Ascending cholangitis diagnosed by percutaneous hepatic aspiration

Ascending cholangitis diagnosed by percutaneous hepatic aspiration

Volume 88 Number 1 B r i e f clinical and laboratory observations Yanagisawa M, Kobayashi N, and Matsuya S: Myocardial infarction due to coronary th...

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Volume 88 Number 1

B r i e f clinical and laboratory observations

Yanagisawa M, Kobayashi N, and Matsuya S: Myocardial infarction due to coronary thromboarteritis, following acute febrile mucoculaneous lymph node syndrome (MLNS) in an infant, Pediatrics 54:277, 1974.

Ascending cholangitis diagnosed by percutaneous hepatic aspiration Charles A. Rogers, M.D.,* J. Nevin Isenberg, M.D., Ph.D.,* Arnold S. Leonard, M.D., and Harvey L. Sharp, M.D.,** Minneapolis, Minn.

ASCENDING CtIOLANGITIS should be suspected in patients with intermittent spiking fever, jaundice, and pain in the right upper q u a d r a n t ? This disease occurs especially in adults with cholelithiasis. 2 Except for biliary atresia, disease of the extrahepatic biliary tract is rare in infancy and childhood. However, as more aggressive measures are attempted to save patients with extrahepatic biliary atresia (i.e., the Kasai p r o c e d u r e - a Roux-en-Y portohepatojejunostomy), the incidence of ascending cholangitis has increased? Recently we have seen three children who presented with only two of the Charcot triad of symptoms, who were subsequently shown to have ascending cholangitis by culture and by histologic evaluation of hepatic tissue obtained by percutaneous liver biopsy. In n o n e of the patients did multiple cultures of blood and urine prior to the biopsy yield an organism.

CULTURE

AND MORPHOLOGY

PROCEDURE Hepatic tissue was obtained by a previously published technique? A 1.6 m m Menghini needle is now routinely used in preference to the 1.2 m m needle. After masking From the Departments o f Pediatrics and Surgery, University o f Minnesota Medical School. *Supported by National Institutes of Health Pediatric departmental training grant (HD 00053) National Foundation, Lutzi Memorial Fund, and Beckman Liver Research Fund. **Reprint address: Box 279, Mayo, University of Minnesota Hospitals, Minneapolis, Minn. 55455.

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Hamashima Y, Kishi K, and Tasaka K: Rickettsia-like bodies in infantile acute febrile mucocutaneous lymph node syndrome, Lancet 2:42, 1973.

and gloving, the operator prepared the skin with a fiveminute cleansing with Betadine surgical scrub followed by Betadine solution (Purdue Frederick Co., Norwalk, Conn.). Immediately following hepatic aspiration, the tissue was divided with a sterile scalpel blade and specimens were placed in anaerobic (CO2 container, Robbins, Fiskville, R. 1.) and aerobic transport tubes in addition to a jar of buffered formalin for morphology. The transport tubes were immediately taken to the laboratory where the hepatic tissue was placed on a sheep blood plate and in trypticase-soy broth agar (Gibco, Madison, Wis.) for aerobic culture. The tissue was also cultured anaerobically on prereduced medias, specifically a chopped meat-glucose broth and a BHIA roll tube (Robbins, Fiskville, R. I.). Blood cultures were obtained at varying intervals prior to the biopsy and within 15 minutes following the procedure. The morphologic diagnosis of ascending cholangitis was made on finding a polymorphonuclear infiltrate in the portal areas.

CASE REPORTS Case 1. Patient K. R. was explored at 4 months of age for extrahepatic biliary atresia. At surgery a tiny probe-patent nonbile containing intrahepatic bile duct was anastamosed to the jejunum by a Roux-en-Y procedure. Following surgery, bile flow was established, and the serum concentration of bilirubin decreased. After discharge she developed cough, fever, and tachypnea and became increasinglyjaundiced. Despite improvement of the respiratory symptoms with ampicillin therapy, she continued to have spiking fever to 104~ F and was readmitted. Physical examination revealed moderate malnutrition, icterus, abdominal distension with ascites, hepatosptenomegaly, and a prominent abdominal venous pattern. Multiple cultures failed to yield an organism responsible for the fever (Table I). A percutaneous liver biopsy specimen was obtained for culture and morphology. Serratia marcescens was cultured from the tissue within 24 hours. She was started on antibiotic therapy and had an initially good response; subsequently the fever recurred. The abdomen was re-explored to rule out obstruction of the biliary tract, but none was found. The patient remained hospitalized for 6V2months during which multiple antibiotic regimens were used in an attempt to sterilize the biliary tree. Most antibiotics which were used inhibited growth of the organism, but levels necessary to kill the organism were not safely obtainable. Finally she was begun on trimethoprim-sulfamethozale orally and discharged to receive the drug on a continuous basis. She remains stable with

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B r i e f c 6 n i c a l and laboratory observations

The Journal ofPediatrics January1976

T a b l e I. S u m m a r y o f clinical, m i c r o b i o l o g i c , a n d l a b o r a t o r y f i n d i n g s in p a t i e n t s w i t h b i o p s y p r o v e d a s c e n d i n g cholangitis

Negative cultures prior to biopsy

Age Case 1 (Patient K. R.)

Case 2 (Patient L. S.)

Case 3 (Patient S.N.)

Post- Operabiopsy tive Liver blood bile culBlood Urine Other culture culture ture

Antibiotic therapy at biopsy

Liver

morphology

Organism

6 mo

6

2

2 (CSF)

+

-

ND

Serratia marce- Severe biliary cirrhosis with acute sans and chronic inflammation

None

7 mo

3

2

ND

-

+

ND

S. marcesans

ND

9 mo*

ND

ND

ND

-

ND

+

S. mamesans

16 yr

3

2

1 (throat)

+

--

ND

Citrobacter freundii

Biliary cirrhosis, no active inflammation ND

None for 3 days Gentamicin

16 yr*

ND

ND

ND

--

ND

+

C. freundii

3 yr

3

1

1 (bone marrow)

+

-

ND

Enterobacter group

None

Biliary cirrhosis with mild focal acute and chronic inflammation Portal fibrosis, bile duct proliferation and marked acute inflammation

Kanamycin None

ND: not done *Liver biopsy and bile culture obtained at surgery. tNormal values: OCT (omithine carbamoyl transferase) < 45 IU/1; SGOT (serum glutamic oxaloacetic transaminase) < 26.5 IU/I; AP (alkaline phosphatase) < 300-500 IU/I (age dependent); 3,GT (gamma glutamyl transpeptidase) < 25 U/l; bilirubin, direct < 0.3 mg/dl; total < 1.6 mg/dl.

cirrhosis and portal hypertension, but without signs of infection at 23 months of age. Case 2. Patient L. S. is a 16-year-old Caucasian female referred for evaluation of five years of intermittent jaundice following exposure to infectious hepatitis; serum glutamic oxaloacetic transaminase values were elevated. Numerous studies failed to define the etiology of the disease during the first two admissions. She was readmitted following recovery from a complication o f retrograde cholangiography. The epigastric pain and a brief episode of mild fever present on admission resolved without therapy. Multiple cultures were obtained to search for infection, but all were negative (Table I). A percutaneous liver biopsy was then done for bacterial culture. Shortly after the procedure the patient became restless. Approximately 30 minutes later she became hypotensive and tachycardic with peripheral vascular constriction. Intravenous plasmanate and blood reversed these manifestations. The hemoglobin, which had not fallen, rose to a level consistent with the volume of blood given. Within 24 hours the bacterial culture from the liver tissue grew Citrobacter freundii, but blood cultures obtained both before and after the biopsy remained negative. With appropriate antibiotic therapy, clinical and laboratory status improved over a week. At laparotomy, a large choledocal cyst was found and drained by a Rouxen-Y choledochojejunostomy. Much stoney debris was removed from the cyst. Cultures obtained from the cyst grew Citrobacter freundii. One month following surgery, serum hepatic enzymes and bilirubin had returned to normal values, and antibiotics were stopped.

Case 3. Patient S. N. is a 3-year-old girl with a large embryomal cell carcinoma of the portahepatis whose surgical procedures included a Roux-en-Y loop to the common duct. The last admission was prompted by spiking fever, right upper quadrant abdominal pain after eating, and weight loss. Since fever had not been a feature of the malignancy, cultures were obtained (Table I). No organism was cultured, but a liver biopsy specimen, obtained for cultures and morphology, grew out an Enterobacter species and had microscopic findings consistent with cholangitis. At the time of biopsy the patient was not jaundiced, but had elevated serum enzyme levels (Table I). She became afebrile within hours after initiation o f antibiotic therapy. Subsequently she became icteric, febrile, and died within weeks following an exploration that demonstrated extensive metastases. DISCUSSION T h e classic C h a r c o t

triad n e e d

not

b e p r e s e n t in

a s c e n d i n g cholangitis as d e m o n s t r a t e d b y o u r patients, n o n e o f w h o m m a n i f e s t e d all t h r e e s y m p t o m s at t h e time o f a n i d e n t i f y i n g liver a s p i r a t i o n ( T a b l e I). E a c h p a t i e n t h a d c h r o n i c biliary tract d i s e a s e as a p r e d i s p o s i n g factor to a s c e n d i n g cholangitis, ~ ~ ~ a n d in e a c h the s e r u m concentrations of enzymes reflecting an obstructive process w e r e m o r e a b n o r m a l t h a n t h o s e reflecting h e p a tocellular injury. T w o (Patients K. R. a n d S. N.) h a d surgical

procedures

allowing

direct

communication

Volume 88 Number 1

Brief clinical and laboratory observations

Charcot triad

Liver enzyrnest Bilirubin

Temperature

yGT

104~

No

4.3

6.9

43

48

ND

Spiking to 103" Afebrile

No

1.7

2.7

178

94

975 ND

No

0.8

2.4

167

82

191 ND

Low grade 100.8~

No

113.t 23.8

476

77

2,115 ~,670

Low grade

No

5.5

11,7

302

ND

1,850 ND

Spiking to 104~

YesRUQ

0.7

1.1

238

74

1,725

522

314

between the gut flora and biliary tree, and one (Patient L. S.) had incomplete biliary obstruction by an unsuspected choledochal cyst obscured by ascites and intermittent decompression. Our three patients represented a diagnostic dilemma. Infection was actively pursued as a diagnostic possibility, but cultures obtained prior to the liver biopsy were negative in atl three patients. Culture of the hepatic tissue not only established the diagnosis, but also was useful in determining treatment. Indeed, Patient K. R. was hospitalized 6'5 months before an antibiotic regimen was found that would keep her cholangitis under control. Without having her microorganism to test against antibiotics for sensitivity, we might never have found an effective drug. On therapy, she has done well for the past year. The biopsy was useful in Patient L. S., despite the complication, since it allo~,~ed us to treat her preoperatively rather than during her sugical procedure. Except in the presence of biliary tract disease, bacteria cannot ordinarily be isolated from the normal or cirrhotic human liver.7. 8 McCloskey and associates9 found positive blood or liver cultures after biopsy in 7-8% of 69 consecuti~,e liver biopsies, but the positive liver cultures and the one positive blood culture were in patients with obstructive liver disease; all other positive blood cultures were in patients with hepatitis or alcoholism. Transient bacteremia was documented in 14.4% of 89 patients following percutaneous liver biopsy, when the blood culture was obtained within 15 minutes after the biopsy procedure. 1~

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The same organism was cultured from the liver in five of the 12 bacteremic patients. Only seven patients (7.8%) had organisms recovered from the liver, but the underlying fiver diseases were not detailed. Sixty-four percent of the 45 patients with partial common bile duct obstruction due to stricture, choledocholithiasis, and bite duct carcinoma had positive cultures of the bile obtained during percutaneous cholangiographyY Nevertheless, only one-third of these patients had symptoms of fever or chills at the time the positive culture were obtained. Five members of the larger asymptomatic subgroup developed classic symptoms of cholangitis. Blood cultures obtained immediately after the onset of symptoms were then positive for the same organism present in their bile. Fever subsided by the next day in all but one patient who required more vigorous treatment for gram-negative septicemia. Based on these observations, the authors suggested that the systemic manifestations of cholangitis are the result of intermittent septicemia? More recently, the complications resulting from 127 percutaneons liver biopsies in patients with large bile duct obstruction were reported- 1' One patient developed biliary peritonitis, lwo developed pain of the right upper quadrant, and two had fever after the biopsy procedure. There was no mortality. In our series of over 1,000 liver biopsies at this institution in children with adequate coagulation profiles at the time of biopsy, mortality has been zero, and morbidity has been less than l%. As pediatricians, we will be forced to recognize and to treat ascending cholangitis more often, since this is a common complication of the Kasai portoenterostomy procedure tbr extrahepatic biliary atresia which is being attempted at many institutions. Therefore we recommend hepatic aspiration for culture and histologic evaluation followed by blood culture in that group of patients with a known predisposition to ascending cholangitis who demonstrate an 3, two symptoms of the Charcot triad. The biopsy should be undertaken only after multiple blood cultures have failed to yield an organism, a liver scan has been done to rule out hepatic abscess, and any coagulation defects have been corrected, Furthermore, we believe that the discovery and treatment of ascending cholangitis is safer prior to surgery than within the operating room. REFERENCES

1. Charcot JM: Le cons sur ies maladies du fete des votes filiares el des reins, Paris, 1877, Facult6 de Meddcin de Paris. 2, Flemma RJ, Flint LM, Osterhout S, and Singleton WW: Bacteroiogic studies of bitiary tract infection, Anr~ Surg 166:563, 1966. 3. Kobayaski A, Utsunomiya T, Ohbe Y, and Shimiza K: Ascending cholangitis after successful repair of biliary atresia, Arch Dis Child. 48:697, 1973.

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4.

Brief clinical and laboratory observations

Walker WA, Krivit W, and Sharp H: Needle biopsies of the fiver in infancy and childhood, Pediatrics 40:946, 1967. 5. Furey AT: Ascending cholangitis, N Y State J Med 66:1299, 1966. 6. Roth P, and Cohen S: Cholangitis, a review of the literature with a report of an illustrative case, Am J Gastroenterol 53:154, 1970. 7. Storov V, Morse WC, Giges B, and Jahnke E J: Bacteriology of the human liver, J Clin Invest 31:986, 1952. 8. Stormont JM, Mackie JE, Kass EH, and Davidson CS:

The Journal of Pediatrics January 1976

Bacteriologic culture of the disease human liver, Ann Intern Med 51:17, 1959. 9. McCloskey RM, Gold M, and Weser E: Bacteremia after liver biopsy, Arch Intern Med 132:213, 1973. 10. LeFroch J, Ellis C, Turclik JB, and Weinstein L:. Transient bacteremia associated with percutaneous liver biopsy, Clin Res 21:843, 1973. 11. Morris JS, Gallo GA, Scheuer PJ, and Sherlock S: Percuta. neous liver biopsy in patients with large bile duct obstruction, Gastroenterology 68:750, 1975.