A 67-year-old Japanese woman with chondrodystrophy was referred to our hospital for obstructive jaundice. Her urine color had become darker, and her appetite had decreased during the past 2 weeks.
Physical examination
The patient had a developmental disorder of chondrodystrophy; her height was 127 cm, and her weight was 37 kg. As a result of her disease, she was found to have weak muscle strength in her lower legs. Palpebral conjunctiva was not anemic, and bulbar conjunctiva was icteric. The abdomen was soft and flat. No physical symptoms associated with immunodeficiency were noted.
Vital signs included a pulse of 86/min, regular blood pressure of 129/59 mm Hg, respirations of 12/min, and temperature of 37.2 °C
At the time of referral, laboratory analysis showed a white blood count of 14,300 × 103/µL with 35.0% neutrophils and C-reactive protein of 2.78 mg/dL (normal range, < 0.50 IU/L). Liver function test showed a total bilirubin of 5.4 mg/dL (normal range, 0.2–1.0 mg/dL), direct bilirubin 4.3 mg/dL (normal range, 0.0–0.4 mg/dL), aspartate 181 IU/L (normal range, 9–35 IU/L), and alanine aminotransferase 265 IU/L (normal range, 5–30 IU/L), lactate dehydrogenase 528 IU/L (normal range, 106–211 IU/L), gamma- glutamyltransferase 538 IU/L (normal range, 10–55 IU/L), and alkaline phosphatase 1232 IU/L (normal range, 104–338 IU/L).
Viral hepatitis screening was negative, with an antinuclear antibody titer of 320 (normal range, < 40) and negative antimitochondrial antibody. Serum IgG4 level was normal at 35.7 mg/dL (normal range, 4.8–105 mg/dL), whereas the serum CA19-9 level was elevated at 742.2 U/mL (normal range, < 37.0 U/mL).
Abdominal echogram has detected a solid mass measuring 19. mm in the hilar bile duct (Fig. 1). Computed tomography of the abdomen revealed a solid mass in the hilar bile duct (Fig. 2a, circle), and a slight dilatation of the intrahepatic bile ducts in the left lobe (Fig. 2b, arrow) was also observed. Abrupt stenosis of the primary biliary confluence was observed on magnetic resonance cholangiopancreatography (Fig. 3, arrow).
In order to improve biliary obstruction, an endoscopic nasobiliary drainage (ENBD) tube was placed in the left biliary duct on the sixth day of hospitalization (Fig. 4). On the 10th day of hospitalization, the patient inappropriately removed the ENBD tube, which was replaced on the 12th day of hospitalization.
Biliary cytology failed to detect any malignant findings. However, abdominal ultrasonography and abdominal computed tomography examination confirmed a solid mass in the hilar bile duct, and cholangiography showed severe stenosis of the bile duct. In addition, serum CA19-9 was found to be elevated at 742.2 U/mL. Thus, the bismuth type II hilar cholangiocarcinoma could not be excluded. Based on the results of the preoperative workup, we considered surgical exploration for a biliary occupying lesion suspicious for cholangiocarcinoma.
Operation
An exploratory laparotomy was performed 2 weeks after biliary drainage. Thorough peritoneal inspection revealed no metastatic disease. The hilar hepatic duct was determined to be enlarged and clogged in the lumen. After confirming the location of the mass in the biliary tract using intraoperative ultrasonography, we resected the extrahepatic bile duct and prepared the intraoperative frozen section diagnosis from the resected specimen. Using blunt dissection, the gallbladder, cystic duct, extrahepatic bile ducts, hepatoduodenal lymph nodes, and soft tissues were dissected from the portal vein and hepatic artery, which were completely skeletonized (Fig. 5a). The isolated distal bile duct was then transected on the side of the pancreas away from the bile duct mass. While pulling the distal stump of the bile duct in a ventral direction, the hilar structures (i.e., the biliary confluence and the bases of the left and right hepatic ducts) were exposed. The proximal ducts were then transected 10 mm or more away from the biliary confluence at both right and left hepatic ducts. From the separated left hepatic duct, three bile duct orifices (i.e., B2 + 3, B4, and B6 + 7) have formed on the liver side, whereas, from the separated right hepatic duct, one orifice (B5 + 8) has formed on the liver side. Aberrant drainage of the right posterior duct into the left hepatic duct was observed. In total, four bile duct orifices were noted at the transected bile plate: B2 + 3, B4, B6 + 7, and B5 + 8 (Figs. 5b, c).
The extrahepatic bile ducts including the biliary confluence were then removed en bloc. The thickness of the ductal wall was observed macroscopically throughout the resected extrahepatic biliary tract. A circumferential mass lesion (0.6 cm x 1.0 cm, white, elastic, and hard) was determined in the bile duct 8 mm distal from the biliary confluence. About 10 black bile duct stones, which are 5–6 mm in size, were detected in the lumen of the resected bile duct. The macroscopic appearance of the mass was indicative for a benign lesion, although we could not completely rule out its malignancy.
From the intraoperative frozen sections of the resection margins, atypical cells were found in the stump on the side of the pancreas, and malignancy could not be ruled out. Thus, we reported the stump as positive. We performed additional excision of the bile duct to just above the pancreatic head. The resected specimens have showed multiple strictures inside the common bile duct, numerous calculi in the lumen, and little free space (Fig. 6).
B2 + 3 and B6 + 7 were neighboring ducts. The two neighboring duct orifices were determined to be joined by two interrupted stiches to prepare them for anastomosis as a common channel. We performed a Roux-en-Y cholangiojejunostomy. In this procedure, three orifices in the jejunum were created because of the distance between the ducts. An anastomosis was performed in three locations at each of the bile ducts and jejunal orifices to complete the retrocolic Roux-en-Y biliojejunal anastomoses.
The patient’s postoperative course was deemed uneventful. No other fungal infection focus was observed. The patient was discharged from our hospital 23 days after the surgery with no antifungal treatment. Approximately 4 years after the operation, she is in good health without any signs of fungal infection.
Histologically, a great number of large granulomatous lesions were found in the left and right hepatic ducts, their confluence, and the lower bile duct, and necrotic tissue was formed in the central part (Fig. 7a). Multinucleated giant cells (Fig. 7b, arrow) were also observed. Infiltration of inflammatory cells and fibrosis were observed around the granuloma, and an associated thickening of the bile duct wall was found remarkable. Erosion and ulceration were noticeable in the bile duct lumen. No obvious malignant findings were noted. Histopathological findings consisted of granulomatous cholangitis with necrosis, accompanied by bile duct thicking. In the necrotic tissue of the central part of the granuloma, Periodic acid–Schiff (PAS) stains positive structures that consider yeast and pseudohyphae are scattered (Figs. 8ab). This finding was consistent with fungus, with unclear branches and septa, and was considered to be Candida. Because Ziehl-Neelsen staining was negative, we ruled out infection with acid-fast bacillus. The final histopathological diagnosis of the surgical specimens showed granulomatous cholangitis based on fungal infection.