Sample records for endocrine pancreatic tumours

  1. Pancreatic endocrine tumours: an out-matching field of cooperation with nuclear medicine; Les tumeurs endocrines du pancreas: un domaine privilegie de la cooperation avec la medecine nucleaire

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    Cadiot, G.; Marmuse, J.P.; Mignon, M.


    The Zollinger-Ellison syndrome (ZES) is taken as an example of the diagnostic and therapeutic strategy in gastro-entero-pancreatic endocrine tumours, given the standard characteristics of this procedure, whatever the nature of the primitive tumour. Management of ZES includes: anatomical localization of gastrinoma and of possible metastases, in 60 % of cases this step conditioning therapeutic indications and chances of cure; search of a type 1-multiple endocrine neoplasia (MEN A), in 25 % of cases; therapeutic indications: ablative surgery with curative intent in case of gastrinoma and of resectable liver metastases, palliative treatment otherwise: anti-secretory drugs, somatostatin analogues, chemotherapy and interferon {alpha}; long-term follow-up of patients with resected tumour. At each step, somatostatin receptor scintigraphy with indium 111-pentetreotide does play a pivotal role. (author). 110 refs.

  2. Positron emission tomography (PET) in endocrine tumours ...

    African Journals Online (AJOL)

    endocrine pancreatic tumours is probably limited to those that are less well differentiated and metabolically active. However, a future role for PET imaging in the detection of endocrine tumours, using more specific substrates, appears very promising. Journal of Endocrinology, Metabolism and Diabetes of South Africa Vol.

  3. Contrast enhancement pattern on multidetector CT predicts malignancy in pancreatic endocrine tumours

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    Cappelli, Carla [University of Pisa, Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Azienda Ospedaliero-Universitaria Pisana-Radiodiagnostica I, Pisa (Italy); Boggi, Ugo [University of Pisa, General and Transplant Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Mazzeo, Salvatore; Cervelli, Rosa; Contillo, Benedetta Pontillo; Bartolozzi, Carlo [University of Pisa, Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Campani, Daniela; Funel, Niccola [University of Pisa, Pathology, Department of Surgical, Medical, Molecular and Critical Area Pathology, Pisa (Italy)


    Preoperative suspicion of malignancy in pancreatic neuroendocrine tumours (pNETs) is mostly based on tumour size. We retrospectively reviewed the contrast enhancement pattern (CEP) of a series of pNETs on multiphasic multidetector computed tomography (MDCT), to identify further imaging features predictive of lesion aggressiveness. Sixty pNETs, diagnosed in 52 patients, were classified based on CEP as: type A showing early contrast enhancement and rapid wash-out; type B presenting even (B1) or only (B2) late enhancement. All tumours were resected allowing pathologic correlations. Nineteen pNETs showed type A CEP (5-20 mm), 29 type B1 CEP (5-80 mm) and 12 type B2 (15-100 mm). All tumours were classified as well differentiated tumours, 19 were benign (WDt-b), 15 with uncertain behaviour (WDt-u) and 26 carcinomas (WDC). None of A lesions were malignant (12 WDt-b; 7 WDt-u), all B2 lesions were WDC, 7 B1 lesions were WDt-b, 8 WDt-u and 14 WDC; 4/34 (12 %) lesions ≤2cm were WDC. CEP showed correlation with all histological prognostic indicators. Correlating with the lesion grading and other histological prognostic predictors, CEP may preoperatively suggest the behaviour of pNETs, assisting decisions about treatment. Moreover CEP allows recognition of malignant small tumours, incorrectly classified on the basis of their dimension. (orig.)

  4. Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours. (United States)

    Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano


    (18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.

  5. Combined endocrine and exocrine tumours of the pancreas

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    Alzein Abdulhalem


    Full Text Available Abstract Background Cystic neoplasms of the pancreas comprise 10%–15% of pancreatic cystic lesions, with the serous cystadenoms being the commonest. The association of exocrine and endocrine tumours of the pancreas unrelated to Von Hipple Lindau disease is very rare. Very few cases have been reported in the literature. We present another case of both these tumours in one patient. Case presentation A female patient was seen in the surgical clinic for a pain in the right groin. Clinical examination and investigations confirmed a diagnosis of combined endocrine and exocrine tumours of the pancreas. She underwent surgery and is under regular follow-up in the surgical clinic. Conclusion Biphasic differentiation of pancreatic stem cell during embryological development could happen and may result in combined endocrine and exocrine tumours of the pancreas. Imaging studies are excellent in diagnosing theses lesions. Surgery has a central role and could be curative.

  6. [Increase of alpha-fetoprotein in pancreatic endocrine tumors with hepatic metastases. Apropos of 2 cases]. (United States)

    Lesur, G; Bergemer, A M; Turner, L; Parlier, H; Bernades, P; Dupuy, P


    We report two cases of metastatic non-functioning pancreatic endocrine tumour with very elevated plasma levels of alpha-fetoprotein. In these two cases, serial plasma levels of alpha-fetoprotein, initially normal, correlated well with hepatic tumour progression and were associated with fatal outcome. These results suggest that elevated plasma concentration of alpha-fetoprotein may be caused by metastatic pancreatic endocrine tumour and than alpha-fetoprotein serial measurement may be useful in prognostic evaluation.

  7. Role of somatostatin receptor scintigraphy with indium 111-pentetreotide in gastro entero pancreatic endocrine tumours; Place de la scintigraphie des recepteurs de la somatostatine dans les tumeurs endocrines gastroentero-pancreatiques

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    Lebtahi, R.; Cadiot, G.; Mignon, M.; Le Guludec, D.


    Somatostatin receptor scintigraphy (SRS) is a new sensitive method used in gastro-entero-pancreatic neuroendocrine tumours. SRS is highly sensitive for the detection of primary tumors and their metastases; we report the sensitivity of SRS in the extension of this tumoral disease. SRS should be part of the pre-therapeutical test set. (author). 110 refs.

  8. Comparison between {sup 68}Ga-DOTA-NOC and {sup 18}F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

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    Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano [Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Unita Operativa di Medicina Nucleare, Bologna (Italy); Policlinico S.Orsola-Malpighi, Unita Operativa di Medicina Internal, Bologna (Italy)


    {sup 18}F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that {sup 18}F-DOPA and {sup 68}Ga-DOTA-NOC are more accurate for disease assessment and {sup 68}Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare {sup 68}Ga-DOTA-NOC and {sup 18}F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for {sup 18}F-DOPA and {sup 68}Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. {sup 68}Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while {sup 18}F-DOPA PET was positive in 9/13. On a lesions basis, {sup 68}Ga-DOTA-NOC identified more lesions than {sup 18}F-DOPA (71 vs 45), especially at liver, lung and lymph node level. {sup 68}Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while {sup 18}F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that {sup 68}Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over {sup 18}F-DOPA. (orig.)

  9. Single photon emission computed tomography procedure improves accuracy of somatostatin receptor scintigraphy in endocrine gastro-entero-pancreatic tumours; Dectection des tumeurs endocrines de l'abdomen: interet de la tomographie et des images planaires

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    Lebtahi, R.; Genin, R.; Rouzet, F.; Bleicner-Perez, S.; Lievre, A.; Scigliano, S.; Vialle, C.; Le Guludec, D. [Hopital Bichat, Service de Medecine Nucleaire, 75 - Paris (France); Cadiot, G. [Hopital de Reims, Service de Gastro-Enterologie, 51 - Reims (France); Sobhani, I. [Hopital Henri-Mondor, Service de Gastro-Enterologie, 94 - Creteil (France); Mignon, M. [Hopital Bichat, Service de Gastro-Enterologie, 75 - Paris (France)


    Somatostatin receptors scintigraphy (SRS) is a sensitive method for the detection of endocrine gastro-entero-pancreatic tumors. The aim of this study was to evaluate the sensitivity of anterior and posterior planar associated to single photon emission computerized tomography (SPECT) compared to anterior and posterior planar associated to additional lateral and oblique views in the detection of abdominal endocrine tumors. One hundred and sixty four patients with endocrine gastro-entero-pancreatic tumors were included in this study. Scintigraphic images were performed after injection of 189 {+-} 23 MBq of {sup 111}In-Pentetreotide. Abdominal planar images were performed 4 h and 24 hours after injection. Abdominal SPECT was performed at 24 hours. The combination of anterior and posterior abdominal planar images with SPECT using iterative reconstruction detected significantly more tumoral sites compared to multiple planar images (298 versus 280 for the liver, p = 0.01 and 90 versus 88 for coeliac area). In particular liver lesions were better delineated on tomographic slices. The combination of {sup 111}In-Pentetreotide SPECT with anterior and posterior planar images is more sensitive than multiple planar images to detect abdominal endocrine tumors. (author)

  10. [Two cases reports of pancreatic endocrine microadenoma incidentally found]. (United States)

    Coulibaly, Béma; Delage-Corre, Manuela; Durand-Fontanier, Sylvaine; Mathonnet, Muriel; Paraf, François; Labrousse, François


    A 59-year-old male, was admitted to our hospital for a tumor of the pancreatic tail. Serum CEA and CA 19-9 levels were normal. Splenopancreasectomy found a desmoid tumour. A 69-year-old male was referred to our institution for chronic anemia and inflammatory syndrome with splenomegaly. Splenectomy showed an important splenic congestion and siderosis. Both patients had a type 2 diabetes mellitus. Furthermore, histological examination revealed pancreatic endocrine microadenomas. The two patients' postoperative course was unremarkable. Eleven and 24 months respectively after the diagnosis, the patients are alive and well, with no tumor recurrence. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Coexistence of an endocrine tumour in a serous cystadenoma (microcystic adenoma) of the pancreas, an unusual association


    Ustun, M; TuGyan, N; Tunakan, M


    A pancreatic endocrine tumour arising within a serous cystadenoma is reported. A 49 year old woman was admitted with a history of epigastric pain, nausea, vomiting, and weight loss of two months duration. She had been diabetic for 12 years. An epigastric mass was palpated in the physical examination, and computed tomography revealed a multiloculated cystic lesion in the pancreas. Pathological examination of the pancreatic tumour revealed the coexistence of a serous cystadenoma and an endocrin...

  12. Primary endocrine-secreting pancreatic tumors. (United States)

    Macaron, C


    Insulinoma, glucagonoma, gastrinoma (Zollinger-Ellison syndrome), vipoma, somatostatinoma and a tumor that secretes human pancreatic polypeptide are the primary endocrine-secreting tumors of the pancreas. hormones are produced by specific tumor cell types and cause a variety of dramatic clinical pictures. Diagnosis often requires hormone assays. Computerized tomography may be helpful. Definitive surgical treatment is possible, but metastases may be present.

  13. Endocrine pancreatic insufficiency in chronic pancreatitis. (United States)

    Angelopoulos, Nicholas; Dervenis, Christos; Goula, Anastasia; Rombopoulos, Grigorios; Livadas, Sarantis; Kaltsas, Dimitrios; Kaltzidou, Victoria; Tolis, George


    Chronic pancreatitis (CP) is considered to be a rare cause of diabetes mellitus. However, in both the developed and developing world, there is an increasing number of patients suffering from pancreatitis probably due to lifestyle changes, which is partially associated with both social factors and the poor health status of immigrants. Owing to these circumstances, CP has evolved with one of the possible causes of diabetes in a selected group of patients and should be included in the differential diagnosis of diabetes. Several studies have shown that the long-term rate of diabetic complications in patients with CP and insulin-dependent diabetes is similar to that in patients with type 1 diabetes of equal duration. The hypothesis that early diagnosis of CP should result in better prognosis is not validated and may complicate the issue, since the risk of diabetes has been shown to increase significantly only once pancreatic calcification has developed. Accumulative evidence suggests that the risk of diabetes is not influenced by elective pancreatic surgical procedures other than distal pancreatectomy. The lack of contemporary data points to the urgent need for large prospective studies in order to accurately evaluate the special characteristics of disorders in glucose homeostasis in patients with CP.

  14. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

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    Marcel Cerqueira Cesar Machado

    Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

  15. Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours. (United States)

    Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav


    The objective of this study was to evaluate the performance and utility of (99m)Tc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent (99m)Tc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of (99m)Tc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with (99m)Tc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. (99m)Tc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). (99m)Tc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options.

  16. Positron emission tomography (PET) and pancreatic tumours; Tomographie par emission de positons (TEP) et tumeurs pancreatiques

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    Montravers, F.; Kerrou, K.; Grahek, D.; Gutman, F.; Beco, V. de; Talbot, J.N. [Hopital Tenon, Service de Medecine, 75 - Paris (France)


    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)

  17. Description of the use of contrast-enhanced ultrasonography in four dogs with pancreatic tumours. (United States)

    Vanderperren, K; Haers, H; Van der Vekens, E; Stock, E; Paepe, D; Daminet, S; Saunders, J H


    Canine pancreatic tumours are rare compared to human medicine and the detection and differentiation of pancreatic neoplasia is challenging with B-mode ultrasonography, which often leads to late clinical diagnosis and poor prognosis. This case report describes the findings of contrast-enhanced ultrasonography in four dogs with pancreatic adenocarcinoma or insulinoma. B-mode ultrasonography of the pancreas revealed a hypoechoic nodule in three dogs and heterogenous tissue in one dog. Contrast-enhanced ultrasonography was able to differentiate between two tumour types: adenocarcinomas showed hypoechoic and hypovascular lesions, whereas insulinomas showed uniformly hypervascular lesions. Contrast-enhanced ultrasonography findings were confirmed by cytology and/or histopathology. The results demonstrated that contrast-enhanced ultrasonography was able to establish different enhancement patterns between exocrine (adenocarcinoma) and endocrine (insulinoma) tumours in dogs.

  18. FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

    DEFF Research Database (Denmark)

    Tornehave, D; Jensen, Charlotte Harken; Teisner, B


    tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing...... development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus......, there was a negative correlation between FA1 and glucagon both in tumours and during development. These results, together with FA1/dlk's similarity with homeotic proteins, point to a role of FA1 in islet cell differentiation. Udgivelsesdato: 1996-Dec...

  19. The Role of ARX in Human Pancreatic Endocrine Specification. (United States)

    Gage, Blair K; Asadi, Ali; Baker, Robert K; Webber, Travis D; Wang, Rennian; Itoh, Masayuki; Hayashi, Masaharu; Miyata, Rie; Akashi, Takumi; Kieffer, Timothy J


    The in vitro differentiation of human embryonic stem cells (hESCs) offers a model system to explore human development. Humans with mutations in the transcription factor Aristaless Related Homeobox (ARX) often suffer from the syndrome X-linked lissencephaly with ambiguous genitalia (XLAG), affecting many cell types including those of the pancreas. Indeed, XLAG pancreatic islets lack glucagon and pancreatic polypeptide-positive cells but retain somatostatin, insulin, and ghrelin-positive cells. To further examine the role of ARX in human pancreatic endocrine development, we utilized genomic editing in hESCs to generate deletions in ARX. ARX knockout hESCs retained pancreatic differentiation capacity and ARX knockout endocrine cells were biased toward somatostatin-positive cells (94% of endocrine cells) with reduced pancreatic polypeptide (rarely detected), glucagon (90% reduced) and insulin-positive (65% reduced) lineages. ARX knockout somatostatin-positive cells shared expression patterns with human fetal and adult δ-cells. Differentiated ARX knockout cells upregulated PAX4, NKX2.2, ISL1, HHEX, PCSK1, PCSK2 expression while downregulating PAX6 and IRX2. Re-expression of ARX in ARX knockout pancreatic progenitors reduced HHEX and increased PAX6 and insulin expression following differentiation. Taken together these data suggest that ARX plays a key role in pancreatic endocrine fate specification of pancreatic polypeptide, somatostatin, glucagon and insulin positive cells from hESCs.

  20. Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours

    NARCIS (Netherlands)

    W.W. de Herder (Wouter); L.J. Hofland (Leo); A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven)


    textabstractFive somatostatin receptor (sst) subtype genes, sst(1), sst(2), sst(3), sst(4) and sst(5), have been cloned and characterised. The five sst subtypes all bind natural somatostatin-14 and somatostatin-28 with high affinity. Endocrine pancreatic and endocrine digestive

  1. Characterization of Endocrine Cells and Tumours in the Stomach


    Tsolakis, Apostolos V.


    Enterochromaffin-like (ECL) and ghrelin cells, in the human gastric mucosa and in gastric endocrine tumours (GETs), were subclassified with respect to immunohistochemical reaction vs. vesicular monoamine transporter 2 (VMAT-2), ghrelin/obestatin, and histidine decarboxylase (HDC). The immunohistochemical expression of ghrelin/obestatin and HDC in GETs was related/correlated to plasma ghrelin/obestatin and urinary methyl imidazole acetic acid (U-MeImAA) excretion respectively, with the intenti...

  2. Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

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    Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)


    Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

  3. REST represses a subset of the pancreatic endocrine differentiation program

    DEFF Research Database (Denmark)

    Martin, David; Kim, Yung-Hae; Sever, Dror


    To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented...... in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic...... endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3...

  4. Examining the effects of hyperglycemia on pancreatic endocrine function in humans

    DEFF Research Database (Denmark)

    Solomon, Thomas P J; Knudsen, Sine H; Karstoft, Kristian


    Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease.......Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease....

  5. CT and US findings in pancreatic ductal tumours

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    Eresue, J.; Drouillard, J.; Philippe, J.C.; Guibert, J.L.; Roux, P.; Tavernier, J.


    Pancreatic cystadenomas and cystadenocarcinomas are rare tumours usually occurring in women. The first symptoms are pain, occasionally associated with a palpable tumour in the left upper quadrant, and in rare cases the clinical and laboratory findings are suggestive of a pseudocyst. US shows a cystic neoplasm with a wall enclosing several polypoid areas. CT allows the diagnosis of the type of septa within the cyst and shows the extension of the lesion and calcifications into the wall. It also permits the assessment of the probable pathological complications associated with the tumour; therefore CT cannot differentiate cystadenoma from cystadenocarcinoma. The analysis of these different phenomena is based on one observation and a review of the literature.


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    Binoy Kumar Mohanty


    Full Text Available BACKGROUND Pituitary tumours are relatively common endocrine tumours. They can present with symptoms related to hormone excess or hormone deficiency. They can also present with compressive symptoms like visual problems and headache. OBJECTIVE To study the various clinical presentations and endocrine profile of patients presenting with pituitary tumours to a tertiary care hospital. DESIGN Cross sectional study. MATERIAL AND METHODS We collected and analysed the clinical data including hormonal status of 33 consecutive patients who presented to our department from March 2014 to February 2016 for evaluation of pituitary tumours. RESULTS Majority of the subjects studied belonged to 40-50 years group (33.34%.The most common type of pituitary tumour in our population was non-functioning pituitary tumours (45.45%. The next common cause was somatotroph adenoma (27.27% followed by prolactinoma (15.15% and corticotroph adenomas (12.13%. There was significant male predominance (60.60% among total cases. Among all patients, headache (54.54% was most common presentation followed by features related to hormone excess (51.51%. CONCLUSIONS Pituitary tumours can present with variety of symptoms. A detailed endocrine workup is essential in each case to reach at correct diagnosis. In our cohort, non-functioning pituitary tumour was the most common tumour subtype.

  7. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients

    DEFF Research Database (Denmark)

    Sausen, Mark; Phallen, Jillian; Adleff, Vilmos


    Pancreatic adenocarcinoma has the worst mortality of any solid cancer. In this study, to evaluate the clinical implications of genomic alterations in this tumour type, we perform whole-exome analyses of 24 tumours, targeted genomic analyses of 77 tumours, and use non-invasive approaches to examine...... imaging. These observations provide genetic predictors of outcome in pancreatic cancer and have implications for new avenues of therapeutic intervention....

  8. Differential diagnosis of pancreatic cancer from other solid tumours arising from the periampullary area on MDCT

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    Jang, Suk Ki [Bundang Jesaeng General Hospital, Departments of Radiology, Daejin Medical Center, Seognam-si, Gyeonggi-do (Korea, Republic of); Kim, Jung Hoon; Joo, Ijin; Jeon, Ju Hyun; Han, Joon Koo; Choi, Byung Ihn [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, Chongno-gu, Seoul (Korea, Republic of); Shin, Kyung Sook [Chungnam National University School of Medicine, Department of Radiology, 266 Munhwa-ro, Jung-gu, Daejeon (Korea, Republic of)


    To investigate CT features and differential diagnosis of pancreatic adenocarcinoma compared to other solid tumours arising in the periampullary area. One hundred and ninety-five patients with pathologically proven, solid periampullary tumours, including pancreatic adenocarcinoma (n = 98), neuroendocrine tumours (n = 52), gastrointestinal stromal tumours (n = 31), and solid pseudopapillary neoplasms (n = 14), underwent preoperative CT. Two radiologists reviewed CT features and rated the possibility of pancreatic adenocarcinoma. Statistically common findings for pancreatic adenocarcinoma included: patient age >50 years; ill-defined margin; completely solid mass; homogeneous enhancement; hypoenhancement on arterial and venous phases; atrophy; and duct dilatation. Statistically common findings for GIST included: heterogeneous enhancement; hyperenhancement on arterial and venous phases; rim enhancement; and prominent feeding arteries. The hyperenhancement on arterial and venous phases is statistically common in NET, and heterogeneous enhancement, hypoenhancement on the arterial and venous phases are statistically common in SPN. Diagnostic performance of CT for differentiating pancreatic adenocarcinomas from other solid periampullary tumours was 0.962 and 0.977 with excellent interobserver agreement (κ = 0.824). CT is useful not only for differentiating pancreatic adenocarcinoma form other solid tumours but also for differentiating between other solid tumours, including NET, SPN, and GIST, arising in the periampullary area. (orig.)

  9. Autoimmune pancreatitis with atypical imaging findings that mimicked an endocrine tumor (United States)

    Neuzillet, Cindy; Lepère, Céline; Hajjam, Mostafa El; Palazzo, Laurent; Fabre, Monique; Turki, Hajer; Hammel, Pascal; Rougier, Philippe; Mitry, Emmanuel


    Autoimmune pancreatitis (AIP) is a rare cause of recurrent acute pancreatitis or chronic pancreatitis in middle-aged patients, and is characterised by a marked infiltration of lymphocytes and plasma cells in pancreatic tissue. Diagnosis of focal forms can be difficult as AIP may mimic pancreatic adenocarcinoma. Pediatric cases of AIP are exceptional. We report the case of a 15-year-old girl who had a focal AIP and associated cholangitis, with a very unusual vascularized mass that mimicked a pancreatic endocrine tumor. The diagnosis was obtained by a pancreatic biopsy, thus avoiding surgical resection, and all the clinical, biological and radiological abnormalities resolved after steroid therapy with 6 mo of follow-up. PMID:20556844

  10. Functional Analysis of Chromosome 18 in Pancreatic Cancer: Strong Evidence for New Tumour Suppressor Genes

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    Liviu P. Lefter


    Conclusion: These data represent strong functional evidence that chromosome 18q encodes strong tumour and metastasis suppressor activity that is able to switch human pancreatic cancer cells to a dormant phenotype.

  11. Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors. (United States)

    Bonnavion, Rémy; Teinturier, Romain; Jaafar, Rami; Ripoche, Doriane; Leteurtre, Emmanuelle; Chen, Yuan-Jia; Rehfeld, Jens F; Lepinasse, Florian; Hervieu, Valérie; Pattou, François; Vantyghem, Marie-Christine; Scoazec, Jean-Yves; Bertolino, Philippe; Zhang, Chang Xian


    The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have migrated from the duodenum. In the current study, we further characterized previously described transient pancreatic gastrin-expressing cells using cell lineage tracing in a pan-pancreatic progenitor and a pancreatic endocrine progenitor model. We provide evidence showing that pancreatic gastrin-expressing cells, found from embryonic day 12.5 until postnatal day 7, are derived from pancreatic Ptf1a(+) and neurogenin 3-expressing (Ngn3(+)) progenitors. Importantly, the majority of them coexpress glucagon, with 4% coexpressing insulin, indicating that they are a temporary subpopulation of both alpha and beta cells. Interestingly, Men1 disruption in both Ngn3 progenitors and beta and alpha cells resulted in the development of pancreatic gastrin-expressing tumors, suggesting that the latter developed from islet cells. Finally, we detected gastrin expression using three human cohorts with pancreatic endocrine tumors (pNETs) that have not been diagnosed as gastrinomas (in 9/34 pNETs from 6/14 patients with multiple endocrine neoplasia type 1, in 5/35 sporadic nonfunctioning pNETs, and in 2/20 sporadic insulinomas), consistent with observations made in mouse models. Our work provides insight into the histogenesis of pancreatic gastrin-expressing tumors. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. [Pancreatic polypeptide secreting endocrine pancreas tumor associated with multiple stomach and duodenal ulcers]. (United States)

    Mehring, U M; Jäger, H J; Klöppel, G; Hasse, F M


    A 58-year-old woman presented with multiple gastroduodenal ulcera caused by a pancreatic polypeptidoma (PPoma) without hypergastrinemia or gastrin-producing tumor cells. After curative resection of the neoplasm, the clinical symptoms disappeared and the patient has now been disease-free for 6 years. We conclude that patients with non-gastrin-producing endocrine pancreatic tumors may demonstrate the clinical features of Zollinger-Ellison syndrome and should be included in the differential diagnosis of this syndrome.

  13. Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche (United States)

    Bankaitis, Eric D.; Bechard, Matthew E.; Wright, Christopher V.E.


    In the mammalian pancreas, endocrine cells undergo lineage allocation upon emergence from a bipotent duct/endocrine progenitor pool, which resides in the “trunk epithelium.” Major questions remain regarding how niche environments are organized within this epithelium to coordinate endocrine differentiation with programs of epithelial growth, maturation, and morphogenesis. We used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. The bulk of endocrine progenitors is maintained in an epithelial “plexus state,” which is a transient intermediate during epithelial maturation within which endocrine cell differentiation is continually robust and surprisingly long-lived. Within the plexus, local feedback effects derived from the differentiating and delaminating endocrine cells nonautonomously regulate the flux of endocrine cell birth as well as proliferative growth of the bipotent cell population using Notch-dependent and Notch-independent influences, respectively. These feedback effects in turn maintain the plexus state to ensure prolonged allocation of endocrine cells late into gestation. These findings begin to define a niche-like environment guiding the genesis of the endocrine pancreas and advance current models for how differentiation is coordinated with the growth and morphogenesis of the developing pancreatic epithelium. PMID:26494792

  14. Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage. (United States)

    Porta, Miquel; Fabregat, Xavier; Malats, Núria; Guarner, Luisa; Carrato, Alfredo; de Miguel, Ana; Ruiz, Laura; Jariod, Manuel; Costafreda, Sergi; Coll, Susana; Alguacil, Juan; Corominas, Josep M; Solà, Ricard; Salas, Antonio; Real, Francisco X


    The need to detect pancreatic cancer at earlier stages is undisputed. We recorded the signs and symptoms of patients presenting with exocrine pancreatic cancer and evaluated their association with clinical characteristics such as tumour site and disease stage. All patients (n = 185) with exocrine pancreatic cancer newly diagnosed at five general hospitals in Eastern Spain were prospectively recruited over 5 years. Symptoms were elicited through personal interviews and signs were recorded by the attending physician on admission. At diagnosis, one third of tumours of the pancreas head were in stage I and another third in stage IV. None of the tumours of the body and tail were in stage I, and over 80% were in stage IV (p head (p semiology of pancreatic cancer which could be of use in studies on the potential of proteomic tests in the early detection of this neoplasm.

  15. Effect of octreotide acetate on pancreatic exocrine and endocrine functions after pancreatoduodenal resection. (United States)

    Petrin, P; Antoniutti, M; Zaramella, D; Da Lio, C; Basso, D; Plebani, M; Panozzo, M P; Costantino, V; Pedrazzoli, S


    In view of forecasting the effect of octreotide acetate (Sandostatin) in preventing fistula formation after pancreatic surgery, 9 patients, who had pancreatoduodenectomy 8-12 days before, underwent a 2-day study. The first day, by means of a catheter located in the jejunal loop separately anastomosed to the pancreatic remnant, basal and after secretin stimulation pancreatic secretion was evaluated. During the 2nd day the possible inhibitory effect of octreotide on basal and stimulated secretion was investigated. Under the experimental conditions of the study Sandostatin showed little effect on the water and bicarbonate increase as stimulated by secretin. A greater hormone inhibitory effect on amylase production and pancreatic endocrine function was seen. On the basis of these results the use of Sandostatin can hardly be seen as useful in preventing fistula formation after pancreatic resection.

  16. Dimethyl fumarate protects pancreatic islet cells and non-endocrine tissue in L-arginine-induced chronic pancreatitis.

    Directory of Open Access Journals (Sweden)

    Lourdes Robles

    Full Text Available Chronic pancreatitis (CP is a progressive disorder resulting in the destruction and fibrosis of the pancreatic parenchyma which ultimately leads to impairment of the endocrine and exocrine functions. Dimethyl Fumarate (DMF was recently approved by FDA for treatment of patients with multiple sclerosis. DMF's unique anti-oxidant and anti-inflammatory properties make it an interesting drug to test on other inflammatory conditions. This study was undertaken to determine the effects of DMF on islet cells and non-endocrine tissue in a rodent model of L-Arginine-induced CP.Male Wistar rats fed daily DMF (25 mg/kg or vehicle by oral gavage were given 5 IP injections of L-Arginine (250 mg/100 g × 2, 1 hr apart. Rats were assessed with weights and intra-peritoneal glucose tolerance tests (IPGTT, 2 g/kg. Islets were isolated and assessed for islet mass and viability with flow cytometry. Non-endocrine tissue was assessed for histology, myeloperoxidase (MPO, and lipid peroxidation level (MDA. In vitro assessments included determination of heme oxygenase (HO-1 protein expression by Western blot.Weight gain was significantly reduced in untreated CP group at 6 weeks. IPGTT revealed significant impairment in untreated CP group and its restoration with DMF therapy (P <0.05. Untreated CP rats had pancreatic atrophy, severe acinar architectural damage, edema, and fatty infiltration as well as elevated MDA and MPO levels, which were significantly improved by DMF treatment. After islet isolation, the volume of non-endocrine tissue was significantly smaller in untreated CP group. Although islet counts were similar in the two groups, islet viability was significantly reduced in untreated CP group and improved with DMF treatment. In vitro incubation of human pancreatic tissue with DMF significantly increased HO-1 expression.Administration of DMF attenuated L-Arginine-induced CP and islet function in rats. DMF treatment could be a possible strategy to improve clinical

  17. Ultrastructure of endocrine pancreatic granules during pancreatic differentiation in the grass snake, Natrix natrix L. (Lepidosauria, Serpentes). (United States)

    Kowalska, Magdalena; Rupik, Weronika


    We used transmission electron microscopy to study the pancreatic main endocrine cell types in the embryos of the grass snake Natrix natrix L. with focus on the morphology of their secretory granules. The embryonic endocrine part of the pancreas in the grass snake contains four main types of cells (A, B, D, and PP), which is similar to other vertebrates. The B granules contained a moderately electron-dense crystalline-like core that was polygonal in shape and an electron-dense outer zone. The A granules had a spherical electron-dense eccentrically located core and a moderately electron-dense outer zone. The D granules were filled with a moderately electron-dense non-homogeneous content. The PP granules had a spherical electron-dense core with an electron translucent outer zone. Within the main types of granules (A, B, D, PP), different morphological subtypes were recognized that indicated their maturity, which may be related to the different content of these granules during the process of maturation. The sequence of pancreatic endocrine cell differentiation in grass snake embryos differs from that in many vertebrates. In the grass snake embryos, the B and D cells differentiated earlier than A and PP cells. The different sequence of endocrine cell differentiation in snakes and other vertebrates has been related to phylogenetic position and nutrition during early developmental stages. © 2017 Wiley Periodicals, Inc.

  18. Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression. (United States)

    Mastracci, Teresa L; Wilcox, Crystal L; Arnes, Luis; Panea, Casandra; Golden, Jeffrey A; May, Catherine Lee; Sussel, Lori


    Nkx2.2 and Arx are essential pancreatic transcription factors. Nkx2.2 is necessary for the appropriate specification of the islet alpha, beta, PP and epsilon cell lineages, whereas Arx is required to form the correct ratio of alpha, beta, delta and PP cells. To begin to understand the cooperative functions of Nkx2.2 and Arx in the development of endocrine cell lineages, we generated progenitor cell-specific deletions of Arx on the Nkx2.2 null background. The analysis of these mutants demonstrates that expansion of the ghrelin cell population in the Nkx2.2 null pancreas is not dependent on Arx; however, Arx is necessary for the upregulation of ghrelin mRNA levels in Nkx2.2 mutant epsilon cells. Alternatively, in the absence of Arx, delta cell numbers are increased and Nkx2.2 becomes essential for the repression of somatostatin gene expression. Interestingly, the dysregulation of ghrelin and somatostatin expression in the Nkx2.2/Arx compound mutant (Nkx2.2(null);Arx(Δpanc)) results in the appearance of ghrelin+/somatostatin+ co-expressing cells. These compound mutants also revealed a genetic interaction between Nkx2.2 and Arx in the regulation of the PP cell lineage; the PP cell population is reduced when Nkx2.2 is deleted but is restored back to wildtype numbers in the Nkx2.2(null);Arx(Δpanc) mutant. Moreover, conditional deletion of Arx in specific pancreatic cell populations established that the functions of Arx are necessary in the Neurog3+ endocrine progenitors. Together, these experiments identify novel genetic interactions between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells. 2011 Elsevier Inc. All rights reserved.

  19. Endocrine tumours in neurofibromatosis type 1, tuberous sclerosis and related syndromes. (United States)

    Lodish, Maya B; Stratakis, Constantine A


    Neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex (TSC) are two familial syndromes known as phakomatoses that may be associated with endocrine tumours. These hereditary cutaneous conditions affect the central nervous system and are characterised by the development of hamartomas. Over the past 20 years, there have been major advances in our understanding of the molecular basis of these diseases. Both NF-1 and TSC are disorders of unregulated progression through the cell cycle, in which causative genes behave as tumour suppressor genes. The pathogenesis of these familial syndromes is linked by the shared regulation of a common pathway, the protein kinase mammalian target of rapamycin (mTOR). Additional related disorders that also converge on the mTOR pathway include Peutz-Jeghers syndrome and Cowden syndrome. All of these inherited cancer syndromes are associated with characteristic skin findings that offer a clue to their recognition and treatment. The discovery of mTOR inhibitors has led to a possible new therapeutic modality for patients with endocrine tumours as part of these familial syndromes. Published by Elsevier Ltd.

  20. SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma-paraganglioma syndromes. (United States)

    Pasini, B; Stratakis, C A


    A genetic predisposition for paragangliomas and adrenal or extra-adrenal phaeochromocytomas was recognized years ago. Beside the well-known syndromes associated with an increased risk of adrenal phaeochromocytoma, Von Hippel Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1, the study of inherited predisposition to head and neck paragangliomas led to the discovery of the novel 'paraganglioma-phaeochromocytoma syndrome' caused by germline mutations in three genes encoding subunits of the succinate dehydrogenase (SDH) enzyme (SDHB, SDHC and SDHD) thus opening an unexpected connection between mitochondrial tumour suppressor genes and neural crest-derived cancers. Germline mutations in SDH genes are responsible for 6% and 9% of sporadic paragangliomas and phaeochromocytomas, respectively, 29% of paediatric cases, 38% of malignant tumours and more than 80% of familial aggregations of paraganglioma and phaeochromocytoma. The disease is characterized by autosomal dominant inheritance with a peculiar parent-of-origin effect for SDHD mutations. Life-time tumour risk seems higher than 70% with variable clinical manifestantions depending on the mutated gene. In this review we summarize the most recent knowledge about the role of SDH deficiency in tumorigenesis, the spectrum and prevalence of SDH mutations derived from several series of cases, the related clinical manifestantions including rare phenotypes, such as the association of paragangliomas with gastrointestinal stromal tumours and kidney cancers, and the biological hypotheses attempting to explain genotype to phenotype correlation.

  1. Detection of multiple endocrine tumours using {sup 131}I-MIBG

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    Reinhardt, C.A. [Royal Brisbane Hospital, Herston, QLD (Australia). Department of Nuclear Medicine


    Full text: An {sup 131}l-MIBG scan was requested in an effort to locate an endocrine tumour after the patient presented with a history of funny turns, intermittent hypertension and elevated urinary catecholamines. The patient was injected with {sup 131}l-MIBG, and scanned 48 and 72 hours post-injection. Anterior and posterior static images of the torso identified several abnormal accumulations of {sup 131}l-MIBG. To help with the diagnosis a {sup 99}mTc-MPP scan followed. Blood pool images showed areas of intense activity matching some of the abnormalities on the {sup 131}l-MIBG scan. The delayed images were unremarkable. Some of these abnormalities were palpable on physical examination and the patient was aware of these lesions since childhood. Surgical excision of five tumours was performed. Histology of {sup 131}l tumours confirmed the diagnosis of ganglioneuroma. The nuclear medicine scans successfully identified the location and type of tumour responsible for the patient``s hormonal problems.

  2. Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression. (United States)

    Nuzhat, Zarin; Kinhal, Vyjayanthi; Sharma, Shayna; Rice, Gregory E; Joshi, Virendra; Salomon, Carlos


    Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer. Extracellular vesicles are membrane-limited structures derived from the cell membrane. They contain specific molecules including proteins, mRNA, microRNAs and non-coding RNAs that are secreted in the extracellular space. Extracellular vesicles can be classified according to their size and/or origin into microvesicles (~150-1000 nm) and exosomes (~40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosomes are released via the endocytic pathway by fusion of multivesicular bodies with the plasmatic membrane. This endosomal origin means that exosomes contain an abundance of cell-specific biomolecules which may act as a 'fingerprint' of the cell of origin. In this review, we discuss our current knowledge in the diagnosis and treatment of pancreatic cancer, particularly the potential role of EVs in these facets of disease management. In particular, we suggest that as exosomes contain cellular protein and RNA molecules in a cell type-specific manner, they may provide extensive information about the signature of the tumour and pancreatic cancer progression.

  3. Impact of nutrition on pancreatic exocrine and endocrine secretion in ruminants: a review. (United States)

    Harmon, D L


    Because of the unique features of the ruminant digestive system, variations in diet composition and intake produce dramatic changes in ruminal fermentation. Optimizing nutritional management requires an understanding of how these variations and changes influence digestion and metabolism. Although the pancreas plays a central role in digestion and subsequent nutrient metabolism, relatively little is known about pancreatic adaptation to nutritional changes in the ruminant. Increasing starch intake has been suggested to increase pancreatic alpha-amylase; however, recent work suggests that dietary energy per se may drive these changes, and interactions with other nutrients, such as protein, may exist. Studies describing the influence of altered protein and lipid intakes on pancreatic adaptation in ruminants are lacking. Pancreatic secretion of both insulin and glucagon respond to the intravenous infusion of VFA in a dramatic fashion; however, feeding studies suggest that the influence of VFA on insulin and glucagon may be more subtle. Interactions exist between stimulatory signals and physiological state, such as lactation. Assessment of pancreatic endocrine secretion is further complicated by a variable removal of insulin and glucagon by hepatic tissues. These studies point out that pancreatic hormone secretion is controlled by integrated and complex mechanisms. Studies of these controlling mechanisms should consider the entire array to more fully understand hormone secretion.

  4. Endocrine pancreatic development: impact of obesity and diet

    Directory of Open Access Journals (Sweden)

    Jacqueline F O'Dowd


    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.

  5. p53 status determines the role of autophagy in pancreatic tumour development (United States)

    Rosenfeldt, Mathias T.; O'Prey, Jim; Morton, Jennifer P.; Nixon, Colin; Mackay, Gillian; Mrowinska, Agata; Au, Amy; Rai, Taranjit Singh; Zheng, Liang; Ridgway, Rachel; Adams, Peter D.; Anderson, Kurt I.; Gottlieb, Eyal; Sansom, Owen J.; Ryan, Kevin M.


    Macroautophagy (hereafter referred to as autophagy) is a process in which organelles termed autophagosomes deliver cytoplasmic constituents to lysosomes for degradation. Autophagy has a major role in cellular homeostasis and has been implicated in various forms of human disease. The role of autophagy in cancer seems to be complex, with reports indicating both pro-tumorigenic and tumour-suppressive roles. Here we show, in a humanized genetically-modified mouse model of pancreatic ductal adenocarcinoma (PDAC), that autophagy's role in tumour development is intrinsically connected to the status of the tumour suppressor p53. Mice with pancreases containing an activated oncogenic allele of Kras (also called Ki-Ras)--the most common mutational event in PDAC--develop a small number of pre-cancerous lesions that stochastically develop into PDAC over time. However, mice also lacking the essential autophagy genes Atg5 or Atg7 accumulate low-grade, pre-malignant pancreatic intraepithelial neoplasia lesions, but progression to high-grade pancreatic intraepithelial neoplasias and PDAC is blocked. In marked contrast, in mice containing oncogenic Kras and lacking p53, loss of autophagy no longer blocks tumour progression, but actually accelerates tumour onset, with metabolic analysis revealing enhanced glucose uptake and enrichment of anabolic pathways, which can fuel tumour growth. These findings provide considerable insight into the role of autophagy in cancer and have important implications for autophagy inhibition in cancer therapy. In this regard, we also show that treatment of mice with the autophagy inhibitor hydroxychloroquine, which is currently being used in several clinical trials, significantly accelerates tumour formation in mice containing oncogenic Kras but lacking p53.

  6. Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

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    Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)


    To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

  7. Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1 : Results from the DutchMEN1 Study Group

    NARCIS (Netherlands)

    Conemans, Elfi B.; Brosens, Lodewijk A. A.; Raicu-Ionita, Gabriela M.; Pieterman, Carolina R. C.; de Herder, Wouter W.; Dekkers, Olaf M.; Hermus, Ad R.; van der Horst-Schrivers, Anouk N.; Bisschop, Peter H.; Havekes, Bas; Drent, Madeleine L.; Timmers, H. Th Marc; Offerhaus, G. Johan; Valk, Gerlof D.; Vriens, Menno R.


    Background: The prognostic value of WHO grade in pancreatic neuroendocrine tumors (PanNETs) in patients with Multiple Endocrine Neoplasia Type 1 (MEN1) is unknown. Methods: We performed a cohort study using the Dutch National MEN1 database, which includes >90% of the Dutch MEN1 population with data

  8. BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion. (United States)

    Klein, Dagmar; Álvarez-Cubela, Silvia; Lanzoni, Giacomo; Vargas, Nancy; Prabakar, Kamalaveni R; Boulina, Maria; Ricordi, Camillo; Inverardi, Luca; Pastori, Ricardo L; Domínguez-Bendala, Juan


    The exocrine pancreas can give rise to endocrine insulin-producing cells upon ectopic expression of key transcription factors. However, the need for genetic manipulation remains a translational hurdle for diabetes therapy. Here we report the conversion of adult human nonendocrine pancreatic tissue into endocrine cell types by exposure to bone morphogenetic protein 7. The use of this U.S. Food and Drug Administration-approved agent, without any genetic manipulation, results in the neogenesis of clusters that exhibit high insulin content and glucose responsiveness both in vitro and in vivo. In vitro lineage tracing confirmed that BMP-7-induced insulin-expressing cells arise mainly from extrainsular PDX-1(+), carbonic anhydrase II(-) (mature ductal), elastase 3a (acinar)(-) , and insulin(-) subpopulations. The nongenetic conversion of human pancreatic exocrine cells to endocrine cells is novel and represents a safer and simpler alternative to genetic reprogramming. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  9. In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model

    Directory of Open Access Journals (Sweden)

    Hadlich Stefan


    Full Text Available Abstract Background Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability. Methods 6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA. Results MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p 3+/-243 mm3 with MRI (mean 918 mm3+/-193 mm3 with MRI being more precise. Histology (n = 5 confirmed MRI tumour measurements (mean size MRI 38.5 mm2+/-22.8 mm2 versus 32.6 mm2+/-22.6 mm2 (histology, p 3+/-56.7 mm3 after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p Conclusions This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.

  10. β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development.

    Directory of Open Access Journals (Sweden)

    Ahmed M Abdellatif

    Full Text Available The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic β-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of β-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced β-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of β-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key β-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the β-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous β-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas.

  11. Thermal therapy of pancreatic tumours using endoluminal ultrasound: Parametric and patient-specific modelling. (United States)

    Adams, Matthew S; Scott, Serena J; Salgaonkar, Vasant A; Sommer, Graham; Diederich, Chris J


    The aim of this study is to investigate endoluminal ultrasound applicator configurations for volumetric thermal ablation and hyperthermia of pancreatic tumours using 3D acoustic and biothermal finite element models. Parametric studies compared endoluminal heating performance for varying applicator transducer configurations (planar, curvilinear-focused, or radial-diverging), frequencies (1-5 MHz), and anatomical conditions. Patient-specific pancreatic head and body tumour models were used to evaluate feasibility of generating hyperthermia and thermal ablation using an applicator positioned in the duodenal or stomach lumen. Temperature and thermal dose were calculated to define ablation (> 240 EM(43 °C)) and moderate hyperthermia (40-45 °C) boundaries, and to assess sparing of sensitive tissues. Proportional-integral control was incorporated to regulate maximum temperature to 70-80 °C for ablation and 45 °C for hyperthermia in target regions. Parametric studies indicated that 1-3 MHz planar transducers are the most suitable for volumetric ablation, producing 5-8 cm(3) lesion volumes for a stationary 5-min sonication. Curvilinear-focused geometries produce more localised ablation to 20-45 mm depth from the GI tract and enhance thermal sparing (T(max) Modelling studies indicate the feasibility of endoluminal ultrasound for volumetric thermal ablation or hyperthermia treatment of pancreatic tumour tissue.

  12. Pancreatic neuroendocrine tumour: Correlation of apparent diffusion coefficient or WHO classification with recurrence-free survival. (United States)

    Kim, Mimi; Kang, Tae Wook; Kim, Young Kon; Kim, Seong Hyun; Kwon, Wooil; Ha, Sang Yun; Ji, Sang A


    To evaluate the correlation between grade of pancreatic neuroendocrine tumours (pNETs) based on the 2010 World Health Organization (WHO) classification and the apparent diffusion coefficient (ADC), and to assess whether the ADC value and WHO classification can predict recurrence-free survival (RFS) after surgery for pNETs. This retrospective study was approved by the Institutional Review Board. The requirement for informed consent was waived. Between March 2009 and November 2014, forty-nine patients who underwent magnetic resonance (MR) imaging with diffusion-weighted image and subsequent surgery for single pNETs were included. Correlations among qualitative MR imaging findings, quantitative ADC values, and WHO classifications were assessed. An ordered logistic regression test was used to control for tumour size as a confounding factor. The association between ADC value (or WHO classification) and RFS was analysed. All tumors (n=49) were classified as low- (n=29, grade 1), intermediate- (n=17, grade 2), and high-grade (n=3, grade 3), respectively. The mean ADC of pNETs was moderately negatively correlated with WHO classification before and after adjustment for tumour size (ρ=-0.64, pcorrelated with WHO tumour grade, regardless of tumour size. However, the WHO tumour classification of pNET may be more suitable for predicting RFS than the ADC value. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Initial cell seeding density influences pancreatic endocrine development during in vitro differentiation of human embryonic stem cells. (United States)

    Gage, Blair K; Webber, Travis D; Kieffer, Timothy J


    Human embryonic stem cells (hESCs) have the ability to form cells derived from all three germ layers, and as such have received significant attention as a possible source for insulin-secreting pancreatic beta-cells for diabetes treatment. While considerable advances have been made in generating hESC-derived insulin-producing cells, to date in vitro-derived glucose-responsive beta-cells have remained an elusive goal. With the objective of increasing the in vitro formation of pancreatic endocrine cells, we examined the effect of varying initial cell seeding density from 1.3 x 10(4) cells/cm(2) to 5.3 x 10(4) cells/cm(2) followed by a 21-day pancreatic endocrine differentiation protocol. Low density-seeded cells were found to be biased toward the G2/M phases of the cell cycle and failed to efficiently differentiate into SOX17-CXCR4 co-positive definitive endoderm cells leaving increased numbers of OCT4 positive cells in day 4 cultures. Moderate density cultures effectively formed definitive endoderm and progressed to express PDX1 in approximately 20% of the culture. High density cultures contained approximately double the numbers of PDX1 positive pancreatic progenitor cells and also showed increased expression of MNX1, PTF1a, NGN3, ARX, and PAX4 compared to cultures seeded at moderate density. The cultures seeded at high density displayed increased formation of polyhormonal pancreatic endocrine cell populations co-expressing insulin, glucagon and somatostatin. The maturation process giving rise to these endocrine cell populations followed the expected cascade of pancreatic progenitor marker (PDX1 and MNX1) expression, followed by pancreatic endocrine specification marker expression (BRN4, PAX4, ARX, NEUROD1, NKX6.1 and NKX2.2) and then pancreatic hormone expression (insulin, glucagon and somatostatin). Taken together these data suggest that initial cell seeding density plays an important role in both germ layer specification and pancreatic progenitor commitment, which

  14. Feline cutaneous and visceral necrotizing panniculitis and steatitis associated with a pancreatic tumour. (United States)

    Fabbrini, Fabrizio; Anfray, Pascal; Viacava, Paolo; Gregori, Michela; Abramo, Francesca


    The association of pancreatic disorders with fat necrosis in domestic animals is rare. This report concerns a case of cutaneous/subcutaneous necrotizing panniculitis and steatitis associated with a pancreatic adenocarcinoma in an 11-year-old male Siamese cat. Clinical investigation revealed variably sized nodules on the trunk, limbs and abdomen. Some of them were ulcerated; others showed a shiny yellow necrotic background featuring irregular sinus tracts. The cat was euthanized at the owner's request before a diagnosis could be made. At necropsy, abundant oily material resembling mustard replaced the subcutaneous tissue and small yellow nodules were disseminated in the omentum, mesentery and serosa of the abdomen. A multilobulated mass arising from the anterior pancreatic head was found along with liver and lymph node metastasis. Histopathology showed wide fistulous tracts draining necrotic fat from the subcutis toward the surface and multifocal areas of necrotic adipocytes replacing the panniculus. Duct-like structures and tubules lined by neoplastic epithelial cells were observed in the primary pancreatic tumour and in the metastatic sites. The aetiology of the fat necrosis was possibly the result of systemic release of lipolytic pancreatic enzymes.

  15. Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours. (United States)

    Buslei, Rolf; Strissel, Pamela L; Henke, Christine; Schey, Regina; Lang, Nadine; Ruebner, Matthias; Stolt, Claus C; Fabry, Ben; Buchfelder, Michael; Strick, Reiner


    Adenohypophysis (AH) hormone-producing cells represent the origin of diverse groups of pituitary adenomas (PA). Deregulation of hypothalamic hormone receptors, growth factors and cAMP signalling have been implicated in the aetiology of PA. Endogenous retroviruses (ERVs) are derived from past exogenous retroviral infections and represent more than 8% of the human genome. Some ERV genes encode open reading frames and produce functional proteins, for example, the ERVW-1 envelope gene Syncytin-1, essential for placentogenesis, but also deregulated in human tumours. Data concerning ERV expression in the AH and related endocrine tumours are missing. Syncytin-1 protein was analysed in normal AH (n = 15) and compared with five PA subtypes (n = 117) by immunohistochemistry. Absolute gene expression of 20 ERV functional envelope genes and ERVW-5 gag was measured. PA tissues were examined for Syncytin-1 and the cAMP signalling marker phospho-CREB-Ser133 using immunohistochemistry. Isolated primary human PA cells were treated with different hormones. Murine embryonic and adult pituitary gland ERV expressions were compared with human AH. Syncytin-1 protein colocalized with corticotropic cells of AH. In contrast, all PA demonstrated significant Syncytin-1 protein overexpression, supporting deregulation. All other ERV genes showed significant up-regulations in different PA subtypes. Phospho-CREB-Ser133 and Syncytin-1 colocalized in PA cells. Cultivated primary PA cells with ACTH or CRH induced their respective receptors and ERV genes. Syncytin-A/-B, murine orthologues to human Syncytin-1/-2, localized to embryonic and adult pituitary glands demonstrating functional mammalian conservation. Deregulated ERV genes may contribute to PA development via cAMP signalling. © 2014 British Neuropathological Society.

  16. Exocrine and endocrine functional reserve in the course of chronic pancreatitis as studied by maximal stimulation tests. (United States)

    Cavallini, G; Bovo, P; Zamboni, M; Bosello, O; Filippini, M; Riela, A; Brocco, G; Rossi, L; Pelle, C; Chiavenato, A


    Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease.

  17. Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD. (United States)

    Picker-Minh, Sylvie; Mignot, Cyril; Doummar, Diane; Hashem, Mais; Faqeih, Eissa; Josset, Patrice; Dubern, Béatrice; Alkuraya, Fowzan S; Kraemer, Nadine; Kaindl, Angela M


    Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.

  18. Effects of acute exercise on pancreatic endocrine function in subjects with type 2 diabetes

    DEFF Research Database (Denmark)

    Knudsen, Sine H; Karstoft, Kristian; Winding, Kamilla


    We determined the effects of exercise on pancreatic endocrine responses to metabolic stimuli in type 2 diabetic (T2D) subjects and examined the influence of the diabetic status. Fourteen subjects underwent a hyperglycaemic clamp with GLP-1 infusion and arginine injection, the morning after a one...... drug naïve subjects. Exercise-induced increases in insulin secretion are blunted in T2D subjects with high hyperglycaemia and in those using anti-diabetic drugs. Clinical Trials Registration Number: NCT01812590.......-hour walk or no exercise. Subjects were stratified by high and low quantiles of fasting plasma glucose (FPG) and HbA1c as well as current use/non-use of anti-diabetic medication. In the entire cohort, exercise did not alter insulin secretion, while glucagon levels were increased in all clamp phases (P 

  19. Histopathological and immunohistochemical study of exocrine and endocrine pancreatic lesions in avian influenza A experimentally infected turkeys showing evidence of pancreatic regeneration. (United States)

    Cavicchioli, Laura; Zappulli, Valentina; Beffagna, Giorgia; Caliari, Diego; Zanetti, Rossella; Nordio, Laura; Mainenti, Marta; Frezza, Federica; Bonfante, Francesco; Patrono, Livia Victoria; Capua, Ilaria; Terregino, Calogero


    In order to investigate the pancreatic lesions caused by the infection with either H7N1 or H7N3 low-pathogenicity avian influenza viruses, 28 experimentally infected turkeys were submitted for histopathology, immunohistochemistry, haematobiochemistry and real-time reverse transcriptase polymerase chain reaction after different days post-infection (DPI). The localization of viral antigen and the measurement of insulin and glucagon expression in the pancreas were assessed to verify the progression from pancreatitis to metabolic disorders, such as diabetes. At the early infection phase (4-7 DPI), a severe acute necrotizing pancreatitis was recognized. During the intermediate phase (8-17 DPI), a mixed acute/chronic change associated with regenerative ductular proliferation was observed. A loss of pancreatic islets was detected in most severe cases and viral antigen was found in the pancreas of 11/28 turkeys (4-10 DPI) with the most severe histological damage. In turkeys euthanized at 39 DPI (late phase), a chronic fibrosing pancreatitis was observed with the reestablishment of both the exocrine and the endocrine pancreas. Insulin and glucagon expression manifested a progressive decrease with subsequent ductular positivity. Haematobiochemistry revealed increased lipasemia in the first week post-infection and hyperglycaemia in the second, with a progressive normalization within 21 DPI. This study allowed the identification of progressive virus-associated exocrine and endocrine pancreatic damage, suggesting that influenza virus might be responsible for metabolic derangements. Moreover, it highlighted a remarkable post-damage hyperplastic and reparative process from a presumptive common exocrine/endocrine precursor. This potential regeneration deserves further investigation for its relevance in a therapeutic perspective to replace lost and non-functional cells in diabetes mellitus.

  20. Pancreatic neuroendocrine tumour (PNET): Staging accuracy of MDCT and its diagnostic performance for the differentiation of PNET with uncommon CT findings from pancreatic adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Hoon; Lee, Jeong Min; Han, Joon Koo; Choi, Byung-Ihn [Seoul National University Hospital, Department of Radiology, 101 Daehangno, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul (Korea, Republic of); Eun, Hyo Won [Yonsei University College of Medicine, Department of Radiology, Severance Hospital, Seodaemun-ku, Seoul (Korea, Republic of); Kim, Young Jae [Soonchunhyang University Hospital, Department of Radiology, 657 Hannam-Dong, Youngsan-Ku, Seoul (Korea, Republic of)


    To investigate staging accuracy of multidetector CT (MDCT) for pancreatic neuroendocrine tumour (PNET) and diagnostic performance for differentiation of PNET from pancreatic adenocarcinoma. We included 109 patients with surgically proven PNET (NETG1 = 66, NETG2 = 31, NEC = 12) who underwent MDCT. Two reviewers assessed stage and presence of predefined CT findings. We analysed the relationship between CT findings and tumour grade. Using PNETs with uncommon findings, we also estimated the possibility of PNET or adenocarcinoma. Accuracy for T stage was 85-88 % and N-metastasis was 83-89 %. Common findings included well circumscribed, homogeneously enhanced, hypervascular mass, common in lower grade tumours (p < 0.05). Uncommon findings included ill-defined, heterogeneously enhanced, hypovascular mass and duct dilation, common in higher grade tumours (p < 0.05). Using 31 PNETs with uncommon findings, diagnostic performance for differentiation from adenocarcinoma was 0.760-0.806. Duct dilatation was an independent predictor for adenocarcinoma (Exp(B) = 4.569). PNETs with uncommon findings were associated with significantly worse survival versus PNET with common findings (62.7 vs. 95.7 months, p < 0.001). MDCT is useful for preoperative evaluation of PNET; it not only accurately depicts the tumour stage but also prediction of tumour grade, because uncommon findings were more common in higher grade tumours. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Giulia Donadel


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

  2. The Insulin Regulatory Network in Adult Hippocampus and Pancreatic Endocrine System

    Directory of Open Access Journals (Sweden)

    Masanao Machida


    Full Text Available There is a very strong correlation between the insulin-mediated regulatory system of the central nervous system and the pancreatic endocrine system. There are many examples of the same transcriptional factors being expressed in both regions in their embryonic development stages. Hormonal signals from the pancreatic islets influence the regulation of energy homeostasis by the brain, and the brain in turn influences the secretions of the islets. Diabetes induces neuronal death in different regions of the brain especially hippocampus, causes alterations on the neuronal circuits and therefore impairs learning and memory, for which the hippocampus is responsible. The hippocampus is a region of the brain where steady neurogenesis continues throughout life. Adult neurogenesis from undifferentiated neural stem cells is greatly decreased in diabetic patients, and as a result their learning and memory functions decline. Might it be possible to reactivate stem cells whose functions have deteriorated and that are present in the tissues in which the lesions occur in diabetes, a lifestyle disease, which plagues modern humans and develops as a result of the behavior of insulin-related factor? In this paper we summarize research in regard to these matters based on examples in recent years.

  3. Palliative or curative treatments: Targeted radiotherapy of endocrine tumours; Traitements a visee palliative ou curative: la radiotherapie vectorisee des tumeurs endocrines

    Energy Technology Data Exchange (ETDEWEB)

    Vuilleza, J.P. [Centre Hospitalier Universitaire, Service de Biophysique et Medecine Nucleaire, Hopital Michallon, 38 - Grenoble (France)


    Internal targeted radiotherapy (I.T.R.), which consists in irradiation of small disseminated tumour lesions using injected radiopharmaceuticals has been for a long time successfully used for differentiated thyroid carcinoma treatment, as an adjuvant treatment after surgery, but as an efficient treatment of metastatic disease (especially lung involvement) as well. New efficient radiopharmaceuticals for tumour targeting become available, making feasible such successful I.T.R. treatment for other endocrine tumours (E.T.). Malignant pheochromocytomas have firstly been treated with {sup 131}I-meta-iodo-benzyl-guanidine (M.I.B.G.) and more recently radiolabeled ligands of somatostatin receptors (S.S.R.) which are over expressed by most of E.T. have been proved to be an effective treatment of these tumours. Moreover, radiolabelled antibodies, which have been used successfully in malignant lymphoma treatment, could have an interest in E.T., mainly medullary thyroid carcinoma. Using I.T.R. for E.T. treatment suppose clinical indications are well defined, according to the new W.H.O. classification of E.T.: only non-differentiated not eradicable and/or metastatic progressive tumours should be treated. Furthermore, efficiency of I.T.R. is greater than could be thought as minor responses and even prolonged stabilizations are now considered as positive responses. Randomized studies are still necessary, however, in order to demonstrate, beyond its efficiency, a clinical impact of I.T.R. on quality of life and survival, and to determine the right place of I.T.R. in the global therapeutic management of E.T.. (author)

  4. Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, M. A de; Pedraza L, M. [Department of Nuclear Medicine, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F. (Mexico); Rodriguez C, J. [Faculty of Medicine, UAEM, Toluca, Estado de Mexico (Mexico); Ferro F, G. [ININ, 52045 Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, Mexico D.F. (Mexico)


    Malignant pancreas tumours induced in athymic mice are a good model for targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses and to evaluate {sup 177}Lu-DOTA-TATE as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells, which over-express somatostatin receptors, were injected in athymic mice and 20 days later the mean tumour size was 3.08 square cm (n=3). A mean of 86.3 MBq {sup 177}Lu-DOTA-TATE, was injected in a tail vein and 19 days after therapy the size of the tumours was 0.81 square cm. There was a partial relapse and after 16 days, when sacrificed, the mean tumour size was 8.28 cubic cm. An epithelial and sarcoma mixed tumour in the kidney of one treated mouse was found. The tumour of the control mouse was 8.61 cubic cm when sacrificed 14 days after tumour induction. Radiotherapy estimates to the tumours was 35.9-39.7 Gy and the tumours might have been completely reduced with a second therapy dose. These preliminary studies justify further therapeutic and dosimetry estimations to ensure that Lu-{sup 177}-DOTA-TATE will act as expected in man, considering kidney radiation. (Author)

  5. FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

    Energy Technology Data Exchange (ETDEWEB)

    Abasolo, Ibane [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Pujal, Judit; Navarro, Pilar [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Rabanal, Rosa M.; Serafin, Anna [Universitat Autonoma de Barcelona, Departament de Medicina i Cirurgia Animals, Barcelona (Spain); Millan, Olga [Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Real, Francisco X. [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Programa de Patologia Molecular, Centro Nacional de Investigaciones Oncologicas, Madrid (Spain)


    The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

  6. High-intensity focused ultrasound (HIFU) for pancreatic carcinoma: evaluation of feasibility, reduction of tumour volume and pain intensity. (United States)

    Marinova, Milka; Rauch, Maximilian; Mücke, Martin; Rolke, Roman; Gonzalez-Carmona, Maria A; Henseler, Jana; Cuhls, Henning; Radbruch, Lukas; Strassburg, Christian P; Zhang, Lian; Schild, Hans H; Strunk, Holger M


    Prognosis of patients with locally advanced pancreatic adenocarcinoma is extremely poor. They often suffer from cancer-related pain reducing their quality of life. This prospective observational study aimed to evaluate feasibility, local tumour response, and changes in quality of life and symptoms in Caucasian patients with locally advanced pancreatic cancer treated by ultrasound-guided high-intensity focused ultrasound (HIFU). Thirteen patients underwent HIFU, five with stage III, eight with stage IV UICC disease. Ten patients received simultaneous palliative chemotherapy. Postinterventional clinical assessment included evaluation of quality of life and symptom changes using standardized questionnaires. CT and MRI follow-up evaluated the local tumour response. HIFU was successfully performed in all patients. Average tumour reduction was 34.2 % at 6 weeks and 63.9 % at 3 months. Complete or partial relief of cancer-related pain was achieved in 10 patients (77 %), five of whom required less analgesics for pain control. Quality of life was improved revealing increased global health status and alleviated symptoms. HIFU treatment was well tolerated. Eight patients experienced transient abdominal pain directly after HIFU. HIFU ablation of pancreatic carcinoma is a feasible, safe and effective treatment with a crucial benefit in terms of reduction of tumour volume and pain intensity. • US-guided HIFU is feasible and safe for patients with unresectable pancreatic cancer. • HIFU can considerably reduce tumour volume and cancer-related pain. • Patients treated with HIFU experienced significant and lasting reduction of pain intensity. • HIFU has a crucial clinical benefit for patients with pancreatic cancer.

  7. A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer (United States)

    Ohnmacht, Stephan A; Marchetti, Chiara; Gunaratnam, Mekala; Besser, Rachael J; Haider, Shozeb M; Di Vita, Gloria; Lowe, Helen L; Mellinas-Gomez, Maria; Diocou, Seckou; Robson, Mathew; Šponer, Jiri; Islam, Barira; Barbara Pedley, R; Hartley, John A; Neidle, Stephen


    We report here that a tetra-substituted naphthalene-diimide derivative (MM41) has significant in vivo anti-tumour activity against the MIA PaCa-2 pancreatic cancer xenograft model. IV administration with a twice-weekly 15 mg/kg dose produces ca 80% tumour growth decrease in a group of tumour-bearing animals. Two animals survived tumour-free after 279 days. High levels of MM41 are rapidly transported into cell nuclei and were found to accumulate in the tumour. MM41 is a quadruplex-interactive compound which binds strongly to the quadruplexes encoded in the promoter sequences of the BCL-2 and k-RAS genes, both of which are dis-regulated in many human pancreatic cancers. Levels of BCL-2 were reduced by ca 40% in tumours from MM41-treated animals relative to controls, consistent with BCL-2 being a target for MM41. Molecular modelling suggests that MM41 binds to a BCL-2 quadruplex in a manner resembling that previously observed in co-crystal structures with human telomeric quadruplexes. This supports the concept that MM41 (and by implication other quadruplex-targeting small molecules) can bind to quadruplex-forming promoter regions in a number of genes and down-regulate their transcription. We suggest that quadruplexes within those master genes that are up-regulated drivers for particular cancers, may be selective targets for compounds such as MM41. PMID:26077929

  8. The transcriptional co-repressor Grg3/Tle3 promotes pancreatic endocrine progenitor delamination and β-cell differentiation (United States)

    Metzger, David E.; Gasperowicz, Malgorzata; Otto, Florian; Cross, James C.; Gradwohl, Gerard; Zaret, Kenneth S.


    Pancreatic β-cells arise from Ngn3+ endocrine progenitors within the trunk epithelium of the embryonic pancreas. The emergence of endocrine cells requires E-cadherin downregulation, but the crucial steps that elicit such are not clear, yet probably important for ultimately being able to efficiently generate β-cells de novo from stem cells. Grg3 (groucho-related gene 3, also known as Tle3), encodes a member of the Groucho/TLE family of co-repressors and its function in various cell contexts is mediated by recruitment to target genes by different transcription factors. Grg proteins broadly regulate the progression of progenitor cells to differentiated cell types, but specific developmental mechanisms have not been clear. We find that Grg3 is expressed in most β-cells and a subset of other endocrine cell types in the pancreas. Grg3 is highly expressed in Ngn3+ endocrine progenitor descendants just after transient Ngn3 expression. Grg3-null embryos die at E14.5, which is associated with placental defects, so we explanted E12.5 pancreata to allow endocrine differentiation to occur in culture. Grg3 knockout explants displayed a drastic decrease in the differentiation of all endocrine cell types owing to defects in the delamination of early endocrine progenitors from the trunk epithelium. We find that Grg3 normally suppresses E-cadherin gene expression, thereby allowing delamination of endocrine cells from the trunk epithelium and revealing how this transcriptional co-repressor modulates this crucial step of β-cell development. PMID:22434868


    Nweke, E N; Ntwasa, M N; Brand, M B; Devar, J D; Smith, M D; Candy, G P


    Pancreatic cancer (PDAC) is a deadly type of cancer with almost an equal amount of new cases and deaths observed yearly. It accounts for about 7% of cancer-related deaths worldwide. In many multi-racial societies including South Africa, the black population has the highest incidence rate. Less than 5% of PDAC patients live up to 5 years. The lack of specific and sensitive diagnostic PDAC biomarkers is strongly responsible for this poor statistic. The discovery of differentially expressed genes and proteins associated with PDAC is crucial to elucidating this condition and may lead to biomarker finding and further understanding of the disease. Tissue samples were obtained from Black South African PDAC patients during the Whipple procedure. Using focused arrays and RNA Sequencing, we have shown differentially expressed genes and proteins between tumour and normal tissue samples of PDAC patients in the quest for potential biomarker discovery. Furthermore, we utilised multiple bioinformatics tools to identify pathways and biological processes enriched by differentially expressed genes/proteins, and to discover novel variants and novel potential PDAC biomarkers. Real-time PCR and ELISA were also employed to validate our novel potential PDAC biomarker. We have identified novel 1) potential transcriptomic and 2) proteomic biomarkers of pancreatic cancer. Our identified transcriptomic biomarker has a sensitivity and specificity of 100% and 80% respectively. Furthermore, we observed novel genetic variants and dysregulated pathways occurring during pancreatic carcinogenesis. This study has identified novel potential biomarkers which can help in the diagnosis of PDAC. Information obtained from enriched signalling pathways help in further understanding the biology of PDAC. Going forward, the identified novel potential biomarkers need to be further validated in a larger sample number using easily accessible samples like blood.

  10. Magnetic catechin-dextran conjugate as targeted therapeutic for pancreatic tumour cells. (United States)

    Vittorio, Orazio; Voliani, Valerio; Faraci, Paolo; Karmakar, Biswajit; Iemma, Francesca; Hampel, Silke; Kavallaris, Maria; Cirillo, Giuseppe


    Catechin-dextran conjugates have recently attracted a lot of attention due to their anticancer activity against a range of cancer cells. Magnetic nanoparticles have the ability to concentrate therapeutically important drugs due to their magnetic-spatial control and provide opportunities for targeted drug delivery. Enhancement of the anticancer efficiency of catechin-dextran conjugate by functionalisation with magnetic iron oxide nanoparticles. Modification of the coating shell of commercial magnetic nanoparticles (Endorem) composed of dextran with the catechin-dextran conjugate. Catechin-dextran conjugated with Endorem (Endo-Cat) increased the intracellular concentration of the drug and it induced apoptosis in 98% of pancreatic tumour cells placed under magnetic field. The conjugation of catechin-dextran with Endorem enhances the anticancer activity of this drug and provides a new strategy for targeted drug delivery on tumour cells driven by magnetic field. The ability to spatially control the delivery of the catechin-dextran by magnetic field makes it a promising agent for further application in cancer therapy.

  11. Targeting somatostatin receptors in gastro entero pancreatic neuroendocrine tumours (G.E.P.N.E.T.): Which radiotracers for which tumours?;Ciblage des recepteurs de la somatostatine dans les tumeurs neuroendocrines gastroenteropancreatiques (TNE-GEP): quels radiotraceurs pour quelles tumeurs?

    Energy Technology Data Exchange (ETDEWEB)

    Cuny, T.; Saveanu, A.; Barlier, A. [CRN2M, UMR 6231, CNRS, laboratoire de neurobiologie et neurophysiologie de Marseille, faculte de medecine, 13 - Marseille (France); Saveanu, A.; Barlier, A. [Hotal de la Conception Assistance publique-hopitaux de Marseille, Laboratoire de biochimie, biologie moleculaire, 13 - Marseille (France); Taieb, D. [Hopital de la Timone, Assistance publique des hopitaux de Marseille, Service de medecine nucleaire, 13 - Marseille (France)


    Topographic and functional imaging hold a key position in endocrine oncology. In vivo somatostatin receptor scintigraphy using Indium-111 labeled DTPA-octreotide, a tracer with preferential affinity for the somatostatin receptor subtype 2 (sst2), is the gold-standard for initial diagnosis of gastro entero pancreatic neuroendocrine tumours (G.E.P.N.E.T.). Due to the detection limits of scintigraphy, other metabolic imaging modalities are required. Positron emission topography (PET) offers whole body scanning, facilitates tumour localization, and assesses the metastasis statement of the tumour. {sup 18}F-F.D.G. is the most frequent radiotracer used in clinical practice because of its availability, but its interest is demonstrated only in undifferentiated G.E.P.N.E.T.. More recently, {sup 18}F-DOPA PET showed a high sensitivity in particular in carcinoid tumours detection. PET using different {sup 68}Ga-labeled-somatostatin analogs with high affinity for sst2 displayed better results than somatostatin receptors scintigraphy (S.R.S.) in G.E.P.N.E.T. primary tumour and metastasis detection, especially when fusion with computerized tomography images was performed. Using similar metabolic targets, peptide receptor radionuclide therapy (P.R.R.T.) with {sup 177}Lu-octreotate and {sup 90}Y-DOTA-TOC, is indicated in disseminated G.E.P.N.E.T. forms with an efficiency of 30 % and a minor toxicity. (authors)

  12. Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors

    DEFF Research Database (Denmark)

    Bonnavion, Rémy; Teinturier, Romain; Jaafar, Rami


    The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have...

  13. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

    DEFF Research Database (Denmark)

    Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir


    signaling promotes the expression of Sox9, which cell-autonomously activates the pro-endocrine gene Ngn3. However, at high Notch activity endocrine differentiation is blocked, as Notch also induces expression of the Ngn3 repressor Hes1. At the transition from high to intermediate Notch activity, only Sox9......, but not Hes1, is maintained, thus de-repressing Ngn3 and initiating endocrine differentiation. In the absence of Sox9 activity, endocrine and ductal cells fail to differentiate, resulting in polycystic ducts devoid of primary cilia. Although Sox9 is required for Ngn3 induction, endocrine differentiation...

  14. Multidetector CT of pancreatic ductal adenocarcinoma: Effect of tube voltage and iodine load on tumour conspicuity and image quality

    Energy Technology Data Exchange (ETDEWEB)

    Loizou, L.; Leidner, B.; Axelsson, E.; Fischer, M.A.; Grigoriadis, A.; Kartalis, N. [Karolinska Institutet, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden); C1-46 Karolinska University Hospital Huddinge, Department of Radiology, Stockholm (Sweden); Albiin, N. [Karolinska Institutet, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden); Ersta Hospital, Department of Radiology, Stockholm (Sweden); Del Chiaro, M.; Segersvaerd, R. [Karolinska University Hospital Huddinge, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Center for Digestive Diseases, Stockholm (Sweden); Verbeke, C. [Karolinska Institutet and Karolinska University Hospital Huddinge, Division of Pathology, Department of Laboratory Medicine, Stockholm (Sweden); Sundin, A. [Uppsala University Hospital, Department of Surgical Sciences, Division of Radiology, Uppsala University and Department of Radiology, Uppsala (Sweden)


    To compare a low-tube-voltage with or without high-iodine-load multidetector CT (MDCT) protocol with a normal-tube-voltage, normal-iodine-load (standard) protocol in patients with pancreatic ductal adenocarcinoma (PDAC) with respect to tumour conspicuity and image quality. Thirty consecutive patients (mean age: 66 years, men/women: 14/16) preoperatively underwent triple-phase 64-channel MDCT examinations twice according to: (i) 120-kV standard protocol (PS; 0.75 g iodine (I)/kg body weight, n = 30) and (ii) 80-kV protocol A (PA; 0.75 g I/kg, n = 14) or protocol B (PB; 1 g I/kg, n = 16). Two independent readers evaluated tumour delineation and image quality blindly for all protocols. A third reader estimated the pancreas-to-tumour contrast-to-noise ratio (CNR). Statistical analysis was performed with the Chi-square test. Tumour delineation was significantly better in PB and PA compared with PS (P = 0.02). The evaluation of image quality was similar for the three protocols (all, P > 0.05). The highest CNR was observed with PB and was significantly better compared to PA (P = 0.02) and PS (P = 0.0002). In patients with PDAC, a low-tube-voltage, high-iodine-load protocol improves tumour delineation and CNR leading to higher tumour conspicuity compared to standard protocol MDCT. (orig.)

  15. Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

    DEFF Research Database (Denmark)

    Lemaire, Laurence A; Goulley, Joan; Kim, Yung Hae


    that PKD2 functions downstream of BICC1 in preventing cyst formation in the pancreas. Moreover, the analysis highlights immune cell infiltration and stromal reaction developing early in the pancreas of Bicc1 knockout mice. In addition to these functions in duct morphogenesis, BICC1 regulates NEUROG3......(+) endocrine progenitor production. Its deletion leads to a late but sustained endocrine progenitor decrease, resulting in a 50% reduction of endocrine cells. We show that BICC1 functions downstream of ONECUT1 in the pathway controlling both NEUROG3(+) endocrine cell production and ductal morphogenesis...

  16. Role of {sup 68}Ga-DOTATOC PET-CT in the diagnosis and staging of pancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rakesh; Sharma, Punit; Karunanithi, Sellam; Naswa, Niraj; Lata, Sneh; Malhotra, Arun [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Garg, Pramod [All India Institute of Medical Sciences, Department of Gastroenterology and Human Nutrition, New Delhi (India); Sharma, Raju; Thulkar, Sanjay [All India Institute of Medical Sciences, Department of Radiodiagnosis, New Delhi (India)


    The objective of the present study was to evaluate the role of {sup 68}Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide ({sup 68}Ga-DOTATOC) positron emission tomography computed tomography (PET-CT) for detection and staging of pancreatic neuroendocrine tumours (NETs). Twenty patients with clinically suspected and/or histopathologically proven pancreatic NET underwent {sup 68}Ga-DOTATOC PET-CT imaging for staging and /or localisation of primary lesion. They also underwent contrast enhanced CT (CECT) and 8 patients underwent {sup 18}F-FDG PET-CT. SUVmax of primary and metastatic lesions were measured. Results were verified with histopathology for primary tumour and with clinical follow up/MRI and /or biopsy for metastatic disease. Results of {sup 68}Ga-DOTATOC PET-CT were compared to CECT and {sup 18}F-FDG PET-CT. {sup 68}Ga-DOTATOC PET-CT correctly localised primary in all 20, CECT in 15 and {sup 18}F-FDG PET-CT in 2 patients. {sup 68}Ga-DOTATOC PET-CT demonstrated metastases in 13 patients, CECT in 7 and {sup 18}F-FDG PET-CT in 2. {sup 68}Ga-DOTATOC PET-CT emerged as the best investigation with 100% sensitivity and PPV for detecting primary tumour and metastatic disease. The detection rate of CECT was lower than {sup 68}Ga-DOTATOC PET-CT, both for primary tumour (20vs.15) or metastatic disease (13vs.7). {sup 18}F-FDG PET-CT performed poorly for primary and metastasis. Ga-DOTATOC PET-CT is a very useful imaging investigation for diagnosing and staging pancreatic NET. (orig.)

  17. Altered distribution of metaplastic Paneth, gastrin and pancreatic acinar cells in atrophic gastritic mucosa with endocrine cell lesions. (United States)

    Deveci, M Salih; Deveci, Güzin


    The mechanism of progression from gastric endocrine cell hyperplasias (ECHs) to carcinoid tumor (GCT) is still unknown. In these lesions, the distribution of metaplastic Paneth, gastrin and pancreatic acinar cells developing due to consequences of corporal mucosal atrophy has not been investigated in detail. In this study, 33 gastric endoscopic biopsies with endocrine cell lesions were examined. In all cases except 6 with solitary GCT, complete-type (small intestine) intestinal metaplasia (IM) with Paneth cells was observed. The density of lysozyme-positive Paneth cells in IMs in cases with GCTs was less than those in ECH alone. The density of gastrin-positive cells in IMs and average number of micronodules of ECHs were similar. Pancreatic acinar metaplasia (PAM) was observed in 6 cases of GCTs with ECH. The size of GCTs with ECH was smaller than those without ECH. By image analysis, the percentage of Ki67 (MIB-1, proliferation marker) expressing cells of GCTs with ECH was 5.1+/-0.6%, and GCT without ECH 7.8+/-1%. Our results indicate that few Paneth cells and many PAMs in atrophic corporal mucosa are seen more frequently in cases of GCTs with ECH, compared to those in ECH alone. Gastrin-positive cells in the corporal IM may stimulate enterochromaffin-like (ECL) cells, which may induce hyperplasia, dysplasia or neoplasia by augmenting the effects of hypergastrinemia through a paracrine mechanism on local gastrin-sensitive cells.

  18. Pancreatic endocrine tumors or apudomas Tumores endocrinos o apudomas pancreáticos

    Directory of Open Access Journals (Sweden)

    Modesto Varas


    Full Text Available Introduction and objective: pancreatic endocrine tumors (PET are difficult to diagnose. Their accurate localization using imaging techniques is intended to provide a definite cure. The goal of this retrospective study was to review a PET series from a private institution. Patients and methods: the medical records of 19 patients with PETs were reviewed, including 4 cases of MEN-1, for a period of 17 years (1994-2010. A database was set up with ten parameters: age, sex, symptoms, imaging techniques, size and location in the pancreas, metastasis, surgery, complications, adjuvant therapies, definite diagnosis, and survival or death. Results: a total of 19 cases were analyzed. Mean age at presentation was 51 years (range: 26-67 y (14 males, 5 females, and tumor size was 5 to 80 mm (X: 20 mm. Metastatic disease was present in 37% (7/19. Most underwent the following imaging techniques: ultrasounds, computed tomography (CT and magnetic resonance imaging (MRI. Fine needle aspiration punction (FNA was performed for the primary tumor in 4 cases. Non-functioning: 7 cases (37%, insulinoma: 2 cases [1 with possible multiple endocrine neoplasia (MEN], Zollinger-Ellison syndrome (ZES from gastrinoma: 5 (3 with MEN-1, glucagonoma: 2 cases, 2 somatostatinomas; carcinoid: 1 case with carcinoide-like syndrome. Most patients were operated upon: 14/19 (73%. Four (4/14: 28% has postoperative complications following pancreatectomy: pancreatitis, pseudocyst, and abdominal collections. Some patients received chemotherapy (4, somatostatin (3 and interferon (2 before or after surgery. Median follow-up was 48 months. Actuarial survival during the study was 73.6% (14/19. Conclusions: age was similar to that described in the literature. Males were predominant. Most cases were non-functioning (37%. Most patients underwent surgery (73% with little morbidity (28% and an actuarial survival of 73.6% at the time of the study.Introducción y objetivo: los tumores endocrinos pancre

  19. Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours). (United States)

    Kos-Kudła, Beata; Blicharz-Dorniak, Jolanta; Strzelczyk, Janusz; Bałdys-Waligórska, Agata; Bednarczuk, Tomasz; Bolanowski, Marek; Boratyn-Nowicka, Agnieszka; Borowska, Małgorzata; Cichocki, Andrzej; Ćwikła, Jarosław B; Falconi, Massimo; Foltyn, Wanda; Handkiewicz-Junak, Daria; Hubalewska-Dydejczyk, Alicja; Jarząb, Barbara; Junik, Roman; Kajdaniuk, Dariusz; Kamiński, Grzegorz; Kolasińska-Ćwikła, Agnieszka; Kowalska, Aldona; Król, Robert; Królicki, Leszek; Krzakowski, Maciej; Kunikowska, Jolanta; Kuśnierz, Katarzyna; Lampe, Paweł; Lange, Dariusz; Lewczuk-Myślicka, Anna; Lewiński, Andrzej; Lipiński, Michał; Londzin-Olesik, Magdalena; Marek, Bogdan; Nasierowska-Guttmejer, Anna; Nawrocki, Sergiusz; Nowakowska-Duława, Ewa; Pilch-Kowalczyk, Joanna; Rosiek, Violetta; Ruchała, Marek; Siemińska, Lucyna; Sowa-Staszczak, Anna; Starzyńska, Teresa; Steinhof-Radwańska, Katarzyna; Sworczak, Krzysztof; Syrenicz, Anhelli; Szawłowski, Andrzej; Szczepkowski, Marek; Wachuła, Ewa; Zajęcki, Wojciech; Zemczak, Anna; Zgliczyński, Wojciech; Zieniewicz, Krzysztof


    Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Żelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.

  20. Exogenous leptin protects rat models of sodium taurocholate‑induced severe acute pancreatitis through endocrinal and immunological pathways. (United States)

    Qi, Haiyu; Lu, Qin; Yin, Chenghong; Xiao, Hongli; Wen, Yan; Zhang, Shuwen; Cui, Qu; Yang, Wei


    group showed significantly alleviated pancreatic inflammation. In addition, the pancreatic expression of OB‑Rb in the LEP group was significantly higher, compared with that in the SAP group at 24 and 48 h. No significant difference in 3‑day mortality rates were observed between the SAP group and the LEP group. Taken together, exogenous leptin administration regulated inflammatory factors and the expression of OB‑Rb at the early stage of AP, which exerted protective effects by through the immunological and endocrinal pathways.

  1. Diagnosis and Management of Multiple Endocrine Neoplasia Type 1 (MEN1

    Directory of Open Access Journals (Sweden)

    Dreijerink Koen MA


    Full Text Available Abstract Multiple endocrine neoplasia type 1 (MEN1 is an autosomal dominantly inherited disorder, characterised by the occurrence of tumours of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands and neuroendocrine carcinoid tumours. Carcinoid tumours of the thymus and pancreatic-duodenal gastrinomas are the most harmful tumour types, since these tumours have malignant potential and curative treatment is difficult to achieve. MEN1 is caused by germline mutations of the MEN1 tumour suppressor gene. Mutation analysis enables mutation carriers to be identified. MEN1 patients and their family members, family members of mutation carriers and patients who are clinically suspected to be carriers of a MEN1 gene mutation are eligible for mutation analysis. MEN1-associated tumours can be detected and treated at an early stage through periodical clinical monitoring of mutation carriers.

  2. PDX1- and NGN3-mediated in vitro reprogramming of human bone marrow-derived mesenchymal stromal cells into pancreatic endocrine lineages

    DEFF Research Database (Denmark)

    Limbert, Catarina; Päth, Günter; Ebert, Regina


    Reprogramming of multipotent adult bone marrow (BM)-derived mesenchymal stromal/stem cells (MSC) (BM-MSC) represents one of several strategies for cell-based therapy of diabetes. However, reprogramming primary BM-MSC into pancreatic endocrine lineages has not yet been consistently demonstrated....

  3. Prediction of pancreatic neuroendocrine tumour grade with MR imaging features: added value of diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lotfalizadeh, Emad; Vullierme, Marie-Pierre; Allaham, Wassim [University Hospitals Paris Nord Val de Seine, Department of Radiology, Clichy, Hauts-de-Seine (France); Ronot, Maxime; Vilgrain, Valerie [University Hospitals Paris Nord Val de Seine, Department of Radiology, Clichy, Hauts-de-Seine (France); University Paris Diderot, Paris (France); INSERM U1149, Centre de Recherche Biomedicale Bichat-Beaujon, CRB3, Paris (France); Wagner, Mathilde [University Hospitals Paris Nord Val de Seine, Department of Radiology, Clichy, Hauts-de-Seine (France); INSERM U1149, Centre de Recherche Biomedicale Bichat-Beaujon, CRB3, Paris (France); Cros, Jerome; Couvelard, Anne [University Paris Diderot, Paris (France); University Hospitals Paris Nord Val de Seine, Department of Pathology, Clichy, Hauts-de-Seine (France); Hentic, Olivia; Ruzniewski, Philippe [University Hospitals Paris Nord Val de Seine, Department of Gastroenterology, Clichy, Hauts-de-Seine (France)


    To evaluate the value of MR imaging including diffusion-weighted imaging (DWI) for the grading of pancreatic neuroendocrine tumours (pNET). Between 2006 and 2014, all resected pNETs with preoperative MR imaging including DWI were included. Tumour grading was based on the 2010 WHO classification. MR imaging features included size, T1-w, and T2-w signal intensity, enhancement pattern, apparent (ADC) and true diffusion (D) coefficients. One hundred and eight pNETs (mean 40 ± 33 mm) were evaluated in 94 patients (48 women, 51 %, mean age 52 ± 12). Fifty-five (51 %), 42 (39 %), and 11 (10 %) tumours were given the following grades (G): G1, G2, and G3. Mean ADC and D values were significantly lower as grade increased (ADC: 2.13 ± 0.70, 1.78 ± 0.72, and 0.86 ± 0.22 10{sup -3} mm{sup 2}/s, and D: 1.92 ± 0.70, 1.75 ± 0.74, and 0.82 ± 0.19 10{sup -3} mm{sup 2}/s G1, G2, and G3, all p < 0.001). A higher grade was associated with larger sized tumours (p < 0.001). The AUROC of ADC and D to differentiate G3 and G1-2 were 0.96 ± 0.02 and 0.95 ± 0.02. Optimal cut-off values for the identification of G3 were 1.19 10{sup -3} mm{sup 2}/s for ADC (sensitivity 100 %, specificity 92 %) and 1.04 10{sup -3} mm{sup 2}/s for D (sensitivity 82 %, specificity 92 %). Morphological/functional MRI features of pNETS depend on tumour grade. DWI is useful for the identification of high-grade tumours. (orig.)

  4. Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy. (United States)

    Di Caro, Giuseppe; Cortese, Nina; Castino, Giovanni Francesco; Grizzi, Fabio; Gavazzi, Francesca; Ridolfi, Cristina; Capretti, Giovanni; Mineri, Rossana; Todoric, Jelena; Zerbi, Alessandro; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica


    Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  5. Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez C, J.; Murphy, C.A. de; Pedraza L, M. [Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, 14000 Mexico D.F. (Mexico); Ferro F, G. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, 06000 Mexico D.F. (Mexico)


    Malignant pancreas tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses after administration of {sup 177}Lu-DOTA-TATE in mice as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (n=18) to obtain the {sup 177}Lu-DOTA-TATE biokinetics and dosimetry. To estimate its therapeutic efficacy 87 MBq were injected in a tail vein of 3 mice and 19 days p.i. there were a partial relapse. There was an epithelial and sarcoma mixed tumour in the kidneys of mouse III. The absorbed dose to tumour, kidney and pancreas was 50.5 {+-} 7.2 Gy, 17.5 {+-} 2.5 Gy and 12.6 {+-} 2.3 Gy respectively. These studies justify further therapeutic and dosimetry estimations to ensure that {sup 177}Lu-DOTA-TATE will act as expected in man considering its kidney radiotoxicity. (Author)

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Pancreatic endocrine and exocrine function in children following near-total pancreatectomy for diffuse congenital hyperinsulinism. (United States)

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


    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 1total 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.

  8. [Two cases of a nonfunctioning pancreatic endocrine tumor found on a medical checkup]. (United States)

    Nio, Kouki; Shimakami, Tetsuro; Yamashita, Taro; Kagaya, Takashi; Sakai, Yoshio; Yamashita, Tatsuya; Mizukoshi, Eishiro; Sakai, Akito; Nakamoto, Yasunari; Honda, Masao; Kaneko, Shuichi; Kitagawa, Hirohisa; Kayahara, Masato; Ohta, Tetsuo; Zen, Yo


    Case 1) A 35-year-old man was admitted to our hospital for detailed examination of a 50-mm pancreas head tumor with surrounding lymph node swelling detected on medical checkup images. Ultrasound-guided lymph node biopsy specimens gave a diagnosis of a nonfunctioning pancreatic neuroendocrine cancer, and adjuvant systemic chemotherapy was given after surgical resection of the tumor. Case 2) A 52-year-old man was admitted to our hospital for detailed examination of an 18-mm pancreas head tumor detected by medical checkup FDG-PET images. Imaging tests gave a diagnosis of a nonfunctioning pancreatic neuroendocrine tumor. He underwent surgical resection, and the tumor was diagnosed as benign pathologically. Both cases showed FDG-PET accumulation in the tumors irrespective of their malignant or benign nature. Increased prevalence of FDG-PET checkup may increase the diagnosis of pancreatic neuroendocrine tumor in asymptomatic subjects.

  9. Immunohistochemical localization of glucagon and pancreatic polypeptide on rat endocrine pancreas: coexistence in rat islet cells

    Directory of Open Access Journals (Sweden)

    YH Huang


    Full Text Available We used immunofluorescence double staining method to investigate the cellular localization of glucagon and pancreatic polypeptide (PP in rat pancreatic islets. The results showed that both A-cells (glucagon-secreting cells and PP-cells (PPsecreting cells were located in the periphery of the islets. However, A-cells and PP-cells had a different regional distribution. Most of A-cells were located in the splenic lobe but a few of them were in the duodenal lobe of the pancreas. In contrast, the majority of PP-cells were found in the duodenal lobe and a few of them were in the splenic lobe of the pancreas. Furthermore, we found that 67.74% A-cells had PP immunoreactivity, 70.92% PP-cells contained glucagon immunoreactivity with immunofluorescence double staining. Our data support the concept of a common precursor stem cell for pancreatic hormone-producing cells.

  10. Preoperative Imaging Overestimates the Tumor Size in Pancreatic Neuroendocrine Neoplasms Associated with Multiple Endocrine Neoplasia Type 1. (United States)

    Polenta, V; Slater, E P; Kann, P H; Albers, M B; Manoharan, J; Ramaswamy, A; Mahnken, A H; Bartsch, D K


    Radiological tumor size of non-functioning pancreatic neuroendocrine neoplasms (Nf-pNENs) associated with multiple endocrine neoplasia type 1 (MEN1) is a crucial parameter to indicate surgery. The aim of this study was to compare radiological size (RS) and pathologic size (PS) of MEN1 associated with pNENs. Prospectively collected data of MEN1 patients who underwent pancreatic resections for pNENs were retrospectively analyzed. RS was defined as the largest tumor diameter measured on endoscopic ultrasound (EUS), magnetic resonance imaging (MRI) or computed tomography (CT). PS was defined as the largest tumor diameter on pathological analysis. Student's t test and linear regression analysis were used to compare the median RS and PS. p  20 mm had in reality a PS < 20 mm. MRI was the imaging technique that best correlated with PS in the total cohort (r = 0.8; p < 0.0001), whereas EUS was the best correlating imaging tool in pNENs < 20 mm (r = 0.5; p = 0.0001). Preoperative imaging, especially EUS, frequently overestimates the size of MEN1-pNENs, especially those with a PS < 20 mm. This should be considered when indicating surgery in MEN1 patients with small Nf-pNENs.

  11. Role of endocrine disrupting chemicals on the tissue levels of AhR and sex steroid receptors in breast tumours

    Directory of Open Access Journals (Sweden)

    Sepideh Arbabi Bidgoli


    Full Text Available Breast cancer affects Iranian women at least one decade younger than their counterparts in other countries and the incidence of breast fibroadenoma is growing in the last two decades in Tehran. This study aimed to compare the AhR levels in premenopausal breast cancer and breast fibroadnemo with appropriate normal groups. Possible associations of AhR with lifestyle and reproductive risk factors and other fundamental genes of breast cancer and reproductive disorders were the other major goals of present study. To conduct the comparisons all possible reproductive, environmental and lifestyle risk factors of mentioned diseases were recorded in 100 breast cancer, 100 breast fibroadenoma and compared with 400 women in normal group from 2009 to 2011. AhR overexpression in epithelial cells of premenopausal patients emphasized the susceptibility of these cells to environmental induced reproductive disorders. The AhR overexpression was contributed to ER-/PgR- immunophenotype in malignant tissues. Weight gain (after 18 and after pregnancy, long term (>5yrs OCP consumption, smoking, severe stress ,history of ovarian cysts, hormonal deregulations, living near PAHs producing sources, were correlated with increased risk of breast cancer and reproductive disorders and were correlated with elevated tissue levels of AhR. It seems that increased risk of breast cancer and other reproductive tumours in Tehran may be the result of exposure to environmental endocrine disruptors. Long term exposure to environmental estrogens can increase the tissue levels of AhR and deregulate the expression pattern of sex steroid receptors and other genes in target tissues.

  12. Risk and protective factors for the occurrence of sporadic pancreatic endocrine neoplasms. (United States)

    Valente, Roberto; Hayes, Alastair J; Haugvik, Sven-Petter; Hedenström, Per; Siuka, Darko; Korsæth, Emilie; Kämmerer, Daniel; Robinson, Stuart M; Maisonneuve, Patrick; Delle Fave, Gianfranco; Lindkvist, Bjorn; Capurso, Gabriele


    Pancreatic neuroendocrine neoplasms (PNENs) represent 10% of all pancreatic tumors by prevalence. Their incidence has reportedly increased over recent decades in parallel with that of pancreatic adenocarcinoma. PNENs are relatively rare, and of the few institutions that have published potential risk factors, findings have been heterogeneous. Our objective was to investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions. A multinational European case-control study was conducted to examine the association of selected environmental, family and medical exposure factors using a standardized questionnaire in face-to-face interviews. A ratio of 1:3 cases to controls were sex and age matched at each study site. Adjusted univariate and multivariate logistic regression analysis were performed for statistically significant factors. The following results were obtained: In 201 cases and 603 controls, non-recent onset diabetes (OR 2.09, CI 1.27-3.46) was associated with an increased occurrence of PNENs. The prevalence of non-recent onset diabetes was higher both in cases with metastatic disease (TNM stage III-IV) or advanced grade (G3) at the time of diagnosis. The use of metformin in combination with insulin was also associated with a more aggressive phenotype. Drinking coffee was more frequent in cases with localized disease at diagnosis. Our study concluded that non-recent onset diabetes was associated with an increased occurrence of PNENs and the combination of metformin and insulin was consistent with a more aggressive PNEN phenotype. In contrast to previous studies, smoking, alcohol and first-degree family history of cancer were not associated with PNEN occurrence. © 2017 Society for Endocrinology.

  13. Lack of Association for Reported Endocrine Pancreatic Cancer Risk Loci in the PANDoRA Consortium. (United States)

    Campa, Daniele; Obazee, Ofure; Pastore, Manuela; Panzuto, Francesco; Liço, Valbona; Greenhalf, William; Katzke, Verena; Tavano, Francesca; Costello, Eithne; Corbo, Vincenzo; Talar-Wojnarowska, Renata; Strobel, Oliver; Zambon, Carlo Federico; Neoptolemos, John P; Zerboni, Giulia; Kaaks, Rudolf; Key, Timothy J; Lombardo, Carlo; Jamroziak, Krzysztof; Gioffreda, Domenica; Hackert, Thilo; Khaw, Kay-Tee; Landi, Stefano; Milanetto, Anna Caterina; Landoni, Luca; Lawlor, Rita T; Bambi, Franco; Pirozzi, Felice; Basso, Daniela; Pasquali, Claudio; Capurso, Gabriele; Canzian, Federico


    Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms for which very little is known about either environmental or genetic risk factors. Only a handful of association studies have been performed so far, suggesting a small number of risk loci.Methods: To replicate the best findings, we have selected 16 SNPs suggested in previous studies to be relevant in PNET etiogenesis. We genotyped the selected SNPs (rs16944, rs1052536, rs1059293, rs1136410, rs1143634, rs2069762, rs2236302, rs2387632, rs3212961, rs3734299, rs3803258, rs4962081, rs7234941, rs7243091, rs12957119, and rs1800629) in 344 PNET sporadic cases and 2,721 controls in the context of the PANcreatic Disease ReseArch (PANDoRA) consortium.Results: After correction for multiple testing, we did not observe any statistically significant association between the SNPs and PNET risk. We also used three online bioinformatic tools (HaploReg, RegulomeDB, and GTEx) to predict a possible functional role of the SNPs, but we did not observe any clear indication.Conclusions: None of the selected SNPs were convincingly associated with PNET risk in the PANDoRA consortium.Impact: We can exclude a major role of the selected polymorphisms in PNET etiology, and this highlights the need for replication of epidemiologic findings in independent populations, especially in rare diseases such as PNETs. Cancer Epidemiol Biomarkers Prev; 26(8); 1349-51. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Pancreatitis (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 ...

  15. Differentiation of pancreatic serous cystadenoma from endocrine tumor and intraductal papillary mucinous neoplasm based on washout pattern on multiphase CT. (United States)

    Sahara, Shinya; Kawai, Nobuyuki; Sato, Morio; Ikoma, Akira; Minamiguchi, Hiroki; Nakai, Motoki; Sanda, Hiroki; Nakata, Kouhei; Takeuchi, Taizou; Tanaka, Takami; Shirai, Shintaro; Sonomura, Tetsuo


    To evaluate the washout (WO) pattern of serous cystadenomas (SCAs) compared with endocrine tumors (ETs) and intraductal papillary mucinous neoplasm (IPMN). Patients with serous cystadenoma (n = 12), ET (n = 29), and IPMN (n = 35) underwent 4-phase computed tomography CT. Tumors were categorized as hyperdense or hypodense. Computed tomographic values measured were unenhanced attenuation (AU), pancreatic attenuation (A12, 12 seconds), portal attenuation (A35), and equilibrium (A158). Computed tomographic parameters calculated were wash-in (WI) = A12 - AU; WO = A12 - A35; and washout ratio (WOR) = WO/WI × 100/22. Hyperdense SCAs had significantly higher WOR than did hyperdense ETs (P = 0.001). Among the 3 hypodense tumors, SCAs had the significantly highest WOR (P < 0.05/3). Relative to the pancreas, the WOR of SCAs were equivalent, whereas the WOR of ETs and IPMNs were significantly lower. Hyperdense SCAs had significantly higher WOR than did hyperdense ETs, and hypodense SCAs had the significantly highest WOR among the three.

  16. Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into beta-cells.

    Directory of Open Access Journals (Sweden)

    Maria Oström

    Full Text Available The identification of secreted factors that can selectively stimulate the generation of insulin producing beta-cells from stem and/or progenitor cells represent a significant step in the development of stem cell-based beta-cell replacement therapy. By elucidating the molecular mechanisms that regulate the generation of beta-cells during normal pancreatic development such putative factors may be identified. In the mouse, beta-cells increase markedly in numbers from embryonic day (e 14.5 and onwards, but the extra-cellular signal(s that promotes the selective generation of beta-cells at these stages remains to be identified. Here we show that the retinoic acid (RA synthesizing enzyme Raldh1 is expressed in developing mouse and human pancreas at stages when beta-cells are generated. We also provide evidence that RA induces the generation of Ngn3(+ endocrine progenitor cells and stimulates their further differentiation into beta-cells by activating a program of cell differentiation that recapitulates the normal temporal program of beta-cell differentiation.

  17. Tumour basement membrane laminin expression predicts outcome following curative resection of pancreatic head cancer

    NARCIS (Netherlands)

    J. van der Zee (Jill); C.H.J. van Eijck (Casper); W.C.J. Hop (Wim); K. Biermann (Katharina); B.M. Dicheva (Bilyana); A.L.B. Seynhaeve (Ann); G.A. Koning (Gerben); A.M.M. Eggermont (Alexander); T.L.M. ten Hagen (Timo)


    textabstractBackground: Although widely fragmented BMs have been associated with adverse outcome in several cancer types, comparatively little is known with respect to its effect on the prognosis of pancreatic cancer. The aim of the current study was therefore to determine the prognostic value of

  18. Pancreatitis (United States)

    ... be present. How is pancreatitis diagnosed? How is pancreatitis treated? Treatment mainly consists of putting the pancreas to rest ( ... not as a definitive basis for diagnosis or treatment in any particular case. It is very ... pancreatitis is suspected, laboratory tests search for higher than ...

  19. Selenium status alters tumour differentiation but not incidence or latency of pancreatic adenocarcinomas in Ela-TGF-alpha p53+/ mice. (United States)

    Aichler, Michaela; Algül, Hana; Behne, Dietrich; Hölzlwimmer, Gabriele; Michalke, Bernhard; Quintanilla-Martinez, Leticia; Schmidt, Jörg; Schmid, Roland M; Brielmeier, Markus


    Genetic predisposition and environmental factors act in concert in the pathogenesis of multi-factorial diseases. Selenoproteins represent fundamental antioxidative systems for the maintenance of cellular redox homeostasis, which is altered in various disease processes. Optimal function of selenoproteins requires availability of sufficient amounts of the essential trace element selenium, but in many countries the nutritive selenium supply is regarded insufficient. Supplemental selenium has been shown to have cancer-protective effects in a variety of experimental settings and clinical studies. Pancreatic carcinoma has so far not been tested as an end-point in such studies. We thus investigated the influence of supplemental nutritive selenium on pancreatic carcinogenesis in selenium-deficient animals by use of a genetically defined disease model. Over a period of 800 days, all animals (n = 131) in the study developed tumours. Within this time, the mean total tumour latency was not influenced by the selenium status (471 versus 472 days). Also, the mean latency of pancreatic carcinomas (n = 83) was not influenced (464 versus 466 days). In contrast, the percentage of pancreatic tumors within all tumours was lower in the selenium-deficient group (55 versus 70%). A highly significant difference in the differentiation grade of the pancreatic tumours was evident between the two groups: selenium-deficient mice (n = 33) developed predominantly undifferentiated anaplastic carcinomas (26 anaplastic versus 7 differentiated), whereas in the selenium-supplemented group (n = 50) mainly well-differentiated carcinomas were detected (20 anaplastic versus 30 differentiated). These data point at a new role of the trace element selenium in carcinogenesis.

  20. Incorporation of bone marrow cells in pancreatic pseudoislets improves posttransplant vascularization and endocrine function.

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    Christine Wittig

    Full Text Available Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×10(3 cells. To create bone marrow cell-enriched pseudoislets 2×10(3 islet cells were co-cultured with 2×10(3 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation.

  1. Metabolic tumour burden assessed by {sup 18}F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection

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    Xu, Hua-Xiang; Chen, Tao; Wang, Wen-Quan; Wu, Chun-Tao; Liu, Chen; Long, Jiang; Xu, Jin; Liu, Liang; Yu, Xian-Jun [Fudan University, Shanghai Cancer Center, Pancreatic Cancer Institute and Department of Pancreatic and Hepatobiliary Surgery, Shanghai (China); Fudan University, Department of Oncology, Shanghai Medical College, Shanghai (China); Zhang, Ying-Jian [Fudan University, Shanghai Cancer Center, Department of Nuclear Medicine, Shanghai (China); Fudan University, Department of Oncology, Shanghai Medical College, Shanghai (China); Chen, Run-Hao [Fudan University, Department of General Surgery, Jinshan Hospital, Shanghai (China)


    Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by {sup 18}F-FDG PET/CT in patients with resectable PDAC. Included in the study were 122 PDAC patients who received preoperative {sup 18}F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). MTV and TLG were significantly associated with baseline serum CA19-9 level (P = 0.001 for MTV, P < 0.001 for TLG) and tumour size (P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size (P < 0.001 for all). MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC. (orig.)


    Directory of Open Access Journals (Sweden)

    Lingam Aruna


    Full Text Available BACKGROUND Solid pseudopapillary tumour of the pancreas is a rare tumour of low malignant potential occurring predominantly in young females. Its incidence has been increasing due to advanced imaging modalities. As this tumour offers a good prognosis, it is important to make a proper diagnosis to offer better treatment and reduce morbidity. MATERIALS AND METHODS This is a prospective study for a period of 2 years (From May 2014 to April 2016. Of the 52 pancreatic specimens we received after surgery, 9 cases had a prior radiological diagnosis of solid pseudopapillary tumour of the pancreas. The clinical and histopathological characteristics of SPT were studied along with review of literature. Whipple resection specimens which were radiologically diagnosed as adenocarcinoma of the periampullary region were excluded. RESULTS Nine cases were reported radiologically as papillary neoplasm of pancreas. On histopathology, 8 of them were confirmed as solid pseudopapillary tumours of the pancreas. One was a case of serous cystadenoma and other one was pancreatic neuroendocrine tumour. One case which was suspected as pancreatic endocrine tumour radiologically was diagnosed as SPT. CONCLUSION SPT typically is limited to the pancreas at the time of diagnosis, and even with metastasis, an extended complete surgical excision offers good prognosis. Hence, it is important to distinguish it from other tumours of similar morphology. In this study, we discuss the process of establishing the diagnosis accurately of SPN in young patients presenting with pancreatic mass.

  3. Glucagon-like peptide 1 immunoreactivity in gastroentero-pancreatic endocrine tumors: a light- and electron-microscopic study. (United States)

    Eissele, R; Göke, R; Weichardt, U; Fehmann, H C; Arnold, R; Göke, B


    The preproglucagon gene encodes, in addition to glucagon, two smaller peptides with structural similarity: glucagon-like peptides 1 and 2. Glucagon-like peptide 1 (GLP-1) 7-36 amide is the most powerful incretin candidate. In the present study, GLP-1 immunoreactivity was investigated in tissue specimens of various types of gastroenteropancreatic tumors, and the serum-levels of GLP-1 were assayed. Immunohistochemical staining of 88 tumors revealed GLP-1 immunoreactivity in 17 neoplasias (19.3%), viz., in 7 out of 33 non-functioning tumors, 4 out of 20 gastrinomas, 4 out of 13 insulinomas, 1 out of 3 vasoactive-intestinal-polypeptide (VIP)omas and 1 adrenocorticotropic-hormone (ACTH)-producing tumor. In these tumors, GLP-1-immunoreactive cells were distributed either diffusely, arranged in clusters, or as single cells. All GLP-1-positive tumors were immunoreactive for glucagon or glicentin, 10 tumors were immunoreactive for pancreatic polypeptide, and 8 tumors for insulin. Ultrastructural analysis of 8 GLP-1-positive tumors, with the immunogold technique, demonstrated GLP-1 immunoreactivity mainly in cells resembling the A-cells of the pancreas or the L-cells of the gut. Of the 17 GLP-1-immunoreactive tumors, 15 were primarily located in the pancreas. Additionally, 2 non-functioning tumors of the rectum were GLP-1 immunoreactive. Five tumors were GLP-1 immunoreactive from 9 patients with multiple endocrine neoplasia I syndrome. Patients with GLP-1-immunoreactive tumors were characterized by a significantly lower rate of distant metastases (P < 0.01) and a higher rate of curative resections (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Basal serum pancreatic polypeptide is dependent on age and gender in an adult population

    DEFF Research Database (Denmark)

    Brimnes Damholt, M; Rasmussen, B K; Hilsted, L


    This study is the first epidemiologically based study of basal levels of serum pancreatic polypeptide (s-PP). The basal level of serum PP has become a field of interest mainly due to the role of PP as an endocrine tumour marker, and as a marker of pancreatic neuroendocrine function after pancreas...... a monospecific radioimmunoassay. Fasting serum pancreatic polypeptide depended on age and gender. The results demonstrated that fasting pancreatic polypeptide levels increase exponentially with age. Fitted separately for each sex, basal serum pancreatic polypeptide was found to increase by approximately 3% per...... reports on the fasting levels of serum pancreatic polypeptide are most likely due to lack of adjustment for age and gender. Thus, variation due to age and gender should be considered in evaluating fasting levels of serum pancreatic polypeptide. Whether similar considerations are important when evaluating...

  5. Growth hormone-releasing hormone-producing pancreatic neuroendocrine tumor in a multiple endocrine neoplasia type 1 family with an uncommon phenotype. (United States)

    Sala, Elisa; Ferrante, Emanuele; Verrua, Elisa; Malchiodi, Elena; Mantovani, Giovanna; Filopanti, Marcello; Ferrero, Stefano; Pietrabissa, Andrea; Vanoli, Alessandro; La Rosa, Stefano; Zatelli, Maria C; Beck-Peccoz, Paolo; Verga, Uberta


    The objective of this study was to describe a multiple endocrine neoplasia type 1 (MEN1) family characterized by primary hyperparathyroidism, in association with acromegaly because of ectopic growth hormone-releasing hormone (GHRH) secretion by a pancreatic neuroendocrine tumor in a young man and with a bronchial carcinoid in his mother. We investigate the clinical, radiological imaging, histopathologic findings, and therapy. An 18-year-old man successfully underwent subtotal parathyroidectomy for primary hyperparathyroidism. A subsequent genetic analysis showed a MEN1 gene mutation. Three years later, acromegaly because of ectopic GHRH secretion was diagnosed (pituitary MRI negative and elevated GHRH levels). A search for an ectopic tumor was unsuccessful and somatostatin analog therapy was started. Successively, scintigraphy with somatostatin analogs (68-Ga-DOTATOC-PET) showed three focal areas in the pancreatic tail. Distal pancreatectomy showed multiple pancreatic neuroendocrine tumors and hormonal status was normalized. Afterwards, the evaluation of the patient's mother, carrying the same mutation, indicated a primary hyperparathyroidism and a 4 cm lung mass. The patient underwent subtotal pneumonectomy and the histological analysis was consistent with the diagnosis of a typical bronchial carcinoid. In conclusion, an atypical phenotype may be recorded in MEN1 families, thus emphasizing the importance of the new imaging and surgical techniques in the diagnosis and treatment of such a rare disease.

  6. Pancreatic enucleation using the da Vinci robotic surgical system: a report of 26 cases. (United States)

    Shi, Yusheng; Peng, Chenghong; Shen, Baiyong; Deng, Xiaxing; Jin, Jiabin; Wu, Zhichong; Zhan, Qian; Li, Hongwei


    As a tissue-sparing procedure, pancreatic enucleation has become an alternative for benign or borderline pancreatic tumours; it has been proved to be safe and feasible. To date, a large sample size of robotic pancreatic enucleation has not been reported. This study aimed to discuss the clinical evaluation and postoperative complications after robotic pancreatic enucleation and compare it with open surgery. Patients who underwent robotic or open pancreatic enucleation during December 2010-December 2014 at Shanghai Ruijin Hospital, affiliated with the Shanghai Jiaotong University School of Medicine in China, were included. Clinical data were collected and analysed. Patients were divided into an open group and a robotic group: 26 patients underwent robotic pancreatic enucleation, of whom 13 patients were female. The mean age was 51.7 years, the operation time was 125.7 ± 58.8 min, blood loss was 49.4 ± 33.4 ml and mean tumour size was 18.8 ± 7.9 mm; 17 patients underwent open pancreatic enucleation, of whom 11 were female. The mean age was 54.6 ± 17.2 min, blood loss was 198.5 ± 70.7 ml and mean tumour size was 3.5 ± 1.9 cm. Pathology included insulinomas, intrapancreatic mucinous neoplasmas (IPMNs), pancreatic neuro-endocrine tumours (PNETs), solid pseudopapillary tumours (SPTs) and serous cystadenomas (SCAs). Robotic pancreatic enucleations were associated with less trauma, shorter operation time, less blood loss and faster wound recovery compared with open pancreatic enucleation. Pancreatic fistulas (PFs) were the main complication that occurred in the robotic group; infection also occurred in the open group. All patients recovered after effective drainage and the use of somatostatin. The mean follow-up time was 25 months. No recurrence was discovered, and one patient in the open group suffered endocrine insufficiency. Robotic pancreatic enucleation is a safe and effective surgical procedure for pancreatic benign and borderline tumours. It produces less

  7. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Kwekkeboom, D.J.; Bakker, W.H.; Kam, B.L.; Teunissen, J.J.M.; Kooij, P.P.M.; Jong, M. de [Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam (Netherlands); Herder, W.W. de; Feelders, R.A. [Department of Internal Medicine, Erasmus Medical Center, Rotterdam (Netherlands); Eijck, C.H.J. van [Department of Surgery, Erasmus Medical Center, Rotterdam (Netherlands); Srinivasan, A.; Erion, J.L. [Mallinckrodt Medical, St. Louis, Missouri (United States); Krenning, E.P. [Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam (Netherlands); Department of Internal Medicine, Erasmus Medical Center, Rotterdam (Netherlands)


    Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [{sup 90}Y-DOTA{sup 0},Tyr{sup 3}]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA{sup 0},Tyr{sup 3}]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA{sup 0},Tyr{sup 3}]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide {sup 177}Lu, it has proved very successful in achieving tumour regression in animal models. The effects of {sup 177}Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi {sup 177}Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours

  8. Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1

    Directory of Open Access Journals (Sweden)

    Grzegorz Piecha


    Full Text Available Primary hyperparathyroidism may occur as a part of an inherited syndrome in a combination with pancreatic endocrine tumours and/or pituitary adenoma, which is classified as Multiple Endocrine Neoplasia type 1 (MEN-1. This syndrome is caused by a germline mutation in MEN-1 gene encoding a tumour-suppressor protein, menin. Primary hyperparathyroidism is the most frequent clinical presentation of MEN-1, which usually appears in the second decade of life as an asymptomatic hypercalcemia and progresses through the next decades. The most frequent clinical presentation of MEN-1-associated primary hyperparathyroidism is bone demineralisation and recurrent kidney stones rarely followed by chronic kidney disease. The aim of this paper is to present the pathomechanism, screening procedures, diagnosis, and management of primary hyperparathyroidism in the MEN-1 syndrome. It also summarises the recent advances in the pharmacological therapy with a new group of drugs—calcimimetics.

  9. A founder MLH1 mutation in Lynch syndrome families from Piedmont, Italy, is associated with an increased risk of pancreatic tumours and diverse immunohistochemical patterns. (United States)

    Borelli, Iolanda; Casalis Cavalchini, Guido C; Del Peschio, Serena; Micheletti, Monica; Venesio, Tiziana; Sarotto, Ivana; Allavena, Anna; Delsedime, Luisa; Barberis, Marco A; Mandrile, Giorgia; Berchialla, Paola; Ogliara, Paola; Bracco, Cecilia; Pasini, Barbara


    The MLH1 c.2252_2253delAA mutation was found in 11 unrelated families from a restricted area south-west of Turin among 140 families with mutations in the mismatch repair genes. The mutation is located in the highly conserved C-terminal region, responsible for dimerization with the PMS2 protein. Twenty-five tumour tissues from 61 individuals with the c.2252_2253delAA mutation were tested for microsatellite instability (MSI) and protein expression. We compared the clinical features of these families versus the rest of our cohort and screened for a founder effect. All but one tumours showed the MSI-high mutator phenotype. Normal, focal and lack of MLH1 staining were observed in 16, 36 and 48 % of tumours, respectively. PMS2 expression was always lost. The mutation co-segregated with Lynch syndrome-related cancers in all informative families. All families but one fulfilled Amsterdam criteria, a frequency higher than in other MLH1 mutants. This was even more evident for AC II (72.7 vs. 57.5 %). Moreover, all families had at least one colon cancer diagnosed before 50 years and one case with multiple Lynch syndrome-related tumours. Interestingly, a statistically significant (p = 0.0057) higher frequency of pancreatic tumours was observed compared to families with other MLH1 mutations: 8.2 % of affected individuals versus 1.6 %. Haplotype analysis demonstrated a common ancestral origin of the mutation, which originated about 1,550 years ago. The mutation is currently classified as having an uncertain clinical significance. Clinical features, tissue analysis and co-segregation with disease strongly support the hypothesis that the MLH1 c.2252_2253delAA mutation has a pathogenic effect.

  10. Well differentiated endocrine carcinomas of the pancreas

    Directory of Open Access Journals (Sweden)

    Čolović Radoje


    Full Text Available Introduction. For the difference from poorly differentiated, well differentiated endocrine carcinomas of the pancreas are the tumours in whom with aggressive surgery and chemotherapy fair results can be achieved. Objective. The aim of the study was to point out the importance of such treatment. Methods. Over a 6-year period eight patients (seven female and one male of average age 51 years (ranging from 23 to 71 years were operated on for well differentiated endocrine carcinoma: six of the head and two of the tail of the pancreas. There were two functional and six nonfunctional tumours. Pain in the upper part of the abdomen in seven, mild loss in weight in two, strong heartburn in two, obstructive jaundice in three, diarrhoea in one, sudden massive bleeding from gastric varicosities due to prehepatic portal hypertension caused by pancreatic head tumour in one, and bruise in one patient were registered preoperatively. US and CT in all, angiography in one, octreoscan in two and PET scan in one patient were performed. Whipple’s procedure was performed in six and distal pancreatectomy in two patients, as well as systemic lymphadenectomy in all and excision of liver secondary tumours in two patients. In the patient with massive gastric bleeding a total gastrectomy was performed first, followed by Whipple’s procedure a month later. Results. R0 resection was achieved in all patients. Lymph nodes metastases were found in six patients. Six patients were given chemotherapy. One patient died 3 years after surgery, seven are still alive, on average 2.5 years. A local recurrence after distal pancreatectomy that occurred 5 years after surgery was successfully reresected and the patient is on peptide-receptor radiotherapy. In other six patients there were no local recurence or distant metastases. Conclusion. With aggressive surgery and chemotherapy fair results can be achieved in well differentiated endocrine carcinomas of the pancreas.

  11. Solid pseudopapillary neoplasm collides with a well-differentiated pancreatic endocrine neoplasm in an adult man: case report and review of histogenesis. (United States)

    Yan, Shirley X; Adair, Carol F; Balani, Jyoti; Mansour, John C; Gokaslan, Sefik T


    Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, clinicopathologically distinct neoplasm with a tendency to affect young women. The histogenesis of SPN is not well defined. Pancreatic endocrine neoplasms (PENs) are also uncommon tumors of the pancreas. Our comprehensive review of the literature did not yield any reported cases of collision tumors of the above two neoplasms. We report a case of such a collision tumor in a 45-year-old man. This tumor was an incidental finding on computed tomography, followed by fine-needle aspiration confirmation of a tumor that was initially diagnosed as an SPN only. A histologic examination of a 2.1-cm mass following distal pancreatectomy revealed a 0.7-cm PEN partly engulfed by an SPN. The tumors showed different morphologic and immunohistochemical features, confirming the presence of a collision tumor. A comparative analysis of immunoprofiles of these tumors yielded interesting findings, enabling us to postulate that SPNs may originate from a multipotential primordial cell that may follow different differentiation pathways, such as endocrine, epithelial, and acinar. The ultrastructures and immunophenotypic characteristics appear to support this hypothesis. Copyright© by the American Society for Clinical Pathology.

  12. Nuclear Receptors and Multiple Endocrine Neoplasia type 1 (MEN1)

    NARCIS (Netherlands)

    Dreijerink, K.M.A.|info:eu-repo/dai/nl/311470238


    Multiple Endocrine Neoplasia type 1 (MEN1) is an inherited syndrome that is characterized by the occurrence of tumours of the parathyroid glands, gastroenteropancreatic tumours, pitui-tary gland adenomas, as well as adrenal adenomas and neuro-endocrine tumours, often at a young age. MEN1 tumours can

  13. Morphofunctional characteristics of endocrine pancreatic damage exposed to imbalanced food with excess nutrients on mother – fetus system

    Directory of Open Access Journals (Sweden)

    O. V. Nikolayeva


    Full Text Available The purpose of the study. The study is devoted to the mechanisms of pancreatic damage by exploring of its morphofunctional state as the result of imbalanced diet with an excess of nutrients on the mother – fetus system. Materials and Methods. Before pregnancy and during pregnancy the female rats were fed with an increased amount of carbohydrates. The control group of animals was maintained in standard vivarium conditions with normal balanced diet. Morphological processing included a set of histological and histochemical methods. Assessment of the secretory activity of the pancreas and hormones-substratum relationships was examined using biochemical method. Statistical investigation included a univariate dispersіon analysis. Results. We have defined the options of the pancreatic dysfunction (hyperpancreatism, hypopancreatism, dispancreatism in rats under the action of high fat and carbohydrates diet on the mother-fetus system. Also, high level of insulin combined with hypercorticosteronemia (in rats and hypocorticosteronemia (in some offspring was revealed, which probably had a compensatory character and caused the activation of catabolic processes. This is evidenced by hyperglycemia, mild hypoproteinemia, insignificant increased level of fatty acids and significant increased level of ketone bodies. We have found that the rats, as well as their mothers, are exposed to marked violation of morphology and function of the pancreas (we have found out the compensatory hypertrophy and hyperplasia, a sufficiently high morphofunctional activity in the structural components of the pancreas while strengthening the dystrophic and sclerotic processes, which persist in the first two months of postnatal life, despite the physiological conditions of existence and balanced diet. We have clarified the mechanism of pancreas damage in rats as a result of an imbalanced diet on the mother – fetus system. Conclusions. The results of the study indicate that the

  14. The ACE2/Ang-(1-7)/Mas Axis Regulates the Development of Pancreatic Endocrine Cells in Mouse Embryos. (United States)

    Wang, Lin; Liang, Juan; Leung, Po Sing


    Angiotensin-converting enzyme 2 (ACE2), its product Angiotensin-(1-7) [Ang-(1-7)], and Ang-(1-7) receptor Mas, have been shown to regulate organogenesis during embryonic development in various species. However, it is not known whether a local ACE2/Ang-(1-7)/Mas axis is present in the fetal pancreas. It is hypothesized that there is a local ACE2/Ang-(1-7)/Mas axis in the embryonic pancreas in mice that is involved in regulating islet cell development. To address this issue, the endogenous expression profile of axis constituents in embryonic mouse pancreata was examined. Involvement of the ACE2 axis in the regulation of pancreatic development was also examined. The present experiments showed in an in vivo animal model that endogenous expression levels of ACE2 and the Mas receptor were upregulated in mouse pancreata in late embryogenesis, peaking on embryonic day E16.5, when it reached 3 folds compared to that seen at E12.5. Consistently, endogenous expression of Ang-(1-7) also peaked at E16.5. Treatment with the ACE2 inhibitor DX600 did not alter islet development. However, prenatal treatment with A779, a Mas receptor antagonist, reduced the β-cell to α-cell ratio in neonatal islets, impaired islet insulin secretory function, and impaired the pups' glucose tolerance. In ex vivo pancreas explant cultures, A779 again decreased the β-cell to α-cell ratio, apparently through its effects on β-cell proliferation (reduced proliferation shown with Ki67 staining), and also decreased Insulin and Ngn3 mRNA expression. Furthermore, treatment of explant cultures with Ang-(1-7) increased mRNA levels of Insulin and pancreatic progenitor marker Ngn3, as well as Nox4, the ROS generation enzyme; these stimulatory effects were attenuated by co-treatment with A779, suggesting that Ang-(1-7), via Mas receptor signaling, may promote differentiation of pancreatic progenitors into insulin-producing cells via modulation of reactive oxygen species. These data together suggest that a Mas

  15. Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic Disease ReseArch (PANDoRA) consortium. (United States)

    Campa, Daniele; Rizzato, Cosmeri; Capurso, Gabriele; Giese, Nathalia; Funel, Niccola; Greenhalf, William; Soucek, Pavel; Gazouli, Maria; Pezzilli, Raffaele; Pasquali, Claudio; Talar-Wojnarowska, Renata; Cantore, Maurizio; Andriulli, Angelo; Scarpa, Aldo; Jamroziak, Krzysztof; Delle Fave, Gianfranco; Costello, Eithne; Khaw, Kay-Tee; Heller, Anette; Key, Tim J; Theodoropoulos, George; Malecka-Panas, Ewa; Mambrini, Andrea; Bambi, Franco; Landi, Stefano; Pedrazzoli, Sergio; Bassi, Claudio; Pacetti, Paola; Piepoli, Ada; Tavano, Francesca; di Sebastiano, Pierluigi; Vodickova, Ludmila; Basso, Daniela; Plebani, Mario; Fogar, Paola; Büchler, Markus W; Bugert, Peter; Vodicka, Pavel; Boggi, Ugo; Neoptolemos, John P; Werner, Jens; Canzian, Federico


    Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n=86), chronic pancreatitis (n=272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  16. Parallel in vivo and in vitro detection of functional somatostatin receptors in human endocrine pancreatic tumors: Consequences with regard to diagnosis, localization, and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lamberts, S.W.; Hofland, L.J.; van Koetsveld, P.M.; Reubi, J.C.; Bruining, H.A.; Bakker, W.H.; Krenning, E.P. (Erasmus Univ., Rotterdam (Netherland))


    The effects of octreotide in vivo and in vitro on hormone release, in vivo ({sup 123}I)Tyr3-octreotide scanning, and in vitro ({sup 125}I)Tyr3-octreotide autoradiography were compared in five patients with endocrine pancreatic tumors. ({sup 123}I)Tyr3-octreotide scanning localized the primary tumor and/or previously unknown metastases in four of the five patients. The patient with a negative scan had an insulinoma that did not respond to octreotide in vivo. No Tyr3-octreotide-binding sites were subsequently found at autoradiography of the tumor, whereas somatostatin-14 receptors were present at a high density. In parallel, culture studies with the cells prepared from this adenoma showed that insulin release was not affected by octreotide, while both somatostatin-14 and -28 significantly suppressed hormone release. Culture studies of the tumor cells from two gastrinomas showed a dose-dependent inhibition of gastrin release by octreotide. Octreotide exerted direct antiproliferative effects in one of these gastrinomas, which had been shown to be rapidly growing in vivo. Both gastrinomas had specific somatostatin receptors, as measured by in vitro receptor autoradiography. Somatostatin release by the cultured somatostatinoma cells from one of these patients was suppressed by octreotide.

  17. Role of Pancreatic Stellate Cells in Chemoresistance in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Joshua eMcCarroll


    Full Text Available Pancreatic cancer is highly chemoresistant. A major contributing factor is the characteristic extensive stromal or fibrotic reaction, which comprises up to 90% of the tumour volume. Over the last decade there has been intensive research into the role of the pro-fibrogenic pancreatic stellate cells (PSCs and their interaction with pancreatic cancer cells. As a result of the significant alterations in the tumour microenvironment following activation of pancreatic stellate cells, tumour progression and chemoresistance is enhanced. This review will discuss how PSCs contribute to chemoresistance in pancreatic cancer.

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

    Directory of Open Access Journals (Sweden)

    Minoti eApte


    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.

  19. Endocrine Drugs in Aircrew (United States)


    intracellular inflammatory action of corticosteroids, the and extracellular communication. The site of action contraceptive action of gonadal steroids...complications occur have results in the disappearance of weakness, malaise allowed more effective methods of prevention and and fatigue. Anorexia and...disease * Osteoporosis "* Pancreatitis * Myopathy Endocrine-Metabolic Neuropsychiatric "* latrogenic Cushing * Psychosis "* Acne, hirsutism, menstrual

  20. Pancreatic islet cell reaggregation systems: efficiency of cell reassociation and endocrine cell topography of rat islet-like aggregates. (United States)

    Matta, S G; Wobken, J D; Williams, F G; Bauer, G E


    Single cells isolated from rat islets of Langerhans were cultured under conditions that support reassociation into islet-like aggregates. Comparisons were made of enzymatic methods of islet dissociation, rotational or static culture conditions, and culture at basal or stimulatory glucose concentrations. Over a period of 4 days the aggregates progressed through three stages of organization: cell coalescence to cellular chains, rearrangement of chains into small spheroids, and growth of spheroids. The numerical yield of aggregates was optimum after islets were dissociated with dispase. Culture under rotation resulted in the production of more aggregates of significantly larger diameter than under static conditions. Medium glucose concentrations of 4 and 11 mM supported cell reassociation under rotator culture, but no aggregation occurred under static culture at the basal (4 mM) glucose level. Aggregates resulting from 4-day rotator culture exhibited endocrine cell distributions similar to intact islets. Islet aggregates released insulin in response to glucose, but nonaggregated cells, maintained in culture, did not. The present comparisons reveal significant variability in the cellular composition, rate of formation, and yield of aggregates, and suggest that the methodology for producing aggregates should be carefully considered in experimental design.

  1. Long-term outcomes of {sup 131}Iodine mIBG therapy in metastatic gastrointestinal pancreatic neuroendocrine tumours: single administration predicts non-responders

    Energy Technology Data Exchange (ETDEWEB)

    Mulholland, Nicola; Chakravartty, Riddhika; Devlin, Lindsey; Kalogianni, Eleni; Corcoran, Ben; Vivian, Gillian [King' s College Hospital, Department of Nuclear Medicine, London (United Kingdom)


    {sup 131}Iodine (I131)-metaiodobenzylguanidine (mIBG) is a radionuclide-based treatment option for metastatic gastrointestinal-pancreatic neuroendocrine tumours (GEP NET). This study aimed at identifying prognostic indicators of long-term outcome based on initial evaluation following a first mIBG treatment (7400 MBq) in a patient cohort with such tumours, with a secondary aim of evaluating progression-free survival (PFS) and overall survival (OS) following mIBG therapy. Retrospective review of the hospital records was performed to identify a cohort of 38 adult patients who underwent {sup 131}Iodine-mIBG therapy over a 9-year period for metastatic GEP NETs and neuroendocrine tumours with an unknown primary. Treatment response was evaluated based on radiological criteria (RECIST1.1), biochemical markers [serum Chromogranin A (CgA)/urinary 5HIAA] and symptomatic response at clinical follow-up, all evaluated at 3-6 months from first mIBG treatment. Progression-free survival (PFS) and overall survival (OS) from the first mIBG treatment were recorded. At 3-6 months following a single mIBG therapy, 75 %, 67 %, and 63 % of patients showed either a partial response (PR) or stable disease (SD) on radiological, biochemical, and symptomatic criteria, respectively. Complete response (CR) was not seen in any patient. OS from the date of diagnosis and from the first therapy was 8 years +/-1.1 (95 % CI 5.7 to 10.2 years) and 4 years+/-0.69 (95 % CI 2.6-5.3 years), respectively. Twenty-nine percent of patients were alive at 10 years. Significant survival advantage was seen in patients with SD/PR as compared to those who had progressive disease (PD) for each of these three criteria. Biochemical, radiological (RECIST 1.1) and symptomatic assessment of disease status at 3 to 6 months after first I131-mIBG therapy stratifies patients with a poor prognosis. This can be used to identify patients who may benefit from alternative strategies of treatment. (orig.)

  2. Paraneoplastic endocrine syndromes. (United States)

    Dimitriadis, Georgios K; Angelousi, Anna; Weickert, Martin O; Randeva, Harpal S; Kaltsas, Gregory; Grossman, Ashley


    The majority of neoplasms are responsible for symptoms caused by mass effects to surrounding tissues and/or through the development of metastases. However, occasionally neoplasms, with or without endocrine differentiation, acquire the ability to secrete a variety of bioactive substances or induce immune cross-reactivity with the normal tissues that can lead to the development of characteristic clinical syndromes. These syndromes are named endocrine paraneoplastic syndromes when the specific secretory components (hormones, peptides or cytokines) are unrelated to the anticipated tissue or organ of origin. Endocrine paraneoplastic syndromes can complicate the patient's clinical course, response to treatment, impact prognosis and even be confused as metastatic spread. These syndromes can precede, occur concomitantly or present at a later stage of tumour development, and along with the secreted substances constitute the biological 'fingerprint' of the tumour. Their detection can facilitate early diagnosis of the underlying neoplasia, monitor response to treatment and/or detect early recurrences following successful initial management. Although when associated with tumours of low malignant potential they usually do not affect long-term outcome, in cases of highly malignant tumours, endocrine paraneoplastic syndromes are usually associated with poorer survival outcomes. Recent medical advances have not only improved our understanding of paraneoplastic syndrome pathogenesis in general but also enhanced their diagnosis and treatment. Yet, given the rarity of endocrine paraneoplastic syndromes, there is a paucity of prospective clinical trials to guide management. The development of well-designed prospective multicentre trials remains a priority in the field in order to fully characterise these syndromes and provide evidence-based diagnostic and therapeutic protocols. © 2017 Society for Endocrinology.

  3. Pancreatic insulinoma co-existing with gastric GIST in the absence of neurofibromatosis-1

    Directory of Open Access Journals (Sweden)

    O'Sullivan Brendan


    Full Text Available Abstract Background Gastrointestinal stromal tumours (GIST frequently occur in patients with neurofibromatosis type 1 (NF-1. It has been reported that GIST may co-exist with pancreatic endocrine tumors but this has only been in association with NF-1. Case presentation A 76 year old woman presented with a 12 month history of hypoglycaemia symptoms. Abdominal CT scan demonstrated a 13 mm insulinoma localized in the tail of her pancreas. She was commenced on diazoxide and later underwent surgery for enucleation of insulinoma when a small ( Conclusion This is the first case report of a pancreatic insulinoma co-existing with a GIST in a patient without NF-1. In addition, we make the first report of rapidly growing cystic GIST recurrence following resection of a primary GIST tumour.

  4. Potential role of {sup 68}Ga-DOTATOC PET/CT in screening for pancreatic neuroendocrine tumour in patients with von Hippel-Lindau disease

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    Prasad, Vikas; Brenner, Winfried [Charite Universitaetsmedizin Berlin, Department of Nuclear Medicine, Campus Virchow-Klinikum, Berlin (Germany); Tiling, Nikolaus; Ploeckinger, Ursula [Charite Universitaetsmedizin Berlin, Interdisziplinaeren Stoffwechsel-Centrum, Campus Virchow Klinikum, Berlin (Germany); Denecke, Timm [Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany)


    Neuroendocrine tumours of the pancreas (pNET) are observed in 8 - 17 % of patients with von Hippel-Lindau disease (vHLD), and 11 - 20 % of these patients develop metastatic disease. MRI and CT have a very high resolution; however, their sensitivity and specificity for the detection of pNET amongst cystic lesions in the pancreas of vHLD patients are generally considered insufficient. In contrast, {sup 68}Ga-DOTATOC PET/CT demonstrates a high sensitivity for the diagnosis and staging of neuroendocrine tumours. In this study we investigated the potential role of {sup 68}Ga-DOTATOC PET/CT in screening of patients with vHLD. {sup 68}Ga-DOTATOC PET/three-phase contrast-enhanced CT was performed according to guidelines in all consecutive vHLD patients between January 2012 and November 2015. All patients underwent additional MRI imaging of the abdomen, spine, and head. Chromogranin A (CgA) was determined at the time of the PET/CT examination. A lesion seen on {sup 68}Ga-DOTATOC PET in the pancreas was defined as positive if the uptake was visually higher than in the surrounding tissues. Lesions were quantified using maximum SUV. Overall, 20 patients (8 men, 12 women; mean age 44.7 ± 11.1 years) were prospectively examined. Genetically, 12 patients had type 1 vHLD and 8 had type 2 vHLD. {sup 68}Ga-DOTATOC PET/CT detected more pNET than morphological imaging (CT or MRI): 11 patients (55 %; 8 type 1, 3 type 2) vs. 9 patients (45 %; 6 type 1, 3 type 2). The concentration of CgA was mildly elevated in 2 of 11 patients with pNET. The mean SUVmax of the pancreatic lesions was 18.9 ± 21.9 (range 5.0 - 65.6). Four patients (36.4 %) had multiple pNETs. The mean size of the lesions on CT and/or MRI was 10.4 ± 8.3 mm (range 4 - 38 mm), and 41.1 % were larger than 10 mm. In addition, somatostatin receptor-positive cerebellar and spinal haemangioblastomas were detected in three patients (SUVmax 2.1 - 10.1). One patient presented with a solitary somatostatin receptor-positive lymph

  5. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

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


    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.

  6. Hereditary pancreatitis for the endoscopist (United States)

    Patel, Milan R.; Eppolito, Amanda L.


    Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 68–81% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) are also associated with hereditary pancreatitis. While chronic alcoholic pancreatitis may develop in the fourth or fifth decades, patients with hereditary pancreatitis may develop symptoms in the first or second decades of life. Hereditary pancreatitis is diagnosed either by detecting a causative gene mutation or by the presence of chronic pancreatitis in two first-degree or three second-degree relatives, in two or more generations, without precipitating factors and with a negative workup for known causes. Patients with hereditary pancreatitis may have recurrent acute pancreatitis and may develop pancreatic exocrine and endocrine insufficiency. Hereditary pancreatitis may involve premature trypsinogen activation or decreased control of trypsin. Recurrent inflammation can lead to acute pancreatitis and subsequently to chronic pancreatitis with parenchymal calcification. There is a markedly increased risk of pancreatic carcinoma compared with the general population. Patients are often referred for evaluation of pancreatitis, biliary or pancreatic ductal dilatation, jaundice, biliary obstruction, pancreatic duct stone or stricture, pancreatic pseudocysts, and for evaluation for malignancy. Medical treatment includes pancreatic enzyme supplementation, nutritional supplementation, diabetes management, and palliation of pain. Patients should avoid tobacco use and alcohol exposure. Hereditary pancreatitis is reviewed and recommendations for

  7. Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours

    Directory of Open Access Journals (Sweden)

    Ajit S Shinto


    Results: 99mTc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P

  8. Pancreatic Cancer Genetics. (United States)

    Amundadottir, Laufey T


    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, 4]. The vast majority of tumors arise in the exocrine pancreas, with pancreatic ductal adenocarcinoma (PDAC) accounting for approximately 95% of tumors. Tumors arising in the endocrine pancreas (pancreatic neuroendocrine tumors) represent less than 5% of all pancreatic tumors [5]. Smoking, type 2 diabetes mellitus (T2D), obesity and pancreatitis are the most consistent epidemiological risk factors for pancreatic cancer [5]. Family history is also a risk factor for developing pancreatic cancer with odds ratios (OR) ranging from 1.7-2.3 for first-degree relatives in most studies, indicating that shared genetic factors may play a role in the etiology of this disease [6-9]. This review summarizes the current knowledge of germline pancreatic cancer risk variants with a special emphasis on common susceptibility alleles identified through Genome Wide Association Studies (GWAS).

  9. Are importance-satisfaction discrepancies with regard to ratings of specific health-related quality-of-life aspects valid indicators of disease- and treatment-related distress among patients with endocrine gastrointestinal tumours? (United States)

    Larsson, G; VON Essen, L; Sjödén, P-O


    The aims of this study were to investigate: (1) whether ratings of importance of, satisfaction with, and symptom/function of specific health-related quality-of-life (HRQoL) aspects are related, and (2) whether an importance-satisfaction discrepancy with regard to ratings of a specific HRQoL aspect is a valid indicator of distress. Eighty-three patients with endocrine gastrointestinal tumours completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and answered questions about importance of, satisfaction with, and symptom/function of 12 HRQoL aspects. The patients reported a relatively high HRQoL in terms of physical, emotional and social function. Most of the HRQoL aspects were considered as important for a good quality of life. High satisfaction was related to fewer symptoms and a better function. Patients who assigned a higher importance than satisfaction rating to an aspect reported a lower quality of life for the same aspect. The findings suggest that importance-satisfaction discrepancies are valid indicators of patient distress and illustrate the importance of asking patients not only about frequency and level of symptoms, but also about importance of and satisfaction with when assessing patient quality of life.

  10. Chronic pancreatitis (United States)

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

  11. Novel therapeutic targets for pancreatic cancer. (United States)

    Tang, Shing-Chun; Chen, Yang-Chao


    Pancreatic cancer has become the fourth leading cause of cancer death in the last two decades. Only 3%-15% of patients diagnosed with pancreatic cancer had 5 year survival rate. Drug resistance, high metastasis, poor prognosis and tumour relapse contributed to the malignancies and difficulties in treating pancreatic cancer. The current standard chemotherapy for pancreatic cancer is gemcitabine, however its efficacy is far from satisfactory, one of the reasons is due to the complex tumour microenvironment which decreases effective drug delivery to target cancer cell. Studies of the molecular pathology of pancreatic cancer have revealed that activation of KRAS, overexpression of cyclooxygenase-2, inactivation of p16(INK4A) and loss of p53 activities occurred in pancreatic cancer. Co-administration of gemcitabine and targeting the molecular pathological events happened in pancreatic cancer has brought an enhanced therapeutic effectiveness of gemcitabine. Therefore, studies looking for novel targets in hindering pancreatic tumour growth are emerging rapidly. In order to give a better understanding of the current findings and to seek the direction in future pancreatic cancer research; in this review we will focus on targets suppressing tumour metastatsis and progression, KRAS activated downstream effectors, the relationship of Notch signaling and Nodal/Activin signaling with pancreatic cancer cells, the current findings of non-coding RNAs in inhibiting pancreatic cancer cell proliferation, brief discussion in transcription remodeling by epigenetic modifiers (e.g., HDAC, BMI1, EZH2) and the plausible therapeutic applications of cancer stem cell and hyaluronan in tumour environment.

  12. Current knowledge on the sensitivity of the {sup 68}Ga-somatostatin receptor positron emission tomography and the SUV{sub max} reference range for management of pancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Virgolini, Irene; Gabriel, Michael; Kroiss, Alexander; Guggenberg, Elisabeth von; Prommegger, Rupert; Warwitz, Boris; Nilica, Bernhard; Roig, Ilanos Geraldo; Rodrigues, Margarida; Uprimny, Christian [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria)


    Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three {sup 68}Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these {sup 68}Ga-sstr-binding peptides in the imaging setting. On {sup 68}Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUV{sub max}) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUV{sub max}-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUV{sub max}-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients

  13. Hereditary pancreatitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Raphael KL


    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

  14. Single-Cell Gene Expression Analysis of a Human ESC Model of Pancreatic Endocrine Development Reveals Different Paths to β-Cell Differentiation. (United States)

    Petersen, Maja Borup Kjær; Azad, Ajuna; Ingvorsen, Camilla; Hess, Katja; Hansson, Mattias; Grapin-Botton, Anne; Honoré, Christian


    The production of insulin-producing β cells from human embryonic stem cells (hESCs) in vitro represents a promising strategy for a cell-based therapy for type 1 diabetes mellitus. To explore the cellular heterogeneity and temporal progression of endocrine progenitors and their progeny, we performed single-cell qPCR on more than 500 cells across several stages of in vitro differentiation of hESCs and compared them with human islets. We reveal distinct subpopulations along the endocrine differentiation path and an early lineage bifurcation toward either polyhormonal cells or β-like cells. We uncover several similarities and differences with mouse development and reveal that cells can take multiple paths to the same differentiation state, a principle that could be relevant to other systems. Notably, activation of the key β-cell transcription factor NKX6.1 can be initiated before or after endocrine commitment. The single-cell temporal resolution we provide can be used to improve the production of functional β cells. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Pancreatitis - discharge (United States)

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

  16. Hereditary Pancreatitis (United States)

    ... E-News Sign-Up Home Hereditary Pancreatitis Hereditary Pancreatitis Hereditary Pancreatitis (HP) is a rare genetic condition characterized by ... of pancreatic attacks, which can progress to chronic pancreatitis . Symptoms include abdominal pain, nausea, and vomiting. Onset ...

  17. Pancreatic Enzymes (United States)

    ... NOW HONOR/MEMORIAL GENERAL DONATION MONTHLY 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 ...

  18. Pancreatitis and pancreatic trauma. (United States)

    Stringer, Mark D


    Many pancreatic disorders in children benefit from a multidisciplinary approach. This is especially true for acute and chronic pancreatitis which has numerous and diverse etiologies. The current management of pancreatitis is reviewed, focusing on recent advances. Children with pancreatitis must be fully investigated, not least to select out those who benefit from specific surgical interventions. The treatment of pancreas divisum, pseudocysts, and fibrosing pancreatitis deserve particular consideration. Management of pancreatic injuries involving the main pancreatic duct is both variable and controversial. Treatment should be individualized depending on the site of injury, timing of referral, presence of associated injuries, and institutional expertise.

  19. Endocrine involvement in systemic amyloidosis. (United States)

    Ozdemir, Didem; Dagdelen, Selcuk; Erbas, Tomris


    To present an overview of the published data on endocrine involvement and endocrine dysfunction in patients with systemic amyloidosis. We conducted a review of the medical literature using MEDLINE data sources, including clinical trials, in vitro studies, and case reports on pituitary, thyroid, parathyroid, pancreatic, adrenal, and gonadal involvement in systemic amyloidosis. Reports of endocrine involvement in systemic amyloidosis seem to consist primarily of small-samplesize clinical trials or case reports, probably because of the rarity of the disease itself. Systemic amyloidosis mainly involves and causes functional impairment in the thyroid and testes in the endocrine system. Evaluation of adrenal function necessitates special consideration because amyloid infiltration of the adrenal glands resulting in failure may be a life-threatening condition. Amyloid deposition commonly seen in the pituitary gland and the pancreas of patients with Alzheimer disease and type 2 diabetes mellitus, respectively, is generally classified as local amyloidosis and should not be confused with systemic involvement. Additionally, detection of amyloid deposition in the thyroid and testes may have a diagnostic role in patients with suspected systemic or renal amyloidosis. Published data suggest that systemic amyloidosis frequently involves the endocrine system, and endocrine dysfunction seems to be not as rare as previously thought. A rapidly growing goiter or symptoms and signs of adrenal or gonadal dysfunction should raise suspicion of amyloid infiltration. Involvement of pituitary, parathyroid, and pancreatic sites in systemic amyloidosis still remains to be clarified. Further studies with larger sample sizes are needed for complete characterization of the effect of systemic amyloidosis on the endocrine system.

  20. Endocrine System (For Teens) (United States)

    ... Counselors Kidney Stones Brain and Nervous System Endocrine System KidsHealth > For Teens > Endocrine System Print A A ... called the endocrine system . What Is the Endocrine System? Although we rarely think about the endocrine system, ...

  1. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection. (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


    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 pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

  2. An Atypical Presentation Of Pancreatic Carcinoma With Malignant ...

    African Journals Online (AJOL)

    Background: Pleural effusion secondary to pancreatic tumour is a relatively rare clinical presentation. Aim of study: To present a case of a patient that had pancreatic tumour who presented with features of left sided pleural effusion with a view to highlighting the clinical features of the presentation. Method of study: The case ...

  3. Adenoviral vectors stimulate glucagon transcription in human mesenchymal stem cells expressing pancreatic transcription factors

    National Research Council Canada - National Science Library

    Zaldumbide, Arnaud; Carlotti, Françoise; Gonçalves, Manuel A; Knaän-Shanzer, Shoshan; Cramer, Steve J; Roep, Bart O; Wiertz, Emmanuel J H J; Hoeben, Rob C


    .... Forced expression of key regulators of pancreatic differentiation in stem cells, liver cells, pancreatic duct cells, or cells from the exocrine pancreas, can lead to the initiation of endocrine...

  4. Establishment and characterization of a novel murine model of pancreatic cancer cachexia (United States)

    Michaelis, Katherine A.; Zhu, Xinxia; Burfeind, Kevin G.; Krasnow, Stephanie M.; Levasseur, Peter R.; Morgan, Terry K.


    Abstract Background Cachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC‐associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRASG12D P53R172H Pdx‐Cre+/+ (KPC) mouse. Methods Male and female C57BL/6 mice were inoculated subcutaneously, intraperitoneally, or orthotopically with KPC tumour cells. We performed rigorous phenotypic, metabolic, and behavioural analysis of animals over the course of tumour development. Results All routes of administration produced rapidly growing tumours histologically consistent with moderate to poorly differentiated PDAC. The phenotype of this model was dependent on route of administration, with orthotopic and intraperitoneal implantation inducing more severe cachexia than subcutaneous implantation. KPC tumour growth decreased food intake, decreased adiposity and lean body mass, and decreased locomotor activity. Muscle catabolism was observed in both skeletal and cardiac muscles, but the dominant catabolic pathway differed between these tissues. The wasting syndrome in this model was accompanied by hypothalamic inflammation, progressively decreasing brown and white adipose tissue uncoupling protein 1 (Ucp1) expression, and increased peripheral inflammation. Haematological and endocrine abnormalities included neutrophil‐dominant leukocytosis and anaemia, and decreased serum testosterone. Conclusions Syngeneic KPC allografts are a robust model for studying cachexia, which recapitulate key features of the PDAC disease process and induce a wide array of cachexia manifestations. This model is therefore ideally suited for future studies exploring the physiological systems involved in cachexia and for preclinical

  5. New advances in pancreatic surgery. (United States)

    Beger, Hans G; Rau, Bettina M


    New understanding of the dynamic of acute pancreatitis, the clinical impact of local pathology in chronic pancreatitis and cystic neoplastic lesions bearing high potential for malignant transformation has changed the management of pancreatic diseases. In acute pancreatitis, risk factors independently determining outcome in severe acute pancreatitis are early and persistent multiorgan failure, infected necrosis and extended sterile necrosis. The management of severe acute pancreatitis is based on early intensive-care treatment and late surgical debridement. In chronic pancreatitis, recent data from randomized controlled clinical trials have demonstrated duodenum-preserving pancreatic head resection with an inflammatory mass of the head as superior to pylorus-preserving Whipple resection. Cystic neoplasms are local lesions of the pancreas with high malignant potential. Local organ-preserving resection techniques have been applied with low morbidity and mortality, replacing a Whipple-type resection. Resection of pancreatic cancer is ineffective to cure patients. After an R0-resection, a significant survival benefit has been achieved when adjuvant chemotherapy has additionally been applied. New knowledge about the nature of inflammatory diseases, cystic neoplastic lesions and malignant pancreatic tumours has changed the indication for surgical treatment and the application of organ-preserving surgical techniques.

  6. Recent developments in the treatment of alcoholic chronic pancreatitis. (United States)

    Tsujimoto, Tatsuhiro; Kawaratani, Hideto; Yoshiji, Hitoshi; Uemura, Masahito; Fukui, Hiroshi


    Chronic pancreatitis is a progressive inflammatory condition characterized by repeated attacks of abdominal pain, and the destruction and fibrosis of the pancreatic parenchyma which causes to reduced exocrine and endocrine functions. Alcohol is the most common cause of chronic pancreatitis. Although abstinence is usually considered a prerequisite for successful treatment of alcoholic chronic pancreatitis, we often encounter patients who have repeated attacks from the compensated stage through the transitional stage. In alcoholic chronic pancreatitis, continued alcohol consumption causes changes in the digestive hormones and vagal nerve function that induce the pancreatic acinar cells to oversecrete protein, increasing the protein concentration and viscosity of the pancreatic juice. This induces protein sedimentation from the pancreatic juice and formation of protein plugs within the pancreatic duct, triggering repeated attacks of acute pancreatitis. The treatment of alcoholic chronic pancreatitis includes alleviation of symptoms, particularly abdominal pain, elimination of trigger factors, prevention of recurrence and disease progression, adjuvant therapies for pancreatic exocrine and endocrine failure. Recently, the main constituent proteins in these protein plugs have been identified, enabling trials of several therapies, such as the administration of secretin formulations and endoscopic removal. Bromhexine hydrochloride, a bronchial mucolytic, has an affinity for the pancreatic acinar cells, inducing them to secrete pancreatic juice of low viscosity. In this review, we summarize the most recent thoughts about alcoholic chronic pancreatitis, and the new treatments, and in particular, we present our findings concerning the efficacy of bromhexine hydrochloride in the treatment of this disease.

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

    Directory of Open Access Journals (Sweden)

    Taylor M. Gilliland


    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

  8. Pancreatic Cancer (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  9. Imaging in the diagnosis of chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Vasile D. Balaban


    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.

  10. Endocrine Disrupting Chemicals (EDCs) (United States)

    ... Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone Abuse Peer ... and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. Fact Steroid ...

  11. [Radioisotopic imaging of neuroendocrine tumours. Which radiopharmaceutical and which diagnostic procedure?]. (United States)

    Bombardieri, E; Maccauro, M; Castellani, M R; Chiti, A; Procopio, G; Bajetta, E; Seregni, E


    Neuroendocrine tumours can be visualized by several nuclear medicine modalities based on different mechanisms of cellular uptake. The most widely used radiopharmaceutical are the metaiodobenzylguanidine (123I/131I MIBG) and pentetreotide (111In pentetreotide). The first tracer follows the metabolic pathway of norephinephrine while the second one binds to somatostatin receptors which are expressed with high intensity on the neuroendocrine tissue. Some radiopharmaceuticals (Anti-CEA, Anti-CgA, Anti-GD2 monoclonal antibodies) have today only an experimental value, others such as 99mTc(V)DMSA had in the past very limited indications (medullary thyroid cancer) but at present their production is going to be stopped. An interesting series of new peptides showing a great affinity for the receptors/structures expressed by the neuroendocrine tissue is under evaluation in order to obtain a better tumour specificity. Among the positron-emitting radiopharmaceuticals, the 18F-fluorodeoxyglucose (FDG), in spite it is considered the most widely used tracer for clinical PET in oncology, did not show a satisfactory uptake in the well differentiated neuroendocrine tissues. On the contrary 18F-FDG is the best radiopharmaceutical to visualize those rare poorly differentiated neurondocrine tumours with a high proliferative index. For this reason also in this area, new radiopharmaceuticals have been studies and developed. A serotonin precursor 5-hydroxytryptophan (5-HTP) labelled with 11C has shown an increased uptake in carcinoids. Another radiopharmaceutical in development for PET is 11C L-DOPA which seems to be useful in visualizing endocrine pancreatic tumours. 18F-DOPA whole body PET may be a more promising imaging approach. Aim of this review is to summarize the potential of nuclear medicine techniques in the diagnosis of neuroendocrine tumours and to stresses the renewed role of nuclear medicine in the management of this disease.

  12. Neuroendocrine tumour in a patient with neurofibromatosis type 1 ...

    African Journals Online (AJOL)


    Jun 26, 2015 ... concomitant gastrin-producing neuroendocrine tumour was found. Neuroendocrine tumours. (NETs) are very rare neoplasms originating from a wide variety of endocrine and nervous system tissue with the ability to produce different hormones. A somatostatin- and gastrin- secreting NET in a patient with HIV ...

  13. Acute Pancreatitis and Pregnancy (United States)

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  14. Update in Endocrine Autoimmunity


    Anderson, Mark S.


    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

  15. Renal cell carcinoma metastasizing to pancreatic neuroendocrine neoplasm - the second case described in the world literature. (United States)

    Bednarek-Rajewska, Katarzyna; Zalewski, Przemysław; Bręborowicz, Danuta; Woźniak, Aldona

    Tumor-to-tumor metastases are very rare events. We report a case of a 64-year-old man who presented with a tumor of the pancreas. The patient underwent partial pancreatectomy. Frozen section diagnosis of the tumor was an endocrine neoplasm. Paraffin block slide examination revealed a tumor consisting of two components: pancreatic endocrine neoplasm at the periphery of the tumor and the central part composed of clear cells with delicate vessels. The results of immunohistochemical stains revealed renal cell carcinoma surrounded by pancreatic endocrine neoplasm, therefore representing an unusual case of renal cell carcinoma metastasizing to a pancreatic endocrine neoplasm.

  16. Alcohol and pancreatic cancer. (United States)

    Go, Vay Liang W; Gukovskaya, Anna; Pandol, Stephen J


    Findings obtained from numerous prospective cohort and case-control studies on alcohol consumption and pancreatic cancer risk have been inconsistent, with many confounding variables present in various investigations. However, heavy alcohol consumption has been known to be a major cause of chronic pancreatitis and a risk factor for type 2 diabetes mellitus, both of which are linked to pancreatic cancer. It has been established that an extensive normal interaction exists between the exocrine and endocrine pancreas, as well as in inflammatory processes and carcinogenesis. Alcohol and its metabolites (acetaldehyde and fatty acid ethyl esters) can alter metabolic pathways involved in the inflammatory response and carcinogenesis, and they are mediated by one or more of the following mechanisms: (1) premature activation of zymogens; (2) induction of the inflammatory response through activation of nuclear transcription factors, including nuclear factor-kappa and activation protein 1; (3) increased production of reactive oxygen species, resulting in oxidative DNA damage and altered effect of dietary antioxidants; (4) activation of pancreatic stellate cells, which leads to fibrosis; (5) gene mutation in enzymes related to cytochrome P450, glutathione S-transferase, aldehyde dehydrogenase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor; (6) synergistic effects of ethanol and tobacco carcinogen on NNK [nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] metabolism; and (7) dysregulation of proliferation and apoptosis. These various metabolic effects of alcohol can lead to or interact with other risk factors (genetic, dietary, environmental, and lifestyle factors) that result in acute and chronic pancreatitis and diabetes mellitus and, ultimately, affect the multistep process of carcinogenesis toward the development of pancreatic cancer.

  17. Endocrine Disruptors

    Directory of Open Access Journals (Sweden)

    Paolo F. Ricci


    Full Text Available Law and science combine in the estimation of risks from endocrine disruptors (EDs and actions for their regulation. For both, dose–response models are the causal link between exposure and probability (or percentage change of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH Regulation and other regulations or directives. The integration of a vast (in kind and in scope number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices.

  18. Endocrine Labomas

    Directory of Open Access Journals (Sweden)

    Deep Dutta


    Full Text Available Laboratory endocrinology forms an integral part of 21 st century endocrinology. Perhaps, no other specialty of medicine is as closely associated with laboratory as endocrinology. This review intends to highlight the challenges faced by an endocrinologist before interpreting a hormone assay report. This review by no means is holistic but intends to highlight some of the pitfalls of laboratory endocrinology and arouse further interest in this important but neglected section of endocrinology. Lack of standardization, as well as rigorous implementation is some of the major challenges facing endocrine assays in our country. It is essential to be aware not only of the details of the method of analysis of a hormone, the pre-analytical requisites, but also disease-specific analytical issues to prevent unnecessary concern both for the patient, as well as the treating physician, as well as needless investigations. Problems with interpretation of serum prolactin, thyroglobulin, steroid hormone assays, rennin assay and vitamin-D assay have been highlighted.

  19. Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients. (United States)

    Faggiano, Antongiulio; Tavares, Lidice Brandao; Tauchmanova, Libuse; Milone, Francesco; Mansueto, Gelsomina; Ramundo, Valeria; De Caro, Maria Laura Del Basso; Lombardi, Gaetano; De Rosa, Gaetano; Colao, Annamaria


    In patients with multiple endocrine neoplasia type 1 (MEN1), expression of somatostatin receptor (SST) in parathyroid adenomas and effectiveness of therapy with somatostatin analogues on primary hyperparathyroidism (PHP) have been scarcely investigated. To evaluate the effects of depot long acting octreotide (OCT-LAR) in patients with MEN1-related PHP. Eight patients with a genetically confirmed MEN1, presenting both PHP and duodeno-pancreatic neuroendocrine tumours (NET), were enrolled. The initial treatment was OCT-LAR 30 mg every 4 weeks. This therapy was established to stabilize the duodeno-pancreatic NET before to perform parathyroidectomy for PHP. Before OCT-LAR therapy, a SST scintigraphy was performed in all patients. SST subtype 2A immunohistochemistry was performed on parathyroid tumour samples from three patients undergone parathyroidectomy after OCT-LAR therapy. Serum concentrations of PTH, calcium and phosphorus as well as the 24-h urine calcium : creatinine ratio and the renal threshold phosphate concentration were evaluated before and after OCT-LAR. After OCT-LAR therapy, hypercalcaemia and hypercalciuria normalized in 75% and 62.5% of patients, respectively, and serum phosphorus and renal threshold phosphate significantly increased. Serum PTH concentrations significantly decreased in all patients and normalized in two of them. SST subtype 2A immunostaining was found in all parathyroid adenomas investigated, while SST scintigraphy showed a positive parathyroid tumour uptake in three of eight patients (37.5%). Six months of OCT-LAR therapy controlled hypercalcaemia and hypercalciuria in two-thirds of patients with MEN1-related PHP. Direct OCT-LAR effects mediated by binding to SST expression on parathyroid tumour cells are likely the main mechanism to explain the activity of this compound on calcium and phosphorus abnormalities in MEN1 PHP.

  20. Nutrition in chronic pancreatitis. (United States)

    Rasmussen, Henrik Højgaard; Irtun, Oivind; Olesen, Søren Schou; Drewes, Asbjørn Mohr; Holst, Mette


    The pancreas is a major player in nutrient digestion. In chronic pancreatitis both exocrine and endocrine insufficiency may develop leading to malnutrition over time. Maldigestion is often a late complication of chronic pancreatic and depends on the severity of the underlying disease. The severity of malnutrition is correlated with two major factors: (1) malabsorption and depletion of nutrients (e.g., alcoholism and pain) causes impaired nutritional status; and (2) increased metabolic activity due to the severity of the disease. Nutritional deficiencies negatively affect outcome if they are not treated. Nutritional assessment and the clinical severity of the disease are important for planning any nutritional intervention. Good nutritional practice includes screening to identify patients at risk, followed by a thoroughly nutritional assessment and nutrition plan for risk patients. Treatment should be multidisciplinary and the mainstay of treatment is abstinence from alcohol, pain treatment, dietary modifications and pancreatic enzyme supplementation. To achieve energy-end protein requirements, oral supplementation might be beneficial. Enteral nutrition may be used when patients do not have sufficient calorie intake as in pylero-duodenal-stenosis, inflammation or prior to surgery and can be necessary if weight loss continues. Parenteral nutrition is very seldom used in patients with chronic pancreatitis and should only be used in case of GI-tract obstruction or as a supplement to enteral nutrition.

  1. Acute pancreatitis. (United States)

    Munsell, Melissa A; Buscaglia, Jonathan M


    Acute pancreatitis is a common disease most frequently caused by gallstone disease or excess alcohol ingestion. Diagnosis is usually based on characteristic symptoms, often in conjunction with elevated serum pancreatic enzymes. Imaging is not always necessary, but may be performed for many reasons, such as to confirm a diagnosis of pancreatitis, rule out other causes of abdominal pain, elucidate the cause of pancreatitis, or to evaluate for complications such as necrosis or pseudocysts. Though the majority of patients will have mild, self-limiting disease, some will develop severe disease associated with organ failure. These patients are at risk to develop complications from ongoing pancreatic inflammation such as pancreatic necrosis, fluid collections, pseudocysts, and pancreatic duct disruption. Validated scoring systems can help predict the severity of pancreatitis, and thus, guide monitoring and intervention.Treatment of acute pancreatitis involves supportive care with fluid replacement, pain control, and controlled initiation of regular food intake. Prophylactic antibiotics are not recommended in acute pancreatitis if there is no evidence of pancreatic infection. In patients who fail to improve, further evaluation is necessary to assess for complications that require intervention such as pseudocysts or pancreatic necrosis. Endoscopy, including ERCP and EUS, and/or cholecystectomy may be indicated in the appropriate clinical setting. Ultimately, the management of the patient with severe acute pancreatitis will require a multidisciplinary approach. (c) 2010 Society of Hospital Medicine.

  2. Pancreatic adenocarcinomas without secondary signs on multiphasic multidetector CT: association with clinical and histopathologic features

    Energy Technology Data Exchange (ETDEWEB)

    Tamada, Tsutomu; Ito, Katsuyoshi; Sone, Teruki; Kanki, Akihiko; Higaki, Atsushi; Hayashida, Minoru; Yamamoto, Akira [Kawasaki Medical School, Departments of Radiology, Kurashiki City, Okayama (Japan); Kanomata, Naoki [Kawasaki Medical School, Department of Pathology, Kurashiki City, Okayama (Japan)


    To determine the clinical, histopathologic and imaging features of pancreatic adenocarcinomas without secondary signs on dynamic CT. Seventy patients (mean age 70 years) with histologically proven pancreatic adenocarcinoma underwent preoperative contrast material-enhanced multiphasic multidetector CT before pancreatic resection. In each patient, clinical data including carbohydrate antigen 19-9, frequency of isoattenuating tumours, and presence of secondary signs and histopathologic findings such as tumour location, tumour stage, and microscopic infiltrative growth grade were evaluated. Ten tumours (14 %) were without secondary signs, and 60 (86 %) were with secondary signs. Tumours without and with secondary signs were located in the uncinate process in 5 (50 %) and 3 (5 %), head in 3 (30 %) and 29 (48 %), body in 2 (20 %) and 22 (37 %), and tail in 0 (0 %) and 6 (10 %), respectively (p =.001). The frequency of isoattenuating pancreatic adenocarcinomas without secondary signs was significantly higher than those with secondary signs (p = 0.034). The tumour stage of pancreatic adenocarcinomas without secondary signs was earlier than that in tumours with secondary signs (p = 0.041). Pancreatic adenocarcinomas without secondary signs is characterized by the presence of uncinate and isoattenuating tumours and earlier tumour stage compared to tumours with secondary signs. (orig.)

  3. Are pancreatic calcifications specific for the diagnosis of chronic pancreatitis? A multidetector-row CT analysis

    Energy Technology Data Exchange (ETDEWEB)

    Campisi, A. [Department of Radiology, University of Palermo, via del Vespro 127, 90127 Palermo (Italy); Brancatelli, G. [Department of Radiology, University of Palermo, via del Vespro 127, 90127 Palermo (Italy); Department of Radiology, University of Pittsburgh School of Medicine, 200 Lothrop street, 15213, Pittsburgh, PA (United States); Radiology Unit, La Maddalena hospital, 90146, Palermo (Italy)], E-mail:; Vullierme, M.-P.; Levy, P.; Ruzniewski, P. [Universite Paris 7 Denis Diderot, Paris, F-75018 (France); AP-HP, Hopital Beaujon, Department of Radiology, Clichy F-92100 (France); Vilgrain, V. [Universite Paris 7 Denis Diderot, Paris, F-75018 (France); AP-HP, Hopital Beaujon, Department of Radiology, Clichy F-92100 (France); INSERM, U773, Centre de recherche biomedicale Bichat-Beaujon, CRB3, Paris F-75018 (France)


    Aim: To retrospectively establish the most frequently encountered diagnoses in patients with pancreatic calcifications and to investigate whether the association of certain findings could be helpful for diagnosis. Materials and methods: One hundred and three patients were included in the study. The location and distribution of calcifications; presence, nature, and enhancement pattern of pancreatic lesions; pancreatic atrophy and ductal dilatation were recorded. Differences between patients with chronic pancreatitis and patients with other entities were compared by using Fisher's exact test. Results: Patients had chronic pancreatitis (n = 70), neuroendocrine tumours (n = 14), intraductal papillary mucinous neoplasm (n = 11), pancreatic adenocarcinoma (n = 4), serous cystadenoma (n = 4). Four CT findings had a specificity of over 60% for the diagnosis of chronic pancreatitis: parenchymal calcifications, intraductal calcifications, parenchymal atrophy, and cystic lesions. When at least two of these four criteria were used in combination, 54 of 70 (77%) patients with chronic pancreatitis could be identified, but only 17 of 33 (51%) patients with other diseases. When at least three of these four criteria were present, a specificity of 79% for the diagnosis of chronic pancreatitis was achieved. Conclusion: Certain findings are noted more often in chronic pancreatitis than in other pancreatic diseases. The presence of a combination of CT findings can suggest chronic pancreatitis and be helpful in diagnosis.

  4. Complicated Pancreatitis

    NARCIS (Netherlands)

    Bakker, O.J.


    Research questions addressed in this thesis: What is the accuracy of serum blood urea nitrogen as early predictor of complicated pancreatitis? ; What is difference in clinical outcome between patients with pancreatic parenchymal necrosis and patients with extrapancreatic necrosis without necrosis

  5. Pancreatitis - children (United States)

    ... this page: // Pancreatitis - children To use the sharing features on this page, please enable JavaScript. Pancreatitis in children occurs when the pancreas becomes swollen ...

  6. Long-Term Outcomes of Pancreatic Function Following Pancreatic Trauma. (United States)

    Morita, Toshio; Takasu, Osamu; Sakamoto, Teruo; Mori, Shinjirou; Nakamura, Atsuo; Nabeta, Masakazu; Hirayu, Nobuhisa; Moroki, Mariko; Yamashita, Norio


    The objective of this study is to retrospectively assess long-term outcomes and late complications of pancreatic trauma. We studied 14 patients with pancreatic trauma who were treated at the Advanced Emergency Medical Service Center, Kurume University Hospital, between 1981 and 2012 and discharged alive. Relevant data were extracted from patient records and a retrospective patient questionnaire and blood test were completed to evaluate pancreatic function. The median patient age at the time of the survey was 49 years; the median post-injury period was 23 years and 5 months. The comorbidity rates for pancreatic endocrine and exocrine dysfunctions were 35.7% and 33.3%, respectively. No new-onset diabetes mellitus (DM) was seen within 3 years of trauma, except in 1 patient who underwent pancreaticoduodenectomy. DM developed >15 years after trauma in 2 patients each in the pancreatectomy and non-pancreatectomy groups. Diarrhea exacerbated by fat intake was seen in 3 and 1 patient in the pancreatectomy and non-pancreatectomy groups, respectively. Both complications were more common in the pancreatectomy group, but without statistical significance. Although post-surgical pancreatic dysfunction may be absent at discharge, treatment for pancreatic trauma should take into account the possibility that pancreatectomy may accelerate DM onset.

  7. Endocrine Treatment of Transsexual Persons (United States)

    ... Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone Abuse Peer ... About Clinical Trials Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone Abuse Peer ...

  8. Unusual Paraneoplastic Syndrome Accompanies Neuroendocrine Tumours of the Pancreas

    Directory of Open Access Journals (Sweden)

    Helga Bertani


    Full Text Available Neuroendocrine tumours comprise a small percentage of pancreatic neoplasia (10% (1. Diagnosis of neuroendocrine tumours is difficult, especially if the tumours are small and nonfunctional. CT scans, MRI, and nuclear scans are sufficiently sensitive assessment tools for tumours with diameters of at least 2 cm; otherwise, the sensitivity and specificity of these techniques is less than 50% (2. Myasthenia gravis (MG is a heterogeneous neuromuscular junction disorder that is primarily caused when antibodies form against the acetylcholine receptors (Ab-AchR. MG can develop in conjunction with neoplasia, making MG a paraneoplastic disease. In those cases, MG is most commonly associated with thymomas and less frequently associated with extrathymic malignancies. The mechanism underlying this paraneoplastic syndrome has been hypothesized to involve an autoimmune response against the tumour cells (3. No published reports have linked malignant pancreatic diseases with MG. Here, we report the case of a young woman, negative for Ab-AchR, with a neuroendocrine tumour in the pancreatic head, who experienced a complete resolution of her MG-like syndrome after surgical enucleation of the tumour.

  9. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Davorin Dajčman


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

  10. Gastric Calcifying Fibrous Tumour

    Directory of Open Access Journals (Sweden)

    Tan Attila


    Full Text Available Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours; however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases.

  11. Primary liver tumour of intermediate (hepatocyte-bile duct cell) phenotype: a progenitor cell tumour? (United States)

    Robrechts, C; De Vos, R; Van den Heuvel, M; Van Cutsem, E; Van Damme, B; Desmet, V; Roskams, T


    A 57-year-old female patient presented with painless obstructive jaundice and mild mesogastric pain; she was in good general condition on admission. Abdominal ultrasonography revealed diffuse tumoral invasion of the liver, suggesting diffuse metastases. A liver biopsy showed a tumour with a trabecular growth pattern, composed of uniform relatively small cells, very suggestive of an endocrine carcinoma. Additional immunohistochemical stains, however, did not show any endocrine differentiation, but showed positivity for both hepatocyte-type cytokeratins (cytokeratin 8 and 18) and bile duct-type cytokeratins (cytokeratin 7 and 19). In addition, parathyroid hormone-related peptide, shown to be a good marker for cholangiocarcinoma, was immunoreactive. Electron microscopy revealed tumour cells with an intermediate phenotype: the cells clearly showed hepatocyte features on one hand and bile duct cell features on the other hand. Nine days after admission, the patient died due to liver failure and hepatic encephalopathy. Autopsy excluded another primary tumour site. Overall, this tumour was a primary liver tumour with an intermediate phenotype and with a very rapid clinical course. The intermediate (between hepatocyte and bile duct cell) phenotype suggests an immature progenitor cell origin, which is concordant with a rapid clinical course. This type of tumour has not been described previously and provides additional evidence for the existence of progenitor cells in human liver.

  12. Dynamic MRI of pancreatic neoplasms

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    Furukawa, Nobuyoshi; Takayasu, Ken-ichi; Muramatu, Yukio [National Cancer Center, Tokyo (Japan). Hospital


    The usefulness of dynamic MRI study using contrast media is studied on pancreatic tumors. This method was useful in detecting small lesion of pancreatic tumor, however, T1-weighted SE method was more useful in detecting swelling lesions or diagnosing degree of tumors. Although endocrine tumors are depicted by contrast media, careful attention is needed since there are some hypovascular cases. T2-weighted image is commonly performed to detect the morphology of cystic content and the correlation between the pancreas and bile duct in cystic tumors, however, dynamic study was more useful in proving vascularity of serous cystadenoma and differentiating malignant or benign mucous cystic tumors by depicting intracystic torous components. In performing MR imaging on pancreatic diseases, it is necessary to select appropriate imaging procedure, and dynamic study should be included and used in a rational manner. (S.Y.).

  13. Chronic pancreatitis. (United States)

    Yang, Dennis; Forsmark, Chris E


    Summarize key clinical advances in chronic pancreatitis reported in 2016. Early diagnosis of chronic pancreatitis remains elusive. Recent studies suggest that endoscopic ultrasound may be less accurate than previously thought and new MRI techniques may be helpful. Genetic predisposition may independently affect the clinical course of chronic pancreatitis and the risk for pancreatic cancer. Cigarette smoking may have a greater negative impact on chronic pancreatitis than previously thought and moderate alcohol consumption may be protective. A multidisciplinary approach is necessary for the treatment of type 3 diabetes and nutritional deficiencies in chronic pancreatitis. Although endoscopic therapy remains a reasonable first-line option in treating chronic pancreatitis and its complications, early surgical intervention may be indicated for pain in select patients. Newer endoscopic ultrasound and MRI techniques are being evaluated to help with the early diagnosis of chronic pancreatitis. Both genetic predisposition and cigarette smoking are increasingly recognized as having a major impact in the course of the disease and the risk for pancreatic cancer. Endoscopic therapy is well tolerated and effective for the treatment of chronic pancreatitis and its complications although an early surgical approach for pain may be associated with improved clinical outcomes.

  14. Tumour-induced osteomalacia: An emergent paraneoplastic syndrome. (United States)

    Alonso, Guillermo; Varsavsky, Mariela


    Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  15. Environmental endocrine disruptors: New diabetogens? (United States)

    Fénichel, Patrick; Chevalier, Nicolas

    The prevalence of type-2 diabetes has dramatically increased worldwide during the last few decades. While lifestyle factors (sedentariness, noxious food), together with genetic susceptibility, are well-known actors, there is accumulating evidence suggesting that endocrine disrupting chemicals (EDCs) may also play a pathophysiological role in the occurrence of metabolic diseases. Both experimental and epidemiological evidence support a role for early and chronic exposure to low doses of chemical pollutants with endocrine and metabolic disrupting effects. Most are present in the food chain and accumulate in the fat mass after absorption. In rodents, bisphenol A stimulates synthesis and secretion of pancreatic β cells and disturbs insulin signaling in liver, muscle and adipose tissue through epigenetic changes leading to insulin resistance and β cell impairment. In humans, epidemiological reports show statistical link between exposure to pesticides, polychlorinated bisphenyls, bisphenol A, phthalates, dioxins or aromatic polycyclic hydrocarbides or heavy metals and DT2 after acute accidental releases or early in life and/or chronic, low doses exposure. More prospective, longitudinal studies are needed to determine the importance of such environmental risk factors. Copyright © 2017. Published by Elsevier Masson SAS.

  16. Pentoxifylline Treatment in Acute Pancreatitis (AP) (United States)


    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  17. Obesity, pancreatitis, and pancreatic cancer. (United States)

    Gumbs, Andrew A


    The only universally accepted risk factors for the development of pancreatic cancer are a positive family history or a history of smoking. Although the contribution of pancreatitis to pancreatic carcinogenesis has been debated for decades in the epidemiology literature, the actual mechanism is still unclear. With the rising epidemic of obesity, scientists have begun to focus on the contribution of chronic inflammatory state of morbidly obese patients in an effort to better understand the contribution of inflammation to the comorbidities of obesity. Notably, population studies are beginning to show that one of the most serious potential comorbidities of obesity is an increased lifetime risk of developing cancer. In this article, the current literature that exists supporting this Chronic Inflammatory Hypothesis as it pertains to obesity and pancreatic carcinogenesis is reviewed. To date, studies have focused on interleukin-6, a cytokine known to play a role in obesity, chronic pancreatitis and pancreatic cancer. The anti-inflammatory adipocytokine, adiponectin, has also shown promise as a key player in this mechanism and has recently been found to be more specific than standard tumor markers in differentiating pancreatic cancer from chronic pancreatitis. If the pathogenesis of pancreatic cancer is related to hormone levels associated with obesity, such as adipocytokines, and cytokines associated with chronic inflammation, this could potentially lead to the development of new pancreatic cancer tumor markers and ultimately new therapies and methods of prevention.

  18. [Chronic pancreatitis: Retrospective review of 121 cases]. (United States)

    Berger F, Zoltán; Mancilla A, Carla


    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.

  19. Targeting senescence cells in pancreatic cancer | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Targeting senescence cells in pancreatic cancer. Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination.

  20. Multimodality Treatment in Pancreatic and Periampullary Cancer

    NARCIS (Netherlands)

    M.J.M. Morak (Marjolein)


    markdownabstract__Abstract__ Pancreatic cancer is the eight most common form of cancer in Europe with 96.000 new cases yearly. This incidence closely matches the mortality rate, thus revealing the aggressive behaviour of this tumour. Five-year survival after diagnosis is only 5% with a median

  1. Multiple endocrine neoplasia: the Chilean experience

    Directory of Open Access Journals (Sweden)

    René E. Diaz


    Full Text Available Multiple endocrine neoplasia (MEN types 1 and 2 are genetic diseases that are inherited as autosomal traits. The major clinical manifestations of multiple endocrine neoplasia type 1 include the so-called "3 P's": parathyroid, pituitary, and pancreatic tumors, including gastroenteroneuroendocrine tumors. Genetic testing can be performed on patients and the potential carriers of the menin gene mutation, but the genotype-phenotype correlation in multiple endocrine neoplasia type 1 is less straightforward than multiple endocrine neoplasia type 2. Most likely, the main advantage of genetic testing in MEN1 is to exclude from further studies those who are negative for the genetic mutation if they belong to a family with a known history of MEN1. In Chile, we started with rearranged during transfection proto-oncogene genetic testing (MEN2 15 years ago. We carried out a prophylactic total thyroidectomy to prevent medullary thyroid carcinoma in a three-year-old girl who presented with microscopic medullary thyroid carcinoma. More than 90% of the individuals who tested positive using a genetic test achieved a biochemical cure compared with only 27% of patients who receive a clinical diagnosis. Mutations are mainly located in exon 11; the most common is C634W, rather than C634R. Hypertensive crisis was the cause of death in three patients, and extensive distant metastases occurred in nine (including two patients with multiple endocrine neoplasia type 2B of 14 patients. Earlier recognition of medullary thyroid carcinoma and the other features of the disease, especially pheochromocytoma, will improve the survival rate of patients with multiple endocrine neoplasia.

  2. Multiple endocrine neoplasia type 1 (MEN-1). Clinical, biochemical and genetical investigations. (United States)

    Oberg, K; Skogseid, B; Eriksson, B


    The syndrome of multiple endocrine neoplasia type 1 is an autosomal dominantly inherited disease affecting several endocrine organs. The affected organs include the pituitary, the parathyroids and endocrine pancreas, where different types of lesions can be found, such as hyperplasia or frank carcinomas. The most life threatening lesions are the endocrine pancreatic tumors, which cause about 80% of all deaths among the MEN-1 members. In our own series of 108 members from 16 families with multiple endocrine neoplasia, 55 members had the MEN-1 trait. Among these members, pituitary lesions were found in 42%, parathyroid involvement in 89% and endocrine pancreatic tumors in 58%. Hyperparathyroidism was the presenting lesion of the MEN-1 trait. By using a specific meal stimulation test we have been able to unveil pancreatic lesions up to a median of five years previous to radiological detection. Very recently we have been able to detect a specific genetic lesion in MEN-1 members by studying DNA rearrangements with recombinant DNA technique, using the method of polymorphic restriction enzyme recognition in three large kindreds. The MEN-1 locus maps to chromosome 11q and the MEN-1 predisposition would be a constitutional mutation in heterozygous form, inherited as an autosomal dominant trait. Tumor development involves a second mutational event which involves the chromosome 11, carrying the remaining 'wild' type allele at the MEN-1 locus by means of chromosome loss event. Survival analysis demonstrates that patients with the MEN-1 syndrome had a significantly better survival from diagnosis than patients with sporadic endocrine pancreatic tumors (median 15.1 years and 5.8 years respectively, p = 0.0068). Earlier diagnosis and start of treatment might account for a longer survival in the MEN-1 group, but a possibility of differences in tumor biology between familial and sporadic endocrine pancreatic tumors cannot be ruled out. The surgical treatment of patients with MEN-1

  3. Animal models for investigating chronic pancreatitis (United States)


    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

  4. Endocrine system: part 1. (United States)

    Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella


    This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

  5. Introduction to the Endocrine System (United States)

    ... Spikes Is mealtime insulin right for you? The Endocrine System Access more 3D visualizations by downloading the Hormone ... Endocrinologist Clinical Trials Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone Abuse Peer ...

  6. Introduction to the Endocrine System (United States)

    ... Resources Featured Resource Find an Endocrinologist Search The Endocrine System Access more 3D visualizations by downloading the Hormone ... About Clinical Trials Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone Abuse Peer ...

  7. Diagnosis and Treatment of Gastrinomas in Multiple Endocrine Neoplasia Type 1 (MEN-1

    Directory of Open Access Journals (Sweden)

    Ursula Plöckinger


    Full Text Available Multiple endocrine neoplasia type 1 (MEN-1 is a rare autosomal-dominant disease. It is associated with a broad range of endocrine tumours, most frequently arising in the parathyroid glands, the pituitary and the pancreas. Most neuroendocrine tumours will be diagnosed in the pancreas as non-functioning neuroendocrine tumours or insulinomas. Forty-two percent of the patients will develop a gastrin-secreting neuroendocrine tumour, a gastrinoma. Gastrinomas in MEN-1 tend to be small, multiple and preferentially located in the duodenum. This paper will focus on the specific characteristics of gastrinomas in the setting of MEN-1 compared to sporadic gastrinomas. The developments in understanding the tumorigenesis of these tumours and the consequences for diagnosis and therapy will be discussed.

  8. [Autoimmune pancreatitis]. (United States)

    Beyer, G; Menzel, J; Krüger, P-C; Ribback, S; Lerch, M M; Mayerle, J


    Autoimmune pancreatitis is a relatively rare form of chronic pancreatitis which is characterized by a lymphoplasmatic infiltrate with a storiform fibrosis and often goes along with painless jaundice and discrete discomfort of the upper abdomen. Clinically we distinguish between two subtypes, which differ in terms of their histology, clinical picture and prognosis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-associated syndrome which also involves other organs. About one third of the patients can only be diagnosed after either histological prove or a successful steroid trail. Type 2 is IgG4-negative with the histological picture of an idiopathic duct centric pancreatitis and is to higher degree associated with inflammatory bowel disease. A definitive diagnosis can only be made using biopsy. Usually both forms show response to steroid treatment, but in type 1 up to 50 % of the patients might develop a relapse. The biggest challenge and most important differential diagnosis remains the discrimination of AIP from pancreatic cancer, because also AIP can cause mass of the pancreatic head, lymphadenopathy and ductal obstruction. This article summarizes recent advances on epidemiology, clinical presentation, diagnostic strategy, therapy and differential diagnosis in this relatively unknown disease. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Archives: Nigerian Endocrine Practice

    African Journals Online (AJOL)

    Archives: Nigerian Endocrine Practice. Journal Home > Archives: Nigerian Endocrine Practice. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives. 1 - 4 of 4 Items. 2013. Vol 7, No 1 ...

  10. Endocrine system and obesity. (United States)

    Ashburn, Doyle D; Reed, Mary Jane


    Obesity is associated with significant alterations in endocrine function. An association with type 2 diabetes mellitus and dyslipidemia has been well documented. This article highlights the complexities of treating endocrine system disorders in obese patients. Copyright © 2010. Published by Elsevier Inc.

  11. The endocrine quiz

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra


    Full Text Available With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject.

  12. Tumours and tumourous diseases; Tumoren, tumoraehnliche Erkrankungen

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    Winkelmann, W. (ed.)


    This book on tumours and tumourous diseases comprises two parts: 1. Bone tumours and tumourous lesions. 2. Soft tissue tumours and tumourous lesions. Details are presented on pathology, diagnosis, conservative and perioperative therapy, surgical therapy, complications after resection, indicators for amputation, recommendations for follow-up treatment, radiotherapy, radionuclide therapy, alternative therapies, therapy concepts in case of metastases, tissue engineering and plastic surgery. (uke) [German] Der vorliegende Band der Reihe Orthopaedie und orthopaedische Chirurgie behandelt das Thema Tumoren und tumoraehnliche Erkrankungen. Der Band teilt sich in zwei Kapitel: 1. Knochentumoren und tumorartige Laesionen und 2. Weichteiltumoren und tumorartige Laesionen. Dargestellt werden Pathologie, Diagnostik, konservative und perioperative Therapie, chirurgische Therapie, Komplikationen nach Resektion, Indikatoren zur Amputation, Nachsorgeempfehlung, Strahlentherapie, Radionuklidtherapie, alternative Therapieverfahren, Therapiekonzepte bei Metastasen, Tissue Engineering und plastisch-chirurgische Massnahmen. (uke)

  13. Acute Pancreatitis in Children (United States)

    ... an episode of pancreatitis. How do you treat pancreatitis? The treatment of pancreatitis is supportive care. There is no ... and Diagnosis Risks and Treatment Complementary Therapies Chronic Pancreatitis ... and Diagnosis Pain Management/Treatment Pediatric Pancreatitis

  14. Chronic Pancreatitis in Children (United States)

    ... Information Children/Pediatric Chronic Pancreatitis in Children Chronic Pancreatitis in Children What symptoms would my child have? ... will develop diabetes in adolescence. Who gets chronic pancreatitis? Those at risk for chronic pancreatitis are children ...

  15. Pancreatic Cysts (United States)

    ... Pancreatic cysts Symptoms & causes Diagnosis & treatment Doctors & departments Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  16. Chronic pancreatitis

    NARCIS (Netherlands)

    Bruno, Marco J.


    In the past 20 years, endoscopic ultrasonography has been added to the already large armamentarium of diagnostic tests for chronic pancreatitis. This article discusses its potential and possible limitations

  17. Pancreatitis - slideshow (United States)

    ... gov/ency/presentations/100149.htm Pancreatitis - series—Normal anatomy To use the sharing features on this page, ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

  18. Robot-assisted spleen preserving pancreatic surgery in MEN1 patients

    NARCIS (Netherlands)

    Nell, Sjoerd; Brunaud, Laurent; Ayav, Ahmet; Bonsing, Bert A.; Koerkamp, Bas Groot; van Dijkum, Els J. Nieveen; Kazemier, Geert; de Kleine, Ruben H. J.; Hagendoorn, Jeroen; Molenaar, I. Quintus; Valk, Gerlof D.; Rinkes, Inne H. M. Borel; Vriens, Menno R.


    BackgroundMultiple Endocrine Neoplasia type 1 (MEN1) patients often undergo multiple pancreatic operations at a young age. ObjectiveTo describe robot-assisted and laparoscopic spleen-preserving pancreatic surgery in MEN1 patients, and to compare both techniques. MethodsRobot-assisted

  19. [Early endocrine complications in childhood cancer survivors]. (United States)

    Sánchez González, Cristina; Andrades Toledo, Mónica; Cárdeno Morales, Álvaro; Gutiérrez Carrasco, Ignacio; Ramírez Villar, Gema Lucía; Pérez Hurtado, José María; García García, Emilio


    The treatment of childhood cancers has increased survival rates, but also the risk of sequelae, such as endocrine complications. The objective of this study is to evaluate the endocrine disorders in survivors of childhood malignant tumors within the first years after treatment and analyze the variables related to their appearance. A retrospective medical record review of patients referred to pediatric endocrinology after treatment of malignancy. Outcome measures were frequency and types of endocrine dysfunction and new-onset obesity. Clinical and laboratory evaluations were performed every 6 months. Statistics tests were: chi square and multiple logistic regression. Fifty five patients (26 women) were included with an age at diagnosis of tumour (mean±standard deviation) 6.0±4.4 years and followed up for 6.8±3.6 years. Thirty endocrine disorders were diagnosed in 26 patients (47.3%), 17 women (P=.01). Eleven adolescents had primary hypogonadism (26.2% to 0.6±0.5 years of follow-up) in relation to local irradiation (adjusted odds ratio [OR] 3.99, P=.005). Eleven patients had a pituitary disorder (20.0%) 5.2±2.4 years after diagnosis in relation to brain irradiation (OR 1.54, P=.039). Six children (10.9%) had primary hypothyroidism from 3.2±1.0 years of follow-up. Two children developed obesity. Endocrine disorders are frequently seen within the first years after diagnosis of a childhood cancer, so hormonal evaluation should start early and be repeated periodically. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  20. Endocrine disorders in pregnancy

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Mathiesen, Elisabeth R


    hormones and their precursors across the foeto-maternal interface. The endocrine system is the earliest system developing in foetal life, and it is functional from early intrauterine existence through old age. Regulation of the foetal endocrine system relies, to some extent, on precursors secreted......The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The vast changes in maternal hormones and their binding proteins complicate assessment of the normal level of most hormones...

  1. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment. (United States)

    Kim-Fuchs, Corina; Le, Caroline P; Pimentel, Matthew A; Shackleford, David; Ferrari, Davide; Angst, Eliane; Hollande, Frédéric; Sloan, Erica K


    Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Controversies in Odontogenic Tumours (United States)

    Siwach, Pooja; Joy, Tabita; Tupkari, Jagdish; Thakur, Arush


    Odontogenic tumours are lesions that occur solely within the oral cavity and are so named because of their origin from the odontogenic (i.e. tooth-forming) apparatus. Odontogenic tumours comprise a variety of lesions ranging from non-neoplastic tissue proliferations to benign or malignant neoplasms. However, controversies exist regarding the pathogenesis, categorisation and clinical and histological variations of these tumours. The recent 2017 World Health Organization classification of odontogenic tumours included new entities such as primordial odontogenic tumours, sclerosing odontogenic carcinomas and odontogenic carcinosarcomas, while eliminating several previously included entities like keratocystic odontogenic tumours and calcifying cystic odonogenic tumours. The aim of the present review article was to discuss controversies and recent concepts regarding odontogenic tumours so as to increase understanding of these lesions. PMID:29062548

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

    LENUS (Irish Health Repository)

    Duggan, SN


    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.

  4. Surgical strategies in endocrine tumors

    NARCIS (Netherlands)

    Schreinemakers, J.M.J.


    Endocrine surgery has become more custom-made throughout the years. Endocrine tumors can be sporadic or develop as part of familial syndromes. Several familial syndromes are known to cause endocrine tumors. The most common are multiple endocrine neoplasia (MEN) syndromes type 1, 2A and 2B. This

  5. Candesartan mediates microcirculation in acute necrotizing pancreatitis. (United States)

    Bostanci, H; Sahin, T T; Dikmen, K; Dikmen, A U; Yuksel, O; Gulbahar, O; Poyraz, A; Tekin, E


    In the present study we aimed to determine the effect of an AT-II antagonist candesartan on pancreatic microcirculation in an experimental model of acute necrotizing pancreatitis. There were five study groups with 10 animals in each. Pancreatitis was induced by intravenous infusion of cerulein and coadministration of glycodeoxycholate into biliopancreatic canal. Candesartan is given at 6th and 18th hour to the 24th and 48th hour groups, respectively. At 24th and 48th hours; following anaesthesia laparotomy was performed and laser Doppler flowmetry was performed in the pancreatic tissue of the animals. Following scarification blood samples were obtained for amylase, myeloperoxidase, IL-6 and tumour necrosis factor alpha. Tissue samples from the pancreas were obtained for histopathological analysis, endothelial cell apoptosis (TUNEL assay) and matrix metalloproteinase-9 immunohistochemistry. Pancreatic microcirculation was higher in the candesartan treated groups (p candesartan treated groups (p candesartan treated groups (p 0.05). Tissue matrix metalloproteinase -9 levels were found to be reduced with candesartan treatment (p candesartan in the early phases of acute necrotizing pancreatitis effective on microcirculation of pancreatic tissue (Tab. 3, Fig. 6, Ref. 28).

  6. CCAR1 is required for Ngn3-mediated endocrine differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Chung-Kuang [Department of Life Science, National Chung Cheng University, Chia-Yi, Taiwan, ROC (China); Lai, Yi-Chyi [Department of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC (China); Lin, Yung-Fu; Chen, Hau-Ren [Department of Life Science, National Chung Cheng University, Chia-Yi, Taiwan, ROC (China); Chiang, Ming-Ko, E-mail: [Department of Life Science, National Chung Cheng University, Chia-Yi, Taiwan, ROC (China)


    Highlights: Black-Right-Pointing-Pointer We identify CCAR1 to directly interact with Ngn3. Black-Right-Pointing-Pointer CCAR1 is co-localized with Ngn3 in the nucleus. Black-Right-Pointing-Pointer CCAR1 cooperates with Ngn3 in activating NeuroD expression. Black-Right-Pointing-Pointer CCAR1 is required for Ngn3-mediated PANC-1 transdifferentiation. -- Abstract: Neurogenin3 (Ngn3) is a basic helix-loop-helix transcription factor that specifies pancreatic endocrine cell fates during pancreas development. It can also initiate a transdifferentiation program when expressed in pancreatic exocrine and ductal cells. However, how Ngn3 initiates a transcriptional cascade to achieve endocrine differentiation is still poorly understood. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1), which is a transcriptional coactivator for nuclear receptors, also interacts with Ngn3. The association between Ngn3 and CCAR1 was verified by pull-down assays and co-immunoprecipitation analyses. Using gene reporter assays, we found that CCAR1 is essential for Ngn3 to activate the expression of the reporter genes containing the NeuroD promoter. Moreover, down-regulation of endogenous CCAR1 in the PANC-1 pancreatic ductal cell line inhibits the transdifferentiation program initiated by Ngn3. CCAR1 is, therefore, a novel partner of Ngn3 in mediating endocrine differentiation.

  7. Endocrine system: part 2. (United States)

    Hendry, Charles; Farley, Alistair; McLafferty, Ella; Johnstone, Carolyn


    This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.

  8. Patients With Long-QT Syndrome Caused by Impaired hERG-Encoded Kv11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated With Reactive Hypoglycemia. (United States)

    Hyltén-Cavallius, Louise; Iepsen, Eva W; Wewer Albrechtsen, Nicolai J; Svendstrup, Mathilde; Lubberding, Anniek F; Hartmann, Bolette; Jespersen, Thomas; Linneberg, Allan; Christiansen, Michael; Vestergaard, Henrik; Pedersen, Oluf; Holst, Jens J; Kanters, Jørgen K; Hansen, Torben; Torekov, Signe S


    Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long-QT syndrome type 2 (LQT2) because of prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic α and β cells and intestinal L and K cells, secreting glucagon, insulin, and the incretins glucagon-like peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide), respectively. These hormones are crucial for glucose regulation, and long-QT syndrome may cause disturbed glucose regulation. We measured secretion of these hormones and cardiac repolarization in response to glucose ingestion in LQT2 patients with functional mutations in hERG and matched healthy participants, testing the hypothesis that LQT2 patients have increased incretin and β-cell function and decreased α-cell function, and thus lower glucose levels. Eleven patients with LQT2 and 22 sex-, age-, and body mass index-matched control participants underwent a 6-hour 75-g oral glucose tolerance test with ECG recording and blood sampling for measurements of glucose, insulin, C-peptide, glucagon, GLP-1, and GIP. In comparison with matched control participants, LQT2 patients had 56% to 78% increased serum insulin, serum C-peptide, plasma GLP-1, and plasma GIP responses (P=0.03-0.001) and decreased plasma glucose levels after glucose ingestion (P=0.02) with more symptoms of hypoglycemia (P=0.04). Sixty-three percent of LQT2 patients developed hypoglycemic plasma glucose levels (QT interval and aggravated the cardiac repolarization disturbances in LQT2 patients. URL: Unique identifier: NCT02775513. © 2017 The Authors.

  9. Multimodality treatment of unresectable hepatic metastases from pancreatic glucagonoma

    Directory of Open Access Journals (Sweden)

    Giovanni Bernardo


    Full Text Available Glucagonomas are pancreatic islet cell tumors arising from the alpha cells which belong to neuroendocrine tumors. They frequently metastasize to the liver. We report the case of a 52- year old man with a pancreatic glucagonoma with synchronous multiple liver metastases treated by surgery, transarterial chemoembolization, percutaneous radiofrequency thermal ablation and long-acting octreotide. Our report confirms that a multimodal approach is very effective in patients with unresectable liver metastases from pancreatic endocrine tumors providing long-lasting palliation and probably prolonging survival.

  10. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    Energy Technology Data Exchange (ETDEWEB)

    Tonelli, Francesco, E-mail:; Giudici, Francesco [Department of Clinical Physiopathology, Surgical Unit, Medical School, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy); Giusti, Francesca; Brandi, Maria Luisa [Department of Internal Medicine, Medical School and Regional Centre for Hereditary Endocrine Tumors, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy)


    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present.

  11. [Pancreatic ultrasonography]. (United States)

    Fernández-Rodríguez, T; Segura-Grau, A; Rodríguez-Lorenzo, A; Segura-Cabral, J M


    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  12. Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer. (United States)

    Zhang, Yaqing; Velez-Delgado, Ashley; Mathew, Esha; Li, Dongjun; Mendez, Flor M; Flannagan, Kevin; Rhim, Andrew D; Simeone, Diane M; Beatty, Gregory L; Pasca di Magliano, Marina


    Pancreatic cancer is characterised by the accumulation of a fibro-inflammatory stroma. Within this stromal reaction, myeloid cells are a predominant population. Distinct myeloid subsets have been correlated with tumour promotion and unmasking of anti-tumour immunity. The goal of this study was to determine the effect of myeloid cell depletion on the onset and progression of pancreatic cancer and to understand the relationship between myeloid cells and T cell-mediated immunity within the pancreatic cancer microenvironment. Primary mouse pancreatic cancer cells were transplanted into CD11b-diphtheria toxin receptor (DTR) mice. Alternatively, the iKras* mouse model of pancreatic cancer was crossed into CD11b-DTR mice. CD11b(+) cells (mostly myeloid cell population) were depleted by diphtheria toxin treatment during tumour initiation or in established tumours. Depletion of myeloid cells prevented Kras(G12D)-driven pancreatic cancer initiation. In pre-established tumours, myeloid cell depletion arrested tumour growth and in some cases, induced tumour regressions that were dependent on CD8(+) T cells. We found that myeloid cells inhibited CD8(+) T-cell anti-tumour activity by inducing the expression of programmed cell death-ligand 1 (PD-L1) in tumour cells in an epidermal growth factor receptor (EGFR)/mitogen-activated protein kinases (MAPK)-dependent manner. Our results show that myeloid cells support immune evasion in pancreatic cancer through EGFR/MAPK-dependent regulation of PD-L1 expression on tumour cells. Derailing this crosstalk between myeloid cells and tumour cells is sufficient to restore anti-tumour immunity mediated by CD8(+) T cells, a finding with implications for the design of immune therapies for pancreatic cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  13. Osteoporosis in Multiple Endocrine Neoplasia Type I: A Case Report – Case Report


    Kurtuluş Kaya; Ebru Özcan; Sumru Özel


    Multiple Endocrine Neoplasia type I (MEN type-I) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary. Primary hyperparathyroidism is the most common clinical expression in affected patients, present in more than 90% of cases. Osteoporosis is a frequent and early complication of primary hyperparathyroidism in MEN type I. A case with a diagnosis of MEN type-I, 39 years old, presented with humeral, fem...

  14. Acute Pancreatitis

    DEFF Research Database (Denmark)

    Bertilsson, Sara; Håkansson, Anders; Kalaitzakis, Evangelos


    Aims: We aimed to evaluate the potential relation between the incidence of (alcoholic and non-alcoholic) acute pancreatitis (AP) and alcohol consumption in the general population, and whether the occurrence of AP shows any seasonal variation, particularly in relation to periods with expected...... consumption in the general population do not appear to be related to changes in the incidence of AP and there are no significant seasonal differences in the occurrence of AP in Sweden. Short summary: The incidence of acute pancreatitis (AP) is increasing, and alcohol is still recognized as one of the most...

  15. Pancreatic insulin content regulation by the estrogen receptor ER alpha.

    Directory of Open Access Journals (Sweden)

    Paloma Alonso-Magdalena

    Full Text Available The function of pancreatic beta-cells is the synthesis and release of insulin, the main hormone involved in blood glucose homeostasis. Estrogen receptors, ER alpha and ER beta, are important molecules involved in glucose metabolism, yet their role in pancreatic beta-cell physiology is still greatly unknown. In this report we show that both ER alpha and ER beta are present in pancreatic beta-cells. Long term exposure to physiological concentrations of 17beta-estradiol (E2 increased beta-cell insulin content, insulin gene expression and insulin release, yet pancreatic beta-cell mass was unaltered. The up-regulation of pancreatic beta-cell insulin content was imitated by environmentally relevant doses of the widespread endocrine disruptor Bisphenol-A (BPA. The use of ER alpha and ER beta agonists as well as ER alphaKO and ER betaKO mice suggests that the estrogen receptor involved is ER alpha. The up-regulation of pancreatic insulin content by ER alpha activation involves ERK1/2. These data may be important to explain the actions of E2 and environmental estrogens in endocrine pancreatic function and blood glucose homeostasis.

  16. Diagnosing Chronic Pancreatitis: Comparison and Evaluation of Different Diagnostic Tools. (United States)

    Issa, Yama; van Santvoort, Hjalmar C; van Dieren, Susan; Besselink, Marc G; Boermeester, Marja A; Ahmed Ali, Usama


    This study aims to compare the M-ANNHEIM, Büchler, and Lüneburg diagnostic tools for chronic pancreatitis (CP). A cross-sectional analysis of the development of CP was performed in a prospectively collected multicenter cohort including 669 patients after a first episode of acute pancreatitis. We compared the individual components of the M-ANNHEIM, Büchler, and Lüneburg tools, the agreement between tools, and estimated diagnostic accuracy using Bayesian latent-class analysis. A total of 669 patients with acute pancreatitis followed-up for a median period of 57 (interquartile range, 42-70) months were included. Chronic pancreatitis was diagnosed in 50 patients (7%), 59 patients (9%), and 61 patients (9%) by the M-ANNHEIM, Lüneburg, and Büchler tools, respectively. The overall agreement between these tools was substantial (κ = 0.75). Differences between the tools regarding the following criteria led to significant changes in the total number of diagnoses of CP: abdominal pain, recurrent pancreatitis, moderate to marked ductal lesions, endocrine and exocrine insufficiency, pancreatic calcifications, and pancreatic pseudocysts. The Büchler tool had the highest sensitivity (94%), followed by the M-ANNHEIM (87%), and finally the Lüneburg tool (81%). Differences between diagnostic tools for CP are mainly attributed to presence of clinical symptoms, endocrine insufficiency, and certain morphological complications.

  17. Pancreatic islet transplantation

    Directory of Open Access Journals (Sweden)

    Corrêa-Giannella Maria


    Full Text Available Abstract Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of

  18. Continuous versus intermittent tamoxifen versus intermittent/alternated tamoxifen and medroxyprogesterone acetate as first line endocrine treatment in advanced breast cancer: an EORTC phase III study (10863).

    NARCIS (Netherlands)

    Beex, L.V.A.M.; Rose, C.; Mouridsen, H.; Jassem, J.; Nooij, M.; Estape, J.; Paridaens, R.; Piccart, M.; Gorlia, T.; Lardenoije, S.; Baila, L.


    BACKGROUND: Continuous ligand depletion of endocrine responsive tumours may enhance resistance to therapy. Intermittent treatment with tamoxifen (T) was considered to mimic (incomplete) ligand depletion and reintroduction. Furthermore it was postulated that alternating tamoxifen with a non-cross

  19. Gastric Endocrine Cell Carcinoma with Long-Term Survival Developing Metachronous Remnant Cancer

    Directory of Open Access Journals (Sweden)

    Tomoyuki Abe


    Full Text Available A rare case of primary gastric endocrine cell carcinoma in a 79-year-old man is reported. Upper gastrointestinal endoscopy showed a large Bormann’s type 2 tumour located in the middle of the stomach. On computed tomography, the gastric wall was thickened by the large tumour, and there were no distant metastases. Distal gastrectomy, lymph node dissection, and partial resection of the transverse colon were performed because the tumour involved the transverse mesocolon. The final pathological diagnosis was endocrine cell carcinoma, with tumour infiltration up to the subserous layer. Adjuvant chemotherapy was given, but metachronous remnant gastric cancer developed 2 years after surgery. Endoscopic submucosal dissection was performed for the early 0-IIc type gastric cancer, and the surgical margin was preserved. The patient has survived for 5 years after the primary surgery, remaining disease-free so far.

  20. Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project (United States)

    Iacobuzio-Donahue, Christine A


    Pancreatic cancer is a disease caused by the accumulation of genetic alterations in specific genes. Elucidation of the human genome sequence, in conjunction with technical advances in the ability to perform whole exome sequencing, have provided new insight into the mutational spectra characteristic of this lethal tumour type. Most recently, exomic sequencing has been used to clarify the clonal evolution of pancreatic cancer as well as provide time estimates of pancreatic carcinogenesis, indicating that a long window of opportunity may exist for early detection of this disease while in the curative stage. Moving forward, these mutational analyses indicate potential targets for personalised diagnostic and therapeutic intervention as well as the optimal timing for intervention based on the natural history of pancreatic carcinogenesis and progression. PMID:21749982

  1. Endosonography of groove pancreatitis

    NARCIS (Netherlands)

    Tio, T. L.; Luiken, G. J.; Tytgat, G. N.


    Groove pancreatitis is a rare form of chronic pancreatitis. Distinction between pancreatitis and pancreatic carcinoma is often difficult. Two cases of groove pancreatitis diagnosed by endosonography are described. A hypoechoic pattern between the duodenal wall and pancreas was clearly imaged in both

  2. Pancreatic cystadenoma

    Energy Technology Data Exchange (ETDEWEB)

    Aspestrand, F.; Oppedal, B.R.; Eide, T.J.


    Two cases of pancreatic cystadenoma are presented, demonstrating the typical angiographic and histologic pattern as given in previous literature. Although computed tomography and ultrasound examinations may be useful, angiography seems to play a decisive role in establishing the diagnosis, demonstrating the localization and extent of the tumor, and permitting the possible differentiation of benign and malignant lesions.

  3. Autoimmune Pancreatitis. (United States)

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


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

  4. Pancreatitis aguda

    National Research Council Canada - National Science Library



    .... La mayoría de los casos en niños son cuadros autolimitados y de buen pronóstico. La clasificación de Atlanta de 1992 define los conceptos de pancreatitis aguda leve, grave, necrosis, colecciones...

  5. Differentiation of a pancreatic metastasis of a renal cell carcinoma from a primary pancreatic carcinoma by echo-enhanced power Doppler sonography. (United States)

    Flath, B; Rickes, S; Schweigert, M; Lochs, H; Possinger, K; Wermke, W


    In a 70-year-old patient who had been treated for a renal cell carcinoma, a pancreatic mass was detected on CT scan. To differentiate a pancreatic metastasis of the renal cell carcinoma from a pancreatic carcinoma, an echo-enhanced power Doppler sonography was performed. The pancreatic mass demonstrated a strong echo enhancement, proving its hypervascularization. This behaviour favoured the diagnosis of a pancreatic metastasis of the renal cell carcinoma which was confirmed by histology. The principles and the role of echo-enhanced power Doppler sonography in the differential diagnosis between a primary pancreatic carcinoma and a metastasis of a renal carcinoma in the pancreas are discussed. We conclude that this technique can provide an important contribution to the diagnosis in this special instance. However, histology is the standard in the differential diagnosis of pancreatic tumours. Copyright 2003 S. Karger AG, Basel and IAP

  6. Endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Mandrup, Karen

    suggested as particularly sensitive to endocrine disruption. Mammary gland examination in toxicological studies may be useful for improving knowledge on possible influences of EDCs on human mammary glands and also be useful for detection of endocrine disrupting effects of chemicals as part of safety testing....... To improve knowledge on possible influences of endocrine disrupters on female reproductive system, the effects of EDCs on genital malformations in females and the development of mammary glands were studied in the present project. AIMS: The aims for the studies on male and female mammary gland development...... effects on prepubertal female rat mammary glands were observed at lower levels than those affecting other endpoints studied. CONCLUSION: The present findings in rats suggest that EDCs may affect mammary gland development in women and men, although risk assessment including comparison with exposure...

  7. Imaging of sacral tumours

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, S.; Ollivier, L.; Brisse, H.; Neuenschwander, S. [Institut Curie, Department of Radiology, Paris (France); Leclere, J. [Institut Gustave Roussy, Department of Radiology, Villejuif (France); Vanel, D. [The Rizzoli Institute, Department of Radiology, Bologna (Italy); Missenard, G. [Institut Gustave Roussy, Comite de pathologie tumorale de l' appareil locomoteur, Villejuif (France); Pinieux, G. de [CHRU de Tours, Department of Pathology, Hopital Trousseau, Tours (France)


    All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed. (orig.)

  8. Pancreatic tuberculosis masquerading as pancreatic serous cystadenoma (United States)

    Hong, Seung Goun; Kim, Jae Seon; Joo, Moon Kyung; Lee, Kwang Gyun; Kim, Key Hyeon; Oh, Cho Rong; Park, Jong-Jae; Bak, Young-Tae


    Solitary pancreatic involvement of tuberculosis is rare, especially in an immunocompetent individual, and it may be misdiagnosed as pancreatic cystic neoplasms. Pancreatic cystic neoplasms are being identified in increasing numbers, probably because of the frequent use of radiology and advances in endoscopic techniques. However, they are composed of a variety of neoplasms with a wide range of malignant potential, and it is often difficult to differentiate pancreatic tuberculosis mimicking cystic neoplasms from benign or malignant pancreatic cystic neoplasms. Non-surgical diagnosis of pancreatic tuberculosis is inconclusive and continues to be a challenge in many cases. If so, then laparotomy should be employed to establish the diagnosis. Therefore, pancreatic tuberculosis should be kept in mind during the differential diagnosis of solitary cystic masses in the pancreas. We report a patient who had solitary pancreatic tuberculosis masquerading as pancreatic serous cystadenoma. PMID:19248204

  9. Is Pancreatic Cancer Hereditary? (United States)

    ... Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? Cancer of the pancreas is a genetic ... found in cigarette smoke. The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins. ...

  10. [Nutritional repercussions and management of chronic pancreatitis]. (United States)

    Botella Romero, F; Alfaro Martínez, J J


    The pancreas is a retroperitoneal organ that releases water, bicarbonate and digestive enzymes by the main pancreatic duct (MPD) into the duodenum. Chronic pancreatitis (CP) is typically caused, in adults, by chronic alcohol abuse and, less frequently hypertriglyceridemia, primary hyperparathyroidism or cystic fibrosis. Exocrine dysfunction results in malabsorption of fat and subsequent steatorrhea. Damage to pancreatic endocrine function is a late finding in CP and results in hyperglycaemia or overt diabetes mellitus. Care of patients with CP principally involves management of pain. A significant change in the pain pattern or the sudden onset of persistent symptoms suggests the need to rule out other potential etiologies, including peptic ulcer disease, biliary obstruction, pseudocysts, pancreatic carcinoma, and pancreatic duct stricture or stones, then is important to establish a secure diagnosis. Management of pain should then proceed in a judicious stepwise approach avoiding opioids dependence. Patients should be advised to stop alcohol intake. Fat malabsorption and other complications may also arise. Management of steatorrhea should begin with small meals and restriction in fat intake. Pancreatic enzyme supplements can relieve symptoms and reduce malabsorption in patients who do not respond to dietary restriction. Enzymes at high doses should be used with meals. Treatment with acid suppression to reduce inactivation of the enzymes from gastric acid are recommended. Supplementation with medium chain triglycerides and fat soluble vitamin replacement may be required. Management of other complications (such as pseudocysts, bile duct or duodenal obstruction, pancreatic ascites, splenic vein thrombosis and pseudoaneurysms) often requires aggressive approach with the patient kept on total parenteral nutrition to minimize pancreatic stimulation.

  11. Parapharyngeal space primary tumours. (United States)

    Grilli, Gianluigi; Suarez, Vanessa; Muñoz, María Gabriela; Costales, María; Llorente, José Luis

    The aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours. This study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study. 74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries. Most parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  12. Bcl-2 expression in pancreas development and pancreatic cancer progression. (United States)

    Campani, D; Esposito, I; Boggi, U; Cecchetti, D; Menicagli, M; De Negri, F; Colizzi, L; Del Chiaro, M; Mosca, F; Fornaciari, G; Bevilacqua, G


    Apoptosis is important for both tissue development and differentiation; its deregulation may contribute to tumourigenesis. In order to clarify the role of Bcl-2, an apoptosis-inhibiting protein, in pancreatic morphogenesis and tumour progression, its immunohistochemical expression was evaluated in 12 samples of fetal pancreas, in 10 samples of adult pancreas with ductal hyperplastic lesions, in 120 cases of primary pancreatic ductal adenocarcinoma, and in 43 synchronous metastatic lymph nodes. To evaluate the role of apoptosis in pancreatic cancer, p53 expression was also studied in tumour samples. Bcl-2 cytoplasmic acinar and ductal immunostaining was found in all fetal and adult tissue samples; ductal hyperplastic lesions were constantly negative. Thirty out of 120 (25%) tumours and 3 out of 43 (7%) lymph nodes expressed Bcl-2, whereas 67 out of 120 (56%) expressed nuclear p53. Well-differentiated tumours (G1) were more frequently Bcl-2-positive (p=0.002); furthermore, there was an inverse correlation between Bcl-2 and p53 expression in primary tumours (p=0.02). Neither Bcl-2 nor p53 influenced patients' prognosis, which was instead affected by N (p=0.02) and M (p<0.0001) status and stage of the disease (p=0.002). It is concluded that Bcl-2 regulates pancreatic morphogenesis and tissue homeostasis from early fetal to adult life and can be considered a phenotypic marker of normal exocrine pancreas. On the other hand, the lack of expression in preneoplastic lesions and the low positivity found in primary tumours and lymph node metastases suggest that Bcl-2 does not play a centralrole in pancreatic tumourigenesis and cancer progression. Copyright 2001 John Wiley & Sons, Ltd.

  13. Multiple endocrine neoplasia (MEN) II (United States)

    ... Multiple endocrine neoplasia (MEN) II To use the sharing features on this page, please enable JavaScript. Multiple endocrine neoplasia, type II (MEN II) is a disorder passed ...

  14. Your Endocrine System (For Kids) (United States)

    ... With Special Needs Glasses and Contact Lenses Your Endocrine System KidsHealth > For Kids > Your Endocrine System Print A A A en español Tu sistema ... a pea, is the "master gland" of the endocrine system. It makes and releases a bunch of hormones ...

  15. Sleep and the endocrine system. (United States)

    Morgan, Dionne; Tsai, Sheila C


    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Nigerian Endocrine Practice

    African Journals Online (AJOL)

    The journal accepts original contributions related to the practice and science of clinical endocrinology, articles updating the clinical endocrinologist on current areas of interest in the diagnosis and treatment of endocrine disorders, articles discussing dilemma facing endocrinologists in the clinical, social, and ethical arena of ...

  17. Nigerian Endocrine Practice: Submissions

    African Journals Online (AJOL)

    Eating disorders: obesity, anorexia nervosa, and bulimia nervosa. In: Wilson JD, Foster ... Original Articles should be restricted to clinical or basic studies, particularly translational research, which add new information to the etiology, treatment, and outcomes of endocrine disorders that have not been published previously.

  18. Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer (United States)

    Lei, Yifeng; Tang, Lixue; Xie, Yangzhouyun; Xianyu, Yunlei; Zhang, Lingmin; Wang, Peng; Hamada, Yoh; Jiang, Kai; Zheng, Wenfu; Jiang, Xingyu


    Pancreatic cancer is one of the deadliest human cancers, whose progression is highly dependent on the nervous microenvironment. The suppression of gene expression of nerve growth factor (NGF) may have great potential in pancreatic cancer treatment. Here we show that gold nanocluster-assisted delivery of siRNA of NGF (GNC-siRNA) allows efficient NGF gene silencing and pancreatic cancer treatment. The GNC-siRNA complex increases the stability of siRNA in serum, prolongs the circulation lifetime of siRNA in blood and enhances the cellular uptake and tumour accumulation of siRNA. The GNC-siRNA complex potently downregulates the NGF expression in Panc-1 cells and in pancreatic tumours, and effectively inhibits the tumour progression in three pancreatic tumour models (subcutaneous model, orthotopic model and patient-derived xenograft model) without adverse effects. Our study constitutes a straightforward but effective approach to inhibit pancreatic cancer via NGF knockdown, suggesting a promising therapeutic direction for pancreatic cancer.


    Directory of Open Access Journals (Sweden)

    Alojz Pleskovič


    Full Text Available Background. The pancreatic cancer is quite common malignant tumor of gastointestinal tract and its incidence is increasing in well developed part of the world. Despite of all advanced diagnostic methods the disease is in most cases recognised too late when the tumor is not resectable.Conclusions. Only in 20–30% of patients with pancreatic cancer surgical resection is possible, and even in this group 5year survival is very low. In the patients where the tumor is not resectable, sometimes only palliative procedures are indicated and sometimes only simptomatic therapy is possible. The average survival period in this group of patients is 12–20 months. Adjuvant chemo and radiotherapy has not shown much of benefit and the prognosis is still very bad.

  20. Endocrine system on chip for a diabetes treatment model. (United States)

    Nguyen, Dao Thi Thuy; van Noort, Danny; Jeong, In-Kyung; Park, Sungsu


    The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an 'endocrine system on chip' to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting β-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion. Thus, we constructed a co-culture of intestinal-pancreatic cells to measure the effect of glucose on the production of glucagon-like peptide-1 (GLP-1) from the L-cell line (GLUTag) and insulin from the pancreatic β-cell line (INS-1). After three days of culture, both cell lines formed aggregates, exhibited 3D cell morphology, and showed good viability (>95%). We separately measured the dynamic profile of GLP-1 and insulin release at glucose concentrations of 0.5 and 20 mM, as well as the combined effect of GLP-1 on insulin production at these glucose concentrations. In response to glucose stimuli, GLUTag and INS-1 cells produced higher amounts of GLP-1 and insulin, respectively, compared to a static 2D cell culture. INS-1 combined with GLUTag cells exhibited an even higher insulin production in response to glucose stimulation. At higher glucose concentrations, the diabetes model on chip showed faster saturation of the insulin level. Our results suggest that the endocrine system developed in this study is a useful tool for observing dynamical changes in endocrine hormones (GLP-1 and insulin) in a glucose-dependent environment. Moreover, it can potentially be used to screen GLP-1 analogues and natural insulin and GLP-1 stimulants for diabetes treatment.

  1. Critical Review of Diagnostic Methods Used in Chronic Pancreatic Disease

    Directory of Open Access Journals (Sweden)

    Ivan T Beck


    Full Text Available This paper provides a balanced assessment of the various pancreatic function tests and imaging techniques used in the differential diagnosis of chronic pancreatic disease. Function tests that study the digestive capacity of the pancreas (fat absorption of dietary lipids, fluorescein- or radiolabelled fats, bentiromide test, etc have high specificity, but very low sensitivity. This is because 90% of pancreas has to be destroyed before steatorrhea or creatorrhea occurs. Tests that directly measure pancreatic bicarbonate and protein secretion (secretin test, etc are more accurate and may detect pancreatic dysfunction even before anatomical changes occur. Measurement of pancreatic enzymes in serum or urine, or the decreased decline of serum amino acids during their incorporation into pancreatic enzymes, are not sufficiently sensitive or specific to help diagnose pancreatic disease. Sensitive and specific tumour markers are not yet available. Thus screening tests are not cost-effective - if they are negative, they do not exclude pancreatic disease; and if positive, they have to be confirmed by more specific tests. Imaging techniques are the most commonly used methods of investigation. The usefulness of abdominal survey films, barium studies, percutaneous transhepatic cholangiography, endoscopic retrograde cholangiopancreatography (ERCP, ultrasonography, computed tomographic scan, magnetic resonance imaging and endoscopic ultrasonography is critically reviewed. Most of the radiological methods can be combined with cytology or biopsy. Histology demonstrating malignancy establishes this diagnosis, but negative biopsies do not exclude malignant tumours. Presently only ERCP and endoscopic ultrasound can diagnose cancers sufficiently early to allow for possible `curative' surgery, and only endoscopic ultrasound is capable to stage tumours for the assessment of resectability.

  2. Warthin's tumour and smoking

    NARCIS (Netherlands)

    de Ru, JA; Majoor, MHJM; van Benthem, PPG; Slootweg, PJ; Peeters, PHM; Hordijk, GJ


    Warthin's tumour and smoking. Objective: In an evaluation of our patients with parotid gland neoplasms, we noticed that patients with a Warthin's tumour were heavy smokers. The aim of this study was to confirm earlier findings in the literature concerning a possible association between smoking and

  3. of brain tumours

    African Journals Online (AJOL)

    Also, tumours in the frontal and temporal lobes are more likely to cause psychiatric symptoms than those in parietal or occipital lobes. Left-sided, frontal tumours also seem to be associated with higher rates of depression, while those in the frontal lobe of the right hemisphere may be associated with features that may be.

  4. Wilms' tumour (nephroblastoma)

    African Journals Online (AJOL)

    cancer cells throughout the body and affects fast-dividing cells. With radiation therapy high-energy X-rays reach cancer cells in a specific area of the body. In. Wilms' tumour, radiation is directed at the site of the tumour in the abdomen, and sometimes also at the lungs or the liver. Surgery. Total nephrectomy is the key step in.

  5. Pancreatic enzyme synthesis in pancreatic disease. (United States)

    Boyd, E J; Clark, G; Dunbar, J; Wormsley, K G


    In a prospective evaluation of patients suspected of having chronic pancreatitis, synthesis of pancreatic enzymes was measured by means of the incorporation of selenium-75-labelled methionine into the proteins of duodenal aspirate during stimulation of pancreatic secretion with secretin (1 CU X kg-1 X h-1) plus cholecystokinin (CCK) (1 IDU X kg-1 X h-1). The rate of pancreatic enzyme synthesis was increased in patients with chronic pancreatitis. Measurement of pancreatic enzyme synthesis was more sensitive in the detection of chronic pancreatitis than either the bicarbonate or the trypsin secretory response to secretin plus CCK. A combination of the bicarbonate secretory response with measurement of the rate of enzyme synthesis provided a positive predictive power of 100% when both tests were abnormal and a negative predictive power of 100% when both tests were normal, so that the combined test can be recommended both for excluding and confirming the presence of chronic pancreatitis.

  6. Regulation of Neurod1 contributes to the lineage potential of Neurogenin3+ endocrine precursor cells in the pancreas. (United States)

    Mastracci, Teresa L; Anderson, Keith R; Papizan, James B; Sussel, Lori


    During pancreatic development, transcription factor cascades gradually commit precursor populations to the different endocrine cell fate pathways. Although mutational analyses have defined the functions of many individual pancreatic transcription factors, the integrative transcription factor networks required to regulate lineage specification, as well as their sites of action, are poorly understood. In this study, we investigated where and how the transcription factors Nkx2.2 and Neurod1 genetically interact to differentially regulate endocrine cell specification. In an Nkx2.2 null background, we conditionally deleted Neurod1 in the Pdx1+ pancreatic progenitor cells, the Neurog3+ endocrine progenitor cells, or the glucagon+ alpha cells. These studies determined that, in the absence of Nkx2.2 activity, removal of Neurod1 from the Pdx1+ or Neurog3+ progenitor populations is sufficient to reestablish the specification of the PP and epsilon cell lineages. Alternatively, in the absence of Nkx2.2, removal of Neurod1 from the Pdx1+ pancreatic progenitor population, but not the Neurog3+ endocrine progenitor cells, restores alpha cell specification. Subsequent in vitro reporter assays demonstrated that Nkx2.2 represses Neurod1 in alpha cells. Based on these findings, we conclude that, although Nkx2.2 and Neurod1 are both necessary to promote beta cell differentiation, Nkx2.2 must repress Neurod1 in a Pdx1+ pancreatic progenitor population to appropriately commit a subset of Neurog3+ endocrine progenitor cells to the alpha cell lineage. These results are consistent with the proposed idea that Neurog3+ endocrine progenitor cells represent a heterogeneous population of unipotent cells, each restricted to a particular endocrine lineage.

  7. Regulation of Neurod1 contributes to the lineage potential of Neurogenin3+ endocrine precursor cells in the pancreas.

    Directory of Open Access Journals (Sweden)

    Teresa L Mastracci

    Full Text Available During pancreatic development, transcription factor cascades gradually commit precursor populations to the different endocrine cell fate pathways. Although mutational analyses have defined the functions of many individual pancreatic transcription factors, the integrative transcription factor networks required to regulate lineage specification, as well as their sites of action, are poorly understood. In this study, we investigated where and how the transcription factors Nkx2.2 and Neurod1 genetically interact to differentially regulate endocrine cell specification. In an Nkx2.2 null background, we conditionally deleted Neurod1 in the Pdx1+ pancreatic progenitor cells, the Neurog3+ endocrine progenitor cells, or the glucagon+ alpha cells. These studies determined that, in the absence of Nkx2.2 activity, removal of Neurod1 from the Pdx1+ or Neurog3+ progenitor populations is sufficient to reestablish the specification of the PP and epsilon cell lineages. Alternatively, in the absence of Nkx2.2, removal of Neurod1 from the Pdx1+ pancreatic progenitor population, but not the Neurog3+ endocrine progenitor cells, restores alpha cell specification. Subsequent in vitro reporter assays demonstrated that Nkx2.2 represses Neurod1 in alpha cells. Based on these findings, we conclude that, although Nkx2.2 and Neurod1 are both necessary to promote beta cell differentiation, Nkx2.2 must repress Neurod1 in a Pdx1+ pancreatic progenitor population to appropriately commit a subset of Neurog3+ endocrine progenitor cells to the alpha cell lineage. These results are consistent with the proposed idea that Neurog3+ endocrine progenitor cells represent a heterogeneous population of unipotent cells, each restricted to a particular endocrine lineage.

  8. Long-term Follow-up of MEN1 Patients Who Do Not Have Initial Surgery for Small ≤2 cm Nonfunctioning Pancreatic Neuroendocrine Tumors, an AFCE and GTE Study: Association Francophone de Chirurgie Endocrinienne & Groupe d'Etude des Tumeurs Endocrines. (United States)

    Triponez, Frederic; Sadowski, Samira M; Pattou, François; Cardot-Bauters, Catherine; Mirallié, Eric; Le Bras, Maëlle; Sebag, Frédéric; Niccoli, Patricia; Deguelte, Sophie; Cadiot, Guillaume; Poncet, Gilles; Lifante, Jean-Christophe; Borson-Chazot, Françoise; Chaffanjon, Philippe; Chabre, Olivier; Menegaux, Fabrice; Baudin, Eric; Ruszniewski, Philippe; Du Boullay, Hélène; Goudet, Pierre


    To report long-term follow-up of patients with multiple endocrine neoplasia type 1 (MEN1) and nonfunctioning pancreatic neuroendocrine tumors (NF-PET). Pancreaticoduodenal tumors occur in almost all patients with MEN1 and are a major cause of death. The natural history and clinical outcome are poorly defined, and management is still controversial for small NF-PET. Clinical outcome and tumor progression were analyzed in 46 patients with MEN1 with 2 cm or smaller NF-PET who did not have surgery at the time of initial diagnosis. Survival data were analyzed using the Kaplan-Meier method. Forty-six patients with MEN1 were followed prospectively for 10.7 ± 4.2 (mean ± standard deviation) years. One patient was lost to follow-up and 1 died from a cause unrelated to MEN1. Twenty-eight patients had stable disease and 16 showed significant progression of pancreaticoduodenal involvement, indicated by increase in size or number of tumors, development of a hypersecretion syndrome, need for surgery (7 patients), and death from metastatic NF-PET (1 patient). The mean event-free survival was 13.9 ± 1.1 years after NF-PET diagnosis. At last follow-up, none of the living patients who had undergone surgery or follow-up had evidence of metastases on imaging studies. Our study shows that conservative management for patients with MEN1 with NF-PET of 2 cm or smaller is associated with a low risk of disease-specific mortality. The decision to recommend surgery to prevent tumor spread should be balanced with operative mortality and morbidity, and patients should be informed about the risk-benefit ratio of conservative versus aggressive management when the NF-PET represents an intermediate risk.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used

  9. Neural plasticity in pancreatitis and pancreatic cancer. (United States)

    Demir, Ihsan Ekin; Friess, Helmut; Ceyhan, Güralp O


    Pancreatic nerves undergo prominent alterations during the evolution and progression of human chronic pancreatitis and pancreatic cancer. Intrapancreatic nerves increase in size (neural hypertrophy) and number (increased neural density). The proportion of autonomic and sensory fibres (neural remodelling) is switched, and are infiltrated by perineural inflammatory cells (pancreatic neuritis) or invaded by pancreatic cancer cells (neural invasion). These neuropathic alterations also correlate with neuropathic pain. Instead of being mere histopathological manifestations of disease progression, pancreatic neural plasticity synergizes with the enhanced excitability of sensory neurons, with Schwann cell recruitment toward cancer and with central nervous system alterations. These alterations maintain a bidirectional interaction between nerves and non-neural pancreatic cells, as demonstrated by tissue and neural damage inducing neuropathic pain, and activated neurons releasing mediators that modulate inflammation and cancer growth. Owing to the prognostic effects of pain and neural invasion in pancreatic cancer, dissecting the mechanism of pancreatic neuroplasticity holds major translational relevance. However, current in vivo models of pancreatic cancer and chronic pancreatitis contain many discrepancies from human disease that overshadow their translational value. The present Review discusses novel possibilities for mechanistically uncovering the role of the nervous system in pancreatic disease progression.

  10. Autoimmune pancreatitis can develop into chronic pancreatitis (United States)


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

  11. Role of SST, CORT and Ghrelin and its receptors at the endocrine pancreas.

    Directory of Open Access Journals (Sweden)

    Belen eChanclón


    Full Text Available Somatostatin (SST, cortistatin (CORT, and its receptors (sst1-5, and ghrelin and its receptors (GHS-R are two highly interrelated neuropeptide systems with a broad range of overlapping biological actions at central, cardiovascular and immune levels among others. Besides their potent regulatory role on GH release, its endocrine actions are highlighted by SST/CORT and ghrelin influence on insulin secretion, glucose homeostasis and insulin resistance. Interestingly, most components of these systems are expressed at the endocrine pancreas and are actively involved in the modulation of pancreatic islet function and, consequently influence glucose homeostasis. In addition, some of them also participate in islet survival and regeneration. Furthermore, under severe metabolic condition as well as in endocrine pathologies, their expression profile is severely deregulated. These finding suggest that SST/CORT and ghrelin systems could play a relevant role in pancreatic function under metabolic and endocrine pathologies. Accordingly, these systems have been therapeutically targeted for the prevention or amelioration of certain metabolic conditions (obesity as well as for tumor growth inhibition and/or hormonal regulation in endocrine pathologies (neuroendocrine tumors. This review focuses on the interrelationship between SST/CORT and ghrelin systems and their role in severe metabolic conditions and some endocrine disorders.

  12. Cellular functional changes in the endocrine system of the rats upon exposure to coal rock dust and during exercise

    Energy Technology Data Exchange (ETDEWEB)

    L.T. Bazeliuk


    Exposure to coal rock dust in combination with exercise for 2 months was found to have a negative impact on cellular metabolism in the endocrine system. The early form of anthracosilicosis developed in this period. Cytomorphological study revealed cellular changes in the pituitary, thyroid, parathyroid, and pancreatic glands. The cells of the endocrine organs are functionally tense upon exposure to toxic and physical factors and they are most vulnerable in this period of an experiment.

  13. Dorsal Pancreatic Agenesis


    Oya Uygur-Bayramiçli; Can Dolapçioglu; Derya Öztas; Resat Dabak; Gamze Kiliçoglu


    Context Agenesis of the dorsal pancreas is a rare entity and might present with various symptoms. We report a case which presented with chronic pancreatitis. Case report The patient presented with epigastric pain and we found dorsal pancreatic agenesis causing chronic pancreatitis. Conclusions Dorsal pancreatic agenesis can be easily diagnosed with new techniques and its association with clinical syndromes can be better understood.

  14. exocrine pancreatic function

    African Journals Online (AJOL)

    Summary. Background:- Faecal pancreatic elastase-l is a laboratory based test used for the diagnosis or exclusion of exocrine pancreatic insufficiencies. Pancreatic elastase-l, is released into blood circulation during inflammation of the pancreas, but unlike most pancreatic enzymes it is stable during in- testinal passage ...

  15. General Information about Pancreatic Cancer (United States)

    ... History Committees of Interest Legislative Resources Recent Public Laws Careers Visitor Information Search Search Home Cancer Types Pancreatic Cancer Patient Pancreatic Cancer Patient Pancreatic ...

  16. Zearalenone endocrine system catch

    Directory of Open Access Journals (Sweden)

    Bursić Vojislava P.


    Full Text Available This paper deals with the contamination of our environment with thousands of both natural and man-made chemicals which affect the endocrine system of humans and animals. These so-called endocrine disrupting chemicals (EDCs are thought to mimic or block the action of hormones and therefore disrupt sexual development in utero. EDCs are organochlorine pesticides, dioxin compounds, polychlorinated biphenyls, alkylpolyethoxylates, plastic additives and phytoestrogens (occurring naturally in foods: isoflavones coumenestans and zearalenone. The structure of zearalenone is similar to the structure of estrogens and it enables binding to the estrogenic receptors. DNA laddering on gel electrophoresis was present 12 h after dosing thus indicating a conclusion that there was apoptosis. Apoptosis is the principal mechanism contributing to germ cell depletion and testicular atrophy following zearalenone exposure.

  17. Endocrine disrupting compounds

    DEFF Research Database (Denmark)

    Bøgh, I B; Christensen, P; Dantzer, V


    With the growing concern that environmental chemicals might impair human and animal fertility, it is important to investigate the possible influence of these substances on sexual differentiation and genital development of mammals. Many of these substances are suspected to interfere with endocrine...... processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use...

  18. Endocrine disorders in pregnancy

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Mathiesen, Elisabeth R


    The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The vast changes in maternal hormones and their binding proteins complicate assessment of the normal level of most hormones...... during gestation. The neuroendocrine events and their timing in the placental, foetal and maternal compartments are critical for initiation and maintenance of pregnancy, for foetal growth and development, and for parturition. As pregnancy advances, the relative number of trophoblasts increase...

  19. Transcriptome analysis of pancreatic cells across distant species highlights novel important regulator genes. (United States)

    Tarifeño-Saldivia, Estefania; Lavergne, Arnaud; Bernard, Alice; Padamata, Keerthana; Bergemann, David; Voz, Marianne L; Manfroid, Isabelle; Peers, Bernard


    Defining the transcriptome and the genetic pathways of pancreatic cells is of great interest for elucidating the molecular attributes of pancreas disorders such as diabetes and cancer. As the function of the different pancreatic cell types has been maintained during vertebrate evolution, the comparison of their transcriptomes across distant vertebrate species is a means to pinpoint genes under strong evolutionary constraints due to their crucial function, which have therefore preserved their selective expression in these pancreatic cell types. In this study, RNA-sequencing was performed on pancreatic alpha, beta, and delta endocrine cells as well as the acinar and ductal exocrine cells isolated from adult zebrafish transgenic lines. Comparison of these transcriptomes identified many novel markers, including transcription factors and signaling pathway components, specific for each cell type. By performing interspecies comparisons, we identified hundreds of genes with conserved enriched expression in endocrine and exocrine cells among human, mouse, and zebrafish. This list includes many genes known as crucial for pancreatic cell formation or function, but also pinpoints many factors whose pancreatic function is still unknown. A large set of endocrine-enriched genes can already be detected at early developmental stages as revealed by the transcriptomic profiling of embryonic endocrine cells, indicating a potential role in cell differentiation. The actual involvement of conserved endocrine genes in pancreatic cell differentiation was demonstrated in zebrafish for myt1b, whose invalidation leads to a reduction of alpha cells, and for cdx4, selectively expressed in endocrine delta cells and crucial for their specification. Intriguingly, comparison of the endocrine alpha and beta cell subtypes from human, mouse, and zebrafish reveals a much lower conservation of the transcriptomic signatures for these two endocrine cell subtypes compared to the signatures of pan-endocrine

  20. [Pancreatic cysts]. (United States)

    Varola, F; Beccaria, A; Oliaro, A; Sasso, D; Villata, E; Cirillo, R


    True and pseudo-cysts of the pancreas are described and their aetiology, pathology, laboratory tests, radiological examination, differential diagnosis, symptomatology and surgical management are illustrated. A series of 22 cases of pancreatic cyst is presented. Surgical management consisted of 14 cystogastrostomies, 3 cystoduodenostomies, 2 resections of the tail of the pancreas, 1 internal drainage between the fistular segment of the gland and the gastric cavity, and 2 external drainages with a Pezzer tube. It is felt that internal drainage is the operation of choice. Of the surgical techniques available, a preference is expressed for cystogastrostomy and cystoduodenostomy.

  1. Obesity and cancer--mechanisms underlying tumour progression and recurrence. (United States)

    Park, Jiyoung; Morley, Thomas S; Kim, Min; Clegg, Deborah J; Scherer, Philipp E


    Over the past several years, the field of cancer research has directed increased interest towards subsets of obesity-associated tumours, which include mammary, renal, oesophageal, gastrointestinal and reproductive cancers in both men and women. The increased risk of breast cancer that is associated with obesity has been widely reported; this has drawn much attention and as such, warrants investigation of the key mechanisms that link the obese state with cancer aetiology. For instance, the obese setting provides a unique adipose tissue microenvironment with concomitant systemic endocrine alterations that favour both tumour initiation and progression. Major metabolic differences exist within tumours that distinguish them from non-transformed healthy tissues. Importantly, considerable metabolic differences are induced by tumour cells in the stromal vascular fraction that surrounds them. The precise mechanisms that underlie the association of obesity with cancer and the accompanying metabolic changes that occur in the surrounding microenvironment remain elusive. Nonetheless, specific therapeutic agents designed for patients with obesity who develop tumours are clearly needed. This Review discusses recent advances in understanding the contributions of obesity to cancer and their implications for tumour treatment.

  2. Obesity and cancer—mechanisms underlying tumour progression and recurrence (United States)

    Kim, Min; Clegg, Deborah J.; Scherer, Philipp E.


    Over the past several years, the field of cancer research has directed increased interest towards subsets of obesity-associated tumours, which include mammary, renal, oesophageal, gastrointestinal and reproductive cancers in both men and women. The increased risk of breast cancer that is associated with obesity has been widely reported; this has drawn much attention and as such, warrants investigation of the key mechanisms that link the obese state with cancer aetiology. For instance, the obese setting provides a unique adipose tissue microenvironment with concomitant systemic endocrine alterations that favour both tumour initiation and progression. Major metabolic differences exist within tumours that distinguish them from non-transformed healthy tissues. Importantly, considerable metabolic differences are induced by tumour cells in the stromal vascular fraction that surrounds them. The precise mechanisms that underlie the association of obesity with cancer and the accompanying metabolic changes that occur in the surrounding microenvironment remain elusive. Nonetheless, specific therapeutic agents designed for patients with obesity who develop tumours are clearly needed. This Review discusses recent advances in understanding the contributions of obesity to cancer and their implications for tumour treatment. PMID:24935119

  3. Metastatic Insulinoma Following Resection of Nonsecreting Pancreatic Islet Cell Tumor

    Directory of Open Access Journals (Sweden)

    Anoopa A. Koshy MD


    Full Text Available A 56-year-old woman presented to our clinic for recurrent hypoglycemia after undergoing resection of an incidentally discovered nonfunctional pancreatic endocrine tumor 6 years ago. She underwent a distal pancreatectomy and splenectomy, after which she developed diabetes and was placed on an insulin pump. Pathology showed a pancreatic endocrine neoplasm with negative islet hormone immunostains. Two years later, computed tomography scan of the abdomen showed multiple liver lesions. Biopsy of a liver lesion showed a well-differentiated neuroendocrine neoplasm, consistent with pancreatic origin. Six years later, she presented to clinic with 1.5 years of recurrent hypoglycemia. Laboratory results showed elevated proinsulin, insulin levels, and c-peptide levels during a hypoglycemic episode. Computed tomography scan of the abdomen redemonstrated multiple liver lesions. Repeated transarterial catheter chemoembolization and microwave thermal ablation controlled hypoglycemia. The unusual features of interest of this case include the transformation of nonfunctioning pancreatic endocrine tumor to a metastatic insulinoma and the occurrence of atrial flutter after octreotide for treatment.

  4. Aurora B kinase inhibitor AZD1152: determinants of action and ability to enhance chemotherapeutics effectiveness in pancreatic and colon cancer. (United States)

    Azzariti, A; Bocci, G; Porcelli, L; Fioravanti, A; Sini, P; Simone, G M; Quatrale, A E; Chiarappa, P; Mangia, A; Sebastian, S; Del Bufalo, D; Del Tacca, M; Paradiso, A


    AZD1152, the prodrug for AZD1152-hydroxyquinazoline pyrazol anilide (HQPA), is a selective inhibitor of Aurora B kinase activity. Preclinical evaluation of AZD1152 has been reported in several human cancer models. The potentiality of this compound in combination therapy warrants further investigation in solid tumours. This study explored the effects of AZD1152-HQPA in colon and pancreatic tumour cells. The antitumour properties of AZD1152, either as single agent or in combination with chemotherapeutics, were evaluated in each study model. The efficacy and the toxicity of AZD1152 alone and in combination with gemcitabine were validated in pancreatic tumour xenograft model. AZD1152-HQPA treatment resulted in a dramatic increase of chromosome number, modification of cell cycle and induction of apoptosis. The most effective combination was that with chemotherapeutics given soon after AZD1152 in both tumour cell types. The effectiveness of the sequential schedule of AZD1152 with gemcitabine was confirmed in nude mice bearing MiaPaCa-2 tumours, showing inhibition of tumour volumes and delaying of tumour growth after the interruption of the treatments. Here we show that AZD1152-HQPA enhances oxaliplatin and gemcitabine effectiveness in colon and pancreatic cancer, respectively. First, we provide advances into administration schedules and dosing regimens for the combination treatment in in vivo pancreatic tumour.

  5. Immunohistochemical study on gastrointestinal endocrine cells of four reptiles (United States)

    Huang, Xu-Gen; Wu, Xiao-Bing


    AIM: To clarify the types, regional distributions and distribution densities as well as morphological features of gastrointestinal (GI) endocrine cells in various parts of the gastrointestinal track (GIT) of four reptiles, Gekko japonicus, Eumeces chinensis, Sphenomorphus indicus and Eumeces elegans. METHODS: Paraffin-embedded sections (5 μm) of seven parts (cardia, fundus, pylorus, duodenum, jejunum, ileum, rectum) of GIT dissected from the four reptiles were prepared. GI endocrine cells were revealed by using immunohistochemical techniques of streptavidin-peroxidase (S-P) method. Seven types of antisera against 5-hydroxy-tryptamine (5-HT), somatostatin (SS), gastrin (GAS), glucagon (GLU), substance P (SP), insulin and pancreatic polypeptide were identified and then GI endocrine cells were photomicrographed and counted. RESULTS: The GI endocrine system of four reptiles was a complex structure containing many endocrine cell types similar in morphology to those found in higher vertebrates. Five types of GI endocrine cells, namely 5-HT, SS, GAS, SP and GLU immunoreactive (IR) cells were identified in the GIT of G. japonicus, E. chinensis and S. indicus; while in the GIT of E. elegans only the former three types of endocrine cells were observed. No PP- and INS- IR cells were found in all four reptiles. 5-HT-IR cells, which were most commonly found in the pylorus or duodenum, distributed throughout the whole GIT of four reptiles. However, their distribution patterns varied from each other. SS-IR cells, which were mainly found in the stomach especially in the pylorus and/or fundus, were demonstrated in the whole GIT of E. chinensis, only showed restricted distribution in the other three species. GAS-IR cells, with a much restricted distribution, were mainly demonstrated in the pylorus and/or the proximal small intestine of four reptiles. GLU-IR cells exhibited a limited and species-dependent variant distribution in the GIT of four reptiles. SP-IR cells were found

  6. Downstream events of neurogenin 3 in pancreatic endocrine differentiation

    DEFF Research Database (Denmark)

    Christ, Louise Christiane Rosenberg

    cells into insulin producing cells in vitro. The hope is that successful production of ß-cells from stem cells combined with a good protocol for the transplantation of these cells into human beings would offer an opportunity for diabetes patients to obtain a normal glucose homeostasis and be relieved......Diabetes affects more than 170 million people world wide and a prognosis suggests that the prevalence will increase over the next 30 year. In Denmark, the prevalence doubled from 1996 to 2007, where 240.000 people were affected. Diabetes is the manifestation of abnormalities regarding glucose...... homeostasis which may have several causes. The most prevalent types are a result of either an auto-immunological destruction of the insulin producing ß-cells (type 1) or a combination of insulin resistance of the tissues and impaired ß-cell function (type 2) in both cases leading to hyperglycaemia. Research...

  7. Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. (United States)

    Esposito, I; Menicagli, M; Funel, N; Bergmann, F; Boggi, U; Mosca, F; Bevilacqua, G; Campani, D


    Inflammatory cells contribute to the growth and spread of human malignancies by producing molecules that enhance tumour invasiveness. To characterise the inflammatory infiltrate in pancreatic ductal adenocarcinoma and to analyse its contribution to angiogenesis and its prognostic relevance. Immunohistochemistry was used to identify inflammatory cells and evaluate the expression of proangiogenic and prolymphangiogenic molecules (vascular endothelial growth factor A (VEGF-A), VEGF-C, and basic fibroblast growth factor (bFGF)) by inflammatory and cancer cells in 137 pancreatic cancers. Intratumorous microvessel density (IMD) was assessed using CD34 as an endothelial cell marker. There were significantly more mast cells and macrophages in pancreatic cancers than in normal pancreas and the number of mast cells directly correlated with the presence of lymph node metastases. However, there was no relation between numbers of infiltrating inflammatory cells and the presence of chronic pancreatitis (CP)-like changes in the parenchyma surrounding the tumour. Double immunostaining revealed that both pancreatic mast cells and macrophages express VEGF-A, VEGF-C, and bFGF. These factors were also expressed in the tumour cells in many cases. The numbers of VEGF-A expressing tumour cells and bFGF expressing tumour and inflammatory cells significantly correlated with IMD. Moreover, tumours with higher IMD had higher numbers of infiltrating mast cells and macrophages. Mononuclear inflammatory cells of the non-specific immune response are recruited to pancreatic cancer tissues independent of the presence of CP-like changes, may influence the metastatic capacity of the cancer cells, and may contribute to the development of tumours with high angiogenic activity.

  8. The endocrine pancreas: insights into development, differentiation, and diabetes. (United States)

    Mastracci, Teresa L; Sussel, Lori


    In the developing embryo, appropriate patterning of the endoderm fated to become pancreas requires the spatial and temporal coordination of soluble factors secreted by the surrounding tissues. Once pancreatic progenitor cells are specified in the developing gut tube epithelium, epithelial-mesenchymal interactions, as well as a cascade of transcription factors, subsequently delineate three distinct lineages, including endocrine, exocrine, and ductal cells. Simultaneous morphological changes, including branching, vascularization, and proximal organ development, also influence the process of specification and differentiation. Decades of research using mouse genetics have uncovered many of the key factors involved in pancreatic cell fate decisions. When pancreas development or islet cell functions go awry, due to mutations in genes important for proper organogenesis and development, the result can lead to a common pancreatic affliction, diabetes mellitus. Current treatments for diabetes are adequate but not curative. Therefore, researchers are utilizing the current understanding of normal embryonic pancreas development in vivo, to direct embryonic stem cells toward a pancreatic fate with the goal of transplanting these in vitro generated 'islets' into patients. Mimicking development in vitro has proven difficult; however, significant progress has been made and the current differentiation protocols are becoming more efficient. The continued partnership between developmental biologists and stem cell researchers will guarantee that the in vitro generation of insulin-producing β cells is a possible therapeutic option for the treatment of diabetes. Copyright © 2012 Wiley Periodicals, Inc.

  9. [Obesity and pancreatic diseases]. (United States)

    Kim, Ho Gak; Han, Jimin


    Obesity is defined as BMI (calculated as weight in kg divided by height in m2) more than 30, and overweight is defined as BMI of 25-29.9. Obesity has been considered as a risk factor for pancreatic diseases, including pancreatitis and pancreatic cancer. Severe acute pancreatitis is significantly more frequent in obese patients. Furthermore, obese patients develop systemic and local complications of acute pancreatitis more frequently. The underlying mechanisms are increased inflammation and necrosis from increased amount of intra- and peri-pancreatic fat. In addition, obesity is a poor prognostic factor in acute pancreatitis, and overweight before disease onset appears to be a risk factor for chronic pancreatitis. Overweight and/or obesity are associated with greater risk of pancreatic cancer and younger age of onset. Physical activity appears to decrease the risk of pancreatic cancer, especially among those who are overweight. Long-standing diabetes increases the risk of pancreatic cancer. The pathogenic mechanism is that obesity and physical inactivity increase insulin resistance. In a state of hypersinulinemia, increased circulating level of insulin-like growth factor-1 induces cellular proliferation of pancreatic cancer. Obesity is associated with negative prognostic factor and increased mortality in pancreatic cancer. However, there are controversies regarding the effects of obesity on long-term post-operative results in the patient with pancreatic cancer.

  10. Do endocrine disruptors cause hypospadias? (United States)

    Botta, Sisir; Cunha, Gerald R.


    Introduction Endocrine disruptors or environmental agents, disrupt the endocrine system, leading to various adverse effects in humans and animals. Although the phenomenon has been noted historically in the cases of diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT), the term “endocrine disruptor” is relatively new. Endocrine disruptors can have a variety of hormonal activities such as estrogenicity or anti-androgenicity. The focus of this review concerns on the induction of hypospadias by exogenous estrogenic endocrine disruptors. This has been a particular clinical concern secondary to reported increased incidence of hypospadias. Herein, the recent literature is reviewed as to whether endocrine disruptors cause hypospadias. Methods A literature search was performed for studies involving both humans and animals. Studies within the past 5 years were reviewed and categorized into basic science, clinical science, epidemiologic, or review studies. Results Forty-three scientific articles were identified. Relevant sentinel articles were also reviewed. Additional pertinent studies were extracted from the reference of the articles that obtained from initial search results. Each article was reviewed and results presented. Overall, there were no studies which definitely stated that endocrine disruptors caused hypospadias. However, there were multiple studies which implicated endocrine disruptors as one component of a multifactorial model for hypospadias. Conclusions Endocrine disruption may be one of the many critical steps in aberrant development that manifests as hypospadias. PMID:26816789

  11. [Hand and endocrine diseases]. (United States)

    Wémeau, Jean-Louis; Ryndak, Amélie; Karrouz, Wassila; Balavoine, Anne-Sophie; Baudoux, Florence


    The whole of hormones likely influence state of hands, modifying colouring and trophicity of the skin and having influence on its muscular, tendineous, osseous, articular components. Thus state of the hands contributes to the recognition of the endocrine diseases: hot and moist hands of the Graves' disease, dry, cold and infiltrated hands in myxoedema, pale and fine hands of hypopituitarism, broad and thick hand of acromegaly, brachymetacarpia in the pseudohypoparathyroidism… Diabetes exposes particularly to tendineous and articular retractions, to whitlows and ungual mycosis. Copyright © 2013. Published by Elsevier Masson SAS.

  12. Women's Health Endocrine Update. (United States)

    Kapoor, Ekta; Faubion, Stephanie; Hines, Stephanie; Stuenkel, Cynthia A


    The clinical update serves as a brief review of recently published, high-impact, and potentially practice changing journal articles summarized for our readers. Topics include menopause, sexual dysfunction, breast health, contraception, osteoporosis, and cardiovascular disease. In this clinical update, we selected four recent high-impact publications related to endocrine issues in women. We have chosen to highlight research on subclinical hypothyroidism during pregnancy and adverse pregnancy outcomes, including cognitive outcomes in offspring; the progression of metabolic syndrome severity during the menopausal transition; and the association of diabetes and metformin use with cancer risk and mortality.

  13. The Role of BRCA2 Mutation Status as Diagnostic, Predictive, and Prognosis Biomarker for Pancreatic Cancer. (United States)

    Martinez-Useros, Javier; Garcia-Foncillas, Jesus


    Pancreatic cancer is one of the deadliest cancers worldwide, and life expectancy after diagnosis is often short. Most pancreatic tumours appear sporadically and have been highly related to habits such as cigarette smoking, high alcohol intake, high carbohydrate, and sugar consumption. Other observational studies have suggested the association between pancreatic cancer and exposure to arsenic, lead, or cadmium. Aside from these factors, chronic pancreatitis and diabetes have also come to be considered as risk factors for these kinds of tumours. Studies have found that 10% of pancreatic cancer cases arise from an inherited syndrome related to some genetic alterations. One of these alterations includes mutation in BRCA2 gene. BRCA2 mutations impair DNA damage response and homologous recombination by direct regulation of RAD51. In light of these findings that link genetic factors to tumour development, DNA damage agents have been proposed as target therapies for pancreatic cancer patients carrying BRCA2 mutations. Some of these drugs include platinum-based agents and PARP inhibitors. However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to target BRCA2. The present systematic review collects and analyses the role of BRCA2 alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.

  14. The Role of BRCA2 Mutation Status as Diagnostic, Predictive, and Prognosis Biomarker for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Javier Martinez-Useros


    Full Text Available Pancreatic cancer is one of the deadliest cancers worldwide, and life expectancy after diagnosis is often short. Most pancreatic tumours appear sporadically and have been highly related to habits such as cigarette smoking, high alcohol intake, high carbohydrate, and sugar consumption. Other observational studies have suggested the association between pancreatic cancer and exposure to arsenic, lead, or cadmium. Aside from these factors, chronic pancreatitis and diabetes have also come to be considered as risk factors for these kinds of tumours. Studies have found that 10% of pancreatic cancer cases arise from an inherited syndrome related to some genetic alterations. One of these alterations includes mutation in BRCA2 gene. BRCA2 mutations impair DNA damage response and homologous recombination by direct regulation of RAD51. In light of these findings that link genetic factors to tumour development, DNA damage agents have been proposed as target therapies for pancreatic cancer patients carrying BRCA2 mutations. Some of these drugs include platinum-based agents and PARP inhibitors. However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to target BRCA2. The present systematic review collects and analyses the role of BRCA2 alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.

  15. Type I interferons mediate pancreatic toxicities of PERK inhibition. (United States)

    Yu, Qiujing; Zhao, Bin; Gui, Jun; Katlinski, Kanstantsin V; Brice, Angela; Gao, Yan; Li, ChangHong; Kushner, Jake A; Koumenis, Constantinos; Diehl, J Alan; Fuchs, Serge Y


    The great preclinical promise of the pancreatic endoplasmic reticulum kinase (PERK) inhibitors in neurodegenerative disorders and cancers is marred by pancreatic injury and diabetic syndrome observed in PERK knockout mice and humans lacking PERK function and suffering from Wolcott-Rallison syndrome. PERK mediates many of the unfolded protein response (UPR)-induced events, including degradation of the type 1 interferon (IFN) receptor IFNAR1 in vitro. Here we report that whole-body or pancreas-specific Perk ablation in mice leads to an increase in IFNAR1 protein levels and signaling in pancreatic tissues. Concurrent IFNAR1 deletion attenuated the loss of PERK-deficient exocrine and endocrine pancreatic tissues and prevented the development of diabetes. Experiments using pancreas-specific Perk knockouts, bone marrow transplantation, and cultured pancreatic islets demonstrated that stabilization of IFNAR1 and the ensuing increased IFN signaling in pancreatic tissues represents a major driver of injury triggered by Perk loss. Neutralization of IFNAR1 prevented pancreatic toxicity of PERK inhibitor, indicating that blocking the IFN pathway can mitigate human genetic disorders associated with PERK deficiency and help the clinical use of PERK inhibitors.

  16. Evaluation of islets derived from human fetal pancreatic progenitor cells in diabetes treatment. (United States)

    Zhang, Wen-Jian; Xu, Shi-Qing; Cai, Han-Qing; Men, Xiu-Li; Wang, Zai; Lin, Hua; Chen, Li; Jiang, Yong-Wei; Liu, Hong-Lin; Li, Cheng-Hui; Sui, Wei-Guo; Deng, Hong-Kui; Lou, Jin-Ning


    With the shortage of donor organs for islet transplantation, insulin-producing cells have been generated from different types of stem cell. Human fetal pancreatic stem cells have a better self-renewal capacity than adult stem cells and can readily differentiate into pancreatic endocrine cells, making them a potential source for islets in diabetes treatment. In the present study, the functions of pancreatic islets derived from human fetal pancreatic progenitor cells were evaluated in vitro and in vivo. Human pancreatic progenitor cells isolated from the fetal pancreas were expanded and differentiated into islet endocrine cells in culture. Markers for endocrine and exocrine functions as well as those for alpha and beta cells were analyzed by immunofluorescent staining and enzyme-linked immunosorbent assay (ELISA). To evaluate the functions of these islets in vivo, the islet-like structures were transplanted into renal capsules of diabetic nude mice. Immunohistochemical staining for human C-peptide and human mitochondrion antigen was applied to confirm the human origin and the survival of grafted islets. Human fetal pancreatic progenitor cells were able to expand in medium containing basic fibroblast growth factor (bFGF) and leukemia inhibitor factor (LIF), and to differentiate into pancreatic endocrine cells with high efficiency upon the actions of glucagon-like peptide-1 and activin-A. The differentiated cells expressed insulin, glucagon, glucose transporter-1 (GLUT1), GLUT2 and voltage-dependent calcium channel (VDCC), and were able to aggregate into islet-like structures containing alpha and beta cells upon suspension. These structures expressed and released a higher level of insulin than adhesion cultured cells, and helped to maintain normoglycemia in diabetic nude mice after transplantation. Human fetal pancreatic progenitor cells have good capacity for generating insulin producing cells and provide a promising potential source for diabetes treatment.

  17. The Scandinavian baltic pancreatic club (SBPC) database

    DEFF Research Database (Denmark)

    Olesen, Søren Maagaard; Poulsen, Jakob L; Drewes, Asbjørn M.


    , we describe the design of the database and characteristics of the study cohort. METHODS: 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......: 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...

  18. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sala Abdalla


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

  19. Pancreatic neuroendocrine neoplasms; Neuroendokrine Neoplasien des Pankreas

    Energy Technology Data Exchange (ETDEWEB)

    Beiderwellen, K.; Lauenstein, T.C. [Universitaetsklinikum Essen, Institut fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Essen (Germany); Sabet, A.; Poeppel, T.D. [Universitaetsklinikum Essen, Klinik fuer Nuklearmedizin, Essen (Germany); Lahner, H. [Universitaetsklinikum Essen, Klinik fuer Endokrinologie und Stoffwechselerkrankungen, Essen (Germany)


    Pancreatic neuroendocrine neoplasms (NEN) account for 1-2 % of all pancreatic neoplasms and represent a rare differential diagnosis. While some pancreatic NEN are hormonally active and exhibit endocrine activity associated with characteristic symptoms, the majority are hormonally inactive. Imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) or as combined PET/CT play a crucial role in the initial diagnosis, therapy planning and control. Endoscopic ultrasound (EUS) and multiphase CT represent the reference methods for localization of the primary pancreatic tumor. Particularly in the evaluation of small liver lesions MRI is the method of choice. Somatostatin receptor scintigraphy and somatostatin receptor PET/CT are of particular value for whole body staging and special aspects of further therapy planning. (orig.) [German] Neuroendokrine Neoplasien (NEN) des Pankreas stellen mit einem Anteil von 1-2 % aller pankreatischen Tumoren eine seltene Differenzialdiagnose dar. Ein Teil der Tumoren ist hormonell aktiv und faellt klinisch durch charakteristische Symptome auf, wohingegen der ueberwiegende Anteil hormonell inaktiv ist. Bildgebende Verfahren wie Sonographie, Computertomographie (CT), Magnetresonanztomographie (MRT) und nicht zuletzt Positronenemissionstomographie (PET oder kombiniert als PET/CT) spielen eine zentrale Rolle fuer Erstdiagnose, Therapieplanung und -kontrolle. Die Endosonographie und die multiphasische CT stellen die Referenzmethoden zur Lokalisation des Primaertumors dar. Fuer die Differenzierung insbesondere kleiner Leberlaesionen bietet die MRT die hoechste Aussagekraft. Fuer das Ganzkoerperstaging und bestimmte Aspekte der Therapieplanung lassen sich die Somatostatinrezeptorszintigraphie und v. a. die Somatostatinrezeptor-PET/CT heranziehen. (orig.)

  20. Data on morphometric analysis of the pancreatic islets from C57BL/6 and BALB/c mice

    Directory of Open Access Journals (Sweden)

    Thiago Aparecido da Silva


    Full Text Available The endocrine portion of the pancreas, which is characterized by pancreatic islets, has been widely investigated among different species. The BALB/c and C57BL/6 mice are extensively used in experimental research, and the morphometric differences in the pancreatic islets of these animals have not been evaluated so far. Thus, our data have a comparative perspective related to the morphometric analysis of area, diameters, circularity, and density of pancreatic islets from BALB/c and C57BL/6 mice. The data presented here are focused to evaluate the differences in morphology of pancreatic islets of two common laboratory mouse strains.

  1. Nigerian Endocrine Practice: Editorial Policies

    African Journals Online (AJOL)

    Focus and Scope. Nigerian Endocrine Practice, a peer reviewed publication published twice a year is the official publication of the Nigerian Chapter of the American Association of Clinical Endocrinologists (AACE-Nigeria). The primary mission of the Nigerian Endocrine Practice is to enhance the health care of patients with ...

  2. Characterization of Insulin-Immunoreactive Cells and Endocrine Cells Within the Duct System of the Adult Human Pancreas. (United States)

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


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

  3. Pancreatic Cancer Genetics

    National Research Council Canada - National Science Library

    Amundadottir, Laufey T


    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1...

  4. Pancreatitis-imaging approach (United States)

    Busireddy, Kiran K; AlObaidy, Mamdoh; Ramalho, Miguel; Kalubowila, Janaka; Baodong, Liu; Santagostino, Ilaria; Semelka, Richard C


    Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrast-enhanced computed tomography (MD-CECT) the most used imaging technique. However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI. PMID:25133027

  5. Surgery for pancreatic cancer (United States)

    ... Surgery for pancreatic cancer To use the sharing features on this page, ... surgeries are used in the surgical treatment of pancreatic cancer. Whipple procedure: This is the most common surgery ...

  6. Pathogenic mechanisms of pancreatitis (United States)

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


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

  7. Autoimmune pancreatitis: a review. (United States)

    Zandieh, Iman; Byrne, Michael-F


    Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the proposed diagnostic criteria and treatment algorithms.

  8. Autoimmune pancreatitis: A review


    Zandieh, Iman; Michael F Byrne


    Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the...

  9. Road accident due to a pancreatic insulinoma: a case report. (United States)

    Parisi, Amilcare; Desiderio, Jacopo; Cirocchi, Roberto; Grassi, Veronica; Trastulli, Stefano; Barberini, Francesco; Corsi, Alessia; Cacurri, Alban; Renzi, Claudio; Anastasio, Fabio; Battista, Francesca; Pucci, Giacomo; Noya, Giuseppe; Schillaci, Giuseppe


    Insulinoma is a rare pancreatic endocrine tumor, typically sporadic and solitary. Although the Whipple triad, consisting of hypoglycemia, neuroglycopenic symptoms, and symptoms relief with glucose administration, is often present, the diagnosis may be challenging when symptoms are less typical. We report a case of road accident due to an episode of loss of consciousness in a patient with pancreatic insulinoma. In the previous months, the patient had occasionally reported nonspecific symptoms. During hospitalization, endocrine examinations were compatible with an insulin-producing tumor. Abdominal computerized tomography and magnetic resonance imaging allowed us to identify and localize the tumor. The patient underwent a robotic distal pancreatectomy with partial omentectomy and splenectomy. Insulin-producing tumors may go undetected for a long period due to nonspecific clinical symptoms, and may cause episodes of loss of consciousness with potentially lethal consequences. Robot-assisted procedures can be performed with the same techniques of the traditional surgery, reducing surgical trauma, intraoperative blood loss, and hospital stays.

  10. Nanotechnologies in Pancreatic Cancer Therapy. (United States)

    Manzur, Ayesha; Oluwasanmi, Adeolu; Moss, Darren; Curtis, Anthony; Hoskins, Clare


    Pancreatic cancer has been classified as a cancer of unmet need. After diagnosis the patient prognosis is dismal with few surviving over 5 years. Treatment regimes are highly patient variable and often the patients are too sick to undergo surgical resection or chemotherapy. These chemotherapies are not effective often because patients are diagnosed at late stages and tumour metastasis has occurred. Nanotechnology can be used in order to formulate potent anticancer agents to improve their physicochemical properties such as poor aqueous solubility or prolong circulation times after administration resulting in improved efficacy. Studies have reported the use of nanotechnologies to improve the efficacy of gemcitabine (the current first line treatment) as well as investigating the potential of using other drug molecules which have previously shown promise but were unable to be utilised due to the inability to administer through appropriate routes-often related to solubility. Of the nanotechnologies reported, many can offer site specific targeting to the site of action as well as a plethora of other multifunctional properties such as image guidance and controlled release. This review focuses on the use of the major nanotechnologies both under pre-clinical development and those which have recently been approved for use in pancreatic cancer therapy.

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


    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.

  12. Pancreatic Cancer Stage 3 (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Pancreatic Cancer Stage 3 Add to My Pictures View /Download : ... 1500x1200 View Download Large: 3000x2400 View Download Title: Pancreatic Cancer Stage 3 Description: Stage III pancreatic cancer; drawing ...

  13. Pancreatic Cancer Stage 4 (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Pancreatic Cancer Stage 4 Add to My Pictures View /Download : ... 1200x1200 View Download Large: 2400x2400 View Download Title: Pancreatic Cancer Stage 4 Description: Stage IV pancreatic cancer; drawing ...

  14. Expression and prognostic significance of thymidylate synthase (TS) in pancreatic head and periampullary cancer. (United States)

    van der Zee, J A; van Eijck, C H J; Hop, W C J; van Dekken, H; Dicheva, B M; Seynhaeve, A L B; Koning, G A; Eggermont, A M M; Ten Hagen, T L M


    Pancreatic cancer has a dismal prognosis. Attempts have been made to improve outcome by several 5-FU based adjuvant treatment regimens. However, the results are conflicting. There seems to be a continental divide with respect to the use of 5-FU based chemoradiotherapy (CRT). Furthermore, evidence has been presented showing a different response of pancreatic head and periampullary cancer to 5-FU based CRT. Expression of thymidylate synthase (TS) has been associated with improved outcome following 5-FU based adjuvant treatment in gastrointestinal cancer. This prompted us to determine the differential expression and prognostic value of TS in pancreatic head and periampullary cancer. TS protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 212 patients following microscopic radical resection (R0) of pancreatic head (n = 98) or periampullary cancer (n = 114). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS), and conventional prognostic factors. High cytosolic TS expression was present in 26% of pancreatic head tumours and 37% of periampullary tumours (p = .11). Furthermore, TS was an independent factor predicting favourable outcome following curative resection of pancreatic head cancer (p = .003, .001 and .001 for RFS, CSS and OS, respectively). In contrast, in periampullary cancer, TS was not associated with outcome (all p > .10). TS, was found to be poorly expressed in both pancreatic head and periampullary cancer and identified as an independent prognostic factor following curative resection of pancreatic head cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Endocrine Actions of Osteocalcin

    Directory of Open Access Journals (Sweden)

    Aurora Patti


    Full Text Available Osteocalcin is the most abundant noncollagenous protein of bone matrix. Once transcribed, this protein undergoes posttranslational modifications within osteoblastic cells before its secretion, including the carboxylation of three glutamic residues in glutamic acid, which is essential for hydroxyapatite binding and deposition in the extracellular matrix of bone. Recent provocative data from experimental observations in mice showed that the circulating undercarboxylated fraction of osteocalcin increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral fat in both genders, while it enhances testosterone production by the testes in males. Moreover, both total and undercarboxylated osteocalcins increase following physical activity with potential positive effects on glucose tolerance. Despite that these evidences have been only in part confirmed in humans, further prospective investigations are needed to definitively establish the endocrine role of osteocalcin both in the general population and cohorts of patients with diabetes or other metabolic disorders.


    DEFF Research Database (Denmark)

    Glintborg, Dorte; Andersen, Marianne


    controls within all diagnose categories including antibiotics. The causal relationship between PCOS and autoimmune disease represents an interesting new area of research. PCOS is a lifelong condition and long term morbidity could be worsened by obesity, sedentary way of life, western style diet and smoking......Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition in premenopausal women. The syndrome is characterized by hyperandrogenism, irregular menses and polycystic ovaries when other etiologies are excluded. Obesity, insulin resistance and low vitamin D levels are present in more...... than 50% patients with PCOS, these factors along with hyperandrogenism could have adverse effects on long term health. Hyperinflammation and impaired epithelial function were reported to a larger extent in women with PCOS and could particularly be associated with hyperandrogenism, obesity and insulin...


    McKee, Alexis; Morley, John E; Matsumoto, Alvin M; Vinik, Aaron


    Sarcopenia is defined as low muscle function (walking speed or grip strength) in the presence of low muscle mass. A simple screening test-the SARC-F-is available to identify persons with sarcopenia. The major endocrine causes of sarcopenia are diabetes mellitus and male hypogonadism. Other causes are decreased physical activity, loss of motor neuron units, weight loss, inflammatory cytokines, reduced blood flow to muscles, very low 25(OH) vitamin D levels, and decreased growth hormone and insulin-like growth factor 1. Treatment for sarcopenia includes resistance and aerobic exercise, leucine-enriched essential amino acids, and vitamin D. In hypogonadal males, testosterone improves muscle mass, strength, and function. Selective androgen receptor molecules and anti-myostatin activin II receptor molecules are under development as possible treatments for sarcopenia. COPD = chronic obstructive pulmonary disease DHEA = dehydroepiandrosterone IGF-1 = insulin-like growth factor 1 GH = growth hormone mTOR = mammalian target of rapamycin SARM = selective androgen receptor molecule.

  18. Chronic pancreatitis: relation to acute pancreatitis and pancreatic cancer. (United States)

    Uomo, G; Rabitti, P G


    The relationship between chronic pancreatitis (CP) and other pancreatic diseases, such as acute pancreatitis (AP) and pancreatic cancer (PK), remains a fairly debated question. The progression from alcoholic AP to CP is controversial, and some long-term epidemiological studies suggest that alcoholic CP might be the result of recurrent alcoholic AP (necrosis-fibrosis sequence) and a subgroup of alcoholics may present recurrent AP without progression to CP. Other predisposing factors (genetic, nutritional, environmental) seems to be important in inducing different outcomes of pancreatic damage due to alcohol. However, recurrent episodes of AP are clearly involved in pathophysiology of CP in patients with hereditary pancreatitis. A relationship between CP and subsequent PK development has long been suspected, but we actually don't know whether this association is direct or is the result of confounding factors, such as alcohol intake or cigarette smoking. Many issues should be considered as indicators of a causal association, and several of them are not fulfilled. Nonetheless, epidemiological studies (case-control or cohort studies) showed that the risk of PK is increased in patients with CP; the risk is significantly higher in tropical calcifying CP and hereditary pancreatitis. Studies on growth factors, oncogenes, tumor-suppressor genes, and angiogenesis suggest that the sequence PC-KP is plausible from the biological standpoint.

  19. Pancreatic adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Schima, Wolfgang; Ba-Ssalamah, Ahmed; Koelblinger, Claus; Kulinna-Cosentini, Christiane [Medical University of Vienna, Department of Radiology, Vienna (Austria); Puespoek, Andreas [Medical University of Vienna, Department of Internal Medicine 4, Division of Gastroenterology and Hepatology, Vienna (Austria); Goetzinger, Peter [Medical University of Vienna, Austria, Department of Surgery, Vienna (Austria)


    Adenocarcinoma is the most common malignant pancreatic tumor, affecting the head of the pancreas in 60-70% of cases. By the time of diagnosis, at least 80% of tumors are unresectable. Helical computed tomography (CT) is very effective in detecting and staging adenocarcinoma, with a sensitivity of up to 90% for detection and an accuracy of 80-90% for staging, but it has limitations in detecting small cancers. Moreover, it is not very accurate for determining nonresectability because small liver metastases, peritoneal carcinomatosis, and subtle signs of vascular infiltration may be missed. Multidetector-row CT (MDCT) has brought substantial improvements with its inherent ability to visualize vascular involvement in three dimensions. MDCT has been found to be at least equivalent to contrast-enhanced magnetic resonance imaging (MRI) for detecting adenocarcinoma. MRI can be used as a problem-solving tool in equivocal CT: MRI may help rule out pitfalls, such as inflammatory pseudotumor, focal lipomatosis, abscess, or cystic tumors. Mangafodipir-enhanced MRI reveals a very high tumor-pancreas contrast, which helps in diagnosing small cancers. Endosonography is, if available, also a very accurate tool for detecting small cancers, with a sensitivity of up to 98%. It is the technique of choice for image-guided biopsy if a histologic diagnosis is required for further therapy. (orig.)

  20. Autoimmune pancreatitis. (United States)

    Pannala, Rahul; Chari, Suresh T


    Autoimmune pancreatitis (AIP) is an increasingly recognized clinical condition. Our objective is to provide a concise review of the advances in the past year in our understanding of AIP. In a hospital survey from Japan, the prevalence of AIP was estimated at 0.82 per 100,000 individuals. The pathogenesis of AIP remains unclear but a recent report noted that T helper type 2 and T regulatory cells predominantly mediate the immune reaction in AIP. Genetic associations that may predispose to relapse of AIP were reported. Multiple case series further described the clinical profile of AIP and its extrapancreatic manifestations. A large series on immunoglobulin G4 (IgG4)-associated cholangitis noted that patients with IgG4-associated cholangitis presented with obstructive jaundice and had increased serum IgG4 levels and IgG4-positive cells in bile duct biopsy specimens. Tissue IgG4 staining is likely to be a useful adjunct to serological diagnosis. AIP is steroid-responsive but maintaining remission continues to remain challenging. Presently low-dose steroids or immunomodulators are being used but efficacy of these medications remains to be determined. There has been significant progress in understanding the clinical profile of AIP but knowledge of pathogenesis remains limited. Treatment practices vary widely and management of refractory disease continues to be challenging.

  1. Immunohistochemical localization of pancreatic spasmolytic polypeptide (PSP) in the pig

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Poulsen, Steen Seier; Thim, L


    Pancreatic spasmolytic polypeptide (PSP) is a peptide that is isolated from the porcine pancreas and that affects intestinal motility and growth of intestinal tumour cells in vitro. The peptide was recently demonstrated to be present in large amounts in pancreatic juice. The cellular origin......, PSP immunoreactivity was seen in some of the cells in the epithelium of the crypts of Lieberkühn. A peptide chromatographically identical to highly purified PSP was identified in pancreas and stomach extracts. Thus epithelial cells in all parts of the stomach and small intestine contribute...

  2. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Miroslav Vujasinovic


    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.

  3. Small amounts of tissue preserve pancreatic function (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


    Abstract 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

  4. Controversies in Odontogenic Tumours: Review. (United States)

    Siwach, Pooja; Joy, Tabita; Tupkari, Jagdish; Thakur, Arush


    Odontogenic tumours are lesions that occur solely within the oral cavity and are so named because of their origin from the odontogenic (i.e. tooth-forming) apparatus. Odontogenic tumours comprise a variety of lesions ranging from non-neoplastic tissue proliferations to benign or malignant neoplasms. However, controversies exist regarding the pathogenesis, categorisation and clinical and histological variations of these tumours. The recent 2017 World Health Organization classification of odontogenic tumours included new entities such as primordial odontogenic tumours, sclerosing odontogenic carcinomas and odontogenic carcinosarcomas, while eliminating several previously included entities like keratocystic odontogenic tumours and calcifying cystic odonogenic tumours. The aim of the present review article was to discuss controversies and recent concepts regarding odontogenic tumours so as to increase understanding of these lesions.

  5. Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis. (United States)

    Grabliauskaite, Kamile; Saponara, Enrica; Reding, Theresia; Bombardo, Marta; Seleznik, Gitta M; Malagola, Ermanno; Zabel, Anja; Faso, Carmen; Sonda, Sabrina; Graf, Rolf


    Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor-β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ-RII) using a Cre-LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein-induced pancreatitis. We show that TGFβ-RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ-RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell-autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ-RII signalling stimulates the expression of cyclin-dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ-RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ-based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. Osteoporosis in Multiple Endocrine Neoplasia Type I: A Case Report – Case Report

    Directory of Open Access Journals (Sweden)

    Kurtuluş Kaya


    Full Text Available Multiple Endocrine Neoplasia type I (MEN type-I is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary. Primary hyperparathyroidism is the most common clinical expression in affected patients, present in more than 90% of cases. Osteoporosis is a frequent and early complication of primary hyperparathyroidism in MEN type I. A case with a diagnosis of MEN type-I, 39 years old, presented with humeral, femural and L4 vertebral fractures after falling is evaluated in the view of the literature in this case report. (From the World of Osteoporosis 2008;14:40-3

  7. Warthin's tumour and smoking.

    NARCIS (Netherlands)

    Ru, J.A. de; Plantinga, R.F.; Majoor, M.H.; Benthem, P.P. van; Slootweg, P.J.; Peeters, P.H.; Hordijk, G.J.


    OBJECTIVE: In an evaluation of our patients with parotid gland neoplasms, we noticed that patients with a Warthin's tumour were heavy smokers. The aim of this study was to confirm earlier findings in the literature concerning a possible association between smoking and the development of a Warthin's

  8. Extracranial glomus faciale tumour. (United States)

    Connor, S E J; Gleeson, M J; Odell, E


    To describe a unique presentation of a predominantly extracranial glomus faciale tumour. To discuss the role of imaging in the differential diagnosis and evaluation of a hypervascular parotid mass. To review the previous literature concerning the glomus faciale tumour. A 54-year-old woman presented with a six-month history of facial weakness, pain and a parotid mass. Ultrasound revealed a hypervascular parotid mass and pre-operative core biopsy suggested a paraganglioma. Computed tomography defined its deep extent and demonstrated involvement of the petrous temporal bone along the descending portion of the facial nerve canal with a pattern of permeative lucency. A tumour was surgically removed which arose from the facial nerve from the second genu to the proximal divisions within the parotid gland and histology confirmed a paraganglioma. A facial nerve glomus faciale tumour should be considered in the differential diagnosis of a hypervascular parotid mass and may present in a predominantly extracranial location. Computed tomography will prove helpful in such a case in order to limit the differential diagnosis and to define the extent of skull base involvement.

  9. Intestinal inflammatory myofibroblastic tumour

    African Journals Online (AJOL)

    Since its first description in 1937,1 the understanding of inflamma- tory myofibroblastic tumour (IMFT) has evolved from a reactive inflammatory process to a neoplasm of intermediate biological potential.2-9 Associated with nosologic, histogenetic and aetiopatho- genetic controversy, IMFTs occur in all age groups and in ...

  10. Pancreatitis Induced by Cocaine

    Directory of Open Access Journals (Sweden)

    Sebastián Pablo Chapela


    Full Text Available Pancreatitis is one of the commonest diseases of the gastrointestinal tract, characterized by epigastric pain of moderate to severe intensity, which radiates to the back, elevation of pancreatic lipase and amylase enzymes, and changes in pancreatic parenchyma in imaging methods. The most common etiologies vary, generally the most frequent being biliary lithiasis and alcohol, followed by hypertriglyceridemia. Among the less frequent causes is drug-induced pancreatitis. We report a case of acute pancreatitis caused by cocaine, rarely described in literature.

  11. Diabetes and Pancreatic Cancer (United States)

    Li, Donghui


    Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5- to 2.0-fold increase in the risk of pancreatic cancer. A causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies. Insulin resistance and associated hyperglycemia, hyperinsulinemia, and inflammation have been suggested to be the underlying mechanisms contributing to development of diabetes-associated pancreatic cancer. Signaling pathways that regulate the metabolic process also play important roles in cell proliferation and tumor growth. Use of the antidiabetic drug metformin has been associated with reduced risk of pancreatic cancer in diabetics and recognized as an antitumor agent with the potential to prevent and treat this cancer. On the other hand, new-onset diabetes may indicate subclinical pancreatic cancer, and patients with new-onset diabetes may constitute a population in whom pancreatic cancer can be detected early. Biomarkers that help define high-risk individuals for clinical screening for pancreatic cancer are urgently needed. Why pancreatic cancer causes diabetes and how diabetes affects the clinical outcome of pancreatic cancer have yet to be fully determined. Improved understanding of the pathological mechanisms shared by diabetes and pancreatic cancer would be the key to the development of novel preventive and therapeutic strategies for this cancer. PMID:22162232

  12. [Pancreatitis: An update]. (United States)

    Schreyer, A G; Grenacher, L; Juchems, M


    Acute and chronic pancreatitis are becoming increasingly more severe diseases in the western world with far-reaching consequences for the individual patient as well as the socioeconomic situation. This article gives an overview of the contribution of radiological imaging to the diagnostics and therapy of both forms of the disease. Acute pancreatitis can be subdivided into severe (20%) and mild manifestations. The diagnostics should be performed with computed tomography (CT) or magnetic resonance imaging (MRI) for assessing necrosis or potential infections only in severe forms of pancreatitis. In chronic pancreatitis transabdominal ultrasound should initially be adequate for assessment of the pancreas. For the differential diagnosis between pancreatic carcinoma and chronic pancreatitis, MRI with magnetic resonance cholangiopancreatography (MRCP) followed by an endoscopic ultrasound-guided fine needle aspiration is the method of choice. For the primary diagnosis for acute and chronic pancreatitis ultrasound examination is the modality of first choice followed by radiological CT and MRI with MRCP examinations.

  13. Are cranial germ cell tumours really tumours of germ cells? (United States)

    Scotting, P J


    Germ cell tumours of the brain and those that occur in the gonads are believed to share a common origin from germ cell progenitors. This 'germ cell theory' rests upon similar histopathology between these tumours in different locations and the belief that endogenous somatic cells of the brain could not give rise to the range of cell types seen in germ cell tumours. An alternative 'embryonic cell theory' has been proposed for some classes of cranial germ cell tumours, but this still relies on the misplacement of cells in the brain (in this case the earliest embryonic stem cells) during early embryonic development. Recent evidence has demonstrated that neural stem cells of the brain can also give rise to many of the cell types seen in germ cell tumours. These data suggest that endogenous progenitor cells of the brain are a plausible alternative origin for these tumours. This idea is of central importance for studies aiming to elucidate the mechanisms of tumour development. The application of modern molecular analyses to reveal how tumour cells have altered with respect to their cell of origin relies on the certain identification of the cell from which the particular tumour arose. If the identity of this cell is mistaken, then studies to elucidate the mechanisms by which the progenitor cell has been subverted from its normal behaviour will not yield useful information. In addition, it will prove impossible to generate an appropriate animal model in which to study the underlying causes of those tumours. This article makes the case that current assumptions of the origins of cranial germ cell tumours are unreliable. It reviews the evidence in favour of the 'germ cell theory' and argues in favour of a 'brain cell theory' in which endogenous neural progenitor cells of the brain are the likely origin for these tumours. Thus, the case is made that cranial germ cell tumours, like other brain tumours, arise by the transformation of progenitor cells normally resident in the

  14. [Multiple Endocrine Neoplasia I (Wermers Syndrome), Forms of Clinical Manifestation, 5 Case Studies]. (United States)

    Drbalová, Karolína; Herdová, Kateřina; Krejčí, Petr; Nývltová, Monika; Solař, Svatopluk; Vedralová, Lenka; Záruba, Pavel; Netuka, David; Bavor, Petr

    Multiple Endocrine Neoplasia (MEN) is a condition in which several endocrine organs of an individual are affected by adenoma, hyperplasia and less often carcinoma, either simultaneously or at different stages of life. Two existing syndromes, MEN1 and MEN2 (2A, 2B), in literature is also mentioned MEN4, are associated also with other non-endocrine disorders. MEN1 (Wermer syndrome) affects the pituitary, parathyroid, and pancreatic area. 95 % of patients show very early manifestation of hyperparathyroidism, often before 40 years of age. Multiple adenomas gradually involve all four parathyroid glands. The first clinical sign of MEN1 includes recurrent nephrolithiasis. The second most frequent manifestation of MEN1 is pancreatic area (pancreas, stomach and duodenum), again multiple malignancies of varying degree which can metastasize. Most often gastrinomas and insulinomas are involved. Pituitary adenomas occur in about one third of MEN1 patients and tend to be larger and less responsive to treatment. Tumors appearing most often are prolactinomas, tumors producing growth hormone, or afunctional adenomas. The other endocrine tumors include carcinoids and adrenal lesions. In the last year we have registered four MEN1 syndrome patients in our center and one patient has been already followed since 2008. In four out of five patients, nephrolithiasis after 30 years of age was the first clinical symptom, but only one of theses cases resulted in MEN1 diagnosis. In all patients, the clinical symptoms intensified and the diagnosis was established between 36 and 40 years of age. A crutial factor is a cooperation with the urology examination of kidney stones formation in young individuals with nephrolithiasis in order to reveal the potential cases of MEN1 syndrome very early on. Consider the MEN1 genetic diagnostics if recurrent primary hyperparathyroidism or recurrent gastroduodenal ulcer disease appear in patients under 40 years of age.Key words: carcinoid - gastrinoma

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

    Directory of Open Access Journals (Sweden)

    Matteo Piciucchi


    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.

  16. [Surgical treatment of gastroentero-pancreatic neuroendocrine tumor]. (United States)

    Ohtsuka, Takao; Takahata, Shunichi; Ueda, Junji; Ueki, Takashi; Nagai, Eishi; Mizumoto, Kazuhiro; Shimizu, Shuji; Tanaka, Masao


    The treatment of choice for gastroentero-pancreatic neuroendocrine tumor(NET)is resection. Because it is difficult to determine the histological grade of NET before operation, the treatment strategy is usually made based on an imaging study including the tumor's size. Some selected gastrointestinal NETs are indicated for endoscopic resection, while others are resected surgically with lymph node dissection. The types of resections for pancreatic NETs vary from enucleation to pancreatectomy with or without regional lymph node dissection, based on the type of excessive hormone, tumor size, distance from the main pancreatic duct, and the presence of type 1 multiple endocrine neoplasia. Hepatic metastases are also resected, if indicated, and even in patients having unresectable metastatic lesions, multidisciplinary therapy including reduction surgery of over 90% of tumor volume might lead to a favorable prognosis. Postoperative adjuvant therapy is recommended for neuroendocrine carcinoma, while there is no evidence to support adjuvant therapy for curatively resected well-differentiated NET.

  17. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert


    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

  18. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert


    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

  19. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert S


    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., -40...

  20. as endocrine disrupting contaminants (EDCs)

    African Journals Online (AJOL)

    The challenges of removing EDCs and other pollutants at South African wastewater treatment .... of a particular component within one endocrine axis may also ...... HPG. Hypothalamic-pituitary gonadal. HPT. Hypothalamic-pituitary thyroid.

  1. "Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR


    Full Text Available Abstract Background In a significant proportion of metastatic breast cancer (MBC patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance, it is generally believed that the chance of achieving clinical benefit (CB with further endocrine therapy is minimal. Methods Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS™ software for statistical analysis. Results In oestrogen receptor (ER positive MBC patients with assessable disease, CB was achieved in 159 (71.3% (1st line patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2nd line, 46.1% (on 3rd line and 20% (on 4th line with a median duration of response (DOR in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64(28.7% patients had de novo resistance on 1st line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2nd line and 22.2% (on 3rd line with a median DOR in those with CB of 22.7 months and 14 months respectively. Conclusion The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4th line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1st line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances.

  2. Recent advances in the investigation of pancreatic inflammation induced by large doses of basic amino acids in rodents. (United States)

    Kui, Balázs; Balla, Zsolt; Végh, Eszter T; Pallagi, Petra; Venglovecz, Viktória; Iványi, Béla; Takács, Tamás; Hegyi, Péter; Rakonczay, Zoltán


    It has been known for approximately 30 years that large doses of the semi-essential basic amino acid L-arginine induce severe pancreatic inflammation in rats. Recently, it has been demonstrated that L-arginine can also induce pancreatitis in mice. Moreover, other basic amino acids like L-ornithine and L-lysine can cause exocrine pancreatic damage without affecting the endocrine parenchyma and the ducts in rats. The utilization of these noninvasive severe basic amino acid-induced pancreatitis models is becoming increasingly popular and appreciated as these models nicely reproduce most laboratory and morphological features of human pancreatitis. Consequently, the investigation of basic amino acid-induced pancreatitis may offer us a better understanding of the pathogenesis and possible treatment options of the human disease.

  3. Trauma and the endocrine system. (United States)

    Mesquita, Joana; Varela, Ana; Medina, José Luís


    The endocrine system may be the target of different types of trauma with varied consequences. The present article discusses trauma of the hypothalamic-pituitary axes, adrenal glands, gonads, and pancreas. In addition to changes in circulating hormone levels due to direct injury to these structures, there may be an endocrine response in the context of the stress caused by the trauma. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

  4. Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. (United States)

    Witt, Heiko; Apte, Minoti V; Keim, Volker; Wilson, Jeremy S


    Chronic pancreatitis (CP) is characterized by progressive pancreatic damage that eventually results in significant impairment of exocrine as well as endocrine functions of the gland. In Western societies, the commonest association of chronic pancreatitis is alcohol abuse. Our understanding of the pathogenesis of CP has improved in recent years, though important advances that have been made with respect to delineating the mechanisms responsible for the development of pancreatic fibrosis (a constant feature of CP) following repeated acute attacks of pancreatic necroinflammation (the necrosis-fibrosis concept). The pancreatic stellate cells (PSCs) are now established as key cells in fibrogenesis, particularly when activated either directly by toxic factors associated with pancreatitis (such as ethanol, its metabolites or oxidant stress) or by cytokines released during pancreatic necroinflammation. In recent years, research effort has also focused on the genetic abnormalities that may predispose to CP. Genes regulating trypsinogen activation/inactivation and cystic fibrosis transmembrane conductance regulator (CFTR) function have received particular attention. Mutations in these genes are now increasingly recognized for their potential 'disease modifier' role in distinct forms of CP including alcoholic, tropical, and idiopathic pancreatitis. Treatment of uncomplicated CP is usually conservative with the major aim being to effectively alleviate pain, maldigestion and diabetes, and consequently, to improve the patient's quality of life. Surgical and endoscopic interventions are reserved for complications such as pseudocysts, abscess, and malignancy.

  5. Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis. (United States)

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


    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.

  6. Diagnosing Musculoskeletal Tumours

    Directory of Open Access Journals (Sweden)

    Robert J. Grimer


    Full Text Available In 1993 we became aware of a worrying increase in apparent errors in the histopathological diagnosis of musculoskeletal tumours in our Unit. As a result all cases seen over the past 8 years were reviewed by an independent panel. Of the 1996 cases reviewed there was an error in 87. In 54 cases (2.7% this had led to some significant change in the active management of the patient. The main areas where errors arose were in those very cases where clinical and radiological features were not helpful in confirming or refuting the diagnosis. The incidence of errors rose with the passage of time, possibly related to a deterioration in the pathologist’s health. The error rate in diagnosing bone tumours in previously published series ranges from 9 to 40%. To ensure as accurate a rate of diagnosis as possible multidisciplinary working and regular audit are essential.

  7. Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development. (United States)

    Gouzi, Mathieu; Kim, Yung Hae; Katsumoto, Keiichi; Johansson, Kerstin; Grapin-Botton, Anne


    During development, pancreatic endocrine cells are specified within the pancreatic epithelium. They subsequently delaminate out of the epithelium and cluster in the mesenchyme to form the islets of Langerhans. Neurogenin3 (Ngn3) is a transcription factor required for the differentiation of all endocrine cells and we investigated its role in their delamination. We observed in the mouse pancreas that most Ngn3-positive cells have lost contact with the lumen of the epithelium, showing that the delamination from the progenitor layer is initiated in endocrine progenitors. Subsequently, in both mouse and chick newly born endocrine cells at the periphery of the epithelium strongly decrease E-cadherin, break-down the basal lamina and cluster into islets of Langerhans. Repression of E-cadherin is sufficient to promote delamination from the epithelium. We further demonstrate that Ngn3 indirectly controls Snail2 protein expression post-transcriptionally to repress E-cadherin. In the chick embryo, Ngn3 independently controls epithelium delamination and differentiation programs. Copyright © 2011 Wiley-Liss, Inc.

  8. Pancreatic mesenchyme regulates epithelial organogenesis throughout development.

    Directory of Open Access Journals (Sweden)

    Limor Landsman


    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. [Advances in acute pancreatitis]. (United States)

    Domínguez-Muñoz, J Enrique


    The present article reports the most recent evidence on the latest advances in the definition, diagnosis and treatment of acute pancreatitis. The concept of acute pancreatitis and its complications is changing and the presence of persistent organ failure is essential to classify a patient as having severe disease. In this context, increased intestinal permeability is seen as an early phenomenon with important prognostic repercussions. Endoscopic ultrasonography is confirmed as the investigation of choice in patients with idiopathic acute pancreatitis or suspected acute biliary pancreatitis. Aggressive water and electrolyte replacement in the first few hours after onset is the key to a favorable clinical course. Conservative treatment and the use of endoscopic necrosectomy are replacing surgery as the treatment of choice of infected pancreatic necrosis. Lastly, the present article discusses the latest evidence on the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis.

  10. Diabetes and Pancreatic Cancer


    Li, Donghui


    Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5- to 2.0-fold increase in the risk of pancreatic cancer. A causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies. Insulin resistance and associat...

  11. Pancreatic Cancer Genetics


    Amundadottir, Laufey T.


    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, ...

  12. Metabolic scaling in solid tumours (United States)

    Milotti, E.; Vyshemirsky, V.; Sega, M.; Stella, S.; Chignola, R.


    Tumour metabolism is an outstanding topic of cancer research, as it determines the growth rate and the global activity of tumours. Recently, by combining the diffusion of oxygen, nutrients, and metabolites in the extracellular environment, and the internal motions that mix live and dead cells, we derived a growth law of solid tumours which is linked to parameters at the cellular level. Here we use this growth law to obtain a metabolic scaling law for solid tumours, which is obeyed by tumours of different histotypes both in vitro and in vivo, and we display its relation with the fractal dimension of the distribution of live cells in the tumour mass. The scaling behaviour is related to measurable parameters, with potential applications in the clinical practice.

  13. Vaginal haemangioendothelioma: an unusual tumour.

    LENUS (Irish Health Repository)

    Mohan, H


    Vaginal tumours are uncommon and this is a particularly rare case of a vaginal haemangioendothelioma in a 38-year-old woman. Initial presentation consisted of symptoms similar to uterovaginal prolapse with "something coming down". Examination under anaesthesia demonstrated a necrotic anterior vaginal wall tumour. Histology of the lesion revealed a haemangioendothelioma which had some features of haemangiopericytoma. While the natural history of vaginal haemangioendothelioma is uncertain, as a group, they have a propensity for local recurrence. To our knowledge this is the third reported case of a vaginal haemangioendothelioma. Management of this tumour is challenging given the paucity of literature on this tumour. There is a need to add rare tumours to our "knowledge bank" to guide management of these unusual tumours.

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

    Directory of Open Access Journals (Sweden)

    Nathalie Swales

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

  15. Association of increased DNA methyltransferase expression with carcinogenesis and poor prognosis in pancreatic ductal adenocarcinoma. (United States)

    Zhang, Jing-Jing; Zhu, Yi; Zhu, Yan; Wu, Jun-Li; Liang, Wen-Biao; Zhu, Rong; Xu, Ze-Kuan; Du, Qing; Miao, Yi


    Epigenetic modifications play an important role in multistage carcinogenesis. The role of the three functional DNA methyltransferases (DNMTs) in pancreatic carcinogenesis has not been fully understood. The main goal of this study was to examine DNMT expression in different stages of pancreatic ductal adenocarcinoma (PDAC), and evaluate their prognostic significance in PDAC. A large number of premalignant and malignant pancreatic lesions were obtained by manual microdissection. Quantitative real-time RT-PCR was used to detect DNMTs mRNA expression. Nonparametric test, logrank test and Cox regression analysis were used to evaluate the clinical significance of DNMT expression. The mRNA expression of the three DNMTs increased with the development of pancreatic cancer from normal duct to pancreatic intraductal neoplasia and further to PDAC, and were statistically correlated with each other. Expression of the three DNMTs was statistically correlated with TNM staging and history of chronic pancreatitis. DNMT3A and DNMT3B, but not DNMT1 expression, was statistically correlated with tumour size. Patients with higher levels of DNMT1, DNMT3A and/or DNMT3B expression had an overall lower survival than those with lower levels of expression. Univariate analysis showed that high expression levels of DNMTs, alcohol consumption, tumour differentiation and TNM staging were statistically significant risk factors. Multivariate analysis showed that high level of DNMT3B expression and tumour differentiation were statistically significant independent poor prognostic factors. These results suggested that pancreatic carcinogenesis involves an increased mRNA expression of three DNMTs, and they may become valuable diagnostic and prognostic markers as well as potential therapeutic targets for pancreatic cancer.

  16. Biliary versus alcohol-related infected pancreatic necrosis: similarities and differences in the follow-up. (United States)

    Reszetow, Jacek; Hać, Stanisław; Dobrowolski, Sebastian; Stefaniak, Tomasz; Wajda, Zdzisław; Gruca, Zbigniew; Sledziński, Zbigniew; Studniarek, Michał


    Infected pancreatic necrosis (IPN) is a serious complication of acute pancreatitis. Data concerning survivors' quality of life and pancreatic functions are scarce. Follow-up of the patients with alcohol and biliary etiology of IPN treated with open necrosectomy was performed. Twenty-eight survivors after operative treatment (Bradley procedure) of IPN were followed up 24 to 96 months after discharge from the hospital (10 biliary and 18 alcohol patients). Their exocrine and endocrine pancreatic functions and quality of life (Functional Assessment of Chronic Illness Therapy scale) were evaluated. Pancreatic tissue remaining after necrosectomy was visualized by use of contrast-enhanced computed tomography (CT). In 44.4% of alcohol-induced IPN patients, the presence of the whole pancreas was shown on the follow-up CT, contrary to the biliary group, where the partial lack of the pancreas was observed in all cases. Pancreatic tissue calcifications were present on CT in 8 patients of alcohol-induced acute pancreatitis group only. Median stool elastase 1 concentrations were 318.1 U/mL in the biliary group and 238.3 U/mL in the alcohol-induced group (not significant). The Functional Assessment of Chronic Illness Therapy scale showed significantly higher social/family and emotional well-being in patients with biliary acute necrotizing pancreatitis. Patients after alcohol-induced IPN had lower quality of life compared with biliary etiology. Biliary and alcohol-induced IPN patients after surgical treatment have nonsignificant differences of endocrine and exocrine pancreatic functions.

  17. Pancreatic metastasis of alveolar soft-part sarcoma: a case report and review of the literature. (United States)

    Kurtz, J E; Andrès, E; Rohr, S; Maloisel, F; Mechine, A; Meyer, C; Dufour, P


    Alveolar soft-part sarcoma is a rare tumour. Patients commonly present with distant metastases both at the time of diagnosis and late in the course of disease. We present a case of pancreatic metastasis, occurring more than six years after diagnosis. Treatment consisted in subtotal pancreatoduodenectomy with pylorus resection. Both specific patterns of relapse and treatment opportunities of this uncommon feature are discussed.

  18. Clinical polymorphism of endocrine ophthalmopathy

    Directory of Open Access Journals (Sweden)

    V. G. Likhvantseva


    Full Text Available Purpose: to analyze clinical polymorphism of endocrine ophthalmopathy in patients with Graves’ disease.Methods: Clinical and radiological data of 18 cases with clinical manifestations of lacrimal gland increase were analyzed and compared with data retrieved from 50 patients without increasing of lacrimal gland.Results: the characteristics of clinical manifestations of endocrine ophthalmopathy with lacrimal gland increase were presented. this form differs, as the organ of the target, along with orbital fat and/or eye muscles becomes the glandula lacrimalis. A correlation between fact involving, on the one hand, and the intensity and severity of the autoimmune process in orbit, on the other hand were identified.Conclusion: Involvement of this secretion organ in the autoimmune process makes the clinical course of endocrine ophthalmopa-thy more complicated, and leads to eye dry syndrome creation.

  19. Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series. (United States)

    Yu, Run; Jih, Lily; Zhai, Jing; Nissen, Nicholas N; Colquhoun, Steven; Wolin, Edward; Dhall, Deepti


    The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas. This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients. Five patients were identified. The median age at presentation was 74 years (range, 59-89 years), and all patients were male. The presenting symptoms were all related to tumor mass effects. The median size of the tumor was 10 cm (range, 3.9-16 cm). Preoperative clinical diagnosis aided by fine-needle aspiration biopsy was incorrect in all 5 cases. Most tumors (3/5) exhibited predominantly endocrine differentiation without hormonal production. Only 10% to 30% of cells were truly amphicrine, whereas most were differentiated into either endocrine or acinar phenotype. The clinical behavior ranged from moderate to aggressive with postoperative survival from 2.5 months to more than 3 years. Four patients received neoadjuvant or adjuvant chemotherapy with variable responses. Mixed acinar-endocrine carcinoma of the pancreas appears to be not uncommon in men, may harbor predominantly endocrine component, is often misdiagnosed by cytology, and exhibits variable clinical behavior. Mixed acinar-endocrine carcinoma of the pancreas should be considered in older patients with sizable pancreatic mass and may warrant aggressive surgical resection and chemotherapy.

  20. Small bowel gastrointestinal stromal tumours and ampullary cancer in Type 1 neurofibromatosis

    Directory of Open Access Journals (Sweden)

    Fisher Cyril


    Full Text Available Abstract Background Type 1 neurofibromatosis (NF-1 is an autosomal dominant disorder with variable penetrance; approximately 50% of cases present as new mutations Case report We report a case of a 56 year-old man with Von Recklinghausen's disease, carcinoma of the ampulla of Vater and incidental benign gastrointestinal stromal tumours of the jejunum. Conclusions Coexistence between ampullary carcinoid, ectopic pancreatic tissue in the jejunum and neurofibroma of the jejunum in NF-1 has been previously described however; the association of synchronous carcinoma of the ampulla of Vater and gastrointestinal stromal tumour of the jejunum in NF-1 has not been previously reported.

  1. α3 Chains of type V collagen regulate breast tumour growth via glypican-1 (United States)

    Huang, Guorui; Ge, Gaoxiang; Izzi, Valerio; Greenspan, Daniel S.


    Pericellular α3(V) collagen can affect the functioning of cells, such as adipocytes and pancreatic β cells. Here we show that α3(V) chains are an abundant product of normal mammary gland basal cells, and that α3(V) ablation in a mouse mammary tumour model inhibits mammary tumour progression by reducing the proliferative potential of tumour cells. These effects are shown to be primarily cell autonomous, from loss of α3(V) chains normally produced by tumour cells, in which they affect growth by enhancing the ability of cell surface proteoglycan glypican-1 to act as a co-receptor for FGF2. Thus, a mechanism is presented for microenvironmental influence on tumour growth. α3(V) chains are produced in both basal-like and luminal human breast tumours, and its expression levels are tightly coupled with those of glypican-1 across breast cancer types. Evidence indicates α3(V) chains as potential targets for inhibiting tumour growth and as markers of oncogenic transformation. PMID:28102194

  2. Lipid effects of endocrine medications. (United States)

    Mihailescu, Dan V; Vora, Avni; Mazzone, Theodore


    Various alterations of lipid homeostasis have a significant role in the pathophysiology of the artherosclerotic process. The effects of usual lipid-lowering agents such as statins, fibrates, or niacin are well known, but other endocrine therapeutic agents could also affect the blood levels of various lipoproteins and, in turn, influence atheroma formation. In this review, we attempt to summarize the effect of several hormonal and non-hormonal endocrine agents on lipid metabolism, including insulin, thyroid hormone, sex hormones, glucocorticoids, growth hormone, and several anti-diabetic agents.

  3. Pancreatic function and enzyme synthesis rates in mild chronic pancreatitis. (United States)

    Hamilton, I; Boyd, E J; Jacyna, M R; Penston, J G; Soutar, J S; Bouchier, I A


    Incorporation of intravenous 75Se-methionine into duodenal juice proteins during pancreatic stimulation was measured as an index of pancreatic enzyme synthesis rates in 12 patients with a normal pancreatogram and in 6 with mild chronic pancreatitis. Isotope incorporation was significantly greater in subjects with mild chronic pancreatitis than in those with a normal pancreatogram. Thus in most patients in whom pancreatography demonstrates the characteristic radiological features of 'mild chronic pancreatitis' pancreatic acinar function is abnormal. The coexistence of morphological and functional abnormality implies that such patients do have chronic pancreatitis.

  4. Treatment of necrotizing pancreatitis

    NARCIS (Netherlands)

    Brunschot, S. van; Bakker, O.J.; Besselink, M.G.; Bollen, T.L.; Fockens, P.; Gooszen, H.G.; Santvoort, H.C. van; Dutch Pancreatitis Study, G.


    Acute pancreatitis is a common and potentially lethal disease. It is associated with significant morbidity and consumes enormous health care resources. Over the last 2 decades, the treatment of acute pancreatitis has undergone fundamental changes based on new conceptual insights and evidence from

  5. Traumatic Brain Injury: Effects on the Endocrine System (United States)

    ... aspect of your health. What is the endocrine system? Your endocrine system includes glands and organs that make and release ... to feel well. How can TBI affect the endocrine system? Two important parts of the endocrine system—the ...

  6. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells

    DEFF Research Database (Denmark)

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna


    The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which...... includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro as well as to perform in vivo efficacy study applying P2X7R inhibitor in an orthotopic xenograft mouse model...... into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120-treated mice showed reduced bioluminescence compared to saline-treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct...

  7. Primary pancreatic plasmacytoma. (United States)

    Deguchi, Yasunori; Nonaka, Atsushi; Takeuchi, Eiji; Funaki, Naomi; Kono, Yukihiro; Mizuta, Kazuhiko


    We report an extremely rare case of primary pancreatic plasmacytoma. A 56-year-old man had a 4-cm mass in the pancreatic tail and received distal pancreatectomy. This mass mainly consisted of plasma cells, but we failed to demonstrate their monoclonality in spite of the immunohistological staining. One and a half years later, this patient's right inguinal node swelled, and this node also showed a dense plasma cell infiltration. A very precise immunohistological staining was performed for this lymph node and the previous pancreatic mass, and both were diffusely positive for kappa light chain, IgG, and CD38. In the absence of myeloma elsewhere, we thus reached the correct diagnosis of primary pancreatic plasmacytoma, which later metastasized to lymph nodes. In the presence of the plasma cell proliferation in a pancreatic mass, plasmacytoma should be taken into consideration, and a more careful immunohistological staining is definitely necessary.

  8. Long non-coding RNAs as regulators of the endocrine system. (United States)

    Knoll, Marko; Lodish, Harvey F; Sun, Lei


    Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers.

  9. Treatment Options by Stage (Pancreatic Cancer) (United States)

    ... History Committees of Interest Legislative Resources Recent Public Laws Careers Visitor Information Search Search Home Cancer Types Pancreatic Cancer Patient Pancreatic Cancer Patient Pancreatic ...

  10. Endocrine emergencies in dogs and cats. (United States)

    Koenig, Amie


    Success in treatment of endocrine emergencies is contingent on early recognition and treatment. Many endocrine diseases presenting emergently have nonspecific signs and symptoms. In addition, these endocrine crises are often precipitated by concurrent disease, further making early identification difficult. This article concentrates on recognition and emergency management of the most common endocrine crises in dogs and cats. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Are tumours angiogenesis-dependent?

    NARCIS (Netherlands)

    Verheul, H. M. W.; Voest, E. E.; Schlingemann, R. O.


    The final proof of principle that cancer patients can be effectively treated with angiogenesis inhibitors is eagerly awaited. Various preclinical in vivo experiments have proven that most tumours need new vessel formation in order to grow and to form metastases. First of all, tumours do not grow in

  12. Tumours in the Small Bowel

    Directory of Open Access Journals (Sweden)

    N. Kurniawan


    Full Text Available Small bowel tumours are rare and originate from a wide variety of benign and malignant entities. Adenocarcinomas are the most frequent primary malignant small bowel tumours. Submucosal tumours like gastrointestinal stromal tumours (GIST or neuroendocrine tumours (NET may show a central umbilication, pathologic vessels, bridging folds or an ulceration of the overlying mucosa. These signs help to differentiate them from harmless bulges caused by impression from outside, e.g. from other intestinal loops. Sarcomas of the small bowel are rare neoplasias with mesenchymal origin, sometimes presenting as protruding masses. Benign tumours like lipoma, fibrolipoma, fibroma, myoma, and heterotopias typically present as submucosal masses. They cannot be differentiated endoscopically from those with malignant potential as GIST or NET. Neuroendocrine carcinomas may present with diffuse infiltration, which may resemble other malignant tumours. The endoscopic appearance of small bowel lymphomas has a great variation from mass lesions to diffuse infiltrative changes. Melanoma metastases are the most frequent metastases to the small bowel. They may be hard to distinguish from other tumours when originating from an amelanotic melanoma.

  13. Sleep disorders in children after treatment for a CNS tumour. (United States)

    Verberne, Lisa M; Maurice-Stam, Heleen; Grootenhuis, Martha A; Van Santen, Hanneke M; Schouten-Van Meeteren, Antoinette Y N


    The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with clinical characteristics and daily performance (fatigue and psychosocial functioning). In a cross-sectional study at the outpatient clinic of the Emma Children's Hospital AMC (February-June 2010), sleep, fatigue and psychosocial functioning were analysed in 31 CNS tumour patients (mean age: 11.8years; 20 boys) and compared with 78 patients treated for a non-CNS malignancy (mean age: 9.7years; 41 boys) and norm data. Questionnaires applied were the Sleep Disorder Scale for Children, the Epworth Sleepiness Scale, the Pediatric Quality of Life Inventory, and the Strengths and Difficulties Questionnaire. Sleeping habits and endocrine deficiencies were assessed with a self-developed questionnaire. Increased somnolence was found in CNS tumour patients compared with those with a non-CNS malignancy (8.8±2.8 versus 7.5±2.7; P<0.05). Both patient groups reported more problems (P<0.01) than the norm with initiating and maintaining sleep. No specific risk factors were identified for a sleep disorder in CNS tumour patients, but their excessive somnolence was correlated with lower fatigue related quality of life (QoL) (r=-0.78, P<0.001) and worse psychosocial functioning (r=0.63, P<0.001). In conclusion, children treated for a CNS tumour have increased somnolence, significantly increasing fatigue and worsening daily functioning. Further investigation should focus on possibilities to improve sleep quality and diminish fatigue. © 2011 European Sleep Research Society.

  14. The Vitamin D Endocrine System. (United States)

    Norman, Anthony W.


    Discusses the physiology and biochemistry of the vitamin D endocrine system, including role of biological calcium and phosphorus, vitamin D metabolism, and related diseases. A 10-item, multiple-choice test which can be used to obtain continuing medical education credit is included. (JN)

  15. GEMMs as preclinical models for testing pancreatic cancer therapies. (United States)

    Gopinathan, Aarthi; Morton, Jennifer P; Jodrell, Duncan I; Sansom, Owen J


    Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs), the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL)-Kras(G12D); LSL-Trp53(R172H); Pdx1-cre (KPC) model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer. © 2015. Published by The Company of Biologists Ltd.

  16. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M


    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  17. GEMMs as preclinical models for testing pancreatic cancer therapies

    Directory of Open Access Journals (Sweden)

    Aarthi Gopinathan


    Full Text Available Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs, the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL-KrasG12D; LSL-Trp53R172H; Pdx1-cre (KPC model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer.

  18. Clonal nature of odontogenic tumours. (United States)

    Gomes, Carolina Cavaliéri; Oliveira, Carla da Silveira; Castro, Wagner Henriques; de Lacerda, Júlio César Tanos; Gomez, Ricardo Santiago


    Although clonal origin is an essential step in the comprehension of neoplasias, there have been no studies to examine whether odontogenic tumours are derived from a single somatic progenitor cell. The purpose of this study was to investigate the clonal origin of odontogenic tumours. Fresh samples of seven ameloblastomas, two odontogenic mixomas, two adenomatoid odontogenic tumour, one calcifying odontogenic cyst, one calcifying epithelial odontogenic tumour (CEOT) and six odontogenic keratocyst (OKC) of female patients were included in this study. After DNA extraction, the HUMARA gene polymorphism assay was performed. Most of the informative odontogenic lesions studied (12 out of 16) showed a monoclonal pattern. Among the polyclonal cases, two were OKC, one CEOT and one odontogenic mixoma. Our results suggest that most odontogenic tumours are monoclonal.

  19. Simultaneous Occurrence of Pancreatic Adenocarcinoma and Brunner's Gland Adenoma in a Siberian Tiger (Panthera tigris altaica). (United States)

    Gombač, M; Dolenšek, T; Jaušovec, D; Kvapil, P; Švara, T; Pogačnik, M


    We describe a case of pancreatic adenocarcinoma and Brunner's gland adenoma in an 18-year-old male Siberian tiger (Panthera tigris altaica) from the Ljubljana Zoo. The tiger was humanely destroyed due to weakness and progressive weight loss. Necropsy examination revealed a large, grey, predominantly necrotic mass replacing the major part of the pancreatic body. Microscopically, the mass was unencapsulated, poorly demarcated, highly cellular and composed of highly pleomorphic, cuboidal to tall columnar cells with basal, round or oval, moderately anisokaryotic nuclei with prominent nucleoli and moderate to large amounts of eosinophilic cytoplasm. The tumour was diagnosed as pancreatic tubular adenocarcinoma with infiltration into the duodenum and mesentery. There were tumour emboli in mesenteric blood vessels and hepatic metastases. The non-affected part of the pancreas exhibited severe chronic pancreatitis. In addition, one firm white neoplastic nodule was observed in the duodenal wall. The nodule was set in the tunica muscularis and was unencapsulated, well demarcated and highly cellular, and consisted of a closely packed layer of normal Brunner's glands and a centrally positioned group of irregularly branched tubules with small amounts of debris in the lumen. The neoplastic nodule was diagnosed as Brunner's gland adenoma. The present case is, to the best of our knowledge, the first report of concurrent pancreatic adenocarcinoma and Brunner's gland adenoma, most probably induced by chronic pancreatitis, either in man or animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Brusgaard, Klaus


    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...... regulator gene (CFTR) and serine protease inhibitor Kazal type 1 gene (SPINK1) mutations with patients who retained the diagnosis of true idiopathic pancreatitis (tIP) after genetic testing for HP, SPINK1, and CFTR mutations. METHODS: Patients with PUO were identified in the Danish National Registry......, 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...

  1. Exocrine pancreatic insufficiency in diabetes mellitus: a complication of diabetic neuropathy or a different type of diabetes? (United States)

    Hardt, Philip D; Ewald, Nils


    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.

  2. Latest advances in chronic pancreatitis. (United States)

    Enrique Domínguez-Muñoz, J


    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the definition of the disease, the etiological diagnosis of idiopathic disease, the correlation between fibrosis degree and pancreatic secretion in the early stages of chronic pancreatitis, the treatment of the disease and of pain, the clinical relevance of pancreatic exocrine insufficiency, and the diagnosis of autoimmune pancreatitis. A new mechanistic definition of chronic pancreatitis has been proposed. Genetic testing is mainly of help in patients with relapsing idiopathic pancreatitis. A significant correlation has been shown between the degree of pancreatic fibrosis as evaluated by elastography and pancreatic secretion of bicarbonate. New data supports the efficacy of antioxidants and simvastatin for the therapy of chronic pancreatitis. The pancreatoscopy-guided intraductal lithotripsy is an effective alternative to extracorporeal shock wave lithotripsy in patients with chronic calcifying pancreatitis. The presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significant risk of cardiovascular events. Fine needle biopsy and contrast enhanced harmonic endoscopic ultrasonography are of help for the diagnosis of autoimmune pancreatitis and its differential diagnosis with pancreatic cancer. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  3. Epidemiology of pancreatic cancer. (United States)

    Ilic, Milena; Ilic, Irena


    Cancer of the pancreas remains one of the deadliest cancer types. Based on the GLOBOCAN 2012 estimates, pancreatic cancer causes more than 331000 deaths per year, ranking as the seventh leading cause of cancer death in both sexes together. Globally, about 338000 people had pancreatic cancer in 2012, making it the 11(th) most common cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends for pancreatic cancer incidence and mortality varied considerably in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. The overall five-year survival rate is about 6% (ranges from 2% to 9%), but this vary very small between developed and developing countries. To date, the causes of pancreatic cancer are still insufficiently known, although certain risk factors have been identified, such as smoking, obesity, genetics, diabetes, diet, inactivity. There are no current screening recommendations for pancreatic cancer, so primary prevention is of utmost importance. A better understanding of the etiology and identifying the risk factors is essential for the primary prevention of this disease.

  4. PKD signaling and pancreatitis. (United States)

    Yuan, Jingzhen; Pandol, Stephen J


    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. 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. 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. 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.

  5. Cytokines and Pancreatic β-Cell Apoptosis

    DEFF Research Database (Denmark)

    Berchtold, L A; Prause, M; Størling, J


    The discovery 30 years ago that inflammatory cytokines cause a concentration, activity, and time-dependent bimodal response in pancreatic β-cell function and viability has been a game-changer in the fields of research directed at understanding inflammatory regulation of β-cell function and survival...... and the causes of β-cell failure and destruction in diabetes. Having until then been confined to the use of pathophysiologically irrelevant β-cell toxic chemicals as a model of β-cell death, researchers could now mimic endocrine and paracrine effects of the cytokine response in vitro by titrating concentrations...... to gene expressional changes, endoplasmic reticulum stress, and triggering of mitochondrial dysfunction. Preclinical studies have shown preventive effects of cytokine antagonism in animal models of diabetes, and clinical trials demonstrating proof of concept are emerging. The full clinical potential...

  6. A common variant of PNPLA3 (p.I148M) is not associated with alcoholic chronic pancreatitis.

    NARCIS (Netherlands)

    Rosendahl, J.; Tonjes, A.; Schleinitz, D.; Kovacs, P.; Wiegand, J.; Ruffert, C.; Jesinghaus, M.; Schober, R.; Herms, M.; Grutzmann, R.; Schulz, H.U.; Stickel, F.; Werner, J.; Bugert, P.; Bluher, M.; Stumvoll, M.; Bohm, S.; Berg, T. van den; Wittenburg, H.; Mossner, J.; Morsche, R.H.M. te; Derikx, M.; Keim, V.; Witt, H.; Drenth, J.P.H.


    BACKGROUND: Chronic pancreatitis (CP) is an inflammatory disease that in some patients leads to exocrine and endocrine dysfunction. In industrialized countries the most common aetiology is chronic alcohol abuse. Descriptions of associated genetic alterations in alcoholic CP are rare. However, a

  7. Danish Pancreatic Cancer Database

    DEFF Research Database (Denmark)

    Fristrup, Claus; Detlefsen, Sönke; Palnæs Hansen, Carsten


    AIM OF DATABASE: The Danish Pancreatic Cancer Database aims to prospectively register the epidemiology, diagnostic workup, diagnosis, treatment, and outcome of patients with pancreatic cancer in Denmark at an institutional and national level. STUDY POPULATION: Since May 1, 2011, all patients......, and survival. The results are published annually. CONCLUSION: The Danish Pancreatic Cancer Database has registered data on 2,217 patients with microscopically verified ductal adenocarcinoma of the pancreas. The data have been obtained nationwide over a period of 4 years and 2 months. The completeness...

  8. Pancreatitis in scrub typhus

    Directory of Open Access Journals (Sweden)

    Alok Bhatt


    Full Text Available Scrub typhus is a rickettsial infection prevalent in most parts of India. Acute pancreatitis with pseudocyst formation is a rare complication of this condition. This paper reports acute renal failure, pancreatitis and pseudocyst formation in a 48-year-old female with scrub typhus. Ultrasonography of the abdomen revealed a bulky pancreas with fluid seen along the body of the pancreas in the lesser sac. The infection was successfully treated with doxycycline and supportive treatment. Pancreatitis was managed conservatively. This case report highlights the importance of identifying and managing uncommon complications of a common tropical disease for optimum outcome.

  9. Influence of vitamin D in endocrine metabolic diseases

    Directory of Open Access Journals (Sweden)

    Rafael Algusto Rafaelli


    Full Text Available The vitamin D deficiency has been linked to the development of several endocrine metabolic diseases such as metabolic syndrome, obesity, hypertension and Type 2 diabetes mellitus. This paper presents an overview of the available scientific evidence for some of the non- calcemic actions of vitamin D in humans, through literature search in scientific databases. The deficiency of vitamin D may predispose to glucose intolerance, changes in insulin secretion and thus the development of type 2 diabetes mellitus. This mechanism is possible due to the presence of the vitamin D receptor in several tissues and cells, including pancreatic ? cells, adipocyte and muscle tissue. In obese individuals, the changes of the vitamin D endocrine system, characterized by high levels of parathyroid hormone and 1,25-dihydroxycholecalciferol are responsible for the negative feedback of hepatic synthesis of 25-hydroxycholecalciferol and also by increased influx of calcium into the intracellular environment, which can damage the secretion and insulin sensitivity. In hypertension, vitamin D could act on the renin-angiotensin system and also in vascular function. There is some evidence that 1,25-dihydroxycholecalciferol inhibits the renin gene expression and blocks the proliferation of vascular smooth muscle cell. Further prospective studies and randomized clinical trials, including studies of supplementation, are required to establish better clinical and metabolic effects of variations in the concentration of 25-hydroxycholecalciferol in the clinical course of these diseases.

  10. Endocrine pancreas development at weaning in goat kids

    Directory of Open Access Journals (Sweden)

    Fabia Rosi


    Full Text Available Eighteen three-day old Saanen goat kids were divided into MILK and WEAN groups. MILK kids received goat milk to age 48 days; WEAN kids were initially fed milk but started weaning at 25 days and were completely weaned by 40 days. Total intake per group was recorded daily. On day 25, 40 and 48, body weights were recorded, and plasma samples were taken and analyzed for glucose, free amino-acids and insulin. On day 48, all animals were slaughtered and pancreas samples were analyzed for total DNA and RNA content. Histological sections of pancreas were examined by light microscope and images analyzed by dedicated software. Seven days after the beginning of the weaning program, dry matter intake in the WEAN group began to decrease compared to the MILK one. Nonetheless, body weight did not differ throughout the study period. Weaning significantly decreased plasma levels of glucose, amino-acids and insulin. No difference was observed in pancreatic DNA and RNA content. Histological analysis of pancreas showed that the size of pancreatic islets was not different, but islet number per section was lower in the pancreas of WEAN animals. In conclusion, weaning affects glucose and amino-acid metabolism and influences endocrine pancreas activity and morphology.

  11. The monocarboxylate transporters exist in the cattle endocrine pancreas. (United States)

    Kirat, Doaa; Kato, Seiyu


    Extensive studies are published concerning the distribution of monocarboxylate transporters (MCTs) in various animal issues including ruminants; nonetheless, nothing is known about their cellular expression and localization in the ruminant pancreas. The present study was carried out to examine the expression and cellular localization of all the fourteen MCT isoforms in cattle pancreas. RT-PCR verified the existence of mRNA transcripts for eight MCT isoforms, namely, MCT1, MCT2, MCT3, MCT4, MCT5, MCT8, MCT13, and MCT14 in cattle pancreas. Western blotting analysis confirmed the protein expression of these eight MCTs in the cattle pancreatic tissue. Immunohistochemical study, within the whole pancreas, was conducted to localize the eight MCTs identified, and the results showed strong positive immunoreactive staining for MCT1, MCT2, MCT4, MCT5, MCT13, and MCT14 on nearly all the islet cells of Langerhans, while we could not detect immunopositive signals in the acinar cells with any of MCTs antibodies used. This study, for the first time, showed the cellular localization and expression of MCT1-MCT5, MCT8, MCT13, and MCT14 within the ruminant pancreas. The distribution and expression pattern of MCT1, MCT2, MCT4, and CD147 in the cattle pancreas are different from that previously published on monogastric pancreas. Our study suggested that MCT1, MCT2, MCT4, MCT5, MCT13, and MCT14 may participate in the regulation of the pancreatic endocrine secretions in ruminants.

  12. Perioperative intensive insulin therapy using artificial endocrine pancreas in patients undergoing pancreatectomy (United States)

    Maeda, Hiromichi; Okabayashi, Takehiro; Yatabe, Tomoaki; Yamashita, Koichi; Hanazaki, Kazuhiro


    Perioperative glycemic control is important for reducing postoperative infectious complications. However, clinical trials have shown that efforts to maintain normoglycemia in intensive care unit patients result in deviation of glucose levels from the optimal range, and frequent attacks of hypoglycemia. Tight glycemic control is even more challenging in those undergoing pancreatic resection. Removal of lesions and surrounding normal pancreatic tissue often cause hormone deficiencies that lead to the destruction of glucose homeostasis, which is termed pancreatogenic diabetes. Pancreatogenic diabetes is characterized by the occurrence of hyperglycemia and iatrogenic severe hypoglycemia, which adversely effects patient recovery. Postoperatively, a variety of factors including surgical stress, inflammatory cytokines, sympathomimetic drug therapy, and aggressive nutritional support can also affect glycemic control. This review discusses the endocrine aspects of pancreatic resection and highlights postoperative glycemic control using a closed-loop system or artificial pancreas. In previous experiments, we have demonstrated the reliability of the artificial pancreas in dogs with total pancreatectomy, and its postoperative clinical use has been shown to be effective and safe, without the occurrence of hypoglycemic episodes, even in patients after total pancreatectomy. Considering the increasing requirement for tight perioperative glycemic control and the recognized risk of hypoglycemia, we propose the use of an artificial endocrine pancreas that is able to monitor continuously blood glucose concentrations with proven accuracy, and administer automatically substances to return blood glucose concentration to the optimal narrow range. PMID:19725142

  13. Endocrine disruptors and their effects on puberty

    Directory of Open Access Journals (Sweden)

    Semra Çetinkaya


    Full Text Available Endocrine disruptors and their possible impact on human health have become a topic of discussion. Endocrine disrupting chemicals are found in plastics, detergents, pesticides and industrial chemicals. Some of these persist in the environment and others do not. Some are lipophilic, sequestered in adipose tissue and secreted in milk, and others may only be present for short periods of time but at critical periods of development. Endocrine disruptors are defined as an extrogenous substance or mixture that alters the function of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny. Endocrine disruptors affect the reproductive system and they may be responsible for oligospermia, abnormality of sperm characteristics, disorders of testicular steroidogenesis, testicular atrophy, uterus weight increases and precocious puberty. In this review, we aimed to assess on exposure to endocrine disruptors and the effects of endocrine disruptors on puberty.

  14. Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma. (United States)

    Henriksen, Stine Dam; Madsen, Poul Henning; Larsen, Anders Christian; Johansen, Martin Berg; Drewes, Asbjørn Mohr; Pedersen, Inge Søkilde; Krarup, Henrik; Thorlacius-Ussing, Ole


    Pancreatic cancer has a 5-year survival rate of only 5-7%. Difficulties in detecting pancreatic cancer at early stages results in the high mortality and substantiates the need for additional diagnostic tools. Surgery is the only curative treatment and unfortunately only possible in localized tumours. A diagnostic biomarker for pancreatic cancer will have a major impact on patient survival by facilitating early detection and the possibility for curative treatment. DNA promoter hypermethylation is a mechanism of early carcinogenesis, which can cause inactivation of tumour suppressor genes. The aim of this study was to examine promoter hypermethylation in a panel of selected genes from cell-free DNA, as a diagnostic marker for pancreatic adenocarcinoma. Patients with suspected or biopsy-verified pancreatic cancer were included prospectively and consecutively. Patients with chronic/acute pancreatitis were included as additional benign control groups. Based on an optimized accelerated bisulfite treatment protocol, methylation-specific PCR of a 28 gene panel was performed on plasma samples. A diagnostic prediction model was developed by multivariable logistic regression analysis using backward stepwise elimination. Patients with pancreatic adenocarcinoma ( n  = 95), chronic pancreatitis ( n  = 97) and acute pancreatitis ( n  = 59) and patients screened, but negative for pancreatic adenocarcinoma ( n  = 27), were included. The difference in mean number of methylated genes in the cancer group (8.41 (95% CI 7.62-9.20)) vs the total control group (4.74 (95% CI 4.40-5.08)) was highly significant ( p  diagnostic prediction model (age >65, BMP3 , RASSF1A , BNC1 , MESTv2 , TFPI2 , APC , SFRP1 and SFRP2 ) had an area under the curve of 0.86 (sensitivity 76%, specificity 83%). The model performance was independent of cancer stage. Cell-free DNA promoter hypermethylation has the potential to be a diagnostic marker for pancreatic adenocarcinoma and differentiate

  15. [Historic malignant tumour: 27 observations]. (United States)

    Sparsa, A; Doffoel-Hantz, V; Durox, H; Gaston, J; Delage-Core, M; Bédane, C; Labrousse, F; Sannajust, J P; Bonnetblanc, J-M


    When used in the French medical literature to describe a pathological state, the word "historic" normally refers to tumours of startling appearance because of their size. It is difficult to understand how a patient can allow such tumours to continue to grow. We attempt to define this concept. Two dermatologists carried out a retrospective, independent and comparative selection of photographs taken between 1978 and 2008 of malignant cutaneous tumours of unusual size given the histological diagnosis. Socio-professional, demographic, clinical, histological psychological data, and details of treatment history and progress were collected. Twenty-seven patients (11 M, 16 F) of mean age 74 years (34-99 years) presented a "historic" tumour. Twelve patients lived in rural regions. Five patients were company executives. The average duration of development of the "historic" tumours was 4.5 years (6-420 months). The tumours were classed histologically as epidermoid carcinomas (nine) and melanomas (seven). The mean size was 13 cm (6-30 cm). Psychiatric problems, membership of sects or dementia were noted for 13 patients. Treatment consisted of chemotherapy, radiotherapy or, less frequently, surgery. Eighteen patients died on average 13 months after diagnosis. "Historic" malignant tumour (also described in the literature as "giant" tumour) is a real-life fact. No studies have been made of a series of such patients. Despite histological diagnosis, the size was associated with slow tumoral progress and/or late treatment, chiefly accounted for by psychiatric disorders. Socio-professional data indicate that "historic" tumours are equally common in urban and rural areas. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Genetic and epigenetic drivers of neuroendocrine tumours (NET). (United States)

    Di Domenico, Annunziata; Wiedmer, Tabea; Marinoni, Ilaria; Perren, Aurel


    Neuroendocrine tumours (NET) of the gastrointestinal tract and the lung are a rare and heterogeneous group of tumours. The molecular characterization and the clinical classification of these tumours have been evolving slowly and show differences according to organs of origin. Novel technologies such as next-generation sequencing revealed new molecular aspects of NET over the last years. Notably, whole-exome/genome sequencing (WES/WGS) approaches underlined the very low mutation rate of well-differentiated NET of all organs compared to other malignancies, while the engagement of epigenetic changes in driving NET evolution is emerging. Indeed, mutations in genes encoding for proteins directly involved in chromatin remodelling, such as DAXX and ATRX are a frequent event in NET. Epigenetic changes are reversible and targetable; therefore, an attractive target for treatment. The discovery of the mechanisms underlying the epigenetic changes and the implication on gene and miRNA expression in the different subgroups of NET may represent a crucial change in the diagnosis of this disease, reveal new therapy targets and identify predictive markers. Molecular profiles derived from omics data including DNA mutation, methylation, gene and miRNA expression have already shown promising results in distinguishing clinically and molecularly different subtypes of NET. In this review, we recapitulate the major genetic and epigenetic characteristics of pancreatic, lung and small intestinal NET and the affected pathways. We also discuss potential epigenetic mechanisms leading to NET development. © 2017 Society for Endocrinology.

  17. [Latest advances in chronic pancreatitis]. (United States)

    Domínguez Muñoz, J Enrique


    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  18. CT appearances of pleural tumours

    Energy Technology Data Exchange (ETDEWEB)

    Salahudeen, H.M. [Department of Radiology, Leeds Teaching Hospitals NHS Trust (United Kingdom)], E-mail:; Hoey, E.T.D. [Department of Radiology, Leeds Teaching Hospitals NHS Trust (United Kingdom); Department of Radiology, Papworth Hospital, Cambridge (United Kingdom); Robertson, R.J.; Darby, M.J. [Department of Radiology, Leeds Teaching Hospitals NHS Trust (United Kingdom)


    Computed tomography (CT) is the imaging technique of choice for characterizing pleural masses with respect to their location, composition, and extent. CT also provides important information regarding invasion of the chest wall and surrounding structures. A spectrum of tumours can affect the pleura of which metastatic adenocarcinoma is the commonest cause of malignant pleural disease, while malignant mesothelioma is the most common primary pleural tumour. Certain CT features help differentiate benign from malignant processes. This pictorial review highlights the salient CT appearances of a range of tumours that may affect the pleura.

  19. Parp-1 genetic ablation in Ela-myc mice unveils novel roles for Parp-1 in pancreatic cancer. (United States)

    Martínez-Bosch, Neus; Iglesias, Mar; Munné-Collado, Jessica; Martínez-Cáceres, Carlos; Moreno, Mireia; Guerra, Carmen; Yélamos, Jose; Navarro, Pilar


    Pancreatic cancer has a dismal prognosis and is currently the fourth leading cause of cancer-related death in developed countries. The inhibition of poly(ADP-ribose) polymerase-1 (Parp-1), the major protein responsible for poly(ADP-ribosy)lation in response to DNA damage, has emerged as a promising treatment for several tumour types. Here we aimed to elucidate the involvement of Parp-1 in pancreatic tumour progression. We assessed Parp-1 protein expression in normal, preneoplastic and pancreatic tumour samples from humans and from K-Ras- and c-myc-driven mouse models of pancreatic cancer. Parp-1 was highly expressed in acinar cells in normal and cancer tissues. In contrast, ductal cells expressed very low or undetectable levels of this protein, both in a normal and in a tumour context. The Parp-1 expression pattern was similar in human and mouse samples, thereby validating the use of animal models for further studies. To determine the in vivo effects of Parp-1 depletion on pancreatic cancer progression, Ela-myc-driven pancreatic tumour development was analysed in a Parp-1 knock-out background. Loss of Parp-1 resulted in increased tumour necrosis and decreased proliferation, apoptosis and angiogenesis. Interestingly, Ela-myc:Parp-1(-/-) mice displayed fewer ductal tumours than their Ela-myc:Parp-1(+/+) counterparts, suggesting that Parp-1 participates in promoting acinar-to-ductal metaplasia, a key event in pancreatic cancer initiation. Moreover, impaired macrophage recruitment can be responsible for the ADM blockade found in the Ela-myc:Parp-1(-/-) mice. Finally, molecular analysis revealed that Parp-1 modulates ADM downstream of the Stat3-MMP7 axis and is also involved in transcriptional up-regulation of the MDM2, VEGFR1 and MMP28 cancer-related genes. In conclusion, the expression pattern of Parp-1 in normal and cancer tissue and the in vivo functional effects of Parp-1 depletion point to a novel role for this protein in pancreatic carcinogenesis and shed light

  20. Obesity and Pancreatic Cancer. (United States)

    Michaud, Dominique S

    Pancreatic cancer has few known risk factors, providing little in the way of prevention, and is the most rapidly fatal cancer with 7 % survival rate at 5 years. Obesity has surfaced as an important risk factor for pancreatic cancer as epidemiological studies with strong methodological designs have removed important biases and solidified the obesity associations. Moreover, studies indicate that obesity early in adulthood is strongly associated with future risk of pancreatic cancer and that abdominal obesity is an independent risk factor. There is increasing evidence suggesting long-standing diabetes type 2 and insulin resistance are important etiological factors of this disease, providing a strong mechanistic link to obesity. The challenge remains to determine whether intended weight loss in midlife will reduce risk of pancreatic cancer and to elucidate the complex underlying pathways directly involved with risk.

  1. Perspectives in Pancreatic Pain

    Directory of Open Access Journals (Sweden)

    A. S. Salim


    Full Text Available This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described.

  2. Pancreatic Neuroendocrine Tumors (PNETs) (United States)

    ... Stories Our signature PurpleStride run/walk events raise spirits, awareness and funds in communities nationwide. FIND YOUR ... two main pancreatic hormones. Insulin lowers blood sugar levels, while glucagon raises blood sugar levels. Together, these ...

  3. Afferent Endocrine Control of Eating

    DEFF Research Database (Denmark)

    Langhans, Wolfgang; Holst, Jens Juul


    The afferent endocrine factors that control eating can be separated into different categories. One obvious categorization is by the time course of their effects, with long-term factors that signal adiposity and short-term factors that operate within the time frame of single meals. The second...... obvious categorization is by the origin of the endocrine signalling molecules. The level of knowledge concerning the physiological mechanisms and relevance of the hormones that are implicated in the control of eating is clearly different. With the accumulating knowledge about the hormones' actions......, various criteria have been developed for when the effect of a hormone can be considered 'physiologic'. This chapter treats the hormones separately and categorizes them by origin. It discusses ALL hormones that are implicated in eating control such as Gastrointestinal (GI) hormone and glucagon-like peptide...

  4. Classical endocrine diseases causing obesity. (United States)

    Weaver, Jolanta U


    Obesity is associated with several endocrine diseases, including common ones such as hypothyroidism and polycystic ovarian syndrome to rare ones such as Cushing's syndrome, central hypothyroidism and hypothalamic disorders. The mechanisms for the development of obesity vary in according to the endocrine condition. Hypothyroidism is associated with accumulation of hyaluronic acid within various tissues, additional fluid retention due to reduced cardiac output and reduced thermogenesis. The pathophysiology of obesity associated with polycystic ovarian syndrome remains complex as obesity itself may simultaneously be the cause and the effect of the syndrome. Net excess of androgen appears to be pivotal in the development of central obesity. In Cushing's syndrome, an interaction with thyroid and growth hormones plays an important role in addition to an increased adipocyte differentiation and adipogenesis. This review also describes remaining rare cases: hypothalamic obesity due to central hypothyroidism and combined hormone deficiencies.

  5. New insights into alcoholic pancreatitis and pancreatic cancer. (United States)

    Apte, Minoti; Pirola, Romano; Wilson, Jeremy


    Pancreatitis and pancreatic cancer represent two major diseases of the exocrine pancreas. Pancreatitis exhibits both acute and chronic manifestations. The commonest causes of acute pancreatitis are gallstones and alcohol abuse; the latter is also the predominant cause of chronic pancreatitis. Recent evidence indicates that endotoxinemia, which occurs in alcoholics due to increased gut permeability, may trigger overt necroinflammation of the pancreas in alcoholics and one that may also play a critical role in progression to chronic pancreatitis (acinar atrophy and fibrosis) via activation of pancreatic stellate cells (PSCs). Chronic pancreatitis is a major risk factor for the development of pancreatic cancer, which is the fourth leading cause of cancer-related deaths in humans. Increasing attention has been paid in recent years to the role of the stroma in pancreatic cancer progression. It is now well established that PSCs play a key role in the production of cancer stroma and that they interact closely with cancer cells to create a tumor facilitatory environment that stimulates local tumor growth and distant metastasis. This review summarizes recent advances in our understanding of the pathogenesis of alcoholic pancreatitis and pancreatic cancer, with particular reference to the central role played by PSCs in both diseases. An improved knowledge of PSC biology has the potential to provide an insight into pathways that may be therapeutically targeted to inhibit PSC activation, thereby inhibiting the development of fibrosis in chronic pancreatitis and interrupting stellate cell-cancer cell interactions so as to retard cancer progression.

  6. Primary Pancreatic Leiomyosarcoma


    Kocakoc, Ercan; Havan, Nuri; Bilgin, Mehmet; Atay, Musa


    Primary pancreatic leiomyosarcomas are rare malignant neoplasms with an aggressive course and a large size. A 56-year-old woman presented with an 8-year history of abdominal pain. Multislice computed tomography revealed a large heterogeneous mass with necrotic, calcified and macroscopic fatty areas. The tumor was excised. Histopathological evaluation revealed leiomyosarcoma of the pancreas. If a patient has a large size mass with a cystic-necrotic component, pancreatic leiomyosarcoma should b...

  7. Severe Hypertriglyceridemia With Pancreatitis


    Sacks, Frank Martin; Stanesa, Maxine; Hegele, Robert A.


    IMPORTANCE Recurrent pancreatitis is a potentially fatal complication of severe hypertriglyceridemia. Genetic defects and lifestyle risk factors may render this condition unresponsive to current treatments. OBSERVATIONS: We report this first case of long-term management of intractable near-fatal recurrent pancreatitis secondary to severe hypertriglyceridemia by a novel use of lomitapide, an inhibitor of microsomal triglyceride transfer protein, recently approved for treatment of familia...

  8. Endocrine therapy of breast cancer. (United States)

    Lumachi, F; Luisetto, G; Basso, S M M; Basso, U; Brunello, A; Camozzi, V


    Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. Selective estrogen-receptor modulators (SERMs), such as tamoxifen and raloxifene, aromatase inhibitors, and GnRH agonists are the drugs of choice. Tamoxifen, a partial nonsteroidal estrogen agonist, is a type II competitive inhibitor of estradiol at its receptor, and the prototype of SERMs. Aromatase inhibitors significantly lower serum estradiol concentration in postmenopausal patients, having no detectable effects on adrenocortical steroids formation, while GnRH agonists suppress ovarian function, inducing a menopause-like condition in premenopausal women. Endocrine therapy has generally a relatively low morbidity, leading to a significant reduction of mortality for breast cancer. The aim of chemoprevention is to interfere early with the process of carcinogenesis, reducing the risk of cancer development. As preventive agents, raloxifene and tamoxifene are equivalent, while raloxifene has more potent antiresorptive effects in postmenopausal osteoporosis. Endocrine treatment is usually considered a standard choice for patients with estrogen-receptor positive cancers and non-life-threatening advanced disease, or for older patients unfit for aggressive chemotherapy regimens. Several therapeutic protocols used in patients with breast cancer are associated with bone loss, which may lead to an increased risk of fracture. Bisphosphonates are the drugs of choice to treat such a drug-induced bone disease. The aim of this review is to outline current understanding on endocrine therapy of breast cancer. © 2011 Bentham Science Publishers Ltd.

  9. Endocrine manifestations in celiac disease


    Freeman, Hugh James


    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid diseas...

  10. Detection, evaluation and treatment of diabetes mellitus in chronic pancreatitis: recommendations from PancreasFest 2012. (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


    Diabetes and glucose intolerance are common complications of chronic pancreatitis, yet clinical guidance on their detection, classification, and management is lacking. A working group reviewed the medical problems, diagnostic methods, and treatment options for chronic pancreatitis-associated diabetes for a consensus meeting at PancreasFest 2012. 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 g 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. Physicians should evaluate and treat glucose intolerance in patients with pancreatitis. Copyright © 2013 IAP and EPC. All rights reserved.

  11. Neurotransmitters act as paracrine signals to regulate insulin secretion from the human pancreatic islet (United States)

    Rodriguez-Diaz, Rayner; Menegaz, Danusa; Caicedo, Alejandro


    In this symposium review we discuss the role of neurotransmitters as paracrine signals that regulate pancreatic islet function. A large number of neurotransmitters and their receptors has been identified in the islet, but relatively little is known about their involvement in islet biology. Interestingly, neurotransmitters initially thought to be present in autonomic axons innervating the islet are also present in endocrine cells of the human islet. These neurotransmitters can thus be released as paracrine signals to help control hormone release. Here we propose that the role of neurotransmitters may extend beyond controlling endocrine cell function to work as signals modulating vascular flow and immune responses within the islet. PMID:24591573

  12. Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma. (United States)

    Hexige, Saiyin; Ardito-Abraham, Christine M; Wu, Yanhua; Wei, Youheng; Fang, Yuan; Han, Xu; Li, Jianang; Zhou, Ping; Yi, Qing; Maitra, Anirban; Liu, Jun O; Tuveson, David A; Lou, Wenhui; Yu, Long


    Pancreatic ductal adenocarcinoma (PDAC) is a nearly lethal neoplasm. It is a remarkably stroma-rich, vascular-poor and hypo-perfused tumour, which prevents efficient drug delivery. Paradoxically, the neoplastic cells have robust glucose uptake, suggesting that the microvasculature has adopted an alternative method for nutrient uptake and cellular trafficking. Using adapted thick tumour section immunostaining and three-dimensional (3D) construction imaging in human tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumours; long, hair-like projections on the basal surface of microvessels that we refer to as 'basal microvilli'. Functionally, these basal microvilli have an actin-rich cytoskeleton and endocytic and exocytic properties, and contain glucose transporter-1 (GLUT-1)-positive vesicles. Clinically, as demonstrated by PET-CT, the tumour microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumour itself. In addition, these basal microvilli were found in regions of the tumour with low GLUT-1 expression, suggesting that their presence could be dependent upon the glucose concentration in the tumour milieu. Similar microvasculature features were also observed in a K-Ras-driven model of murine PDAC. Altogether, these basal microvilli mark a novel pathological feature of PDAC microvasculature. Because basal microvilli are pathological features with endo- and exocytic properties, they may provide a non-conventional method for cellular trafficking in PDAC tumours. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


    Directory of Open Access Journals (Sweden)

    I. V. Misnikova


    Full Text Available In the recent years, an association between sleep apnea and a  number of endocrine diseases has been established. The secretion of many hormones after falling asleep is considerably changed, compared to the period of wakefulness. In patients with endocrine disorders, abnormal hormonal secretion and its pathological consequences may contribute to sleep apnea. Sleep fragmentation and intermittent hypoxia arising in sleep apnea result in a decrease in insulin sensitivity, which contributes to the development of type 2 diabetes mellitus. The prevalence of sleep apnea increases in acromegaly, which may affect the risk of cardio-pulmonary complications. There is an association between sleep apnea and testosterone treatment in men, as well as in postmenopausal women. Sleep apnea in hypothyroidism is most frequently related to the development of hypothyroidism per se and can therefore be reversed with thyroid hormone replacement therapy. Timely detection and treatment of sleep apnea in patients with endocrine disorders can improve their survival prognosis and quality of life.

  14. Endocrine manifestations in celiac disease. (United States)

    Freeman, Hugh James


    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison's disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet.

  15. Autoantibodies in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel S. Smyk


    Full Text Available Autoimmune pancreatitis (AIP was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.


    Directory of Open Access Journals (Sweden)

    L. A. Kirsanova


    Full Text Available Newborn rabbit pancreatic cell monolayer was obtained as we described earlier.The cultivated epithelial cells were shown by immunofluorescence to express special ductal marker CK19 and were insulin-and glucagon- negative for 10–15 days. A few fusiforms of nestin-positive cells were found in monolayer. Over 2 weeks in serum-free medium the plaques of epithelial cells became crowded and formed 3-dimentional structures – islet- like clusters. Islet-like clusters contain some insulin- and glucagon-positive cells recognized by immunohysto- chemistry staining. Pancreatic endocrine cell generation in 3-dimentional structures is discussed. 

  17. The Heidelberg classification of renal cell tumours

    NARCIS (Netherlands)

    Kovacs, G; Akhtar, M; Beckwith, BJ; Bugert, P; Cooper, CS; Delahunt, B; Eble, JN; Fleming, S; Ljungberg, B; Medeiros, LJ; Moch, H; Reuter, VE; Ritz, E; Roos, G; Schmidt, D; Srigley, [No Value; Storkel, S; VandenBerg, E; Zbar, B


    This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996, The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic

  18. Paediatric laryngeal granular cell tumour

    Directory of Open Access Journals (Sweden)

    Dauda Ayuba


    Full Text Available Granular cell tumour (GCT affecting the larynx is not common, especially in children. Most cases are apt to be confused with respiratory papilloma and may even be mistaken for a malignant neoplasia. We present a case of laryngeal GCT in a 12-year-old child to emphasize that the tumour should be regarded in the differential of growths affecting the larynx in children.

  19. Complete absence of M2-pyruvate kinase expression in benign pancreatic ductal epithelium and pancreaticobiliary and duodenal neoplasia

    Directory of Open Access Journals (Sweden)

    Rowlands Brian J


    Full Text Available Abstract Background Elevated serum concentrations of M2-pyruvate kinase (M2-PK correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. We aimed to characterise the immunohistochemical expression of M2-PK in archived specimens of pancreaticobiliary and duodenal cancers, premalignant lesions, chronic pancreatitis, and normal pancreas. Methods Immunohistochemical staining was performed with mouse anti-M2-PK monoclonal antibody (clone DF-4 at an optimal dilution of 1:25 on tissue microarrays constructed from formalin-fixed paraffin-embedded pancreatic tissue of 126 consecutive patients undergoing pancreatic resections between June 2001 and June 2006. 104 underwent resection for cancer and 22 for chronic pancreatitis. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. A further 11 premalignant pancreaticobiliary and duodenal lesions were studied. M2-PK expression was quantified with the immunohistochemical score (IHS; Range 0-12. Results Benign non-ductal tissue in chronic pancreatitis and normal pancreas showed variable expression of M2-PK (IHS = 1 in 25%, IHS = 2-3 in 40%, IHS>3 in 40%. Benign pancreatic ductal epithelium, all primary pancreaticobiliary and duodenal premalignant lesions and cancers (and lymph node metastasis showed complete lack of expression (IHS = 0. Conclusion Complete lack of M2-PK expression was observed in benign pancreatic ducts, premalignant lesions and cancer. M2-PK is present only in benign non-ductal epithelium in normal pancreas and peri-tumoural tissue.

  20. Five-year actual survival after pancreatoduodenectomy for pancreatic head cancer. (United States)

    Perysinakis, Iraklis; Avlonitis, Spyridon; Georgiadou, Despoina; Tsipras, Hercules; Margaris, Ilias


    The aim of this study was to analyse retrospectively the long-term results of patients who were operated for adenocarcinoma of the pancreatic head and identify significant prognostic factors. Eighty patients who were surgically treated for adenocarcinoma of the pancreatic head between 1995 and 2006 met the inclusion criteria and were subject to retrospective analysis. Possible prognostic factors were evaluated and independent predictors of survival were determined. A classic Whipple procedure was performed in 47 patients and a pylorus-preserving pancreatoduodenectomy in 32 patients; one patient underwent total pancreatectomy. Five-year survival rate in this group of patients was 13.6%. Median survival time was 24 months. Univariable analysis demonstrated stage of disease, tumour size and grade and nodal status as significant predictive factors of survival. Multivariable analysis indicated tumour size, nodal status and disease stage as significant prognostic indicators in terms of survival. Long-term survival in pancreatic cancer is still very low. Prognostic factors include differentiation of the tumour, disease stage and nodal status. So far, there has been no reliable method that can accurately predict which patient will mostly benefit from surgical resection. This means that pancreatic cancer resection should nearly always be attempted. © 2013 Royal Australasian College of Surgeons.

  1. Pancreatitis in dogs and cats: definitions and pathophysiology. (United States)

    Watson, P


    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.

  2. MRI characteristics of midbrain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sun, B. [Chinese Academy of Medical Science, Beijing (China). Neurosurgical Inst.]|[Department of Neuroradiology, Beijing Tiantan Hospital (China); Wang, C.C.; Wang, J. [Chinese Academy of Medical Science, Beijing (China). Neurosurgical Inst.


    We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were 39 males and 21 females, aged 2-64 years, mean 25.6 years. We found 38 patients with true intramedullary midbrain tumours, 11 predominantly in the tectum, 20 in the tegmentum and 7 with a downward extension to the pons; there were 7 within the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours extending from adjacent structures, 11 cases each from the thalamus and pineal region. All patients received surgical treatment. Gross total resection was achieved in 42 cases, subtotal (> 75 %) resection in 18. Pathological diagnoses included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas; 2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours. Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in clinical and MRI features, related to the site and type of tumour. MRI not only allows precise analysis of their growth pattern, but also can lead to a correct preoperative diagnosis in the majority of cases. (orig.) (orig.) With 3 figs., 3 tabs., 19 refs.

  3. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P


    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  4. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh


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

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

    NARCIS (Netherlands)

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


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

  6. Endoscopic treatment of pancreatic stones in patients with chronic pancreatitis

    NARCIS (Netherlands)

    Smits, M. E.; Rauws, E. A.; Tytgat, G. N.; Huibregtse, K.


    The aim of our study was to evaluate the long-term results of endoscopic pancreatic stone removal in patients with chronic pancreatitis. We retrospectively included 53 patients with chronic pancreatitis, in whom an attempt was made at endoscopic stone removal between 1984 and 1993. Patients

  7. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds

    NARCIS (Netherlands)

    Klein, Alison P.; Brune, Kieran A.; Petersen, Gloria M.; Goggins, Michael; Tersmette, Anne C.; Offerhaus, G. Johan A.; Griffin, Constance; Cameron, John L.; Yeo, Charles J.; Kern, Scott; Hruban, Ralph H.


    Individuals with a family history of pancreatic cancer have an increased risk of developing pancreatic cancer. Quantification of this risk provides a rational basis for cancer risk counseling and for screening for early pancreatic cancer. In a prospective registry-based study, we estimated the risk

  8. Pancreatic trauma: A concise review (United States)

    Debi, Uma; Kaur, Ravinder; Prasad, Kaushal Kishor; Sinha, Saroj Kant; Sinha, Anindita; Singh, Kartar


    Traumatic injury to the pancreas is rare and difficult to diagnose. In contrast, traumatic injuries to the liver, spleen and kidney are common and are usually identified with ease by imaging modalities. Pancreatic injuries are usually subtle to identify by different diagnostic imaging modalities, and these injuries are often overlooked in cases with extensive multiorgan trauma. The most evident findings of pancreatic injury are post-traumatic pancreatitis with blood, edema, and soft tissue infiltration of the anterior pararenal space. The alterations of post-traumatic pancreatitis may not be visualized within several hours following trauma as they are time dependent. Delayed diagnoses of traumatic pancreatic injuries are associated with high morbidity and mortality. Imaging plays an important role in diagnosis of pancreatic injuries because early recognition of the disruption of the main pancreatic duct is important. We reviewed our experience with the use of various imaging modalities for diagnosis of blunt pancreatic trauma. PMID:24379625

  9. Latest advances in chronic pancreatitis

    National Research Council Canada - National Science Library

    Domínguez Muñoz, J Enrique


    .... These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis...

  10. Metabolic pancreatitis: Etiopathogenesis and management

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota


    Full Text Available Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis. Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson′s disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

  11. Surgery for pancreatic cancer -- discharge (United States)

    ... Surgery for pancreatic cancer - discharge To use the sharing features on this ... please enable JavaScript. You had surgery to treat pancreatic cancer . Now that you're going home, follow instructions ...

  12. Efficient and persistent transduction of exocrine and endocrine pancreas by adeno-associated virus type 8. (United States)

    Cheng, Henrique; Wolfe, Stephanie H; Valencia, Valery; Qian, Keping; Shen, Leping; Phillips, M Ian; Chang, Lung-Ji; Zhang, Y Clare


    Efficient delivery of therapeutic proteins into the pancreas represents a major obstacle to gene therapy of pancreatic disorders. The current study compared the efficiency of recombinant lentivirus and adeno-associated virus (AAV) serotypes 1, 2, 5, 8 vectors delivered by intrapancreatic injection for gene transfer in vivo. Our results indicate that lentivirus and AAV 1, 2, 8 are capable of transducing pancreas with the order of efficiency AAV8 >AAV1 > AAV2 >/= lentivirus, whereas AAV5 was ineffective. AAV8 resulted in an efficient, persistent (150 days) and dose-dependent transduction in exocrine acinar cells and endocrine islet cells. Pancreatic ducts and blood vessels were also transduced. Extrapancreatic transduction was restricted to liver. Leukocyte infiltration was not observed in pancreas and blood glucose levels were not altered. Thus, AAV8 represents a safe and effective vehicle for therapeutic gene transfer to pancreas in vivo.

  13. Metronomic chemotherapy following the maximum tolerated dose is an effective anti-tumour therapy affecting angiogenesis, tumour dissemination and cancer stem cells. (United States)

    Vives, Marta; Ginestà, Mireia M; Gracova, Kristina; Graupera, Mariona; Casanovas, Oriol; Capellà, Gabriel; Serrano, Teresa; Laquente, Berta; Viñals, Francesc


    In this article, the effectiveness of a multi-targeted chemo-switch (C-S) schedule that combines metronomic chemotherapy (MET) after treatment with the maximum tolerated dose (MTD) is reported. This schedule was tested with gemcitabine in two distinct human pancreatic adenocarcinoma orthotopic models and with cyclophosphamide in an orthotopic ovarian cancer model. In both models, the C-S schedule had the most favourable effect, achieving at least 80% tumour growth inhibition without increased toxicity. Moreover, in the pancreatic cancer model, although peritoneal metastases were observed in control and MTD groups, no dissemination was observed in the MET and C-S groups. C-S treatment caused a decrease in angiogenesis, and its effect on tumour growth was similar to that produced by the MTD followed by anti-angiogenic DC101 treatment. C-S treatment combined an increase in thrombospondin-1 expression with a decrease in the number of CD133+ cancer cells and triple-positive CD133+/CD44+/CD24+ cancer stem cells (CSCs). These findings confirm that the C-S schedule is a challenging clinical strategy with demonstrable inhibitory effects on tumour dissemination, angiogenesis and CSCs. Copyright © 2013 UICC.

  14. Protease-activated receptor 2 suppresses lymphangiogenesis and subsequent lymph node metastasis in a murine pancreatic cancer model

    NARCIS (Netherlands)

    Shi, Kun; Queiroz, Karla C. S.; Roelofs, Joris J. T. H.; van Noesel, Carel J. M.; Richel, Dirk J.; Spek, C. Arnold


    Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that functions as a cell-surface sensor for coagulation factors and other proteases associated with the tumour microenvironment. Pancreatic cancer cells express high levels of PAR-2 and activation of PAR-2 may induce their

  15. Nutrition, Inflammation, and Acute Pancreatitis (United States)

    Petrov, Max


    Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis. PMID:24490104

  16. Clinical advances in acute pancreatitis


    Qian, Jiaming


    Acute pancreatitis (AP) is a common gastroenterological emergency. Because of the diverse prognosis in AP, it is crucial to identify severe acute pancreatitis (SAP) early and provide timely treatment. Thus, there are a number of clinical advances in this aspect. This paper reviews two advances in AP. Firstly, AP is classified into mild acute pancreatitis, moderately severe acute pancreatitis (MSAP), and SAP according to 2012 revision of the Atlanta Classification; SAP is distinguished from MS...

  17. Alcohol consumption on pancreatic diseases


    Herreros-Villanueva, Marta; Hijona, Elizabeth; Bañales, Jesus Maria; Cosme, Angel; Bujanda, Luis


    Although the association between alcohol and pancreatic diseases has been recognized for a long time, the impact of alcohol consumption on pancreatitis and pancreatic cancer (PC) remains poorly defined. Nowadays there is not consensus about the epidemiology and the beverage type, dose and duration of alcohol consumption causing these diseases. The objective of this study was to review the epidemiology described in the literature for pancreatic diseases as a consequence of alcoholic behavior t...

  18. [Disperse endocrine system and APUD concept]. (United States)

    Mil'to, I V; Sukhodolo, I V; Gereng, E A; Shamardina, L A


    This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

  19. Update on endocrine disturbances in anorexia nervosa

    DEFF Research Database (Denmark)

    Støving, R K; Hangaard, J; Hagen, C


    The marked endocrine changes that occur in anorexia nervosa have aroused a great deal of interest, and over the last decade much research has been conducted in this field. The endocrine disturbances are not specific to this disorder, as they also occur in starvation states secondary to other causes...... of the large body of literature concerning endocrine aspects of anorexia nervosa with the main focus on the latest results, which provide leads for potential etiological theories....

  20. Fetal adrenal demedullation lowers circulating norepinephrine and attenuates growth restriction but not reduction of endocrine cell mass in an ovine model of intrauterine growth restriction. (United States)

    Davis, Melissa A; Macko, Antoni R; Steyn, Leah V; Anderson, Miranda J; Limesand, Sean W


    Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE) that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses.

  1. Poorly differentiated endocrine carcinoma of the pancreas responded to gemcitabine: Case report (United States)

    Nakazuru, Shoichi; Yoshio, Toshiyuki; Suemura, Shigeki; Itoh, Mari; Araki, Manabu; Yoshioka, Chiaki; Ohta, Makiyo; Sueyoshi, Yuka; Ohta, Takashi; Hasegawa, Hiroko; Morita, Kaori; Toyama, Takashi; Kuzushita, Noriyoshi; Kodama, Yoshinori; Mano, Masayuki; Mita, Eiji


    Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as third-line chemotherapy. After two cycles of gemcitabine (1000 mg/m2 on days 1, 8 and 15 every 4 wk), a partial tumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments. PMID:20698050

  2. Perioperative management of endocrine insufficiency after total pancreatectomy for neoplasia. (United States)

    Maker, Ajay V; Sheikh, Raashid; Bhagia, Vinita


    Indications for total pancreatectomy (TP) have increased, including for diffuse main duct intrapapillary mucinous neoplasms of the pancreas and malignancy; therefore, the need persists for surgeons to develop appropriate endocrine post-operative management strategies. The brittle diabetes after TP differs from type 1/2 diabetes in that patients have absolute deficiency of insulin and functional glucagon. This makes glucose management challenging, complicates recovery, and predisposes to hospital readmissions. This article aims to define the disease, describe the cause for its occurrence, review the anatomy of the endocrine pancreas, and explain how this condition differs from diabetes mellitus in the setting of post-operative management. The morbidity and mortality of post-TP endocrine insufficiency and practical treatment strategies are systematically reviewed from the literature. Finally, an evidence-based treatment algorithm is created for the practicing pancreatic surgeon and their care team of endocrinologists to aid in managing these complex patients. A PubMed, Science Citation Index/Social sciences Citation Index, and Cochrane Evidence-Based Medicine database search was undertaken along with extensive backward search of the references of published articles to identify studies evaluating endocrine morbidity and treatment after TP and to establish an evidence-based treatment strategy. Indications for TP and the etiology of pancreatogenic diabetes are reviewed. After TP, ~80% patients develop hypoglycemic episodes and 40% experience severe hypoglycemia, resulting in 0-8% mortality and 25-45% morbidity. Referral to a nutritionist and endocrinologist for patient education before surgery followed by surgical reevaluation to determine if the patient has the appropriate understanding, support, and resources preoperatively has significantly reduced morbidity and mortality. The use of modern recombinant long-acting insulin analogues, continuous subcutaneous insulin

  3. Osmoregulation and endocrine glands of teleosts

    National Research Council Canada - National Science Library

    Oguri, M


    ...), have indicated that the following endocrine glands: thyroid gland, hypophysis, interrenal body, urophysis, corpuscle of stannius and juxtaglomerular cells, are involved in the osmoregulation in teleosts...

  4. Effect of Endocrine Disruptor Pesticides: A Review

    Directory of Open Access Journals (Sweden)

    Benoit Roig


    Full Text Available Endocrine disrupting chemicals (EDC are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air. For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

  5. Effect of endocrine disruptor pesticides: a review. (United States)

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit


    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

  6. Effect of Endocrine Disruptor Pesticides: A Review (United States)

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit


    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health. PMID:21776230

  7. Genetic basis of chronic pancreatitis

    NARCIS (Netherlands)

    Jansen, JBMJ; Morsche, RT; van Goor, Harry; Drenth, JPH


    Background: Pancreatitis has a proven genetic basis in a minority of patients. Methods: Review of the literature on genetics of pancreatitis. Results: Ever since the discovery that in most patients with hereditary pancreatitis a mutation in the gene encoding for cationic trypsinogen (R122H) was

  8. Drug-induced acute pancreatitis

    NARCIS (Netherlands)

    I.A. Eland (Ingo)


    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are

  9. Pancreatic Cancer Stage 2B (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Pancreatic Cancer Stage 2B Add to My Pictures View /Download : ... 1500x1200 View Download Large: 3000x2400 View Download Title: Pancreatic Cancer Stage 2B Description: Stage IIB pancreatic cancer; drawing ...

  10. Pancreatic Cancer Stage 2A (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Pancreatic Cancer Stage 2A Add to My Pictures View /Download : ... 1500x1200 View Download Large: 3000x2400 View Download Title: Pancreatic Cancer Stage 2A Description: Stage IIA pancreatic cancer; drawing ...

  11. Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer. (United States)

    Rosenberger, I; Strauss, A; Dobiasch, S; Weis, C; Szanyi, S; Gil-Iceta, L; Alonso, E; González Esparza, M; Gómez-Vallejo, V; Szczupak, B; Plaza-García, S; Mirzaei, S; Israel, L L; Bianchessi, S; Scanziani, E; Lellouche, J-P; Knoll, P; Werner, J; Felix, K; Grenacher, L; Reese, T; Kreuter, J; Jiménez-González, M


    Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI). Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Diffusion-weighted imaging in characterization of cystic pancreatic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Sandrasegaran, K., E-mail: [Department of Radiology, Indiana University School of Medicine, Indianapolis, IN (United States); Akisik, F.M.; Patel, A.A.; Rydberg, M. [Department of Radiology, Indiana University School of Medicine, Indianapolis, IN (United States); Cramer, H.M.; Agaram, N.P. [Department of Pathology, Indiana University School of Medicine, Indianapolis, IN (United States); Schmidt, C.M. [Department of Surgery, Indiana University School of Medicine, Indianapolis, IN (United States)


    Aim: To evaluate whether apparent diffusion coefficient (ADC) measurements from diffusion-weighted imaging (DWI) can characterize or predict the malignant potential of cystic pancreatic lesions. Materials and methods: Retrospective review of the magnetic resonance imaging (MRI) database over a 2-year period revealed 136 patients with cystic pancreatic lesions. Patients with DWI studies and histological confirmation of cystic mass were included. In patients with known pancreatitis, lesions with amylase content of >1000 IU/l that resolved on subsequent scans were included as pseudocysts. ADC of cystic lesions was measured by two independent reviewers. These values were then compared to categorize these lesions as benign or malignant using conventional MRI sequences. Results: Seventy lesions were analysed: adenocarcinoma (n = 4), intraductal papillary mucinous neoplasm (IPMN; n = 28), mucinous cystic neoplasm (MCN; n = 9), serous cystadenoma (n = 16), and pseudocysts (n = 13). There was no difference between ADC values of malignant and non-malignant lesions (p = 0.06), between mucinous and serous tumours (p = 0.12), or between IPMN and MCN (p = 0.42). ADC values for low-grade IPMN were significantly higher than those for high-grade or invasive IPMN (p = 0.03). Conclusion: ADC values may be helpful in deciding the malignant potential of IPMN. However, they are not useful in differentiating malignant from benign lesions or for characterizing cystic pancreatic lesions.

  13. Thoracoscopic Splanchnicectomy for Pain Control in Irresectable Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Alireza Tavassoli


    Full Text Available Introduction : Severepain is a major problem in patients with unresectable pancreatic cancer. The goal of this study is to evaluate the effects of Thoracoscopic Splanchnicectomy (TS on pain control in these patients suffering from unresectable pancreatic cancer. Methods:Between years 2000 to 2011, 20 patients suffering from unresectable pancreatic cancer underwent TS due to severe pain. They were studied in terms of age, sex, location of pancreas tumor, history of previous surgery, response to treatments for pain control (assessed with VAS scoring system and complications of surgery. Results:M/F = 14/6 with a mean age of 63 years. The most common tumour site was at the pancreas head (in 8 patients. The most cause of unresectability was local expansion to critical adjacent elements (in 10 patients. Surgery was performed successfully in all patients. Post-operative complication included only pleural effusion on the left side which was cured by proper treatment. There were no post-op mortalities.  15 patients had acceptable levels of pain at the end of a six month follow-up period. ConclusionTS provides good pain control, little side effects and minimal invasiveness, the technique is recommended for pain control in patients with unresectable pancreatic cancer.

  14. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results (United States)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.


    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  15. Autoantibodies in chronic pancreatitis

    DEFF Research Database (Denmark)

    Rumessen, J J; Marner, B; Pedersen, N T


    In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and reti......In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane......, and reticulin, and the IgG- and IgA-type pancreas-specific antibodies against islet cells, acinus cells, and ductal cells (DA) were estimated blindly. In 23 of the patients chronic pancreatitis was verified, whereas chronic pancreatitis was rejected in 37 patients (control group). IgG and IgA were found...... in significantly higher concentrations in the patients with chronic pancreatitis than in the control group but within the normal range. ANA and DA occurred very frequently in both groups but with no statistical difference. Other autoantibodies only occurred sporadically. The findings of this study do not support...

  16. Hepatobiliary and pancreatic ascariasis (United States)

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S


    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease. PMID:27672273

  17. Therapeutics for Equine Endocrine Disorders. (United States)

    Durham, Andy E


    Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin may apply. Therapeutic options exist in rare cases of diabetes mellitus, diabetes insipidus, hyperthyroidism, and critical illness-related corticosteroid insufficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Endocrine Resistance in Breast Cancer

    Directory of Open Access Journals (Sweden)

    J. M. Dixon


    Full Text Available Around 70% of all breast cancers are estrogen receptor alpha positive and hence their development is highly dependent on estradiol. While the invention of endocrine therapies has revolusioned the treatment of the disease, resistance to therapy eventually occurs in a large number of patients. This paper seeks to illustrate and discuss the complexity and heterogeneity of the mechanisms which underlie resistance and the approaches proposed to combat them. It will also focus on the use and development of methods for predicting which patients are likely to develop resistance.

  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)


    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. Obestatin enhances in vitro generation of pancreatic islets through regulation of developmental pathways


    Alessandra Baragli; Cristina Grande; Iacopo Gesmundo; Fabio Settanni; Marina Taliano; Davide Gallo; Eleonora Gargantini; Ezio Ghigo; Riccarda Granata


    Availability of large amounts of in vitro generated β-cells may support replacement therapy in diabetes. However, methods to obtain β-cells from stem/progenitor cells are limited by inefficient endocrine differentiation. We have recently shown that the ghrelin gene product obestatin displays beneficial effects on pancreatic β-cell survival and function. Obestatin prevents β-cell apoptosis, preserves β-cell mass and stimulates insulin secretion in vitro and in vivo, in both normal and diabetic...

  1. Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by beta-adrenergic receptor blockade. (United States)

    Partecke, Lars Ivo; Speerforck, Sven; Käding, André; Seubert, Florian; Kühn, Sandra; Lorenz, Eric; Schwandke, Sebastian; Sendler, Matthias; Keßler, Wolfram; Trung, Dung Nguyen; Oswald, Stefan; Weiss, Frank Ulrich; Mayerle, Julia; Henkel, Christin; Menges, Pia; Beyer, Katharina; Lerch, Markus M; Heidecke, Claus-Dieter; von Bernstorff, Wolfram


    Chronic stress could promote tumour growth and reduce survival of pancreatic cancer patients via beta-adrenergic receptors of tumour cells. We have tested the impact of chronic acoustic and restraint stress on tumour development in an orthotopic syngeneic murine model of pancreatic cancer. Tumour-bearing C57BL/6 mice exposed to chronic stress had 45% (p = 0.0138) higher circulating steroid and 111% (p = 0.0052) higher adrenal tyrosine hydroxylase levels. Their immune response was significantly suppressed: The in vitro LPS response of splenocytes was significantly reduced regarding Th1- and Th2-cytokines including IFN-gamma, IL-6, IL-10 and MCP-1 (0.0011  0.05). TGF-beta in vitro was increased by 23.4% using catecholamines (p Beta-catecholamines increased proliferation in tumour cells by 18% (p beta-blocker propranolol reduced these effects by 25% (p beta-blockers of patients with pancreatic cancer or other malignancies should be further evaluated as an adjuvant anti-neoplastic agent in clinical trials. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  2. PTEN hamartoma tumour syndrome: early tumour development in children. (United States)

    Smpokou, Patroula; Fox, Victor L; Tan, Wen-Hann


    The aim of this study was to report the earliest age of diagnosis of common clinical findings in children with PTEN hamartoma tumour syndrome (PHTS). Medical records of children with PHTS were reviewed; data included growth measurements, presence or absence of specific clinical manifestations and tumours, and documented ages of diagnosis. Children with PHTS evaluated at Boston Children's Hospital from 1996 to 2011. The cohort included 34 children diagnosed with PHTS via genetic testing, under the age of 21 years. Of these, 23 were male and 11 female. The mean age at their last documented clinical evaluation was 13.6 years. The mean follow-up time was 7.5 years. Macrocephaly and developmental/intellectual disability were consistent findings. Pigmented penile macules were noted in all males examined for this finding. Thyroid nodules, found in half the children screened with ultrasound, were diagnosed as early as at 5 years of age. Thyroid carcinoma, identified in 12% of the children in this cohort, was diagnosed as early as at 7 years of age. Other tumours included renal cell carcinoma diagnosed at 11 years of age and granulosa cell tumour of the ovary and colonic ganglioneuroma, each diagnosed at 16 years of age. Specific clinical findings and tumours are characteristic in children with PHTS. Tumour development occurs in young children with this condition, which necessitates early surveillance, especially of the thyroid. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  3. 68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT. (United States)

    Kroiss, A; Putzer, D; Decristoforo, C; Uprimny, C; Warwitz, B; Nilica, B; Gabriel, M; Kendler, D; Waitz, D; Widmann, G; Virgolini, I J


    We wanted to establish the range of (68)Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 (68)Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUVmax (mean ± standard deviation) values of (68)Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (p TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUVmax can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUVmax, except in liver metastases of patients with NET.

  4. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C.; Bakker, Olaf J.; van Goor, Harry; Nieuwenhuijs, Vincent B.; Bollen, Thomas L.; van Ramshorst, Bert; Witteman, Ben J.; Brink, Menno A.; Schaapherder, Alexander F.; Dejong, Cornelis H.; Spanier, B. W. Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H.; Besselink, Marc G.; Gooszen, Hein G.; van Santvoort, Hjalmar C.; Boermeester, Marja A.


    Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch

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

    African Journals Online (AJOL)

    Exocrine pancreatic response was evaluated in patients with varying degrees of pancreatic damage and in control subjects by means of an extended pancreatic function test (PFT). A second injection of secretin and pancreozymin was given after com- pletion of the standard test. The discriminatory value of the standard PFT ...

  6. An Update on Pediatric Pancreatitis. (United States)

    Shukla-Udawatta, Monica; Madani, Shailender; Kamat, Deepak


    There has been a rise in the incidence and number of admissions of children with pancreatitis over the past 20 years. Current management practices for pancreatitis in children are adapted from standards of care for adults, and there are a lack of multicenter, prospective research studies on pancreatitis in children. There are inherent differences in the clinical presentation and natural course of pancreatitis between adults and children. This review focuses on the current understanding of the epidemiology, etiologies, evaluation, and management of children with pancreatitis. [Pediatr Ann. 2017;46(5):e207-e211.]. Copyright 2017, SLACK Incorporated.

  7. Pitfalls in colour photography of choroidal tumours. (United States)

    Schalenbourg, A; Zografos, L


    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

  8. Pitfalls in colour photography of choroidal tumours (United States)

    Schalenbourg, A; Zografos, L


    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  9. Neuroimmune endocrine effects of antidepressants

    Directory of Open Access Journals (Sweden)

    Antonioli M


    Full Text Available Marco Antonioli, Joanna Rybka, LA CarvalhoPsychoimmunology Translational Laboratory, Health Science Research Centre, Roehampton University, London, UKAbstract: Antidepressant pharmacotherapy is to date the most often used treatment for depression, but the exact mechanism of action underlying its therapeutic effect is still unclear. Many theories have been put forward to account for depression, as well as antidepressant activity, but none of them is exhaustive. Neuroimmune endocrine impairment is found in depressed patients; high levels of circulating corticosteroids along with hyperactivation of the immune system, high levels of proinflammatory cytokines, low levels of melatonin in plasma and urine, and disentrainment of circadian rhythms have been demonstrated. Moreover, antidepressant treatment seems to correct or at least to interfere with these alterations. In this review, we summarize the complex neuroimmune endocrine and chronobiological alterations found in patients with depression and how these systems interact with each other. We also explain how antidepressant therapy can modify these systems, along with some possible mechanisms of action shown in animal and human models.Keywords: antidepressant agents, biological markers, human, cytokines, neuroinflammation, psychoneuroimmunology, endophenotype

  10. Multiple endocrine neoplasia type 2. (United States)

    Lodish, Maya


    Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome characterized by variable penetrance of medullary thyroid carcinoma(MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT). MEN2 consists of two clinical subtypes, MEN2A and MEN2B. Familial medullary thyroid cancer is now viewed as a phenotypic variant of MEN2A with decreased penetrance for PHEO and PHPT rather than a distinct entity. All subtypes are caused by gain-of-function mutations of the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. Recognition of the clinical entity in individuals and families at risk of harboring a germline RET mutation is crucial for the management and prevention of associated malignancies. Recent guidelines released by the American Thyroid Association regarding the management of MTC will be summarized in this chapter. Copyright © 2013 S. Karger AG, Basel.

  11. Cystic pancreatic lymphangioma

    Directory of Open Access Journals (Sweden)

    Alihan Gurkan


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

  12. Pancreatic Cancer Diagnostics and Treatment – Current State

    Directory of Open Access Journals (Sweden)

    Zdeněk Krška


    Full Text Available Pancreatic ductal adenocarcinoma (PDAC represents permanent and ever rising issue worldwide. Five-year survival does not exceed 3 to 6%, i.e. the worst result among solid tumours. The article evaluates the current state of PDAC diagnostics and treatment specifying also development and trends. Percentage of non-resectable tumours due to locally advanced or metastatic condition varies 60–80%, mostly over 80%. Survival with non-resectable PDAC is 4 to 8 months (median 3.5. In contrast R0 resection shows the survival 18–27 months. Laboratory and imaging screening methods are not indicated on large scale. Risk factors are smoking, alcohol abuse, chronic pancreatitis, diabetes mellitus. Genetic background in most PDAC has not been detected yet. Some genes connected with high risk of PDAC (e.g. BRCA2, PALB2 have been identified as significant and highly penetrative, but link between PDAC and these genes can be seen only in 10–20%. This article surveys perspective oncogenes, tumour suppressor genes, microRNA. Albeit CT is still favoured over other imaging methods, involvement of NMR rises. Surgery prefers the “vessel first” approach, which proves to be justified especially in R0 resection. According to EBM immunotherapy same as radiotherapy are not significant in PDAC treatment. Chemotherapy shows limited importance in conversion treatment of locally advanced or borderline tumours or in case of metastatic spread. Unified procedures cannot be defined due to inhomogenous arrays. Surgical resection is the only chance for curative treatment of PDAC and depends mainly on timely indication for surgery and quality of multidisciplinary team in a high-volume centre.

  13. Concurrent PEDF deficiency and Kras mutation induce invasive pancreatic cancer and adipose-rich stroma in mice. (United States)

    Grippo, Paul J; Fitchev, Philip S; Bentrem, David J; Melstrom, Laleh G; Dangi-Garimella, Surabhi; Krantz, Seth B; Heiferman, Michael J; Chung, Chuhan; Adrian, Kevin; Cornwell, Mona L; Flesche, Jan B; Rao, Sambasiva M; Talamonti, Mark S; Munshi, Hidayatullah G; Crawford, Susan E


    Pigment epithelium-derived factor (PEDF), a non-inhibitory SERPIN with potent antiangiogenic activity, has been recently implicated in metabolism and adipogenesis, both of which are known to influence pancreatic cancer progression. Increased pancreatic fat in human pancreatic tumour correlates with greater tumour dissemination while PEDF deficiency in mice promotes pancreatic hyperplasia and visceral obesity. Oncogenic Ras, the most common mutation in pancreatic ductal adenocarcinoma (PDAC), has similarly been shown to promote adipogenesis and premalignant lesions. In order to determine whether concurrent loss of PEDF is sufficient to promote adipogenesis and tumorigenesis in the pancreas, the authors ablated PEDF in an EL-Kras(G12D) mouse model of non-invasive cystic papillary neoplasms. EL-Kras(G12D)/PEDF deficient mice developed invasive PDAC associated with enhanced matrix metalloproteinase (MMP)-2 and MMP-9 expression and increased peripancreatic fat with adipocyte hypertrophy and intrapancreatic adipocyte infiltration (pancreatic steatosis). In support of increased adipogenesis, the stroma of the pancreas of EL-Kras(G12D)/PEDF deficient mice demonstrated higher tissue levels of two lipid droplet associated proteins, tail-interacting protein 47 (TIP47, perilipin 3) and adipose differentiation-related protein (ADRP, Pperilipin 2), while adipose triglyceride lipase, a key factor in lipolysis, was decreased. In patients with PDAC, both tissue and serum levels of PEDF were decreased, stromal TIP47 expression was higher and the tissue VEGF to PEDF ratio was increased (p<0.05). These data highlight the importance of lipid metabolism in the tumour microenvironment and identify PEDF as a critical negative regulator of both adiposity and tumour invasion in the pancreas.

  14. Genetic susceptibility to pancreatic cancer. (United States)

    Klein, Alison P


    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited genetic factors also play an important role, with approximately 5-10% of pancreatic cancer patients reporting family history of pancreatic cancer. While the genetic basis for the majority of the familial clustering of pancreatic cancer remains unclear, several important pancreatic cancer genes have been identified. These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus. Recent advances in genotyping and genetic sequencing have accelerated the rate at which novel pancreatic cancer susceptibility genes have been identified with several genes identified within the past few years. This review addresses our current understanding of the familial aggregation of pancreatic cancer, established pancreatic cancer susceptablity genes and how this knowledge informs risk assessment and screening for high-risk families. Copyright © 2011 Wiley Periodicals, Inc.

  15. Genetic Susceptibility to Pancreatic Cancer (United States)

    Klein, Alison P.


    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited genetic factors also play an important role, with approximately 5–10% of pancreatic cancer patients reporting family history of pancreatic cancer. While the genetic basis for the majority of the familial clustering of pancreatic cancer remains unclear, several important pancreatic cancer genes have been identified. These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus. Recent advances in genotyping and genetic sequencing have accelerated the rate at which novel pancreatic cancer susceptibility genes have been identified with several genes identified within the past few years. This review addresses our current understanding of the familial aggregation of pancreatic cancer, established pancreatic cancer susceptablity genes and how this knowledge informs risk assessment and screening for high-risk families. PMID:22162228

  16. Gut microbiota and pancreatic diseases. (United States)

    Signoretti, Marianna; Roggiolani, Roberta; Stornello, Caterina; Delle Fave, Gianfranco; Capurso, Gabriele


    Changes in diet, lifestyle, and exposure to environmental risk factors account for the increased incidence of pancreatic disorders, including acute and chronic pancreatitis, and pancreatic cancer. The role of the microbiota in the development of pancreatic disorders is increasingly acknowledged. The translocation of gut bacteria and endotoxins following gut barrier failure is a key event contributing to the severity of acute pancreatitis, while small intestine bacterial overgrowth is common in patients with chronic pancreatitis and further worsens their symptoms and malnutrition. Specific molecular mimicry link the microbiota and Helicobacter pylori with autoimmune pancreatitis. Changes in the oral microbiota typical of periodontitis seem to be associated with an increased risk of developing pancreatic cancer. The composition of the gut microbiota is also unbalanced in the presence of risk factors for pancreatic cancer, such as obesity, smoking and diabetes. Helicobacter pylori infection, atrophic body gastritis and related decreased gastric acid secretion also seem associated with the risk of pancreatic cancer, although this area needs further research. The link between dysbiosis, immune response and proinflammatory status is most likely the key for these associations. The present review article will discuss current available evidence on the role of gut microbiota in pancreatic disorders, highlighting potential areas for future research.

  17. [Pancreatic serous cystadenoma associated with pancreatic heterotopia]. (United States)

    Mohamed, Hedfi; Dorra, Belghachem; Hela, Bouhafa; Cherif, Abdelhedi; Azza, Sridi; Karim, Sassi; Khadija, Bellil; Adnen, Chouchene


    Pancreatic heterotopias (HP) are rare. They can occur at any age with a slight male predominance. These lesions are usually asymptomatic and they are often found incidentally during upper or lower GI endoscopy or during the anatomo-pathological examination of an organ which was resected for other reasons; they can be isolated or associated with a digestive pathology. We report, through observation, the association of HP with serous cystadenoma of the pancreas discovered during examinations to identify the etiology of isolated abdominal pain. The aim of this study is to analyse clinical and histological features of this rare pathology.

  18. 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


    BACKGROUND & AIMS: The genetic specification of the compartmentalized pancreatic acinar/centroacinar unit is poorly understood. Growth factor independence-1 (Gfi1) is a zinc finger transcriptional repressor that regulates hematopoietic stem cell maintenance, pre-T-cell differentiation, formation...... of pancreatic acinar cells as well as the centroacinar cells (CACs) in Gfi1(-/-) mice when compared with wild-type littermates. Pancreatic endocrine differentiation, islet architecture, and function were unaffected. Organ domain patterning and the formation of ductal cells occurred normally during the murine...... 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...

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

    Directory of Open Access Journals (Sweden)

    Jamie Trott


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

  20. Nigerian Endocrine Practice: About this journal

    African Journals Online (AJOL)

    Nigerian Endocrine Practice: About this journal. Journal Home > Nigerian Endocrine Practice: About this journal. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives. People. » Contact ...


    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.

  2. Genetic testing by cancer site: endocrine system. (United States)

    Pilarski, Robert; Nagy, Rebecca


    Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.

  3. The molecular classification of hereditary endocrine diseases. (United States)

    Ye, Lei; Ning, Guang


    Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

  4. Disease and treatment factors associated with lower quality of life scores in adults with multiple endocrine neoplasia type I. (United States)

    Goswami, Sneha; Peipert, Benjamin J; Helenowski, Irene; Yount, Susan E; Sturgeon, Cord


    Physical and psychosocial morbidity of multiple endocrine neoplasia type-1 is ill-defined. How disease and treatment-related factors relate to patient-reported outcomes including health-related quality of life is unknown. We hypothesized that disease and treatment burden negatively impacts health-related quality of life in adults with multiple endocrine neoplasia type-1. Adults (≥18 years) with multiple endocrine neoplasia type-1 completed an online survey of demographics, disease features, treatments, and Patient-Reported Outcomes Measurement Information System 29-item profile measure, and scores were compared with normative US data. Multivariable modeling was performed to evaluate factors associated with decreased health-related quality of life. Multiple endocrine neoplasia type-1 patients (n = 207) reported worse health-related quality of life compared with US normative data in all health-related quality of life domains (P 50 miles for doctor appointments and ≥20 doctor appointments/year (P quality of life. History of pancreatic neuroendocrine tumors was not associated with worse health-related quality of life. This is the largest study to assess clinical and treatment factors associated with health-related quality of life in multiple endocrine neoplasia type-1. Persistent hyperparathyroidism, increased travel distance and frequency of doctor appointments were all associated with worse health-related quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas (United States)

    Saisho, Yoshifumi


    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

  6. Chronic pancreatitis: Multicentre prospective data collection and analysis by the Hungarian Pancreatic Study Group.

    Directory of Open Access Journals (Sweden)

    Ákos Szücs

    Full Text Available Chronic pancreatitis is an inflammatory disease associated with structural and functional damage to the pancreas, causing pain, maldigestion and weight loss and thus worsening the quality of life.Our aim was to find correlations from a multicentre database representing the epidemiological traits, diagnosis and treatment of the disease in Hungary. The Hungarian Pancreatic Study Group collected data prospectively from 2012 to 2014 on patients suffering from chronic pancreatitis. Statistical analysis was performed on different questions.Data on 229 patients (74% male and 26% female were uploaded from 14 centres. Daily alcohol consumption was present in the aetiology of 56% of the patients. 66% of the patients were previously treated for acute exacerbation. One third of the patients had had previous endoscopic or surgical interventions. Pain was present in 69% of the cases, endocrine insufficiency in 33%, diarrhoea in 13% and weight loss in 39%. Diagnosis was confirmed with US (80%, CT scan (52%, MRI-MRCP (6%, ERCP (39%, and EUS (7,4%. A functional test was carried out in 5% of the patients. In 31% of the cases, an endoscopic intervention was performed with the need for re-intervention in 5%. Further elective surgical intervention was necessitated in 44% of endoscopies. 20% of the registered patients were primarily treated with surgery. The biliary complication rate for surgery was significantly smaller (2% than endoscopy (27%; however, pancreatic complications were higher in the patients treated with surgery. Patients who smoked regularly needed significantly more surgical intervention following endoscopy (66.7% vs. 26.9%, p = 0.002 than non-smokers, and the ratio of surgical intervention alone was also significantly higher (27.3% vs. 10.8%, p = 0.004. The ratio of surgery in patients who smoked and drank was significantly higher (30.09% vs. 12.5%, p = 0.012 than in abstinent and non-smoking patients, similarly to the need for further surgical

  7. Pancreatitis before pancreatic cancer: clinical features and influence on outcome. (United States)

    Dzeletovic, Ivana; Harrison, M Edwyn; Crowell, Michael D; Pannala, Rahul; Nguyen, Cuong C; Wu, Qing; Faigel, Douglas O


    Pancreatitis is considered a possible risk factor for and a presentation of pancreatic adenocarcinoma (PA). We aimed to evaluate a large PA patient registry to determine whether prior history of pancreatitis influenced survival. We retrospectively analyzed the Mayo Clinic Biospecimen Resource for Pancreas Research database from January 1992 to September 2011. Data collected included demographic characteristics, history of tobacco or alcohol use, diabetes mellitus (DM), cholelithiasis, pseudocyst, and details regarding PA. Clinical characteristics and outcomes of PA patients with pancreatitis were compared with PA patients without pancreatitis history. We analyzed 2573 patients with PA diagnosis. Among these patients, 195 (8%) were identified who had pancreatitis diagnosis ≥ 10 days before PA diagnosis. The cohort with pancreatitis history included more patients with DM (30% vs. 18%; Ppancreatitis history, these patients received diagnoses of PA at a younger age (63 vs. 65 y; P=0.005) and earlier stage (stages I and II; 52% vs. 37%; Ppancreatitis had more weight loss and DM, but had PA diagnosis at an earlier stage, were more likely to have pancreatic surgery, and therefore better survival than PA patients without pancreatitis, likely due to the earlier diagnosis. Further studies are needed to evaluate whether screening for PA in patients with pancreatitis history would provide survival benefit.

  8. [Pancreatic phlegmon: a potentially fatal form of acute pancreatitis]. (United States)

    Maroun Marun, C; Uscanga, L; Lara, F; Passareli, L; Quiroz-Ferrari, F; Robles-Díaz, G; Campuzano-Fernández, M


    To report the clinical characteristics of a group of patients with pancreatic phlegmon (PF) seen at the Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City. We reviewed all the cases of acute pancreatitis hospitalized from January 1981 to December 1989. The diagnosis of pancreatic phlegmon was established when the CT scan showed a solid mass in the pancreas and peripancreatic region with more than 20 Hounsfield units without liquid collections or a fibrous capsule. We analyzed clinical, biochemical, and radiological data. Acute pancreatitis was diagnosed in 132 patients. In 14 a pancreatic phlegmon was observed (10.6%). Twelve were men; the mean age was 44.7 years. In six cases acute pancreatitis was secondary to alcohol abuse and in four to gallstones. Abdominal pain was present in all patients. Ten had leucocitosis and seven fever and/or jaundice. An abdominal mass was detected in three cases. The severity of pancreatitis was graded according to our institutional criteria as mild (0-2 signs) or severe (3-5 signs). In 10 patients AP was graded as mild: no mortality was observed in this group but three presented complications (two liquid collections and one an abscess). The four patients with severe pancreatitis presented complications and three died (one abscess, two multiorgan failure). Five patients were operated on. In three an abscess was drained. Pancreatic phlegmon is a potentially severe form of AP. All patients who died presented, in addition to PF, clinical criteria of severe pancreatitis.

  9. Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma. (United States)

    Park, Shin-Young; Park, Keun-Myoung; Shin, Woo Young; Choe, Yun-Mee; Hur, Yoon-Seok; Lee, Keon-Young; Ahn, Seung-Ik


    Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma is investigated.The medical records of 45 patients who had undergone radical resection for pancreatic adenocarcinoma from March 2010 to September 2013 were reviewed retrospectively. There were 34 patients in the pancreaticoduodenectomy (PD) group and 10 patients in the distal pancreatectomy (DP) group. One patient received total pancreatectomy. The endocrine function was measured using the glucose tolerance index (GTI), which was derived by dividing daily maximum serum glucose fluctuation by daily minimum glucose. Remnant pancreas volume (RPV) was estimated by considering pancreas body and tail as a column, and head as an ellipsoid, respectively. The pancreatic atrophic index (PAI) was defined as the ratio of pancreatic duct width to total pancreas width. Representative indices of each patient were compared before and after resection up to 2 years postoperatively.The area under receiver operating characteristic curve of GTI for diagnosing DM was 0.823 (95% confidence interval, 0.699-0.948, P < .001). Overall, GTI increased on postoperative day 1 (POD#1, mean ± standard deviation, 1.79 ± 1.40 vs preoperative, 1.02 ± 1.41; P = .001), and then decreased by day 7 (0.89 ± 1.16 vs POD#1, P < .001). In the PD group, the GTI on POD#14 became lower than preoperative (0.51 ± 0.38 vs 0.96 ± 1.37; P = .03). PAI in the PD group was significantly lower at 1 month postoperatively (0.22 ± 0.12 vs preoperative, 0.38 ± 0.18; P < .001). In the PD group, RPV was significantly lower at 1 month postoperatively (25.3 ± 18.3 cm vs preoperative, 32.4 ± 20.1 cm; P = .02), due to the resolution of pancreatic duct dilatation. RPV of the DP group showed no significant change. GTI was negatively related to RPV preoperatively (r = -0.317, P = .04), but this correlation disappeared postoperatively (r = -0

  10. Pancreatic cystic neoplasms: Review of current knowledge, diagnostic challenges, and management options (United States)

    Jana, Tanima; Shroff, Jennifer; Bhutani, Manoop S.


    Pancreatic cystic lesions are being detected with increasing frequency, largely due to advances in cross-sectional imaging. The most common neoplasms include serous cystadenomas, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary neoplasms, and cystic pancreatic endocrine neoplasms. Computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS) are currently used as imaging modalities. EUS-guided fine needle aspiration has proved to be a useful diagnostic tool, and enables an assessment of tumor markers, cytology, chemistries, and DNA analysis. Here, we review the current literature on pancreatic cystic neoplasms, including classification, diagnosis, treatment, and recommendations for surveillance. Data for this manuscript was acquired via searching the literature from inception to December 2014 on PubMed and Ovid MEDLINE. PMID:25821410

  11. G protein-coupled receptor 39 deficiency is associated with pancreatic islet dysfunction

    DEFF Research Database (Denmark)

    Holst, Birgitte; Egerod, Kristoffer L; Jin, Chunyu


    tolerance both during oral and iv glucose tolerance tests, and Gpr39(-/-) mice had decreased plasma insulin response to oral glucose. Islet architecture was normal in the Gpr39 null mice, but expression of Pdx-1 and Hnf-1alpha was reduced. Isolated, perifused islets from Gpr39 null mice secreted less......alpha, and in the present study, we addressed the importance of GPR39 for glucose homeostasis and pancreatic islets function. The expression and localization of GPR39 were characterized in the endocrine pancreas and pancreatic cell lines. Gpr39(-/-) mice were studied in vivo, especially in respect...... of glucose tolerance and insulin sensitivity, and in vitro in respect of islet architecture, gene expression, and insulin secretion. Gpr39 was down-regulated on differentiation of the pluripotent pancreatic cell line AR42J cells toward the exocrine phenotype but was along with Pdx-1 strongly up...


    Murad, Shatha; Eisenberg, Yuval


    Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder of oxalate overproduction. It is associated with urolithiasis and nephrocalcinosis which progress to ESRD and systemic oxalosis. As oxalate deposits in tissues, non-parathyroid hormone (nonPTH) mediated hypercalcemia, oxalate osteopathy, primary hypothyroidism and primary hypogonadism develop. In this review, we will present a case of PH1 and provide an overview of this clinical entity and its endocrine manifestations. We conducted a PubMed search for articles related to PH1. The terms "primary hyperoxaluria," "nonPTH mediated hypercalcemia," "hypothyroidism," and "hypogonadism" were used to identify pertinent literature. Given the rarity of PH1, there is scant literature regarding the incidence and clinical significance of endocrine manifestations of this disorder. There are rare reports of hypercalcemia secondary to osteoclast-stimulating activity of macrophages in bone granulomas, which occur in response to oxalate deposits. We report that hypercalcemia may also be mediated by 1,25-dihydroxyvitamin D (1,25 (OH)2D) and parathyroid hormone-related protein (PTHrP). Primary hypothyroidism and primary hypogonadism are thought to be due partly to calcium oxalate deposition in thyroid and testicular tissue. The presented case is the first to report PTHrP mediated hypercalcemia and primary hypogonadism in a patient with PH1. PH1 is a metabolic disease with significant morbidity and mortality. Owing to its rarity, it is not widely recognized in the field of endocrinology, despite presenting with several endocrinopathies. Recognition of endocrine disturbances can result in early and successful treatment, limiting morbidity and improving quality of life in these challenging patients. PH = primary hyperoxaluria; ESRD = end stage renal disease; PTH = parathyroid hormone; 1,25 (OH)2D = 1,25 dihydoxyvitamin D; PTHrP = parathyroid hormone related protein; CKD = chronic kidney disease; AGT = alanine: glyoxylate

  13. CANCER Escape from senescence boosts tumour growth

    NARCIS (Netherlands)

    Medema, Jan Paul


    Some chemotherapies block cancer growth by driving tumour cells into a state of cell-division arrest termed senescence. It emerges that such cells have a boosted capacity to drive tumour growth if they exit senescence

  14. Follicular infundibulum tumour presenting as cutaneous horn

    Directory of Open Access Journals (Sweden)

    Jayaraman M


    Full Text Available Tumour of follicular infundibulum is an organoid tumour with a plate like growth attached to the epidermis with connection from the follicular epithelium. We are reporting such a case unusually presenting as cutaneous horn.

  15. Effects of growth hormone, prolactin, and placental lactogen on insulin content and release, and deoxyribonucleic acid synthesis in cultured pancreatic islets

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis


    The direct effects of human GH (hGH), ovine pituitary PRL (oPRL), and human chorionic somatomammotropin [placental lactogen (hPL)] on the endocrine pancreas were studied in isolated pancreatic islets maintained in tissue culture. Islets of Langerhans were isolated by collagenase treatment of panc...

  16. Pancreatitis del surco

    Directory of Open Access Journals (Sweden)

    Susana Araújo-Fernández


    It is a rare disease, but we must keep it in mind when we make the differential diagnosis of patients with abdominal pain of unknown origin. It is very important to distinguish this pathology from a pancreatic head carcinoma, as both treatments and prognosis differ greatly, so we believe important communication of a new case.

  17. Familial pancreatic cancer

    NARCIS (Netherlands)

    Hruban, R. H.; Petersen, G. M.; Goggins, M.; Tersmette, A. C.; Offerhaus, G. J.; Falatko, F.; Yeo, C. J.; Kern, S. E.


    For many years anecdotal case reports have suggested that pancreatic cancer aggregates in some families. Two recent advances have established that this is in fact the case. First, large registries, such as the National Familial Pancreas Tumor Registry (NFPTR) at Johns Hopkins, have identified a

  18. Medullary thyroid carcinoma and duodenal calcitonin-secreting neuroendocrine tumour: more than coincidence? (United States)

    Huguet, I; Lamas, C; Vera, R; Lomas, A; Quilez, R P; Grossman, A; Botella, F


    Summary Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms whose management can be problematic. In many cases, multiple tumours may occur in the same patient or his or her family, and some of these have now been defined genetically, although in other cases the underlying gene or genes involved remain unclear. We describe a patient, a 63-year-old female, who was diagnosed with a medullary thyroid carcinoma (MTC), which was confirmed pathologically after thyroidectomy, but whose circulating calcitonin levels remained elevated after thyroidectomy with no evidence of metastatic disease. Subsequently, an entirely separate and discrete duodenal NET was identified; this was 2.8 cm in diameter and was removed at partial duodenectomy. The tumour stained immunohistochemically for calcitonin, and its removal led to persistent normalisation of the circulating calcitonin levels. There was no germline mutation of the RET oncogene. This is the first identification of a duodenal NET secreting calcitonin and also the first demonstration of a second tumour secreting calcitonin in a patient with MTC. We suggest that where calcitonin levels remain high after removal of a MTC a search for other NETs should be conducted. Learning points NETs are a complex and heterogeneous group of related neoplasms, and multiple tumours may occur in the same patient.Calcitonin can be produced ectopically by several tumours outside the thyroid.Persistently elevated calcitonin levels after removal of a MTC may not necessarily indicate persisting or metastatic disease from the tumour.The real prevalence of calcitonin-producing NETs may be underestimated, as serum determination is only recommended in the diagnosis of pancreatic NETs. PMID:24616764

  19. Scintigraphy in benign bone tumours

    African Journals Online (AJOL)


    Aug 5, 1989 ... Ackerman LV, Spjut AJ. Tumors of Bone and Carrilage. Washington, DC: US Armed Forces Institute of Pathology, 1962: 84-89. 4. Evans RW. HislOlogical Appearances of Tumours. Edinburgh: E & S Living- stone, 1966: 187-191. 5. Lichtenstein L. Bane Tumors. 5th ed. St Louis, Mo.: CV Mosby, 1977: 30-39.

  20. Neuropathological diagnosis of brain tumours. (United States)

    Pollo, Bianca


    With recent progress in radiological, pathological, immunohistochemical, molecular and genetic diagnoses, the characterisation of brain tumours has improved. The last World Health Organization (WHO) Classification of Tumours of the Central Nervous System was done in 2007, based on morphological features, growth pattern and molecular profile of neoplastic cells, defined malignancy grade. The neuropathological diagnosis and the grading of each histotype are based on identification of histopathological criteria and immunohistochemical data. Molecular and genetic profiles may identify different tumour subtypes varying in biological and clinical behaviour, indicating prognostic and predictive factors. In order to investigate new therapeutic approaches, it is important to study the molecular pathways responsible for proliferation, invasion, angiogenesis, and anaplastic transformation. Different prognostic and predictive factors for glioma patients were identified by genetic studies, such as the loss of heterozygosis on chromosome 1p and 19q for oligodendrogliomas, proangiogenic factors such as Vascular Endothelial Growth Factor for glioblastomas and the methylation status of gene promoter of MethylGuanine-MethylTransferase. In conclusion, the prognostic evaluation and the therapeutic strategies for patients depend on the synthesis of histological diagnosis, malignancy grade, gene-molecular profile, radiological images, surgical resection and clinical findings (age, tumour location, and "performance status").

  1. Endocrine Consequences of Anorexia Nervosa (United States)

    Misra, Madhusmita; Klibanski, Anne


    Summary Anorexia nervosa (AN) is prevalent in adolescents and young adults, and endocrine changes include hypothalamic amenorrhea, a nutritionally acquired growth hormone resistance with low insulin like growth factor-1 (IGF-1), relative hypercortisolemia, decreases in leptin, insulin, amylin and incretins, and increases in ghrelin, PYY and adiponectin. These changes in turn have deleterious effects on bone, and may affect neurocognition, anxiety, depression and eating disorder psychopathology. Low bone density is particularly concerning; clinical fractures occur and changes in both bone microarchitecture and strength estimates have been reported. Recovery causes improvement of many, but not all, hormonal changes, and deficits in bone accrual may persist despite recovery. Physiologic, primarily transdermal, estrogen replacement increases bone density in adolescents, although catch-up is incomplete. In adults, oral estrogen co-administered with rhIGF-1 in one study, and bisphosphonates in another increased bone density, though not to normal. More studies are necessary to determine the optimal therapeutic approach in AN. PMID:24731664

  2. Behcet's Disease and Endocrine System

    Directory of Open Access Journals (Sweden)

    Onur Ozhan


    Full Text Available Behcet's disease (BD is a chronic disease which is characterized by recurrent oral apthous ulcerations, recurrent genital ulcerations, skin eruptions, ocular involvements and other various systemic manifestations as well as systemic vasculitis. Endocrine involvement in BD regarding various systems can be seen. Hypophysis is one of the best and dense vascularized organs of the body, thus it is likely that it can be affected by BD. Not only anterior hypophysis functions, but posterior hypophysis functions as well can be affected. As BD is a disease of autoimmune process, it may be possible that adrenal insufficiency or alterations in the cortisol levels could be expected. Another concern is whether or not there is insulin resistance in patients with BD. The avaliable data suggests that there is an increased susceptibility to insulin resistance in patients with BD.

  3. Chronic pancreatitis: An international draft consensus proposal for a new mechanistic definition. (United States)

    Whitcomb, David C; Frulloni, Luca; Garg, Pramod; Greer, Julia B; Schneider, Alexander; Yadav, Dhiraj; Shimosegawa, Tooru


    A definition of chronic pancreatitis (CP) is needed for diagnosis and distinguishing CP from other disorders. Previous definitions focused on morphology. Advances in epidemiology, genetics, molecular biology, modeling and other disciplines provide new insights into pathogenesis of CP, and allow CP to be better defined. Expert physician-scientists from the United States, India, Europe and Japan reviewed medical and scientific literature and clinical experiences. Competing views and approaches were debated until a new consensus definition was reached. CP has been defined as 'a continuing inflammatory disease of the pancreas, characterized by irreversible morphological change, and typically causing pain and/or permanent loss of function'. Focusing on abnormal morphology makes early diagnosis challenging and excludes inflammation without fibrosis, atrophy, endocrine and exocrine dysfunction, pain syndromes and metaplasia. A new mechanistic definition is proposed--'Chronic pancreatitis is a pathologic fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress.' In addition, "Common features of established and advanced CP include pancreatic atrophy, fibrosis, pain syndromes, duct distortion and strictures, calcifications, pancreatic exocrine dysfunction, pancreatic endocrine dysfunction and dysplasia." This definition recognizes the complex nature of CP, separates risk factors from disease activity markers and disease endpoints, and allows for a rational approach to early diagnosis, classification and prognosis. Initial agreement on a mechanistic definition of CP has been reached. This definition should be debated in rebuttals and endorsements, among experts and pancreatic societies until international consensus is reached. Copyright © 2016 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.

  4. Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold. (United States)

    Berman, Dora M; Molano, R Damaris; Fotino, Carmen; Ulissi, Ulisse; Gimeno, Jennifer; Mendez, Armando J; Kenyon, Norman M; Kenyon, Norma S; Andrews, David M; Ricordi, Camillo; Pileggi, Antonello


    Transplantation of pancreatic islets is a therapeutic option to preserve or restore β-cell function. Our study was aimed at developing a clinically applicable protocol for extrahepatic transplantation of pancreatic islets. The potency of islets implanted onto the omentum, using an in situ-generated adherent, resorbable plasma-thrombin biologic scaffold, was evaluated in diabetic rat and nonhuman primate (NHP) models. Intraomental islet engraftment in the biologic scaffold was confirmed by achievement of improved metabolic function and preservation of islet cytoarchitecture, with reconstitution of rich intrainsular vascular networks in both species. Long-term nonfasting normoglycemia and adequate glucose clearance (tolerance tests) were achieved in both intrahepatic and intraomental sites in rats. Intraomental graft recipients displayed lower levels of serum biomarkers of islet distress (e.g., acute serum insulin) and inflammation (e.g., leptin and α2-macroglobulin). Importantly, low-purity (30:70% endocrine:exocrine) syngeneic rat islet preparations displayed function equivalent to that of pure (>95% endocrine) preparations after intraomental biologic scaffold implantation. Moreover, the biologic scaffold sustained allogeneic islet engraftment in immunosuppressed recipients. Collectively, our feasibility/efficacy data, along with the simplicity of the procedure and the safety of the biologic scaffold components, represented sufficient preclinical testing to proceed to a pilot phase I/II clinical trial. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  5. Melanotic neuroectodermal tumour of the pineal region

    Energy Technology Data Exchange (ETDEWEB)

    Gorhan, C.; Soto-Ares, G.; Pruvo, J.P. [Dept. of Neuroradiology, Hopital Roger Salengro, CHRU Lille, Lille (France); Ruchoux, M.M. [Dept. of Neuropathology, Hopital Roger Salengro, CHRU Lille (France); Blond, S. [Dept. of Neurosurgery, Hopital Roger Salengro, CHRU Lille (France)


    We describe CT and MR findings in a 23-month-old infant with a melanotic neuroectodermal tumour of the pineal gland. The tumour has been stereotactically biopsied and surgically resected. The pathological diagnosis was made on the resected piece. Embryology of the pineal gland and the histology of melanotic neuroectodermal tumour of infancy are discussed. (orig.)

  6. Radiofrequency for the treatment of liver tumours

    NARCIS (Netherlands)

    Ruers, TJM; de Jong, KP; Ijzermans, JNM


    Resection should still be considered the gold standard for many liver tumours. There is, however, growing interest in the use of radiofrequency (RFA) for the treatment of liver tumours. By RFA, tumour tissue can be destructed selectively without significant damage to vascular structures in the

  7. Radiofrequency for the treatment of liver tumours.

    NARCIS (Netherlands)

    Ruers, T.J.M.; Jong, K.P. de; Ijzermans, J.N.M.


    Resection should still be considered the gold standard for many liver tumours. There is, however, growing interest in the use of radiofrequency (RFA) for the treatment of liver tumours. By RFA, tumour tissue can be destructed selectively without significant damage to vascular structures in the

  8. Mohs micrographic surgery of rare cutaneous tumours

    NARCIS (Netherlands)

    Flohil, S.C.; Lee, C.B. van; Beisenherz, J.; Mureau, M.A.M.; Overbeek, L.I.H.; Nijsten, T.; Bos, R.R.


    BACKGROUND: Recurrence rates after Mohs micrographic surgery (MMS) for rare cutaneous tumours are poorly defined. OBJECTIVE: To investigate the recurrence rate after MMS for rare cutaneous tumours at a university centre. METHODS & MATERIALS: Retrospective review of all rare cutaneous tumours treated


    African Journals Online (AJOL)

    Major Adebayo

    Abstract. Background: Metastatic tumours make up approximately one per cent of all oral malignancies. Such tumours may present in the jawbones and oral soft tissues. The commonest oral site is the mandible. Nigerian reports of metastatic tumours to the jaws are very rare. Method: This is a retrospective study of six cases ...

  10. Imaging of salivary gland tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y.Y.P.; Wong, K.T.; King, A.D. [Department of Diagnostic Radiology and Organ Imaging, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin NT, Hong Kong (Hong Kong); Ahuja, A.T. [Department of Diagnostic Radiology and Organ Imaging, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin NT, Hong Kong (Hong Kong)], E-mail:


    Salivary gland neoplasms account for <3% of all tumors. Most of them are benign and parotid gland is the commonest site. As a general rule, the smaller the involved salivary gland, the higher is the possibility of the tumor being malignant. The role of imaging in assessment of salivary gland tumour is to define intra-glandular vs. extra-glandular location, detect malignant features, assess local extension and invasion, detect nodal metastases and systemic involvement. Image guided fine needle aspiration cytology provides a safe means to obtain cytological confirmation. For lesions in the superficial parotid and submandibular gland, ultrasound is an ideal tool for initial assessment. These are superficial structures accessible by high resolution ultrasound and FNAC which provides excellent resolution and tissue characterization without a radiation hazard. Nodal involvement can also be assessed. If deep tissue extension is suspected or malignancy confirmed on cytology, an MRI or CT is mandatory to evaluate tumour extent, local invasion and perineural spread. For all tumours in the sublingual gland, MRI should be performed as the risk of malignancy is high. For lesions of the deep lobe of parotid gland and the minor salivary glands, MRI and CT are the modalities of choice. Ultrasound has limited visualization of the deep lobe of parotid gland which is obscured by the mandible. Minor salivary gland lesions in the mucosa of oral cavity, pharynx and tracheo-bronchial tree, are also not accessible by conventional ultrasound. Recent study suggests that MR spectroscopy may differentiate malignant and benign salivary gland tumours as well as distinguishing Warthin's tumor from pleomorphic adenoma. However, its role in clinical practice is not well established. Similarly, the role of nuclear medicine and PET scan, in imaging of parotid masses is limited. Sialography is used to delineate the salivary ductal system and has limited role in assessment of tumour extent.

  11. Acute Pancreatitis: Surgery, Pathophysiology and Probiotic Prophylaxis

    NARCIS (Netherlands)

    Minnen, L.P. van


    Acute pancreatitis is a challenging disease with a clinical course that is often difficult to predict. In severe acute pancreatitis, mortality increases significantly if intestinal bacteria translocate from the intestine and infect pancreatic necrosis. Surgical and prophylactic treatment strategies

  12. Analyzing endocrine system conservation and evolution. (United States)

    Bonett, Ronald M


    Analyzing variation in rates of evolution can provide important insights into the factors that constrain trait evolution, as well as those that promote diversification. Metazoan endocrine systems exhibit apparent variation in evolutionary rates of their constituent components at multiple levels, yet relatively few studies have quantified these patterns and analyzed them in a phylogenetic context. This may be in part due to historical and current data limitations for many endocrine components and taxonomic groups. However, recent technological advancements such as high-throughput sequencing provide the opportunity to collect large-scale comparative data sets for even non-model species. Such ventures will produce a fertile data landscape for evolutionary analyses of nucleic acid and amino acid based endocrine components. Here I summarize evolutionary rate analyses that can be applied to categorical and continuous endocrine traits, and also those for nucleic acid and protein-based components. I emphasize analyses that could be used to test whether other variables (e.g., ecology, ontogenetic timing of expression, etc.) are related to patterns of rate variation and endocrine component diversification. The application of phylogenetic-based rate analyses to comparative endocrine data will greatly enhance our understanding of the factors that have shaped endocrine system evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Fat, epigenome and pancreatic diseases. Interplay and common pathways from a toxic and obesogenic environment. (United States)

    Di Ciaula, Agostino; Portincasa, Piero


    The worldwide obesity epidemic is paralleled by a rise in the incidence of pancreatic disorders ranging from "fatty" pancreas to pancreatitis and cancer. Body fat accumulation and pancreatic dysfunctions have common pathways, mainly acting through insulin resistance and low-grade inflammation, frequently mediated by the epigenome. These mechanisms are affected by lifestyle and by the toxic effects of fat and pollutants. An early origin is common, starting in pediatric age or during the fetal life in response to nutritional factors, endocrine disruptor chemicals (EDCs) or parental exposure to toxics. A "fatty pancreas" is frequent in obese and is able to induce pancreatic damage. The fat is a target of EDCs and of the cytotoxic/mutagenic effects of heavy metals, and is the site of bioaccumulation of lipophilic and persistent pollutants related with insulin resistance and able to promote pancreatic cancer. Increased Body Mass Index (BMI) can act as independent risk factor for a more severe course of acute pancreatitis and obesity is also a well-known risk factor for pancreatic cancer, that is related with BMI, insulin resistance, and duration of exposure to the toxic effects of fat and/or of environmental pollutants. All these mechanisms involve gene-environment interactions through epigenetic factors, and might be manipulated by primary prevention measures. Further studies are needed, pointing to better assess the interplays of modifiable factors on both obesity and pancreatic diseases, and to verify the efficacy of primary prevention strategies involving lifestyle and environmental exposure to toxics. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  14. Peculiarities of death and regeneration of pancreas cells at early stages of alcoholic chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    N. Y. Oshmyanska


    Full Text Available The study has been conducted on 39 white laboratory male rats which formed 5 groups: experimental occlusal pancreatitis caused by ligation of the main pancreatic duct (n = 6, experimental alcoholic pancreatitis caused by oral intake of alcohol (n = 6, against the background of an excess (n = 6 or deficiency (n = 6 of nitric oxide, as well as a control group (n = 15. This study provides the detailed description of the processes of death and regeneration in the islets of Langerhans, typical for early stages of the disease. The expression of the proliferation markers (PCNA and Neurogenin-3 has been analyzed using histological and immunohistochemical methods along with the changes of morphological structure, that led to initiation of the alcoholic chronic pancreatitis against the background of imbalance in NO-ergic regulatory system caused by an excess or deficiency of nitric oxide. It has been found that ligation of the pancreatic duct in the experiment reconstructedthe circumstances of chronic pancreatitis in rats and caused the activation of fibrosis and regeneration of endocrine and exocrine tissue. Compared with occlusion, the effects of ethanol on the pancreas also manifested in the activation of fibrogenesis, but the structural changes were negligible and could unlikely lead to advanced fibrosis and chronic pancreatitis in the future. On the other side, an imbalance of NO-system in alcoholic rats leads to disruption of the zymogens secretion in the acinar cells and dilatation of the capillary network in islets. Uneven distribution of zymogen granules may lead to their intracellular activation as evidenced by the deformation of acini and focal apoptosis without inflammatory response. In this case, violation of the key adaptive responses in the pancreas makes it more vulnerable to the effects of ethanol, its metabolites, and other environmental factors, and may increase the probability of chronic pancreatitis development. At the same time


    Directory of Open Access Journals (Sweden)

    Ya. M. Vahrushev


    Full Text Available The aim. Research the clinical features, functional state of duodenum among patients with chronic pancreatitis and accompanying duodenostasis.Materials and methods. The clinical course of chronic pancreatitis with accompanying duodenostasis (85 cases and isolated chronic pancreatitis (56 cases has been studied. Along with the general clinical data the study includes the results of exocrine pancreatic function examination (fecal elastase-1, blood alpha amylase and lipase and its endocrine function (insulin and С-peptide. Regulating hormonal factors (gastrin and somatotropin have been studied. Was used results of rentgenology and endoscopic examinations, intraduodenal manometry results in verification of duodenostasis.Results. In the observation group resistant pain syndrome was revealed in 93% cases (at patient with isolated pancreatitis in 57% cases and in more degree was expressed coprological syndromes (amilorhea in 82,29% cases, creatorhea in 82,14% cases, steatorhea in 87,5% cases. In the observation group were significantly more diagnosed hyperperistaltic (in 88% cases of observation group and in 9,4% cases of the comparison group and duodenal hypertension (in 22% cases of observation group and in 0.0% cases of the comparison group. The phenomenon of «semolina» was reveals more often in observation group (in 31,9% cases of observation group and in 5% cases of the comparison group.Among patients with chronic pancreatitis and accompanying duodenostasis decrease the level of C-peptid and increase secretion of insulin, somatotropin and gastrin.Conclusion. It reveals that according to the comprehensive clinical and functional investigation chronic pancreatitis with accompanying duodenostasis gets a more severe course in comparison with isolated pancreatitis.

  16. Pancreatic encephalopathy- a rare complication of severe acute biliary pancreatitis

    Directory of Open Access Journals (Sweden)

    Vlad Denis Constantin


    Full Text Available Background. Pancreatic encephalopathy is a rare complication of severe acute pancreatitis, with high mortality, being difficult to diagnose and treat, thus requiring continuous research regarding its management. Materials and Methods. Of 20 patients diagnosed with severe acute pancreatitis on admission at Department of Emergency and Admission (DEA, from January 1st 2010 to March 31st 2014, 5 cases complicated by pancreatic encephalopathy were analyzed using a descriptive observational, retrospective, single-center study. Results. The study shows different types of diagnostic algorithm and therapeutical approaches, in correlation with morbidity and mortality rates. Conclusions. Our study highlighted the fact that speed is critical, early management being the key to outcome.

  17. Pancreatic islet autotransplantation with total pancreatectomy for chronic pancreatitis. (United States)

    Kuroki, Tamotsu; Adachi, Tomohiko; Ono, Shinichiro; Tanaka, Takayuki; Kitasato, Amane; Eguchi, Susumu


    Achieving pain relief and improving the quality of life are the main targets of treatment for patients with chronic pancreatitis. The use of total pancreatectomy to treat chronic pancreatitis is a radical and in some ways ideal strategy. However, total pancreatectomy is associated with severe diabetic control problems. Total pancreatectomy with islet autotransplantation can relieve severe pain and prevent the development of postsurgical diabetes. With islet autotransplantation, patients with chronic pancreatitis receive their own islet cells and therefore do not require immunosuppressive therapy. In the future, total pancreatectomy with islet autotransplantation may be considered a treatment option for chronic pancreatitis patients.

  18. Endoscopic Treatment of Recurrent Acute Pancreatitis and Smoldering Acute Pancreatitis. (United States)

    Das, Rohit; Yadav, Dhiraj; Papachristou, Georgios I


    Recurrent acute pancreatitis (RAP) is a challenging condition that can lead to chronic pancreatitis and long-term morbidity. Etiology-based treatment can potentially have an impact on the natural history of RAP and its progression to chronic pancreatitis. In cases of divisum-associated RAP and idiopathic RAP, several studies have been performed to evaluate the efficacy of endoscopic therapy in alleviation of symptoms and frequency of AP events. This review discusses the literature available on these topic as well as touching on the role of endoscopic therapy in smoldering acute pancreatitis. Published by Elsevier Inc.

  19. Genetically Determined Chronic Pancreatitis but not Alcoholic Pancreatitis Is a Strong Risk Factor for Pancreatic Cancer. (United States)

    Midha, Shallu; Sreenivas, Vishnubhatla; Kabra, Madhulika; Chattopadhyay, Tushar Kanti; Joshi, Yogendra Kumar; Garg, Pramod Kumar


    To study if chronic pancreatitis (CP) is a risk factor for pancreatic cancer. Through a cohort and a case-control study design, CP and other important risk factors including smoking, diabetes, alcohol, obesity, and genetic mutations were studied for their association with pancreatic cancer. In the cohort study, 402 patients with CP were included. During 3967.74 person-years of exposure, 5 of the 402 patients (4 idiopathic CP, 1 hereditary CP) developed pancreatic cancer after 16.60 ± 3.51 years of CP. The standardized incidence ratio was 121. In the case-control study, 249 pancreatic cancer patients and 1000 healthy controls were included. Of the 249 patients with pancreatic cancer, 24 had underlying idiopathic CP, and none had alcoholic pancreatitis. SPINK1 gene mutation was present in 16 of 26 patients with idiopathic CP who had pancreatic cancer. Multivariable analysis showed CP (odds ratio [OR], 97.67; 95% confidence interval [CI], 12.69-751.36), diabetes (>4 years duration) (OR, 3.05; 95% CI, 1.79-5.18), smoking (OR, 1.93; 95% CI, 1.38-2.69) as significant risk factors for pancreatic cancer. The population attributable risk was 9.41, 9.06, and 9.50 for diabetes, CP, and smoking, respectively. Genetically determined CP but not alcoholic CP is a strong risk factor for pancreatic cancer.

  20. Role of bacterial infections in pancreatic cancer


    Michaud, Dominique S.


    Established risk factors for pancreatic cancer, including tobacco smoking, chronic pancreatitis, obesity and type 2 diabetes, collectively account for less than half of all pancreatic cancer cases. Inflammation plays a key role in pancreatic carcinogenesis, but it is unclear what causes local inflammation, other than pancreatitis. Epidemiological data suggest that Helicobacter pylori may be a risk factor for pancreatic cancer, and more recently, data suggest that periodontal disease, and Porp...