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Acute acalculous cholecystitis
Acute Acalculous Cholecystitis
Richard J. Howard, MD, PhD, FACS, Gainesville, Florida
Acute cholecystitis is accompanied by cholelithiasis in 85 to 95 percent of cases, and gallbladder stones are believed to play a major role in the etiology of cholecystitis [l-4]. Although acalculous gallbladders are found infrequently among all patients with acute cholecystitis, they occur in a high percentage of patients with acute cholecystitis occurring after operation [.!I-81 and after trauma [9-B] and in children [13,141. In these instances the incidence of acalculous gallbladders is 50 to 100 percent [5-241. Acute cholecystitis without stones runs a more fulminant course than when stones are present, and the likelihood of gangrene and perforation are very high [IO]. In order to better delineate the clinical setting in which acute acalculous cholecystitis can occur, all cases of acute cholecystitis occurring at the University of Minnesota Health Sciences Center and affiliated hospitals during the 25 year period 1954 through 1978 were reviewed. Sixty-three patients had acute cholecystitis without gallbladder stones and are the subject of this article. Patient Population
the onset of cholecystitis. Seven other patients had previous trauma from automobile accidents, falls or burns. Three of these seven patients had operations in connection with the trauma such aa internal fixation of fractures, tracheostomy and laparotomy for intraabdominal bleeding. Nine other patients were alcoholic, and acute acalculous cholecystitis developed in one man while he was being treated for bleeding esophageal varices. Fourteen patients had previously been treated for cancer including cancer of the lung, stomach, prostrate, thyroid, breast, cervix, testes, colon and melanoma. Several patients had associated medical problems such as arteriosclerotic peripheral vascular disease, peptic ulcer disease, ulcerative colitis and congestive heart failure. Results
Signs and symptoms: The signs and symptoms of acute acalculous cholecystitis did not differ from those of acute cholecystitis with stones. Pain in the right upper abdominal quadrant was the most common symptom and occurred in 44 (70 percent) of the 63 patients. Five patients had diffuse abdominal pain, and in three the pain was limited to the epigastrium and periumbilical region. Eight patients had no pain associated with acute cholecystitis and three were comatose and could not be evaluated. The latter 11 patients generally were operated upon because of suspected intraabdominal disease. Clinical findings included abdominal distention, unexplained fever, positive peritoneal lavage, loss of bowel sounds, abdominal rigidity and tenderness, and sudden deterioration of the overall clinical condition. Right upper quadrant tenderness was the most common abdominal finding and was detected in 46
In the 25 year period January 1,1954 through December 31, 1978, 1,045 patients underwent cholecystectomy for acute cholecystitis at the University of Minnesota Health Sciences Center and affiliated teaching hospitals. The diagnosis was confirmed by pathologic examination in all instances. No calculi were found in 63 specimens (5.9 percent). There were 49 men and 14 women. The male predominance reflects in part the fact that one of the affiliated teaching hospitals is the Minneapolis Veterans Administration Hospital; 18 male patients were from this hospital. The patients ranged in age from 18 to 87 years (average 58.1). Only 8 of the 63 patients had previous symptoms suggestive of gallbladder disease such as fatty food intolerance and pain in the right upper quadrant of the abdomen after meals. Acute cholecystitis occurred in 17 patients while they were recovering from operative procedures (Table I). Only 8 of these 17 patients had intraabdominal operations before
patients (73 percent). Seven patients had diffuse abdominal tenderness, and tenderness was absent in 10. Other findings were vomiting in 22 patients, distention in 13, decreased bowel sounds in 16, jaundice in 8, and a right upper quadrant mass in 10. Forty-six patients had fever.
From the Department of Surgery, University of Minnesota Health Sciences Center. Minneaoolis. Minnesota. Req;ests for-repkts should be addressed to Richard J. Howard, MO, University of Florida, College of Medicine, Department of Surgery, Gainesville, Florida 32610.
Laboratory and roentgenographic studies: The white blood cell count ranged from 4,700 to 44,200 cells/mm3 and was above 10,000 cells/mm3 in 45 patients. Glutamic oxalacetic transaminase was increased in 18 of 33 patients, and alkaline phosphatase
194
The American Journal of Surgery
Acute Acalculous
was increased in 24 of 42 patients. Roentgenographic studies of the biliary tract were obtained in 20 patients. The gallbladder did not visualize in any study. Air was seen in the gallbladder lumen in one patient. Postoperative course in patients with postoperative cholecystitis: Over half of the patients who
developed acute acalculous cholecystitis while recovering from other operative procedures had prolonged complicated courses, and only 6 of the 17 patients were “doing well” at the time cholecystitis developed. Nine patients had infections at the time they developed cholecystitis including pneumonia, wound infection, bacteremia and intraabdominal abscess. Renal failure occurred in four patients. Other significant problems before the development of acute cholecystitis were prolonged postoperative jaundice, fever not attributable to a specific cause, respiratory arrest and cardiac arrest. Operation performed: Acute cholecystitis was not suspected preoperatively in 17 (27 percent) of the
TABLE I
63 patients. Incorrect diagnoses included subhepatic abscess, hepatic abscess, acute appendicitis, mesenteric vein thrombosis, small intestinal obstruction, perforated duodenal ulcer and pancreatitis. A ruptured spleen was diagnosed preoperatively in one comatose patient transferred from another hospital 8 days after sustaining trauma in an automobile accident. He was operated on because blood was found on peritoneal lavage. Acute cholecystitis was an unsuspected finding. Operation was performed in 60 patients within 48 hours of the onset of signs and symptoms. Thus incorrect preoperative diagnoses, or the occasional confusing clinical picture when cholecystitis developed after operation or trauma, did not delay operative intervention. In two patients operation was performed within 5 days. One patient was initially treated medically and elective cholecystectomy was performed 67 days later. Cholecystectomy was performed in all 63 patients. However, cholecystostomy was performed initially
Operations in Patients Who Developed Postoperative Acalculous Cholecystitis Interval (days) Symptoms to Operation
Patient
Age (yr) & Sex
1’
74M
Tracheostomy (rib fracture)
Fever, renal failure
4
2’
69M 47M
4
46M
2
5
58M
Gastroenterostomy and colon resection for carcinoma of hepatic flexure Vagotomy and pyloroplasty
Renal failure, respiratory arrest, tracheostomy, pneumonia Fecal fistula, jejunal perforation, fever, renal failure Bacteremia
1
3
Excision, scapula, proximal humerus, distal clavicle Resection sigmoid carcinoma
Doing well at onset of cholecystitis
2
6’
61M
Tracheostomy (multiple fractures)
Respiratory arrest
2
7
57M
Doing well at onset of cholecystitis
4
8
63M
Abdominoperineal resection for rectal carcinoma Aortic valve prosthesis
1
9
61M
2
10
18M
Adrenalectomy, retroperitoneal node dissection Spinal fusion T4 to L2
Respiratory failure, confusion, cardiac arrest Wound infection, septicemia Doing well at onset of cholecystitis
1
11
60M
Resection necrotic jejunum
Doing well at onset of cholecystitis
2
12
41F
Bilateral hip arthroplasty
Woundabscess
1
13
89F
Urethral dilatation
Lower lobe pneumonia
1
14
56M
Right upper lobectomy
Doing well at onset of cholecystitis
1
15
42M
50 percent gastrectomy
Prolonged jaundice
1
16
70M
Left hemicolectomy
Oliguria, electrolyte imbalance
2
17
87F
Austin-Moore hip prosthesis
Doing well at onset of cholecystitis
2
l
Cholecystitis
Operation
Postoperative Course
2
Findinos Gangrenous cholecystitis Gangrenous cholecystitis Acute cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Acute cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Acute cholecystitis Acute cholecystitis Acute cholecystitis Acute cholecystitis
These patients also had extensive trauma.
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in three instances because inflammation obscured the anatomy. Elective cholecystectomy was performed 1 to 2 months later. Common bile duct exploration was carried out in eight patients. Six of the eight patients had common duct exploration because of an elevated bilirubin level. The two other ducts were explored because no stones were found in the gallbladder. In seven other jaundiced patients the common duct was not explored. Four of these seven patients had a normal operative cholangiogram. Pathologic and microbiologic findings: Acute cholecystitis was confirmed by histologic examination in all cases. Thirty (47.6 percent) of the 63 gallbladders had areas of gangrene; perforation occurred in five instances, and empyema of the gallbladder was noted in four patients. Bile was cultured from 43 patients. In 15 instances it was sterile. Escherichia coli was the most common organism, cultured 17 times. Other organisms cultured were alpha hemolysin, Streptococcus, Staphylococcus, Klebsiella, Clostridium perfringens, enterococcus, Serratia marcescens, Citrobacter, Proteus, Enterobacter and Aspergillus fumigatus. The same organism found in the bile had previously been cultured from the blood in five instances. The failure to find significant anaerobes and so many sterile cultures probably reflects in part inappropriate anaerobic techniques. Many of these cultures were obtained before many surgeons realized the importance of anaerobic techniques. Using suitable anaerobic techniques, England and Rosenblatt [15] showed that 41 percent of bile cultures contained anaerobes. Mortality: Fifty-two patients recovered and were discharged from the hospital. There were 11 deaths. Four deaths occurred in patients with extensive trauma. Two additional deaths occurred in patients recovering from other operative procedures. Two patients died from cardiac arrest and one from congestive heart failure. One patient with alcoholic cirrhosis died from bleeding esophageal varices and hepatic coma. One patient was unresponsive before cholecystectomy and remained so afterwards. She died when support was stopped. Comments The clinical and laboratory manifestations of acute cholecystitis are similar whether gallbladder calculi are present or not. However, it appears that the incidence of advanced disease is greater when acute cholecystitis is not associated with stones, especially when cholecystitis follows unrelated operation or trauma: The incidence of gangrene is 52.2 percent in collected series and the incidence of perforation is 11.1 percent [IO]. The mortality rate is higher when acute cholecystitis after unrelated operation or trauma occurs in the abscence of stones (35.1 percent) than when they are present (14.3 percent). Furthermore, in the collected series of DuPriest et
196
al [IO], acute cholecystitis after trauma had a mortality rate of 16.1 percent when cholecystectomy was performed. However, the rate was 46.2 percent if cholecystostomy was done and 86.7 percent if there was no operation. No doubt some patients were not operated on because they were “too sick.” However, a more appropriate view is that these patients are too sick not to undergo operation. Because of the high incidence of gangrene and perforation, therefore, every effort should be made to perform cholecystectomy for cholecystitis occurring after trauma or operation. Gangrene and perforation cannot be distinguished clinically from simple acute cholecystitis. Acute cholecystitis is easily recognized in most patients. However, when it occurs after trauma or operation the typical signs and symptoms may be atypical or misinterpreted, or they may not occur at all. Lack of clinical and laboratory specificity may contribute to delay in diagnosis and treatment [7101. In this series acute cholecystitis was not suspected in 17 of the 63 cases, but even the incorrect diagnosis did not excessively delay operation in most cases. It is important to recognize that the patient has an acute abdominal disorder. As noted by Glenn and McSherry [16], “the penalty for misdiagnosis for a patient subjected to operation who proves not to have cholecystitis is much less than the penalty for failure to recognize an acutely inflamed and infected gallbladder that later perforates.” Therefore, early operation should be carried out in a patient developing abdominal signs or symptoms after trauma or another operation. Although acute acalculous cholecystitis occurs in approximately 5 to 15 percent of all cases of acute cholecystitis, the incidence is much higher when cholecystitis occurs after operation or trauma in children. DuPriest et al [JO] reviewed acute cholecystitis occurring after trauma, and in data collected from 20 reports they found an 86.7 percent incidence of acalculous gallbladders. Acute cholecystitis can occur after injury even when there has been no abdominal trauma and when the patient has not been operated on because of the trauma. The incidence of acalculous cholecystitis is also high when acute cholecystitis occurs after an operative procedure. The incidence of acalculous cholecystitis ranges from 0 to 100 percent with an average of 40 percent [7]. Acute cholecystitis in the postoperative period can occur even if the abdominal cavity has not been entered, thus eliminating operative injury to the gallbladder as a cause. When acute acalculous cholecystitis occurs after trauma or operation or even in the absence of these predisposing causes, the proportion of male patients (85 percent) is higher than when cholecystitis is associated with stones. This male predominance no doubt reflects the fact that some of the series were obtained from military hospitals [9,11]. However, in this series even
The American Journal
of Surgery
Acute Acalculous Cholecystitis
when the male patients from the Veterans Administration Hospital are excluded the male to female ratio is still 2 to 1, compared with a ratio of 1 to 2 for acute acalculous cholecystitis. Acute acalculous cholecystitis occurs in children in approximately 50 percent of cases [13]. Pathogenesis of acute acalculous cholecystitis: Studies in dogs by Thomas and Womack [17] and Womack and Bricker [18] indicate that obstruction of the cystic duct, concentrated bile and impairment of the blood supply are important in the pathogenesis of acute cholecystitis. They showed that two of these three insults were necessary before acute cholecystitis occurred. They believed that infection occurred secondarily and was not of primary importance in the etiology of acute cholecystitis. Clinically cystic duct obstruction in the absence of cholelithiasis has been attributed to a kinked duct, periductal adhesions, an enlarged lymph node adjacent to the cystic duct, a neoplasm in the region of the cystic duct, a tortuous cystic artery compressing the duct, and malformation of the cystic duct [19-221. Functional obstruction has been attributed to increased tone of the sphincter of Oddi caused by narcotic analgesics and starvation [23,24]. Decreased blood flow through the cystic artery can occur in shock and other low flow states, congestive heart failure and atherosclerotic disease involving the cystic artery [22,25,26]. Golden et al [27] demonstrated that hypotension and shock can cause focal areas of necrosis in the gallbladder wall of experimental animals. Sympathetic discharge during shock may constrict the cystic artery, and Howard et al [ZS] showed sympathectomy to be protective in canine acute cholecystitis. Vasoactive drugs such as epinephrine, levarterenol and dopamine may also decrease blood flow to the gallbladder. Bile stasis is an important factor in experimental cholecystitis [I 7,181. Concentrated bile may act as a chemical irritant. Blood in the gallbladder as a result of trauma may also cause chemical irritation. Pancreatic enzymes can be found in gallbladder bile [29] and may also produce chemical irritation leading to cholecystitis. Wolfer [30] produced cholecystitis by injecting pancreatic juice into the gallbladders of dogs. Systemic diseases such as diabetes mellitus, systemic lupus erythematosis, pernicious anemia and collagen vascular diseases have also been thought to contribute to development of acute cholecystitis [23]. Infection has been proposed as a cause of cholecystitis [23,31], but others believe that infection is secondary, occurring after the onset of cholecystitis: A lower incidence of positive bile and gallbladder cultures is found if the specimen is taken early rather than late in the course of acute cholecystitis. However, in the series of Lindberg et al [9], six of nine patients who had bacteria cultured from the bile had previous wound infections with the same organism,
Volume 141, February 1981
suggesting that infection may also have a role in the etiology of acute cholecystitis. Acute acalculous cholecystitis has also been ascribed to other causes such as altered gallbladder motility caused by bed rest, fasting, increased intraabdominal pressure and narcotics [5,6]. Glenn and McSherry [16], who first described postoperative cholecystitis, observed that cholecystitis usually occurred within 48 hours of resuming oral intake in the postoperative period. They believed that cholecystitis was due to the gallbladder attempting to contract against the concentrated, viscid bile [5,6]. The resistance to gallbladder contraction was further increased by increased tone of the sphincter of Oddi caused by morphine or other analgesics. Others, however, have observed no relation between refeeding and the onset of cholecystitis. Many reports emphasize the absence of direct injury to the gallbladder or abdomen in patients with acute cholecystitis complicating trauma [10,26,27]. None of our previously reported patients had abdominal trauma [26], and only two of the seven patients reported here had trauma to the abdomen. However, DuPriest et al [IO] reported that 10 of 12 patients who developed acute cholecystitis after trauma had injury to the abdomen, and 6 had liver lacerations. Clearly, no single explanation can account for all cases of acute acalculous cholecystitis.
Summary Sixty-three patients, 49 men and 14 women, developed acute cholecystitis without gallbladder stones. Only eight patients had a history suggestive of gallbladder disease. In 17 patients cholecystitis developed in the postoperative period, and cholecystitis occurred in 7 patients who had extensive trauma. The signs and symptoms did not differ markedly from those found when acute cholecystitis is associated with cholelithiasis. Pain and tenderness in the right upper abdominal quadrant, vomiting, abdominal distention, decreased bowel sounds, jaundice and fever were common. Thirty (47.6 percent) gallbladder specimens had gangrene, and perforation occurred in five instances. Bacteria were cultured from 28 of 43 bile specimens. E. coli was the most common organism. A high incidence of acalculous gallbladders is found when acute cholecystitis occurs in the postoperative period or after trauma and in children. Decreased blood flow to the gallbladder, cystic duct obstruction and concentrated bile are necessary to produce experimental cholecystitis. These factors are probably necessary in humans also. Decreased gallbladder perfusion caused by shock, congestive heart failure and arteriosclerosis probably contributed to the development of acute acalculous cholecystitis in these patients.
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Howard
References 1. Berk JE. Management of acute cholecystitis. Am J Dig Dis 1940;7:325-32. 2. DeCamp PT, Ochsner A. Baffes TG, Bancroft H, Bendei W. Timing in the surgical treatment of acute cholecystitis. Ann Surg 1952;135:734-50. 3. Glenn F. A 26 year experience in the surgical treatment of 5,037 patients with nonmalignant biliary tract disease. Surg Gynecoi Obstet 1959; 10959 l-606. 4. Judd ES, Phillips JR. Acute cholecystic disease. Ann Surg 1933;98:771-9. 5. Glenn F, Wantz GE. Acute cholecystitis following the surgical treatment of unrelated disease. Surg Gynecol Obstet 1956;102:145-53. 6. Glenn F. Acute cholecystitis following the surgical treatment of unrelated disease. Ann Surg 1947;126:41 l-20. 7. Jlinsson PE, Anderson A. Postoperative acute acalculous cholecystitis. Arch Surg 1976:lil: 1097-101. 6. Howard RJ, Delaney JP. Postoperative choiecystitis. Am J Dig Dis 1972;17:213-16. 9. Lindberg EF, Grinnan GLB. Smith L. Acalculous choiecystitis invietnam casualties. Ann Surg 1970;171:152-7. 10. DuPriest RW Jr, Khaneja SC, Cowley RA. Acute cholecystitis complicating trauma. Ann Surg 1979;189:84-9. 11. Munster AM. Goodwin MN, Pruitt BA Jr. Acalculous cholecystitis in burned patients. Am J Surg 1971:122:591-3. 12. Winegarner FC, Jackson GF. Post-traumatic acalculous cholecystitis: a highly lethal complication. J Trauma 1971;11:567-9. 13. Brenner RW, Stewart CF. Cholecystitis in children. Rev Surg 1964;21:327-35. 14. Ulin AW, Nosal JL. Martin L. Cholecystitis in childhood associated obstructive jaundice. Surgery 1952;31:312-26. 15. England DM, Rosenbiatt JE. Anaerobes in human biliary tracts. J Clin Microbial 1977;6:494-8.
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16. Glenn F, McSherry CK. Caiculous biliary tract disease. Curr Probl Surg June 1975;1-38. 17. Thomas CG Jr, Womack NA. Acute cholecystitis. its pathogenesis and repair. Arch Surg 1952:64:590-600. 18. Womack NA, Bricker EM. Pathogenesis of choiecystitis. Arch Surg 1942;44:658-76. 19. Gibbons TB, Baker JW. Acute stoneless cholecystitis. Arch Surg 1958;72:773-9. 20. Munster AM. Brown JR. Acalculous cholecystitis. Am J Surg 1967;113:730-4. 21. Forshall I, Rickham PP. Choiecystitis and cholelithiasis in childhood. Br J Surg 1954;42:161-4. 22. Hoerr SO, Hazard JB. Acute cholecystitis without gallbladder stones. Am J Surg 1966;111:47-55. 23. Walters W, McGowan JM. Butsch WL, Knepper PA. Pathological physiology of common bile duct: its relation to biliary colic. JAMA 1937;109:1591-7. 24. Elman R, M&laster PD. Physiologic variations in resistance to bile flow to intestine. J Exp Med 1926;44:151-71. 25. Thompson JW ill, Ferris DO, Baggenstoss AH. Acute cholecystitis complicating operation for other diseases. Ann Surg 1962;155:489-94. 26. Howard RJ. Delaney JP. Post-traumatic cholecystitis. JAMA 1971;218:1006-7. 27. Golden GT, Sears HF II, Wangensteen SL. Post-traumatic cholecystitis. Am Surg 1973;39:275-8. 28. Howard JM, Milford MT, DeBakey ME. The significance of the sympathetic nervous system in acute choiecystitis. Surgery 1952;32:251-8. 29. Colp R, Gerber IE, Doubilet H. Acute cholecystitis associated with pancreatic refiux. Ann Surg 1936;103:67-76. 30. Wolfer JA. The role of pancreatic juice in the production of gallbladder disease. Surg Gynecol Obstet 1931;53:43347. 31. Lucas CE, Walt AJ. Acute gangrenous acalculous cholecystitis in infancy: report of a case. Surgery 1968;64:847-9.
The American Journal of Surgery
Richard J. Howard, MD, PhD, FACS, Gainesville, Florida
Acute cholecystitis is accompanied by cholelithiasis in 85 to 95 percent of cases, and gallbladder stones are believed to play a major role in the etiology of cholecystitis [l-4]. Although acalculous gallbladders are found infrequently among all patients with acute cholecystitis, they occur in a high percentage of patients with acute cholecystitis occurring after operation [.!I-81 and after trauma [9-B] and in children [13,141. In these instances the incidence of acalculous gallbladders is 50 to 100 percent [5-241. Acute cholecystitis without stones runs a more fulminant course than when stones are present, and the likelihood of gangrene and perforation are very high [IO]. In order to better delineate the clinical setting in which acute acalculous cholecystitis can occur, all cases of acute cholecystitis occurring at the University of Minnesota Health Sciences Center and affiliated hospitals during the 25 year period 1954 through 1978 were reviewed. Sixty-three patients had acute cholecystitis without gallbladder stones and are the subject of this article. Patient Population
the onset of cholecystitis. Seven other patients had previous trauma from automobile accidents, falls or burns. Three of these seven patients had operations in connection with the trauma such aa internal fixation of fractures, tracheostomy and laparotomy for intraabdominal bleeding. Nine other patients were alcoholic, and acute acalculous cholecystitis developed in one man while he was being treated for bleeding esophageal varices. Fourteen patients had previously been treated for cancer including cancer of the lung, stomach, prostrate, thyroid, breast, cervix, testes, colon and melanoma. Several patients had associated medical problems such as arteriosclerotic peripheral vascular disease, peptic ulcer disease, ulcerative colitis and congestive heart failure. Results
Signs and symptoms: The signs and symptoms of acute acalculous cholecystitis did not differ from those of acute cholecystitis with stones. Pain in the right upper abdominal quadrant was the most common symptom and occurred in 44 (70 percent) of the 63 patients. Five patients had diffuse abdominal pain, and in three the pain was limited to the epigastrium and periumbilical region. Eight patients had no pain associated with acute cholecystitis and three were comatose and could not be evaluated. The latter 11 patients generally were operated upon because of suspected intraabdominal disease. Clinical findings included abdominal distention, unexplained fever, positive peritoneal lavage, loss of bowel sounds, abdominal rigidity and tenderness, and sudden deterioration of the overall clinical condition. Right upper quadrant tenderness was the most common abdominal finding and was detected in 46
In the 25 year period January 1,1954 through December 31, 1978, 1,045 patients underwent cholecystectomy for acute cholecystitis at the University of Minnesota Health Sciences Center and affiliated teaching hospitals. The diagnosis was confirmed by pathologic examination in all instances. No calculi were found in 63 specimens (5.9 percent). There were 49 men and 14 women. The male predominance reflects in part the fact that one of the affiliated teaching hospitals is the Minneapolis Veterans Administration Hospital; 18 male patients were from this hospital. The patients ranged in age from 18 to 87 years (average 58.1). Only 8 of the 63 patients had previous symptoms suggestive of gallbladder disease such as fatty food intolerance and pain in the right upper quadrant of the abdomen after meals. Acute cholecystitis occurred in 17 patients while they were recovering from operative procedures (Table I). Only 8 of these 17 patients had intraabdominal operations before
patients (73 percent). Seven patients had diffuse abdominal tenderness, and tenderness was absent in 10. Other findings were vomiting in 22 patients, distention in 13, decreased bowel sounds in 16, jaundice in 8, and a right upper quadrant mass in 10. Forty-six patients had fever.
From the Department of Surgery, University of Minnesota Health Sciences Center. Minneaoolis. Minnesota. Req;ests for-repkts should be addressed to Richard J. Howard, MO, University of Florida, College of Medicine, Department of Surgery, Gainesville, Florida 32610.
Laboratory and roentgenographic studies: The white blood cell count ranged from 4,700 to 44,200 cells/mm3 and was above 10,000 cells/mm3 in 45 patients. Glutamic oxalacetic transaminase was increased in 18 of 33 patients, and alkaline phosphatase
194
The American Journal of Surgery
Acute Acalculous
was increased in 24 of 42 patients. Roentgenographic studies of the biliary tract were obtained in 20 patients. The gallbladder did not visualize in any study. Air was seen in the gallbladder lumen in one patient. Postoperative course in patients with postoperative cholecystitis: Over half of the patients who
developed acute acalculous cholecystitis while recovering from other operative procedures had prolonged complicated courses, and only 6 of the 17 patients were “doing well” at the time cholecystitis developed. Nine patients had infections at the time they developed cholecystitis including pneumonia, wound infection, bacteremia and intraabdominal abscess. Renal failure occurred in four patients. Other significant problems before the development of acute cholecystitis were prolonged postoperative jaundice, fever not attributable to a specific cause, respiratory arrest and cardiac arrest. Operation performed: Acute cholecystitis was not suspected preoperatively in 17 (27 percent) of the
TABLE I
63 patients. Incorrect diagnoses included subhepatic abscess, hepatic abscess, acute appendicitis, mesenteric vein thrombosis, small intestinal obstruction, perforated duodenal ulcer and pancreatitis. A ruptured spleen was diagnosed preoperatively in one comatose patient transferred from another hospital 8 days after sustaining trauma in an automobile accident. He was operated on because blood was found on peritoneal lavage. Acute cholecystitis was an unsuspected finding. Operation was performed in 60 patients within 48 hours of the onset of signs and symptoms. Thus incorrect preoperative diagnoses, or the occasional confusing clinical picture when cholecystitis developed after operation or trauma, did not delay operative intervention. In two patients operation was performed within 5 days. One patient was initially treated medically and elective cholecystectomy was performed 67 days later. Cholecystectomy was performed in all 63 patients. However, cholecystostomy was performed initially
Operations in Patients Who Developed Postoperative Acalculous Cholecystitis Interval (days) Symptoms to Operation
Patient
Age (yr) & Sex
1’
74M
Tracheostomy (rib fracture)
Fever, renal failure
4
2’
69M 47M
4
46M
2
5
58M
Gastroenterostomy and colon resection for carcinoma of hepatic flexure Vagotomy and pyloroplasty
Renal failure, respiratory arrest, tracheostomy, pneumonia Fecal fistula, jejunal perforation, fever, renal failure Bacteremia
1
3
Excision, scapula, proximal humerus, distal clavicle Resection sigmoid carcinoma
Doing well at onset of cholecystitis
2
6’
61M
Tracheostomy (multiple fractures)
Respiratory arrest
2
7
57M
Doing well at onset of cholecystitis
4
8
63M
Abdominoperineal resection for rectal carcinoma Aortic valve prosthesis
1
9
61M
2
10
18M
Adrenalectomy, retroperitoneal node dissection Spinal fusion T4 to L2
Respiratory failure, confusion, cardiac arrest Wound infection, septicemia Doing well at onset of cholecystitis
1
11
60M
Resection necrotic jejunum
Doing well at onset of cholecystitis
2
12
41F
Bilateral hip arthroplasty
Woundabscess
1
13
89F
Urethral dilatation
Lower lobe pneumonia
1
14
56M
Right upper lobectomy
Doing well at onset of cholecystitis
1
15
42M
50 percent gastrectomy
Prolonged jaundice
1
16
70M
Left hemicolectomy
Oliguria, electrolyte imbalance
2
17
87F
Austin-Moore hip prosthesis
Doing well at onset of cholecystitis
2
l
Cholecystitis
Operation
Postoperative Course
2
Findinos Gangrenous cholecystitis Gangrenous cholecystitis Acute cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Acute cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Gangrenous cholecystitis Acute cholecystitis Acute cholecystitis Acute cholecystitis Acute cholecystitis
These patients also had extensive trauma.
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in three instances because inflammation obscured the anatomy. Elective cholecystectomy was performed 1 to 2 months later. Common bile duct exploration was carried out in eight patients. Six of the eight patients had common duct exploration because of an elevated bilirubin level. The two other ducts were explored because no stones were found in the gallbladder. In seven other jaundiced patients the common duct was not explored. Four of these seven patients had a normal operative cholangiogram. Pathologic and microbiologic findings: Acute cholecystitis was confirmed by histologic examination in all cases. Thirty (47.6 percent) of the 63 gallbladders had areas of gangrene; perforation occurred in five instances, and empyema of the gallbladder was noted in four patients. Bile was cultured from 43 patients. In 15 instances it was sterile. Escherichia coli was the most common organism, cultured 17 times. Other organisms cultured were alpha hemolysin, Streptococcus, Staphylococcus, Klebsiella, Clostridium perfringens, enterococcus, Serratia marcescens, Citrobacter, Proteus, Enterobacter and Aspergillus fumigatus. The same organism found in the bile had previously been cultured from the blood in five instances. The failure to find significant anaerobes and so many sterile cultures probably reflects in part inappropriate anaerobic techniques. Many of these cultures were obtained before many surgeons realized the importance of anaerobic techniques. Using suitable anaerobic techniques, England and Rosenblatt [15] showed that 41 percent of bile cultures contained anaerobes. Mortality: Fifty-two patients recovered and were discharged from the hospital. There were 11 deaths. Four deaths occurred in patients with extensive trauma. Two additional deaths occurred in patients recovering from other operative procedures. Two patients died from cardiac arrest and one from congestive heart failure. One patient with alcoholic cirrhosis died from bleeding esophageal varices and hepatic coma. One patient was unresponsive before cholecystectomy and remained so afterwards. She died when support was stopped. Comments The clinical and laboratory manifestations of acute cholecystitis are similar whether gallbladder calculi are present or not. However, it appears that the incidence of advanced disease is greater when acute cholecystitis is not associated with stones, especially when cholecystitis follows unrelated operation or trauma: The incidence of gangrene is 52.2 percent in collected series and the incidence of perforation is 11.1 percent [IO]. The mortality rate is higher when acute cholecystitis after unrelated operation or trauma occurs in the abscence of stones (35.1 percent) than when they are present (14.3 percent). Furthermore, in the collected series of DuPriest et
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al [IO], acute cholecystitis after trauma had a mortality rate of 16.1 percent when cholecystectomy was performed. However, the rate was 46.2 percent if cholecystostomy was done and 86.7 percent if there was no operation. No doubt some patients were not operated on because they were “too sick.” However, a more appropriate view is that these patients are too sick not to undergo operation. Because of the high incidence of gangrene and perforation, therefore, every effort should be made to perform cholecystectomy for cholecystitis occurring after trauma or operation. Gangrene and perforation cannot be distinguished clinically from simple acute cholecystitis. Acute cholecystitis is easily recognized in most patients. However, when it occurs after trauma or operation the typical signs and symptoms may be atypical or misinterpreted, or they may not occur at all. Lack of clinical and laboratory specificity may contribute to delay in diagnosis and treatment [7101. In this series acute cholecystitis was not suspected in 17 of the 63 cases, but even the incorrect diagnosis did not excessively delay operation in most cases. It is important to recognize that the patient has an acute abdominal disorder. As noted by Glenn and McSherry [16], “the penalty for misdiagnosis for a patient subjected to operation who proves not to have cholecystitis is much less than the penalty for failure to recognize an acutely inflamed and infected gallbladder that later perforates.” Therefore, early operation should be carried out in a patient developing abdominal signs or symptoms after trauma or another operation. Although acute acalculous cholecystitis occurs in approximately 5 to 15 percent of all cases of acute cholecystitis, the incidence is much higher when cholecystitis occurs after operation or trauma in children. DuPriest et al [JO] reviewed acute cholecystitis occurring after trauma, and in data collected from 20 reports they found an 86.7 percent incidence of acalculous gallbladders. Acute cholecystitis can occur after injury even when there has been no abdominal trauma and when the patient has not been operated on because of the trauma. The incidence of acalculous cholecystitis is also high when acute cholecystitis occurs after an operative procedure. The incidence of acalculous cholecystitis ranges from 0 to 100 percent with an average of 40 percent [7]. Acute cholecystitis in the postoperative period can occur even if the abdominal cavity has not been entered, thus eliminating operative injury to the gallbladder as a cause. When acute acalculous cholecystitis occurs after trauma or operation or even in the absence of these predisposing causes, the proportion of male patients (85 percent) is higher than when cholecystitis is associated with stones. This male predominance no doubt reflects the fact that some of the series were obtained from military hospitals [9,11]. However, in this series even
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of Surgery
Acute Acalculous Cholecystitis
when the male patients from the Veterans Administration Hospital are excluded the male to female ratio is still 2 to 1, compared with a ratio of 1 to 2 for acute acalculous cholecystitis. Acute acalculous cholecystitis occurs in children in approximately 50 percent of cases [13]. Pathogenesis of acute acalculous cholecystitis: Studies in dogs by Thomas and Womack [17] and Womack and Bricker [18] indicate that obstruction of the cystic duct, concentrated bile and impairment of the blood supply are important in the pathogenesis of acute cholecystitis. They showed that two of these three insults were necessary before acute cholecystitis occurred. They believed that infection occurred secondarily and was not of primary importance in the etiology of acute cholecystitis. Clinically cystic duct obstruction in the absence of cholelithiasis has been attributed to a kinked duct, periductal adhesions, an enlarged lymph node adjacent to the cystic duct, a neoplasm in the region of the cystic duct, a tortuous cystic artery compressing the duct, and malformation of the cystic duct [19-221. Functional obstruction has been attributed to increased tone of the sphincter of Oddi caused by narcotic analgesics and starvation [23,24]. Decreased blood flow through the cystic artery can occur in shock and other low flow states, congestive heart failure and atherosclerotic disease involving the cystic artery [22,25,26]. Golden et al [27] demonstrated that hypotension and shock can cause focal areas of necrosis in the gallbladder wall of experimental animals. Sympathetic discharge during shock may constrict the cystic artery, and Howard et al [ZS] showed sympathectomy to be protective in canine acute cholecystitis. Vasoactive drugs such as epinephrine, levarterenol and dopamine may also decrease blood flow to the gallbladder. Bile stasis is an important factor in experimental cholecystitis [I 7,181. Concentrated bile may act as a chemical irritant. Blood in the gallbladder as a result of trauma may also cause chemical irritation. Pancreatic enzymes can be found in gallbladder bile [29] and may also produce chemical irritation leading to cholecystitis. Wolfer [30] produced cholecystitis by injecting pancreatic juice into the gallbladders of dogs. Systemic diseases such as diabetes mellitus, systemic lupus erythematosis, pernicious anemia and collagen vascular diseases have also been thought to contribute to development of acute cholecystitis [23]. Infection has been proposed as a cause of cholecystitis [23,31], but others believe that infection is secondary, occurring after the onset of cholecystitis: A lower incidence of positive bile and gallbladder cultures is found if the specimen is taken early rather than late in the course of acute cholecystitis. However, in the series of Lindberg et al [9], six of nine patients who had bacteria cultured from the bile had previous wound infections with the same organism,
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suggesting that infection may also have a role in the etiology of acute cholecystitis. Acute acalculous cholecystitis has also been ascribed to other causes such as altered gallbladder motility caused by bed rest, fasting, increased intraabdominal pressure and narcotics [5,6]. Glenn and McSherry [16], who first described postoperative cholecystitis, observed that cholecystitis usually occurred within 48 hours of resuming oral intake in the postoperative period. They believed that cholecystitis was due to the gallbladder attempting to contract against the concentrated, viscid bile [5,6]. The resistance to gallbladder contraction was further increased by increased tone of the sphincter of Oddi caused by morphine or other analgesics. Others, however, have observed no relation between refeeding and the onset of cholecystitis. Many reports emphasize the absence of direct injury to the gallbladder or abdomen in patients with acute cholecystitis complicating trauma [10,26,27]. None of our previously reported patients had abdominal trauma [26], and only two of the seven patients reported here had trauma to the abdomen. However, DuPriest et al [IO] reported that 10 of 12 patients who developed acute cholecystitis after trauma had injury to the abdomen, and 6 had liver lacerations. Clearly, no single explanation can account for all cases of acute acalculous cholecystitis.
Summary Sixty-three patients, 49 men and 14 women, developed acute cholecystitis without gallbladder stones. Only eight patients had a history suggestive of gallbladder disease. In 17 patients cholecystitis developed in the postoperative period, and cholecystitis occurred in 7 patients who had extensive trauma. The signs and symptoms did not differ markedly from those found when acute cholecystitis is associated with cholelithiasis. Pain and tenderness in the right upper abdominal quadrant, vomiting, abdominal distention, decreased bowel sounds, jaundice and fever were common. Thirty (47.6 percent) gallbladder specimens had gangrene, and perforation occurred in five instances. Bacteria were cultured from 28 of 43 bile specimens. E. coli was the most common organism. A high incidence of acalculous gallbladders is found when acute cholecystitis occurs in the postoperative period or after trauma and in children. Decreased blood flow to the gallbladder, cystic duct obstruction and concentrated bile are necessary to produce experimental cholecystitis. These factors are probably necessary in humans also. Decreased gallbladder perfusion caused by shock, congestive heart failure and arteriosclerosis probably contributed to the development of acute acalculous cholecystitis in these patients.
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