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Acalculous cholecystitis in children
Acalculous Cholecystitis By Dimitris
E. Tsakayannis,
in Children
Harry P.W. Kozakewich, Boston, Massachusetts
l Acalculous cholecystitis (AC) is a rare disease in children, and its spectrum has not been well established. Twenty-five children with AC were identified (treated between 1970 and 1994) by retrospective clinical and pathological review. The authors recognized two distinct forms of this disease: acute (duration of symptoms 3 months). Thirteen children had acute AC. Seventy-five percent were males; the age range was from 2 months to 20 years. Of these cases, six occurred in the immediate postoperative period, five were in association with a systemic medical illness, and two had an infectious cause (Sabnonella). The mean time of onset of symptoms ranged from 4 to 30 days after surgery or hospitalization (mean, 16 days). All children presented with fever, right-upper-quadrant pain, and vomiting. Other manifestations included jaundice (38%) and right-upper-quadrant mass (23%). Most had leukocytosis (76%) and abnormal liver function test results (62%). Ultrasonography was the most commonly used radiological test, and all 10 cases tested met the ultrasonographic criteria for acute AC. Cholecystectomy was performed in nine children, and pathological examination confirmed cholecystitis. No postoperative complications occurred. The other four children were managed nonoperatively with intravenous antibiotics. One died, but the other three recovered fully. Twelve children had chronic AC. Sixty-seven percent were females; the age range was 7 to 18 years. All presented with chronic symptoms of right-upper-quadrant pain and nausea or vomiting. The leukocyte count and results of liver function tests were normal. Seventy-five percent had evidence of abnormal gallbladder function (noted by a radionuclide hepatobiliary scan or cholecystography). All children in this group underwent cholecystectomy, with pathological confirmation of chronic inflammation. No complications occurred, and all patients had complete resolution of symptoms. The authors conclude that AC in children occurs in two distinct patterns. The acute and chronic forms differ in their clinical setting and presentation. Cholecystectomy is effective treatment of AC, although there may be a role for nonoperative management in selected cases. Copyright Q 1996 by WA Saunders Company
and Craig W. Lillehei
and clinical spectrum of this disease in childhood have not been we11 established. To define the etiology, clinical presentation, and management, we retrospectively reviewed the records of all children with AC treated at our institution. MATERIALS
AND
METHODS
Twenty-five children with AC were treated at Children’s Hospital, Boston, over a 24-year period (1970 to 1994). There were 14 boys and I1 girls (male:female ratio, 1.3:l.O). The age range was 2 months to 20 years (median, 14 years). The clinical presentation, presence of other associated conditions, laboratory findings, diagnostic radiological tests, and associated risk factors were recorded. Treatment, presence of complications, and outcome also were documented. All surgical specimens were reviewed by a pediatric pathologist (H.P.W.K.). RESULTS
ALLBLADDER DISEASE is rare in the pediG atric age group. For every 1,000 adult cases, there are 1.3 pediatric cases1 Acalculous cholecystitis
Thirteen children were classified as having acute AC (symptoms present for < 1 month), and 12 had chronic AC (symptoms present for >3 months). Seventy-five percent of those with acute AC were males; the age range was 2 months to 20 years. Among those with chronic AC, 67% were females; their age range was 7 to 18 years. The clinical conditions of those with acute AC are shown in Table 1. The time of onset of symptoms ranged from 4 to 30 days after hospitalization or surgery (mean, 16 days). No preexistent clinical conditions were identified in patients with chronic AC. The clinical and laboratory findings also differed. All children with acute AC presented with fever, right-upper-quadrant pain, and vomiting. Other manifestations included jaundice (38%) and right-upperquadrant mass (23%). Most had leukocytosis (76%) and abnormal liver function with elevated bilirubin (62%). All children with chronic AC presented with chronic symptoms of right-upper-quadrant pain and nausea or vomiting. Their leukocyte count and results of liver function tests were normal.
(AC) occurs in 2% to 17% of adult cases of cholecystitis2; 30% to 50% of the pediatric cases of cholecystitis are acalculous.3 Most cases of AC in children reported in the literature are associated with a systemic infection4-8 such as typhoid fever, scarlet fever, measles, or AIDS. However, this condition has also been associated with disorders such as Kawasaki’s disease and periarteritis nodosa.9J0 In light of the sporadic presentation of AC, the etiologic pattern
From* the Departments of Surgery and Pathology, Children’s Hospital and Harvard Medical School, Boston, MA. Presented at the 26th Annual Meeting of the American Pediatn’c Surgical Association, Boca Raton, Florida, May 20-23, 1995. Address reprint requests to Craig K Lillehei, MD, Children’s Hospital, 300 Longwood Ave, Boston, MA 021 I5 Copyright D 1996 by WI. Saunders Company 0022.3468/9613101-0024$03.00/0
INDEX
WORDS:
JournalofPediatric
Cholecystitis,
Surgery,
acalculous.
Vol31,
No 1 (January),
1996: pp 127-131
127
TSAKAYANNIS.
128
Table
1. Clinical
Condition
of Children Cholecystitis
Clinical Condition
Infectious
Orthopedic surgery Cardiac surgery
Acalculous
2
(.Salmonella)
uremic
Acute
No. of Patients
Systemic medical illness Cystic fibrosis End-stage liver disease Hemolytic Leukemia Postoperative
With
1 I* I* 2
syndrome
(spinal
fusion)
2
Repair of aortic stenosis Repair of ventral septal defect
I* 1*
Tetralogy of Fallot, cardiac catheter Repair of double-origin right ventricle
1
*Nonoperative
treatment
(four
1
cases).
The radiological tests used for the diagnosis of AC included ultrasonography (19), radionuclide hepatobiliary scan (ll), computed tomography (3), endoscopic retrograde cholangiopancreatography (4), oral cholecystogram (6), intravenous cholangiogram (6), and transhepatic cholangiogram (1). Ultrasonographic criteria for acute AC consisted of gallbladderwall thickness of greater than 3.5 mm, hydrops, sludge, and pericholqystic fluid collection. All 10 children with acute AC who had ultrasonography had all the above criteria (Fig 1). Ultrasonographically, the gallbladder was normal in all children with
KOZAKEWICH,
LILLEHEI
chronic AC. Nine children with chronic AC (75%) had abnormal function and delayed emptying of the gallbladder, noted by HIDA scan or cholecystography (oral cholecystogram, intravenous cholangiogram). Possible risk factors such as prolonged fasting, sepsis, shock, use of total parental nutrition, intravenous narcotics, and multiple transfusions were identified in children with acute AC (Table 2), but not in those with chronic AC. Open cholecystectomy was performed in nine children who had acute AC; there were no significant complications. Four other patients were treated nonsurgically, with intravenous antibiotics. Three of them recovered fully, but one (who had previous repair of a congenital cardiac anomaly) died of cardiac failure and fungal sepsis. All children with chronic AC underwent cholecystectomy (10 open, 2 laparoscopic) that resulted in complete resolution of symptoms. No significant perioperative complications occurred in any of the children with AC. In the clinically acute group (nine specimens), the gallbladder usually was described as edematous, purple, or focally hemorrhagic upon gross inspection. Acute inflammation was present in five cases and characterized by polymorphonuclear infiltration, fibrinous exudate, edema, and focal hemorrhage (Fig 2). Within these five specimens, there were gangrenous changes in two, vascular thromboemboli in three, and eosinophilic infiltration in one. The remainwas ing four specimens, two from which Salmonella isolated, showed inflammation with a polymorphonuclear infiltrate predominantly within the mucosa. The child with cystic fibrosis had a very small gallbiadder, with mural fibrosis, mild mucosal inflammation, and arterial intimal sclerosis. A child with neqtropenit leukemia had a slight increase in mucosal lymphocytes as well as rare eosinophils. In the chronic AC group (12 specimens), six appeared unremarkable upon gross examination; the others had an edematous walI and/or mucosal reddening. Microscopic examination showed transmural chronic inflammation consisting of lymphocytes, occasional plasma cells, and eosinophils. Rokitansky-Aschoff sinuses were present Table
2. Possible
Risk Factors for Children Cholecystitis
Factor
Prolonged
With
Multiple Sepsis NOTE. There
Acute
Acalculous
No. of Patients (%)
fasting
10 (77) IO (77)
Total parenteral nutrition Shock, inotropic support Intravenous narcotics Fig 1. Ultrasonographic image of the gallbladder in child with acute AC. Note the distension of the gallbladder, thickening of the wall (straight arrow), pericholecystic fluid collection (curved arrow), and sludge.
AND
4 (31) 8 (fm 10 (77)
transfusions
6 (46) were
13 patients
with acute
acalculous
cholecystitis.
ACALCULOUS
CHOLECYSTITIS
Fig 2. Acute cholecystitis with transmural polymorphonuclear infiltration and mucosal fibrinous exudate (H&E, original magnification x 100).
in four specimens, and cholesterolosis was noted in one. DISCUSSION
In the present series, AC presented in two distinct patterns: acute ( < 1 month) and chronic (> 3 months). These groups differed in their clinical setting and presentation. Most adult cases of acute AC are encountered after trauma, abdominal surgery,3 burns,” or other illnesses.12 Ternberg and KeatingO analyzed 74 cases of acute AC in children, 60% of which developed in association with a systemic infection. The acute AC in our series was more commonly associated with a systemic medical illness or occurred after surgery. Although the incidence of AC after open heart surgery in adults is very low ( <0.5%r3), four children in our series had a previous cardiac procedure. The pathogenesis of acute AC has been debated extensively. The exact cause remains uncertain, but multiple risk factors have been identified and probably play an interrelated role.i4 Shock, sepsis, total
129
parenteral nutrition, prolonged fasting, intravenous narcotics, and multiple transfusions have been implicated in gallbladder ischemia and biliary stasis, two probable pathogenic mechanisms for acute AC.15-17 The majority of our patients with acute AC had at least four of the above risk factors. The condition of acalculous biliary colic is well recognized in adults, separable from the gallstonerelated disease.18 The pathophysiology remains unclear, but a functional abnormality that leads to either contraction of the gallbladder or increased wall tension (with an inability to expel its contents) has been postulated. W” Some investigators have advocated a provocative test-the infusion of cholecystokinin to select cases that will respond well to cholecystectomy.2fl The clinical signs and symptoms were different for the two types of AC. All children with chronic AC otherwise were healthy, without associated conditions. They presented with chronic symptomatology of right-upper-quadrant pain and nausea or vomiting. All children with acute AC had fever, vomiting, and right-upper-quadrant pain. More than 60% had abnormal liver function and white blood cell counts, similar to adult cases.?l Ultrasonography and computed tomography are the diagnostic imaging procedures of choice for patients with acute AC. 22,23 Ultrasonography has several advantages. It is portable, noninvasive, and relatively inexpensive. In our experience, it accurately diagnosed acute AC. In contrast, the results of ultrasonography of the gallbladder were normal for children with chronic AC. Biliary scintigraphy was the most useful diagnostic test in these cases. Therapeutic management strategies for acute AC range from nonoperative treatment to cholecystostomy or cholecystectomy. Some investigators believe that tube cholecystostomy is adequate treatment9 and should be considered if a patient is too ill to survive cholecystectomy.24 However, in adults, the presence of gangrene of the gallbladder in acute AC reportedly has been as high as 50%, in which circumstance tube cholecystostomy is associated with mortality rates of 16% to 66%. Most investigators consider cholecystectomy the procedure of choice.25 Others have advocated a strategy of serial ultrasonographic examinations to select individual patients for cholecystectomy, only if specific ultrasonographic criteria develop.23 In cases of AC that are secondary to infection (such as typhoid cholecystitis), management with appropriate intravenous antibiotics has been shown to be adequate.6 In our series, all children with chronic AC underwent cholecystectomy, with complete resolu-
TSAKAYANNIS,
130
tion of symptoms. For acute AC, cholecystectomy also was the procedure of choice, but it was deferred in four children who were critically ill when the diagnosis of AC was made. Treatment with intrave-
KOZAKEWICH,
AND
LILLEHEI
nous antibiotics led to uneventful recovery in three of them. Nonoperative management of acute AC may be appropriate for selected critically ill children who have an underlying disorder.
REFERENCES 1. Hawkins PE, Graham FB, Holliday P, et al: Gallbladder disease in children. Am J Surg 111:741-744,1966 2. Silvert M, Vakil NE: Emergence of biliary tract. Gastroenterol Clin North Am 17:245-247,1988 3. Glenn F: Acute acalculous cholecystitis. Ann Surg 189:458465,1979 4. Winkler AP, Gleich S: Acute acalculous cholecystitis caused by Salmonella typhi in an 11 year old. Pediatr Infect Dis J 7:125-128, 1988 5. Rota M, Sellier N, Mensire A, et al: Acute acalculous cholecystitis in salmonella infection. Pediatr Radio1 18:421-423, 1988 6. Subba Rao SD, Lewin S, Shetty B, et al: Acute acalculous cholecystitis in typhoid fever. Indian Pediatr 29:1431-1435,1992 7. Horii Y, Sugimoto T, Sakamoto I, et al: Acute acalculous cholecystitis complicating Mycoplusma pneumonia infection. Clin Pediatr 31:376-378, 1992 8. Yulevich A, Cohen Z, Maor E, et al: Acute acalculous cholecystitis caused by salmonella typhi in a B-year-old child. Eur J Pediatr Surg 2:301-301,1992 9. Ternberg JL, Keating JP: Acute acalculous cholecystitis, complication of other illnesses in childhood. Arch Surg 110:543547,1975 10. Richard B, Nadal D, Meuli M, et al: Acute acalculous cholecystitis in infective endocarditis. J Pediatr Gastroenterol Nutr 17:215-216,1993 11. Munster AM, Goodwin MN, Pruit BA: Acalculous cholecystitis in burn patients. Am J Surg 122:591-594,197l 12. Robertson RD: Noncalculous acute cholecystitis following surgery, trauma and illness. Am Surg 36:610-614,197O
13. Sessions SC, Scoma RS, Sheikh FA, et al: Acute acalculous cholecystitis following open heart surgery. Am Surg 59:74-77, 1993 14. Glenn F, Becker C: Acute acalculous cholecystitis. Ann Surg 195:131-136,1982 15. Sessions SC, Scoma RS, Sheikh FA, et al: Acute acalculous cholecystitis following open heart surgery. Am Surg 59:74-77, 1993 16. Orlando R, Gleason E, Drezner A: Acute acalculous cholecystitis in the critically ill patient. Am J Surg 145:472-476, 1983 17. Lin KY: Acute acalculous cholecystitis: a limited review of the literature. Mt Sinai J Med 53:305-309,1986 18. Munster AM, Brown JR: Acalculous cholecystitis. Am J Surg 113:730-734,1967 19. Griffen WO, Bivins BA, Rogers EL, et al: Cholecystokinin cholecystography in the diagnosis of gallbladder disease. Br J Surg 191:636-639,198O 20. Lennard TW, Farndon JR, Taylor RM: Acalculous biliary pain: Diagnosis and selection for cholecystectomy using the cholecystokinin test for pain reproduction. Br J Surg 71:368-370,1984 21. Fabian TC, Hickerson WL, Mangiante EC: Posttraumatic and postoperative acute cholecystitis. Am Surg 52:188-192, 1986 22. Mirvis SE, Vainright JR, Nelson AW: The diagnosis of acute acalculous cholecystitis: A comparison of sonography, scintigraphy and CT. AJR 147:1171-1175,1986 23. Imhof M, Raunest J, Ohmann C, et al: Acute acalculous cholecystitis complicating trauma: A prospective sonographic study. World J Surg 16:1160-1166,1992 24. Skillings JC, Kumai C, Hinshaw JR: Cholecystostomy: A place in modern biliary surgery? Am J Surg 139:865-869,198O 25. Krasna MJ, Flancbaum L, Trooskin SZ, et al: Gastrointestinal complications after cardiac surgery. Surgery 104:773-780, 1988
Discussion T.R. Weber (St Louis, MO): Could you tell us more about the ultrasound findings? Some would argue that sludge ‘in the gallbladder is more related to calculous disease than it is to acalculous disease. Did all of the acute patients have sludge and a distended gallbladder? D.E. Tsakayannis (response): Most of the acute patients had sludge. Of the 13 patients, nine patients were treated operatively, and upon examination of the pathology specimens there was no presence of gallstones. Of the 10 patients who had chronic acalculous cholecystitis, six had the presence of sludge by ultrasound. M. Hadad {Dharhan, Saudi Arabia): There are two questions I would like to ask you. Did you do any bacteriological studies on the gallbladders that were removed? And was there any difference between the
acute and chronic cholecystitis? I wonder if the chronic stage is actually a continuation of the acute stage, and whether the presence of sludge actually causes an obstructive lesion causing the cholecystitis, in which case you can’t call it acalculous cholecystitis. D.E. Tsakayannis (response): Two children had E coli as the pathogenic organism from the gallbladder. We did see a significant difference in both the chronic and the acute state. All children with acute acalculous cholecystitis were severely ill. The subgroup with chronic acalculous cholecystitis was a totally different group of children. They were what we call the “walking patients” with chronic symptomatology. Many of the children actually had a lot of radiographic tests, searching for the origin of symptoms. Seventy-five percent of them with scintigraphy did show abnormal function of the gallbladder.
ACALCULOUS
CHOLECYSTITIS
Surgery was diagnostic and brought complete resolution of symptoms in all of this group, so we do think it is a distinct population. C. Goodwin (Dayton, OH): We too have been seeing a fair number of kids with chronic cholecystitis with similar findings. Based on Pima Indians, one factor is about Native American background. We are finding a very high correlation with a Cherokee background. I wondered if we just had an inordinate number of people with Cherokee Indian background; so we looked at 50 consecutive hernia patients, and our hernia patients didn’t seem to correlate with that background. Have you questioned Native American background in your patients?
131
D.E. Tsakayannis (response): No, we didn’t find any correlation with any ethnic group. R. T. &huller, Jr (Seattle, WA): In the acute form of the disease, did you consider percutaneous ultrasoundguided drainage of the gallbladder under local anesthesia while you’re treating the underlying disease? We’ve had some success with that approach. D.E. Tsakayannis (response): No, this was not considered. This was a retrospective study. From the adult literature, in acute acalculous cholecystitis, over 50 percent of cases were gangrenous. Thus, many feel that percutaneous or tube cholecystostomy might not be the treatment of choice.
E. Tsakayannis,
in Children
Harry P.W. Kozakewich, Boston, Massachusetts
l Acalculous cholecystitis (AC) is a rare disease in children, and its spectrum has not been well established. Twenty-five children with AC were identified (treated between 1970 and 1994) by retrospective clinical and pathological review. The authors recognized two distinct forms of this disease: acute (duration of symptoms 3 months). Thirteen children had acute AC. Seventy-five percent were males; the age range was from 2 months to 20 years. Of these cases, six occurred in the immediate postoperative period, five were in association with a systemic medical illness, and two had an infectious cause (Sabnonella). The mean time of onset of symptoms ranged from 4 to 30 days after surgery or hospitalization (mean, 16 days). All children presented with fever, right-upper-quadrant pain, and vomiting. Other manifestations included jaundice (38%) and right-upper-quadrant mass (23%). Most had leukocytosis (76%) and abnormal liver function test results (62%). Ultrasonography was the most commonly used radiological test, and all 10 cases tested met the ultrasonographic criteria for acute AC. Cholecystectomy was performed in nine children, and pathological examination confirmed cholecystitis. No postoperative complications occurred. The other four children were managed nonoperatively with intravenous antibiotics. One died, but the other three recovered fully. Twelve children had chronic AC. Sixty-seven percent were females; the age range was 7 to 18 years. All presented with chronic symptoms of right-upper-quadrant pain and nausea or vomiting. The leukocyte count and results of liver function tests were normal. Seventy-five percent had evidence of abnormal gallbladder function (noted by a radionuclide hepatobiliary scan or cholecystography). All children in this group underwent cholecystectomy, with pathological confirmation of chronic inflammation. No complications occurred, and all patients had complete resolution of symptoms. The authors conclude that AC in children occurs in two distinct patterns. The acute and chronic forms differ in their clinical setting and presentation. Cholecystectomy is effective treatment of AC, although there may be a role for nonoperative management in selected cases. Copyright Q 1996 by WA Saunders Company
and Craig W. Lillehei
and clinical spectrum of this disease in childhood have not been we11 established. To define the etiology, clinical presentation, and management, we retrospectively reviewed the records of all children with AC treated at our institution. MATERIALS
AND
METHODS
Twenty-five children with AC were treated at Children’s Hospital, Boston, over a 24-year period (1970 to 1994). There were 14 boys and I1 girls (male:female ratio, 1.3:l.O). The age range was 2 months to 20 years (median, 14 years). The clinical presentation, presence of other associated conditions, laboratory findings, diagnostic radiological tests, and associated risk factors were recorded. Treatment, presence of complications, and outcome also were documented. All surgical specimens were reviewed by a pediatric pathologist (H.P.W.K.). RESULTS
ALLBLADDER DISEASE is rare in the pediG atric age group. For every 1,000 adult cases, there are 1.3 pediatric cases1 Acalculous cholecystitis
Thirteen children were classified as having acute AC (symptoms present for < 1 month), and 12 had chronic AC (symptoms present for >3 months). Seventy-five percent of those with acute AC were males; the age range was 2 months to 20 years. Among those with chronic AC, 67% were females; their age range was 7 to 18 years. The clinical conditions of those with acute AC are shown in Table 1. The time of onset of symptoms ranged from 4 to 30 days after hospitalization or surgery (mean, 16 days). No preexistent clinical conditions were identified in patients with chronic AC. The clinical and laboratory findings also differed. All children with acute AC presented with fever, right-upper-quadrant pain, and vomiting. Other manifestations included jaundice (38%) and right-upperquadrant mass (23%). Most had leukocytosis (76%) and abnormal liver function with elevated bilirubin (62%). All children with chronic AC presented with chronic symptoms of right-upper-quadrant pain and nausea or vomiting. Their leukocyte count and results of liver function tests were normal.
(AC) occurs in 2% to 17% of adult cases of cholecystitis2; 30% to 50% of the pediatric cases of cholecystitis are acalculous.3 Most cases of AC in children reported in the literature are associated with a systemic infection4-8 such as typhoid fever, scarlet fever, measles, or AIDS. However, this condition has also been associated with disorders such as Kawasaki’s disease and periarteritis nodosa.9J0 In light of the sporadic presentation of AC, the etiologic pattern
From* the Departments of Surgery and Pathology, Children’s Hospital and Harvard Medical School, Boston, MA. Presented at the 26th Annual Meeting of the American Pediatn’c Surgical Association, Boca Raton, Florida, May 20-23, 1995. Address reprint requests to Craig K Lillehei, MD, Children’s Hospital, 300 Longwood Ave, Boston, MA 021 I5 Copyright D 1996 by WI. Saunders Company 0022.3468/9613101-0024$03.00/0
INDEX
WORDS:
JournalofPediatric
Cholecystitis,
Surgery,
acalculous.
Vol31,
No 1 (January),
1996: pp 127-131
127
TSAKAYANNIS.
128
Table
1. Clinical
Condition
of Children Cholecystitis
Clinical Condition
Infectious
Orthopedic surgery Cardiac surgery
Acalculous
2
(.Salmonella)
uremic
Acute
No. of Patients
Systemic medical illness Cystic fibrosis End-stage liver disease Hemolytic Leukemia Postoperative
With
1 I* I* 2
syndrome
(spinal
fusion)
2
Repair of aortic stenosis Repair of ventral septal defect
I* 1*
Tetralogy of Fallot, cardiac catheter Repair of double-origin right ventricle
1
*Nonoperative
treatment
(four
1
cases).
The radiological tests used for the diagnosis of AC included ultrasonography (19), radionuclide hepatobiliary scan (ll), computed tomography (3), endoscopic retrograde cholangiopancreatography (4), oral cholecystogram (6), intravenous cholangiogram (6), and transhepatic cholangiogram (1). Ultrasonographic criteria for acute AC consisted of gallbladderwall thickness of greater than 3.5 mm, hydrops, sludge, and pericholqystic fluid collection. All 10 children with acute AC who had ultrasonography had all the above criteria (Fig 1). Ultrasonographically, the gallbladder was normal in all children with
KOZAKEWICH,
LILLEHEI
chronic AC. Nine children with chronic AC (75%) had abnormal function and delayed emptying of the gallbladder, noted by HIDA scan or cholecystography (oral cholecystogram, intravenous cholangiogram). Possible risk factors such as prolonged fasting, sepsis, shock, use of total parental nutrition, intravenous narcotics, and multiple transfusions were identified in children with acute AC (Table 2), but not in those with chronic AC. Open cholecystectomy was performed in nine children who had acute AC; there were no significant complications. Four other patients were treated nonsurgically, with intravenous antibiotics. Three of them recovered fully, but one (who had previous repair of a congenital cardiac anomaly) died of cardiac failure and fungal sepsis. All children with chronic AC underwent cholecystectomy (10 open, 2 laparoscopic) that resulted in complete resolution of symptoms. No significant perioperative complications occurred in any of the children with AC. In the clinically acute group (nine specimens), the gallbladder usually was described as edematous, purple, or focally hemorrhagic upon gross inspection. Acute inflammation was present in five cases and characterized by polymorphonuclear infiltration, fibrinous exudate, edema, and focal hemorrhage (Fig 2). Within these five specimens, there were gangrenous changes in two, vascular thromboemboli in three, and eosinophilic infiltration in one. The remainwas ing four specimens, two from which Salmonella isolated, showed inflammation with a polymorphonuclear infiltrate predominantly within the mucosa. The child with cystic fibrosis had a very small gallbiadder, with mural fibrosis, mild mucosal inflammation, and arterial intimal sclerosis. A child with neqtropenit leukemia had a slight increase in mucosal lymphocytes as well as rare eosinophils. In the chronic AC group (12 specimens), six appeared unremarkable upon gross examination; the others had an edematous walI and/or mucosal reddening. Microscopic examination showed transmural chronic inflammation consisting of lymphocytes, occasional plasma cells, and eosinophils. Rokitansky-Aschoff sinuses were present Table
2. Possible
Risk Factors for Children Cholecystitis
Factor
Prolonged
With
Multiple Sepsis NOTE. There
Acute
Acalculous
No. of Patients (%)
fasting
10 (77) IO (77)
Total parenteral nutrition Shock, inotropic support Intravenous narcotics Fig 1. Ultrasonographic image of the gallbladder in child with acute AC. Note the distension of the gallbladder, thickening of the wall (straight arrow), pericholecystic fluid collection (curved arrow), and sludge.
AND
4 (31) 8 (fm 10 (77)
transfusions
6 (46) were
13 patients
with acute
acalculous
cholecystitis.
ACALCULOUS
CHOLECYSTITIS
Fig 2. Acute cholecystitis with transmural polymorphonuclear infiltration and mucosal fibrinous exudate (H&E, original magnification x 100).
in four specimens, and cholesterolosis was noted in one. DISCUSSION
In the present series, AC presented in two distinct patterns: acute ( < 1 month) and chronic (> 3 months). These groups differed in their clinical setting and presentation. Most adult cases of acute AC are encountered after trauma, abdominal surgery,3 burns,” or other illnesses.12 Ternberg and KeatingO analyzed 74 cases of acute AC in children, 60% of which developed in association with a systemic infection. The acute AC in our series was more commonly associated with a systemic medical illness or occurred after surgery. Although the incidence of AC after open heart surgery in adults is very low ( <0.5%r3), four children in our series had a previous cardiac procedure. The pathogenesis of acute AC has been debated extensively. The exact cause remains uncertain, but multiple risk factors have been identified and probably play an interrelated role.i4 Shock, sepsis, total
129
parenteral nutrition, prolonged fasting, intravenous narcotics, and multiple transfusions have been implicated in gallbladder ischemia and biliary stasis, two probable pathogenic mechanisms for acute AC.15-17 The majority of our patients with acute AC had at least four of the above risk factors. The condition of acalculous biliary colic is well recognized in adults, separable from the gallstonerelated disease.18 The pathophysiology remains unclear, but a functional abnormality that leads to either contraction of the gallbladder or increased wall tension (with an inability to expel its contents) has been postulated. W” Some investigators have advocated a provocative test-the infusion of cholecystokinin to select cases that will respond well to cholecystectomy.2fl The clinical signs and symptoms were different for the two types of AC. All children with chronic AC otherwise were healthy, without associated conditions. They presented with chronic symptomatology of right-upper-quadrant pain and nausea or vomiting. All children with acute AC had fever, vomiting, and right-upper-quadrant pain. More than 60% had abnormal liver function and white blood cell counts, similar to adult cases.?l Ultrasonography and computed tomography are the diagnostic imaging procedures of choice for patients with acute AC. 22,23 Ultrasonography has several advantages. It is portable, noninvasive, and relatively inexpensive. In our experience, it accurately diagnosed acute AC. In contrast, the results of ultrasonography of the gallbladder were normal for children with chronic AC. Biliary scintigraphy was the most useful diagnostic test in these cases. Therapeutic management strategies for acute AC range from nonoperative treatment to cholecystostomy or cholecystectomy. Some investigators believe that tube cholecystostomy is adequate treatment9 and should be considered if a patient is too ill to survive cholecystectomy.24 However, in adults, the presence of gangrene of the gallbladder in acute AC reportedly has been as high as 50%, in which circumstance tube cholecystostomy is associated with mortality rates of 16% to 66%. Most investigators consider cholecystectomy the procedure of choice.25 Others have advocated a strategy of serial ultrasonographic examinations to select individual patients for cholecystectomy, only if specific ultrasonographic criteria develop.23 In cases of AC that are secondary to infection (such as typhoid cholecystitis), management with appropriate intravenous antibiotics has been shown to be adequate.6 In our series, all children with chronic AC underwent cholecystectomy, with complete resolu-
TSAKAYANNIS,
130
tion of symptoms. For acute AC, cholecystectomy also was the procedure of choice, but it was deferred in four children who were critically ill when the diagnosis of AC was made. Treatment with intrave-
KOZAKEWICH,
AND
LILLEHEI
nous antibiotics led to uneventful recovery in three of them. Nonoperative management of acute AC may be appropriate for selected critically ill children who have an underlying disorder.
REFERENCES 1. Hawkins PE, Graham FB, Holliday P, et al: Gallbladder disease in children. Am J Surg 111:741-744,1966 2. Silvert M, Vakil NE: Emergence of biliary tract. Gastroenterol Clin North Am 17:245-247,1988 3. Glenn F: Acute acalculous cholecystitis. Ann Surg 189:458465,1979 4. Winkler AP, Gleich S: Acute acalculous cholecystitis caused by Salmonella typhi in an 11 year old. Pediatr Infect Dis J 7:125-128, 1988 5. Rota M, Sellier N, Mensire A, et al: Acute acalculous cholecystitis in salmonella infection. Pediatr Radio1 18:421-423, 1988 6. Subba Rao SD, Lewin S, Shetty B, et al: Acute acalculous cholecystitis in typhoid fever. Indian Pediatr 29:1431-1435,1992 7. Horii Y, Sugimoto T, Sakamoto I, et al: Acute acalculous cholecystitis complicating Mycoplusma pneumonia infection. Clin Pediatr 31:376-378, 1992 8. Yulevich A, Cohen Z, Maor E, et al: Acute acalculous cholecystitis caused by salmonella typhi in a B-year-old child. Eur J Pediatr Surg 2:301-301,1992 9. Ternberg JL, Keating JP: Acute acalculous cholecystitis, complication of other illnesses in childhood. Arch Surg 110:543547,1975 10. Richard B, Nadal D, Meuli M, et al: Acute acalculous cholecystitis in infective endocarditis. J Pediatr Gastroenterol Nutr 17:215-216,1993 11. Munster AM, Goodwin MN, Pruit BA: Acalculous cholecystitis in burn patients. Am J Surg 122:591-594,197l 12. Robertson RD: Noncalculous acute cholecystitis following surgery, trauma and illness. Am Surg 36:610-614,197O
13. Sessions SC, Scoma RS, Sheikh FA, et al: Acute acalculous cholecystitis following open heart surgery. Am Surg 59:74-77, 1993 14. Glenn F, Becker C: Acute acalculous cholecystitis. Ann Surg 195:131-136,1982 15. Sessions SC, Scoma RS, Sheikh FA, et al: Acute acalculous cholecystitis following open heart surgery. Am Surg 59:74-77, 1993 16. Orlando R, Gleason E, Drezner A: Acute acalculous cholecystitis in the critically ill patient. Am J Surg 145:472-476, 1983 17. Lin KY: Acute acalculous cholecystitis: a limited review of the literature. Mt Sinai J Med 53:305-309,1986 18. Munster AM, Brown JR: Acalculous cholecystitis. Am J Surg 113:730-734,1967 19. Griffen WO, Bivins BA, Rogers EL, et al: Cholecystokinin cholecystography in the diagnosis of gallbladder disease. Br J Surg 191:636-639,198O 20. Lennard TW, Farndon JR, Taylor RM: Acalculous biliary pain: Diagnosis and selection for cholecystectomy using the cholecystokinin test for pain reproduction. Br J Surg 71:368-370,1984 21. Fabian TC, Hickerson WL, Mangiante EC: Posttraumatic and postoperative acute cholecystitis. Am Surg 52:188-192, 1986 22. Mirvis SE, Vainright JR, Nelson AW: The diagnosis of acute acalculous cholecystitis: A comparison of sonography, scintigraphy and CT. AJR 147:1171-1175,1986 23. Imhof M, Raunest J, Ohmann C, et al: Acute acalculous cholecystitis complicating trauma: A prospective sonographic study. World J Surg 16:1160-1166,1992 24. Skillings JC, Kumai C, Hinshaw JR: Cholecystostomy: A place in modern biliary surgery? Am J Surg 139:865-869,198O 25. Krasna MJ, Flancbaum L, Trooskin SZ, et al: Gastrointestinal complications after cardiac surgery. Surgery 104:773-780, 1988
Discussion T.R. Weber (St Louis, MO): Could you tell us more about the ultrasound findings? Some would argue that sludge ‘in the gallbladder is more related to calculous disease than it is to acalculous disease. Did all of the acute patients have sludge and a distended gallbladder? D.E. Tsakayannis (response): Most of the acute patients had sludge. Of the 13 patients, nine patients were treated operatively, and upon examination of the pathology specimens there was no presence of gallstones. Of the 10 patients who had chronic acalculous cholecystitis, six had the presence of sludge by ultrasound. M. Hadad {Dharhan, Saudi Arabia): There are two questions I would like to ask you. Did you do any bacteriological studies on the gallbladders that were removed? And was there any difference between the
acute and chronic cholecystitis? I wonder if the chronic stage is actually a continuation of the acute stage, and whether the presence of sludge actually causes an obstructive lesion causing the cholecystitis, in which case you can’t call it acalculous cholecystitis. D.E. Tsakayannis (response): Two children had E coli as the pathogenic organism from the gallbladder. We did see a significant difference in both the chronic and the acute state. All children with acute acalculous cholecystitis were severely ill. The subgroup with chronic acalculous cholecystitis was a totally different group of children. They were what we call the “walking patients” with chronic symptomatology. Many of the children actually had a lot of radiographic tests, searching for the origin of symptoms. Seventy-five percent of them with scintigraphy did show abnormal function of the gallbladder.
ACALCULOUS
CHOLECYSTITIS
Surgery was diagnostic and brought complete resolution of symptoms in all of this group, so we do think it is a distinct population. C. Goodwin (Dayton, OH): We too have been seeing a fair number of kids with chronic cholecystitis with similar findings. Based on Pima Indians, one factor is about Native American background. We are finding a very high correlation with a Cherokee background. I wondered if we just had an inordinate number of people with Cherokee Indian background; so we looked at 50 consecutive hernia patients, and our hernia patients didn’t seem to correlate with that background. Have you questioned Native American background in your patients?
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D.E. Tsakayannis (response): No, we didn’t find any correlation with any ethnic group. R. T. &huller, Jr (Seattle, WA): In the acute form of the disease, did you consider percutaneous ultrasoundguided drainage of the gallbladder under local anesthesia while you’re treating the underlying disease? We’ve had some success with that approach. D.E. Tsakayannis (response): No, this was not considered. This was a retrospective study. From the adult literature, in acute acalculous cholecystitis, over 50 percent of cases were gangrenous. Thus, many feel that percutaneous or tube cholecystostomy might not be the treatment of choice.