(Journal Article): Glucose Tolerance, Insulin Secretion and Insulin Sensitivity in Polycystic Ovary Syndrome.
Pasquali R, Pelusi C, Ragazzini C, Hasanaj R, Gambineri A (Endocrinology Unit, Department of Internal Medicine, S.Orsola-Malpighi Hospital, University Alma Mater Studiorum. Bologna, Italy,
rpasqual@almadns.unibo.it
)
IN:
JOP. J Pancreas (Online)
2002; 03(1):1-7
TYPE OF PUBLICATION: Editorial
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(Journal Article): Analysis and Optimization of Nutritional Set-up for Murine Pancreatic Acinar Cells.
Kurup S, Bhonde RR (National Center for Cell Science, University of Pune Campus. Ganeshkhind, Pune, India,
rrbhonde(at)hotmail.com
)
IN:
JOP. J Pancreas (Online)
2002; 03(1):8-15
ABSTRACT: CONTEXT: Pancreatic acinar cell cultivation poses a serious problem due to limitations in the in vitro survival time despite variations of dissociation protocols, culture media and nutrient supplements. OBJECTIVE: To establish a long term culture of murine pancreatic acinar cells which retain their viability, monolayer formation and responsiveness to secretagogues. In order to investigate the mechanism of the short-life of acinar cells studied in vitro, we studied their survival under the influence of different supplements on nutrient media. INTERVENTIONS: Dissociated pancreatic acini were prepared from BALB/c mice pancreata by collagenase digestion supplemented with bovine serum albumin fraction V and soybean trypsin inhibitor. A nutrient set-up was designed for their long term survival in vitro. RESULTS: It was observed that mouse pancreatic acinar cells dissociated in presence of bovine serum albumin fraction V and soybean trypsin inhibitor result in 95% viability. Further cultivation of these acinar cells in Waymouth's MB 752/1 medium supplemented with 10% fetal calf serum (v/v), soybean trypsin inhibitor, bovine serum albumin, dexamethasone, and epidermal growth factor results in their survival for more than 6 days in culture with 85% viability, retention of the secretagogue responsiveness and formation of a monolayer without any extracellular matrix coating. CONCLUSIONS: Our study clearly demonstrates that the addition of soybean trypsin inhibitor to culture medium reduces zymogen granule fragility and acinar cell death, thus increasing their viability for sufficiently long periods. The present study offers an excellent, in vitro model for the investigation of exocrine dysfunction in response to acinar cell injury.
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(Journal Article): A New Classification Plot for the C-Peptide Suppression Test.
Saddig C, Bender R, Starke AAR (Department of Metabolism and Nutrition, Heinrich-Heine-University. Duesseldorf, Germany. Department of Epidemiology and Medical Statistics, School of Public Health, University of Bielefeld. Bielefeld, Germany,
starkea@uni-duesseldorf.de
)
IN:
JOP. J Pancreas (Online)
2002; 03(1):16-25
ABSTRACT: CONTEXT AND OBJECTIVE: To evaluate the C-peptide suppression test as a screening test in patients with symptoms of hypoglycemia as compared to the standard fasting test. DESIGN: Retrospective discriminant analysis of data from C-peptide suppression tests. SETTING: Clinical study. PATIENTS: Patients with insulinomas and patients without insulinomas but having symptoms compatible with hypoglycemia. INTERVENTIONS: The results from C-peptide suppression tests of 26 patients with insulinomas and 100 patients without insulinomas were compared. MAIN OUTCOME MEASURES: A classification plot which introduces two discriminant parameters for the C-peptide suppression test: the ratio of [blood glucose]/[C-peptide] at the lowest C-peptide concentration and mean glycemia during insulin infusion. RESULTS: In patients with insulinomas, minimal serum C-peptide levels were higher (1.81+/- 0.87 ng/mL; median 1.83 ng/mL; maximal suppression 37 +/- 24% of basal C-peptide levels) as compared to patients without insulinoma (0.40 +/- 0.15 ng/mL; median 0.30 ng/mL; maximal suppression of 75 +/- 9%; P less than 0.001). Mean glycemia during the test was lower in patients with insulinomas (30.8 +/- 3.3 vs. 47.5 +/- 8.3 mg/dL; P less than 0.001) as was the [blood glucose]/[C-peptide] ratio (21.9 +/- 14.6 vs. 139.2 +/- 43.8; P less than 0.001). Discriminant analysis revealed a specificity of 96% to rule out the diagnosis of insulinoma at a 1% probability threshold with a sensitivity of 100%. CONCLUSIONS: We developed a new classification plot for the C-peptide suppression test in order to accurately identify those patients whose symptoms of hypoglycemia are not due to endogenous hyperinsulinemia/insulinomas. Thus, the need for fasting tests and hospitalization costs can be reduced.
TYPE OF PUBLICATION: Original Article
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(Journal Article): Neurology and Neuropathology of the Pancreatic Innervation
Salvioli B, Bovara M, Barbara G, De Ponti F, Stanghellini V, Tonini M, Guerrini S, Cremon C, Degli Esposti M, Koumandou M, Corinaldesi R, Sternini C, De Giorgio R (Department of Internal Medicine and Gastroenterology and Department of Pharmacology, University of Bologna. Bologna, Italy. University of Pavia. Pavia, Italy. UCLA School of Medicine. Los Angeles, CA, USA,
deg@orsola-malpighi.med.unibo.it
)
IN:
JOP. J Pancreas (Online)
2002; 03(2):26-33
TYPE OF PUBLICATION: Editorial
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(Journal Article): Trypsin-Based Laboratory Methods and Carboxypeptidase Activation Peptide in Acute Pancreatitis
Kylänpää-Bäck ML, Kemppainen E, Puolakkainen P (Department of Surgery, Helsinki University Central Hospital. Helsinki, Finland. The Hope Heart Institute and the University of Washington. Seattle, WA, USA,
ppuolakkainen@hopeheart.org
)
IN:
JOP. J Pancreas (Online)
2002; 03(2):34-48
ABSTRACT: Acute pancreatitis is a common disease varying widely in severity. At present, there is no 'gold standard' for the diagnosis of acute pancreatitis. Currently, the diagnosis of acute pancreatitis is based on measurements of serum amylase and/or lipase activity, which are considered unsatisfactory due to their low level of accuracy. Early identification of acute pancreatitis and especially detection of patients with a severe form of the disease is of utmost importance. Premature intrapancreatic activation of trypsinogen is a crucial early event in the pathophysiology of acute pancreatitis. The conversion of trypsinogen to active trypsin is mediated by the release of its activation peptide (TAP). The active trypsin is then able to activate other pancreatic zymogens (i.e. procarboxypeptidase) leading to tissue damage and eventually to autodigestion of the pancreas. To improve the laboratory diagnostics of AP, new methods have been developed to measure this primary pancreatic proteolytic insult. Here we review the current knowledge and clinical implications of trypsin based laboratory methods and carboxypeptidase activation peptide (CAPAP) in the diagnosis and severity assessment of acute pancreatitis.
TYPE OF PUBLICATION: Review
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(Journal Article): Increased Early Rejection Rate after Conversion from Tacrolimus in Kidney and Pancreas Transplantation
Barone GW, Ketel BL, Abul-Ezz SR, Lightfoot ML (Department of Surgery and Department of Medicine, University of Arkansas for Medical Sciences. Little Rock, AR, USA,
baronegary@uams.edu
)
IN:
JOP. J Pancreas (Online)
2002; 03(2):49-53
ABSTRACT: CONTEXT: A successful immunosuppression regimen for combined kidney and pancreas transplants is tacrolimus, mycophenolate mofetil, and prednisone. However, not all patients tolerate these immunosuppressants especially tacrolimus. OBJECTIVE: To evaluate the efficacy of cyclosporine as a rescue agent for tacrolimus toxicity in combined kidney and pancreas transplants. DESIGN: Retrospective. SETTING: Single center. PATIENTS: Thirty-five combined kidney and pancreas transplants were performed between July 1994 and January 1999. All patients were insulin dependent diabetics with end-stage renal disease. Twenty-eight (mean age: 36 years and 57% female) were available with at least 12 month follow-up. INTERVENTIONS: Conversion to cyclosporine following renal (biopsy proven) or pancreatic dysfunction. MAIN OUTCOME MEASURES: Toxicity, rejection rate, and patient/transplant organ survival. RESULTS: Nineteen transplant recipients (68%) were continuously maintained on tacrolimus while nine (32%) required conversion to cyclosporine 75 +/- 20 days post-transplant. Reasons for conversion included: hyperglycemia (n=2), hemolytic-uremic syndrome (n=1), and severe tacrolimus nephrotoxicity (n=6). By 12 months post-transplant, the 19 patients maintained on tacrolimus had 5 rejections (26%). Three of the 9 patients (33%) converted to cyclosporine had an acute rejection prior to conversion. Seven of these 9 patients (78%; P=0.017 vs. patients maintained on tacrolimus) had rejections an average of 25 +/- 4 days post-conversion. Four of the 7 patients had no previous rejections prior to conversion. In spite of increased rejections, the 1- and 2-year patient/graft survivals were unchanged by converting. CONCLUSIONS: Converting to cyclosporine from tacrolimus was associated with an increased risk of acute rejection especially within the first 30 days post conversion.
TYPE OF PUBLICATION: Original Article
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(Journal Article): Pancreatic Stone Protein of Pancreatic Calculi in Chronic Calcified Pancreatitis in Man
Jin CX, Naruse S, Kitagawa M, Ishiguro H, Kondo T, Hayakawa S, Hayakawa T (Second Department of Internal Medicine, Nagoya University School of Medicine. Nagoya, Japan. Department of Clinical Chemistry, Maruko Pharmaceutical Co. Kasugai, Japan,
thayaka@med.nagoya-u.ac.jp
)
IN:
JOP. J Pancreas (Online)
2002; 03(2):54-61
ABSTRACT: CONTEXT: The role of protein components of pancreatic secretions has been controversial in pancreatic stone formation. OBJECTIVE: To study the lithogenic role of pancreatic stone protein and lactoferrin in stone formation in chronic pancreatitis. PATIENTS: Pancreatic stones were collected from 13 patients with alcoholic (n=6) and nonalcoholic (n=7) chronic calcified pancreatitis. MAIN OUTCOME MEASURES: Pancreatic stone extracts were analyzed for pancreatic stone protein and lactoferrin using enzyme immunoassay. The localization of pancreatic stone protein immunoreactivity in the stone was observed using immunogold staining and scanning electron microscopy. RESULTS: Immunoreactivities for pancreatic stone protein were detected in the stones from all 13 patients with chronic calcified pancreatitis and for lactoferrin in the stones from five of the 13 patients. Pancreatic stone protein immunoreactivity distributed diffusely from the center to the periphery of the pancreatic stones. CONCLUSIONS: Involvement of pancreatic stone protein seems to be constant from the initial step of the stone formation to subsequent steps of the stone growth. However, pancreatic stone protein is only one of the precipitating proteins in pancreatic secretions such as lactoferrin, trypsinogen, etc.
TYPE OF PUBLICATION: Original Article
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(Journal Article): How Far Are we From the Most Accurate Classification System for Chronic Pancreatitis ?
Uomo G (Internal Medicine Department, 3rd Division, Cardarelli Hospital. Naples, Italy,
g.f.uomo@digimaint.it
)
IN:
JOP. J Pancreas (Online)
2002; 03(3):62-65
TYPE OF PUBLICATION: Editorial
|
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(Journal Article): Localization and Expression of CCR3 and CCR5 by Interleukin-1? in the RIN-5AH Insulin-Producing Model System: A Protective Mechanism Involving Down-Regulation of Chemokine Receptors
Vassiliadis S, Balabanidou V, Papadopoulos GK, Athanassakis I (Laboratory of Immunology, Department of Biology, University of Crete. Heraklion, Crete, Greece,
simon@biology.uoc.gr
)
IN:
JOP. J Pancreas (Online)
2002; 03(3):66-75
ABSTRACT: CONTEXT AND OBJECTIVE: The inflammatory cytokine interleukin-1beta has been considered to be an immune effector molecule in insulin dependent diabetes mellitus. As such, we examined its role on chemokine receptors which, when expressed in the pancreas, have also been associated with the development of type I autoimmune diabetes. DESIGN AND MAIN OUTCOME MEASURES: The presence of membrane and cytoplasmic levels of CCR3 and CCR5 expression is assessed by immunofluorescence in control and interleukin-1beta-treated RIN-5AH cells. The cytoplasmic expression is also shown by confocal microscopy as assessed by the brightness of the cells whereas enzyme-linked immunosorbent assay detects secreted CCR3 and CCR5 molecules by comparing optical density values as these derive from the control and the treated cells. Cell-fractionation experiments show the exact location of the intracellular pools of the chemokine receptors by using the rab7 monoclonal antibody as a guiding molecule. RESULTS: Interleukin-1beta down-regulates constitutively expressed surface CCR3 and CCR5 levels implying receptor internalization for re-utilization or destruction, secretion or both. Cytoplasmic immunofluorescence and confocal microscopy demonstrate cellular retention of chemokine receptors by interleukin-1beta which may be released in the absence of interleukin-1beta as assessed by enzyme-linked immunosorbent assay. Finally, cell-fractionation shows the presence of both receptors in endosomes exhibiting an increasing density after interleukin-1beta treatment. CONCLUSIONS: Given the association of chemokine receptors with progression to diabetes, it appears that interleukin-1beta-induced down-regulation of CCR3 and CCR5 promotes a protective mechanism against cellular destruction. The major role of interleukin-1beta is to maintain these molecules within the endosomes. Thus, interleukin-1beta modulates the movement and the expression of constitutively expressed chemokine receptors and does not accentuate the total destructive effect suffered by the cells.
TYPE OF PUBLICATION: Original Article
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(Journal Article): A Single Treatment with IL-4 via Retrovirally Transduced Lymphocytes Partially Protects Against Diabetes in BioBreeding (BB) Rats
Zipris D, Karnieli E (The Institute of Endocrinology, Diabetes, and Metabolism, Rambam Medical Center. B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology. Haifa, Israel,
eddy@tx.technion.ac.il
)
IN:
JOP. J Pancreas (Online)
2002; 03(3):76-82
ABSTRACT: CONTEXT: Type 1 diabetes mellitus is a T cell mediated autoimmune disease with no known methods of prevention. The BioBreeding rat is used as an animal model for the study of human Type 1 diabetes. In spite of a severe lymphopenia, these animals develop spontaneous diabetes at the age of 10-12 weeks. OBJECTIVE: To examine whether anti-inflammatory gene therapy could be used to prevent autoimmune diabetes in the BioBreeding rat. DESIGN: A retroviral DNA vector, MSCVneo.IL-4, carrying the DNA sequence encoding the rat interleukin-4, was designed to transfer interleukin-4 to BioBreeding rats. Spleen cells of prediabetic animals were activated and transduced in vitro with replication-defective retroviruses expressing the MSCVneo.IL-4 vector. These lymphocytes were subsequently administered intraperitoneally to 3-4 week old prediabetic BioBreeding rats. Control animals were reconstituted with spleen cells transduced with MSCVneo vector. RESULTS: The neo gene marker was detectable by RT-PCR in rat spleen cells of up to 6 to 12 months after treatment. Fifty percent (6 out of 12) of the animals treated were protected from autoimmune disease development. CONCLUSION: Our results suggest that the BioBreeding rat can be used as a useful model to develop gene therapy regimens for diabetes. These studies provide further support for the hypothesis that interleukin-4 based gene therapy may have potential clinical value for preventing autoimmune diabetes in humans.
TYPE OF PUBLICATION: Original Article
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(Journal Article): Sphincter of Oddi and Acute Pancreatitis: A New Treatment Option
Lai KH (Department of Internal Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang Ming University. Taiwan, ROC,
khlai@isca.vghks.gov.tw
)
IN:
JOP. J Pancreas (Online)
2002; 03(4):83-85
TYPE OF PUBLICATION: Editorial
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(Journal Article): Islet Redox Stress: The Manifold Toxicities of Insulin Resistance, Metabolic Syndrome and Amylin Derived Islet Amyloid in Type 2 Diabetes Mellitus
Hayden MR, Tyagi SC (Department of Cardiovascular Atherosclerosis, Metabolism and Aging, Camdenton Community Health Center. Camdenton, Missouri, USA,
mrh29@usmo.com
)
IN:
JOP. J Pancreas (Online)
2002; 03(4):86-108
ABSTRACT: CONTEXT: Redox stress, reactive oxygen species, reactive nitrogen species, and oxygen free radicals ('toxic oxygen') are increasingly being reported as important cellular signaling mechanisms. It has been known for over a hundred years that type 2 diabetes mellitus is a manifold disease, not only in its etiology, but also in its associated manifold toxicities and multiple complications of the diabetic opathies. The presence of islet amyloid has also been described in association with type 2 diabetes mellitus for a century. OBJECTIVE: This review will attempt to remain focused on the relationship between redox stress, the reactive oxygen species and the reactive nitrogen species in the islet, and how these interact with the multiplicative effect of the toxicities of insulin resistance, metabolic syndrome, amylin (hyperamylinemia), amylin derived islet amyloid and type 2 diabetes mellitus. CONCLUSIONS: Redox sensitive cellular signaling systems play an important role in the development, progressive nature (remodeling) and damaging effects on the beta cell within the islet of the pancreas. Furthermore, redox stress may play an important role in the remodeling and development of islet amyloid creating a space-occupying lesion with a resultant secretory and absorptive defect within the islet. The presence of manifold toxicities necessitates an approach of global risk reduction in the prevention and treatment of type 2 diabetes mellitus. An improved understanding of the dynamic relationship between these toxicities and redox stress within the islet will aid both the researcher and the clinician.
TYPE OF PUBLICATION: Review
Articles citing this article:
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(Journal Article): Overexpression of the Sm-Like Proto-Oncogene in Primary and Metastatic Pancreatic Endocrine Tumors
Gumbs AA, Bassi C, Moore PS, Falconi M, Frigerio I, Baron A, Piemonti L, Modlin I, Scarpa A (Department of Surgical and Gastroenterological Sciences and Department of Pathology, University of Verona. Verona, Italy,
a.scarpa@univr.it
)
IN:
JOP. J Pancreas (Online)
2002; 03(4):109-115
ABSTRACT: CONTEXT: The cancer associated Sm-like proto-oncogene mRNA has been found to be overexpressed in the majority of pancreatic adenocarcinomas and is necessary for the transformed phenotype in pancreatic cancer cell lines. However, expression levels have not been examined in other types of pancreatic neoplasms, such as pancreatic endocrine tumors. SETTING: Fifteen primary pancreatic endocrine tumors, including five insulinomas and 10 non-functioning tumors, along with seven hepatic metastatic pancreatic endocrine tumors. MAIN OUTCOME MEASURES: Quantitative expression levels of cancer associated Sm-like mRNA were measured by real-time PCR. Overexpression was defined as a two-fold or greater value when compared to the expression levels found in normal pancreatic islet cells obtained from healthy donors. RESULTS: In primary tumors, four of the 10 non-functioning pancreatic endocrine tumors were found to overexpress cancer associated Sm-like mRNA (40%). Three of the five (60%) insulinomas also overexpressed cancer associated Sm-like mRNA. In total, cancer associated Sm-like mRNA was overexpressed in seven of 15 primary tumors (47%) and in the majority (71%, 5 of 7) of the hepatic metastases. CONCLUSIONS: Our results indicate that the cancer associated Sm-like mRNA gene may also play a role in the tumorigenesis of pancreatic endocrine tumors.
TYPE OF PUBLICATION: Original Article
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(Journal Article): Early Prediction of Severity in Acute Pancreatitis. Is This Possible?
Sandberg ÅA, Borgström A (Department of Surgery, Malmö University Hospital, University of Lund/Malmö. Malmö, Sweden,
anders.borgstrom@exp.mas.lu.se
)
IN:
JOP. J Pancreas (Online)
2002; 03(5):116-125
ABSTRACT: One out of ten cases of acute pancreatitis develops into severe acute pancreatitis which is a life threatening disorder with a high mortality rate. The other nine cases are self limiting and need very little therapy. The specificity of good clinical judgement on admission, concerning the prognosis of the attack, is high (high specificity) but misses a lot of severe cases (low sensitivity). The prediction of severity in acute pancreatitis was first suggested by John HC Ranson in 1974. Much effort has been put into finding a simple scoring system or a good biochemical marker for selecting the severe cases of acute pancreatitis immediately on admission. Today C-reactive protein is the method of choice although this marker is not valid until 48-72 hours after the onset of pain. Inflammatory mediators upstream from CRP like interleukin-6 and other cytokines are likely to react faster and preliminary results for some of these mediators look promising. Another successful approach has been to study markers for the activation of trypsinogen such as TAP and CAPAP. This is based on studies showing that active trypsin is the initial motor of the inflammatory process in acute pancreatitis. In the near future a combined clinical and laboratory approach for early severity prediction will be the most reliable. Clinical judgement predicts 1/3 of the severe cases on admission and early markers for either inflammation or trypsinogen activation should accurately identify 50-60% of the mild cases among the rest, thus missing only 2-4% of the remaining severe cases. One problem is that there is no simple and fast method to analyze any of these parameters.
TYPE OF PUBLICATION: Editorial
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(Journal Article): Islet Amyloid, Metabolic Syndrome, and the Natural Progressive History of Type 2 Diabetes Mellitus
Hayden MR (Department of Family and Community Medicine. University of Missouri School of Medicine. Columbia, Missouri, USA,
mrh29@usmo.com
)
IN:
JOP. J Pancreas (Online)
2002; 03(5):126-138
ABSTRACT: The presence of amyloid within the islet of the pancreas may be one of the best kept secrets in clinical medicine and translation of this century old finding may help to better understand the progressive nature of type 2 diabetes mellitus. Insulin resistance, metabolic syndrome, and type 2 diabetes mellitus are associated with multiple metabolic toxicities which result in an elevated tension of redox stress within the islet. Redox stress is associated with damage to proteins, lipids, and nucleic acids which may have a profound affect upon the structure and function of the islet. Earlier diagnosis at the stage of impaired glucose tolerance (prediabetes) and intervention may have a positive outcome on stabilization of the vulnerable islet and beta cell as well as the multiple diabetic complications. The natural history and a shift in the treatment paradigm of type 2 diabetes mellitus is explored as a result of these century old findings.
TYPE OF PUBLICATION: Review
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(Journal Article): Pancreatic Involvement During the Early Phase of Shock
Pezzilli R, Morselli-Labate AM, Romboli E, Dibenedetti F, Massa M, Migliori M, Barakat B, Merlini G, Corinaldesi R, Melzi d'Eril GV (Dipartimento di Medicina Interna e Gastroenterologia, Ospedale Sant'Orsola - Università di Bologna. Bologna, Italy,
pezzilli@orsola-malpighi.med.unibo.it
)
IN:
JOP. J Pancreas (Online)
2002; 03(5):139-143
ABSTRACT: BACKGROUND: There is a lack of data concerning pancreatic involvement during shock. AIM: To evaluate possible pancreatic alterations in the early phase of shock. SETTING: Twelve consecutive patients with shock were studied within 2 hours from the onset of illness. Seven patients died during the hospital stay: 3 within 4 hours from admission, 3 within 4-8 hours and 1 within 12 hours. MAIN OUTCOME MEASURES: Amylase, lipase, C-reactive protein, amyloid A, interleukin 6, procalcitonin and vascular cell adhesion molecule-1 serum concentrations were determined on admission and 4, 8, and 12 hours afterward. All patients underwent imaging studies of the pancreas. RESULTS: None of the patients developed clinical signs or morphological alterations compatible with acute pancreatitis. Serum amylase levels were above the upper reference limit in 7 patients (58.3%) and serum lipase levels in 2 patients (16.7%; P=0.062). There were no significant differences found between survivors and non-survivors in the serum concentrations of all the proteins studied. CONCLUSIONS: In patients with shock, amylase seems to be more frequently elevated than lipase. None of the patients showed pancreatic alterations at imaging techniques.
TYPE OF PUBLICATION: Original Article
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(Journal Article): Detection of K-ras Point Mutation at Codon 12 in Pancreatic Diseases: A Study in a Brazilian Casuistic
Kubrusly MS, Cunha JEM, Bacchella T, Abdo EE, Jukemura J, Penteado S, Morioka CY, de Souza LJ, Machado MCC (Department of Gastroenterology, Faculty of Medicine, University of São Paulo. São Paulo, Brazil,
morioka@gvmail.br
)
IN:
JOP. J Pancreas (Online)
2002; 03(5):144-151
ABSTRACT: OBJECTIVE: To clarify the sensitivity and the validity of K-ras point mutational analysis at codon 12 in Brazilian patients with pancreatic diseases, and the possible correlation between the presence of the mutation and the histopathological findings. PATIENTS: Ninety-seven Brazilian patients with pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumors and chronic pancreatitis were enrolled in this study. Forty-five patients (46%) were female and 52 patients (54%) were male, having an average age of 60.2+/-9.2 years for adenocarcinoma (n=52), 45.1+/-19.4 years for pancreatic neuroendocrine tumors (n=20), and 46.4+/-11.2 years for chronic pancreatitis (n=25). DNA extracted from 11 normal human peripheric lymphocytes was utilized as a control. RESULTS: The sensitivity of K-ras mutational analysis was 83.3% (25/30) in paraffin-embedded samples and 72.7% (16/22) in surgically resected specimens of the malignancy. On the other hand, no mutations were found in pancreatic neuroendocrine tumors or in chronic pancreatitis. Regarding the histopathological grading, the higher positivity rate was found in poorly-differentiated adenocarcinoma (100%), and progressively decreased in moderately-differentiated adenocarcinoma (72.2%), and well-differentiated adenocarcinoma (66.6%). The positivity rate in non-classified adenocarcinoma was 81.8%. CONCLUSION: K-ras point mutation, in our study, is notably prevalent in malignancies and is absent in chronic pancreatitis and pancreatic neuroendocrine tumors. These results encourage us to consider the possibility of treatment strategies for this oncogene in the future.
TYPE OF PUBLICATION: Original Article
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(Journal Article): Neuropharmacological Factors, Biliary Motility and Pancreatitis
Lechin F, van der Dijs B, Lechin ME (Instituto de Medicina Experimental, Universidad Central de Venezuela. Caracas, Venezuela,
flechin@telcel.net.ve
)
IN:
JOP. J Pancreas (Online)
2002; 03(5):152-154
TYPE OF PUBLICATION: Letter
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(Journal Article): Neuropharmacological Factors, Biliary Motility and Pancreatitis: Is Clonidine a True Clinical Option?
Lai KH (Department of Internal Medicine, Kaohsiung Veterans General Hospital, School of Medicine, National Yang Ming University. Taiwan, ROC,
khlai@isca.vghks.gov.tw
)
IN:
JOP. J Pancreas (Online)
2002; 03(5):155
TYPE OF PUBLICATION: Reply
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(Journal Article): Unresolved Issues about Post-ERCP Pancreatitis: An Overview
Testoni PA (Division of Gastroenterology and Gastrointestinal Endoscopy, University Vita-Salute San Raffaele, IRCCS San Raffaele Hospital. Milan, Italy,
testoni.pieralberto@hsr.it
)
IN:
JOP. J Pancreas (Online)
2002; 03(6):156-161
ABSTRACT: Pancreatitis represents the most common and feared complication after endoscopic retrograde cholangio-pancreatography. Since the introduction of ERCP into clinical practice, many attempts have been made to identify the mechanisms and conditions that can place patients at risk of developing post-procedure pancreatitis, with conflicting and in most cases unsatisfactory results. The following questions about post-ERCP pancreatitis still remain unanswered: the knowledge of the mechanisms involved in the onset of pancreatitis, procedural factors that can induce pancreatic damage, patient conditions that can increase the risk of developing pancreatitis in the post-procedure period, criteria for predicting the occurrence of pancreatitis, and possible methods of preventing the complication. Moreover, the criteria used to define post-ERCP pancreatitis differ in various studies and, consequently, there is a wide variation in the literature of the incidence of this complication and it is still not clear what its real incidence is. In the last six years, a significant advance in knowledge has been achieved in most of the above-mentioned fields. Four large prospective multicentre trials seemed to definitely identify patient- and technique-related risk factors that can place patients at risk of developing post-ERCP pancreatitis; clinical conditions, procedure- and patient-related factors, and laboratory tests able to predict the occurrence of post-ERCP pancreatitis in the early phase have been identified. An attempt to identify criteria for defining post-ERCP pancreatitis has also been carried out, although these proposed criteria have not been widely adopted by all Authors.
TYPE OF PUBLICATION: Round Table
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(Journal Article): Mechanisms Involved in the Onset of Post-ERCP Pancreatitis
Pezzilli R, Romboli E, Campana D, Corinaldesi R (Department of Internal Medicine and Gastroenterology, Sant'Orsola-M.Malpighi Hospital, University of Bologna. Bologna, Italy,
pezzilli@orsola-malpighi.med.unibo.it
)
IN:
JOP. J Pancreas (Online)
2002; 03(6):162-168
ABSTRACT: In various prospective studies, the frequency of post-ERCP pancreatitis ranges from 1 to 14%. After exposure to trigger events, injury to the gland occurs extremely rapidly. In experimental models of acute pancreatitis, it has been suggested that digestive enzyme activation might occur within acinar cells and it has been shown that in the early stages of acute pancreatitis induced by secretagogues or by diet, there is a co-localization of digestive enzymes and lysosomal hydrolases within large cytoplasm vacuoles; this co-localization mechanism might result in activation of the digestive enzyme. In this article, we will review the trigger events which may determine the final effect of acute pancreatitis during ERCP and endoscopic sphincterotomy: mechanical, chemical, enzymatic and microbiological. Nonetheless, factors related to the patient and the physician will be considered. Finally, the hypothesis of activation of chemokines by endoscopic maneuvers as a cause of acute pancreatitis will be described.
TYPE OF PUBLICATION: Round Table
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(Journal Article): Post-ERCP Pancreatitis: Patient and Technique-Related Risk Factors
Freeman ML (Division of Gastroenterology, University of Minnesota, Hennepin County Medical Center. Minneapolis, MN, USA,
freem020@tc.umn.edu
)
IN:
JOP. J Pancreas (Online)
2002; 03(6):169-176
TYPE OF PUBLICATION: Round Table
|
||
(Journal Article): Post-ERCP Pancreatitis: Is the Endoscopist´s Experience the Major Risk Factor?
Rabenstein T, Hahn EG (Department of Medicine II, Faculty of Clinical Medicine, Mannheim, Rupprecht-Karls-University Heidelberg. Mannheim, Germany,
thomas.rabenstein@med.ma.uni-heidelberg.de
)
IN:
JOP. J Pancreas (Online)
2002; 03(6):177-187
ABSTRACT: The assumption that the endoscopist is an important factor in outcome of ERCP is not easy to document. There are plenty of reasons for the difficulties in defining experience and skill of an endoscopist, and establishing suitable endpoints for their measurement. Suitable proxy variables are ERCP-frequency (ongoing volumes) and ERCP-experience (life-time volumes) of the endoscopist, as well as individual and institutional conditions. Important confounders are difficulty of ERCP, patient-related and procedure-related risk factors and risk-reducing factors. Endpoints should include success and (specific) complications of ERCP. Only few studies are available that analyse the influence of the endoscopist's skills on post-ERCP pancreatitis. Studies with a high preponderance of dominating patient-related risk factors for post-ERCP pancreatitis, e.g. suspect of SOD and unexplained abdominal pain, failed to prove such a dependence. On the other hand, evidence increases from studies with patient populations of more traditional indications for ERCP that suggests the existence of an association between ERCP-frequency of the endoscopist or ERCP-frequency of the environment and the incidence of post-ERCP pancreatitis and other complications. ERCP-experience measured in overall live-time volumes, however, does not seem to influence the risk of pancreatitis due to ERCP, although the data are very limited. During the ERCP-training of young endoscopists an impaired success rate appears more important than an increased complication rate. Nevertheless, all undesired outcomes of ERCP should be applied to the endpoints of quality assessment in ERCP-training. Further studies on this topic are needed. Since many variables significantly interact with the endpoints post-ERCP pancreatitis and complications of ERCP, a special study design appears indispensable to conclusively prove a relationship between an endoscopist's expertise and specific complications of ERCP.
TYPE OF PUBLICATION: Round Table
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(Journal Article): What Are the Predictors of Post-ERCP Pancreatitis, and How Useful Are They?
Sultan S, Baillie J (Division of Gastroenterology, Duke University Medical Center. Durham, NC, USA,
baill001@mc.duke.edu
)
IN:
JOP. J Pancreas (Online)
2002; 03(6):188-194
ABSTRACT: Acute pancreatitis is one of the major complications of ERCP. It is of paramount importance that we accurately identify which patients will go on to develop post-ERCP pancreatitis. As most ERCPs are performed on an outpatient basis, early evaluation can allow safe discharge of the majority of patients who will not develop post-ERCP pancreatitis or develop only mild symptoms that will be self-limited. Alternatively, early detection of those patients who will go on to develop moderate or severe post-ERCP pancreatitis can guide decisions regarding hospital admission and aggressive management and can help direct the use of targeted therapies that have the potential to prevent or mitigate pancreatic inflammation. Thus, significant efforts have focused on trying to identify predictors of post-ERCP pancreatitis. These parameters can be organized into three categories of tests: 1) pancreatic enzymes as markers of pancreatic injury: serum amylase/urine amylase; 2) markers of proteolytic activation: trypsinogen, trypsinogen activation peptide; 3) markers of systemic inflammation: C-reactive protein, various interleukins such as IL-6 and IL-10. A serum amylase level greater than 4-5 times the upper reference limit in conjunction with clinical symptoms has been shown to be an accurate and reliable predictor of post-ERCP pancreatitis. However, the exact timing and level of amylase elevation remains debatable. Urine testing of amylase and trypsinogen-2 in post-ERCP patients has also been shown to be highly sensitive and specific for detecting pancreatitis. The main advantage of these urinary markers is that they are available as rapid dipstick tests. Serum trypsinogen-2 levels have also been studied in post-ERCP pancreatitis patients; high levels seem to correlate with severity of disease. Among the markers of systemic inflammation, serum CRP is an accurate and readily available laboratory test for predicting severity of post-ERCP pancreatitis, but it appears to be helpful at 24-48 hours and, therefore, is not an early marker. Several other markers remain investigational and have not yet found wide clinical applicability.
TYPE OF PUBLICATION: Round Table
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(Journal Article): Why the Incidence of Post-ERCP Pancreatitis Varies Considerably? Factors Affecting the Diagnosis and the Incidence of This Complication
Testoni PA (Division of Gastroenterology and Gastrointestinal Endoscopy, University Vita-Salute San Raffaele, IRCCS San Raffaele Hospital. Milan, Italy,
testoni.pieralberto@hsr.it
)
IN:
JOP. J Pancreas (Online)
2002; 03(6):195-201
ABSTRACT: The reported incidence of post-ERCP/sphincterotomy pancreatitis ranges between 1.3 and 24.4% in non-selected series. This varying incidence likely reflects on the one hand difference in patient populations, indications and endoscopic expertise and, on the other hand, different definitions of pancreatitis and methods of data collection. Among a number of patient-related factors recognized at risk for post-ERCP pancreatitis in four recent large prospective studies, the combination of female gender, normal serum bilirubin levels and recurrent abdominal pain suggesting sphincter of Oddi dysfunction and previous post-ERCP pancreatitis placed patients at an increasingly higher risk of pancreatitis. Among the technique-related risk factors for post-ERCP pancreatitis, biliary sphincter balloon dilation, difficult cannulation, sphincter of Oddi manometry and pancreatic sphincterotomy have also been recognized as significant risk factors. However, since the case mix in non-selected series does not significantly differ in the different studies, it is logical to assume that the different criteria adopted for defining the post-ERCP pancreatitis play a key role in the reported wide variation of incidence reported for this complication. The occurrence and duration of pain and the amplitude of serum amylase after ERCP are critical points in the definition of post-ERCP pancreatitis. Although a consensus conference identified 24-hour persisting pain associated with hyperamylasemia greater than 3 times the upper reference limit as an indicator of pancreatitis, these two parameters are however considered in a different manner in the studies available up to now. In a prospective study where we calculated the incidence of post-ERCP pancreatitis by using the most widely used criteria, for both occurrence and duration of pancreatic pain and serum amylase amplitude, the incidence of post-procedure pancreatitis ranged from 1.9 to 11.7% depending on the criteria adopted.
TYPE OF PUBLICATION: Round Table
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