Acute Surgical Diseases of the Pancreas

Symposium on Surgical Emergencies

Acute Surgical Diseases of the Pancreas Robert J. Baker, M.D.*

Acute disease states involving the pancreas have been managed by nonoperative means only until rather recently. The pancreas, a friable, remote, and difficult organ to manipulate surgically, is prey to several common disease states; operative intervention, despite frank indications, is frequently delayed until the condition has deteriorated beyond salvage. During the past 15 years, a more aggressive approach to acute pancreatic conditions has been adopted. Improvement in results has varied considerably from place to place and from entity to entity, but more satisfactory and precise operative treatment when indicated, coupled with intensive diagnostic investigation of acutely ill patients, has resulted in lesser morbidity and mortality. To be excluded from this discussion are the congenital malformations and dysfunctions of the pancreas, primarily mucoviscidosis, manifest as meconium ileus, and annular pancreas, with neonatal gastroduodenal obstruction. Concern will center about acquired acute lesions of the pancreas and parapancreatic structures, specifically inflammatory and traumatic conditions.

ACUTE PANCREATITIS One of the most puzzling of all states causing acute abdominal pain, acute pancreatitis is an enigma to students and house officers, and a frequently overlooked possibility even by the accomplished clinician. All surgeons have had one or several humbling experiences in which ruptured viscus or other abdominal catastrophe was diagnosed, and exploration revealed the true condition to be, embarrassingly, acute pancreatitis. Unfortunately, the mortality rate in such patients explored varies from 20 to 80 per cent, depending on the series reportedY· 13 It would appear that some operative maneuvers can improve the mortality in the critically ill patient with pancreatitis; similarly, earlier operation in those From the Department of Surgery, The Abraham Lincoln School of Medicine, University of Illinois at the Medical Center, Chicago *Professor of Surgery Surgical Clinics of North America- Vol. 52, No. 1, February 1972

239

240

RoBERT

J.

BAKER

patients with certain complications of the basic disease process may be life-saving.

Etiology Acute pancreatitis has been characterized, in part, by the suspected triggering mechanism, which varies in frequency with the type of patient under consideration (Table 1) and the reporting institution. In the patients seen in public hospitals, from city-county to federal veterans' care facilities, the incidence of pancreatitis triggered by alcoholism is much higher than all other causes combined. 4 • 11 • 20 The precise relationship between ingestion of large amounts of alcohol and the development of pancreatitis remains a mystery, but may bear on the effects of alcohol in simultaneously stimulating secretin production and causing sphincter of Oddi spasm with partial obstruction to pancreatic ductal outfiow. 11 Zieve's syndrome, the concurrent finding of chronic alcoholism, acute pancreatitis, and hyperlipemia, has been frequently recognized; however, hyperlipemia as a secondary phenomenon in acute pancreatitis is common enough to be of passing concern only. Incidentally, hyperlipemia appears to have serious prognostic implication when observed in the course of acute pancreatitis. Despite its frequency, and an extraordinary investigative effort to elaborate the effect of alcohol on the pancreatic acinar cell, it would appear that the effect is subcellular in locus, and that electron microscopic studies of experimental and human pancreatitis will elaborate more information than the mechanistic approach utilized thus far. Equally difficult to explain is the striking relationship between acute pancreatitis and disease of the biliary tract. Most remarkable is the relative infrequency of this cause of pancreatitis in tax-based hospitals, despite the frequency with which calculous disease of the gallbladder and bile ducts is observed. Speculation has centered about the marked dietary differences between affluent and non-affluent patients, in part supported by the information available throughout the United States, but definitely counter to experiences garnered in the Orient and Southeast Asia; there, protein deficiency and lack of alcohol result in a very high incidence of pancreatitis, with and without gallstones. Many of these patients (50 to 60 per cent) are thought to have diabetes consequent upon acute and chronic pancreatitis and pancreatic fibrosis. The common channel theory of Opie, proposed in 1901, suggests that gallstones cause pancreatitis by mechanical block to outflow of bile and

Table 1.

Incidence of Causes of Acute Pancreatitis

Alcoholic pancreatitis Biliary tract disease Metabolic derangements Postoperative Traumatic Idiopathic

TAX-SUPPORTED

COMMUNITY

HOSPITALS

HOSPITALS

65-80% 10-15% 1-2% 1-8% 0.5-3% 3-15%

10-20% 45-65% 1-2% 2% 0.5-1.5% 10-30%

ACUTE SURGICAL DISEASES OF

THE PANCREAS

241

pancreatic juice from a common channel, or that calculous gallbladder disease causes sphincter spasm with resulting obstruction. Inherent in this explanation for the causation of pancreatitis is the assumption that a bile-pancreatic juice mixture in the common bile duct will enter and destroy the ductal and ductular structures of the pancreas. However, intrapancreatic secretory pressure is considerably higher than intracholedochal pressure, and such a concept is generally not tenable. Nevertheless, the definite, strongly positive correlation between biliary tract calculous disease and pancreatitis is extremely important in terms of treatment. Patients have been reported who have harbored various parasites, worms, and flukes in the biliary tree, some even obstructing the pancreatic duct, a very rare cause of acute pancreatitis. Parenthetically, it should be noted that many surgeons routinely ligate the pancreatic duct when performing pancreaticoduodenectomy, the Whipple operation, for carcinoma of the head of the pancreas. This obstruction does not lead to postoperative pancreatitis, provided the ligation is not accompanied by extensive destruction of pancreatic parenchyma. Weiner and associates have implicated lymphatic communications between the extrahepatic biliary apparatus and the pancreas in the genesis of pancreatitis associated with biliary tract disease. 18 The supposition is that inflammatory products transmitted from gallbladder to pancreas in the experimental preparation will cause pancreatitis. An incidental observation in experimental pancreatitis is that lymphatic obstruction occurs early, primarily with red cells and necrotic debris. Further, fibrotic obliteration of lymphatics with acute recurrent pancreatitis would make thoracic duct drainage in pancreatic ascites appear to be an attractive maneuver; it has not proven so in clinical trial. Metabolic causes of acute pancreatitis include hyperparathyroidism, congenital or familial hyperlipemia, prolonged steroid administration, and nutritional deficiencies, primarily in one or several essential amino acids. 10 • 19 Hyperparathyroidism with hypercalcemia has been investigated, and the assumption that calcium levels in the high ranges convert the proenzyme trypsinogen to trypsin, causing gland autolysis, appears attractive. However, other causes of hypercalcemia, notably metastatic and metabolic bone disease, do not result in pancreatitis. Conversely, renal transplant recipients have been shown to have a 2 per cent incidence of severe pancreatitis, and a very definite correlation between steroid therapy and pancreatitis has been demonstrated in patients with collagen disease. 10 It is likely that immunosuppressive doses of steroids in the transplant recipients can be implicated as the causative factor, although the effect of steroids on pancreatic tissue is not known. Postoperative and traumatic pancreatitis will be discussed in a subsequent section, as these are unique forms of the disease, requiring different treatment. Idiopathic pancreatitis is a wastebasket term for a group of patients who probably have undetected metabolic derangement or, more often, hidden alcoholism, to which the patient is reluctant to admit.

Diagnosis Acute pancreatitis, regardless of etiology, can simulate almost any known abdominal catastrophe. The protean manifestations, ranging from

242

RoBERT

Table 2.

J.

BAKER

Differential Diagnosis of Acute Pancreatitis PERFORATED

HISTORY

ACUTE PANCREATITIS

Vomiting

Invariable; frequent episodes Location of pain Upper abdominal, primarily epigastric Radiation of pain Straight through to back Quality of pain Constant, boring Nature of onset Gradual to sudden Duration of pain 2-24 hours Previous attacks 35% have Fatty food intolerance 10-35% Alcoholism 10-75% (Table 1) Age 20-40 years 7 male/1 female Sex

Physical Findings Tachycardia Habitus

Tenderness Rebound tendemess Rigidity

Peristaltic sounds Costovertebral angle tenderness Ascites (paracentesis) Shock Cullen-Grey-Tumer signs Mass

Psychosis

Early, 120-140 Lie on side with knees flexed, or sit on edge of bed; "thrash about" Epigastric, may be diffuse Late, moderate "Pseudorigid"-abdominal musculature gives with gentle pressure Hypoactive; may cease after 8-12 hours Common on left After 12-24 hours, serous to "prune-juice" Usually after 16-24 hours, if present Rare, after 48 hours when seen After 48 hours, may be in epigastrium or left upper quadrant Late (2-4 days) with very severe pancreatitis

ACUTE CHOLECYSTITIS

PEPTIC ULCER

Usual

Occasional

Right upper quadrant

Epigastric and/or right upper quadrant Through entire abdomen Diffuse Sudden, precipitous 1-12 hours 10% have 5-10% 5-15% 15-50 years 9 male/1 female

Around to right scapula Constant or episodic Gradual 4-48 hours 20% have 50-60% 10-20% 30-75 + years 4 female/1 male

Late, proportional to fever Early, severe Lie flat, or relatively Lie supine, immobile immobile Right upper quadrant Usually localized Absent; unilateral rectus spasm (right)

Diffuse Early, profound Early, severe

Hypoactive

Disappear early

Rare on right

Absent

Absent Absent

Early, bile-stained frequently Early (4 hours+)

Absent

Absent

With complication, in right upper quadrant

None

Absent

Absent

gastrointestinal hemorrhage to pleural effusion, can be extremely confusing if chemical evidence of the disease is lacking. The primary differential diagnosis, however, centers about the presence of upper abdominal pain, seen in 97 per cent of cases during the first 48 hours of illness. Since this is so prominent a finding, it is useful to contrast the findings in acute pancreatitis with those of acute cholecystitis and perforated peptic ulcer, the other two acute conditions so easily confused with acute pancreatitis (Table 2). Several of these historical findings warrant emphasis. Vomiting is invariably present with acute pancreatitis; emeses may be few in number but are generally frequent, at short intervals, and do not relieve discomfort. Bile may or may not be present. The pain is usually upper abdominal, but the patient will indicate the worst discomfort to be in the epigastrium if questioned closely. Pain may be generalized, especially

ACUTE SURGICAL DISEASES OF THE PANCREAS

243

after 12 to 18 hours, and simulate that of a perforated viscus. Back pain is usual, and occasionally is equal in intensity to the anterior abdominal pain; flank pain is rare. Onset of pain characteristically is gradual, but in alcoholic pancreatitis is sometimes reported as sudden and catastrophic in onset, similar to perforated ulcer. Cramping pain is rare; ordinarily the pain is boring, knife-like and unremitting. A history of previous similar attacks is helpful, ruling out perforated ulcer or other perforated viscus. If associated with alcoholic debauch, greater reliance can be placed on pancreatitis as the working diagnosis. The physical examination can be extremely helpful in establishing the diagnosis. Tachycardia out of proportion to the fever appears early, after 6 to 12 hours, with pulse rates of 120 to 140 per minute regularly seen. The habitus or position the patient voluntarily assumes is characteristic; the patients are restless, moving about in a attempt to obtain relief, or lie on either side with hips and knees flexed. Occasionally, the patient will be found sitting on the edge of the bed, knees drawn up. Hip flexion, and forward flexion of the spine, relaxes the iliopsoas muscle; the inflammatory process in acute pancreatitis is retroperitoneal in that area, and relaxation of the psoas muscle mass affords a slight measure of pain relief. Tenderness and rebound tenderness are frequently less impressive than the patient's symptoms would lead the examiner to expect. "Pseudorigidity" is common, and appears superficially to be severe, like that of perforated ulcer. However, if the examining hand is gently but firmly pressed against the abdominal wall, the muscles will yield somewhat to pressure. Distention, due to ileus, and loss of peristaltic sounds, are not observed until after 8 to 12 hours of illness. Most significant is the finding of left costovertebral angle tenderness in well over two-thirds of patients with acute pancreatitis. The tail of the pancreas overlies the left kidney, and interstitial inflammation of the left kidney as well as perinephric reaction results in this finding. Ascites may be present, is generally modest in amount, but abdominal paracentesis is helpful with this disease, yielding straw-colored, hemorrhagic, or classical "prune-juice" fluid, of brownish-purple color. This fluid is turbid, loaded with polymorphonuclear leucocytes, and generally has extremely high amylase values. Shock occurs relatively late, and is due to sequestration of large amounts of fluid in the properitoneal space, peritoneal cavity, and intestinal lumen. Early onset of shock is suggestive of massive pancreatic necrosis, "pancreatic apoplexy," or major retroperitoneal hemorrhage from a complication such as pseudocyst. Upper gastrointestinal bleeding occurs in 15 per cent of patients with hemorrhagic pancreatitis, is rarely major, and is manifest as "coffee-ground" gastric suction return, or occasionally intermittent bleeding. Perforated ulcers, of course, may also bleed, sometimes massively. Cullen's sign, periumbilical and umbilical ecchymosis, is frequently mentioned but rarely seen in acute hemorrhagic pancreatitis. Even less frequent is Grey-Turner's sign, a blotchy, bluish-purple ecchymotic discoloration in the left flank, due to dissection of blood and activated pro-

RoBERT ]. BAKER

teolytic enzymes through fascia and muscle to the subcutaneous tissue. Both signs signify massive necrosis, enzyme release and hemorrhage, and require vigorous resuscitative measures. An epigastric mass seen after 48 hours rarely is palpable inflamed pancreas, but usually either is a large area of omental fat necrosis or, after 4 days, may represent a pseudocyst. In very severe forms of pancreatitis, frank psychosis may develop.U The patients hallucinate, are difficult to control, and are frequently thought to have delirium tremens. However, gross tremor is absent, and alcoholic intake may not have preceded the attack. The mechanism of production is thought to be protease or lipase effect on the central nervous system, consequent upon the release of large amounts of activated enzyme into the circulation. Experimentation with intravenous infusion of human and bovine enzymes in conscious animals, however, does not produce discernible or elecJ:roencephalographic changes suggestive of the psychosis seen in these patients. Apparently, unidentified metabolites or derangements of function are operative. The prognosis in patients with psychosis due to acute pancreatitis is grave, mortality rates exceeding 40 per cent. jaundice is frequently listed as a positive finding in acute pancreatitis, but is uncommon in most reported series. 20 When present, it is chemical, with serum bilirubin levels between 1.5 and 3.0 mg. per 100 ml. If the bilirubin is above 5.0 mg. per 100 ml. in the first week of illness, common bile duct calculus with pancreatobiliary obstruction should be suspected and appropriately managed. Jaundice with pancreatic pseudocyst is much more common, but occurs later in the course of the disease.

Laboratory Studies

Elevation of serum amylase is the time-honored test utilized to diagnose acute pancreatitis. The normal value in the serum in most laboratories utilizing the Somogyi technique is 60 to 180 units. Any intra-abdominal inflammatory process, especially with peritonitis, will cause elevation; perforated duodenal ulcer, with spill of enzyme-rich duodenal fluid into the peritoneal cavity and absorption of enzymes into serum, usually causes some elevation of serum amylase. Abdominal trauma, renal insufficiency, and intestinal obstruction also cause moderate amylase elevation. Morphine administration causes considerable rise in amylase level, and opiates should never be used until amylases have been drawn when pancreatitis is a serious consideration. 15 As a rule, serum amylase levels over 500 Somogyi units are due to acute pancreatitis or a complication thereof, and serum levels over 700 units are diagnostic of pancreatitis or pseudocyst in the absence of severe renal failure. Unfortunately, the more severe forms of pancreatitis, specifically necrotizing and hemorrhagic, often have normal or low levels. Therefore, an elevation to diagnostic levels is extremely helpful, but normal levels or modest elevations are difficult to interpret. Serum levels remain elevated for only 24 to 36 hours with pancreatitis, as a rule. Frequently overlooked, but of much greater value than serum amylase, is urine amylase, performed on a random sample or a 2 hour speci-

ACUTE SURGICAL DISEASES OF THE PANCREAS

245

men. 15 It has been shown that canine and human renal clearance of amylase is not directly related to serum amylase levels. 7 For this reason, diagnostic elevations of urine amylase are frequently seen with slight serum rise or with normal serum values. Urine values over 800 Somogyi units are highly suggestive, and over 1000 units diagnostic for acute pancreatitis or pseudocyst. If the clinical condition permits, 24 hour urine collection for amylase content is the most accurate test available. Urine amylase elevations persist for 2 to 5 days, are obviously complementary to serum amylase, and should never be omitted in the investigation of acute upper abdominal pain. Serum lipase is frequently used, but must be measured on a fresh specimen and is a tedious and time-consuming laboratory determination. Current enthusiasm for serum lipase is based on a longer elevation than is seen with serum amylase, and therefore greater accuracy can be expected. Urinary amylase, however, is much easier to perform, and is obtainable at night, since the technique is identical to serum amylase. Serum lipase is not widely used for diagnostic purposes. Peritoneal fluid amylase is extremely helpful if fluid can be obtained by paracentesis, provided no bile is present in the specimen. Elevation over 1000 Somogyi units is suggestive of pancreatitis in bile-free specimens, and elevations to 1500 units or more are diagnostic. Methemalbuminemia has been reported to be diagnostic for hemorrhagic pancreatitis, as blood liberated from the pancreas is broken down to hemin, the hemin is converted to hematin, and this substance enters the serum. The hematin combines with albumin to form methemalbumin. Unfortunately, any patient with free peritoneal blood can form methemalbumin in serum, and numerous patients and experimental preparations with hemorrhagic infarction of intestine have likewise demonstrated abnormal methemalbumin levels. 8 Nonspecific abnormalities associated with severe acute pancreatitis are elevation of blood sugar, fall in serum calcium and fall in serum magnesium. Variable degrees of glucose intolerance are seen during and after trauma and other acute surgical diseases, and particularly with sepsis. Islet cell edema in pancreatitis is the specific cause of elevated blood sugar but has prognostic and therapeutic, rather than diagnostic, significance. Calcium and magnesium are deposited as metallic salts of fatty acids, or soaps, in areas of fat necrosis in the abdomen and in the vicinity of the pancreas. If these are large and lipase release is considerable, hypocalcemia and hypomagnesemia may occur, but rarely before the fourth to sixth days of illness. Because of this time lag, calcium and magnesium levels are obtained as baseline studies on admission, and are then obtained daily in order to gauge the progress of the disease. Although not specific for acute pancreatitis, albuminuria is usually observed with this entity. The presence of trace to 1+ albuminuria is a consequence of the proximity of the tail of the pancreas to the left kidney; when pancreatitis develops, interstitial nephritis and perinephritis of a temporary type result in abnormal solute and some white cells in the urine. Absence of albumin in the urine makes pancreatitis a less likely diagnosis.

::

246

u:a

_ass

RoBERT

J.

BAKER

Radiographic Study The value of radiographs in acute pancreatitis lies primarily in the area of ruling out other surgical entities requiring early or immediate operation. It is desirable to obtain four plain films as soon as the patient's condition is stable and initial examination has been done and laboratory material obtained. These views are: upright posteroanterior chest film (to rule out subphrenic free air), supine film of the abdomen (gas distribution), upright abdominal film (air-fluid levels, "J -loops" for intestinal obstruction) and left lateral decubitus view (free air between liver and lateral parietes). In these views, certain signs are suggestive of acute pancreatitis, though none is diagnostic. The sentinel loop is frequently described, a loop of gas-filled small intestine, transversely oriented, in the upper abdomen between the 12th thoracic and 3rd lumbar vertebrae. This is probably due to local ileus of the transverse duodenum, consequent upon bathing of that loop with blood and activated enzymes. The colon cut-off sign has been described later in the course of the disease at which time ileus is prominent, with moderate small intestinal and right-transverse colon gas, but no significant air is seen beyond the left transverse colon. This sign, too, is due to dissection of enzymes and irritating fluid through the transverse mesocolon to the colon wall. It is important to recall that the transverse mesocolon is close to and invests the neck and part of the body of the pancreas; it is common for the transverse mesocolon to be edematous, and the radiographic sign develops because of transverse colon paralysis. Roughly 10 per cent of patients with acute pancreatitis have minimal left pleural effusion, usually manifest as blunting of the costophrenic sinus. This fluid is a result of transphrenic lymphatic transport of peripancreatic fluid, primarily retroperitoneal in location, and contains elevated levels of enzymes. The amount of fluid present is small and it is difficult and unnecessary to obtain a sample for study. The presence of such a unilateral left-sided effusion is highly significant from a diagnostic standpoint. The plain film of the abdomen demonstrates calcification in the projection of the pancreas in 10 to 15 per cent of patients with alcoholic pancreatitis. Interestingly, nonalcoholic pancreatitis rarely, if ever, causes similar calcification, although diffuse gland calcinosis is seen in an occasional patient with hyperparathyroidism, with or without pancreatitis. Barium contrast study of the upper gastrointestinal tract is seldom used in acute pancreatitis, but may demonstrate widening of the duodenal sweep or flattening of the mucosal folds on the inner aspect of the curve of the duodenum. More commonly, such contrast studies are helpful in delineating pancreatic pseudocyst, as will be discussed. Pancreatic scanning with selenomethionine (7 5 Se) is of little, if any, benefit in chronic pancreatitis, and none whatever in acute pancreatitis.6

Treatment Treatment of acute pancreatitis is initially divided into four phases: first, resuscitation based on replacement of sequestered fluid, with ther-

1

AcUTE SURGICAL DISEASES OF THE pANCREAS

247

apy designed to prevent serious hypovolemia; second, decrease in gastric acid secretion with consequent fall in secretin output; third, measures designed to diminish acinar cell output directly or to decrease the effects of liberated enzymes; fourth, relief of pain. Most patients with acute pancreatitis have a rise in hematocrit, reflecting the magnitude of fluid sequestration. If hematocrit levels rise above 50 per cent, major colloid and crystalloid infusion is necessary, monitoring with central venous pressure and urine output. If frank hypovolemic shock develops, whole blood and other colloids are used, irrespective of the hematocrit level. The type of fluid used varies, but generally consists of Ringer's lactate solution buffered with 45 mEq. of sodium bicarbonate per liter. One to 2 liters of free water, administered as dextrose in water, are given every 24 hours. With adequate urine output, 60 to 120 mEq. of potassium chloride is provided, divided between three or four liters of infusate. Serum albumin and standard clinical dextran are excellent colloids for intravascular volume expansion, and are used freely to maintain adequate urine flow. Mannitol is often infused in 20 gram doses every 12 to 24 hours if urine output is marginal. Failure to respond signifies renal insufficiency or, more commonly, inadequate fluid loading. Low molecular weight dextran (M.M.W. 40,000) has been advocated to prevent stasis in pancreatic vessels with subsequent thrombosis, which aggravates the damage of the inflammatory process. 22 However, this substance has a demonstrated propensity to increase bleeding from damaged vessels, and its use in any but the milder forms of the disease is to be discouraged. Measures designed to decrease gastric acid entry into the duodenum include gastric suction by Levine tube, and large doses of vagolytic drugs, the most effective of which is atropine, given in 0.6 to 1.0 mg. doses intramuscularly every 4 hours. Antacids have not been given by mouth, as these generally result in vomiting. Gastric suction is effective in removing significant amounts of acid as well as relieving the troublesome symptoms of retching and vomiting. No drugs should be used to relieve emesis under any circumstances. Decrease in acinar cell output would appear to be desirable, both experimentally and clinically. Several agents have been proposed to accomplish this purpose, the most popular of which was acetazolamide (Diamox), a diuretic and carbonic anhydrase inhibitor. Numerous studies have shown that drug to have no appreciable effect on exocrine pancreatic secretory volume, and it is no longer used. 2 • 20 A more interesting material is Trasylol, widely used in Europe; this drug represents a group of kallikrein inhibitors, thought to prevent conversion of trypsinogen to trypsin. Trasylol is impressive in preventing deaths from pancreatitis in experimental animals, but numerous studies in patients using the imported drug have been disappointing; no discernible change in the clinical course can be detected. Currently undergoing intensive study in acute pancreatitis is the infusion of25 per cent dextrose via central venous pressure catheter. This was stimulated by several reports showing remarkable decrease in pancreatic juice output with blood sugars in excess of 300 mg. per 100 mP· 5 • 23 Although serious theoretical disadvantages of this regimen can

248

ROBERT ]. BAKER

be proposed, it has been employed in numerous acute afflictions of the pancreas with considerable success, and should now be used as part of the treatment of acute pancreatitis. A convenient method is to infuse 3000 ml. per day, with urine glucose testing every 6 hours, and blood glucose determinations every 24 hours. It is usually necessary to add 35 units of crystalline insulin to each liter of fluid in treating patients with acute pancreatitis, as endogenous insulin production is unpredictable. Appropriate amounts of electrolyte and 5 per cent amino acid solutions are also added to the same fluid. Meticulous catheter care is critical, and has been well outlined.5 In the event that high blood sugar levels are found, or that significant glycosuria is detected on the 6 hour samples, it is wise to administer 15 to 25 units of crystalline insulin subcutaneously in order to keep extracellular fluid glucose concentration below 400 to 450 mg. per 100 ml. Atropine also is moderately effective in decreasing pancreatic activity, through the vagus and its action on the gland. Vagal stimulation is known to increase enzyme output independent of its effect on gastric secretion. Vagolysis, therefore, should help to put the gland at rest, and 1.0 mg. of atropine is administered intramuscularly every 4 hours until signs of toxicity appear (malar flush, mild disorientation). Pain relief is best accomplished with morphine sulfate or meperidine, despite the theoretical disadvantage of sphincter of Oddi spasm with these agents. Pain is severe, and less potent agents prove ineffective in all except the mildest forms of disease. In addition, phenobarbital is usually administered, not only for its sedative effect but also as it diminishes pancreatic secretory volume and enzyme content somewhat. Recently popularized is the use of peritoneal lavage to diminish inflammation, reduce pain, and decrease toxicity. 9 • 17 This is accomplished by the introduction of a standard peritoneal dialysis catheter in the infraumbilical midline; 10 to 20 liters of peritoneal dialysis fluid are used as an irrigant every 24 hours. The use of this technique is limited to those patients with marked deterioration on active management, shock, or frank psychosis. The benefits of the procedure are difficult to evaluate, but a few patients appear to improve when dialyzed. If frank pancreatic ascites is detected during the acute attack, such dialysis is definitely indicated and should be employed. Antibiotic administration is advised as a prophylactic measure against the development of pancreatic abscess. Cephalothin is generally used for this purpose, in intermittent doses of 2 gm. intravenously every 6 hours. The merit of this particular antibiotic, indeed, of antibiotics in general, is open to question, but it seems wise to provide a modicum of protection in this area. Indications for Operation As a general rule, uncomplicated acute pancreatitis is best treated by nonoperative means. However, if symptoms persist unabated for more than 5 to 7 days, with constant hyperamylasemia and/or hyperamylasuria, a complication must be assumed to be present, and operation becomes necessary. Another indication is persistent jaundice in the acute episode, with serum bilirubin levels consistently in excess of 5.0 mg. per 100 ml.; it must be supposed that a common bile duct calculus is present,

ACUTE SURGICAL DISEASES OF THE PANCREAS

249

and appropriate surgical decompression of the biliary tree undertaken. Intravenous cholangiography is essentially useless during this period, as acute pancreatitis prevents dye visualization of either gallbladder or ductal system. The edema and inflammatory reaction are such that neither plain films nor tomographic studies after intravenous cholangiographic dye injection are helpful. The usual circumstances surrounding operation for acute pancreatitis are those in which the true diagnosis is not suspected, and exploration is undertaken for ruptured viscus or acute cholecystitis. Even when pancreatitis is considered as a possible cause, if amylase elevation is at nondiagnostic levels and the patient is critically ill, operation may be deemed necessary to avoid missing a surgically correctable condition. When acute pancreatitis is found, the appropriate procedures are: 1. Irrigate the peritoneal cavity with copious amounts of warm saline solution. 2. Open the gastrocolic omentum, inspect the pancreas, and open the posterior peritoneum over the pancreas if a hematoma or collection of fluid is seen. 3. Avoid needless manipulation of the pancreas and duodenum. 4. Gently palpate the portal triad to detect common duct calculus. 5. Perform a cholecystostomy, of questionable benefit in decompressing the biliary tree, but valuable to study the gallbladder and ductal system at a later date. 6. Drain both right and left sides of the lesser sac with sump drains of the soft plastic variety. If stones are found in the gallbladder, cholecystectomy should probably be left till later, but all palpable stones are removed. An operative cholangiogram via the cholecystostomy tube is indicated only when stones are discovered in the gallbladder or palpated in the ductal system. Undue delay in obtaining such a study can frequently be avoided if the Radiology Department is alerted to the need for a technician in the operating room as soon as the diagnosis of acute pancreatitis is established. Under no circumstances should the procedure be prolonged in waiting for films to be taken. During the postoperative period, the sump drains can be used to irrigate the retrogastric space with dialysis fluid, making a separate peritoneal catheter unnecessary. In the event that a stone is discovered in the common bile duct, by palpation or cholecystocholangiography, it must be removed by choledochotomy. If the stone is impacted in the ampulla of Vater, as displayed by x-ray study, simple catheter drainage of the common bile duct is all that should be done, as extensive manipulation in the distal duct system is most likely to make the process worse. It is not desirable to incise pancreatic substance or attempt major pancreatic resection with severe acute pancreatitis, as the morbidity and mortality, of such maneuvers are prohibitive.

SURGICAL COMPLICATIONS OF ACUTE PANCREATITIS Pancreatic Pseudocyst The commonest serious complication of acute pancreatitis is pseudocyst formation, occurring in 10 to 20 per cent of patients immediately or

ROBERT

J.

BAKER

as a delayed finding weeks or months later. Pseudocyst is a collection of pancreatic juice, old blood, partially digested tissue, fat, and occasionally sequestered bits of pancreatic tissue which collect as a consequence of inflammation and duct disruption. These are usually located in the lesser omental sac, and typically the anterior wall of the pseudocyst is the posterior wall of the stomach, the inferior is transverse mesocolon, the posterior is pancreas and parapancreatic structures, and superiorly the spleen and diaphragm or the cardia of the stomach are incorporated into the cyst. Less common locations are in or behind the head of the pancreas, between the leaves of the transverse mesocolon, and between the stomach and the spleen or left parietal peritoneum; rarely, these may extend into the posterior inferior mediastinum. All of the involved structures are thickened by the inflammatory process, and organization and fibrosis of this reactive material gives substance to the pseudocyst "wall." This pseudocapsule varies from a few mm. to 3 em. in thickness. The findings are most commonly persistent pain, vomiting, and the presence of a mass in the epigastrium or left upper quadrant. Characteristically, amylase elevations persist beyond the usual time limit of the acute inflammatory disease, or amylases fall to normal levels and then again become elevated. Any patient in whom acute pancreatitis does not subside in 5 to 7 days should be suspected of having a pseudocyst and should be investigated by the usual radiographic methods: Upright Posteroanterior and Left Lateral Chest Films. At least 40 per cent of patients with pseudocyst will have a left-sided pleural effusion of slight to moderate degree. Indeed, pseudocyst may be manifest weeks or months after the original episode by the development of left pleural effusion or, much less commonly, ascites. 14 Barium Enema (With Lateral Views of the Splenic Flexure and Transverse Colon). The pseudocyst typically located in the lesser sac will displace the transverse colon downward and the splenic flexure inferiorly or anteriorly (the lateral projection is most helpful in detection). Barium Meal. Anterior displacement of the stomach with a large pressure defect on the lesser curvature is most common. Occasionally a laterally located pseudocyst may push the stomach far to the right, with flattening and indentation of the greater curvature. Other Studies. Selenomethionine scan may show a large area of decreased uptake in the body and tail areas. Selective celiac artery angiography can be employed and will show splaying or widening of the pancreatic arcades with no vessel filling in the pseudocyst area. Neither of these studies contributes greatly, and they are rarely necessary. Intravenous pyelography is always used to rule out renal mass as the cause of the symptoms, and frequently shows inferior displacement of the left intrarenal collecting system when pseudocyst pushes the left kidney downward. TREATMENT. Treatment of pseudocyst should be intemal drainage of some type as soon as the diagnosis is made. The tendency to wait until the pseudocyst wall "matures," or thickens so that it will hold sutures, is hazardous, as it may rupture into the free peritoneal cavity or erode a splenic or pancreatoduodenal vessel as it enlarges. Both of these catastrophes are likely to result in death, and earlier definitive treatment of pseudocyst is to be strongly encouraged.

ACUTE SURGICAL DISEASES OF THE PANCREAS

251

The simplest form of internal drainage is cystogastrostomy, in which the pseudocyst wall is entered through the posterior wall of the stomach. This technique is useful in the majority of cases, as the posterior gastric wall is incorporated into the pseudocyst. In the event that the pseudocyst is not intimately adherent to the stomach, or is located at some distance from it, Roux-en-Y cystojejunostomy is the preferred procedure. Simple drainage should be reserved for those patients who are critically ill and in whom exploration is considered too great a risk. A trocar is used to empty the cyst, a sump drain is placed into the cyst, and suction is applied. Persistent pancreatic fistula will result in roughly onehalf of patients treated by pseudocyst drainage alone, 30 to 40 per cent of which will require surgical correction when pancreatitis is the underlying process. Marsupialization of the pseudocyst is no longer used. When pseudocysts are found in or adjacent to the head of the pancreas, cystoduodenostomy is sometimes technically feasible, but the relatively thin duodenal wall and the likelihood of leakage from that anastomosis militate against it, and cystoduodenostomy is not recommended. Roux-en-Y cystojejunostomy is always the most desirable drainage procedure if cystogastrostomy is not possible. Pancreatic Ascites An occasional patient will develop persistent ascites following acute pancreatitis, or with relatively small leaks from a pancreatic pseudocyst. The ascites represents a fistula between the pancreatic duct and the peritoneal cavity, and some patients tolerate pancreatic juice in the abdomen remarkably well. With release of enzymes into the general peritoneal space, inflammatory peritoneal response may prevent effective reabsorption and the ascites then becomes progressive. Conservative measures to control ascites of this type include: parenteral hyperalimentation, not only to diminish pancreatic exocrine volume, but also to replace protein loss from the pancreatic duct; diuretics; intermittent paracentesis; large doses of atropine. If the ascites does not disappear in 7 to 10 days, operation is necessary to obliterate the ductal rent. If the damage is confined to the body or tail, resection of the distal portion with drainage of the duct by retrograde pancreatojejunostomy (DuVal procedure) is the preferred treatment. If the lesion is in the head or neck of the pancreas, or the specific site cannot be identified, distal resection is carried out, but the Roux-en-Y loop of jejunum is used to cover the head and neck of the pancreas like an onlay graft. The open filleted end of jejunum is sewn to the pancreatic capsule and peripancreatic inflammatory tissue with two layers of fine silk. It is important that the Roux loop of jejunum be 12 to 18 inches in length, so that there is no chance of reflux to the pancreas of intestinal chyme. Pancreatic Abscess The most feared complication of acute necrotizing or hemorrhagic pancreatitis is sepsis and abscess formation. The necrotic tissue, blood, and activated enzymes in and about the residual viable pancreas consti-

252

RoBERT

J.

BAKER

tute an ideal site for bacterial proliferation, and lymphatic or venous entry by coliform or other bacteria is a real hazard. Clinically, the development of suppuration is heralded by a sudden rise in temperature to 103 to 105° F., severe tachycardia with pulse rates over 140, and sepsis. Septic shock may ensue, or may be the first development in the patient with severe pancreatitis with abscess. Prompt steps must be taken to exclude other systemic sources of the fever with careful examination, chest x-ray, and urinalysis. Blood cultures should be drawn so that the organism causing the pancreatic sepsis can be identified as promptly as possible. Exploration of the lesser omental sac and drainage of the pancreas is undertaken immediately, since the pancreatic infection pursues an extremely rapid and invariably fatal course unless detected and treated early. When the peripancreatic tissue is incised, necrotic pieces of pancreas present; these should be removed by blunt or finger dissection to avoid damage to splenic and other major vessels. Two large sump drains are placed through bilateral flank stabwounds into the lesser sac. Cephalothin and kanamycin, or gentamicin, in large intravenous doses are currently the antibiotics of choice until culture and sensitivities of material obtained at operation are returned. Considerable caution must be exercised in parenteral hyperalimentation with these septic patients; diabetes usually becomes severe when abscess develops, and exogenous insulin requirements may be tripled or quadrupled. Further, severe sepsis may be followed by nonketotic hyperosmolar coma, probably due to cellular and subcellular failure with accumulation of enormous amounts of glucose in the extracellular fluid. It is essential that blood sugar or osmolality be monitored every 4 hours if hyperalimentation regimes are to be used. If either blood glucose or osmolality rises in spite of large exogenous insulin administration, the so-called "insulin resistance" or sepsis, concentrated glucose infusion must be terminated immediately. Miscellaneous Complications

Upper gastrointestinal hemorrhage has been alluded to, probably occurring on the basis of edema and mucosal friability in the antrum and duodenum. The bleeding is seldom alarming, but may be persistent and require transfusion. Massive gastrointestinal hemorrhage is rarely seen, but is reported with necrosis of the colon (thrombosis of the midcolic vein), and with major hemorrhage into a pseudocyst. In the latter circumstance, the cyst fills with blood clot and ruptures into the stomach or duodenum, causing exsanguinating hemorrhage. Such massive bleeding is rare, but if present requires exploration and appropriate control of the bleeding source. Recurrent attacks in the hospital on management must be assumed to be due to biliary calculi or to pseudocyst in the head or neck of the pancreas, and operation is required to decompress the biliary tree or to drain a pseudocyst. If a large boggy mass is felt in the head of the pancreas, frequently 10 em. or more in circumference, the mass should be aspirated with an 18 gauge needle and syringe. This usually represents an intrapancreatic pseudocyst, requiring Roux-en-Y drainage.

AcUTE SURGICAL DISEASES OF THE PANCREAS

253

Persistent ileus is suggestive of low grade infection or acute pancreatic ascites, and generally will subside with nonoperative treatment. Duodenal obstruction is due to local edema, and should be treated expectantly. Upper gastrointestinal barium studies are necessary to exclude pseudocyst.

POSTOPERATIVE PANCREATITIS One of the most perplexing problems seen in the postoperative period is the occurrence of acute necrotizing or hemorrhagic pancreatitis after operation. It is more or less expected after manipulation of the gland itself, as in surgery for carcinoma or chronic pancreatitis. However, operative procedures performed on other upper abdominal structures can also be at fault, specifically exploration of the common bile duct, gastric resection, and even splenectomy or left nephrectomy. In addition, the complication can occur after aneurysmectomy, prostatic resection, hemicolectomy, and other operations on remote organs. 21 The overall mortality rate when the pancreatitis is recognized or is the autopsy-proven cause of death is roughly 40 per cent. 13 • 21 Several obvious factors can be recognized in many instances: (1) Frank operative trauma, in which the gland is sectioned, biopsy is performed, or the duodenum is dissected free of the pancreas, leading to release of enzymes from the damaged gland; (2) Trauma to the pancreatic ductal system by vigorous dilatation of the common bile duct, or by passage of large dilators. Additionally, forcible injection of cholangiographic dye with a syringe can suddenly increase intrapancreatic ductal pressure to levels considerably higher than the 40 to 50 em. of water necessary to rupture the ductular apparatus; (3) Inadvertent damage to pancreatic blood supply, specifically interference with venous drainage from a segment of pancreas. Of these factors, those related to exploration of the common duct and operative cholangiography are obviously most important, since this procedure results in postoperative pancreatitis more frequently than any other.U If any of the preceding factors is involved in an operative procedure, it might be well to start Trasylol in the immediate postoperative period, since any benefit from this agent would appear to accrue before the full-blown disease develops. The diagnosis should be suspected in any patient with unexplained fever, tachycardia, abdominal distention, or low-grade jaundice in the immediate postoperative period, usually within 48 hours of operation. Shock may develop rapidly, and the patient with severe pancreatitis usually expires despite treatment, 12 to 48 hours after the symptoms appear. Pain is not a prominent symptom, nor is tenderness helpful in this variety of the disease. Amylase elevation should be looked for in serum and urine, as well as peritoneal fluid obtained by paracentesis or from drains placed at the initial operation. If morphine has been used for analgesia, the results must be interpreted with cognizance of the fact that spurious amylase elevations can be caused by that drug. The other signs of acute pancreatitis previously detailed are usually absent. Treatment is supportive, and is the same as the outlined treatment

254

RoBERT]. BAKER

for other types of acute pancreatitis. Re-exploration should be carried out only if severe sepsis appears and other nonabdominal causes for such sepsis have been excluded. If operation appears necessary for survival, only drainage of the area should be attempted, with limited blunt debridement of necrotic pancreas.

PANCREATIC INJURY FROM ABDOMINAL TRAUMA Blunt Trauma The diagnosis of blunt injury to the pancreas may be extremely difficult, as attested to by the fact that one-third of patients are operated upon only after a mass is discovered, and two-thirds of patients are operated upon more than 48 hours after the injury. 3 • 16 Pain and tenderness with pancreatic injury may be minimal early and are frequently overshadowed by concomitant remote injury. Amylase elevation, the only confirming finding, occurs early in peritoneal fluid, but only after 12 to 24 hours in serum and urine in most observed cases. Radiographic studies are not helpful until a complication, such as pseudocyst, occurs. The possibility of pancreatic trauma should be kept in mind with all lower thoracic and abdominal injuries, and amylases routinely investigated in all such injuries. If amylases in serum or urine are elevated to a diagnostic level and the patient's general condition is satisfactory, exploration is indicated, unless the patient is pain-free and has no paralytic ileus. When operation is carried out, the appropriate procedure depends on the nature of the injury. As a rule, resection of pancreas to the left of the superior mesenteric vessels has been satisfactory when injury is severe enough to involve the duct of Wirsung and is limited to the body and tail. The distal end of remaining pancreas can be closed with interrupted mattressed silk sutures, or the duct can be ligated and the end allowed to drain. Meticulous hemostasis with fine silk suture ligatures is imperative in all pancreatic injuries prior to any other procedure. When injury is modest, as with cracks of parenchyma or capsular tears, no repair should be attempted, but the area should be drained. Adequate drainage of all pancreatic wounds requires sump drains in both flanks, or a sump drain adjacent to remaining pancreas and a soft rubber or latex drain in the left flank. 3 The most difficult injuries in this group are the tears of the pancreas at or to the right of the superior mesenteric vessels. Pancreatoduodenal resection is reserved for those patients with combined pancreatic and duodenal injuries, in whom the damage to the duodenum demands resection as the safest course. 12 ' 16 Pancreatic injury alone has been successfully handled by liberal use of Roux-en-Y pancreatojejunostomy, in which the end of the Roux limb of jejunum is opened along the antimesenteric border and the pancreatic defect is covered by suture of the open jejunal end to pancreatic capsule at a distance of one or two centimeters from the damage. The duodenum can be used, as can peri pancreatic soft tissue or fat, to buttress the jejunal limb; a second layer of silk

ACUTE SURGICAL DISEASES OF THE pANCREAS

255

sutures is always desirable to seal the Roux limb and prevent pancreatic juice escape. Penetrating Wounds Diagnosis is established at operation by the finding of a retroperitoneal hematoma in the vicinity of the pancreas, or an actual bullet tract or knife wound may be seen. Unlike blunt trauma, concomitant adjacent organ injury is common, particularly injury to the duodenum or great vessels. Retroperitoneal hematomas must be explored in penetrating wounds, and vascular instruments readied in advance of opening the retroperitoneum. The approach to the pancreas is usually through the gastrocolic omentum, and pancreatic injury management is similar to that outlined for blunt trauma. However, wounds of the duodenum or common bile duct may require choledochostomy and T-tube drainage. If the duodenum is intact, but the knife or projectile traversed the head of the pancreas, it is wise to decompress the common bile duct with aT-tube. Longlimbed T-tubes extending into the duodenum are never used because of the obstructive effect on the pancreatic duct with subsequent postoperative pancreatitis. 1 • 20 Pancreatoduodenectomy would be indicated only for severe, unmanageable disruption of the duodenum.

SUMMARY Most patients with acute pancreatic disease are treated by nonoperative means, but certain absolute indications for operation exist, namely: (1) Pancreatic pseudocyst; (2) Pancreatic abscess; (3) Massive hemorrhage into a pseudocyst or into the gastrointestinal tract; (4) Decreasing bilirubinemia; (5) Blunt and penetrating pancreatic trauma. Results of operation in these conditions are variable, but are far superior to nonoperative methods.

REFERENCES 1. Anderson, M. C., and Bergan, J. J.: Experimental study of pancreatitis trauma and its

relationship to pancreatic inflammation. Arch. Surg., 86:1044-1050, 1963. 2. Baker, R. J., Bass, R. T., Zajtchuk, R., and Amato, J. J.: External pancreatic fistula following abdominal injury. Arch. Surg., 95:556-566, 1967. 3. Baker, R. J., Dippel, W. C., Freeark, R. J., and Strohl, E. L.: Surgical significance of trauma to the pancreas. Arch. Surg., 86:1038-1044, 1963. 4. Cogbill, C. L., and Song, K. T.: Acute pancreatitis. Arch. Surg., 100:673-676, 1970. 5. Dudrick, S. J., Wilmore, D. W., Steiger, E., Mackie, J. A., and Fitts, W. T., Jr.: Spontaneous closure of traumatic pancreatoduodenal fistulas with total intravenous nutrition. J. Trauma,10:542-553,1970. 6. Eaton, S. B., Aeischli, D. J., Pollard, J. J., Nebesar, R. A., and Potsaid, M.S.: Comparison of current radiographic approaches to the diagnosis of pancreatic disease. New Eng. J. Med., 279:389-396, 1968. 7. Eto, K., Pairent, F. W., Appert, H. E., and Howard, J. M.: Renal excretion of amylase and lipase by dogs. Arch. Surg., 98:241-244, 1969. 8. Goodhead, H.: Significance of methemalbuminemia in acute abdominal emergencies. Arch. Surg., 101:376-378, 1970. 9. Lawson, D. W., Daggett, W. M., Ciretta, J. M., Corry, R. J., and Bartlett, M. K.: Surgical treatment of acute necrotizing pancreatitis. Ann. Surg., 172:605-617, 1970.

.

256

ROBERT

J.

BAKER

10. Libertino, J. A., Zinman, L., Dowd, J. B., and Braasch, J. W.: Gastrointestinal complications related to human renal homotransplantation. SuRG. CLIN. N. AMER., 51:733-737, 1971. 11. Lowenfels, A. B., Rohman, M., and Shibutain, K.: Surgical consequences of alcoholism. Surg. Gynec. Obstet., 131:129-138, 1970. 12. Nance, F. C., and DeLoach, D. H.: Pancreaticoduodenectomy following abdominal trauma. J. Trauma, 11:577-585, 1971. 13. Peterson, L. M., Collins, J. J., and Wilson, R. E.: Acute pancreatitis occurring after operation. Surg. Gynec. Obstet., 127:23-28, 1968. 14. Schindler, S. C., Schaefer, J. W., Hull, D., and Griffen, W. 0., Jr.: Chronic pancreatic ascites. Gastroenterology, 59:453-459, 1970. 15. Seward, C. W.: Diagnosing pancreatitis the first day. Southern Med. J, 63:286-289, 1970. 16. Smith, A. D., Woolverton, W. C., Weichert, R. F., III, and Drapanas, T. C.: Operative management of pancreatic and duodenal injuries. J. Trauma, 11:570-576, 1971. 17. Waterman, N. G., Walsky, R. S., Kasdan, M. L., and Abrams, B. L.: Treatment of acute hemorrhagic pancreatitis by sump drainage. Surg. Gynec. Obstet., 126:963-968, 1968. 18. Weiner, S., Gramatica, L., Voegle, L. D., Hauman, R. L., and Anderson, M. C.: Role of the lymphatic system in the pathogenesis of inflammatory disease in the biliary tract and pancreas. Amer. J. Surg.,119:55-61,1970. 19. White, T. T.: Radiologic diagnosis of pancreatic disease. In Cooper, P., and Nyhus, L. M.: Surgery Annual. New York, Appleton-Century-Crofts, 1970. 20. White, T. T.: Pancreatitis. London, E. A. Arnold, 1966, pp. 186-196. 21. White, T. T., Morgan, A., and Hopton, M. B.: Postoperative pancreatitis. Amer. J. Surg., 120:132-135, 1970. 22. Wright, P. W. and Goodhead, B.: Value of dextrans in the treatment of experimental pancreatitis. Surgery, 67:807-815, 1970. 23. Zajtchuk, R., Amato, J. C., Shoemaker, W. C., and Baker, R. J.: Relationship between blood glucose levels and external pancreatic secretion in man. J. Trauma, 9:629-637, 1969.