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Cholecystitis
Cholecystitis Prom the Department of Medicine, Division of gastroenterology, the Jefferson Medical College and Hospital, Philadelphia, Pennsylvania
C. WILMER WIRTS, M.D. Associate Professor of Medicine and Director, Division of Gastroenterology
EXPERIENCE in the recognition and management of cholecystitis is especially important to the general practitioner because he is the one most frequently called to see patients during the early phase of the illness. In the presence of a fulminating attack the diagnosis may be complex, requiring differentiation from such conditions as peptic ulcer, pancreatitis, renal colic, intestinal obstruction, mesenteric thrombosis, myocardial infarction, diverticulitis coli, irritable bowel syndrome and, in the female, a ruptured ectopic pregnancy. 4. 8 Frequently the urgency of the circumstances requires a bedside diagnosis to determine the need for surgical intervention. Such a decision may have to rest on clinical judgment, history and physical examination. However, if time permits, considerable help in making the differential diagnosis is gained by having a blood count, urine analysis, liver function test, serum amylase, chest and plain abdominal x-ray and an electrocardiogram. It is now generally accepted that acute and chronic cholecystitis are secondary to an obstruction of the bile flow due to calculus or inspissated bile in the lumen, or pressure on the cystic duct due to kinking, inflammation, enlarged nodes, adhesions or tumor. Only about one-third of the cases show bacterial growth in the gallbladder in spite of the stasis that may exist there.
ACUTE CHOLECYSTITIS
Acute cholecystitis is characterized by the sudden development of severe, sharp epigastric pain soon moving to the right upper quadrant and radiating beneath the right scapula. It is frequently associated with nausea, vomiting, fever, leukocytosis and the development of jaundice. Tenderness in the right upper quadrant is due to an enlarged, tender gallbladder or liver, or both. An enlarged liver, jaundice and absence of
1469
1470
c.
W ILMEH W IRTS
air under the diaphragm tend to rule out a perforated viscus. The absence of distended small bowel loops and diarrhea makes intestinal obstruction or mesenteric thrombosis unlikely. One looks for blood in the urine if renal stone is suspected. Vaginal spotting of blood and a delayed or absent menstrual period are usually present with an ectopic pregnancy. An elevation of the serum amylase is not uncommonly present in cholecystitis, but the level is not often as high as in primary acute pancreatitis. In the latter condition the liver is less often palpable and the degree of jaundice is less. Myocardial infarction is usually associated vvith a greater electrocardiographic change and higher transaminase levels than cholecystitis. In pneumonitis physical and x-ray changes are found in the lungs which are not present with cholecystitis. After all these conditions are excluded, one is still confronted with the problem of determining whether the jaundice is due to intrahepatic or extrahepatic cause. Frequently the liver function profile permits this differentiation by showing a predominant rise of the alkaline phosphatase with slight to moderate elevation of the cephalin cholesterol flocculation and thymol turbidity tests in extrahepatic block and the reverse in hepatocellular jaundice. Some cases of cholecystitis are associated with common duct stone but in many, some obstruction of the common bile duct occurs by contiguous inflammatory reaction. In either event surgical treatment is required, preferably after rest, antibiotics and supportive measures have permitted some amelioration of symptoms and improvement in hepatic function. 3 If a reversal of the acute process cannot be obtained, a limited drainage procedure such as cholecystostomy may have to be undertaken. CHRONIC CHOLECYSTITIS
Chronic cholecystitis is also associated with right upper quadrant pain, but the attacks are less severe and less acute. The pain is more apt to be a dragging or boring sensation and the tenderness is milder. Fever, leukocytosis and jaundice are uncommon and nausea and vomiting less frequent. Livcr function tests are usually normal. The cholecystogram usually shows gallstones or a failure of visualization of the gallbladder. If gallstones are present, or if there is rcpeated failure to visualize the gallbladder and one has excludcd other causes of the patient's symptoms, cholecystectomy should be recommended, if there is no contraindication to surgery. The most difficult decisions in regard to surgery occur when there is poor visualization of the gallbladder but no definite evidence of stones is found preopcratively. It is well recognized that nonvisualization on x-ray may occur even in the presence of a normal gallbladder and that surgical removal of a non-stone-bearing gallbladder which is histologically normal does not relieve symptoms. Consequently, cholecystec-
Cholecystitis
1471
tomy for "cholecystitis" usually is not recommended unless gallstones are present. Under these circumstances, clinical judgment based on experience must be used. Occasionally duodenal-biliary drainage according to the technique of Lyon or the use of secretin and pancreozymin may be of supplementary help. Failure to obtain an adequate gallbladder fraction of bile on duodenal drainage or contraction of the gallbladder on x-ray following intravenous administration of these hormones suggests impaired biliary function. I , 2, 5, 6,7,9 CHOLECYSTITIS WITHOUT STONES
To explore the problem of cholecystitis in the absence of stone somewhat further, we reviewed our own recent experience. During 1960, 309 patients were admitted to the Jefferson Medical College Hospital with the diagnosis of cholelithiasis or cholecystitis. Of these, 287 were shown to have gallstones, but cholecystectomy was performed in only 2]4 or 74.5 per cent. Patients who were not operated upon had refused surgery, were too feeble to withstand it or had an illness that required priority of treatment. Twenty-two patients or 7.3 per cent of the entire group in whom stones were not demonstrated by x-ray or surgery had cholecystectomy for cholecystitis. The cholecystograms in these patients showed poor or absent visualization in each instance. Histopathologic examination of the gallbladders showed chronic cholecystitis in 17, chronic cholecystitis with cholesterosis in two, chronic cholecystitis with papilloma of the gallbladder in one and acute cholecystitis in two. Of 126 private patients whom I treated for biliary tract disease, between 1951 and 1961, 84 were female and 42 male. Cholecystectomy was performed in 88 (82 per cent) of those patients with gallstones and in only two of the seven patients who had cholecystitis without stones. In the remaining five patients the cholecystogram sho" ed poor visualization of the gallbladder in three and nonvisualization in two. Biliary drainage in each of these patients was within normal limits and it was therefore decided to treat them on a medical regimen. MEDICAL MANAGEMENT
Patients in whom surgery is contraindicated because of age or debility should be given a special diet, treated with antispasmodics and encouraged to maintain good hygiene.
Diet In gallbladder disease, free use of the following foods is permitted: bread and bread stuffs, cereals, egg white, fish low in fat, lean meat, skim milk, syrups, most vegetables, mild cheeses and fruits. The following foods should be eliminated or taken only in small amounts: liver,
c.
1472
WILMER WIRTS
kidney, sweetbreads, brain, caviar, egg yolk, fatty meats (sausage, bacon, pork, veal), fatty fish (mackerel, blue fish, sardines), fatty fowl (goose, duck), rich cake and pastry, butter, cream, olive oil and all fried foods or those rich in condiments. Certain vegetables also should be avoided (broccoli, cauliflower and cabbage), and certain beverages (alcohol, effervescent and aerated water). SPECIMEN DIET
Breakfast Fruit or fruit juice Cereal with skim milk Dried bread or toast, or Melba toast with marmalade, jelly, honey or small amount of butter Hot cakes or waffles with syrup, occasionally weak tea, Sanka or skim milk Lunch Soup made with milk Two vegetables or toasted sandwich of lettuce and tomato, cheese or lean meat Rice or tapioca pudding, Jello, fresh or cooked fruit Weak tea, Sanka or skim milk
Dinner Fruit or fruit juice or nonfatty soup Lean meat: steak, roast beef, lamb chops, lamb or ham, or Any fish or fowl containing little fat or oil Potatoes, rice, macaroni, vermicelli or spaghetti Two green vegetables (except as noted above) Dry bread, toast or Melba toast Pudding, Jello, fresh or cooked fruits, plain cake or mild cheese and crackers Weak tea, Sanka or skim milk
Bowel Hygiene Normal bowel hygiene should be maintained by adding sufficient bulk to the diet, establishing regularity in going to stool and avoiding laxatives. Drugs Probably the most effective medication for a moderate-to-severe attack is either morphine sulfate 7.5 to 15 mg. (Vs to ~ grain) or Demerol 50 to 100 mg., given':parenterally, with or without atropine sulfate 0.4 mg. (1/150 grain). The need for repeated administration must be judged critically. For milder symptoms codeine sulfate 60 mg. (1 grain), sodium phenobarbital 120 mg. (2 grains), methantheline bromide (Banthine) 50 mg., or propantheline bromide (Pro-Banthine) 30 mg. may be tried intramuscularly. Prophylactic antibacterial therapy is indicated in severe, prolonged or complicated attacks; procaine penicillin or crystacillin, 300,000 units given intramuscularly, either alone or with streptomycin 0.5 gram, every 12 hours; or a broad-spectrum antibiotic, such as Achromycin or Terramycin, 500 mg. in 500 cc. of physiologic salt solution may be given intravenously. During the period of nausea and
Cholecystitis
1473
vomiting, all oral food and fluid intake should be stopped and infusions of dextrose or physiologic salt solution given intravenously. CHOLECYSTITIS AND ASSOCIATED DISEASE
Other types of gastrointestinal disease and extraintestinal conditions frequently co-exist with cholecystitis and require consideration in the management of these patients. The following is a list of associated conditions found in the 88 of my patients who were operated upon: Empyema Duodenal ulcer Obstructive jaundice Pancreatitis Common duct stone Anemia Hypertension Hiatal hernia Cirrhosis of liver Diabetes
13
10 6 4 4
3 3 3 2 2
Meckel's diverticulum Pregnancy Hepatitis Renal stone Gastric ulcer Esophageal ulcer Cystic duct stone Ulcerative colitis Gastritis
2 2 2 2 1 1 1 1 1
Peptic ulcer is the commonest non-biliary tract condition which may require simultaneous treatment. Combined disease of this type undoubtedly makes the treatment of either one more difficult. It would appear that in most instances the peptic ulcer is amenable to medical therapy, whereas cholecystitis associated with cholelithiasis almost always requires surgical treatment. The significance of the other associated conditions appears obvious. Management must be individualized as in patients with peptic ulcer. SUMMARY
Acute and chronic cholecystitis is an inflammatory disease of the gallbladder usually due to some obstruction to bile flow and less often associated with pyogenic infection. Depending upon the severity and extent of the inflammatory reaction, the symptoms vary from empyema, gangrene and rupture of the gallbladder to the mildest right upper quadrant distress. Although laboratory studies are very helpful, it is frequently necessary to base the decision regarding surgical or medical treatment upon clinical judgment. Most cases of cholecystitis are associated with cholelithiasis and require surgical treatment. Preferably this is done when the symptoms are minimal and under elective conditions. However, under circumstances of persistent activity with threatening rupture it may be necessary to undertake emergency operative intervention. Medical treatment is reserved for those few patients who are thought to have slight functional impairment of the gallbladder but no convincing
C.
1474
WILMER WIRTS
evidence of cholelithiasis or true cholecystitis. Finally, it may be necessary to treat patients with cholelithiasis and cholecystitis medically because they are poor surgical risks or because they refuse surgical treatment. REFERENCES 1. Burton, P. et al.: Use of Secretin and Pancreozymin in Man. Gastroenterologia 86: 463, 1956.
2. Dreiling, D. A.: Technique of Secretin Test: Normal Ranges. J. Mt. Sinai Hosp. 21: 363, 1954. 3. Glenn, F. and Guida, P. M.: Surgery in Biliary Tract Disease. J.A.M.A. 174: 44, 1960. 4. Heffernon, E. W., Millhon, W. A. and Rosen, S. W.: Irritable Colon and Gallbladder Disease. J.A.M.A. 173: 1, 1960. 5. Jorpes, J. E. and Mutt, V.: Secretin, Pancreozymin and Cholecystokinin, Thcir Preparation and Properties. Gastroenterology 36: 377, 1960. 6. Jorpes, J. E., Mutt, V., Tomenius, J. and Blacklund, V.: Cholecystokinin in Roentgenologic Examination of Biliary Tract. Roentgenblatter. 11: 145, 1958. 7. Raskin, H. F. et al.: Diagnosis of Cancer of Pancreas, Biliary Tract and Duodenum by Cytologic and Secretory Methods. Gastroenterology 34: 886, 1958. 8. Smith, L. A.: Left-sided Pain in Disease of Gallbladder. Proc. Staff. Meet., Mayo Clin. 34: 597, 1959. 9. Sun, D. C. H. and Shay, H.: Pancreozymin-Secretin Test. Combined Study of Enzymes and Duodenal Contents in Diagnosis of Pancreatic Disease. Gastroenterology 38: 570, 1960. 1025 Walnut Street Philadelphia 7, Pennsylvania
C. WILMER WIRTS, M.D. Associate Professor of Medicine and Director, Division of Gastroenterology
EXPERIENCE in the recognition and management of cholecystitis is especially important to the general practitioner because he is the one most frequently called to see patients during the early phase of the illness. In the presence of a fulminating attack the diagnosis may be complex, requiring differentiation from such conditions as peptic ulcer, pancreatitis, renal colic, intestinal obstruction, mesenteric thrombosis, myocardial infarction, diverticulitis coli, irritable bowel syndrome and, in the female, a ruptured ectopic pregnancy. 4. 8 Frequently the urgency of the circumstances requires a bedside diagnosis to determine the need for surgical intervention. Such a decision may have to rest on clinical judgment, history and physical examination. However, if time permits, considerable help in making the differential diagnosis is gained by having a blood count, urine analysis, liver function test, serum amylase, chest and plain abdominal x-ray and an electrocardiogram. It is now generally accepted that acute and chronic cholecystitis are secondary to an obstruction of the bile flow due to calculus or inspissated bile in the lumen, or pressure on the cystic duct due to kinking, inflammation, enlarged nodes, adhesions or tumor. Only about one-third of the cases show bacterial growth in the gallbladder in spite of the stasis that may exist there.
ACUTE CHOLECYSTITIS
Acute cholecystitis is characterized by the sudden development of severe, sharp epigastric pain soon moving to the right upper quadrant and radiating beneath the right scapula. It is frequently associated with nausea, vomiting, fever, leukocytosis and the development of jaundice. Tenderness in the right upper quadrant is due to an enlarged, tender gallbladder or liver, or both. An enlarged liver, jaundice and absence of
1469
1470
c.
W ILMEH W IRTS
air under the diaphragm tend to rule out a perforated viscus. The absence of distended small bowel loops and diarrhea makes intestinal obstruction or mesenteric thrombosis unlikely. One looks for blood in the urine if renal stone is suspected. Vaginal spotting of blood and a delayed or absent menstrual period are usually present with an ectopic pregnancy. An elevation of the serum amylase is not uncommonly present in cholecystitis, but the level is not often as high as in primary acute pancreatitis. In the latter condition the liver is less often palpable and the degree of jaundice is less. Myocardial infarction is usually associated vvith a greater electrocardiographic change and higher transaminase levels than cholecystitis. In pneumonitis physical and x-ray changes are found in the lungs which are not present with cholecystitis. After all these conditions are excluded, one is still confronted with the problem of determining whether the jaundice is due to intrahepatic or extrahepatic cause. Frequently the liver function profile permits this differentiation by showing a predominant rise of the alkaline phosphatase with slight to moderate elevation of the cephalin cholesterol flocculation and thymol turbidity tests in extrahepatic block and the reverse in hepatocellular jaundice. Some cases of cholecystitis are associated with common duct stone but in many, some obstruction of the common bile duct occurs by contiguous inflammatory reaction. In either event surgical treatment is required, preferably after rest, antibiotics and supportive measures have permitted some amelioration of symptoms and improvement in hepatic function. 3 If a reversal of the acute process cannot be obtained, a limited drainage procedure such as cholecystostomy may have to be undertaken. CHRONIC CHOLECYSTITIS
Chronic cholecystitis is also associated with right upper quadrant pain, but the attacks are less severe and less acute. The pain is more apt to be a dragging or boring sensation and the tenderness is milder. Fever, leukocytosis and jaundice are uncommon and nausea and vomiting less frequent. Livcr function tests are usually normal. The cholecystogram usually shows gallstones or a failure of visualization of the gallbladder. If gallstones are present, or if there is rcpeated failure to visualize the gallbladder and one has excludcd other causes of the patient's symptoms, cholecystectomy should be recommended, if there is no contraindication to surgery. The most difficult decisions in regard to surgery occur when there is poor visualization of the gallbladder but no definite evidence of stones is found preopcratively. It is well recognized that nonvisualization on x-ray may occur even in the presence of a normal gallbladder and that surgical removal of a non-stone-bearing gallbladder which is histologically normal does not relieve symptoms. Consequently, cholecystec-
Cholecystitis
1471
tomy for "cholecystitis" usually is not recommended unless gallstones are present. Under these circumstances, clinical judgment based on experience must be used. Occasionally duodenal-biliary drainage according to the technique of Lyon or the use of secretin and pancreozymin may be of supplementary help. Failure to obtain an adequate gallbladder fraction of bile on duodenal drainage or contraction of the gallbladder on x-ray following intravenous administration of these hormones suggests impaired biliary function. I , 2, 5, 6,7,9 CHOLECYSTITIS WITHOUT STONES
To explore the problem of cholecystitis in the absence of stone somewhat further, we reviewed our own recent experience. During 1960, 309 patients were admitted to the Jefferson Medical College Hospital with the diagnosis of cholelithiasis or cholecystitis. Of these, 287 were shown to have gallstones, but cholecystectomy was performed in only 2]4 or 74.5 per cent. Patients who were not operated upon had refused surgery, were too feeble to withstand it or had an illness that required priority of treatment. Twenty-two patients or 7.3 per cent of the entire group in whom stones were not demonstrated by x-ray or surgery had cholecystectomy for cholecystitis. The cholecystograms in these patients showed poor or absent visualization in each instance. Histopathologic examination of the gallbladders showed chronic cholecystitis in 17, chronic cholecystitis with cholesterosis in two, chronic cholecystitis with papilloma of the gallbladder in one and acute cholecystitis in two. Of 126 private patients whom I treated for biliary tract disease, between 1951 and 1961, 84 were female and 42 male. Cholecystectomy was performed in 88 (82 per cent) of those patients with gallstones and in only two of the seven patients who had cholecystitis without stones. In the remaining five patients the cholecystogram sho" ed poor visualization of the gallbladder in three and nonvisualization in two. Biliary drainage in each of these patients was within normal limits and it was therefore decided to treat them on a medical regimen. MEDICAL MANAGEMENT
Patients in whom surgery is contraindicated because of age or debility should be given a special diet, treated with antispasmodics and encouraged to maintain good hygiene.
Diet In gallbladder disease, free use of the following foods is permitted: bread and bread stuffs, cereals, egg white, fish low in fat, lean meat, skim milk, syrups, most vegetables, mild cheeses and fruits. The following foods should be eliminated or taken only in small amounts: liver,
c.
1472
WILMER WIRTS
kidney, sweetbreads, brain, caviar, egg yolk, fatty meats (sausage, bacon, pork, veal), fatty fish (mackerel, blue fish, sardines), fatty fowl (goose, duck), rich cake and pastry, butter, cream, olive oil and all fried foods or those rich in condiments. Certain vegetables also should be avoided (broccoli, cauliflower and cabbage), and certain beverages (alcohol, effervescent and aerated water). SPECIMEN DIET
Breakfast Fruit or fruit juice Cereal with skim milk Dried bread or toast, or Melba toast with marmalade, jelly, honey or small amount of butter Hot cakes or waffles with syrup, occasionally weak tea, Sanka or skim milk Lunch Soup made with milk Two vegetables or toasted sandwich of lettuce and tomato, cheese or lean meat Rice or tapioca pudding, Jello, fresh or cooked fruit Weak tea, Sanka or skim milk
Dinner Fruit or fruit juice or nonfatty soup Lean meat: steak, roast beef, lamb chops, lamb or ham, or Any fish or fowl containing little fat or oil Potatoes, rice, macaroni, vermicelli or spaghetti Two green vegetables (except as noted above) Dry bread, toast or Melba toast Pudding, Jello, fresh or cooked fruits, plain cake or mild cheese and crackers Weak tea, Sanka or skim milk
Bowel Hygiene Normal bowel hygiene should be maintained by adding sufficient bulk to the diet, establishing regularity in going to stool and avoiding laxatives. Drugs Probably the most effective medication for a moderate-to-severe attack is either morphine sulfate 7.5 to 15 mg. (Vs to ~ grain) or Demerol 50 to 100 mg., given':parenterally, with or without atropine sulfate 0.4 mg. (1/150 grain). The need for repeated administration must be judged critically. For milder symptoms codeine sulfate 60 mg. (1 grain), sodium phenobarbital 120 mg. (2 grains), methantheline bromide (Banthine) 50 mg., or propantheline bromide (Pro-Banthine) 30 mg. may be tried intramuscularly. Prophylactic antibacterial therapy is indicated in severe, prolonged or complicated attacks; procaine penicillin or crystacillin, 300,000 units given intramuscularly, either alone or with streptomycin 0.5 gram, every 12 hours; or a broad-spectrum antibiotic, such as Achromycin or Terramycin, 500 mg. in 500 cc. of physiologic salt solution may be given intravenously. During the period of nausea and
Cholecystitis
1473
vomiting, all oral food and fluid intake should be stopped and infusions of dextrose or physiologic salt solution given intravenously. CHOLECYSTITIS AND ASSOCIATED DISEASE
Other types of gastrointestinal disease and extraintestinal conditions frequently co-exist with cholecystitis and require consideration in the management of these patients. The following is a list of associated conditions found in the 88 of my patients who were operated upon: Empyema Duodenal ulcer Obstructive jaundice Pancreatitis Common duct stone Anemia Hypertension Hiatal hernia Cirrhosis of liver Diabetes
13
10 6 4 4
3 3 3 2 2
Meckel's diverticulum Pregnancy Hepatitis Renal stone Gastric ulcer Esophageal ulcer Cystic duct stone Ulcerative colitis Gastritis
2 2 2 2 1 1 1 1 1
Peptic ulcer is the commonest non-biliary tract condition which may require simultaneous treatment. Combined disease of this type undoubtedly makes the treatment of either one more difficult. It would appear that in most instances the peptic ulcer is amenable to medical therapy, whereas cholecystitis associated with cholelithiasis almost always requires surgical treatment. The significance of the other associated conditions appears obvious. Management must be individualized as in patients with peptic ulcer. SUMMARY
Acute and chronic cholecystitis is an inflammatory disease of the gallbladder usually due to some obstruction to bile flow and less often associated with pyogenic infection. Depending upon the severity and extent of the inflammatory reaction, the symptoms vary from empyema, gangrene and rupture of the gallbladder to the mildest right upper quadrant distress. Although laboratory studies are very helpful, it is frequently necessary to base the decision regarding surgical or medical treatment upon clinical judgment. Most cases of cholecystitis are associated with cholelithiasis and require surgical treatment. Preferably this is done when the symptoms are minimal and under elective conditions. However, under circumstances of persistent activity with threatening rupture it may be necessary to undertake emergency operative intervention. Medical treatment is reserved for those few patients who are thought to have slight functional impairment of the gallbladder but no convincing
C.
1474
WILMER WIRTS
evidence of cholelithiasis or true cholecystitis. Finally, it may be necessary to treat patients with cholelithiasis and cholecystitis medically because they are poor surgical risks or because they refuse surgical treatment. REFERENCES 1. Burton, P. et al.: Use of Secretin and Pancreozymin in Man. Gastroenterologia 86: 463, 1956.
2. Dreiling, D. A.: Technique of Secretin Test: Normal Ranges. J. Mt. Sinai Hosp. 21: 363, 1954. 3. Glenn, F. and Guida, P. M.: Surgery in Biliary Tract Disease. J.A.M.A. 174: 44, 1960. 4. Heffernon, E. W., Millhon, W. A. and Rosen, S. W.: Irritable Colon and Gallbladder Disease. J.A.M.A. 173: 1, 1960. 5. Jorpes, J. E. and Mutt, V.: Secretin, Pancreozymin and Cholecystokinin, Thcir Preparation and Properties. Gastroenterology 36: 377, 1960. 6. Jorpes, J. E., Mutt, V., Tomenius, J. and Blacklund, V.: Cholecystokinin in Roentgenologic Examination of Biliary Tract. Roentgenblatter. 11: 145, 1958. 7. Raskin, H. F. et al.: Diagnosis of Cancer of Pancreas, Biliary Tract and Duodenum by Cytologic and Secretory Methods. Gastroenterology 34: 886, 1958. 8. Smith, L. A.: Left-sided Pain in Disease of Gallbladder. Proc. Staff. Meet., Mayo Clin. 34: 597, 1959. 9. Sun, D. C. H. and Shay, H.: Pancreozymin-Secretin Test. Combined Study of Enzymes and Duodenal Contents in Diagnosis of Pancreatic Disease. Gastroenterology 38: 570, 1960. 1025 Walnut Street Philadelphia 7, Pennsylvania