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Sample records for exocrine pancreatic enzymes

  1. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Miroslav Vujasinovic

    2017-02-01

    Full Text Available Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  2. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

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    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract : Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  3. Pancreatic exocrine function testing

    International Nuclear Information System (INIS)

    Goff, J.S.

    1981-01-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each

  4. Pancreatic Exocrine Function Testing

    OpenAIRE

    Berk, J. Edward

    1982-01-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and par...

  5. Diagnosis and management of pancreatic exocrine insufficiency.

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    Nikfarjam, Mehrdad; Wilson, Jeremy S; Smith, Ross C

    2017-08-21

    In 2015, the Australasian Pancreatic Club (APC) published the Australasian guidelines for the management of pancreatic exocrine insufficiency (http://pancreas.org.au/2016/01/pancreatic-exocrine-insufficiency-guidelines). Pancreatic exocrine insufficiency (PEI) occurs when normal digestion cannot be sustained due to insufficient pancreatic digestive enzyme activity. This may be related to a breakdown, at any point, in the pancreatic digestive chain: pancreatic stimulation; synthesis, release or transportation of pancreatic enzymes; or synchronisation of secretions to mix with ingested food. Main recommendations: The guidelines provide advice on diagnosis and management of PEI, noting the following: A high prevalence of PEI is seen in certain diseases and conditions, such as cystic fibrosis, acute and chronic pancreatitis, pancreatic cancer and pancreatic surgery. The main symptoms of PEI are steatorrhoea or diarrhoea, abdominal pain, bloating and weight loss. These symptoms are non-specific and often go undetected and untreated. PEI diagnosis is predominantly based on clinical findings and the presence of underlying disease. The likelihood of PEI in suspected patients has been categorised into three groups: definite, possible and unlikely. If left untreated, PEI may lead to complications related to fat malabsorption and malnutrition, and have an impact on quality of life. Pancreatic enzyme replacement therapy (PERT) remains the mainstay of PEI treatment with the recommended adult initial enzyme dose being 25 000-40 000 units of lipase per meal, titrating up to a maximum of 75 000-80 000 units of lipase per meal. Adjunct acid-suppressing therapy may be useful when patients still experience symptoms of PEI on high dose PERT. Nutritional management by an experienced dietitian is essential. Changes in management as a result of these guidelines: These are the first guidelines to classify PEI as being definite, possible or unlikely, and provide a diagnostic algorithm to

  6. Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations.

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    Toouli, James; Biankin, Andrew V; Oliver, Mark R; Pearce, Callum B; Wilson, Jeremy S; Wray, Nicholas H

    2010-10-18

    Pancreatic exocrine insufficiency (PEI) occurs when the amounts of enzymes secreted into the duodenum in response to a meal are insufficient to maintain normal digestive processes. The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea. Pancreatic exocrine function is commonly assessed by conducting a 3-day faecal fat test and by measuring levels of faecal elastase-1 and serum trypsinogen. Pancreatic enzyme replacement therapy is the mainstay of treatment for PEI. In adults, the initial recommended dose of pancreatic enzymes is 25,000 units of lipase per meal, titrating up to a maximum of 80,000 units of lipase per meal. In infants and children, the initial recommended dose of pancreatic enzymes is 500 units of lipase per gram of dietary fat; the maximum daily dose should not exceed 10,000 units of lipase per kilogram of bodyweight. Oral pancreatic enzymes should be taken with meals to ensure adequate mixing with the chyme. Adjunct therapy with acid-suppressing agents may be useful in patients who continue to experience symptoms of PEI despite high-dose enzyme therapy. A dietitian experienced in treating PEI should be involved in patient management. Dietary fat restriction is not recommended for patients with PEI. Patients with PEI should be encouraged to consume small, frequent meals and to abstain from alcohol. Medium-chain triglycerides do not provide any clear nutritional advantage over long-chain triglycerides, but can be trialled in patients who fail to gain or to maintain adequate bodyweight in order to increase energy intake.

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

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    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.

  8. Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis

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    Devi Mukkai Krishnamurty

    2009-07-01

    Full Text Available Devi Mukkai Krishnamurty,1 Atoosa Rabiee,2 Sanjay B Jagannath,1 Dana K Andersen2Johns Hopkins University School of Medicine; 1Department of Medicine; 2Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; 2Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USAAbstract: Pancreatic enzyme supplements (PES are used in chronic pancreatitis (CP for correction of pancreatic exocrine insufficiency (PEI as well as pain and malnutrition. The use of porcine pancreatic enzymes for the correction of exocrine insufficiency is governed by the pathophysiology of the disease as well as pharmacologic properties of PES. Variability in bioequivalence of PES has been noted on in vitro and in vivo testing and has been attributed to the differences in enteric coating and the degree of micro-encapsulation. As a step towards standardizing pancreatic enzyme preparations, the Food and Drug Administration now requires the manufacturers of PES to obtain approval of marketed formulations by April 2010. In patients with treatment failure, apart from evaluating drug and dietary interactions and compliance, physicians should keep in mind that patients may benefit from switching to a different formulation. The choice of PES (enteric coated versus non-enteric coated and the need for acid suppression should be individualized. There is no current standard test for evaluating adequacy of therapy in CP patients and studies have shown that optimization of therapy based on symptoms may be inadequate. Goals of therapy based on overall patient presentation and specific laboratory tests rather than mere correction of steatorrhea are needed.Keywords: pancreatic exocrine insufficiency, chronic pancreatitis, pancreatic enzyme supplement

  9. Acute effects of irradiation on exocrine pancreatic secretion in the pig

    International Nuclear Information System (INIS)

    Monti, P.; Scanff, P.; Joubert, C.; Vergnet, M.; Grison, S.

    1997-01-01

    Several reports on irradiation damages to the pancreas deal essentially with long-term morphologic changes but give few informations on pancreatic exocrine function. Therefore, the aim of the present work was to study the effects of a whole body gamma irradiation on the volume and enzyme activities of the pancreatic juice. The volume of pancreatic juice daily secreted decreased one day after irradiation (-40%, p < 0.01) and remained lower that the control value all over the experimental period (-65%, p < 0.01). Same response was observed for the total proteins secreted in the pancreatic juice but significant decrease was observed only the fourth and the fifth days after irradiation. Therefore, concentration of total protein secreted in the pancreatic juice was not altered all over the experimental period. Total activities of proteolytic enzymes, lipase and amylase led to decrease on day after irradiation and except for trypsin, the attenuated activity became significant from the third day after exposure. On the other hand, specific activities of the proteolytic enzymes and amylase did not show marked modifications after irradiation, whereas lipase specific activity was decreased. In conclusion, a whole body gamma irradiation resulted in a rapid and marked decrease of exocrine pancreatic secretion, in terms of volume as well as secreted enzymes. These modifications may, in part, contribute to the malabsorption of nutrients and these acute effects may be due to some modifications in the regulation of the exocrine pancreatic secretion

  10. Acute effects of irradiation on exocrine pancreatic secretion in the pig

    Energy Technology Data Exchange (ETDEWEB)

    Monti, P; Scanff, P; Joubert, C; Vergnet, M; Grison, S [CEA Fontenay-aux-Roses, 92 (France). Inst. de Protection et de Surete Nucleaire

    1997-03-01

    Several reports on irradiation damages to the pancreas deal essentially with long-term morphologic changes but give few informations on pancreatic exocrine function. Therefore, the aim of the present work was to study the effects of a whole body gamma irradiation on the volume and enzyme activities of the pancreatic juice. The volume of pancreatic juice daily secreted decreased one day after irradiation (-40%, p < 0.01) and remained lower that the control value all over the experimental period (-65%, p < 0.01). Same response was observed for the total proteins secreted in the pancreatic juice but significant decrease was observed only the fourth and the fifth days after irradiation. Therefore, concentration of total protein secreted in the pancreatic juice was not altered all over the experimental period. Total activities of proteolytic enzymes, lipase and amylase led to decrease on day after irradiation and except for trypsin, the attenuated activity became significant from the third day after exposure. On the other hand, specific activities of the proteolytic enzymes and amylase did not show marked modifications after irradiation, whereas lipase specific activity was decreased. In conclusion, a whole body gamma irradiation resulted in a rapid and marked decrease of exocrine pancreatic secretion, in terms of volume as well as secreted enzymes. These modifications may, in part, contribute to the malabsorption of nutrients and these acute effects may be due to some modifications in the regulation of the exocrine pancreatic secretion

  11. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century.

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    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-09-07

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.

  12. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century

    Science.gov (United States)

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-01-01

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy. PMID:25206255

  13. Diabetes mellitus and exocrine pancreatic insufficiency (review of literature

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    L.T. Daminova

    2018-02-01

    Full Text Available Currently, an increasing importance is given to the study of the problem of exocrine pancreatic insufficiency, which is observed in a significant number of patients with diabetes mellitus (DM type 1 and 2 and can potentially affect the compensation of DM. The mechanism of reducing the external secretion of the pancreas in DM is associated with an imbalance of inhibitory and stimulating pancreatic secretion of hormones, with fibrosis of the gland as a result of diabetic angiopathy. In type 2 DM, the mechanisms that result from the metabolic syndrome are involved in the pathogenesis of exocrine pancreatic insufficiency. Enzyme replacement the­rapy should be considered as one of the promising methods of treating DM patients.

  14. The Proteomic Analysis of Pancreatic Exocrine Insufficiency Protein Marker in Type 2 Diabetes Mellitus Patients

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    Srihardyastutie, Arie; Soeatmadji, DW; Fatchiyah; Aulanni'am

    2018-01-01

    Type 2 Diabetes Mellitus (T2D) is the vast majority case of diabetes. Patient with T2D is at higher risk for developing acute or chronic pancreatitis. Prolonged hyperglycemia results in damages to tissue, which also causes dysfunctions of some organ systems, including enzyme or hormone secretions. Commonly, dysfunction or insufficiency of pancreatic exocrine is evaluated by increasing activity of serum pancreatic enzyme, such as amylase and lipase. Although incidence of pancreatitis was found in Indonesian T2D, the pathogenic mechanism still unclear. The aim of this study was to characterize the marker protein that indicated the correlation of pancreatic exocrine insufficiency with progression of T2D. Proteomic analysis using LC-MS/MS was used in identification and characterization of protein marker which indicates insufficiency pancreatic exocrine. First step, protein profile was analyzed by SDS-PAGE methods using serum sample of T2D compared with normal or healthy control, as negative control, and pancreatitis patients, as positive control. Protein with 18 kDa was found as a candidate protein marker which indicated the pancreatic exocrine insufficiency in T2D. The further identification of that protein using LC-MS/MS showed 4 peptide fragments. In silico analysis of the peptide fragment indicated the correlation of pancreatic exocrine insufficiency with progression of T2D was METTL10 - methyltransferase like protein-10.

  15. Acute effects of whole body gamma irradiation on exocrine pancreatic secretion in the pig

    International Nuclear Information System (INIS)

    Monti, P.; Scanff, P.; Joubert, C.; Vergnet, M.; Grison, S.; Griffiths, N.

    2004-01-01

    Reports on radiation damage to the pancreas deal essentially with long-term morphological changes with few data on pancreatic exocrine function. The aim of this work was to study the acute effects of whole body irradiation on volume and enzyme activities in the pancreatic juice. A whole body gamma irradiation (6 Gy) was investigated in pigs with continuous sampling of pancreatic juice before and after exposure via an indwelling catheter in the pancreatic duct. For each sample collected, total protein concentration and enzyme activities of trypsin, chymotrypsin, elastase, lipase and amylase were determined. Pancreatic juice volume was monitored during all periods of collection. The volume of pancreatic juice secreted daily decreased one day after irradiation and remained lower than the control values over the experimental period. Total proteins secreted in the pancreatic juice and total activities of pancreatic enzymes were reduced similarly. On the other hand, only specific activities of elastase and lipase were affected by irradiation. Whole body gamma irradiation resulted in a rapid and marked decrease of exocrine pancreatic secretion, in terms of volume as well as secreted enzymes. This may contribute in part to the intestinal manifestations of the acute and/or late radiation syndrome. (author)

  16. Kinetic test of pancreatic exocrine function

    International Nuclear Information System (INIS)

    Sawabu, Norio; Hirose, Shoichiro; Nakazima, Shin; Yoneda, Masao; Nishimura, Keigo

    1975-01-01

    In order to improve the diagnostic evaluation of pancreatic exocrine function, 75 Se-activity in the duodenal aspirate of twenty control subjects and 131 subjects with pancertic and/or gastrointestinal disease was measured following intravenous injection of 75 Se-selenomethionine. Radioactivity in the duodenal aspirate of the control subjects remained low until 80 min. It then rose rapidly and reached a plateau at 115 min. In contrast, radioactivity in the subjects with pancreatic diseases remained low, or rose only slowly throughout the period of collection. Radioactivity of the protein fraction (TCA-precipitable) in the 80 to 130 min. duodenal aspirates showed good separation between controls and subjects with pancreatic disease. The incidence of abnormalities of TCA-precipitable radioactivity in the 80 to 130 min. duodenal aspirates was significantly higher than that of the conventional PS-test parameters in groups with various pancreatic diseases. All of the subjects having an abnormal maximal ratio of TCA-precipitable radioactivity to protein (representing pancreatic enzyme synthesis) showed an abnormal distribution in output of TCA-precipitable radioactivity in 80 to 130 min. collection (representing both enzyme synthesis and excretion). On the other hand, subjects with an abnormal output of TCA-precipitable radioactivity in 80 to 130 min. could be separated into those with normal and abnormal ratios of TCA-precipitable radioactivity, suggesting the presence of two types of disturbance in pancreatic function. In the latter group both synthesis and secretion of enzyme were impaired. In the former group, secretion of enzyme was depressed, although enzyme synthesis was fairly well preserved. (author)

  17. Kinetic test of pancreatic exocrine function

    Energy Technology Data Exchange (ETDEWEB)

    Sawabu, N; Hirose, S; Nakazima, S; Yoneda, M; Nishimura, K [Kanazawa Univ. (Japan). School of Medicine

    1975-01-01

    In order to improve the diagnostic evaluation of pancreatic exocrine function, /sup 75/Se-activity in the duodenal aspirate of twenty control subjects and 131 subjects with pancertic and/or gastrointestinal disease was measured following intravenous injection of /sup 75/Se-selenomethionine. Radioactivity in the duodenal aspirate of the control subjects remained low until 80 min. It then rose rapidly and reached a plateau at 115 min. In contrast, radioactivity in the subjects with pancreatic diseases remained low, or rose only slowly throughout the period of collection. Radioactivity of the protein fraction (TCA-precipitable) in the 80 to 130 min. duodenal aspirates showed good separation between controls and subjects with pancreatic disease. The incidence of abnormalities of TCA-precipitable radioactivity in the 80 to 130 min. duodenal aspirates was significantly higher than that of the conventional PS-test parameters in groups with various pancreatic diseases. All of the subjects having an abnormal maximal ratio of TCA-precipitable radioactivity to protein (representing pancreatic enzyme synthesis) showed an abnormal distribution in output of TCA-precipitable radioactivity in 80 to 130 min. collection (representing both enzyme synthesis and excretion). On the other hand, subjects with an abnormal output of TCA-precipitable radioactivity in 80 to 130 min. could be separated into those with normal and abnormal ratios of TCA-precipitable radioactivity, suggesting the presence of two types of disturbance in pancreatic function. In the latter group both synthesis and secretion of enzyme were impaired. In the former group, secretion of enzyme was depressed, although enzyme synthesis was fairly well preserved.

  18. COMPARING THE ENZYME REPLACEMENT THERAPY COST IN POST PANCREATECTOMY PATIENTS DUE TO PANCREATIC TUMOR AND CHRONIC PANCREATITIS.

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    Fragoso, Anna Victoria; Pedroso, Martha Regina; Herman, Paulo; Montagnini, André Luis

    2016-01-01

    Among late postoperative complications of pancreatectomy are the exocrine and endocrine pancreatic insufficiencies. The presence of exocrine pancreatic insufficiency imposes, as standard treatment, pancreatic enzyme replacement. Patients with chronic pancreatitis, with intractable pain or any complications with surgical treatment, are likely to present exocrine pancreatic insufficiency or have this condition worsened requiring adequate dose of pancreatic enzymes. The aim of this study is to compare the required dose of pancreatic enzyme and the enzyme replacement cost in post pancreatectomy patients with and without chronic pancreatitis. Observational cross-sectional study. In the first half of 2015 patients treated at the clinic of the Department of Gastrointestinal Surgery at Hospital das Clínicas, Universidade de São Paulo, Brazil, who underwent pancreatectomy for at least 6 months and in use of enzyme replacement therapy were included in this series. The study was approved by the Research Ethics Committee. The patients were divided into two groups according to the presence or absence of chronic pancreatitis prior to pancreatic surgery. For this study, Ptreatment was R$ 2150.5 ± 729.39; R$ 2118.18 ± 731.02 in patients without pancreatitis and R$ 2217.74 ± 736.30 in patients with pancreatitis. There was no statistically significant difference in the cost of treatment of enzyme replacement post pancreatectomy in patients with or without chronic pancreatitis prior to surgical indication.

  19. 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

  20. Predictive factors for exocrine pancreatic insufficiency after pancreatoduodenectomy with pancreaticogastrostomy.

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    Nakamura, Hiroyuki; Murakami, Yoshiaki; Uemura, Kenichiro; Hayashidani, Yasuo; Sudo, Takeshi; Ohge, Hiroki; Sueda, Taijiro

    2009-07-01

    The aim of this study was to determine risk factors for exocrine pancreatic insufficiency after pancreatoduodenectomy (PD) with pancreaticogastrostomy (PG). A (13)C-labeled mixed triglyceride breath test was performed in 61 patients after PD to assess exocrine pancreatic function. Percent (13)CO(2) cumulative dose at 7 h pancreatic insufficiency. Abdominal computed tomography scans were utilized to assess the dilatation of the main pancreatic duct (MPD dilatation) in the remnant. Thirty-eight of 61 patients (62.3%) were diagnosed with exocrine pancreatic insufficiency. Univariate analysis identified significant associations between two preoperative factors (preoperative impaired endocrine function and a hard pancreatic texture induced by preexisting obstructive pancreatitis), plus one postoperative factor (MPD dilatation caused by PG stricture) and exocrine pancreatic insufficiency (P pancreatic insufficiency after PD may be partly explainable by preexisting obstructive pancreatitis prior to surgery, surgeons desiring to obtain better postoperative exocrine pancreatic function after PD would be well-advised to devote considerable attention to preventing PG stricture.

  1. Pancreatic endocrine and exocrine function in children following near-total pancreatectomy for diffuse congenital hyperinsulinism.

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    Ved Bhushan Arya

    Full Text Available Congenital hyperinsulinism (CHI, the commonest cause of persistent hypoglycaemia, has two main histological subtypes: diffuse and focal. Diffuse CHI, if medically unresponsive, is managed with near-total pancreatectomy. Post-pancreatectomy, in addition to persistent hypoglycaemia, there is a very high risk of diabetes mellitus and pancreatic exocrine insufficiency.International referral centre for the management of CHI.Medically unresponsive diffuse CHI patients managed with near-total pancreatectomy between 1994 and 2012.Near-total pancreatectomy.Persistent hypoglycaemia post near-total pancreatectomy, insulin-dependent diabetes mellitus, clinical and biochemical (faecal elastase 1 pancreatic exocrine insufficiency.Of more than 300 patients with CHI managed during this time period, 45 children had medically unresponsive diffuse disease and were managed with near-total pancreatectomy. After near-total pancreatectomy, 60% of children had persistent hypoglycaemia requiring medical interventions. The incidence of insulin dependent diabetes mellitus was 96% at 11 years after surgery. Thirty-two patients (72% had biochemical evidence of severe pancreatic exocrine insufficiency (Faecal elastase 1<100 µg/g. Clinical exocrine insufficiency was observed in 22 (49% patients. No statistically significant difference in weight and height standard deviation score (SDS was found between untreated subclinical pancreatic exocrine insufficiency patients and treated clinical pancreatic exocrine insufficiency patients.The outcome of diffuse CHI patients after near-total pancreatectomy is very unsatisfactory. The incidence of persistent hypoglycaemia and insulin-dependent diabetes mellitus is very high. The presence of clinical rather than biochemical pancreatic exocrine insufficiency should inform decisions about pancreatic enzyme supplementation.

  2. Relationship between the exocrine and endocrine pancreas after acute pancreatitis.

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    Das, Stephanie L M; Kennedy, James I C; Murphy, Rinki; Phillips, Anthony R J; Windsor, John A; Petrov, Maxim S

    2014-12-07

    To determine the prevalence and time course of pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis. Relevant literature cited in three major biomedical journal databases (EMBASE, MEDLINE, and Scopus) was reviewed independently by two authors. There were no language constraints but the search was limited to human studies. Studies included were cohort studies of adult patients who were discharged after an attack of acute pancreatitis. Patients were excluded if they were under 18 years of age or had a previous diagnosis of prediabetes or diabetes mellitus, pancreatic exocrine insufficiency, or chronic pancreatitis. The main outcome measure was the prevalence of concomitant pancreatic exocrine insufficiency in patients who were diagnosed with prediabetes and diabetes mellitus after an attack of acute pancreatitis. Subgroup analysis was conducted for patients who were diagnosed with prediabetes only and those who were diagnosed with diabetes mellitus only. Subgroup analysis looking at the time course of concomitant pancreatic exocrine and endocrine insufficiency was also conducted. Pooled prevalence and corresponding 95% confidence intervals were calculated for all outcome measures and P-values pancreatitis was 43% (95%CI: 30%-56%). The pooled prevalence of pancreatic exocrine insufficiency in individuals after acute pancreatitis was 29% (95%CI: 19%-39%). The prevalence of concomitant pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes was 40% (95%CI: 25%-55%). The prevalence of concomitant pancreatic exocrine insufficiency among individuals with prediabetes alone and diabetes mellitus alone was 41% (95%CI: 12%-75%) and 39% (95%CI: 28%-51%), respectively. Further analysis showed that the prevalence of concomitant pancreatic exocrine insufficiency in individuals with prediabetes or diabetes decreases over time after an attack of acute pancreatitis

  3. COMPARING THE ENZYME REPLACEMENT THERAPY COST IN POST PANCREATECTOMY PATIENTS DUE TO PANCREATIC TUMOR AND CHRONIC PANCREATITIS

    Directory of Open Access Journals (Sweden)

    Anna Victoria FRAGOSO

    Full Text Available ABSTRACT Background - Among late postoperative complications of pancreatectomy are the exocrine and endocrine pancreatic insufficiencies. The presence of exocrine pancreatic insufficiency imposes, as standard treatment, pancreatic enzyme replacement. Patients with chronic pancreatitis, with intractable pain or any complications with surgical treatment, are likely to present exocrine pancreatic insufficiency or have this condition worsened requiring adequate dose of pancreatic enzymes. Objective - The aim of this study is to compare the required dose of pancreatic enzyme and the enzyme replacement cost in post pancreatectomy patients with and without chronic pancreatitis. Methods - Observational cross-sectional study. In the first half of 2015 patients treated at the clinic of the Department of Gastrointestinal Surgery at Hospital das Clínicas, Universidade de São Paulo, Brazil, who underwent pancreatectomy for at least 6 months and in use of enzyme replacement therapy were included in this series. The study was approved by the Research Ethics Committee. The patients were divided into two groups according to the presence or absence of chronic pancreatitis prior to pancreatic surgery. For this study, P<0.05 was considered statistically significant. Results - The annual cost of the treatment was R$ 2150.5 ± 729.39; R$ 2118.18 ± 731.02 in patients without pancreatitis and R$ 2217.74 ± 736.30 in patients with pancreatitis. Conclusion - There was no statistically significant difference in the cost of treatment of enzyme replacement post pancreatectomy in patients with or without chronic pancreatitis prior to surgical indication.

  4. Pancreatic endocrine and exocrine function in children following near-total pancreatectomy for diffuse congenital hyperinsulinism.

    Science.gov (United States)

    Arya, Ved Bhushan; Senniappan, Senthil; Demirbilek, Huseyin; Alam, Syeda; Flanagan, Sarah E; Ellard, Sian; Hussain, Khalid

    2014-01-01

    Congenital hyperinsulinism (CHI), the commonest cause of persistent hypoglycaemia, has two main histological subtypes: diffuse and focal. Diffuse CHI, if medically unresponsive, is managed with near-total pancreatectomy. Post-pancreatectomy, in addition to persistent hypoglycaemia, there is a very high risk of diabetes mellitus and pancreatic exocrine insufficiency. International referral centre for the management of CHI. Medically unresponsive diffuse CHI patients managed with near-total pancreatectomy between 1994 and 2012. Near-total pancreatectomy. Persistent hypoglycaemia post near-total pancreatectomy, insulin-dependent diabetes mellitus, clinical and biochemical (faecal elastase 1) pancreatic exocrine insufficiency. Of more than 300 patients with CHI managed during this time period, 45 children had medically unresponsive diffuse disease and were managed with near-total pancreatectomy. After near-total pancreatectomy, 60% of children had persistent hypoglycaemia requiring medical interventions. The incidence of insulin dependent diabetes mellitus was 96% at 11 years after surgery. Thirty-two patients (72%) had biochemical evidence of severe pancreatic exocrine insufficiency (Faecal elastase 1insufficiency was observed in 22 (49%) patients. No statistically significant difference in weight and height standard deviation score (SDS) was found between untreated subclinical pancreatic exocrine insufficiency patients and treated clinical pancreatic exocrine insufficiency patients. The outcome of diffuse CHI patients after near-total pancreatectomy is very unsatisfactory. The incidence of persistent hypoglycaemia and insulin-dependent diabetes mellitus is very high. The presence of clinical rather than biochemical pancreatic exocrine insufficiency should inform decisions about pancreatic enzyme supplementation.

  5. Role of pancreatic polypeptide in the regulation of pancreatic exocrine secretion in dogs

    International Nuclear Information System (INIS)

    Shiratori, Keiko; Lee, K.Y.; Chang, Tamin; Jo, Y.H.; Coy, D.H.; Chey, W.Y.

    1988-01-01

    The effect of intravenous infusion of synthetic human pancreatic polypeptide (HPP) or a rabbit anti-PP serum on pancreatic exocrine secretion was studied in 10 dogs with gastric and Thomas duodenal cannulas. The infusion of HPP, achieved a plasma PP concentration that mimicked the peak plasma concentration of PP in both interdigestive and postprandial states. This dose of HPP significantly inhibited pancreatic secretion in the interdigestive state. By contrast, immunoneutralization of circulating PP by a rabbit anti-PP serum resulted in significant increases in both interdigestive and postprandial pancreatic secretion, including water, bicarbonate, and protein. The increase in the pancreatic secretion paralleled a decrease in circulating PP level, which lasted for as long as 5 days. Furthermore, the anti-PP serum blocked the inhibitory action of exogenous HPP on pancreatic exocrine secretion. The present study indicates that endogenous PP plays a significant role in the regulation of the pancreatic exocrine secretion in both interdigestive and digestive states. Thus the authors conclude that PP is another hormone regulating pancreatic exocrine secretion in dogs

  6. Staging chronic pancreatitis with exocrine function tests: Are we better?

    Science.gov (United States)

    Sperti, Cosimo; Moletta, Lucia

    2017-10-14

    Chronic pancreatitis (CP) is an inflammatory disease of the pancreas evolving in progressive fibrotic disruption of the gland with exocrine and endocrine pancreatic insufficiency. Although imaging features of CP are well known, their correlation with exocrine pancreatic function tests are not obvious, particularly in the early stage of the disease. There are many clinical classification of CP, all suggested for better distinguish and manage different forms based on etiological and clinical factors, and severity of the disease. Recently, a new classification of CP has been suggested: the M-ANNHEIM multiple risk factor classification that includes etiology, stage classification and degree of clinical severity. However, more accurate determination of clinical severity of CP requires a correct determination of exocrine function of the pancreas and fecal fat excretion. Recently, Kamath et al demonstrated that the evaluation of exocrine pancreatic function by acid steatocrit and fecal elastase-1 (EF-1) was helpful, but EF-1 was able to detect exocrine pancreatic insufficiency in more patients, upgrading some patients in higher stage of disease according to M-ANNHEIM classification. So, EF-1 is a more accurate test to determine exocrine pancreatic insufficiency and to stage chronic pancreatitis in the M-ANNHEIM classification. On the contrary, EF-1 determination shows low sensitivity in detecting exocrine pancreatic insufficiency in early stage of the disease.

  7. Endocrine and exocrine pancreatic insufficiency after acute pancreatitis: long-term follow-up study.

    Science.gov (United States)

    Tu, Jianfeng; Zhang, Jingzhu; Ke, Lu; Yang, Yue; Yang, Qi; Lu, Guotao; Li, Baiqiang; Tong, Zhihui; Li, Weiqin; Li, Jieshou

    2017-10-27

    Patients could develop endocrine and exocrine pancreatic insufficiency after acute pancreatitis (AP), but the morbidity, risk factors and outcome remain unclear. The aim of the present study was to evaluate the incidence of endocrine and exocrine pancreatic insufficiency after AP and the risk factors of endocrine pancreatic insufficiency through a long-term follow-up investigation. Follow-up assessment of the endocrine and exocrine function was conducted for the discharged patients with AP episodes. Oral Glucose Tolerance Test (OGTT) and faecal elastase-1(FE-1) test were used as primary parameters. Fasting blood-glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin HBA1c, 2-h postprandial blood glucose (2hPG), Homa beta cell function index (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR) and FE-1 were collected. Abdominal contrast-enhanced computed tomography (CECT) was performed to investigate the pancreatic morphology and the other related data during hospitalization was also collected. One hundred thirteen patients were included in this study and 34 of whom (30.1%) developed diabetes mellitus (DM), 33 (29.2%) suffered impaired glucose tolerance (IGT). Moreover, 33 patients (29.2%) developed mild to moderate exocrine pancreatic insufficiency with 100μg/gpancreatic insufficiency with FE-1pancreatic necrosis was significant higher than that in the non-pancreatic necrosis group (X 2  = 13.442,P = 0.001). The multiple logistic regression analysis showed that extent of pancreatic necrosisendocrine pancreatic insufficiency. HOMA-IR (P = 0.002, OR = 6.626), Wall-off necrosis (WON) (P = 0.013, OR = 184.772) were the risk factors. The integrated morbidity of DM and IGT after AP was 59.25%, which was higher than exocrine pancreatic insufficiency. 6.2% and 29.2% of patients developed severe and mild to moderate exocrine pancreatic insufficiency, respectively. The extent of pancreatic necrosis>50%, WON and insulin resistance were

  8. Exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with pancreatic adenocarcinoma.

    Science.gov (United States)

    Ritchey, J W; Degernes, L A; Brown, T T

    1997-01-01

    This report describes exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with complete effacement of the pancreas by a pancreatic adenocarcinoma. The bird presented with a 3-month history of weight loss and voluminous, foul-smelling droppings. Clinically, routine hematologic findings were normal and fecal tests were performed to evaluate exocrine pancreatic function. The fecal function tests were positive for neutral and split fats and negative for trypsin. Oral administration of corn oil did not result in elevation of blood triglyceride levels. Two days later, the triglyceride tolerance test was repeated using corn oil mixed with pancreatic enzymes. This time, there was a 70% elevation of blood triglyceride levels. Because of a poor prognosis, the bird was euthanatized. At necropsy, the pancreas was diffusely enlarged, white, nodular, and firm. The liver contained multiple, 1-2-mm-diameter, randomly located, tan nodules. Microscopically, the pancreas was effaced by numerous lobules of neoplastic ductular structures surrounded by abundant fibrous connective tissue. In the liver, the hepatic parenchyma was replaced by multiple, well-demarcated, nonencapsulated foci of neoplastic tissue similar to that in the pancreas.

  9. Gastrin is not a physiological regulator of pancreatic exocrine secretion in the dog

    International Nuclear Information System (INIS)

    Koehler, E.; Beglinger, C.; Eysselein, V.; Groetzinger, U.; Gyr, K.

    1987-01-01

    The role of gastrin as a regulator of exocrine pancreatic secretion has not been proven adequately. In the present study the authors therefore compared the relative molar potencies of sulfated and unsulfated gastrin 17 with structurally related CCK peptides (synthetic CCK-8 and natural porcine CCK-33) in stimulating exocrine pancreatic secretion in conscious dogs. Dose response curves were constructed for pancreatic and gastric acid secretion. Plasma gastrin levels after exogenous gastrin 17-I and -II were compared with postprandial gastrin concentrations. The molar potency estimates calculated with synthetic CCK8 as standard for pancreatic protein secretion were natural porcine 50% pure CCK-33 1.60, gastrin 17-I 0.12, and gastrin 17-II 0.16. All four peptides induced a dose-dependent increase in pancreatic bicarbonate output. However, the blood concentrations needed to stimulate pancreatic secretion were above the postprandial gastrin levels. The data indicate that both gastrin 17 peptides are not physiological regulators of pancreatic enzyme secretion in dogs

  10. 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.

  11. The effect of pancreatic polypeptide and peptide YY on pancreatic blood flow and pancreatic exocrine secretion in the anesthetized dog

    International Nuclear Information System (INIS)

    DeMar, A.R.; Lake, R.; Fink, A.S.

    1991-01-01

    Pancreatic polypeptide (PP) and peptide YY (PYY) are inhibitors of pancreatic exocrine secretion in vivo but not in vitro, which suggests intermediate mechanisms of action. To examine the role of pancreatic blood flow in these inhibitory effects, xenon-133 gas clearance was used to measure pancreatic blood flow while simultaneously measuring pancreatic exocrine secretion. PP or PYY (400 pmol/kg/h) was administered during the intermediate hour of a 3-h secretin (125 ng/kg/h)/cholecystokinin octapeptide (CCK-8) (50 ng/kg/h) infusion. Exocrine secretion and pancreatic blood flow during the PP or PYY hours were compared with that observed in the first and third hours of the secretin/CCK-8 infusion. PP and PYY significantly inhibited secretin/CCK-8-induced pancreatic exocrine secretion. In addition, PYY (but not PP) significantly reduced pancreatic blood flow during secretin/CCK-8 stimulation. Nevertheless, there was no correlation between pancreatic blood flow and bicarbonate or protein outputs. It is concluded that changes in pancreatic blood flow do not mediate the inhibitory effects of PP or PYY on the exocrine pancreas

  12. Exocrine pancreatic insufficiency in the Eurasian dog breed - inheritance and exclusion of two candidate genes

    DEFF Research Database (Denmark)

    Proschowsky, Helle Friis; Fredholm, Merete

    2007-01-01

    Exocrine pancreatic insufficiency is considered an inherited disease in several dog breeds. Affected dogs show polyphagia, weight loss and voluminous faeces of light colour due to the lack of pancreatic enzymes. In the study described herein, we performed a segregation analysis using the SINGLES ...

  13. Pancreatic Endocrine and Exocrine Function in Children following Near-Total Pancreatectomy for Diffuse Congenital Hyperinsulinism

    Science.gov (United States)

    Arya, Ved Bhushan; Senniappan, Senthil; Demirbilek, Huseyin; Alam, Syeda; Flanagan, Sarah E.; Ellard, Sian; Hussain, Khalid

    2014-01-01

    Context Congenital hyperinsulinism (CHI), the commonest cause of persistent hypoglycaemia, has two main histological subtypes: diffuse and focal. Diffuse CHI, if medically unresponsive, is managed with near-total pancreatectomy. Post-pancreatectomy, in addition to persistent hypoglycaemia, there is a very high risk of diabetes mellitus and pancreatic exocrine insufficiency. Setting International referral centre for the management of CHI. Patients Medically unresponsive diffuse CHI patients managed with near-total pancreatectomy between 1994 and 2012. Intervention Near-total pancreatectomy. Main Outcome Measures Persistent hypoglycaemia post near-total pancreatectomy, insulin-dependent diabetes mellitus, clinical and biochemical (faecal elastase 1) pancreatic exocrine insufficiency. Results Of more than 300 patients with CHI managed during this time period, 45 children had medically unresponsive diffuse disease and were managed with near-total pancreatectomy. After near-total pancreatectomy, 60% of children had persistent hypoglycaemia requiring medical interventions. The incidence of insulin dependent diabetes mellitus was 96% at 11 years after surgery. Thirty-two patients (72%) had biochemical evidence of severe pancreatic exocrine insufficiency (Faecal elastase 1pancreatectomy is very unsatisfactory. The incidence of persistent hypoglycaemia and insulin-dependent diabetes mellitus is very high. The presence of clinical rather than biochemical pancreatic exocrine insufficiency should inform decisions about pancreatic enzyme supplementation. PMID:24840042

  14. Exocrine pancreatic insufficiency in diabetic patients: prevalence, mechanisms, and treatment.

    Science.gov (United States)

    Piciucchi, Matteo; Capurso, Gabriele; Archibugi, Livia; Delle Fave, Martina Maria; Capasso, Marina; Delle Fave, Gianfranco

    2015-01-01

    Pancreas is a doubled-entity organ, with both an exocrine and an endocrine component, reciprocally interacting in a composed system whose function is relevant for digestion, absorption, and homeostasis of nutrients. Thus, it is not surprising that disorders of the exocrine pancreas also affect the endocrine system and vice versa. It is well-known that patients with chronic pancreatitis develop a peculiar form of diabetes (type III), caused by destruction and fibrotic injury of islet cells. However, less is known on the influence of diabetes on pancreatic exocrine function. Pancreatic exocrine insufficiency (PEI) has been reported to be common in diabetics, with a prevalence widely ranging, in different studies, in both type I (25-74%) and type II (28-54%) diabetes. A long disease duration, high insulin requirement, and poor glycemic control seem to be risk factors for PEI occurrence. The impact of pancreatic exocrine replacement therapy on glycemic, insulin, and incretins profiles has not been fully elucidated. The present paper is aimed at reviewing published studies investigating the prevalence of PEI in diabetic patients and factors associated with its occurrence.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Should we Investigate Gastroenterology Patients for Pancreatic Exocrine Insufficiency? A Dual Centre UK Study.

    Science.gov (United States)

    Campbell, Jennifer A; Sanders, David S; Francis, Katherine A; Kurien, Matthew; Lee, Sai; Taha, Hatim; Ramadas, Arvind; Joy, Diamond; Hopper, Andrew D

    2016-09-01

    Pancreatic exocrine insufficiency may be under recognised in gastroenterological practice. We aimed to identify the prevalence of pancreatic insufficiency in secondary care gastroenterology clinics and determine if co-morbidity or presenting symptoms could predict diagnosis. A secondary aim was to assess response to treatment. A dual centre retrospective analysis was conducted in secondary care gastroenterology clinics. Patients tested for pancreatic exocrine insufficiency with faecal elastase-1 (FEL-1) between 2009 and 2013 were identified in two centres. Demographics, indication and co-morbidities were recorded in addition to dose and response to pancreatic enzyme replacement therapy. Binary logistic regression was used to assess if symptoms or co-morbidities could predict pancreatic insufficiency. 1821 patients were tested, 13.1% had low FEL-1 (<200µg/g). This prevalence was sub-analysed with 5.4% having FEL-1 100-200µg/g (mild insufficiency) and 7.6% having faecal elastase readings <100µg/g. Low FEL-1 was most significantly associated with weight loss or steatorrhoea. Co-morbidity analysis showed that low levels were significantly associated with excess alcohol intake, diabetes mellitus or human immunodeficiency virus; 80.0% treated with enzyme supplements reported symptomatic benefit with no difference in response between high and low dose supplementation (p=0.761). Targeting the use of FEL-1 in individuals with specific symptoms and associated conditions can lead to improved recognition of pancreatic exocrine insufficiency in a significant proportion of secondary care patients. Intervening with lifestyle advice such as smoking cessation and minimising alcohol intake could improve outcomes. In addition, up to 80% of patients with low faecal elastase respond to supplementation.

  17. Remnant pancreatic parenchymal volume predicts postoperative pancreatic exocrine insufficiency after pancreatectomy.

    Science.gov (United States)

    Okano, Keisuke; Murakami, Yoshiaki; Nakagawa, Naoya; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Takahashi, Shinya; Sueda, Taijiro

    2016-03-01

    Pancreatectomy, including pancreatoduodenectomy and distal pancreatectomy, often causes postoperative pancreatic exocrine insufficiency (PEI). Our aim was to clarify a relationship between remnant pancreatic volume and postoperative PEI. A total of 227 patients who underwent pancreatoduodenectomy or distal pancreatectomy were enrolled in this study. All patients underwent a (13)C-labeled mixed triglyceride breath test to assess pancreatic exocrine function and abdominal dynamic computed tomography for assessing remnant pancreatic volume after pancreatectomy at a median of 7 months postoperatively. The percent (13)CO2 cumulative dose at 7 hours (% dose (13)C cum 7 h) pancreatectomy were performed in 174 (76.7%) and 53 (23.3%) patients, respectively. Of the 227 patients, 128 (56.3%) developed postoperative PEI. Postoperative % dose (13)C cum 7 h was strongly correlated with remnant pancreatic volume (r = .509, P pancreatectomy (P pancreatectomy. Remnant pancreatic volume may predict postoperative PEI in patients who undergo pancreatectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. A prospective evaluation of pancreatic exocrine function in patients with acute pancreatitis: correlation with extent of necrosis and pancreatic endocrine insufficiency.

    Science.gov (United States)

    Boreham, B; Ammori, B J

    2003-01-01

    The aim of this prospective study was to assess pancreatic exocrine function in patients recovering from a first attack of acute pancreatitis, and to evaluate its relationship to severity of attack, extent of pancreatic necrosis and severity of pancreatic endocrine insufficiency. Between December 2000 and November 2001, 23 patients were prospectively evaluated. Pancreatic exocrine function was measured by the faecal elastase-1 test and insufficiency was classified as moderately impaired or severely impaired. Pancreatic necrosis was determined by contrast-enhanced CT scan, and its extent was categorised according to Balthazar's classification. The severity of pancreatic endocrine insufficiency was categorised according to insulin dependence. Attacks were classified as mild (n = 16) or severe (n = 7) according to the Atlanta criteria. Pancreatic exocrine insufficiency was significantly more frequent in patients recovering from severe attacks than mild (n = 6, 86% vs. n = 2, 13%; p = 0.002), and in those who developed pancreatic necrosis or pseudocyst than those who did not (6 of 7 patients vs. 2 of 16 patients, and 5 of 5 patients vs. 3 of 18 patients respectively; p = 0.002). The development of exocrine insufficiency correlated strongly with the extent of pancreatic necrosis (r = -0.754, p pancreatic endocrine insufficiency (n = 4, r = -0.453, p = 0.03). Pancreatic exocrine insufficiency is a common occurrence in patients recovering from severe acute pancreatitis, and its severity correlates with the extent of pancreatic necrosis and the severity of concomitant pancreatic endocrine insufficiency. Copyright 2003 S. Karger AG, Basel and IAP

  19. Exocrine Pancreatic Insufficiency in Diabetic Patients: Prevalence, Mechanisms, and Treatment

    Directory of Open Access Journals (Sweden)

    Matteo Piciucchi

    2015-01-01

    Full Text Available Pancreas is a doubled-entity organ, with both an exocrine and an endocrine component, reciprocally interacting in a composed system whose function is relevant for digestion, absorption, and homeostasis of nutrients. Thus, it is not surprising that disorders of the exocrine pancreas also affect the endocrine system and vice versa. It is well-known that patients with chronic pancreatitis develop a peculiar form of diabetes (type III, caused by destruction and fibrotic injury of islet cells. However, less is known on the influence of diabetes on pancreatic exocrine function. Pancreatic exocrine insufficiency (PEI has been reported to be common in diabetics, with a prevalence widely ranging, in different studies, in both type I (25–74% and type II (28–54% diabetes. A long disease duration, high insulin requirement, and poor glycemic control seem to be risk factors for PEI occurrence. The impact of pancreatic exocrine replacement therapy on glycemic, insulin, and incretins profiles has not been fully elucidated. The present paper is aimed at reviewing published studies investigating the prevalence of PEI in diabetic patients and factors associated with its occurrence.

  20. Romanian guidelines on the diagnosis and treatment of exocrine pancreatic insufficiency

    DEFF Research Database (Denmark)

    Gheorghe, Cristian; Seicean, Andrada; Saftoiu, Adrian

    2015-01-01

    In assessing exocrine pancreatic insufficiency (EPI), its diverse etiologies and the heterogeneous population affected should be considered. Diagnosing this condition remains a challenge in clinical practice especially for mild-to-moderate EPI, with the support of the time-consuming breath test o...... indicated in patients with celiac disease, who have chronic diarrhea (in spite of gluten-free diet), and in patients with cystic fibrosis with proven EPI....... on an individual's weight and clinical symptoms. The main indication for PERT is chronic pancreatitis, in patients who have clinically relevant steatorrhea, abnormal pancreatic function test or abnormal function tests associated with symptoms of malabsorption such as weight loss or meteorism. While enzyme...

  1. A pancreatic exocrine-like cell regulatory circuit operating in the upper stomach of the sea urchin Strongylocentrotus purpuratus larva.

    Science.gov (United States)

    Perillo, Margherita; Wang, Yue Julia; Leach, Steven D; Arnone, Maria Ina

    2016-05-26

    Digestive cells are present in all metazoans and provide the energy necessary for the whole organism. Pancreatic exocrine cells are a unique vertebrate cell type involved in extracellular digestion of a wide range of nutrients. Although the organization and regulation of this cell type is intensively studied in vertebrates, its evolutionary history is still unknown. In order to understand which are the elements that define the pancreatic exocrine phenotype, we have analyzed the expression of genes that contribute to specification and function of this cell-type in an early branching deuterostome, the sea urchin Strongylocentrotus purpuratus. We defined the spatial and temporal expression of sea urchin orthologs of pancreatic exocrine genes and described a unique population of cells clustered in the upper stomach of the sea urchin embryo where exocrine markers are co-expressed. We used a combination of perturbation analysis, drug and feeding experiments and found that in these cells of the sea urchin embryo gene expression and gene regulatory interactions resemble that of bona fide pancreatic exocrine cells. We show that the sea urchin Ptf1a, a key transcriptional activator of digestive enzymes in pancreatic exocrine cells, can substitute for its vertebrate ortholog in activating downstream genes. Collectively, our study is the first to show with molecular tools that defining features of a vertebrate cell-type, the pancreatic exocrine cell, are shared by a non-vertebrate deuterostome. Our results indicate that the functional cell-type unit of the vertebrate pancreas may evolutionarily predate the emergence of the pancreas as a discrete organ. From an evolutionary perspective, these results encourage to further explore the homologs of other vertebrate cell-types in traditional or newly emerging deuterostome systems.

  2. Obstructed pancreaticojejunostomy partly explains exocrine insufficiency after pancreatic head resection.

    Science.gov (United States)

    Nordback, Isto; Parviainen, Mickael; Piironen, Anneli; Räty, Sari; Sand, Juhani

    2007-02-01

    The majority of patients with long-term survival after pancreatic head resection suffer from pancreatic exocrine insufficiency. The objective of this study was to investigate whether this is due to glandular malfunction or obstructed pancreaticojejunal anastomosis. Twenty-six patients (10 M, 16 F, mean age 61 years, range 34-81 years) were re-examined a median of 52 months (range 3-76 months) after pancreatic head resection and end-to-end invaginated pancreaticojejunostomy. Pancreatic exocrine function was measured by fecal elastase-1 assay. The size of the pancreatic remnant, glandular secretion and the flow through the anastomosis were analyzed with secretin-stimulated dynamic magnetic resonance pancreatography (D-MRP). All patients had pancreatic exocrine insufficiency, 24 (92%) of them having severe insufficiency. Eighteen patients (69%) reported moderate to severe diarrhea. Lowest fecal elastase-1 concentrations were associated with the initial diagnosis of chronic pancreatitis or ductal adenocarcinoma, suggesting preoperative primary or secondary chronic pancreatitis as important determinants. The size of the remnant gland did not correlate with the fecal elastase-1 concentrations. D-MRP failed in three patients. Severe glandular malfunctions were found in 7 (30%) of the 23 successful D-MRP examinations. The anastomosis was totally obstructed in 5 patients (22%) or partially obstructed in 6 (26%) but remained perfectly open in 5 patients (22%). The five patients with perfect anastomoses had the highest measured median fecal elastase-1 activity. Although late diarrhea and pancreatic exocrine insufficiency may be partly induced already by the disease treated with resection, at least half may be explained by obstructed anastomosis. To obtain better late functional results, improvements may be required in the surgical techniques.

  3. Zinc status in chronic pancreatitis and its relationship with exocrine and endocrine insufficiency.

    Science.gov (United States)

    Girish, Banavara Narasimhamurthy; Rajesh, Gopalakrishna; Vaidyanathan, Kannan; Balakrishnan, Vallath

    2009-11-05

    A major role of the pancreas in zinc homeostasis has been suggested. To assess erythrocyte zinc status in chronic pancreatitis and to correlate it with pancreatic exocrine and endocrine insufficiency. One hundred and one patients with chronic pancreatitis (34 alcoholic chronic pancreatitis, 67 tropical chronic pancreatitis) were prospectively studied. Disease characteristics and imaging features were recorded. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. Exocrine insufficiency was assessed using polyclonal antibody ELISA for pancreatic stool elastase1. Endocrine insufficiency was assessed by serum glucose levels and insulin requirement. Erythrocyte zinc was significantly lower in chronic pancreatitis patients than in the controls (26.5+/-9.5 microg/g Hb vs. 38.0+/-6.6 microg/g Hb; Ppancreatitis than in alcoholic chronic pancreatitis (25.0+/-10.4 microg/g Hb vs. 29.6+/-6.5 microg/g Hb, P=0.001). In chronic pancreatitis patients who had exocrine insufficiency, erythrocyte zinc positively correlated with stool elastase1 (r=0.587, Ppancreatitis patients, and that zinc deficiency correlates with exocrine and endocrine insufficiency. Further studies may clarify the possible benefits of zinc supplementation in chronic pancreatitis.

  4. Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities.

    Science.gov (United States)

    Hayden, Melvin R; Patel, Kamlesh; Habibi, Javad; Gupta, Deepa; Tekwani, Seema S; Whaley-Connell, Adam; Sowers, James R

    2008-01-01

    Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet-exocrine interface appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts-pancreatic stellate cells. Of importance, some pericyte cellular processes traverse both the connecting islet-exocrine interface and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal-incretin gut hormone axis, resulting in pancreatic insufficiency and glucagon-like peptide deficiency, which are known to exist in prediabetes and overt T2DM in humans.

  5. [Pancreatic infringement exocrine and endocrine in cystic fibrosis].

    Science.gov (United States)

    Kessler, L; Abély, M

    2016-12-01

    The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine (Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent

  6. Pancreatic endocrine and exocrine function and salivary gland function in autoimmune pancreatitis before and after steroid therapy.

    Science.gov (United States)

    Kamisawa, Terumi; Egawa, Naoto; Inokuma, Shigeko; Tsuruta, Kouji; Okamoto, Atsutake; Kamata, Noriko; Nakamura, Teruo; Matsukawa, Masakatsu

    2003-10-01

    Autoimmune pancreatitis (AIP) is a distinct clinical entity in which an autoimmune mechanism may be involved in pathogenesis. To investigate salivary gland function in addition to pancreatic endocrine and exocrine function in patients with AIP, and to determine changes occurring after steroid therapy. Fasting serum glucose levels, oral glucose tolerance tests or glycosylated hemoglobin values were examined in 19 patients with AIP. N-benzoyl-L-tyrosyl-p-aminobenzoic acid excretion test, sialochemistry and parotid gland scintigraphy were performed in 8 patients. Eight patients had evidence of DM. Steroid therapy subsequently improved insulin secretion and glycemic control in 3 of 5 patients treated. Pancreatic exocrine function was reduced in 88% of patients. Impaired pancreatic exocrine function improved after steroid therapy in 3 of 6 patients treated. The 3 patients also showed treatment-related improvement in endocrine function. Concentration of beta2-microglobulin in saliva was significantly raised in patients with AIP compared with controls (P gland dysfunction improved after steroid therapy in all 5 patients treated. Pancreatic endocrine and exocrine and salivary gland function were frequently impaired in patients with AIP, and steroid therapy was occasionally effective for these dysfunctions.

  7. Radioselenium pancreozymin-secretin test as a clinical test for pancreatic exocrine function

    International Nuclear Information System (INIS)

    Shichiri, M.; Etani, N.; Yoshida, M.; Harano, Y.; Hoshi, M.; Shigeta, Y.; Abe, H.

    1975-01-01

    The appearance of radioselenium in the protein fraction of duodenal aspirates has been studied after an intravenous injection of 75 Se-selenomethionine. The continuous flow of pancreatic juice was stimulated by pancreozymin at 120 minutes and by secretin at 140 minutes. A good distinction between normal subjects and patients with pancreatic disease was obtained by measuring 75 Se-radioactivity in the protein fraction of duodenal aspirates; either cumulative radioactivity during the combined 80-minute post-pancreozymin-secretin period, or maximum 75 Se-specific activity during the postsecretin period was used as an index. The test presented here might be a useful and sufficiently reliable method for detecting abnormal pancreatic exocrine function. This test can be performed along with the conventional pancreozymin-secretin test, serum enzyme response to pancreozymin and secretin, and pancreatic scintiscanning

  8. Thirty-day outcomes underestimate endocrine and exocrine insufficiency after pancreatic resection.

    Science.gov (United States)

    Lim, Pei-Wen; Dinh, Kate H; Sullivan, Mary; Wassef, Wahid Y; Zivny, Jaroslav; Whalen, Giles F; LaFemina, Jennifer

    2016-04-01

    Long-term incidence of endocrine and exocrine insufficiency after pancreatectomy is poorly described. We analyze the long-term risks of pancreatic insufficiency after pancreatectomy. Subjects who underwent pancreatectomy from 2002 to 2012 were identified from a prospective database (n = 227). Subjects who underwent total pancreatectomy or pancreatitis surgery were excluded. New post-operative endocrine and exocrine insufficiency was defined as the need for new pharmacologic intervention within 1000 days from resection. 28 (16%) of 178 subjects without pre-existing endocrine insufficiency developed post-operative endocrine insufficiency: 7 (25%) did so within 30 days, 8 (29%) between 30 and 90 days, and 13 (46%) after 90 days. 94 (43%) of 214 subjects without pre-operative exocrine insufficiency developed exocrine insufficiency: 20 (21%) did so within 30 days, 29 (31%) between 30 and 90 days, and 45 (48%) after 90 days. Adjuvant radiation was associated with new endocrine insufficiency. On multivariate regression, pancreaticoduodenectomy and chemotherapy were associated with a greater risk of exocrine insufficiency. Reporting 30-day functional outcomes for pancreatic resection is insufficient, as nearly 45% of subjects who develop disease do so after 90 days. Reporting of at least 90-day outcomes may more reliably assess risk for post-operative endocrine and exocrine insufficiency. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  9. Exocrine pancreatic insufficiency in diabetes mellitus: a complication of diabetic neuropathy or a different type of diabetes?

    Science.gov (United States)

    Hardt, Philip D; Ewald, Nils

    2011-01-01

    Pancreatic exocrine insufficiency is a frequently observed phenomenon in type 1 and type 2 diabetes mellitus. Alterations of exocrine pancreatic morphology can also be found frequently in diabetic patients. Several hypotheses try to explain these findings, including lack of insulin as a trophic factor for exocrine tissue, changes in secretion and/or action of other islet hormones, and autoimmunity against common endocrine and exocrine antigens. Another explanation might be that diabetes mellitus could also be a consequence of underlying pancreatic diseases (e.g., chronic pancreatitis). Another pathophysiological concept proposes the functional and morphological alterations as a consequence of diabetic neuropathy. This paper discusses the currently available studies on this subject and tries to provide an overview of the current concepts of exocrine pancreatic insufficiency in diabetes mellitus.

  10. Exocrine Pancreatic Insufficiency in Diabetes Mellitus: A Complication of Diabetic Neuropathy or a Different Type of Diabetes?

    Directory of Open Access Journals (Sweden)

    Philip D. Hardt

    2011-01-01

    Full Text Available Pancreatic exocrine insufficiency is a frequently observed phenomenon in type 1 and type 2 diabetes mellitus. Alterations of exocrine pancreatic morphology can also be found frequently in diabetic patients. Several hypotheses try to explain these findings, including lack of insulin as a trophic factor for exocrine tissue, changes in secretion and/or action of other islet hormones, and autoimmunity against common endocrine and exocrine antigens. Another explanation might be that diabetes mellitus could also be a consequence of underlying pancreatic diseases (e.g., chronic pancreatitis. Another pathophysiological concept proposes the functional and morphological alterations as a consequence of diabetic neuropathy. This paper discusses the currently available studies on this subject and tries to provide an overview of the current concepts of exocrine pancreatic insufficiency in diabetes mellitus.

  11. ESPGHAN and NASPGHAN Report on the Assessment of Exocrine Pancreatic Function and Pancreatitis in Children

    NARCIS (Netherlands)

    Taylor, Christopher J.; Chen, Kathy; Horvath, Karoly; Hughes, David; Lowe, Mark E.; Mehta, Devendra; Orabi, Abrahim I.; Screws, Jeremy; Thomson, Mike; Van Biervliet, Stephanie; Verkade, Henkjan J.; Husain, Sohail Z.; Wilschanski, Michael

    The purpose of this clinical report is to discuss several recent advances in assessing exocrine pancreatic insufficiency (EPI) and pancreatitis in children, to review the array of pancreatic function tests, to provide an update on the inherited causes of EPI, with special emphasis on newly available

  12. Pancreatic exocrine secretion in atomic bomb survivors

    International Nuclear Information System (INIS)

    Hiraoka, Masataka; Kawanishi, Masahiro; Ohtaki, Megu

    1989-01-01

    This study was designed to examine the effect of A-bombing on pancreatic exocrine secretion in 6 A-bomb survivors (an average age of 57 years) and the age- and sex-matched non-exposed 6 persons (an average age of 58 years). Six A-bomb survivors consisted of: three who had been directly exposed to A-bombing, one who had entered the city within 3 days after bombing, one who had worked in caring for A-bomb survivors, and one who had later entered the city. Caerulein-Secretin test revealed no significant difference in the total secretion of lipase, maximum bicarbonate, amylase output, or lipase output between the exposed and non-exposed groups. The concentration of lipase ten min after stimulation was significantly decreased in the exposed group than the control group. This suggests that radiation may be responsible for abnormality in the ability of pancreatic exocrine secretion. (N.K.)

  13. Negotiating the complexities of exocrine and endocrine dysfunction in chronic pancreatitis.

    Science.gov (United States)

    Duggan, Sinead N

    2017-11-01

    Chronic pancreatitis is a chronic inflammatory disease of the pancreas characterised by irreversible morphological change and typically causing pain and/or permanent loss of function. This progressive, irreversible disease results in destruction of healthy pancreatic tissue and the development of fibrous scar tissue. Gradual loss of exocrine and endocrine function follows, along with clinical manifestations such as steatorrhoea, abdominal pain and diabetes. Nutrition in chronic pancreatitis has been described as a problem area and, until recently, there was little research on the topic. It is often asserted that >90 % of the pancreas must be damaged before exocrine insufficiency occurs; however, an exploration of the original studies from the 1970s found that the data do not support this assertion. The management of steatorrhoea with pancreatic enzyme replacement therapy is the mainstay of nutritional management, and early identification and treatment is a key. The presence of steatorrhoea, coupled with poor dietary intake (due to intractable abdominal pain, gastrointestinal side effects and often alcoholism) renders the chronic pancreatitis patients at considerable risk for undernutrition, muscle depletion and fat-soluble vitamin deficiency. Premature osteoporosis/osteopenia afflicts two-thirds of patients as a consequence of poor dietary intake of calcium and vitamin D, low physical activity, low sunlight exposure, heavy smoking, as well as chronic low-grade inflammation. Bone metabolism studies show increased bone formation as well as bone resorption in chronic pancreatitis, indicating that bone turnover is abnormally high. Loss of the pancreatic islet cells occurs later in the disease process as the endocrine cells are diffusely distributed throughout the pancreatic parenchyma. Patients may develop type 3c (pancreatogenic) diabetes, which is complicated by concurrent decreased glucagon secretion, and hence an increased risk of hypoglycaemia. Diabetes control is

  14. Gene delivery to pancreatic exocrine cells in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Houbracken Isabelle

    2012-10-01

    Full Text Available Abstract Background Effective gene transfer to the pancreas or to pancreatic cells has remained elusive although it is essential for studies of genetic lineage tracing and modulation of gene expression. Different transduction methods and viral vectors were tested in vitro and in vivo, in rat and mouse pancreas. Results For in vitro transfection/transduction of rat exocrine cells lipofection reagents, adenoviral vectors, and Mokola- and VSV-G pseudotyped lentiviral vectors were used. For in vivo transduction of mouse and rat pancreas adenoviral vectors and VSV-G lentiviral vectors were injected into the parenchymal tissue. Both lipofection of rat exocrine cell cultures and transduction with Mokola pseudotyped lentiviral vectors were inefficient and resulted in less than 4% EGFP expressing cells. Adenoviral transduction was highly efficient but its usefulness for gene delivery to rat exocrine cells in vitro was hampered by a drastic increase in cell death. In vitro transduction of rat exocrine cells was most optimal with VSV-G pseudotyped lentiviral vectors, with stable transgene expression, no significant effect on cell survival and about 40% transduced cells. In vivo, pancreatic cells could not be transduced by intra-parenchymal administration of lentiviral vectors in mouse and rat pancreas. However, a high efficiency could be obtained by adenoviral vectors, resulting in transient transduction of mainly exocrine acinar cells. Injection in immune-deficient animals diminished leukocyte infiltration and prolonged transgene expression. Conclusions In summary, our study remarkably demonstrates that transduction of pancreatic exocrine cells requires lentiviral vectors in vitro but adenoviral vectors in vivo.

  15. The impact of pancreaticoduodenectomy on endocrine and exocrine pancreatic function: A prospective cohort study based on pre- and postoperative function tests.

    Science.gov (United States)

    Roeyen, Geert; Jansen, Miet; Hartman, Vera; Chapelle, Thiery; Bracke, Bart; Ysebaert, Dirk; De Block, Christophe

    Studies reporting on function after pancreatic surgery are frequently based on diabetes history, fasting glycemia or random glycemia. The aim of this study was to investigate prospectively the evolution of pancreatic function in patients undergoing pancreaticoduodenectomy based on proper pre- and postoperative function tests. It was hypothesised that pancreatic function deteriorates after pancreaticoduodenectomy. Between 2013 and 2016, 78 patients undergoing pancreaticoduodenectomy for oncologic indications had a prospective evaluation of their endocrine and exocrine pancreatic function. Endocrine function was evaluated with the 75 g oral glucose tolerance test (OGTT) and the 1 mg intravenous glucagon test. Exocrine function was evaluated with a 13C-labelled mixed-triglyceride breath test. Tests were performed pre- and postoperatively. In 90.5% (19/21) of patients with preoperatively known diabetes, no change in endocrine function was observed. In contrast, endocrine function improved in 68.1% (15/22) of patients with newly diagnosed diabetes. 40% (14/35) of patients with a preoperative normal OGTT or prediabetes experienced deterioration in function. In multivariate analysis, improvement of newly diagnosed diabetes was correlated with preoperative bilirubin levels (p = 0.045), while progression towards diabetes was correlated with preoperative C-peptidogenic index T 30 (p = 0.037). A total of 20.5% (16/78) of patients had pancreatic exocrine insufficiency preoperatively. Another 51.3% (40/78) of patients deteriorated on exocrine level. In total, 64.1% (50/78) of patients required pancreatic enzyme-replacement therapy postoperatively. Although deterioration of endocrine function was expected after pancreatic resection, improvement is frequently observed in patients with newly diagnosed diabetes. Exocrine function deteriorates after pancreaticoduodenectomy. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  16. Identification of proteins involved in the pancreatic exocrine by exogenous ghrelin administration in Sprague-Dawley rats.

    Science.gov (United States)

    Lee, Kyung-Hoon; Wang, Tao; Jin, Yong-Cheng; Lee, Sang-Bum; Oh, Jin-Ju; Hwang, Jin-Hee; Lim, Ji-Na; Lee, Jae-Sung; Lee, Hong-Gu

    2014-01-01

    The aims of study were to investigate the effects of intraperitoneal (i.p.) infusion of ghrelin on pancreatic α-amylase outputs and the responses of pancreatic proteins to ghrelin that may relate to the pancreatic exocrine. Six male Sprague-Dawley rats (300 g) were randomly divided into two groups, a control group (C, n = 3) and a treatment group (T, 10.0μg/kg BW, n = 3). Blood samples were collected from rat caudal vein once time after one hour injection. The concentrations of plasma ghrelin, cholecystokinin (CCK) and alfa-amylase activity were evaluated by enzyme immunoassay (EIA) kit. Two-dimensional gel electrophoresis (2-DE) analysis was conducted to separate the proteins in pancreas tissue. Results showed that the i.p. infusion of ghrelin at doses of 10.0 μg/kg body weight (BW) increased the plasma ghrelin concentrations (p = 0.07) and elevated the plasma CCK level significantly (p amylase activity tended to increase. The proteomics analysis indicated that some pancreatic proteins with various functions were up- or down- regulated compared with control group. In conclusion, ghrelin may have role in the pancreatic exocrine, but the signaling pathway was still not clear. Therefore, much more functional studies focus on these found proteins are needed in the near future.

  17. A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor.

    Science.gov (United States)

    Sikkens, Edmée C M; Cahen, Djuna L; de Wit, Jill; Looman, Caspar W N; van Eijck, Casper; Bruno, Marco J

    2014-01-01

    In cancer of the pancreatic head region, exocrine insufficiency is a well-known complication, leading to steatorrhea, weight loss, and malnutrition. Its presence is frequently overlooked, however, because the primary attention is focused on cancer treatment. To date, the risk of developing exocrine insufficiency is unspecified. Therefore, we assessed this function in patients with tumors of the pancreatic head, distal common bile duct, or ampulla of Vater. Between March 2010 and August 2012, we prospectively included patients diagnosed with cancer of the pancreatic head region at our tertiary center. To preclude the effect of a resection, we excluded operated patients. Each month, the exocrine function was determined with a fecal elastase test. Furthermore, endocrine function, steatorrhea-related symptoms, and body weight were evaluated. Patients were followed for 6 months, or until death. Thirty-two patients were included. The tumor was located in the pancreas in 75%, in the bile duct in 16%, and in the ampullary region in 9%, with a median size of 2.5 cm. At diagnosis, the prevalence of exocrine insufficiency was 66%, which increased to 92% after a median follow-up of 2 months (interquartile range, 1 to 4 mo). Most patients with cancer of the pancreatic head region were already exocrine insufficient at diagnosis, and within several months, this function was impaired in almost all cases. Given this high prevalence, physicians should be focused on diagnosing and treating exocrine insufficiency, to optimize the nutritional status and physical condition, especially for those patients undergoing palliative chemotherapy and/or radiotherapy.

  18. Bone mineral metabolism, bone mineral density, and body composition in patients with chronic pancreatitis and pancreatic exocrine insufficiency

    DEFF Research Database (Denmark)

    Haaber, Anne Birgitte; Rosenfalck, A M; Hansen, B

    2000-01-01

    Calcium and vitamin D homeostasis seem to be abnormal in patients with exocrine pancreatic dysfunction resulting from cystic fibrosis. Only a few studies have evaluated and described bone mineral metabolism in patients with chronic pancreatitis and pancreatic insufficiency....

  19. Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis.

    Science.gov (United States)

    Vujasinovic, Miroslav; Tepes, Bojan; Makuc, Jana; Rudolf, Sasa; Zaletel, Jelka; Vidmar, Tjasa; Seruga, Maja; Birsa, Bostjan

    2014-12-28

    To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP). Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria. One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks. As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful.

  20. 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.

  1. 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.)

  2. Monitoring the effect of substitution therapy in patients with exocrine pancreatic insufficiency

    International Nuclear Information System (INIS)

    Joergensen, B.B.; Pedersen, N.T.; Worning, H.

    1991-01-01

    Twenty-three outpatients with chronic pancreatitis and severe exocrine insufficiency were studied for the purpose of comparing the effect of Pancrease, Pankreon and Pankreatin by estimation of duodenal enzyme activity, the faecal fat excretion, and the faecal 14 C-triolein- 3 H-oleic acid test and, at the same time, to evaluate these tests when monitoring outpatients. The three preparations did not disclose any significant difference in treating steatorrhoea. Pankreatin increased the meal-stimulated duodenal enzyme activity (p 14 -C-triolein- 3 H-oleic acid test showed significant improvement in the 14 C-triolein digestion with all three preparations (p 14 -C-triolein- 3 H-oleic acid test was the most reliable when monitoring outpatients. 17 refs., 1 fig., 3 tabs

  3. Studies on zinc-induced pancreatic exocrine insufficiency and its consequences in the chick

    International Nuclear Information System (INIS)

    Lue, J.

    1989-01-01

    Experiments were conducted to investigate the nature of zinc (Zn)-induced pancreatic exocrine damage, some of its consequences and its interaction with other nutrients, especially selenium (Se) and vitamin E (VE) in the chick. When fed excess Zn, the chick pancreas accumulated as much as an order of magnitude more Zn than the liver on a unit weight basis. The levels of activities of pancreatic secretory enzymes were significantly reduced by excess dietary Zn and distortion of the acinar pancreas structure, losses of zymogen granules and varying degree of fibrotic infiltration were observed histologically. The reduction of the level of pancreatic secretory enzyme activities was accompanied by a reduction of the quantity of enzyme proteins rather than a modification of enzyme activity. The rate of synthesis of pancreatic amylase, as assessed by the incorporation of 3 H-leucine, was significantly decreased by excess dietary Zn. As consequences of Zn-induced pancreatic damage, the digestibility of dietary starch and tissue VE status were decreased, the latter effect being caused primarily by an impaired utilization of dietary source of the vitamin as determined by the appearance of 3 H-α-tocopherol in the blood after an oral dose. Excess dietary Zn increased the Se status of the pancreas, but not those of the plasma and the liver. Supranutritional levels of Se and/or VE did not protect the pancreas against Zn-induced damage, nor did Se-deficiency exacerbate this damage. An in vitro inhibitory effect of Zn and some heavy metal ions on α-amylase activity was discovered and characterized by a non-competitive mechanism. This inhibitory effect could become an important modular of utilization of dietary starch under conditions of Zn toxicosis

  4. [Relation between gene mutations and pancreatic exocrine function in patients with cystic fibrosis].

    Science.gov (United States)

    Radivojević, D; Guć-Sćekić, M; Djurisić, M; Lalić, T; Minić, P; Kanavakis, E

    2001-01-01

    Cystic fibrosis (CF), is the most common autosomal-recessive disease in Caucasians, with an incidence of approximately 1:2500 live births and a carrier frequency of approximately 4-5%. Causes of the disease are mutations in the CF gene which is located on chromosome 7 (region 7q31). Although a single mutation, a deletion of phenylalanine at position 508 (DF508) in exon 10, accounts for almost 70% of all CF chromosomes, over 900 other mutations have been identified in this large gene. CF gene encodes a membrane protein, which functions as aion channel- CFTR (cystic fibrosis transmembrane regulator protein). The exocrine pancreas is a gland that secretes water, enzymes and electrolytes into the intestinal lumen. These enzymes are needed for the normal digestion of food, and their reduced secretion in cystic fibrosis will cause malabsortion and malnutrition in CF patients. Pancreatic dysfunction in CF begins in uteri. Most patients with CF typically present insufficient pancreatic exocrine function (PI phenotype) and 10-15% of CF patients are pancreatic sufficient (PS phenotype). It has been shown elsewhere that the pancreatic function status in CF could be correlated to mutations in the CFTR gene. To determine the relation between genotype and pancreatic status, we analyzed 32 CF patients in whom both CF gene mutant alleles were identified (Table 1). Patients included in this study attended the Paediatric Department of Mother and Child Health Institute in Belgrade. The diagnosis was based on typical clinical manifestations and high levels of sweat chloride concentration (higher than 60 mmol/L). Of the 32 patients studied, only one (3.12%) was PS and the rest (96.88%) had PI phenotype. For each CF genotype the number of patients who were PI or PS is given in Table 1. The most striking observation was that all given genotypes correlated with either PI or PS, but not with both. On the basis of both preceding hypotheses and our present data (Table 2 and Table 3), it was

  5. An update on pancreatic pathophysiology (do we have to rewrite pancreatic pathophysiology?).

    Science.gov (United States)

    Hammer, Heinz F

    2014-02-01

    This review focuses on seven aspects of physiology and pathophysiology of the exocrine pancreas that have been intensively discussed and studied within the past few years: (1) the role of neurohormonal mechanisms like melatonin, leptin, or ghrelin in the stimulation of pancreatic enzyme secretion; (2) the initiation processes of acute pancreatitis, like fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen by the lysosomal enzyme cathepsin B, or autoactivation of trypsinogen; (3) the role of genes in the pathogenesis of acute pancreatitis; (4) the role of alcohol and constituents of alcoholic beverages in the pathogenesis of acute pancreatitis; (5) the role of pancreatic hypertension, neuropathy, and central mechanisms for the pathogenesis of pain in chronic pancreatitis; (6) the relation between exocrine pancreatic function and diabetes mellitus; and (7) pathophysiology, diagnosis and treatment of pancreatic steatorrhea.

  6. Non-invasive quantification of pancreatic exocrine function using secretin-stimulated MRCP

    International Nuclear Information System (INIS)

    Punwani, S.; Gillams, A.R.; Lees, W.R.

    2003-01-01

    Our objective was to quantify water volume using magnetic resonance cholangiopancreatography (MRCP) sequences and apply this to secretin-stimulated studies with the aim of quantifying pancreatic exocrine function. A commercially available single-shot MRCP sequence was used in conjunction with a body phased-array coil and a 1.5-T MR system. Signal intensity was measured in samples of water, pancreatic, duodenal juice, and secretin-stimulated pancreatic juice. A water phantom was made and MR calculated volumes compared with known water volumes within the phantom. Changes in small intestinal volume in response to secretin were measured in a group of 11 patients with no evidence of pancreatic disease. Changes in water volume were plotted over time. The pancreatic duct diameter before and after secretin was noted and filling defects were sought. All patients also underwent an axial breath-hold T1-weighted gradient-echo sequence and the pancreatic parenchyma was evaluated for size and signal intensity. There was no difference in the signal intensity of the different juice samples. There was excellent correlation between known and calculated MRCP volumes (χ 2 =0.99). All patients demonstrated normal duct morphology on MRCP and normal pancreatic parenchyma on T1-weighted imaging. The mean flow rate in the patient population was 8.1±2.5 ml/s over a median of 7 min (range 5-9 min). The MRCP sequence can be used to measure water volume. Sequential MRCP measurements following secretin permitted calculation of volume change and flow rate. This should prove useful as an indicator of pancreatic exocrine function. (orig.)

  7. Population-Level Incidence and Predictors of Surgically Induced Diabetes and Exocrine Insufficiency after Partial Pancreatic Resection.

    Science.gov (United States)

    Elliott, Irmina A; Epelboym, Irene; Winner, Megan; Allendorf, John D; Haigh, Philip I

    2017-01-01

    Endocrine and exocrine insufficiency after partial pancreatectomy affect quality of life, cardiovascular health, and nutritional status. However, their incidence and predictors are unknown. To identify the incidence and predictors of new-onset diabetes and exocrine insufficiency after partial pancreatectomy. We retrospectively reviewed 1165 cases of partial pancreatectomy, performed from 1998 to 2010, from a large population-based database. Incidence of new onset diabetes and exocrine insufficiency RESULTS: Of 1165 patients undergoing partial pancreatectomy, 41.8% had preexisting diabetes. In the remaining 678 patients, at a median 3.6 months, diabetes developed in 274 (40.4%) and pancreatic insufficiency developed in 235 (34.7%) patients. Independent predictors of new-onset diabetes were higher Charlson Comorbidity Index (CCI; hazard ratio [HR] = 1.62 for CCI of 1, p = 0.02; HR = 1.95 for CCI ≥ 2, p pancreatitis (HR = 1.51, p = 0.03). There was no difference in diabetes after Whipple procedure vs distal pancreatic resections, or malignant vs benign pathologic findings. Independent predictors of exocrine insufficiency were female sex (HR = 1.32, p = 0.002) and higher CCI (HR = 1.85 for CCI of 1, p insufficiency (HR = 0.35, p endocrine and exocrine insufficiency were 40% and 35%, respectively. These data are critical for informing patients' and physicians' expectations.

  8. 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.

  9. Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.

    Science.gov (United States)

    Lowery, Maeve A; Wong, Winston; Jordan, Emmet J; Lee, Jonathan W; Kemel, Yelena; Vijai, Joseph; Mandelker, Diana; Zehir, Ahmet; Capanu, Marinela; Salo-Mullen, Erin; Arnold, Angela G; Yu, Kenneth H; Varghese, Anna M; Kelsen, David P; Brenner, Robin; Kaufmann, Erica; Ravichandran, Vignesh; Mukherjee, Semanti; Berger, Michael F; Hyman, David M; Klimstra, David S; Abou-Alfa, Ghassan K; Tjan, Catherine; Covington, Christina; Maynard, Hannah; Allen, Peter J; Askan, Gokce; Leach, Steven D; Iacobuzio-Donahue, Christine A; Robson, Mark E; Offit, Kenneth; Stadler, Zsofia K; O'Reilly, Eileen M

    2018-02-28

    Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board-approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

  10. 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

  11. 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 ...

  12. Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency.

    Science.gov (United States)

    Smith, Ross C; Smith, Sarah F; Wilson, Jeremy; Pearce, Callum; Wray, Nick; Vo, Ruth; Chen, John; Ooi, Chee Y; Oliver, Mark; Katz, Tamarah; Turner, Richard; Nikfarjam, Mehrdad; Rayner, Christopher; Horowitz, Michael; Holtmann, Gerald; Talley, Nick; Windsor, John; Pirola, Ron; Neale, Rachel

    2016-01-01

    Because of increasing awareness of variations in the use of pancreatic exocrine replacement therapy, the Australasian Pancreatic Club decided it was timely to re-review the literature and create new Australasian guidelines for the management of pancreatic exocrine insufficiency (PEI). A working party of expert clinicians was convened and initially determined that by dividing the types of presentation into three categories for the likelihood of PEI (definite, possible and unlikely) they were able to consider the difficulties of diagnosing PEI and relate these to the value of treatment for each diagnostic category. Recent studies confirm that patients with chronic pancreatitis receive similar benefit from pancreatic exocrine replacement therapy (PERT) to that established in children with cystic fibrosis. Severe acute pancreatitis is frequently followed by PEI and PERT should be considered for these patients because of their nutritional requirements. Evidence is also becoming stronger for the benefits of PERT in patients with unresectable pancreatic cancer. However there is as yet no clear guide to help identify those patients in the 'unlikely' PEI group who would benefit from PERT. For example, patients with coeliac disease, diabetes mellitus, irritable bowel syndrome and weight loss in the elderly may occasionally be given a trial of PERT, but determining its effectiveness will be difficult. The starting dose of PERT should be from 25,000-40,000 IU lipase taken with food. This may need to be titrated up and there may be a need for proton pump inhibitors in some patients to improve efficacy. Copyright © 2016 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.

  13. Identification of risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy using a 13C-labeled mixed triglyceride breath test.

    Science.gov (United States)

    Hirono, Seiko; Murakami, Yoshiaki; Tani, Masaji; Kawai, Manabu; Okada, Ken-ichi; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Nakagawa, Naoya; Kondo, Naru; Yamaue, Hiroki

    2015-02-01

    There are only a few reports concerning long-term exocrine function after pancreaticoduodenectomy (PD), although the number of long-term survivors has increased. We assessed pancreatic exocrine function after PD in 189 patients to identify risk factors for pancreatic exocrine insufficiency. We evaluated patients' exocrine function by using the (13)C-labeled mixed triglyceride breath test, a noninvasive test feasible in outpatient service units. The present study included 99 patients that underwent pancreaticojejunostomy (PJ) at Wakayama Medical University Hospital and 90 patients that underwent pancreaticogastrostomy (PG) at Hiroshima University Hospital, the standard reconstruction techniques during PD at the respective hospitals. We also analyzed long-term morphological changes of remnant pancreas by computed tomography (main pancreatic duct dilation and parenchymal atrophy), nutritional status, and endocrine function. Independent risk factors for exocrine insufficiency after PD include hard pancreas (P = 0.003, odds ratio; 3.157) and PG reconstruction (P = 0.040, odds ratio; 2.321). Breath test results correlated significantly with post-operative morphological changes, nutritional status, and endocrine function. Atrophic changes of the remnant pancreas in the PG group were more severe than those in the PJ group. Furthermore, for patients with a soft pancreas, postoperative body weight changes, prognostic nutritional index, serum total protein levels as well as exocrine test were worse in the PG group, compared with the PJ group. Our results showed that PJ reconstruction might be superior to PG during PD, from the viewpoint of long-term pancreatic exocrine function, although further prospective studies are needed.

  14. Influence of SPK with Enteric Drainage on the Pancreatic Exocrine Function in Diabetic Patients with Uremia

    Directory of Open Access Journals (Sweden)

    Guanghui Pei

    2017-01-01

    Full Text Available Objective. This study aimed to determine the use of fecal elastase in evaluating the effect of simultaneous pancreas–kidney transplantation with enteric drainage on the pancreatic exocrine function of diabetic patients with uremia. Methods. A total of 19 patients with simultaneous pancreas–kidney transplantation (SPK with enteric drainage, 31 diabetic patients with uremia (chronic renal failure (CRF, 22 diabetic patients with uremia who underwent renal transplantation (RT, and 20 normal individuals (CON were included in the study. Pancreatic exocrine insufficiency was determined using fecal elastase. Results. The fecal pancreatic elastase level in SPK patients with enteric drainage was 479 μg/g, which was significantly higher than 229 μg/g in CRF patients and 197 μg/g in RT patients. Using 200 μg/g as the established threshold, a reduced fecal pancreatic elastase level was found in 14/31 of CRF patients, 12/22 of RT patients, 1/19 of SPK patients with enteric drainage, and 1/20 of CON patients. The correlation analysis revealed a significant association between fecal elastase and glycosylated hemoglobin. Conclusions. The present study indicated that SPK with enteric drainage improves pancreatic endocrine and exocrine functions. Fecal elastase may be a clinically relevant means to determine the therapeutic effects.

  15. [Inflammatory pancreatic disease due to enzyme autodigestion: an exceptional model of glandular crinophagy].

    Science.gov (United States)

    Sánchez-Fayos Calabuig, P; Martín Relloso, M Jesús; González Guirado, Agustina; Porres Cubero, Juan Carlos

    2007-01-01

    The exocrine pancreas is a functionally dangerous structure since it is exposed to digestion by its most aggressive enzymes (proteases, etc) despite self-protective measures such as the synthesis of some of these enzymes in the form of inactive zymogens (trypsinogen, etc.). We review inflammatory pancreatic disease by separately analyzing its classical forms of onset: acute and chronic pancreatitis (AP and CP). There is general consensus that the initial pathogenic event in AP is intraacinar activation of trypsinogen into trypsin, followed by that of the remaining proenzymes, giving rise to an unusual model of autophagic inflammation. In contrast, consensus is lacking on the initial pathogenic event in CP (toxic-metabolic lesion, oxidative stress, ductal hypertension, etc.?), although in some cases a sequence due to recurrent episodes of AP seems evident. The pathogenic features shared by both forms of the disease and which justify some recent attempts to formulate an overall explanation of the pathogenesis of pancreatitis are discussed. Such an explanation would place both forms of pancreatitis within the conceptual framework of an pancreatic disease due to enzyme autodigestion>.

  16. Monitoring the effect of substitution therapy in patients with exocrine pancreatic insufficiency

    Energy Technology Data Exchange (ETDEWEB)

    Joergensen, B.B. (Glostrup Hospital (Denmark)); Pedersen, N.T.; Worning, H. (Central Hospital, Herning (Denmark))

    1991-01-01

    Twenty-three outpatients with chronic pancreatitis and severe exocrine insufficiency were studied for the purpose of comparing the effect of Pancrease, Pankreon and Pankreatin by estimation of duodenal enzyme activity, the faecal fat excretion, and the faecal {sup 14}C-triolein-{sup 3}H-oleic acid test and, at the same time, to evaluate these tests when monitoring outpatients. The three preparations did not disclose any significant difference in treating steatorrhoea. Pankreatin increased the meal-stimulated duodenal enzyme activity (p<0.01) and caused reduction in the faecal fat excretion (p<0.05), whereas no change in these variables were observed with Pankreon or Pancrease. The faecal {sup 14}-C-triolein-{sup 3}H-oleic acid test showed significant improvement in the {sup 14}C-triolein digestion with all three preparations (p<0.001). The faecal {sup 14}-C-triolein-{sup 3}H-oleic acid test was the most reliable when monitoring outpatients. 17 refs., 1 fig., 3 tabs.

  17. Noninvasive investigation of exocrine pancreatic function: Feasibility of cine dynamic MRCP with a spatially selective inversion-recovery pulse.

    Science.gov (United States)

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

    2015-11-01

    To investigate the feasibility of noncontrast-enhanced cine dynamic magnetic resonance cholangiopancreatography (MRCP) with a spatially selective inversion-recovery (IR) pulse for evaluating exocrine pancreatic function in comparison with the N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test as a pancreatic exocrine function test. Twenty subjects with or without chronic pancreatitis were included. MRCP with a spatially selective IR pulse was repeated every 15 seconds for 5 minutes to acquire a total of 20 images (cine-dynamic MRCP). The median and mean frequency of the observation (the number of times) and the moving distance (mean secretion grading scores) of pancreatic juice inflow on cine-dynamic MRCP were compared with a BT-PABA test. The urinary PABA excretion rate (%) had significant positive correlations with both the mean secretion grade (r = 0.66, P = 0.002) and frequency of secretory inflow (r = 0.62, P = 0.004) in cine dynamic MRCP. Both the mean frequency of observations of pancreatic secretory inflow (1.4 ± 1.6 times vs. 14.3 ± 4.2 times, P Cine dynamic MRCP with a spatially selective IR pulse may have potential for estimating the pancreatic exocrine function noninvasively as a substitute for the BT-PABA test. © 2015 Wiley Periodicals, Inc.

  18. Giessen international workshop on interactions of exocrine and endocrine pancreatic diseases. Castle of Rauischholzhausen of the Justus-Liebig-University, Giessen, Germany. March 18-19, 2005.

    Science.gov (United States)

    Andren-Sandberg, Ake; Hardt, Philip D

    2005-07-08

    The 'Giessen International Workshop on Interactions of Exocrine and Endocrine Pancreatic Diseases' was held on March 18-19, 2005 at the Castle of Rauischolzhausen, Giessen University, Germany. About 50 international clinicians and researchers attended the workshop. It was structured into three sessions: A: Pancreatic Autoimmunity - Interaction Between Exocrine and Endocrine Tissue; B: Diabetes Mellitus - Possible Implications of Exocrine Pancreatic Insufficiency; C: Chronic Pancreatitis - Update on Prevalence, Understanding and Pathophysiological Concepts. Several new aspects of pancreatic diseases were discussed, including new classifications of pancreatitis, new insights into prevalence, pathophysiology and new therapeutical considerations. The meeting resulted in more cooperation and a number of new concepts for clinical study which will provide data for future developments.

  19. 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.

  20. Exocrine pancreatic insufficiency in type 1 and type 2 diabetes mellitus: do we need to treat it? A systematic review.

    Science.gov (United States)

    Zsóri, Gábor; Illés, Dóra; Terzin, Viktória; Ivány, Emese; Czakó, László

    2018-05-17

    The exocrine and endocrine pancreata are very closely linked both anatomically and physiologically. Abdominal symptoms such as nausea, bloating, diarrhea, steatorrhea, and weight loss can often occur in diabetic patients. Impairments of the exocrine pancreatic function seem to be a frequent complication of diabetes mellitus; however, they are largely overlooked. The aim of this paper is to provide an overview of the current concepts of exocrine pancreatic insufficiency (PEI) in diabetes mellitus. The prevalence and symptoms of PEI in diabetes mellitus, the pathomechanism, and difficulties of diagnosis and therapy of PEI are summarized in this systematic review. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  1. A radiopharmaceutical for pancreatic exocrine functional diagnosis: 62Zn-EDDA metabolism in pancreas.

    Science.gov (United States)

    Fujibayashi, Y; Saji, H; Kawai, K; Unuma, Y; Miyata, S; Okuno, T; Hosotani, R; Inoue, K; Adachi, H; Horiuchi, K

    1986-01-01

    The metabolic pathway of radioactive 62Zn-EDDA (ethylenediamine-N,N'-diacetic acid), in the exocrine pancreas was studied with respect to that of endogenous Zn. In pancreatic duct cannulated dog, the secretion of intravenously injected exogenous 62Zn into pancreatic juice increased under the stimulation of CCK-PZ (pancreatic protein secretion stimulating hormone), which closely correlated to endogenous Zn. Moreover, in pancreatic juice, 62Zn as well as endogenous Zn was selectively bound to Zn-metalloenzymes, carboxypeptidase A and B. These results demonstrated the close correlation between the endogenous and the exogenously-administered Zn (62Zn-EDDA), as well as the high availability of 62Zn-EDDA as a marker of pancreatic function for the follow up of carboxypeptidase metabolism.

  2. CA 19-9 in the diagnosis and differential diagnosis of exocrine pancreatic carcinoma

    International Nuclear Information System (INIS)

    Klapdor, R.; Lehmann, U.; Bahlo, M.; Greten, H.; Ackeren, H. v.; Dallek, M.; Schreiber, W.H.

    1983-01-01

    CA 19-9 serum concentrations were determined in 56 controls and 66 patients with various pancreatic diseases using a commercially available radioimmunoassay. 56 controls showed mean serum concentrations of 7.3 +- 9.6 U/ml (anti x +- 2 SD) range 0-24, median 6), n = 21 patients suffering from chronic pancreatitis mean values of 16 +- 24 U/ml (anti x +- 2 SD) (range 4.9-42, median 13). The majority of the patients with exocrine pancreatic carcinoma demonstrated significantly elevated values: in 91% and 82% respectively, CA 19-9 levels were elevated above the upper limit of 95% of the controls (> 15 U/ml) and of the patients with chronic pancreatitis (> 37 U/ml) (P [de

  3. Comparison of 72-hour fecal fat quantification and the 13C-mixed triglyceride breath test in assessing pancreatic exocrine sufficiency in children with chronic pancreatitis.

    Science.gov (United States)

    Wejnarska, Karolina; Kołodziejczyk, Elwira; Ryżko, Józef; Oracz, Grzegorz

    Chronic pancreatitis (CP) in children is still a rare, although increasingly recognized entity. Over the duration of the disease several complications can be observed, two of which are major ones: endo- and exocrine insufficiency. In the medical care of children with CP it is crucial to diagnose the decreased endo- and exocrine function of the pancreas, in order to preserve patients from malnutrition and the failure to thrive. The aim of the study was to compare the usefulness of two indirect methods of assessing the pancreas exocrine function in children with CP. Ninety one patients with CP were enrolled in the study (41 boys, 50 girls, aged 2-17.8 years). Only Patients who had had both the 72-hour fecal fat quantification and the 13C-mixed triglyceride breath test (13C -MTBT) performed were selected. We compared the results of both tests for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) in detecting exocrine pancreatic insufficiency. Out of 91 patients, 12 were diagnosed with exocrine pancreatic insufficiency (EPI). The sensitivity of the fecal fat quantification was 50%, the specificity for the test was 100%. PPV and NPV were 100% and 93%, respectively. 13C-MTBT had the sensitivity of 42% and the specificity of 99%. PPV and NPV for the breath test were of 83% and 92%, respectively. No statistically significant discrepancy between the values obtained was found. Although the 72-hour fecal fat quantification remains the gold standard in detecting EPI, both of the methods that had been investigated were shown to be comparable regarding sensitivity, specificity, PPV and NPV in assessing pancreas exocrine sufficiency in children with CP. Due to the easier execution of the breath test, both for the patient and for medical personnel, its importance may increase.

  4. Exocrine and endocrine pancreatic function in 21 patients suffering from autoimmune pancreatitis before and after steroid treatment.

    Science.gov (United States)

    Frulloni, Luca; Scattolini, Chiara; Katsotourchi, Anna Maria; Amodio, Antonio; Gabbrielli, Armando; Zamboni, Giuseppe; Benini, Luigi; Vantini, Italo

    2010-01-01

    Autoimmune pancreatitis (AIP) responds rapidly and dramatically to steroid therapy. The aim of this study was to evaluate pancreatic exocrine and endocrine function in patients suffering from AIP both before and after steroid therapy. Fecal elastase 1 and diabetes were evaluated before steroid therapy and within 1 month of its suspension in 21 patients (13 males and 8 females, mean age 43 +/- 16.5 years) diagnosed as having AIP between 2006 and 2008. At clinical onset, fecal elastase 1 was 107 +/- 126 microg/g stool. Thirteen patients (62%) showed severe pancreatic insufficiency (insufficiency (100-200 microg/g stool), while 4 (19%) had normal pancreatic function (>200 microg/g stool). Before steroids, diabetes was diagnosed in 5 patients (24%), all of whom had very low levels of fecal elastase 1 (endocrine pancreatic insufficiency at clinical onset. These insufficiencies improve after steroid therapy. Copyright 2010 S. Karger AG, Basel.

  5. Exocrine pancreatic function in hepatocyte nuclear factor 1β-maturity-onset diabetes of the young (HNF1B-MODY) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas.

    Science.gov (United States)

    Tjora, E; Wathle, G; Erchinger, F; Engjom, T; Molven, A; Aksnes, L; Haldorsen, I S; Dimcevski, G; Raeder, H; Njølstad, P R

    2013-08-01

    To examine the exocrine pancreatic function in carriers of the hepatocyte nuclear factor 1β gene (HNF1B) mutation by direct testing. Patients with HNF1B mutations and control subjects were assessed using rapid endoscopic secretin tests and secretin-stimulated magnetic resonance imaging. Seven patients and 25 controls underwent endoscopy, while eight patients and 20 controls had magnetic resonance imaging. Ductal function was assessed according to peak bicarbonate concentrations and acinar function was assessed according to peak digestive enzyme activities in secretin-stimulated duodenal juice. The association of pancreatic exocrine function and diabetes status with pancreatic gland volume was examined. The mean increase in secretin-stimulated duodenal fluid was smaller in patients than controls (4.0 vs 6.4 ml/min; P = 0.003). We found lower ductal function in patients than controls (median peak bicarbonate concentration: 73 vs 116 mEq/L; P function (median peak lipase activity: 6.4 vs 33.5 kU/ml; P = 0.01; median peak elastase activity: 0.056 vs 0.130 U/ml; P = 0.01). Pancreatic fluid volume outputs correlated significantly with pancreatic gland volumes (r² = 0.71, P = 0.008) in patients. The total fluid output to pancreatic gland volume ratios were higher in patients than controls (4.5 vs 1.3 ml/cm³; P = 0.03), suggesting compensatory hypersecretion in the remaining gland. Carriers of the HNF1B mutation have lower exocrine pancreatic function involving both ductal and acinar cells. Compensatory hypersecretion suggests that the small pancreas of HNF1B mutation carriers is attributable to hypoplasia, not atrophy. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  6. Early morphological and functional changes in pancreas following necrosectomy for acute severe necrotizing pancreatitis.

    Science.gov (United States)

    Bavare, Charudatta; Prabhu, Ramkrishna; Supe, Avinash

    2004-01-01

    Morphological and functional changes in the pancreas after surgical pancreatic necrosectomy have not been studied extensively. To study morphological changes in the pancreas, and exocrine and endocrine pancreatic function following pancreatic necrosectomy. Eighteen adult patients surviving at least one month after pancreatic necrosectomy for acute necrotizing pancreatitis were followed up. Contrast-enhanced computed tomography was done every six months. Stool fat was estimated at 3-month intervals, and need for and response to enzyme supplements were recorded. Blood sugar was measured every fortnight; in patients with hyperglycemia, need for oral hypoglycemic agents or insulin was recorded. Additional pancreatic imaging was done in some cases. Six weeks after surgery, nine of 18 patients had exocrine insufficiency. Thirteen patients developed endocrine insufficiency, including 5 who also had exocrine insufficiency. At the end of the study, 13 patients had endocrine insufficiency and 2 had exocrine insufficiency. Pancreatic size was subnormal in all patients at the end of six months. Pancreatography in three cases did not reveal any ductal abnormality. Necrotizing pancreatitis affects pancreatic exocrine or endocrine function in more than half the patients.

  7. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis.

    Science.gov (United States)

    de la Iglesia-García, Daniel; Huang, Wei; Szatmary, Peter; Baston-Rey, Iria; Gonzalez-Lopez, Jaime; Prada-Ramallal, Guillermo; Mukherjee, Rajarshi; Nunes, Quentin M; Domínguez-Muñoz, J Enrique; Sutton, Robert

    2017-08-01

    The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, pregression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Absence of diabetes and pancreatic exocrine dysfunction in a transgenic model of carboxyl-ester lipase-MODY (maturity-onset diabetes of the young.

    Directory of Open Access Journals (Sweden)

    Helge Ræder

    Full Text Available CEL-MODY is a monogenic form of diabetes with exocrine pancreatic insufficiency caused by mutations in CARBOXYL-ESTER LIPASE (CEL. The pathogenic processes underlying CEL-MODY are poorly understood, and the global knockout mouse model of the CEL gene (CELKO did not recapitulate the disease. We therefore aimed to create and phenotype a mouse model specifically over-expressing mutated CEL in the pancreas.We established a monotransgenic floxed (flanking LOX sequences mouse line carrying the human CEL mutation c.1686delT and crossed it with an elastase-Cre mouse to derive a bitransgenic mouse line with pancreas-specific over-expression of CEL carrying this disease-associated mutation (TgCEL. Following confirmation of murine pancreatic expression of the human transgene by real-time quantitative PCR, we phenotyped the mouse model fed a normal chow and compared it with mice fed a 60% high fat diet (HFD as well as the effects of short-term and long-term cerulein exposure.Pancreatic exocrine function was normal in TgCEL mice on normal chow as assessed by serum lipid and lipid-soluble vitamin levels, fecal elastase and fecal fat absorption, and the normoglycemic mice exhibited normal pancreatic morphology. On 60% HFD, the mice gained weight to the same extent as controls, had normal pancreatic exocrine function and comparable glucose tolerance even after resuming normal diet and follow up up to 22 months of age. The cerulein-exposed TgCEL mice gained weight and remained glucose tolerant, and there were no detectable mutation-specific differences in serum amylase, islet hormones or the extent of pancreatic tissue inflammation.In this murine model of human CEL-MODY diabetes, we did not detect mutation-specific endocrine or exocrine pancreatic phenotypes, in response to altered diets or exposure to cerulein.

  9. Absence of diabetes and pancreatic exocrine dysfunction in a transgenic model of carboxyl-ester lipase-MODY (maturity-onset diabetes of the young).

    Science.gov (United States)

    Ræder, Helge; Vesterhus, Mette; El Ouaamari, Abdelfattah; Paulo, Joao A; McAllister, Fiona E; Liew, Chong Wee; Hu, Jiang; Kawamori, Dan; Molven, Anders; Gygi, Steven P; Njølstad, Pål R; Kahn, C Ronald; Kulkarni, Rohit N

    2013-01-01

    CEL-MODY is a monogenic form of diabetes with exocrine pancreatic insufficiency caused by mutations in CARBOXYL-ESTER LIPASE (CEL). The pathogenic processes underlying CEL-MODY are poorly understood, and the global knockout mouse model of the CEL gene (CELKO) did not recapitulate the disease. We therefore aimed to create and phenotype a mouse model specifically over-expressing mutated CEL in the pancreas. We established a monotransgenic floxed (flanking LOX sequences) mouse line carrying the human CEL mutation c.1686delT and crossed it with an elastase-Cre mouse to derive a bitransgenic mouse line with pancreas-specific over-expression of CEL carrying this disease-associated mutation (TgCEL). Following confirmation of murine pancreatic expression of the human transgene by real-time quantitative PCR, we phenotyped the mouse model fed a normal chow and compared it with mice fed a 60% high fat diet (HFD) as well as the effects of short-term and long-term cerulein exposure. Pancreatic exocrine function was normal in TgCEL mice on normal chow as assessed by serum lipid and lipid-soluble vitamin levels, fecal elastase and fecal fat absorption, and the normoglycemic mice exhibited normal pancreatic morphology. On 60% HFD, the mice gained weight to the same extent as controls, had normal pancreatic exocrine function and comparable glucose tolerance even after resuming normal diet and follow up up to 22 months of age. The cerulein-exposed TgCEL mice gained weight and remained glucose tolerant, and there were no detectable mutation-specific differences in serum amylase, islet hormones or the extent of pancreatic tissue inflammation. In this murine model of human CEL-MODY diabetes, we did not detect mutation-specific endocrine or exocrine pancreatic phenotypes, in response to altered diets or exposure to cerulein.

  10. The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI).

    Science.gov (United States)

    Ní Chonchubhair, Hazel M; Bashir, Yasir; Dobson, Mark; Ryan, Barbara M; Duggan, Sinead N; Conlon, Kevin C

    2018-02-24

    Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates. We evaluated the prevalence of SIBO among a defined cohort of non-surgical chronic pancreatitics with mild to severe PEI compared with matched healthy controls. Thirty-five patients and 31 age-, gender- and smoking status-matched healthy controls were evaluated for SIBO by means of a fasting glucose hydrogen breath test (GHBT). The relationship between SIBO and clinical symptoms in chronic pancreatitis was evaluated. SIBO was present in 15% of chronic pancreatitis patients, while no healthy controls tested positive (P = 0.029). SIBO was more prevalent in those taking pancreatic enzyme replacement therapy (PERT) (P = 0.016), with proton pump inhibitor use (PPI) (P = 0.022) and in those with alcohol aetiology (P = 0.023). Patients with concurrent diabetes were more often SIBO-positive and this was statistically significant (P = 0.009). There were no statistically significant differences in reported symptoms between patients with and without SIBO, with the exception of 'weight loss', with patients reporting weight loss more likely to have SIBO (P = 0.047). The prevalence of SIBO in this study was almost 15% and consistent with other studies of SIBO in non-surgical chronic pancreatitis patients. These data support the testing of patients with clinically-relevant PEI unresolved by adequate doses of PERT, particularly in those patients with concurrent diabetes. SIBO can be easily diagnosed therefore allowing more specific and more targeted symptom

  11. Pancreatic exocrine insufficiency following acute pancreatitis: Systematic review and study level meta-analysis.

    Science.gov (United States)

    Hollemans, Robbert A; Hallensleben, Nora D L; Mager, David J; Kelder, Johannes C; Besselink, Marc G; Bruno, Marco J; Verdonk, Robert C; van Santvoort, Hjalmar C

    2018-04-01

    This study systematically explores the prevalence of pancreatic exocrine insufficiency (PEI) after acute pancreatitis in different subgroups of etiology (biliary/alcoholic/other), disease severity and follow-up time ( 36 months after index admission). PubMed and EMBASE databases were searched, 32 studies were included in this study level meta-analysis. In a total of 1495 patients with acute pancreatitis, tested at a mean of 36 months after index admission, the pooled prevalence of PEI was 27.1% (95%-confidence interval [CI]: 20.3%-35.1%). Patients from seven studies (n = 194) underwent direct tests with pooled prevalence of 41.7% [18.5%-69.2%]. Patients from 26 studies (n = 1305) underwent indirect tests with pooled prevalence of 24.4% [18.3%-31.8%]. In subgroup analyses on patients that underwent fecal elastase-1 tests, PEI occurred more often in alcoholic pancreatitis (22.7% [16.6%-30.1%]) than in biliary pancreatitis (10.2% [6.2%-16.4%]) or other etiology (13.4% [7.7%-22.4%]; P = 0.02). Pooled prevalence of PEI after mild and severe pancreatitis was 19.4% [8.6%-38.2%] and 33.4% [22.6%-46.3%] respectively in studies using fecal elaste-1 tests (P = 0.049). Similar results were seen in patients without (18.9% [9.3%-34.6%]) and with necrotizing pancreatitis (32.0% [18.2%-49.8%]; P = 0.053). Over time, the prevalence of PEI decreased in patients who underwent the fecal elastase-1 test and increased in patients who underwent the fecal fat analysis. After acute pancreatitis, a quarter of all patients develop PEI during follow-up. Alcoholic etiology and severe and necrotizing pancreatitis are associated with higher risk of PEI. The prevalence of PEI may change as time of follow-up increases. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  12. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

    Science.gov (United States)

    Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

    2004-05-01

    E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

  13. Chronic pancreatitis: review and update of etiology, risk factors, and management [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Angela Pham

    2018-05-01

    Full Text Available Chronic pancreatitis is a syndrome involving inflammation, fibrosis, and loss of acinar and islet cells which can manifest in unrelenting abdominal pain, malnutrition, and exocrine and endocrine insufficiency. The Toxic-Metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and Severe Acute Pancreatitis, Obstructive (TIGAR-O classification system categorizes known causes and factors that contribute to chronic pancreatitis. Although determining disease etiology provides a framework for focused and specific treatments, chronic pancreatitis remains a challenging condition to treat owing to the often refractory, centrally mediated pain and the lack of consensus regarding when endoscopic therapy and surgery are indicated. Further complications incurred include both exocrine and endocrine pancreatic insufficiency, pseudocyst formation, bile duct obstruction, and pancreatic cancer. Medical treatment of chronic pancreatitis involves controlling pain, addressing malnutrition via the treatment of vitamin and mineral deficiencies and recognizing the risk of osteoporosis, and administering appropriate pancreatic enzyme supplementation and diabetic agents. Cornerstones in treatment include the recognition of pancreatic exocrine insufficiency and administration of pancreatic enzyme replacement therapy, support to cease smoking and alcohol consumption, consultation with a dietitian, and a systematic follow-up to assure optimal treatment effect.

  14. Efficacy and Safety of a New Formulation of Pancrelipase (Ultrase MT20 in the Treatment of Malabsorption in Exocrine Pancreatic Insufficiency in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Michael W. Konstan

    2010-01-01

    Full Text Available Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF and exocrine pancreatic insufficiency (PI. Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20 in patients with CF and PI. Coefficients of fat absorption (CFA% and nitrogen absorption (CNA% were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs, and overall signs and symptoms. Methods. Patients (n=31 were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each. Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared. Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp., P<.0001 for both, reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE. Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.

  15. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial.

    Science.gov (United States)

    Bartels, Rosalie H; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A; Mponda, John S; Muller Kobold, Anneke C; Bandsma, Robert H; Boele van Hensbroek, Michael; Voskuijl, Wieger P

    2017-11-01

    To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central Hospital in Malawi. All children received standard care; the intervention group also received PERT for 28 days. Children treated with PERT for 28 days did not gain more weight than controls (13.7 ± 9.0% in controls vs 15.3 ± 11.3% in PERT; P = .56). Exocrine pancreatic insufficiency was present in 83.1% of patients on admission and fecal elastase-1 levels increased during hospitalization mostly seen in children with nonedematous severe acute malnutrition (P Children who died had low fecal fatty acid split ratios at admission. Exocrine pancreatic insufficiency was not improved by PERT, but children receiving PERT were more likely to be discharged with every passing day (P = .02) compared with controls. PERT does not improve weight gain in severely malnourished children but does increase the rate of hospital discharge. Mortality was lower in patients on PERT, a finding that needs to be investigated in a larger cohort with stratification for edematous and nonedematous malnutrition. Mortality in severe acute malnutrition is associated with markers of poor digestive function. ISRCTN.com: 57423639. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Risk factors of exocrine and endocrine pancreatic insufficiency after pancreatic resection: A multi-center prospective study.

    Science.gov (United States)

    Maignan, A; Ouaïssi, M; Turrini, O; Regenet, N; Loundou, A; Louis, G; Moutardier, V; Dahan, L; Pirrò, N; Sastre, B; Delpero, J-R; Sielezneff, I

    2018-01-26

    Management of functional consequences after pancreatic resection has become a new therapeutic challenge. The goal of our study is to evaluate the risk factors for exocrine (ExoPI) and endocrine (EndoPI) pancreatic insufficiency after pancreatic surgery and to establish a predictive model for their onset. Between January 1, 2014 and June 19, 2015, 91 consecutive patients undergoing pancreatoduodenectomy (PD) or left pancreatectomy (LP) (72% and 28%, respectively) were followed prospectively. ExoPI was defined as fecal elastase content126mg/dL or aggravation of preexisting diabetes. The volume of residual pancreas was measured according to the same principles as liver volumetry. The ExoPI and EndoPI rates at 6 months were 75.9% and 30.8%, respectively. The rate of ExoPI after PD was statistically significantly higher than after LP (98% vs. 21%; Ppancreatic volume less than 39.5% was predictive of ExoPI. ExoPI occurs quasi-systematically after PD irrespective of the reconstruction scheme. The rate of EndoPI did not differ between PD and LP. Copyright © 2017. Published by Elsevier Masson SAS.

  17. [Delayed complications after pancreatic surgery: Pancreatic insufficiency, malabsorption syndrome, pancreoprivic diabetes mellitus and pseudocysts].

    Science.gov (United States)

    Nitsche, U; Siveke, J; Friess, H; Kleeff, J

    2015-06-01

    Benign and malignant pathologies of the pancreas can result in a relevant chronic disease burden. This is aggravated by morbidities resulting from surgical resections as well as from progression of the underlying condition. The aim was to summarize the current evidence regarding epidemiology, pathophysiology, diagnosis and treatment of endocrine and exocrine pancreatic insufficiency, as well as of pancreatic pseudocysts. A selective literature search was performed and a summary of the currently available data on the surgical sequelae after pancreatic resection is given. Reduction of healthy pancreatic parenchyma down to 10-15 % leads to exocrine insufficiency with malabsorption and gastrointestinal complaints. Orally substituted pancreatic enzymes are the therapy of choice. Loss of pancreatic islets and/or islet function leads to endocrine insufficiency and pancreoprivic diabetes mellitus. Inflammatory, traumatic and iatrogenic injuries of the pancreas can lead to pancreatic pseudocysts, which require endoscopic, interventional or surgical drainage if symptomatic. Finally, pancreatic surgery harbors the long-term risk of gastrointestinal anastomotic ulcers, bile duct stenosis, portal vein thrombosis and chronic pain syndrome. As the evidence is limited, an interdisciplinary and individually tailored approach for delayed pancreatic morbidity is recommended.

  18. PPARγ regulates exocrine pancreas lipase.

    Science.gov (United States)

    Danino, Hila; Naor, Ronny Peri-; Fogel, Chen; Ben-Harosh, Yael; Kadir, Rotem; Salem, Hagit; Birk, Ruth

    2016-12-01

    Pancreatic lipase (triacylglycerol lipase EC 3.1.1.3) is an essential enzyme in hydrolysis of dietary fat. Dietary fat, especially polyunsaturated fatty acids (PUFA), regulate pancreatic lipase (PNLIP); however, the molecular mechanism underlying this regulation is mostly unknown. As PUFA are known to regulate expression of proliferator-activated receptor gamma (PPARγ), and as we identified in-silico putative PPARγ binding sites within the putative PNLIP promoter sequence, we hypothesized that PUFA regulation of PNLIP might be mediated by PPARγ. We used in silico bioinformatics tools, reporter luciferase assay, PPARγ agonists and antagonists, PPARγ overexpression in exocrine pancreas AR42J and primary cells to study PPARγ regulation of PNLIP. Using in silico bioinformatics tools we mapped PPARγ binding sites (PPRE) to the putative promoter region of PNLIP. Reporter luciferase assay in AR42J rat exocrine pancreas acinar cells transfected with various constructs of the putative PNLIP promoter showed that PNLIP transcription is significantly enhanced by PPARγ dose-dependently, reaching maximal levels with multi PPRE sites. This effect was significantly augmented in the presence of PPARγ agonists and reduced by PPARγ antagonists or mutagenesis abrogating PPRE sites. Over-expression of PPARγ significantly elevated PNLIP transcript and protein levels in AR42J cells and in primary pancreas cells. Moreover, PNLIP expression was up-regulated by PPARγ agonists (pioglitazone and 15dPGJ2) and significantly down-regulated by PPARγ antagonists in non-transfected rat exocrine pancreas AR42J cell line cells. PPARγ transcriptionally regulates PNLIP gene expression. This transcript regulation resolves part of the missing link between dietary PUFA direct regulation of PNLIP. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Determinants of exocrine pancreatic function as measured by fecal elastase-1 concentrations (FEC in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ewald N

    2009-03-01

    Full Text Available Abstract Objective Recently it has been shown that there is not only endocrine insufficiency in diabetic patients, but a frequent co-morbidity of both, the endocrine and exocrine pancreas. The present study was performed to further analyse the determinants of exocrine pancreatic function in patients with diabetes mellitus. Methods The records of 1992 patients with diabetes mellitus who had been treated in our hospital during a 2-year period were re-evaluated. Defined parameters were documented in standardized data sheets. Records were further checked for the results of imaging procedures of the pancreas. In 307 patients FEC had been performed and documented. Only these patients were included in further evaluation. Results FEC was inversely correlated with diabetes duration and HbA1c-levels but not with age. C-peptide levels correlated positively with FEC. BMI and FEC were also significantly correlated. There was no correlation between diabetes therapy and exocrine pancreatic function as there was no correlation with any concomitant medication. The presence of diabetes-associated antibodies was not related to FEC. According to the documented data 38 were classified as type-1 diabetes (12.4%, 167 as type-2 (54.4%, and 88 patients met the diagnostic criteria of type-3 (28.7%. Fourteen patients could not be classified because of lacking information (4.6%. Conclusions Exocrine insufficiency might be explained as a complication of diabetes mellitus. However, it is more likely that type-3 diabetes is much more frequent than previously believed. Consequently the evaluation of exocrine function and morphology should be included into the clinical workup of any diabetic patient at least at the time of manifestation.

  20. Pancreatic enzyme replacement therapy.

    Science.gov (United States)

    Layer, P; Keller, J; Lankisch, P G

    2001-04-01

    Malabsorption due to severe pancreatic exocrine insufficiency is one of the most important late features of chronic pancreatitis. Generally, steatorrhea is more severe and occurs several years prior to malabsorption of other nutrients because synthesis and secretion of lipase are impaired more rapidly, its intraluminal survival is shorter, and the lack of pancreatic lipase activity is not compensated for by nonpancreatic mechanisms. Patients suffer not only from nutritional deficiencies but also from increased nutrient delivery to distal intestinal sites, causing symptoms by profound alteration of upper gastrointestinal secretory and motor functions. Adequate nutrient absorption requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. The following recommendations are based on modern therapeutic concepts: 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres, with dosage increases, compliance checks, and differential diagnosis in case of treatment failure. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed to optimize treatment.

  1. Clinical usefulness of dual-label Schilling test for pancreatic exocrine function

    Energy Technology Data Exchange (ETDEWEB)

    Chen, W.L.; Morishita, R.; Eguchi, T.; Kawai, T.; Sakai, M.; Tateishi, H.; Uchino, H.

    1989-05-01

    The usefulness of the pancreatic dual-label Schilling test as an indirect test of pancreatic exocrine function was evaluated. This dual-label Schilling test was based on the difference of absorption for (58Co)cobalamin bound to hog R protein and (57Co)cobalamin bound to intrinsic factor. In this study, the test was performed in 7 normal subjects, 5 patients with pancreatectomy, 12 patients with chronic pancreatitis, 10 patients with suspicion of chronic pancreatitis, and 13 patients without chronic pancreatitis. The normal lower limit (mean -2 SD) of excretion ratio for (58Co)/(57Co) in 24-h urine was 0.68. Of the 26 patients on whom endoscopic retrograde pancreatography was performed, none of the 9 patients with normal pancreatogram, 4 of the 9 patients with mild to moderate pancreatitic changes in pancreatogram, and 7 of the 8 patients with advanced pancreatitic changes in pancreatogram showed a positive value lower than the ratio of 0.68 in this test. In 28 patients examined with the direct test of pancreatic secretory capacity, 2 of the 13 patients with normal function, 6 of the 9 patients with mild dysfunction, and 5 of the 6 patients with definite dysfunction were positive in this test. The results of the pancreatic dual-label Schilling test significantly correlated with those of a direct test of pancreatic secretory capacity and the findings of pancreatitic changes in pancreatogram (p less than 0.01, chi 2 test). The ratio for (58Co)/(57Co) correlated (r = 0.73) with the maximal bicarbonate concentration in duodenal juice of the direct test of pancreatic secretory capacity. The impairment of bicarbonate output by the pancreas may adversely affect the transfer of cobalamin from R protein to intrinsic factor.

  2. Clinical usefulness of dual-label Schilling test for pancreatic exocrine function

    International Nuclear Information System (INIS)

    Chen, W.L.; Morishita, R.; Eguchi, T.; Kawai, T.; Sakai, M.; Tateishi, H.; Uchino, H.

    1989-01-01

    The usefulness of the pancreatic dual-label Schilling test as an indirect test of pancreatic exocrine function was evaluated. This dual-label Schilling test was based on the difference of absorption for [58Co]cobalamin bound to hog R protein and [57Co]cobalamin bound to intrinsic factor. In this study, the test was performed in 7 normal subjects, 5 patients with pancreatectomy, 12 patients with chronic pancreatitis, 10 patients with suspicion of chronic pancreatitis, and 13 patients without chronic pancreatitis. The normal lower limit (mean -2 SD) of excretion ratio for [58Co]/[57Co] in 24-h urine was 0.68. Of the 26 patients on whom endoscopic retrograde pancreatography was performed, none of the 9 patients with normal pancreatogram, 4 of the 9 patients with mild to moderate pancreatitic changes in pancreatogram, and 7 of the 8 patients with advanced pancreatitic changes in pancreatogram showed a positive value lower than the ratio of 0.68 in this test. In 28 patients examined with the direct test of pancreatic secretory capacity, 2 of the 13 patients with normal function, 6 of the 9 patients with mild dysfunction, and 5 of the 6 patients with definite dysfunction were positive in this test. The results of the pancreatic dual-label Schilling test significantly correlated with those of a direct test of pancreatic secretory capacity and the findings of pancreatitic changes in pancreatogram (p less than 0.01, chi 2 test). The ratio for [58Co]/[57Co] correlated (r = 0.73) with the maximal bicarbonate concentration in duodenal juice of the direct test of pancreatic secretory capacity. The impairment of bicarbonate output by the pancreas may adversely affect the transfer of cobalamin from R protein to intrinsic factor

  3. Purinergic receptors in the endocrine and exocrine pancreas.

    Science.gov (United States)

    Novak, I

    2008-09-01

    The pancreas is a complex gland performing both endocrine and exocrine functions. In recent years there has been increasing evidence that both endocrine and exocrine cells possess purinergic receptors, which influence processes such as insulin secretion and epithelial ion transport. Most commonly, these processes have been viewed separately. In beta cells, stimulation of P2Y(1) receptors amplifies secretion of insulin in the presence of glucose. Nucleotides released from secretory granules could also contribute to autocrine/paracrine regulation in pancreatic islets. In addition to P2Y(1) receptors, there is also evidence for other P2 and adenosine receptors in beta cells (P2Y(2), P2Y(4), P2Y(6), P2X subtypes and A(1) receptors) and in glucagon-secreting alpha cells (P2X(7), A(2) receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors are prominent in pancreatic ducts, and several studies indicate that P2Y(2), P2Y(4), P2Y(11), P2X(4) and P2X(7) receptors could regulate secretion, primarily by affecting Cl(-) and K(+) channels and intracellular Ca(2+) signalling. In order to understand the physiology of the whole organ, it is necessary to consider the full complement of purinergic receptors on different cells as well as the structural and functional relation between various cells within the whole organ. In addition to the possible physiological function of purinergic receptors, this review analyses whether the receptors could be potential therapeutic targets for drug design aimed at treatment of pancreatic diseases.

  4. Are there still roles for exocrine bladder drainage and portal venous drainage for pancreatic allografts?

    Science.gov (United States)

    Young, Carlton J

    2009-02-01

    Controversy remains regarding the best methodology of handling exocrine pancreatic fluid and pancreatic venous effluent. Bladder drainage has given way to enteric drainage. However, is there an instance in which bladder drainage is preferable? Also, hyperinsulinemia, as a result of systemic venous drainage (SVD), is claimed to be proatherosclerotic, whereas portal venous drainage (PVD) is more physiologic and less atherosclerotic. Bladder drainage remains a viable method of exocrine pancreas drainage, but evidence is sparse that measuring urinary amylase has a substantial benefit in the early detection of acute rejection in all types of pancreas transplants. Currently, there is no incontrovertible evidence that systemic hyperinsulinemia is proatherosclerotic, whereas recent metabolic studies on SVD and PVD showed that there was no benefit to PVD. Given the advent of newer immunosuppressive agents and overall lower acute rejection rates, the perceived benefit of bladder drainage as a means to measure urinary amylase as an early marker of rejection has not been substantiated. However, there may be a selective role for bladder drainage in 'high risk' pancreases. Also, without a clear-cut metabolic benefit to PVD over SVD, it remains the surgeon's choice as to which method to use.

  5. Feeder-cell-independent culture of the pig-embryonic-stem-cell-derived exocrine pancreatic cell line, PICM-31

    Science.gov (United States)

    The adaptation to feeder-independent growth of a pig embryonic stem cell-derived pancreatic cell line is described. The parental PICM-31 cell line, previously characterized as an exocrine pancreas cell line, was colony-cloned two times in succession resulting in the subclonal cell line, PICM-31A1. P...

  6. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, U.C.; Semb, S.; Nøjgaard, Camilla

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

  7. Serglycin proteoglycan is not implicated in localizing exocrine pancreas enzymes to zymogen granules

    DEFF Research Database (Denmark)

    Niemann, Carsten U; Cowland, Jack B; Ralfkiaer, Elisabeth

    2009-01-01

    Storage and release of proteins from granules forms the basis of cellular functions as diverse as cell mediated cytotoxicity, neuronal communication, activation of muscle fibres, and release of hormones or digestive enzymes from endocrine and exocrine glands, such as the pancreas. Serglycin...... is the major intracellular proteoglycan of haematopoietic cells. Serglycin is important for localization of proteins in granules of different haematopoietic cell types. Previous reports have indicated a role for serglycin in granule formation and localization of zymogens in granules of the exocrine pancreas...... in rat. We here present data showing that serglycin is not present at the protein level in human or murine pancreas. Furthermore, the amount and localization of three exocrine pancreas zymogens (amylase, trypsinogen, and carboxypeptidase A) is not affected by the absence of serglycin in a serglycin knock...

  8. Pancreas Transplantation With Portal-Enteric Drainage for Patients With Endocrine and Exocrine Insufficiency From Extensive Pancreatic Resection.

    Science.gov (United States)

    Barbas, Andrew S; Al-Adra, David P; Goldaracena, Nicolas; Dib, Martin J; Selzner, Markus; Sapisochin, Gonzalo; Cattral, Mark S; McGilvray, Ian D

    2017-09-01

    Although the primary indication for pancreas transplantation is type I diabetes, a small number of patients requires pancreas transplantation to manage combined endocrine and exocrine insufficiency that develops after extensive native pancreatic resection. The objective of this case report was to describe the operative and clinical course in 3 such patients and present an alternative technical approach.

  9. Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis.

    Science.gov (United States)

    Jaworek, Jolanta; Leja-Szpak, Anna; Nawrot-Porąbka, Katarzyna; Szklarczyk, Joanna; Kot, Michalina; Pierzchalski, Piotr; Góralska, Marta; Ceranowicz, Piotr; Warzecha, Zygmunt; Dembinski, Artur; Bonior, Joanna

    2017-05-08

    Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N ¹-acetyl- N ¹-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1) Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK) release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2) Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3) In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated.

  10. Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Jolanta Jaworek

    2017-05-01

    Full Text Available Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N1-acetyl-N1-formyl-5-methoxykynuramine (AFMK. Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1 Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2 Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3 In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated.

  11. Insulin dependence and pancreatic enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis.

    Science.gov (United States)

    Winny, Markus; Paroglou, Vagia; Bektas, Hüseyin; Kaltenborn, Alexander; Reichert, Benedikt; Zachau, Lea; Kleine, Moritz; Klempnauer, Jürgen; Schrem, Harald

    2014-02-01

    This retrospective, single-center, observational study on postoperative long-term results aims to define yet unknown factors for long-term outcome after operation for chronic pancreatitis. We analyzed 147 consecutive patients operated for chronic pancreatitis from 2000 to 2011. Mean follow-up was 5.3 years (range, 1 month to 12.7 years). Complete long-term survival data were provided by the German citizen registration authorities for all patients. A quality-of-life questionnaire was sent to surviving patients after a mean follow-up of 5.7 years. Surgical principles were resection (n = 86; 59%), decompression (n = 29; 20%), and hybrid procedures (n = 32; 21%). No significant influences of different surgical principles and operative procedures on survival, long-term quality of life and pain control could be detected. Overall 30-day mortality was 2.7%, 1-year survival 95.9%, and 3-year survival 90.8%. Multivariate Cox regression analysis revealed that only postoperative insulin dependence at the time of hospital discharge (P = .027; Exp(B) = 2.111; 95% confidence interval [CI], 1.089-4.090) and the absence of pancreas enzyme replacement therapy at the time of hospital discharge (P = .039; Exp(B) = 2.102; 95% CI, 1.037-4.262) were significant, independent risk factors for survival with significant hazard ratios for long-term survival. Long-term improvement in quality of life was reported by 55 of 76 long-term survivors (73%). Pancreatic enzyme replacement should be standard treatment after surgery for chronic pancreatitis at the time of hospital discharge, even when no clinical signs of exocrine pancreatic failure exist. This study underlines the potential importance of early operative intervention in chronic pancreatitis before irreversible endocrine dysfunction is present. Copyright © 2014 Mosby, Inc. All rights reserved.

  12. Pancreatic Cancer—Patient Version

    Science.gov (United States)

    Pancreatic cancer can form in exocrine cells and neuroendocrine cells. The exocrine type is more common and is usually found at an advanced stage. Pancreatic neuroendocrine tumors are less common but have a better prognosis. Start here to find information on pancreatic cancer treatment, research, and statistics.

  13. Yarrowia lipolytica Lipase 2 Is Stable and Highly Active in Test Meals and Increases Fat Absorption in an Animal Model of Pancreatic Exocrine Insufficiency.

    Science.gov (United States)

    Aloulou, Ahmed; Schué, Mathieu; Puccinelli, Delphine; Milano, Stéphane; Delchambre, Chantal; Leblond, Yves; Laugier, René; Carrière, Frédéric

    2015-12-01

    Pancreatic exocrine insufficiency (PEI) reduces pancreatic secretion of digestive enzymes, including lipases. Oral pancreatic enzyme replacement therapy (PERT) with pancreatin produces unsatisfactory results. The lipase 2 produced by the yeast Yarrowia lipolytica (YLLIP2; GenBank: AJ012632) might be used in PERT. We investigated its ability to digest triglycerides in a test meal and its efficacy in reducing fecal fat in an animal model of PEI. YLLIP2 was produced by genetically engineered Y lipolytica and purified from culture media. YLLIP2 or other gastric (LIPF) and pancreatic (PNLIPD) lipases were added to a meal paste containing dietary triglycerides, at a range of pH values (pH 2-7), with and without pepsin or human bile and incubated at 37°C. We collected samples at various time points and measured lipase activities and stabilities. To create an animal model of PEI, steatorrhea was induced by embolization of the exocrine pancreas gland and pancreatic duct ligation in minipigs. The animals were given YLLIP2 (1, 4, 8, 40, or 80 mg/d) or pancreatin (100,000 US Pharmacopeia lipase units/d, controls) for 9 days. We then collected stool samples, measured fat levels, and calculated coefficient of fat absorption (CFA) values. YLLIP2 was highly stable and poorly degraded by pepsin, and had the highest activity of all lipases tested on meal triglyceride at pH 4-7 (pH 6 with bile: 94 ± 34 U/mg; pH 4 without bile: 43 ± 13 U/mg). Only gastric lipase was active and stable at pH 3, whereas YLLIP2 was sensitive to pepsin hydrolysis after pH inactivation. From in vitro test meal experiments, the lipase activity of YLLIP2 (10 mg) was estimated to be equivalent to that of pancreatin (1200 mg; 100,000 US Pharmacopeia units) at pH 6. In PEI minipigs, CFA values increased from 60.1% ± 9.3% before surgery to 90.5% ± 3.2% after administration of 1200 mg pancreatin (P meal triglycerides in a large pH range, with and without bile. Oral administration of milligram amounts of

  14. Prevalence of exocrine pancreatic insufficiency in patients with chronic pancreatitis without follow-up. PANCR-EVOL Study.

    Science.gov (United States)

    Marra-Lopez Valenciano, Carlos; Bolado Concejo, Federico; Marín Serrano, Eva; Millastre Bocos, Judith; Martínez-Moneo, Emma; Pérez Rodríguez, Esperanza; Francisco González, María; Del Pozo-García, Andrés; Hernández Martín, Anaiansi; Labrador Barba, Elena; Orera Peña, María Luisa; de-Madaria, Enrique

    2018-02-01

    Exocrine pancreatic insufficiency (EPI) is an important complication of chronic pancreatitis (CP). Guidelines recommend to rule out EPI in CP, to detect those patients who would benefit from pancreatic enzyme replacement therapy. The aim of this study was to evaluate the prevalence of EPI in patients with CP without follow-up in the last 2 years and to describe their nutritional status and quality of life (QoL). This was a cross-sectional, multicenter Spanish study. CP patients without follow-up by a gastroenterologist or surgeon in at least 2 years were included. EPI was defined as fecal elastase test <200mcg/g. For nutritional assessment, laboratory and anthropometric data were obtained. QoL was investigated using the EORTC QLQ-C30 questionnaire. 64 patients (mean age 58.8±10.3 years, 85.9% men) from 10 centers were included. Median time since diagnosis of CP was 58.7 months [37.7-95.4]. Forty-one patients (64.1%) had EPI. Regarding nutritional status, the following differences were observed (EPI vs. Non-EPI): BMI (23.9±3.5kg/m 2 vs. 25.7±2.5, p=0.03); glucose (121 [96-189] mg/dL vs. 98 [90-116], p=0.006); HbA1c 6.6% [6.0-8.4] vs. 5.5 [5.3-6.0], p=0.0005); Vitamin A (0.44mg/L [0.35-0.57] vs. 0.53 [0.47-0.63], p=0.048) and Vitamin E (11.2±5.0μg/ml vs. 14.4±4.3, p=0.03). EPI group showed a worse EORTC QLQ-C30 score on physical (93.3 [66.7-100] vs. 100 [93.3-100], p=0.048) and cognitive function (100 [83.3-100] vs. 100 [100-100], p=0.04). Prevalence of EPI is high in patients with CP without follow-up. EPI group had higher levels of glucose, lower levels of vitamins A and E and worse QoL. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  15. Pancreas Transplantation With Portal-Enteric Drainage for Patients With Endocrine and Exocrine Insufficiency From Extensive Pancreatic Resection

    Directory of Open Access Journals (Sweden)

    Andrew S. Barbas, MD

    2017-09-01

    Full Text Available Abstract. Although the primary indication for pancreas transplantation is type I diabetes, a small number of patients requires pancreas transplantation to manage combined endocrine and exocrine insufficiency that develops after extensive native pancreatic resection. The objective of this case report was to describe the operative and clinical course in 3 such patients and present an alternative technical approach.

  16. Exocrine Dysfunction Correlates with Endocrinal Impairment of Pancreas in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Prasanna Kumar, H R; Gowdappa, H Basavana; Hosmani, Tejashwi; Urs, Tejashri

    2018-01-01

    Diabetes mellitus (DM) is a chronic abnormal metabolic condition, which manifests elevated blood sugar level over a prolonged period. The pancreatic endocrine system generally gets affected during diabetes, but often abnormal exocrine functions are also manifested due to its proximity to the endocrine system. Fecal elastase-1 (FE-1) is found to be an ideal biomarker to reflect the exocrine insufficiency of the pancreas. The aim of this study was conducted to assess exocrine dysfunction of the pancreas in patients with type-2 DM (T2DM) by measuring FE levels and to associate the level of hyperglycemia with exocrine pancreatic dysfunction. A prospective, cross-sectional comparative study was conducted on both T2DM patients and healthy nondiabetic volunteers. FE-1 levels were measured using a commercial kit (Human Pancreatic Elastase ELISA BS 86-01 from Bioserv Diagnostics). Data analysis was performed based on the important statistical parameters such as mean, standard deviation, standard error, t -test-independent samples, and Chi-square test/cross tabulation using SPSS for Windows version 20.0. Statistically nonsignificant ( P = 0.5051) relationship between FE-1 deficiency and age was obtained, which implied age as a noncontributing factor toward exocrine pancreatic insufficiency among diabetic patients. Statistically significant correlation ( P = 0.003) between glycated hemoglobin and FE-1 levels was also noted. The association between retinopathy ( P = 0.001) and peripheral pulses ( P = 0.001) with FE-1 levels were found to be statistically significant. This study validates the benefit of FE-1 estimation, as a surrogate marker of exocrine pancreatic insufficiency, which remains unmanifest and subclinical.

  17. New Onset of Diabetes and Pancreatic Exocrine Insufficiency After Pancreaticoduodenectomy for Benign and Malignant Tumors: A Systematic Review and Meta-analysis of Long-term Results.

    Science.gov (United States)

    Beger, Hans G; Poch, Bertram; Mayer, Benjamin; Siech, Marco

    2018-02-01

    The aim of this study was to assess the frequency and severity of new onset of diabetes mellitus (NODM) and pancreatic exocrine insufficiency (PEI) after pancreaticoduodenectomy (PD) for benign and malignant tumors. When PD is performed on patients for benign tumors, the question of long-term metabolic dysfunctions becomes of importance. Medline/PubMed, Embase, and Cochrane Library were searched for articles reporting results of measuring endocrine and exocrine pancreatic functions after PD. The methodological quality of 19 studies was assessed by means of the Newcastle-Ottawa scale and Moga-Score. The mean weighted overall percentages of NODM and PEI after PD were calculated with a 95% confidence interval (CI). Of 1295 patients, data valid-for-efficacy-analysis are based on 845 patients measuring pancreatic endocrine and on 964 patients determining exocrine functions after PD. The cumulative incidence of NODM was 40 of 275 patients (14.5%; 95% CI: 10.3-18.7) in the benign tumor group, 25 of 161 (15.5%; 95% CI: 9.9-21.2) in the malignant tumor group, and 91 of 409 patients (22.2%; 95% CI: 18.2-26.3) in the benign and malignant tumor group. Comparing the frequency of NODM after PD revealed significant differences between the groups (benign vs benign and malignant P benign and malignant P benign and malignant tumors and a significant decrease of exocrine functions contribute to a rational weighting of metabolic long-term risks following PD.

  18. Mouse Pancreas Tissue Slice Culture Facilitates Long-Term Studies of Exocrine and Endocrine Cell Physiology in situ

    OpenAIRE

    Marciniak, Anja; Selck, Claudia; Friedrich, Betty; Speier, Stephan

    2013-01-01

    Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To ove...

  19. Bombesin-stimulated serum immunoreactive trypsin in the different diagnosis between endocrine and exocrine tumors of the pancreas

    International Nuclear Information System (INIS)

    Bonora, G.; De Giorgio, R.; Toni, R.; Fanti, M.P.; Cariani, G.; Vezzadini, P.

    1987-01-01

    Bombesin administration was recently found to induce a marked increase in circulating immunoreactive trypsin (IRT), whose magnitude seems to reflect the functional capacity of pancreatic acinar cell mass. The purpose of the present study was to assess the effect of bombesin infusion on serum IRT concentration in patients with endocrine or exocrine tumors of the pancreas. Fifteen patients with pancreatic endocrine tumor, 17 patients with pancreatic exocrine carcinoma and 15 healty subjects were investigated. Serum IRT was measured by radioimmunoassay before and for 120 minutes after the start of bombesin infusion (9 ng/kg/min over 30 min). The integrated serum IRT response to bombesin administration in patients with endocrine tumor of the pancreas did not differ significantly from controls, but were significantly higher than in patients with exocrine carcinoma. In the latter the integrated IRT responses to bombesin infusion in patients with endocrine tumor can probably be explained by small tumor size and/or little invasion of the glandular parenchyma, resulting in an undetectable impairment of exocrine pancreatic function. The very low IRT responses in patients with exocrine carcinoma could reflect the presence of severe pancreatic damage. The results suggest that this newly proposed bombesin test may be useful in the preoperative differential diagnosis between endocrine and exocrine tumors of the pancreas

  20. Exocrine dysfunction correlates with endocrinal impairment of pancreas in Type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    H R Prasanna Kumar

    2018-01-01

    Full Text Available Background: Diabetes mellitus (DM is a chronic abnormal metabolic condition, which manifests elevated blood sugar level over a prolonged period. The pancreatic endocrine system generally gets affected during diabetes, but often abnormal exocrine functions are also manifested due to its proximity to the endocrine system. Fecal elastase-1 (FE-1 is found to be an ideal biomarker to reflect the exocrine insufficiency of the pancreas. Aim: The aim of this study was conducted to assess exocrine dysfunction of the pancreas in patients with type-2 DM (T2DM by measuring FE levels and to associate the level of hyperglycemia with exocrine pancreatic dysfunction. Methodology: A prospective, cross-sectional comparative study was conducted on both T2DM patients and healthy nondiabetic volunteers. FE-1 levels were measured using a commercial kit (Human Pancreatic Elastase ELISA BS 86-01 from Bioserv Diagnostics. Data analysis was performed based on the important statistical parameters such as mean, standard deviation, standard error, t-test-independent samples, and Chi-square test/cross tabulation using SPSS for Windows version 20.0. Results: Statistically nonsignificant (P = 0.5051 relationship between FE-1 deficiency and age was obtained, which implied age as a noncontributing factor toward exocrine pancreatic insufficiency among diabetic patients. Statistically significant correlation (P = 0.003 between glycated hemoglobin and FE-1 levels was also noted. The association between retinopathy (P = 0.001 and peripheral pulses (P = 0.001 with FE-1 levels were found to be statistically significant. Conclusion: This study validates the benefit of FE-1 estimation, as a surrogate marker of exocrine pancreatic insufficiency, which remains unmanifest and subclinical.

  1. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  2. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Nandy, Debashis; Mukhopadhyay, Debabrata

    2011-01-01

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  3. Evaluation of the marker technique for measurement of exocrine pancreatic secretion rate

    International Nuclear Information System (INIS)

    Rune, S.J.; Worning, H.

    1985-01-01

    A secretin-cholecystokinin test was performed in 103 patients, representing both normal and reduced exocrine pancreatic function. The duodenum was intubated with a triple-lumen tube. The gastric and duodenal contents were aspirated separately and sampled in 10-min. periods. An inert, water-soluble marker ( 58 Co-vitamin B 12 dissolved in isotonic saline) was infused at a constant rate into the duodenum. Exocrine panreatic secretion was stimulated by continuous intravenous infusion of secretin for 60 min. and a combination of secretin and cholecystokinin for another 60 min. The total recovery of the infused marker was 80%. The concentration of marker in the aspriate did not vary significantly between consecutive 10-min. periods during the last 20 min. of the secretin stimulation period, or during the last 50 min. of the combined secretin-cholecystokinin stimulation period, indicating a steady secretion rate into the duodenum. By means of the marker, concentrations in the aspirate, the duodenal volumes were calculated and found to vary significantly less than the aspirated volumes. This finding demonstrates that the duodenal volume calculated from the recovery of an inert marker, is a closer estimate of the true volume than that obtained by the usual apsiration technique without a volume indicator

  4. Pancreatic enzyme supplementation after gastrectomy for gastric cancer: a randomized controlled trial.

    Science.gov (United States)

    Catarci, Marco; Berlanda, Manuele; Grassi, Giovanni Battista; Masedu, Francesco; Guadagni, Stefano

    2018-05-01

    Gastrectomy for gastric cancer is a significant cause of secondary exocrine pancreatic insufficiency. Pancreatic enzyme replacement therapy may influence nutritional status and quality of life after gastrectomy, but the pertinent clinical research to date remains controversial. A randomized controlled trial to test this hypothesis was carried out. After gastrectomy, 43 patients with gastric cancer were randomly assigned to a normal diet (Normal-d; n = 21) or to a pancreatic enzyme supplementation diet (PES-d; n = 22) and were followed up during a 12-month period, assessing nutritional status and quality of life through body mass index (BMI), instant nutritional assessment (INA) class status, serum pre-albumin (SPA) values, and GastroiIntestinal Quality of Life Index (GIQLI). BMI was not significantly influenced by the type of diet; INA class status was significantly improved in the PES-d arm, particularly during the first 3 months after gastrectomy; SPA levels increased in both arms at 6 months after gastrectomy, reaching significantly higher values in the PES-d arm at 12 months. GIQLI was not significantly influenced by the type of diet throughout the follow-up period; however, this index significantly improved in the PES-d arm between the first and third month after gastrectomy. PES-d improves nutritional status and quality of life after gastrectomy for gastric cancer, particularly within 3 months from the operation. A larger, multicenter trial is necessary to address the potential influence of several confounding variables such as disease stage and adjuvant treatments.

  5. Undiagnosed pancreatic exocrine insufficiency and chronic pancreatitis in functional GI disorder patients with diarrhea or abdominal pain.

    Science.gov (United States)

    Talley, Nicholas J; Holtmann, Gerald; Nguyen, Quoc Nam; Gibson, Peter; Bampton, Peter; Veysey, Martin; Wong, James; Philcox, Stephen; Koloski, Natasha; Bunby, Lisa; Jones, Michael

    2017-11-01

    A previous UK study showed that 6.1% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) had evidence of severe pancreatic exocrine insufficiency (PEI), but these findings need replication. We aimed to identify the prevalence of PEI based on fecal elastase stool testing in consecutive outpatients presenting with chronic unexplained abdominal pain and/or diarrhea and/or IBS-D. Patients aged over 40 years presenting to hospital outpatient clinics from six sites within Australia with unexplained abdominal pain and/or diarrhea for at least 3 months and/or IBS-D were studied. Patients completed validated questionnaires and donated a stool sample in which elastase concentration was measured by ELISA. A concentration of abdominal CT. Two hundred eighteen patients (mean age of 60 years, 29.4% male) were studied. PEI was found in 4.6% (95% CI 2.2-8.3%) (n = 10), with five patients (2.3% (95% CI 0.8-5.3%) having severe PEI. Only male sex and heavy alcohol use were significantly associated with abnormal versus normal pancreatic functioning. Of seven patients who underwent endoscopic ultrasound or CT, two had features indicative of chronic pancreatitis. One in 50 patients with IBS-D or otherwise unexplained abdominal pain or diarrhea have an abnormal fecal elastase, but unexpected pancreatic insufficiency was detected in only a minority of these. This study failed to confirm the high prevalence of PEI among patients with unexplained GI symptoms previously reported. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  6. Hereditary pancreatitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Raphael KL

    2016-07-01

    Full Text Available Kara L Raphael, Field F Willingham Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA Abstract: Hereditary pancreatitis (HP is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. Keywords: pancreatic cancer, chronic pancreatitis, idiopathic pancreatitis, pancreatitis, familial pancreatitis, genetic mutations

  7. Stabilised 111In-labelled DTPA- and DOTA-conjugated neurotensin analogues for imaging and therapy of exocrine pancreatic cancer

    International Nuclear Information System (INIS)

    Visser, M. de; Krenning, E.P.; Jong, M. de; Janssen, P.J.J.M.; Srinivasan, A.; Reubi, J.C.; Waser, B.; Erion, J.L.; Schmidt, M.A.

    2003-01-01

    Neurotensin (NT) receptors are overexpressed in exocrine pancreatic cancer and Ewing's sarcoma. The potential utility of native NT in cancer diagnosis and therapy is, however, limited by its rapid degradation in vivo. Therefore, NT analogues were synthesised with modified lysine and arginine derivatives to enhance stability and coupled either to DTPA, to enable high specific activity labelling with indium-111 for imaging, or to DOTA, to enable high specific activity labelling with β-emitting radionuclides, such as lutetium-177 and yttrium-90. Based on serum stability (4 h incubation at 37 C in human serum) and receptor binding affinity, the five most promising analogues were selected and further evaluated in in vitro internalisation studies in human colorectal adenocarcinoma HT29 cells, which overexpress NT receptors. All five NT analogues bound with high affinity to NT receptors on human exocrine pancreatic tumour sections. The analogues could be labelled with 111 In to a high specific activity. The 111 In-labelled compounds were found to be very stable in serum. Incubation of HT29 cells with the 111 In-labelled analogues at 37 C showed rapid receptor-mediated uptake and internalisation. The most promising analogue, peptide 2530 [DTPA-(Pip)Gly-Pro-(PipAm)Gly-Arg-Pro-Tyr-tBuGly-Leu-OH] was further tested in vivo in a biodistribution study using HT29 tumour-bearing nude mice. The results of this study showed low percentages of injected dose per gram tissue of this 111 In-labelled 2530 analogue in receptor-negative organs like blood, spleen, pancreas, liver, muscle and femur. Good uptake was found in the receptor-positive HT29 tumour and high uptake was present in the kidneys. Co-injection of excess unlabelled NT significantly reduced tumour uptake, showing that tumour uptake is a receptor-mediated process. With their enhanced stability, maintained high receptor affinity and rapid receptor-mediated internalisation, the 111 In-labelled DTPA- and DOTA-conjugated NT

  8. Total pancreatic lipomatosis with malabsorption syndrome

    Directory of Open Access Journals (Sweden)

    Rama Anand

    2011-01-01

    Full Text Available Total fat replacement of the pancreas is rare. Focal fatty replacement is the most common degenerative lesion of pancreas. Focal fatty deposits have no major clinical significance; however, extreme fat replacement is of pathologic significance, as it is associated with marked reduction in exocrine function of pancreas, resulting in malabsorption due to pancreatic enzyme insufficiency.

  9. Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Merrell, Kenneth W.; Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Quevedo, J. Fernando [Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States); Harmsen, William S. [Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota (United States); Kendrick, Michael L. [Department of General Surgery, Mayo Clinic, Rochester, Minnesota (United States); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Hallemeier, Christopher L., E-mail: hallemeier.christopher@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2016-03-01

    Purpose: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). Methods and Materials: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gy in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. Results: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). Conclusions: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as

  10. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer

    Science.gov (United States)

    Hart, Phil A; Bellin, Melena D; Andersen, Dana K; Bradley, David; Cruz-Monserrate, Zobeida; Forsmark, Christopher E; Goodarzi, Mark O; Habtezion, Aida; Korc, Murray; Kudva, Yogish C; Pandol, Stephen J; Yadav, Dhiraj; Chari, Suresh T

    2017-01-01

    Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps. PMID:28404095

  11. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection.

    Science.gov (United States)

    Gilliland, Taylor M; Villafane-Ferriol, Nicole; Shah, Kevin P; Shah, Rohan M; Tran Cao, Hop S; Massarweh, Nader N; Silberfein, Eric J; Choi, Eugene A; Hsu, Cary; McElhany, Amy L; Barakat, Omar; Fisher, William; Van Buren, George

    2017-03-07

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995-2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

  12. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Hart, Phil A; Bellin, Melena D; Andersen, Dana K; Bradley, David; Cruz-Monserrate, Zobeida; Forsmark, Christopher E; Goodarzi, Mark O; Habtezion, Aida; Korc, Murray; Kudva, Yogish C; Pandol, Stephen J; Yadav, Dhiraj; Chari, Suresh T

    2016-11-01

    Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. an extended pancreatic normal subjects and ~in pancreatItIs In ...

    African Journals Online (AJOL)

    function . . patIents. N. H. GILlNSKY, A. S. MEE, I. N. MARKS. Summary. Exocrine pancreatic response was evaluated in patients with varying degrees of pancreatic damage and in control subjects by ... hormones, the Lundh meal and an oral pancreatic function test .... is any different from that of the cells in me normal gland.

  14. Proteins are secreted from heterogeneous prestored sources in the exocrine pancreas

    International Nuclear Information System (INIS)

    Miller, P.E.; Adelson, J.W.

    1987-01-01

    Recent studies demonstrating nonparallel regulated secretion of prestored digestive enzymes in tightly linked groups consistent with the exocytosis mechanisms led the authors to predict that digestive enzymes would be found to be secreted from heterogeneous sources within the exocrine pancreas. They explored whether the gland was heterogeneous with respect to its sources of prestored secretory proteins with a double isotopic label method not dependent on activity of secreted digestive enzymes. Rabbit pancreatic proteins were double labeled in vivo by injection of each animal with chemically identical but isotopically distinct mixtures of 3 H- and 14 C-labeled amino acids, which were administered separately or together on consecutive days after partial depletion of prestored proteins by administration of cholecystokinin (CCK), methacholine chloride, or saline in a protocol in which order of both isotope and secretagogue administration was varied. Three days after labeling, proteins were recovered by collection from cannulated pancreatic ducts of anesthetized animals after stimulation with alternating increasing doses of CCK and methacholine chloride. Correlation and regression analysis of isotopic outputs and variance analysis of specific radioactivities of secreted proteins showed sequestration into and secretion from heterogeneous pools of secretory proteins, directly confirming the hypothesis. These results provide a cell biological mechanism explaining regulated nonparallel secretion of digestive enzymes

  15. Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

    Science.gov (United States)

    Hu, Wenyan; Fu, Ling

    2013-05-01

    Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (ppancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

  16. Endocrine pancreatic function changes after acute pancreatitis.

    Science.gov (United States)

    Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

    2011-10-01

    This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

  17. AN EMBRYONIC CHICK PANCREAS ORGAN CULTURE MODEL: CHARACTERIZATION AND NEURAL CONTROL OF EXOCRINE RELEASE

    Science.gov (United States)

    An embryonic chick (Gallus domesticus) whole-organ pancreas culture system was developed for use as an in vitro model to study cholinergic regulation of exocrine pancreatic function. The culture system was examined for characteristic exocrine function and viability by measuring e...

  18. Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ.

    Science.gov (United States)

    Marciniak, Anja; Selck, Claudia; Friedrich, Betty; Speier, Stephan

    2013-01-01

    Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To overcome these limitations, we aimed to establish a pancreas tissue slice culture platform to allow long-term studies on exocrine and endocrine cells in the intact pancreatic environment. Mouse pancreas tissue slice morphology was assessed to determine optimal long-term culture settings for intact pancreatic tissue. Utilizing optimized culture conditions, cell specificity and function of exocrine acinar cells and endocrine beta cells were characterized over a culture period of 7 days. We found pancreas tissue slices cultured under optimized conditions to have intact tissue specific morphology for the entire culture period. Amylase positive intact acini were present at all time points of culture and acinar cells displayed a typical strong cell polarity. Amylase release from pancreas tissue slices decreased during culture, but maintained the characteristic bell-shaped dose-response curve to increasing caerulein concentrations and a ca. 4-fold maximal over basal release. Additionally, endocrine beta cell viability and function was well preserved until the end of the observation period. Our results show that the tissue slice culture platform provides unprecedented maintenance of pancreatic tissue specific morphology and function over a culture period for at least 4 days and in part even up to 1 week. This analytical advancement now allows mid -to long-term studies on the cell biology of pancreatic disorder pathogenesis and therapy in an intact surrounding in situ.

  19. Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ.

    Directory of Open Access Journals (Sweden)

    Anja Marciniak

    Full Text Available Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To overcome these limitations, we aimed to establish a pancreas tissue slice culture platform to allow long-term studies on exocrine and endocrine cells in the intact pancreatic environment. Mouse pancreas tissue slice morphology was assessed to determine optimal long-term culture settings for intact pancreatic tissue. Utilizing optimized culture conditions, cell specificity and function of exocrine acinar cells and endocrine beta cells were characterized over a culture period of 7 days. We found pancreas tissue slices cultured under optimized conditions to have intact tissue specific morphology for the entire culture period. Amylase positive intact acini were present at all time points of culture and acinar cells displayed a typical strong cell polarity. Amylase release from pancreas tissue slices decreased during culture, but maintained the characteristic bell-shaped dose-response curve to increasing caerulein concentrations and a ca. 4-fold maximal over basal release. Additionally, endocrine beta cell viability and function was well preserved until the end of the observation period. Our results show that the tissue slice culture platform provides unprecedented maintenance of pancreatic tissue specific morphology and function over a culture period for at least 4 days and in part even up to 1 week. This analytical advancement now allows mid -to long-term studies on the cell biology of pancreatic disorder pathogenesis and therapy in an intact surrounding in situ.

  20. Predictive factors of endocrine and exocrine insufficiency after resection of a benign tumour of the pancreas.

    Science.gov (United States)

    Neophytou, Hélène; Wangermez, Marc; Gand, Elise; Carretier, Michel; Danion, Jérôme; Richer, Jean-Pierre

    2018-04-01

    The aim of the present study is to evaluate the risk factors of endocrine and exocrine insufficiency occurring few years after pancreatic resections in a consecutive series of patients who underwent pancreatoduodenectomy (PD), left pancreatectomy (LP) or enucleation for benign neoplasms at a referral centre. Pancreatic exocrine insufficiency (PEI) was defined by the onset of steatorrhea associated with weight loss, and endocrine insufficiency was determinate by fasting plasma glucose. Association between pancreatic insufficiency and clinical, pathological, and perioperative features was studied using univariate and multivariate Cox regression analysis. A prospective cohort of 92 patients underwent PD (48%), LP (44%) or enucleation (8%) for benign tumours, from 2005 to 2016 in the University Hospital in Poitiers (France). The median follow-up was 68.6±42.4months. During the following, 54 patients developed exocrine insufficiency whereas 32 patients presented endocrine insufficiency. In the Cox model, a BMI>28kg/m 2 , being a man and presenting a metabolic syndrome were significantly associated with a higher risk to develop postoperative diabetes. The risks factors for the occurrence of PEI were preoperative chronic pancreatitis, a BMIpancreatic head, biological markers of chronic obstruction and fibrotic pancreas. Undergoing LP or enucleation were protective factors of PEI. Histological categories such as neuroendocrine tumours and cystadenomas were also associated with a decreased incidence of PEI. Men with metabolic syndrome and obesity should be closely followed-up for diabetes, and patients with obstructive tumours, pancreatic fibrosis or chronic pancreatitis require a vigilant follow up on their pancreatic exocrine function. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Action of a new cholinergic agonist, aclatonium napadisilate, on isolated rat pancreatic acini

    International Nuclear Information System (INIS)

    Fujii, M.; Okabayashi, Y.; Nakamura, T.; Tani, S.; Fujisawa, T.; Otsuki, M.

    1990-01-01

    The effect of aclatonium napadisilate, a newly synthesized choline ester, on pancreatic exocrine function was compared with that of the muscarinic agonist carbamylcholine in isolated rat pancreatic acini. Both compounds increased amylase release and 45 Ca 2+ efflux in a dose-dependent fashion, and similarly decreased the binding of [N-methyl- 3 H]scopolamine to isolated rat pancreatic acini. While aclatonium napadisilate was 20-30 times less potent than carbamylcholine in stimulations of amylase release and 45 Ca 2+ efflux, the potency of aclatonium napadisilate in inhibiting [N-methyl- 3 H]scopolamine binding was nearly the same as that of carbamylcholine. These results indicate that aclatonium napadisilate stimulates pancreatic exocrine secretion via muscarinic receptors and Ca 2+ mobilization, and its intrinsic activity is less than carbamylcholine in the isolated rat pancreatic acini. Since aclatonium napadisilate is known to increase motility and peristalsis of the gastrointestinal tract, stimulatory effects of aclatonium napadisilate, shown in the present study, on digestive enzyme secretion from the pancreas may provide additional benefit of aclatonium napadisilate in the treatment of various gastrointestinal disorders

  2. [Clinical significance of the tests used in the diagnosis of pancreatic diseases].

    Science.gov (United States)

    Lenti, G; Emanuelli, G

    1976-11-14

    Different methods available for investigating patients for pancreatic disease are discussed. They first include measurement of pancreatic enzymes in biological fluids. Basal amylase and/or lipase in blood are truly diagnostic in acute pancreatitis but their utility is low in chronic pancreatic diseases. Evocative tests have been performed to increase the sensitivity of blood enzyme measurement. The procedure is based on enzyme determination following administration of pancreozymin and secretin, and offers a valuable aid in diagnosis of chronic pancreatitis and cancer of the pancreas. They are capable of discerning pancreatic lesions but are not really discriminatory because similar changes are observed in both diseases. The measurement of urinary enzyme levels in patients with acute pancreatitis is a sensitive indicator of disease. The urinary amylase excretion rises to abnormal levels and persists at significant values for a longer period of time than the serum amylase in acute pancreatitis. The fractional urinary amylase escretion seems to be more sensitive than daily urinary measurement. The pancreatic exocrin function can be assessed by examining the duodenal contents after intravenous administration of pancreozymin and secretin. Different abnormal secretory patterns can be determinated. Total secretory deficiency is observed in patients with obstruction of excretory ducts by tumors of the head of the pancreas and in the end stage of chronic pancreatitis. Low volume with normal bicarbonate and enzyme concentration is another typical pattern seen in neoplastic obstruction of escretory ducts. In chronic pancreatitis the chief defect is the inability of the gland to secrete a juice with a high bicarbonate concentration; but in the advanced stage diminution of enzyme and volume is also evident. Diagnostic procedures for pancreatic diseases include digestion and absorption tests. The microscopic examination and chemical estimation of the fats in stool specimens in

  3. Pancreatic insufficiency after different resections for benign tumours.

    Science.gov (United States)

    Falconi, M; Mantovani, W; Crippa, S; Mascetta, G; Salvia, R; Pederzoli, P

    2008-01-01

    Pancreatic resections for benign diseases may lead to long-term endocrine/exocrine impairment. The aim of this study was to compare postoperative and long-term results after different pancreatic resections for benign disease. Between 1990 and 1999, 62 patients underwent pancreaticoduodenectomy (PD), 36 atypical resection (AR) and 64 left pancreatectomy (LP) for benign tumours. Exocrine and endocrine pancreatic function was evaluated by 72-h faecal chymotrypsin and oral glucose tolerance test. The incidence of pancreatic fistula was significantly higher after AR than after LP (11 of 36 versus seven of 64; P = 0.028). The long-term incidence of endocrine pancreatic insufficiency was significantly lower after AR than after PD (P insufficiency was more common after PD (P endocrine and exocrine insufficiency was higher for PD and LP than for AR (32, 27 and 3 per cent respectively at 1 year; 58, 29 and 3 per cent at 5 years; P pancreatic resections are associated with different risks of developing long-term pancreatic insufficiency. AR represents the best option in terms of long-term endocrine and exocrine function, although it is associated with more postoperative complications. Copyright (c) 2007 British Journal of Surgery Society Ltd.

  4. 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.

  5. Imaging in the diagnosis of chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Vasile D. Balaban

    2014-12-01

    Full Text Available Chronic pancreatitis is characterised by progressive and irreversible damage of the pancreatic parenchyma and ductal system, which leads to chronic pain, loss of endocrine and exocrine functions. Clinically, pancreatic exocrine insufficiency becomes apparent only after 90% of the parenchima has been lost. Despite the simple definition, diagnosing chronic pancreatitis remains a challenge, especially for early stage disease. Because pancreatic function tests can be normal until late stages and have significant limitations, there is an incresing interest in the role of imaging techniques for the diagnosis of chronic pancreatitis. In this article we review the utility and accuracy of different imaging methods in the diagnosis of chronic pancreatitis, focusing on the role of advanced imaging (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.

  6. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    Directory of Open Access Journals (Sweden)

    Taylor M. Gilliland

    2017-03-01

    Full Text Available Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL. The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016 addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC. We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1 patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2 patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3 enteral nutrition (EN should be preferred as a nutritional intervention over total parenteral nutrition (TPN postoperatively; and, (4 a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of

  7. 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.

  8. Pancreatic adenocarcinoma, chronic pancreatitis, and MODY-8 diabetes: is bile salt-dependent lipase (or carboxyl ester lipase) at the crossroads of pancreatic pathologies?

    Science.gov (United States)

    Lombardo, Dominique; Silvy, Françoise; Crenon, Isabelle; Martinez, Emmanuelle; Collignon, Aurélie; Beraud, Evelyne; Mas, Eric

    2018-02-23

    Pancreatic adenocarcinomas and diabetes mellitus are responsible for the deaths of around two million people each year worldwide. Patients with chronic pancreatitis do not die directly of this disease, except where the pathology is hereditary. Much current literature supports the involvement of bile salt-dependent lipase (BSDL), also known as carboxyl ester lipase (CEL), in the pathophysiology of these pancreatic diseases. The purpose of this review is to shed light on connections between chronic pancreatitis, diabetes, and pancreatic adenocarcinomas by gaining an insight into BSDL and its variants. This enzyme is normally secreted by the exocrine pancreas, and is diverted within the intestinal lumen to participate in the hydrolysis of dietary lipids. However, BSDL is also expressed by other cells and tissues, where it participates in lipid homeostasis. Variants of BSDL resulting from germline and/or somatic mutations (nucleotide insertion/deletion or nonallelic homologous recombination) are expressed in the pancreas of patients with pancreatic pathologies such as chronic pancreatitis, MODY-8, and pancreatic adenocarcinomas. We discuss the possible link between the expression of BSDL variants and these dramatic pancreatic pathologies, putting forward the suggestion that BSDL and its variants are implicated in the cell lipid metabolism/reprogramming that leads to the dyslipidemia observed in chronic pancreatitis, MODY-8, and pancreatic adenocarcinomas. We also propose potential strategies for translation to therapeutic applications.

  9. Abnormal serum pancreatic enzymes, but not pancreatitis, are associated with an increased risk of malignancy in patients with intraductal papillary mucinous neoplasms.

    Science.gov (United States)

    Roch, Alexandra M; Parikh, Janak A; Al-Haddad, Mohammad A; DeWitt, John M; Ceppa, Eugene P; House, Michael G; Nakeeb, Attila; Schmidt, C Max

    2014-10-01

    Pancreatitis is associated with intraductal papillary mucinous neoplasm (IPMN). This association is in part due to inflammation from pancreatic ductal obstruction. Although the correlation between pancreatitis and the malignant potential of IPMN is unclear, the 2012 International Consensus Guidelines (ICG) consider pancreatitis a "worrisome feature." We hypothesized that serum pancreatic enzymes, markers of inflammation, are a better predictor of malignancy than pancreatitis in patients with IPMN. Between 1992 and 2012, 364 patients underwent resection for IPMN at a single university hospital. In the past decade, serum amylase and lipase were collected prospectively as an inflammatory marker in 203 patients with IPMN at initial surveillance and "cyst clinic" visits. The latest serum pancreatic enzyme values within 3 months preoperatively were studied. Pancreatitis was defined according to the 2012 revision of the Atlanta Consensus. Of the 203 eligible patients, there were 76 with pancreatitis. Pancreatitis was not associated with an increased rate of malignancy (P = .51) or invasiveness (P = .08). Serum pancreatic enzymes categorically outside of normal range (high or low) were also not associated with malignancy or invasiveness. In contrast, as a continuous variable, the higher the serum pancreatic enzymes were, the greater the rate of invasive IPMN. Of the 127 remaining patients without pancreatitis, serum pancreatic enzymes outside of normal range (low and high) were each associated with a greater rate of malignancy (P enzyme levels above normal range (high) were associated with a greater rate of invasiveness (P = .02). In patients with IPMN without a history of pancreatitis, serum pancreatic enzymes outside of the normal range are associated with a greater risk of malignancy. In patients with a history of pancreatitis, there is a positive correlation between the levels of serum pancreatic enzymes and the presence of invasive IPMN. These data suggest

  10. Chronic ethanol feeding modulates the synthesis of digestive enzymes

    International Nuclear Information System (INIS)

    Ponnappa, B.C.; Hoek, J.B.; Rubin, E.

    1987-01-01

    The effects of chronic ethanol feeding on pancreatic protein synthesis were investigated. Protein synthesis was assessed by studying the rate of incorporation of 3 H-leucine into TCA-precipitable proteins in isolated pancreatic acini from rats. Chronic ethanol ingestion increased the rate of pancreatic protein synthesis by 2-4 fold. The onset of the increase in protein synthesis was detectable two days after ethanol feeding, reached a maximum after 7 days and remained unchanged after 4 months on the ethanol-containing diet. The rate of synthesis of individual digestive enzymes was studied by SDS-PAGE on extracts obtained from purified zymogen granules. Ethanol feeding induced an increase in the rate of synthesis of most of the digestive enzymes; chymotrypsinogen, trypsinogen and an unidentified protein were increased to a greater extent than other digestive enzymes. By contrast, the synthesis of amylase was selectively decreased after ethanol feeding. These results suggest that chronic ethanol ingestion has specific effects on the rate of synthesis of individual digestive enzymes in the exocrine pancreas

  11. Quantitative characterization of the protein contents of the exocrine pancreatic acinar cell by soft x-ray microscopy and advanced digital imaging methods

    Energy Technology Data Exchange (ETDEWEB)

    Loo, Jr., Billy W. [Univ. of California, Berkeley, CA (United States)

    2000-06-01

    The study of the exocrine pancreatic acinar cell has been central to the development of models of many cellular processes, especially of protein transport and secretion. Traditional methods used to examine this system have provided a wealth of qualitative information from which mechanistic models have been inferred. However they have lacked the ability to make quantitative measurements, particularly of the distribution of protein in the cell, information critical for grounding of models in terms of magnitude and relative significance. This dissertation describes the development and application of new tools that were used to measure the protein content of the major intracellular compartments in the acinar cell, particularly the zymogen granule. Soft x-ray microscopy permits image formation with high resolution and contrast determined by the underlying protein content of tissue rather than staining avidity. A sample preparation method compatible with x-ray microscopy was developed and its properties evaluated. Automatic computerized methods were developed to acquire, calibrate, and analyze large volumes of x-ray microscopic images of exocrine pancreatic tissue sections. Statistics were compiled on the protein density of several organelles, and on the protein density, size, and spatial distribution of tens of thousands of zymogen granules. The results of these measurements, and how they compare to predictions of different models of protein transport, are discussed.

  12. Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

    International Nuclear Information System (INIS)

    Cameron, R.S.; Cameron, P.L.; Castle, J.D.

    1986-01-01

    A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pI and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion

  13. Constitutive protein secretion from the exocrine pancreas of fetal rats

    International Nuclear Information System (INIS)

    Arvan, P.; Chang, A.

    1987-01-01

    Two general kinds of exocytotic secretion of proteins are known: that which is stimulated by secretagogues; and constitutive exocytosis, which is unable to be stimulated. The exocrine pancreas has often been cited as a model system for the first kind of secretion. However, the release of digestive enzymes from the exocrine pancreas of 1-day prenatal rats cannot be stimulated by secretagogues; therefore, its secretion is constitutive. To gain insight into the intracellular pathways which mediate secretion in the fetal gland, we examined the kinetics of release of newly synthesized proteins. We find that fetal pancreas in a steady state of secretion releases pulse-labeled secretory proteins in two kinetically distinct phases. The first phase occurring during 0-6.5 h of chase comprises approximately 12% of total incorporated radioactivity, the second phase beginning at greater than 7 h of chase comprises the remainder. Based on analysis by electron microscope autoradiography, radiolabel is localized during the first phase of secretion in immature granules/condensing vacuoles, Golgi compartments, and few mature granules. The second phase of secretion occurs when radiolabel is predominantly in mature granules. We propose that secretion occurs via (at least) 2 exocytotic routes, both of which are constitutive in fetal pancreatic tissue

  14. 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.

  15. 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.

  16. The Relation Between Malnutrition and the Exocrine Pancreas: A Systematic Review

    NARCIS (Netherlands)

    Bartels, Rosalie H.; van den Brink, Deborah A.; Bandsma, Robert H.; Boele van Hensbroek, Michael; Tabbers, Merit M.; Voskuijl, Wieger P.

    2018-01-01

    Objective: The relation between malnutrition and exocrine pancreatic insufficiency (EPI) has been described previously, but it is unclear if malnutrition leads to EPI or vice versa. We systematically synthesized current evidence evaluating the association between malnutrition and EPI in children.

  17. Effect of long-term administration of dietary fiber on the exocrine pancreas in the rat.

    Science.gov (United States)

    Sommer, H; Kasper, H

    1984-08-01

    Male Sprague-Dawley rats (50--70g) were fed a standard laboratory diet containing 6% dietary fiber substances (diet I), the same diet supplemented with 5% guar (diet II), 10% wheat bran (diet III), or 5% pectin of high (76%) methylic esterification (diet IV), or a fiber-free diet (diet V). After a 6-week feeding period, the body weight of the animals had increased to 300--350g. The common bile duct was then canulated and the exocrine pancreatic function tested under urethane anesthesia (1.5 g/kg body weight). The tested fiber substances had no effect on the basal pancreatic secretion of volume, bicarbonate, lipase, amylase or protein, or on the wet weight and histological appearance of the organ. However, the fiber substances influenced the pancreatic response to maximal exogenous stimulation with secretin (3.0 CU/100 g X hour) and cholecystokinin (0.6 IDU/100 g X hour) and the enzyme content of the gland significantly. Compared with diet V, diet I increased the DNA content of the pancreas and its secretion of bicarbonate and protein, and decreased the protein concentration in the gland. Diet II reduced the pancreatic content of trypsinogen and protein. Diet III decreased the protein content, but increased the bicarbonate secretion, which was also increased by diet IV. -- We conclude that fiber substances influence stimulated secretion and the enzyme content of the pancrease to a varying degree.

  18. Accelerated radiochemotherapy in pancreatic cancer is not necessarily related to a pathologic pancreatic function decline in the early period

    International Nuclear Information System (INIS)

    Horst, Eckehard; Seidel, Matthias; Micke, Oliver; Ruebe, Christian; Glashoerster, Marco; Schaefer, Ulrich; Willich, Normann A.

    2002-01-01

    Purpose: To evaluate the functional effects of ionizing radiation in patients with unresectable pancreatic cancer in the early period after accelerated radiochemotherapy (ART). Methods and Materials: To analyze the exocrine component, the amino acid consumption test and fecal elastase 1 were performed in 13 patients immediately before and 4-8 weeks after ART. Pancreatic duct morphology was evaluated before therapy. Weight loss and clinical steatorrhea were recorded. Endocrine parameters were examined according to standardized criteria. Results: The relative change of the amino acid consumption test results and the median elastase concentration was 41.2% and 56.4%, respectively. Five patients still had normal test results after ART and 5 patients developed pathologic values. The median relative weight loss of the total body weight was 7.7% ± 4.5%. No steatorrhea occurred. Of the 5 patients with normal values, 3 had a mean organ dose of 41 Gy. The endocrine function measurements remained unchanged. Conclusion: Although a nominal reduction of exocrine function parameters occurred in most patients, ART was not necessarily related to a pathologic level in the early period. Diabetes was not established. The functional impairment that was existent in the patient population presumably contributed to the weight loss. Pancreatic enzyme preparations may also play a role in maintaining an anabolic state during and after radiochemotherapy

  19. Update on endoscopic pancreatic function testing

    Institute of Scientific and Technical Information of China (English)

    Tyler Stevens; Mansour A Parsi

    2011-01-01

    Hormone-stimulated pancreatic function tests (PFTs) are considered the gold standard for measuring pancreatic exocrine function. PFTs involve the administration of intravenous secretin or cholecystokinin, followed by collection and analysis of pancreatic secretions. Because exocrine function may decline in the earliest phase of pancreatic fibrosis, PFTs are considered accurate for diagnosing chronic pancreatitis. Unfortunately, these potentially valuable tests are infrequently performed except at specialized centers, because they are time consuming and complicated. To overcome these limitations, endoscopic PFT methods have been developed which include aspiration of pancreatic secretions through the suction channel of the endoscope. The secretin endoscopic pancreatic function test (ePFT) involves collection of duodenal aspirates at 15, 30, 45 and 60 min after secretin stimulation. A bicarbonate concentration greater than 80 mmol/L in any of the samples is considered a normal result. The secretin ePFT has demonstrated good sensitivity and specificity compared with various reference standards, including the "Dreiling tube" secretin PFT, endoscopic ultrasound, and surgical histology. Furthermore, a standard autoanalyzer can be used for bicarbonate analysis, which allows the secretin ePFT to be performed at any hospital. The secretin ePFT may complement imaging tests like endoscopic ultrasound (EUS) in the diagnosis of early chronic pancreatitis.This paper will review the literature validating the use of ePFT in the diagnosis of exocrine insufficiency and chronic pancreatitis. Newer developments will also be discussed, including the feasibility of combined EUS/ePFT, the use of cholecystokinin alone or in combination with secretin, and the discovery of new protein and lipid pancreatic juice biomarkers which may complement traditionalfluid analysis.

  20. 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.

  1. Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction.

    Science.gov (United States)

    Araya, S; Kuster, E; Gluch, D; Mariotta, L; Lutz, C; Reding, T V; Graf, R; Verrey, F; Camargo, S M R

    2018-04-01

    Glutamine (Gln) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state, Gln has been suggested to have a trophic effect on the exocrine pancreas and small intestine. However, the Gln transport capacity, the functional relationship of these two organs, and the potential role of the Gln-glutamate (Glu) cycle are unknown. We observed that pancreatic acinar cells express lower levels of Glu than Gln transporters. Consistent with this expression pattern, the rate of Glu influx into acinar cells was approximately sixfold lower than that of Gln. During protein restriction, acinar cell glutaminase expression was increased and Gln accumulation was maintained. Moreover, Glu secretion by acinar cells into pancreatic juice and thus into the lumen of the small intestine was maintained. In the intestinal lumen, Glu absorption was preserved and Glu dehydrogenase expression was augmented, potentially providing the substrates for increasing energy production via the TCA cycle. Our findings suggest that one mechanism by which Gln exerts a positive effect on exocrine pancreas and small intestine involves the Gln metabolism in acinar cells and the secretion of Glu into the small intestine lumen. The exocrine pancreas acinar cells not only avidly accumulate Gln but metabolize Gln to generate energy and to synthesize Glu for secretion in the pancreatic juice. Secreted Glu is suggested to play an important role during malnourishment in sustaining small intestinal homeostasis. NEW & NOTEWORTHY Glutamine (Gln) has been suggested to have a trophic effect on exocrine pancreas and small intestine in malnourished states, but the mechanism is unknown. In this study, we suggest that this trophic effect derives from an interorgan relationship between exocrine pancreas and small intestine for Gln

  2. Chronic pancreatitis. Diagnosis, therapy and follow-up results

    International Nuclear Information System (INIS)

    Moessner, J.

    1996-01-01

    The incidence of chronic pancreatitis is increasing in industrialized countries due to the steady increase of alcohol abuse. The pathogenesis of this disease is still incompletely understood. A cure is not possible. The knowledge of the patients history and a thorough clinical investigation together with the availability of a wide array of laboratory tests and imaging procedures enable the physician to characterize the stage of the disease. Exact knowledge of the present pancreatic morphology, potential complications of the disease, and knowledge about the present exocrine and endocrine function capacity are prerequisites for adequate therapeutic decision making. The therapeutic possibilities include termination of alcohol abuse, various options of treatment of pain according to the various pathogenetic possibilities leading to pain, pancreatic digestive enzyme supplementation, treatment of diabetes, and either endoscopic or surgical treatments of complications of the disease. (orig.) [de

  3. Pancreatic enzyme replacement therapy for people with cystic fibrosis.

    Science.gov (United States)

    Somaraju, Usha Rani; Solis-Moya, Arturo

    2016-11-23

    Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One

  4. Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe deer.

    Science.gov (United States)

    Guilloteau, Paul; Vitari, Francesca; Metzinger-Le Meuth, Valérie; Le Normand, Laurence; Romé, Véronique; Savary, Gérard; Delaby, Luc; Domeneghini, Cinzia; Morisset, Jean

    2012-05-28

    Physiology of the exocrine pancreas has been well studied in domestic and in laboratory animals as well as in humans. However, it remains quite unknown in wildlife mammals. Roe deer and cattle (including calf) belong to different families but have a common ancestor. This work aimed to evaluate in the Roe deer, the adaptation to diet of the exocrine pancreatic functions and regulations related to animal evolution and domestication. Forty bovine were distributed into 2 groups of animals either fed exclusively with a milk formula (monogastric) or fed a dry feed which allowed for rumen function to develop, they were slaughtered at 150 days of age. The 35 Roe deer were wild animals living in the temperate broadleaf and mixed forests, shot during the hunting season and classified in two groups adult and young. Immediately after death, the pancreas was removed for tissue sample collection and then analyzed. When expressed in relation to body weight, pancreas, pancreatic protein weights and enzyme activities measured were higher in Roe deer than in calf. The 1st original feature is that in Roe deer, the very high content in pancreatic enzymes seems to be related to specific digestive products observed (proline-rich proteins largely secreted in saliva) which bind tannins, reducing their deleterious effects on protein digestion. The high chymotrypsin and elastase II quantities could allow recycling of proline-rich proteins. In contrast, domestication and rearing cattle resulted in simplified diet with well digestible components. The 2nd feature is that in wild animal, both receptor subtypes of the CCK/gastrin family peptides were present in the pancreas as in calf, although CCK-2 receptor subtype was previously identified in higher mammals. Bovine species could have lost some digestive capabilities (no ingestion of great amounts of tannin-rich plants, capabilities to secrete high amounts of proline-rich proteins) compared with Roe deer species. CCK and gastrin could play

  5. Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe Deer

    Directory of Open Access Journals (Sweden)

    Guilloteau Paul

    2012-05-01

    Full Text Available Abstract Background Physiology of the exocrine pancreas has been well studied in domestic and in laboratory animals as well as in humans. However, it remains quite unknown in wildlife mammals. Roe deer and cattle (including calf belong to different families but have a common ancestor. This work aimed to evaluate in the Roe deer, the adaptation to diet of the exocrine pancreatic functions and regulations related to animal evolution and domestication. Results Forty bovine were distributed into 2 groups of animals either fed exclusively with a milk formula (monogastric or fed a dry feed which allowed for rumen function to develop, they were slaughtered at 150 days of age. The 35 Roe deer were wild animals living in the temperate broadleaf and mixed forests, shot during the hunting season and classified in two groups adult and young. Immediately after death, the pancreas was removed for tissue sample collection and then analyzed. When expressed in relation to body weight, pancreas, pancreatic protein weights and enzyme activities measured were higher in Roe deer than in calf. The 1st original feature is that in Roe deer, the very high content in pancreatic enzymes seems to be related to specific digestive products observed (proline-rich proteins largely secreted in saliva which bind tannins, reducing their deleterious effects on protein digestion. The high chymotrypsin and elastase II quantities could allow recycling of proline-rich proteins. In contrast, domestication and rearing cattle resulted in simplified diet with well digestible components. The 2nd feature is that in wild animal, both receptor subtypes of the CCK/gastrin family peptides were present in the pancreas as in calf, although CCK-2 receptor subtype was previously identified in higher mammals. Conclusions Bovine species could have lost some digestive capabilities (no ingestion of great amounts of tannin-rich plants, capabilities to secrete high amounts of proline-rich proteins

  6. Functional and morphological changes in pancreatic remnant after pancreaticoduodenectomy.

    Science.gov (United States)

    Fang, Wen-Liang; Su, Cheng-Hsi; Shyr, Yi-Ming; Chen, Tien-Hua; Lee, Rheun-Chuan; Tai, Ling-Chen; Wu, Chew-Wun; Lui, Wing-Yiu

    2007-11-01

    Pancreatic exocrine insufficiency has been reported to be more common in pancreaticogastrostomy (PG) than in pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD). This study aimed to evaluate the long-term outcome after PD between these 2 groups. We evaluated the long-term functional status of 42 surviving patients diagnosed with periampullary lesions who underwent PJ or PG after PD and followed up for more than 1 year. Among these, 23 patients underwent PJ and 19 patients underwent PG. To compare the 2 groups, we analyzed the (1) pancreatic exocrine insufficiency by questioning the presence or absence of steatorrhea, (2) pancreatic endocrine function by measuring glycohemoglobin A1c, fasting blood glucose, and history of new-onset diabetes, (3) nutritional status by measuring serum total protein, albumin, cholesterol, and triglyceride, (4) gastric emptying time, (5) panendoscopic findings, (6) changes of pancreatic duct diameter by computed tomography, and (7) relaparotomy rate. The mean follow-up time for PG and PJ were 37 +/- 23 and 103 +/- 52 months, respectively (P pancreatic exocrine insufficiency, and 11.9% had new-onset diabetes. There was no significant difference between PJ and PG groups. A significantly improved postoperative nutritional state regarding serum total protein and albumin were noticed in both groups. There was no significant difference in terms of gastric emptying time, positive panendoscopic findings, and changes in pancreatic duct diameter. The pancreatic remnant-related relaparotomy rate was higher in the PJ group as compared with the PG group (17.4% vs 0%; P = 0.056). There is no significant difference in pancreatic exocrine or endocrine insufficiency, gastric emptying time, and positive panendoscopic findings between PJ and PG. Pancreaticojejunostomy was associated with a higher pancreatic remnant-related relaparotomy rate; however, because of a shorter follow-up in the PG group, a continuous long-term follow-up is still

  7. Pharmacological challenges in chronic pancreatitis

    OpenAIRE

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-01-01

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal ...

  8. Rational drug use in acute pancreatitis: Case report

    Directory of Open Access Journals (Sweden)

    Rosić Nikola

    2011-01-01

    Full Text Available Acute pancreatitis is a sudden inflammation of pancreas where its enzymes autodigest the gland. Two main causes of acute pancreatitis are alcoholism and billiar calculosis. Treatment consists of preventing dehydration, analgesia, decrease of pancreatic exocrine function, enteral nutritional support , respiratory and renal function support and surgery. The patient presents with abdominal pain that lasts for few days and is followed by vomiting. Laboratory tests first revealed abnormal values of blood count and pancreas enzymes (leucocytes -19,7 x 109/L, hematocrit - 0,32, amylase - 52569 IU/L, lypase - 4750 IU/L, CRP - 152 IU/L, albumins - 25 g/L, followed by abnormal values of liver enzymes (AST - 80 IU/L, ALT - 127 IU/L, GGT - 362 IU/L. Further diagnostic procedures showed billiary calculosis, pleural effusion and acute pancreatitis with ascites. No surgery was performed, due to the lack of infect ion and the signs of the patient going into recovery. It was observed that not all diagnostic procedures that exist in the protocol of treatment, such as ERCP or biopsy of pancreatic t issue with microbiological investigation, were performed. Considering the rules of rat ional drug therapy, as well as the protocols that are to be applied in Clinical center 'Kragujevac' in Kragujevac, it was observed that some drugs (antibiotics and albumin were not used in a proper manner, i.e. in compliance with the protocol, which increased the cost of the treatment without improving the patient health or shortening the hospital stay.

  9. 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.

  10. Protein-losing enteropathy in a dog with lymphangiectasia, lymphoplasmacytic enteritis and pancreatic exocrine insufficiency.

    Science.gov (United States)

    Rodríguez-Alarcón, C A; Beristaín-Ruiz, D M; Pérez-Casio, F; Rivera, R; Ochoa, G; Martín-Orozco, U

    2012-01-01

    This is a report of seven-year-old male Akita mixed dog, with protein-losing enteropathy (PLE). He had a history of chronic vomiting and diarrhea with anorexia/hyporexia. Previously he suffered acute abdomen about eight months prior to this visit. Our dog showed uncommon combination of diseases that could cause PLE since it was affected by inflammatory bowel disease (IBD), intestinal lymphangiectasia (IL), and exocrine pancreatic insufficiency (EPI). The dog had most of the abnormalities found in IL, as well as hypoalbuminemia, hyperglobulinemia, lymphopenia, hypocalcemia, and hypercholesterolemia. During endoscopy exam, we found changes characteristic of IL such as irregular small white spots. We took biopsies from stomach, duodenum, and cecum. These biopsies showed infiltration by lymphocytes and plasmatic cells in the lamina propria also, the duodenal biopsies showed moderate dilation of the lymphatic vessels. The patient had 2.1 µg/mL of TLI, this result was compatible with EPI. We assume that the first pathology in this animal was IBD, which caused chronic pancreatitis (CP) that in turn progressed to EPI. It is also possible that IL was secondary to IBD. We have reported for the first time the correlation of IBD and EPI in dogs. This should change our approach to treating chronic diarrhea in dogs. Therefore, we propose that dogs diagnosed with EPI should also be subjected to endoscopy and intestinal biopsy. Similarly, to rule out secondary EPI, TLI should be measured routinely in dogs with IBD.

  11. Secretin-stimulated ultrasound estimation of pancreatic secretion in cystic fibrosis validated by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Engjom, Trond; Dimcevski, Georg; Tjora, Erling; Wathle, Gaute; Erchinger, Friedemann; Laerum, Birger N.; Gilja, Odd H.; Haldorsen, Ingfrid Salvesen

    2018-01-01

    Secretin-stimulated magnetic resonance imaging (s-MRI) is the best validated radiological modality assessing pancreatic secretion. The purpose of this study was to compare volume output measures from secretin-stimulated transabdominal ultrasonography (s-US) to s-MRI for the diagnosis of exocrine pancreatic failure in cystic fibrosis (CF). We performed transabdominal ultrasonography and MRI before and at timed intervals during 15 minutes after secretin stimulation in 21 CF patients and 13 healthy controls. To clearly identify the subjects with reduced exocrine pancreatic function, we classified CF patients as pancreas-sufficient or -insufficient by secretin-stimulated endoscopic short test and faecal elastase. Pancreas-insufficient CF patients had reduced pancreatic secretions compared to pancreas-sufficient subjects based on both imaging modalities (p < 0.001). Volume output estimates assessed by s-US correlated to that of s-MRI (r = 0.56-0.62; p < 0.001). Both s-US (AUC: 0.88) and s-MRI (AUC: 0.99) demonstrated good diagnostic accuracy for exocrine pancreatic failure. Pancreatic volume-output estimated by s-US corresponds well to exocrine pancreatic function in CF patients and yields comparable results to that of s-MRI. s-US provides a simple and feasible tool in the assessment of pancreatic secretion. (orig.)

  12. Pancreatic scintigraphy in diabetes mellitus

    International Nuclear Information System (INIS)

    Shio, Hiroshi; Ueki, Jyuichi; Nomura, Kozi; Nakamura, Yoshifumi

    1983-01-01

    Pancreatic scintigraphy was performed on 67 diabetic patients (42 males and 25 females) in order to study exocrine pancreatic functions in primary diabetes. Relationships between visualization and the onset age, sex, morbid period, presence or absence of retinitis, good or poor control of blood glucose control and the therapeutic modality of diabetes were examined. Abnormality was detected in 34 cases (50.7%), being frequent among male patients in their 50s. The more serious the diabetes, i.e., with a longer morbid period, poorer blood glucose control and worse retinitis, the higher was the frequency of abnormality in pancreatic visualization. The frequency of abnormality was high in association with insulin treatment, oral tablets and single dietary treatment in that order. The more severe the hypoinsulinism, the higher was the frequency of abnormality. This technique can be used as a screening means for exocrine pancreatic function tests on diabetics. (Chiba, N.)

  13. Starch Origin and Thermal Processing Affect Starch Digestion in a Minipig Model of Pancreatic Exocrine Insufficiency.

    Science.gov (United States)

    Mößeler, Anne; Vagt, Sandra; Beyerbach, Martin; Kamphues, Josef

    2015-01-01

    Although steatorrhea is the most obvious symptom of pancreatic exocrine insufficiency (PEI), enzymatic digestion of protein and starch is also impaired. Low praecaecal digestibility of starch causes a forced microbial fermentation accounting for energy losses and meteorism. To optimise dietetic measures, knowledge of praecaecal digestibility of starch is needed but such information from PEI patients is rare. Minipigs fitted with an ileocaecal fistula with (n = 3) or without (n = 3) pancreatic duct ligation (PL) were used to estimate the rate of praecaecal disappearance (pcD) of starch. Different botanical sources of starch (rice, amaranth, potato, and pea) were fed either raw or cooked. In the controls (C), there was an almost complete pcD (>92%) except for potato starch (61.5%) which was significantly lower. In PL pcD of raw starch was significantly lower for all sources of starch except for amaranth (87.9%). Thermal processing increased pcD in PL, reaching values of C for starch from rice, potato, and pea. This study clearly underlines the need for precise specification of starch used for patients with specific dietetic needs like PEI. Data should be generated in suitable animal models or patients as tests in healthy individuals would not have given similar conclusions.

  14. Starch Origin and Thermal Processing Affect Starch Digestion in a Minipig Model of Pancreatic Exocrine Insufficiency

    Directory of Open Access Journals (Sweden)

    Anne Mößeler

    2015-01-01

    Full Text Available Although steatorrhea is the most obvious symptom of pancreatic exocrine insufficiency (PEI, enzymatic digestion of protein and starch is also impaired. Low praecaecal digestibility of starch causes a forced microbial fermentation accounting for energy losses and meteorism. To optimise dietetic measures, knowledge of praecaecal digestibility of starch is needed but such information from PEI patients is rare. Minipigs fitted with an ileocaecal fistula with (n=3 or without (n=3 pancreatic duct ligation (PL were used to estimate the rate of praecaecal disappearance (pcD of starch. Different botanical sources of starch (rice, amaranth, potato, and pea were fed either raw or cooked. In the controls (C, there was an almost complete pcD (>92% except for potato starch (61.5% which was significantly lower. In PL pcD of raw starch was significantly lower for all sources of starch except for amaranth (87.9%. Thermal processing increased pcD in PL, reaching values of C for starch from rice, potato, and pea. This study clearly underlines the need for precise specification of starch used for patients with specific dietetic needs like PEI. Data should be generated in suitable animal models or patients as tests in healthy individuals would not have given similar conclusions.

  15. 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 ...

  16. 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.

  17. ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

    OpenAIRE

    P. V. Novokhatny

    2014-01-01

    Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study...

  18. Purinergic receptors in the endocrine and exocrine pancreas

    DEFF Research Database (Denmark)

    Novak, I

    2008-01-01

    The pancreas is a complex gland performing both endocrine and exocrine functions. In recent years there has been increasing evidence that both endocrine and exocrine cells possess purinergic receptors, which influence processes such as insulin secretion and epithelial ion transport. Most commonly......, there is also evidence for other P2 and adenosine receptors in beta cells (P2Y(2), P2Y(4), P2Y(6), P2X subtypes and A(1) receptors) and in glucagon-secreting alpha cells (P2X(7), A(2) receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors...

  19. Pancreatic Aquaporin-7: A Novel Target for Anti-diabetic Drugs?

    Science.gov (United States)

    Méndez-Giménez, Leire; Ezquerro, Silvia; da Silva, Inês V; Soveral, Graça; Frühbeck, Gema; Rodríguez, Amaia

    2018-01-01

    Aquaporins comprise a family of 13 members of water channels (AQP0-12) that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5, and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells) is composed by the islets of Langerhans, which are distributed in α, β, δ, ε, and pancreatic polypeptide (PP) cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic β-cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced β-cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in β-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion through the increase of intracytoplasmic glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function mutations of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is focused on the role

  20. Pancreatic aquaporin-7: a novel target for anti-diabetic drugs?

    Science.gov (United States)

    Méndez-Giménez, Leire; Ezquerro, Silvia; da Silva, Inês V.; Soveral, Graça; Frühbeck, Gema; Rodríguez, Amaia

    2018-04-01

    Aquaporins comprise a family of 13 members of water channels (AQP0-12) that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5 and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells) is composed by the islets of Langerhans, which are distributed in ,, ,  and pancreatic polypeptide (PP) cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic -cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced -cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in β-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function variants of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is focused on the role of

  1. Pancreatic Aquaporin-7: A Novel Target for Anti-diabetic Drugs?

    Directory of Open Access Journals (Sweden)

    Leire Méndez-Giménez

    2018-04-01

    Full Text Available Aquaporins comprise a family of 13 members of water channels (AQP0-12 that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5, and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells is composed by the islets of Langerhans, which are distributed in α, β, δ, ε, and pancreatic polypeptide (PP cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic β-cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced β-cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in β-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion through the increase of intracytoplasmic glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function mutations of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is

  2. [Exocrine function of the pancreas in rats with experimental obesity].

    Science.gov (United States)

    Leshchenko, I V; Shevchuk, V H; Savcheniuk, O A; Falalieieva, T M; Sukhodolia, S A; Berehova, T V

    2014-01-01

    The influence of neonatal administration of hyperosmolar sodium chloride and sodium glutamate on the exocrine function of the pancreas in rats has been investigated. It was observed the development of acute pancreatitis under experimental obesity. The cross-section area of acini reduced by 12%, the cross-section area of acinocytes nuclei increased by 10%, the length between the lobes of the gland has grown by 48%. The level of amylase was increased by 43%, the levels of pancreatic amylase and lipase were increased by 68% and 24%, respectively.

  3. Exocrine cell-derived microparticles in response to lipopolysaccharide promote endocrine dysfunction in cystic fibrosis.

    Science.gov (United States)

    Constantinescu, Andrei Alexandru; Gleizes, Céline; Alhosin, Mahmoud; Yala, Elhassan; Zobairi, Fatiha; Leclercq, Alexandre; Stoian, Gheorghe; Mitrea, Ioan Liviu; Prévost, Gilles; Toti, Florence; Kessler, Laurence

    2014-03-01

    Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas alteration followed by endocrine dysfunction at a later stage. Microparticles (MPs) are plasma membrane fragments shed from stimulated or damaged cells that act as cellular effectors. Our aim was to identify a new form of interaction between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the context of recurrent infection in CF. MPs from either human exocrine CFTRΔF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1) cells were collected after treatment by LPS from Pseudomonas aeruginosa and applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane integration in target cells was established by confocal microscopy and flow cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin secretion were measured after 18 h. MP-mediated NF-κB activation was measured in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by Western blot. In endocrine normal cells, CFTR inhibition was achieved using Inhibitor-172. Compared to PANC-1, MPs from CFPAC-1 significantly reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF-κB activation by increasing the level of IκB phosphorylation. Moreover, the inhibition of NF-κB activation using specific inhibitors was associated with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN-m5F cells promoted apoptosis and decreased insulin secretion. During recurrent infections associated with CF, exocrine MPs may contribute to endocrine cell dysfunction via NF-κB pathways. Membrane CFTR dysfunction is associated with decreased insulin secretion. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

  4. ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

    Directory of Open Access Journals (Sweden)

    P. V. Novokhatny

    2014-02-01

    Full Text Available Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study the endocrine function of pancreas in acute pancreatitis. To define the role of endocrine pancreatic function in the etiology and pathogenesis of the acute pancreatitis. To assess the prospects of the use of pancreatic hormones in the treatment and predicting the outcomes of acute pancreatitis. Materials and methods of the research Survey of publications in specialized periodical medical journals, PubMed sources developed by the National Center for Biotechnology Information. Search in PubMed was carried out in the following databases: MEDLINE, Pre MEDLINE. Results of the research. In a significant proportion of patients who recovered from acute pancreatitis, exocrine and endocrine functional impairments were found. This finding was not detected only in patients after severe acute pancreatitis. Routine evaluation of pancreatic function after acute pancreatitis should be considered. The comparative analysis of the synthetic analogues (somatostatin, calcitonin, leu-enkefalin-dalargin influence on the glucose metabolism of rats in acute pancreatitis of was made. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon. It was detected that pancreatic renin-angiotensin system is markedly activated in the experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic renin-angiotensin system by

  5. The modified Puestow procedure for chronic relapsing pancreatitis in children.

    Science.gov (United States)

    Crombleholme, T M; deLorimier, A A; Way, L W; Adzick, N S; Longaker, M T; Harrison, M R

    1990-07-01

    Chronic relapsing pancreatitis in children is an unusual condition that often goes undiagnosed and untreated for years. In light of recent reports in adults that endocrine and exocrine function may be preserved by early pancreaticojejunostomy, we reviewed our experience with this procedure (one Duval, 10 Puestows) in 10 children between 1969 and 1989. The underlying etiology was familial pancreatitis in four patients, one case of unknown etiology, congenital ductal anomalies in four (one pancreas divisum, one annular pancreas, one choledochal cyst, and one ductal stenosis), and posttraumatic in one. All 10 had intractable recurrent abdominal pain. Preoperatively, only three patients evidenced exocrine insufficiency and none had endocrine insufficiency. There was complete resolution of pain in eight patients and improvement in two during a mean observation period of 4 years (range, 7 months to 19.75 years). Exocrine insufficiency resolved in two patients but has persisted in the third patient now on Viokase. Endocrine insufficiency has developed during follow-up in one patient. Pancreaticojejunostomy provides excellent relief of recurrent pain in chronic relapsing pancreatitis in children. Endoscopic retrograde cholangiopancreatography (ERCP) is indicated when the diagnosis of chronic relapsing pancreatitis is suspected to define the ductal anatomy. Pancreaticojejunostomy may prevent the progression of exocrine and endocrine insufficiency if performed early in the course of the disease.

  6. Effects of pancreatic intraductal injection of a radioisotope in dogs

    International Nuclear Information System (INIS)

    Devonec, M.; Faure, J.L.; Blanc-Brunat, N.; Dubernard, J.M.; Traeger, J.

    1980-01-01

    The effects on exocrine and endocrine pancreatic functions of local irradiation by the intraductal injection of Rhenium 186 were investigated as an alternative to neoprene for exocrine secretion suppression. The results indicate that Rhenium 186 irradiation suppressed exocrine secretion of the pancreas while conserving the endocrine function. Although some edema and fibrosis were observed, the effects were not excessive

  7. On the regulatory functions of neuropeptide Y (NPY) with respect to vascular resistance and exocrine and endocrine secretion in the pig pancreas

    DEFF Research Database (Denmark)

    Holst, J J; Orskov, C; Knuhtsen, S

    1989-01-01

    We compared the effects of electrical stimulation of the splanchnic nerves and infusions of neuropeptide Y, noradrenaline or a combination of the two on pancreatic vascular resistance and exocrine and endocrine secretion. For these studies we used isolated perfused pig pancreas with preserved...... splanchnic nerve supply. The exocrine secretion was stimulated with physiological concentrations of secretin and cholecystokinin octapeptide. Noradrenaline and NPY at 10(-8) M both increased pancreatic perfusion pressure. Their effects were additive and similar in magnitude to that of electrical stimulation...

  8. The significance of pancreatic juice trace-element concentration in chronic pancreatitis

    International Nuclear Information System (INIS)

    Persigehl, M.; Loeffler, A.; Hoeck, A.

    1979-01-01

    The diagnosis of exocrine pancreas insufficiency in patients with chronic pancreatitis is still not easy. The best-suited method to confirm the diagnosis seems to be the secretin pancreozymin test (SPT). As previous results have shown, the determination of trace elements in the pancreatic juice can improve the diagnostic value of the SPT. During the SPT, the concentrations of Zn, Fe, Rb, Co, Cr, Se, Sb, Cs, Sc and Ag were measured in the duodenal aspirate of 50 patients by instrumental neutron activation analysis. Of the 50 patients, 24 suffered from pancreatic insufficiency in chronic pancreatitis and 26 had no signs of pancreatic insufficiency. Only the concentration of zinc differed significantly in the two groups; the other elements showed a similar behaviour. In patients without disease of the exocrine pancreas the zinc content of the pancreatic juice during the SPT ws 0.46+-0.13μg/ml, whereas in patients with pancreatic insufficiency it was only 0.18+-0.07μg/ml. The corresponding output was 171+-49.3μg zinc in controls and 41+-17.4μg in patients. After stimulation with pancreozymin the concentrations of zinc increased in normal patients to 1.13+-0.14μg/ml and to 0.22+-0.12μg/ml in patients with pancreatic insufficiency. The data demonstrate that the measurement of zinc in the duodenal juice during the SPT improves the diagnostic value of the test and that zinc should also be determined in doubtful cases of pancreatic insufficiency. (author)

  9. Prececal digestibility of various sources of starch in minipigs with or without experimentally induced exocrine pancreatic insufficiency.

    Science.gov (United States)

    Mösseler, A; Kramer, N; Becker, C; Gregory, P C; Kamphues, J

    2012-12-01

    Low prececal digestibility of starch leads to a higher starch flux into the hindgut, causing a forced microbial fermentation, energy losses, and meteorism. For exocrine pancreatic insufficiency (EPI), lack of pancreatic amylase can be compensated mostly by hindgut fermentation of starch. Even in pigs with complete loss of pancreatic secretion, starch digestibility over the entire tract is reaching levels of controls. To optimize diets for human patients with EPI, the proportion of starch that is digested by the ileum is important. Minipigs were fitted with an ileocecal reentrant fistula (n = 8) to determine prececal digestibility of starch. In 5 minipigs the pancreatic duct was ligated (PL) to induce EPI; 3 minipigs served as controls (Con). Various starch sources were tested in a 1-d screening test; therefore, disappearance rate (DR) instead of digestibility was used. Test meals consisted of 169 g DM of a basal diet plus 67.5 g DM of the starch (without thermal treatment; purified; starch content of 89 to 94.5%) and Cr(2)O(3). The test meal contained (% of DM) starch, 67; crude fat, 1.69; CP, 15; crude fiber, 2.0; and Cr(2)O(3), 0.25. In PL, prececal DR of starch was lower than in Con (P 90%) but was lower (P < 0.05) for potato (Solanum tuberosum) starch (75.4%). In PL, prececal DR of starch was higher (P < 0.05) for wheat (Triticum aestivum) starch (61.2%) than corn (Zea mays) starch (43.0%) and rice (Oryza sativa) starch (29.2%) and intermediate for potato and field pea (Pisum sativum) starch. For patients with EPI, wheat starch seems favorable due to the higher prececal digestibility whereas raw corn and rice starch should be avoided.

  10. 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.

  11. Pancreatic cellular injury after cardiac surgery with cardiopulmonary bypass: frequency, time course and risk factors.

    Science.gov (United States)

    Nys, Monique; Venneman, Ingrid; Deby-Dupont, Ginette; Preiser, Jean-Charles; Vanbelle, Sophie; Albert, Adelin; Camus, Gérard; Damas, Pierre; Larbuisson, Robert; Lamy, Maurice

    2007-05-01

    Although often clinically silent, pancreatic cellular injury (PCI) is relatively frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and time course are largely unknown. We defined PCI as the simultaneous presence of abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The frequency and time evolution of PCI were assessed in this condition using assays for specific exocrine pancreatic enzymes. Correlations with inflammatory markers were searched for preoperative risk factors. One hundred ninety-three patients submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase, pancreatic isoamylase, lipase, and markers of inflammation (alpha1-protease inhibitor, alpha2-macroglobulin, myeloperoxidase) were measured preoperatively and postoperatively until day 8. The postoperative increase in plasma levels of pancreatic enzymes and urinary IRT was biphasic in all patients: early after surgery and later (from day 4 to 8 after surgery). One hundred thirty-three patients (69%) experienced PCI, with mean IRT, isoamylase, and alpha1-protease inhibitor values higher for each sample than that in patients without PCI. By multiple regression analysis, we found preoperative values of plasma IRT >or=40 ng/mL, amylase >or=42 IU/mL, and pancreatic isoamylase >or=20 IU/L associated with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a significant correlation was found between the 4 pancreatic enzymes and urinary IRT, total calcium, myeloperoxidase, alpha1-protease inhibitor, and alpha2-macroglobulin. These data support a high prevalence of postoperative PCI after cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically silent, especially when pancreatic enzymes were elevated preoperatively.

  12. 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

  13. Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe Deer

    OpenAIRE

    Guilloteau, Paul; Vitari, Francesca; Meuth, Valérie Metzinger-Le; Le Normand, Laurence; Romé, Véronique; Savary, Gérard; Delaby, Luc; Domeneghini, Cinzia; Morisset, Jean

    2012-01-01

    Abstract Background Physiology of the exocrine pancreas has been well studied in domestic and in laboratory animals as well as in humans. However, it remains quite unknown in wildlife mammals. Roe deer and cattle (including calf) belong to different families but have a common ancestor. This work aimed to evaluate in the Roe deer, the adaptation to diet of the exocrine pancreatic functions and regulations related to animal evolution and domestication. Results Forty bovine were distributed into...

  14. Early postoperative and late metabolic morbidity after pancreatic resections: An old and new challenge for surgeons - A review.

    Science.gov (United States)

    Beger, Hans G; Mayer, Benjamin

    2018-02-16

    The metrics for measuring early postoperative morbidity after resection of pancreatic neoplastic tumors are overall morbidity, severe surgery-related morbidity, frequency of reoperation and reintervention, in-hospital, 30-day and 90-day mortality and length of hospital stay. Thirty-day readmission after discharge is additionally an indispensable criterion to assess quality of surgery. The metrics for surgery-associated long-term results after pancreatic resections are survival times, new onset of diabetes (DM), impaired glucose tolerance, exocrine pancreatic insufficiency, body mass index and GI motility dysfunctions. Following pancreaticoduodenectomy (PD) performed on pancreatic normo-glycemic patients for malignant and benign tumors, 4-30% develop postoperative new onset of diabetes. Long-term persistence of diabetes mellitus is observed after surgery for benign tumors in 14% and in 15.5% of patients after cancer resection. Pancreatic exocrine insufficiency after PD is observed in the early postoperative period in 23-80% of patients. Persistence of exocrine dysfunctions exists in 25% and 49% of patients. Following left-sided pancreatic resection, new onset DM is observed in 14% of cases; an exocrine insufficiency persisting in the long-term outcome is observed in 16-28% of patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Central pancreatectomy for benign pancreatic pathology/trauma: is it a reasonable pancreas-preserving conservative surgical strategy alternative to standard major pancreatic resection?

    Science.gov (United States)

    Johnson, Maria A; Rajendran, Shanmugasundaram; Balachandar, Tirupporur G; Kannan, Devy G; Jeswanth, Satyanesan; Ravichandran, Palaniappan; Surendran, Rajagopal

    2006-11-01

    The aim of this study was to assess the technical feasibility, safety and outcome of central pancreatectomy (CP) with pancreaticogastrostomy or pancreaticojejunostomy in appropriately selected patients with benign central pancreatic pathology/trauma. Benign lesions/trauma of the pancreatic neck and proximal body pose an interesting surgical challenge. CP is an operation that allows resection of benign tumours located in the pancreatic isthmus that are not suitable for enucleation. Between January 2000 and December 2005, eight central pancreatectomies were carried out. There were six women and two men with a mean age of 35.7 years. The cephalic pancreatic stump is oversewn and the distal stump is anastomosed end-to-end with a Roux-en-Y jejunal loop in two and with the stomach in six patients. The indications for CP were: non-functional islet cell tumours in two patients, traumatic pancreatic neck transection in two and one each for insulinoma, solid pseudopapillary tumour, splenic artery pseudoaneurysm and pseudocyst. Pancreatic exocrine function was evaluated by a questionnaire method. Endocrine function was evaluated by blood glucose level. Morbidity rate was 37.5% with no operative mortality. Mean postoperative hospital stay was 10.5 days. Neither of the patients developed pancreatic fistula nor required reoperations or interventional radiological procedures. At a mean follow up of 26.4 months, no patient had evidence of endocrine or exocrine pancreatic insufficiency, all the patients were alive and well without clinical and imaging evidence of disease recurrence. When technically feasible, CP is a safe, pancreas-preserving pancreatectomy for non-enucleable benign pancreatic pathology/trauma confined to pancreatic isthmus that allows for cure of the disease without loss of substantial amount of normal pancreatic parenchyma with preservation of exocrine/endocrine function and without interruption of enteric continuity.

  16. The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas.

    Science.gov (United States)

    Hegyi, Péter; Rakonczay, Zoltán

    2011-11-15

    Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role of NO in the pathogenesis of acute pancreatitis and pancreatic ischemia/reperfusion injury. Unfortunately, the role of NO in pancreatic physiology and pathophysiology remains controversial in numerous areas. Many questions regarding the messenger molecule still remain unanswered. Probably the least is known about the downstream targets of NO, which need to be identified, especially at the molecular level.

  17. Elevation of serum pancreatic amylase and distortion of pancreatic ...

    African Journals Online (AJOL)

    Background: Diabetes mellitus has been shown to cause severe impairment in exocrine pancreatic function and cyto-architecture. Ocimum grattissimum has been reported to lower blood glucose levels in experimental diabetic animals. This study, therefore, aims to investigate if treatment with O. grattissimum can alleviate ...

  18. The density of parasympathetic axons is reduced in the exocrine pancreas of individuals recently diagnosed with type 1 diabetes.

    Science.gov (United States)

    Lundberg, Marcus; Lindqvist, Andreas; Wierup, Nils; Krogvold, Lars; Dahl-Jørgensen, Knut; Skog, Oskar

    2017-01-01

    To elucidate the etiology of type 1 diabetes, the affected pancreas needs to be thoroughly characterized. Pancreatic innervation has been suggested to be involved in the pathology of the disease and a reduction of sympathetic innervation of the islets was recently reported. In the present study, we hypothesized that parasympathetic innervation would be altered in the type 1 diabetes pancreas. Human pancreatic specimens were obtained from a unique cohort of individuals with recent onset or long standing type 1 diabetes. Density of parasympathetic axons was assessed by immunofluorescence and morphometry. Our main finding was a reduced density of parasympathetic axons in the exocrine, but not endocrine compartment of the pancreas in individuals with recent onset type 1 diabetes. The reduced density of parasympathetic axons in the exocrine compartment could have functional implications, e.g. be related to the exocrine insufficiency reported in type 1 diabetes patients. Further studies are needed to understand whether reduced parasympathetic innervation is a cause or consequence of type 1 diabetes.

  19. 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.

  20. surgical treatment for chronic pancreatitis: report of three cases

    Directory of Open Access Journals (Sweden)

    Abdollahi A

    2009-01-01

    Full Text Available "nBackground: Chronic pancreatitis is a progressive fibrosis of the pancreas that leads to loss of endocrine and exocrine function of pancreas. The most common symptom is intractable pain. Which adversely effects quality of life, remains the most common indication for surgery in patients with chronic pancreatitis. Case report: Three patients underwent operations for chronic pancreatitis at the Ghaem hospital, Mashhad University of Medical Sciences Mashhad, Iran. Indication for operation in all cases were intractable abdominal pain. In all of the three patients complete relief of symptoms was obtained. There was no morbidity and mortality. In one patient exocrine function of pancreas and malabsorpation resolved after surgery. Conclusions: Although chronic pancreatitis is uncommon, but in persistent abdominal pain surgery should be considered. Surgery for patients with chronic pancreatitis can be performed safely with minimal morbidity and effective in control of pain and malabsorption.  

  1. Effects of pancreatic digestive enzymes, sodium bicarbonate, and a proton pump inhibitor on steatorrhoea caused by pancreatic diseases.

    Science.gov (United States)

    Nakamura, T; Takebe, K; Kudoh, K; Ishii, M; Imamura, K; Kikuchi, H; Kasai, F; Tandoh, Y; Yamada, N; Arai, Y

    1995-01-01

    Forty-five patients with pancreatic steatorrhoea (27 with calcified pancreatitis, 13 with non-calcified pancreatitis, two with pancreaticoduodenectomy, one with total pancreatectomy, and two with pancreatic cancer) were divided into four groups and given the following medication for 2 to 4 weeks: 4 to 6 g/day of sodium bicarbonate (group I); 9 g/day of high-lipase pancreatin (lipase, 56,600 U/g, Fédération Internationale Pharmaceutique (FIP); group II); 12 to 24 tablets or 9.0 g of commercial pancreatic enzyme preparations (group III); or 50 mg of omeprazole (group IV). Faecal fat excretion was evaluated before and after drug administration. Faecal fat excretion was reduced by 2.9 g (range, 1.7 to 5.0 g) in group I; 8.8 g (range, 2.9 to 39.9 g) in group II; 10.8 g (range, 2.3 to 21.8 g) in group III; and 4.3 g (range, 3.6 to 5.6 g) in group IV. The pancreatic digestive enzyme preparation was more effective than sodium bicarbonate and agents that raise the pH of the upper small intestine (such as proton-pump inhibitors) in reducing faecal fat excretion. The results indicate that all of the preparations used are effective against mild pancreatic steatorrhoea. If the condition is more advanced, however, a massive dosage of pancreatic digestive enzyme and possibly the combined use of an agent to raise the pH of the upper small intestine are likely to be effective.

  2. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-03

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  3. 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.

  4. Functional pancreatic insufficiency after surgical treatment in the light of the latest international recommendations

    Directory of Open Access Journals (Sweden)

    D. S. Bordin

    2017-01-01

    Full Text Available Exocrine  and  endocrine   insufficiencies  are  frequent complications of surgical treatment for pancreatic diseases. The presence  and  extent  of the insufficiency depend on the underlying  disorder, type of surgical procedure, extent of pancreatic resection, and anatomical reconstruction. Increased surgical  activity  determines  the  importance  of the  evidence-based guidelines  for management of patients  after  pancreatic  surgery. The article presents  an  overview of international Evidence-based Guidelines for the Management of Exocrine Pancreatic  Insufficiency after  Pancreatic  Surgery (2016 and United European Gastroenterology evidence-based guidelines  for the  diagnosis  and therapy of chronic pancreatitis (HaPanEU, 2017.

  5. Asymptomatic and persistent elevation of pancreatic enzymes in an ulcerative colitis patient.

    Science.gov (United States)

    Liverani, Elisa; Leonardi, Filippo; Castellani, Lucia; Cardamone, Carla; Belluzzi, Andrea

    2013-01-01

    Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis at imaging. This evidence brought us to reassess the drug dosage, without achieving a normalization of biochemical analysis. Autoimmune pancreatitis was excluded. One year after the suspension of azathioprine, we still face persistent high levels of amylase/lipase. Normalization of enzymatic values in patients who develop intolerance to azathioprine, in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis, is usually achieved in about two months after stopping drug intake. Asymptomatic elevation in serum pancreatic enzymes in the absence of pancreatic disease is reported in the literature and defined as "Gullo's syndrome," but nobody of the subjects studied had been treated in the past with pancreatotoxic drugs. Might this case be defined as "benign pancreatic hyperenzymemia"?

  6. Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Idziak Joanna

    2011-01-01

    Full Text Available Abstract Background Structural changes occur in the pancreas as a part of the natural aging process. With aging, also the incidence of maldigestive symptoms and malnutrition increases, raising the possibility that these might be caused at least in part by inadequate pancreatic enzyme secretion due to degenerative processes and damage of the gland. Fecal elastase-1 is a good marker of pancreatic exocrine secretion. The aim of this study was to investigate the fecal elastase-1 levels among over 60 years old Finnish and Polish healthy individuals without any special diet, known gastrointestinal disease, surgery or diabetes mellitus. Methods A total of 159 patients participated in this cross-sectional study. 106 older individuals (aged 60-92 years were recruited from outpatient clinics and elderly homes. They were divided to three age groups: 60-69 years old (n = 31; 70-79 years old (n = 38 and over 80 years old (n = 37. 53 young subjects (20-28 years old were investigated as controls. Inclusion criteria were age over 60 years, normal status and competence. Exclusion criteria were any special diet, diabetes mellitus, any known gastrointestinal disease or prior gastrointestinal surgery. Fecal elastase-1 concentration was measured from stool samples with an ELISA that uses two monoclonal antibodies against different epitopes of human elastase-1. Results Fecal elastase-1 concentrations correlated negatively with age (Pearson r = -0,3531, P P Conclusion In our study one fifth of healthy older individuals without any gastrointestinal disorder, surgery or diabetes mellitus suffer from pancreatic exocrine insufficiency and might benefit from enzyme supplementation therapy.

  7. Effect of acute irradiation on the exocrine secretion of the pancreas in the pig

    International Nuclear Information System (INIS)

    Corring, T.; Daburon, F.; Remy, J.

    1975-01-01

    Six fistulated pigs have been used in this experiment to study the effect on the exocrine pancreatic secretion of a partial acute irradiation at 600 rd and 800 rd. Whatever the dose, the irradiation provoked an immediate and temporary decrease of the pancreatic secretion. The normal values were reached after the 8th day post-irradiation. Furthermore, a direct effect on the synthesis of amylase and lipase was shown. The synthesis of trypsin and chymotrypsin was scarcely modified by irradiation. (orig.) [de

  8. Ten years of experience with transgastric necrosectomy for walled-off necrosis in acute pancreatitis

    DEFF Research Database (Denmark)

    Busse, Malene Just; Ainsworth, Alan Patrick

    2015-01-01

    : Acute pancreatitis with walled-off necrosis has a high mortality rate. Need for additional therapy following necrosectomy was associated with fatal outcome. Endocrine and exocrine insufficiency was often seen at follow-up. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Danish Data....... Ten patients (20%) died during their admission to our department. In total, 18 (45%) patients developed late complications defined as endocrine and/or exocrine malfunction of the pancreas (diabetes (n = 10), exocrine insufficiency (n = 4), both diabetes and exocrine insufficiency (n = 4)). CONCLUSION......INTRODUCTION: The aim of this study was to report our results with open transgastric necrosectomy for walled-off necrosis in acute pancreatitis over a period of ten years. METHODS: Patients operated at the department from 2003 until 2012 were studied retrospectively. RESULTS: A total of 50 patients...

  9. 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.)

  10. 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.)

  11. [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.

  12. The density of parasympathetic axons is reduced in the exocrine pancreas of individuals recently diagnosed with type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Marcus Lundberg

    Full Text Available To elucidate the etiology of type 1 diabetes, the affected pancreas needs to be thoroughly characterized. Pancreatic innervation has been suggested to be involved in the pathology of the disease and a reduction of sympathetic innervation of the islets was recently reported. In the present study, we hypothesized that parasympathetic innervation would be altered in the type 1 diabetes pancreas. Human pancreatic specimens were obtained from a unique cohort of individuals with recent onset or long standing type 1 diabetes. Density of parasympathetic axons was assessed by immunofluorescence and morphometry. Our main finding was a reduced density of parasympathetic axons in the exocrine, but not endocrine compartment of the pancreas in individuals with recent onset type 1 diabetes. The reduced density of parasympathetic axons in the exocrine compartment could have functional implications, e.g. be related to the exocrine insufficiency reported in type 1 diabetes patients. Further studies are needed to understand whether reduced parasympathetic innervation is a cause or consequence of type 1 diabetes.

  13. Asymptomatic and Persistent Elevation of Pancreatic Enzymes in an Ulcerative Colitis Patient

    Directory of Open Access Journals (Sweden)

    Elisa Liverani

    2013-01-01

    Full Text Available Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis at imaging. This evidence brought us to reassess the drug dosage, without achieving a normalization of biochemical analysis. Autoimmune pancreatitis was excluded. One year after the suspension of azathioprine, we still face persistent high levels of amylase/lipase. Normalization of enzymatic values in patients who develop intolerance to azathioprine, in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis, is usually achieved in about two months after stopping drug intake. Asymptomatic elevation in serum pancreatic enzymes in the absence of pancreatic disease is reported in the literature and defined as “Gullo’s syndrome,” but nobody of the subjects studied had been treated in the past with pancreatotoxic drugs. Might this case be defined as “benign pancreatic hyperenzymemia”?

  14. The experimental study of the pancreatic enhancement on MR imaging with Mn-DPDP

    International Nuclear Information System (INIS)

    Gong Jingshan; Zhou Kangrong; Zeng Mengsu; Peng Weijun; Yan Fuhua; Shen Jizhang; Chen Caizhong; Shi Weibin; Zhang Shujie

    2002-01-01

    Objective: To investigate whether the exocrine glandular cells of the pancreas take in Mn-DPDP or its metabolite. Methods: A fistula tube was inserted into the major pancreatic duct through the major duodenal papillae in a group of six male dogs. The pancreatic juice was collected before and after the intravenous infusion of Mn-DPDP at a rate of 2-3 ml/min with a dose of 2 ml/kg body weight. The Mn content of pancreatic juice was measured using atomic absorption spectroscopy (AAS). T 1 -weighted spin-echo images and SPGR T 1 W images were obtained prior to and approximately 30 min after the administration of Mn-DPDP. Results: The Mn content of the pancreatic juice increased by (6.17 x 10 -3 - 1.58 x 10 -2 ) mmol/L (median 1.09 x 10 -2 mmol/L) after the administration of Mn-DPDP with statistical significance (Z = 2.20, P 1 -weighted spin echo images and SPGR images, respectively. Conclusion: The experimental study confirmed that the exocrine glandular cells of the pancreas could take in the manganese and excrete it through the pancreatic juice, which played a leading role in pancreatic enhancement on MR imaging with Mn-DPDP. The Mn-DPDP-enhanced MRI can be used for diagnosing pancreatic abnormality and has the potential ability to evaluate the exocrine function of the pancreas

  15. Exocrine pancreatic secretion is stimulated in piglets fed Fish oil compared with those fed Coconut Oil or Lard

    DEFF Research Database (Denmark)

    Hedemann, Mette Skou; Pedersen, Asger Roer; Engberg, Ricarda M.

    2001-01-01

    An experiment was conducted to study the effect of feeding diets containing fat sources with different fatty acid composition (fish oil, coconut oil or lard, 10 g/100 g diet) on exocrine pancreatic secretion in piglets after weaning. A total of 16 barrows were weaned at 4 wk of age; 3 d later...... the coconut oil or lard diets. The output [U/(h. kg(0.75))] of lipase was higher in piglets fed fish oil than in piglets fed lard or coconut oil. The output of colipase was greater in piglets fed fish oil and coconut oil than in those fed lard. The dietary treatments did not affect the output of carboxylester...... hydrolase. The output of trypsin was significantly lower in piglets fed lard than in piglets fed fish oil or coconut oil diets and the output of carboxypeptidase B was greater in those fed the fish oil diet. Protein, chymotrypsin, carboxypeptidase A, elastase and amylase outputs did not differ among...

  16. 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...

  17. Polyamine biosynthesis is critical for growth and differentiation of the pancreas

    Science.gov (United States)

    Mastracci, Teresa L.; Robertson, Morgan A.; Mirmira, Raghavendra G.; Anderson, Ryan M.

    2015-01-01

    The pancreas, in most studied vertebrates, is a compound organ with both exocrine and endocrine functions. The exocrine compartment makes and secretes digestive enzymes, while the endocrine compartment, organized into islets of Langerhans, produces hormones that regulate blood glucose. High concentrations of polyamines, which are aliphatic amines, are reported in exocrine and endocrine cells, with insulin-producing β cells showing the highest concentrations. We utilized zebrafish as a model organism, together with pharmacological inhibition or genetic manipulation, to determine how polyamine biosynthesis functions in pancreatic organogenesis. We identified that inhibition of polyamine biosynthesis reduces exocrine pancreas and β cell mass, and that these reductions are at the level of differentiation. Moreover, we demonstrate that inhibition of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, phenocopies inhibition or knockdown of the enzyme deoxyhypusine synthase (DHS). These data identify that the pancreatic requirement for polyamine biosynthesis is largely mediated through a requirement for spermidine for the downstream posttranslational modification of eIF5A by its enzymatic activator DHS, which in turn impacts mRNA translation. Altogether, we have uncovered a role for polyamine biosynthesis in pancreatic organogenesis and identified that it may be possible to exploit polyamine biosynthesis to manipulate pancreatic cell differentiation. PMID:26299433

  18. High fat diet and GLP-1 drugs induce pancreatic injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Rouse, Rodney, E-mail: rodney.rouse@fda.hhs.gov; Xu, Lin; Stewart, Sharron; Zhang, Jun

    2014-04-15

    Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment.

  19. High fat diet and GLP-1 drugs induce pancreatic injury in mice

    International Nuclear Information System (INIS)

    Rouse, Rodney; Xu, Lin; Stewart, Sharron; Zhang, Jun

    2014-01-01

    Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment

  20. Magnetic resonance hydrometry: non-invasive quantification of the exocrine pancreatic function

    International Nuclear Information System (INIS)

    Heverhagen, J.T.; Battmann, A.; Kirsch, M.; Klose, K.J.; Boehm, D.; Eissele, R.; Wagner, H.J.

    2002-01-01

    Aims: To show the ability of magnetic resonance hydrometry (MRH) to quantify the pancreatic secretion after secretin stimulation in order to distinguish between physiological excretion and reduced output in chronic pancreatitis. Methods: MRH images were acquired in a 1.0-T-clinical scanner using a body-array coil and a heavily T 2 -weighted standard single-shot TSE sequence. Thirty-one patients (14 male/17 female) who routinely underwent ERCP for suspected choledocholithiasis (n = 22), recurring abdominal pain (n = 1), icterus (n = 6) and suspected pancreatitis (n = 2) were included. During the investigation 1 CU/kg BW secretin were administered intravenously. Secreted volume of fluid, start of secretion, achievement of a plateau of secretion and a combined score of these parameters (MRH score) were assessed and evaluated. Sensitivity and specificity were calculated for these parameters. Results: 27 patients had no pancreatic pathology, and four suffered from chronic pancreatitis. Patients without pancreatic disorders produced a mean pancreatic fluid volume of 183±86 mL, whereas patients with chronic pancreatitis secreted 61±39 mL. Secretion started after a mean time of 95±94 seconds (no pancreatic impairment) and 62±13 seconds (chronic pancreatitis). The MRH score achieved a high accuracy in the detection of chronic pancreatitis. Conclusions: Our study demonstrated the feasibility of measuring pancreatic output by MRH after stimulation with secretin. Moreover, a distinction between normal secretion and patients with chronic pancreatitis is possible. (orig.) [de

  1. 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)

  2. Immunohistochemical study of tumor markers (CEA, TPA, CA19-9, POA and Ferritin) and pancreatic exocrine enzymes(Amylase and Elastase 1) in pancreatic tumors

    OpenAIRE

    脇谷, 勇夫

    1987-01-01

    The distribution of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA19-9), pancreatic oncofetal antigen (POA), Ferritin, Amylase and Elastase 1 was studied immunohistochemically using an immunoperoxidase method in 26 conventional histopathologic sections of pancreatic tumor. CEA and CA19-9 were regarded as markers secreted into the glandular lumina from cancer cells, but TPA and POA were not. The expression of these markers was different from one...

  3. Phytobiotic Utilization as Feed Additive in Feed for Pancreatic Enzyme Activity of Broiler Chicken

    Directory of Open Access Journals (Sweden)

    Sri Purwanti

    2015-09-01

    Full Text Available This research was conducted to evaluate the effect of turmeric water extract, garlic and combination turmeric and garlic as a feed additive in the broiler diet on pancreatic enzyme activity of broiler chicken. Effectivity of treatments was assessed by addition of phytobiotic (control, 015% zinc bacitracin, 2.5% TE, 2.0% GE, 2.5% TGE which were arranged Completely Randomized Design with 4 replications. The variables measured were pancreatic enzyme activity(amylase enzyme activity, protease enzyme activity  and lipase enzyme activity.The results showed that enzyme protein activity content of 2.5% TE supplementation is also high at 82.02 U/ml, then supplemented 2.5% TGE, 2.0% GE, negative control and positive control respectively 75.98 ; 72.02; 68.74; and 66.57 U/ml. The lipase enzyme activity whereas the negative control and a positive control differ significantly higher (P<0.05 to treatment with the addition of 2.5% TE, 2.0% GE and 2.5% TGE phytobiotic. The research concluded that the incorporation of 2.5% TE, 2% GE and combined 2.5% TGE as feed additive enhanced pancreatic enzyme activity.

  4. The long-term follow up study of acute pancreatitis by means of pancreatic scintigraphy, secretin test and oral glucose tolerance test

    International Nuclear Information System (INIS)

    Satoh, Harukuni

    1975-01-01

    Morphologic and functional alternations of the pancreas following acute pancreatitis were studied in 29 patients. At the time of attack a diagnosis of acute pancreatitis had been confirmed by laparotomy in 27 cases, and by clinical picture and by serum amylase levels in 2 cases. The average duration of follow up was 56.3 months. Normal images were obtained in 17 of 29 cases. According to secretin tests, 4 of these had slight to moderately decreased exocrine function; the test were within normal limits. 12 cases with normal image had abnormal oral glucose tolerance curves similar to those fund in mild to moderate diabetes. 10 of the 12 cases with abnormal scintigrams showed decreased isotope uptake in all or part of the pancreas, while 2 showed no uptake at all. These changes were mast apparent in the tail of the pancreas. Ten of the 12 cases with abnormal images had some degree of decreased exocrine function. All 12 had the abnormal GTT curve of diabetes, 4 who had severe diabetes with markedly decreased exocrine function and poor image of the pancreas. In 4 cases the histopathological findings obtained at the time of laparotomy, were shown to be very consistent with the scintigraphic features. It was demonstrated by both scintigraphs and function tests that the alcoholic factor plays a very important role in the prognosis of acute pancreatitis. Acute pancreatitis resulted in chronic pancreatitis in 4 cases, (14 %) of the remaining 8 cases with abnormal scintigram, it is postulated that the inflamatory process subsided allowing time for cicatrical fibrosis to occur. Follow-up to trace and study of these alternations of the pancreas necessary in future. (Evans, J.)

  5. The long-term follow up study of acute pancreatitis by means of pancreatic scintigraphy, secretin test and oral glucose tolerance test

    Energy Technology Data Exchange (ETDEWEB)

    Satoh, H [Tohoku Univ., Sendai (Japan). School of Medicine

    1975-03-01

    Morphologic and functional alternations of the pancreas following acute pancreatitis were studied in 29 patients. At the time of attack a diagnosis of acute pancreatitis had been confirmed by laparotomy in 27 cases, and by clinical picture and by serum amylase levels in 2 cases. The average duration of follow up was 56.3 months. Normal images were obtained in 17 of 29 cases. According to secretin tests, 4 of these had slight to moderately decreased exocrine function; the test were within normal limits. 12 cases with normal image had abnormal oral glucose tolerance curves similar to those fund in mild to moderate diabetes. 10 of the 12 cases with abnormal scintigrams showed decreased isotope uptake in all or part of the pancreas, while 2 showed no uptake at all. These changes were mast apparent in the tail of the pancreas. Ten of the 12 cases with abnormal images had some degree of decreased exocrine function. All 12 had the abnormal GTT curve of diabetes, 4 who had severe diabetes with markedly decreased exocrine function and poor image of the pancreas. In 4 cases the histopathological findings obtained at the time of laparotomy, were shown to be very consistent with the scintigraphic features. It was demonstrated by both scintigraphs and function tests that the alcoholic factor plays a very important role in the prognosis of acute pancreatitis. Acute pancreatitis resulted in chronic pancreatitis in 4 cases, (14 %) of the remaining 8 cases with abnormal scintigram, it is postulated that the inflamatory process subsided allowing time for cicatrical fibrosis to occur. Follow-up to trace and study of these alternations of the pancreas necessary in future.

  6. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran

    2014-01-01

    food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids......Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases...

  7. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran

    2014-01-01

    food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases......Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion...

  8. Vacuolization of mucolipidosis type II mouse exocrine gland cells represents accumulation of autolysosomes.

    Science.gov (United States)

    Boonen, Marielle; van Meel, Eline; Oorschot, Viola; Klumperman, Judith; Kornfeld, Stuart

    2011-04-15

    We previously reported that mice deficient in UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase (mucolipidosis type II or Gnptab -/- mice), the enzyme that initiates the addition of the mannose 6-phosphate lysosomal sorting signal on acid hydrolases, exhibited extensive vacuolization of their exocrine gland cells, while the liver, brain, and muscle appeared grossly unaffected. Similar pathological findings were observed in several exocrine glands of patients with mucolipidosis II. To understand the basis for this cell type-specific abnormality, we analyzed these tissues in Gnptab -/- mice using a combined immunoelectron microscopy and biochemical approach. We demonstrate that the vacuoles in the exocrine glands are enlarged autolysosomes containing undigested cytoplasmic material that accumulate secondary to deficient lysosomal function. Surprisingly, the acid hydrolase levels in these tissues ranged from normal to modestly decreased, in contrast to skin fibroblasts, which accumulate enlarged lysosomes and/or autolysosomes also but exhibit very low levels of acid hydrolases. We propose that the lysosomal defect in the exocrine cells is caused by the combination of increased secretion of the acid hydrolases via the constitutive pathway along with their entrapment in secretory granules. Taken together, our results provide new insights into the mechanisms of the tissue-specific abnormalities seen in mucolipidosis type II.

  9. Asparaginase-associated pancreatitis is not predicted by hypertriglyceridemia or pancreatic enzyme levels in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, Kjeld; Sørensen, Ditte Nørbo

    2017-01-01

    Background: l-Asparaginase is an important drug for treatment of childhood acute lymphoblastic leukemia (ALL), but is associated with serious toxicities, including pancreatitis and hypertriglyceridemia (HTG). Asparaginase-associated pancreatitis (AAP) is a common reason for stopping asparaginase...... treatment. The aim of this study was to explore if HTG or early elevations in pancreatic enzymes were associated with the subsequent development of AAP. Method: Children (1.0–17.9 years) diagnosed with ALL, treated with asparaginase for 30 weeks, according to the NOPHO ALL2008 protocol at the University...

  10. [Chronic pancreatitis: Retrospective review of 121 cases].

    Science.gov (United States)

    Berger F, Zoltán; Mancilla A, Carla

    2016-12-01

    Chronic pancreatitis (CP) is a rare disease in Chile, without a clear explanation for this low prevalence. To analyze the characteristics of our patients with pancreatitis. Retrospective analysis of a database of patients with pancreatitis of a clinical hospital. Morphological proof of diagnosis (calcifications/calculi, alterations of ducts, local complication or histology) was obtained for every patient. History of acute pancreatitis was recorded and exocrine-endocrine function was assessed. We retrieved information of 121 patients with pancreatitis (86 males) in a period of 20 years. The number of cases increased markedly every five years. The calculated incidence and prevalence was 0.8/100,000/year and 6/100,000, respectively. Pancreatic calcifications were initially observed in 93 patients and became evident during the follow-up in another six patients. Severe pain or local complications occurred in 27 patients, requiring surgery in 10 or endoscopic treatment in 15. During the years of follow-up, 55 patients were free of symptoms. Exocrine and endocrine insufficiency was demonstrated and treated in 81 and 67 patients, respectively. Alcoholic etiology was evident in 40% of patients. In 29% no etiology was identified. Mapuche origin was exceptional. Late diagnosis of CP is common, since most of our patients presented with advanced stages. Even though CP is increasingly diagnosed in our hospitals, the number of cases is still far fewer when compared to other countries. Underdiagnosis alone cannot explain this difference and genetic factors might be of importance.

  11. 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.

  12. 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.

  13. Time course and cellular source of pancreatic regeneration following acute pancreatitis in the rat

    International Nuclear Information System (INIS)

    Elsaesser, H.P.A.; Adler, G.; Kern, H.F.

    1986-01-01

    The regenerative capacity of the different cell types in the rat exocrine pancreas has been studied in a model of hormone-induced acute pancreatitis in which pancreatic edema, inflammation, and acinar cell destruction were induced within 12 h of infusion of supramaximal concentrations of cerulein (5 micrograms/kg/h). A sequential biochemical and structural analysis of the pancreas in daily intervals was combined with the autoradiographic quantitation of labeling indices of five cell populations following 3 H-thymidine injection at days 1-7 after induction of pancreatitis. Desquamation of acinar cell apical cytoplasm and release of cytoplasmic segments into the acinar lumen on the first day following induction of pancreatitis led to formation of duct-like tubular complexes. Enzyme content in the pancreas decreased progressively following the formation of the edema to levels 15-20% of controls and remained reduced during the initial 5 days. Thymidine incorporation into total DNA showed a biphasic pattern with a distinct peak at day 1 and a second broader peak between days 4 and 7. Autoradiographic quantitation of labeling indices demonstrated the exclusive incorporation into intercalated duct cells and interstitial cells during the initial 24 h, while the second peak was predominantly due to labeling of acinar cells. Larger interlobular ducts and islets did not show changes in labeling index. In vivo labeling with 3 H-thymidine during the first day and analysis of labeling indices 14 days later showed the persistence of label in intercalated duct cells and interstitial cells and argued against the stem cell hypothesis and against transformation of duct cells into acinar cells

  14. 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.)

  15. Prevalence of chronic pancreatitis: Results of a primary care physician-based population study.

    Science.gov (United States)

    Capurso, Gabriele; Archibugi, Livia; Pasquali, Piera; Aceti, Alessandro; Balducci, Paolo; Bianchi, Patrizia; Buono, Francesco; Camerucci, Stefano; Cantarini, Rosanna; Centofanti, Sergio; Colantonio, Patrizia; Cremaschi, Riccarda; Crescenzi, Sergio; Di Mauro, Caterina; Di Renzi, Davide; Filabozzi, Andrea; Fiorillo, Alfonso; Giancaspro, Giuseppe; Giovannetti, Paola; Lanna, Giuseppe; Medori, Claudio; Merletti, Emilio; Nunnari, Enzo; Paris, Francesca; Pavone, Marco; Piacenti, Angela; Rossi, Almerindo; Scamuffa, Maria Cristina; Spinelli, Giovanni; Taborchi, Marco; Valente, Biagio; Villanova, Antonella; Chiriatti, Alberto; Delle Fave, Gianfranco

    2017-05-01

    Data on chronic pancreatitis prevalence are scanty and usually limited to hospital-based studies. Investigating chronic pancreatitis prevalence in primary care. Participating primary care physicians reported the prevalence of chronic pancreatitis among their registered patients, environmental factors and disease characteristics. The data were centrally reviewed and chronic pancreatitis cases defined according to M-ANNHEIM criteria for diagnosis and severity and TIGAR-O classification for etiology. Twenty-three primary care physicians participated in the study. According to their judgment, 51 of 36.401 patients had chronic pancreatitis. After reviewing each patient data, 11 turned out to have definite, 5 probable, 19 borderline and 16 uncertain disease. Prevalence was 30.2/100.000 for definite cases and 44.0/100.000 for definite plus probable cases. Of the 16 patients with definite/probable diagnosis, 8 were male, with mean age of 55.6 (±16.7). Four patients had alcoholic etiology, 5 post-acute/recurrent pancreatitis, 6 were deemed to be idiopathic. Four had pancreatic exocrine insufficiency, 10 were receiving pancreatic enzymes, and six had pain. Most patients had initial stage and non-severe disease. This is the first study investigating the prevalence of chronic pancreatitis in primary care. Results suggest that the prevalence in this context is higher than in hospital-based studies, with specific features, possibly representing an earlier disease stage. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  16. Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology.

    Science.gov (United States)

    Gryshchenko, Oleksiy; Gerasimenko, Julia V; Peng, Shuang; Gerasimenko, Oleg V; Petersen, Ole H

    2018-02-09

    Ca 2+ signalling in different cell types in exocrine pancreatic lobules was monitored simultaneously and signalling responses to various stimuli were directly compared. Ca 2+ signals evoked by K + -induced depolarization were recorded from pancreatic nerve cells. Nerve cell stimulation evoked Ca 2+ signals in acinar but not in stellate cells. Stellate cells are not electrically excitable as they, like acinar cells, did not generate Ca 2+ signals in response to membrane depolarization. The responsiveness of the stellate cells to bradykinin was markedly reduced in experimental alcohol-related acute pancreatitis, but they became sensitive to stimulation with trypsin. Our results provide fresh evidence for an important role of stellate cells in acute pancreatitis. They seem to be a critical element in a vicious circle promoting necrotic acinar cell death. Initial trypsin release from a few dying acinar cells generates Ca 2+ signals in the stellate cells, which then in turn damage more acinar cells causing further trypsin liberation. Physiological Ca 2+ signals in pancreatic acinar cells control fluid and enzyme secretion, whereas excessive Ca 2+ signals induced by pathological agents induce destructive processes leading to acute pancreatitis. Ca 2+ signals in the peri-acinar stellate cells may also play a role in the development of acute pancreatitis. In this study, we explored Ca 2+ signalling in the different cell types in the acinar environment of the pancreatic tissue. We have, for the first time, recorded depolarization-evoked Ca 2+ signals in pancreatic nerves and shown that whereas acinar cells receive a functional cholinergic innervation, there is no evidence for functional innervation of the stellate cells. The stellate, like the acinar, cells are not electrically excitable as they do not generate Ca 2+ signals in response to membrane depolarization. The principal agent evoking Ca 2+ signals in the stellate cells is bradykinin, but in experimental alcohol

  17. Defect in assimilation following combined radiation and chemotherapy in patients with locally unresectable pancreatic carcinoma

    International Nuclear Information System (INIS)

    Barkin, J.S.; Kalser, M.H.; Thomsen, S.; Redlhammer, D.

    1982-01-01

    The relative contributions of high-dose irradiation and/or chemotherapy to the nutritional problems of patients with inoperable pancreatic carcinoma were evaluated by study of pancreatic exocrine function and jejunal function and morphologic findings in ten patients before and after treatment. Nutrient assimilation studies included determination of serum carotene levels, D-xylose absorption and fat absorption. Crosby capsule biopsy specimen of jejunal mucosa were evaluated with light microscopy. Fat assimilation was the only parameter of nutritional function to significantly worsen after therapy. Low serum carotene levels present in the patients before therapy remained low but did not significantly change after treatment. D-xylose absorption and the morphologic structure of the jejunal mucosa were normal before and after treatment. These findings support the previous observations that the nutritional problems of the patient with inoperable pancreatic carcinoma are due to pancreatic insufficiency and that high dose irradiation and chemotherapy can exacerbate the pancreatic insufficiency but do not produce jejunal dysfunction. Therefore, it is suggested that pancreatic exocrine replacement therapy may improve the nutritional status of these patients

  18. New advances in cell physiology and pathophysiology of the exocrine pancreas.

    Science.gov (United States)

    Mössner, Joachim

    2010-01-01

    This review provides some aspects on the physiology of stimulation and inhibition of pancreatic digestive enzyme secretion and the pathophysiology of pancreatic acinar cell function leading to pancreatitis. Cholecystokinin (CCK) stimulates both directly via CCK-A receptors on acinar cells and indirectly via CCK-B receptors on nerves, followed by acetylcholine release, pancreatic enzyme secretion. It is still not known whether CCK-A receptors exist in human acinar cells, in contrast to acinar cells of rodents where CCK-A receptors have been well described. CCK has numerous actions both in the periphery and in the central nervous systems. CCK inhibits gastric motility and regulates satiety. Another major function of CCK is stimulation of gallbladder contraction. This function enables that bile acids act simultaneously with pancreatic lipolytic enzymes. Secretin is a major stimulator of bicarbonate secretion. Trypsinogen is activated by the gut mucosal enzyme enterokinase. The other pancreatic proenzymes are activated by trypsin. Termination of enzyme secretion may be regulated by negative feedback mechanisms via destruction of CCK-releasing peptides by trypsin. Furthermore, the ileum may act as a brake by release of inhibitory hormones such as PYY and somatostatin. In the pathophysiology of acute pancreatitis, fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen is regarded as an initiation step. This activation of trypsinogen may be caused by the lysosomal enzyme cathepsin B. However, autoactivation of trypsinogen itself may be a possibility in pathogenesis. Autoactivation is enhanced in certain mutations of trypsinogen. Furthermore, an imbalance of protease inhibitors and active proteases may be involved. The role of pancreatic lipolytic enzymes, the role of bicarbonate secretion, and toxic Ca(2+) signals by excessive liberation from the endoplasmic reticulum have to be discussed in the pathogenesis of acute pancreatitis

  19. Effect of bacterial or porcine lipase with low- or high-fat diets on nutrient absorption in pancreatic-insufficient dogs.

    Science.gov (United States)

    Suzuki, A; Mizumoto, A; Rerknimitr, R; Sarr, M G; DiMango, E P

    1999-02-01

    Treatment of human exocrine pancreatic insufficiency is suboptimal. This study assessed the effects of bacterial lipase, porcine lipase, and diets on carbohydrate, fat, and protein absorption in pancreatic-insufficient dogs. Dogs were given bacterial or porcine lipase and 3 diets: a 48% carbohydrate, 27% fat, and 25% protein standard diet; a high-carbohydrate, low-fat, and low-protein diet; or a low-carbohydrate, high-fat, and high-protein diet (66%/18%/16% and 21%/43%/36% calories). With the standard diet, coefficient of fat absorption increased dose-dependently with both lipases (P vs. low-fat and -protein diet). There were no interactions among carbohydrate, fat, and protein absorption. Correcting steatorrhea requires 75 times more porcine than bacterial lipase (18 vs. 240 mg). High-fat and high-protein diets optimize fat absorption with both enzymes. High-fat diets with bacterial or porcine lipase should be evaluated in humans with pancreatic steatorrhea.

  20. Laboratory diagnosis of pancreatitis and cancer of the pancreas

    International Nuclear Information System (INIS)

    Degtyareva, I.I.; Gajsenko, A.V.; Putseva, N.M.

    1989-01-01

    The content of fibrin fibrinogen splitting products (FSP), radioimmune trypsine, C-peptide and carbohydrate antigen (CA) 19-9 in the blood of 82 patients with acute pancreatitis (edematous and hemorrhagic), and chronic recurrent pancreatitis at the stage of exacerbation, 42 patients with chronic pancreatitis, 34 patients with cancer of the pancreas (stages 3-4) and 22 healthy persons were studied. Results indicate a high diagnostic value of determination FSP, trypsin and C-peptide in patients with acute pancreatitis and chronic recurring pancreatitis at the stage of exacerbation, trypsin and C-peptide in patients with chronic pancreatitis associated with severe exocrinous insufficiency of the pancreas, KA 19-9 in patients with cancer of the pancreas

  1. 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.

  2. Adaptive changes of pancreatic protease secretion to a short-term vegan diet: influence of reduced intake and modification of protein.

    Science.gov (United States)

    Walkowiak, Jaroslaw; Mądry, Edyta; Lisowska, Aleksandra; Szaflarska-Popławska, Anna; Grzymisławski, Marian; Stankowiak-Kulpa, Hanna; Przysławski, Juliusz

    2012-01-01

    In our previous study, we demonstrated that abstaining from meat, for 1 month, by healthy omnivores (lacto-ovovegetarian model) resulted in a statistical decrease in pancreatic secretion as measured by faecal elastase-1 output. However, no correlation between relative and non-relative changes of energy and nutrient consumption and pancreatic secretion was documented. Therefore, in the present study, we aimed to assess the changes of exocrine pancreatic secretion with a more restrictive dietetic modification, by applying a vegan diet. A total of twenty-one healthy omnivores (sixteen females and five males) participated in the prospective study lasting for 6 weeks. The nutrient intake and faecal output of pancreatic enzymes (elastase-1, chymotrypsin and lipase) were assessed twice during the study. Each assessment period lasted for 7 d: the first before the transition to the vegan diet (omnivore diet) and the second during the last week of the study (vegan diet). The dietary modification resulted in a significant decrease in faecal elastase-1 (P vegan diet resulted in an adaptation of pancreatic protease secretion in healthy volunteers.

  3. A case control study of possible additional risk factors for chronic alcoholic pancreatitis

    OpenAIRE

    Sri Vengadesh Gopal; Ashley Solomon; Jaahnavi Konidala

    2016-01-01

    Background: Chronic pancreatitis (CP) is characterised by irreversible damage to pancreas leading to endocrine and exocrine insufficiency with considerable morbidity. Etiopathogenesis is multifactorial with interplay between genetics and environmental toxins. Alcoholism is more commonly associated with chronic pancreatitis. But it is not very clear why only certain proportion of the alcoholics develop pancreatitis. So this study was conducted to find the possible additional risk factors inv...

  4. Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

    Directory of Open Access Journals (Sweden)

    Jakub Bukowczan

    Full Text Available Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and

  5. Long-term Outcomes Favor Duodenum-preserving Pancreatic Head Resection over Pylorus-preserving Pancreaticoduodenectomy for Chronic Pancreatitis: A Meta-analysis and Systematic Review.

    Science.gov (United States)

    Sukharamwala, Prashant B; Patel, Krishen D; Teta, Anthony F; Parikh, Shailraj; Ross, Sharona B; Ryan, Carrie E; Rosemurgy, Alexander S

    2015-09-01

    Pylorus-preserving pancreaticoduodenectomy (PPPD) and duodenum-preserving pancreatic head resection (DPPHR) are important treatment options for patients with chronic pancreatitis. This meta-analysis was undertaken to compare the long-term outcomes of DPPHR versus PPPD in patients with chronic pancreatitis. A systematic literature search was conducted using Embase, MEDLINE, Cochrane, and PubMed databases on all studies published between January 1991 and January 2013 reporting intermediate and long-term outcomes after DPPHR and PPPD for chronic pancreatitis. Long-term outcomes of interest were complete pain relief, quality of life, professional rehabilitation, exocrine insufficiency, and endocrine insufficiency. Other outcomes of interest included perioperative morbidity and length of stay (LOS). Ten studies were included comprising of 569 patients. There was no significant difference in complete pain relief (P = 0.24), endocrine insufficiency (P = 0.15), and perioperative morbidity (P = 0.13) between DPPHR and PPPD. However, quality of life (P insufficiency (P = 0.005), and LOS (P = 0.00001) were significantly better for patients undergoing DPPHR compared with PPPD. In conclusion, there is no significant difference in endocrine insufficiency, postoperative pain relief, and perioperative morbidity for patients undergoing DPPHR versus PPPD. Improved intermediate and long-term outcomes including LOS, quality of life, professional rehabilitation, and preservation of exocrine function make DPPHR a more favorable approach than PPPD for patients with chronic pancreatitis.

  6. Effect of localized intraoperative x-rays irradiation followed by intermittent external exposure on certain histochemical parameters related to pancreatic function

    International Nuclear Information System (INIS)

    Abdel-Azeem, M.G.

    2005-01-01

    The present study was carried out to evaluate the pancreatic enzyme activities in rabbits, whose splenic part of pancreas was exposed to local intraoperative radiation therapy (IORT) at level of 30 Gy X-rays followed by fractionated external radiation therapy (ERT) at a total dose of 40 Gy (2 Gy day after day) starting from the 15th day following the local intraoperative irradiation. The control pancreas was that received only external X-rays radiation without local irradiation. The exocrine pancreatic functions were assessed by determination of insulin hormone and enzyme activity of lipase as well as alkaline and acid phosphatases. After local X-rays irradiation on days 2 and 10 and after external X-rays irradiation on days 23 , 33 , 43 and 53, technovit-8100 plastic embedding (Kulzer and Heraeus) was used to prepare the cold blocks. The quantitative morphometric method was used to evaluate the histochemical pancreatic activity of the irradiated and control pancreas of each rabbit. Most of the studied parameters recorded non-significant changes as a result of the applied different levels of X-rays irradiation, which would give the chance to use this type of irradiation in pancreatic radiotherapy without any hazards to the pancreas

  7. Pancreatic Stellate Cells : A Starring Role in Normal and Diseased Pancreas

    Directory of Open Access Journals (Sweden)

    Minoti eApte

    2012-08-01

    Full Text Available While the morphology and function of cells of the exocrine and endocrine pancreas have been studied over several centuries, one important cell type in the gland, the pancreatic stellate cell (PSC, had remained undiscovered until as recently as twenty years ago. Even after its first description in 1982, it was to be another 16 years before its biology could begin to be studied, because it was only in 1998 that methods were developed to isolate and culture PSCs from rodent and human pancreas. PSCs are now known to play a critical role in pancreatic fibrosis, a consistent histological feature of two major diseases of the pancreas - chronic pancreatitis and pancreatic cancer. In health, PSCs maintain normal tissue architecture via regulation of the synthesis and degradation of extracellular matrix (ECM proteins. Recent studies have also implied other additional functions for PSCs as progenitor cells, immune cells or intermediaries in exocrine pancreatic secretion in humans.During pancreatic injury, PSCs transform from their quiescent phase into an activated, myofibroblast-like phenotype that secretes excessive amounts of ECM proteins leading to the fibrosis of chronic pancreatitis and pancreatic cancer. An ever increasing number of factors that stimulate and/or inhibit PSC activation via paracrine and autocrine pathways are being identified and characterized. It is also now established that PSCs interact closely with pancreatic cancer cells to facilitate cancer progression. Based on these findings, several therapeutic strategies have been examined in experimental models of chronic pancreatitis as well as pancreatic cancer, in a bid to inhibit/retard PSC activation and thereby alleviate chronic pancreatitis or reduce tumour growth in pancreatic cancer. The challenge that remains is to translate these pre-clinical developments into clinically applicable treatments for patients with chronic pancreatitis and pancreatic cancer.

  8. Association of foetal haemoglobin with pancreatic enzymes in sickle ...

    African Journals Online (AJOL)

    Background/Aim: There are conflicting reports on the potential protective effects of foetal haemoglobin (HbF) in the elimination of symptoms of Sickle cell disease in the patients and reports which correlate the levels of HbF with pancreatic enzymes in SCD are scarce in the literature.This study correlates the levels of HbF on ...

  9. Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas.

    Science.gov (United States)

    Saisho, Yoshifumi

    2016-01-01

    The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better.

  10. Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

    Science.gov (United States)

    Saisho, Yoshifumi

    2016-01-01

    The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better. PMID:28012279

  11. The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families

    DEFF Research Database (Denmark)

    Grocock, Christopher J; Rebours, Vinciane; Delhaye, Myriam

    2010-01-01

    Pancreatitis (HP); idiopathic disease; or pancreatitis in a single generation. HP was defined as 2 cases in 2 generations. MAIN OUTCOME MEASURES: Onset of painful episodes of pancreatitis, death from pancreatic cancer, diagnosis of diabetes mellitus and exocrine pancreatic failure. RESULTS: Ten families with p...... or Mann-Whitney-U tests. CONCLUSIONS: Penetrance of p.A16V is highly variable and family dependent, suggesting it contributes to a multigenic inheritance of a predisposition to pancreatitis....

  12. A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer.

    Science.gov (United States)

    Perán, Macarena; López-Ruiz, Elena; García, María Ángel; Nadaraia-Hoke, Shorena; Brandt, Ralf; Marchal, Juan A; Kenyon, Julian

    2017-10-25

    Proteolytic enzymes have shown efficacy in cancer therapy. We present a combination of the two pro-enzymes Trypsinogen and Chymotrypsinogen A with potent in vitro and in vivo anti-tumour efficacy. A synergetic anti-tumour effect for Trypsinogen and Chymotrypsinogen A was determined at a ratio 1:6 (named PRP) using 24 human cancer cell lines. The antiangiogenic effect of PRP was analysed by matrigel-based tube formation and by fibrous capsule formation assays. Furthermore, cell invasion and wound healing assays together with qRT-PCR determination of epithelial-to-mesenchymal transition (EMT) markers were performed on human cancer cells treated with PRP. Additionally, in vivo pharmacokinetic studies were implemented and the PRP's anti-tumour efficacy was explored against orthotopic pancreatic and ovarian cancer tumours. PRP formulation was proven to inhibit in vitro angiogenesis, tumour growth, cancer cell migration and invasiveness; and to be an effective and well tolerated in vivo anti-tumour treatment. Finally, the clinical efficacy of a suppository formulation containing both pancreatic pro-enzymes in the context of a UK Pharmaceuticals Special Scheme was evaluated in advanced cancer patients. Consequently, PRP could have relevant oncological clinical applications for the treatment of advanced or metastatic pancreatic adenocarcinoma and advanced epithelial ovarian cancer.

  13. Dendritic Cells Promote Pancreatic Viability in Mice with Acute Pancreatitis

    Science.gov (United States)

    Bedrosian, Andrea S.; Nguyen, Andrew H.; Hackman, Michael; Connolly, Michael K.; Malhotra, Ashim; Ibrahim, Junaid; Cieza-Rubio, Napoleon E.; Henning, Justin R.; Barilla, Rocky; Rehman, Adeel; Pachter, H. Leon; Medina-Zea, Marco V.; Cohen, Steven M.; Frey, Alan B.; Acehan, Devrim; Miller, George

    2011-01-01

    Background & Aims Acute pancreatitis increases morbidity and mortality from organ necrosis by mechanisms that are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. Methods Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier analysis. Results Numbers of MHC II+CD11c+DC increased 100-fold in pancreas of mice with acute pancreatitis, to account for nearly 15% of intra-pancreatic leukocytes. Intra-pancreatic DC acquired an immune phenotype in mice with acute pancreatitis; they expressed higher levels of MHC II and CD86 and increased production of interleukin-6, membrane cofactor protein (MCP)-1, and tumor necrosis factor (TNF)-α. However, rather than inducing an organ-destructive inflammatory process, DC were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DC and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DC died from acinar cell death within 4 days. Depletion of DC from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DC did not require infiltrating neutrophils, activation of NF-κB, or signaling by mitogen-activated protein kinase or TNF-α. Conclusions DC are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress. PMID:21801698

  14. Nutrition treatment of deficiency and malnutrition in chronic pancreatitis: a review.

    LENUS (Irish Health Repository)

    Duggan, SN

    2010-08-01

    Chronic pancreatitis results in exocrine and endocrine dysfunction, affecting normal digestion and absorption of nutrients. In individuals with chronic pancreatitis, nutrition status may be further affected by poor dietary intake, often related to alcoholism. However, some deficiencies may be overlooked, potentially leading to nutrition-related problems with bone health and fatigue. The aim of this article is to describe the deficiencies that occur and to propose an evidence-based algorithm for the nutrition assessment and treatment of patients with chronic pancreatitis.

  15. ERP in chronic pancreatitis - ductal morphology, relation to exocrine function and pain - clinical value

    International Nuclear Information System (INIS)

    Norup Lauridsen, K.; Raahede, J.; Kruse, A.; Thommesen, P.; Aarhus Univ.

    1985-01-01

    ERP was analyzed in 87 patients with chronic pancreatitis with special reference to its clinical value in management of pain, the dominating symptom in uncomplicated chronic pancreatitis. A significant correlation was found between ductal changes due to pancreatitis and decrease in pancreatic function. However, no association was found between severe pancreatic pain and pancreatic function or pancreatic morphology. The significance of ERP in management of patients with persistent severe pancreatic pain is discussed. (orig.) [de

  16. 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.

  17. Parental Depression and Pancreatic Enzymes Adherence in Children With Cystic Fibrosis.

    Science.gov (United States)

    Barker, David H; Quittner, Alexandra L

    2016-02-01

    Treatment adherence in cystic fibrosis (CF) is often poor, however, less is known about adherence to pancreatic enzymes, a critical component of the CF treatment regimen. Parent caregivers often report elevations in depression, and parental depression may adversely affect children's adherence. This prospective study evaluated adherence to pancreatic enzymes in 83 patients (1-13 years) . Adherence was measured across 3 months with electronic pill-caps . Weight was measured at baseline and a 3-month follow-up. Parental depressive symptoms were evaluated by using the Center for Epidemiologic Studies Depression Scale (CES-D). Adherence to pancreatic enzymes was 49.4% ± 3.4%. Adherence was higher at school (94.4% ± 6.1%) than at home (42.3% ± 3.1%), and higher for toddlers (50.6% ± 5.2%) than for school-aged children (37.5% ± 3.7%). Parents reported high rates of depressive symptoms (30% in the clinical range, 18% with moderate symptoms). Children of parents with symptoms of depression versus those without were less adherent (34.8% ± 4.5% vs 48.5% ± 4.1%), and adherence to enzymes was significantly related to 3-month weight outcomes. Average gain in weight z scores across 3 months was 0.5 ± 0.2for children who were >50% adherent and -0.1 ± 6.1for children who were <33% adherent. Parental depression had a signifcant, indirect effect on weight via adherence (-0.005 ± 0.003 gain in weight z score per CES-D unit ). High rates of parental depressive symptoms, coupled with its negative effects on adherence, suggest that measuring and treating parental depression may improve children's adherence to therapy. Copyright © 2016 by the American Academy of Pediatrics.

  18. Chronic pancreatitis: indications to surgery and remote results assessment criteria

    Directory of Open Access Journals (Sweden)

    A. V. Klimenko

    2013-06-01

    Full Text Available Present indications to surgery include intractable pain syndrome, severe dilation of the Wirsung’s duct, strictures and stones in the Wirsung’s duct, pancreatic pseudocysts, duodenal stenosis and obstructive jaundice because of “inflammatory mass” in the pancreatic head. But these absolute indications mean that in the most cases pancreatic exocrine and endocrine functions are already decompensated. Therefore it is important to produce new indications to surgical treatment of the CP in early stages. Also it is necessary to make such remote results assessment criteria that will allow to range among parenchymapreserving and resectional technics according to anatomical and functional parameters. Goal: to adjust indications to surgical treatment of the CP according to leading pathogenetic factors and develop criteria to assess remote results. Patients and methods: 122 CP patients have undergone surgery. There were 103 (84,4% men and – 19 (15,6% women, mean age - 45. Alcohol etiology of the CP was in 79 (64,8% patients, postpancreonecrotic – in 29 (23,8%, biliary – in 6 (4,9%, idiopathic – in 8 (6,6%. Wirsung’s duct diameter of 4 – 8 mm – was in 65 (53,3% patients, 8 – 12 and more – in 57 (46,7%. By Shalimov classification there were “pseudotumorous” – in 39 (31,9%, “calculouse” – in 40 (32,8%, fibrose-cystic – in 17 (13,9%, fibrose-degenerative with adjacent organs involvement and hampering of their function – in 26 (21,4% patients. All patients had pain syndrome and 79 (64,8% – exocrine and endocrine insufficiency. All patients underwent abdominal CT-scan, fecal elastase test, C-peptide, endogenic insulin, glucose, immunehystochemical investigation of biopsy samples taken from body corpus and tale simultaneously etc. Results: We have found that gastroenterologists poorly recognize “surgical” type of CP and restrain patients from being directed to surgical pancreatologists for surgical therapy. We

  19. Mitochondrial function and malfunction in the pathophysiology of pancreatitis.

    Science.gov (United States)

    Gerasimenko, Oleg V; Gerasimenko, Julia V

    2012-07-01

    As a primary energy producer, mitochondria play a fundamental role in pancreatic exocrine physiology and pathology. The most frequent aetiology of acute pancreatitis is either gallstones or heavy alcohol consumption. Repeated episodes of acute pancreatitis can result in the development of chronic pancreatitis and increase the lifetime risk of pancreatic cancer 100-fold. Pancreatic cancer is one of the most common causes of cancer mortality with only about 3-4 % of patients surviving beyond 5 years. It has been shown that acute pancreatitis involves Ca²⁺ overload and overproduction of reactive oxygen species in pancreatic acinar cells. Both factors significantly affect mitochondria and lead to cell death. The pathogenesis of inflammation in acute and chronic pancreatitis is tightly linked to the induction of necrosis and apoptosis. There is currently no specific therapy for pancreatitis, but recent findings of an endogenous protective mechanism against Ca²⁺ overload--and particularly the potential to boost this protection--bring hope of new therapeutic approaches.

  20. Genetic ontogeny of pancreatic enzymes in Labrus bergylta larvae and the effect of feed type on enzyme activities and gene expression.

    Science.gov (United States)

    Hansen, Truls Wergeland; Folkvord, Arild; Grøtan, Espen; Sæle, Øystein

    2013-03-01

    A newly cultivated wrasse species, Labrus bergylta, have shown great potential for use in Atlantic salmon (Salmo salar) farms in the battle against sea lice (Lepeoptheirus salmonis) infections. Hatchery reared L. bergylta were studied from 2 to 55 DPH to examine the molecular basis of digestive ontogeny related to the pancreas. An isolated feeding trial was performed on 27-34 DPH larvae to compare the effect of diet on enzyme activity and the possible exogenous contribution by live feed. The following genes coding for key pancreatic enzymes were analyzed by qPCR: trypsin, Cyp7 A1, BAL, sPLA(2) 1B, amylase and pancreatic chitinase. Enzyme activity was measured on trypsin, neutral lipase, sPLA(2), amylase and chitinase in fed and unfed larvae. We did not observe any effects of the formulated diet v.s. rotifers on enzyme activities of neutral lipase, chitinase and sPLA(2). However, a probable feed-dependency was observed at a transcriptional level, where rotifers seem to stimulate upregulation. The regulation of BAL was the only exception, where an upregulation was observed after weaning both in the ontogeny series and the experimental part. Our data on pancreatic chitinase and amylase mRNA levels suggest the importance of carbohydrates in the diet of early larval and juvenile L. bergylta. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Pancreatic changes in cystic fibrosis: CT and sonographic appearances

    International Nuclear Information System (INIS)

    Daneman, A.; Gaskin, K.; Martin, D.J.; Cutz, E.

    1983-01-01

    The computed tomographic (CT) and sonographic appearances of the late stages of pancreatic damage in three patients with cystic fibrosis are illustrated. All three had severe exocrine pancreatic insufficiency with steatorrhea. In two patients CT revealed complete fatty replacement of the entire pancreas. In the third, increased echogenicity of the pancreas on sonography and the inhomogeneous attenuation on CT were interpreted as being the result of a combination of fibrosis, fatty replacement, calcification, and probable cyst formation

  2. 11C-L-methionine for evaluation of pancreatic exocrine function

    International Nuclear Information System (INIS)

    Syrota, A.; Dop-Ngassa, M.; Cerf, M.; Paraf, A.; Crouzel, M.; Ricard, S.

    1981-01-01

    Pancreatic uptake of 11 C labelled L-methionine, was measured in 58 patients using a scintillation camera. Time-activity-curves obtained in areas of interest selected over the pancreas in 25 normal subjects and in 14 alcoholic patients showed a plateau or slight increase of activity with time. In contrast, in 19 patients with chronic pancreatitis, an initial increase in radioactivity was followed by a decrease for 10 to 20 minutes and then by a plateau. The ratio of the height of the plateau at the 50th minute to the height of the peak was 0.74 +- 0.21 in these patients, whereas it was 0.96 +- 0.09 in the other subjects (p 11 C radioactivity and of amylase and bicarbonate in duodenal aspirate. The median amount of 11 C incorporated into protein at the 70th minute was 53% of total activity in the control group, 28% in alcoholic patients, and only 3% in chronic pancreatitis. The absence of a peak of radioactivity in the duodenal juice, and the existence of a correlation between total 11 C output and amylase output suggested that there was no release of protein in the duodenum in chronic pancreatitis, and that the peak observed by external detection could be due to amino acid back-diffusion from the pancreas into the blood. (author)

  3. Effect of Cereal Type and Enzyme Addition on Performance, Pancreatic Enzyme Activity, Intestinal Microflora and Gut Morphology of Broilers

    Directory of Open Access Journals (Sweden)

    Kalantar M

    2016-06-01

    Full Text Available The effects of grain and carbohydrase enzyme supplementation were investigated on digestive physiology of chickens. A total of 625 one-day-old chicks (Ross 308 were randomly assigned to five treatments in a completely randomized design. Treatments included two different types of grains (wheat, and barley with or without a multi-carbohydrase supplement. A corn-based diet was also considered to serve as a control. Feeding barley-based diet with multi-carbohydrase led to higher feed intake (P < 0.01 than those fed corn- and wheat-based diets. Birds fed on barley and wheat diets had lower weight gain despite a higher feed conversion ratio (P < 0.01. Total count and number of different type of bacteria including Gram-negative, E. coli, and Clostridia increased after feeding wheat and barley but the number of Lactobacilli and Bifidobacteria decreased (P < 0.01. Feeding barley and wheat diets reduced villus height in different parts of the small intestine when compared to those fed on a corn diet. However, enzyme supplementation of barley and wheat diets improved weight gain and feed conversion ratio and resulted in reduced number of E. coli and Clostridia and increased number of Lactobacilli and Bifidobacteria, and also restored the negative effects on intestinal villi height (P < 0.01. The activities of pancreatic α-amylase and lipase were (P < 0.01 increased in chickens fed wheat and barley diets when compared to the control fed on a corn diet. Enzyme supplementation reduced the activities of pancreatic α-amylase and lipase (P < 0.01. In conclusion, various dietary non-starch polysaccharides without enzyme supplementation have an adverse effect on digesta viscosity, ileal microflora, villi morphology, and pancreatic enzyme activity.

  4. Pancreaticoduodenectomy versus duodenum-preserving pancreatic head resection for the treatment of chronic pancreatitis.

    Science.gov (United States)

    Zheng, Zhenjiang; Xiang, Guangming; Tan, Chunlu; Zhang, Hao; Liu, Baowang; Gong, Jun; Mai, Gang; Liu, Xubao

    2012-01-01

    The objective of this study was to assess the efficacy and safety of pancreaticoduodenectomy (PD) and duodenum-preserving pancreatic head resection (DPPHR) for the treatment of chronic pancreatitis (CP). The 123 patients with CP who underwent pancreatic head resection between January 2004 and June 2009 were retrospectively analyzed. The preoperative variables, operative data, postoperative complications, and follow-up information were examined. There were no significant differences in clinical and morphological characteristics, pain relief, and jaundice status between the PD and DPPHR groups. The duration of operation was shorter (251.8 [SD, 43.1] vs 324.5 [SD, 41.4] minutes, P endocrine insufficiency was higher in PD group as compared with DPPHR group. Both procedures are equally effective in pain relief, but DPPHR is superior to PD in operative data, postoperative morbidity, improving quality of life, and preservation of exocrine and endocrine function.

  5. Genetic, epidemiological, and clinical aspects of hereditary pancreatitis: a population-based cohort study in Denmark

    DEFF Research Database (Denmark)

    Brusgaard, Klaus

    2010-01-01

    , respectively, and among tIP patients 9 and 12%, respectively. Pancreatic cancer was diagnosed in 5% of the HP families. CONCLUSIONS: The genotype of the Danish population with HP differs from that of previously described cohorts. The occurrence of exocrine and endocrine insufficiency is higher among patients......-degree relatives of the 18 initially identified HP patients, 38 HP patients in total were identified, and 28 patients had SPINK1-CFTR mutations. Among HP patients, no p.N29I mutations were found and the p.A16V mutation was more frequent than previously reported, 45 and 32% had exocrine and endocrine insufficiency......OBJECTIVES: In a population-based, well-defined group of patients first regarded as having pancreatitis of unknown origin (PUO), we identified, described, and compared the clinical and genetic aspects of patients with hereditary pancreatitis (HP) and with cystic fibrosis transmembrane conductance...

  6. Utility of serum pancreatic enzyme levels in diagnosing blunt trauma to the pancreas: a prospective study with systematic review.

    Science.gov (United States)

    Mahajan, Abhishek; Kadavigere, Rajagopal; Sripathi, Smiti; Rodrigues, Gabriel Sunil; Rao, Vedula Rajanikanth; Koteshwar, Prakashini

    2014-09-01

    Reliability of serum pancreatic enzyme levels in predicting pancreatic injuries has been a parameter of interest and the present recommendations on its utility are based primarily on anecdotal observations. The aim of this study was to evaluate the utility of serum pancreatic enzyme assessment in predicting blunt pancreatic injury with imaging and surgical correlation and compare our results with a systematic review of literature till date. A prospective cohort study conducted over 4 years in a tertiary care referral centre with 164 consecutive patients who presented to the emergency department with a history of blunt abdominal trauma and had serum pancreatic enzyme assessment, USG and subsequent diagnostic CECT were analyzed. The CT findings and AAST grade of pancreatic injury, various intra-abdominal injuries and time elapsed since injury and other associated factors were correlated with serum pancreatic enzyme levels. For systematic review of literature MEDLINE database was searched between 1940 and 2012, also the related citations and bibliographies of relevant articles were analyzed and 40 articles were included for review. We compared our results with the systematic critique of literature till date to formulate recommendations. 33(21%) patients had pancreatic injury documented on CT and were graded according to AAST. Statistically significant elevated serum amylase levels were observed in patients with pancreatic and bowel injuries. However, elevated serum lipase was observed specifically in patients with pancreatic injury with or without bowel injury. Combined serum amylase and lipase showed 100% specificity, 85% sensitivity in predicting pancreatic injury. Elevated (n=28, 85%) vs. normal (n=5, 15%) serum amylase and lipase levels showed sole statistically significant association with time elapse since injury to admission, with a cutoff of 3h. Based on our results and the systematic review of the literature till date we conclude, persistently elevated or

  7. Short and long-term post-operative outcomes of duodenum preserving pancreatic head resection for chronic pancreatitis affecting the head of pancreas: a systematic review and meta-analysis.

    Science.gov (United States)

    Jawad, Zaynab A R; Tsim, Nicole; Pai, Madhava; Bansi, Dev; Westaby, David; Vlavianos, Panagiotis; Jiao, Long R

    2016-02-01

    To evaluate the short and long term outcomes of duodenum preserving pancreatic head resection (DPPHR) procedures in the treatment of painful chronic pancreatitis. A systematic literature search was performed to identify all comparative studies evaluating long and short term postoperative outcomes (pain relief, morbidity and mortality, pancreatic exocrine and endocrine function). Five published studies fulfilled the inclusion criteria including 1 randomized controlled trial comparing the Beger and Frey procedure. In total, 323 patients underwent surgical procedures for chronic pancreatitis, including Beger (n = 138) and Frey (n = 99), minimal Frey (n = 32), modified Frey (n = 25) and Berne's modification (n = 29). Two studies comparing the Beger and Frey procedure were entered into a meta-analysis and showed no difference in post-operative pain (RD = -0.06; CI -0.21 to 0.09), mortality (RD = 0.01; CI -0.03 to 0.05), morbidity (RD = 0.12; CI -0.00 to 0.24), exocrine insufficiency (RD = 0.04; CI -0.10 to 0.18) and endocrine insufficiency (RD = -0.14 CI -0.28 to 0.01). All procedures are equally effective for the management of pain for chronic pancreatitis. The choice of procedure should be determined by other factors including the presence of secondary complications of pancreatitis and intra-operative findings. Registration number CRD42015019275. Centre for Reviews and Dissemination, University of York, 2009. Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  8. American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: Evidence-Based Report on Diagnostic Guidelines

    Science.gov (United States)

    Conwell, Darwin L.; Lee, Linda S.; Yadav, Dhiraj; Longnecker, Daniel S.; Miller, Frank H.; Mortele, Koenraad J.; Levy, Michael J.; Kwon, Richard; Lieb, John G.; Stevens, Tyler; Toskes, Philip P.; Gardner, Timothy B.; Gelrud, Andres; Wu, Bechien U.; Forsmark, Christopher E.; Vege, Santhi S.

    2016-01-01

    The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed and evidence based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable or insufficient evidence. A diagnostic (STEP-wise; S-survey, T-tomography, E-endoscopy and P-pancreas function testing) algorithm is proposed that proceeds from a non-invasive to a more invasive approach. This algorithm maximizes specificity (low false positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Futhermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (T-toxic, I-idiopathic, G-genetic, A- autoimmune, R-recurrent and O-obstructive) etiology, gland morphology (Cambridge criteria) and physiologic state (exocrine, endocrine function) for uniformity across future multi-center research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves. PMID:25333398

  9. American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines.

    Science.gov (United States)

    Conwell, Darwin L; Lee, Linda S; Yadav, Dhiraj; Longnecker, Daniel S; Miller, Frank H; Mortele, Koenraad J; Levy, Michael J; Kwon, Richard; Lieb, John G; Stevens, Tyler; Toskes, Phillip P; Gardner, Timothy B; Gelrud, Andres; Wu, Bechien U; Forsmark, Christopher E; Vege, Santhi S

    2014-11-01

    The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

  10. TREATMENT COMPLIANCE AMONG PATIENTS WITH CHRONIC PANCREATITIS IN THE MOSCOW REGION

    Directory of Open Access Journals (Sweden)

    S. V. Beljakova

    2014-01-01

    Full Text Available Background: In the past decade, incidence of chronic pancreatitis among different age groups has been growing globally and in Russia. Chronic pancreatitis is a progressive disease characterized by development of complications and decrease of exocrine function of pancreas. Treatment should be initiated early, before the complications occur; therapy should account for international experience and established Russian guidelines. Continuous usage of high-dose enzyme preparations preferably in modern dosage forms (microgranules, minimicrospheres or microtablets is one of the key principles in the management of chronic pancreatitis. Patient’s cooperative behavior and good compliance is crucial for achieving treatment targets. Aim: To assess treatment compliance among patients with chronic pancreatitis in the Moscow Region and to identify sources of information on the disease used by the patients. Materials and methods: One hundred patients with chronic pancreatitis in Moscow Region were questionnaired anonymously on their adherence to the medical recommendations for diet, alcohol consumption and medications, particularly enzyme preparations. Patients’ sources of information on the disease were also determined. Results: Poor compliance results were shown: only 28% of patients were fully adherent to medical recommendations; other patients took their medications irregularly, changed drug doses or preparations choosing less expensive and effective drugs. The majority of patients (89% were aware of the main treatment principles, though, 53% didn’t adhere to them. Patients used varied sources of information on the disease including special literature and the web; nevertheless, the information could be incorrectly understood. Only some patients received disease-related information from their physician, and many of the patients described physician-derived information as insufficient. As a result, treatment was often inadequate. Conclusion:  Improved

  11. 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.

  12. 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

  13. [Culture of pancreatic progenitor cells in hanging drop and on floating filter].

    Science.gov (United States)

    Ma, Feng-xia; Chen, Fang; Chi, Ying; Yang, Shao-guang; Lu, Shi-hong; Han, Zhong-chao

    2013-06-01

    To construct a method to culture pancreatic progenitor cells in hanging drop and on floating filter,and to examine if pancreatic progenitor cells can differentiate into mature endocrine cells with this method. Murine embryos at day 12.5 were isolated and digested into single cells,which were then cultured in hanging drop for 24h and formed spheres.Spheres were cultured on the filter for 6 days,which floated in the dish containing medium.During culture,the expressions of pancreas duodenum homeobox-1(PDX-1)and neurogenin3(Ngn3)were determined.The expressions of endocrine and exocrine markers,insulin,glucagon,and carboxypeptidase(CPA)were determined on day 7 by immunohistochemistry.Insulin secretion of spheres stimulated by glucose was detected by ELISA.The changes of pancreatic marker expressions during culture were monitored by real-time polymerase chain reaction(PCR). One day after the culture,there were still a large amount of PDX-1 positive cells in pancreatic spheres,and these cells proliferated.On day 3,high expression of Ngn3 was detected,and the Ngn3-positive cells did not proliferate.On day 7,The expressions of endocrine and exocrine markers in the differentiated pancreatic progenitor cells were detected,which were consistent with that in vivo.Insulin was secreted by spheres upon the stimulation of glucose. In hanging drop and on floating filter,pancreatic progenitor cells can differentiate into mature endocrine cells.

  14. Evidence-Based Surgical Treatments for Chronic Pancreatitis.

    Science.gov (United States)

    Kleeff, Jörg; Stöß, Christian; Mayerle, Julia; Stecher, Lynne; Maak, Matthias; Simon, Peter; Nitsche, Ulrich; Friess, Helmut

    2016-07-25

    If conservative treatment of chronic pancreatitis is unsuccessful, surgery is an option. The choice of the most suitable surgical method can be difficult, as the indications, advantages, and disadvantages of the available methods have not yet been fully documented with scientific evidence. In April 2015, we carried out a temporally unlimited systematic search for publications on surgery for chronic pancreatitis. The target parameters were morbidity, mortality, pain, endocrine and exocrine insuffi - ciency, weight gain, quality of life, length of hospital stay, and duration of urgery. Differences between surgical methods were studied with network meta-analysis, and duodenum-preserving operations were compared with partial duodenopancreatectomy with standard meta-analysis. Among the 326 articles initially identified, 8 randomized controlled trials on a total of 423 patients were included in the meta-analysis. The trials were markedly heterogeneous in some respects. There was no significant difference among surgical methods with respect to perioperative morbidity, pain, endocrine and exocrine insufficiency, or quality of life. Duodenumpreserving procedures, compared to duodenopancreatectomy, were associated with a long-term weight gain that was 3 kg higher (p chronic pancreatitis is superior to partial duodenopancreatectomy in multiple respects. Only limited recommendations can be given, however, on the basis of present data. The question of the best surgical method for the individual patient, in view of the clinical manifestations, anatomy, and diagnostic criteria, remains open.

  15. Hypotonic duodenography and secretin-CCK test in the diagnosis of pancreatic disease

    International Nuclear Information System (INIS)

    Lukes, P.J.; Rolny, P.; Nilson, A.E.; Gamklou, R.

    1981-01-01

    Sixty-five patients with possible pancreatic disease or long-standing upper abdominal symptoms were examined by means of the secretin-CCK test and hypotonic duodenography. Both examinations were performed after one duodenal intubation. In patients with pancreatitis functional abnomalities were revealed in 85 per cent while the duodenography was abnormal in 43 per cent. In patients with carcinoma, 77 per cent had abnormal exocrine pancreas function and 70 per cent had abnormalities demonstrated at duodenography. The value of the two examinations for assessment of patients with upper abdominal symptoms and pancreatic disease is discussed. (Auth.)

  16. Generation of Functional Beta-Like Cells from Human Exocrine Pancreas.

    Directory of Open Access Journals (Sweden)

    Maria J Lima

    Full Text Available Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells. The efficiency was further increased by culture on laminin-coated plates in media containing low glucose concentrations. Immunocytochemistry revealed that reprogrammed cultures were composed of ~45% islet-like clusters comprising >80% monohormonal insulin+ cells. The resultant β-like cells expressed insulin protein levels at ~15-30% of that in adult human islets, efficiently processed proinsulin and packaged insulin into secretory granules, exhibited glucose responsive insulin secretion, and had an immediate and prolonged effect in normalising blood glucose levels upon transplantation into diabetic mice. We estimate that approximately 3 billion of these cells would have an immediate therapeutic effect following engraftment in type 1 diabetes patients and that one pancreas would provide sufficient tissue for numerous transplants.

  17. Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction

    Science.gov (United States)

    Tulpule, Asmin; Kelley, James M.; Lensch, M. William; McPherson, Jade; Park, In Hyun; Hartung, Odelya; Nakamura, Tomoka; Schlaeger, Thorsten M.; Shimamura, Akiko; Daley, George Q.

    2013-01-01

    Summary Shwachman-Diamond syndrome (SDS), a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency and hematopoietic dysfunction, is caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. We created human pluripotent stem cell models of SDS by knock-down of SBDS in human embryonic stem cells (hESCs) and generation of induced pluripotent stem cell (iPSC) lines from two SDS patients. SBDS-deficient hESCs and iPSCs manifest deficits in exocrine pancreatic and hematopoietic differentiation in vitro, enhanced apoptosis and elevated protease levels in culture supernatants, which could be reversed by restoring SBDS protein expression through transgene rescue or by supplementing culture media with protease inhibitors. Protease-mediated auto-digestion provides a mechanistic link between the pancreatic and hematopoietic phenotypes in SDS, highlighting the utility of hESCs and iPSCs in obtaining novel insights into human disease. PMID:23602541

  18. The cholesteryl octanoate breath test: a new procedure for detection of pancreatic insufficiency in the rat.

    Science.gov (United States)

    Mundlos, S; Rhodes, J B; Hofmann, A F

    1987-09-01

    A breath test for the detection of pancreatic insufficiency was developed and tested in rats. The test features the hydrophobic molecule cholesteryl-1-14C-octanoate, which liberates 14C-octanoic acid when hydrolyzed by carboxyl ester lipase (cholesterol esterase). The 14C-octanoate is absorbed passively and rapidly metabolized to 14CO2, which is excreted in expired air. The compound was administered as an emulsion of cholesteryl octanoate, triglyceride, and lecithin to rats with mild pancreatic insufficiency induced by injecting the pancreatic duct with zein. The animals had exocrine pancreatic hypofunction based on the enzyme content of pancreas at autopsy. Amylase was reduced by 97.1 +/- 1.4%, whereas chymotrypsin was reduced by 73 +/- 14%. The p-aminobenzoic acid test was abnormal at 1 wk (21.68 +/- 8.4%), but become normal at 3 months (72.08 +/- 5.8%) after zein injection. Despite this, the animals gained weight and absorbed fat normally. The 14CO2 excretion rate in the 110-min interval after feeding was significantly reduced to 60% of sham-operated animals. Peak 14CO2 collections 20 min after feeding were reduced by 75 +/- 11%. 14CO2 output was completely normalized by administration of pancreatin prior to the test meal. The results suggest that a sensitive, noninvasive method for detecting deficiency of pancreatic carboxyl ester lipase (cholesterol esterase) secretion in the rat has been developed.

  19. Pharmacological challenges in chronic pancreatitis.

    Science.gov (United States)

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-11-14

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids are often prescribed as pain treatment. Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time. Furthermore, the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby affect absorption of the drug. As stated above many factors can influence drug absorption and metabolism in patients with chronic pancreatitis. The factors may not have clinical relevance, but may explain inter-individual variations in responses to a given drug, in patients with chronic pancreatitis.

  20. Kinetics of amino acid and glucose absorption following pancreatic diversion in the pig

    Science.gov (United States)

    Rerat, A.; Calmes, R.; Corring, T.; Vaissade, P.

    1996-01-01

    An experiment was conducted in the pig to determine the consequences of deprivation of exocrine pancreatic secretion on the composition and quantity of nutrients absorbed after intake of a balanced diet. Five growing pigs (53.8 kg body weight) were fitted with permanent catheters in the portal vein and the carotid artery and with an electromagnetic flow probe around the portal vein to measure the exchanges between the blood and the intestinal lumen. They were also fitted with a permanent catheter in the duct of Wirsung to educe the exocrine pancreatic secretion and another one in the duodenum in order to reintroduce it. In each animal, glucose, amino-N and amino acid absorption as well as insulin and glucagon production were measured over a period of 10 h after the meal (semi-purified diet based on purified starch and containing 180 g fish meal/kg, DM content of the meal 731 g), either in the presence of pancreatic juice (group C: immediate reintroduction), or in the absence of pancreatic juice (group D: deprivation). The deprivation of pancreatic juice provoked a marked depression in the absorption of glucose (D 67.9 (SEM 27.9) g/10 h, C 437.7 (SEM 39.5) g/10 h, P juice. Insulin production was much lower (by 64%, P juice whereas that of glucagon was not affected.

  1. Cigarette smoke-induced differential expression of the genes involved in exocrine function of the rat pancreas.

    Science.gov (United States)

    Wittel, Uwe A; Singh, Ajay P; Henley, Brandon J; Andrianifahanana, Mahefatiana; Akhter, Mohammed P; Cullen, Diane M; Batra, Surinder K

    2006-11-01

    Little is known about the molecular and biological aspects of the epidemiological association between smoking and pancreatic pathology, such as chronic pancreatitis and pancreatic cancer. Recently, we reported that tobacco smoke exposure induced morphological alterations in the rat pancreas. Here, we have investigated the alterations in the expression of genes associated with exocrine pancreatic function and cellular differentiation upon exposure to cigarette smoke. Female rats were exposed to environmental smoke inhalation for 2 d/wk (70 min/d) for 12 weeks. The expression profiles of trypsinogen, pancreas-specific trypsin inhibitor, cholecystokinin A receptor, cystic fibrosis transmembrane conductance regulator (CFTR), carbonic anhydrase, and Muc1 and Muc4 mucins transcripts were analyzed by RNA slot blot analysis. Muc4 expression was also examined by immunohistochemistry. Our data revealed that the ratio of trypsinogen to that of the protective pancreas-specific trypsin inhibitor was elevated upon cigarette smoke exposure. The expression of carbonic anhydrase and CFTR remained unaltered when inflammatory signs were not detected in histological examinations. On the other hand, when pancreatic inflammation was present, the levels of CFTR and carbonic anhydrase were increased, indicating ductal and/or centroacinar cell involvement. No changes in the expression of Muc1 and Muc4 mucins were observed. Our data show that cigarette smoke exposure leads to an increased vulnerability to pancreatic self-digestion. Moreover, the concomitant involvement of pancreatic ducts occurs only when focal pancreatic inflammation is present.

  2. SEC23B is required for pancreatic acinar cell function in adult mice

    Science.gov (United States)

    Khoriaty, Rami; Vogel, Nancy; Hoenerhoff, Mark J.; Sans, M. Dolors; Zhu, Guojing; Everett, Lesley; Nelson, Bradley; Durairaj, Haritha; McKnight, Brooke; Zhang, Bin; Ernst, Stephen A.; Ginsburg, David; Williams, John A.

    2017-01-01

    Mice with germline absence of SEC23B die perinatally, exhibiting massive pancreatic degeneration. We generated mice with tamoxifen-inducible, pancreatic acinar cell–specific Sec23b deletion. Inactivation of Sec23b exclusively in the pancreatic acinar cells of adult mice results in decreased overall pancreatic weights from pancreatic cell loss (decreased pancreatic DNA, RNA, and total protein content), as well as degeneration of exocrine cells, decreased zymogen granules, and alterations in the endoplasmic reticulum (ER), ranging from vesicular ER to markedly expanded cisternae with accumulation of moderate-density content or intracisternal granules. Acinar Sec23b deletion results in induction of ER stress and increased apoptosis in the pancreas, potentially explaining the loss of pancreatic cells and decreased pancreatic weight. These findings demonstrate that SEC23B is required for normal function of pancreatic acinar cells in adult mice. PMID:28539403

  3. Clinical Characteristics and Risk Factors for the Development of Postoperative Hepatic Steatosis After Total Pancreatectomy.

    Science.gov (United States)

    Hata, Tatsuo; Ishida, Masaharu; Motoi, Fuyuhiko; Sakata, Naoaki; Yoshimatsu, Gumpei; Naitoh, Takeshi; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

    2016-03-01

    The occurrence of hepatic steatosis after pancreatectomy is known to be associated with the remnant pancreatic function. However, other risk factors for hepatic steatosis after pancreatectomy remain unknown. The aims of this study were to identify other risk factors in addition to the remnant pancreatic function and elucidate the relationship between postoperative hepatic steatosis and pancreatic exocrine insufficiency in totally pancreatomized patients. Forty-three patients who underwent total pancreatectomy were analyzed. Hepatic steatosis was defined as the attenuation of unenhanced computed tomography values. Clinical findings and laboratory data were compared between patients with and without hepatic steatosis. Sixteen (37.2%) patients developed hepatic steatosis after total pancreatectomy, with marked declines in the Controlling Nutritional Status score and body mass index. Multiple linear regression analysis revealed that the attenuation of computed tomography values was correlated with female sex (P = 0.002), early postoperative serum albumin levels (P = 0.003), and pancreatic enzyme replacement therapy with high-dose pancrelipase (P = 0.032). Postoperative hepatic steatosis after pancreatectomy is associated with sex, malnutrition, and pancreatic exocrine insufficiency. High-dose pancreatic enzyme replacement therapy may have preventive effects on hepatic steatosis occurring after pancreatectomy.

  4. Hepatocyte growth factor signaling in intrapancreatic ductal cells drives pancreatic morphogenesis.

    Directory of Open Access Journals (Sweden)

    Ryan M Anderson

    Full Text Available In a forward genetic screen for regulators of pancreas development in zebrafish, we identified donut(s908 , a mutant which exhibits failed outgrowth of the exocrine pancreas. The s908 mutation leads to a leucine to arginine substitution in the ectodomain of the hepatocyte growth factor (HGF tyrosine kinase receptor, Met. This missense mutation impedes the proteolytic maturation of the receptor, its trafficking to the plasma membrane, and diminishes the phospho-activation of its kinase domain. Interestingly, during pancreatogenesis, met and its hgf ligands are expressed in pancreatic epithelia and mesenchyme, respectively. Although Met signaling elicits mitogenic and migratory responses in varied contexts, normal proliferation rates in donut mutant pancreata together with dysmorphic, mislocalized ductal cells suggest that met primarily functions motogenically in pancreatic tail formation. Treatment with PI3K and STAT3 inhibitors, but not with MAPK inhibitors, phenocopies the donut pancreatic defect, further indicating that Met signals through migratory pathways during pancreas development. Chimera analyses showed that Met-deficient cells were excluded from the duct, but not acinar, compartment in the pancreatic tail. Conversely, wild-type intrapancreatic duct and "tip cells" at the leading edge of the growing pancreas rescued the donut phenotype. Altogether, these results reveal a novel and essential role for HGF signaling in the intrapancreatic ducts during exocrine morphogenesis.

  5. Secretin-stimulated MRI characterization of pancreatic morphology and function in patients with chronic pancreatitis.

    Science.gov (United States)

    Madzak, Adnan; Olesen, Søren Schou; Haldorsen, Ingfrid Salvesen; Drewes, Asbjørn Mohr; Frøkjær, Jens Brøndum

    Chronic pancreatitis (CP) is characterized by abnormal pancreatic morphology and impaired endocrine and exocrine function. However, little is known about the relationship between pancreatic morphology and function, and also the association with the etiology and clinical manifestations of CP. The aim was to explore pancreatic morphology and function with advanced MRI in patients with CP and healthy controls (HC) METHODS: Eighty-two patients with CP and 22 HC were enrolled in the study. Morphological imaging parameters included pancreatic main duct diameter, gland volume, fat signal fraction and apparent diffusion coefficient (ADC) values. Functional secretin-stimulated MRI (s-MRI) parameters included pancreatic secretion (bowel fluid volume) and changes in pancreatic ADC value before and after secretin stimulation. Patients were classified according to the modified Cambridge and M-ANNHEIM classification system and fecal elastase was collected. All imaging parameters differentiated CP patients from HC; however, correlations between morphological and functional parameters in CP were weak. Patients with alcoholic and non-alcoholic etiology had comparable s-MRI findings. Fecal elastase was positively correlated to pancreatic gland volume (r = 0.68, P = 0.0016) and negatively correlated to Cambridge classification (r = -0.35, P pancreatic gland volume was significantly decreased in the severe stages of CP (P = 0.001). S-MRI provides detailed information about pancreatic morphology and function and represents a promising non-invasive imaging method to characterize pancreatic pathophysiology and may enable monitoring of disease progression in patients with CP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  6. English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis.

    Science.gov (United States)

    Hoffmeister, A; Mayerle, J; Beglinger, C; Büchler, M W; Bufler, P; Dathe, K; Fölsch, U R; Friess, H; Izbicki, J; Kahl, S; Klar, E; Keller, J; Knoefel, W T; Layer, P; Loehr, M; Meier, R; Riemann, J F; Rünzi, M; Schmid, R M; Schreyer, A; Tribl, B; Werner, J; Witt, H; Mössner, J; Lerch, M M

    2015-12-01

    Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Earlier surgery improves outcomes from painful chronic pancreatitis

    Science.gov (United States)

    Ke, Nengwen; Jia, Dan; Huang, Wei; Nunes, Quentin M.; Windsor, John A.; Liu, Xubao; Sutton, Robert

    2018-01-01

    Abstract The timing of surgery for painful chronic pancreatitis (CP) may affect outcomes. Clinical course, Izbicki pain scores, and pancreatic function were retrospectively compared and analyzed between patients undergoing either early or late surgery (pancreatic mass +/− ductal dilatation (47% vs 27%, P insufficiency (60% vs 72%, P = .034); there were no other significant differences. The early group had longer hospital stay (14.4 vs 12.2 days, P = .009), but no difference in complications. Significantly greater pain relief followed early surgery (complete 69% vs 47%, partial 22% vs 37%, none 8% vs 16%, P = .01) with lower rates of exocrine (60% vs 80%, P = .005) and endocrine insufficiency (36% vs 53%, P = .033). Our data indicate that early surgery results in higher rates of pain relief and pancreatic sufficiency than late surgery for chronic pancreatitis patients. Frey and Berne procedures showed better results than other surgical procedures. PMID:29742705

  8. Tuberculosis alters pancreatic enzymes in the absence of pancreatitis

    Directory of Open Access Journals (Sweden)

    Modisa S. Motswaledi

    2014-10-01

    Objective: To compare serum lipase and amylase activity levels in patients with tuberculosis (TB against those of healthy controls. Methods: Serum lipase and amylase activity levels were measured in 99 patients and 143 healthy controls using the Vitros 250 Chemistry analyser. Reference ranges for serum lipase and amylase were 23–300 U/L and 30–110 U/L, respectively. Results: Lipase was higher in patients with MTB than in controls (81.5 IU/L versus 66.5 IU/L, p = 0.006. Similarly, amylase was higher in the MTB patient group (76 IU/L versus 60 IU/L, p < 0.001. The Pearson correlation coefficient for lipase versus amylase (R was higher in the controls (R = 0.351, p < 0.0001 compared with MTB patients (R = 0.217, p = 0.035. Amongst MTB patients, lipase activity correlated positively with erythrocyte sedimentation rate (ESR (R = 0.263, p = 0.013, but not with haemoglobin concentration or treatment duration. A weak inverse correlation was noted between ESR and treatment duration (R = -0.222, p = 0.028. Conclusion: Pancreatic enzyme levels differ between MTB patients and normal controls; however, this difference still lies within the normal range. The concomitant increase of lipase with ESR, an inflammatory marker, could conceivably suggest a causal relationship. Further research is necessary to characterise MTB-derived enzymes for diagnostic and therapeutic utility.

  9. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

    Science.gov (United States)

    Pierre, Joseph F.; Neuman, Joshua C.; Brill, Allison L.; Brar, Harpreet K.; Thompson, Mary F.; Cadena, Mark T.; Connors, Kelsey M.; Busch, Rebecca A.; Heneghan, Aaron F.; Cham, Candace M.; Jones, Elaina K.; Kibbe, Carly R.; Davis, Dawn B.; Groblewski, Guy E.; Kudsk, Kenneth A.

    2015-01-01

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

  10. [Update on chronic pancreatitis: review article].

    Science.gov (United States)

    Czul, Frank; Coronel, Emmanuel; Donet, Jean A

    2017-01-01

    Chronic pancreatitis is a progressive fibro-inflammatory disease of the pancreas characterized by irreversible fibrosis of the gland with eventual failure of exocrine and endocrine functions and hallmark features of abdominal pain, malabsorption, malnutrition, diabetes mellitus and pancreatic calcifications. In many patients this disease results from a complex mix of environmental (eg, alcohol, cigarettes, and occupational chemicals), genetic factors and a few patients with hereditary or autoimmune disease. The management includes medical, endoscopic and surgical approaches with the need for interaction between various specialties, calling for a concerted multidisciplinary approach. This review provides the reader with a comprehensive overview of the studies summarizing the epidemiology, etiology, physiopatology, clinical manifestation, diagnosis and treatments of the disease.

  11. RIP3 attenuates the pancreatic damage induced by deletion of ATG7.

    Science.gov (United States)

    Zhou, Xiaodong; Xie, Li; Xia, Leizhou; Bergmann, Frank; Büchler, Markus W; Kroemer, Guido; Hackert, Thilo; Fortunato, Franco

    2017-07-13

    Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and exocrine insufficiency and pancreatitis. The aim of this study was to investigate whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death, inflammation and fibrosis were evaluated by using of a compendium of immunofluorescence methods and immunoblots. Mice deficient for pancreatic Atg7 developed acute pancreatitis, which progressed to chronic pancreatitis. This phenotype reduces autophagy, increase apoptosis and necroptosis, inflammation and fibrosis, as well as premature death of the animals. Knockout of Rip3 exacerbated the apoptotic death of acinar cells, increased tissue damage, reduced macrophage infiltration and further accelerated the death of the mice with Atg7-deficient pancreas. The pancreatic degeneration induced by autophagy inhibition was exacerbated by Rip3 deletion.

  12. 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. ...

  13. Pancreatic neuroendocrine tumor - incidental finding during a follow-up CT for primary ovarian carcinoma

    International Nuclear Information System (INIS)

    Ivanova, D.; Balev, B.

    2013-01-01

    Pancreatic neuroendocrine tumors (PNET) are primary, usually we 11-differentiated pancreatic tumors. Their origin is not fully understood, but they are thought to develop from the pluripotent cells in the exocrine part of the pancreas. PNET are a heterogeneous group with different malignant potential. In some of the patients with sporadical forms of PNET there is association with other malignancies such as ovarian cancer, breast cancer, bladder and prostate cancers. We present a case of 50-year-old woman, with incidentally found pancreatic neoplasm, during a follow-up CT for ovarian cancer. Laparotomy and pancreatic biopsy are performed. Histological diagnosis confirms a well- differentiated endocrine tumor of the pancreas. (authors)

  14. The Scandinavian baltic pancreatic club (SBPC) database: design, rationale and characterisation of the study cohort.

    Science.gov (United States)

    Olesen, Søren S; Poulsen, Jakob L; Drewes, Asbjørn M; Frøkjær, Jens B; Laukkarinen, Johanna; Parhiala, Mikael; Rix, Iben; Novovic, Srdan; Lindkvist, Björn; Bexander, Louise; Dimcevski, Georg; Engjom, Trond; Erchinger, Friedemann; Haldorsen, Ingfrid S; Pukitis, Aldis; Ozola-Zālīte, Imanta; Haas, Stephan; Vujasinovic, Miroslav; Löhr, J Matthias; Gulbinas, Antanas; Jensen, Nanna M; Jørgensen, Maiken T; Nøjgaard, Camilla

    2017-08-01

    Chronic pancreatitis (CP) is a multifaceted disease associated with several risk factors and a complex clinical presentation. We established the Scandinavian Baltic Pancreatic Club (SBPC) Database to characterise and study the natural history of CP in a Northern European cohort. Here, we describe the design of the database and characteristics of the study cohort. Nine centres from six different countries in the Scandinavian-Baltic region joined the database. Patients with definitive or probable CP (M-ANNHEIM diagnostic criteria) were included. Standardised case report forms were used to collect several assessment variables including disease aetiology, duration of CP, preceding acute pancreatitis, as well as symptoms, complications, and treatments. The clinical stage of CP was characterised according to M-ANNNHEIM. Yearly follow-up is planned for all patients. The study cohort comprised of 910 patients (608 men: 302 women; median age 58 (IQR: 48-67) years with definite 848 (93%) or probable CP 62 (7%). Nicotine (70%) and alcohol (59%) were the most frequent aetiologies and seen in combination in 44% of patients. A history of recurrent acute pancreatitis was seen in 49% prior to the development of CP. Pain (69%) and exocrine pancreatic insufficiency (68%) were the most common complications followed by diabetes (43%). Most patients (30%) were classified as clinical stage II (symptomatic CP with exocrine or endocrine insufficiency). Less than 10% of the patients had undergone pancreatic surgery. The SBPC database provides a mean for future prospective, observational studies of CP in the Northern European continent.

  15. Autoimmune Pancreatitis Can Transform Into Chronic Features Similar to Advanced Chronic Pancreatitis With Functional Insufficiency Following Severe Calcification.

    Science.gov (United States)

    Kanai, Keita; Maruyama, Masahiro; Kameko, Fumiko; Kawasaki, Kenji; Asano, Junpei; Oguchi, Takaya; Watanabe, Takayuki; Ito, Tetsuya; Muraki, Takashi; Hamano, Hideaki; Matsumoto, Akihiro; Arakura, Norikazu; Kawa, Shigeyuki

    2016-09-01

    Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction. Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R. The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 μg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 μU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP. Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP.

  16. 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...

  17. Role of Melatonin, Galanin, and RFamide Neuropeptides QRFP26 and QRFP43 in the Neuroendocrine Control of Pancreatic β-Cell Function

    Directory of Open Access Journals (Sweden)

    Iacopo Gesmundo

    2017-07-01

    Full Text Available Glucose homeostasis is finely regulated by a number of hormones and peptides released mainly from the brain, gastrointestinal tract, and muscle, regulating pancreatic secretion through cellular receptors and their signal transduction cascades. The endocrine function of the pancreas is controlled by islets within the exocrine pancreatic tissue that release hormones like insulin, glucagon, somatostatin, pancreatic polypeptide, and ghrelin. Moreover, both exocrine and endocrine pancreatic functions are regulated by a variety of hormonal and neural mechanisms, such as ghrelin, glucagon-like peptide, glucose-dependent insulinotropic polypeptide, or the inhibitory peptide somatostatin. In this review, we describe the role of neurohormones that have been less characterized compared to others, on the regulation of insulin secretion. In particular, we will focus on melatonin, galanin, and RFamide neuropeptides QRFP26 and QRFP43, which display either insulinotropic or insulinostatic effects. In fact, in addition to other hormones, amino acids, cytokines, and a variety of proteins, brain-derived hormones are now considered as key regulators of glucose homeostasis, representing potential therapeutic targets for the treatment of diabetes and obesity.

  18. 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 ...

  19. Comparative evaluation of structural and functional changes in pancreas after endoscopic and surgical management of pancreatic necrosis.

    Science.gov (United States)

    Rana, Surinder Singh; Bhasin, Deepak Kumar; Rao, Chalapathi; Sharma, Ravi; Gupta, Rajesh

    2014-01-01

    Patients with acute necrotizing pancreatitis may develop pancreatic insufficiency and this is commonly seen in patients who have undergone surgery for pancreatic necrosis. Owing to the paucity of relative data, we retrospectively evaluated the structural and functional changes in the pancreas after endoscopic and surgical management of pancreatic necrosis. The records of patients who underwent endoscopic transmural drainage of walled off pancreatic necrosis (WOPN) over the last 3 years and who completed at least 6 months of follow up were analyzed. Structural and functional changes in these patients were compared with 25 historical surgical controls (operated in 2005-2006). Twenty six patients (21 M; mean age 35.4±8.1 years) who underwent endoscopic drainage for WOPN were followed up for 22.3±8.6 months. During the follow up, five (19.2%) patients developed diabetes with 3 patients requiring insulin and 1 patient with steatorrhea requiring pancreatic enzyme supplementation. The pancreatic fluid collection (PFC) recurred in 1 patient whose stents spontaneously migrated out. On follow up, in the surgery group, 2 (8%) patients developed steatorrhea and 11 (44%) developed diabetes. Five (20%) of these patients had recurrence of PFC. On comparison of follow up results of endoscopic drainage with surgery, recurrence rates as well as frequency of endocrine and exocrine insufficiency was lower in the endoscopic group but difference was not significant. Structural and functional impairment of pancreas is seen less frequently in patients with pancreatic necrosis treated endoscopically compared to patients undergoing surgery, although the difference was insignificant. Further studies with large sample size are needed to confirm these initial results.

  20. The evolution of the surgical treatment of chronic pancreatitis.

    Science.gov (United States)

    Andersen, Dana K; Frey, Charles F

    2010-01-01

    To establish the current status of surgical therapy for chronic pancreatitis, recent published reports are examined in the context of the historical advances in the field. The basis for decompression (drainage), denervation, and resection strategies for the treatment of pain caused by chronic pancreatitis is reviewed. These divergent approaches have finally coalesced as the head of the pancreas has become apparent as the nidus of chronic inflammation. The recent developments in surgical methods to treat the complications of chronic pancreatitis and the results of recent prospective randomized trials of operative approaches were reviewed to establish the current best practices. Local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancreatic head resection offer outcomes as effective as pancreaticoduodenectomy, with lowered morbidity and mortality. Local resection or excavation of the pancreatic head offers the advantage of lowest cost and morbidity and early prevention of postoperative diabetes. The late incidences of recurrent pain, diabetes, and exocrine insufficiency are equivalent for all 3 surgical approaches. Local resection of the pancreatic head appears to offer best outcomes and lowest risk for the management of the pain of chronic pancreatitis.

  1. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition : A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Celine; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Kobold, Anneke C. Muller; Bandsma, Robert H.; van Hensbroek, Michael Boele; Voskuijl, Wieger P.

    Objective: To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design: We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth

  2. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Muller Kobold, Anneke C.; Bandsma, Robert H.; Boele van Hensbroek, Michael; Voskuijl, Wieger P.

    2017-01-01

    Objective To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central

  3. Disease: H00920 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00920 Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial ...hyperostosis Patients with this disease suffer from exocrine pancreatic insufficiency, dyserythropoietic anemia...eleg O ... TITLE ... Exocrine pancreatic insufficiency, dyserythropoeitic anemia, a

  4. Specific Radiological Imaging Findings in Patients With Hereditary Pancreatitis During a Long Follow-up of Disease.

    Science.gov (United States)

    van Esch, Aura A J; Drenth, Joost P H; Hermans, John J

    2017-03-01

    Hereditary pancreatitis (HP) is characterized by recurrent episodes of inflammation of the pancreas. Radiological imaging is used to diagnose HP and to monitor complications. The aim of this study was to describe specific imaging findings in HP. We retrospectively collected data of HP patients with serial imaging and reviewed all radiological imaging studies (transabdominal ultrasonography, computed tomography, and magnetic resonance imaging). We included 15 HP patients, with a mean age of 32.5 years (range, 9-61 years) and mean disease duration of 24.1 years (range, 6-42 years). In total, 152 imaging studies were reviewed. Seventy-three percent of patients had a dilated main pancreatic duct (MPD) (width 3.5-18 mm). The MPD varied in size during disease course, with temporary reduction in diameter after drainage procedures. A severe dilated MPD (>10 mm) often coincided with presence of intraductal calcifications (size, 1-12 mm). In 73% of patients, pancreatic parenchyma atrophy occurred, which did not correlate with presence of exocrine or endocrine insufficiency. In HP, the MPD diameter increases with time, mostly without dilated side branches, and is often accompanied by large intraductal calcifications. The size of the MPD is independent of disease state. Atrophy of pancreatic parenchyma is not correlated with exocrine or endocrine insufficiency.

  5. A computer-based automated algorithm for assessing acinar cell loss after experimental pancreatitis.

    Directory of Open Access Journals (Sweden)

    John F Eisses

    Full Text Available The change in exocrine mass is an important parameter to follow in experimental models of pancreatic injury and regeneration. However, at present, the quantitative assessment of exocrine content by histology is tedious and operator-dependent, requiring manual assessment of acinar area on serial pancreatic sections. In this study, we utilized a novel computer-generated learning algorithm to construct an accurate and rapid method of quantifying acinar content. The algorithm works by learning differences in pixel characteristics from input examples provided by human experts. HE-stained pancreatic sections were obtained in mice recovering from a 2-day, hourly caerulein hyperstimulation model of experimental pancreatitis. For training data, a pathologist carefully outlined discrete regions of acinar and non-acinar tissue in 21 sections at various stages of pancreatic injury and recovery (termed the "ground truth". After the expert defined the ground truth, the computer was able to develop a prediction rule that was then applied to a unique set of high-resolution images in order to validate the process. For baseline, non-injured pancreatic sections, the software demonstrated close agreement with the ground truth in identifying baseline acinar tissue area with only a difference of 1% ± 0.05% (p = 0.21. Within regions of injured tissue, the software reported a difference of 2.5% ± 0.04% in acinar area compared with the pathologist (p = 0.47. Surprisingly, on detailed morphological examination, the discrepancy was primarily because the software outlined acini and excluded inter-acinar and luminal white space with greater precision. The findings suggest that the software will be of great potential benefit to both clinicians and researchers in quantifying pancreatic acinar cell flux in the injured and recovering pancreas.

  6. [Roles of protease-activated receptor-2 (PAR-2), a G protein-coupled receptor, in modulation of exocrine gland functions].

    Science.gov (United States)

    Nishikawa, Hiroyuki

    2006-07-01

    Protease-activated receptor-2 (PAR-2), a G protein-coupled receptor, is activated by proteolytic unmasking of the N-terminal extracellular tethered ligand that presumably binds to the extracellular loop 2 of the receptor itself. PAR-2 is widely distributed in the mammalian body and plays various roles in biological events in the cardiovascular, respiratory, alimentary, and central neurons systems. PAR-2-activating peptides administered systemically to mice and rats trigger prompt salivation in vivo. In an in vitro study, PAR-2 agonists including the endogenous PAR-2 activator trypsin induce secretion of amylase and mucin from isolated rat parotid glands and sublingual glands, respectively. PAR-2-activating peptides administered systemically also modulate pancreatic exocrine secretion in vivo as well as in vitro. In the gastric mucosa, PAR-2 stimulation enhances secretion of mucus and pepsinogen and suppresses acid secretion. Tear secretion can also be caused by PAR-2-related peptides in PAR-2-dependent and -independent manners. PAR-2 thus plays a general or key role in the regulation of exocrine secretion. This review focuses on the physiologic and/or pathophysiologic roles of PAR-2 in glandular exocrine secretion. The possibility of PAR-2 as a target for drug development is also discussed.

  7. New stable isotope method to measure protein digestibility and response to pancreatic enzyme intake in cystic fibrosis.

    Science.gov (United States)

    Engelen, M P K J; Com, G; Anderson, P J; Deutz, N E P

    2014-12-01

    Adequate protein intake and digestion are necessary to prevent muscle wasting in cystic fibrosis (CF). Accurate and easy-to-use methodology to quantify protein maldigestion is lacking in CF. To measure protein digestibility and the response to pancreatic enzyme intake in CF by using a new stable isotope methodology. In 19 CF and 8 healthy subjects, protein digestibility was quantified during continuous (sip) feeding for 6 h by adding (15)N-labeled spirulina protein and L-[ring-(2)H5]phenylalanine (PHE) to the nutrition and measuring plasma ratio [(15)N]PHE to [(2)H5]PHE. Pancreatic enzymes were ingested after 2 h in CF and the response in protein digestibility was assessed. To exclude difference in mucosal function, postabsorptive whole-body citrulline (CIT) production rate was measured by L-[5-(13)C-5,5-(2)H2]-CIT pulse and blood samples were taken to analyze tracer-tracee ratios. Protein digestibility was severely reduced in the CF group (47% of healthy subjects; P digestibility in CF until 90% of values obtained by healthy subjects. Maximal digestibility was reached at 100 min and maintained for 80 min. Stratification into CF children (n = 10) and adults showed comparable values for protein digestibility and similar kinetic responses to pancreatic enzyme intake. Whole-body citrulline production was elevated in CF indicating preserved mucosal function. Protein digestibility is severely compromised in patients with CF as measured by this novel and easy-to-use stable isotope approach. Pancreatic enzymes are able to normalize protein digestibility in CF, albeit with a severe delay. Registration ClinicalTrials.gov = NCT01494909. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  8. Pancreatic mesenchyme regulates epithelial organogenesis throughout development.

    Directory of Open Access Journals (Sweden)

    Limor Landsman

    2011-09-01

    Full Text Available The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for the mesenchyme in regulating the expansion of progenitor cells in the early pancreas epithelium. However, due to the lack of genetic tools directing expression specifically to the mesenchyme, the potential roles of this supporting tissue in vivo, especially in guiding later stages of pancreas organogenesis, have not been elucidated. We employed transgenic tools and fetal surgical techniques to ablate mesenchyme via Cre-mediated mesenchymal expression of Diphtheria Toxin (DT at the onset of pancreas formation, and at later developmental stages via in utero injection of DT into transgenic mice expressing the Diphtheria Toxin receptor (DTR in this tissue. Our results demonstrate that mesenchymal cells regulate pancreatic growth and branching at both early and late developmental stages by supporting proliferation of precursors and differentiated cells, respectively. Interestingly, while cell differentiation was not affected, the expansion of both the endocrine and exocrine compartments was equally impaired. To further elucidate signals required for mesenchymal cell function, we eliminated β-catenin signaling and determined that it is a critical pathway in regulating mesenchyme survival and growth. Our study presents the first in vivo evidence that the embryonic mesenchyme provides critical signals to the epithelium throughout pancreas organogenesis. The findings are novel and relevant as they indicate a critical role for the mesenchyme during late expansion of endocrine and exocrine compartments. In addition, our results provide a molecular mechanism for mesenchymal expansion and survival by identifying β-catenin signaling as an

  9. Progress of pancreatitis disease biomarker alpha amylase enzyme by new nano optical sensor.

    Science.gov (United States)

    Attia, M S; Al-Radadi, Najlaa S

    2016-12-15

    A new nano optical sensor binuclear Pd-(2-aminothiazole) (urea), Pd(atz,ur) complex was prepared and characterized for the assessment of the activity of alpha amylase enzyme in urine and serum samples for early diagnosis of Pancreatitis disease. The assessment of alpha amylase activity is carried out by the quenching of the luminescence intensity of the nano optical sensor binuclear Pd(atz,ur) complex at 457nm by the 2-chloro-4-nitrophenol (2-CNP) which produced from the reaction of the enzyme with 2-chloro-4-nitrophenyl-α-d-maltotrioside (CNPG3) substrate. The remarkable quenching of the luminescence intensity at 457nm of nano Pd(atz,ur) doped in sol-gel matrix by various concentrations of the 2-CNP was successfully used as an optical sensor for the assessment of α-amylase activity. The calibration plot was achieved over the concentration range 8.5×10(-6) to 1.9×10(-9)molL(-1) 2-CNP with a correlation coefficient of (0.999) and a detection limit of (7.4×10(-10)molL(-1)). The method was used satisfactorily for the assessment of the α-amylase activity over activity range (3-321U/L) in different urine and serum samples of pancreatitis patients. The assessment of the alpha amylase biomarker by the proposed method increases its sensitivity (96.88%) and specificity (94.41%) for early diagnosis of pancreatitis diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. [Current alternatives in the surgical treatment of chronic pancreatitis--a review article].

    Science.gov (United States)

    Kat'uchová, Jana; Radonak, Jozef

    2011-01-01

    Chronic pancreatitis is characterized as an inflammatory process affecting the pancreas that causes progressive destruction of the gland and fibrosis, with subsequent endocrine and exocrine insufficiency. The most common cause of chronic pancreatitis is alcohol use in combination with nicotine. Manifestations are persistent or recurrent painful attacks. The only parameter of successful treatment of chronic pancreatitis is a relieve from long-lasting pain and improvement of the quality of life. Surgical treatment options include drainage operations on the pancreas, pancreatic resection or a combination of both. With optimal surgical treatment performed and good patient's compliance, operations for chronic pancreatitis have low number of post-operative complications and relatively good long-term results. The continued consumption of alcohol and drugs bring about worse outcomes, sometimes even a complete failure of therapy. Chronic pancreatitis also has considerable socio-economic consequences. Due to the persisting pain and frequent hospitalization it can lead to long-term disability and early retirement predominantly in young patients.

  11. Chronic pancreatitis. Diagnosis, therapy and follow-up results; Chronische Pankreatitis. Diagnostik, Therapie und Langzeitergebnisse

    Energy Technology Data Exchange (ETDEWEB)

    Moessner, J. [Medizinische Klinik und Poliklinik 2, Zentrum fuer Innere Medizin, Univ. Leipzig (Germany)

    1996-09-01

    The incidence of chronic pancreatitis is increasing in industrialized countries due to the steady increase of alcohol abuse. The pathogenesis of this disease is still incompletely understood. A cure is not possible. The knowledge of the patients history and a thorough clinical investigation together with the availability of a wide array of laboratory tests and imaging procedures enable the physician to characterize the stage of the disease. Exact knowledge of the present pancreatic morphology, potential complications of the disease, and knowledge about the present exocrine and endocrine function capacity are prerequisites for adequate therapeutic decision making. The therapeutic possibilities include termination of alcohol abuse, various options of treatment of pain according to the various pathogenetic possibilities leading to pain, pancreatic digestive enzyme supplementation, treatment of diabetes, and either endoscopic or surgical treatments of complications of the disease. (orig.) [Deutsch] Die Inzidenz der chronischen Pankreatitis nimmt in den Industrienationen aufgrund der Zunahme des Alkoholabusus an Haeufigkeit zu. Die Diagnose der chronischen Pankreatitis wird oft spaet gestellt. Eine Heilung ist noch nicht moeglich. Eine detailierte Anamnese, Beurteilung der Klinik, Laborparameter, Pankreasfunktionsanalysen und eine ganze Palette unterschiedlicher bildgebender Verfahren ermoeglichen eine Charakterisierung des jeweiligen Krankheitszustandes. Dies ist die Voraussetzung zur differenzierten Einleitung einer medikamentoesen und/oder interventionellen endoskopischen und/oder chirurgischen Therapie. Wie bei jedem nicht heilbaren chronischen Krankheitsbild ist eine stadiengerechte Therapie erforderlich. (orig.)

  12. Ca2+-dependent K+ Channels in Exocrine Salivary Glands

    Science.gov (United States)

    Catalán, Marcelo A.; Peña-Munzenmayer, Gaspar; Melvin, James E.

    2014-01-01

    In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca2+-dependent K+ channels take part in key functions including membrane potential regulation, fluid movement and K+ secretion in exocrine glands. Two K+ channels have been identified in exocrine salivary glands: 1) a Ca2+-activated K+ channel of intermediate single channel conductance encoded by the KCNN4 gene; and, 2) a voltage- and Ca2+-dependent K+ channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca2+-dependent K+ channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca2+-dependent K+ channels by protein-protein interactions that may significantly impact exocrine gland physiology. PMID:24559652

  13. Differences in serum concentrations of organochlorine compounds by occupational social class in pancreatic cancer

    International Nuclear Information System (INIS)

    Porta, Miquel; Bosch de Basea, Magda; Benavides, Fernando G.; Lopez, Tomas; Fernandez, Esteve; Marco, Esther; Alguacil, Juan; Grimalt, Joan O.; Puigdomenech, Elisa

    2008-01-01

    Background: The relationships between social factors and body concentrations of environmental chemical agents are unknown in many human populations. Some chemical compounds may play an etiopathogenic role in pancreatic cancer. Objective: To analyze the relationships between occupational social class and serum concentrations of seven selected organochlorine compounds (OCs) in exocrine pancreatic cancer: dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethene (p,p'-DDE), 3 polychlorinated biphenyls (PCBs), hexachlorobenzene, and β-hexachlorocyclohexane. Methods: Incident cases of exocrine pancreatic cancer were prospectively identified, and interviewed face-to-face during hospital admission (n=135). Serum concentrations of OCs were analyzed by high-resolution gas chromatography with electron-capture detection. Social class was classified according to occupation. Results: Multivariate-adjusted concentrations of all seven compounds were higher in occupational social classes IV-V (the less affluent) than in classes I-II; they were higher as well in class III than in classes I-II for four compounds. Concentrations of six OCs were higher in manual workers than in non-manual workers (p<0.05 for PCBs). Social class explained statistically between 3.7% and 5.7% of the variability in concentrations of PCBs, and 2% or less variability in the other OCs. Conclusions: Concentrations of most OCs were higher in the less affluent occupational social classes. In pancreatic cancer the putative causal role of these persistent organic pollutants may not be independent of social class. There is a need to integrate evidence on the contribution of different social processes and environmental chemical exposures to the etiology of pancreatic and other cancers

  14. Tests of pancreatic function using /sup 75/Se--Selenomethionine

    Energy Technology Data Exchange (ETDEWEB)

    Krasner, N; Brodie, M J; Sumner, D J; Thomson, T J

    1976-04-01

    Pancreatic function was investigated in 43 patients using a combination of conventional and subtraction scans of the pancreas and duodenal aspiration of the /sup 75/Se-Selenomethionine injected, in the time periods 60 to 150 minutes, 90 to 120 minutes and 105 to 150 minutes after injection. Patients with chronic alcoholism, chronic pancreatitis, pancreatic carcinoma, extrahepatic biliary obstruction and liver disease were included. Seven patients with no evidence of gastro-intestinal disease served as controls. Pancreatic scanning provided eight false positive and two false negative results (23.3 percent) and with /sup 75/Se-Selenomethionine excretion at 105 to 150 minutes, six false results were obtained (14 percent). In only one patient was a false positive result obtained with both scans and the /sup 75/Se-Selenomethionine test. The performance of conventional and subtraction scans of the pancreas with measurement of /sup 75/Se-Selenomethionine activity in the duodenal aspirate collected from 105 to 150 minutes after injection provides a convenient means of testing pancreatic exocrine function in a single three hour session.

  15. Long-term results and quality of life of patients undergoing sequential surgical treatment for severe acute pancreatitis complicated by infected pancreatic necrosis.

    Science.gov (United States)

    Cinquepalmi, Lorenza; Boni, Luigi; Dionigi, Gianlorenzo; Rovera, Francesca; Diurni, Mario; Benevento, Angelo; Dionigi, Renzo

    2006-01-01

    Infected pancreatic necrosis (IPN) is one of the most severe complications of acute pancreatitis (AP). Sequential surgical debridement represents one of the most effective treatments in terms of morbidity and mortality. The aim of this paper is to describe the quality of life and long-term results (e.g., nutritional, muscular, and pancreatic function) of patients treated by sequential necrosectomy at the Department of Surgery of the University of Insubria (Varese, Italy). Data were collected on patients undergoing sequential surgical debridement as treatment for IPN. The severity of AP was evaluated using the Ranson criteria, the Acute Physiology and Chronic Health Evaluation (APACHE II) Score, and the Sepsis Score, as well as the extent of necrosis. The surgical approach was through a midline or subcostal laparotomy, followed by exploration of the peritoneal cavity, wide debridement, and peritoneal lavage. The abdomen was either left open or closed partially with a surgical zipper, with multiple re-laparotomies scheduled until debridement of necrotic tissue was complete. The long-term evaluation focused on late morbidity, performance status, and abdominal wall function. In the majority of patients (68%), mixed flora were isolated. Pseudomonas aeruginosa was the microorganism identified most commonly (59%), often associated with Candida albicans or C. glabrata. The mean total hospital stay was 71+/-38 days (range 13-146 days), of which 24+/-19 days (range 0-66 days) were in the intensive care unit. Eight patients died, the deaths being caused by multiple organ dysfunction syndrome in seven patients and hemorrhage from the splenic artery in one. Normal exocrine and endocrine pancreatic function was observed in 28 patients (88%). At discharge, four patients had steatorrhea, which was temporary. Eight patients (23%) developed pancreatic pseudocysts, and in six, cystogastostomy was performed. Most patients (29/32, 91%) developed a post-operative hernia, but only five

  16. PET in diagnosing exocrine pancreatic cancer; PET bei Tumoren des exokrinen Pankreas

    Energy Technology Data Exchange (ETDEWEB)

    Bares, R.; Besenfelder, H.; Dohmen, B.M. [Abt. Nuklearmedizin, Radiologische Klinik des Universitaetsklinikums Tuebingen (Germany)

    2003-06-01

    Despite dramatic improvements in diagnostic imaging (ultrasonography, in particular endoscopic ultrasound, CT, MRI) treatment results of pancreatic cancer are still poor. Due to the lack of early symptoms, most tumors are diagnosed at an advanced stage of disease which excludes curative surgical treatment. FDG-PET has been shown to be effective in detecting pancreatic cancer as well as differentiating benign from malignant pancreatic tumors. Results might be further improved by applying quantitative analyses, in particular kinetic modelling of FDG metabolism. Nevertheless false negative as well as false positive findings may occur. Small lesions (lymphnode or liver metastases < 1 cm) might be missed, furthermore hyperglycemia often present in patients with pancreatic disease might reduce tumor uptake and subsequently tumor detectability by PET. False positive findings were reported in active pancreatitis and some benign tumors. Although PET proved to be superior to CT or ERCP in detecting cancer, clinical relevance of PET is limited due to the absence of therapeutic consequences to be derived from PET. As a consequence PET should only be used in patients with equivocal findings of morphological imaging (CT, ERCP) who are potential candidates for surgical treatment. (orig.) [German] Trotz verbesserter diagnostischer Moeglichkeiten (endoskopischer Ultraschall, Spiral-CT, MRT) sind die Behandlungsergebnisse bei Tumoren des exokrinen Pankreas nach wie vor unbefriedigend. Aufgrund der spaet einsetzenden klinischen Symptomatik wird die Diagnose meist erst bei lokaler Inoperabilitaet gestellt. Die FDG-PET has sich sowohl im Nachweis von Pankreaskarzinomen als auch bei der Differenzialdiagnose pankreatischer Raumforderungen bewaehrt und den etablierten bildgebenden Verfahren (Ultraschall, CT) als ueberlegen erwiesen. Weitere Verbesserungen erscheinen durch absolute Quantifizierung der FDG-Kinetik moeglich. Dennoch koennen falsch negative wie auch falsch positive Ergebnisse

  17. Transplantable pancreatic acinar carcinoma

    International Nuclear Information System (INIS)

    Warren, J.R.; Reddy, J.K.

    1981-01-01

    Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with [3H]-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with [3H]-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed

  18. Endoscopic therapy for chronic pancreatitis: technical success, clinical outcomes, and complications.

    Science.gov (United States)

    Kowalczyk, Lukasz M; Draganov, Peter V

    2009-04-01

    Chronic pancreatitis (CP) can cause failure of both the exocrine and endocrine portions of the gland. Pain is the most recalcitrant clinical complaint in CP. Generally, conservative measures are first attempted to manage pain. These include cessation of alcohol use and smoking, enzyme replacement therapy, and finally, opioid analgesia. Endoscopy can be employed to treat the pain and complications due to CP. The results of the only two prospective randomized controlled trials suggest that surgery has a more durable effect than endoscopic therapy in controlling pain. Both trials suffer from severe limitations, however, and endoscopy remains the preferred approach for many patients because of its minimally invasive nature. Endoscopic ultrasound celiac plexus block has limited value in helping to control pain. More randomized trials are needed, along with further technologic innovation to improve the current treatment modalities. When considering interventional therapy for a patient with CP, a tailored and multidisciplinary therapeutic approach should be taken.

  19. Positron emission tomography (PET) and pancreatic tumours

    International Nuclear Information System (INIS)

    Montravers, F.; Kerrou, K.; Grahek, D.; Gutman, F.; Beco, V. de; Talbot, J.N.

    2005-01-01

    Neoplasms of the pancreas may originate front both exocrine and endocrine cells but in 90% of the cases, they correspond to ductal adenocarcinomas. For adenocarcinomas, the major indication of FDG-PET corresponds to the pre-operative staging because unexpected distant metastases can be detected by FDG-PET in about 20 to 40% of the cases, which results in avoidance of unnecessary surgical procedures. FDG PET is also useful in evaluation of the treatment effect, monitoring after the operation and detection of recurrent pancreatic cancers. For the characterisation of the pancreatic tumour, the performance of FDG-PET is sometimes limited due to poor cellularity, hyperglycemia or inflammatory processes. especially for large tumours and is indicated only in cases of doubtful results of CT or MRI. For endocrine pancreatic tumours, FDG-PET is useful only in case of poorly-differentiated and aggressive tumours. F-DOPA PET can he useful, complementary to pentetreotide scintigraphy, in well-differentiated endocrine tumours. (authors)

  20. Nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: association of pancreatic exocrine deficiency and infection.

    Science.gov (United States)

    Murata, Yasuhiro; Mizuno, Shugo; Kato, Hiroyuki; Kishiwada, Masashi; Ohsawa, Ichiro; Hamada, Takashi; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami; Nishimura, Keisuke; Fukutome, Kazuo; Isaji, Shuji

    2011-08-01

    Previous clinical study has demonstrated that 30-40% of patients undergoing pancreaticoduodenectomy (PD) developed hepatic steatosis. However, nonalcoholic steatohepatitis (NASH) is a little-known complication after PD. Recently we encountered two patients with PD who later developed NASH diagnosed by liver biopsy. Case 1 was a 79-year-old woman who underwent PD for intraductal papillary mucinous neoplasm (IPMN). She had postoperative severe diarrhea due to pseudomembranous enterocolitis. Severe liver dysfunction was observed on the 31st postoperative day. Abdominal computed tomography (CT) on the 32nd day showed remarkably decreased hepatic CT value of 6 HU. Immediate liver biopsy revealed NASH (Brunt criteria: grade 2, stage 2). Case 2 was a 71-year-old woman who underwent PD for IPMN. Liver biopsy on 70th postoperative day, which was performed for assessment of moderate liver dysfunction and decreased hepatic CT value of 44 HU, demonstrated simple steatosis. In the 21st postoperative month, she developed severe urinary tract infection together with marked liver dysfunction. Immediate liver biopsy revealed NASH (Brunt criteria: grade 1, stage 1). For each patient, treatment of infection and high-dose pancreatic enzyme supplements improved liver dysfunction and liver steatosis. Clinical features of our cases seem to support the current leading hypothesis of the pathogenesis of NASH, i.e., the two-hit theory.

  1. Reflection on design and testing of pancreatic alpha-amylase inhibitors: an in silico comparison between rat and rabbit enzyme models

    Directory of Open Access Journals (Sweden)

    Khalil-Moghaddam Shiva

    2012-11-01

    Full Text Available Abstract Background Inhibitors of pancreatic alpha-amylase are potential drugs to treat diabetes and obesity. In order to find compounds that would be effective amylase inhibitors, in vitro and in vivo models are usually used. The accuracy of models is limited, but these tools are nonetheless valuable. In vitro models could be used in large screenings involving thousands of chemicals that are tested to find potential lead compounds. In vivo models are still used as preliminary mean of testing compounds behavior in the whole organism. In the case of alpha-amylase inhibitors, both rats and rabbits could be chosen as in vivo models. The question was which animal could present more accuracy with regard to its pancreatic alpha-amylase. Results As there is no crystal structure of these enzymes, a molecular modeling study was done in order to compare the rabbit and rat enzymes with the human one. The overall result is that rabbit enzyme could probably be a better choice in this regard, but in the case of large ligands, which could make putative interactions with the −4 subsite of pancreatic alpha-amylase, interpretation of results should be made cautiously. Conclusion Molecular modeling tools could be used to choose the most suitable model enzyme that would help to identify new enzyme inhibitors. In the case of alpha-amylase, three-dimensional structures of animal enzymes show differences with the human one which should be taken into account when testing potential new drugs.

  2. Effect of irradiation on the canine exocrine pancreas

    International Nuclear Information System (INIS)

    Pieroni, P.L.; Rudick, J.; Adler, M.; Nacchiero, M.; Rybak, B.J.

    1976-01-01

    Effects of irradiation on the pancreas was studied in 6 dogs receiving a dose equivalent to the biologic effect of 4000 R/6 weeks (with a nominal standard dose of 1175 rets) given to patients with Hodgkins disease. After control secretory, histologic and pancreatographic studies, 6 Thomas fistula dogs were subjected to 2400 R tumor dose over two weeks. There was a biphasic response to secretin alone or secretin with cholecystokininpancreozymin. An initial hypersecretion occurred at 2 weeks--volume was increased, but bicarbonate and enzyme output remained unchanged. Thereafter there was a progressive reduction in volume, bicarbonate and enzyme outputs (greater than 90 percent after 3 months). Histology showed early ductal reduplication but with progressive fibrosis, features compatible with chronic pancreatitis. Pancreatic insufficiency may contribute to post-irradiation gastrointestinal symptomatology. Close field irradiation of the pancreas results in actual destruction of the parenchyma

  3. 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

  4. Two cases of chronic pancreatitis associated with anomalous pancreaticobiliary ductal union and SPINK1 mutation

    Directory of Open Access Journals (Sweden)

    Eun Sam Rho

    2013-05-01

    Full Text Available Chronic pancreatitis is a progressive inflammatory disease resulting from repeated episodes of acute pancreatitis that impair exocrine function and eventually produce endocrine insufficiency. Some causes of chronic pancreatitis appear to be associated with alterations in the serine&#8211;protease inhibitor, Kazal type 1 (SPINK1 , cationic trypsinogen (PRSS1 , and cystic fibrosis&#8211;transmembrane conductance regulator (CFTR genes, or with structural disorders in the pancreaticobiliary ductal system, such as pancreatic divisum or anomalous pancreaticobiliary ductal union (APBDU. However, it is unusual to observe both genetic alteration and structural anomaly. Here, we report 2 cases with both APBDU and a mutation in the SPINK1 genes, and we discuss the implications of these findings in clinical practice.

  5. Pancreatitis in dogs and cats: definitions and pathophysiology.

    Science.gov (United States)

    Watson, P

    2015-01-01

    Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats and presents a spectrum of disease severities from acute to chronic and mild to severe. It is usually sterile, but the causes and pathophysiology remain poorly understood. The acute end of the disease spectrum is associated with a high mortality but the potential for complete recovery of organ structure and function if the animal survives. At the other end of the spectrum, chronic pancreatitis in either species can cause refractory pain and reduce quality of life. It may also result in progressive exocrine and endocrine functional impairment. There is confusion in the veterinary literature about definitions of acute and chronic pancreatitis and there are very few studies on the pathophysiology of naturally occurring pancreatitis in dogs and cats. This article reviews histological and clinical definitions and current understanding of the pathophysiology and causes in small animals by comparison with the much more extensive literature in humans, and suggests many areas that need further study in dogs and cats. © 2015 British Small Animal Veterinary Association.

  6. Cirugías Conservadoras del Parénquima Pancreático / Converving Parenchyma Pancreatic Surgeries

    Directory of Open Access Journals (Sweden)

    Giunippero Alejandro

    2015-11-01

    Full Text Available After a classical pancreatic resection the risk of endocrine and exocrine insufficiency is in the order of : 8-20 % and 20-50 % respectively 1. Conservative surgery of pancreatic parenchyma decrease the risk of insufficiency and represents the clearest benefits of this type of surgery. They are optional techniques that help the surgeon to evaluate the decision which is best for each patient and each type of lesion. Among them we will approach three of them: uncinate process resection, enucleation, median pancreatectomy.

  7. Epidermal growth factor inhibits rat pancreatic cell proliferation, causes acinar cell hypertrophy, and prevents caerulein-induced desensitization of amylase release.

    Science.gov (United States)

    Morisset, J; Larose, L; Korc, M

    1989-06-01

    The in vivo effects of epidermal growth factor (EGF) on pancreatic growth and digestive enzyme concentrations were compared with the actions of the pancreatic secretagogue caerulein in the adult rat. EGF (10 micrograms/kg BW) did not alter pancreatic weight or protein content. However, this concentration of EGF inhibited [3H]thymidine incorporation into DNA by 44%, decreased DNA content by 20%, and increased the concentrations of amylase, chymotrypsinogen, and protein by 106%, 232%, and 42%, respectively. Pancreatic acini prepared from EGF-treated rats exhibited a characteristic secretory response to caerulein that was superimposable to that obtained in acini from saline-treated rats. In both groups of acini half-maximal and maximal stimulation of amylase release occurred at approximately 5 pM and 50 pM caerulein, respectively. In contrast to EGF, caerulein (1 microgram/kg BW) increased pancreatic weight by 29% and protein content by 59%, and enhanced [3H]thymidine incorporation into DNA by 70%. Although caerulein increased the concentrations of pancreatic amylase and chymotrypsinogen by 38% and 297%, respectively, pancreatic acini prepared from caerulein-treated rats were less sensitive to the actions of caerulein in vitro when compared with acini from control rats. Indeed, the EC50 was shift from 4.8 pM to 9.8 pM after 4 days of treatment. EGF potentiated the actions of caerulein on pancreatic weight, protein content, and chymotrypsinogen concentration, and prevented the caerulein-induced alteration in the secretory responsiveness of the acinar cell. Conversely, caerulein reversed the inhibitory effect of EGF on thymidine incorporation. These findings suggest that EGF may modulate the trophic effects of certain gastrointestinal hormones, and may participate in the regulation of pancreatic exocrine function in vivo.

  8. The effect of moderate sedation on exocrine pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test (ePFT).

    Science.gov (United States)

    Conwell, Darwin L; Zuccaro, Gregory; Purich, Edward; Fein, Seymor; Vanlente, Frederick; Vargo, John; Dumot, John; O'laughlin, Cathy; Trolli, Patricia

    2005-05-01

    We have developed a purely endoscopic collection method for the assessment of pancreatic secretory function (ePFT). The pancreatic secretory effects of sedation medications utilized during endoscopic procedures are not completely known. To study the effect of moderate sedation on the exocrine pancreas gland in a prospective, randomized trial. Healthy volunteers were randomized by computers to one of two treatments (A-no sedation, B-sedation) in period 1 and crossed-over to the other treatment in period 2 with a minimal washout interval of 7 days. Sedation dosage was standardized for each patient based on age, gender and weight from a previously published dosing nomogram. Synthetic porcine secretin (ChiRhoClin, Inc., Burtonsville, Maryland) was used as the pancreatic stimulant. Duodenal fluid samples were aspirated via the endoscope every 5 min for 1 h and sent on ice to our hospital laboratory for the measurement of pancreatic secretory electrolyte concentrations by autoanalyzer. A total of 17 healthy volunteers were enrolled. Sixteen subjects (8 males and 8 females) completed the randomized prospective trial. Median intravenous meperidine and midazolam sedation dose was 62.5 mg and 2.5 mg, respectively. Maximum pancreatic juice flow occurred during the early phase of secretion and maximum bicarbonate concentration occurred during the late phase of secretion. Analysis of the electrolyte composition of the endoscopically collected duodenal drainage fluid revealed a constant cation concentration for both sodium and potassium over the 1 h collection period. The anions, chloride and bicarbonate, exhibited a reciprocal relationship identical to that seen in traditional gastroduodenal tube collection studies. There was no statistical difference observed between the sedation and no sedation groups. The estimated total bicarbonate output (area under curve, AUC) for the sedated and non-sedated groups were 5,017 meq + 724 (range 3,663-6,173) and 5,364 meq +/- 583 (range 4

  9. [Membranous nephropathy associated to autoimmune thyroiditis, chronic pancreatitis and suprarrenal insufficiency].

    Science.gov (United States)

    Merino, J L; Fernández Lucas, M; Teruel, J L; Valer, P; Moreira, V; Arambarri, M; Ortuño, J

    2004-01-01

    A 33 year old female was admitted to the hospital to study aedema and bocio, A nephrotic syndrome was diagnosed and the renal biopsy demonstrated membranous glomerulonephritis, stage II. She was also diagnosed of Hashimoto's autoinmmune thyroiditis: TSH (41.5 uUl/ml), T4 (0.07 ng/dl), antithyroglobuline (1/2560) and antimicrosome (1/6400). Four year latter she was diagnosed of autoinmmune pancreatitis, without evidence of diabetes mellitus or exocrine pancreatic insufficiency. Eight years latter she was diagnosed of primary autoimmune suprarrenal insufficiency: basal cortisol: 2.7 mcg/dl, post ACTH estimulated cortisol: 5.6 mcg/dl, antinuclear antibody (1/160) and antiparietal (1/320). We present a pluriglandular autoimmune syndrome with membranous glomerulonephritis, thyroiditis, pancreatitis and suprarrenal insufficiency. To the best of our knowledge this complex syndrome has not been previously described.

  10. Pancreatitis associated with the helminth Serpinema microcephalus (Nematoda: Camallanidae) in exotic red-eared slider turtles (Trachemys scripta elegans).

    Science.gov (United States)

    Hidalgo-Vila, Judit; Martínez-Silvestre, Albert; Ribas, Alexis; Casanova, Joan Carles; Pérez-Santigosa, Natividad; Díaz-Paniagua, Carmen

    2011-01-01

    Pancreatitis associated with the helminth Serpinema microcephalus was found in three of 19 free-ranging red-eared slider turtles (Trachemys scripta elegans) captured between March 2003 and September 2004 in southern Spain. Microscopic changes were associated with parasite migrations and were characterized by central areas of necrosis surrounded by leukocytes and resulted in destruction of exocrine tissue. The blood profile of one of the three female turtles revealed eosinophilia and hyperglycemia, common in helminth infections and pancreatic disorders respectively. These are the first reported cases of pancreatitis caused by the nematode S. microcephalus in the exotic and newly colonized host T. s. elegans.

  11. Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology

    OpenAIRE

    Gryshchenko, Oleksiy; Gerasimenko, Julia V.; Peng, Shuang; Gerasimenko, Oleg V.; Petersen, Ole Holger

    2018-01-01

    Physiological Ca2+ signals in pancreatic acinar cells control fluid and\\ud enzyme secretion, whereas excessive Ca2+ signals induced by pathological agents\\ud induce destructive processes leading to acute pancreatitis. Ca2+ signals in the periacinar\\ud stellate cells may also play a role in the development of acute pancreatitis. In\\ud this study, we have explored Ca2+ signalling in the different cell types to be found in\\ud the acinar environment of the pancreatic tissue. We have, for the firs...

  12. Short- and long-term outcomes after enucleation of pancreatic tumors: An evidence-based assessment.

    Science.gov (United States)

    Zhou, Yanming; Zhao, Min; Wu, Lupeng; Ye, Feng; Si, Xiaoying

    Enucleation of pancreatic tumors is rarely performed. The aim of this study was to evaluate the published evidence for its short- and long-term outcomes. PubMed (MEDLINE) and EMBASE databases were searched from 1990 to March 2016. Studies including at least ten patients who underwent enucleation of pancreatic lesions were included. Data on the outcomes were synthesized and meta-analyzed where appropriate. Twenty-seven studies involving 1316 patients were included in the systematic review. The postoperative mortality was 0.3%, and the postoperative morbidity was 50.3%, mainly represented by pancreatic fistula (38.1%). Endocrine insufficiency, exocrine insufficiency and tumor recurrence was observed in 2.4%, 1.1% and 2.3% of the patients respectively. Compared with typical resection, the operation time, blood loss, length of hospital stay, and the incidence of endocrine and exocrine insufficiency were all significantly reduced after enucleation. The occurrence of pancreatic fistula was significantly higher in enucleation group, but overall morbidity, the reoperation rate and mortality were comparable between the two groups. There was no significant difference in disease recurrence between the two groups. Compared with central pancreatectomy, enucleation had a shorter operation time, lower blood loss, less morbidity, and better pancreatic function. Compared with open enucleation, minimally invasive enucleation had a shorter operation time and a shorter length of hospital stay. Enucleation is an appropriate surgical procedure in selected patients with benign or low-malignant lesions of the pancreas. The benefits of minimally invasive approach need to be validated in further investigations with larger groups of patients. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  13. Is the Whipple procedure harmful for long-term outcome in treatment of chronic pancreatitis? 15-years follow-up comparing the outcome after pylorus-preserving pancreatoduodenectomy and Frey procedure in chronic pancreatitis.

    Science.gov (United States)

    Bachmann, Kai; Tomkoetter, Lena; Kutup, Asad; Erbes, Johannes; Vashist, Yogesh; Mann, Oliver; Bockhorn, Maximilian; Izbicki, Jakob R

    2013-11-01

    The aim of this study was to report on 15-year long-term results of a randomized controlled trial comparing extended drainage procedure (Frey) and classical resectional procedure [pylorus-preserving pancreatoduodenectomy (PD)] in patients with chronic pancreatitis. Chronic pancreatitis is a common inflammatory disease with a prevalence of 10 to 30 cases per 100,000 inhabitants. It is characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. Different surgical procedures are used in treatment of persistent pain. Sixty-four patients suffering from chronic pancreatitis with inflammatory mass in the pancreatic head were randomly assigned in 2 treatment groups (PD, n = 32) and (Frey, n = 32). The perioperative course of the randomized controlled trial and the 7 years follow-up have been previously published. All participating patients were contacted with a standardized, validated questionnaire (EORTC QLQ C30) to evaluate the long-term survival, quality-of-life pain, and exocrine and endocrine function. In the 15-year long-term follow-up, the pain control was good and comparable between both groups, but the quality of life was better after Frey procedure in regard of the physical status [PD: 100 (0-100) vs PD: 60 (0-100) (P = 0.011)]. No significant differences in terms of the Pain Score were detected between both groups [PD: 7 (0-100) vs Frey 4 (0-100) P = 0.258]. Seven patients after Frey OP and 6 patients after PD were free of pain. Analyzing the postoperative overall survival, a higher long-term mortality was found after PD (53%) than that found after Frey procedure (30%) resulting in a longer mean survival (14.5 ± 0.8 vs 11.3 ± 0.8 years; P = 0.037). No correlation between endocrine or exocrine pancreatic function and pain was found, whereas continuous alcohol consumption was associated with poorer outcome regarding quality of life (P treatment of chronic pancreatitis.

  14. Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model

    Directory of Open Access Journals (Sweden)

    Karilyn E. Sant

    2016-09-01

    Full Text Available The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio. Using endogenously expressed fluorescent protein markers for developing zebrafish beta cells and exocrine pancreas tissue, we documented differences in islet area and incidence rates of islet morphological variants in zebrafish embryos between 48 and 96 h post fertilization (hpf, raised under control conditions commonly used in embryotoxicity assays. We identified critical windows for chemical exposures during which increased incidences of endocrine pancreas abnormalities were observed following exposure to cyclopamine (2–12 hpf, Mono-2-ethylhexyl phthalate (MEHP (3–48 hpf, and Perfluorooctanesulfonic acid (PFOS (3–48 hpf. Both islet area and length of the exocrine pancreas were sensitive to oxidative stress from exposure to the oxidant tert-butyl hydroperoxide during a highly proliferative critical window (72 hpf. Finally, pancreatic dysmorphogenesis following developmental exposures is discussed with respect to human disease.

  15. Diagnostic CT and percutaneous procedures after pancreatic transplantation

    International Nuclear Information System (INIS)

    Letourneau, J.G.; Hunter, D.W.; Thompson, W.M.; Sutherland, D.E.R.

    1987-01-01

    CT evaluation of the abdomen and pelvis is of great value after pancreatic transplantation. The expected CT appearance after pancreas transportation with both enteric and bladder drainage of exocrine function are presented, as is the appearance of infected and ischemic grafts. The CT detection and CT- and US-guided percutaneous aspiration and drainage of abdominal fluid collections are described. At the authors' institution, such aspiration and drainage procedures have obviated transplant pancreatectomy or surgical abscess drainage in 29% of patients

  16. ptf1a+, ela3l− cells are developmentally maintained progenitors for exocrine regeneration following extreme loss of acinar cells in zebrafish larvae

    Science.gov (United States)

    Schmitner, Nicole; Kohno, Kenji

    2017-01-01

    ABSTRACT The exocrine pancreas displays a significant capacity for regeneration and renewal. In humans and mammalian model systems, the partial loss of exocrine tissue, such as after acute pancreatitis or partial pancreatectomy induces rapid recovery via expansion of surviving acinar cells. In mouse it was further found that an almost complete removal of acinar cells initiates regeneration from a currently not well-defined progenitor pool. Here, we used the zebrafish as an alternative model to study cellular mechanisms of exocrine regeneration following an almost complete removal of acinar cells. We introduced and validated two novel transgenic approaches for genetically encoded conditional cell ablation in the zebrafish, either by caspase-8-induced apoptosis or by rendering cells sensitive to diphtheria toxin. By using the ela3l promoter for exocrine-specific expression, we show that both approaches allowed cell-type-specific removal of >95% of acinar tissue in larval and adult zebrafish without causing any signs of unspecific side effects. We find that zebrafish larvae are able to recover from a virtually complete acinar tissue ablation within 2 weeks. Using short-term lineage-tracing experiments and EdU incorporation assays, we exclude duct-associated Notch-responsive cells as the source of regeneration. Rather, a rare population of slowly dividing ela3l-negative cells expressing ptf1a and CPA was identified as the origin of the newly forming exocrine cells. Cells are actively maintained, as revealed by a constant number of these cells at different larval stages and after repeated cell ablation. These cells establish ela3l expression about 4-6 days after ablation without signs of increased proliferation in between. With onset of ela3l expression, cells initiate rapid proliferation, leading to fast expansion of the ela3l-positive population. Finally, we show that this proliferation is blocked by overexpression of the Wnt-signaling antagonist dkk1b. In

  17. ptf1a+ , ela3l- cells are developmentally maintained progenitors for exocrine regeneration following extreme loss of acinar cells in zebrafish larvae.

    Science.gov (United States)

    Schmitner, Nicole; Kohno, Kenji; Meyer, Dirk

    2017-03-01

    The exocrine pancreas displays a significant capacity for regeneration and renewal. In humans and mammalian model systems, the partial loss of exocrine tissue, such as after acute pancreatitis or partial pancreatectomy induces rapid recovery via expansion of surviving acinar cells. In mouse it was further found that an almost complete removal of acinar cells initiates regeneration from a currently not well-defined progenitor pool. Here, we used the zebrafish as an alternative model to study cellular mechanisms of exocrine regeneration following an almost complete removal of acinar cells. We introduced and validated two novel transgenic approaches for genetically encoded conditional cell ablation in the zebrafish, either by caspase-8-induced apoptosis or by rendering cells sensitive to diphtheria toxin. By using the ela3l promoter for exocrine-specific expression, we show that both approaches allowed cell-type-specific removal of >95% of acinar tissue in larval and adult zebrafish without causing any signs of unspecific side effects. We find that zebrafish larvae are able to recover from a virtually complete acinar tissue ablation within 2 weeks. Using short-term lineage-tracing experiments and EdU incorporation assays, we exclude duct-associated Notch-responsive cells as the source of regeneration. Rather, a rare population of slowly dividing ela3l- negative cells expressing ptf1a and CPA was identified as the origin of the newly forming exocrine cells. Cells are actively maintained, as revealed by a constant number of these cells at different larval stages and after repeated cell ablation. These cells establish ela3l expression about 4-6 days after ablation without signs of increased proliferation in between. With onset of ela3l expression, cells initiate rapid proliferation, leading to fast expansion of the ela3l -positive population. Finally, we show that this proliferation is blocked by overexpression of the Wnt-signaling antagonist dkk1b In conclusion, we

  18. Trend Toward Individualization of the Endocrine and Exocrine Portions of the Giant Anteater Pancreas (Myrmecophaga Tridactyla, Xenarthra).

    Science.gov (United States)

    Iglesias, Luciana Pedrosa; Favaron, Phelipe Oliveira; Borghesi, Jéssica; Oliveira Carreira, Ana Claudia; Miglino, Maria Angelica; de Melo, Alan Perez Ferraz

    2017-06-01

    Considering the physiological importance of the pancreas as an endocrine and exocrine organ, this study described the characteristics of the gross and microscopic morphology of this organ using 16 Myrmecophaga tridactyla individuals. The pancreas was located in the left antimere of the body, was pale in colour and exhibited an elongated shape with a central body and lobulated surface. It was positioned in the abdomen, following the curvatura ventriculi major of the stomach, and was attached to the initial portion of the duodenum. The corpus pancreatis was elongated and showed a caudal curvature of 45°. The pancreas exhibited a facies dorsalis (related to the spleen and stomach) and a facies ventralis (related to the renal capsule and intestine). Macroscopically, a craniodorsal, medial, and caudoventral regions were identified, in addition to the left lobe. Structurally, the organ exhibited two distinct parts: the first had exocrine characteristics, consisting of acini and ducts; the second, which was the endocrine portion, consisted of the pancreatic islets, which were located in the medial, caudoventral and left lobe regions. Ultrastructural analysis identified secretory vesicles containing zymogen granules, mitochondria, Golgi apparatus and rough endoplasmic reticulum in pancreatic centroacinar cells. Morphological data on the anatomy of members of the Xenarthra have revealed important peculiarities of several organs and systems, adding great biological value to the representatives of this group. In addition, these studies significantly contribute not only to knowledge of the biology, taxonomy and, consequently, preservation of these animals but also to the discovery of new experimental models. Anat Rec, 300:1104-1113, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Gamma radiation induced alterations in the ultrastructure of pancreatic islet, metabolism and enzymes in wistar rat

    Energy Technology Data Exchange (ETDEWEB)

    Daoo, J.V.; Suryawanshi, S.A. [Inst. of Science, Bombay (India)

    1992-07-01

    Effects of gamma irradiation (600 rads) on the ultrastructure of pancreatic islet, metabolism and some enzymes in wistar rat, are reported. Electron microscopic observations of endocrine pancreas revealed prominent changes in beta cells while alpha and delta cells were not much affected. Irradiation also inflicted hyperglycemia, increase in liver and muscle glycogen and decrease in insulin level. It has also increased the activity of enzymes but failed to produce significant changes in protein, lipid and mineral metabolism. (auth0008.

  20. Occupational exposures and risk of pancreatic cancer

    International Nuclear Information System (INIS)

    Santibanez, Miguel; Vioque, Jesus; Alguacil, Juan; Hera, Manuela Garcia de la; Moreno-Osset, Eduardo; Carrato, Alfredo; Porta, Miquel; Kauppinen, Timo

    2010-01-01

    The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of exocrine pancreatic cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, p-trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with exocrine pancreatic cancer.

  1. The role of positron emission tomography in the detection of pancreatic disease

    International Nuclear Information System (INIS)

    Syrota, A.; Duquesnoy, N.; Paraf, A.; Kellershohn, C.

    1982-01-01

    Positron emission tomography (PET) was used to assess possible pancreatic disease in 100 patients. Following injection of 10-15 mCi (370-740 MBq) of 11C-L-methionine, 4-12 transverse sections 2 cm thick were obtained. In 85 patients with a definite diagnosis (45 normal, 9 acute pancreatitis, 18 chronic pancreatitis, and 13 cancer), PET showed a sensitivity of 85.0%, a specificity of 97.8%, and an accuracy of 91.8%, higher than with transmission computed tomography (CT) or ultrasonography, despite relatively low spatial resolution; this can be explained by the fact that exocrine pancreatic function was altered prior to morphological change. In 22 normal subjects, 0.011 +/- 0.003% (mean +/- S.D). of injected 11C was found in 1 ml of liver tissue and 0.015 +/- 0.005% in 1 ml of pancreatic tissue; the pancreas-to-liver concentration ratio was 1.3 +/- 0.4. Hepatic 11C concentration was identical in the four groups of patients. Pancreatic uptake of 11C-L-methionine was significantly lower in patients with chronic pancreatitis (n . 13) and pancreatic carcinoma (n . 10) (p less than 0.001); however, it was not possible to distinguish cancer from chronic pancreatitis because the same functional alteration occurred in both

  2. The role of positron emission tomography in the detection of pancreatic disease

    International Nuclear Information System (INIS)

    Syrota, A.; Duquesnoy, N.; Paraf, A.; Kellershohn, C.

    1982-01-01

    Positron emission tomography (PET) was used to assess possible pancreatic disease in 100 patients. Following injection of 10-15 mCi (370-740 MBq) of 11 C-L-methionine, 4-12 transverse sections 2 cm thick were obtained. In 85 patients with a definite diagnosis (45 normal, 9 acute pancreatitis, 18 chronic pancreatitis, and 13 cancer), PET showed a sensitivity of 85.0%, a specificity of 97.8%, and an accuracy of 91.8%, higher than with transmission computed tomography (CT) or ultrasonography, despite relatively low spatial resolution; this can be explained by the fact that exocrine pancreatic function was altered prior to morphological change. In 22 normal subjects, 0.011 +/- 0.003% (mean +/- S.D.) of injected 11 C was found in 1 ml of liver tissue and 0.015 +/- 0.005% in 1 ml of pancreatic tissue; the pancreas-to-liver concentration ratio was 1.3 +/- 0.4. Hepatic 11 C concentration was identical in the four groups of patients. Pancreatic uptake of 11 C-L-methionine was significantly lower in patients with chronic pancreatitis (n = 13) and pancreatic carcinoma (n = 10) (p <0.001); however, it was not possible to distinguish cancer from chronic pancreatitis because the same functional alteration occurred in both

  3. Successful Partial Pancreatotomy as a Salvage Procedure for Massive Intraoperative Bleeding During Head Coring for Chronic Pancreatitis. Report of a Case

    OpenAIRE

    Savio G Barreto; Harshil Shah; Chirayu Choksi; Nilesh H Doctor

    2007-01-01

    Context Chronic pancreatitis is a continuous inflammatory disease of the pancreas resulting in scarring and fibrosis with consequent decline in exocrine and endocrine function. The inflammatory process leads to the development of a head mass, and strictures and stones in the pancreatic duct which present as pain, or loco regional complications such as duodenal obstruction and biliary obstruction. The gold standard for the treatment of pain and loco regional complications remains surgery, whic...

  4. Marked differences in immunocytological localization of [3H]estradiol-binding protein in rat pancreatic acinar tumor cells compared to normal acinar cells

    International Nuclear Information System (INIS)

    Beaudoin, A.R.; Grondin, G.; St Jean, P.; Pettengill, O.; Longnecker, D.S.; Grossman, A.

    1991-01-01

    [ 3 H]Estradiol can bind to a specific protein in normal rat pancreatic acinar cells. Electron microscopic immunocytochemical analysis has shown this protein to be localized primarily in the rough endoplasmic reticulum and mitochondria. Rat exocrine pancreatic tumor cell lines, whether grown in tissue culture (AR42J) or as a tumor mass after sc injection into rats (DSL-2), lacked detectable amounts of this [ 3 H]estradiol-binding protein (EBP), as determined by the dextran-coated charcoal assay. Furthermore, primary exocrine pancreatic neoplasms induced with the carcinogen azaserine contained little or no detectable [ 3 H]estradiol-binding activity. However, electron immunocytochemical studies of transformed cells indicated the presence of material that cross-reacted with antibodies prepared against the [ 3 H]EBP. The immunopositive reaction in transformed cells was localized almost exclusively in lipid granules. Such lipid organelles in normal acinar cells, although present less frequently than in transformed cells, have never been observed to contain EBP-like immunopositive material. Presumably, the aberrant localization of EBP in these acinar tumor cells results in loss of function of this protein, which in normal pancreatic acinar cells appears to exert a modulating influence on zymogen granule formation and the process of secretion

  5. Patterns of Pathomorphological Changes in Acute Necrotizing Pancreatitis

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    I. Kovalska

    2012-01-01

    Full Text Available Acinar necrosis is the basic microscopic sign of acute necrotizing pancreatitis (ANP. Microcirculation disorder is one of the major factors in the pathogenesis and morphogenesis of ANP besides free radicals and damage of enzymatic origin. This study is dedicated to the description of microscopic changes in the pancreatic stroma in ANP, which leads to destruction of the exocrine pancreas with a putative mechanism of endocrine function preservation. This study has been carried out on histological samples of pancreas from 224 patients with ANP. Histological staining was performed with hematoxylin-eosin (H&E, Masson, Gomori methods, and PAS. Microscopy was performed with magnifications of 40×, 100×, and 400×. Vascular endothelial desquamation, stasis, and sludge are typical changes in microcirculation observed in early stages of ANP. Initially, parietal circular intravascular microthrombosis accompanied by endothelial desquamation as early as stromal swelling occurs with no detectable necrosis. Residual stroma appears between areas of necrosis and intact pancreatic tissue. Mucoid swelling is first seen in the perivascular spaces extending to the parenchyma and changing into fibrinoid imbibition causing further necrosis. Reticulin argyrophilic backbone surrounding the pancreatic acini and small ducts decompose. Pancreatic structures, which may be preserved in necrotic tissue, include nerves, major ducts, and Langerhans islets.

  6. Pancreatic Enzyme Therapy and Coefficient of Fat Absorption in Children and AdolReplacement escents With Cystic Fibrosis

    NARCIS (Netherlands)

    Woestenenk, Janna W; van der Ent, Cornelis K.; Houwen, Roderick H J; van der Ent, CK

    Objectives: Pancreatic enzyme replacement therapy (PERT) is the proven therapy to substantially reduce fat malabsorption in patients with cystic fibrosis (CF). Few details of the daily practice regarding PERT and the resulting coefficient of fat absorption (CFA) are known. We therefore recorded the

  7. Combined pancreatic and duodenal transection injury: A case report.

    Science.gov (United States)

    Mungazi, Simbarashe Gift; Mbanje, Chenesa; Chihaka, Onesai; Madziva, Noah

    2017-01-01

    Combined pancreatic-duodenal injuries in blunt abdominal trauma are rare. These injuries are associated with high morbidity and mortality, and their emergent management is a challenge. We report a case of combined complete pancreatic (through the neck) and duodenal (first part) transections in a 24-year-old male secondary to blunt abdominal trauma following a motor vehicle crash. The duodenal stumps were closed separately and a gastrojejunostomy performed for intestinal continuity. The transacted head of pancreas main duct was suture ligated and parenchyma was over sewn and buttressed with omentum. The edge of the body and tail pancreatic segment was freshened and an end to side pancreatico-jejunostomy was fashioned. A drain was left in situ. Post operatively the patient developed a pancreatic fistula which resolved with conservative management. After ten months of follow up the patient was well and showed no signs and symptoms of pancreatic insufficiency. Lengthy, complex procedures in pancreatic injuries have been associated with poor outcomes. Distal pancreatectomy or Whipple's procedure for trauma are viable options for complete pancreatic transections. But when there is concern that the residual proximal pancreatic tissue is inadequate to provide endocrine or exocrine function, preservation of the pancreatic tissue distal to the injury becomes an option. Combined pancreatic and duodenal injuries are rare and often fatal. Early identification, resuscitation and surgical intervention is warranted. Because of the large number of possible combinations of injuries to the pancreas and duodenum, no one form of therapy is appropriate for all patients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis.

    Science.gov (United States)

    Gillies, Nicola; Pendharkar, Sayali A; Asrani, Varsha M; Mathew, Juby; Windsor, John A; Petrov, Maxim S

    2016-01-01

    Diabetes is a pervasive disease, with a mounting prevalence and burden on health care systems. Under this collective term of diabetes falls diabetes after diseases of the exocrine pancreas, a condition which was previously under-recognised and often mislabeled as type 2 diabetes mellitus and is now increasingly acknowledged as a stand-alone entity. However, there is a paucity of clinical studies investigating the underlying pathophysiology of diabetes after acute pancreatitis, the most frequent disease of the pancreas. This study aimed to investigate the role of adipocytokines in glucose metabolism after acute pancreatitis. This was a cross-sectional follow-up study of a patient cohort diagnosed with acute pancreatitis. Fasting venous blood samples were collected to analyse markers of glucose metabolism (fasting blood glucose, haemoglobin A1c, homeostasis model assessment (HOMA-IR) as a measure of insulin resistance) and adypocytokines (adiponectin, interleukin-6, leptin, monocyte chemoattractant protein-1, retinol binding protein-4, resistin, and tumor necrosis factor-α). Participants were categorized into two groups: normoglycemia after acute pancreatitis and chronic hyperglycemia after acute pancreatitis (CHAP). Binary logistic regression and linear regression analyses were used to investigate the association between each of the adipocytokines and markers of glucose metabolism. Potential confounders were adjusted for in multivariate analyses. A total of 83 patients with acute pancreatitis were included, of whom 19 developed CHAP. Interleukin-6 was significantly associated with CHAP in both unadjusted and adjusted models (p = 0.030 and p = 0.018, respectively). Further, it was also significantly associated with HOMA-IR in both unadjusted and adjusted models (p = 0.029 and p = 0.037, respectively). Other adipocytokines were not significantly associated with markers of glucose metabolism. Interleukin-6 appears to be implicated in the development of chronic

  9. Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters.

    Science.gov (United States)

    Keomanivong, F E; Lemley, C O; Camacho, L E; Yunusova, R; Borowicz, P P; Caton, J S; Meyer, A M; Vonnahme, K A; Swanson, K C

    2016-03-01

    Primiparous ewes (n=32) were assigned to dietary treatments in a 2×2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. Treatments consisted of nutrient intake with 60% (RES) or 100% (ADQ) of requirements and melatonin supplementation at 0 (CON) or 5 mg/day (MEL). Treatments began on day 50 of gestation and continued until day 130. On day 130, blood was collected under general anesthesia from the uterine artery, uterine vein, umbilical artery and umbilical vein for plasma insulin analysis. Ewes were then euthanized and the pancreas removed from the ewe and fetus, trimmed of mesentery and fat, weighed and snap-frozen until enzyme analysis. In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. Nutrient restriction decreased (P⩽0.001) maternal pancreatic mass (g) and α-amylase activity (U/g, kU/pancreas, U/kg BW). Ewes supplemented with melatonin had increased pancreatic mass (P=0.03) and α-amylase content (kU/pancreas and U/kg BW). Melatonin supplementation decreased (P=0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster (P=0.04). Nutrient restriction decreased pancreatic insulin-positive tissue area (P=0.03) and percent of large (32 001 to 512 000 µm2) and giant (⩾512 001 µm2) insulin-containing cell clusters (P=0.04) in the fetus. Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater (P⩽0.01) in animals receiving 100% requirements. When comparing ewes to fetuses, ewes had a greater percentage of medium insulin-containing cell clusters (2001 to 32 000 µm2) while fetuses

  10. Morphology and diversity of exocrine glands in lepidopteran larvae.

    Science.gov (United States)

    Vegliante, Francesca; Hasenfuss, Ivar

    2012-01-01

    The morphology of 21 exocrine glands and 13 supposedly exocrine structures recorded for lepidopteran larvae is reviewed. The epitracheal glands, for which a double role (exocrine and endocrine) has been demonstrated, are examined as well. Function is well known for at least 8 glands but completely unknown for 6 glands, for 10 putative glandular structures, and for the exocrine component of the epitracheal glands. Functional studies on the remaining structures are insufficient; in some cases (mandibular gland and adenosma) homologous glands may play a different role depending on the species, and only a few taxa have been examined. The secretions of 13 glandular types have been analyzed chemically. The histology of 11 glands is known at the ultrastructural level, whereas that of 6 glands and 7 putative glandular structures is completely unknown. Comparative anatomical studies of the osmeterium, adenosma, and Verson's glands may yield useful information for phylogenetic reconstructions. Copyright © 2012 by Annual Reviews. All rights reserved.

  11. Clinical application of duodenum-preserving pancreatic head resection

    Directory of Open Access Journals (Sweden)

    ZHOU Songqiang

    2018-01-01

    Full Text Available 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 intraductal papillary mucinous neoplasm, 2 had serous cystadenoma of the pancreatic head, and 1 had mucinous cystadenoma of the pancreatic head. Results The time of operation was 200-360 minutes (mean 304.0±45.3 minutes, and the intraoperative blood loss was 50-500 ml (mean 267.5±116.1 ml. No patient died in the perioperative period. After surgery, 5 experienced biochemical leak, 2 experienced grade B pancreatic fistula, no patient experienced grade C pancreatic fistula, and 1 experienced gastroplegia; all these patients were cured and discharged after conservative treatment. The length of postoperative hospital stay was 17-78 days (mean 30.8±14.3 days. The 17 patients were followed up for 2 months to 4 years after surgery, and no patient experienced tumor recurrence, new-onset diabetes, dyspepsia, or common bile duct stenosis after surgery. Conclusion Besides ensuring the complete resection of tumor, DPPHR can reduce the incidence rate of surgical trauma and complications and shorten the time of operation and the length of hospital stay. Compared with pancreaticoduodenectomy, DPPHR can better preserve the endocrine and exocrine functions of the pancreas and improve patients′ postoperative quality of life.

  12. Proton microprobe analysis of pancreatic. beta. cells

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    Lindh, U [Uppsala Univ. (Sweden). Gustaf Werner Inst.; Juntti-Berggren, L; Berggren, P O; Hellman, B [Uppsala Univ. (Sweden)

    1985-01-01

    Freeze-dried pancreas sections from obese hyperglycemic mice were subjected to proton bombardment and the elemental contents in the ..beta.. cells and the exocrine part were obtained from the characteristic X-rays emitted. Quantitative data were provided for 18 different elements. The mole ratio between K and Na exceeded 10, implying that neither the sample preparation nor the irradiation had induced significant diffuse changes. With the demonstration of this high K/Na ratio it seems likely that also the ..beta.. cells are equipped with an efficient Na/sup +//K/sup +/ pump. The ..beta.. cells contained about 70 mmoles Cl per litre cell water. Observed amounts of Ca and Mg were equivalent to those previously recorded by electrothermal atomic absorption spectroscopy. The significant role of Zn for the storage of insulin was emphasized by the demonstration of 3 times as much of this element in the ..beta.. cells as compared with the exocrine pancreas. In addition, the sensitivity of the proton microprobe enabled measurements of various trace elements such as Rb, Cr, Cu, Al and Pb not previously demonstrated in the pancreatic ..beta.. cells.

  13. 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.

  14. Diagnosis and treatment of diabetes mellitus in chronic pancreatitis.

    Science.gov (United States)

    Ewald, Nils; Hardt, Philip D

    2013-11-14

    Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus. It is a clinically relevant condition with a prevalence of 5%-10% among all diabetic subjects in Western populations. In nearly 80% of all type 3c diabetes mellitus cases, chronic pancreatitis seems to be the underlying disease. The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far. In contrast to the management of type 1 or type 2 diabetes mellitus, the endocrinopathy in type 3c is very complex. The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition. General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus (up to 90% of all cases) is rather good. However, in a patient first presenting with diabetes mellitus, chronic pancreatitis as a potential causative condition is seldom considered. Thus many patients are misdiagnosed. The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy. In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency, preventing or treating a lack of fat-soluble vitamins (especially vitamin D) and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.

  15. Long-term follow-up of a randomized clinical trial comparing Beger with pylorus-preserving Whipple procedure for chronic pancreatitis.

    Science.gov (United States)

    Müller, M W; Friess, H; Martin, D J; Hinz, U; Dahmen, R; Büchler, M W

    2008-03-01

    Duodenum-preserving pancreatic head resection according to Beger and the pylorus-preserving Whipple (ppWhipple) procedure were compared in patients with chronic pancreatitis (CP) in a randomized clinical trial. Perioperative data and short-term outcome have been reported previously. The present study evaluated long-term follow-up. Forty patients were enrolled originally, 20 in each group. Long-term follow-up included mortality, morbidity, pain status, occupational rehabilitation, quality of life (QoL), and endocrine and exocrine function at median follow-up of 7 and 14 years. One patient who had a ppWhipple procedure was lost to follow-up. There were five late deaths in each group. No differences were noted in pain status and exocrine pancreatic function. Loss of appetite was significantly worse in the ppWhipple group at 14 years' follow-up, but there were no other differences in QoL parameters examined. After 14 years, diabetes mellitus was present in seven of 15 patients who had the Beger procedure and 11 of 14 patients after ppWhipple resection (P = 0.128). After long-term follow-up of up to 14 years early advantages of the Beger procedure were no longer present. 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  16. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides.

    Science.gov (United States)

    Chen, W; Kelly, M A; Opitz-Araya, X; Thomas, R E; Low, M J; Cone, R D

    1997-12-12

    The effects of pituitary-derived melanocortin peptides are primarily attributed to ACTH-mediated adrenocortical glucocorticoid production. Identification of a widely distributed receptor for ACTH/MSH peptides, the melanocortin-5 receptor (MC5-R), suggested non-steroidally mediated systemic effects of these peptides. Targeted disruption of the MC5-R produced mice with a severe defect in water repulsion and thermoregulation due to decreased production of sebaceous lipids. High levels of MC5-R was found in multiple exocrine tissues, including Harderian, preputial, lacrimal, and sebaceous glands, and was also shown to be required for production and stress-regulated synthesis of porphyrins by the Harderian gland and ACTH/MSH-regulated protein secretion by the lacrimal gland. These data show a requirement for the MC5-R in multiple exocrine glands for the production of numerous products, indicative of a coordinated system for regulation of exocrine gland function by melanocortin peptides.

  17. Evidence of a generalized defect of acinar cell function in Shwachman-Diamond syndrome.

    Science.gov (United States)

    Stormon, Michael O; Ip, Wan F; Ellis, Lynda; Schibli, Susanne; Rommens, Johanna M; Durie, Peter R

    2010-07-01

    : Because the acinar cells of the exocrine pancreas in patients with Shwachman-Diamond syndrome (SDS) are severely depleted, we hypothesized that a similar deficiency may be present in acinar cells of the parotid gland. : We determined serum pancreatic isoamylase and parotid amylase activities in 16 patients with SDS, 13 healthy controls, and 13 disease controls (cystic fibrosis or fibrosing pancreatitis). Parotid amylase and electrolyte concentrations were measured in stimulated parotid gland secretions. Starch digestion was assessed by breath hydrogen testing in patients with SDS (with and without enzyme supplements) and healthy controls. : Serum pancreatic and parotid isoamylase values were lower in the patients with SDS than in the healthy controls (P gland amylase concentration (units per milligram of protein) in patients with SDS was lower than that in the healthy controls (P = 0.04), whereas the disease controls were comparable to the healthy subjects (P = 0.09). Secreted parotid chloride concentration was inversely correlated with amylase concentration in the patients with SDS (P = 0.01), but no correlation was seen in the healthy controls or disease controls. When patients with SDS ingested starch without enzyme supplementation, their breath hydrogen excretion was significantly higher than that in the healthy controls (P = 0.009). Following starch ingestion with enzymes, breath hydrogen in the patients with SDS was lower (P functional abnormality of exocrine acinar cells.

  18. Ca²⁺-dependent K⁺ channels in exocrine salivary glands.

    Science.gov (United States)

    Catalán, Marcelo A; Peña-Munzenmayer, Gaspar; Melvin, James E

    2014-06-01

    In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca(2+)-dependent K(+) channels take part in key functions including membrane potential regulation, fluid movement and K(+) secretion in exocrine glands. Two K(+) channels have been identified in exocrine salivary glands: (1) a Ca(2+)-activated K(+) channel of intermediate single channel conductance encoded by the KCNN4 gene, and (2) a voltage- and Ca(2+)-dependent K(+) channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca(2+)-dependent K(+) channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca(2+)-dependent K(+) channels by protein-protein interactions that may significantly impact exocrine gland physiology. Published by Elsevier Ltd.

  19. Effect of P2X(7) receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands.

    Science.gov (United States)

    Novak, Ivana; Jans, Ida M; Wohlfahrt, Louise

    2010-09-15

    The purinergic P2X(7) receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X(7) receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X(7) receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X(7)(-/-) (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca(2+) activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X(7)(-/-) mice, and in contrast, tear secretion was increased in P2X(7)(-/-) mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X(7) receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X(7) receptor expression. ATP and carbachol increased intracellular Ca(2+) activity, but responses depended on the gland type, presence of the P2X(7) receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X(7) receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptor signalling and that function of the P2X(7) receptor is suppressed in females. We conclude that the P2X(7) receptors are important in short-term physiological regulation of exocrine gland secretion.

  20. Effect of P2X7 receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands

    Science.gov (United States)

    Novak, Ivana; Jans, Ida M; Wohlfahrt, Louise

    2010-01-01

    The purinergic P2X7 receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X7 receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X7 receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X7−/− (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca2+ activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X7−/− mice, and in contrast, tear secretion was increased in P2X7−/− mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X7 receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X7 receptor expression. ATP and carbachol increased intracellular Ca2+ activity, but responses depended on the gland type, presence of the P2X7 receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X7 receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptor signalling and that function of the P2X7 receptor is suppressed in females. We conclude that the P2X7 receptors are important in short-term physiological regulation of exocrine gland secretion. PMID:20643770

  1. Growth Factor Independence-1 (Gfi1) Is Required for Pancreatic Acinar Unit Formation and Centroacinar Cell Differentiation

    DEFF Research Database (Denmark)

    Qu, Xiaoling; Nyeng, Pia; Xiao, Fan

    2015-01-01

    of granulocytes, inner ear hair cells, and the development of secretory cell types in the intestine. As GFI1/Gfi1 is expressed in human and rodent pancreas, we characterized the potential function of Gfi1 in mouse pancreatic development. METHODS: Gfi1 knockout mice were analyzed at histological and molecular...... levels, including qRT-PCR, in situ hybridization, immunohistochemistry, and electron microscopy. RESULTS: Loss of Gfi1 impacted formation and structure of the pancreatic acinar/centroacinar unit. Histologic and ultrastructural analysis of Gfi1-null pancreas revealed specific defects at the level...... was correlated with an exocrine organ defect. Postnatally, Gfi1 deficiency resulted in severe pancreatic acinar dysplasia, including loss of granulation, autolytic vacuolation, and a proliferative and apoptotic response. CONCLUSIONS: Gfi1 plays an important role in regulating the development of pancreatic CACs...

  2. Influence of feeding on serum canine pancreatic lipase immunoreactivity concentrations

    Directory of Open Access Journals (Sweden)

    Steiner JM

    2014-10-01

    Full Text Available Jörg M Steiner, Craig G Ruaux, David A Williams Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA Abstract: Measurement of serum concentration of pancreatic lipase immunoreactivity (PLI has been shown to be highly specific for exocrine pancreatic function and sensitive for the diagnosis of canine pancreatitis. Currently, it is recommended that food be withheld for at least 12 hours before collecting a blood sample for analysis from dogs. However, it is unknown whether feeding has any influence on serum canine PLI concentration. Thus, the goal of this study was to evaluate the influence of feeding on serum canine PLI concentrations in healthy dogs. Food was withheld from eight healthy adult Beagle dogs for at least 17 hours and a baseline serum sample (0 minutes was collected. Dogs were fed and serum samples were collected at 15, 30, 45, 60, 75, 90, 105, 150, 180, 210, 240, 300, 360, 420, and 480 minutes. There was no significant difference in serum canine PLI concentrations at any time after feeding (P=0.131. We conclude that feeding has no significant influence on serum canine PLI concentrations. Keywords: dog, pancreatic function, pancreatitis, biomarker, diagnostic test

  3. Surgical strategies in the treatment of chronic pancreatitis: An updated systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhao, Xin; Cui, Naiqiang; Wang, Ximo; Cui, Yunfeng

    2017-03-01

    Chronic pancreatitis (CP) is a common and frequently occurring disease. Pancreaticoduodenectomy (PD), pylorus-preserving pancreaticoduodenectomy (PPPD), and duodenum-preserving pancreatic head resection (DPPHR) are important treatment options for patients with chronic pancreatitis. The Beger and Frey procedures are 2 main duodenum-preserving techniques in duodenum-preserving pancreatic head resection (DPPHR) strategies. We conducted this systematic review and meta-analysis to compare the clinical efficacy of DPPHR versus PD, the Beger procedure versus PD, the Frey procedure versus PD, and the Beger procedure versus the Frey procedure in the treatment of pancreatitis. The optimal surgical option for chronic pancreatitis is still under debate. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of different surgical strategies for chronic pancreatitis. Five databases (PubMed, Medline, SinoMed, Embase, and Cochrane Library) were searched with the limitations of human subjects and randomized controlled trials (RCTs) text. Data were extracted by 2 of the coauthors independently and analyzed using the RevMan statistical software, version 5.3. Weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool was used to assess the risk of bias. Seven studies involving a total of 385 patients who underwent the surgical treatments were assessed. The methodological quality of the trials ranged from low to moderate and included PD (n = 134) and DPPHR (n = 251 [Beger procedure = 100; Frey procedure = 109; Beger or Frey procedure = 42]). There were no significant differences between DPPHR and PD in post-operation mortality (RR = 2.89, 95% CI = 0.31-26.87, P = 0.36), pain relief (RR = 1.09, 95% CI = 0.94-1.25, P = 0.26), exocrine insufficiency (follow-up time > 60 months: RR = 0.91, 95% CI = 0.72-1.15, P

  4. Surgical treatment of pancreas divisum causing chronic pancreatitis: the outcome benefits of duodenum-preserving pancreatic head resection.

    Science.gov (United States)

    Schlosser, W; Rau, B M; Poch, B; Beger, H G

    2005-01-01

    Pancreas divisum (PD) represents a duct anomaly in the pancreatic head ducts, leading frequently leading to recurrent acute pancreatitis (rAP) or chronic pancreatitis (CP). Based on endoscopic retrograde cholangiopancreatography, pancreas divisum can be found in 1% to 6% of patients with pancreatitis. The correlation of this abnormality with pancreatic disease is an issue of continuing controversy. Because of the underlying duct anomalies and major pathomorphological changes in the pancreatic head, duodenum-preserving pancreatic head resection (DPPHR) offers an option for causal treatment. Thirty-six patients with pancreatitis caused by PD were treated surgically. Thirty patients suffered from CP, 6 from rAP. The mean duration of the disease was 47.5 and 49.8 months, respectively. The age at the time of surgery was 39.2 years in the CP group, and 27.6 years in the rAP group. Median hospitalization since diagnosis was 18.8 weeks for CP patients and 24.6 weeks for rAP patients. Previous procedures performed in these patients included endoscopic papillotomy (30%), duct stenting (14%), and surgical treatment (17%). The median preoperative pain score was 8 on a visual analog scale. According to the classification of pancreas divisum, 10 patients demonstrated a complete PD, 25 had a functionally incomplete PD, and 1 had a dorsal duct type. The pain status as well as the endocrine (oral glucose tolerance test) and exocrine (pancreolauryl test) function were evaluated preoperatively and early and late postoperatively with a median follow-up time of 39.3 months. There was no operative-related mortality. The follow-up was 100%; 4 patients died (1 from suicide, 1 from cardiac arrest, and 2 from cancer of the esophagus). Fifty percent of the patients were completely pain-free, 31% had a significant reduction of pain with a median pain score of 2 (P pancreatitis with a need for hospitalization. DPPHR reduced pain and preserved the endocrine function in the majority of patients

  5. The prevalence of malnutrition and fat-soluble vitamin deficiencies in chronic pancreatitis.

    Science.gov (United States)

    Duggan, Sinead N; Smyth, Niamh D; O'Sullivan, Maria; Feehan, Sinead; Ridgway, Paul F; Conlon, Kevin C

    2014-06-01

    Patients with chronic pancreatitis are at risk of malnutrition and nutrient deficiency due to malabsorption, pain, and poor diet. We sought to examine fat-soluble vitamin levels and malnutrition parameters in patients with chronic pancreatitis. In a prospective controlled cohort study, 128 subjects (62 chronic pancreatitis patients and 66 age-/sex-matched controls) were recruited. Body mass index (BMI), handgrip strength (measure of functional capacity), fat stores (triceps skin fold), muscle stores (mid-arm muscle circumference), exocrine function, and serum levels of fat-soluble vitamins (A, D, E) were measured. Half of patients in the chronic pancreatitis group were overweight or obese, although the mean BMI was lower in patients than in controls (P = .007). Handgrip strength (P = .048), fat stores (P = .000), and muscle stores (P = .001) were lower in patients than in controls. Of the patients, 14.5% and 24.2% were deficient in vitamins A and E, respectively. Nineteen percent of patients had excess serum vitamin A levels. Despite the prevalence of overweight and obesity, patients had lower muscle stores, strength, and abnormal vitamin levels. Detailed nutrition assessment including anthropometry and vitamin status is warranted in chronic pancreatitis.

  6. Two enzymes catalyze vitamin K 2,3-epoxide reductase activity in mouse: VKORC1 is highly expressed in exocrine tissues while VKORC1L1 is highly expressed in brain.

    Science.gov (United States)

    Caspers, Michael; Czogalla, Katrin J; Liphardt, Kerstin; Müller, Jens; Westhofen, Philipp; Watzka, Matthias; Oldenburg, Johannes

    2015-05-01

    VKORC1 and VKORC1L1 are enzymes that both catalyze the reduction of vitamin K2,3-epoxide via vitamin K quinone to vitamin K hydroquinone. VKORC1 is the key enzyme of the classical vitamin K cycle by which vitamin K-dependent (VKD) proteins are γ-carboxylated by the hepatic γ-glutamyl carboxylase (GGCX). In contrast, the VKORC1 paralog enzyme, VKORC1L1, is chiefly responsible for antioxidative function by reduction of vitamin K to prevent damage by intracellular reactive oxygen species. To investigate tissue-specific vitamin K 2,3-epoxide reductase (VKOR) function of both enzymes, we quantified mRNA levels for VKORC1, VKORC1L1, GGCX, and NQO1 and measured VKOR enzymatic activities in 29 different mouse tissues. VKORC1 and GGCX are highly expressed in liver, lung and exocrine tissues including mammary gland, salivary gland and prostate suggesting important extrahepatic roles for the vitamin K cycle. Interestingly, VKORC1L1 showed highest transcription levels in brain. Due to the absence of detectable NQO1 transcription in liver, we assume this enzyme has no bypass function with respect to activation of VKD coagulation proteins. Our data strongly suggest diverse functions for the vitamin K cycle in extrahepatic biological pathways. Copyright © 2015. Published by Elsevier Ltd.

  7. Antimuscarinic effects of chloroquine in rat pancreatic acini

    International Nuclear Information System (INIS)

    Habara, Y.; Williams, J.A.; Hootman, S.R.

    1986-01-01

    Chloroquine inhibited carbachol-induced amylase release in a dose-dependent fashion in rat pancreatic acini; cholecystokinin- and bombesin-induced secretory responses were almost unchanged by the antimalarial drug. The inhibition of carbachol-induced amylase release by chloroquine was competitive in nature with a K/sub i/ of 11.7 μM. Chloroquine also inhibited [ 3 H]N-methylscopolamine binding to acinar muscarinic receptors. The IC 50 for chloroquine inhibition of [ 3 H]N-methylscopolamine binding was lower than that for carbachol or the other antimalarial drugs, quinine and quinidine. These results demonstrate that chloroquine is a muscarinic receptor antagonist in the exocrine pancreas

  8. 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

  9. Seventy years of pancreatic physiology: take a look back.

    Science.gov (United States)

    Morisset, Jean

    2014-11-01

    This review article has 4 major objectives to follow pancreatic physiology development more than close to 70 years of intensive and productive basic research. At first, the review will focus on secretion of the pancreatic enzymes with (1) the controls involved, (2) the interrelations existing between secretion and synthesis of these enzymes, (3) the enzymes' adaptation to the constituents of the diet, and (4) whether secretion of the different enzymes is parallel or nonparallel. Second, growth and regeneration of the pancreatic gland will be looked at in relation to the factors involved and the target cells implicated.

  10. [Surgical treatment of chronic pancreatitis, 2010].

    Science.gov (United States)

    Farkas, Gyula

    2011-04-01

    Chronic pancreatitis (CP) is a benign inflammatory process, which can cause enlargement of the pancreatic head accompanied by severe pain and weight loss, and often leads to a significant reduction in quality of life (QoL). Basically, the disease is characterised by pain and functional disorders which are initially treated with conservative therapy, but in case of complications (uncontrollable pain or obstruction) surgical treatment is required. This article reviews the relevant literature of CP treatment, in particular randomized controlled trials and meta-analyses were involved with a comparison of different surgical treatment options for the management of CP complications. Recent studies have demonstrated that surgical procedures are superior to endoscopic therapy as regards long-term results of QoL and pain control. There was no significant difference found in postoperative pain relief and overall mortality when duodenum-preserving pancreatic head resection (DPPHR) of Beger and its modification (duodenum and organ-preserving pancreatic head resection [DOPPHR]) were compared with pancreatoduodenectomy (PD), but hospital stay, weight gain, exocrine and endocrine insufficiency, and QoL were significantly better in the DPPHR and DOPPHR groups. DPPHR and PD seem to be equally effective in terms of postoperative pain relief and overall mortality. However, recent data suggest that DOPPHR is superior in the treatment of CP with regard to several peri- and postoperative outcome parameters and QoL. Therefore, this should be the preferable treatment option for CP complications.

  11. Prescription patterns of enzyme-containing products in South Africa over a 2-year period

    Directory of Open Access Journals (Sweden)

    Ilse Truter

    2014-09-01

    Full Text Available Enzymes are traded in five categories, namely medical (intervention, diagnostic (detection and quantification, molecular biology, biofuel and industrial. Therapeutic enzymes have been investigated for different uses, for example, for the treatment of genetic disorders, blood clotting disorders, cancer and infectious diseases and for burn debridement. No studies on the prescription of enzyme-containing products in South Africa could be found. Enzymes are classified in the Monthly Index of Medical Specialities under digestants, enzymes and fibrinolytics. The primary aim of this study was to investigate the prescription patterns and cost of enzyme-containing products in South Africa. A private health-care medicines claims database for 2010 and 2011 of approximately 4.5 million records was analysed retrospectively. Enzyme-containing products constituted a small percentage of medical insurance claims (only 0.02% of approximately 4.5 million claims for products and procedures, yet they were relatively expensive. A total of 906 products was prescribed at a cost of almost ZAR2 million over the 2 years. Hyaluronidase was the most frequently prescribed (60.04%, followed by pancreatin-containing products (34.66%. Pancreatin (lipase/ protease/amylase is primarily used in the management of pancreatic exocrine insufficiency. The average cost per hyaluronidase prescription paid by the medical insurance schemes was ZAR280. Other enzyme-containing products prescribed were imiglucerase, alteplase and tenecteplase. Imiglucerase was overall the most expensive. Alteplase, tenecteplase and streptokinase are antithrombotic enzymes that are used in the treatment of acute myocardial infarction or ischaemic stroke. Streptokinase, regarded as the most affordable antithrombotic enzyme, was not prescribed during the period under study. With the growing opportunities for enzymes for therapeutics, the use of enzyme-containing products which are comparatively expensive require

  12. Effects of protease and non-starch polysaccharide enzyme on performance, digestive function, activity and gene expression of endogenous enzyme of broilers.

    Directory of Open Access Journals (Sweden)

    Lin Yuan

    Full Text Available Three hundred one-day-old male broiler chickens (Ross-308 were fed corn-soybean basal diets containing non-starch polysaccharide (NSP enzyme and different levels of acid protease from 1 to 42 days of age to investigate the effects of exogenous enzymes on growth performance, digestive function, activity of endogenous digestive enzymes in the pancreas and mRNA expression of pancreatic digestive enzymes. For days 1-42, compared to the control chickens, average daily feed intake (ADFI and average daily gain (ADG were significantly enhanced by the addition of NSP enzyme in combination with protease supplementation at 40 or 80 mg/kg (p<0.05. Feed-to-gain ratio (FGR was significantly improved by supplementation with NSP enzymes or NSP enzyme combined with 40 or 80 mg/kg protease compared to the control diet (p<0.05. Apparent digestibility of crude protein (ADCP was significantly enhanced by the addition of NSP enzyme or NSP enzyme combined with 40 or 80 mg/kg protease (p<0.05. Cholecystokinin (CCK level in serum was reduced by 31.39% with NSP enzyme combined with protease supplementation at 160 mg/kg (p<0.05, but the CCK level in serum was increased by 26.51% with NSP enzyme supplementation alone. After 21 days, supplementation with NSP enzyme and NSP enzyme combined with 40 or 80 mg/kg protease increased the activity of pancreatic trypsin by 74.13%, 70.66% and 42.59% (p<0.05, respectively. After 42 days, supplementation with NSP enzyme and NSP enzyme combined with 40 mg/kg protease increased the activity of pancreatic trypsin by 32.45% and 27.41%, respectively (p<0.05. However, supplementation with NSP enzyme and 80 or 160 mg/kg protease decreased the activity of pancreatic trypsin by 10.75% and 25.88%, respectively (p<0.05. The activities of pancreatic lipase and amylase were significantly higher in treated animals than they were in the control group (p<0.05. Supplementation with NSP enzyme, NSP enzyme combined with 40 or 80 mg/kg protease increased

  13. Legumain is activated in macrophages during pancreatitis

    NARCIS (Netherlands)

    Edgington-Mitchell, L.E.; Wartmann, T.; Fleming, A.K.; Gocheva, V.; Linden, W.A. van der; Withana, N.P.; Verdoes, M.; Aurelio, L.; Edgington-Mitchell, D.; Lieu, T.; Parker, B.S.; Graham, B.; Reinheckel, T.; Furness, J.B.; Joyce, J.A.; Storz, P.; Halangk, W.; Bogyo, M.; Bunnett, N.W.

    2016-01-01

    Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked

  14. Pancreaticojejunal bridge-anastomosis: a novel option for surgeon to preserve pancreatic body and tail in urgent reoperation for intra-abdominal massive hemorrhage after pancreaticoduodenectomy.

    Science.gov (United States)

    Xu, Jin; Dai, Xianwei; Bu, Xianmin; Gao, Feng; Zhang, Xiaobo

    2010-10-01

    Postoperative intra-abdominal massive bleeding is a rare and life-threatening complication associated with pancreaticoduodenectomy. Completion pancreatectomy (CP) was usually performed during reexploration for the complication. The management could decrease the complications, such as the pancreatic leakage or intraluminal infection after reexploration, but could increase mortality during the perioperative period. It also could result in loss of pancreatic function forever. This study evaluated an alternative surgical management for intra-abdominal massive hemorrhage to prevent pancreas function, simplify the surgical processes, and decrease the mortality of relaparotomy. Outcome after pancreaticojejunal bridge-anastomosis (PJBA) performed between January 2006 and June 2009 was compared with that after CP performed between February 1984 and December 2005. Between February 1984 and June 2009, 963 patients underwent the Whipple procedure (PD) or pylorus-preserving pancreaticoduodectomy (PPPD). Pancreatic leakage occurred in 103 patients (10.7%); 22 cases (21.4%) developed into intra-abdominal massive bleeding. Nonsurgical procedures of transarterial embolization (TAE) were performed in ten (45.45%) patients, of whom one died (10%). Twelve (54.55%) underwent reoperation. Five had CP with one death (20%). Pancreatic remnant was preserved by pancreaticojejunal bridge-anastomosis (PJBA) in seven patients with no deaths. The reexploration time was 340 +/- 48.2 min vs. 247.9 +/- 40.8 min (P endocrine insufficiency ("brittle" diabetes) and diarrhea (exocrine insufficiency). There were no evidences of exocrine and endocrine insufficiency in patients with PJBA. Pancreaticojejunal bridge-anastomosis is an easy, simple, and safe procedure for intra-abdominal massive hemorrhage associated with pancreaticoduodenectomy. It could decrease the mortality of reoperation and preserve the pancreatic function.

  15. Current options for palliative treatment in patients with pancreatic cancer.

    Science.gov (United States)

    Ridwelski, K; Meyer, F

    2001-01-01

    Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression. Copyright 2001 S. Karger AG, Basel

  16. 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.

  17. Digestion of atopic allergens with trypsin α-chymotrypsin and pancreatic kallikrein, and influence of the allergens upon the proteolytic and esterolytic activity of these enzymes

    NARCIS (Netherlands)

    Berrens, L.

    1968-01-01

    The action of bovine trypsin, α-chymotrypsin and pancreatic kallikrein upon a number of atopic allergens has been studied by pH-stat measurements during short-term incubation. Most atopic allergens proved chemically resistant towards these enzymes. Graphs of enzyme susceptibility vs. the ratio of

  18. Decreased α-cell mass and early structural alterations of the exocrine pancreas in patients with type 1 diabetes: An analysis based on the nPOD repository.

    Directory of Open Access Journals (Sweden)

    Fidéline Bonnet-Serrano

    Full Text Available Abnormal glucagon secretion and functional alterations of the exocrine pancreas have been described in patients with type 1 diabetes (T1D, but their respective anatomical substrata have seldom been investigated. Our aim was to develop an automated morphometric analysis process to characterize the anatomy of α-cell and exocrine pancreas in patients with T1D, using the publicly available slides of the Network for Pancreatic Organ Donors (nPOD.The ratio of β- and α-cell area to total tissue area were quantified in 75 patients with T1D (thereafter patients and 66 control subjects (thereafter controls, on 2 insulin-stained and 4 glucagon-stained slides from both the head and the tail of the pancreas. The β- and α-cell masses were calculated in the 66 patients and the 50 controls for which the pancreas weight was available. Non-exocrine-non-endocrine tissue area (i.e. non-acinar, non-insular tissue to total tissue area ratio was evaluated on both insulin- and glucagon-stained slides. Results were expressed as mean ±SD.An automated quantification method was set up using the R software and was validated by quantification of β-cell mass, a well characterized parameter. β-cell mass was 29.6±112 mg in patients and 628 ±717 mg in controls (p<0.0001. α-cell mass was 181±176 mg in patients and 349 ±241mg in controls (p<0.0001. Non-exocrine-non-endocrine area to total tissue area ratio was 39±9% in patients and 29± 10% in controls (p<0.0001 and increased with age in both groups, with no correlation with diabetes duration in patients.The absolute α-cell mass was lower in patients compared to controls, in proportion to the decrease in pancreas weight observed in patients. Non-exocrine-non-endocrine area to total tissue area ratio increased with age in both groups but was higher in patients at all ages.

  19. Morphological and functional alterations of small intestine in chronic pancreatitis.

    Science.gov (United States)

    Gubergrits, Natalya B; Linevskiy, Yuri V; Lukashevich, Galina M; Fomenko, Pavel G; Moroz, Tatyana V; Mishra, Tapan

    2012-09-10

    The small intestine in chronic pancreatitis has not been investigated yet thoroughly. It would be important to understand fat metabolism in the course of this disease and could be explained if the small intestine has some pathological conditions and, due to this reason, pancreatic enzyme substitution does not work in all patients. To investigate the pathophysiology of small intestine in chronic pancreatitis and to show the reason why in some cases pancreatic enzyme substitution does not work properly. In the process of the study 33 chronic pancreatitis patients have been examined. The control group includes 30 subjects without chronic pancreatitis similar for age, sex and alcohol consumption to the patients with chronic pancreatitis patients. Aspiration biopsy of jejunum mucosa followed by histological examination and investigation of intestinal enzymes by aspiration has been performed. Metabolism at membranic level has been studied by enzymatic activity of amylase and lipase in the small intestine. Production of enzymes (monoglyceride lipase, lactase, saccharase, maltase, glycyl-l-leucine dipeptidase) promoting metabolism in enterocytes has been estimated as to their activity in homogenates of jejunum mucosa samples. Participation of mucosa in intestinal digestion has been assessed by alkaline phosphatase activity in a secretory chyme from proximal portion of jejunum. Absorptive capacity of jejunum was evaluated by D-xylose test results. DNA, lysozyme, immunoglobulin contents of chyme have also been calculated and bacteriological study of chyme has been also performed. Secondary enteritis, accompanied by moderate dystrophic changes of mucous membrane, thinning of limbus, and decrease of Paneth cell mitotic index, was found to occur in chronic pancreatitis patients. Enteritis is followed by changes in enzymatic processes in the sphere of membrane and intestinal digestion, decrease of absorption, accelerated desquamation of epithelium, fall in local immunity and

  20. Is endoscopic therapy the treatment of choice in all patients with chronic pancreatitis?

    Science.gov (United States)

    Jabłońska, Beata

    2013-01-07

    Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas characterized by destruction of the pancreatic parenchyma with subsequent fibrosis that leads to pancreatic exocrine and endocrine insufficiency. Abdominal pain and local complications (bile duct or duodenal stenosis and pancreatic tumor) secondary to CP are indications for therapy. At the beginning, medical therapy is used. More invasive treatment is recommended for patients with pancreatic duct stones (PDS) and pancreatic obstruction in whom standard medical therapy is not sufficient. Recently, Clarke et al assessed the long-term effectiveness of endoscopic therapy (ET) in CP patients. The authors compared ET with medical treatment. They reported that ET was clinically successful in 50% of patients with symptomatic CP. In this commentary, current CP treatment, including indications for ET and surgery in CP patients, is discussed. Recommendations for endoscopic treatment of CP according to the European Society of Gastrointestinal Endoscopy Clinical Guidelines are reviewed. Different surgical methods used in the treatment of CP patients are also discussed. ET is the most useful in patients with large PDS, pancreatic duct obstruction and dilation. It should be the first-line option because it is less invasive than surgery. Surgery should be the first-line option in patients in whom ET has failed or in those with a pancreatic mass with suspicion of malignancy. ET is a very effective and less invasive procedure, but it cannot be recommended as the treatment of choice in all CP patients.

  1. Acinar cell carcinoma of the pancreas presenting as diffuse pancreatic enlargement: Two case reports and literature review.

    Science.gov (United States)

    Luo, Yaping; Hu, Guilan; Ma, Yanru; Guo, Ning; Li, Fang

    2017-09-01

    Pancreatic acinar cell carcinoma (ACC) is a rare malignant tumor of exocrine pancreas. It is typically a well-marginated large solid mass arising in a certain aspect of the pancreas. Diffuse involvement of ACC in the pancreas is very rare, and may simulate pancreatitis in radiological findings. We report 2 cases of ACC presenting as diffuse enlargement of the pancreas due to tumor involvement without formation of a distinct mass. The patients consisted of a 41-year-old man with weight loss and a 77-year-old man who was asymptomatic. Computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed diffuse enlargement of the pancreas forming a sausage-like shape with homogenously increased FDG activity. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy of the pancreatic lesion was performed. Histopathology results from the pancreas confirmed the diagnosis of pancreatic ACC. Because diffuse enlargement of the pancreas is a common imaging feature of pancreatitis, recognition of this rare morphologic pattern of ACC is important for radiological diagnosis of this tumor.

  2. Quality of life and functional outcome after resection of pancreatic cystic neoplasm.

    Science.gov (United States)

    van der Gaag, Niels A; Berkhemer, Olvert A; Sprangers, Mirjam A; Busch, Olivier R C; Bruno, Marco J; de Castro, Steve M; van Gulik, Thomas M; Gouma, Dirk J

    2014-07-01

    The objectives of this study were to assess the long-term quality of life (QOL) after the resection of a primary pancreatic cyst and to determine predictors of outcome. Secondary outcomes were pancreatic function and survival. One hundred eight consecutive patients, who underwent resection between 1992 and 2007 and had nearly 60 months follow-up, were reviewed. Questionnaires and function tests were collected during scheduled outpatient clinic visits. At follow-up, 20 patients had died. Five-year overall survival was 94% for benign and 62% for malignant neoplasia. Of 88 living patients, 65 (74%) returned questionnaires. Generic physical and mental QOL scores were equal or better compared with healthy references. None of the disease-specific symptom scales were above mean 50, implicating none to mild complaints. Independent predictors for good generic QOL were young age (P endocrine insufficiency (P Endocrine insufficiency prevalence was 40%, and 59% for exocrine insufficiency. After cyst resection, long-term QOL is equal to healthy references, pancreatic insufficiency is prevalent but does not impair QOL, and survival relates positive compared with solid pancreatic adenocarcinoma. The excellent long-term outcome justifies proceeding with surgery once a medical indication for resection has been established.

  3. 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.

  4. Impaired acid neutralization in the duodenum in pancreatic insufficiency.

    Science.gov (United States)

    Dutta, S K; Russell, R M; Iber, F L

    1979-10-01

    The influence of severe exocrine pancreatic disease on the acid-neutralizing capacity of the duodenum was studied in five patients with pancreatic insufficiency (PI) and six control subjects using duodenal perfusion-marker technique. Hydrochloric acid (0.1 N containing 1% PEG) was infused at constant rates (1.2, 4.5 and 7.0 ml/min) into the duodenum just distal to the duodenal bulb. Samples were aspirated from the tip of the duodenal perfusion tube located at the ligament of Treitz. All samples were analyzed for volume, pH, titrable acidity, PEG and [14C]PEG (gastric marker) determination. Patients with PI demonstrated significantly diminished ability to neutralize various acid loads as compared to controls who virtually completely neutralized acid loads in the range of maximal gastric acid secretion. Exogenous secretin did not significantly improve percent acid neutralized in PI. These data clearly indicate that patients with PI have significantly impaired ability to neutralize even small loads of acid in the duodenum.

  5. Lnx2 ubiquitin ligase is essential for exocrine cell differentiation in the early zebrafish pancreas.

    Science.gov (United States)

    Won, Minho; Ro, Hyunju; Dawid, Igor B

    2015-10-06

    The gene encoding the E3 ubiquitin ligase Ligand of Numb protein-X (Lnx)2a is expressed in the ventral-anterior pancreatic bud of zebrafish embryos in addition to its expression in the brain. Knockdown of Lnx2a by using an exon 2/intron 2 splice morpholino resulted in specific inhibition of the differentiation of ventral bud derived exocrine cell types, with little effect on endocrine cell types. A frame shifting null mutation in lnx2a did not mimic this phenotype, but a mutation that removed the exon 2 splice donor site did. We found that Lnx2b functions in a redundant manner with its paralog Lnx2a. Inhibition of lnx2a exon 2/3 splicing causes exon 2 skipping and leads to the production of an N-truncated protein that acts as an interfering molecule. Thus, the phenotype characterized by inhibition of exocrine cell differentiation requires inactivation of both Lnx2a and Lnx2b. Human LNX1 is known to destabilize Numb, and we show that inhibition of Numb expression rescues the Lnx2a/b-deficient phenotype. Further, Lnx2a/b inhibition leads to a reduction in the number of Notch active cells in the pancreas. We suggest that Lnx2a/b function to fine tune the regulation of Notch through Numb in the differentiation of cell types in the early zebrafish pancreas. Further, the complex relationships among genotype, phenotype, and morpholino effect in this case may be instructive in the ongoing consideration of morpholino use.

  6. The effect of the modified puestow procedure on diabetes in patients with tropical chronic pancreatitis--a prospective study.

    Science.gov (United States)

    Sidhu, S S; Nundy, S; Tandon, R K

    2001-01-01

    Surgical decompression of the pancreatic duct in patients with chronic pancreatitis relieves pain in 80-90% of subjects, but its effect on exocrine and endocrine pancreatic function is not clear. We sought to further examine such effects. We performed the modified Puestow procedure (lateral pancreaticojejunostomy) in 53 patients with chronic tropical pancreatitis. Pain evaluation was done subjectively and objectively, and the fasting and postprandial blood glucose, insulin requirements, and 72-h fecal fat levels were estimated before and at 3 months and 5 yr after operation. We compared 46 operated patients who completed 5 yr of follow-up with 40 patients who did not undergo operation. Forty-one patients (89%) had complete pain relief. The mean fasting (209 mg/dl) and postprandial (320 mg/dl) blood glucose and insulin requirements (40 U/day) decreased postoperatively (fasting, 162 mg/dl; postprandial blood glucose, 254mg/dl; insulin requirement, 18.2 U/day; p Puestow procedure not only have relief from pain but also improvement of diabetes.

  7. Chronic Pancreatitis

    International Nuclear Information System (INIS)

    Vavrecka, A.; Bilicky, J.

    2011-01-01

    Chronic pancreatitis is an ongoing inflammatory process that may over time lead to mal digestion, malabsorption and diabetic syndrome. Identification of risk (etiological) factors based on classifications TIGAR-O or later M-ANNHEIM. These factors (environmental and / or genetic) leads to failure of the stability of the digestive and lysosomal enzymes in the acinar cells, resulting in premature activation of digestive enzymes in the pancreas, and repeated nekroinflamation and fibrosis. The incidence has of the upward trend. Clinically the disease manifests itself in most cases with pain and possibly with nonspecific dyspeptic troubles. Decisive role in the diagnosis playing imaging methods, trans abdominal ultrasonography, computed tomography, magnetic resonance imaging, magnetic cholangiopancretography and foremost endoscopic ultrasonography, which has the highest sensitivity and specificity. Endoscopic retrograde cholangiopancreatography is currently regarded as a method for therapy, not for diagnosis. Less importance is now attached to a functional test. Symptomatic treatment is usually conservative. Abstinence is necessary, easily digestible, but calorie-rich diet with reduced fat. Most patients needed treatment with analgesics. In case of insufficient effect of analgesics is necessary to consider endoscopic therapy or surgery. If the external secretory insufficiency is present are served pancreatic extracts. Diabetic syndrome requires insulin delivery. Generally, chronic pancreatitis is a disease treatable but incurable. Proportion of patients are also dying of pancreatic cancer. (author)

  8. Pancreatitis associated with the helminth serpinema microcephalus (Nematoda: Camallanidae) in exotic red-eared slider turtles (Trachemys scripta elegans)

    OpenAIRE

    Hidalgo-Vila, J.; Martínez-Silvestre, A.; Ribas, A.; Casanova, J.C.; Pérez-Santigosa, N.; Díaz-Paniagua, Carmen

    2011-01-01

    Pancreatitis associated with the helminth Serpinema microcephalus was found in three of 19 free-ranging red-eared slider turtles (Trachemys scripta elegans) captured between March 2003 and September 2004 in southern Spain. Microscopic changes were associated with parasite migrations and were characterized by central areas of necrosis surrounded by leukocytes and resulted in destruction of exocrine tissue. The blood profile of one of the three female turtles revealed eosinophilia and hyperglyc...

  9. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol

    International Nuclear Information System (INIS)

    Kaphalia, Bhupendra S.; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel

    2010-01-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH - ) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH - and hepatic ADH-normal (ADH + ) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ∼ 1.5-fold greater in ADH - vs. ADH + deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH - deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

  10. Surgical strategies for treatment of malignant pancreatic tumors: extended, standard or local surgery?

    Directory of Open Access Journals (Sweden)

    Jacob Dietmar

    2008-11-01

    Full Text Available Abstract Tumor related pancreatic surgery has progressed significantly during recent years. Pancreatoduodenectomy (PD with lymphadenectomy, including vascular resection, still presents the optimal surgical procedure for carcinomas in the head of pancreas. For patients with small or low-grade malignant neoplasms, as well as small pancreatic metastases located in the mid-portion of pancreas, central pancreatectomy (CP is emerging as a safe and effective option with a low risk of developing de-novo exocrine and/or endocrine insufficiency. Total pancreatectomy (TP is not as risky as it was years ago and can nowadays safely be performed, but its indication is limited to locally extended tumors that cannot be removed by PD or distal pancreatectomy (DP with tumor free surgical margins. Consequently, TP has not been adopted as a routine procedure by most surgeons. On the other hand, an aggressive attitude is required in case of advanced distal pancreatic tumors, provided that safe and experienced surgery is available. Due to the development of modern instruments, laparoscopic operations became more and more successful, even in malignant pancreatic diseases. This review summarizes the recent literature on the abovementioned topics.

  11. Clinical significance of enzymatic deficiencies in the gastrointestinal tract with particular reference to lactase deficiency.

    Science.gov (United States)

    Rossi, E; Lentze, M J

    1984-12-01

    The study of deficiencies of small intestinal brush-border hydrolases increased our knowledge about the specific functions of hydrolases in the digestion of smaller molecules on the microvillus surface of the absorptive cells. The sucrase-isomaltase (SI) complex has been shown to be synthesized as a precursor (pro-sucrase-isomaltase) which is then incorporated into the membrane. The hydrophobic N-terminal end of the molecule is anchored in the lipid bilayer. In SI deficiency the molecular base of the disease is still not clear. Absence of SI activity could be due to complete lack of precursor synthesis or to structural changes within the N-terminal end of the SI-complex. Deficiencies of peptide hydrolases have not been reported with the exception of enteropeptidase (EP). Here a congenital deficiency of the enzyme was observed as the primary defect in enzyme synthesis within the enterocytes and as a secondary defect due to exocrine pancreatic insufficiency. In contrast to the primary EP deficiency, the activity of EP can be restored in the cases of exocrine pancreatic insufficiency by treatment with pancreatic extracts. Primary lactase deficiency exists in various forms. Besides congenital lactase deficiency, the late onset or adult type of lactase deficiency has been observed. The latter occurs in many different ethnic groups around the world. Here, using gel electrophoresis and immunoelectrophoresis, the lack of enzyme activity could be shown to be a primary defect in enzyme protein synthesis. In man and in the rat, two different lactases have been identified. In contrast to adult lactase, fetal lactase contains sialic acid at the end of carbohydrate side chains.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Both Exocrine Pancreatic Insufficiency and Signs of Pancreatic Inflammation Are Prevalent in Children with Complicated Severe Acute Malnutrition: An Observational Study

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Meyer, Sophie L.; Stehmann, Tijs A.; Bourdon, Céline; Bandsma, Robert H. J.; Voskuijl, Wieger P.

    2016-01-01

    Objectives To assess whether pancreatic function is impaired in children with severe acute malnutrition, is different between edematous vs nonedematous malnutrition, and improves by nutritional rehabilitation. Study design We followed 89 children with severe acute malnutrition admitted to Queen

  13. Both Exocrine Pancreatic Insufficiency and Signs of Pancreatic Inflammation Are Prevalent in Children with Complicated Severe Acute Malnutrition : An Observational Study

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Meyer, Sophie L.; Stehmann, Tijs A.; Bourdon, Celine; Bandsma, Robert H. J.; Voskuijl, Wieger P.

    Objectives To assess whether pancreatic function is impaired in children with severe acute malnutrition, is different between edematous vs nonedematous malnutrition, and improves by nutritional rehabilitation. Study design We followed 89 children with severe acute malnutrition admitted to Queen

  14. Small amounts of tissue preserve pancreatic function: Long-term follow-up study of middle-segment preserving pancreatectomy.

    Science.gov (United States)

    Lu, Zipeng; Yin, Jie; Wei, Jishu; Dai, Cuncai; Wu, Junli; Gao, Wentao; Xu, Qing; Dai, Hao; Li, Qiang; Guo, Feng; Chen, Jianmin; Xi, Chunhua; Wu, Pengfei; Zhang, Kai; Jiang, Kuirong; Miao, Yi

    2016-11-01

    Middle-segment preserving pancreatectomy (MPP) is a novel procedure for treating multifocal lesions of the pancreas while preserving pancreatic function. However, long-term pancreatic function after this procedure remains unclear.The aims of this current study are to investigate short- and long-term outcomes, especially long-term pancreatic endocrine function, after MPP.From September 2011 to December 2015, 7 patients underwent MPP in our institution, and 5 cases with long-term outcomes were further analyzed in a retrospective manner. Percentage of tissue preservation was calculated using computed tomography volumetry. Serum insulin and C-peptide levels after oral glucose challenge were evaluated in 5 patients. Beta-cell secreting function including modified homeostasis model assessment of beta-cell function (HOMA2-beta), area under the curve (AUC) for C-peptide, and C-peptide index were evaluated and compared with those after pancreaticoduodenectomy (PD) and total pancreatectomy. Exocrine function was assessed based on questionnaires.Our case series included 3 women and 2 men, with median age of 50 (37-81) years. Four patients underwent pylorus-preserving PD together with distal pancreatectomy (DP), including 1 with spleen preserved. The remaining patient underwent Beger procedure and spleen-preserving DP. Median operation time and estimated intraoperative blood loss were 330 (250-615) min and 800 (400-5500) mL, respectively. Histological examination revealed 3 cases of metastatic lesion to the pancreas, 1 case of chronic pancreatitis, and 1 neuroendocrine tumor. Major postoperative complications included 3 cases of delayed gastric emptying and 2 cases of postoperative pancreatic fistula. Imaging studies showed that segments representing 18.2% to 39.5% of the pancreas with good blood supply had been preserved. With a median 35.0 months of follow-ups on pancreatic functions, only 1 patient developed new-onset diabetes mellitus of the 4 preoperatively euglycemic

  15. Secretin-enhanced magnetic resonance cholangiopancreaticography: value for the diagnosis of chronic pancreatitis

    International Nuclear Information System (INIS)

    Heverhagen, J.T.; Burbelko, M.; Schenck zu Schweinsberg, T.; Funke, C.; Wecker, C.; Walthers, E.M.; Rominger, M.

    2007-01-01

    Endoscopic retrograde cholangiopancreaticography (ERCP) is the morphologic gold standard for the diagnosis of chronic pancreatitis. Magnetic Resonance Imaging (MRI) enables the visualization of not only the pancreatic duct but also the surrounding parenchyma using T2- and T1-weighted sequences before and after the application of a contrast agent. Moreover, it allows the depiction of ductal segments distal to a stenosis or occlusion. However, conventional Magnetic Resonance Cholangiopancreaticography (MRCP) was not able to achieve accuracy similar to that of ERCP. Despite many technological innovations, such as fast breath-hold acquisitions or respiratory-gated 3D sequences, this drawback could not be overcome. In recent years, secretin-enhanced MRCP has been used for the diagnosis of chronic pancreatitis. A recent study showed that secretin not only improves the visibility of the pancreatic duct and its side branches but it also enhances the diagnostic accuracy of MRCP. The sensitivity, specificity, and positive and negative predictive values were improved by the application of secretin. Moreover, the agreement between independent observers increased after the use of secretin. In addition, quantitative post-processing tools have been developed that enable the measurement of the exocrine pancreatic output non-invasively using secretin-enhanced MRCP. These tools facilitate applications, such as functional follow-up after pancreaticogastrostomy and pancreaticogastric anastomoses, evaluation of the functional status of the graft after pancreas transplantation and follow-up of pancreatic drainage procedures and duct disruption. (orig.)

  16. Hematologic and pancreatic endocrine abnormalities after ionisingirradiation

    International Nuclear Information System (INIS)

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.

    1986-01-01

    Besides the use of ionizing irradiation in the treatment of malignant tumours of the abdominal cavity, irradiation has also been documented to suppress the classical organ allograft rejection response in man and experimental models. Recently, fractionated total lymphoid irradiation (TLI) and subtotal bone-marrow irradiation has been proved successfull in suppressing rejection of liver and kidney allografts in primates resulting in permanent tolerance. This study evaluates the detrimental side-effects of fractionated irradiation on peripheral blood, bone-marrow, pancreatic morphology and function in our primate model. Twenty primates received fractionated irradiation in doses of 800 (8 Gy) and 1000 (10 Gy) rads respectively administered at 100 rad (1 Gy) biweekly over a 4 to 5 week period. During the last weeks of irradiation 300 millilitres (ml) of donor specific blood was transfused in 50 ml aliquotes to combat the myelosuppressive effects of irradiation. Within 1 week of irradiation marked bonemarrow suppression was characterized by pancytopaenia and hypoplasia Pancreatic endocrine disturbances include hypoin-sulinaemia associated with mild glucose intolerance and reduced K-values. Significant pathological changes of the pancreas included nuclear and cytocavitary network changes affecting both endocrine and exocrine pancreatic elements. Although irradiation has proved to be a powerful immunosuppressive modality, significant haematological and organ damage occurred despite fractionation over a 4 to 5 week period

  17. Surgical approaches to chronic pancreatitis: indications and imaging findings.

    Science.gov (United States)

    Hafezi-Nejad, Nima; Singh, Vikesh K; Johnson, Stephen I; Makary, Martin A; Hirose, Kenzo; Fishman, Elliot K; Zaheer, Atif

    2016-10-01

    Chronic pancreatitis (CP) is an irreversible, inflammatory process characterized by progressive fibrosis of the pancreas that can result in abdominal pain, exocrine insufficiency, and diabetes. Inadequate pain relief using medical and/or endoscopic therapies is an indication for surgery. The surgical management of CP is centered around three main operations including pancreaticoduodenectomy (PD), duodenum-preserving pancreatic head resection (DPPHR) and drainage procedures, and total pancreatectomy with islet autotransplantation (TPIAT). PD is the method of choice when there is a high suspicion for malignancy. Combined drainage and resection procedures are associated with pain relief, higher quality of life, and superior short-term and long-term survival in comparison with the PD. TPIAT is a reemerging treatment that may be promising in subjects with intractable pain and impaired quality of life. Imaging examinations have an extensive role in pre-operative and post-operative evaluation of CP patients. Pre-operative advanced imaging examinations including CT and MRI can detect hallmarks of CP such as calcifications, pancreatic duct dilatation, chronic pseudocysts, focal pancreatic enlargement, and biliary ductal dilatation. Post-operative findings may include periportal hepatic edema, pneumobilia, perivascular cuffing and mild pancreatic duct dilation. Imaging can also be useful in the detection of post-operative complications including obstructions, anastomotic leaks, and vascular lesions. Imaging helps identify unique post-operative findings associated with TPIAT and may aid in predicting viability and function of the transplanted islet cells. In this review, we explore surgical indications as well as pre-operative and post-operative imaging findings associated with surgical options that are typically performed for CP patients.

  18. Endocrine pancreatic development: impact of obesity and diet

    Directory of Open Access Journals (Sweden)

    Jacqueline F O'Dowd

    2013-07-01

    Full Text Available During embryonic development, multipotent endodermal cells differentiate to form the pancreas. Islet cell clusters arising from the pancreatic bud form the acini tissue and exocrine ducts whilst pancreatic islets form around the edges of the clusters. The successive steps of islet differentiation are controlled by a complex network of transcription factors and signals that influence cell differentiation, growth and lineage. A Westernised lifestyle has led to an increased consumption of a high saturated fat diet, and an increase in maternal obesity. The developing fetus is highly sensitive to the intrauterine environment, therefore any alteration in maternal nutrition during gestation and lactation which affects the in-utero environment during the key developmental phases of the pancreas may change the factors controlling β-cell development and β-cell mass. Whilst the molecular mechanisms behind the adaptive programming of β-cells are still poorly understood it is established that changes arising from maternal obesity and/or over-nutrition may affect the ability to maintain fetal β-cell mass resulting in an increased risk of type 2 diabetes in adulthood.

  19. Derivation and characterization of a pig embryonic stem cell-derived exocrine pancreatic cell line

    Science.gov (United States)

    The establishment and initial characterization of a pig embryonic stem cell-derived pancreatic cell line, PICM-31, and a colony-cloned derivative cell line, PICM-31A, is described. The cell lines were propagated for several months at split ratios of 1:3 or 1:5 at each passage on STO feeder cells af...

  20. Organ culture studies for pancreatic islet transplantation

    International Nuclear Information System (INIS)

    Reemtsma, K.; Weber, C.J.; Pi-Sunyer, F.X.; Lerner, R.; Zimmerman, E.; Hardy, M.A.

    1979-01-01

    Data support the usefulness of tissue culture in isolation and preservation of islets prior to transplantation. Rodent islet viability in culture was demonstrated histologically and by functional analyses of hormone production. For reasons that remain to be defined, acinar cells disappeared rapidly in tissue culture, yielding an implant preparation relatively rich in islets and devoid of pancreatic exocrine elements. Isografts of cultured and noncultured islets were well tolerated intraperitoneally and intramuscularly; and prompt and lasting reversal of short- and long-standing experimental diabetes was observed regularly. In vitro studies of rodent islet viability after immunosuppressive treatment of donors or islet cultures showed insulin production comparable to that of control experiments, suggesting that immunologic modification of donors or islets might be feasible in eventual human islet allotransplantation

  1. Middle-preserving pancreatectomy for advanced transverse colon cancer invading the duodenun and non-functioning endocrine tumor in the pancreatic tail.

    Science.gov (United States)

    Noda, Hiroshi; Kato, Takaharu; Kamiyama, Hidenori; Toyama, Nobuyuki; Konishi, Fumio

    2011-02-01

    A 73-year-old female was referred to our hospital with a diagnosis of advanced transverse colon cancer with severe anemia and body weight loss. Preoperative evaluations, including colonoscopy, gastroduodenoscopy, and computed tomography, revealed not only a transverse colon cancer massively invading the duodenum, but also a non-functioning endocrine tumor in the pancreatic tail. We performed middle-preserving pancreatectomy (MPP) with right hemicolectomy for these tumors with a curative intent. After the resection, about 6 cm of the body of the pancreas was preserved, and signs of diabetes mellitus have not appeared. The postoperative course was complicated by a grade B pancreatic fistula, but this was successfully treated with conservative management. After a 33-day hospital stay, the patient returned to daily life without signs of pancreatic exocrine insufficiency. Although the long-term follow-up of the patient is indispensable, in this case, MPP might be able to lead to the curative resection of transverse colon cancer massively invading the duodenum and non-functioning endocrine tumor in the pancreatic tail with preservation of pancreatic function.

  2. Positron emission tomography (PET) and pancreatic tumours; Tomographie par emission de positons (TEP) et tumeurs pancreatiques

    Energy Technology Data Exchange (ETDEWEB)

    Montravers, F.; Kerrou, K.; Grahek, D.; Gutman, F.; Beco, V. de; Talbot, J.N. [Hopital Tenon, Service de Medecine, 75 - Paris (France)

    2005-07-15

    Neoplasms of the pancreas may originate front both exocrine and endocrine cells but in 90% of the cases, they correspond to ductal adenocarcinomas. For adenocarcinomas, the major indication of FDG-PET corresponds to the pre-operative staging because unexpected distant metastases can be detected by FDG-PET in about 20 to 40% of the cases, which results in avoidance of unnecessary surgical procedures. FDG PET is also useful in evaluation of the treatment effect, monitoring after the operation and detection of recurrent pancreatic cancers. For the characterisation of the pancreatic tumour, the performance of FDG-PET is sometimes limited due to poor cellularity, hyperglycemia or inflammatory processes. especially for large tumours and is indicated only in cases of doubtful results of CT or MRI. For endocrine pancreatic tumours, FDG-PET is useful only in case of poorly-differentiated and aggressive tumours. F-DOPA PET can he useful, complementary to pentetreotide scintigraphy, in well-differentiated endocrine tumours. (authors)

  3. Chronic Pancreatitis in the 21st Century - Research Challenges and Opportunities

    Science.gov (United States)

    Uc, Aliye; Andersen, Dana K.; Bellin, Melena D.; Bruce, Jason I.; Drewes, Asbjørn M.; Engelhardt, John F.; Forsmark, Christopher E.; Lerch, Markus M.; Lowe, Mark E.; Neuschwander-Tetri, Brent A.; O’Keefe, Stephen J.; Palermo, Tonya M.; Pasricha, Pankaj; Saluja, Ashok K.; Singh, Vikesh K.; Szigethy, Eva M.; Whitcomb, David C.; Yadav, Dhiraj; Conwell, Darwin L.

    2016-01-01

    A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to focus on research gaps and opportunities in chronic pancreatitis (CP) and its sequelae. This conference marked the 20th year anniversary of the discovery of the cationic trypsinogen (PRSS1) gene mutation for hereditary pancreatitis. The event was held on July 27, 2016, and structured into 4 sessions: (1) pathophysiology; (2) exocrine complications; (3) endocrine complications; and (4) pain. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to design better tools to diagnose CP and its sequelae early and reliably, identify predisposing risk factors for disease progression, develop standardized protocols to distinguish type 3c diabetes mellitus from other types of diabetes and design effective therapeutic strategies through novel cell culture technologies, animal models mimicking human disease, and pain management tools. Gene therapy and cystic fibrosis conductance regulator (CFTR) potentiators as possible treatments for CP were discussed. Importantly, the need for chronic pancreatitis endpoints and intermediate targets for future drug trials was emphasized. PMID:27748719

  4. 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

  5. A pancreas-preserving technique for the management of symptomatic pancreatic anastomotic insufficiency refractory to conservative treatment after pancreas head resection.

    Science.gov (United States)

    Königsrainer, Ingmar; Zieker, Derek; Beckert, Stefan; Glatzle, Jörg; Schroeder, Torsten H; Heininger, Alexandra; Nadalin, Silvio; Königsrainer, Alfred

    2010-08-01

    Management of symptomatic pancreatic anastomotic insufficiency after pancreas head resection remains controversial. Completion pancreatectomy as one frequently performed option is associated with poor prognosis. During a 4-year period, a two-step strategy was applied in four consecutive patients suffering from pancreatic anastomotic insufficiency refractory to conservative management after a pancreas head resection. In the first step, sepsis was overbridged by meticulous debridement and resection of the pancreaticojejunostomy, leaving the biliary anastomosis untouched, and selective drainage of the pancreatic duct as well as the peripancreatic area. In the second step, after recovery, the procedure was completed with a novel pancreaticojejunostomy. The surgical procedure was completed in three patients after a mean of 164 (range: 112-213) days. One patient died from cardiac arrest 54 days after the reoperation with resolved abdominal sepsis. No pancreatic anastomotic insufficiency occurred after the new pancreaticojejunostomy had been performed. Three patients are alive and tumor-free with normal exocrine and endocrine pancreatic function after a mean follow-up of 20.3 (3-38) months following the definitive reconstruction. The two-step pancreas-preserving strategy can be used as an alternative to completion pancreatectomy for patients suffering from severe pancreatic anastomotic insufficiency.

  6. LAPAROSCOPIC PANCREATIC RESECTION. FROM ENUCLEATION TO PANCREATODUODENECTOMY. 11-YEAR EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Marcel Autran Cesar MACHADO

    Full Text Available Context Our experience with laparoscopic pancreatic resection began in 2001. During initial experience, laparoscopy was reserved for selected cases. With increasing experience more complex laparoscopic procedures such as central pancreatectomy and pancreatoduodenectomies were performed. Objectives The aim of this paper is to review our personal experience with laparoscopic pancreatic resection over 11-year period. Methods All patients who underwent laparoscopic pancreatic resection from 2001 through 2012 were reviewed. Preoperative data included age, gender, and indication for surgery. Intraoperative variables included operative time, bleeding, blood transfusion. Diagnosis, tumor size, margin status were determined from final pathology reports. Results Since 2001, 96 patients underwent laparoscopic pancreatectomy. Median age was 55 years old. 60 patients were female and 36 male. Of these, 88 (91.6% were performed totally laparoscopic; 4 (4.2% needed hand-assistance, 1 robotic assistance. Three patients were converted. Four patients needed blood transfusion. Operative time varied according type of operation. Mortality was nil but morbidity was high, mainly due to pancreatic fistula (28.1%. Sixty-one patients underwent distal pancreatectomy, 18 underwent pancreatic enucleation, 7 pylorus-preserving pancreatoduodenectomies, 5 uncinate process resection, 3 central and 2 total pancreatectomies. Conclusions Laparoscopic resection of the pancreas is a reality. Pancreas sparing techniques, such as enucleation, resection of uncinate process and central pancreatectomy, should be used to avoid exocrine and/or endocrine insufficiency that could be detrimental to the patient's quality of life. Laparoscopic pancreatoduodenectomy is a safe operation but should be performed in specialized centers by highly skilled laparoscopic surgeons.

  7. Detection, Evaluation and Treatment of Diabetes Mellitus in Chronic Pancreatitis: Recommendations from PancreasFest 2012

    Science.gov (United States)

    Rickels, Michael R.; Bellin, Melena; Toledo, Frederico G.S.; Robertson, R. Paul; Andersen, Dana K.; Chari, Suresh T.; Brand, Randall; Frulloni, Luca; Anderson, Michelle A.; Whitcomb, David C.

    2013-01-01

    Description Diabetes and glucose intolerance are common complications of chronic pancreatitis, yet clinical guidance on their detection, classification, and management is lacking. Methods A working group reviewed the medical problems, diagnostic methods, and treatment options for chronic pancreatitis-associated diabetes for a consensus meeting at PancreasFest 2012. Results Guidance Statement 1.1 Diabetes mellitus is common in chronic pancreatitis. While any patient with chronic pancreatitis should be monitored for development of diabetes, those with long-standing duration of disease, prior partial pancreatectomy, and early onset of calcific disease may be at higher risk. Those patients developing diabetes mellitus are likely to have co-existing pancreatic exocrine insufficiency. Guidance Statement 1.2 Diabetes occurring secondary to chronic pancreatitis should be recognized as pancreatogenic diabetes (type 3c diabetes). Guidance Statement 2.1 The initial evaluation should include fasting glucose and HbA1c. These tests should be repeated annually. Impairment in either fasting glucose or HbA1c requires further evaluation. Guidance Statement 2.2 Impairment in either fasting glucose or HbA1c should be further evaluated by a standard 75 gram oral glucose tolerance test. Guidance Statement 2.3 An absent pancreatic polypeptide response to mixed-nutrient ingestion is a specific indicator of type 3c diabetes. Guidance Statement 2.4 Assessment of pancreatic endocrine reserve, and importantly that of functional beta-cell mass, should be performed as part of the evaluation and follow-up for total pancreatectomy with islet autotransplantation (TPIAT). Guidance Statement 3 Patients with pancreatic diabetes shall be treated with specifically tailored medical nutrition and pharmacologic therapies. Conclusions Physicians should evaluate and treat glucose intolerance in patients with pancreatitis. PMID:23890130

  8. Substantion of Choosing the Method of Surgical Treatment of Complicated Forms of Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    I.Ya. Budzak

    2013-04-01

    Full Text Available In the Institute’s clinic during 2010–2012, 43 patients were operated for complicated forms of chronic pancreatitis. Based on the data of computed tomography and endoscopic retrograde cholangiopancreatography, the variants of pathology of the pancreas, which are significant for the selection of operation method, were chosen. Evaluation of intraoperative biopsies showed that the main manifestation of chronic pancreatitis in all cases was evident fibrosis of gland tissue. In this evaluation, in patients with III degree of fibrosis, fibrous tissue was 68.2–76.4 % of the area of pancreas, and exocrine one — 16.2–24.8 %, in patients with IV degree of fibrosis, respectively 79.5–95.5 and 2.3–10.8 %. Indications for organ-preserving resection, resection-draining interventions and isolated, draining pancreatic ductal system operations have been indicated. Specific weight of combined resection-draining interventions with preservation of the duodenum was 30.2 %, the overall mortality rate — 2.3 %, duration of postoperative bed-day (9.1 ± 0.8.

  9. Bile acid effects are mediated by ATP release and purinergic signalling in exocrine pancreatic cells

    DEFF Research Database (Denmark)

    Kowal, Justyna Magdalena; Haanes, Kristian Agmund; Christensen, Nynne

    2015-01-01

    BACKGROUND: In many cells, bile acids (BAs) have a multitude of effects, some of which may be mediated by specific receptors such the TGR5 or FXR receptors. In pancreas systemic BAs, as well as intra-ductal BAs from bile reflux, can affect pancreatic secretion. Extracellular ATP and purinergic...

  10. Walled-off pancreatic necrosis and other current concepts in the radiological assessment of acute pancreatitis

    International Nuclear Information System (INIS)

    Cunha, Elen Freitas de Cerqueira; Rocha, Manoel de Souza; Pereira, Fabio Payao; Blasbalg, Roberto; Baroni, Ronaldo Hueb

    2014-01-01

    Acute pancreatitis is an inflammatory condition caused by intracellular activation and extravasation of inappropriate proteolytic enzymes determining destruction of pancreatic parenchyma and peripancreatic tissues. This is a fairly common clinical condition with two main presentations, namely, endematous pancreatitis - a less severe presentation - and necrotizing pancreatitis - the most severe presentation that affects a significant part of patients. The radiological evaluation, particularly by computed tomography, plays a fundamental role in the definition of the management of severe cases, especially regarding the characterization of local complications with implications in the prognosis and in the definition of the therapeutic approach. New concepts include the subdivision of necrotizing pancreatitis into the following presentations: pancreatic parenchymal necrosis with concomitant peripancreatic tissue necrosis, and necrosis restricted to peripancreatic tissues. Moreover, there was a systematization of the terms acute peripancreatic fluid collection, pseudocyst, post-necrotic pancreatic/peripancreatic fluid collections and walled-off pancreatic necrosis. The knowledge about such terms is extremely relevant to standardize the terminology utilized by specialists involved in the diagnosis and treatment of these patients. (author)

  11. Walled-off pancreatic necrosis and other current concepts in the radiological assessment of acute pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Elen Freitas de Cerqueira [Image Memorial/DASA and Diagnoson Medicina Diagnostica, Salvador, BA (Brazil); Rocha, Manoel de Souza; Pereira, Fabio Payao; Blasbalg, Roberto; Baroni, Ronaldo Hueb [Universidade de Sao Paulo (FM/USPU), Sao Paulo, SP (Brazil). Faculdade de Medicina

    2014-05-15

    Acute pancreatitis is an inflammatory condition caused by intracellular activation and extravasation of inappropriate proteolytic enzymes determining destruction of pancreatic parenchyma and peripancreatic tissues. This is a fairly common clinical condition with two main presentations, namely, endematous pancreatitis - a less severe presentation - and necrotizing pancreatitis - the most severe presentation that affects a significant part of patients. The radiological evaluation, particularly by computed tomography, plays a fundamental role in the definition of the management of severe cases, especially regarding the characterization of local complications with implications in the prognosis and in the definition of the therapeutic approach. New concepts include the subdivision of necrotizing pancreatitis into the following presentations: pancreatic parenchymal necrosis with concomitant peripancreatic tissue necrosis, and necrosis restricted to peripancreatic tissues. Moreover, there was a systematization of the terms acute peripancreatic fluid collection, pseudocyst, post-necrotic pancreatic/peripancreatic fluid collections and walled-off pancreatic necrosis. The knowledge about such terms is extremely relevant to standardize the terminology utilized by specialists involved in the diagnosis and treatment of these patients. (author)

  12. Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic {beta}-cell mass

    Energy Technology Data Exchange (ETDEWEB)

    Cline, Gary W., E-mail: gary.cline@yale.edu [Yale University School of Medicine (United States); Zhao, Xiaojian [Yale University School of Medicine (United States); Jakowski, Amy B.; Soeller, Walter C.; Treadway, Judith L. [Pfizer Global Research and Development, Pfizer Inc., Groton CT (United States)

    2011-09-02

    Highlights: {yields} We screened G-protein coupled receptors for imaging pancreatic. {yields} Database mining and immunohistochemistry identified GPCRs enriched in {beta}-cells. {yields} In vitro and in vivo assays were used to determine exocrine vs endocrine specificity. {yields} GPCR candidates for imaging of {beta}-cell mass are Prokineticin-1R, mGluR5, and GLP-1R. -- Abstract: A critical unmet need exists for methods to quantitatively measure endogenous pancreatic {beta}-cell mass (BCM) for the clinical evaluation of therapies to prevent or reverse loss of BCM and diabetes progression. Our objective was to identify G-protein coupled receptors (GPCRs) that are expressed with a high degree of specificity to islet {beta}-cells for receptor-targeted imaging of BCM. GPCRs enriched in pancreatic islets relative to pancreas acinar and hepatic tissue were identified using a database screen. Islet-specific expression was confirmed by human pancreas immunohistochemistry (IHC). In vitro selectivity assessment was determined from the binding and uptake of radiolabeled ligands to the rat insulinoma INS-1 832/13 cell line and isolated rat islets relative to the exocrine pancreas cell-type, PANC-1. Tail-vein injections of radioligands into rats were used to determine favorable image criteria of in vivo biodistribution to the pancreas relative to other internal organs (i.e., liver, spleen, stomach, and lungs). Database and IHC screening identified four candidate receptors for further in vitro and in vivo evaluation for PET imaging of BCM: prokineticin-1 receptor (PK-1R), metabotropic glutamate receptor type-5 (mGluR5), neuropeptide Y-2 receptor (NPY-2R), and glucagon-like peptide 1 receptor (GLP-1R). In vitro specificity ratios gave the following receptor rank order: PK-1R > GLP-1R > NPY-2R > mGluR5. The biodistribution rank order of selectivity to the pancreas was found to be PK-1R > VMAT2 {approx} GLP-1R > mGluR5. Favorable islet selectivity and biodistribution

  13. Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic β-cell mass

    International Nuclear Information System (INIS)

    Cline, Gary W.; Zhao, Xiaojian; Jakowski, Amy B.; Soeller, Walter C.; Treadway, Judith L.

    2011-01-01

    Highlights: → We screened G-protein coupled receptors for imaging pancreatic. → Database mining and immunohistochemistry identified GPCRs enriched in β-cells. → In vitro and in vivo assays were used to determine exocrine vs endocrine specificity. → GPCR candidates for imaging of β-cell mass are Prokineticin-1R, mGluR5, and GLP-1R. -- Abstract: A critical unmet need exists for methods to quantitatively measure endogenous pancreatic β-cell mass (BCM) for the clinical evaluation of therapies to prevent or reverse loss of BCM and diabetes progression. Our objective was to identify G-protein coupled receptors (GPCRs) that are expressed with a high degree of specificity to islet β-cells for receptor-targeted imaging of BCM. GPCRs enriched in pancreatic islets relative to pancreas acinar and hepatic tissue were identified using a database screen. Islet-specific expression was confirmed by human pancreas immunohistochemistry (IHC). In vitro selectivity assessment was determined from the binding and uptake of radiolabeled ligands to the rat insulinoma INS-1 832/13 cell line and isolated rat islets relative to the exocrine pancreas cell-type, PANC-1. Tail-vein injections of radioligands into rats were used to determine favorable image criteria of in vivo biodistribution to the pancreas relative to other internal organs (i.e., liver, spleen, stomach, and lungs). Database and IHC screening identified four candidate receptors for further in vitro and in vivo evaluation for PET imaging of BCM: prokineticin-1 receptor (PK-1R), metabotropic glutamate receptor type-5 (mGluR5), neuropeptide Y-2 receptor (NPY-2R), and glucagon-like peptide 1 receptor (GLP-1R). In vitro specificity ratios gave the following receptor rank order: PK-1R > GLP-1R > NPY-2R > mGluR5. The biodistribution rank order of selectivity to the pancreas was found to be PK-1R > VMAT2 ∼ GLP-1R > mGluR5. Favorable islet selectivity and biodistribution characteristics suggest several GPCRs as potential

  14. Malnutrition and the Ways of its Correction in Infants with Food Intolerance

    Directory of Open Access Journals (Sweden)

    O.H. Shadrin

    2016-02-01

    Full Text Available Objective: to examine the status of digestion and the efficiency of correction of its disorders in infants with food intolerance. Patients and methods. We observed 40 infants (from 6 months to 3 years of life with food intolerance, including 14 children with gastrointestinal food allergy, 26 — with non-allergic food intolerance caused by organic or functional disorders of the gastrointestinal tract. Clinical and paraclinical studies (clinical observations, stool test, ultrasound examination were performed during the treatment. Results. All children had clinical manifestations of malnutrition caused by exocrine pancreatic insufficiency, as indicated by the corresponding clinical signs and symptoms of maldigestion according to coprogram parameters. When using pancreatin-contaning enzyme preparation Ermital 10 000 in the combination treatment of infants with food intolerance, a significant clinical effect has been observed in almost 90 % of children. In 77.5 % of infants, coprogram parameters were completely normal on the 14th day of treatment. Conclusions. In the pathogenesis of malnutrition of children with food intolerance, essential role is played by the exocrine pancreatic insufficiency, making inclusion of pancreatin-contaning enzyme preparation in the therapy pathogenetically reasonable. High clinical efficacy of Ermital 10 000, no side effects allow to recommend it for use in young children.

  15. Aberrant innate immune activation following tissue injury impairs pancreatic regeneration.

    Directory of Open Access Journals (Sweden)

    Alexandra E Folias

    Full Text Available Normal tissue architecture is disrupted following injury, as resident tissue cells become damaged and immune cells are recruited to the site of injury. While injury and inflammation are critical to tissue remodeling, the inability to resolve this response can lead to the destructive complications of chronic inflammation. In the pancreas, acinar cells of the exocrine compartment respond to injury by transiently adopting characteristics of progenitor cells present during embryonic development. This process of de-differentiation creates a window where a mature and stable cell gains flexibility and is potentially permissive to changes in cellular fate. How de-differentiation can turn an acinar cell into another cell type (such as a pancreatic β-cell, or a cell with cancerous potential (as in cases of deregulated Kras activity is of interest to both the regenerative medicine and cancer communities. While it is known that inflammation and acinar de-differentiation increase following pancreatic injury, it remains unclear which immune cells are involved in this process. We used a combination of genetically modified mice, immunological blockade and cellular characterization to identify the immune cells that impact pancreatic regeneration in an in vivo model of pancreatitis. We identified the innate inflammatory response of macrophages and neutrophils as regulators of pancreatic regeneration. Under normal conditions, mild innate inflammation prompts a transient de-differentiation of acinar cells that readily dissipates to allow normal regeneration. However, non-resolving inflammation developed when elevated pancreatic levels of neutrophils producing interferon-γ increased iNOS levels and the pro-inflammatory response of macrophages. Pancreatic injury improved following in vivo macrophage depletion, iNOS inhibition as well as suppression of iNOS levels in macrophages via interferon-γ blockade, supporting the impairment in regeneration and the

  16. 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.

  17. The Research of Acellular pancreatic bioscaffoldas a natural 3D platform In Vitro

    Science.gov (United States)

    Wang, Xin; Li, Zhao

    2018-03-01

    AIM: To investigate the biochemical and functional properties of a rat acellular pancreatic bioscaffold (APB). METHODS: Fresh pancreata were soaked and perfused. The histological structure, the extracellular matrix (ECM) composition, and the DNA content of the APBs were evaluated. After biocompatibility studies, the proliferation, apoptosis and differentiation of AR42J pancreatic acinar cells cultured on APBs were assessed. RESULTS: The pancreatic tissues became translucent after decellularization. The native macroscopic 3D architecture and the ECM ultrastructure were preserved, with large ductal structures and vascular tissue branching from the greater pancreatic artery, but there were no visible vascular endothelial cells, cellular components or cracked cellular debris. The ECM components, including collagen I, collagen IV, fibronectin, laminin and sGAG, were not decreased after decellularization of the APB (P>0.05) however, the DNA content was decreased significantly (P<0.05). The subcutaneous implantation sites showed low immunological response and low cytotoxicity around the APB. The proliferation rate was higher and the apoptosis rate was lower when AR42J cells were cultured on APB than when they were cultured in media alone, on artificial scaffold or ECM (P<0.05). The gene expression of pancreatic duodenal homeodomain containing transcription factor (PDX-1) and pancreatic exocrine transcription factor (PTF-1) and the protein expression of α-Amy, cytokeratin 7 (CK7) and fetal liver kinase-1 (Flk-1) were higher for the APB group than for the other groups (P<0.001). CONCLUSION: Our findings support the biological utility of whole pancreas APBs as biomaterial scaffolds, which provides an improved approach for regenerative medicine.

  18. Effect of inhibition of microsomal Ca(2+)-ATPase on cytoplasmic calcium and enzyme secretion in pancreatic acini.

    Science.gov (United States)

    Metz, D C; Pradhan, T K; Mrozinski, J E; Jensen, R T; Turner, R J; Patto, R J; Gardner, J D

    1994-01-13

    We used thapsigargin (TG), 2,5-di-tert-butyl-1,4-benzohydroquinone (BHQ) and cyclopiazonic acid (CPA), each of which inhibits microsomal Ca(2+)-ATPase, to evaluate the effects of this inhibition on cytoplasmic free calcium ([Ca2+]i) and secretagogue-stimulated enzyme secretion in rat pancreatic acini. Using single-cell microspectrofluorimetry of fura-2-loaded acini we found that all three agents caused a sustained increase in [Ca2+]i by mobilizing calcium from inositol-(1,4,5)-trisphosphate-sensitive intracellular calcium stores and by promoting influx of extracellular calcium. Concentrations of all three agents that increased [Ca2+]i potentiated the stimulation of enzyme secretion caused by secretagogues that activate adenylate cyclase but inhibited the stimulation of enzyme secretion caused by secretagogues that activate phospholipase C. With BHQ, potentiation of adenylate cyclase-mediated enzyme secretion occurred immediately whereas inhibition of phospholipase C-mediated enzyme secretion occurred only after several min of incubation. In addition, the effects of BHQ and CPA on both [Ca2+]i and secretagogue-stimulated enzyme secretion were reversed completely by washing whereas the actions of TG could not be reversed by washing. Concentrations of BHQ in excess of those that caused maximal changes in [Ca2+]i inhibited all modes of stimulated enzyme secretion by a mechanism that was apparently unrelated to changes in [Ca2+]i. Finally, in contrast to the findings with TG and BHQ, CPA inhibited bombesin-stimulated enzyme secretion over a range of concentrations that was at least 10-fold lower than the range of concentrations over which CPA potentiated VIP-stimulated enzyme secretion.

  19. Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter

    International Nuclear Information System (INIS)

    Wan Haiyan; Korzh, Svitlana; Li Zhen; Mudumana, Sudha Puttur; Korzh, Vladimir; Jiang Yunjin; Lin Shuo; Gong Zhiyuan

    2006-01-01

    In contrast to what we know on development of endocrine pancreas, the formation of exocrine pancreas remains poorly understood. To create an animal model that allows observation of exocrine cell differentiation, proliferation, and morphogenesis in living animals, we used the zebrafish elastaseA (elaA) regulatory sequence to develop transgenic zebrafish that display highly specific exocrine pancreas expression of GFP in both larvae and adult. By following GFP expression, we found that the pancreas in early development was a relatively compact organ and later extended posterior along the intestine. By transferring the elaA:gfp transgene into slow muscle omitted mutant that is deficient in receiving Hedgehog signals, we further showed that Hedgehog signaling is required for exocrine morphogenesis but not for cell differentiation. We also applied the morpholino knockdown and toxin-mediated cell ablation approaches to this transgenic line. We showed that the development of exocrine pancreas is Islet-1 dependent. Injection of the diphtheria toxin A (DTA) construct under the elastaseA promoter resulted in selective ablation of exocrine cells while the endocrine cells and other endodermal derivatives (liver and intestine) were not affected. Thus, our works demonstrated the new transgenic line provided a useful experimental tool in analyzing exocrine pancreas development

  20. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis: LAMP-2 deficient mice develop pancreatitis.

    Science.gov (United States)

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-11-01

    The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated membrane proteins (LAMPs) in pancreatitis. We analyzed changes in LAMPs in experimental models and human pancreatitis, and the underlying mechanisms: LAMP de-glycosylation and degradation. LAMP cleavage by cathepsin B (CatB) was analyzed by mass spectrometry. We used mice deficient in LAMP-2 to assess its role in pancreatitis. Pancreatic levels of LAMP-1 and LAMP-2 greatly decrease across various pancreatitis models and in human disease. Pancreatitis does not trigger LAMPs' bulk de-glycosylation, but induces their degradation via CatB-mediated cleavage of LAMP molecule close to the boundary between luminal and transmembrane domains. LAMP-2 null mice spontaneously develop pancreatitis that begins with acinar cell vacuolization due to impaired autophagic flux, and progresses to severe pancreas damage characterized by trypsinogen activation, macrophage-driven inflammation, and acinar cell death. LAMP-2 deficiency causes a decrease in pancreatic digestive enzymes content, stimulates the basal and inhibits CCK-induced amylase secretion by acinar cells. The effects of LAMP-2 knockout and acute cerulein pancreatitis overlap, which corroborates the pathogenic role of LAMP decrease in experimental pancreatitis models. The results indicate a critical role for LAMPs, particularly LAMP-2, in maintaining pancreatic acinar cell homeostasis, and provide evidence that defective lysosomal function, resulting in impaired autophagy, leads to pancreatitis. Mice with LAMP-2 deficiency present a novel genetic model of human pancreatitis caused by lysosomal/autophagic dysfunction.

  1. Patient and Disease Characteristics Associated With the Presence of Diabetes Mellitus in Adults With Chronic Pancreatitis in the United States.

    Science.gov (United States)

    Bellin, Melena D; Whitcomb, David C; Abberbock, Judah; Sherman, Stuart; Sandhu, Bimaljit S; Gardner, Timothy B; Anderson, Michelle A; Lewis, Michele D; Alkaade, Samer; Singh, Vikesh K; Baillie, John; Banks, Peter A; Conwell, Darwin; Cote, Gregory A; Guda, Nalini M; Muniraj, Thiruvengadam; Tang, Gong; Brand, Randall E; Gelrud, Andres; Amann, Stephen T; Forsmark, Christopher E; Wilcox, C Mel; Slivka, Adam; Yadav, Dhiraj

    2017-09-01

    Diabetes mellitus (DM) is a common complication of chronic pancreatitis (CP). Past studies for DM risk factors in CP have been limited to single centers or highly focused on a single etiology such as alcoholic or hereditary disease. We studied risk factors for DM in a large population of patients with CP of all etiologies enrolled in the North American Pancreatitis 2 studies. Participants (1,171) with CP (n=383 with DM, n=788 without DM) were enrolled prospectively from 26 participating centers. Questionnaires were completed by patients and physicians in a cross-sectional assessment. Patient demographics and disease characteristics were compared for CP with DM vs. without DM. Logistic regression was performed to assess the variables associated with DM diagnosis in a multivariable model. Diabetics were more likely to be black (P=0.02), overweight, or obese (Ppancreatic calcifications (63% vs. 54%, P=0.002), atrophy (44% vs. 32%, Prisk factors for DM were obesity (odds ratio (OR) 2.8, 95% confidence interval (CI) 1.9, 4.2) and exocrine insufficiency (OR 2.4, 95% CI 1.8, 3.2). In this large multicenter cohort of patients with CP, exocrine insufficiency, calcifications, and pancreas surgery conveyed higher odds of having DM. However, the traditional 'type 2 DM' risk factors of obesity and family history were similarly important in conveying risk for DM.

  2. Microarray analysis of pancreatic gene expression during biotin repletion in biotin-deficient rats.

    Science.gov (United States)

    Dakshinamurti, Krishnamurti; Bagchi, Rushita A; Abrenica, Bernard; Czubryt, Michael P

    2015-12-01

    Biotin is a B vitamin involved in multiple metabolic pathways. In humans, biotin deficiency is relatively rare but can cause dermatitis, alopecia, and perosis. Low biotin levels occur in individuals with type-2 diabetes, and supplementation with biotin plus chromium may improve blood sugar control. The acute effect on pancreatic gene expression of biotin repletion following chronic deficiency is unclear, therefore we induced biotin deficiency in adult male rats by feeding them a 20% raw egg white diet for 6 weeks. Animals were then randomized into 2 groups: one group received a single biotin supplement and returned to normal chow lacking egg white, while the second group remained on the depletion diet. After 1 week, pancreata were removed from biotin-deficient (BD) and biotin-repleted (BR) animals and RNA was isolated for microarray analysis. Biotin depletion altered gene expression in a manner indicative of inflammation, fibrosis, and defective pancreatic function. Conversely, biotin repletion activated numerous repair and anti-inflammatory pathways, reduced fibrotic gene expression, and induced multiple genes involved in pancreatic endocrine and exocrine function. A subset of the results was confirmed by quantitative real-time PCR analysis, as well as by treatment of pancreatic AR42J cells with biotin. The results indicate that biotin repletion, even after lengthy deficiency, results in the rapid induction of repair processes in the pancreas.

  3. The effect of insulin on amino acid incorporation into exocrine pancreatic cells of the rat

    International Nuclear Information System (INIS)

    Kramer, M.F.; Poort, C.

    1975-01-01

    The rate of incorporation of radioactive leucine per cell in the acinar pancreatic cells of the rat increases by 50 per cent within one hour after subcutaneous administration of insulin, an effect that lasts for at least one more hour. The rate of incorporation has been measured by quantitative radioautography and by determination of the radioactivity per μg DNA in TCA-precipitable material from tissue homogenates. The capacity for amino acid (leucine and lysine) incorporation as measured by incubating pancreatic fragments in vitro is not enhanced by insulin treatment of the rat in vivo during one or more hours. Insulin was found to lower the serum concentration of most amino acids significantly, leucine by 50 per cent. The apparent effect of insulin on the incorporation of radioactive leucine in vivo can be explained by the difference in the specific radioactivity of the circulating amino acid in the treated rats as compared to the untreated ones. A change in amino acid concentration in the serum may likewise be the explanation of the decrease in amino acid incorporation rate in alloxan diabetic rats. (orig./GSE) [de

  4. Current knowledge on exocrine glands in carabid beetles: structure, function and chemical compounds.

    Science.gov (United States)

    Giglio, Anita; Brandmayr, Pietro; Talarico, Federica; Brandmayr, Tullia Zetto

    2011-01-01

    Many exocrine products used by ground beetles are pheromones and allomones that regulate intra- and interspecific interactions and contribute to their success in terrestrial ecosystems. This mini-review attempts to unify major themes related to the exocrine glands of carabid beetles. Here we report on both glandular structures and the role of secretions in carabid adults, and that little information is available on the ecological significance of glandular secretions in pre-imaginal stages.

  5. 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...

  6. Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions.

    Science.gov (United States)

    Zhou, Jing; Jin, Jun-O; Patel, Ekta S; Yu, Qing

    2015-12-01

    Interleukin (IL)-6 is a multi-functional cytokine that can either promote or suppress tissue inflammation depending on the specific disease context. IL-6 is elevated in the exocrine glands and serum of patients with Sjögren's syndrome (SS), but the specific role of IL-6 in the pathogenesis of this disease has not been defined. In this study, we showed that IL-6 expression levels were increased with age in C56BL/6.NOD-Aec1Aec2 mice, a primary SS model, and higher than the control C57BL/6 mice. To assess the role of IL-6 during the immunological phase of SS development, a neutralizing anti-IL-6 antibody was administered into 16 week-old female C56BL/6.NOD-Aec1Aec2 mice, 3 times weekly for a consecutive 8 weeks. Neutralization of endogenous IL-6 throughout the immunological phase of SS development led to increased apoptosis, caspase-3 activation, leukocytic infiltration, and IFN-γ- and TNF-α production in the salivary gland. To further determine the effect of IL-6 on the apoptosis of exocrine gland cells, recombinant human IL-6 or the neutralizing anti-IL-6 antibody was injected into female C57BL/6 mice that received concurrent injection of anti-CD3 antibody to induce the apoptosis of exocrine gland tissues. Neutralization of IL-6 enhanced, whereas administration of IL-6 inhibited apoptosis and caspase-3 activation in salivary and lacrimal glands in this model. The apoptosis-suppressing effect of IL-6 was associated with up-regulation of Bcl-xL and Mcl-1 in both glands. Moreover, IL-6 treatment induced activation of STAT3 and up-regulated Bcl-xL and Mcl-1 gene expression in a human salivary gland epithelial cell line. In conclusion, IL-6 inhibits the apoptosis of exocrine gland tissues and exerts a tissue-protective effect under inflammatory conditions including SS. These findings suggest the possibility of using this property of IL-6 to preserve exocrine gland tissue integrity and function under autoimmune and inflammatory conditions. Copyright © 2015 Elsevier

  7. Current knowledge on exocrine glands in carabid beetles: structure, function and chemical compounds

    Directory of Open Access Journals (Sweden)

    Anita Giglio

    2011-05-01

    Full Text Available Many exocrine products used by ground beetles are pheromones and allomones that regulate intra- and interspecific interactions and contribute to their success in terrestrial ecosystems. This mini-review attempts to unify major themes related to the exocrine glands of carabid beetles. Here we report on both glandular structures and the role of secretions in carabid adults, and that little information is available on the ecological significance of glandular secretions in pre-imaginal stages.

  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. Chronic pancreatitis: The case for surgery

    Directory of Open Access Journals (Sweden)

    H Ramesh

    2012-01-01

    Full Text Available Treatment of pain in chronic pancreatitis includes medical, endoscopic and surgical therapy. Medical treatment may involve the use of analgesics, pancreatic enzymes, antioxidants and removal of risk factors. However, a substantial number of patients do not experience pain relief with medical treatment, and those with local complications cannot be treated medically indefinitely. These require endoscopic or surgical therapy. Endoscopic therapy has involved the use of a pancreatic sphincterotomy, b stent placement, c nasopancreatic drainage, d pseudocyst drainage, e extra corporeal shock wave lithotripsy (ESWL, and f dilatation of strictures. The current options for surgical therapy include: a partial pancreatic resections, b extended pancreatic drainage procedures (which involve additional subtotal resection of the head or a deep coring out of the head, or c pure pancreatic drainage procedures. In effect surgical procedures provide a more thorough drainage of the ductal system than pancreatic stent placement. This is especially true in the complex ductal arrangement of the head of the pancreas, where simple drainage of the duct or stent placement by endoscopy is unlikely to provide thorough drainage and relief of symptoms.

  10. Queen Specific Exocrine Glands in Legionary Ants and Their Possible Function in Sexual Selection.

    Science.gov (United States)

    Hölldobler, Bert

    2016-01-01

    The colonies of army ants and some other legionary ant species have single, permanently wingless queens with massive post petioles and large gasters. Such highly modified queens are called dichthadiigynes. This paper presents the unusually rich exocrine gland endowment of dichthadiigynes, which is not found in queens of other ant species. It has been suggested these kinds of glands produce secretions that attract and maintain worker retinues around queens, especially during migration. However, large worker retinues also occur in non-legionary species whose queens do not have such an exuberance of exocrine glands. We argue and present evidence in support of our previously proposed hypothesis that the enormous outfit of exocrine glands found in dichthadiigynes is due to sexual selection mediated by workers as the main selecting agents.

  11. Queen Specific Exocrine Glands in Legionary Ants and Their Possible Function in Sexual Selection.

    Directory of Open Access Journals (Sweden)

    Bert Hölldobler

    Full Text Available The colonies of army ants and some other legionary ant species have single, permanently wingless queens with massive post petioles and large gasters. Such highly modified queens are called dichthadiigynes. This paper presents the unusually rich exocrine gland endowment of dichthadiigynes, which is not found in queens of other ant species. It has been suggested these kinds of glands produce secretions that attract and maintain worker retinues around queens, especially during migration. However, large worker retinues also occur in non-legionary species whose queens do not have such an exuberance of exocrine glands. We argue and present evidence in support of our previously proposed hypothesis that the enormous outfit of exocrine glands found in dichthadiigynes is due to sexual selection mediated by workers as the main selecting agents.

  12. The management of acute and chronic pancreatitis.

    Science.gov (United States)

    Banks, Peter A; Conwell, Darwin L; Toskes, Phillip P

    2010-02-01

    Pancreatitis, which is most generally described as any inflammation of the pancreas, is a serious condition that manifests in either acute or chronic forms. Chronic pancreatitis results from irreversible scarring of the pancreas, resulting from prolonged inflammation. Six major etiologies for chronic pancreatitis have been identified: toxic/ metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis, and obstruction. The most common symptom associated with chronic pancreatitis is pain localized to the upper-to-middle abdomen, along with food malabsorption, and eventual development of diabetes. Treatment strategies for acute pancreatitis include fasting and short-term intravenous feeding, fluid therapy, and pain management with narcotics for severe pain or nonsteroidal anti-inflammatories for milder cases. Patients with chronic disease and symptoms require further care to address digestive issues and the possible development of diabetes. Dietary restrictions are recommended, along with enzyme replacement and vitamin supplementation. More definitive outcomes may be achieved with surgical or endoscopic methods, depending on the role of the pancreatic ducts in the manifestation of disease.

  13. The P2X7 Receptor Supports Both Life and Death in Fibrogenic Pancreatic Stellate Cells

    DEFF Research Database (Denmark)

    Haanes, Kristian; Schwab, Albrecht; Novak, Ivana

    2012-01-01

    The pancreatic stellate cells (PSCs) have complex roles in pancreas, including tissue repair and fibrosis. PSCs surround ATP releasing exocrine cells, but little is known about purinergic receptors and their function in PSCs. Our aim was to resolve whether PSCs express the multifunctional P2X7...... versions of the receptor. In culture, the proliferation rate of the KO PSCs was significantly lower. Inclusion of apyrase reduced the proliferation rate in both WT and KO PSCs, indicating importance of endogenous ATP. Exogenous ATP had a two-sided effect. Proliferation of both WT and KO cells...... inhibitor az10606120. The P2X7 receptor-pore inhibitor A438079 partially prevented cell death induced by millimolar ATP concentrations. This study shows that ATP and P2X7 receptors are important regulators of PSC proliferation and death, and therefore might be potential targets for treatments of pancreatic...

  14. PKD signaling and pancreatitis

    Science.gov (United States)

    Yuan, Jingzhen; Pandol, Stephen J.

    2016-01-01

    Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

  15. A comparative immunohistochemical study on amylase localization in the rat and human exocrine pancreas

    International Nuclear Information System (INIS)

    Aughsteen, Adib A.

    2001-01-01

    Objective was to localize amylase enzyme immunohistochemically in the pancreatic acinar cells of rats and humans using polyclonal sheep anti-human amylase antibody, and to compare between the intensities of their amylase-immunostaining. Indirect immunofluorescence method was applied on formaldehyde-fixed, and paraffin-embedded pancreatic sections obtained from adult male Wistar rats and autopsied human samples. Primary incubation was performed using sheep anti-amylase antibody followed by secondary incubation with fluorescein isothiocyanate-labeled rabbit anti-sheep IgG serum. Control tests of amylase immunospecificity were also undertaken either by incubation with primary antibodies previously pre-adsorbed with an excess of human pancreatic amylase, or only with secondary antibodies. The amylase immunofluorescence was positively and homogenously detected in all acinar cells of both rat and human pancreatic stained sections. The immunostaining was clearly demonstrated in the cell apices and peri-nuclear areas, but it was consistently brighter and more intense in the human acinar cells compared with that of the rat pancreas. Control tests of amylase immunofluorescence revealed the specificity of the antibodies applied for amylase localization in rat and human pancreas. Although many previous immunohisto- and cytochemical reports have successfully localized amylase in the pancreas of different mammalian species, but all of them have used locally prepared anti-amylase antibodies. The present report successfully illustrates immuno-localization of amylase in the pancreatic acinar cells of rats and humans using commercial polyclonal sheep anti-human pancreatic amylase antibodies, and also suggests their useful application in the immunochemical studies on various mammalian species. Additionally, the results indicate a structural similarity between the human and rat pancreatic amylases, a concept required further exploration. (author)

  16. Endoscopic retrograde cholangiopancreatography with rendezvous cannulation reduces pancreatic injury.

    Science.gov (United States)

    Swahn, Fredrik; Regnér, Sara; Enochsson, Lars; Lundell, Lars; Permert, Johan; Nilsson, Magnus; Thorlacius, Henrik; Arnelo, Urban

    2013-09-28

    To examine whether rendezvous endoscopic retrograde cholangiopancreatography (ERCP) is associated with less pancreatic damage, measured as leakage of proenzymes, than conventional ERCP. Patients (n = 122) with symptomatic gallstone disease, intact papilla and no ongoing inflammation, were prospectively enrolled in this case-control designed study. Eighty-one patients were subjected to laparoscopic cholecystectomy and if intraoperative cholangiography suggested common bile duct stones (CBDS), rendezvous ERCP was performed intraoperatively (n = 40). Patients with a negative cholangiogram constituted the control group (n = 41). Another 41 patients with CBDS, not subjected to surgery, underwent conventional ERCP. Pancreatic proenzymes, procarboxypeptidase B and trypsinogen-2 levels in plasma, were analysed at 0, 4, 8 and 24 h. The proenzymes were determined in-house with a double-antibody enzyme linked immunosorbent assay. Pancreatic amylase was measured by an enzymatic colourimetric modular analyser with the manufacturer's reagents. All samples were blinded at analysis. Post ERCP pancreatitis (PEP) occurred in 3/41 (7%) of the patients cannulated with conventional ERCP and none in the rendezvous group. Increased serum levels indicating pancreatic leakage were significantly higher in the conventional ERCP group compared with the rendezvous ERCP group regarding pancreatic amylase levels in the 4- and 8-h samples (P = 0.0015; P = 0.03), procarboxypeptidase B in the 4- and 8-h samples (P rendezvous cannulation technique compared with patients that underwent cholecystectomy alone (control group). Post procedural concentrations of pancreatic amylase and procarboxypeptidase B were significantly correlated with pancreatic duct cannulation and opacification. Rendezvous ERCP reduces pancreatic enzyme leakage compared with conventional ERCP cannulation technique. Thus, laparo-endoscopic technique can be recommended with the ambition to minimise the risk for post ERCP

  17. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    OpenAIRE

    Borini, Paulo; Guimarães, Romeu Cardoso

    1999-01-01

    Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehy...

  18. A Spanish multicenter study to estimate the prevalence and incidence of chronic pancreatitis and its complications

    Directory of Open Access Journals (Sweden)

    J. Enrique Domínguez-Muñoz

    2014-04-01

    Full Text Available Background and objective: No nation-wide epidemiological study on the incidence and prevalence of chronic pancreatitis (CP had been thus far carried out in Spain. Our goal is to estimate the prevalence and incidence of CP, as well as to determine the diagnostic and therapeutic criteria used in Spanish pancreas units. Methods: An observarional, descriptive study of hospital pancreas units in Spain. CP-related epidemiology, etiology, manifestations, diagnostic tests, functional complications, and treatments were all assessed using a structured questionnaire. Overall results were estimated by weighting cases in each site. Results: Information was collected from six pancreas units with a sample frame of 1,900,751 inhabitants. Overall prevalence was 49.3 cases per 10(5 population (95 % CI, 46 to 52 and incidence was 5.5 cases per 10(5 inhabitant-years (95 % CI, 5.4 to 5.6. Most common etiologies included tobacco and alcoholism, which were associated with three in every four cases. The most prevalent symptoms were recurring pain (48.8 % and chronic abdominal pain (30.6 %. The most widely used diagnostic method was echoendoscopy (79.8 %, CT (computerized tomography (58.7 %, and MRI (magnetic resonance imaging/MRCP (magnetic resonance cholangiopancreatography (55.9 %. Most prevalent morphologic findings included calcifications (35 % and pseudocysts (27 %. Exocrine (38.8 % and endocrine (35.2 % pancreatic insufficiency had both a similar frequency. Treatments used were rather heterogeneous among sites, with enzyme replacement therapy (40.7 % and insulin (30.9 % being most commonly used. Conclusions: Pancreas units amass a significant number of both prevalent and incident CP cases. Patients seen in these units share a similar typology, and differences between units are greater regarding diagnostic and therapeutic strategies.

  19. Assimilation of wheat starch in patients with chronic pancreatitis. Positive effect of enzyme replacement

    DEFF Research Database (Denmark)

    Nordgaard, I; Rumessen, J J; Gudmand-Høyer, E

    1992-01-01

    Pancreatic insufficiency due to chronic pancreatitis may lead to symptomatic malabsorption of both starch and fat. The absorption capacity of wheat starch has not been studied previously in patients with chronic pancreatitis, although this carbohydrate is a quantitatively important component of t...

  20. Influence of Interferon-Alpha Combined with Chemo (Radio Therapy on Immunological Parameters in Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Svetlana Karakhanova

    2014-03-01

    Full Text Available Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of 17 patients with pancreatic cancer from the CapRI-2 study, and tumor-bearing mice treated with combination of chemo (radio therapies with interferon-2α. Low doses of interferon-2α led to a decrease in total leukocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2α therapy on the dendritic cells and NK (natural killer cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-γ and IL-10 in the serum following the interferon-2α therapy. These data clearly demonstrate that pancreatic carcinoma patients also show an immunomodulatory response to interferon-2α therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumors of the mice treated with interferon-2α and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of immunosuppressive mechanisms induced by combined chemo-immunotherapy.

  1. Legumain is activated in macrophages during pancreatitis

    Science.gov (United States)

    Wartmann, Thomas; Fleming, Alicia K.; Gocheva, Vasilena; van der Linden, Wouter A.; Withana, Nimali P.; Verdoes, Martijn; Aurelio, Luigi; Edgington-Mitchell, Daniel; Lieu, TinaMarie; Parker, Belinda S.; Graham, Bim; Reinheckel, Thomas; Furness, John B.; Joyce, Johanna A.; Storz, Peter; Halangk, Walter; Bogyo, Matthew; Bunnett, Nigel W.

    2016-01-01

    Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked to inflammatory diseases such as atherosclerosis, stroke, and cancer. Until now, legumain activation has not been studied during pancreatitis. We used a fluorescently quenched activity-based probe to assess legumain activation during caerulein-induced pancreatitis in mice. We detected activated legumain by ex vivo imaging, confocal microscopy, and gel electrophoresis. Compared with healthy controls, legumain activity in the pancreas of caerulein-treated mice was increased in a time-dependent manner. Legumain was localized to CD68+ macrophages and was n