The Experts below are selected from a list of 15798 Experts worldwide ranked by ideXlab platform
Markus M Lerch - One of the best experts on this subject based on the ideXlab platform.
-
spontaneous flow of bile through the human Pancreatic Duct in the absence of pancreatitis nature s human experiment
Endoscopy, 2003Co-Authors: Thorsten Pohle, J W Konturek, W Domschke, Markus M LerchAbstract:One hundred years ago E. L. Opie proposed two distinct hypotheses to address the pathogenesis of gallstone-induced pancreatitis. These hypotheses appear mutually exclusive. The first predicts that impediment to the flow of Pancreatic juice causes pancreatitis (the Pancreatic Duct obstruction hypothesis), whereas the second predicts that bile flow into the Pancreatic Duct behind an impacted gallstone would trigger the onset of acute pancreatitis (the common-channel hypothesis). One of the more convincing arguments against the latter hypothesis is the observation that bile, when experimentally perfused through the Pancreatic Duct of dogs, does not induce pancreatitis. This experimental situation had spontaneously developed in the patient we describe here: a bilioPancreatic fistula had permitted the continuous flow of bile through a large portion of the pancreas, which was associated with cholangitis but had apparently never led to pancreatitis. This patient's case would suggest that in humans, just as in experimental animals, bile flow through the Pancreatic Duct is not necessarily involved in the onset of gallstone-induced pancreatitis and lends further support to Opie's Pancreatic Duct obstruction hypothesis.
-
early changes in Pancreatic acinar cell calcium signaling after Pancreatic Duct obstruction
Journal of Biological Chemistry, 2003Co-Authors: Frank C Mooren, Verena Hlouschek, Till Finkes, S Turi, Ina Alexandra Weber, Jaipaul Singh, Wolfram Domschke, Jurgen Schnekenburger, Burkhard Kruger, Markus M LerchAbstract:Abstract Intracellular Ca2+-changes not only participate in important signaling pathways but have also been implicated in a number of disease states including acute pancreatitis. To investigate the underlying mechanisms in an experimental model mimicking human gallstone-induced pancreatitis, we ligated the Pancreatic Duct of Sprague-Dawley rats and NMRI mice for up to 6 h and studied intraPancreatic changes including the dynamics of [Ca2+]i in isolated acini. In contrast to bile Duct ligation, Pancreatic Duct obstruction induced intra-Pancreatic trypsinogen activation, leukocytosis, hyperamylasemia, and Pancreatic edema and increased lung myeloperoxidase activity. Although resting [Ca2+]i in isolated acini rose by 45% to 205 ± 7 nmol, the acetylcholine- and cholecystokinin (CCK)-stimulated calcium peaks as well as the amylase secretion declined, but neither the [Ca2+]i-signaling pattern nor the amylase output in response to the Ca2+-ATPase inhibitor thapsigargin nor the secretin-stimulated amylase release were impaired by Pancreatic Duct ligation. On the single cell level Pancreatic Duct ligation reduced the percentage of cells in which submaximal secretagogue stimulation was followed by a physiological response (i.e.Ca2+ oscillations) and increased the percentage of cells with a pathological response (i.e. peak plateau or absent Ca2+ signal). Moreover, it reduced the frequency and amplitude of Ca2+ oscillation as well as the capacitative Ca2+ influx in response to secretagogue stimulation. Serum Pancreatic enzyme elevation as well as trypsinogen activation was significantly reduced by pretreatment of animals with the calcium chelator BAPTA-AM. These experiments suggest that Pancreatic Duct obstruction rapidly changes the physiological response of the exocrine pancreas to a Ca2+-signaling pattern that has been associated with premature digestive enzyme activation and the onset of pancreatitis, both of which can be prevented by administration of an intracellular calcium chelator.
-
Pancreatic Duct obstruction triggers acute necrotizing pancreatitis in the opossum
Gastroenterology, 1993Co-Authors: Markus M Lerch, Ashok K Saluja, Michael Runzi, Rajinder Dawra, Manju SalujaAbstract:Abstract Background : The common channel theory suggests that bile reflux, through a common bilioPancreatic channel, triggers acute pancreatitis. In the present study, this controversial issue was evaluated using an experimental model of hemorrhagic necrotizing pancreatitis. Methods : American opossums underwent ligation of the Pancreatic Duct alone, bile and Pancreatic Duct separately, or common bilioPancreatic Duct; the severity of pancreatitis was evaluated at selected times after ligation. Results : Animals in all three experimental groups developed hemorrhagic necrotizing pancreatitis; the severity of pancreatitis was similar in each group, although only those subjected to common bilioPancreatic Duct ligation experienced bile reflux. Conclusions : Bile reflux into the Pancreatic Duct, via a common bilioPancreatic channel, is not necessary for the development of pancreatitis and does not worsen the severity of pancreatitis associated with Pancreatic Duct obstruction in this model.
Mingsound Tsao - One of the best experts on this subject based on the ideXlab platform.
-
human Pancreatic Duct epithelial cell model for kras transformation
Methods in Enzymology, 2008Co-Authors: Nikolina Radulovich, Mingsound Tsao, Jiaying QianAbstract:Abstract Mutations on the KRAS gene occur early during Pancreatic Duct cell carcinogenesis and have been identified in up to 90% of Ductal adenocarcinoma. However, the functional role of KRAS mutations in the malignant transformation of normal Pancreatic Duct epithelial cells into cancer cells remains unknown. We have developed an in vitro model for KRAS transformation using near‐normal HPV‐16E6E7‐immortalized human Pancreatic Ductal epithelial (HPDE‐E6E7) cells. The expression of mutant KRASG12V in HPDE cells by retroviral transDuction resulted in weak tumorigenic transformation, with tumors formed in 50% of immune‐deficient scid mice implanted by these KRAS‐transformed cells. The model provides an opportunity to dissect further the molecular and cellular mechanisms associated with human Pancreatic Duct cell carcinogenesis.
-
immortal human Pancreatic Duct epithelial cell lines with near normal genotype and phenotype
American Journal of Pathology, 2000Co-Authors: Hong Ouyang, Mingsound Tsao, Lunjun Mou, Catherine Luk, Ni Liu, Jana Karaskova, Jeremy A SquireAbstract:Immortal epithelial cell lines were previously established after transDuction of the HPV16-E6E7 genes into primary cultures of normal Pancreatic Duct epithelial cells. Single clones were isolated that demonstrated near normal genotype and phenotype. The proliferation of HPDE6-E6E7c7 and c11 cells is anchorage-dependent, and they were nontumorigenic in SCID mice. The cell lines demonstrated many phenotypes of normal Pancreatic Duct epithelium, including mRNA expression of carbonic anhydrase II, MUC-1, and cytokeratins 7, 8, 18, and 19. These cells have normal Ki- ras, p53 , c- myc , and p16 INK4A genotypes. Cytogenetic studies demonstrated losses of 3p, 10p12, and 13q14, the latter included the Rb1 gene. The wild-type p53 protein was detectable at very low levels consistent with the presence of E6 gene proDuct, and the lack of functional p53 pathway was confirmed by the inability for γ-irradiation to up-regulate p53 and p21 waf1/cip1 protein. The p110/Rb protein level was also not detectable consistent with the expression of E7 protein and haploid loss of Rb1 gene. Despite this, the proliferation of both c7 and c11 cells were markedly inhibited by transforming growth factor-β1. This was associated with up-regulation of p21 cip1/waf1 but not p27 kip1 . Further studies showed that p130/Rb2 and cyclin D3 were expressed, suggesting that p130/Rb2 may have partially assumed the maintenance of G 1 cell cycle checkpoint regulation. These results indicate that except for the loss of p53 functional pathway, the two clones of HPDE6-E6E7 cells demonstrated a near normal genotype and phenotype of Pancreatic Duct epithelial cells. These cell lines will be useful for future studies on the molecular basis of Pancreatic Duct cell carcinogenesis and islet cell differentiation.
Manju Saluja - One of the best experts on this subject based on the ideXlab platform.
-
Pancreatic Duct obstruction triggers acute necrotizing pancreatitis in the opossum
Gastroenterology, 1993Co-Authors: Markus M Lerch, Ashok K Saluja, Michael Runzi, Rajinder Dawra, Manju SalujaAbstract:Abstract Background : The common channel theory suggests that bile reflux, through a common bilioPancreatic channel, triggers acute pancreatitis. In the present study, this controversial issue was evaluated using an experimental model of hemorrhagic necrotizing pancreatitis. Methods : American opossums underwent ligation of the Pancreatic Duct alone, bile and Pancreatic Duct separately, or common bilioPancreatic Duct; the severity of pancreatitis was evaluated at selected times after ligation. Results : Animals in all three experimental groups developed hemorrhagic necrotizing pancreatitis; the severity of pancreatitis was similar in each group, although only those subjected to common bilioPancreatic Duct ligation experienced bile reflux. Conclusions : Bile reflux into the Pancreatic Duct, via a common bilioPancreatic channel, is not necessary for the development of pancreatitis and does not worsen the severity of pancreatitis associated with Pancreatic Duct obstruction in this model.
Yasushi Hashimoto - One of the best experts on this subject based on the ideXlab platform.
-
circumportal pancreas with retroportal main Pancreatic Duct
Pancreas, 2009Co-Authors: Yasushi Hashimoto, Andrew S Ross, L W TraversoAbstract:There have been 6 cases of circumportal pancreas reported, and 2 of them had the main Pancreatic Duct in a retroportal dorsal portion. This extremely uncommon anomaly is asymptomatic and therefore incidentally discovered. For the surgeon, it is important to discover this during Pancreatic resection so the Pancreatic Duct can be closed and fistula is avoided. We describe the third case where a circumportal pancreas had its main Pancreatic Duct passing under the portal vein. The Duct was identified and ligated. A fistula did not occur.
-
main Pancreatic Duct obstruction due to a small nonfunctioning endocrine tumor of the pancreas
Hiroshima journal of medical sciences, 2009Co-Authors: Kenichiro Uemura, Hiroki Ohge, Tamito Sasaki, Koji Arihiro, Yasushi Hashimoto, Yoshiaki Murakami, Yasuo Hayashidani, Takeshi Sudo, Taijiro SuedaAbstract:A 65-year-old Japanese male was referred to our hospital for evaluation of a main Pancreatic Duct obstruction. Two months previously, he had suffered an attack of acute pancreatitis that was resolved with conservative treatment. Dynamic contrast-enhanced study by multidetector row computed tomography revealed a well-enhanced 5 x 5 mm mass in the head of the pancreas with dilatation of the main Pancreatic Duct in the body and tail. On endoscopic retrograde pancreatography, obstruction of the main Pancreatic Duct in the head of the pancreas was noted. Pancreatic juice cytology was nondiagnostic. Endoscopic ultrasonography demonstrated a well-defined hypoechoic mass, about 5 mm in size, with distal main Pancreatic Duct dilatation. The patient underwent elective pylorus-preserving Pancreaticoduodenectomy. Pathological examination revealed a well-differentiated endocrine tumor of the pancreas of uncertain behavior, 5 mm in size. Immunohistochemically, the tumor was diffusely positive for chromogranin A and synaptophysin, and focally it was positive for insulin, glucagon, and CA19-9; it was negative for gastrin. The final diagnosis was main Pancreatic Duct obstruction secondary to a nonfunctioning endocrine tumor of the pancreas of uncertain behavior. Of note, a small nonfunctioning endocrine tumor of the pancreas is important in the differential diagnosis of main Pancreatic Duct obstruction demonstrated by radiographic examinations.
-
main Pancreatic Duct obstruction due to a small nonfunctioning endocrine tumor of the pancreas
Hiroshima journal of medical sciences, 2009Co-Authors: Kenichiro Uemura, Hiroki Ohge, Tamito Sasaki, Koji Arihiro, Yasushi Hashimoto, Yoshiaki Murakami, Yasuo Hayashidani, Takeshi Sudo, Taijiro SuedaAbstract:A 65-year-old Japanese male was referred to our hospital for evaluation of a main Pancreatic Duct obstruction. Two months previously, he had suffered an attack of acute pancreatitis that was resolved with conservative treatment. Dynamic contrast-enhanced study by multidetector row computed tomography revealed a well-enhanced 5 x 5 mm mass in the head of the pancreas with dilatation of the main Pancreatic Duct in the body and tail. On endoscopic retrograde pancreatography, obstruction of the main Pancreatic Duct in the head of the pancreas was noted. Pancreatic juice cytology was nondiagnostic. Endoscopic ultrasonography demonstrated a well-defined hypoechoic mass, about 5 mm in size, with distal main Pancreatic Duct dilatation. The patient underwent elective pylorus-preserving Pancreaticoduodenectomy. Pathological examination revealed a well-differentiated endocrine tumor of the pancreas of uncertain behavior, 5 mm in size. Immunohistochemically, the tumor was diffusely positive for chromogranin A and synaptophysin, and focally it was positive for insulin, glucagon, and CA19-9; it was negative for gastrin. The final diagnosis was main Pancreatic Duct obstruction secondary to a nonfunctioning endocrine tumor of the pancreas of uncertain behavior. Of note, a small nonfunctioning endocrine tumor of the pancreas is important in the differential diagnosis of main Pancreatic Duct obstruction demonstrated by radiographic examinations.
Santhi Swaroop Vege - One of the best experts on this subject based on the ideXlab platform.
-
disconnected Pancreatic Duct syndrome endoscopic stent or surgeon s knife
Pancreas, 2015Co-Authors: Nikhil A Nadkarni, Vikram Kotwal, Michael G Sarr, Santhi Swaroop VegeAbstract:Disconnected Pancreatic Duct syndrome is a sequela of necrotizing pancreatitis or Pancreatic trauma in which necrosis of a segment of the pancreas leads to lack of continuity between viable secreting Pancreatic tissue (eg, body or tail) and the gastrointestinal tract. The endoscopic retrograde cholangiopancreatography showing total cutoff of the Pancreatic Duct along with an enhancing distal pancreas on contrast-enhanced computed tomography remains the criterion standard for diagnosis. Recently, the evolving literature supports a role for magnetic resonance cholangioPancreaticography, especially with secretin stimulation. A multidisciplinary approach is extremely important in the management of this condition. Conservative measures are usually not helpful, and interventional radiology, endoscopic, or surgical intervention is almost always needed for management of these patients. Recently, endoscopic ultrasonography-guided drainage procedures in conjunction with endoscopic retrograde cholangiopancreatography-assisted Pancreatic Duct stenting have emerged as a novel technique to manage this condition. The aim of this review was to give a detailed overview about the diagnosis and management of disconnected Pancreatic Duct syndrome with emphasis on the changing paradigm in endoscopic and surgical management.
