Acute Suppurative Cholangitis Secondary to Calcific Pancreatitis

Vol. 71. No. 5 U.S.A .

GASTROENTEROLOGY 71 :847-850, 1976 Copyright «> 1916 by The William. & Wilkin' Co.

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ACUTE SUPPURATIVE CHOLANGITIS SECONDARY TO CALCIFIC PANCREATITIS ALAN

I.

HARRIS ,

M.D.,

AND

MARK A.

KORSTEN ,

M.D.

Section of Liver Di8ease and Nutrition. Vett'rans Administration Hospital. Bronx. New York. and Department of Medicine. Mount Sinai School of Medicine (City University of New York). New York. Nt'w York

In the absence of calculi or carcinoma, the occurrence of acute suppurative cholangitis secondary to calcific pancreatitis is extremely rare. This report describes the successful management of acute suppurative cholangitis by surgical decompression and use of a new aminoglycoside, amikacin. In the absence of calculus disease, partial or complete obstruction of the common bile duct (CBD) by chronic pancreatitis is an unusual, but well established clinical entity, which is capable of producing jaundice'" and/or radiographic evidence of dilatation of the CBD.·· • Acute suppurative cholangitis (ASC) is a clinicopathological syndrome characterized by high fever, jaundic~, chills, right upper quadrant pain, rebound ten~erness 10 the right upper quadrant, sepsis, purulent bl.le under increased pressure, shock, mental obtundatlOn, and hepatic abscesses 1. ' . Laboratory studie~ revealle~kocy­ tosis, jaundice of variable severity, ~Il~ elevatlOns of alkaline phosphatase, and normal or minimally elevated transaminases. 1 Not all aspects of the syndrome are present in each case. The responsible organisms are usually part of the enteric. f1~ra: The us~al cause~ of ASC include choledochohthlasls, prevIous surglcal manipulation, and tumor.1. "11 The foll.o~ing case demonstrates that chronic calcific pancreatitis can also cause ASC and that amikacin (a new aminoglycoside) combined ~ith surgical therapy was effective in eradicating the disease. Case History A 46-year-old black man was admitted.~ the ~astroint~sti­ nal-Liver Service of the Veterans Administration Hospital. Bronx New York because of a week of epigastric pain radiating into the right upper quadrant, and 3 days of fev~r accompanied by shaking chills. The pain was W?f6e on Iymg down, ~nd improved in the upright position, AhIstory of heavy alcoholism was obtained but the patient denied any intake of alcohol for the past 3 mo~ths. The patient ~dmitted to .previous atta~k~ of similar pain, but there was no hlstory,of weight loss, vomltmg, jaundice, or change in the color of urine or stools. On admission, the patient was alert. The blood pressure ~as 110/80 mm Hg, temperature, 38. 5~C, pulse, 11.6, ~nd r~spl!a­ tions, 40 per min. There were no SignS Qf chrOniC hver disease. Abdominal examination revealed only moderate tenderness to palpation in the epigastrium and right upper quadrant. The remainder of the examination was unremarkable. Received February 2, 1976. Accepted April 23. 1976. Address requests for reprints to: Mark A. Korsten. M.D., Liver and Nutrition Laboratory. Veterans Administration HOlIpital. 130 West Kingsbridge Road, Bronx. New York 10468.

Laboratory data obtained on admission. Hematocrit, 38.9%, white cell count, 12,000 per mm' with a shift to the left, prothrombin time, 12.0 sec (control. 11.0 sec). Urinalysis revealed 2+ protein, 6 to 8 white cells, and 8 to 10 red cells per high power field. Serum sodium, 134 mEq per liter; potassium, 2.8 mEq per liter; chloride, 91 mEq per liter; carbon dioxide, 29 mEq per liter; blood urea nitrogen per 13 mg per dl; and glucose, 170 mg per dl. The serum amylase was 190 dye U per dl (normal up to 200 U); albumin, 2.9 g per dl; total protein, 7.4 g per dl; SGOT, 40 IV per ml; SGPf, 20 IV per ml; alkaline phosphatase, 143 IV per ml (normal <85); and creatinine, 0.8 mg per dl. Chest X-ray revealed evidence of healed right upper lobe tuberculosis. Abdominal films showed marked calcific changes in the region of the pancreas. Hospital course (fig. 1). Daily temperature peaks reached 40.6°C, epigastric and right upper quadrant tenderness increased. The liver became palpable 3 finger-breadths below the right costal margin, with direct and punch tenderness now present. Because of failure to respond to ampicillin, the patient was placed on intravenous oxacillin and gentamicin on the 2nd hospital day. At this time, an intravenous cholangiogram with delayed films failed to visualize the biliary tree, and total serum bilirubin was 1.4 mg per 100 ml. On the 3rd hospital day, a tlmTc sulfur colloid scan of the liver demonstrated homogeneous uptake, slight hepatomegaly, and no cold areas. The same day, an endoscopic retrograde cholangiopancreatogram failed to visualize the biliary system, but revealed a dilated and beaded pancreatic ductal system. Because of increasing bilirubin, persistent sepsis, and possibility of cholangitis, a laparotomy was undertaken on the 6th hospital day. At laparotomy, the pancreas was diffusely nodular, enlarged, and fibrotic. There was no pseudocyst. abscess. or obvious carcinoma in the pancreas. The intrapancreatic CBD was encased in the fibrotic process. The extrapancreatic CBn was markedly dilated (3 em). A cholecystectomy was performed. On opening the CBn, yellow bile under increased pressure was obtained. This bile was not grossly purulent but Gram's stain showed gram-negative rods and gram-positive cocci. A thin probe was passed successfully down the CBn into the duodenum. A careful search of both the gallbladder and CBD failed to reveal stones or gravel. A T -t ube cholangiogram obtained several days after surgery revealed marked narrowing oC the intra pancreatic CBD, and a dilated extra pancreatic CBD (fig. 2) . Biopsies obtained at surgery revealed acute inflammation in the gallbladder and regional lymph nodes. No microscopic calculi were detected . The liver biopsy demonstrated marked polymorphonuclear neutrophil infiltration of the portal tracts, with edema. In addition. multiple microab-

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Vol. 71, No.5

CASE REPORTS

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FIG. l. Summary of patient's clinical course: rapid improvement after beginning amikacin therapy is apparent.

scesses were present in the lobular parenchyma (fig. 3). Preoperative blood cultures and intraoperative bile cultures demonstrated a Klebsiella species (fig. 1). Despite an initial response, signs of sepsis recurred, and additional organisms were isolated from the blood and bile (fig. 1) . However. no response to the combination of carbenicillin, tobramycin , and colistin was obtained. By disc sensitivities, it was suspected that the new aminoglycoside amikacin might he effective. Therefore, on the :34th hospital day the patient was started on amikacin. With the amikacin therapy. the patient became afebrile. and all subsequent blood cultures became negative. However. the bile cultures remained positive. The bile did not exhibit significant in vitro inhibition against any of the isolated organisms at 1:2 dilution using the Kirby -Bauer method . All specimens were obtained 1 hr after the dose of amikacin. Absolute serum and biliary levels were not obtained. As seen in figure I. after 11 days of thera py the dosage of amikacin was reduced. This was necessitated by bilateral high frequency hearing loss. There was no deterioration of renal function during amikacin therapy. Three months after admission. a repeat T-tube cholangiogram was unchanged and the patient underwent a cholednchnduodennstomy to bypass the distally obstructed intra pancreatie CHD. Despite an exhaustive search and multiple pancreatic biopsies. nn evidence of carcinoma could be documented . The patient was without pain. afebrile and gaining weight :l months after cholednchoduodenostomy.

Discussion Fie; . ~. T ·tuhe cholangiogram : common hi Ie fiuet is dilated proxi · mal to a narrllwt'd portion in tht~ n·gion oflh~ pane rrat i{' hE'aci . Th£"rr is pafH'rl'lI ti ('

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In the set ting of alcoholism. the occurrence of abdominal pain. jaundice. and fever may indicate alcoholic hepatitis. pancreatitis. and pancreatic abscess or infected pseudocyst, I t as well a s a wide range of non-

849

CASE REPORTS

November 1976

FIG. 3. Photomicro!(raph from surgical wedge biopsy of the liver. A microabscess is seen to the ri~ht of ('enter (orrou' ) (H

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alcohol related pathology . This case illustrates that alcohol-induced calcific pancreatitis in the absence of calculi or carcinoma, may result in the syndrome of ASC, As stressed in the literature, early diagnosis and surgical intervention are critical factors in the survival of patients with ASC,7. • This may be important not only for surgical decompression of the CBD, but also in determining the offending pathogen(s), so that appropriate antimicrobial therapy can be determined, Blood cultures alone may not detect the pathogenetic organism ,7 The response to amikacin was dramatic, Amikacin is a new semisynthetic aminoglycoside obtained by the acylation of kanamycin.' 3 It has shown both in vitro and in vivo activity against many gram-negative organisms that have acquired resistance to the currently available aminoglycosides. The effectiveness of amikacin appears to involve its resistance to several of the enzymes that inactivate the other aminoglycosides,'3 Two clinical reviews on the usefulness of amikacin have recentlv appeared. '3 . . . However, neither paper discussed the us'e of the drug in patients with biliary sepsis or hepatic abscesses. It should be noted. that although the amikacin was effective in treating the patient's sepsis and liver abscesses, it did not sterilize the biliary tract. Although absolute amikacin levels were not obtained. in vitro testing of serum and biliary levels correlated with the observed clinical response, as stated in the Case History. The ineffective levels of amikacin obtained in our patient's bile contrast with the therapeutically effective levels obtainable in the bile with its parent compound. kanamycin. "

In summary. we have demonstrated that ASC can occur secondary to CBD obstruction in chronic calcific pancreatitis, This entity. although rare. should be considered in the evaluation of an alcoholic patient with fever. jaundice. and abdominal pain. In combination with surgical drainage of the biliary system, amikacin may be successful in treating the hepatic and systemic complications of this syndrome. REFERENCES I. Peterson LW. Cole, WHo Chronic sclerosing pancreatitis causing

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3.

4.

5. 6.

i. 8.

9.

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complete sten,,,,is of the common bile duct. Arl'h Surg 51: 15-21. 1945 Behrend M, Behrend A: Chronic pancreatitis l'ausing complete and incomplete obstruetion of the common bile du('t. Areh Surg 5i:51 -61. 194A McCullum WH .•Iordan PH: Obstrul'tive jaundice in patients witb pancreatitis wit bout associated biliary tral't disease. Ann Surg IA2: I \fi·· 120, 1975 Snape WJ. Long WB, Trotman H\\'. et al: Marked alkaline phosphatase elevation with partial common hi Ie dect ohstruction due to calcific panaeatitis. C~lIstroenter(lI(l~y 70:70- .;1. 19.6 Sarles. H. Gewlami·Santandrea A: Chronic pancreatitis. (,\in Gaslroentewl I: 16. 19:1, 19i:? Guinn C : General radioloKY "I' the pancreas. !'lin C;astrupnternl 1:61 - !,!:1.19'2 Andre", D.l, .Iohnson SE: Acute suppurative cholangitis. a medical and surgical emergency. Am .J Gastroenternl :>4: 141-1'>4. l!l'() Hinshaw DH: Acute obstrul'Iive suppurat ive cholangit is. Surg Clin ~(lrth Am 5:1: 1089 109-t. 19,;1 Haupert p, Casey L. Evans W. et al : Acute sllppurat i,'p ('hoillng.· tis : fxperipnc(' with If) ('onSP('utivt.\ l'as('!'. Arch SUTK ~-1:-U)O-4fi7, 1%, Hin c h,,~· E.I. C"uper (,E: A"ut,>obstructive suppurati"e cholangi · t is . Am .l Surg II .. :li:?I;'>!. J!lIi!l

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11. Ostermiller W, Thompson R. Carter R, et a1: Acute obstructive cholangitis. Arch Surg 90:392-395, 1965 12. Warshaw AL: Pancreatic abscesses. N Engl J Med 287:1234-1236. 1972

13. Tally FP. Louie TJ, Weinstein WN, et al: Amikacin therapy for severe gram-negative sepsis. Ann Intern Med 83:484-488, 1975

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14. Meyer RD, Lewis RP, Carmalt ED, et a1: Amikacin therapy for serious gram-negative bacillary infections. Ann Intern Med 83:79O-aOO. 1975 15. Preston FW, Silverman M, Henegan GC, et al: The excretion of

kanamycin in bile and pancreatic fluid. Antibiotics Annu

7:857-861, 1959-1960