0/15 [0%], P < 0.05). Conclusion: The portal venous phase may be helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis.

  11. Phenotype and cell proliferation activity of duct-like structures in human sublingual glands: a histological and immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Elen de Souza TOLENTINO

    2015-06-01

    Full Text Available There are several age-related microscopic changes in the salivary glands, including the increase in the number of duct-like structures (DLS. However, the true origin and the phenotype of the DLS are not known. Objective To evaluate the phenotype and the cell proliferation index of the DLS of human sublingual glands. Material and Methods Sixty sublingual glands obtained from human cadavers were divided into two groups - 0-30 and 61-90 years old. The phenotype was estimated by immunostaining for cytokeratin 19 (CK 19 and the S-100 protein as well as by the presence of mucin and glycogen. The cell proliferation index was determined by the Ki-67 antibody. The histochemical techniques used periodic acid-Schiff (PAS and Alcian Blue. In each captured microscopic field, the DLS were counted to establish a percentage for the staining profile. The statistical analysis was accomplished using Student's t-test, the Mann-Whitney test and Pearson's correlation coefficient (p<0.05. Results Comparing both groups, only CK 19 showed a statistically significant difference (p=0.033, with the strongest expression in the elderly group. There was no significant difference between PAS and Alcian Blue (p=0.270. In both groups, the immunostaining for CK 19 was stronger than that for S-100 (p=0.004;p<0.001, but there was no correlation between the two immunomarkers (ρ=-0.163; p=0.315. There was no immunostaining for Ki-67. Conclusions DLS demonstrate a ductal phenotypic profile and do not present cell proliferation activity. DLS may represent a regressive process arising from acini or represent the result of metaplasia.

  12. Normal pancreatic exocrine function does not exclude MRI/MRCP chronic pancreatitis findings.

    Science.gov (United States)

    Alkaade, Samer; Cem Balci, Numan; Momtahen, Amir Javad; Burton, Frank

    2008-09-01

    Abnormal pancreatic function tests have been reported to precede the imaging findings of chronic pancreatitis. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is increasingly accepted as the primary imaging modality for the detection of structural changes of early mild chronic pancreatitis. The aim of this study was to evaluate MRI/MRCP findings in patients with symptoms consistent with chronic pancreatitis who have normal Secretin Endoscopic Pancreatic Function test. A retrospective study of 32 patients referred for evaluation of chronic abdominal pain consistent with chronic pancreatitis and reported normal standard abdominal imaging (ultrasound, computed tomography, or MRI). All patients underwent Secretin Endoscopic Pancreatic Function testing and pancreatic MRI/MRCP at our institution. We reviewed the MRI/MRCP images in patients who had normal Secretin Endoscopic Pancreatic Function testing. MRI/MRCP images were assessed for pancreatic duct morphology, gland size, parenchymal signal and morphology, and arterial contrast enhancement. Of the 32 patients, 23 had normal Secretin Endoscopic Pancreatic Function testing, and 8 of them had mild to marked spectrum of abnormal MRI/MRCP findings that were predominantly focal. Frequencies of the findings were as follows: pancreatic duct stricture (n=3), pancreatic duct dilatation (n=3), side branch ectasia (n=4), atrophy (n=5), decreased arterial enhancement (n=5), decreased parenchymal signal (n=1), and cavity formation (n=1). The remaining15 patients had normal pancreatic structure on MRI/MRCP. Normal pancreatic function testing cannot exclude abnormal MRI/MRCP especially focal findings of chronic pancreatitis. Further studies needed to verify significance of these findings and establish MRI/MRCP imaging criteria for the diagnosis of chronic pancreatitis.

  13. Protease-activated receptor 2 agonist increases cell proliferation and invasion of human pancreatic cancer cells

    Science.gov (United States)

    XIE, LIQUN; DUAN, ZEXING; LIU, CAIJU; ZHENG, YANMIN; ZHOU, JING

    2015-01-01

    The aim of this study was to determine the expression of protease-activated receptor 2 (PAR-2) in the human pancreatic cancer cell line SW1990, and to evaluate its effect on cell proliferation and invasion. The expression of PAR-2 protein and mRNA in SW1990 cells was determined by immunocytochemistry and reverse transcription polymerase chain reaction (PCR), respectively. MTT and cell invasion and migration assays, as well as semi-quantitative PCR and zymography analysis, were additionally performed. PAR-2 mRNA was significantly upregulated in the cells treated with trypsin or the PAR-2 activating peptide Ser-Leu-Ile-Gly-Lys-Val (SLIGKV) (P0.05). Trypsin and SLIGKV significantly promoted SW1990 cell proliferation in a dose- and time-dependent manner (P<0.05). Compared with the control group, trypsin and SLIGKV significantly increased the mRNA expression (P<0.01) and gelatinolytic activity (P<0.01) of matrix metalloproteinase (MMP)-2. In conclusion, PAR-2 is expressed in SW1990 cells. PAR-2 activation may promote the invasion and migration of human pancreatic cancer cells by increasing MMP-2 expression. PMID:25452809

  14. Inhibition of Fatty Acid Synthesis Induces Apoptosis of Human Pancreatic Cancer Cells.

    Science.gov (United States)

    Nishi, Koji; Suzuki, Kenta; Sawamoto, Junpei; Tokizawa, Yuma; Iwase, Yumiko; Yumita, Nagahiko; Ikeda, Toshihiko

    2016-09-01

    Cancer cells tend to have a high requirement for lipids, including fatty acids, cholesterol and triglyceride, because of their rapid proliferative rate compared to normal cells. In this study, we investigated the effects of inhibition of lipid synthesis on the proliferation and viability of human pancreatic cancer cells. Of the inhibitors of lipid synthesis that were tested, 5-(tetradecyloxy)-2-furoic acid (TOFA), which is an inhibitor of acetyl-CoA carboxylase, and the fatty acid synthase (FAS) inhibitors cerulenin and irgasan, significantly suppressed the proliferation of MiaPaCa-2 and AsPC-1 cells. Treatment of MiaPaCa-2 cells with these inhibitors significantly increased the number of apoptotic cells. In addition, TOFA increased caspase-3 activity and induced cleavage of poly (ADP-ribose) polymerase in MiaPaCa-2 cells. Moreover, addition of palmitate to MiaPaCa-2 cells treated with TOFA rescued cells from apoptotic cell death. These results suggest that TOFA induces apoptosis via depletion of fatty acids and that, among the various aspects of lipid metabolism, inhibition of fatty acid synthesis may be a notable target for the treatment of human pancreatic cancer cells. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Indicative findings of pancreatic cancer in prediagnostic CT

    International Nuclear Information System (INIS)

    Ahn, Sung Soo; Choi, Jin-Young; Hong, Hye-Suk; Chung, Yong Eun; Lim, Joon Seok; Kim, Myeong-Jin

    2009-01-01

    We examined 20 prediagnostic CTs from 16 patients for whom the diagnosis of pancreatic cancer was delayed until full diagnostic CT was performed. Three radiologists independently reviewed the prediagnostic CTs along with 50 CTs of control subjects, including patients without pancreatic disease (n = 38) or with chronic pancreatitis without calcification visible on CT (n=12). The reviewers recorded the presence of biliary or pancreatic ductal dilation, interruption of the pancreatic duct, distal parenchymal atrophy, contour abnormality and focal hypoattenuation. Frequency, sensitivity and specificity of the significant findings were calculated. Logistic regression analysis was performed. Findings indicative of pancreatic cancer were seen on 85% (17/20) of the prediagnostic CTs. Patients with pancreatic cancer were significantly (p<0.05) more likely to show focal hypoattenuation, pancreatic duct dilation, interruption of the pancreatic duct, and distal parenchymal atrophy, with sensitivities and specificities of 75%/84%, 50%/78%, 45%/82% and 45%/96%, respectively. Focal hypoattenuation and distal parenchymal atrophy were the independent predictors of pancreatic cancer with odds ratios of 20.92 and 11.22, respectively. In conclusion, focal hypoattenuation and pancreatic duct dilation with or without interruption, especially when accompanied by distal parenchymal atrophy, were the most useful findings for avoiding delayed diagnosis of pancreatic cancer. (orig.)

  16. Endoscopic or surgical intervention for painful obstructive chronic pancreatitis

    NARCIS (Netherlands)

    Ahmed Ali, Usama; Pahlplatz, Johanna M.; Nealon, Wiliam H.; van Goor, Harry; Gooszen, Hein G.; Boermeester, Marja A.

    2015-01-01

    Endoscopy and surgery are the treatment modalities of choice for patients with chronic pancreatitis and dilated pancreatic duct (obstructive chronic pancreatitis). Physicians face, without clear consensus, the choice between endoscopy or surgery for this group of patients. To assess and compare the

  17. Analysis of related risk factors for pancreatic fistula after pancreaticoduodenectomy

    Directory of Open Access Journals (Sweden)

    Qi-Song Yu

    2016-08-01

    Full Text Available Objective: To explore the related risk factors for pancreatic fistula after pancreaticoduodenectomy to provide a theoretical evidence for effectively preventing the occurrence of pancreatic fistula. Methods: A total of 100 patients who were admitted in our hospital from January, 2012 to January, 2015 and had performed pancreaticoduodenectomy were included in the study. The related risk factors for developing pancreatic fistula were collected for single factor and Logistic multi-factor analysis. Results: Among the included patients, 16 had pancreatic fistula, and the total occurrence rate was 16% (16/100. The single-factor analysis showed that the upper abdominal operation history, preoperative bilirubin, pancreatic texture, pancreatic duct diameter, intraoperative amount of bleeding, postoperative hemoglobin, and application of somatostatin after operation were the risk factors for developing pancreatic fistula (P<0.05. The multi-factor analysis showed that the upper abdominal operation history, the soft pancreatic texture, small pancreatic duct diameter, and low postoperative hemoglobin were the dependent risk factors for developing pancreatic fistula (OR=4.162, 6.104, 5.613, 4.034, P<0.05. Conclusions: The occurrence of pancreatic fistula after pancreaticoduodenectomy is closely associated with the upper abdominal operation history, the soft pancreatic texture, small pancreatic duct diameter, and low postoperative hemoglobin; therefore, effective measures should be taken to reduce the occurrence of pancreatic fistula according to the patients’ own conditions.

  18. [Robot-assisted pancreatic resection].

    Science.gov (United States)

    Müssle, B; Distler, M; Weitz, J; Welsch, T

    2017-06-01

    Although robot-assisted pancreatic surgery has been considered critically in the past, it is nowadays an established standard technique in some centers, for distal pancreatectomy and pancreatic head resection. Compared with the laparoscopic approach, the use of robot-assisted surgery seems to be advantageous for acquiring the skills for pancreatic, bile duct and vascular anastomoses during pancreatic head resection and total pancreatectomy. On the other hand, the use of the robot is associated with increased costs and only highly effective and professional robotic programs in centers for pancreatic surgery will achieve top surgical and oncological quality, acceptable operation times and a reduction in duration of hospital stay. Moreover, new technologies, such as intraoperative fluorescence guidance and augmented reality will define additional indications for robot-assisted pancreatic surgery.

  19. Establishment of H2Mab-119, an Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody, Against Pancreatic Cancer.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Chang, Yao-Wen; Harada, Hiroyuki; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2017-12-01

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer and is associated with poor clinical outcomes. In addition, HER2 expression has been reported in other cancers, such as gastric, colorectal, lung, and pancreatic cancers. An anti-HER2 humanized antibody, trastuzumab, leads to significant survival benefits in patients with HER2-overexpressing breast cancers and gastric cancers. Herein, we established a novel anti-HER2 monoclonal antibody (mAb), H 2 Mab-119 (IgG 1 , kappa), and characterized its efficacy against pancreatic cancers using flow cytometry, Western blot, and immunohistochemical analyses. H 2 Mab-119 reacted with pancreatic cancer cell lines, such as KLM-1, Capan-2, and MIA PaCa-2, but did not react with PANC-1 in flow cytometry analysis. Western blot analysis also revealed a moderate signal for KLM-1 and a weak signal for MIA PaCa-2, although H 2 Mab-119 reacted strongly with LN229/HER2 cells. Finally, immunohistochemical analyses with H 2 Mab-119 revealed sensitive and specific reactions against breast and colon cancers but did not react with pancreatic cancers, indicating that H 2 Mab-119 is useful for detecting HER2 overexpression in pancreatic cancers using flow cytometry and Western blot analyses.

  20. Evaluation of Traditional Indian Antidiabetic Medicinal Plants for Human Pancreatic Amylase Inhibitory Effect In Vitro

    Directory of Open Access Journals (Sweden)

    Sudha Ponnusamy

    2011-01-01

    Full Text Available Pancreatic α-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia via control of starch breakdown. Eleven Ayurvedic Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for α-amylase inhibition, in order to assess and evaluate their inhibitory potential on pancreatic α-amylase. Analysis of 91 extracts, showed that 10 exhibited strong Human Pancreatic Amylase (HPA inhibitory potential. Of these, 6 extracts showed concentration dependent inhibition with IC50 values, namely, cold and hot water extracts from Ficus bengalensis bark (4.4 and 125 μgmL-1, Syzygium cumini seeds (42.1 and 4.1 μgmL-1, isopropanol extracts of Cinnamomum verum leaves (1.0 μgmL-1 and Curcuma longa rhizome (0.16 μgmL-1. The other 4 extracts exhibited concentration independent inhibition, namely, methanol extract of Bixa orellana leaves (49 μgmL-1, isopropanol extract from Murraya koenigii leaves (127 μgmL-1, acetone extracts from C. longa rhizome (7.4 μgmL-1 and Tribulus terrestris seeds (511 μgmL-1. Thus, the probable mechanism of action of the above fractions is due to their inhibitory action on HPA, thereby reducing the rate of starch hydrolysis leading to lowered glucose levels. Phytochemical analysis revealed the presence of alkaloids, proteins, tannins, cardiac glycosides, flavonoids, saponins and steroids as probable inhibitory compounds.

  1. “Puestow modified procedure in the era of advanced endoscopic interventions for the management of chronic lithiasic pancreatitis. A two cases report”

    OpenAIRE

    Georgios P. Fragulidis; Αntonios Vezakis; Dionissios Dellaportas; Ira Sotirova; Vassilis Koutoulidis; Elliseos Kontis; Andreas Polydorou

    2015-01-01

    Introduction: Pancreatic duct calculi in chronic pancreatitis (CP) patients are the main cause of intractable pain which is their main symptom. Decompression options of for the main pancreatic duct are both surgical and advanced endoscopic procedures. Presentation of cases: A 64-year-old male with known CP due to alcohol consumption and a 36-year-old female with known idiopathic CP and pancreatic duct calculi were managed recently in our hospital where endoscopic procedures were unsuccessf...

  2. Computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography in the diagnosis of pancreatic disease

    International Nuclear Information System (INIS)

    Foley, W.D.; Stewart, E.T.; Lawson, T.L.; Maher, L.; Unger, G.F.; Geenan, J.; Loguidice, J.

    1980-01-01

    A prospective study was performed comparing the sensitivity of computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of pancreatic disease. Forty patients with suspected pancreatic carcinoma, acute recurrent or chronic pancreatitis, and/or jaundice were studied. CT was the most sensitive study in evaluation of pancreatitis. ERCP was most accurate in evaluation of pancreatic malignancy. Ultrasonography was the least sensitive method in detecting pancreatic disease and dilatation of the extrahepatic biliary ducts. (orig.) [de

  3. Understanding the Mechanical forces of Self-Expandable Metal Stents in the Biliary Ducts.

    Science.gov (United States)

    Isayama, Hiroyuki; Nakai, Yousuke; Hamada, Tsuyoshi; Matsubara, Saburo; Kogure, Hirofumi; Koike, Kazuhiko

    2016-12-01

    Self-expandable metallic stent (SEMS) was an effective biliary endoprosthesis. Mechanical properties of SEMS, radial and axial force (RF, AF), may play important roles in the bile duct after placement. RF was well known dilation force and influenced on the occurrence of migration. AF, newly proposed by this author, was defined as the recovery force when the SEMS vended. AF was related with the cause of bile duct kinking, pancreatitis, and cholecystitis due to the compression of the bile duct, orifice of the cystic duct, and pancreatic orifice. Ideal SEMS may show high RF and low AF.

  4. Combined Endoscopic-Radiological Rendezvous for Distal Tail Postoperative Pancreatic Fistula (POPF).

    Science.gov (United States)

    Lucatelli, Pierleone; Sacconi, Beatrice; Cereatti, Fabrizio; Argirò, Renato; Corona, Mario; Bezzi, Mario; Fanelli, Fabrizio; Fiocca, Fausto; Saba, Luca; Catalano, Carlo

    2016-09-01

    Postoperative pancreatic fistula (POPF) with leakage of pancreatic juice is a rare, severe complication following pancreatic resection or, less commonly, splenectomy. Definitive treatment can require multidisciplinary approaches. We report a case of stenosis of the main pancreatic duct with distal tail GRADE C POPF, occurred after splenectomy for Hodgkin lymphoma, successfully treated with combined radiological-endoscopic approach.

  5. Combined Endoscopic-Radiological Rendezvous for Distal Tail Postoperative Pancreatic Fistula (POPF)

    International Nuclear Information System (INIS)

    Lucatelli, Pierleone; Sacconi, Beatrice; Cereatti, Fabrizio; Argirò, Renato; Corona, Mario; Bezzi, Mario; Fanelli, Fabrizio; Fiocca, Fausto; Saba, Luca; Catalano, Carlo

    2016-01-01

    Postoperative pancreatic fistula (POPF) with leakage of pancreatic juice is a rare, severe complication following pancreatic resection or, less commonly, splenectomy. Definitive treatment can require multidisciplinary approaches. We report a case of stenosis of the main pancreatic duct with distal tail GRADE C POPF, occurred after splenectomy for Hodgkin lymphoma, successfully treated with combined radiological-endoscopic approach.

  6. Combined Endoscopic-Radiological Rendezvous for Distal Tail Postoperative Pancreatic Fistula (POPF)

    Energy Technology Data Exchange (ETDEWEB)

    Lucatelli, Pierleone, E-mail: pierleone.lucatelli@gmail.com; Sacconi, Beatrice, E-mail: beatrice.sacconi@fastwebnet.it [“Sapienza” University of Rome, Department of Radiological Sciences, Oncological and Anatomo-pathological Sciences, Vascular and Interventional Radiology Unit (Italy); Cereatti, Fabrizio, E-mail: fcereatti@yahoo.com [“Sapienza” University of Rome, Department of General Surgery Paride Stefanini, Interventional Endoscopy Unit (Italy); Argirò, Renato, E-mail: renato.argiro@gmail.com; Corona, Mario, E-mail: mario.corona68@gmail.com; Bezzi, Mario, E-mail: mario.bezzi@uniroma1.it; Fanelli, Fabrizio, E-mail: fabrizio.fanelli@uniroma1.it [“Sapienza” University of Rome, Department of Radiological Sciences, Oncological and Anatomo-pathological Sciences, Vascular and Interventional Radiology Unit (Italy); Fiocca, Fausto, E-mail: fausto.fiocca@uniroma1.it [“Sapienza” University of Rome, Department of General Surgery Paride Stefanini, Interventional Endoscopy Unit (Italy); Saba, Luca, E-mail: lucasabamd@gmail.com [Azienda Ospedaliero Universitaria di Cagliari-Polo di Monserrato, Department of Radiology (Italy); Catalano, Carlo, E-mail: carlo.catalano@uniroma1.it [“Sapienza” University of Rome, Department of Radiological Sciences, Oncological and Anatomo-pathological Sciences, Vascular and Interventional Radiology Unit (Italy)

    2016-09-15

    Postoperative pancreatic fistula (POPF) with leakage of pancreatic juice is a rare, severe complication following pancreatic resection or, less commonly, splenectomy. Definitive treatment can require multidisciplinary approaches. We report a case of stenosis of the main pancreatic duct with distal tail GRADE C POPF, occurred after splenectomy for Hodgkin lymphoma, successfully treated with combined radiological-endoscopic approach.

  7. Phospholipase D is involved in the formation of Golgi associated clathrin coated vesicles in human parotid duct cells.

    Directory of Open Access Journals (Sweden)

    Lorena Brito de Souza

    Full Text Available Phospholipase D (PLD has been implicated in many cellular functions, such as vesicle trafficking, exocytosis, differentiation, and proliferation. The aim of this study was to characterize the role of PLD in HSY cells, a human cell line originating from the intercalated duct of the parotid gland. As the function and intracellular localization of PLD varies according to cell type, initially, the intracellular localization of PLD1 and PLD2 was determined. By immunofluorescence, PLD1 and PLD2 both showed a punctate cytoplasmic distribution with extensive co-localization with TGN-46. PLD1 was also found in the nucleus, while PLD2 was associated with the plasma membrane. Treatment of cells with the primary alcohol 1-butanol inhibits the hydrolysis of phosphatidylcoline by PLD thereby suppressing phosphatidic acid (PA production. In untreated HSY cells, there was only a slight co-localization of PLD with the clathrin coated vesicles. When HSY cells were incubated with 1-butanol the total number of clathrin coated vesicles increased, especially in the juxtanuclear region and the co-localization of PLD with the clathrin coated vesicles was augmented. Transmission electron microscopy confirmed that the number of Golgi-associated coated vesicles was greater. Treatment with 1-butanol also affected the Golgi apparatus, increasing the volume of the Golgi saccules. The decrease in PA levels after treatment with 1-butanol likewise resulted in an accumulation of enlarged lysosomes in the perinuclear region. Therefore, in HSY cells PLD appears to be involved in the formation of Golgi associated clathrin coated vesicles as well as in the structural maintenance of the Golgi apparatus.

  8. Cystic pancreatic lymphangioma

    Directory of Open Access Journals (Sweden)

    Alihan Gurkan

    2012-04-01

    Full Text Available Lymphangioma of the pancreas is a rare benign tumor of lymphatic origin. Retroperitoneal lymphangiomas account for 1% of all lymphangiomas. Herein, we report a case of cystic pancreatic lymphangioma diagnosed in 34 year-old female patient who was hospitalized for a slight pain in the epigastrium and vomiting. Radiological imaging revealed a large multiloculated cystic abdominal mass with enhancing septations involving the upper retroperitoneum. During the laparoscopic surgery, a well circumscribed polycystic tumor was completely excised preserving the pancreatic duct. The patient made a complete recovery and is disease-free 12 months postoperatively.

  9. Pancreaticobiliary duct changes of periampullary carcinomas: Quantitative analysis at MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dong Sheng, E-mail: victoryhope@163.com [Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041 (China); Department of Radiology, No.4 West China Teaching Hospital of Sichuan University, Chengdu 610041 (China); Chen, Wei Xia, E-mail: wxchen25@126.com [Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041 (China); Wang, Xiao Dong, E-mail: tyfs03yz@163.com [Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041 (China); Acharya, Riwaz, E-mail: riwaz007@hotmail.com [Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041 (China); Jiang, Xing Hua, E-mail: 13881865517@163.com [Department of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041 (China)

    2012-09-15

    Purpose: To quantitatively analyse the pancreaticobiliary duct changes of periampullary carcinomas with volumetric interpolated breath-hold examination (VIBE) and true fast imaging with steady-state precession (true FISP) sequence, and investigate the value of these findings in differentiation and preoperative evaluation. Materials and methods: Magnetic resonance (MR) images of 71 cases of periampullary carcinomas (34 cases of pancreatic head carcinoma, 16 cases of intrapancreatic bile duct carcinoma and 21 cases of ampullary carcinoma) confirmed histopathologically were analysed. The maximum diameter of the common bile duct (CBD) and main pancreatic duct (MPD), dilated pancreaticobiliary duct angle and the distance from the end of the proximal dilated pancreaticobiliary duct to the major papilla were measured. Analysis of variance and the Chi-squared test were performed. Results: These findings showed significant differences among the three subtypes: the distance from the end of proximal dilated pancreaticobiliary duct to the major papilla and pancreaticobiliary duct angle. The distance and the pancreaticobiliary duct angle were least for ampullary carcinoma among the three subtypes. The percentage of dilated CBD was 94.1%, 93.8%, and 100% for pancreatic head carcinoma, intrapancreatic bile duct carcinoma and ampullary carcinoma, respectively. And that for the dilated MPD was 58.8%, 43.8%, and 42.9%, respectively. Conclusion: Quantitative analysis of the pancreaticobiliary ductal system can provide accurate and objective assessment of the pancreaticobiliary duct changes. Although benefit in differential diagnosis is limited, these findings are valuable in preoperative evaluation for both radical resection and palliative surgery.

  10. Autophagy sustains the survival of human pancreatic cancer PANC-1 cells under extreme nutrient deprivation conditions.

    Science.gov (United States)

    Kim, Sang Eun; Park, Hye-Jin; Jeong, Hye Kyoung; Kim, Mi-Jung; Kim, Minyeong; Bae, Ok-Nam; Baek, Seung-Hoon

    2015-07-31

    Pancreatic ductal adenocarcinomas are an extremely aggressive and devastating type of cancer with high mortality. Given the dense stroma and poor vascularization, accessibility to nutrients is limited in the tumor microenvironment. Here, we aimed to elucidate the role of autophagy in promoting the survival of human pancreatic cancer PANC-1 cells exposed to nutrient-deprived media (NDM) lacking glucose, amino acids, and serum. NDM inhibited Akt activity and phosphorylation of p70 S6K, and induced AMPK activation and mitochondrial depolarization. NDM also time-dependently increased LC3-II accumulation, number of GFP-LC3 puncta, and colocalization between GFP-LC3 and lysosomes. These results suggested that autophagy was progressively activated through Akt- and AMPK-mTOR pathway in nutrient-deficient PANC-1 cells. Autophagy inhibitors (chloroquine and wortmannin) or silencing of Atg5 augmented PANC-1 cell death in NDM. In cells exposed to NDM, chloroquine and wortmannin induced apoptosis and Z-VAD-fmk inhibited cytotoxicity of these inhibitors. These data demonstrate that autophagy is anti-apoptotic and sustains the survival of PANC-1 cells following extreme nutrient deprivation. Autophagy modulation may be a viable therapeutic option for cancer cells located in the core of solid tumors with a nutrient-deficient microenvironment. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Effects of disulfiram on apoptosis in PANC-1 human pancreatic cancer cell line.

    Science.gov (United States)

    Dastjerdi, M Nikbakht; Babazadeh, Z; Rabbani, M; Gharagozloo, M; Esmaeili, A; Narimani, M

    2014-01-01

    Pancreatic carcinoma is currently considered as a rapidly progressive and fatal disease, and is typically diagnosed late in its natural course. It is characterized by a poor diagnosis and lack of response to conventional therapy. Recent studies have suggested that disulfiram (DSF), a member of the dithiocarbamate family, may have antitumor activity. This study aimed to evaluate the in vitro effect of DSF on apoptosis in human pancreatic cancerous cell line (PANC-1). PANC-1 cells were cultured and treated with DSF at doses of 5, 10, 13 μM for 24 h and apoptosis was measured. Methylation specific PCR (MS-PCR) and real-time quantitative PCR were carried out to detect the methylation pattern and to estimate the mRNA expression levels of RASSF1A, p21 and Bax. MS-PCR analysis demonstrated that no unmethylated band was apeared in PANC-1 cell line after DSF treatments. The real-time quantitative PCR results showed no significant mRNA expression for RASSF1A (p>0.05); whereas p21 and Bax expression were significantly (pPANC-1 through p21 and Bax pathway but not through RASSF1A.

  12. Efficient Generation of NKX6-1+ Pancreatic Progenitors from Multiple Human Pluripotent Stem Cell Lines

    Directory of Open Access Journals (Sweden)

    M. Cristina Nostro

    2015-04-01

    Full Text Available Human pluripotent stem cells (hPSCs represent a renewable source of pancreatic beta cells for both basic research and therapeutic applications. Given this outstanding potential, significant efforts have been made to identify the signaling pathways that regulate pancreatic development in hPSC differentiation cultures. In this study, we demonstrate that the combination of epidermal growth factor (EGF and nicotinamide signaling induces the generation of NKX6-1+ progenitors from all hPSC lines tested. Furthermore, we show that the size of the NKX6-1+ population is regulated by the duration of treatment with retinoic acid, fibroblast growth factor 10 (FGF10, and inhibitors of bone morphogenetic protein (BMP and hedgehog signaling pathways. When transplanted into NOD scid gamma (NSG recipients, these progenitors differentiate to give rise to exocrine and endocrine cells, including monohormonal insulin+ cells. Together, these findings provide an efficient and reproducible strategy for generating highly enriched populations of hPSC-derived beta cell progenitors for studies aimed at further characterizing their developmental potential in vivo and deciphering the pathways that regulate their maturation in vitro.

  13. Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors

    Directory of Open Access Journals (Sweden)

    Jacqueline Ameri

    2017-04-01

    Full Text Available Stem cell-based therapy for type 1 diabetes would benefit from implementation of a cell purification step at the pancreatic endoderm stage. This would increase the safety of the final cell product, allow the establishment of an intermediate-stage stem cell bank, and provide a means for upscaling β cell manufacturing. Comparative gene expression analysis revealed glycoprotein 2 (GP2 as a specific cell surface marker for isolating pancreatic endoderm cells (PECs from differentiated hESCs and human fetal pancreas. Isolated GP2+ PECs efficiently differentiated into glucose responsive insulin-producing cells in vitro. We found that in vitro PEC proliferation declines due to enhanced expression of the cyclin-dependent kinase (CDK inhibitors CDKN1A and CDKN2A. However, we identified a time window when reducing CDKN1A or CDKN2A expression increased proliferation and yield of GP2+ PECs. Altogether, our results contribute tools and concepts toward the isolation and use of PECs as a source for the safe production of hPSC-derived β cells.

  14. Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes

    DEFF Research Database (Denmark)

    Rosengren, Anders H; Braun, Matthias; Mahdi, Taman

    2012-01-01

    The majority of genetic risk variants for type 2 diabetes (T2D) affect insulin secretion, but the mechanisms through which they influence pancreatic islet function remain largely unknown. We functionally characterized human islets to determine secretory, biophysical, and ultrastructural features ...

  15. Comparison of Oct4, Sox2 and Nanog Expression in Pancreatic Cancer Cell Lines and Human Pancreatic Tumor

    Directory of Open Access Journals (Sweden)

    Vahideh Assadollahi

    2015-12-01

    Full Text Available Background: Genes are involved in the control of stem cell self-renewal as a new class of molecular markers of cancer. Objectives: In this study, the expression of Oct4, Nanog and Sox2 in cell lines MIA Paca-2, PA-TU-8902 and AsPC-1 and pancreatic cancer tissue were examined. Materials and Methods: In this experimental study, cell lines, MIA Paca-2, PA-TU-8902 and AsPC-1, were cultured in DMEM (Dulbecco’s Modified Eagles Medium and RPMI-1640 (Roswell Park Memorial Institute containing FBS 10% (fetal bovine serum in a 37°C incubator containing Co2 5% and humidity 90%. Samples of tumor and non-cancer pancreatic tumor were purchased Iran tumor bank. Extraction of RNA and synthesis of cDNA was performed. Expression levels of Oct4, Nanog and Sox2 were determined using Real-time PCR. The protein expression levels of target genes in the cell lines were studied by flow cytometry and immunocytochemistry. Results: The expression rate of Oct4, Nanog and Sox2 is more in the cancer cell lines than those in the control (normal tissue samples. The protein expression levels of target genes in the cell lines were confirmed by flow cytometry and immunocytochemistry. Conclusions: The genes are involved in stem cell self-renewal as a new class of molecular markers of cancer that detected in the pancreatic cell lines. Maybe, these genes play important role in the uncontrolled proliferation of cancer cells.

  16. Acute and chronic pancreatitis: surgical management.

    Science.gov (United States)

    Dzakovic, Alexander; Superina, Riccardo

    2012-08-01

    Pancreatitis is becoming increasingly prevalent in children, posing new challenges to pediatric health care providers. Although some general adult treatment paradigms are applicable in the pediatric population, diagnostic workup and surgical management of acute and chronic pancreatitis have to be tailored to anatomic and pathophysiological entities peculiar to children. Nonbiliary causes of acute pancreatitis in children are generally managed nonoperatively with hydration, close biochemical and clinical observation, and early initiation of enteral feeds. Surgical intervention including cholecystectomy or endoscopic retrograde cholangiopancreatography is often required in acute biliary pancreatitis, whereas infected pancreatic necrosis remains a rare absolute indication for pancreatic debridement and drainage via open, laparoscopic, or interventional radiologic procedure. Chronic pancreatitis is characterized by painful irreversible changes of the parenchyma and ducts, which may result in or be caused by inadequate ductal drainage. A variety of surgical procedures providing drainage, denervation, resection, or a combination thereof are well established to relieve pain and preserve pancreatic function. Copyright © 2012. Published by Elsevier Inc.

  17. The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Lou, Hai-zhou; Weng, Xiao-chuan; Pan, Hong-ming; Pan, Qin; Sun, Peng; Liu, Li-li; Chen, Bin

    2014-01-01

    Highlights: • INK-128 inhibits the survival and growth of human pancreatic cancer cells. • INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. • INK-128 blocks mTORC1/2 activation simultaneously in pancreatic cancer cells. • INK-128 down-regulates cyclin D1 and causes pancreatic cancer cell cycle arrest. • INK-128 significantly increases sensitivity of pancreatic cancer cells to gemcitabine. - Abstract: Pancreatic cancer has one of worst prognosis among all human malignancies around the world, the development of novel and more efficient anti-cancer agents against this disease is urgent. In the current study, we tested the potential effect of INK-128, a novel mammalian target of rapamycin (mTOR) complex 1 and 2 (mTORC1/2) dual inhibitor, against pancreatic cancer cells in vitro. Our results demonstrated that INK-128 concentration- and time-dependently inhibited the survival and growth of pancreatic cancer cells (both primary cells and transformed cells). INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. Further, INK-128 dramatically inhibited phosphorylation of 4E-binding protein 1 (4E-BP1), ribosomal S6 kinase 1 (S6K1) and Akt at Ser 473 in pancreatic cancer cells. Meanwhile, it downregulated cyclin D1 expression and caused cell cycle arrest. Finally, we found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment

  18. The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lou, Hai-zhou [Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016 (China); Weng, Xiao-chuan [Department of Anesthesiology, Hangzhou Xia-sha Hospital, Hangzhou 310018 (China); Pan, Hong-ming; Pan, Qin [Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016 (China); Sun, Peng [Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060 (China); Liu, Li-li [Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016 (China); Chen, Bin, E-mail: chenbinhangzhou126@126.com [Department of Hepatopancreatobiliary Surgery, First People’s Hospital of Hangzhou, Hangzhou 310006 (China)

    2014-07-25

    Highlights: • INK-128 inhibits the survival and growth of human pancreatic cancer cells. • INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. • INK-128 blocks mTORC1/2 activation simultaneously in pancreatic cancer cells. • INK-128 down-regulates cyclin D1 and causes pancreatic cancer cell cycle arrest. • INK-128 significantly increases sensitivity of pancreatic cancer cells to gemcitabine. - Abstract: Pancreatic cancer has one of worst prognosis among all human malignancies around the world, the development of novel and more efficient anti-cancer agents against this disease is urgent. In the current study, we tested the potential effect of INK-128, a novel mammalian target of rapamycin (mTOR) complex 1 and 2 (mTORC1/2) dual inhibitor, against pancreatic cancer cells in vitro. Our results demonstrated that INK-128 concentration- and time-dependently inhibited the survival and growth of pancreatic cancer cells (both primary cells and transformed cells). INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. Further, INK-128 dramatically inhibited phosphorylation of 4E-binding protein 1 (4E-BP1), ribosomal S6 kinase 1 (S6K1) and Akt at Ser 473 in pancreatic cancer cells. Meanwhile, it downregulated cyclin D1 expression and caused cell cycle arrest. Finally, we found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment.

  19. Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, Ann H., E-mail: ann.rosendahl@med.lu.se [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden); Lund University and Skåne University Hospital, Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund (Sweden); Gundewar, Chinmay; Said Hilmersson, Katarzyna [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden); Ni, Lan; Saleem, Moin A. [University of Bristol, School of Clinical Sciences, Children' s Renal Unit and Academic Renal Unit, Bristol (United Kingdom); Andersson, Roland [Lund University, Department of Clinical Sciences Lund, Division of Surgery, Lund (Sweden)

    2015-01-15

    Pancreatic stellate cells (PSCs) play a key role in the dense desmoplastic stroma associated with pancreatic ductal adenocarcinoma. Studies on human PSCs have been minimal due to difficulty in maintaining primary PSC in culture. We have generated the first conditionally immortalized human non-tumor (NPSC) and tumor-derived (TPSC) pancreatic stellate cells via transformation with the temperature-sensitive SV40 large T antigen and human telomerase (hTERT). These cells proliferate at 33°C. After transfer to 37°C, the SV40LT is switched off and the cells regain their primary PSC phenotype and growth characteristics. NPSC contained cytoplasmic vitamin A-storing lipid droplets, while both NPSC and TPSC expressed the characteristic markers αSMA, vimentin, desmin and GFAP. Proteome array analysis revealed that of the 55 evaluated proteins, 27 (49%) were upregulated ≥3-fold in TPSC compared to NPSC, including uPA, pentraxin-3, endoglin and endothelin-1. Two insulin-like growth factor binding proteins (IGFBPs) were inversely expressed. Although discordant IGFBP-2 and IGFBP-3 levels, IGF-I was found to stimulate proliferation of both NPSC and TPSC. Both basal and IGF-I stimulated motility was significantly enhanced in TPSC compared to NPSC. In conclusion, these cells provide a unique resource that will facilitate further study of the active stroma compartment associated with pancreatic cancer. - Highlights: • Generation of human conditionally immortalized human pancreatic stellate cell lines. • Temperature-sensitive SV40LT allows switch to primary PSC phenotype characteristics. • Proteome profiling revealed distinct expression patterns between TPSC and NPSC. • Enhanced IGF-I-stimulated proliferation and motility by TPSC compared to NPSC.

  20. Chronic Continuous Exenatide Infusion Does Not Cause Pancreatic Inflammation and Ductal Hyperplasia in Non-Human Primates

    Science.gov (United States)

    Fiorentino, Teresa Vanessa; Owston, Michael; Abrahamian, Gregory; La Rosa, Stefano; Marando, Alessandro; Perego, Carla; Di Cairano, Eliana S.; Finzi, Giovanna; Capella, Carlo; Sessa, Fausto; Casiraghi, Francesca; Paez, Ana; Adivi, Ashwin; Davalli, Alberto; Fiorina, Paolo; Guardado Mendoza, Rodolfo; Comuzzie, Anthony G.; Sharp, Mark; DeFronzo, Ralph A.; Halff, Glenn; Dick, Edward J.; Folli, Franco

    2016-01-01

    In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67–positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67–positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67–positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30–positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates. PMID:25447052

  1. Morphohistological Features of Pancreatic Stump Are the Main Determinant of Pancreatic Fistula after Pancreatoduodenectomy

    Directory of Open Access Journals (Sweden)

    Cristina Ridolfi

    2014-01-01

    Full Text Available Introduction. Pancreatic surgery is challenging and associated with high morbidity, mainly represented by postoperative pancreatic fistula (POPF and its further consequences. Identification of risk factors for POPF is essential for proper postoperative management. Aim of the Study. Evaluation of the role of morphological and histological features of pancreatic stump, other than main pancreatic duct diameter and glandular texture, in POPF occurrence after pancreaticoduodenectomy. Patients and Methods. Between March 2011 and April 2013, we performed 145 consecutive pancreaticoduodenectomies. We intraoperatively recorded morphological features of pancreatic stump and collected data about postoperative morbidity. Our dedicated pathologist designed a score to quantify fibrosis and inflammation of pancreatic tissue. Results. Overall morbidity was 59,3%. Mortality was 4,1%. POPF rate was 28,3%, while clinically significant POPF were 15,8%. Male sex (P=0.009, BMI≥25 (P=0.002, prolonged surgery (P=0.001, soft pancreatic texture (P<0.001, small pancreatic duct (P<0.001, pancreatic duct decentralization on stump anteroposterior axis, especially if close to the posterior margin (P=0.031, large stump area (P=0.001, and extended stump mobilization (P=0.001 were related to higher POPF rate. Our fibrosis-and-inflammation score is strongly associated with POPF (P=0.001. Discussion and Conclusions. Pancreatic stump features evaluation, including histology, can help the surgeon in fitting postoperative management to patient individual risk after pancreaticoduodenectomy.

  2. Morphohistological features of pancreatic stump are the main determinant of pancreatic fistula after pancreatoduodenectomy.

    Science.gov (United States)

    Ridolfi, Cristina; Angiolini, Maria Rachele; Gavazzi, Francesca; Spaggiari, Paola; Tinti, Maria Carla; Uccelli, Fara; Madonini, Marco; Montorsi, Marco; Zerbi, Alessandro

    2014-01-01

    Pancreatic surgery is challenging and associated with high morbidity, mainly represented by postoperative pancreatic fistula (POPF) and its further consequences. Identification of risk factors for POPF is essential for proper postoperative management. Evaluation of the role of morphological and histological features of pancreatic stump, other than main pancreatic duct diameter and glandular texture, in POPF occurrence after pancreaticoduodenectomy. Between March 2011 and April 2013, we performed 145 consecutive pancreaticoduodenectomies. We intraoperatively recorded morphological features of pancreatic stump and collected data about postoperative morbidity. Our dedicated pathologist designed a score to quantify fibrosis and inflammation of pancreatic tissue. Overall morbidity was 59,3%. Mortality was 4,1%. POPF rate was 28,3%, while clinically significant POPF were 15,8%. Male sex (P = 0.009), BMI ≥ 25 (P = 0.002), prolonged surgery (P = 0.001), soft pancreatic texture (P < 0.001), small pancreatic duct (P < 0.001), pancreatic duct decentralization on stump anteroposterior axis, especially if close to the posterior margin (P = 0.031), large stump area (P = 0.001), and extended stump mobilization (P = 0.001) were related to higher POPF rate. Our fibrosis-and-inflammation score is strongly associated with POPF (P = 0.001). Pancreatic stump features evaluation, including histology, can help the surgeon in fitting postoperative management to patient individual risk after pancreaticoduodenectomy.

  3. Recycling of epidermal growth factor in a human pancreatic carcinoma cell line

    International Nuclear Information System (INIS)

    Korc, M.; Magun, B.E.

    1985-01-01

    PANC-1 human pancreatic carcinoma cells readily bound and internalized 125 I-labeled epidermal growth factor (EGF). Bound 125 I-labeled EGF was then partially processed to a number of high molecular weight acidic species. Percoll gradient centrifugation of cell homogenates indicated that the majority of 125 I activity localized to several intracellular vesicular compartments. Both intact EGF and its processed species were subsequently released into the incubation medium. A major portion of the released radioactivity was capable of rebinding to the cell. Only a small amount of bound 125 I-labeled EGF was degraded to low molecular weight products, and this degradation was completely blocked by methylamine. These findings suggest that in PANC-1 cells, bound EGF undergoes only limited processing. Both intact EGF and its major processed species bypass the cellular degradative pathways, are slowly released from the cell, and then rebind to the cell

  4. Vitamin D and pancreatic cancer

    OpenAIRE

    Stolzenberg-Solomon, Rachael Z.

    2008-01-01

    Sun exposure has been associated with lower death rates for pancreatic cancer in ecological studies. Skin exposure to solar ultra-violet B radiation induces cutaneous production of precursors to 25-hydroxy (OH) vitamin D (D) and is considered the primary contributor to vitamin D status in most populations. Pancreatic islet and duct cells express 25-(OH) D3-1α-hydroxylase that generates the biologically active 1,25-dihydroxy(OH)2 D form. Thus, 25(OH)D concentrations could affect pancreatic fun...

  5. the Size of the Common Bile Duct on Routine Radiography Variation

    African Journals Online (AJOL)

    ... fatty meal stimulus showed reduction in the diameter of the common bile duct ... pancreatic pathology was noted. ... JOURNAL. 2149. Fig. 1. ... fatty meal stimulus is mediated through the endocrine action of ... 1O Histological studies have all ...

  6. Magnetic resonance cholangiopancreatography findings of pancreatic diseases: quantitative analysis

    International Nuclear Information System (INIS)

    Xu Jun; Lu Jianping; Wang Jian; Wang Fei; Liu Qi; Wang Li; Gong Jianguo; Jin Aiguo; Zeng Hao

    2004-01-01

    Objective: To study the MR cholangiopancreatography (MRCP) characteristics of different pancreatic diseases, and to identify the diagnostic value of MRCP for pancreatic diseases. Methods: One hundred and eleven patients with suspected pancreatic diseases underwent MRCP examination. The MRCP sequences included thick-slice turbo spin echo (TSE) and thin-slice half-Fourier acquisition single shot turbo spin echo (HASTE) sequences. The pancreatic diseases included pancreatic carcinoma (n=46), chronic pancreatitis (n=39), peri-ampullar carcinoma (n=23), and choledocholith (n=3). Results: (1) The abnormal manifestation of pancreatic duct was observed in 37 cases of pancreatic carcinoma, 24 cases of chronic pancreatitis, and 12 cases of peri-ampullar carcinoma. Dilated pancreatic duct with smooth and regular caliber was observed in 33 cases of pancreatic carcinoma, 0 case of chronic pancreatitis, and 12 cases of peri-ampullar carcinoma, and statistical analysis showed significant difference (χ 2 =57.911, P 2 =60.343, P 2 =61.217, P 2 =34.654, P 2 =54.593, P<0.01). Conclusion: Different MRI characteristics were observed in various pancreatic diseases respectively. MRCP can show the subtle differences among the pancreatic diseases, and is very helpful in the diagnosis and differential diagnosis of pancreatic diseases

  7. Radiologic features of cystic, endocrine and other pancreatic neoplasms

    International Nuclear Information System (INIS)

    Balci, N. Cem; Semelka, Richard C.

    2001-01-01

    This article presents imaging features of cystic, endocrine and other pancreatic neoplasms. Microcystic adenoma which is composed of small cysts ( 2 cm) are accounted for mucinous cystic neoplasms, its variant along pancreatic duct is ductectatic mucinous cystic neoplasm. Endocrine tumors of pancreas are hypervascular and can be depicted on early dynamic enhanced crosssectional imaging modalities or on angiography when they are <1 cm. Pancreatic metastases and lymphomas are rare neoplasms which should also be included in differential diagnosis for pancreatic masses

  8. Characteristic findings in images of extra-pancreatic lesions associated with autoimmune pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Fujinaga, Yasunari, E-mail: fujinaga@shinshu-u.ac.jp [Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan); Kadoya, Masumi [Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan); Kawa, Shigeyuki [Center of Health, Safety and Environmental Management, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan); Hamano, Hideaki [Department of Medicine, Gastroenterology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan); Ueda, Kazuhiko; Momose, Mitsuhiro; Kawakami, Satoshi; Yamazaki, Sachie; Hatta, Tomoko; Sugiyama, Yukiko [Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan)

    2010-11-15

    Purpose: Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by a variety of extra-pancreatic involvements which are frequently misdiagnosed as lesions of corresponding organs. The purpose of this study was to clarify the diagnostic imaging features of extra-pancreatic lesions associated with autoimmune pancreatitis. Materials and methods: We retrospectively analyzed diagnostic images of 90 patients with autoimmune pancreatitis who underwent computer-assisted tomography, magnetic resonance imaging, and/or gallium-67 scintigraphy before steroid therapy was initiated. Results: AIP was frequently (92.2%) accompanied by a variety of extra-pancreatic lesions, including swelling of lachrymal and salivary gland lesions (47.5%), lung hilar lymphadenopathy (78.3%), a variety of lung lesions (51.2%), wall thickening of bile ducts (77.8%), peri-pancreatic or para-aortic lymphadenopathy (56.0%), retroperitoneal fibrosis (19.8%), a variety of renal lesions (14.4%), and mass lesions of the ligamentum teres (2.2%). Characteristic findings in CT and MRI included lymphadenopathies of the hilar, peri-pancreatic, and para-aortic regions; wall thickening of the bile duct; and soft tissue masses in the kidney, ureters, aorta, paravertebral region, ligamentum teres, and orbit. Conclusions: Recognition of the diagnostic features in the images of various involved organs will assist in the diagnosis of autoimmune pancreatitis and in differential diagnoses between autoimmune pancreatitis-associated extra-pancreatic lesions and lesions due to other pathologies.

  9. Mass-forming chronic pancreatitis : CT and ERCP features

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Dong Jin; Ha, Hyun Kwon; Lee, Yong Suk; Lee, Jin Hwa; Kim, Pyo Nyun; Lee, Moon Gyu; Auh, Yong Ho [Asan Medical Center, Ulsan Univ. College of Medicine, Ulsan (Korea, Republic of)

    1999-11-01

    To describe the CT and ERCP findings of mass-forming chronic pancreatitis. CT and ERCP features were assessed in 13 patients suffering from mass-forming chronic pancreatitis. Diagnosis was on the basis of surgery (n=5), percutaneous needle biopsy (n=3), and clinical follow-up (n=5). Contrast-enhanced CT was available for all patients : five underwent dynamic study and ERCP was performed in 12. On CT and ERCP, both groups were evaluated with regard to the presence and degree of pancreatic ductal dilatation (greater or less than 50 % of total gland width), double duct sign, enhancement pattern, pancreatic parenchymal calcification (site and distribution pattern), mass identification, the direction of infiltration, pancreatic parenchymal atrophy, configuration at the site of obstruction in the pancreatic and common bile duct, lymphadenopathy, vascular encasement, and vascular engorgement or increased collateral vessels in the peripancreatic space. Seven of 13 patients had suffered chronic alcoholism. Serum CA19-9 levels were normal in all patients except one. Common CT and ERCP findings of mass-forming chronic pancreatitis included pancreatic duct dilatation (92.3%), double duct sign (69.2%), inhomogeneous enhancement of the mass (69.2%), and the presence of calcification (61.5%). Patterns of pancreatic duct dilation were irregular in five patients (38.4%) and smooth in three (23.1%). In all patients, duct dilatation was less than 50% of total gland width. Enhancement patterns of the pancreatic mass were inhomogeneous (69.2%), a nonenhancing low attenuation mass (15.3%), and homogeneous enhancement (15.3%). Configuration at the site of obstruction in the pancreatic duct was abrupt termination in two patients (15.4%) and smooth termination in two (15.4%). The common bile duct teminated abruptly in three patients (23.1%), and in four (30.8%) smooth narrowing was abserved. Common findings of mass-forming chronic pancreatitis were duct dilatation of less than 50% of total

  10. Mass-forming chronic pancreatitis : CT and ERCP features

    International Nuclear Information System (INIS)

    Jung, Dong Jin; Ha, Hyun Kwon; Lee, Yong Suk; Lee, Jin Hwa; Kim, Pyo Nyun; Lee, Moon Gyu; Auh, Yong Ho

    1999-01-01

    To describe the CT and ERCP findings of mass-forming chronic pancreatitis. CT and ERCP features were assessed in 13 patients suffering from mass-forming chronic pancreatitis. Diagnosis was on the basis of surgery (n=5), percutaneous needle biopsy (n=3), and clinical follow-up (n=5). Contrast-enhanced CT was available for all patients : five underwent dynamic study and ERCP was performed in 12. On CT and ERCP, both groups were evaluated with regard to the presence and degree of pancreatic ductal dilatation (greater or less than 50 % of total gland width), double duct sign, enhancement pattern, pancreatic parenchymal calcification (site and distribution pattern), mass identification, the direction of infiltration, pancreatic parenchymal atrophy, configuration at the site of obstruction in the pancreatic and common bile duct, lymphadenopathy, vascular encasement, and vascular engorgement or increased collateral vessels in the peripancreatic space. Seven of 13 patients had suffered chronic alcoholism. Serum CA19-9 levels were normal in all patients except one. Common CT and ERCP findings of mass-forming chronic pancreatitis included pancreatic duct dilatation (92.3%), double duct sign (69.2%), inhomogeneous enhancement of the mass (69.2%), and the presence of calcification (61.5%). Patterns of pancreatic duct dilation were irregular in five patients (38.4%) and smooth in three (23.1%). In all patients, duct dilatation was less than 50% of total gland width. Enhancement patterns of the pancreatic mass were inhomogeneous (69.2%), a nonenhancing low attenuation mass (15.3%), and homogeneous enhancement (15.3%). Configuration at the site of obstruction in the pancreatic duct was abrupt termination in two patients (15.4%) and smooth termination in two (15.4%). The common bile duct teminated abruptly in three patients (23.1%), and in four (30.8%) smooth narrowing was abserved. Common findings of mass-forming chronic pancreatitis were duct dilatation of less than 50% of total

  11. Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site

    Directory of Open Access Journals (Sweden)

    Andrew R. Pepper

    2017-06-01

    Full Text Available Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of “healthy” human donor pancreata restricts the broader application of this effective curative therapy. “β-Like” cells derived from human embryonic stem cells (hESC, with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion. Here we report long-term diabetes correction in mice transplanted with hESC-derived pancreatic endoderm cells (PECs in a prevascularized subcutaneous site. This advancement mitigates chronic foreign-body response, utilizes a device- and growth factor-free approach, facilitates in vivo differentiation of PECs into glucose-responsive insulin-producing cells, and reliably restores glycemic control. Basal and stimulated human C-peptide secretion was detected throughout the study, which was abolished upon graft removal. Recipient mice demonstrated physiological clearance of glucose in response to metabolic challenge and safely retrieved grafts contained viable glucose regulatory cells.

  12. Chronic Pancreatitis.

    Science.gov (United States)

    Stram, Michelle; Liu, Shu; Singhi, Aatur D

    2016-12-01

    Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. A unifying concept: pancreatic ductal anatomy both predicts and determines the major complications resulting from pancreatitis.

    Science.gov (United States)

    Nealon, William H; Bhutani, Manoop; Riall, Taylor S; Raju, Gottumukkala; Ozkan, Orhan; Neilan, Ryan

    2009-05-01

    Precepts about acute pancreatitis, necrotizing pancreatitis, and pancreatic fluid collections or pseudocyst rarely include the impact of pancreatic ductal injuries on their natural course and outcomes. We previously examined and established a system to categorize ductal changes. We sought a unifying concept that may predict course and direct therapies in these complex patients. We use our system categorizing ductal changes in pseudocyst of the pancreas and severe necrotizing pancreatitis (type I, normal duct; type II, duct stricture; type III, duct occlusion or "disconnected duct"; and type IV, chronic pancreatitis). From 1985 to 2006, a policy was implemented of routine imaging (cross-sectional, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography). Clinical outcomes were measured. Among 563 patients with pseudocyst, 142 resolved spontaneously (87% of type I, 5% of type II, and no type III, and 3% of type IV). Percutaneous drainage was successful in 83% of type I, 49% of type II, and no type III or type IV. Among 174 patients with severe acute pancreatitis percutaneous drainage was successful in 64% of type I, 38% of type II, and no type III. Operative debridement was required in 39% of type I and 83% and 85% of types II and III, respectively. Persistent fistula after debridement occurred in 27%, 54%, and 85% of types I, II, and III ducts, respectively. Late complications correlated with duct injury. Pancreatic ductal changes predict spontaneous resolution, success of nonoperative measures, and direct therapies in pseudocyst. Ductal changes also predict patients with necrotizing pancreatitis who are most likely to have immediate and delayed complications.

  14. Efficacy of irreversible electroporation in human pancreatic adenocarcinoma: advanced murine model

    Directory of Open Access Journals (Sweden)

    Prejesh Philips

    Full Text Available Irreversible electroporation (IRE is a promising cell membrane ablative modality for pancreatic cancer. There have been recent concerns regarding local recurrence and the potential use of IRE as a debulking (partial ablation modality. We hypothesize that incomplete ablation leads to early recurrence and a more aggressive biology. We created the first ever heterotopic murine model by inoculating BALB/c nude mice in the hindlimb with a subcutaneous injection of Panc-1 cells, an immortalized human pancreatic adenocarcinoma cell line. Tumors were allowed to grow from 0.75 to 1.5 cm and then treated with the goal of complete ablation or partial ablation using standard IRE settings. Animals were recovered and survived for 2 days (n = 6, 7 (n = 6, 14 (n = 6, 21 (n = 6, 30 (n = 8, and 60 (n = 8 days. All 40 animals/tumors underwent successful IRE under general anesthesia with muscle paralysis. The mean tumor volume of the animals undergoing ablation was 1,447.6 mm3 ± 884. Histologically, in the 14-, 21-, 30-, and 60-day survival groups the entire tumor was nonviable, with a persistent tumor nodule completely replaced fibrosis. In the group treated with partial ablation, incomplete electroporation/recurrences (N = 10 animals were seen, of which 66% had confluent tumors and this was a significant predictor of recurrence (P < 0.001. Recurrent tumors were also significantly larger (mean 4,578 mm3 ± SD 877 versus completed electroporated tumors 925.8 ± 277, P < 0.001. Recurrent tumors had a steeper growth curve (slope = 0.73 compared with primary tumors (0.60, P = 0.02. Recurrent tumors also had a significantly higher percentage of EpCAM expression, suggestive of stem cell activation. Tumors that recur after incomplete electroporation demonstrate a biologically aggressive tumor that could be more resistant to standard of care chemotherapy. Clinical correlation of this data is limited, but should be considered when IRE of pancreatic cancer is being

  15. Nickel nanowires induced and reactive oxygen species mediated apoptosis in human pancreatic adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Kleve MG

    2011-07-01

    Full Text Available Md. Zakir Hossain1, Maurice G Kleve21Applied Biosciences (Bionanotechnology Research, Department of Applied Science, 2Molecular Biotechnology and Microscopy Laboratory, Department of Biology, University of Arkansas at Little Rock, Little Rock, Arkansas, USABackground: The ability to evade apoptosis is one of the key properties of cancer. The apoptogenic effect of nickel nanowires (Ni NWs on cancer cell lines has never been adequately addressed. Due to the unique physicochemical characteristics of Ni NWs, we envision the development of a novel anticancer therapeutics specifically for pancreatic cancer. Thus, we investigated whether Ni NWs induce ROS-mediated apoptosis in human pancreatic adenocarcinoma (Panc-1 cells. Methods: In this study Ni NWs were fabricated using the electrodeposition method. Synthesized Ni NWs were physically characterized by energy dispersive X-ray analysis, UV-Vis spectroscopy of NanoDrop 2000 (UV-Vis, magnetization study, scanning electron microscopy, and transmission electron microscopy. Assessment of morphological apoptotic characteristics by phase contrast microscopy (PCM, Ni-NWs-induced apoptosis staining with ethidium bromide (EB and acridine orange (AO followed by fluorescence microscopy (FM was performed. For molecular biological and biochemical characterization, Panc-1 cell culture and cytotoxic effect of Ni NWs were determined by using 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT assay. Quantitative apoptosis was analyzed by flow cytometry staining with propidium iodide through cell cycle arrest and generation of ROS using 2', 7'-dichlorofluorescein diacetate fluorescence intensity. In all experiments, Panc-1 cancer cells without any treatment were used as the negative controls.Results: The intracellular uptake of Ni NWs through endocytosis by Panc-1 cells was observed by PCM. EB and AO staining of FM and MTT assay qualitatively and quantitatively confirmed the extent of apoptosis. Flow

  16. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  17. [CCL21 promotes the metastasis of human pancreatic cancer Panc-1 cells via epithelial- mesenchymal transition].

    Science.gov (United States)

    Liu, Qing; Chen, Fangfang; Duan, Tanghai; Zhu, Haitao; Xie, Xiaodong; Wu, Yingying; Zhang, Zhijian; Wang, Dongqing

    2015-01-01

    To investigate the mechanism underlying that chemokine (C-C motif) ligand 21 (CCL21) promotes the metastasis ability of human pancreatic cancer Panc-1 cells. Transwell(TM) was used to access the chemotaxis effect of CCL21 on Panc-1 cells. Real-time quantitative PCR was performed to detect the expression of C-C chemokine receptor type 7 (CCR7) mRNA in the upper and lower chambers. Immunofluorescence staining and Western blotting were employed to examine the expressions of the epithelial-mesenchymal transition (EMT)-related proteins and CD133 of Panc-1 cells in the lower chamber, which were compared with those of the upper chamber as the control. The numbers of the Panc-1 cells induced by 0, 50, 100, 200 ng/mL CCL21 were 13.00 ± 3.00, 78.00 ± 9.00, 161.00 ± 11.00, 281.00 ± 17.00, respectively; with the increase of the concentration of CCL21, there were more cells migrating from the upper to the lower chamber; and the cells in the lower chamber expressed higher level of CCR7 mRNA than the ones staying in the upper chamber. The relative protein expressions of MMP-9, vimentin, E-cadherin and CD133 in the lower chamber were 0.42 ± 0.04, 0.36 ± 0.03, 0.12 ± 0.02, 0.46 ± 0.03, respectively, which were statistically significantly different from those in the upper chamber (0.15 ± 0.02, 0.25 ± 0.02, 0.25 ± 0.03, 0.13 ± 0.02, respectively). CCL21/CCR7 axis maybe play an important role in the metastasis of pancreatic cancer stem cells by EMT and up-regulation of MMP-9.

  18. Structure of Human Pancreatic Lipase-Related Protein 2 with the Lid in an Open Conformation

    Energy Technology Data Exchange (ETDEWEB)

    Eydoux, Cecilia; Spinelli, Silvia; Davis, Tara L.; Walker, John R.; Seitova, Alma; Dhe-Paganon, Sirano; De Caro, Alain; Cambillau, Christian; Carriere, Frederic (CNRS-UMR); (Toronto)

    2008-10-02

    Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, the lid, which normally undergoes conformational changes only upon addition of lipids or amphiphiles. Structures of PL with their lids in the open and functional conformation have required cocrystallization with amphiphiles. Here we report two crystal structures of wild-type and unglycosylated human pancreatic lipase-related protein 2 (HPLRP2) with the lid in an open conformation in the absence of amphiphiles. These structures solved independently are strikingly similar, with some residues of the lid being poorly defined in the electron-density map. The open conformation of the lid is however different from that previously observed in classical liganded PL, suggesting different kinetic properties for HPLRP2. Here we show that the HPLRP2 is directly inhibited by E600, does not present interfacial activation, and acts preferentially on substrates forming monomers or small aggregates (micelles) dispersed in solution like monoglycerides, phospholipids and galactolipids, whereas classical PL displays reverse properties and a high specificity for unsoluble substrates like triglycerides and diglycerides forming oil-in-water interfaces. These biochemical properties imply that the lid of HPLRP2 is likely to spontaneously adopt in solution the open conformation observed in the crystal structure. This open conformation generates a large cavity capable of accommodating the digalactose polar head of galactolipids, similar to that previously observed in the active site of the guinea pig PLRP2, but absent from the classical PL. Most of the structural and kinetic properties of HPLRP2 were found to be different from those of rat PLRP2, the structure of which was previously obtained with the lid in a closed conformation. Our findings illustrate the essential role of the lid in determining the substrate specificity and the mechanism of action of lipases.

  19. Experimental study of 32P-CP-PLLA microparticle on human pancreatic carcinoma in nude mice

    International Nuclear Information System (INIS)

    Wang Lizhen; Yang Min; Xu Yuping; Pan Donghui; Huang Peilin; Liu Lu; Shao Guoqiang

    2011-01-01

    Objective: To study the therapeutic and toxic effects of 32 P-chromic phosphate-poly (L-lactic) acid ( 32 P-CP-PLLA) microparticle intratumoral administration into BALB/c nude mice bearing BxPc-3 human pancreatic carcinoma. Methods: Twenty four nude mice bearing tumors were injected with 0, 9.3, 18.5 and 37.0 M Bq 32 P-CP-PLLA microparticle, respectively. The relative tumor growth rates were observed every day, and white blood cells, platelets and body weight were measured. At 14 d after administration, the tumors were removed, histological examination and immunohistochemical analysis were performed. Results: The relative tumor growth rates of each treatment group was lower than 40%. Histological examination showed the degenerative necrosis at the site nearby the microparticle. Immunohistochemical analysis showed that the Microvessel density (MVD) and the expression of Bcl-2 in treated group were lower than those in control group.In contrast, the expression of bax in treated group were higher than those in control group. The ratio of Bcl-2/Bax protein significantly decreased in the treatment group,which were 3.83 ± 0.43, 0.47 ± 0.13, 1.10 ± 0.32, 2.19 ± 0.57 for 0, 9.3, 18.5 and 37.0 MBq 32 P-CP-PLLA microparticle, respectively (t=2.36-2.77, P<0.05). MVD were 31.2 ± 2.3, 23.8 ± 1.5, 14.8 ±0.8, 11.0 ± 1.2, respectively. Dose dependence was observed in both HE and IHC staining after 14 d treatment (t=2.30-2.57, P<0.05). Conclusions: Intratumoral injection of 32 P-CP-PLLA microparticle might be a safe, easy and effective radionuclide interventional therapy for pancreatic carcinoma. (authors)

  20. Computed tomographic appearance of resectable pancreatic carcinoma

    International Nuclear Information System (INIS)

    Itai, Y.; Araki, T.; Tasaka, A.; Maruyama, M.

    1982-01-01

    Thirteen patients with resectable pancreatic carcinoma were examined by computed tomography (CT). Nine had a mass, 2 had dilatation of the main pancreatic duct, 1 appeared to have ductal dilatation, and 1 had no sign of abnormality. Resectable carcinoma was diagnosed retrospectively in 8 cases, based on the following criteria: a mass with a distinct contour, frequently containing a tiny or irregular low-density area and accompanied by dilatation of the caudal portion of the main pancreatic duct without involvement of the large vessels, liver, or lymph nodes. Including unresectable cancer, chronic pancreatitis, and obstructive jaundice from causes other than cancer, the false-positive rate was less than 6%. However, a small cancer without change in pancreatic contour is difficult to detect with CT

  1. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Karnevi, Emelie; Said, Katarzyna; Andersson, Roland; Rosendahl, Ann H

    2013-01-01

    Epidemiological studies have shown direct associations between type 2 diabetes and obesity, both conditions associated with hyperglycaemia and hyperinsulinemia, and the risk of pancreatic cancer. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent population studies indicate that the incidence of pancreatic cancer is reduced among diabetics taking metformin. In this study, the effects of exposure of pancreatic cancer cells to high glucose levels on their growth and response to metformin were investigated. The human pancreatic cancer cell lines AsPC-1, BxPC-3, PANC-1 and MIAPaCa-2 were grown in normal (5 mM) or high (25 mM) glucose conditions, with or without metformin. The influence by metformin on proliferation, apoptosis and the AMPK and IGF-IR signalling pathways were evaluated in vitro. Metformin significantly reduced the proliferation of pancreatic cancer cells under normal glucose conditions. Hyperglycaemia however, protected against the metformin-induced growth inhibition. The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPK Thr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt. Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, exposure to high glucose levels promoted a more robust IGF-I response and Akt activation which correlated to stimulated AMPK Ser485 phosphorylation and impaired AMPK Thr172 phosphorylation, resulting in reduced anti-proliferative and apoptotic effects by metformin. Our results indicate that metformin has direct anti-tumour activities in pancreatic cancer cells involving AMPK Thr172 activation and suppression of the insulin/IGF signalling pathways

  2. New developments in diagnosis and non-surgical treatment of chronic pancreatitis.

    Science.gov (United States)

    Inui, Kazuo; Yoshino, Junji; Miyoshi, Hironao; Yamamoto, Satoshi; Kobayashi, Takashi

    2013-12-01

    Chronic pancreatitis is progressive and irreversible, leading to digestive and absorptive disorders by destruction of the exocrine pancreas and to diabetes mellitus by destruction of the endocrine pancreas. When complications such as pancreatolithiasis and pseudocyst occur, elevated pancreatic ductal pressure exacerbates pain and induces other complications, worsening the patient's general condition. Combined treatment with extracorporeal shock-wave lithotripsy and endoscopic lithotripsy is a useful, minimally invasive, first-line treatment approach that can preserve pancreatic exocrine function. Pancreatic duct stenosis elevates intraductal pressure and favor both pancreatolithiasis and pseudocyst formation, making effective treatment vitally important. Endoscopic treatment of benign pancreatic duct stenosis stenting frequently decreases pain in chronic pancreatitis. Importantly, stenosis of the main pancreatic duct increases risk of stone recurrence after treatment of pancreatolithiasis. Recently, good results were reported in treating pancreatic duct stricture with a fully covered self-expandable metallic stent, which shows promise for preventing stone recurrence after lithotripsy in patients with pancreatic stricture. Chronic pancreatitis has many complications including pancreatic carcinoma, pancreatic atrophy, and loss of exocrine and endocrine function, as well as frequent recurrence of stones after treatment of pancreatolithiasis. As early treatment of chronic pancreatitis is essential, the new concept of early chronic pancreatitis, including characteristics findings in endoscopic ultrasonograms, is presented. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  3. Bile duct stricture

    Science.gov (United States)

    ... duct, the tube that moves bile from the liver to the small intestine. Bile is a substance that helps with digestion. ... causes of this condition include: Cancer of the bile duct, liver or pancreas Damage and scarring due to a ...

  4. A case of fascioliasis in common bile duct

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Soo Youn; Park, Cheol Min; Chung, Kyu Byung; Lee, Chang Hong; Park, Seung Chul; Choi, Sang Yong; Lim, Han Jong [Korea University College of Medicine, Seoul (Korea, Republic of)

    1989-10-15

    A case of Fascioliasis of common bile duct is confirmed by visualization of adult fluke. Fascioliasis caused by Fasciola hepatica, is common parasitic disease in cattle and sheep. Human is an accidental host. ERCP demonstrated irregular linear conglomerated filling defects in common bile duct. Through surgical intervention, we found adult flukes of F. hepatica and adenomatous hyperplasia of common bile duct.

  5. A case of fascioliasis in common bile duct

    International Nuclear Information System (INIS)

    Ham, Soo Youn; Park, Cheol Min; Chung, Kyu Byung; Lee, Chang Hong; Park, Seung Chul; Choi, Sang Yong; Lim, Han Jong

    1989-01-01

    A case of Fascioliasis of common bile duct is confirmed by visualization of adult fluke. Fascioliasis caused by Fasciola hepatica, is common parasitic disease in cattle and sheep. Human is an accidental host. ERCP demonstrated irregular linear conglomerated filling defects in common bile duct. Through surgical intervention, we found adult flukes of F. hepatica and adenomatous hyperplasia of common bile duct

  6. Congenital double bile duct presenting as recurrent cholangitis in a child

    Directory of Open Access Journals (Sweden)

    K.D. Chakravarty

    2015-12-01

    Full Text Available Double common bile duct (DCBD is a rare congenital anomaly. Most of these bile duct anomalies are associated with bile duct stones, anomalous pancreaticobiliary junction (APBJ, pancreatitis and bile duct or gastric cancers. Early detection and treatment is important to avoid long term complications. Surgical resection of the anomalous bile duct and reconstruction of the biliary enteric anastomosis is the treatment of choice. We report a rare case of DCBD anomaly in a girl, who presented with recurrent cholangitis. She had type Va DCBD anomaly. She underwent successful resection of the bile duct and reconstruction of the biliary enteric anastomosis. Preoperative imaging and diagnosis of the congenital biliary anomaly is very important to avoid intraoperative bile duct injury. Review of the literature shows very few cases of type Va DCBD, presenting with either bile duct stones or APBJ.

  7. Conservative treatment of chronic pancreatitis.

    Science.gov (United States)

    Löhr, J-Matthias; Haas, Stephen L; Lindgren, Fredrik; Enochsson, Lars; Hedström, Aleksandra; Swahn, Fredrik; Segersvärd, Ralf; Arnelo, Urban

    2013-01-01

    Chronic pancreatitis is a progressive inflammatory disease giving rise to several complications that need to be treated accordingly. Because pancreatic surgery has significant morbidity and mortality, less invasive therapy seems to be an attractive option. This paper reviews current state-of-the-art strategies to treat chronic pancreatitis without surgery and the current guidelines for the medical therapy of chronic pancreatitis. Endoscopic therapy of complications of chronic pancreatitis such as pain, main pancreatic duct strictures and stones as well as pseudocysts is technically feasible and safe. The long-term outcome, however, is inferior to definitive surgical procedures such as resection or drainage. On the other hand, the medical therapy of pancreatic endocrine and exocrine insufficiency is well established and evidence based. Endoscopic therapy may be an option to bridge for surgery and in children/young adolescents and those unfit for surgery. Pain in chronic pancreatitis as well as treatment of pancreatic exocrine insufficiency follows established guidelines. Copyright © 2013 S. Karger AG, Basel.

  8. [Acute pancreatitis associated with hypercalcaemia].

    Science.gov (United States)

    Tun-Abraham, Mauro Enrique; Obregón-Guerrero, Gabriela; Romero-Espinoza, Larry; Valencia-Jiménez, Javier

    2015-01-01

    Hypercalcaemia due to primary hyperparathyroidism is a rare cause of acute pancreatitis, with a reported prevalence of 1.5 to 8%. There is no clear pathophysiological basis, but elevated parathyroid hormone and high serum calcium levels could be responsible for calcium deposit in the pancreatic ducts and activation of pancreatic enzymes, which may be the main risk factor for developing acute pancreatitis. The aim of this report is to describe four cases. Four cases are reported of severe pancreatitis associated with hypercalcaemia secondary to primary hyperparathyroidism; three of them with complications (two pseudocysts and one pancreatic necrosis). Cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, studies showed the parathyroid adenoma. Surgical resection was the definitive treatment in all four cases. None of the patients had recurrent acute pancreatitis events during follow-up. Acute pancreatitis secondary to hypercalcaemia of primary hyperparathyroidism is rare; however, when it occurs it is associated with severe pancreatitis. It is suspected in patients with elevated serum calcium and high parathyroid hormone levels. Imaging techniques such as cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, should be performed, to confirm clinical suspicion. Surgical resection is the definitive treatment with excellent results. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  9. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells.

    Science.gov (United States)

    Pavlikova, Nela; Smetana, Pavel; Halada, Petr; Kovar, Jan

    2015-10-01

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Establishment and characterization of a new human pancreatic adenocarcinoma cell line with high metastatic potential to the lung

    International Nuclear Information System (INIS)

    Kalinina, Tatyana; Simon, Ronald; Otto, Benjamin; Dierlamm, Judith; Schwarzenbach, Heidi; Effenberger, Katharina E; Bockhorn, Maximilian; Izbicki, Jakob R; Yekebas, Emre F; Güngör, Cenap; Thieltges, Sabrina; Möller-Krull, Maren; Murga Penas, Eva Maria; Wicklein, Daniel; Streichert, Thomas; Schumacher, Udo; Kalinin, Viacheslav

    2010-01-01

    Pancreatic cancer is still associated with devastating prognosis. Real progress in treatment options has still not been achieved. Therefore new models are urgently needed to investigate this deadly disease. As a part of this process we have established and characterized a new human pancreatic cancer cell line. The newly established pancreatic cancer cell line PaCa 5061 was characterized for its morphology, growth rate, chromosomal analysis and mutational analysis of the K-ras, EGFR and p53 genes. Gene-amplification and RNA expression profiles were obtained using an Affymetrix microarray, and overexpression was validated by IHC analysis. Tumorigenicity and spontaneous metastasis formation of PaCa 5061 cells were analyzed in pfp -/- /rag2 -/- mice. Sensitivity towards chemotherapy was analysed by MTT assay. PaCa 5061 cells grew as an adhering monolayer with a doubling time ranging from 30 to 48 hours. M-FISH analyses showed a hypertriploid complex karyotype with multiple numerical and unbalanced structural aberrations. Numerous genes were overexpressed, some of which have previously been implicated in pancreatic adenocarcinoma (GATA6, IGFBP3, IGFBP6), while others were detected for the first time (MEMO1, RIOK3). Specifically highly overexpressed genes (fold change > 10) were identified as EGFR, MUC4, CEACAM1, CEACAM5 and CEACAM6. Subcutaneous transplantation of PaCa 5061 into pfp -/- /rag2 -/- mice resulted in formation of primary tumors and spontaneous lung metastasis. The established PaCa 5061 cell line and its injection into pfp -/- /rag2 -/- mice can be used as a new model for studying various aspects of the biology of human pancreatic cancer and potential treatment approaches for the disease

  11. Examining the effects of hyperglycemia on pancreatic endocrine function in humans

    DEFF Research Database (Denmark)

    Solomon, Thomas P J; Knudsen, Sine H; Karstoft, Kristian

    2012-01-01

    Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease.......Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease....

  12. Chronic pancreatitis with pancreaticolithiasis and pseudocyst in a 5-year-old boy with homozygous SPINK1 mutation

    Energy Technology Data Exchange (ETDEWEB)

    Kuehn, Axel C.; Hirsch, Wolfgang [University of Leipzig, Department of Diagnostic Radiology - Pediatric Radiology, Faculty of Medicine, Leipzig (Germany); Teich, Niels; Caca, Karel [University of Leipzig, Department of Internal Medicine II - Gastroenterology / Hepatology, Faculty of Medicine, Leipzig (Germany); Limbach, Anne [University of Leipzig, Department of Pediatrics, Faculty of Medicine, Leipzig (Germany)

    2005-09-01

    We report a 5-year-old boy with a 5-month history of symptoms owing to chronic pancreatitis. Abdominal imaging revealed a large pseudocyst in the pancreatic tail and concretions in the main pancreatic duct. Successful endoscopic papillotomy and stent implantation were performed. Genetic testing showed homozygous SPINK1-N34S mutation, which is an established risk factor for chronic pancreatitis. (orig.)

  13. Chronic pancreatitis with pancreaticolithiasis and pseudocyst in a 5-year-old boy with homozygous SPINK1 mutation

    International Nuclear Information System (INIS)

    Kuehn, Axel C.; Hirsch, Wolfgang; Teich, Niels; Caca, Karel; Limbach, Anne

    2005-01-01

    We report a 5-year-old boy with a 5-month history of symptoms owing to chronic pancreatitis. Abdominal imaging revealed a large pseudocyst in the pancreatic tail and concretions in the main pancreatic duct. Successful endoscopic papillotomy and stent implantation were performed. Genetic testing showed homozygous SPINK1-N34S mutation, which is an established risk factor for chronic pancreatitis. (orig.)

  14. Histone modification enhances the effectiveness of IL-13 receptor targeted immunotoxin in murine models of human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Puri Raj K

    2011-04-01

    Full Text Available Abstract Background Interleukin-13 Receptor α2 (IL-13Rα2 is a tumor-associated antigen and target for cancer therapy. Since IL-13Rα2 is heterogeneously overexpressed in a variety of human cancers, it would be highly desirable to uniformly upregulate IL-13Rα2 expression in tumors for optimal targeting. Methods We examined epigenetic regulation of IL-13Rα2 in a murine model of human pancreatic cancer by Bisulfite-PCR, sequencing for DNA methylation and chromatin immunoprecipitation for histone modification. Reverse transcription-PCR was performed for examining changes in IL-13Rα2 mRNA expression after treatment with histone deacetylase (HDAC and c-jun inhibitors. In vitro cytotoxicity assays and in vivo testing in animal tumor models were performed to determine whether HDAC inhibitors could enhance anti-tumor effects of IL-13-PE in pancreatic cancer. Mice harboring subcutaneous tumors were treated with HDAC inhibitors systemically and IL-13-PE intratumorally. Results We found that CpG sites in IL-13Rα2 promoter region were not methylated in all pancreatic cancer cell lines studied including IL-13Rα2-positive and IL-13Rα2-negative cell lines and normal cells. On the other hand, histones at IL-13Rα2 promoter region were highly-acetylated in IL-13Rα2-positive but much less in receptor-negative pancreatic cancer cell lines. When cells were treated with HDAC inhibitors, not only histone acetylation but also IL-13Rα2 expression was dramatically enhanced in receptor-negative pancreatic cancer cells. In contrast, HDAC inhibition did not increase IL-13Rα2 in normal cell lines. In addition, c-jun in IL-13Rα2-positive cells was expressed at higher level than in negative cells. Two types of c-jun inhibitors prevented increase of IL-13Rα2 by HDAC inhibitors. HDAC inhibitors dramatically sensitized cancer cells to immunotoxin in the cytotoxicity assay in vitro and increased IL-13Rα2 in the tumors subcutaneously implanted in the immunodeficient

  15. [Pancreatic anastomosis in operative treatment of chronic pancreatitis].

    Science.gov (United States)

    Bellon, E; Izbicki, J R; Bockhorn, M

    2017-01-01

    Chronic pancreatitis (CP) is an irreversible, inflammatory process, which is characterized by progressive fibrosis of the pancreas and leads to abdominal pain, endocrine and exocrine insufficiency. Surgical therapy is indicated by the absence of pain relief and local complications. The target of the surgical approach is to relieve the pancreatic and bile ducts and resection of the fibrotic and calcified parenchyma. Drainage procedures, such as the Partington-Rochelle method, are used in patients with isolated congestion of the pancreatic duct without further organ complications, such as inflammatory processes of the pancreatic head; however, patients with CP often have an inflammatory swelling of the pancreatic head. In this case classical pancreatoduodenectomy (PD) or organ-sparing duodenum-preserving pancreatic head resection (DPPHR) with its various techniques (e.g. Beger, Frey, Bern and V‑shape) can be applied. Due to similar long-term results PD should be carried out in cases of suspicion or detection of malignancies and DPPHR for treatment of CP.

  16. The functional performance of microencapsulated human pancreatic islet-derived precursor cells.

    Science.gov (United States)

    Montanucci, Pia; Pennoni, Ilaria; Pescara, Teresa; Blasi, Paolo; Bistoni, Giovanni; Basta, Giuseppe; Calafiore, Riccardo

    2011-12-01

    We have examined long-term cultured, human islet-derived stem/precursor cells (hIPC). Whole human islets (HI) were obtained by multi-enzymatic digestion of cadaveric donor pancreases, plated on tissue flasks, and allowed to adhere and expand for several in vitro passages, in order to obtain hIPC. We detected specific stem cell markers (Oct-4, Sox-2, Nanog, ABCG2, Klf-4, CD117) in both intact HI and hIPC. Moreover, hIPC while retaining the expression of Glut-2, Pdx-1, CK-19, and ICA-512, started re-expressing Ngn3, thereby indicating acquisition of a specific pancreatic islet beta cell-oriented phenotype identity. The intrinsic plasticity of hIPC was documented by their ability to differentiate into various germ layer-derived cell phenotypes (ie, osteocytic, adipocytic and neural), including endocrine cells associated with insulin secretory capacity. To render hIPC suitable for transplantation we have enveloped them within our highly purified, alginate-based microcapsules. Upon intraperitoneal graft in NOD/SCID mice we have observed that the microcapsules acted as three-dimensional niches favouring post-transplant hIPC differentiation and acquisition of beta cell-like functional competence. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Radioimmunodetection of human pancreatic tumor xenografts using DU-PAN II monoclonal antibody

    International Nuclear Information System (INIS)

    Nakamura, Kayoko; Kubo, Atsushi; Hashimoto, Shozo; Furuuchi, Takayuki; Abe, Osahiko; Takami, Hiroshi.

    1988-01-01

    The potential of DU-PAN II, monoclonal antibody (IgM), which was raised against the human tumor cell line, was evaluated for radioimmunodetection of human pancreatic tumors (PAN-5-JCK and EXP-58) grown in nude mice. 125 I-labeled DU-PAN II was accumulated into PAN-5-JCK producing DU-PAN II antigen with a tumor-to-blood ratio of 2.72 ± 3.00, but it did not localize in EXP-58 because of insufficient DU-PAN II. There was no significant uptake of 125 I-nonimmunized IgM in PAN-5-JCK. These facts indicated the specific tumor uptake of DU-PAN II. Excellent images of the tumor PAN-5-JCK were obtained 3 days after the injection of 125 I-DU-PAN II. Gel chromatography was also investigated with respect to the plasma taken from mice injected with antibody, or incubated with antibody in vitro. The results indicate that circulating antigen affected the tumor uptake of DU-PAN II: The more the tumor grew, the higher the amount of antigen excreted into the blood, leading to the degradation of DU-PAN II before it reached the tumor sites. Consequently, the immunoscintigram of the small tumor was remarkably clear. The catabolism and the radiolysis of the labeled IgM injected are critical points in applying immunoscintigraphy. (author)

  18. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel

    2011-01-01

    of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP...

  19. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic ß-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel

    2011-01-01

    of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic ß-cells, and to examine this in relation to ß-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP...

  20. Constituents of the Rhizomes of Boesenbergia pandurata and Their Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Line.

    Science.gov (United States)

    Nguyen, Nhan Trung; Nguyen, Mai Thanh Thi; Nguyen, Hai Xuan; Dang, Phu Hoang; Dibwe, Dya Fita; Esumi, Hiroyasu; Awale, Suresh

    2017-01-27

    Human pancreatic cancer cell lines have a remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions represents a novel antiausterity strategy in anticancer drug discovery. In this investigation, a methanol extract of the rhizomes of Boesenbergia pandurata showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC 50 value of 6.6 μg/mL. Phytochemical investigation of this extract led to the isolation of 15 compounds, including eight new cyclohexene chalcones (1-8). The structures of the new compounds were elucidated by NMR spectroscopic data analysis. Among the isolated compounds obtained, isopanduratin A1 (14) and nicolaioidesin C (15) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions, with PC 50 values of 1.0 and 0.84 μM, respectively.

  1. Chemical Constituents of Mangifera indica and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line.

    Science.gov (United States)

    Nguyen, Hai Xuan; Do, Truong Nhat Van; Le, Tho Huu; Nguyen, Mai Thanh Thi; Nguyen, Nhan Trung; Esumi, Hiroyasu; Awale, Suresh

    2016-08-26

    Human pancreatic cancer cell lines such as PANC-1 have an altered metabolism, enabiling them to tolerate and survive under extreme conditions of nutrient starvation. The search for candidates that inhibit their viability during nutrition starvation represents a novel antiausterity strategy in anticancer drug discovery. A methanol extract of the bark of Mangifera indica was found to inhibit the survival of PANC-1 human pancreatic cancer cells preferentially under nutrient-deprived conditions with a PC50 value of 15.5 μg/mL, without apparent toxicity, in normal nutrient-rich conditions. Chemical investigation on this bioactive extract led to the isolation of 19 compounds (1-19), including two new cycloartane-type triterpenes, mangiferolate A (1) and mangiferolate B (2). The structures of 1 and 2 were determined by NMR spectroscopic analysis. Among the isolated compounds, mangiferolate B (2) and isoambolic acid (12) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under the nutrition-deprived condition with PC50 values of 11.0 and 4.8 μM, respectively.

  2. Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice.

    Science.gov (United States)

    Bruin, Jennifer E; Rezania, Alireza; Xu, Jean; Narayan, Kavitha; Fox, Jessica K; O'Neil, John J; Kieffer, Timothy J

    2013-09-01

    Islet transplantation is a promising cell therapy for patients with diabetes, but it is currently limited by the reliance upon cadaveric donor tissue. We previously demonstrated that human embryonic stem cell (hESC)-derived pancreatic progenitor cells matured under the kidney capsule in a mouse model of diabetes into glucose-responsive insulin-secreting cells capable of reversing diabetes. However, the formation of cells resembling bone and cartilage was a major limitation of that study. Therefore, we developed an improved differentiation protocol that aimed to prevent the formation of off-target mesoderm tissue following transplantation. We also examined how variation within the complex host environment influenced the development of pancreatic progenitors in vivo. The hESCs were differentiated for 14 days into pancreatic progenitor cells and transplanted either under the kidney capsule or within Theracyte (TheraCyte, Laguna Hills, CA, USA) devices into diabetic mice. Our revised differentiation protocol successfully eliminated the formation of non-endodermal cell populations in 99% of transplanted mice and generated grafts containing >80% endocrine cells. Progenitor cells developed efficiently into pancreatic endocrine tissue within macroencapsulation devices, despite lacking direct contact with the host environment, and reversed diabetes within 3 months. The preparation of cell aggregates pre-transplant was critical for the formation of insulin-producing cells in vivo and endocrine cell development was accelerated within a diabetic host environment compared with healthy mice. Neither insulin nor exendin-4 therapy post-transplant affected the maturation of macroencapsulated cells. Efficient differentiation of hESC-derived pancreatic endocrine cells can occur in a macroencapsulation device, yielding glucose-responsive insulin-producing cells capable of reversing diabetes.

  3. Localization of a membrane glycoprotein in benign fibrocystic disease and infiltrating duct carcinomas of the human breast with the use of a monoclonal antibody to guinea pig milk fat globule membrane.

    Science.gov (United States)

    Greenwalt, D. E.; Johnson, V. G.; Kuhajda, F. P.; Eggleston, J. C.; Mather, I. H.

    1985-01-01

    With monoclonal antibody D-274, raised against guinea pig milk fat globule membrane, the distribution of mucinlike glycoproteins of Mrs greater than or equal to 400,000 was determined in benign fibrocystic disease and infiltrating duct carcinoma of the human breast. These glycoproteins, called collectively PAS-I, were detected in 19 out of 20 cases of benign fibrocystic disease and in at least 26 out of 47 cases of infiltrating duct carcinoma. PAS-I was concentrated on luminal surfaces of ducts and alveoli in morphologically differentiated regions of the tumors. In areas where the glandular nature of the tissue was less evident in infiltrating duct carcinoma, the PAS-I determinant recognized by antibody D-274 was present on irregular luminal surfaces and in the cytoplasm. There was a negative correlation between the short-term recurrence (less than 2 years) of infiltrating duct carcinoma and the detection of strong positive staining with antibody D-274. The results are discussed with reference to recent studies on PAS-I in human breast tissue using monoclonal antibodies raised against human milk fat globule membrane. Images Figure 1 Figure 2 Figure 3 PMID:2579563

  4. Pancreatic Cancer

    Science.gov (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  5. Pancreatic Cysts

    Science.gov (United States)

    ... enzymes become prematurely active and irritate the pancreas (pancreatitis). Pseudocysts can also result from injury to the ... alcohol use and gallstones are risk factors for pancreatitis, and pancreatitis is a risk factor for pseudocysts. ...

  6. Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Ozaki, Yayoi; Hamano, Hideaki; Oguchi, Kazuhiro

    2008-01-01

    Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-PET findings between the two conditions. We compared FDG-PET findings between 15 patients with autoimmune pancreatitis and 26 patients with pancreatic cancer. The findings were evaluated visually or semiquantitatively using the maximum standardized uptake value and the accumulation pattern of FDG. FDG uptake was found in all 15 patients with autoimmune pancreatitis, whereas it was found in 19 of 26 patients (73.1%) with pancreatic cancer. An accumulation pattern characterized by nodular shapes was significantly more frequent in pancreatic cancer, whereas a longitudinal shape indicated autoimmune pancreatitis. Heterogeneous accumulation was found in almost all cases of autoimmune pancreatitis, whereas homogeneous accumulation was found in pancreatic cancer. Significantly more cases of pancreatic cancer showed solitary localization, whereas multiple localization in the pancreas favored the presence of autoimmune pancreatitis. FDG uptake by the hilar lymph node was significantly more frequent in autoimmune pancreatitis than in pancreatic cancer, and uptake by the lachrymal gland, salivary gland, biliary duct, retroperitoneal space, and prostate were seen only in autoimmune pancreatitis. FDG-PET is a useful tool for differentiating autoimmune pancreatitis from suspected pancreatic cancer, if the accumulation pattern and extrapancreatic involvement are considered. IgG4 measurement and other current image tests can further confirm the diagnosis. (author)

  7. Extraperitoneal Fluid Collection due to Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Takeo Yasuda

    2013-08-01

    Full Text Available A 39-year-old man was referred to our hospital for the investigation of abdominal fluid collection. He was pointed out to have alcoholic chronic pancreatitis. Laboratory data showed inflammation and slightly elevated serum direct bilirubin and amylase. An abdominal computed tomography demonstrated huge fluid collection, multiple pancreatic pseudocysts and pancreatic calcification. The fluid showed a high level of amylase at 4,490 IU/l. Under the diagnosis of pancreatic ascites, endoscopic pancreatic stent insertion was attempted but was unsuccessful, so surgical treatment (Frey procedure and cystojejunostomy was performed. During the operation, a huge amount of fluid containing bile acid (amylase at 1,474 IU/l and bilirubin at 13.5 mg/dl was found to exist in the extraperitoneal space (over the peritoneum, but no ascites was found. His postoperative course was uneventful and he shows no recurrence of the fluid. Pancreatic ascites is thought to result from the disruption of the main pancreatic duct, the rupture of a pancreatic pseudocyst, or possibly leakage from an unknown site. In our extremely rare case, the pancreatic pseudocyst penetrated into the hepatoduodenal ligament with communication to the common bile duct, and the fluid flowed into the round ligament of the liver and next into the extraperitoneal space.

  8. Pathobiological implications of MUC16 expression in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Dhanya Haridas

    Full Text Available MUC16 (CA125 belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC, the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

  9. Preferentially Cytotoxic Constituents of Andrographis paniculata and their Preferential Cytotoxicity against Human Pancreatic Cancer Cell Lines.

    Science.gov (United States)

    Lee, Sullim; Morita, Hiroyuki; Tezuka, Yasuhiro

    2015-07-01

    In the course of our search for anticancer agents based on a novel anti-austerity strategy, we found that the 70% EtOH extract of the crude drug Andrographis Herba (aerial parts of Andrographis paniculata), used in Japanese Kampo medicines, killed PANC-1 human pancreatic cancer cells preferentially in nutrient-deprived medium (NDM). Phytochemical investigation of the 70% EtOH extract led to the isolation of 21 known compounds consisting of six labdane-type diterpenes (11, 15, 17-19, 21), six flavones (5, 7, 10, 12, 14, 20), three flavanones (2, 6, 16), two sterols (3, 8), a fatty acid (1), a phthalate (4), a triterpene (9), and a monoterpene (13). Among them, 14-deoxy-11,12-didehydroandrographolide (17) displayed the most potent preferential cytotoxicity against PANC-1 and PSN-1 cells with PC50 values of 10.0 μM and 9.27 μM, respectively. Microscopical observation, double staining with ethidium bromide (EB) and acridine orange (AO), and flow cytometry with propidium iodide/annexin V double staining indicated that 14-deoxy-11,12-didehydroandrographolide (17) triggered apoptosis-like cell death in NDM with an amino acids and/or serum-sensitive mode.

  10. Effect of allicin on the radiosensitivity of human pancreatic carcinoma BXPC3 cells

    International Nuclear Information System (INIS)

    Ma Hongbing; Di Zhengli; He Na; Wen Jiao; Ke Yue

    2014-01-01

    Objective: To study the effect of allicin on the growth and radiosensitivity of human pancreatic carcinoma BXPC3 cells. Methods: BXPC3 cells were exposed to X-rays in the presence or absence of allicin. Cell proliferation was measured by MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometry assay. Cell radiosensitivity and the influence of allicin on it was evaluated by colony formation assay. The expressions of Bax and Bcl-2 proteins were assayed by RT-PCR and Western blot. Results: IC 50 values of allicin on cell growth were 76.24, 58.34 and 43.58 μmol/L under 12, 24 and 48 h treatment, respectively. Treatment of cells with allicin obviously inhibited cell growth after irradiation and hence increased radiosensitivity (t = 2.74, P < 0.05). This treament also enhanced radiation-induced cell cycle arrest at G 2 /M phase (t = 11.41, P < 0.05), apoptosis induction (t = 12.36, P < 0.05), and Bax expression (t = 4.83, P < 0.05), but it decreased Bcl-2 expression (t = 3.69, P < 0.05). Conclusions: Allicin could inhibit cell growth, induce cell cycle arrest and apoptosis via Bax/Bcl-2 pathway and hence increases radiosensitivity of BXPC3 cells. (authors)

  11. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

    Energy Technology Data Exchange (ETDEWEB)

    Pavlikova, Nela, E-mail: nela.pavlikova@lf3.cuni.cz [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Smetana, Pavel [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Halada, Petr [Laboratory of Molecular Structure Characterization, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague (Czech Republic); Kovar, Jan [Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic)

    2015-10-15

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin

  12. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

    International Nuclear Information System (INIS)

    Pavlikova, Nela; Smetana, Pavel; Halada, Petr; Kovar, Jan

    2015-01-01

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin

  13. Pathophysiology of chronic pancreatitis.

    Science.gov (United States)

    Brock, Christina; Nielsen, Lecia Møller; Lelic, Dina; Drewes, Asbjørn Mohr

    2013-11-14

    Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma. Despite the heterogeneity in pathogenesis and involved risk factors, processes such as necrosis/apoptosis, inflammation or duct obstruction are involved. This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas, deformation of the large ducts and severe changes in the arrangement and composition of the islets. These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions. The prevalence of the disease is largely dependent on culture and geography. The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors. Throughout this review the M-ANNHEIM classification system will be used, comprising a detailed description of risk factors such as: alcohol-consumption, nicotine-consumption, nutritional factors, hereditary factors, efferent duct factors, immunological factors and miscellaneous and rare metabolic factors. Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools, which potentially will help clinicians to diagnose CP at an earlier stage. However, in view of the multi factorial disease and the complex clinical picture, it is not surprising that treatment of patients with CP is challenging and often unsuccessful.

  14. Pathophysiology of chronic pancreatitis

    Science.gov (United States)

    Brock, Christina; Nielsen, Lecia Møller; Lelic, Dina; Drewes, Asbjørn Mohr

    2013-01-01

    Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma. Despite the heterogeneity in pathogenesis and involved risk factors, processes such as necrosis/apoptosis, inflammation or duct obstruction are involved. This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas, deformation of the large ducts and severe changes in the arrangement and composition of the islets. These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions. The prevalence of the disease is largely dependent on culture and geography. The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors. Throughout this review the M-ANNHEIM classification system will be used, comprising a detailed description of risk factors such as: alcohol-consumption, nicotine-consumption, nutritional factors, hereditary factors, efferent duct factors, immunological factors and miscellaneous and rare metabolic factors. Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools, which potentially will help clinicians to diagnose CP at an earlier stage. However, in view of the multi factorial disease and the complex clinical picture, it is not surprising that treatment of patients with CP is challenging and often unsuccessful. PMID:24259953

  15. Risk factors for pancreatic stone formation in autoimmune pancreatitis over a long-term course.

    Science.gov (United States)

    Maruyama, Masahiro; Arakura, Norikazu; Ozaki, Yayoi; Watanabe, Takayuki; Ito, Tetsuya; Yoneda, Suguru; Maruyama, Masafumi; Muraki, Takashi; Hamano, Hideaki; Matsumoto, Akihiro; Kawa, Shigeyuki

    2012-05-01

    Autoimmune pancreatitis (AIP) has the potential to progress to a chronic state that forms pancreatic stones. The aim of this study was to clarify the risk factors underlying pancreatic stone formation in AIP. Sixty-nine patients with AIP who had been followed for at least 3 years were enrolled for evaluation of clinical and laboratory factors as well as computed tomography and endoscopic retrograde cholangiopancreatography findings. During the course of this study, increased or de novo stone formation was seen in 28 patients, who were defined as the stone-forming group. No stones were observed in 32 patients, who were defined as the non-stone-forming group. Nine patients who had stones at diagnosis but showed no change during the course of this study were excluded from our cohort. Univariate analysis revealed no significant differences in clinical or laboratory factors associated with AIP-specific inflammation between the two groups. However, pancreatic head swelling (P = 0.006) and narrowing of both Wirsung's and Santorini's ducts in the pancreatic head region (P = 0.010) were significantly more frequent in the stone-forming group. Furthermore, multivariate analysis identified Wirsung and Santorini duct narrowing at diagnosis as a significant independent risk factor for pancreatic stone formation (OR 4.4, P = 0.019). A primary risk factor for pancreatic stone formation in AIP was narrowing of both Wirsung's and Santorini's ducts, which most presumably led to pancreatic juice stasis and stone development.

  16. Pancreatic tissue fluid pressure and pain in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N

    1992-01-01

    A casual relation between pancreatic pressure and pain has been searched for decades but lack of appropriate methods for pressure measurements has hindered progress. During the 1980's the needle method has been used for direct intraoperative pancreatic tissue fluid pressure measurements and later...... for percutaneous sonographically-guided pressure measurements. Clinical and experimental evaluation of the method showed comparable results at intraoperative and percutaneous measurements and little week-to-week variation. Furthermore, comparable pressures in duct and adjacent pancreatic tissue were found, i.......e. the needle pressure mirrors the intraductal pressure. Comparisons of pain registrations, morphological and functional parameters with pancreatic tissue fluid pressure measurements have revealed a relation between pressure and pain which probably is causal. In patients with pain the high pressures previously...

  17. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  18. Incidental intraoperative discovery of a pancreatic neuroendocrine tumor associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Surlin Valeriu

    2012-09-01

    Full Text Available Abstract Pancreatic neuroendocrine tumors are a rare entity with an incidence between 2 per million to 5 per 100 000. Association with pancreatitis (acute or chronic is rare and is considered to be determined by the tumoral obstruction of pancreatic ducts, but sometimes occurs without any apparent relationship between them. Non-functional neuroendocrine pancreatic tumors are usually diagnosed when either very large or metastatic. Small ones are occasionally diagnosed when imagery is performed for other diagnostic reasons. Intraoperative discovery is even rarer and poses problems of differential diagnosis with other pancreatic tumors. Association with chronic pancreatitis is rare and usually due to pancreatic duct obstruction by the tumor. We describe the case of a patient with a small non-functioning neuroendocrine tumor in the pancreatic tail accidentally discovered during surgery for delayed traumatic splenic rupture associated with chronic alcoholic pancreatitis. The tumor of 1.5cm size was well differentiated and confined to the pancreas, and was resected by a distal splenopancreatectomy. Conclusions Surgeons should be well aware of the rare possibility of a non-functional neuroendocrine tumor in the pancreas, associated with chronic pancreatitis, surgical resection being the optimal treatment for cure. Histopathology is of utmost importance to establish the correct diagnosis, grade of differentiation, malignancy and prognosis. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2114470176676003.

  19. Akut pancreatitis forårsaget af galdesten i barnealderen

    DEFF Research Database (Denmark)

    Zachariassen, G; Saffar, D F; Mortensen, J

    1999-01-01

    A 10 year-old girl presented with acute abdominal pain. Serum-amylase was 3959 U/l. Ultrasonography showed dilatation of both the common bile duct and the pancreatic duct and a high density area near the ampulla. Endoscopic retrograde cholangiography (ERC) verified a stone near the ampulla, which...

  20. Echovirus 6 Infects Human Exocrine and Endocrine Pancreatic Cells and Induces Pro-Inflammatory Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Luis Sarmiento

    2017-01-01

    Full Text Available Human enteroviruses (HEV, especially coxsackievirus serotype B (CVB and echovirus (E, have been associated with diseases of both the exocrine and endocrine pancreas, but so far evidence on HEV infection in human pancreas has been reported only in islets and ductal cells. This study aimed to investigate the capability of echovirus strains to infect human exocrine and endocrine pancreatic cells. Infection of explanted human islets and exocrine cells with seven field strains of E6 caused cytopathic effect, virus titer increase and production of HEV protein VP1 in both cell types. Virus particles were found in islets and acinar cells infected with E6. No cytopathic effect or infectious progeny production was observed in exocrine cells exposed to the beta cell-tropic strains of E16 and E30. Endocrine cells responded to E6, E16 and E30 by upregulating the transcription of interferon-induced with helicase C domain 1 (IF1H1, 2'-5'-oligoadenylate synthetase 1 (OAS1, interferon-β (IFN-β, chemokine (C–X–C motif ligand 10 (CXCL10 and chemokine (C–C motif ligand 5 (CCL5. Echovirus 6, but not E16 or E30, led to increased transcription of these genes in exocrine cells. These data demonstrate for the first time that human exocrine cells represent a target for E6 infection and suggest that certain HEV serotypes can replicate in human pancreatic exocrine cells, while the pancreatic endocrine cells are permissive to a wider range of HEV.

  1. A case of annular pancreas with Wirsung's duct encircling the duodenum: embryological hypothesis based on cholangiopancreatographic and immunohistochemical findings.

    Science.gov (United States)

    Fukai, Manami; Kamisawa, Terumi; Horiguchi, Shin-Ichirou; Hishima, Tsunekazu; Kuruma, Sawako; Chiba, Kazuro; Koizumi, Satomi; Tabata, Taku; Nagao, Sayaka; Kikuyama, Masataka; Honda, Goro; Kurata, Masanao

    2017-06-01

    We present a resected case of annular pancreas in which Wirsung's duct encircled the duodenum and continued directly to the main pancreatic duct in the body and tail. Furthermore, Wirsung's duct coursed along the right side of the lower bile duct near the major duodenal papilla. Histologically, the islets of Langerhans in the annular pancreas were irregular in shape and were characterized by a striking abundance of pancreatic polypeptide (PP)-positive cells. The PP-rich area that encircled the duodenum was fused with the PP-poor area in the head of the pancreas. The following embryological hypothesis is proposed. The tip of the ventral pancreatic anlage adhered to the duodenal wall and stretched to form a ring during clockwise rotation. The rotation was incomplete, and the pancreatic duct did not cross over the lower bile duct. Since there was adequate ventral anlage in the lower part of the head of the pancreas, fusion between the ducts of the ventral and dorsal anlagen did not occur. The tip of the ventral anlage overgrew and adhered to the dorsal anlage, and the annular duct fused with the main duct of the dorsal anlage.

  2. Surgical management of failed endoscopic treatment of pancreatic disease.

    Science.gov (United States)

    Evans, Kimberly A; Clark, Colby W; Vogel, Stephen B; Behrns, Kevin E

    2008-11-01

    Endoscopic therapy of acute and chronic pancreatitis has decreased the need for operative intervention. However, a significant proportion of patients treated endoscopically require definitive surgical management for persistent symptoms. Our aim was to determine which patients are likely to fail with endoscopic therapy, and to assess the clinical outcome of surgical management. Patients were identified using ICD-9 codes for pancreatic disease as well as CPT codes for endoscopic therapy followed by surgery. Patients with documented acute or chronic pancreatitis treated endoscopically prior to surgical therapy were included (N = 88). The majority of patients (65%) exhibited chronic pancreatitis due to alcohol abuse. Common indicators for surgery were: persistent symptoms, anatomy not amenable to endoscopic treatment and unresolved common bile duct or pancreatic duct strictures. Surgical salvage procedures included internal drainage of a pseudocyst or an obstructed pancreatic duct (46%), debridement of peripancreatic fluid collections (25%), and pancreatic resection (31%). Death occurred in 3% of patients. The most common complications were hemorrhage (16%), wound infection (13%), and pulmonary complications (11%). Chronic pancreatitis with persistent symptoms is the most common reason for pancreatic surgery following endoscopic therapy. Surgical salvage therapy can largely be accomplished by drainage procedures, but pancreatic resection is common. These complex procedures can be performed with acceptable mortality but also with significant risk for morbidity.

  3. Proximal migration of a 5 French pancreatic stent during bile stone ...

    African Journals Online (AJOL)

    ERCP pancreatitis and facilitate bilitary cannulation in difficult cases. Proximal migration of a pancreatic stent during bile duct stone extraction is an infrequent event, but its management can be technically challenging. We present a case that a double flanged pancreatic stent (5 French (Fr), 5 cm) was placed to facilitate the ...

  4. Secondary obstructive jaundice to pancreatic calculus impacted in the papilla

    International Nuclear Information System (INIS)

    Rafael Angel, Luis M. Limas; Lazaro Arango

    2004-01-01

    Bile duct stones obstructing the papilla are a quite common finding. On the other hand a pancreatic stone obstructing the papilla is quite rare. There are few reports of this complication of chronic pancreatitis in the literature. Here we inform of another unique case

  5. MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4

    International Nuclear Information System (INIS)

    Wei, Xueju; Wang, Weibin; Wang, Lanlan; Zhang, Yuanyuan; Zhang, Xian; Chen, Mingtai; Wang, Fang; Yu, Jia; Ma, Yanni; Sun, Guotao

    2016-01-01

    Pancreatic cancer patients are often resistant to chemotherapy treatment, which results in poor prognosis. The objective of this study was to delineate the mechanism by which miR-21 induces drug resistance to 5-fluorouracil (5-FU) in human pancreatic cancer cells (PATU8988 and PANC-1). We report that PATU8988 cells resistant to 5-FU express high levels of miR-21 in comparison to sensitive primary PATU8988 cells. Suppression of miR-21 expression in 5-Fu-resistant PATU8988 cells can alleviate its 5-FU resistance. Meanwhile, lentiviral vector-mediated overexpression of miR-21 not only conferred resistance to 5-FU but also promoted proliferation, migration, and invasion of PATU8988 and PANC-1 cells. The proresistance effects of miR-21 were attributed to the attenuated expression of tumor suppressor genes, including PTEN and PDCD4. Overexpression of PTEN and PDCD4 antagonized miR-21-induced resistance to 5-FU and migration activity. Our work demonstrates that miR-21 can confer drug resistance to 5-FU in pancreatic cancer cells by regulating the expression of tumor suppressor genes, as the target genes of miR-21, PTEN and PDCD4 can rescue 5-FU sensitivity and the phenotypic characteristics disrupted by miR-21

  6. Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

    Directory of Open Access Journals (Sweden)

    Jennifer E. Bruin

    2015-04-01

    Full Text Available Human embryonic stem cell (hESC-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

  7. Surgical Approaches to Chronic Pancreatitis: Indications and Techniques.

    Science.gov (United States)

    Dua, Monica M; Visser, Brendan C

    2017-07-01

    There are a number of surgical strategies for the treatment of chronic pancreatitis. The optimal intervention should provide effective pain relief, improve/maintain quality of life, preserve exocrine and endocrine function, and manage local complications. Pancreaticoduodenectomy was once the standard operation for patients with chronic pancreatitis; however, other procedures such as the duodenum-preserving pancreatic head resections and its variants have been introduced with good long-term results. Pancreatic duct drainage via a lateral pancreaticojejunostomy continues to be effective in ameliorating symptoms and expediting return to normal lifestyle in many patients. This review summarizes operative indications and gives an overview of the different surgical strategies in treating chronic pancreatitis.

  8. Silver nanoparticles of different sizes induce a mixed type of programmed cell death in human pancreatic ductal adenocarcinoma

    Science.gov (United States)

    Zielinska, Ewelina; Zauszkiewicz-Pawlak, Agata; Wojcik, Michal; Inkielewicz-Stepniak, Iwona

    2018-01-01

    Pancreatic ductal adenocarcinoma, with the high resistance to chemotherapeutic agents, remains the fourth leading cause of cancer-death in the world. Due to the wide range of biological activity and unique properties, silver nanoparticles (AgNPs) are indicated as agents with potential to overcome barriers involved in chemotherapy failure. Therefore, in our study we decided to assess the ability of AgNPs to kill pancreatic cancer cells, and then to identify the molecular mechanism underlying this effect. Moreover, we evaluated the cytotoxicity of AgNPs against non-tumor cell of the same tissue (hTERT-HPNE cells) for comparison. Our results indicated that AgNPs with size of 2.6 and 18 nm decreased viability, proliferation and caused death of pancreatic cancer cells in a size- and concentration-dependent manner. Ultrastructural analysis identified that cellular uptake of AgNPs resulted in apoptosis, autophagy, necroptosis and mitotic catastrophe. These alterations were associated with increased pro-apoptotic protein Bax and decreased level of anti-apoptotic protein Bcl-2. Moreover, AgNPs significantly elevated the level of tumor suppressor p53 protein as well as necroptosis- and autophagy-related proteins: RIP-1, RIP-3, MLKL and LC3-II, respectively. In addition, we found that PANC-1 cells were more vulnerable to AgNPs-induced cytotoxicity compared to pancreatic non-tumor cells. In conclusion, AgNPs by inducing mixed type of programmed cell death in PANC-1 cells, could provide a new therapeutic strategy to overcome chemoresistance in one of the deadliest human cancer. PMID:29435134

  9. Early to Late Endosome Trafficking Controls Secretion and Zymogen Activation in Rodent and Human Pancreatic Acinar Cells.

    Science.gov (United States)

    Messenger, Scott W; Thomas, Diana Dh; Cooley, Michelle M; Jones, Elaina K; Falkowski, Michelle A; August, Benjamin K; Fernandez, Luis A; Gorelick, Fred S; Groblewski, Guy E

    2015-11-01

    Pancreatic acinar cells have an expanded apical endosomal system, the physiological and pathophysiological significance of which is still emerging. Phosphatidylinositol-3,5-bisphosphate (PI(3,5)P 2 ) is an essential phospholipid generated by PIKfyve, which phosphorylates phosphatidylinositol-3-phosphate (PI(3)P). PI(3,5)P 2 is necessary for maturation of early endosomes (EE) to late endosomes (LE). Inhibition of EE to LE trafficking enhances anterograde endosomal trafficking and secretion at the plasma membrane by default through a recycling endosome (RE) intermediate. We assessed the effects of modulating PIKfyve activity on apical trafficking and pancreatitis responses in pancreatic acinar cells. Inhibition of EE to LE trafficking was achieved using pharmacological inhibitors of PIKfyve, expression of dominant negative PIKfyve K1877E, or constitutively active Rab5-GTP Q79L. Anterograde endosomal trafficking was manipulated by expression of constitutively active and dominant negative Rab11a mutants. The effects of these agents on secretion, endolysosomal exocytosis of lysosome associated membrane protein (LAMP1), and trypsinogen activation in response to high-dose CCK-8, bile acids and cigarette toxin was determined. PIKfyve inhibition increased basal and stimulated secretion. Adenoviral overexpression of PIKfyve decreased secretion leading to cellular death. Expression of Rab5-GTP Q79L or Rab11a-GTP Q70L enhanced secretion. Conversely, dominant-negative Rab11a-GDP S25N reduced secretion. High-dose CCK inhibited endolysosomal exocytosis that was reversed by PIKfyve inhibition. PIKfyve inhibition blocked intracellular trypsin accumulation and cellular damage responses to high CCK-8, tobacco toxin, and bile salts in both rodent and human acini. These data demonstrate that EE-LE trafficking acutely controls acinar secretion and the intracellular activation of zymogens leading to the pathogenicity of acute pancreatitis.

  10. Escin Chemosensitizes Human Pancreatic Cancer Cells and Inhibits the Nuclear Factor-kappaB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    A. Rimmon

    2013-01-01

    Full Text Available Background. There is an urgent need to develop new treatment strategies and drugs for pancreatic cancer that is highly resistant to radio-chemotherapy. Aesculus hippocastanum (the horse chestnut known in Chinese medicine as a plant with anti-inflammatory, antiedema, antianalgesic, and antipyretic activities. The main active compound of this plant is Escin (C54H84O23. Objective. To evaluate the effect of Escin alone and combined with chemotherapy on pancreatic cancer cell survival and to unravel mechanism(s of Escin anticancer activity. Methods. Cell survival was measured by XTT colorimetric assay. Synergistic effect of combined therapy was determined by CalcuSyn software. Cell cycle and induction of apoptosis were evaluated by FACS analysis. Expression of NF-κB-related proteins (p65, IκBα, and p-IκBα and cyclin D was evaluated by western blot analysis. Results. Escin decreased the survival of pancreatic cancer cells with IC50 = 10–20 M. Escin combined with gemcitabine showed only additive effect, while its combination with cisplatin resulted in a significant synergistic cytotoxic effect in Panc-1 cells. High concentrations of Escin induced apoptosis and decreased NF-κB-related proteins and cyclin D expression. Conclusions. Escin decreased pancreatic cancer cell survival, induced apoptosis, and downregulated NF-κB signaling pathway. Moreover, Escin sensitized pancreatic cancer cells to chemotherapy. Further translational research is required.

  11. Exosomal lipids impact notch signaling and induce death of human pancreatic tumoral SOJ-6 cells.

    Directory of Open Access Journals (Sweden)

    Sadia Beloribi

    Full Text Available Exosomes are of increasing interest as alternative mode of cell-to-cell communication. We previously reported that exosomes secreted by human SOJ-6 pancreatic tumor cells induce (glycoprotein ligand-independent cell death and inhibit Notch-1 pathway, this latter being particularly active during carcinogenesis and in cancer stem cells. Therefore, we asked whether exosomal lipids were key-elements for cell death and hypothesized that cholesterol-rich membrane microdomains were privileged sites of exosome interactions with tumor cells. To address these questions and based on the lipid composition of exosomes from SOJ-6 cells (Ristorcelli et al. (2008 FASEB J. 22; 3358-3369 enriched in cholesterol and sphingomyelin (lipids forming liquid-ordered phase, Lo and depleted in phospholipids (lipids forming liquid-disordered phase, Ld, we designed Synthetic Exosome-Like Nanoparticles (SELN with ratios Lo/Ld from 3.0 to 6.0 framing that of SOJ-6 cell exosomes. SELN decreased tumor cell survival, the higher the Lo/Ld ratio, the lower the cell survival. This decreased survival was due to activation of cell death with inhibition of Notch pathway. FRET analyses indicated fusions/exchanges of SELN with cell membranes. Fluorescent SELN co-localized with the ganglioside GM1 then with Rab5A, markers of lipid microdomains and of early endosomes, respectively. These interactions occurred at lipid microdomains of plasma and/or endosome membranes where the Notch-1 pathway matures. We thus demonstrated a major role for lipids in interactions between SELN and tumor cells, and in the ensued cell death. To our knowledge this is the first report on such effects of lipidic nanoparticles on tumor cell behavior. This may have implications in tumor progression.

  12. Human embryonic stem cell-derived pancreatic endoderm alleviates diabetic pathology and improves reproductive outcome in C57BL/KsJ-Lep(db/+) gestational diabetes mellitus mice.

    Science.gov (United States)

    Xing, Baoheng; Wang, Lili; Li, Qin; Cao, Yalei; Dong, Xiujuan; Liang, Jun; Wu, Xiaohua

    2015-07-01

    Gestational diabetes mellitus is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal maldevelopment. The cause of gestational diabetes mellitus can be attributed to both genetic and environmental factors, hence complicating its diagnosis and treatment. Pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice. In this study, we have developed a system of treating diabetes using human embryonic stem cell-derived pancreatic endoderm in a mouse model of gestational diabetes mellitus. Human embryonic stem cells were differentiated in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus. The transplant greatly improved glucose metabolism and reproductive outcome of the females compared with the control groups. Our findings support the feasibility of using differentiated human embryonic stem cells for treating gestational diabetes mellitus patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 3H-cyclosporine internalization and secretion by human fetal pancreatic islets

    International Nuclear Information System (INIS)

    Formby, B.; Walker, L.; Peterson, C.M.

    1988-01-01

    Human fetal pancreatic islets were isolated from 16- to 20-week-old fetuses by a collagenase technique and cultured 48 hr in RPMI 1640 containing 10% human adult serum and unlabeled 0 to 5 micrograms cyclosporine A (CsA)/ml. Insulin secretory capacity of human fetal islets was expressed as a fractional stimulatory ratio FSR = F2/F1 of the fractional secretion rates during two successive 1 hr static incubations first with 2 mM glucose (F1) to stabilize secretion followed by maximal stimulus, i.e., 25 mM glucose plus 10 mM L-leucine and 10 mM L-arginine (F2). Unlabeled CsA at the above concentrations had no significant effects on the insulin secretory capacity expressed by FSR-values. Studies of net uptake of 3H-CsA by islets cultured for varying periods up to 40 hr and expressed as picomole 3H-CsA per picomole islet insulin content demonstrated that uptake rate was slow and did not reach isotopic equilibrium over the 40 hr of culture. When isolated fetal islets were cultured for 48 hr in the presence of 3H-CsA and varying concentrations of unlabeled CsA it was found during two successive 1 hr static incubations that fetal islets secrete insulin concomitantly with 3H-CsA following maximal stimulus for secretion. An optimal secretory molar ratio of 3H-CsA to insulin of 4.0 +/- 1.3 (n = 7) was found after islets were cultured 48 hr in the presence of a saturating 2.128 micrograms 3H-CsA per milliliter culture medium. In three successive 30-min static incubations of 3H-CsA loaded islets, first with low glucose, followed by high glucose plus L-arginine and L-leucine, and finally with high glucose plus L-arginine and L-leucine and 10 mM theophylline, the proportional fractional secretion rates of insulin and 3H-CsA were of the same magnitude

  14. Isolation of Human Islets for Autologous Islet Transplantation in Children and Adolescents with Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Rita Bottino

    2012-01-01

    Full Text Available Chronic pancreatitis is an inflammatory disease of the pancreas that causes permanent changes in the function and structure of the pancreas. It is most commonly a complication of cystic fibrosis or due to a genetic predisposition. Chronic pancreatitis generally presents symptomatically as recurrent abdominal pain, which becomes persistent over time. The pain eventually becomes disabling. Once specific medical treatments and endoscopic interventions are no longer efficacious, total pancreatectomy is the alternative of choice for helping the patient achieve pain control. While daily administrations of digestive enzymes cannot be avoided, insulin-dependent diabetes can be prevented by transplanting the isolated pancreatic islets back to the patient. The greater the number of islets infused, the greater the chance to prevent or at least control the effects of surgical diabetes. We present here a technical approach for the isolation and preservation of the islets proven to be efficient to obtain high numbers of islets, favoring the successful treatment of young patients.

  15. Lateral Pancreaticojejunostomy for Chronic Pancreatitis and Pancreatic Ductal Dilation in Children.

    Science.gov (United States)

    Shah, Adil A; Petrosyan, Mikael; Kane, Timothy D

    2018-06-06

    Pancreatic ductal obstruction leading to ductal dilation and recurrent pancreatitis is uncommon in children. Treatment is dependent upon etiology but consists of decompression of the pancreatic duct (PD) proximally, if possible, by endoscopic retrograde cholangiopancreatography (ERCP) intervention or surgical decompression with pancreaticojejunal anastomosis. After institutional review board approval, we retrospectively reviewed the records for 2 children who underwent lateral pancreaticojejunostomy for pancreatic ductal dilation. Data, including demographics, diagnostic studies, operative details, complications, outcomes, and follow-up, were analyzed. Case 1 was a 4-year-old female with pancreatic ductal obstruction with multiple episodes of recurrent pancreatitis and failure of ERCP to clear her PD of stones. She underwent a laparoscopic cholecystectomy with a lateral pancreaticojejunostomy (Puestow procedure). She recovered well with no further episodes of pancreatitis and normal pancreatic function 4 years later. Case 2 was a 2-year-old female who developed recurrent pancreatitis and was found to have papillary stenosis and long common bile-PD channel. Despite multiple sphincterotomies, laparoscopic cholecystectomy, and laparoscopic hepaticoduodenostomy, she continued to experience episodes of pancreatitis. She underwent a laparoscopy converted to open lateral pancreaticojejunostomy. Her recovery was also smooth having had no episodes of pancreatitis or hospital admissions for over 2 years following the Puestow. Indication for lateral pancreaticojejunostomy or Puestow procedure is rare in children and even less often performed using laparoscopy. In our small experience, both patients with pancreatic ductal obstruction managed with Puestow's procedure enjoy durable symptom and pain relief in the long term.

  16. Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory.

    Science.gov (United States)

    Rheinheimer, Jakeline; Bauer, Andrea C; Silveiro, Sandra P; Estivalet, Aline A F; Bouças, Ana P; Rosa, Annelise R; Souza, Bianca M de; Oliveira, Fernanda S de; Cruz, Lavínia A; Brondani, Letícia A; Azevedo, Mirela J; Lemos, Natália E; Carlessi, Rodrigo; Assmann, Taís S; Gross, Jorge L; Leitão, Cristiane B; Crispim, Daisy

    2015-04-01

    Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre - Rio Grande do Sul, Brazil.

  17. Imaging of pancreatic tumors

    International Nuclear Information System (INIS)

    Brambs, Hans-Juergen; Juchems, Markus

    2010-01-01

    Ductal adenocarcinoma is the most frequent solid tumor of the pancreas. This tumor has distinct features including early obstruction of the pancreatic duct, diminished enhancement after administration of contrast material due to desmoplastic growth, high propensity to infiltrate adjacent structures and to metastasize into the liver and the peritoneum. Hormone active endocrine tumors cause specific clinical symptoms. Imaging is aimed at localization of these hypervascular tumors. Non hormone active tumors are most frequently malignant and demonstrate very varying features. Cystic pancreatic tumors are increasingly detected by means of cross sectional imaging. Exact classification can be achieved with knowledge of the macropathology and considering clinical presentation as well as age and gender of the patients. (orig.)

  18. Extracorporeal shock wave lithotripsy on pancreatic duck stones in patients with chronic pancreatitis: evaluation of therapeutic results with CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Moon Gyu [Asan Medical Center, Seoul (Korea, Republic of); Lee, Yong Suk [Gunpo Medical Center, Gunpo (Korea, Republic of)

    2003-03-01

    To demonstrate by CT scanning the effect of extracorporeal shock wave lithotripsy (ESWL) on pancreatic duct stones in patients with chronic pancreatitis. Pancreatic duct stones in 11 patients with chronic pancreatitis were subject to ESWL using an electrohydraulic lithotripter. Endoscopic stone removal using a basket had failed in ten patients, and in one, endoscopy was impossible due to a previous Whipple's operation. CT scans obtained before and after ESWL were evaluated by two radiologists: the longest and shortest diameters of the target stone were measured, and according to the degree of fragmentation, determined by comparing the area of the stone before and after ESWL, a grade (1-5) was assigned. In each case, the pre- and post- treatment diameter of the main pancreatic duct, measured at the pancreatic body, was also compared. Disintegration of the target stone was achieved in all patients: grade 1 (over 75% of the area remained, compared with that of the initial stone) was assigned in two patients; grade 2 (51-75% of the original area) in one; grade 3 (26-50%) in four; grade 4 (under 25%) in two; and grade 5 (complete clearance of the target stone) in two. The mean area decreased from 175 mm{sup 2} to 69 mm{sup 2} after ESWL (p<0.05); a decrease of more than 50% was observed in eight patients (73%). The mean diameter of the main pancreatic duct decreased from 7.36 to 4.81 mm (p<0.05). No severe adverse effects or complications were noted, and all patients showed clinical improvement. Follow-up studies indicated that pancreatic duct stones recurred in three patients. ESWL can cause the fragmentation of pancreatic duct stones without significant complications, and should be considered where endoscopic stone removal has failed. CT is a suitable non-invasive and accurate tool for evaluating the therapeutic results of ESWL.

  19. Extracorporeal shock wave lithotripsy on pancreatic duck stones in patients with chronic pancreatitis: evaluation of therapeutic results with CT

    International Nuclear Information System (INIS)

    Lee, Moon Gyu; Lee, Yong Suk

    2003-01-01

    To demonstrate by CT scanning the effect of extracorporeal shock wave lithotripsy (ESWL) on pancreatic duct stones in patients with chronic pancreatitis. Pancreatic duct stones in 11 patients with chronic pancreatitis were subject to ESWL using an electrohydraulic lithotripter. Endoscopic stone removal using a basket had failed in ten patients, and in one, endoscopy was impossible due to a previous Whipple's operation. CT scans obtained before and after ESWL were evaluated by two radiologists: the longest and shortest diameters of the target stone were measured, and according to the degree of fragmentation, determined by comparing the area of the stone before and after ESWL, a grade (1-5) was assigned. In each case, the pre- and post- treatment diameter of the main pancreatic duct, measured at the pancreatic body, was also compared. Disintegration of the target stone was achieved in all patients: grade 1 (over 75% of the area remained, compared with that of the initial stone) was assigned in two patients; grade 2 (51-75% of the original area) in one; grade 3 (26-50%) in four; grade 4 (under 25%) in two; and grade 5 (complete clearance of the target stone) in two. The mean area decreased from 175 mm 2 to 69 mm 2 after ESWL (p<0.05); a decrease of more than 50% was observed in eight patients (73%). The mean diameter of the main pancreatic duct decreased from 7.36 to 4.81 mm (p<0.05). No severe adverse effects or complications were noted, and all patients showed clinical improvement. Follow-up studies indicated that pancreatic duct stones recurred in three patients. ESWL can cause the fragmentation of pancreatic duct stones without significant complications, and should be considered where endoscopic stone removal has failed. CT is a suitable non-invasive and accurate tool for evaluating the therapeutic results of ESWL

  20. MRI assessed pancreatic morphology and exocrine function are associated with disease burden in chronic pancreatitis.

    Science.gov (United States)

    Madzak, Adnan; Olesen, Søren Schou; Lykke Poulsen, Jakob; Bolvig Mark, Esben; Mohr Drewes, Asbjørn; Frøkjær, Jens Brøndum

    2017-11-01

    The aim of this study was to explore the association between morphological and functional secretin-stimulated MRI parameters with hospitalization, quality of life (QOL), and pain in patients with chronic pancreatitis (CP). This prospective cohort study included 82 patients with CP. Data were obtained from clinical information, QOL, and pain as assessed by questionnaires (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and modified Brief Pain Inventory short form). Secretin-stimulated MRI morphological parameters included pancreatic gland volume, main pancreatic duct diameter, the modified Cambridge Classification of Duct Abnormality, apparent diffusion coefficient, fat signal fraction, and the pancreatic secretion volume as a functional parameter. The primary outcomes were time to first hospitalization related to the CP, as well as annual hospitalization frequency and duration. The secondary outcomes were pain severity, QOL, and pain interference scores. A main pancreatic duct diameter below 5 mm was associated with reduced time to first hospitalization (hazard ratio=2.06; 95% confidence interval: 1.02-4.17; P=0.043). Pancreatic secretion volume was correlated with QOL (r=0.31; P=0.0072) and pain interference score (r=-0.27; P=0.032), and fecal elastase was also correlated with QOL (r=0.28; P=0.017). However, functional and morphological findings were not related to pain intensity. Advanced pancreatic imaging techniques may be a highly sensitive tool for prognostication and monitoring of disease activity and its consequences.

  1. Blocked Tear Duct

    Science.gov (United States)

    ... of the nose (lacrimal sac). From there tears travel down a duct (the nasolacrimal duct) draining into your nose. Once in the nose, tears are reabsorbed. A blockage can occur at any point in the tear drainage system, from the puncta ...

  2. Identification of RegIV as a novel GLI1 target gene in human pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Feng Wang

    2011-04-01

    Full Text Available GLI1 is the key transcriptional factor in the Hedgehog signaling pathway in pancreatic cancer. RegIV is associated with regeneration, and cell growth, survival, adhesion and resistance to apoptosis. We aimed to study RegIV expression in pancreatic cancer and its relationship to GLI1.GLI1 and RegIV expression were evaluated in tumor tissue and adjacent normal tissues of pancreatic cancer patients and 5 pancreatic cancer cell lines by qRT-PCR, Western blot, and immunohistochemistry (IHC, and the correlation between them. The GLI1-shRNA lentiviral vector was constructed and transfected into PANC-1, and lentiviral vector containing the GLI1 expression sequence was constructed and transfected into BxPC-3. GLI1 and RegIV expression were evaluated by qRT-PCR and Western blot. Finally we demonstrated RegIV to be the target of GLI1 by chromatin immunoprecipitation (CHIP and electrophoretic mobility shift assays (EMSA.The results of IHC and qRT-PCR showed that RegIV and GLI1 expression was higher in pancreatic cancer tissues versus adjacent normal tissues (p<0.001. RegIV expression correlated with GLI1 expression in these tissues (R = 0.795, p<0.0001. These results were verified for protein (R = 0.939, p = 0.018 and mRNA expression (R = 0.959, p = 0.011 in 5 pancreatic cancer cell lines. RegIV mRNA and protein expression was decreased (94.7±0.3%, 84.1±0.5%; respectively when GLI1 was knocked down (82.1±3.2%, 76.7±2.2%; respectively by the RNAi technique. GLI1 overexpression in mRNA and protein level (924.5±5.3%, 362.1±3.5%; respectively induced RegIV overexpression (729.1±4.3%, 339.0±3.7%; respectively. Moreover, CHIP and EMSA assays showed GLI1 protein bound to RegIV promotor regions (GATCATCCA in pancreatic cancer cells.GLI1 promotes RegIV transcription by binding to the RegIV gene promoter in pancreatic cancer.

  3. RAS/ERK modulates TGFβ-regulated PTEN expression in human pancreatic adenocarcinoma cells

    OpenAIRE

    Chow, Jimmy Y.C.; Quach, Khai T.; Cabrera, Betty L.; Cabral, Jennifer A.; Beck, Stayce E.; Carethers, John M.

    2007-01-01

    Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is rarely mutated in pancreatic cancers, but its regulation by transforming growth factor (TGF)-β might mediate growth suppression and other oncogenic actions. Here, we examined the role of TGFβ and the effects of oncogenic K-RAS/ERK upon PTEN expression in the absence of SMAD4. We utilized two SMAD4-null pancreatic cell lines, CAPAN-1 (K-RAS mutant) and BxPc-3 (WT-K-RAS), both of which express TGFβ surface receptors. Cells were t...

  4. The management of complex pancreatic injuries.

    Science.gov (United States)

    Krige, J E J; Beningfield, S J; Nicol, A J; Navsaria, P

    2005-08-01

    Major injuries of the pancreas are uncommon, but may result in considerable morbidity and mortality because of the magnitude of associated vascular and duodenal injuries or underestimation of the extent of the pancreatic injury. Prognosis is influenced by the cause and complexity of the pancreatic injury, the amount of blood lost, duration of shock, speed of resuscitation and quality and nature of surgical intervention. Early mortality usually results from uncontrolled or massive bleeding due to associated vascular and adjacent organ injuries. Late mortality is a consequence of infection or multiple organ failure. Neglect of major pancreatic duct injury may lead to life-threatening complications including pseudocysts, fistulas, pancreatitis, sepsis and secondary haemorrhage. Careful operative assessment to determine the extent of gland damage and the likelihood of duct injury is usually sufficient to allow planning of further management. This strategy provides a simple approach to the management of pancreatic injuries regardless of the cause. Four situations are defined by the extent and site of injury: (i) minor lacerations, stabs or gunshot wounds of the superior or inferior border of the body or tail of the pancreas (i.e. remote from the main pancreatic duct), without visible duct involvement, are best managed by external drainage; (ii) major lacerations or gunshot or stab wounds in the body or tail with visible duct involvement or transection of more than half the width of the pancreas are treated by distal pancreatectomy; (iii) stab wounds, gunshot wounds and contusions of the head of the pancreas without devitalisation of pancreatic tissue are managed by external drainage, provided that any associated duodenal injury is amenable to simple repair; and (iv) non-reconstructable injuries with disruption of the ampullary-biliary-pancreatic union or major devitalising injuries of the pancreatic head and duodenum in stable patients are best treated by

  5. A Recombinant Fragment of Human Surfactant Protein D induces Apoptosis in Pancreatic Cancer Cell Lines via Fas-Mediated Pathway.

    Science.gov (United States)

    Kaur, Anuvinder; Riaz, Muhammad Suleman; Murugaiah, Valarmathy; Varghese, Praveen Mathews; Singh, Shiv K; Kishore, Uday

    2018-01-01

    Human surfactant protein D (SP-D) is a potent innate immune molecule, which is emerging as a key molecule in the recognition and clearance of altered and non-self targets. Previous studies have shown that a recombinant fragment of human SP-D (rfhSP-D) induced apoptosis via p53-mediated apoptosis pathway in an eosinophilic leukemic cell line, AML14.3D10. Here, we report the ability of rfhSP-D to induce apoptosis via TNF-α/Fas-mediated pathway regardless of the p53 status in human pancreatic adenocarcinoma using Panc-1 (p53 mt ), MiaPaCa-2 (p53 mt ), and Capan-2 (p53 wt ) cell lines. Treatment of these cell lines with rfhSP-D for 24 h caused growth arrest in G1 cell cycle phase and triggered transcriptional upregulation of pro-apoptotic factors such as TNF-α and NF-κB. Translocation of NF-κB from the cytoplasm into the nucleus of pancreatic cancer cell lines was observed via immunofluorescence microscopy following treatment with rfhSP-D as compared to the untreated cells. The rfhSP-D treatment caused upregulation of pro-apoptotic marker Fas, as analyzed via qPCR and western blot, which then triggered caspase cascade, as evident from cleavage of caspase 8 and 3 analyzed via western blot at 48 h. The cell number following the rfhSP-D treatment was reduced in the order of Panc-1 (~67%) > MiaPaCa-2 (~60%) > Capan-2 (~35%). This study appears to suggest that rfhSP-D can potentially be used to therapeutically target pancreatic cancer cells irrespective of their p53 phenotype.

  6. Diagnostic value of computer tomography in chronic pancreatitis

    International Nuclear Information System (INIS)

    Kolmannskog, F.; Schrumpf, E.; Bergan, A.; Larsen, S.

    1981-01-01

    During a 3-year-period 39 patients with chronic pancreatitis were subjected to roentgen examinations and exocrine pancreatic function tests (EPFT). Computer tomography (CT) was carried out in 36 of these, and revealed pancreatic disease in 29, while characteristic findings of chronic pancreatitis were demonstrated in 24 patients. CT was particularly valuable in diagnosing intra- and extrapancreatic pseudocysts and pancreatic abscesses complicating chronic pancreatitis. At endoscopic retrograde pancreatography (ERP) pathologic alterations were demonstrated in 23 of 24 patients, and was diagnostic for chronic pancreatitis in 20 patients. The cannulation failed in 7 patients. The results indicate that ERP cannot be replaced by CT. ERP is still needed for detailed demonstration of the pancreatic duct system, especially preoperatively. Conventional films of the abdomen, EPFT and angiography were the least sensitive tests. (Auth.)

  7. Ultrasonographic diagnosis of pancreatic and peripancreatic cancer

    International Nuclear Information System (INIS)

    Park, Churl Min; Kim, Ho Kyun; Yoon, Yup; Lee, Sun Wha; Kim, Soon Yong; Ahn, Chi Yul

    1982-01-01

    Seventeen cases of cancers in and adjacent to the pancreas were studied by high resolution and wide field real time ultrasonographic scanner with 3.5 MHz linear array electronically focusing transducer. The result were as follows: 1. In a total of 17 cases, 7 cases were pancreatic cancers and the rests were 3 cases of ampulla of Vaster cancer, 3 cases of distal CBD cancers, and 4 cases of metastatic cancers, respectively. 2. Pancreatic cancers were located mainly in head portion, and metastatic cancers were noted in head, tail, and retropancreatic areas. 3. The sizes of all distal CBD cancer were less than 1.8 cm, usually smaller than other tumors, and the size of metastatic cancers were variable (1-6 cm). 4. The shape, margin, contour and echogenicity of the tumors were variable. 5. Pancreatic duct showed marked dilatation in one of pancreatic cancer, and mild dilatation in one of ampulla of Vater cancer. 6. The caliber of extrahepatic duct were moderately or markedly dilated in nearly all cases except 2 cases of pancreatic body cancer. 7. The pancreatic margin is partially obliterated in pancreatic and ampulla of Vater cancers but not in distal CBD cancer. 8. Gallbladder enlargement is secondary change due to the obstruction of extrahepatic bile duct. 9. Effects on the vessels are due to not only direct mass effect but direct invasion resulting in obliteration. The most commonly involved vessels are spleno-portal junction, splenic vein and portal vein. In case of pancreatic cancer in uncinate process, the superior mesenteric vessels are displaced anteriorly. 10. Surrounding metastatic lesions were suspected in pancreatic and ampulla of Vater cancer, but not seen in distal CBD cancer. 11. Ascites were seen in only two cases of metastasis

  8. Stenting and extracorporeal shock wave lithotripsy in chronic pancreatitis

    DEFF Research Database (Denmark)

    Holm, M; Matzen, Peter

    2003-01-01

    BACKGROUND: Early observational studies of endoscopic treatment and extracorporeal shock wave lithotripsy (ESWL) reported considerable or complete relief of pain in 50%-80% of patients with chronic pancreatitis. There is no consensus on the measurement of pain, making comparison of observational...... studies difficult, and little attention has been paid to the type and amount of analgesics used by patients before and after decompressive treatment. METHODS: We performed a retrospective study of all patients with chronic pancreatitis and large-duct disease and receiving decompressing treatment between 1...... November 1994 and 31 July 1999. Primary parameters were type and amount of analgesics used. RESULTS: Forty-nine patients with chronic pancreatitis and large-duct disease received stenting of the pancreatic duct (28 patients), ESWL (6 patients) or both (15 patients). After a median follow-up of 21 months...

  9. Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts

    Directory of Open Access Journals (Sweden)

    Rangarajan Sambathkumar

    2016-01-01

    Full Text Available Reprogramming can occur by the introduction of key transcription factors (TFs as well as by epigenetic changes. We demonstrated that histone deacetylase inhibitor (HDACi Trichostatin A (TSA combined with a chromatin remodeling medium (CRM induced expression of a number of definitive endoderm and early and late pancreatic marker genes. When CRM was omitted, endoderm/pancreatic marker genes were not induced. Furthermore, treatment with DNA methyltransferase inhibitor (DNMTi 5-azacytidine (5AZA CRM did not affect gene expression changes, and when 5AZA was combined with TSA, no further increase in gene expression of endoderm, pancreatic endoderm, and endocrine markers was seen over levels induced with TSA alone. Interestingly, TSA-CRM did not affect expression of pluripotency and hepatocyte genes but induced some mesoderm transcripts. Upon removal of TSA-CRM, the endoderm/pancreatic gene expression profile returned to baseline. Our findings underscore the role epigenetic modification in transdifferentiation of one somatic cell into another. However, full reprogramming of fibroblasts to β-cells will require combination of this approach with TF overexpression and/or culture of the partially reprogrammed cells under β-cell specific conditions.

  10. Peptide-Conjugated Quantum Dots Act as the Target Marker for Human Pancreatic Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Shuang-ling Li

    2016-03-01

    Full Text Available Background/Aims: In the present study, we describe a novel and straightforward approach to produce a cyclic- arginine-glycine-aspartic (RGD-peptide-conjugated quantum dot (QD probe as an ideal target tumor biomarker. Due to its specific structure, the probe can be used for targeted imaging of pancreatic carcinoma cells. Methods: Pancreatic carcinoma cells were routinely cultured and marked with QD-RGD probe. The QD-RGD probe on the fluorescence-labeled cancer cell was observed by fluorescence microscopy and laser confocal microscopy. Cancer cell viability was detected by MTT assay after culturing with QD-RGD probe. Results: Fluorescence microscopy and laser confocal microscopy displayed that 10nmol/L QD-RGD probe was able to effectively mark pancreatic carcinoma cells. In comparison with organic dyes and fluorescent proteins, the quantum dot-RGD probe had unique optical and electronic properties. Conclusion: QD-RGD probe has a low cytotoxicity with an excellent optical property and biocompatibility. These findings support further evaluation of QD-RGD probes for the early detection of pancreatic cancer.

  11. Diagnosis and treatment of traumatic pancreatic injury

    International Nuclear Information System (INIS)

    Hirakawa, Akihiko; Isayama, Kenji; Nakatani, Toshio

    2011-01-01

    The diagnosis of traumatic pancreatic injury in the acute stage is difficult to establish blood tests and abdominal findings alone. Moreover, to determine treatment strategies, it is important not only that a pancreatic injury is diagnosed but also whether a pancreatic ductal injury can be found. At our center, to diagnose isolated pancreatic injuries, we actively perform endoscopic retrograde pancreatography (ERP) in addition to abdominal CT at the time of admission. For cases with complications such as abdominal and other organ injuries, we perform a laparotomy to ascertain whether a pancreatic duct injury is present. In regard to treatment options, for grade III injuries to the pancreatic body and tail, we basically choose distal pancreatectomy, but we also consider the Bracy method depending on the case. As for grade III injuries to the pancreatic head, we primarily choose pancreaticoduodenectomy, but also apply drainage if the situation calls for it. However, pancreatic injuries are often complicated by injuries of other regions of the body. Thus, diagnosis and treatment of pancreatic injury should be based on a comprehensive decision regarding early prioritization of treatment, taking hemodynamics into consideration after admission, and how to minimize complications such as anastomotic leak and pancreatic fistulas. (author)

  12. Adoptive immunotherapy of human pancreatic cancer with lymphokine-activated killer cells and interleukin-2 in a nude mouse model

    International Nuclear Information System (INIS)

    Marincola, F.M.; Da Pozzo, L.F.; Drucker, B.J.; Holder, W.D. Jr.

    1990-01-01

    A pancreatic cancer cell line was grown in orthotopic and heterotopic positions in young Swiss/NIH nude mice, which were tested with adoptive immunotherapy. Mice were injected with 1 x 10(7) human cancer cells in the subcutaneous tissue and duodenal lobe of the pancreas. The mice were randomly divided into four groups: group IA (LAK + IL-2) (N = 25) received 2 X 10(7) human lymphokine-activated killer (LAK) cells from normal donors by tail vein injection followed by 10,000 units of human recombinant interleukin-2 (IL-2) given intraperitoneally every 12 hours for 28 days; group IB (IL-2) (N = 27) was given the same dose of IL-2 alone; group IC (RPMI-1640) (N = 18) received a placebo consisting of 1 ml of RPMI-1640 intraperitoneally every 12 hours; and group ID (LAK) (N = 14) received 2 X 10(7) LAK cells but no IL-2. Toxicity was significantly higher in group IB, with a mortality rate of 45.5% (10/22 animals) versus a 0% mortality (0/25) in group IA. None of the group IA or IB animals died of pancreatic cancer during the experiment. The animals that did not receive IL-2 died before 28 days in 14.2% of group IC and in 16.7% of group ID. The area under the growth curve of subcutaneous tumors during the course of treatment and the pancreatic tumor weight at the end of treatment were compared in each group. Subcutaneous tumors had a reduced rate of growth in group IA animals compared to all the other treatments. Pancreatic tumor growth was slowed in group IA. The animals treated with IL-2 alone (group IB) showed some slowing of tumor growth that was intermediate between group IA, group IC, and group ID. A similar experiment was done with irradiated (375 rad) mice. Nine nude mice with tumors were treated with LAK + IL-2 (group IIA), eight received IL-2 alone (group IIB), and seven received placebo (group IIC)

  13. Volumetric gain of the human pancreas after left partial pancreatic resection: A CT-scan based retrospective study.

    Science.gov (United States)

    Phillip, Veit; Zahel, Tina; Danninger, Assiye; Erkan, Mert; Dobritz, Martin; Steiner, Jörg M; Kleeff, Jörg; Schmid, Roland M; Algül, Hana

    2015-01-01

    Regeneration of the pancreas has been well characterized in animal models. However, there are conflicting data on the regenerative capacity of the human pancreas. The aim of the present study was to assess the regenerative capacity of the human pancreas. In a retrospective study, data from patients undergoing left partial pancreatic resection at a single center were eligible for inclusion (n = 185). Volumetry was performed based on 5 mm CT-scans acquired through a 256-slice CT-scanner using a semi-automated software. Data from 24 patients (15 males/9 females) were included. Mean ± SD age was 68 ± 11 years (range, 40-85 years). Median time between surgery and the 1st postoperative CT was 9 days (range, 0-27 days; IQR, 7-13), 55 days (range, 21-141 days; IQR, 34-105) until the 2nd CT, and 191 days (range, 62-1902; IQR, 156-347) until the 3rd CT. The pancreatic volumes differed significantly between the first and the second postoperative CT scans (median volume 25.6 mL and 30.6 mL, respectively; p = 0.008) and had significantly increased further by the 3rd CT scan (median volume 37.9 mL; p = 0.001 for comparison with 1st CT scan and p = 0.003 for comparison with 2nd CT scan). The human pancreas shows a measurable and considerable potential of volumetric gain after partial resection. Multidetector-CT based semi-automated volume analysis is a feasible method for follow-up of the volume of the remaining pancreatic parenchyma after partial pancreatectomy. Effects on exocrine and endocrine pancreatic function have to be evaluated in a prospective manner. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  14. Ellagic acid inhibits the proliferation of human pancreatic carcinoma PANC-1 cells in vitro and in vivo.

    Science.gov (United States)

    Cheng, Hao; Lu, Chenglin; Tang, Ribo; Pan, Yiming; Bao, Shanhua; Qiu, Yudong; Xie, Min

    2017-02-14

    Ellagic aicd (EA), a dietary polyphenolic compound found in plants and fruits, possesses various pharmacological activities. This study investigated the effect of EA on human pancreatic carcinoma PANC-1 cells both in vitro and in vivo; and defined the associated molecular mechanisms. In vitro, the cell growth and repairing ability were assessed by CCK-8 assay and wound healing assay. The cell migration and invasion activity was evaluated by Tanswell assay. In vivo, PANC-1 cell tumor-bearing mice were treated with different concentrations of EA. We found that EA significantly inhibited cell growth, cell repairing activity, and cell migration and invasion in a dose-dependent manner. Treatment of PANC-1 xenografted mice with EA resulted in significant inhibition in tumor growth and prolong mice survival rate. Furthermore, flow cytometric analysis showed that EA increased the percentage of cells in the G1 phase of cell cycle. Western blot analysis revealed that EA inhibited the expression of COX-2 and NF-κB. In addition, EA reversed epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. In summary, the present study demonstrated that EA inhibited cell growth, cell repairing activity, cell migration and invasion in a dose-dependent manner. EA also effectively inhibit human pancreatic cancer growth in mice. The anti-tumor effect of EA might be related to cell cycle arrest, down-regulating the expression of COX-2 and NF-κB, reversing epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. Our findings suggest that the use of EA would be beneficial for the management of pancreatic cancer.

  15. RAS/ERK modulates TGFbeta-regulated PTEN expression in human pancreatic adenocarcinoma cells.

    Science.gov (United States)

    Chow, Jimmy Y C; Quach, Khai T; Cabrera, Betty L; Cabral, Jennifer A; Beck, Stayce E; Carethers, John M

    2007-11-01

    Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is rarely mutated in pancreatic cancers, but its regulation by transforming growth factor (TGF)-beta might mediate growth suppression and other oncogenic actions. Here, we examined the role of TGFbeta and the effects of oncogenic K-RAS/ERK upon PTEN expression in the absence of SMAD4. We utilized two SMAD4-null pancreatic cell lines, CAPAN-1 (K-RAS mutant) and BxPc-3 (WT-K-RAS), both of which express TGFbeta surface receptors. Cells were treated with TGFbeta1 and separated into cytosolic/nuclear fractions for western blotting with phospho-SMAD2, SMAD 2, 4 phospho-ATP-dependent tyrosine kinases (Akt), Akt and PTEN antibodies. PTEN mRNA levels were assessed by reverse transcriptase-polymerase chain reaction. The MEK1 inhibitor, PD98059, was used to block the downstream action of oncogenic K-RAS/ERK, as was a dominant-negative (DN) K-RAS construct. TGFbeta increased phospho-SMAD2 in both cytosolic and nuclear fractions. PD98059 treatment further increased phospho-SMAD2 in the nucleus of both pancreatic cell lines, and DN-K-RAS further improved SMAD translocation in K-RAS mutant CAPAN cells. TGFbeta treatment significantly suppressed PTEN protein levels concomitant with activation of Akt by 48 h through transcriptional reduction of PTEN mRNA that was evident by 6 h. TGFbeta-induced PTEN suppression was reversed by PD98059 and DN-K-RAS compared with treatments without TGFbeta. TGFbeta-induced PTEN expression was inversely related to cellular proliferation. Thus, oncogenic K-RAS/ERK in pancreatic adenocarcinoma facilitates TGFbeta-induced transcriptional down-regulation of the tumor suppressor PTEN in a SMAD4-independent manner and could constitute a signaling switch mechanism from growth suppression to growth promotion in pancreatic cancers.

  16. Pancreatic stone and treatment using ERCP and ESWL procedures: a case study and review.

    Science.gov (United States)

    Hayes, James M; Ding, Steven L

    2012-09-07

    Pancreatic duct stones are found in 22 to 60% of patients with chronic pancreatitis (CP). The stones can lead to obstruction of the outflow of pancreatic secretions causing increased intraductal pressure. The pancreas is relatively noncompliant. Therefore the rise in intraductal pressure can induce tissue hypertension and ischemia. This can be a major factor causing pain in patients with CP. This hypothesis is supported by the observation that symptoms may improve following pancreatic duct drainage. A 62-year-old woman presented with persistent epigastric pain. Investigations revealed calcifications within the main pancreatic duct and head of the gland. Treatment with endoscopic retrograde cholangiopancreatography (ERCP) and extracorporeal shock wave lithotripsy (ESWL) achieved a good outcome. Standard endoscopic removal of the stones proved impossible so treatment with ESWL was undertaken. Following fragmentation, the calculi and fragments passed spontaneously or were removed endoscopically. If pancreatic stones cannot be removed endoscopically, ESWL should be considered prior to surgery.

  17. Role of chymotrypsin C in development and progression of pancreatitis and pancreatic cancer

    Directory of Open Access Journals (Sweden)

    LIU Zejie

    2016-11-01

    Full Text Available Chymotrypsin C (CTRC is a trypsinogen synthesized by pancreatic acinar cells and secreted by pancreatic duct cells and belongs to the family of serine chymotrypsin. The main function of CTRC is to regulate the balance between activation and degradation of trypsin and maintain the structural and functional integrity of the pancreas. CTRC gene mutations can cause abnormal activation of trypsinogen and abnormal degradation of trypsin and then lead to the development of pancreatitis. The downregulation or absence of CTRC expression may be associated with the development and metastasis of pancreatic cancer. This article introduces the structure and biological function of CTRC and its mechanism of action in the development and progression of pancreatitis and pancreatic cancer.

  18. Pancreatic tissue fluid pressure in chronic pancreatitis. Relation to pain, morphology, and function

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Bülow, J

    1990-01-01

    The relation between pancreatic tissue fluid pressure and pain, morphology, and function was studied in a cross-sectional investigation. Pressure measurements were performed by percutaneous fine-needle puncture. Thirty-nine patients with chronic pancreatitis were included, 25 with pain and 14...... without (p = 0.004 and p = 0.0003, respectively). The pressure was significantly related (inversely) to pancreatic duct diameter only in the group of 19 patients with earlier pancreatic surgery (R = -0.57, p = 0.02). The pressure was not related to functional factors or the presence of pancreatic...... without pain. The pressure was higher in patients with pain than in patients without pain (p = 0.000001), and this was significantly related to a pain score from a visual analogue scale (p less than 0.001). Patients with pancreatic pseudocysts had both higher pressure and higher pain score than patients...

  19. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ayesha Salahuddin

    2014-01-01

    Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.

  20. Adenomas of the common bile duct in familial adenomatous polyposis

    Science.gov (United States)

    Yan, Mao-Lin; Pan, Jun-Yong; Bai, Yan-Nan; Lai, Zhi-De; Chen, Zhong; Wang, Yao-Dong

    2015-01-01

    Familial adenomatous polyposis (FAP) or Gardner’s syndrome is often accompanied by adenomas of the stomach and duodenum. We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis. Only 8 cases of adenomas or adenocarcinoma of the common bile duct have been reported in the literature in patients with FAP or Gardner’s syndrome. Those patients presented with acute cholangitis or pancreatitis. Local excision or Whipple procedure may be the reasonable surgical option. PMID:25780319

  1. Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg2+-sensitive Socs3a signaling in development and cancer

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2011-03-01

    Genetic analysis of pancreatic development has provided new insights into the mechanisms underlying the formation of exocrine pancreatic neoplasia. Zebrafish sweetbread (swd mutants develop hypoplastic acini and dysmorphic ducts in the exocrine pancreas, with impeded progression of cell division cycle and of epithelial growth. Positional cloning and allelic complementation have revealed that the swd mutations affect the transient receptor potential melastatin-subfamily member 7 (trpm7 gene, which encodes a divalent cation-permeable channel with kinase activity. Supplementary Mg2+ partially rescued the exocrine pancreatic defects of the trpm7 mutants by improving cell-cycle progression and growth and repressing the suppressor of cytokine signaling 3a (socs3a gene. The role of Socs3a in Trpm7-mediated signaling is supported by the findings that socs3a mRNA level is elevated in the trpm7 mutants, and antisense inhibition of socs3a expression improved their exocrine pancreatic growth. TRPM7 is generally overexpressed in human pancreatic adenocarcinoma. TRPM7-deficient cells are impaired in proliferation and arrested in the G0-G1 phases of the cell division cycle. Supplementary Mg2+ rescued the proliferative defect of the TRPM7-deficient cells. Results of this study indicate that Trpm7 regulates exocrine pancreatic development via the Mg2+-sensitive Socs3a pathway, and suggest that aberrant TRPM7-mediated signaling contributes to pancreatic carcinogenesis.

  2. Growth inhibition of human pancreatic cancer cells by lipofection mediated IGF-1R antisense oligodeoxynucletides in combination with ionizing radiation

    International Nuclear Information System (INIS)

    Pan Yaozhen; Sun Chengyi; Wang Yuzhi

    2004-01-01

    Objective: To study the growth inhibition of human pancreatic cancer cells (PC-3) by lipofection-mediated and ionizing radiation improving transfection of IGF-1R antisense oligodeoxynucletides (ASON) in vitro. Methods: Colonigenicity of PC-3 cells in vitro after 60 Co γ-radiation was observed for ascertaining their radiosensitivity and optimal radiation dose was selected according to the radiation sensitivity. PC-3 cells were transfected by two ways: 1) by lipofection-mediated IGF-1R ASON combined with ionizing radiation. 2) by lipo-ASON alone without ionizing radiation. Cell growth was assessed by MTT method. The expression of IGF-1R at mRNA level was examined by RT-PCR. Flow cytometry was used to demonstrate apoptotic changes in lipo-ASON-treated cells. Results: The inhibitory efficiency of lipo-ASON combined with ionizing radiation was higher than that without ionizing radiation (P < 0.05). The apoptotic efficiency and the decreased level of IGF-1R at mRNA were significantly improved (P < 0.05). Conclusion: Lipofection-mediated and ionizing radiation-promoted transfection of IGF-1R antisense oligodeoxynucletides (ASON) significantly decreases IGF-1R at mRNA level and induces apoptosis of human pancreatic cancer cells in vitro

  3. Palmitate activates autophagy in INS-1E β-cells and in isolated rat and human pancreatic islets.

    Directory of Open Access Journals (Sweden)

    Luisa Martino

    Full Text Available We have investigated the in vitro effects of increased levels of glucose and free fatty acids on autophagy activation in pancreatic beta cells. INS-1E cells and isolated rat and human pancreatic islets were incubated for various times (from 2 to 24 h at different concentrations of glucose and/or palmitic acid. Then, cell survival was evaluated and autophagy activation was explored by using various biochemical and morphological techniques. In INS-1E cells as well as in rat and human islets, 0.5 and 1.0 mM palmitate markedly increased autophagic vacuole formation, whereas high glucose was ineffective alone and caused little additional change when combined with palmitate. Furthermore, LC3-II immunofluorescence co-localized with that of cathepsin D, a lysosomal marker, showing that the autophagic flux was not hampered in PA-treated cells. These effects were maintained up to 18-24 h incubation and were associated with a significant decline of cell survival correlated with both palmitate concentration and incubation time. Ultrastructural analysis showed that autophagy activation, as evidenced by the occurrence of many autophagic vacuoles in the cytoplasm of beta cells, was associated with a diffuse and remarkable swelling of the endoplasmic reticulum. Our results indicate that among the metabolic alterations typically associated with type 2 diabetes, high free fatty acids levels could play a role in the activation of autophagy in beta cells, through a mechanism that might involve the induction of endoplasmic reticulum stress.

  4. Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Falzon, Miriam, E-mail: mfalzon@utmb.edu; Bhatia, Vandanajay [Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2015-06-18

    Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation.

  5. Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Miriam Falzon

    2015-06-01

    Full Text Available Chronic pancreatitis (CP, a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation.

  6. Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

    International Nuclear Information System (INIS)

    Falzon, Miriam; Bhatia, Vandanajay

    2015-01-01

    Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation

  7. Diagnosis of pancreatic tumors : comparison of MR pancreatography(MRP) and endoscopic retrograde pancreatography(ERP)

    International Nuclear Information System (INIS)

    Noh, Ki Suh; Seo, Jung Hoon; Kim, Myeong Jin; Chung, Jae Bok; Chung, Jae Joon; Lee, Jong Tae; Yoo, Hyung Sik

    1999-01-01

    Magnetic resonance pancreatography(MRP) is a non-invasive imaging technique for visualization of the pancreatic duct system, and is similar to those obtained by means of endoscopic retrograde pancreatography(ERP). To determine the role of MRP in the diagnosis of pancreatic tumors, the diagnostic confidence and imaginal difference of MRP and ERP were compared. Twenty patients(13 male and 7 female, mean age 59 years) with pancreatic tumors underwent MRP and ERP. The former involved the use of a single shot fast spin-echo sequence on a 1.5T system. All images were retrospectively reviewed by a radiologist and a gastroenterologist, working together. Both MRP and ERP were compared for separate visualization of the head, body and tail portion of the pancreatic duct, and scored as excellent (4), good (3), fair (2), poor (1), or no visualization (0). In addition, the overall diagnostic confidence of both modalities was graded subjectively from non-diagnoses (0) to definite information (4). The final diagnoses derived from surgical findings (n=9) or imaging findings and clinical follow-up (n=7) were as follows : pancreatic cancer (n=12), mucin-producing pancreatic cancer (n=2), mucinous ductectatic tumor (n=4), serous cystadenoma (n=2). To assess the statistical significance of difference, the paired t-test was used. Mean scores of visualization of the pancreatic duct by MRP and ERP were 2.91 and 3.15 in the pancreatic head (p=NS), 3.11 and 2.18 in the pancreatic body (p=NS), and 3.07 and 1.09 in the pancreatic tail (p<0.01). The mean score of diagnostic confidence was 4.03 for MRP and 2.51 for ERP, a statistically significant difference (p<0.05). In 11 patients with obstruction of the pancreatic duct due to malignant lesions, MRP visualized the duct both proximally and distally to the site of obstruction, while ERP visualized only the distal duct to the site of obstruction. MRP was also better at defining the extent of tumor by visualization of surrounding pancreatic

  8. Chronic pancreatitis: from guidelines to clinical practice

    Directory of Open Access Journals (Sweden)

    Generoso Uomo

    2012-10-01

    Full Text Available Introduction The paucity of specific standardized criteria leads to uncertainties in clinical practice regarding the management of chronic pancreatitis (CP.Objectives This paper reports some of the systematic guidelines for the diagnosis and treatment of CP recently elaborated by an Italian multicenter study group. We review recommendations on clinical and nutritional aspects of the disease, assessment of pancreatic function, treatment of exocrine pancreatic failure and secondary diabetes, treatment of pain, and prevention of painful relapses. The review also looks at the role of endoscopy in the management of pancreatic pain, pancreatic stones, duct narrowing and dilation, and complications; the appropriate use of various imaging techniques, including endoscopic ultrasound; and the indications for and techniques used in surgical management of CP.

  9. Primary structure of human pancreatic elastase 2 determined by sequence analysis of the cloned mRNA

    International Nuclear Information System (INIS)

    Fletcher, T.S.; Shen, W.F.; Largman, C.

    1987-01-01

    A cDNA encoding elastase 2 has been cloned from a human pancreatic cDNA library. The cDNA contains a translation initiation site and a poly(A) recognition site and encodes a protein of 269 amino acids, including a proposed 16-residue signal peptide. The amino acid sequence of the deduced mature protein contains a 12-residue activation peptide containing a cysteine at residue 1 similar to that of chymotryspin. The proposed active enzyme contains all of the characteristic active-site amino acids, including His-57, Asp-102, and Ser-195. The S1 binding pocket is bounded by Gly-216 and Ser-226, making this pocket intermediate in size between chymotrypsins and elastase 1 or protease E, consistent with the substrate specificity of elastase 2 for long-chain aliphatic or aromatic amino acids. Computer modeling studies using the amino acid sequence of elastase 2 superimposed on the X-ray structure of porcine elastase 1 suggest that a change of Gln-192 in elastase 1 to Asn-192 in elastase 2 may account for the lower catalytic efficiency of the latter enzyme. Several basic residues appear to be near the ends of the extended binding pocket of elastases which might serve to anchor the enzyme to the elastin substrate. These studies indicate that elastases 2 and elastase 1 both contain an Arg-65A as well as a basic dipeptide at 223/224 which is not present in chymotrypsins. In addition, Arg-217A is present in humaan elastase 2 but absent in rat pancreatic protein which has been proposed to be an elastase 2 on the basis of sequence homology, but which was not isolated during screening of rat pancreatic tissue extracts for elastolytic activity

  10. Metformin targets the metabolic achilles heel of human pancreatic cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Enza Lonardo

    Full Text Available Pancreatic ductal adenocarcinomas contain a subset of exclusively tumorigenic cancer stem cells (CSCs, which are capable of repopulating the entire heterogeneous cancer cell populations and are highly resistant to standard chemotherapy. Here we demonstrate that metformin selectively ablated pancreatic CSCs as evidenced by diminished expression of pluripotency-associated genes and CSC-associated surface markers. Subsequently, the ability of metformin-treated CSCs to clonally expand in vitro was irreversibly abrogated by inducing apoptosis. In contrast, non-CSCs preferentially responded by cell cycle arrest, but were not eliminated by metformin treatment. Mechanistically, metformin increased reactive oxygen species production in CSC and reduced their mitochondrial transmembrane potential. The subsequent induction of lethal energy crisis in CSCs was independent of AMPK/mTOR. Finally, in primary cancer tissue xenograft models metformin effectively reduced tumor burden and prevented disease progression; if combined with a stroma-targeting smoothened inhibitor for enhanced tissue penetration, while gemcitabine actually appeared dispensable.

  11. Modified nasolacrimal duct stenting

    International Nuclear Information System (INIS)

    Tian Min; Jin Mei; Chen Huanjun; Li Yi

    2008-01-01

    Objective: Traditional nasolacrimal duct stenting possesses some shortcoming including difficulty of pulling ball head guide wire from the nasal cavity with turbinate hypertrophy and nasal septal deviation. The new method of nose-oral tube track establishment can overcome the forementioned and increase the successful rate. Methods: 5 F catheter and arterial sheath were modified to be nasolacrimal duct stent delivery device respectively. Antegrade dacryocystography was taken firstly to display the obstructed site and followed by the modified protocol of inserting the guide wire through nasolacrimal duct and nasal cavity, and establishing the stent delivery track for retrograde stent placement. Results: 5 epiphora patients with failure implantation by traditional method were all succeeded through the modified stenting (100%). During 6-mouth follow-up, no serious complications and reocclusion occurred. Conclusion: The establishment of eye-nose-mouth-nose of external nasal guide wire track can improve the successful rate of nasolacrimal duct stenting. (authors)

  12. Bile duct obstruction

    Science.gov (United States)

    ... Tumors that have spread to the biliary system Liver and bile duct worms (flukes) The risk factors include: History of ... Increased bilirubin level Increased alkaline phosphatase level Increased liver enzymes The ... CT scan Endoscopic retrograde cholangiopancreatography ( ...

  13. Ducted fuel injection

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Charles J.

    2018-03-06

    Various technologies presented herein relate to enhancing mixing inside a combustion chamber to form one or more locally premixed mixtures comprising fuel and charge-gas with low peak fuel to charge-gas ratios to enable minimal, or no, generation of soot and other undesired emissions during ignition and subsequent combustion of the locally premixed mixtures. To enable sufficient mixing of the fuel and charge-gas, a jet of fuel can be directed to pass through a bore of a duct causing charge-gas to be drawn into the bore creating turbulence to mix the fuel and the drawn charge-gas. The duct can be located proximate to an opening in a tip of a fuel injector. The duct can comprise of one or more holes along its length to enable charge-gas to be drawn into the bore, and further, the duct can cool the fuel and/or charge-gas prior to combustion.

  14. A "rendezvous technique" for treating a pancreatic fistula after distal pancreatectomy.

    Science.gov (United States)

    Imai, Daisuke; Yamashita, Yo-ichi; Ikegami, Toru; Toshima, Takeo; Harimoto, Norifumi; Yoshizumi, Tomoharu; Soejima, Yuji; Shirabe, Ken; Ikeda, Tetsuo; Maehara, Yoshihiko

    2015-01-01

    Pancreatic fistulae are a major complication of distal pancreatectomy (DP). Some cases of severe pancreatic fistula require invasive procedures. There have been some reports concerning the effectiveness of pancreatic duct drainage through an endoscopic transpapillary approach for pancreatic fistulae. We herein present a case of a pancreatic fistula after DP that was successfully treated with percutaneous pancreatic duct drainage, which was performed using a combined percutaneous and endoscopic approach, named the "rendezvous technique". In our case, we performed distal pancreatectomy with celiac artery resection for a locally advanced pancreatic body cancer. On postoperative day (POD) 7, the drain amylase level increased up to 37,460 IU/l. Computed tomography (CT) revealed peripancreatic fluid collections. On POD 10, we placed a catheter in the main pancreatic duct using the rendezvous technique. CT on POD 14 revealed a decrease in the size of the peripancreatic fluid collection, and contrast imaging from the drains on POD 22 revealed almost complete disappearance of the fluid collection. We withdrew the pigtail catheter on POD 27 and the percutaneous pancreatic duct drain on POD 36. This patient was discharged from our hospital on POD 40. We herein report a new approach called the "rendezvous technique" for the management of pancreatic fistulae after DP that can be used instead of a stressful nasopancreatic tube.

  15. Differences in antitumor effects of various statins on human pancreatic cancer

    Czech Academy of Sciences Publication Activity Database

    Gbelcová, H.; Leníček, M.; Zelenka, J.; Knejzlík, Z.; Dvořáková, G.; Zadinová, M.; Poučková, P.; Kudla, M.; Balaž, P.; Ruml, Tomáš; Vítek, L.

    2008-01-01

    Roč. 122, č. 6 (2008), s. 1214-1221 ISSN 0020-7136 R&D Projects: GA ČR(CZ) GD204/03/H066 Grant - others:GA MZd(CZ) NR8132 Institutional research plan: CEZ:AV0Z40550506 Keywords : statins * pancreatic cancer * K-ras oncogene Subject RIV: CE - Biochemistry Impact factor: 4.734, year: 2008

  16. Dynamic MRI of pancreatic neoplasms

    International Nuclear Information System (INIS)

    Furukawa, Nobuyoshi; Takayasu, Ken-ichi; Muramatu, Yukio

    1995-01-01

    The usefulness of dynamic MRI study using contrast media is studied on pancreatic tumors. This method was useful in detecting small lesion of pancreatic tumor, however, T1-weighted SE method was more useful in detecting swelling lesions or diagnosing degree of tumors. Although endocrine tumors are depicted by contrast media, careful attention is needed since there are some hypovascular cases. T2-weighted image is commonly performed to detect the morphology of cystic content and the correlation between the pancreas and bile duct in cystic tumors, however, dynamic study was more useful in proving vascularity of serous cystadenoma and differentiating malignant or benign mucous cystic tumors by depicting intracystic torous components. In performing MR imaging on pancreatic diseases, it is necessary to select appropriate imaging procedure, and dynamic study should be included and used in a rational manner. (S.Y.)

  17. [Effects of cucurmosin on the cell proliferation and apoptosis in human pancreatic PANC-1 cells].

    Science.gov (United States)

    Xu, Chun-Sen; Huang, He-Guang; Chen, Ming-Huang

    2012-02-01

    To observe the effects of cucurmosin (CUS) on the cell proliferation and apoptosis in pancreatic PANC-1 cells. The inhibition of CUS on the PANC-1 cell growth was observed using MTT assay. The inhibition ratio of CUS on the pancreatic orthotopic transplantation was in vivo observed in the NOD/SCID mouse model. The changes of microstructure of the apoptosis-inducing effect of CUS on PANC-1 was observed under electron microscope. The cell cycle and apoptosis after CUS intervention was detected using flow cytometry. The Caspase-3 activity after CUS treatment was detected using enzyme linked immunospecific assay (ELISA). Treatment with CUS at the dose of 0.125, 0.25, and 0.5 mg/kg inhibited the growth of pancreatic carcinoma PANC-1 xenografs with the ratio of 45.2%, 50.0%, and 59.7%, respectively (P PANC-1 cells in a dose-dependent maner. Being exposed to 40.0 microg/mL of the CUS for 24, 48, and 72 h, the percentage of G0/ G1 phase cells was 56.60% +/- 6.65%, 67.83% +/- 6.76%, and 77.00% +/- 6.73%, respectively (P PANC-1 cells in the G0/G1 phase of the cell cycle in a time-dependent maner. CUS significantly inhibited the growth of PANC-1 cells possibly through the G0/G1 cell cycle arrest and apoptosis.

  18. Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment

    Science.gov (United States)

    Testoni, Pier Alberto

    2014-01-01

    Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches. PMID:25493002

  19. Laparoscopic side-to-side pancreaticojejunostomy for chronic pancreatitis in children

    Directory of Open Access Journals (Sweden)

    Kyoichi Deie

    2016-01-01

    Full Text Available Surgical pancreatic duct (PD drainage for chronic pancreatitis in children is relatively rare. It is indicated in cases of recurrent pancreatitis and PD dilatation that have not responded to medical therapy and therapeutic endoscopy. We performed laparoscopic side-to-side pancreaticojejunostomy for two paediatric patients with chronic pancreatitis. The main PD was opened easily by electrocautery after locating the dilated PD by intraoperative ultrasonography. The dilated PD was split longitudinally from the pancreatic tail to the pancreatic head by laparoscopic coagulation shears or electrocautery after pancreatography. A laparoscopic side-to-side pancreaticojejunostomy was performed by a one-layered technique using continuous 4-0 polydioxanone (PDS sutures from the pancreatic tail to the pancreatic head. There were no intraoperative or postoperative complications or recurrences. This procedure has cosmetic advantages compared with open surgery for chronic pancreatitis. Laparoscopic side-to-side pancreaticojejunostomy in children is feasible and effective for the treatment of chronic pancreatitis.

  20. Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.

    Science.gov (United States)

    José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

  1. Acetylshikonin Inhibits Human Pancreatic PANC-1 Cancer Cell Proliferation by Suppressing the NF-κB Activity.

    Science.gov (United States)

    Cho, Seok-Cheol; Choi, Bu Young

    2015-09-01

    Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-κB signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-α (TNF-α)-induced NF-κB reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-κB activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.

  2. Downregulation of Type II Diabetes Mellitus and Maturity Onset Diabetes of Young Pathways in Human Pancreatic Islets from Hyperglycemic Donors

    Directory of Open Access Journals (Sweden)

    Jalal Taneera

    2014-01-01

    Full Text Available Although several molecular pathways have been linked to type 2 diabetes (T2D pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemia n=20 and normoglycemia n=58 were subjected to Gene Set Enrichment Analysis (GSEA. About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM and maturity onset diabetes of the young (MODY pathways are downregulated in hyperglycemic donors, while proteasome and spliceosome pathways are upregulated. The mean centroid of gene expression of T2DM and MODY pathways was shown to be associated positively with insulin secretion and negatively with HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in islet function and might be involved in T2D. Also, the study demonstrates that gene expression profiles from pancreatic islets can reveal some of the biological processes related to regulation of glucose hemostats and diabetes pathogenesis.

  3. Human leukocyte and porcine pancreatic elastase: X-ray crystal structures, mechanism, substrate specificity, and mechanism-based inhibitors

    International Nuclear Information System (INIS)

    Bode, W.; Meyer, E. Jr.; Powers, J.C.

    1989-01-01

    The serine protease family of enzymes is one of the most widely studied group of enzymes, as evidenced by the fact that more crystal structures are available for individuals of this superfamily than for any other homologous group of enzymes. These enzymes contain a conserved triad of catalytic residues including Ser-195, His-57, and Asp-102. The active-site serine is very nucleophilic, and serine proteases are inhibited by specific serine protease reagents such as diisopropyl phosphorofluoridate (DFP), phenylmethanesulfonyl fluoride, and 3,4-dichloroisocoumarin. Elastases are a group of proteases that possess the ability to cleave the important connective tissue protein elastin. Elastin has the unique property of elastic recoil, is widely distributed in vertebrate tissue, and is particularly abundant in the lungs, arteries, skin, and ligaments. Human neutrophil elastase and pancreatic elastase are two major serine proteases that cleave elastin. Neutrophil elastase is found in the dense granules of polymorphonuclear leukycytes and is essential for phagocytosis and defense against infection by invading microorganisms. Pancreatic elastase is stored as an inactive zymogen in the pancreas and is secreted into the intestines where it becomes activated by trypsin and then participates in digestion. Both elastases cleave substrates at peptide bonds where the P 1 residue is an amino acid residue with a small alkyl side chain

  4. Effect of oridonin-mediated hallmark changes on inflammatory pathways in human pancreatic cancer (BxPC-3) cells.

    Science.gov (United States)

    Chen, Ru-Yi; Xu, Bin; Chen, Su-Feng; Chen, Si-Si; Zhang, Ting; Ren, Jun; Xu, Jian

    2014-10-28

    To investigate the effect of oridonin on nuclear transcription factors and to study the relationship between biological behavior and inflammatory factors in human pancreatic cancer (BxPC-3) cells. BxPC-3 cells were treated with various concentrations of oridonin, and viability curves were generated to test for inhibitory effects of the drug on cells. The expression of cytokines such as interleukin-1β (IL-1β), IL-6, or IL-33 was detected in BxPC-3 cell supernatants using an enzyme-linked immunosorbent assay (ELISA), and the protein expression of nuclear transcription factors including nuclear factor κB, activating protein-1, signal transducer and activator of transcription 3, bone morphogenetic protein 2, transforming growth factor β1 and sma and mad homologues in BxPC-3 cells was detected using Western blot. Carcinoma hallmark-related proteins such as survivin, vascular endothelial growth factor, and matrix metallopeptidase 2 were also detected using immunoblotting, and intra-nuclear IL-33 expression was detected using immunofluorescent staining. Treatment with oridonin reduced the viability of BxPC-3 cells in a dose dependent manner. The cells exhibited reduced growth following treatment with 8 μg/mL oridonin (13.05% ± 3.21%, P hallmarks and regulated the expression of various nuclear transcription factors. The results obtained suggest that oridonin alters the hallmarks of pancreatic cancer cells through the regulation of nuclear transcription factors.

  5. Surgical therapy in chronic pancreatitis.

    Science.gov (United States)

    Neal, C P; Dennison, A R; Garcea, G

    2012-12-01

    Chronic pancreatitis (CP) is an inflammatory disease of the pancreas which causes chronic pain, as well as exocrine and endocrine failure in the majority of patients, together producing social and domestic upheaval and a very poor quality of life. At least half of patients will require surgical intervention at some stage in their disease, primarily for the treatment of persistent pain. Available data have now confirmed that surgical intervention may produce superior results to conservative and endoscopic treatment. Comprehensive individual patient assessment is crucial to optimal surgical management, however, in order to determine which morphological disease variant (large duct disease, distal stricture with focal disease, expanded head or small duct/minimal change disease) is present in the individual patient, as a wide and differing range of surgical approaches are possible depending upon the specific abnormality within the gland. This review comprehensively assesses the evidence for these differing approaches to surgical intervention in chronic pancreatitis. Surgical drainage procedures should be limited to a small number of patients with a dilated duct and no pancreatic head mass. Similarly, a small population presenting with a focal stricture and tail only disease may be successfully treated by distal pancreatectomy. Long-term results of both of these procedure types are poor, however. More impressive results have been yielded for the surgical treatment of the expanded head, for which a range of surgical options now exist. Evidence from level I studies and a recent meta-analysis suggests that duodenum-preserving resections offer benefits compared to pancreaticoduodenectomy, though the results of the ongoing, multicentre ChroPac trial are awaited to confirm this. Further data are also needed to determine which of the duodenum-preserving procedures provides optimal results. In relation to small duct/minimal change disease total pancreatectomy represents the only

  6. Prospective assessment of the influence of pancreatic cancer resection on exocrine pancreatic function.

    Science.gov (United States)

    Sikkens, E C M; Cahen, D L; de Wit, J; Looman, C W N; van Eijck, C; Bruno, M J

    2014-01-01

    Exocrine insufficiency frequently develops in patients with pancreatic cancer owing to tumour ingrowth and pancreatic duct obstruction. Surgery might restore this function by removing the primary disease and restoring duct patency, but it may also have the opposite effect, as a result of resection of functional parenchyma and anatomical changes. This study evaluated the course of pancreatic function, before and after pancreatic resection. This prospective cohort study included patients with tumours in the pancreatic region requiring pancreatic resection in a tertiary referral centre between March 2010 and August 2012. Starting before surgery, exocrine function was determined monthly by measuring faecal elastase 1 levels (normal value over 0.200 µg per g faeces). Endocrine function, steatorrhoea-related symptoms and bodyweight were also evaluated before and after surgery. Subjects were followed from diagnosis until 6 months after surgery, or until death. Twenty-nine patients were included, 12 with pancreatic cancer, 14 with ampullary carcinoma and three with bile duct carcinoma (median tumour size 2.6 cm). Twenty-six patients underwent pancreaticoduodenectomy and three distal pancreatectomy. Thirteen patients had exocrine insufficiency at preoperative diagnosis. After a median follow-up of 6 months, this had increased to 24 patients. Diabetes was present in seven patients at diagnosis, and developed in one additional patient within 1 month after surgery. Most patients with tumours in the pancreatic region requiring pancreatic resection either had exocrine insufficiency at diagnosis or became exocrine-insufficient soon after surgical resection. © 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  7. Long-term follow-up of nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children.

    Science.gov (United States)

    Sugito, Kiminobu; Furuya, Takeshi; Kaneda, Hide; Masuko, Takayuki; Ohashi, Kensuke; Inoue, Mikiya; Ikeda, Taro; Koshinaga, Tsugumichi; Tomita, Ryouichi; Maebayashi, Toshiya

    2012-05-01

    The objectives of the present study were to determine nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children. The nutritional status was evaluated by the patterns of growth. Pancreatic function was evaluated by using a questionnaire, the Bristol stool form chart, the serum levels of fasting blood glucose, and hemoglobin A1c (HbA1c). Morphological changes of the pancreatic remnant were evaluated by computed tomography, magnetic resonance image, or magnetic resonance cholangiopancreatography. The present study consisted of 6 patients with pancreatic tumor (5 solid pseudopapillary tumors of the pancreas and 1 pancreatoblastoma) who underwent the following operations: tumor enucleation (3), distal pancreatectomy with splenectomy (1), and pylorus-preserving pancreatoduodenectomy (PPPD [2]). The serum levels of HbA1c have been gradually elevated in 2 patients with PPPD. A significant decrease in pancreatic parenchymal thickness and dilatation of the main pancreatic duct were observed in 2 patients with PPPD. Endocrine pancreatic insufficiency after PPPD may be explainable by obstructive pancreatitis after operation. Taking together the results of pancreatic endocrine function and morphological changes of pancreatic remnant after PPPD, tumor enucleation should be considered as surgical approach in children with pancreas head tumor whenever possible.

  8. Chmp 1A is a mediator of the anti-proliferative effects of All-trans Retinoic Acid in human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Nguyen Hanh

    2009-02-01

    Full Text Available Abstract Background We recently have shown that Charged multivesicular protein/Chromatin modifying protein1A (Chmp1A functions as a tumor suppressor in human pancreatic tumor cells. Pancreatic cancer has the worst prognosis of all cancers with a dismal 5-year survival rate. Preclinical studies using ATRA for treating human pancreatic cancer suggest this compound might be useful for treatment of pancreatic cancer patients. However, the molecular mechanism by which ATRA inhibits growth of pancreatic cancer cells is not clear. The objective of our study was to investigate whether Chmp1A is involved in ATRA-mediated growth inhibition of human pancreatic tumor cells. Results We performed microarray studies using HEK 293T cells and discovered that Chmp1A positively regulated Cellular retinol-binding protein 1 (CRBP-1. CRBP-1 is a key regulator of All-trans retinoic acid (ATRA through ATRA metabolism and nuclear localization. Since our microarray data indicates a potential involvement of Chmp1A in ATRA signaling, we tested this hypothesis by treating pancreatic tumor cells with ATRA in vitro. In the ATRA-responsive cell lines, ATRA significantly increased the protein expression of Chmp1A, CRBP-1, P53 and phospho-P53 at serine 15 and 37 position. We found that knockdown of Chmp1A via shRNA abolished the ATRA-mediated growth inhibition of PanC-1 cells. Also, Chmp1A silencing diminished the increase of Chmp1A, P53 and phospho-P53 protein expression induced by ATRA. In the ATRA non-responsive cells, ATRA did not have any effect on the protein level of Chmp1A and P53. Chmp1A over-expression, however, induced growth inhibition of ATRA non-responsive cells, which was accompanied by an increase of Chmp1A, P53 and phospho-P53. Interestingly, in ATRA responsive cells Chmp1A is localized to the nucleus, which became robust upon ATRA treatment. In the ATRA-non-responsive cells, Chmp1A was mainly translocated to the plasma membrane upon ATRA treatment. Conclusion

  9. Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats

    OpenAIRE

    Matveyenko, Aleksey V.; Georgia, Senta; Bhushan, Anil; Butler, Peter C.

    2010-01-01

    Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in ...

  10. Postoperative Biliary Leak Treated with Chemical Bile Duct Ablation Using Absolute Ethanol: A Report of Two Cases.

    Science.gov (United States)

    Sasaki, Maho; Hori, Tomohide; Furuyama, Hiroaki; Machimoto, Takafumi; Hata, Toshiyuki; Kadokawa, Yoshio; Ito, Tatsuo; Kato, Shigeru; Yasukawa, Daiki; Aisu, Yuki; Kimura, Yusuke; Takamatsu, Yuichi; Kitano, Taku; Yoshimura, Tsunehiro

    2017-08-08

    BACKGROUND Postoperative bile duct leak following hepatobiliary and pancreatic surgery can be intractable, and the postoperative course can be prolonged. However, if the site of the leak is in the distal bile duct in the main biliary tract, the therapeutic options may be limited. Injection of absolute ethanol into the bile duct requires correct identification of the bile duct, and balloon occlusion is useful to avoid damage to the surrounding tissues, even in cases with non-communicating biliary fistula and bile leak. CASE REPORT Two cases of non-communicating biliary fistula and bile leak are presented; one case following pancreaticoduodenectomy (Whipple's procedure), and one case following laparoscopic cholecystectomy. Both cases were successfully managed by chemical bile duct ablation with absolute ethanol. In the first case, the biliary leak occurred from a fistula of the right posterior biliary tract following pancreaticoduodenectomy. Cannulation of the leaking bile duct and balloon occlusion were achieved via a percutaneous route, and seven ablation sessions using absolute ethanol were required. In the second case, perforation of the bile duct branch draining hepatic segment V occurred following laparoscopic cholecystectomy. Cannulation of the bile duct and balloon occlusion were achieved via a transhepatic route, and seven ablation sessions using absolute ethanol were required. CONCLUSIONS Chemical ablation of the bile duct using absolute ethanol is an effective treatment for biliary leak following hepatobiliary and pancreatic surgery, even in cases with non-communicating biliary fistula. Identification of the bile duct leak is required before ethanol injection to avoid damage to the surrounding tissues.

  11. Curved-Duct

    Directory of Open Access Journals (Sweden)

    Je Hyun Baekt

    2000-01-01

    Full Text Available A numerical study is conducted on the fully-developed laminar flow of an incompressible viscous fluid in a square duct rotating about a perpendicular axis to the axial direction of the duct. At the straight duct, the rotation produces vortices due to the Coriolis force. Generally two vortex cells are formed and the axial velocity distribution is distorted by the effect of this Coriolis force. When a convective force is weak, two counter-rotating vortices are shown with a quasi-parabolic axial velocity profile for weak rotation rates. As the rotation rate increases, the axial velocity on the vertical centreline of the duct begins to flatten and the location of vorticity center is moved near to wall by the effect of the Coriolis force. When the convective inertia force is strong, a double-vortex secondary flow appears in the transverse planes of the duct for weak rotation rates but as the speed of rotation increases the secondary flow is shown to split into an asymmetric configuration of four counter-rotating vortices. If the rotation rates are increased further, the secondary flow restabilizes to a slightly asymmetric double-vortex configuration. Also, a numerical study is conducted on the laminar flow of an incompressible viscous fluid in a 90°-bend square duct that rotates about axis parallel to the axial direction of the inlet. At a 90°-bend square duct, the feature of flow by the effect of a Coriolis force and a centrifugal force, namely a secondary flow by the centrifugal force in the curved region and the Coriolis force in the downstream region, is shown since the centrifugal force in curved region and the Coriolis force in downstream region are dominant respectively.

  12. Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.

    Science.gov (United States)

    Ota, Shinichi; Geschwind, Jean-Francois H; Buijs, Manon; Wijlemans, Joost W; Kwak, Byung Kook; Ganapathy-Kanniappan, Shanmugasundaram

    2013-06-01

    Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer.

  13. Immunoscintigraphy of human pancreatic carcinoma in nude mice with I-131-F(ab')/sub 2/-fragments of monoclonal antibodies

    International Nuclear Information System (INIS)

    Senekowitsch, R.; Maul, F.D.; Wenisch, H.J.C.; Kriegel, H.; Hor, G.

    1985-01-01

    In the present study radioiodinated F(ab')/sub 2/-fragments of CA19-9 and antibody that reacts specifically with human gastrointestinal cancer were examined for their ability to detect human pancreatic carcinoma hosted in nude mice. Tumor-bearing mice received 80μCi of I-131-F(ab')/sub 2/ with a specific activity of 1.8μCi/μg. All mice were imaged after the injection and every 24hr up to 6 days. The retained radioactivity was also registered with a whole-body counter immediately after imaging. As a control F(ab's)/sub 2/ of a nonspecific antibody were administered in parallel to another group of animals bearing the same tumor. Three animals of each group were killed at 1,2,4 and 8 days for determination of the distribution of both labeled antibody-fragments. On scintigraphic images obtained with the CA19-9-F(ab')/sub 2/ the tumors could be visualized 24hr after injection, the best dilineation however was achieved 96hr p.i.. The biodistribution data exhibited a more rapid blood clearance for the specific fragments compared to that for the unspecific ones. Tumors showed an increase in uptake up to 48hr reaching 1.7% of the injected dose per gram, declining to values of 0.08%/g at day 6 p.i.. The highest tumor-to-blood ratios were found after 96h. They were 7 for the CA19-9-fragments compared to 1.5 for the unspecific fragments. The whole body counting revealed a more rapid excretion for the fragments of the specific monoclonal antibodies than for the unspecific ones. In summary the authors were able to show that CA19-9-F(ab')/sub 2/-fragments can be used for immunodetection of human pancreatic carcinoma hosted in nude mice

  14. New developments in endoscopic treatment of chronic pancreatitis.

    Science.gov (United States)

    Didden, P; Bruno, M; Poley, J W

    2012-12-01

    The aim of endoscopic therapy of chronic pancreatitis (CP) is to treat pain by draining the pancreatic duct or managing loco-regional complications. Recent decennia were characterized by continuous improvement of endoscopic techniques and devices, resulting in a better clinical outcome. Novel developments now also provide the opportunity to endoscopically treat refractory CP-related complications. Especially suboptimal surgical candidates could potentially benefit from these new developments, consequently avoiding invasive surgery. The use of fully covered self-expandable metal stents (SEMS) has been explored in pancreatic and CP-related biliary duct strictures, resistant to conventional treatment with plastic endoprotheses. Furthermore, endosonography-guided transmural drainage of the main pancreatic duct via duct-gastrostomy is an alternative treatment option in selected cases. Pancreatic pseudocysts represent an excellent indication for endoscopic therapy with some recent case series demonstrating effective drainage with the use of a fully covered SEMS. Although results of these new endoscopic developments are promising, high quality randomized trials are required to determine their definite role in the management of chronic pancreatitis.

  15. Anterior Roux‑en‑Y Pancreatico‑jejunostomy for Pancreatic Trauma

    African Journals Online (AJOL)

    compression injury of the upper abdomen with a concrete tile 5 days ago. Pain was ... pancreas was anastomosed to the lateral opening made in a. Roux loop of the ... Pancreatic duct is shown cannulated with feeding tube. Figure 1: CECT ...

  16. Frey procedure combined with biliary diversion in chronic pancreatitis.

    Science.gov (United States)

    Merdrignac, Aude; Bergeat, Damien; Rayar, Michel; Harnoy, Yann; Turner, Kathleen; Courtin-Tanguy, Laetitia; Boudjema, Karim; Meunier, Bernard; Sulpice, Laurent

    2016-11-01

    The Frey procedure has become the standard operative treatment in chronic painful pancreatitis. Biliary diversion could be combined when associated with common bile duct obstruction. The aim of the present study was to evaluate the impact of the type of biliary diversion combined with the Frey procedure on late morbidity. The data from consecutive patients undergoing the Frey procedure and having a minimum follow-up of 2 years were extracted from a maintained prospective database. The mean endpoint was the rate of secondary biliary stricture after the Frey procedure combined with biliary diversion (bilioenteric anastomosis or common bile duct reinsertion in the resection cavity). Between 2006 and 2013, 55 consecutive patients underwent the Frey procedure. Twenty-nine patients had common bile duct obstruction (52.7%). The technique of biliary diversion resulted in bilioenteric anastomosis in 19 patients (65.5%) and common bile duct reinsertion in 10 patients (34.5%). Preoperative characteristics and early surgical outcomes were comparable. Pain control was similar. There was significantly more secondary biliary stricture after common bile duct reinsertion than after bilioenteric anastomosis (60% vs 11%, P = .008). Combined bilioenteric anastomosis during the Frey procedure is an efficient technique for treating common bile duct obstruction that complicates chronic painful pancreatitis. Bilioenteric anastomosis was associated with less secondary biliary stricture than common bile duct reinsertion in the pancreatic resection cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Caffeine Inhibits Fluid Secretion by Interlobular Ducts From Guinea Pig Pancreas.

    Science.gov (United States)

    Mochimaru, Yuka; Yamamoto, Akiko; Nakakuki, Miyuki; Yamaguchi, Makoto; Taniguchi, Ituka; Ishiguro, Hiroshi

    2017-04-01

    Caffeine is contained in coffee, tea, and numerous beverages and foods. We examined the direct effects of caffeine on the physiological function of pancreatic duct cells by using interlobular duct segments isolated from guinea pig pancreas. The rate of fluid secretion was continuously measured by monitoring the luminal volume of isolated duct segments. Changes in intracellular Ca concentration ([Ca]i) were estimated by microfluorometry in ducts loaded with Fura-2. Both secretin-stimulated and acetylcholine (ACh)-stimulated fluid secretions were substantially and reversibly inhibited by relatively low concentrations of caffeine as low as 0.03 mM relevant to blood levels after ingestion of caffeine-containing beverages. Caffeine inhibited ACh-induced elevation of [Ca]i and secretin-induced fluctuation of [Ca]i. Caffeine abolished thapsigargin-induced intracellular Ca release but did not affect the entry of extracellular Ca. Caffeine (0.05 mM) abolished ethanol (1 mM)-induced fluid hypersecretion in secretin-stimulated pancreatic duct. Low concentrations of caffeine directly inhibit pancreatic ductal fluid secretion stimulated by secretin or ACh and also ethanol-induced fluid hypersecretion. The inhibition by caffeine seems to be mediated by the blockade of intracellular Ca mobilization. Daily intake of caffeine may reduce the volume of pancreatic juice secretion.

  18. Dickkopf-3 maintains the PANC-1 human pancreatic tumor cells in a dedifferentiated state.

    Science.gov (United States)

    Zenzmaier, Christoph; Hermann, Martin; Hengster, Paul; Berger, Peter

    2012-01-01

    Pancreatic cancer (PaCa) is the fourth leading cause of cancer deaths in Western societies, with pancreatic ductal adenocarcinomas (PDACs) accounting for >90% of such cases. PDAC is a heterogeneous disease that includes a subset showing overexpression of the secreted glycoprotein Dickkopf-related protein 3 (Dkk-3), a protein shown to be downregulated in various cancers of different tissues. The biological function of Dkk-3 in this subset was studied using the Dkk-3 expressing PANC-1 cell line as a model for PDACs. The influence of Dkk-3 overexpression and knockdown on cellular differentiation and proliferation of PANC-1 was investigated. Confocal microscopy showed that Dkk-3 was expressed in a fraction of PANC-1 cells. While lentiviral-mediated overexpression of DKK3 did not alter cellular proliferation, knockdown of DKK3 resulted in significant reduction of cellular proliferation and concomitant induction of cell cycle inhibitors CDKN2B (p15INK4b), CDKN1A (p21CIP1) and CDKN1B (p27KIP1). In parallel, pancreatic epithelial cell differentiation markers AMY2A, CELA1, CTRB1, GCG, GLB1 and INS were significantly upregulated. PANC-1 cells differentiated using exendin-4 showed analogous induction of cell cycle inhibitors and differentiation markers. Thus, we conclude that Dkk-3 is required to maintain a highly dedifferentiated and consequently proliferative state in PANC-1, indicating a similar function in the Dkk-3 overexpressing subset of PDACs. Therefore, Dkk-3 represents a potential target for the treatment of Dkk-3-positive subtypes of PaCa to drive cells into cell cycle arrest and differentiation.

  19. Adipose stem cells from chronic pancreatitis patients improve mouse and human islet survival and function.

    Science.gov (United States)

    Song, Lili; Sun, Zhen; Kim, Do-Sung; Gou, Wenyu; Strange, Charlie; Dong, Huansheng; Cui, Wanxing; Gilkeson, Gary; Morgan, Katherine A; Adams, David B; Wang, Hongjun

    2017-08-30

    Chronic pancreatitis has surgical options including total pancreatectomy to control pain. To avoid surgical diabetes, the explanted pancreas can have islets harvested and transplanted. Immediately following total pancreatectomy with islet autotransplantation (TP-IAT), many islet cells die due to isolation and transplantation stresses. The percentage of patients remaining insulin free after TP-IAT is therefore low. We determined whether cotransplantation of adipose-derived mesenchymal stem cells (ASCs) from chronic pancreatitis patients (CP-ASCs) would protect islets after transplantation. In a marginal mass islet transplantation model, islets from C57BL/6 mice were cotransplanted with CP-ASCs into syngeneic streptozotocin-treated diabetic mice. Treatment response was defined by the percentage of recipients reaching normoglycemia, and by the area under the curve for glucose and c-peptide in a glucose tolerance test. Macrophage infiltration, β-cell apoptosis, and islet graft vasculature were measured in transplanted islet grafts by immunohistochemistry. mRNA expression profiling of 84 apoptosis-related genes in islet grafts transplanted alone or with CP-ASCs was measured by the RT 2 Profiler™ Apoptosis PCR Array. The impact of insulin-like growth factor-1 (IGF-1) on islet apoptosis was determined in islets stimulated with cytokines (IL-1β and IFN-γ) in the presence and absence of CP-ASC conditioned medium. CP-ASC-treated mice were more often normoglycemic compared to mice receiving islets alone. ASC cotransplantation reduced macrophage infiltration, β-cell death, suppressed expression of TNF-α and Bcl-2 modifying factor (BMF), and upregulated expressions of IGF-1 and TNF Receptor Superfamily Member 11b (TNFRSF11B) in islet grafts. Islets cultured in conditioned medium from CP-ASCs showed reduced cell death. This protective effect was diminished when IGF-1 was blocked in the conditioned medium by the anti-IGF-1 antibody. Cotransplantation of islets with ASCs

  20. Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines

    International Nuclear Information System (INIS)

    Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

    2011-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin 1β. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression.

  1. Patent arterial duct

    Directory of Open Access Journals (Sweden)

    Martin Robin P

    2009-07-01

    Full Text Available Abstract Patent arterial duct (PAD is a congenital heart abnormality defined as persistent patency in term infants older than three months. Isolated PAD is found in around 1 in 2000 full term infants. A higher prevalence is found in preterm infants, especially those with low birth weight. The female to male ratio is 2:1. Most patients are asymptomatic when the duct is small. With a moderate-to-large duct, a characteristic continuous heart murmur (loudest in the left upper chest or infraclavicular area is typical. The precordium may be hyperactive and peripheral pulses are bounding with a wide pulse pressure. Tachycardia, exertional dyspnoea, laboured breathing, fatigue or poor growth are common. Large shunts may lead to failure to thrive, recurrent infection of the upper respiratory tract and congestive heart failure. In the majority of cases of PAD there is no identifiable cause. Persistence of the duct is associated with chromosomal aberrations, asphyxia at birth, birth at high altitude and congenital rubella. Occasional cases are associated with specific genetic defects (trisomy 21 and 18, and the Rubinstein-Taybi and CHARGE syndromes. Familial occurrence of PAD is uncommon and the usual mechanism of inheritance is considered to be polygenic with a recurrence risk of 3%. Rare families with isolated PAD have been described in which the mode of inheritance appears to be dominant or recessive. Familial incidence of PAD has also been linked to Char syndrome, familial thoracic aortic aneurysm/dissection associated with patent arterial duct, and familial patent arterial duct and bicuspid aortic valve associated with hand abnormalities. Diagnosis is based on clinical examination and confirmed with transthoracic echocardiography. Assessment of ductal blood flow can be made using colour flow mapping and pulsed wave Doppler. Antenatal diagnosis is not possible, as PAD is a normal structure during antenatal life. Conditions with signs and symptoms of

  2. Autoimmune pancreatitis - the story so far

    International Nuclear Information System (INIS)

    Jackson, S.

    2015-01-01

    Full text: Learning objectives: to learn about the main imaging diagnostic findings of AIP and the International Consensus Diagnostic Criteria (ICDC); to understand the best strategies for distinguishing AIP from pancreatic cancer; to emphasise the central role of radiology in the era of “clinical decision making” Autoimmune Pancreatitis (AIP) was first described in 1961 and represents a rare form of immune mediated chronic pancreatitis which is characterised by a marked infiltration of lymphocytes and plasma cells into pancreatic tissue. Whilst the majority of cases present with diffuse gland involvement, approximately 30% of patient’s demonstrate either segmental or focal involvement of the pancreas. Clinical presentation is very variable with patients describing a range of symptoms. Imaging plays a central role in the diagnosis and management of AIP and knowledge of the radiological appearances, which can vary significantly due to the various degrees of fibrosis and inflammatory infiltrate, is critical. Cardinal features include focal or diffuse pancreatic enlargement with the loss of normal lobular architecture. Post contrast enhancement features of the pancreas may also be useful. In addition, pancreatic duct involvement as demonstrated by single or multiple focal strictures with limited more proximal dilatation is common as well as infiltration of the common bile duct.Whilst multimodality appearances may suggest a diagnosis of AIP correlation with clinical history, serology and histopathology is mandatory in order to accurately diagnose atypical cases

  3. Lignans from the root of Wikstroemia indica and their cytotoxic activity against PANC-1 human pancreatic cancer cells.

    Science.gov (United States)

    Chang, Hang; Wang, Yuwei; Gao, Xue; Song, Zehai; Awale, Suresh; Han, Na; Liu, Zhihui; Yin, Jun

    2017-09-01

    Six new compounds, wikstronin A (1), wikstronin B (2), wikstresinol (3), acetylwikstresinol (4), bis-5',5'-(+)-matairesinol (5), bis-5,5'-(+)-matairesinol (6), together with 20 known compounds (7-26) were isolated from the CH 2 Cl 2 extract of roots of Wikstroemia indica. Structures of compounds 1-6 were determined by extensive NMR and CD spectroscopic analysis. In vitro preferential cytotoxicity of all the isolates was evaluated against a PANC-1 human pancreatic cell line. Compounds 8 and 12 displayed mild preferential cytotoxicity in the nutrient-deprived medium (NDM) and without causing toxicity in normal nutrient-rich conditions. Copyright © 2017 Elsevier B.V. All rights reserved.