Bile Duct Obstruction Secondary to Chronic Pancreatitis in Seven Dogs Alastair E. Cribb, David C. Burgener and Keith A. Reimann

Abstract Seven icteric dogs were determined to have bile duct dence la prisence de pancreatite chronique. Les biopsies obstruction secondary to chronic pancreatitis. All dogs hepatiques ont demontre de la cholestase. La pancrea- had histories of intermittent vomiting and diarrhea. tite chronique devrait donc etre incluse comme cause Alkaline phosphatase and alanine aminotransferase possible d'ictere, d'obstruction du canal choledoque activities and total bilirubin concentrations were et de la formation de masses dans le pancreas. markedly elevated. Diagnosis was based on exploratory laparotomy and histological examination. Each dog Can Vet J 1988; 29: 654-657 had a 3 to 10 cm mass in the body of the pancreas and obstruction of the common bile duct. Three dogs treated with pancreatectomy, gastrojejunostomy, and cholecystojejunostomy died within five weeks. Three Introduction dogs treated with conservative surgical procedures were alive at 8, 16, and 26 months postoperatively. One dog Because of the close association of the distal end was euthanized because of suspected neoplasia. Hepatic of the common bile duct and the pancreas (1), enzyme activity and bilirubin levels decreased markedly lesions in the pancreas may cause bile duct obstruc- in the surviving dogs. Histological examination of the tion. Tumors of the pancreas and of the bile duct pancreatic masses indicated chronic pancreatitis. epithelia are cited as the most common causes of post- Hepatic biopsies revealed evidence of cholestasis. hepatic obstruction in the dog (2). Acute pancreatitis Chronic pancreatitis should be included in the differen- may cause icterus and biochemical changes which mimic tial diagnoses of icterus, bile duct obstruction, and posthepatic chlolestasis without causing obstruction masses in the pancreas. (2). Although chronic pancreatitis has been cited as a potential cause of cholestasis in dogs (3) and is well- Resum6 documented in human medicine (4,5,6,7), veterinary literature on the subject is lacking. Une obstruction du canal chol6doque secon- When icterus occurs in a dog without concurrent cli- daire A une pancr6atite chronique chez sept nical and biochemical changes diagnostic of pan- chiens creatitis or another specific cause, diagnosis of obstruc- On a identifie une obstruction du canal choledoque tion and its origin must frequently be based on explor- secondaire a une pancreatite chronique chez sept atory laparotomy with hepatic and pancreatic biopsy chiens. Tous les chiens prwsentaient des vomissements (3). Pancreatic adenocarcinomas are uncommon in the et de la diarrhee de facon intermittente. On a observe dog (8). They usually occur as multilobular, infiltra- une augmentation marquee de la concentration de bili- tive masses 2-15 cm in diameter and they frequently rubine ainsi que des activites enzymatiques de la phos- metastasize to the liver. When the tumor obstructs the phatase alcaline et de l'alanine aminotransferase. Le bile duct, icterus occurs (8). The gross similarity of diagnostic final a ete fait lors de la laparotomie explo- chronic pancreatitis and neoplasia in some cases led ratrice et par l'examen histologique. Chez chacun des us to conduct a retrospective study of cases of obstruc- chiens, on a retrouve une masse de 3 A 10 cm dans le tive jaundice secondary to chronic pancreatitis. pancreas ainsi qu'une obstruction du canal chole- In this paper, we document the occurrence of inflam- doque. Trois chiens, ayant subi une pancreatectomie, matory masses caused by chronic pancreatitis. Differ- une gastrojejunostomie et une cholecystojejunostomie entiation between neoplasia and inflammation was sont morts en dedans de trois a cinq semaines. Trois only possible with histological examination of the autres chiens, ayant subi des interventions chirurgicales involved tissues. palliatives mineures etaient encore en vie a 8, 16 et 26 mois plus tard. Un des chiens a ete euthanasie parce que l'on soupconnait un neoplasme. Chez les chiens qu ont survecu, les taux de bilirubine et l'activite enzy- Materials and Methods matique ont diminue de facon significative. L'examen The source materials used were the case records of the histologique des masses pancreatiques a mis en evi- Veterinary Clinical Center (VCC), Michigan State University from January 1980 to June 1985. Dogs having concurrent diagnoses of icterus and pancreatitis Department of Small Animal Clinical Sciences, College of in those Veterinary Medicine, Michigan State University, East were identified. We only included the study Lansing, Michigan 48824. dogs in which the diagnosis of posthepatic obstruction was confirmed on laparotomy and which did not have Reprint requests to Dr. A.E. Cribb, Division of Clinical significant concurrent medical problems. The diagnosis Pharmacology, Hospital for Sick Children, 555 University of pancreatitis was based on histological examination. Avenue, Toronto, Ontario M5G 1X8. Seven dogs meeting the above criteria were identified. L 654 Can Vet J Volume 29, August 1988 CAse S(U/L).

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Case Reports Case I-A 12-year-old spayed female mixed-breed dog normal. Thoracic and abdominal radiographs were was referred to the VCC with a chief complaint of normal. icterus noted during a routine exam. Physical exam On exploratory laparotomy, a 3 cm firm mass was was unremarkable except for marked icterus. A CBC located in the body of the pancreas. The gallbladder was normal. Alkaline phosphatase (AP) and alanine was distended and could not be expressed. Based on a aminotransferase (ALT) activities and total bilirubin presumptive diagnosis of pancreatic neoplasia, an 80% concentration were markedly elevated (Table 1). pancreatectomy, duodenal resection, gastrojejunos- Thoracic and abdominal radiographs were within nor- tomy, and cholecystojejunostomy were performed. mal limits. The dog developed diabetes mellitus and peritonitis Exploratory laparotomy revealed a 3 cm mass in the postoperatively. He died of Klebsiella pneumoniae body of the pancreas. A cholecystoduodenostomy was septicemia eight days postoperatively. performed. Biopsy of the pancreatic mass revealed Histological examination revealed chronic granu- steatitis suggestive of pancreatitis. Hepatic biopsy lomatous pancreatitis with no evidence of malignancy. revealed cholestasis. Bacterial culture of the mass was Multifocal suppurative hepatitis and cholestasis were negative. The icterus resolved (Table 2) and the dog present. The final diagnosis was bile duct obstruction was doing well eight months postoperatively. A diag- caused by chronic pancreatitis with secondary hepatitis. nosis of bile duct obstruction caused by chronic Case 3-An obese eight-year-old spayed female pancreatitis was made. Beagle dog was presented because of an eight month history Case 2-A ten-year-old intact male Gordon Setter dog of recurrent diarrhea and recent onset of vomiting. The was presented because of a three-week history of vomit- dog was pyrexic (39.5°C), dehydrated, icteric, and ing and weight loss. The dog had developed icterus ten exhibited pain on abdominal palpation. A CBC days prior to referral, and an exploratory laparotomy revealed marked leukocytosis, mature neutrophilia, by the referring veterinarian had revealed a 3 cm mass lymphopenia, and monocytosis. Abnormal biochemistry in the body of the pancreas. The dog was pyrexic values included markedly elevated bilirubin concen- (39.5°C), tachycardic, thin, and had icteric mucous tration and ALT and AP activities (Table 1). Serum membranes. A CBC revealed leukocytosis, mature amylase and lipase activities were normal. Thoracic neutrophilia, and monocytosis. Alkaline phosphatase radiographs were normal. Abdominal radiographs and alanine aminotransferase activities were markedly revealed mild hepatosplenomegaly. elevated (Table 1). Total bilirubin concentration was An exploratory laparotomy was performed. A 5-8 cm mildly increased. Amylase and lipase levels were firm mass with extensive adhesions was identified in L C,an Vet J Volume 29, August 1988 655 the pancreas. The gallbladder was distended and could Cholecystoduodenostomy alone was performed in not be expressed. An enterotomy was performed and one case; pancreatectomy and gastrojejunostomy with the bile duct cannulated. The cannula was then passed cholecystojejunostomy were performed in three cases; through the body wall to allow drainage. It was the bile duct was cannulated for one week in one case; removed one week postoperatively. The ALT, AP, and no corrective surgery was attempted in one case; and bilirubin concentrations decreased markedly post- one dog was euthanized intraoperatively because of operatively (Table 2). Hepatic biopsy revealed chronic suspected neoplasia. The three dogs treated with pan- multifocal hepatitis and cholestasis. The dog was doing createctomy, gastrojejunostomy, and cholecystoje- well 26 months postoperatively, making pancreatic or junostomy all died within five weeks: two died from biliary neoplasia unlikely. The final diagnosis was peritonitis and subsequent septicemia within two weeks biliary obstruction caused by chronic pancreatitis with and the third died from severe cholangitis and sep- secondary hepatitis. ticemia in five weeks. The three dogs treated conser- vatively (cholecystoduodenostomy, cannulation of bile duct, or no treatment) were doing well 8 to 26 months postoperatively Results In those dogs surviving longer than one week post- Seven dogs with bile duct obstruction secondary to operatively, there were marked decreases in the AP, chronic pancreatitis were identified. The above case ALT, and bilirubin values (Talbe 2). Postoperative reports are representative. The majority of the dogs values were determined at various intervals and so may (5/7) were middle-aged females (Table 1). Six of seven not represent baseline concentrations. dogs had a history of vomiting and/or diarrhea of 2 to 32 weeks duration. All dogs were icteric at the time of presentation. Total bilirubin concentrations ranged from Discussion 41-313 Amol/L with a median of 124 tmol/L. Gen- Seven dogs with histories of recurrent vomiting and erally, conjugated bilirubin was greater than uncon- diarrhea had posthepatic icterus secondary to chronic jugated. Alkaline phosphatase activity was elevated in pancreatitis. In all cases, inflammatory masses in the all cases (range: 1040- >4000 U/L; median: 3560 U/L) pancreas caused by chronic pancreatitis resulted in as was alanine aminotransferase activity (range: obstruction of the bile duct. 68-3370; median: 1180). Amylase activity was elevated In this series of cases, the serum biochemical abnor- in only one of six dogs. Of five dogs, two had mild malities (markedly elevated bilirubin concentrations, elevations of lipase activity. Resting ammonia concen- AP, and ALT activities) were consistent with, but not trations were normal in three dogs tested. Bromsul- diagnostic of, bile duct obstruction. In contrast to the phalein (BSP) retention was 15% in the one dog eval- six other reported cases of bile duct obstruction sec- uated. The most common hematological finding was ondary to chronic pancreatitis (3), amylase and lipase mature neutrophilia. Plain abdominal and thoracic activities in the present cases were not elevated con- radiographs were not helpful in identifying the cause sistently. In an experimental model of chronic pan- of icterus or the presence of pancreatic masses. creatitis produced by infusion of oleic acid into the Exploratory laparotomies were performed in all accessory pancreatic duct (9), amylase and lipase ac- cases. A mass was present in the body of the pancreas tivities were normal despite the presence of pancreatic in all dogs. They ranged from 3-10 cm in diameter and inflammation and necrosis. Therefore, normal amylase most were adherent to the omentum. The right limb and lipase activities do not rule out chronic pancreatitis of the pancreas was also involved in two dogs. The as a diagnosis (9). gallbladder was distended and could not be expressed Bile duct obstruction occurs in approximately 27%o in six dogs. of humans with chronic pancreatitis (5,10,1 1). Clinical Biopsy of the pancreatic mass performed in six dogs and laboratory findings are similar to those in dogs. confirmed the presence of pancreatitis, with various However, the most frequent complaint and reason for degrees of fibrosis, suppuration, and steatitis. Pancrea- surgical intervention is abdominal pain (4,10,12,13). tic biopsy was unavailable in one dog but the dog has The occurrence of abdominal pain in dogs may be dif- lived for two more years, making pancreatic neoplasia ficult to assess. unlikely. No evidence of malignancy was present in In humans, the intrapancreatic segment of the com- any of the biopsies. In two cases where cytology was mon bile duct is frequently surrounded by a fibrous performed intraoperatively, the results were consistent sheath and associated pancreatic acinar tissue (10,11). with inflammation. Thus, the dense sclerosis that characterizes advanced During the time period covered by this study, an chronic pancreatitis may cause obstruction without an additional 17 dogs with pancreatic masses at the VCC inflammatory mass being present. In the dog, the rela- were diagnosed as having pancreatic adenocarcinomas. tionship between the pancreas and bile duct is not as Thus, approximately 30% of dogs with pancreatic close (1). Space-occupying lesions may therefore be re- masses did not have neoplasia. quired to cause obstruction in the absence of acute, The liver was grossly normal in five of seven dogs; diffuse inflammation of the pancreas and surrounding two dogs had gross changes consisting of hepatomegaly tissue. In these seven cases and six previously reported and raised areas on the surface. There was histological cases, an inflammatory mass was always present. evidence of cholestasis in six dogs biopsied and mild Histological examination was required to definitively multifocal hepatitis in three. differentiate pancreatitis and pancreatic neoplasia.

5 anC Vet JVolume 29 A u u 1- , 656 Can Vet J Volume 29, August 1988 Percutaneous transhepatic cholangiography, in- not indicated in such cases in bilirubin levels and hepa- travenous cholangiography, and endoscopic retrograde tic enzyme activities decrease. cholangiopancreatography are well-developed These seven cases demonstrate that biliary obstruc- radiographic techniques in man which allow visualiza- tion caused by chronic pancreatitis should be consid- tion of the common bile duct and prediction of the ered in the differential diagnoses of posthepatic icte- potential cause of obstruction (i.e. pancreatitis versus rus in dogs. It is one of the few causes with a favor- neoplasia) (5,12,14). Ultrasonography has also been able prognosis. Exploratory laparotomy and histol- shown to be a helpful adjunct (9). Specialized ogical examination of involved tissues is the most reli- radiographic techniques were not attempted in these able means of diagnosis. The presence of a mass in cases because exploratory laparotomy was felt to be the pancreas should not be assumed to be neoplastic the best method of arriving at a final diagnosis and since pancreatitis can result in inflammatory masses treatment. causing bile duct obstruction. Conservative surgical When pancreatectomy, gastrojejunostomy, and procedures such as decompression of the gallbladder cholecystojejunostomy were performed, survival was via cholecystoduodenostomy appear to be the treat- decreased. In man, aggressive procedures involving ment of choice. cv. pancreatectomies are rare (4,10,12). Simultaneous pro- cedures to relieve concurrent bile and pancreatic duct obstruction are sometimes used, but the most common are simple procedures to relieve bile duct obstruction References (10,13). Therefore, it appears that conservative sur- 1. Miller ME, Christensen GC, Evans HE. Anatomy of the Dog. gical therapy is the of Philadelphia: WB Saunders, 1964: 680, 706-716. treatment choice for biliary 2. Meyer DJ, Burrows CF. The liver. Part II. Biochemical diag- obstruction secondary to chronic pancreatitis. nosis of hepatobiliary disorders in the dog. Compend Cont in Cholangitis has been reported to occur in 6-15% of Educ Pract Vet 1982; 4: 706-714. human cases of bile duct obstruction secondary to 3. Mathiesen DT, Rosin E, Common bile duct obstruction sec- chronic pancreatitis (4,13). Bradley and Salam (4) feel ondary to chronic fibrosing pancreatitis: treatment by use of cholecystoduodenostomy. J Am Vet Med Assoc 1986; 189: that persistence of hyperbilirubinemia for greater than 1443-1446. ten days in human patients warrants surgical interven- 4. Bradley EL, Salam AA. Hyperbilirubinemia in inflammatory tion as obstruction of this duration predisposes the pancreatic disease. Ann Surg 1978; 188: 626-629. patient to developing cholangitis. In addition, asymp- 5. Sarles H, Sahel J. Cholestasis and lesions of the biliary tract tomatic patients with biochemical in chronic pancreatitis. Gut 1978; 19: 851-857. evidence of choles- 6. Scott J, Summerfield JA, Elias E, Dick R, Sherlock S. Chronic tasis have been shown to develop progressive hepatic pancreatitis: a cause of cholestasis. Gut 1977; 18: 196-201. pathology. Multifocal hepatitis was present in three 7. McCollum WB, Jordan PH. Obstructive jaundice in patients dogs at the time of surgery. Suppurative cholangitis with pancreatitis without associated biliary tract disease. Ann developed postoperatively in dog 5 and the dog died Surg 1975; 182: 116-120. five weeks 8. Twedt DC. Exocrine pancreatic neoplasia. In: Withrow SJ, ed. postoperatively. With simple relief of Oncology Notes. Fort Collins, Colorado: Colorado State Uni- obstruction and no further specific therapy, there was versity, 1981: 397-398. a marked decrease in the activities of hepatic enzymes 9. Strombeck DR, Wheeldon E, Harrold D. Model of chronic pan- and serum bilirubin concentrations (Table 2) in those creatitis in the dog. Am J Vet Res 1984; 45: 131-136. dogs that survived greater than one week. 10. Eckhauser FE, Knol JA, Strodel WE, Achem S, Nostrant T. The icte- Common bile duct strictures associated with chronic pancrea- rus, elevated hepatic enzymes, and hepatic changes titis. Am Surg 1983; 49: 350-358. were probably the result of obstruction. 11. Grodinsky C, Block MA. Persistent obstructive jaundice asso- The syndrome described in this paper appears dis- ciated with chronic pancreatitis. Henry Ford Hosp J 1980; 28: tinct from that occuring during or immediately after 55-59. an attack of 12. Aranha GV, Prinz RA, Freeark RJ, Greenlee HB. The spec- acute pancreatitis. In that instance, icte- trum of biliary tract obstruction from chronic pancreatitis. Arch rus is usually associated with elevations of amylase and Surg 1984; 119: 595-600. lipase activities and typical clinical signs. The exact 13. Creaghe SB, Roseman, DM, Saik RP. Biliary obstruction in cause of this transient icterus during acute pancreatitis chronic pancreatitis: indications for surgical intervention. Am is not known (2), however of Surg 1981; 47: 243-246. release proteases and 14. Burcharth F, Kam-Hansen L. Obstructive jaundice in pancrea- inflammation of the pancreas surrounding the bile duct titis investigated by percutaneous transhepatic cholangiography. are thought to be responsible. Surgical intervention is Scan J Gastroenterol 1979; 13: 589-591.

physiological disturbance present in the atrioven- cardiographic features of second degree heart block tricular node, in the bundle of His and/or in both of Mobitz Type II, particularly as distinct from second the bundle branches of the His-Purkinje system. These degree heart block Mobitz Type I. Second degree atrio- disorders which interrupt transmission of the sinoatrial ventricular block occurs when some P waves are not impulse to the ventricular myocardium tend to be followed by a QRS complex; however, each QRS com- irreversible. However, second degree heart block, plex is associated with and preceded by a P wave. Mobitz Type I, usually involves a disorder at the level Second degree atrioventricular block is classically of the atrioventricular node which is frequently divided into Mobitz Type I, and Mobitz Type II. There reversible. has been some interest in further dividing second Given the tendency to progress to third degree heart degree atrioventricular block based on QRS duration; block, it behooves us to be familiar with the electro- (continued on page 670)

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