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The Treatment of Gallbladder Disease
Medical Clinics oj North America September, 1941. Boston Number
THE TREATMENT OF GALLBLADDER DISEASE EDWARD S. EMERY, JR., M.D.
THE treatment of any patient with gallbladder disease involves a decision on when to use surgery and what is the best medical therapy for the patient for whom surgery is contraindicated. Generally speaking, patients with acute cholecystitis always require surgery whether or not stones are present. The presence of chronic cholecystitis with stones will necessitate surgery if a cure is to be effected, although an operation may not be imperative. The best treatment for chronic cholecystitis without stones cannot be stated so dogmatically. Before answering this question, it is necessary to consider the reliability of the diagnosis and the effectiveness of medical treatment. ACUTE CHOLECYSTITIS
Symptoms and Signs.-The symptoms of acute inflammation of the gallbladder are, characteristically, distress in the right upper quadrant which frequently radiates to the angle of the scapula, and the presence of local soreness and tenderness. The intensity of the symptoms varies widely, depending upon the severity of the process and, in part, upon the local anatomical relationship. The distress may be little more than a disagreeable heaviness or burning, or may become excruciatingly severe. Likewise, the local tenderness may be slight or assume such proportions that mild pressure produces agonizing pain. It is well to remember that severity of the symptoms may appear out of proportion to the localized tenderness, which depends upon the degree of peritoneal involvement and the amount of protection which the liver affords the gallbladder from the examining hand. I.n addition, many of these patients have epigastric distress From the Dept. of Medicine, Harvard Medical School, and the Medical Clinic, Peter Bent Brigham' Hospital. Instructor in Medicine, Harvard Medical School; Associate in Medicine, Peter Bent Brigham Hospital. 1377
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EDWARD S. EMERY, JR.
as well as pain in the right upper quadrant. Some individuals complain only of the epigastric distress. Occasionally the chief complaint is localized pain or tenderness in the left upper quadrant and a few patients localize it in the right lower quadrant. Experimental studies have shown that acute distention of the gallbladder or its ducts produces epigastric discomfort instead of localized pain in the region of the gallbladder. These observations probably explain the high incidence of epigastric distress in the early stages of acute cholecystitis. The physical examination reveals localized tenderness in the region of the gallbladder accompanied by a tender mass in about one third of the cases. In about 60 per cent of cases the patients have involuntary muscle spasm. Its absence in the remaining 40 per cent is probably due to a separation of the diseased organ and the parietal peritoneum by the liver. Treatment.-Acute cholecystitis is a serious disease and the inflamed organ ultimately should be removed. However, cases behave somewhat differently, and there is a difference of opinion concerning the most desirable time for surgery. One group of practitioners holds that immediate surgery is always indicated, while a more conservative element has stressed the dangers of manipulating an acutely infected gallbladder and recommends a period of watchful waiting with the hope that the acute inflammation will quiet down. In any event, it is desirable for the internist who does not operate to call in the surgeon as soon as the diagnosis of acute cholecystitis is suspected. With our present knowledge the following routine of treatment, the object of which is to prepare the patient for operation, is the best course to pursue. During this period the physician may determine the direction which the disease is . taking. As soon as the diagnosis is suspected the patient is put to bed with the head of the bed raised from 6 to 12 inches. Heat or cold, whichever the patient finds more acceptable, is applied to the upper abdomen. Adequate fluids are given, the administration of which can be best asspred by the intravenous route. Three thousand cc. of normal saline should be introduced during the first twenty-four hours. If the patient is very uncomfortable or unduly restless the use of morphine or sedatives is indicated. If the pain is severe, morphine sulfate 0.015 gm.
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o~ grain) is given hypodermically and if this does not provide adequate relief at the end of thirty minutes, a second injection is made. Chloral hydrate, 0.3 gm. (5 grains), may be given by mouth if the patient is able to retain it, or it may if necessary be introduced rectally. This drug may be repeated as often as every four hours, depending upon the degree of restlessness of the patient. Nembutal 0.1 gm. (1 % grains) repeated as often as every six hours, is also effective in allaying restlessness. Some patients are bothered by abdominal distention, in which event constant gastric suction is instituted. During this period of treatment, a close watch must be kept of the patient's temperature, pulse and white blood cell count. Most patients will show marked improvement under such a regimen. Approximately 40 per cent will improve so that surgery may be carried out safely within forty-eight hours. Another 50 per cent will improve more slowly. If the fever, local pain and tenderness and leukocytosis are decreasing, one may feel justified in delaying operation for several days. A small group of patients, usually not over 10 per cent, become worse. The fever· remains high or increases, leukocytosis becomes greater and local tenderness and spasm increase. Under these conditions immediate surgery is indicated, as perforation is imminent. A word of caution should be interjected about relying too heavily on the leukocyte counL An occasional case will show a steady drop in the leukocytosis, all the while the gallbladder condition is developing into gangrene. In these instances the gallbladder becomes effectively walled off from the general system, thus preventing a leukocytic response, although the local condition is progressing from bad to worse. The rationale for this regimen is that a large proportion of patients have a mechanical lesion in which obstruction to the lymphatic escape occurs, with resultant edema of the gallbladder wall. Infection is a secondary factor. The time taken for improving the patient's general condition by the administration of sufficient fluids and the relief of pain and rest makes him. a better surgical risk. However, a certain number of patients suffer from a serious bacterial invasion. The infection may develop rapidly, with sudden perforation or rapid spread. Und('r these conditions, a delay in drainage may prove disas-
1380
EDWARD S. EMERY, JR.
trous, SO that patients must be watched constantly and their temperature chart and leukocyte count followed closely. CHRONIC CHOLECYSTITIS WITH STONES
Symptoms and Signs.-This condition presents a different problem from that of the acutely inflamed gallbladder. In most patients the symptoms depend more upon the cholelithiasis than upon the cholecystitis, the severity of which varies greatly in different individuals. Cases present two different groups of symptoms and it is important to keep their differences in mind, particularly as they have a bearing on our attitude toward the character of treatment in chronic cholecystitis without stones. 1. The first group of symptoms consists of discomfort in the right upper quadrant which is referred characteristically to the back and to the region of the gallbladder. It may vary in intensity. Of patients with sufficiently severe symptoms to bring them to the operating table, approximately 90 per cent give a history of biliary colic or severe pain at some time during the course of their disease. Some patients describe a dull, heavy distress, while others refer to seizures with acute cramps or colic. The pain may last steadily for a matter of hours or it may be remittent, periodically becoming worse and better. In other cases it may be transient. The most typical point of reference is to the tip of the scapula, although the pain may go straight through to the back, to the interscapular area, or to the tip of the right shoulder. I saw one patient whose greatest complaint was hyperesthesia of both shoulders, so marked that the weight of his overcoat was distressing. At times the pain may be referred to the right lower quadrant and occasionally to the left side. Approximately two thirds of the patients experience pain in the right upper quadrant which is referred to the back. Approximately 10 per cent may complain at some time of pain in the left upper quadrant or left infrascapular region. Approximately a third of all patients suffer from severe epigastric distress. Vomiting may occur spontaneously, but frequently it is induced by the patient in an attempt to overcome the associated nausea. Spontaneous vomiting is usually indicative of a stone in the cystic or common duct. The physical examination reveals tenderness with varying
THE TREATMENT OF GALLBLADDER DISEASE
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degrees of spasm. At times, no spasm can be elicited. A characteristic observation is the persistence of soreness and tenderness after the acute symptoms have disappeared. Visible jaundice mayor may not develop after an attack. As it is often an important finding in a differential diagnosis it must be looked for closely. Frequently it is minimal, lasts only a short while and may be missed by the physician if the patient is observed only by artificial light. The foregoing symptoms and signs can be explained by blockage and distention of the biliary tract and gallbladder by a stone. The. inflammatory changes may be minimal. 2. Patients with cholelithiasis may also experience another group of less characteristic symptoms. These may be limited to the epigastrium or involve the whole abdomen. They consist of epigastric fulness and distention coming on particularly during or after eating. The epigastric symptoms are those which are sometimes described as dyspepsia. Patients may also complain of julness in the lower abdomen, distention, rumbling and gurgling, and report that these symptoms are relieved, or at least modified, by belching, the passage of flatus and a bowel movement. They often resort to the taking of bicarbonate of soda because of the temporary relief which it seems to produce. A careful analysis of this group of symptoms reveals that they are similar to those suffered by patients with purely functional disorders. They are produced by the stomach or intestines, and they will respond temporarily to the same measures which relieve individuals suffering from nervous indigestion. Therefore, one must deduce that these symptoms are, in fact, a functional disturbance of the gastro-intestinal tract, dependent upon a reflex action from a pathologic biliary system. The presence of these symptoms is not diagnostic of gallbladder disease, but merely suggestive, because disease of the biliary system is only one cause of functional disorders. It is only when these symptoms are combined with those which are more specific for the biliary tract, that one can be sure of the diagnosis on the basis of symptoms alone. Failure to discriminate between these two sets of symptoms wa~ responsible for much unnecessary surgery before cholecystograms became available. Because it was known that these functional symptoms could depend upon a pathologic gall-
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bladder and because a certain number of patients lose these symptoms after a cholecystectomy, many normal gallbladders were operated upon. Cholecystograms are a definite test of gallbladder function and the presence of stones. Intravenous cholecystograms are accurate in about 97 or 98 per cent of cases. Therefore, there is not the same need for relying upon symptoms as formerly. Treatment.-Surgery.--Once the diagnosis of cholelithiasis has been made, cure can be effected only by surgery because, all the claims of patent medicine dispensers to the contrary, no method has yet been devised for the dissolution of gallstones. In spite of this knowledge, certain conservative clinicians do not advocate surgery for all patients. They point out that stones are found at autopsy in many cases in which no previous history of indigestion was obtained. Furthermore, it is well known that a patient may go many years before having a second attack of colic. Therefore, they argue, why subject a patient to an operation until it has been demonstrated that his gallstones are going to give him continuous trouble. Although there is much to be said for these arguments, careful statistics show that it is better to remove the stones provided the general condition of the patient does not contraindicate an operation. Whenever stones are present there is a potential danger of acute blockage of the cystic or common ducts which may be followed by the onset of a severe infection. Large stones may set up a chronic inflammation and may ultimately perforate unexpectedly. The mortality from an uncomplicated cholecystectomy has now decreased to a point where the danger of keeping the stones outweighs the danger of an operation. It is a good rule, therefore, that gallstones should be removed surgically, particularly if the patient has suffered, or is suffering from acute attacks of biliary colic or chronic indigestion. One exception to this is the gallstone of an individual suffering from very definite complications which contraindicate the use of surgery-as, for example, active pulmonary tuberculosis. But it must be remembered that in most diseases the patient withstands the operation quite well. Another exception arises in the elderly person in whom the presence of stones produces little or no trouble. It may well be that such an individual may live the rest of his or her life without discomfort,
THE TREATMENT OF GALLBLADDER DISEASE
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ultimately to die from some unrelated condition. The physician will do well not to advise an operation which will inflict unnecessary danger and discomfort. Medical Measures.-If it is decided not to use surgery, medical measures may be recommended for the patient who suffers mild, intermittent distress. When instigating medical treatment in these cases, the physician should have in mind what he is attempting to accomplish. The very fact that the patient is experiencing little discomfort indicates an absence of active inflammation. It may be that there is no associated cholecystitis, or any past inflammation may have become quiescent. The discomfort comes largely from transient pressure exerted by the stones and requires temporary measures for relief. The diet should be simple. It is desirable to eliminate the coarser and more irritating foods. Such vegetables as cabbage, turnips and onions and such fruits as melons and raw apples, which tend to stimulate an irritable intestinal tract, should be forbidden. For the same reason, highly seasoned and spiced foods should be eliminated. It is customary to recommend a decreased intake of fats because of the knowledge that fats activate the gallbladder and on the assumption that the flow of bile may be somewhat impaired. However, it is impossible to eliminate all fats from the diet for any length of time, partly for reasons of nutrition and partly because it is impossible to make a palatable diet without fats. Normally, individuals take from 80 to 90 gm. of fat a day and it is very difficult to restrict the intake of fats below 40 gm. a day. If one attempts to keep it between 60 and 80 gm., it is questionable whether such a moderate reduction will make any great difference in the degree to which the gallbladder is activated. There is also a question whether the cholecystitis really interferes with the absorption of fats from the intestinal tract. It will do no harm and may be of some benefit to introduce bile by mouth with the hope that such a procedure may improve the digestion of fats and serve to increase the flow of bile or improve the quality of bile secreted. Any of the standard preparations of bile may be used in doses of 1 to 2 tablets or capsules after meals. Patients react differently to the oral administration of bile. If such medication produces cramps or
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EDWARD S. EMERY, JR.
diarrhea it should be stopped. Antispasmodics reduce the tone of the biliary tract. The inhalation of an amyl nitrite pearl or the use of nitroglycerin, 112 mg. (Yt20 grain), repeated if necessary two or three times, is sometimes helpful. However, if the pain is more severe an opiate, either codeine sul/ate, 30 mg. (112 grain) or morphine sul/ate, 15 mg. ( ~ grain), taken orally, will be needed. CHRONIC CHOLECYSTITIS WITHOUT STONES
There is less agreement about the treatment of this condition, partly owing to a lack of unanimity concerning the definition and partly to uncertainty in the diagnosis. Various degrees of chronic inflammation of the gallbladder occur. On the one extreme is the thickened, shrunken organ about which there can be no question. At the other extreme are those conditions in which the gallbladder shows few or no gross changes and the microscope reveals only slight evidence of disease. It seems to the writer that the subject of chronic cholecystitis today is in much the same state that chronic appendicitis was in a number of years ago. We have learned not to make a diagnosis of chronic appendicitis on vague symptoms and localized tenderness alone. The diagnosis of a pathologic appendix can only be made with reasonable assurance on the basis of three conditions: the history of characteristic symptoms, the presence of local signs and evidence of infection, i.e., fever and leukocytosis. These three requirements hold equally true for chronic cholecystitis. As previously pointed out, pathologic gallbladders can cause functional symptoms from the gastrointestinal tract, but these symptoms are not diagnostic of a diseased gallbladder. They suggest merely that cholecystitis may be present. This is analogous to the difficulty in deciding whether the abdominal symptoms come from a low grade inflammation of the appendix or whether a functional disorder is simulating appendicitis. Just as tenderness in the right lower quadrant does not alone make the diagnosis of appendicitis, tenderness in the right upper quadrant is not always the result of an inflamed gallbladder. We have learned that minor histological changes can occur in the appendix without being evidence of clinical appendicitis. A similar situation exists in regard to the gallbladder.
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Cholecystograms are an invaluable aid in the diagnosis of gallbladder disease. However, a physician must be cautious in evaluating minor changes, even by the intravenous method. There are too many variables, such as the size of the patient and the possibility of slow movement, to make the intensity of the shadow an accurate index of the functional capacity of the gallbladder. I have gone into the uncertainty of what constitutes a pathologic condition and the difficulties in its diagnosis to this extent, because it seems to me that the reports on the efficacy of medical treatment alone, depend in large measure upon the standards which the individual investigators have set up for controlling their studies. Treatment.-Surgery is the accepted treatment for cases of cholecystitis in which the gallbladder has completely lost its function of concentration as demonstrated by the x-ray. Medical treatment is reserved for those patients whose symptoms are so mild as not to require surgery, or in whom surgery is con traindica ted. The object of medical procedures is to assist in draining an infected organ. There are two ways in which stasis can theoretically be overcome. One is to relieve any spasm of the sphincter of Oddi. The other is to increase the flow of bile. It has been shown that the antispasmodic drugs will, in fact, cause a decrease in tone of the sphincter. It is also true that the use of certain bile derivatives will increase the amount or flow of bile. Based on these considerations, the following routine has been suggested and favorable results have been reported from its use in certain clinics. The patient is placed on nitroglycerin, Y2 mg. (7{20 grain) every four hours. If there is a tendency for more acute pain to develop, the use of amyl nitrite may be undertaken at the time of the distress. Any of the wellknown bile preparations may be given, as for example, Decholin, 1 tablet three times a day, bile salts (Fairchild or Armour) 0.2 gm. (3 grains) three times a day, or Bilron (Lilly) 1 or 2 capsules three times a day. A low fat diet as previously desctibed is usually recommended, the theoretical object of which, among other things, is to decrease the amount of cholesterol in the diet. Most physicians also recommend a somewhat bland diet. Many of these patients complain of constipation for which the saline laxatives are the best. The use of
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EDWARD S. EMERY, JR.
two or three teaspoonfuls of sodium phosphate in hot water before breakfast, or a moderate dose of magnesium sulfate, 2 teaspoonfuls before breakfast, will usually take care of bowel elimination in a satisfactory manner. The magnesium sulfate has the added value of tending to relax the sphincter of Oddi and, therefore, of assisting in overcoming biliary stasis. In passing, a word should be said about the use of so-called duodenal drainage. When it was first discovered that it was practical to inject magnesium sulfate into the duodenum, with a resulting relaxation of the sphincter and a contraction of the gallbladder, this therapy seemed indicated. When it later became evident that fat was an even greater activator of the gallbladder it seemed hard to understand how this maneuver could be of value. In view of the observations which have been made through the ensuing years it seems probable that whatever beneficial effect this treatment has, can be attributed partly to the psychic effect and partly to its laxative action. Irrespective of the basis underlying the medical therapy of gallbladder disease, it must be pointed out that it is very difficult to evaluate its results. The subsidence of true biliary symptoms after its use may only be coincidence, as it is well known that cholecystitis may become quiescent at any time. The improvement of nonspecific symptoms or the so-called "functional" symptoms may result from the regulation of diet and the better hygiene afforded the patient under treatment. It must always be kept in mind that antispasmodics may relieve purely gastro-intestinal symptoms. The only accurate way to determine the results of therapy is by observing what effect such treatment has on the x-ray appearance. As pointed out, this is, in itself, a difficult thing to evaluate and there have been too few reports, with the x-ray employed as a criterion of treatment from which to draw accurate conclusions. From the foregoing it appears that the medical therapy which has been outlined for chronic cholecystitis is based on sound physiologic and pharmacologic considerations, but more careful and critical studies are needed to determine the clinical efficacy of this treatment. With our present knowledge, one is justified in making use of this procedure for patients with mild cholecystitis. Obviously it cannot correct a more advanced condition, for which one has to utilize surgery.
THE TREATMENT OF GALLBLADDER DISEASE EDWARD S. EMERY, JR., M.D.
THE treatment of any patient with gallbladder disease involves a decision on when to use surgery and what is the best medical therapy for the patient for whom surgery is contraindicated. Generally speaking, patients with acute cholecystitis always require surgery whether or not stones are present. The presence of chronic cholecystitis with stones will necessitate surgery if a cure is to be effected, although an operation may not be imperative. The best treatment for chronic cholecystitis without stones cannot be stated so dogmatically. Before answering this question, it is necessary to consider the reliability of the diagnosis and the effectiveness of medical treatment. ACUTE CHOLECYSTITIS
Symptoms and Signs.-The symptoms of acute inflammation of the gallbladder are, characteristically, distress in the right upper quadrant which frequently radiates to the angle of the scapula, and the presence of local soreness and tenderness. The intensity of the symptoms varies widely, depending upon the severity of the process and, in part, upon the local anatomical relationship. The distress may be little more than a disagreeable heaviness or burning, or may become excruciatingly severe. Likewise, the local tenderness may be slight or assume such proportions that mild pressure produces agonizing pain. It is well to remember that severity of the symptoms may appear out of proportion to the localized tenderness, which depends upon the degree of peritoneal involvement and the amount of protection which the liver affords the gallbladder from the examining hand. I.n addition, many of these patients have epigastric distress From the Dept. of Medicine, Harvard Medical School, and the Medical Clinic, Peter Bent Brigham' Hospital. Instructor in Medicine, Harvard Medical School; Associate in Medicine, Peter Bent Brigham Hospital. 1377
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EDWARD S. EMERY, JR.
as well as pain in the right upper quadrant. Some individuals complain only of the epigastric distress. Occasionally the chief complaint is localized pain or tenderness in the left upper quadrant and a few patients localize it in the right lower quadrant. Experimental studies have shown that acute distention of the gallbladder or its ducts produces epigastric discomfort instead of localized pain in the region of the gallbladder. These observations probably explain the high incidence of epigastric distress in the early stages of acute cholecystitis. The physical examination reveals localized tenderness in the region of the gallbladder accompanied by a tender mass in about one third of the cases. In about 60 per cent of cases the patients have involuntary muscle spasm. Its absence in the remaining 40 per cent is probably due to a separation of the diseased organ and the parietal peritoneum by the liver. Treatment.-Acute cholecystitis is a serious disease and the inflamed organ ultimately should be removed. However, cases behave somewhat differently, and there is a difference of opinion concerning the most desirable time for surgery. One group of practitioners holds that immediate surgery is always indicated, while a more conservative element has stressed the dangers of manipulating an acutely infected gallbladder and recommends a period of watchful waiting with the hope that the acute inflammation will quiet down. In any event, it is desirable for the internist who does not operate to call in the surgeon as soon as the diagnosis of acute cholecystitis is suspected. With our present knowledge the following routine of treatment, the object of which is to prepare the patient for operation, is the best course to pursue. During this period the physician may determine the direction which the disease is . taking. As soon as the diagnosis is suspected the patient is put to bed with the head of the bed raised from 6 to 12 inches. Heat or cold, whichever the patient finds more acceptable, is applied to the upper abdomen. Adequate fluids are given, the administration of which can be best asspred by the intravenous route. Three thousand cc. of normal saline should be introduced during the first twenty-four hours. If the patient is very uncomfortable or unduly restless the use of morphine or sedatives is indicated. If the pain is severe, morphine sulfate 0.015 gm.
THE TREATMENT OF GALLBLADDER DISEASE
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o~ grain) is given hypodermically and if this does not provide adequate relief at the end of thirty minutes, a second injection is made. Chloral hydrate, 0.3 gm. (5 grains), may be given by mouth if the patient is able to retain it, or it may if necessary be introduced rectally. This drug may be repeated as often as every four hours, depending upon the degree of restlessness of the patient. Nembutal 0.1 gm. (1 % grains) repeated as often as every six hours, is also effective in allaying restlessness. Some patients are bothered by abdominal distention, in which event constant gastric suction is instituted. During this period of treatment, a close watch must be kept of the patient's temperature, pulse and white blood cell count. Most patients will show marked improvement under such a regimen. Approximately 40 per cent will improve so that surgery may be carried out safely within forty-eight hours. Another 50 per cent will improve more slowly. If the fever, local pain and tenderness and leukocytosis are decreasing, one may feel justified in delaying operation for several days. A small group of patients, usually not over 10 per cent, become worse. The fever· remains high or increases, leukocytosis becomes greater and local tenderness and spasm increase. Under these conditions immediate surgery is indicated, as perforation is imminent. A word of caution should be interjected about relying too heavily on the leukocyte counL An occasional case will show a steady drop in the leukocytosis, all the while the gallbladder condition is developing into gangrene. In these instances the gallbladder becomes effectively walled off from the general system, thus preventing a leukocytic response, although the local condition is progressing from bad to worse. The rationale for this regimen is that a large proportion of patients have a mechanical lesion in which obstruction to the lymphatic escape occurs, with resultant edema of the gallbladder wall. Infection is a secondary factor. The time taken for improving the patient's general condition by the administration of sufficient fluids and the relief of pain and rest makes him. a better surgical risk. However, a certain number of patients suffer from a serious bacterial invasion. The infection may develop rapidly, with sudden perforation or rapid spread. Und('r these conditions, a delay in drainage may prove disas-
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EDWARD S. EMERY, JR.
trous, SO that patients must be watched constantly and their temperature chart and leukocyte count followed closely. CHRONIC CHOLECYSTITIS WITH STONES
Symptoms and Signs.-This condition presents a different problem from that of the acutely inflamed gallbladder. In most patients the symptoms depend more upon the cholelithiasis than upon the cholecystitis, the severity of which varies greatly in different individuals. Cases present two different groups of symptoms and it is important to keep their differences in mind, particularly as they have a bearing on our attitude toward the character of treatment in chronic cholecystitis without stones. 1. The first group of symptoms consists of discomfort in the right upper quadrant which is referred characteristically to the back and to the region of the gallbladder. It may vary in intensity. Of patients with sufficiently severe symptoms to bring them to the operating table, approximately 90 per cent give a history of biliary colic or severe pain at some time during the course of their disease. Some patients describe a dull, heavy distress, while others refer to seizures with acute cramps or colic. The pain may last steadily for a matter of hours or it may be remittent, periodically becoming worse and better. In other cases it may be transient. The most typical point of reference is to the tip of the scapula, although the pain may go straight through to the back, to the interscapular area, or to the tip of the right shoulder. I saw one patient whose greatest complaint was hyperesthesia of both shoulders, so marked that the weight of his overcoat was distressing. At times the pain may be referred to the right lower quadrant and occasionally to the left side. Approximately two thirds of the patients experience pain in the right upper quadrant which is referred to the back. Approximately 10 per cent may complain at some time of pain in the left upper quadrant or left infrascapular region. Approximately a third of all patients suffer from severe epigastric distress. Vomiting may occur spontaneously, but frequently it is induced by the patient in an attempt to overcome the associated nausea. Spontaneous vomiting is usually indicative of a stone in the cystic or common duct. The physical examination reveals tenderness with varying
THE TREATMENT OF GALLBLADDER DISEASE
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degrees of spasm. At times, no spasm can be elicited. A characteristic observation is the persistence of soreness and tenderness after the acute symptoms have disappeared. Visible jaundice mayor may not develop after an attack. As it is often an important finding in a differential diagnosis it must be looked for closely. Frequently it is minimal, lasts only a short while and may be missed by the physician if the patient is observed only by artificial light. The foregoing symptoms and signs can be explained by blockage and distention of the biliary tract and gallbladder by a stone. The. inflammatory changes may be minimal. 2. Patients with cholelithiasis may also experience another group of less characteristic symptoms. These may be limited to the epigastrium or involve the whole abdomen. They consist of epigastric fulness and distention coming on particularly during or after eating. The epigastric symptoms are those which are sometimes described as dyspepsia. Patients may also complain of julness in the lower abdomen, distention, rumbling and gurgling, and report that these symptoms are relieved, or at least modified, by belching, the passage of flatus and a bowel movement. They often resort to the taking of bicarbonate of soda because of the temporary relief which it seems to produce. A careful analysis of this group of symptoms reveals that they are similar to those suffered by patients with purely functional disorders. They are produced by the stomach or intestines, and they will respond temporarily to the same measures which relieve individuals suffering from nervous indigestion. Therefore, one must deduce that these symptoms are, in fact, a functional disturbance of the gastro-intestinal tract, dependent upon a reflex action from a pathologic biliary system. The presence of these symptoms is not diagnostic of gallbladder disease, but merely suggestive, because disease of the biliary system is only one cause of functional disorders. It is only when these symptoms are combined with those which are more specific for the biliary tract, that one can be sure of the diagnosis on the basis of symptoms alone. Failure to discriminate between these two sets of symptoms wa~ responsible for much unnecessary surgery before cholecystograms became available. Because it was known that these functional symptoms could depend upon a pathologic gall-
1382
EDWARD S. EMERY, JR.
bladder and because a certain number of patients lose these symptoms after a cholecystectomy, many normal gallbladders were operated upon. Cholecystograms are a definite test of gallbladder function and the presence of stones. Intravenous cholecystograms are accurate in about 97 or 98 per cent of cases. Therefore, there is not the same need for relying upon symptoms as formerly. Treatment.-Surgery.--Once the diagnosis of cholelithiasis has been made, cure can be effected only by surgery because, all the claims of patent medicine dispensers to the contrary, no method has yet been devised for the dissolution of gallstones. In spite of this knowledge, certain conservative clinicians do not advocate surgery for all patients. They point out that stones are found at autopsy in many cases in which no previous history of indigestion was obtained. Furthermore, it is well known that a patient may go many years before having a second attack of colic. Therefore, they argue, why subject a patient to an operation until it has been demonstrated that his gallstones are going to give him continuous trouble. Although there is much to be said for these arguments, careful statistics show that it is better to remove the stones provided the general condition of the patient does not contraindicate an operation. Whenever stones are present there is a potential danger of acute blockage of the cystic or common ducts which may be followed by the onset of a severe infection. Large stones may set up a chronic inflammation and may ultimately perforate unexpectedly. The mortality from an uncomplicated cholecystectomy has now decreased to a point where the danger of keeping the stones outweighs the danger of an operation. It is a good rule, therefore, that gallstones should be removed surgically, particularly if the patient has suffered, or is suffering from acute attacks of biliary colic or chronic indigestion. One exception to this is the gallstone of an individual suffering from very definite complications which contraindicate the use of surgery-as, for example, active pulmonary tuberculosis. But it must be remembered that in most diseases the patient withstands the operation quite well. Another exception arises in the elderly person in whom the presence of stones produces little or no trouble. It may well be that such an individual may live the rest of his or her life without discomfort,
THE TREATMENT OF GALLBLADDER DISEASE
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ultimately to die from some unrelated condition. The physician will do well not to advise an operation which will inflict unnecessary danger and discomfort. Medical Measures.-If it is decided not to use surgery, medical measures may be recommended for the patient who suffers mild, intermittent distress. When instigating medical treatment in these cases, the physician should have in mind what he is attempting to accomplish. The very fact that the patient is experiencing little discomfort indicates an absence of active inflammation. It may be that there is no associated cholecystitis, or any past inflammation may have become quiescent. The discomfort comes largely from transient pressure exerted by the stones and requires temporary measures for relief. The diet should be simple. It is desirable to eliminate the coarser and more irritating foods. Such vegetables as cabbage, turnips and onions and such fruits as melons and raw apples, which tend to stimulate an irritable intestinal tract, should be forbidden. For the same reason, highly seasoned and spiced foods should be eliminated. It is customary to recommend a decreased intake of fats because of the knowledge that fats activate the gallbladder and on the assumption that the flow of bile may be somewhat impaired. However, it is impossible to eliminate all fats from the diet for any length of time, partly for reasons of nutrition and partly because it is impossible to make a palatable diet without fats. Normally, individuals take from 80 to 90 gm. of fat a day and it is very difficult to restrict the intake of fats below 40 gm. a day. If one attempts to keep it between 60 and 80 gm., it is questionable whether such a moderate reduction will make any great difference in the degree to which the gallbladder is activated. There is also a question whether the cholecystitis really interferes with the absorption of fats from the intestinal tract. It will do no harm and may be of some benefit to introduce bile by mouth with the hope that such a procedure may improve the digestion of fats and serve to increase the flow of bile or improve the quality of bile secreted. Any of the standard preparations of bile may be used in doses of 1 to 2 tablets or capsules after meals. Patients react differently to the oral administration of bile. If such medication produces cramps or
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diarrhea it should be stopped. Antispasmodics reduce the tone of the biliary tract. The inhalation of an amyl nitrite pearl or the use of nitroglycerin, 112 mg. (Yt20 grain), repeated if necessary two or three times, is sometimes helpful. However, if the pain is more severe an opiate, either codeine sul/ate, 30 mg. (112 grain) or morphine sul/ate, 15 mg. ( ~ grain), taken orally, will be needed. CHRONIC CHOLECYSTITIS WITHOUT STONES
There is less agreement about the treatment of this condition, partly owing to a lack of unanimity concerning the definition and partly to uncertainty in the diagnosis. Various degrees of chronic inflammation of the gallbladder occur. On the one extreme is the thickened, shrunken organ about which there can be no question. At the other extreme are those conditions in which the gallbladder shows few or no gross changes and the microscope reveals only slight evidence of disease. It seems to the writer that the subject of chronic cholecystitis today is in much the same state that chronic appendicitis was in a number of years ago. We have learned not to make a diagnosis of chronic appendicitis on vague symptoms and localized tenderness alone. The diagnosis of a pathologic appendix can only be made with reasonable assurance on the basis of three conditions: the history of characteristic symptoms, the presence of local signs and evidence of infection, i.e., fever and leukocytosis. These three requirements hold equally true for chronic cholecystitis. As previously pointed out, pathologic gallbladders can cause functional symptoms from the gastrointestinal tract, but these symptoms are not diagnostic of a diseased gallbladder. They suggest merely that cholecystitis may be present. This is analogous to the difficulty in deciding whether the abdominal symptoms come from a low grade inflammation of the appendix or whether a functional disorder is simulating appendicitis. Just as tenderness in the right lower quadrant does not alone make the diagnosis of appendicitis, tenderness in the right upper quadrant is not always the result of an inflamed gallbladder. We have learned that minor histological changes can occur in the appendix without being evidence of clinical appendicitis. A similar situation exists in regard to the gallbladder.
THE TREATMENT OF GALLBLADDER DISEASE
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Cholecystograms are an invaluable aid in the diagnosis of gallbladder disease. However, a physician must be cautious in evaluating minor changes, even by the intravenous method. There are too many variables, such as the size of the patient and the possibility of slow movement, to make the intensity of the shadow an accurate index of the functional capacity of the gallbladder. I have gone into the uncertainty of what constitutes a pathologic condition and the difficulties in its diagnosis to this extent, because it seems to me that the reports on the efficacy of medical treatment alone, depend in large measure upon the standards which the individual investigators have set up for controlling their studies. Treatment.-Surgery is the accepted treatment for cases of cholecystitis in which the gallbladder has completely lost its function of concentration as demonstrated by the x-ray. Medical treatment is reserved for those patients whose symptoms are so mild as not to require surgery, or in whom surgery is con traindica ted. The object of medical procedures is to assist in draining an infected organ. There are two ways in which stasis can theoretically be overcome. One is to relieve any spasm of the sphincter of Oddi. The other is to increase the flow of bile. It has been shown that the antispasmodic drugs will, in fact, cause a decrease in tone of the sphincter. It is also true that the use of certain bile derivatives will increase the amount or flow of bile. Based on these considerations, the following routine has been suggested and favorable results have been reported from its use in certain clinics. The patient is placed on nitroglycerin, Y2 mg. (7{20 grain) every four hours. If there is a tendency for more acute pain to develop, the use of amyl nitrite may be undertaken at the time of the distress. Any of the wellknown bile preparations may be given, as for example, Decholin, 1 tablet three times a day, bile salts (Fairchild or Armour) 0.2 gm. (3 grains) three times a day, or Bilron (Lilly) 1 or 2 capsules three times a day. A low fat diet as previously desctibed is usually recommended, the theoretical object of which, among other things, is to decrease the amount of cholesterol in the diet. Most physicians also recommend a somewhat bland diet. Many of these patients complain of constipation for which the saline laxatives are the best. The use of
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two or three teaspoonfuls of sodium phosphate in hot water before breakfast, or a moderate dose of magnesium sulfate, 2 teaspoonfuls before breakfast, will usually take care of bowel elimination in a satisfactory manner. The magnesium sulfate has the added value of tending to relax the sphincter of Oddi and, therefore, of assisting in overcoming biliary stasis. In passing, a word should be said about the use of so-called duodenal drainage. When it was first discovered that it was practical to inject magnesium sulfate into the duodenum, with a resulting relaxation of the sphincter and a contraction of the gallbladder, this therapy seemed indicated. When it later became evident that fat was an even greater activator of the gallbladder it seemed hard to understand how this maneuver could be of value. In view of the observations which have been made through the ensuing years it seems probable that whatever beneficial effect this treatment has, can be attributed partly to the psychic effect and partly to its laxative action. Irrespective of the basis underlying the medical therapy of gallbladder disease, it must be pointed out that it is very difficult to evaluate its results. The subsidence of true biliary symptoms after its use may only be coincidence, as it is well known that cholecystitis may become quiescent at any time. The improvement of nonspecific symptoms or the so-called "functional" symptoms may result from the regulation of diet and the better hygiene afforded the patient under treatment. It must always be kept in mind that antispasmodics may relieve purely gastro-intestinal symptoms. The only accurate way to determine the results of therapy is by observing what effect such treatment has on the x-ray appearance. As pointed out, this is, in itself, a difficult thing to evaluate and there have been too few reports, with the x-ray employed as a criterion of treatment from which to draw accurate conclusions. From the foregoing it appears that the medical therapy which has been outlined for chronic cholecystitis is based on sound physiologic and pharmacologic considerations, but more careful and critical studies are needed to determine the clinical efficacy of this treatment. With our present knowledge, one is justified in making use of this procedure for patients with mild cholecystitis. Obviously it cannot correct a more advanced condition, for which one has to utilize surgery.