A 57-year-old male was referred to our hospital due to symptomless dilation of the intrahepatic bile duct in January 2010. Mild liver dysfunction was detected during a laboratory examination, while jaundice was not observed [total bilirubin (T-bil), 0.9 mg/dL; alkaline phosphatase (ALP), 599 U/L; aspartate aminotransferase (AST), 44 U/L]. Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) showed dilation of the bilateral intrahepatic and extrahepatic bile ducts and a nodule measuring 1.5 cm in the common hepatic duct. Endoscopic retrograde cholangiography (ERC) revealed bile duct irregularities extending from the bilateral hepatic ducts to the peripheral bile duct. In addition, the common bile duct was dilated (to 1.5 cm in diameter) and contained a nodule measuring 1 cm in diameter (Fig. 1A). Peroral cholangioscopy (POCS) revealed mucinous discharge from the ampulla of Vater, and the bile duct was full of mucus. In addition, many round tumors (salmon roe-like lesions) were observed in the region from the middle common bile duct to the common hepatic duct (Fig. 1B/C). The nodule in the common hepatic duct was biopsied, and a pathological examination revealed intraductal papillary adenoma. The lower bile duct and the left hepatic duct were also biopsied, which led to the lesions within them being diagnosed as intraductal papillary adenoma. A cytological examination of the mucus did not reveal any evidence of malignancy. Based on these findings, the patient was diagnosed with IPNB, which was mainly located in the region from the middle common bile duct to the intrahepatic bile duct of the right and left hepatic lobes.
A watchful waiting strategy was employed because total resection of the irregular bile duct was impossible, and none of the histological examinations had detected findings that were suggestive of malignancy. However, 6 months later he was admitted to our hospital with jaundice and liver dysfunction [T-bil, 6.1 mg/dL; ALP, 1456 U/L; AST, 827 U/L]. MRCP and CT revealed that the nodule in the common hepatic duct had increased in size from 1.5 cm to 3 cm and that the hilar bile duct was obstructed (Fig. 2A/B/C/D/E). On the other hand, CT demonstrated that the irregularities extending from the left hepatic duct to the umbilical portion had disappeared (Fig. 2F/G). At this time, we determined that the IPNB, including the nodule and the irregular bile duct, could be resected via right hepatectomy and extrahepatic bile duct resection. An endoscopic nasobiliary drainage tube was inserted into the left hepatic duct, and the patient's jaundice was ameliorated. At the same time, the nodule was biopsied again, and a pathological examination revealed intraductal papillary adenoma. It was estimated that the remnant liver would be 27.7% of its original size after right hepatectomy combined with resection of the caudate lobe, and percutaneous transhepatic portal vein embolization was performed. Three weeks later, the estimated size of the remnant liver had increased to 36.6%. Right hepatectomy combined with resection of the caudate lobe and extra-hepatic bile duct followed by reconstruction via left hepaticojejunostomy combined with regional lymph node resection was conducted in April 2010.
An intraoperative histological examination of frozen sections demonstrated that the stumps of the left hepatic duct and lower common bile duct were not malignant, but intraductal papillary adenoma was detected. The duration of the operation was 400 min, and the estimated amount of intraoperative blood loss was 1400 g. During a macroscopic examination, a papillary tumor measuring 3.0 x 1.5 cm was observed in the region extending from the right hepatic duct to the middle common bile duct (Fig. 3A). A histological examination showed that the tumor was mainly composed of intraductal papillary adenoma; however, some part of it was composed of intraductal papillary adenocarcinoma in situ (Fig. 3B/C). An immunohistochemical examination of the tumor revealed positivity for mucin 6 (MUC-6) and negativity for mesothelin, cyclin D1, caudal type homeobox transcription factor 2 (CDX-2), and HIK. Consequently, the tumor was diagnosed as a gastric type IPNB containing carcinoma in situ. No lymph node metastasis (0/8) was detected, and the lesions in the stump of the lower bile duct and the left hepatic duct were diagnosed as intraductal papillary adenoma. Postoperative bile leakage (International Study Group of Liver Surgery grade B) occurred and was cured by drain management. The patient was discharged at 41 days after surgery.
No adjuvant chemotherapy was administered, but 3-monthly abdominal CT or magnetic resonance imaging (MRI) scans and blood examinations were performed. The patient's T-bil, ALP, and AST levels normalized after the liver resection, while the intrahepatic bile duct of the remnant liver was slightly dilated (to 1 cm) at its junction with the left hepatic duct. At 14 postoperative months, the patient was admitted to our hospital due to cholangitis combined with jaundice and liver dysfunction [C-reactive protein (CRP), 7.7 mg/dL; T-bil, 6.2 mg/dL; ALP, 1486 U/L; AST, 140 U/L]. CT revealed dilation of the B2 and B3 ducts (to 0.5 cm). However, no tumors or stones were present in the hepaticojejunostomy or the intrahepatic bile duct. Antibiotic treatment improved the patient's jaundice and liver dysfunction. At 23 postoperative months, cholangitis combined with jaundice and liver dysfunction recurred, but they were successfully treated with antibiotics. At 39 postoperative months, cholangitis combined with severe jaundice and liver dysfunction was detected [CRP, 12.6 mg/dL; T-bil, 13.1 mg/dL; ALP, 3236 U/L; AST, 327 U/L]. MRI revealed dilation of the B3 and B4 ducts (to 1 cm), and small papillary tumors were detected in the intrahepatic bile duct (Fig. 4A/B). We considered that the IPNB had recurred and that the cholangitis and liver dysfunction had been caused by mucus. Antibiotic treatment was administered, and the cholangitis disappeared. However, 1 month later the cholangitis recurred again. We decided to perform percutaneous transhepatic bile duct drainage (PTBD) to drain the mucus in the intrahepatic bile duct. A PTBD tube was inserted into the region from the B3 duct to the reconstructed jejunal limb through the hepaticojejunostomy. The discharge from the PTBD tube contained crystallized mucus, but not bile, and could not be drained through a thin tube. The size of the PTBD tube was increased from 7.2 Fr to 12 Fr, and irrigation of the bile duct via the PTBD tube was performed every day concurrently with antibiotic treatment. A cytological examination of the mucus did not reveal any signs of malignancy. The discharge from the PTBD tube gradually changed from crystallized mucus to pure bile, and the patient's jaundice and liver dysfunction were ameliorated. However, cholangitis recurred frequently (at 44, 45, and 47 postoperative months). At 48 postoperative months, a PTBD tube was inserted from the B3 to B2 duct (Fig. 4C). Thereafter, the frequency of cholangitis decreased (it was seen at 51, 57, 63, 65, and 74 postoperative months). The discharge collected from the PTBD tube inserted into the region extending from the B3 duct to the reconstructed jejunum limb contained crystallized mucin, but not bile, while the PTBD discharge collected from the region extending from the B3 duct to the B2 duct was composed of pure bile (amount: 200 ml daily) (Fig. 4D). MRI revealed dilation of the B3 and B4 ducts together with small papillary tumors and dilation of the bile duct in the pancreas combined with papillary tumors. The peripheral side of the B2 duct was not dilated, and no papillary tumors were observed in this region. Thus, the PTBD discharge collected from the region extending from the B3 duct to the B2 duct was important for biliary drainage. The patient has survived for over 7 years since the initial treatment in spite of the frequent occurrence of cholangitis and jaundice, which was treated via careful management of his biliary tract (Fig. 4E).