Pancreas divisum

Acute pancreatitis is a common intra-abdominal disorder with potential for serious complications and mortality. The incidence of acute pancreatitis ranges from 54 to 238 episodes per 1 million per year,(1) with up to 80 percent of the cases secondary to alcohol use or gallstones. The potential severity of this disease should sharpen the clinician's vigilance for complications.

Definitions

At the Marseilles Symposium of 1984, the classification of pancreatitis was revised and divided into only two categories: acute pancreatitis and chronic pancreatitis.(2) The older terms, "relapsing acute pancreatitis" and "chronic relapsing pancreatitis," were discarded, since patients with chronic pancreatitis may have acute exacerbations and patients with acute pancreatitis may have repeated attacks of acute pancreatitis.

The clinical course of acute pancreatitis ranges from mild to severe. Eighty percent of patients have mild edematous pancreatitis.(3) Patients with mild pancreatitis respond well to conservative therapy, but those with severe pancreatitis may have a progressively downhill course to respiratory failure, sepsis and death. When hemorrhage occurs with necrotizing pancreatitis, it is termed hemorrhagic pancreatitis.

Etiology

Numerous conditions are associated with acute pancreatitis (Table 1). Foremost in the United States are excessive ethanol intake and cholelithiasis, accounting for 65 to 80 percent of cases. Alcohol-induced pancreatitis can usually be established by a careful history. The patient typically has consumed large quantities of alcohol before the onset of symptoms. Morphologically, the pancreas sustains irreversible damage. Rarely, patients will present with a case of acute pancreatitis after an initial exposure to ethanol, but this is the exception rather than the rule. Most patients with alcoholic pancreatitis already have chronic pancreatitis and present with an acute exacerbation.

TABLE 1 Selected Causes of Acute Pancreatitis

Following alcoholic and gallstone-related pancreatitis, the next largest category is idiopathic pancreatitis. It is estimated that in approximately 10 percent of patients no cause can be found.(4) Even this approximation may be high in light of recent reports implicating biliary microlithiasis and biliary sludge as etiologic in patients believed to have idiopathic pancreatitis.(5)(6) Indeed, it is recommended that patients without an easily identified cause of acute pancreatitis undergo endoscopic retrograde cholangiopan-creatography (ERCP) with bile aspiration to exclude microcrystals as an etiology.

Acute pancreatitis caused by the passage of biliary tract stones is referred to as "gallstone pancreatitis." Gallstones may be recovered in the feces in up to 88 percent of patients with gallstone pancreatitis.(7)

Marked elevation of serum triglycerides has been causally linked with acute pancreatitis in 12 percent to 38 percent of patients.(8) A triglyceride level greater than 1,000 mg per dL (11.29 mmol per L) should prompt a search for an underlying hyperlipidemic disorder, even if alcohol intake is verified. Values above this threshold indicate preexisting defects in lipid metabolism.(9) A Type V lipid profile is the most common pattern seen in patients with lipid-associated pancreatitis. The pathogenesis of acute pancreatitis due to elevated lipid fractions is not known.

Several medications have been associated with acute pancreatitis (Table 2). The mechanism of pancreatic injury is not well defined but may range from hypersensitivity reactions to accumulation of a toxic metabolite.

TABLE 2 Medications Associated with Acute Pancreatitis

Hyperparathyroidism, when associated with hypercalcemia, is reported to cause acute pancreatitis.(10) Hypercalcemia due to other disorders, such as parathyroid adenoma or carcinoma, excessive doses of vitamin D, familial hypocalciuric hypercalcemia and hypercalcemia in patients receiving total parenteral nutrition, has been reported to cause acute pancreatitis as well. In humans, secretion of pancreatic enzymes is enhanced by infusion of calcium salts. It is postulated that increased concentrations of calcium ions may promote activation of trypsinogen, thereby initiating the enzymatic cascade to acute pancreatitis.(11) However, some authors have questioned the validity of this association.(12)

Lesions that produce pancreatic ductal obstruction, such as pancreatic, duodenal or ampullary tumors, may cause acute pancreatitis.(13)(14) An analogous situation occurs in the anatomic variant, pancreas divisum.(15) Pancreas divisum, present in about 10 percent of the population, is the result of failure of the ventral and dorsal pancreatic anlages to fuse. Thus, the uncinate process and a portion of the pancreatic head drain via the duct of Wirsung through the papilla of Vater while the balance of the head, the neck, body and tail drain via the duct of Santorini through the minor papilla. The association of pancreas divisum with acute pancreatitis is controversial, but this anomaly appears to be the etiology of symptoms in some patients. This entity may be diagnosed via ERCP (Figure 1).

[ILLUSTRATION OMITTED]

The ability to perform Oddi's sphincter manometry has allowed biliary endoscopists to identify abnormal pressures within the sphincter. Dysfunction of Oddi's sphincter has been implicated in some patients with acute pancreatitis, and this disorder may respond well to sphincterotomy.(16)

ERCP itself is associated with a 1 to 7 percent risk of initiating acute pancreatitis.(17) This complication is usually mild and may be related to the degree of filling of the pancreatic duct.

Trauma-induced pancreatitis is generally due to blunt trauma rather than penetrating damage.(18) Complications such as pseudocysts are common due to resulting damage to the pancreatic duct. Injury to the gland is difficult to diagnose, and frequently patients present months after the initial injury with obstructive pancreatitis secondary to a post-traumatic stricture. ERCP is valuable in making this diagnosis.

Postoperative pancreatitis occurs as a potential complication of surgical procedures. Typically, this is a consequence of operations involving the pancreas or periampullary area, although acute pancreatitis after surgery involving areas remote to the pancreas has been reported.(19) Numerous factors may be involved in the pathogenesis of postoperative pancreatitis, including direct injury to the pancreas, infection and hypotension or hypoperfusion.

Acute pancreatitis occurs in up to 7 percent of patients who have had organ transplant, predominantly cardiac and renal transplantation.(20)(21) Hypotension, hypoperfusion, immunosuppressants and infections have been cited as factors.

Numerous infectious agents have been linked with acute pancreatitis, including mumps, cytomegalovirus, hepatitis virus, tuberculosis and parasites such as ascaris and clonorchiasis. Ascaris, in particular, should be suspected in patients who have recently traveled to the Middle East or Asia (Figure 2). Endoscopy can be used to extract these helminths from the biliary tree.(22)

[ILLUSTRATION OMITTED]

Hereditary pancreatitis, an autosomally dominant disorder, is a rare cause of acute pancreatitis.(23) Other infrequent causes of acute pancreatitis include rheumatologic disorders such as systemic lupus erythematosus,(24) mixed connective tissue disease(25) and scleroderma.(26)

Pathophysiology

Autodigestion of the pancreas, believed to be primarily due to activation of trypsin, causes the pathologic changes found in acute pancreatitis. Normally, several mechanisms prevent this occurrence. The pancreatic proteases, such as trypsin, chymotrypsin, elastase, carboxypeptidase and phospholipase A, are secreted as proenzymes requiring activation for catalytic activity. Trypsin is central to this activation and is known to be activated by a duodenal brush-border enzyme, enteropeptidase (enterokinase). Trypsin, in turn, activates the other proteolytic enzymes. Phospholipase A may be responsible for the pulmonary manifestations of acute pancreatitis, such as adult respiratory distress syndrome. Elastase produces vascular damage and hemorrhage by a direct effect on the elastic fibers of blood vessels. Fat necrosis occurs as a result of the action of lipase. Chymotrypsin elicits edema and vascular injury. Various other vasoactive and cytotoxic substances are similarly activated.

Clinical Presentation

SYMPTOMS

Midepigastric pain, nausea and vomiting are the typical symptoms associated with acute pancreatitis. The abdominal pain frequently radiates to the back. The pain is sudden in onset, progressively increases in intensity and becomes constant after maximum severity is reached.

PHYSICAL EXAMINATION

Patients with acute pancreatitis appear ill and complain of severe abdominal pain. Usually the severity of pain causes the patient to move continuously in search of a more comfortable position. Findings that suggest severe pancreatitis include hypotension due to the massive amounts of fluid sequestered, tachypnea with decreased basilar breath sounds due to pleural effusion, and flank (Grey Turner's sign) or periumbilical (Cullen's sign) ecchymoses indicative of hemorrhagic pancreatitis. Fever does not necessarily imply infection, although infection should be ruled out.

Some patients may have abdominal distention. Tenderness in the epigastrium is uniformly found. Patients may have voluntary and/or involuntary guarding. Rebound tenderness with hypoactive or absent bowel sounds indicates generalized peritoneal irritation.

Laboratory Tests

Routine laboratory tests usually reveal leukocytosis with a left shift and an elevated hematocrit (reflecting hemoconcentration). Hyperglycemia is common and is believed to be a result of catecholamine and glucagon release, coupled with diminished insulin secretion. Prerenal azotemia may be evident secondary to dehydration. Hypoalbuminemia, hypertriglyceridemia and hypocalcemia may all be variably present. Hyperbilirubinemia with mild elevations of transaminases and alkaline phosphatase is common, although higher levels are seen with gallstone-induced pancreatitis.

Diagnostic Tests

AMYLASE

The most widely used blood test for the diagnosis of pancreatitis is the serum amylase level. With the appropriate findings on history and physical examination, an elevated amylase level often confirms the clinical diagnosis. Although most patients present with hyperamylasemia, this is not found in all cases. A limitation of the amylase level relates to its rapid release (typically within hours of an attack) and its subsequent decline to normal over the next two to five days. As with all tests, its sensitivity and specificity is dependent on the cutoff value used.(27) Hyperamylasemia is found in many other conditions and is not unique to acute pancreatitis (Table 3). Lastly, due to renal excretion of amylase, patients with renal failure may have elevated serum amylase levels as a result of prolonged renal clearance.(28)

TABLE 3 Selected Conditions Other Than Pancreatitis Associated with

Amylase Elevation

ERCP=endoscopic retrograde cholangiopancreatography.

In order to determine the origin of serum amylase elevation, isoenzyme measurements are generally used. The two main sources of isoenzymes are the pancreas and the salivary glands. Amylase fractionation may be most useful in patients with elevated serum amylase levels and an atypical clinical presentation.

Early optimism regarding the utility of the amylase/creatinine clearance ratio as another laboratory measure of acute pancreatitis has waned because of frequent false-positive and false-negative results.

LIPASE

Serum lipase measurements are more specific for pancreatitis than amylase levels but less sensitive.(27) Although the pancreas is the main source of lipase, hyperlipasemia may also occur in patients with renal failure,(28) perforated ulcer disease, bowel infarction and bowel obstruction. An added advantage of a lipase determination is the longer clearance time of this enzyme, compared with amylase.

ABDOMINAL RADIOGRAPHS

Abdominal radiographs may reveal nonspecific findings such as "sentinel loops" (dilated loops of small bowel in the vicinity of the pancreas), ileus and, occasionally, pancreatic calcifications indicative of chronic pancreatitis. However, the chief value of the abdominal radiograph is in the detection of nonpancreatic sources of abdominal pain such as a perforated viscus or bowel obstruction.

ULTRASONOGRAPHY

The use of ultrasonography to evaluate the pancreas in acute pancreatitis is limited by the associated ileus in most patients. This modality demonstrates the entire pancreas in only approximately 20 percent of patients with acute pancreatitis.(29) Thus, ultrasound examination is of limited value in the initial evaluation of pancreatitis. Its greatest utility is in evaluation of patients with possible gallstone disease and in following the progression of pancreatic pseudocysts.

COMPUTED TOMOGRAPHY

Computed tomography (CT) using highresolution scanners is the imaging modality of choice in acute pancreatitis. Findings vary with the severity of disease (Figures 3a and 3b). In approximately 14 percent to 29 percent of patients, CT findings will be normal, usually indicating mild disease.(30) The mild form of pancreatitis may be seen on CT scans as focal or diffuse enlargement of the gland with its interface with the peripancreatic fat obscured. Additionally, pancreatic necrosis, a marker for the severity of pancreatitis and potential infection, may be discerned by CT. After rapid intravenous injection of contrast medium (dynamic sequential pancreatography), necrotic pancreatic tissue will have less enhancement than mildly inflamed or normal pancreatic tissue.(31)

[ILLUSTRATION OMITTED]

The complications of acute pancreatitis, particularly pseudocysts and abscesses, are well-delineated with CT scanning. Fineneedle aspiration of suspected abscesses, using ultrasound or CT guidance, may be valuable in planning further therapy.

Prognosis

The two major scoring systems used to determine prognosis in acute pancreatitis are Ranson's criteria and Glasgow criteria. Ranson and colleagues(32) developed a list of 11 risk factors (Table 4), five on admission and six within the first 48 hours, to help determine severity of disease. Patients with two or fewer risk factors had a mortality rate of less than 1 percent; those with three or four risk factors, a mortality rate of 16 percent; five or six risk factors, a mortality rate of 40 percent; and seven or eight risk factors, a mortality rate approaching 100 percent. Clinicians in Glasgow simplified Ranson's criteria by reducing the number of risk factors from 11 to eight. Table 4 also gives the modification of the Glasgow criteria that is currently used.(33)

TABLE 4 Prognostic Criteria for Acute Pancreatitis

WBC = white blood cell count;

LDH = lactate dehydrogenase;

AST = aspartate aminotransferase;

SGOT = serum glutamic-oxaloacetic transaminase;

BUN = blood urea nitrogen;

P[O.sub.2] = oxygen partial pressure.

Derived from references 32 and 33.

Investigators in the United Kingdom advocate the use of a peritoneal tap to gauge prognosis in acute pancreatitis. This procedure is not widely used in this country due to its invasiveness, risk of complications, and the equal sensitivity and specificity of Ranson's criteria or Glasgow criteria.

CT scanning is being used increasingly in the evaluation of the severity of acute pancreatitis. Although the sensitivity of this technique may approach 85 to 95 percent in the detection of necrosis,(34) patients with little or no perfusion defects on CT still may have a complicated course.

Treatment

Although most cases of acute pancreatitis will improve within three to seven days with conservative therapy, the key to management is prevention and early detection of the complications of severe pancreatitis. Although a detailed discussion of the various local and systemic complications is beyond the scope of this review, a few salient points will be discussed.

The cornerstone of management in acute pancreatitis is vigorous intravenous hydration. Patients may sequester liters of fluid, leading to intravascular depletion, prerenal azotemia and shock. A decrease in urine output to less than 30 mL per hour is a good indication of inadequate fluid replacement. Vital signs and oxygenation should be monitored frequently, since any change could herald the onset of severe pancreatitis and its complications.

Pulmonary complications may be manifested by only a decrease in oxygen saturation. It is not uncommon for patients to be hypoxic, yet manifest no distress or cyanosis. Deterioration of oxygen saturation mandates measurement of arterial blood gases for an accurate assessment of oxygen levels. The physician must be vigilant for the pulmonary complications of pleural effusions and adult respiratory distress syndrome.

Frequent laboratory tests, particularly measurement of electrolyte levels, will enable the clinician to detect the electrolyte alterations associated with acute pancreatitis: hypocalcemia, hypokalemia and hypomagnesemia. Disseminated intravascular coagulation occurs in severe cases.

Traditionally, patients take nothing by mouth to minimize pancreatic secretions. Total parenteral nutrition should be instituted in those patients fasting for a prolonged period of time (generally more than five days) in order to prevent malnutrition.

The use of a nasogastric tube is warranted primarily in patients with nausea and vomiting or ileus, but is not universally required.(35)

Pain control is also a key element in the management of patients with pancreatitis. The use of morphine is discouraged due to its effect on Oddi's sphincter (spasm), which may exacerbate the pancreatitis. Meperidine (Demerol) is favored. Other injectable agents such as ketorolac (Toradol) are also used.

A host of newer therapies have been proposed, but controlled, prospective trials have not shown consistent benefits. Use of prophylactic antibiotics, to prevent the septic complications such as abscess formation, has not been shown to have any additional beneficial effects.(36) Hormonal suppression of pancreatic secretions with somatostatin or its analogue, octreotide, is appealing in theory, but the current data are conflicting.(37)(38) Studies of protease inhibitors such as aprotinin have been disappointing.(39)

Other treatments that have been shown to be of no benefit in the treatment of acute pancreatitis include cimetidine (Tagamet), anticholinergic drugs and glucagon.(40)

The clinician must be vigilant for "treatable" causes of acute pancreatitis, such as medication-induced injury, gallstone pancreatitis and pancreatitis due to occult microlithiasis. Patients with pancreatitis due to cholelithiasis will benefit from endoscopic intervention. Optimally, these patients should undergo ERCP with sphincterotomy and stone extraction (Figure 4). In patients presenting with severe pancreatitis and those with cholangitis, recent studies suggest that ERCP and sphincterotomy within 48 hours of admission decrease morbidity and mortality.(41)

[ILLUSTRATION OMITTED]

Resolving pancreatitis is marked by the absence of pain, declining amylase levels, evidence of improvement on imaging studies and normalization of vital signs.

The Role of Surgery

CT scanning should be performed to detect local complications of acute pancreatitis (i.e., pseudocyst and/or abscess) in a patient with continued clinical deterioration or failure to improve. It is generally agreed that pseudocysts smaller than 5 cm in diameter will resorb without intervention. Pseudocysts greater than 5 cm usually require surgical intervention after the wall has matured. Any question of abscess or infected pancreatic material mandates fine-needle aspiration under CT guidance. Patients found to have complicated pancreatitis with abscess should undergo drainage. The mortality rate for pancreatic abscess is exceedingly high when left untreated.

Final Comment

The approach to patients with acute pancreatitis is watchful waiting. Once clinical suspicion is confirmed by either laboratory and/or radiographic studies, patients should receive adequate intravenous hydration with serial determinations of vital signs and chemistries. Potentially treatable causes of acute pancreatitis should be addressed. Vigilance for systemic complications is mandatory. If complications are suspected or discovered, there should be a low threshold for transferring the patient to the intensive care unit for hemodynamic monitoring. Infected pancreatic tissue should be diagnosed by means of fine-needle aspiration under CT guidance. Surgical intervention may be required if infection is confirmed. Although the vast majority of patients have mild pancreatitis and hence a relatively uneventful hospital course, early recognition of severe pancreatitis and its complications may further decrease the risk of mortality.

REFERENCES

(1.)Levelle-Jones M, Neoptolemos JP. Recent advances in the treatment of acute pancreatitis. Surg Annu 1990; 22:235-61.

(2.)Singer MV, Gyr K, Sarles H. Revised classification of pancreatitis. Report of the Second International Symposium on the Classification of Pancreatitis in Marseille, France, March 28-30, 1984. Gastroenterology 1985; 89:683-5.

(3.)Leese T, Shaw D. Comparison of three Glasgow multifactor prognostic scoring systems in acute pancreatitis. Br J Surg 1988; 75:460-2.

(4.)Steer ML. Classification and pathogenesis of pancreatitis. Surg Clin North Am 1989; 69:467-80.

(5.)Lee SP, Nicholls JF, Park HZ. Biliary sludge as a cause of acute pancreatitis. N Engl J Med 1992; 326:589-93.

(6.)Ros E, Navarro S, Bru C, Garcia-Puges A, Valderrama R. Occult microlithiasis in 'idiopathic' acute pancreatitis: prevention of relapses by cholecystectomy or ursodeoxycholic acid therapy. Gastroenterology 1991; 101:1701-9.

(7.)Acosta JM, Ledesma CL. Gallstone migration as a cause of acute pancreatitis. N Engl J Med 1974; 290:484-7.

(8.)Farmer RG, Winkelman EI, Brown HB, Lewis LA. Hyperlipoproteinemia and pancreatitis. Am J Med 1973; 54:161-5.

(9.)Toskes PP. Hyperlipidemic pancreatitis. Gastroenterol Clin North Am 1990; 19:783-91.

(10.)Sitges-Serra A, Alonso M, de Lecea C, Gores PF, Sutherland DE. Pancreatitis and hyperparathyroidism. Br J Surg 1988; 75:158-60.

(11.)Geokas MC, Baltaxe HA, Banks PA, Silva J Jr, Frey CF. Acute pancreatitis. Ann Intern Med 1985; 103:86-100.

(12.)Bess MA, Edis AJ, van Heerden JA. Hyperparathyroidism and pancreatitis. Chance or a causal association? JAMA 1980; 243:246-7.

(13.)Lin A, Feller ER. Pancreatic carcinoma as a cause of unexplained pancreatitis: report of ten cases. Ann Intern Med 1990; 113:166-7.

(14.)Guzzardo G, Kleinman MS, Krackov JH, Schwartz SI. Recurrent acute pancreatitis caused by ampullary villous adenoma. J Clin Gastroenterol 1990; 12:200-2.

(15.)Delhaye M, Engelholm L, Cremer M. Pancreas divisum: congenital anatomic variant or anomaly? Contribution of endoscopic retrograde dorsal pancreatography. Gastroenterology 1985; 89:951-8.

(16.)Neoptolemos JP, Bailey IS, Carr-Locke DL. Sphincter of Oddi dysfunction: results of treatment by endoscopic sphincterotomy. Br J Surg 1988; 75:454-9.

(17.)Sherman S, Lehman GA. ERCP- and endoscopic sphincterotomy-induced pancreatitis. Pancreas 1991; 6:350-67 [Published erratum appears in Pancreas 1992; 7:402].

(18.)Northrup WF 3d, Simmons RL. Pancreatic trauma: a review. Surgery 1972; 71:27-43.

(19.)Thompson JS, Bragg LE, Hodgson PE, Rikkers LF. Postoperative pancretitis. Surg Gynecol Obstet 1988; 167:377-80.

(20.)Fernandez-Cruz L, Targarona EM, Cugat E, Alcaraz A, Oppenheimer F. Acute pancreatitis after renal transplantation. Br J Surg 1989; 76:1132-5.

(21.)Aziz S, Bergdahl L, Baldwin JC, Weiss LM, Jamieson SW, Oyer PE, et al. Pancreatitis after cardiac and cardiopulmonary transplantation. Surgery 1985; 97:653-61.

(22.)Leung JW, Chung SC. Endoscopic management of biliary ascariasis. Gastrointest Endosc 1988; 34:318-20.

(23.)Girard RM, Dube S, ARchambault AP. Hereditary pancreatitis: report of an affected Canadian kindred and review of the disease. Can Med Assoc J 1981; 125:576-80.

(24.)Eaker EY, Toskes PP. Systemic lupus erythematosus presenting initially with acute pancreatitis and a review of the literature. Am J Med Sci 1989; 297:38-41.

(25.)Marshall JB, Kretschmar JM, Gerhardt DC, Winship DH, Winn D, Treadwell EL, et al. Gastrointestinal manifestations of mixed connective tissue disease. Gastroenterology 1990; 98(5 Pt 1):1232-8.

(26.)Greif JM, Wolff WI. Idiopathic calcific pancreatitis, CRST syndrome and progressive systemic sclerosis. Am J Gastroenterol 1979; 71:177-82.

(27.)Steinberg WM, Goldstein SS, Davis ND, Shamma'a J, Anderson K. Diagnostic assays in acute pancreatitis. A study of sensitivity and specificity. Ann Intern Med 1985; 102:576-80.

(28.)Collen MJ, Ansher AF, Chapman AB, Mackow RC, Lewis JH. Serum amylase in patients with renal insufficiency and renal failure. Am J Gastroenterol 1990; 85:1377-80.

(29.)Silverstein W, Isikoff MB, Hill MC, Barkin J. Diagnostic imaging of acute pancreatitis: prospective study using CT and sonography. Am J Roentgenol 1981; 137:497-502.

(30.)Balthazar EJ. CT diagnosis and staging of acute pancreaatitis. Radiol Clin North Am 1989; 27:19-37.

(31.)Bradley EL 3d, Murphy F, Ferguson C. Prediction of pancreatic necrosis by dynamic pancreatography. Ann Surg 1989; 210:495-503.

(32.)Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet 1974; 139:69-81.

(33.)Blamey SL, Imrie CW, O'Neill J, Gilmour WH, Carter DC. Prognostic factors in acute pancreatitis. Gut 1984; 25:1340-6.

(34.)Maier W. Early objective diagnosis and staging of acute pancreatitis by contrast enhanced computed tomography. In: Beger HG, Buchler M, eds. Acute pancreatitis. New York: Springer Verlag, 1987:132-40.

(35.)Sarr MG, Sanfey H, Cameron JL. Prospective, randomized trial of nasogastric suction in patients with acute pancreatitis. Surgery 1986; 100:500-4.

(36.)Finch WT, Sawyers JL, Schenker S. A prospective study to determine the efficacy of antibiotics in acute pancreatitis. Ann Surg 1976; 183:667-71.

(37.)Choi TK, Mok F, Zhan WH, Fan ST, Lai EC, Wong J. Somatostatin in the treatment of acute pancreatitis: a prospective randomised controlled trial. Gut 1989; 30:223-7.

(38.)Baxter JN, Imrie CW, McKay CJ. Acute pancreatitis and octreotide [Letter]. Lancet 1991; 338:389.

(39.)Imrie CW, Benjamin IS, Ferguson JC, McKay AJ, Mackenzie I, O'Neill J, et al. A single-centre double-blind trial of Trasylol therapy in primary acute pancreatitis. Br J Surg 1978; 65:337-41.

(40.)Marshall JB. Acute pancreatitis. A review with an emphasis on new developments. Arch Intern Med 1993; 153:1185-98.

(41.)Neoptolemos JP, Carr-Locke DL, London NJ, Bailey IA, James D, Fossard DP. Controlled trial of urgent endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to gallstones. Lancet 1988; 2(8618):979-83.

COPYRIGHT 1995 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group