PANCREAS ALERTS
Gastroenterology 2003; 124(3):725-36. (AN 22499341, PMID 12612911)
Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis.
Sakai Y, Masamune A, Satoh A, Nishihira J, Yamagiwa T, Shimosegawa T.
Division of Gastroenterology, Tohoku University Graduate School of Medicine. Sendai. Central Research Institute, Hokkaido University Graduate School of Medicine. Sapporo. Japan.
Macrophage migration inhibitory factor, originally described as an inhibitor of the random migration of macrophages, has been shown recently to be involved in the pathogenesis of several inflammatory diseases such as sepsis.
The aim of this study was to clarify the role of Macrophage migration inhibitory factor in acute pancreatitis.
Hemorrhagic necrotizing pancreatitis and edematous pancreatitis were induced by the injection of taurocholic acid (TCA pancreatitis) and cerulein (cerulein pancreatitis), respectively, on male Wistar rats.
Serum and ascitic macrophage migration inhibitory factor levels in TCA pancreatitis were increased rapidly and decreased gradually thereafter. Ascitic macrophage migration inhibitory factor levels were also increased in cerulein pancreatitis, but to a lesser degree.
The authors concluded that the results suggest a role of macrophage migration inhibitory factor in the pathogenesis of severe acute pancreatitis.
Macrophage migration inhibitory factor levels in ascitic fluids, serum, and the organs were determined.
The effects of anti-macrophage migration inhibitory factor antibody were examined on the prognosis of rats with TCA pancreatitis and of female CD-1 mice with choline-deficient, ethionine-supplemented, diet-induced model of severe acute pancreatitis.
In addition, serum macrophage migration inhibitory factor levels in acute pancreatitis patients and in healthy controls were measured.
Macrophage migration inhibitory factor level was increased in the lung in TCA pancreatitis, but not in the pancreas and the liver.
Prophylactic (1 hour before and immediately after induction) administration of anti-macrophage migration inhibitory factor antibody significantly improved the survival rate of rats with TCA pancreatitis.
The survival rate of mice with severe acute pancreatitis was also improved significantly by the antibody treatment.
Serum macrophage migration inhibitory factor levels were higher in severe acute pancreatitis patients than mild acute pancreatitis patients and healthy controls.
Pancreas 2003; 26(2):E32-5. (AN 22493239, PMID 12604925)
The biochemical detection of biliary etiology of acute pancreatitis on admission: a revisit in the modern era of biliary imaging.
Ammori BJ, Boreham B, Lewis P, Roberts SA.
Royal Gwent Hospital, Cardiff Road. Newport, Gwent. Department of Radiology, University Hospital of Wales. Cardiff, Wales. UK.
Compared with traditional radiologic methods for the detection of cholelithiasis, early transient hypertransaminasemia had provided a useful prediction of biliary etiology in patients with acute pancreatitis.
The Authors investigated whether this application remains valid in the modern era of imaging for microlithiasis.
The biochemical detection of cholelithiasis was based on an increase in serum alanine transaminase of =>80 IU/L (normal range, 0-45 IU/L) within 24 hours of admission.
Of 68 patients with acute pancreatitis who were treated between October 2000 and December 2001, cholelithiasis was the etiological factor in 44 patients (65%).
In patients with acute pancreatitis, the biochemical analysis within 24 hours of admission provided a simple, rapid, and more accurate prediction of cholelithiasis than abdominal ultrasound.
The collective findings of abdominal ultrasound, endoscopic ultrasound, and postmortem examination to represent the denominator for the diagnosis of cholelithiasis against which comparison with biochemical detection was made.
Endoscopic ultrasound detected microlithiasis in 5 of 10 patients examined. The etiology remained idiopathic in 3 patients (4.4%). The sensitivity, specificity, and positive and negative predictive values for abdominal ultrasound were 86%, 100%, 100%, and 80% respectively; for biochemical detection, they were 91%, 100%, 100%, and 86%; and for abdominal ultrasound and biochemical detection combined, they were 98%, 100%, 100%, and 96%, respectively.
The combination of biochemical detection and abdominal ultrasound detected or excluded a biliary etiology in almost all patients.
Pancreas 2003; 26(2):E27-31. (AN 22493238, PMID 12604924)
Spirits and gastrectomy increase risk for chronic pancreatitis in Japanese male alcoholics.
Nakamura Y, Ishikawa A, Sekiguchi S, Kuroda M, Imazeki H, Higuchi S.
Institute of Clinical Research, National Alcoholism Center, Kurihama Hospital. Kanagawa, Japan.
Most cases of chronic pancreatitis are alcohol-related, but not all alcoholics develop pancreatitis.
The aim of the Authors was to elucidate historical and biologic risk factors for this disease.
One-hundred-thirty-two alcoholic Japanese men consecutively admitted to the National Alcoholism Center over 24 months, including 54 with chronic pancreatitis diagnosed by endoscopic retrograde cholangiopancreatography and 78 without, were surveyed about drinking history, smoking, education, and marital status, and tested for amylase, glycosylated hemoglobin, body mass, alcohol and aldehyde dehydrogenase genotypes, and K- gene mutations in pancreatic juice.
Higher risk for chronic pancreatitis was associated with drinking spirits rather than lower-alcohol beverages (odds ratio, OR=2.58; P=0.01).
This study strongly suggested that spirits and partial gastrectomy increase the risk for chronic pancreatitis in male alcoholics.
Daily ethanol consumption by those who drank spirits was greater than that among those who drank lower-alcohol beverages; however, no differences in either daily ethanol consumption or duration of drinking were observed between alcoholics with and without chronic pancreatitis.
Postgastrectomy patients were at higher risk for chronic pancreatitis than unoperated comparison subjects (OR=4.35, P<0.05).
Elevated glycosylated hemoglobin (OR=4.62, P<0.01), decreased amylase (OR=4.20, P<0.02), and low body mass (OR=1.89, P<0.1) were more frequent in alcoholics with chronic pancreatitis.
K- gene mutations existed in 18.8% of alcoholics with chronic pancreatitis but in only 11.4% of those without the disorder.
The frequencies of alcohol and aldehyde dehydrogenase genotypes in alcoholics with and without pancreatitis did not differ significantly.
Pancreas 2003; 26(2):185-9. (AN 22493232, PMID 12604918)
Comparative study of adult porcine pancreatic endocrine cell preparation using a technique of multiple injections and pancreatic duct cannulation without a proteolytic enzyme.
Morimoto Y, Nasu K, Iwami Y, Nagai K, Edamura K, Ohgawara H.
Division of Cell Replacement and Regenerative Medicine, Medical Research Institute, and Department of Medicine IV, School of Medicine, Tokyo Women's Medical University. Tokyo, Japan.
It is very important for the pancreatic endocrine cell preparation to expand the pancreas to separate pancreatic endocrine cells from acinar cells. For this purposethe Authors developed a pancreatic injection system.
The Authors compared two pancreatic injection methods: perfusion from an accessory pancreatic duct (cannulation method) and the traditional pancreatic tissue injection method (multiple injection method).
A comparison of the results of the two methods revealed that the pancreatic endocrine cell yield was significantly higher (P<0.001) with the cannulation method than with the multiple injection method.
The Authors concluded that pancreatic duct perfusion is useful for obtaining a high yield of pancreatic endocrine cells from porcine pancreases.
The number of dithizone-positive cells was significantly higher (P<0.001) with the cannulation method than with the multiple injection method.
The number of adhesion cells after 7 days of culture following isolation was higher (P<0.001) with the cannulation method than with the multiple injection method.
The glucose stimulation index of insulin secretion was higher (P<0.01) with the cannulation method than with the multiple injection method.
Mol Cancer 2003; 2(1):14. (PMID 12605717)
Invasion and metastasis in pancreatic cancer.
Keleg S, Buechler P, Ludwig R, Buechler MW, Friess H.
University of Heidelberg, Department of Surgery. Heidelberg, Germany.
Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate below 1%. The process of cancer initiation, progression and metastasis is still not understood well.
In this review the Authors highlighted the most important genetic alterations involved in tumor invasion and metastasis and further outline the role of tumor angiogenesis and lymphangiogenesis in systemic tumor dissemination.
Invasion and tumor metastasis are closely related and both occur within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate cell migration, and promote cell proliferation and tumor cell survival.
During the last decade considerable progress has been made in understanding genetic alterations of genes involved in local and systemic tumor growth.
The most important changes occur in genes which regulate cell cycle progression, extracellular matrix homeostasis and cell migration. Furthermore, there is growing evidence that epigenetic factors including angiogenesis and lymphangiogenesis may participate in the formation of tumor metastasis.
Mol Cancer 2003; 2(1):15. (PMID 12605716)
Genetic alterations in pancreatic carcinoma.
Schneider G, Schmid RM.
Klinikum rechts der Isar, II, Department of Internal Medicine. Munich Germany.
Cancer of the exocrine pancreas represents the fifth leading cause of cancer death in the Western population with an average survival after diagnosis of 3 to 6 months and a five-year survival rate under 5%.
The Authors describe major genetic alterations of pancreatic cancer, mutations in the proto-oncogene K-RAS and the tumor suppressors INK4A, TP53 and DPC4/SMAD4.
The knowledge of the underlying molecular mechanisms will offer new therapeutic and diagnostic options and hopefully improve the outcome of this aggressive disease.
Our understanding of the molecular carcinogenesis has improved in the last few years due to the development of novel molecular biological techniques.
Pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells.
The accumulation of these genetic changes leads to a profound disturbance in cell cycle regulation and continuous growth.
J Gastrointest Surg 2003; 7(2):220-8. (PMID 12600446)
Evaluation of vascular endothelial growth factor blockade and matrix metalloproteinase inhibition as a combination therapy for experimental human pancreatic cancer.
Hotz HG, Hines OJ, Hotz B, Foitzik T, Buhr HJ, Reber HA.
Department of Surgery, UCLA School of Medicine. Los Angeles, CA, USA.
Blockade of vascular endothelial growth factor and inhibition of matrix metalloproteinases are promising therapies for cancer.
This study assessed the effects of a neutralizing anti-endothelial growth factor antibody (A4.6.1) and a matrix metalloproteinases inhibitor (BB-94) on pancreatic cancer in vivo.
Five million cells of two human pancreatic cancer cell lines (AsPC-1 and HPAF-2) were injected subcutaneously into nude mice; 1 mm3 fragments of the resulting tumors were implanted into the pancreas of other mice.
Both monotherapies reduced tumor volume, spread, and microvessel density, resulting in a tendency toward increased survival.
Combination treatment results in additive effects in moderately differentiated HPAF-2 tumors.
Animals were randomized into a control group and three treatment groups: A4.6.1 (100 mg intraperitoneally twice weekly); BB-94 (50 mg/kg every other day); and combination (A4.6.1 plus BB-94).
Treatment was started after 3 days and continued for 14 weeks.
Tumor volume, local and distant spread (score), and ascites were determined at autopsy.
Microvessel density as a parameter of neoangiogenesis was analyzed in CD31-stained tumor sections.
Combination therapy yielded additional effects in the HPAF-2 group with regard to tumor volume and development of ascites.
Both endothelial growth factor blockade and matrix metalloproteinases inhibition reduce primary tumor size, metastasis, and angiogenesis, thereby increasing survival in experimental pancreatic cancer.