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Cholecystitis and Cholelithiasis
Cholecystitis and Cholelithiasis EDMUND F. FOLEY, M.D., F.A.C.P.*
THE gallbladder bears a striking resemblance to the trap under the kitchen sink, in that sludge from the (biliary) drainage system accumulates. For reasons as yet unknown concretions are formed in this material. The contents of the gallbladder, being external to the epithelial barrier, are outside of the body and, therefore, constitute a foreign substance. Any solids occurring in the bile are foreign bodies, and as such pose the usual hazards of foreign bodies, namely inflammation, ulceration, displacement or dysfunction. The presence of stones in the biliary tract is the focal point about which all disorders of the bile passages are constellated. It is clinically convenient to consider as cholecystitis those conditions in which inflammation or the results thereof dominates the picture even though displacement of stones may be present, and as cholelithiasis those situations where stones are roentgenologically demonstrated or where the effects of migration of the stones predominate, and as dysfunction, those gallbladder syndromes occurring in the absence of inflammation and/or stones. ACUTE CHOLECYSTITIS
Aeute cholecystitis-what is it? In retrospect the cases may be divided into two artificial groups, (1) a mild catarrhal form and (2) a severe suppurative phlegmonous or gangrenous type with empyema of the gallbladder. The chief difference is the point of interruption of the sequence of the pathologic events. Following the description of Saint,! in the production of acute cholecystitis the steps are as follows: (1) obstruction of the cystic duct due to a stone (92 per cent) or edema; (2) distention of the gallbladder and/or torsion leading to congestion and edema; (3) decreased blood supply; (4) ischemia of the wall; (5) further distention of the vesicle with establishment of a vicious circle. The question of the role of bacterial invasion or of chemical irritation has been the object of consideraple study. The consensus of opinion favors chemical irritation from the abnormal bile or regurgitated pancreatic juice as being the primary offender, with infection as a secondary event.
* Professor of Medicine, University of Illinois College of Medicine; Attending Physician, llesearch and Educational Hospitals, University of Illinois. 145
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Depending on the state of the gallbladder at the time of obstruction of the cystic duct, either hydrops or empyema develops. If the gallbladder is emptied at time of impaction then it becomes filled with the bile-free secretion from the mucosa of the wall of the gallbladder and forms a hydrops. As long as the obstruction is unrelieved this material continues to form and to distend the gallbladder even up to the size of a football. On the other hand, if the gallbladder is filled with altered or infected bile at the time of the corking of the outlet, toxic or infected contents are trapped and empyema results. Subsequently as the ischemia and edema of the gallbladder wall advances, hemorrhagic areas appear, with ulcers forming at the sites of pressure from stones. Rokitansky-Aschoff sinuses are papillary infoldings of the mucosa forming deep crypts which contain the purulent contents and by inclusion lead to the formation of intramural abscesses and phlegmon. Gangrenous spots may occur, usually at pressure points, or the entire organ may be infarcted. This is the "point of no return" and further progression is characterized by penetration of the gallbladder wall, usually by perforation. In the majority of cases the tempo of development has been so slow as to permit some walling off by the omentum or by loops of bowel, so that the perforation is either directly into the digestive tract producing a direct internal biliary fistula, or into a localized space, which subsequently ruptures into the hollow viscus producing an internal indirect biliary fistula. Spontaneous external biliary fistulas are pathologic curiosities. Occasionally, in fulminating cases, there is free perforation into the peritoneal cavity with an exceedingly noxious peritonitis. A few cases have been reported of penetration through an apparently intact wall and are spoken of as "filtrating cholecystitis." Not infrequently, instead of perforation through the gallbladder wall, extension may be along the biliary passage, particularly upward into the hepatic duct producing an ascending suppurative cholangitis with resulting multiple liver abscess. In other cases, burrowing may occur in a variety of directions leading to the formation of fantastic abscesses in unsuspected areas. The progression in the development of the complete picture may be interrupted at several levels. Cessation of the process at the stage of congestion (probably before bacterial invasion) constitutes the mild or catarrhal form. At the level of empyema with inclusion abscesses in the wall without gangrenous area resolution may occur and be followed by fibrosis or even calcification of the wall which OsIer spoke of as ossification of the gallbladder and more recently has been termed "porcelain gallbladder." Clinical Picture
Following a gluttonous or greasy meal the patient experiences upper abdominal pain, usually high in the epigastrium. This pain is usually
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sharp, relentless and severe. It may cause her to double up and writhe. There is an associated distress described as a ball-like fulness or "something stuck" in the epigastrium with salivation, air s\vallowing, and loud urgent belching. Nausea and vomiting may dominate the picture. The nausea is insistent and is usually so intense as to cause induced vomiting. The pain soon shifts to the right hypochondriac region and may be referred to the back or to the scapula and rarely may be colicky. If the patient is seen at this time (about six hours after onset) there is found marked muscle guarding in the upper abdomen with disproportionate tenderness in the right upper quadrant. The tentative diagnosis of biliary colic is made and an injection of morphine is given. The episode may terminate at this level. If it progresses the pain is present when the opiate wears off. Chilly sensations or actual chills may occur. The pain mounts to a peak and persists in the gallbladder area which now becomes sore and tender. The soreness is aggravated by motion, coughing or sneezing so that the patient holds her side in an attempt at mobilization. The belching has stopped, the nausea persists (unless the stone has reached the common duct when vomiting occurs without nausea) and the patient is unable to retain even water. At this level (thirty-six to forty-eight hours) examination reveals an apprehensive patient with an elevation of temperature to 100°F., evidences of dehydration on tongue and breath, rapid pulse, localized right upper quadrant tenderness with muscle guarding, involuntary rigidity and some local rebound tenderness. The gallbladder mayor may not be palpable depending on the degree of distention, amount of muscle spasm, and location. There may be a slight icterus and a leukocytosis of 10,000 to 20,000. A gallbladder that can be felt at this stage indicates a serious cystic duct obstruction, carrying the threat of perforation unless relieved. From here on the course becomes stormy and violent, probably coincidental with the bacterial invasion and tissue necrosis. All the symptoms and findings become exaggerated. The patient becomes "toxic," with rapid pulse and respirations, soft eyeballs, acetone odor to the breath, marked right upper quadrant tenderness and muscle guarding, and decreased urinary output. There may be a septic type of temperature, chills with sweating, increased leukocytosis, and urobilinoginuria. It should be emphasized, however, that in some patients, especially the elderly obese, these clinical criteria of a progressive toxic state may be mild or absent and hence deceptively distract the attention from the severity of the disease. Treatment
Acute cholecystitis-what to do? The definitive treatment is surgery. The variations in the stage of development of the pathologic lesion
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existing at the time of the first examination coupled with the unpredictable future course pose hurdles in the standardization of treatment. Gallbladder disorder being particularly a disease of older age, the general condition of the patient frequently offers further hazard. If the patient is seen after the effects of the initial opiate or nitroglycerin has worn off (first twenty-four hours) and the symptoms are sufficiently prominent to permit a fairly definite diagnosis, it is safe to assume that the cystic duct is obstructed. Will it spontaneously be relieved or will it relentlessly progress? If the answer could be predicted the treatment could be standardized but because of the many possible variations it must be individualized. In order to obtain the answer the patient should be hospitalized and a record established to be used as a base to refer back to in evaluating future development. During this period of observation (twelve to twenty-four hours) the temperature and white blood count are useful for appraisal. Symptomatic treatment is instituted, consisting of penicillin and streptomycin, continuous duodenal suction, balanced intravenous fluids, nitroglycerin under the tongue and morphine or Demerol for severe pain, with a careful check on the fluid intake and output. If examination at the end of the twenty-four hour period indicates progression, operative intervention should be employed. Otherwise the patient progresses to the fourth day "critical period" which lasts until about the twelfth day unless perforation occurs. During the "critical period" if the decision is to "sit it out," meticulous attention must be given to maintenanee of hydration and electrolyte balanee. If during this period the gallbladder becomes palpable it is safe to assume that perforation will soon follow. "lTnless some overwhelming eontraindication to imperative surgery exists the waiting-out period is not justified. CHRONIC CHOLECYSTITIS
Under this term there is included a variety of gallbladder syndromes generally characterized by slow progression with acute exacerbations and remissions. It is acute cholecystitis set at a slower tempo, with the cystic duct still the vulnerable zone. When stones (which are suspected of being present in all cases) are known to be present, the term "calculous cholecystitis" is used for emphasis. The symptoms may be of recurrent attacks of acute cholecystitis, or of biliary colic, or of digestive disturbances of the "dyspeptic" type commonly identified with gallbladder dysfunction. In other less typical cases there may be obscure diagnostic enigmas masquerading as heart disease, Meniere's disease, pylorospasm, spastic colitis, and so on. Recurrent Acute Cholecystitis
That the gallbladder is a susceptible target under many circumstances is widely appreciated. Decreased gallbladder function occurs during
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the third trimester of pregnancy and acute attacks of cholecystitis tend to occur during this period. Every other diabetic female has gallstones. Following an acute attack of appendicitis, diverticulitis or renal colic a chronic gallbladder may be activated or a new disability may be initiated. These observations are cited to point up that the recurring acute episodes indicate an underlying chronic disorder. In this group of cases the predominating symptoms are not of biliary colic but rather of "indigestion" with "biliousness, belching and bloating" as the common complaint. There is a history of "selective food dyspepsia," an intolerance to greasy and highly seasoned food, with a self-imposed dietary restriction based on the patient's personal observation that certain foods disagree with her and "make gas." In severe cases the discomfort is brought on not by what she eats but rather that she eats. There is frequently a history of repeated attacks of vomiting with variable degrees of pain. The attack usually is precipitated by a violation of the diet, either qualitative or quantitative. The onset is that of an attack of acute cholecystitis but in a milder form. There is upper epigastric or right hypochondriac region pain with nausea and vomiting. The vomiting usually occurs several hours after the offending meal has been eaten and the emesis contains food remnants which should not have been in the stomach were it emptying in the normal time. The vomiting continues until the emesis contains "green gall" which usually indicates that the cystic duct obstruction or torsion has been relieved and that the attack is over. Biliary Colic
Biliary colie is due to futile attempts of gallstones to escape through the gallbladder. T'he pain results from distention of the cystic duct by the aggressor. As long as the foreign bodies remain quiescent in the insensitive fundus of the gallbladder, no pain occurs. It is postulated that as a result of a meal which vigorously stimulates gallbladder contractions small stones are forced into the cystic duct, producing the typical gallstone colic. The pain persists as long as the cystic duct is impacted, and ceases as soon as the stone drops back into the fundus or escapes into the common duct. If the stone remains in the cystic duct acute cholecystitis occurs with resulting empyema or hydrops. If it escapes into the common duct the picture of "common duct stone" follows. Atypical Types
There is a large group of cases in which the diseased gallbladder acts as a trigger mechanism to set off a chain of symptoms referable to other organs while the symptoms usually associated with gallbladder disease lurk in the background. 1"'his is especially true when the stomach is the
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participating organ and responds by hyperfunction. Hypersecretion, hypermotility and hyperacidity result in the familiar pjcture of "postprandial pyrosis," suggesting a peptic ulcer. The gallbladder is only incriminated when the roentgen study of the upper gastrointestinal tract accidentally reveals stones in the adjacent gallbladder or a "gallbladder sea," in the simultaneous barium study of the outflow tract flow of the stomach. Labyrinthine Type. Not infrequently the attack of cholecystitis displays itself by nausea, vomiting and vertigo of such severity as to literally throw the patient on the floor. The proof that these attacks are in reality due to the gallbladder rests in the demonstration of stones and the cessation of the attacks following surgical cure. Anginal Type. Arteriosclerosis, diabetes and gallbladder disease are notorious companions. There is a relationship between coronary sclerosis and gallbladder disease other than age group incidence. Gallbladder attacks initiate angina pectoris through vagal influences. 2 There is, however, another possible relationship. Angina pectoris results from transient myocardial ischemia due to a decreased blood supply to the heart muscle. The decreased supply is prooiea~~n the existence of narrowed sclerotic coronary arteries and an increased need for blood to the myocardium as the result of increased work. The work commonly results from such exertion as walking. It is likely that in acgallbladder attack there is also increased work due to physiologic exertion, such as hyperfunction, pylorospasm, vomiting, pain and apprehension. If this is so, then there is a real indication for serious consideration of the aggressive treatment of gallbladder disease in the presence of certain cases of angina pectoris. Diagnosis of Chronic Cholecystitis
In a discussion of the diagnosis of chronic cholecystitis it is necessary to establish a mutual agreement on what is included and excluded under this term. Included are those cases in which there are anatomical changes in the gallbladder and excluded are those rare cases of dysfunction or dyskinesia occurring in the absence of structural deformities. The pathological picture is determined by the presence or absence of stone~, the vigor of the reaction to previous injury or bacterial invasion, the status of the blood supply and the degree of cystic duct obstruction. The gallbladder may be small, thickened and fibrotic, thin and opaque, or distended by hydrops even to an enormous size. It may be "strawberry," calculous, porcelain, emphysematous or gaseous, and/or bound down by pericholecystic adhesions. The diagnosis is suggested or establish~d by the history of a previous event, such as biliary colic or acute cholecystitis, which could have led to one of the pathological pictures. Symptoms of "selective food dyspepsia," belching, flatulence and the like
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do not constitute sufficient evidence to warrant a diagnosis of cholecystitis in the absence of the definite tokens of gallbladder disease. Carefully controlled Graham-Cole tests which on repeating fail to show any visualization of the gallbladder or actually show the presence of calculi or of calcification constitute the best evidence of cholecystitis. Practically, a gallbladder that fails to visualize on two attempts with an adequate dosage of dye can be considered as a pathologic gallbladder. The hypermotile, hypertonic or hypotonic gallbladder as demonstrated by cholecystography does not necessarily represent cholecystitis. Needless to say, the diagnosis of cholecystitis should not be made on roentgen studies confined to cholecystography but should include a complete radiologic gastrointestinal examination. Treatment
With such an agreement on what is meant by cholecystitis the natural corollary is that such a gallbladder is actively or potentially symptomatic and hazardous, and that the ultimate and eventual treatment is radical eradication of an irreversible or progressive pathologic state. The time for the employment of surgery is determined by an evaluation of the local factors in the individual case, using the urgency of the symptoms and the radiologic evidence of deformity as the criteria. It is of utmost importance to relate the symptoms to the diseased organ. Cholecystectomy, if performed for the relief of "dyspeptic" symptoms (which usually are not caused by disorder of the gallbladder), will be followed by a return of those annoying complaints. During the period of waiting until the surgical indications are imperative the customary medical management is purely symptomatic. CHOLELITHIASIS
The separation of cholelithiasis as a clinical entity distinct from other forms of biliary tract disease is artificial. In any individual case the existence of stones cannot be denied by clinical means. The diagnosis of cholelithiasis is made when stones are demonstrated on roentgen study, is presumed when the symptoms are those of biliary colic, and is suspected in all cases of cholecystitis. The migration of all calculi usually precipitates an episode of acute cholecystitis or of common duct obstruction and frequently initiates the symptoms of chronic cholecystitis. Carcinoma of the gallbladder is revealed at the operating table by the surgeon performing an operation for gallstones. Incidence. Studies of autopsy material would indicate an incidence of gallstones of from 5 to 10 per cent, with a progressive increase by decades, reaching a peak between 50 to 60 years of age. The wider use of cholecystography and the increasing frequency of cholecystectomy for stones in the younger age groups would indicate a surprisingly high incidence in young women. The percentage is higher in females by a
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rate of 2 to 1 to 4 to 1, according to various authors. In the Negro male gallstones are very uncommon, the ratio between females and males being 7 to 1. In a study of 29,777 autopsies in patients over 20 years of age, Lieber 3 reported that gallstones were found in 11.6 per cent. In diabetics, his material showed gallstones in 30 per cent of all (over 20 years of age), in every other white female (diabetic), in every third Negro female, and every fifth male. In correlation with other diseases frequently suspected of having a high incidence of stones, namely peptic ulcer, pernicious anemia and portal cirrhosis, the frequency of occurrence paralleled the over-all general incidence of about 10 per cent. ~'-;ymptoms. 1'he only symptoms distinctively characteristic of gallstones are those resulting from the futile attempt of the calculi to escape from the site of manufacture, usually the gallbladder, occasionally the bile duct and rarely the liver. The stones in motion produce biliary colic, the futility results in signs or symptoms of obstruction (tenderness, jaundice or an enlarged gallbladder) when the flight is impeded in the natural channel, or in signs of erosion or perforation when the course or the flight is in an abnormally formed passageway. The sites of predilection for obstruction in the bile passages are the cystic duct, the ampulla of Vater and/or the ileocecal valve, leading respectively to acute cholecystitis, empyema or hydrops of the gallbladder, to choledocholithiasis, or to gallstone ileus, each with a distinctive clinical picture. Escape of the stones by penetration through the gallbladder wall leads to the formation of various types of fistulas, abscess or peritonitis. (}allstones impacted in the ileocecal valve are being recognized more and more frequently as a cause of mechanical obstruction of the bowel occurring especially in the aged. Since gallstones occur most commonly in the gallbladder, biliary colic most frequently results from migration of a stone into the cystic duet. 1-'his is the first step in the production of acute cholecystitis. If the advance of the stone is successfully repulsed the stone docilely falls back into the gallbladder to await a more propitious opportunity. Biliary colic is the only true identifying symptom of gallstones. The pain is located in the epigastrium or right upper quadrant, is knifelike in character, constant and crescendo, radiates through to the back or to the scapula and is aggravated by respiration. This pattern fingerprints the condition. There may be many variations from this stigmatizing demonstration, e.g. the pain may be dull, it may be in the left abdomen, it may be colicky, it may radiate to the precordium or down the left arm. This distorted pain complex is correlated to biliary colic by inference and established as sueh in retrospect. 'l'he patient is given nitroglycerin with the hopeful expectancy that the stone will "pass"~ meaning that it either retreats into a state of quiescence or advances into the common duct.
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ar~d
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Common Duct Stone
The classical symptoms of stone in the common duct result from various grades of obstruction, ranging from minimal to complete and from intermittent to constant. The colorful symptom of jaundice parallels the degree of closure of the common duct. It may be slow or rapid in onset, mild or intense, complete or incomplete, constant or intermittent. These vagaries are clinically important in helping to establish that the jaundice is due to extrahepatic obstruction (surgical jaundice) rather than intrahepatic destruction with or without block (medical jaundice). In extrahepatic obstruction the important positive clues are a history of preceding attacks of biliary colic or of acute cholecystitis, a stormy onset, right upper quadrant tenderness, choluria with urobilinuria varying directly with the degree of obstruction, relatively unaffected metabolic liver functions as reflected in unaltered serum proteins either quantitative or qualitative (negative flocculation and turbidity tests), and a high alkaline phosphatase. Unrelieved calculous extrahepatic obstruction has a ruthlessly destructive effect on the liver, determined by the degree, duration and associated infection, and can be as malignant as the obstruction due to neoplastic disease. Complete extrahepatic obstruction in 9 cases out of 10 is due to carcinoma. Hence because of the malignant conduct (literal sense) and for the sake of the 1 out of 10 who does not have carcinoma, surgery is mandatory. Other Symptoms
As with cholecystitis, many vague digestive disturbances described by "biliousness," "dyspepsia" and similar terms are not characteristie of cholelithiasis but are common in many disorders of the gastrointestinal tract. Hiatal hernia, epigastric hernia, duodenal ileus, paraduodenal fossa hernia, splenic flexure syndrome and spastic colitis produce a digestive system consciousness variously interpreted as "dyspepsia." In view of the over-all 10 per cent incidence of gallstones the occurrence of those symptoms may overlay and be present coincidentally without causal relationship. It is, therefore, extremely important to evaluate the correlation of these symptoms to the stones in formulation of a decision as to the type of therapy and the prognosis as to the anticipated relief following cholecystectomy if this is the selected treatment. Prophylactic Cholecystectomy
The question of quiescent gallstones is highly controversial, with sharp lines drawn pro and con. It is not too unusual to find the shadows of opaque stones on x-ray films taken to reveal unrelated pathology. Careful study may fail to reveal any symptoms referable to disturbance in the biliary tract. For the moment the stones are quiescent and how
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long this state of repose will continue is unpredictable. To forestall the perilous result of gallstones in motion prophylactic cholecystectomy has been advised. This recommendation to the patient must be adjudicated solely on an individual basis with due consideration for operative risk from all angles. Whether the presence of gallstones predisposes to carcinoma of the gallbladder (since calculi are found in more than 90 per cent of neoplastic disease of the organ) or whether the stones are formed as the result of a pre-existing malignancy is open to question. If the foreign bodies predispose to carcinoma then prophylactic cholecystectomy is imperative because at present the diagnosis is made only by direct inspection at operation and the five year survival rate is nil. REFERENCES 1. Saint, J. H.: Surg., Gynec. & Obst. 75: 323-332 (Sept.) 1942. 2. Lieber, M. M.: Ann. Surg. 135: 394 (March) 1952. 3. Harrison, T. R.: Principles of Internal Medicine. Philadelphia, Blakiston Co., 1950, p. 924.
THE gallbladder bears a striking resemblance to the trap under the kitchen sink, in that sludge from the (biliary) drainage system accumulates. For reasons as yet unknown concretions are formed in this material. The contents of the gallbladder, being external to the epithelial barrier, are outside of the body and, therefore, constitute a foreign substance. Any solids occurring in the bile are foreign bodies, and as such pose the usual hazards of foreign bodies, namely inflammation, ulceration, displacement or dysfunction. The presence of stones in the biliary tract is the focal point about which all disorders of the bile passages are constellated. It is clinically convenient to consider as cholecystitis those conditions in which inflammation or the results thereof dominates the picture even though displacement of stones may be present, and as cholelithiasis those situations where stones are roentgenologically demonstrated or where the effects of migration of the stones predominate, and as dysfunction, those gallbladder syndromes occurring in the absence of inflammation and/or stones. ACUTE CHOLECYSTITIS
Aeute cholecystitis-what is it? In retrospect the cases may be divided into two artificial groups, (1) a mild catarrhal form and (2) a severe suppurative phlegmonous or gangrenous type with empyema of the gallbladder. The chief difference is the point of interruption of the sequence of the pathologic events. Following the description of Saint,! in the production of acute cholecystitis the steps are as follows: (1) obstruction of the cystic duct due to a stone (92 per cent) or edema; (2) distention of the gallbladder and/or torsion leading to congestion and edema; (3) decreased blood supply; (4) ischemia of the wall; (5) further distention of the vesicle with establishment of a vicious circle. The question of the role of bacterial invasion or of chemical irritation has been the object of consideraple study. The consensus of opinion favors chemical irritation from the abnormal bile or regurgitated pancreatic juice as being the primary offender, with infection as a secondary event.
* Professor of Medicine, University of Illinois College of Medicine; Attending Physician, llesearch and Educational Hospitals, University of Illinois. 145
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Edmund F. Foley
Depending on the state of the gallbladder at the time of obstruction of the cystic duct, either hydrops or empyema develops. If the gallbladder is emptied at time of impaction then it becomes filled with the bile-free secretion from the mucosa of the wall of the gallbladder and forms a hydrops. As long as the obstruction is unrelieved this material continues to form and to distend the gallbladder even up to the size of a football. On the other hand, if the gallbladder is filled with altered or infected bile at the time of the corking of the outlet, toxic or infected contents are trapped and empyema results. Subsequently as the ischemia and edema of the gallbladder wall advances, hemorrhagic areas appear, with ulcers forming at the sites of pressure from stones. Rokitansky-Aschoff sinuses are papillary infoldings of the mucosa forming deep crypts which contain the purulent contents and by inclusion lead to the formation of intramural abscesses and phlegmon. Gangrenous spots may occur, usually at pressure points, or the entire organ may be infarcted. This is the "point of no return" and further progression is characterized by penetration of the gallbladder wall, usually by perforation. In the majority of cases the tempo of development has been so slow as to permit some walling off by the omentum or by loops of bowel, so that the perforation is either directly into the digestive tract producing a direct internal biliary fistula, or into a localized space, which subsequently ruptures into the hollow viscus producing an internal indirect biliary fistula. Spontaneous external biliary fistulas are pathologic curiosities. Occasionally, in fulminating cases, there is free perforation into the peritoneal cavity with an exceedingly noxious peritonitis. A few cases have been reported of penetration through an apparently intact wall and are spoken of as "filtrating cholecystitis." Not infrequently, instead of perforation through the gallbladder wall, extension may be along the biliary passage, particularly upward into the hepatic duct producing an ascending suppurative cholangitis with resulting multiple liver abscess. In other cases, burrowing may occur in a variety of directions leading to the formation of fantastic abscesses in unsuspected areas. The progression in the development of the complete picture may be interrupted at several levels. Cessation of the process at the stage of congestion (probably before bacterial invasion) constitutes the mild or catarrhal form. At the level of empyema with inclusion abscesses in the wall without gangrenous area resolution may occur and be followed by fibrosis or even calcification of the wall which OsIer spoke of as ossification of the gallbladder and more recently has been termed "porcelain gallbladder." Clinical Picture
Following a gluttonous or greasy meal the patient experiences upper abdominal pain, usually high in the epigastrium. This pain is usually
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sharp, relentless and severe. It may cause her to double up and writhe. There is an associated distress described as a ball-like fulness or "something stuck" in the epigastrium with salivation, air s\vallowing, and loud urgent belching. Nausea and vomiting may dominate the picture. The nausea is insistent and is usually so intense as to cause induced vomiting. The pain soon shifts to the right hypochondriac region and may be referred to the back or to the scapula and rarely may be colicky. If the patient is seen at this time (about six hours after onset) there is found marked muscle guarding in the upper abdomen with disproportionate tenderness in the right upper quadrant. The tentative diagnosis of biliary colic is made and an injection of morphine is given. The episode may terminate at this level. If it progresses the pain is present when the opiate wears off. Chilly sensations or actual chills may occur. The pain mounts to a peak and persists in the gallbladder area which now becomes sore and tender. The soreness is aggravated by motion, coughing or sneezing so that the patient holds her side in an attempt at mobilization. The belching has stopped, the nausea persists (unless the stone has reached the common duct when vomiting occurs without nausea) and the patient is unable to retain even water. At this level (thirty-six to forty-eight hours) examination reveals an apprehensive patient with an elevation of temperature to 100°F., evidences of dehydration on tongue and breath, rapid pulse, localized right upper quadrant tenderness with muscle guarding, involuntary rigidity and some local rebound tenderness. The gallbladder mayor may not be palpable depending on the degree of distention, amount of muscle spasm, and location. There may be a slight icterus and a leukocytosis of 10,000 to 20,000. A gallbladder that can be felt at this stage indicates a serious cystic duct obstruction, carrying the threat of perforation unless relieved. From here on the course becomes stormy and violent, probably coincidental with the bacterial invasion and tissue necrosis. All the symptoms and findings become exaggerated. The patient becomes "toxic," with rapid pulse and respirations, soft eyeballs, acetone odor to the breath, marked right upper quadrant tenderness and muscle guarding, and decreased urinary output. There may be a septic type of temperature, chills with sweating, increased leukocytosis, and urobilinoginuria. It should be emphasized, however, that in some patients, especially the elderly obese, these clinical criteria of a progressive toxic state may be mild or absent and hence deceptively distract the attention from the severity of the disease. Treatment
Acute cholecystitis-what to do? The definitive treatment is surgery. The variations in the stage of development of the pathologic lesion
Edmund F. Foley
148
existing at the time of the first examination coupled with the unpredictable future course pose hurdles in the standardization of treatment. Gallbladder disorder being particularly a disease of older age, the general condition of the patient frequently offers further hazard. If the patient is seen after the effects of the initial opiate or nitroglycerin has worn off (first twenty-four hours) and the symptoms are sufficiently prominent to permit a fairly definite diagnosis, it is safe to assume that the cystic duct is obstructed. Will it spontaneously be relieved or will it relentlessly progress? If the answer could be predicted the treatment could be standardized but because of the many possible variations it must be individualized. In order to obtain the answer the patient should be hospitalized and a record established to be used as a base to refer back to in evaluating future development. During this period of observation (twelve to twenty-four hours) the temperature and white blood count are useful for appraisal. Symptomatic treatment is instituted, consisting of penicillin and streptomycin, continuous duodenal suction, balanced intravenous fluids, nitroglycerin under the tongue and morphine or Demerol for severe pain, with a careful check on the fluid intake and output. If examination at the end of the twenty-four hour period indicates progression, operative intervention should be employed. Otherwise the patient progresses to the fourth day "critical period" which lasts until about the twelfth day unless perforation occurs. During the "critical period" if the decision is to "sit it out," meticulous attention must be given to maintenanee of hydration and electrolyte balanee. If during this period the gallbladder becomes palpable it is safe to assume that perforation will soon follow. "lTnless some overwhelming eontraindication to imperative surgery exists the waiting-out period is not justified. CHRONIC CHOLECYSTITIS
Under this term there is included a variety of gallbladder syndromes generally characterized by slow progression with acute exacerbations and remissions. It is acute cholecystitis set at a slower tempo, with the cystic duct still the vulnerable zone. When stones (which are suspected of being present in all cases) are known to be present, the term "calculous cholecystitis" is used for emphasis. The symptoms may be of recurrent attacks of acute cholecystitis, or of biliary colic, or of digestive disturbances of the "dyspeptic" type commonly identified with gallbladder dysfunction. In other less typical cases there may be obscure diagnostic enigmas masquerading as heart disease, Meniere's disease, pylorospasm, spastic colitis, and so on. Recurrent Acute Cholecystitis
That the gallbladder is a susceptible target under many circumstances is widely appreciated. Decreased gallbladder function occurs during
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the third trimester of pregnancy and acute attacks of cholecystitis tend to occur during this period. Every other diabetic female has gallstones. Following an acute attack of appendicitis, diverticulitis or renal colic a chronic gallbladder may be activated or a new disability may be initiated. These observations are cited to point up that the recurring acute episodes indicate an underlying chronic disorder. In this group of cases the predominating symptoms are not of biliary colic but rather of "indigestion" with "biliousness, belching and bloating" as the common complaint. There is a history of "selective food dyspepsia," an intolerance to greasy and highly seasoned food, with a self-imposed dietary restriction based on the patient's personal observation that certain foods disagree with her and "make gas." In severe cases the discomfort is brought on not by what she eats but rather that she eats. There is frequently a history of repeated attacks of vomiting with variable degrees of pain. The attack usually is precipitated by a violation of the diet, either qualitative or quantitative. The onset is that of an attack of acute cholecystitis but in a milder form. There is upper epigastric or right hypochondriac region pain with nausea and vomiting. The vomiting usually occurs several hours after the offending meal has been eaten and the emesis contains food remnants which should not have been in the stomach were it emptying in the normal time. The vomiting continues until the emesis contains "green gall" which usually indicates that the cystic duct obstruction or torsion has been relieved and that the attack is over. Biliary Colic
Biliary colie is due to futile attempts of gallstones to escape through the gallbladder. T'he pain results from distention of the cystic duct by the aggressor. As long as the foreign bodies remain quiescent in the insensitive fundus of the gallbladder, no pain occurs. It is postulated that as a result of a meal which vigorously stimulates gallbladder contractions small stones are forced into the cystic duct, producing the typical gallstone colic. The pain persists as long as the cystic duct is impacted, and ceases as soon as the stone drops back into the fundus or escapes into the common duct. If the stone remains in the cystic duct acute cholecystitis occurs with resulting empyema or hydrops. If it escapes into the common duct the picture of "common duct stone" follows. Atypical Types
There is a large group of cases in which the diseased gallbladder acts as a trigger mechanism to set off a chain of symptoms referable to other organs while the symptoms usually associated with gallbladder disease lurk in the background. 1"'his is especially true when the stomach is the
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participating organ and responds by hyperfunction. Hypersecretion, hypermotility and hyperacidity result in the familiar pjcture of "postprandial pyrosis," suggesting a peptic ulcer. The gallbladder is only incriminated when the roentgen study of the upper gastrointestinal tract accidentally reveals stones in the adjacent gallbladder or a "gallbladder sea," in the simultaneous barium study of the outflow tract flow of the stomach. Labyrinthine Type. Not infrequently the attack of cholecystitis displays itself by nausea, vomiting and vertigo of such severity as to literally throw the patient on the floor. The proof that these attacks are in reality due to the gallbladder rests in the demonstration of stones and the cessation of the attacks following surgical cure. Anginal Type. Arteriosclerosis, diabetes and gallbladder disease are notorious companions. There is a relationship between coronary sclerosis and gallbladder disease other than age group incidence. Gallbladder attacks initiate angina pectoris through vagal influences. 2 There is, however, another possible relationship. Angina pectoris results from transient myocardial ischemia due to a decreased blood supply to the heart muscle. The decreased supply is prooiea~~n the existence of narrowed sclerotic coronary arteries and an increased need for blood to the myocardium as the result of increased work. The work commonly results from such exertion as walking. It is likely that in acgallbladder attack there is also increased work due to physiologic exertion, such as hyperfunction, pylorospasm, vomiting, pain and apprehension. If this is so, then there is a real indication for serious consideration of the aggressive treatment of gallbladder disease in the presence of certain cases of angina pectoris. Diagnosis of Chronic Cholecystitis
In a discussion of the diagnosis of chronic cholecystitis it is necessary to establish a mutual agreement on what is included and excluded under this term. Included are those cases in which there are anatomical changes in the gallbladder and excluded are those rare cases of dysfunction or dyskinesia occurring in the absence of structural deformities. The pathological picture is determined by the presence or absence of stone~, the vigor of the reaction to previous injury or bacterial invasion, the status of the blood supply and the degree of cystic duct obstruction. The gallbladder may be small, thickened and fibrotic, thin and opaque, or distended by hydrops even to an enormous size. It may be "strawberry," calculous, porcelain, emphysematous or gaseous, and/or bound down by pericholecystic adhesions. The diagnosis is suggested or establish~d by the history of a previous event, such as biliary colic or acute cholecystitis, which could have led to one of the pathological pictures. Symptoms of "selective food dyspepsia," belching, flatulence and the like
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do not constitute sufficient evidence to warrant a diagnosis of cholecystitis in the absence of the definite tokens of gallbladder disease. Carefully controlled Graham-Cole tests which on repeating fail to show any visualization of the gallbladder or actually show the presence of calculi or of calcification constitute the best evidence of cholecystitis. Practically, a gallbladder that fails to visualize on two attempts with an adequate dosage of dye can be considered as a pathologic gallbladder. The hypermotile, hypertonic or hypotonic gallbladder as demonstrated by cholecystography does not necessarily represent cholecystitis. Needless to say, the diagnosis of cholecystitis should not be made on roentgen studies confined to cholecystography but should include a complete radiologic gastrointestinal examination. Treatment
With such an agreement on what is meant by cholecystitis the natural corollary is that such a gallbladder is actively or potentially symptomatic and hazardous, and that the ultimate and eventual treatment is radical eradication of an irreversible or progressive pathologic state. The time for the employment of surgery is determined by an evaluation of the local factors in the individual case, using the urgency of the symptoms and the radiologic evidence of deformity as the criteria. It is of utmost importance to relate the symptoms to the diseased organ. Cholecystectomy, if performed for the relief of "dyspeptic" symptoms (which usually are not caused by disorder of the gallbladder), will be followed by a return of those annoying complaints. During the period of waiting until the surgical indications are imperative the customary medical management is purely symptomatic. CHOLELITHIASIS
The separation of cholelithiasis as a clinical entity distinct from other forms of biliary tract disease is artificial. In any individual case the existence of stones cannot be denied by clinical means. The diagnosis of cholelithiasis is made when stones are demonstrated on roentgen study, is presumed when the symptoms are those of biliary colic, and is suspected in all cases of cholecystitis. The migration of all calculi usually precipitates an episode of acute cholecystitis or of common duct obstruction and frequently initiates the symptoms of chronic cholecystitis. Carcinoma of the gallbladder is revealed at the operating table by the surgeon performing an operation for gallstones. Incidence. Studies of autopsy material would indicate an incidence of gallstones of from 5 to 10 per cent, with a progressive increase by decades, reaching a peak between 50 to 60 years of age. The wider use of cholecystography and the increasing frequency of cholecystectomy for stones in the younger age groups would indicate a surprisingly high incidence in young women. The percentage is higher in females by a
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rate of 2 to 1 to 4 to 1, according to various authors. In the Negro male gallstones are very uncommon, the ratio between females and males being 7 to 1. In a study of 29,777 autopsies in patients over 20 years of age, Lieber 3 reported that gallstones were found in 11.6 per cent. In diabetics, his material showed gallstones in 30 per cent of all (over 20 years of age), in every other white female (diabetic), in every third Negro female, and every fifth male. In correlation with other diseases frequently suspected of having a high incidence of stones, namely peptic ulcer, pernicious anemia and portal cirrhosis, the frequency of occurrence paralleled the over-all general incidence of about 10 per cent. ~'-;ymptoms. 1'he only symptoms distinctively characteristic of gallstones are those resulting from the futile attempt of the calculi to escape from the site of manufacture, usually the gallbladder, occasionally the bile duct and rarely the liver. The stones in motion produce biliary colic, the futility results in signs or symptoms of obstruction (tenderness, jaundice or an enlarged gallbladder) when the flight is impeded in the natural channel, or in signs of erosion or perforation when the course or the flight is in an abnormally formed passageway. The sites of predilection for obstruction in the bile passages are the cystic duct, the ampulla of Vater and/or the ileocecal valve, leading respectively to acute cholecystitis, empyema or hydrops of the gallbladder, to choledocholithiasis, or to gallstone ileus, each with a distinctive clinical picture. Escape of the stones by penetration through the gallbladder wall leads to the formation of various types of fistulas, abscess or peritonitis. (}allstones impacted in the ileocecal valve are being recognized more and more frequently as a cause of mechanical obstruction of the bowel occurring especially in the aged. Since gallstones occur most commonly in the gallbladder, biliary colic most frequently results from migration of a stone into the cystic duet. 1-'his is the first step in the production of acute cholecystitis. If the advance of the stone is successfully repulsed the stone docilely falls back into the gallbladder to await a more propitious opportunity. Biliary colic is the only true identifying symptom of gallstones. The pain is located in the epigastrium or right upper quadrant, is knifelike in character, constant and crescendo, radiates through to the back or to the scapula and is aggravated by respiration. This pattern fingerprints the condition. There may be many variations from this stigmatizing demonstration, e.g. the pain may be dull, it may be in the left abdomen, it may be colicky, it may radiate to the precordium or down the left arm. This distorted pain complex is correlated to biliary colic by inference and established as sueh in retrospect. 'l'he patient is given nitroglycerin with the hopeful expectancy that the stone will "pass"~ meaning that it either retreats into a state of quiescence or advances into the common duct.
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Common Duct Stone
The classical symptoms of stone in the common duct result from various grades of obstruction, ranging from minimal to complete and from intermittent to constant. The colorful symptom of jaundice parallels the degree of closure of the common duct. It may be slow or rapid in onset, mild or intense, complete or incomplete, constant or intermittent. These vagaries are clinically important in helping to establish that the jaundice is due to extrahepatic obstruction (surgical jaundice) rather than intrahepatic destruction with or without block (medical jaundice). In extrahepatic obstruction the important positive clues are a history of preceding attacks of biliary colic or of acute cholecystitis, a stormy onset, right upper quadrant tenderness, choluria with urobilinuria varying directly with the degree of obstruction, relatively unaffected metabolic liver functions as reflected in unaltered serum proteins either quantitative or qualitative (negative flocculation and turbidity tests), and a high alkaline phosphatase. Unrelieved calculous extrahepatic obstruction has a ruthlessly destructive effect on the liver, determined by the degree, duration and associated infection, and can be as malignant as the obstruction due to neoplastic disease. Complete extrahepatic obstruction in 9 cases out of 10 is due to carcinoma. Hence because of the malignant conduct (literal sense) and for the sake of the 1 out of 10 who does not have carcinoma, surgery is mandatory. Other Symptoms
As with cholecystitis, many vague digestive disturbances described by "biliousness," "dyspepsia" and similar terms are not characteristie of cholelithiasis but are common in many disorders of the gastrointestinal tract. Hiatal hernia, epigastric hernia, duodenal ileus, paraduodenal fossa hernia, splenic flexure syndrome and spastic colitis produce a digestive system consciousness variously interpreted as "dyspepsia." In view of the over-all 10 per cent incidence of gallstones the occurrence of those symptoms may overlay and be present coincidentally without causal relationship. It is, therefore, extremely important to evaluate the correlation of these symptoms to the stones in formulation of a decision as to the type of therapy and the prognosis as to the anticipated relief following cholecystectomy if this is the selected treatment. Prophylactic Cholecystectomy
The question of quiescent gallstones is highly controversial, with sharp lines drawn pro and con. It is not too unusual to find the shadows of opaque stones on x-ray films taken to reveal unrelated pathology. Careful study may fail to reveal any symptoms referable to disturbance in the biliary tract. For the moment the stones are quiescent and how
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long this state of repose will continue is unpredictable. To forestall the perilous result of gallstones in motion prophylactic cholecystectomy has been advised. This recommendation to the patient must be adjudicated solely on an individual basis with due consideration for operative risk from all angles. Whether the presence of gallstones predisposes to carcinoma of the gallbladder (since calculi are found in more than 90 per cent of neoplastic disease of the organ) or whether the stones are formed as the result of a pre-existing malignancy is open to question. If the foreign bodies predispose to carcinoma then prophylactic cholecystectomy is imperative because at present the diagnosis is made only by direct inspection at operation and the five year survival rate is nil. REFERENCES 1. Saint, J. H.: Surg., Gynec. & Obst. 75: 323-332 (Sept.) 1942. 2. Lieber, M. M.: Ann. Surg. 135: 394 (March) 1952. 3. Harrison, T. R.: Principles of Internal Medicine. Philadelphia, Blakiston Co., 1950, p. 924.