| Abstract|| |
The past few years have witnessed a tremendous progress in our knowledge regarding the pathogenesis, diagnosis, prognostic evaluation and classification of acute pancreatitis. The role of ischemia, lysosomal enzymes, oxygen free radicals, polymorphnuclear cells-byproducts and inflammatory mediators in the pathogenesis of pancreatic necrosis and multiple organ failure has been emphasized. Furthermore, the recent knowledge about agents infecting pancreatic necrosis, routes of infection, bacteriological examination of fine needle aspirate and appropriate antibiotics have changed the concept of acute pancreatitis. New diagnostic tests such as rapid urinary trypsinogen-2 test and inflammatory mediators including polymorphnuclear elastase, C-reactive protein and interleukin-6 contribute to early diagnosis, prognostic evaluation and initiation of an appropriate therapy.
|How to cite this article:|
Al Mofleh IA. Acute pancreatitis. Saudi J Gastroenterol 1997;3:113-20
Acute pancreatitis remains a serious disease associated with high rates of morbidity and mortality. Acute pancreatitis has been defined as an acute inflammatory pancreatic process with possible involvement of the peripancreatic tissue and other organs causing multiple organ failure (MOF) with increasing mortality rate  . Approximately 20% of patients run a severe course with considerable morbidity and mortality. The overall mortality rate for acute pancreatitis is 6% and may exceed 50% in the presence of six or more Ranson's criteria. Several factors including aging, obesity, unidentified etiology, chronic renal failure, surgery and delayed transfer to specialized units are associated with an increased risk ,,,,,, .
Approximately 80% of acute pancreatitis cases are induced by biliary stones and ethanol. In patients with cholelithiasis, the relative risk for acute pancreatitis is approximately seven times higher than those without gallstones  . While various conditions including surgery, ERCP, metabolic causes, viral infections, drugs and others contribute to 10% of the etiology of acute pancreatitis [Table 1], in 10-20%, the cause remains obscure  . Further search for idiopathic, acute pancreatitis has revealed that a considerable portion of this group is due to biliary diseases including sludge, Sphincter of Oddi More Details dysfunction and anatomic anomalies , .
Recent advances have contributed to a better understanding of the pathophysiology, diagnosis and management of acute pancreatitis. Several factors contribute to the pathogenesis and severity of acute pancreatitis. Such factors include the intraacinar colocalisation of lysosomal enzymes with digestive pancreatic enzymes, ischemia, neutrophilesbyproducts, vasoactive mediators and activation of the complement system ,,,, .
The rapid measurement of urinary trypsinogen-2 utilizing a dipstick, is a very reliable test that differentiates acute pancreatitis from other acute upper abdominal conditions (18). It allows an early diagnosis and therefore early initiation of appropriate therapy.
Approximately 80% of acute pancreatitis run a mild course, are self-limiting and require only supportive treatment with close observation in a general ward. In contrast, severe cases of pancreatitis, defined as those associated with organ failure and/or local complications such as necrosis, pseudocyst and abscess  , require special care. Multifactorial scoring systems (MFSS) have been used to predict the outcome of acute pancreatitis. Recently several other reliable methods have also been applied as prognostic predictors such as contrast-enhanced computed tomography (CECT), inflammatory mediators and peritoneal aspirate/ lavage ,, .
The aim of his article is to provide a review of the current advances in the pathophysiology, diagnosis and prognostic evaluation of acute pancreatitis.
| Pathophysiology|| |
Acute pancreatitis is caused mainly by biliary stones and alcohol. The exact mechanism by which biliary stones induce pancreatitis is not well explained. Pancreatic duct outflow obstruction has been considered as the critical event in biliary pancreatitis in experimental animals and in man , . The mechanism of alcohol induced acute pancreatitis is also not clear. However, experimental studies have shown that chronic alcohol administration increases pancreatic zymogen granules  and pancreatic lysosomal fragility  and may facilitate lysosomal and digestive enzymes contact with consequent autodigestion. Acute administration of high doses of alcohol has induced intracellular oxidative changes. This together with consumption of gluthathion, which has a protective effect against alcohol toxicity, may contribute to the pathogenesis of alcohol-induced acute pancreatitis  .
It has been assumed, that the initial event in the pathogenesis of acute pancreatitis is induced by intraacinar activation of digestive enzymes and pancreatic tissue injury. The severe pathophysiological alterations are probably mediated by cascade system activation by protease-antiprotease imbalance induced by leucocytes proteases  . The autodigestion is initiated by intracellular activation of pancreatic enzymes by the lysosomal enzymes  . In case of colocalisation of digestive and lysosomal enzymes, autodigestion is triggered by block in exocytosis  . Experimental studies have suggested an important role of oxygen free radicals (OFR) in the initiation and progression of acute biliary, alcoholic and ischemic pancreatitis. This has been evident by increased OFR concentration  and reduction of pancreatic tissue damage in animals pretreated with OFR scavengers such as superoxide desmutase, catalase and allupurinol , . It has been suggested that the oxidative burst takes place in the intraacinar level and results in membrane damage with subsequent leakage of pancreatic enzymes, OFR and debris into the interstitium  . Oxygen free radicals originate from various sources including xanthine oxidases, mitochondrial cytochrome oxidases, arachidonic acid metabolism and polymorphnuclear (PMN) cells , . Polymorphnuclear cells are considered as one of the important sources for OFR. The pancreatic enzyme, elastase, has an enhancing effect on the superoxide production and therefore on the initiation of acute pancreatitis  .
Several factors such as ischemia, lysozymal enzymes and vasoactive mediators may be responsible for the development of pancreatic necrosis.
Ischemia in acute pancreatitis may result from capillary ischemic compromise due to increased permeability and subsequent fluid loss. Ischemia induces OFR release  . It is believed that the lysosomal protease, cathepsin B, which activates trypsinogen in the presence of intraacinar digestive and lysosomal enzymes .colocalisation, is responsible for the acinar necrosis  . The effect of vasoactive mediators on the severity of pancreatitis and development of necrosis has been evaluated in an animal model. While administration and inhibition of adrenergic mediators and nitric oxide (NO) had no effect, bradykinin inhibition has been associated with development of necrosis and hemorrhage  . Also Endothelein, a potent longacting vasoconstrictor peptide, is known to induce micro circulatory alterations of the pancreas and aggrevate the course of acute pancreatitis  . Pancreatic phosphalipase A2 (PLA2) has also been considered to contribute to pancreatic necrosis in a setting of acute pancreatitis  . Bacterial lipopolysaccharide, a component of the wall of Gram-negative bateria induces pancreatic PLA2 activation and development of aptosis  .
Multiple organ failure:
The pathogenesis of MOF is unclear. Several factors including ischemia, toxic products, OFR, inflammatory mediators, pancreatic enzymes and activation of the complement system may contribute to MOF mainly through their vascular effect and increased permeability ,,,, .
Ischemia due to hypovolemia as a result of fluid extravasation and release of OFR may alter the endothelial barrier in several organs and induce MOF  . Beside OFR, calcium flux also may have a role in the pathogenesis of MOF in acute pancreatitis through their injurious effect on the endothelial barrier , . Pretreatment with antioxidants and calcium channel antagonists has been associated with an organ-dependent protective effect  . Also, leukocytes-byproducts such as OFR, cytokines and NO have been found to contribute to the inflammatory process and severity of acute pancreatitis  . Furthermore, some pancreatic enzymes such as pancreatic elastase and PLA2 contribute to the severity of pancreatitis and MOF. Elastase enhances superoxide generation from PMN and induces vascular injuries through its elastolytic effect on the vessel wall , .
| Diagnosis|| |
In the early stage, it may be difficult to differentiate acute pancreatitis from other conditions, associated with severe upper abdominal pain including biliary colic, ischemic bowl injuries, intestinal obstruction, peptic ulcer penetration or perforation, and inferior myocardial infarction. A high suspicion index, would improve the yield of diagnosis. The history of biliary stones, jaundice, ethanol drugs and recent viral infections should be explored.
The pain of acute pancreatitis is frequently of sudden onset and persists for hours or a few days. It is often localized in the upper abdomen or in the epigastrium and penetrates or radiates to the back. It is commonly associated with nausea, vomiting, fever and tachycardia. In severe cases, the physical examination reveals abdominal tenderness and guarding  .
A clinically suspected acute pancreatitis should be confirmed by laboratory findings of hyperamylasemia and/or hyperlipasemia. Serum amylase with a cut off value of 300 IU/L has an 85% sensitivity and 91% sepcifity  . Increase of amylase concentration in the peritoneal aspirate and lavage differentiate acute pancreatitis from other causes of hyperamylasemias  . Other tests include PLA2, pancreatic elastase, carboxypepti das e, trypsin, urinary trypsinogen A2 and urinary amylase dipstick tests. Due to assay difficulties, the estimation of trypsin, PLA2, carboxypeptidase and elastase have not been used in the routine work up of acute pancreatitis  . Serum amylase, urinary amylase dipstick and urinary trypsinogen-A2 dipstick test are the standard and most accurate tests [Table - 2].
Biliary stones and alcohol are the two major etiological factors contributing to approximately 80% of acute pancreatitis cases. Alanin and aspartate transaminases (ALT, AST) and alkaline phosphatase (ALP) may help to differentiate biliary from ethanol induced acute pancreatitis. ALT, AST and ALP have been significantly higher in biliary pancreatitis, while the mean corpuscular volume (MCV) and lipase-amylase ratio are significantly higher in acute pancreatitis due to ethanol  . Other studies have shown that AST above 80 IU/L alone was able to detect 80% of cases of biliary pancreatitis, similar to AST, ALP and bilrubin combined together  .
Plain abdominal radiograph has limited value in the diagnosis of acute pancreatitis, however it helps to differentiate acute pancreatitis from other conditions such as ileus and peptic ulcer perforation  . Ultrasonography may reveal important information such as swelling of the pancreas, bile duct dilatation and the presence of cholelithiasis, choledocholithiasis, fluid collections and pseudocysts. However, ultrasonography has a low diagnostic sensitivity in the presence of intraabdominal gas , . In a setting of acute pancreatitis ultrasonography has detected upto 80% of cholelithiasis compared to 25% of choledocholithiasis  . Also computed tomography (CT) scan has a low diagnostic sensitivity in mild cases of acute pancreatitis and detects less than 30% of cases  . In contrast, CECT detects 95% of pancreatic necrosis and has been considered as the standard method for detection of necrotizing pancreatitis  Because of low sensitivity in mild cases and the high cost, CT is not used routinely in acute pancreatitis  .
| Clinical Course|| |
In the vast majority of patients, acute pancreatitis is a self-limiting disease, which resolves spontaneously within a short period of time. In an experimental model of acute necrotizing biliary pancreatitis, a fast and complete recovery has been described. The authors have suggested an acinar cell replication reaching a peak 1-2 weeks after relief of bile duct and pancreatic duct obstruction without development of fibrosis or chronic pancreatitis  . In an early phase of acute mild to moderate pancreatitis in man, the exocrine pancreatic function remains unaltered  . However, impaired exocrine function has been reported after an acute pancreatitis with a subsequent gradual improvement  . Approximately 25% develop organ dysfunction  and 10-20% develop a severe form with intra and extra pancreatic necrosis and MOF  . The death rate is well correlated with MFSS. No mortality has been recorded among patients with score zero of the modified Goris Score System compared to 9% with score 1-4 and 67% among those scoring 5 points or more  . Furthermore, the same authors have found mortality to be influenced by the age, the cause such as, post ERCP pancreatitis and a 10-fold increase in mortality in patients transferred from other units. In an experimental model, hyperlipidemia has intensified the course of acute pancreatitis  .
| Assessment of Severity|| |
Criteria determining the severity are shown in [Table - 3]. Several methods have been used to predict those who might develop a severe course and to evaluate the severity of acute pancreatitis [Table - 4]. The severity is indicated by the development of local and/or systemic complications.
Multi-factorial score systems such as Ranson's, Glasgow and the acute physiology and chronic health evaluation (APACHE II) are used more commonly. The sensitivity and specificity of Glasgow Score System is around 80% . The mortality has been correlated with the number of Ranson's criteria [Table - 5]. It has been less than 20% in the presence of three to five criteria and exceeded 50% when six or more criteria are present , . In acute pancreatitis, organ failure was found to be the most important indicator of severity  .
The value of peritoneal aspirate and lavage in assessment of acute pancreatitis severity has been recognized two decades ago  . Dark color of the aspirate and volume over 10 ml with estimation of WBC, ALP, AST, bilirubin, total protein, albumin, urea, calcium and potassium have been correlated with the severity. A modified method comparing the fluid color with a fluid color chart has been able to detect 72% of severe cases at seven hours of admission compared to 39% detected by clinical assessment  .
Due to the time factor and difficulties faced when applying the MFSS, the need for a simpler and faster techniques is required. On admission 34% and at 48 firs. 83% of severe attacks of acute pancreatitis can be detected clinically, which correlates well with results obtained by utilizing MFSS  . Recently several markers have been introduced in the procedure of acute pancreatitis severity assessment. Such biological parameters include markers for activation of pancreatic enzymes such as urinary trypsinogen activation peptide (TAP) and inflammatory mediators including PMN-elastase, creactive protein (CRP) and Interleukin-6 (IL-6).
Trypsinogen activation peptide reflects the activation of trypsinogen to trypsin and the severity in the early stage of acute pancreatitis within the first 12 hours  . There has also been a good correlation between CRP concentration and disease severity. IL-6 serum levels exceeding 120 mg were comparable with CECT and 95% of pancreatic necrosis confirmed by laparotomy  . Similarly PMN-elastase has an overall accuracy of 90% during the first 48 hours  . A recent study has also suggested a close relationship between IL-6 and CRP. Both inflammatory mediators have been higher in severe acute pancreatitis, however IL-6 predicts the severity earlier than CRP. Sensitivity and specificity are comparable for IL-6 (>130 U/L) and CRP (>150 mg/L) at 100% and 71% vs 90% and 79% respectively  other methods including urine trypsinogen  and whole blood chemiluminescence  have been valuable in the evaluation of acute pancreatitis severity.
The recent technical advances and the utilization of large bolus intravenous contrast have made CECT among the most important advances in the prognostic evaluation of patients with acute pancreatitis  . It has been considered as the method of choice for detection and grading [Table - 6] of pancreatic necrosis  . CECT is also indicated in a deteriorating course of acute pancreatitis prior to surgery and for a guided fine needle aspiration to determine the presence of infection the infecting, organism and other complications  . Preliminary results of magnetic resonance imaging (MRI) have not provided any advantages to CECT  .
| Conclusion|| |
The vast majority of acute pancreatitis cases are due to biliary diseases, mainly stones, and ethanol. The pathogenesis is multifactorial. Intracinar activation of digestive enzymes, lysosomal enzymes, ischemia, OFR and inflammatory mediators play an important role in the development of necrosis and organ failure.
The clinical diagnosis of acute pancreatitis should be supported by byperamylasemia. Urinary trypsinogen-A2 dipstick test and plain abdomen are useful for the differential diagnosis. A two-fold rise of the AST concentration, accurately differentiate acute biliary from ethanol-induced pancreatitis. In severe cases, CECT provide informations about the presence and extent of necrosis. A CT-guided fine needle aspiration is required in suspected infection. Inflammatory mediators, such as PMN-elastase CRP and IL-6 provide early prognostic evaluation. The mortality rate remains high and is well correlated with infection and MFSS. Early diagnosis and appropriate management may help to reduce the morbidity and mortality.
| References|| |
|1.||Bradly EL III. A clinically based classification system for acute pancreatitis. Arch Surg 1993;128:586-90. |
|2.||De Beaux AC, Palmer KR, Carter DC. Factors influencing morbidity and mortality in acute pancreatitis; an analysis of 279 cases. Gut 1995;37:121-6. [PUBMED] [FULLTEXT]|
|3.||Agarwal N, Pitchumoni CS. Assessment of severity in acute pancreatitis. Am J Gastroenterol 1991;86:1385-91. [PUBMED] |
|4.||Fan ST, Choi TK, Lai ESC, Wong J. Prediction of severity of acute pancreatitis: an alternative approach. Gut 1989;30:1591-5. |
|5.||Funell IC, Borman PC, Weakly SP, Terblanche J, Marks in obesity: an important prognostic factor in acute pancreatitis. Br J Surg 1993;80:484-6. |
|6.||Browder W, Patterson MD, Thompson JL, Walters DN. Acute pancreatitis of unknown etiology in the elderly. Ann Surg 1993;217:469-75. [PUBMED] [FULLTEXT]|
|7.||Pitchumoni CS, Arguello P, Agarwal N, Yoo J. Acute pancreatitis in chronic renal failure. Am J Gastroenterol 1996;91:2477-82. [PUBMED] |
|8.||Cameron JL, Clemens JA. Etiology and pathogenesis of acute pancreatitis. In Trede M, Carter DC (Eds.) Surgery of the pancreas. Churchill Livingstone, London 1993:165-92. |
|9.||Carballo F, Dominguez-Munoz JE, Martinez Pancorbo C, de la Momea J. Epidemiology of acute pancreatitis. In Berger HG, Buchler M, Malfertheiner P (Eds.) Standards in pancreatic surgery. Springer Verlag: Berlin-Heidelberg 1993:25-33. |
|10.||Ballinger AB, Barnes E, Alstead EM, Fairclough PD. Is intervention necessary after a first episode of acute pancreatitis ? Gut 1996;38:293-5. [PUBMED] [FULLTEXT]|
|11.||Venu RP, Geenen JE, Hogan W, Stone J, Johnson GK, Soergel K. Idiopathic recurrent pancreatitis. Dig Dis Sci 1989;34:56-60. [PUBMED] |
|12.||Lee SP, Nicholls JF, Park HZ. Biliary sludge as a cause of acute pancreatitis. N Engl J Med 1992;326:589-93. [PUBMED] |
|13.||Steer ML, Meldolesi J, Figarella C. Pancreatitis: The role of lysosomes. Dig Dis Sci 1984;29:934-8. [PUBMED] |
|14.||Adler G. Acute pancreatitis. Curr Opin Gastroenterol 1991;7:714-9. |
|15.||Rinderknecht H. Genetic determinants of mortality in acute necrotizing pancreatitis. Int J Pancreatol 1994;16:11-5. [PUBMED] |
|16.||Weidenbach H, Lerch MM, Gress TM, Pfaff D, Turi S, Adler G. Vasoactive mediators and the progression from edematous to necrotizing experimental acute pancreatitis. Gut 1995;37:434-40. [PUBMED] [FULLTEXT]|
|17.||Roxvall LI, Bengston LA, Heidemann JMI. Anaphylatoxin and terminal complement complexes in pancreatitis. Arch Surg 1990;125:918-21. |
|18.||Kemppainen EA, Hedstrom JA, Puolakkainen PA, et al. Rapid measurement of urinary trypsinogen-2 as a screening test for acute pancreatitis. N Engl J Med 1997;336:1788-93. |
|19.||Balthazer EJ, Freeny PC, Van Sonnenberg E. Immaging and intervention in acute pancreatitis. Radiology 1994;193:297-306. |
|20.||Heath DI, Gruickshank A, Gudgeon M, Jehanli A, Shinken A, Imrie CW. Role of interleukin-6 in mediating the acute phase protein response and potential as an early means of severity assessment in acute pancreatitis. Gut 1993;34:41-5. |
|21.||Pickford IR, Blackett RL, McMahon MJ. Early assessment of severity of acute pancreatitis using peritoneal lavage. Br Med J 1977; ii:1377-9. |
|22.||Lerch MM, Saluja AK, Runzi M, Dawra R, Saluja M, Steer ML. Pancreatic duct obstruction triggers acute necrotizing pancreatitis in the opossum. Gastroenterology 1993;104:853-61. |
|23.||Lerch MM, Weidenbach H, Hemandez CA, Preclik G, Adler G. Pancreatic outflow obstruction as the critical event for human gallstone pancreatitis. Gut 1994;35:1501-3. |
|24.||Haber PS, Wilson JS, Apte MV, Korsten MA, Pirola RC. Chronic ethanol consumption increases the fragility of rat pancreatic zymogen granules. Gut 1994;35:1474-8. [PUBMED] [FULLTEXT]|
|25.||Wilson JS, Korsten MA. Apte MV, Thomas MC, Haber PS, Pirola RC. Both ethanol consumption and protein deficiency increase the fragility of pancreatic lysosomes. J Lab Clin Med 1990;115:749-55. |
|26.||Altomare E, Grattagliano I, Vendemiale G, Palmieri V, Palasciano G. Acute ethanol administration induces oxidative changes in rat pancreatic tissue. Gut 1996;38:742-6. [PUBMED] [FULLTEXT]|
|27.||Dominguez-Munoz JE, Carballo F, Garcia MJ, et al. Monitoring of serum proteinase-antiproteinase balance and systemic inflammatory response in the prognostic evaluation of acute pancreatitis: results of a prospective multicenter study. Dig Dis Sci 1993;38:507-13. |
|28.||Lerch MM, Saluja AK, Dawra R, Saluja M, Steer ML. The effect of chloroquine on two experimental models of acute pancreatitis. Gastroenterology 1993;104:1768-79. [PUBMED] |
|29.||Gough DB, Boyle B, Joyce WP, et al. Free radicals inhibition and serial chemluminescence in evolving experimental pancreatitis. Br J Surg 1990;77:1256-9. |
|30.||Sanfey H, Bulkley GB, Cameron JL. The role of oxygenderived free radicals in the pathogenesis of acute pancreatitis. Ann Surg 1984;200:105-13. |
|31.||Steer ML, Rutledge PL, Powers RE, Saluja M, Saluja AK. The role of oxygen-derived free radicals in two models of experimental acute pancreatitis: effects of catalas, superoxide desmutase, dimethyl sulfoxide and allupurinol. Klin Wochenschr1991;69:1012-7. [PUBMED] |
|32.||Guice KS, Oldham KT, Johnson KJ, et al. Mechanism of pancreatic capillary endothelial injury in acute pancreatitis. Surg Forum 1987;34:144-6. |
|33.||Reilly PM, Schiller HJ, Bulkley GB. Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am J Surg 1991;161:488-503. [PUBMED] [FULLTEXT]|
|34.||Ali ATMM, Al Swayeh OA, Al Rashed RS, Al Mofleh IA, Al Dohayan AD, Al Tuwaijri RS. Role of oxygen-derived free radicals on gastric mucosal injury induced by ischemiareperfusion. Saudi J Gastroenterol 1996;2:19-28. |
|35.||Tsuji N, Watanabe N, Okamoto T, Niitsu Y. Specific interaction of pancreatic elastase and leucocytes to produce oxygen radicals and its implication in pancreatitis. Gut 1994;35:1659-64. [PUBMED] [FULLTEXT]|
|36.||Liu XH, Kimura T, Ishikawa H, Yamaguchi H, Furukawa M, Nakan I. Effect of endothelin-1 on the development of hemorrhagic pancreatitis in rats. Scan J Gastroenterol 1995;30:276-82. |
|37.||Laine VJO, Nyman KM, Peuravuori HJ, Henriksen K, Parvinen M, Nevalainen TJ. Lipopolysaccharide induced apoptosis of rat pancreatic acinar cells. Gut 1996;38:747-52. |
|38.||Wang XD, Deng XM, Haraldsen P, Andersson R, Ihse-1. Antioxidant and calcium channel blockers counteract endothelial barrier injury induced by acute pancreatitis in rats. Scan J Gastroenterol 1995;30:1129-36. |
|39.||Klar E, Messmer K, Warshaw AL, Herfarth C. Pancreatic ischemia in experimental acute pancreatitis. Mechanism, significance and therapy. Br J Surg 1990;77:1205-10. |
|40.||Sanfey H, Bulkley GB, Cameron JL. The pathogenesis of acute pancreatitis: The source and the role of oxygen-derived free radicals in three different experimental models. Ann Surg 1985;201:633-40. [PUBMED] [FULLTEXT]|
|41.||Lum H, Aschner JL, Philips PG. Time course of thrombin induced increase in endothelial permeability: relationship to Ca 2+ and inositol polyphosphate. Am J Physiol I992;263:L219-25. |
|42.||Geokas MC, Rinderknecht H, Swanson V, Haverback BJ. The role of elastase in acute hemorrhagic pancreatitis in man. Lab Invest 1968:235-9. |
|43.||Banks PA. Guidelines in Acute pancreatitis. Am J Gastroenterol 1977;92:377-86. |
|44.||Heath DI, Imrie CW. The diagnosis and assessment of severity in acute pancreatitis. In Johnson CD, Imrie CW (Eds) Pancreatic disease: Progress and prospects. SpringerVerlag, London 1991:263-85. |
|45.||Stimac D, Rubinec M, Lenac T, Kovac D. Vcev A, Miletic D. Biochemical parameters in the early differentiation of the etiology of acute pancreatitis. Am J Gastroenterol 1996;91:2355-9. |
|46.||Sadowski DC, Todd JK, Sutherland LR. Biochemical models as early predictors of the etiology of acute pancreatitis. Dig Dis Sc. 1993;38:637-43. |
|47.||Moosa AR. The impact of computed tomography and ultrasound on surgical practice. Bull Am Coll Surg 1982;67:10-14. |
|48.||Mckay AJ, Imrie CW, O' Neill J, Duncan JG. Is an early ultrasound scan of value in acute pancreatitis ? Br J Surg 1982;69:369-72. |
|49.||Wang SS, Lin XZ, Tsai YT, et al. Clinical significance of ultrasonography, computed tomography and biochemical tests in the rapid diagnosis of gallstones related pancreatitis. A prospective study. Pancreas 1988;3:153-8. |
|50.||Clovien PA, Hauser H, Mayer P, Rohner A. Value of contrast enhanced computerised tomography in the early diagnosis and prognosis of acute pancreatitis. Am J Surg 1988; 155:475-66. |
|51.||Buchler M, Malfertheiner P, Berger HG. Correlation of imaging procedures, biochemical parameters and clinical stage in acute pancreatitis. In Malfertheiner P, Ditschuneit H (Eds). Diagnostic procedures in pancreatic disease. Springer-Verlog, Berlin, 1986:123-9. |
|52.||Runzi M, Saluja A, Kaiser A, Gerdes D, Sengupta A, Steer ML. Biochemical and morphological changes that characterise recovery from necrotizing pancreatitis in the opossum. Gut 1995;37:427-33. |
|53.||Dorninguez-Munoz JE, Pieramico O, Buchler M, Malfertheiner P. Exocrine pancreatic function in the early phase of human acute pancreatitis. Scan J Gastroenterol 1995;30:186-91. |
|54.||Glasbrenner B, Buchler M, Uhl W, Malfertheiner P. Exocrine pancreatic function in the early recovery phase of acute edematous pancreatitis. Eur J Gastroenterol Hepatol 1992;4:563-7. |
|55.||Larvin M, McMahon MJ. APACHE 11 score for assessment and monitoring of acute pancreatitis. Lancet 1989; ii:201-5. |
|56.||McFadden DW. Organ failure and multiple organ failure in pancreatitis. Pancreas 1991;6:37-43. |
|57.||Hofbauer B, Friess H, Weber A, et al. Hyperlipidemia intensifies the course of acute edematous and acute necrotizing pancreatitis in the rat. Gut 1996;38:753-8. [PUBMED] [FULLTEXT]|
|58.||Blarney SL, Imrie CW, O' Neill J, Gilmour WH, Carter DC. Prognostic factors in acute pancreatitis. Gut 1984;25:1340-6. |
|59.||Bradly EL. A clinically based classification system for acute pancreatitis. Arch Surg 1993; 128-586-90. |
|60.||McMahon MJ, Playforth MJ, Pickford IR. A comparative methods for the prediction severity of attacks of Acute pancreatitis. Br J Surg 1980;67: 22-5. [PUBMED] |
|61.||Corfield AP, Cooper MJ, Williamson RCN, et al. Prediction of severity of acute pancreatitis: a prospective comparison of three prognostic indices. Lancet 1985; ii:403-6. |
|62.||Gudgeon AM, Heath DI, Hurley P, et al. Trypsinogen activation peptide assay in the early prediction of severity of acute pancreatitis. Lancet 1990;335:4-8. [PUBMED] |
|63.||Balthazar EJ, Freeny PC. Contrast-enhanced computed tomography in acute pancreatitis: Is it beneficial or harmful ? (Editorial). Gastroenterol 1994;106:259-62. |
|64.||Balthazer EJ, Freeny PC, Van Sonnenberg E. Imaging and intervention in acute pancreatitis. Radiology 1994;193:297-306. |
Ibrahim Abdulkarim Al Mofleh
Professor of Medicine, Gastroenterology Division (59), King Khalid University Hospital, P.O. Box 2925, Riyadh 11461
Source of Support: None, Conflict of Interest: None
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]