Intraductal papillary mucinous neoplasm of the bile duct with choledochoduodenal fistula: a case report and literature review

Introduction

The intraductal papillary tumor originates from the biliary epithelial cells and often has a papillary structure and lacks an ovarian-like stroma. In 2010, the World Health Organization (WHO) classified intraductal papillary neoplasm of the bile duct (IPNB) as a separate group of biliary neoplastic diseases, accounting for 10% of all bile duct tumors; as a precancerous lesion, 28–37% of IPNB can secrete mucus and is characterized as intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) (1,2).

We presented a case of IPMN-B that complicated with choledochoduodenal fistula and conducted a thorough review of all similar cases from the PubMed database to provide important references for clinical practice (Table 1) (3-10). We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-54/rc).

Case presentation

A 61-year-old female patient was admitted to Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University due to repeated abdominal pain with fever for more than 9 years. The patient was diagnosed with left intrahepatic bile duct and cholecystolithiasis 9 years ago and her symptoms were relieved after receiving partial left hepatectomy as well as cholecystectomy. The patient had occasional episodes of abdominal pain with mild symptoms during the past few years. Physical examination upon hospital admission revealed severe icteric sclera and epigastric tenderness. Laboratory results were as follow: white blood cell (WBC) count 5.8×10⁹/L, neutrophilic granulocyte percentage 74.9%, C-reactive protein (CRP) 37 mg/L; alanine aminotransferase (ALT) 299 U/L, aspartate aminotransferase (AST) 152 U/L, γ-glutamyl transpeptidase (γ-GTP) 718 U/L, alkaline phosphatase (ALP) 620 U/L, total bilirubin (TBil) 350 µmol/L, conjugated bilirubin (CB) 248.3 µmol/L, carcinoembryonic (CEA) 1.46 µg/L, carbohydrate antigen 199 (CA199) 11 kU/L, alpha-fetoprotein (AFP) 5.9 µg/L. Contrast-enhanced computerized tomography (CT) (Figure 1) showed severe dilatation of common bile duct and extrahepatic bile duct. The maximum diameter of the common bile duct was about 3.6 cm, with homogeneous low-density shadow in the lumen. No obvious abnormity was observed after enhancement. In addition, the CT results showed that the wall of common hepatic duct near the bifurcation was unevenly thickened and identified a few irregular soft tissue shadow processes with mild enhancement after enhancement. Magnetic resonance cholangiopancreatography (MRCP) (Figure 2) showed the intra- and extrahepatic bile ducts were markedly dilated, and the signal of the bile ducts was uneven, with flocculent short T2 signal shadows. Endoscopy (Figure 3) showed a large amount of mucus flowing out from the fistula above the papilla. Selective bile duct cannulation through the fistula was conducted successfully and cholangiography showed significant dilatation of the extrahepatic bile duct. The SpyGlass examination (Figure 4) showed “fish-scaly or coral-like” changes in the mucosa of the right anterior branch bile duct, hilum and lower common bile duct, slightly protruding from the bile duct lumen, with extensive local accumulation of mucus. IPMN-B was diagnosed and nasobiliary drainage was placed for the patient. Aspiration through endoscopic nasobiliary drainage (ENBD) was conducted when the drainage volume was small. About 100–250 mL of bile was drained per day. Reexamination after receiving 1 week of treatment showed ALT 103 U/L, AST 56 U/L, γ-GT 371 U/L, AKP 309 U/L, TBil 191 µmol/L, and CB 148 µmol/L. SpyGlass showed that IPMN-B diffused the intra- and extrahepatic bile ducts, and partial hepatectomy apparently failed to remove the lesion; the patient had chronic liver disease, hepatic insufficiency, and cholestasis, and was poorly treated with conservative medical therapy, liver transplantation was recommended. However, the transplantation was refused by the patient and her family who deceived to only receive conservative treatment. The patient was then discharged with nasal biliary drainage and oral antipyretic and hepatoprotective drugs. Two weeks later, the patient’s outpatient follow-up showed ALT 157 U/L, AST 87 U/L, γ-GT 183 U/L, AKP 307 U/L, TBil 59 µmol/L, and CB 45 µmol/L, then the patient’s nasobiliary duct were removed. One month later, the patient again showed abdominal pain, fever, jaundice and other signs of obstruction with infection, and was discharged from the hospital after ERCP biliary stenting. The patient’s condition worsened and passed away 9 months later. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s son for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 Contrast-enhanced CT showed severe dilatation of intra- and extrahepatic bile duct, the wall of duct was unevenly thickened. (A) Dilated intrahepatic bile ducts (white arrows); (B) dilated common hepatic bile ducts (white arrow), unevenly thickened duct wall (red arrow), residual cystic duct (thick white arrow); (C) dilated common bile ducts (white arrow), unevenly thickened duct wall (red arrow). CT, computerized tomography.

Figure 2 MRCP showed the intra- and extrahepatic bile ducts were markedly dilated, and the signal of the bile ducts was uneven, with flocculent short T2 signal shadows. (A) Dilated intrahepatic bile ducts (white arrow), flocculent density shadow in the lumen (red arrow); (B) dilated common bile ducts (white arrows), residual cystic duct (thick white arrow). MRCP, magnetic resonance cholangiopancreatography.

Figure 3 ERCP: endoscopy showed a large amount of sticky mucus flowing out from the fistula above the papilla and cholangiography showed significant dilatation of the common bile duct. (A) Sticky mucus (red arrow) and the fistula (white arrow); (B) the fistula (red arrow) and the papilla (white arrow); (C) the dilated common bile duct (white arrow). ERCP, endoscopic retrograde cholangiopancreatography.

Figure 4 The SpyGlass examination showed “fish-scaly or coral-like” changes in the mucosa.

Discussion

IPMN-B is often regarded as a similar disease as intraductal papillary mucinous neoplasm of the pancreas (IPMN-P) disease in the bile duct. The incidence of IPMN-P with fistula formation is 1.9–6.6% (11,12), which is more common than IPMN-B. This difference may be related to the higher occurrence of pancreatic enzymes induced pancreatic autodigestion in IPMN-P. Combining the 8 cases of IPMN-B with fistula formation that were retrieved from the PubMed database and the case mentioned in this report, a total of 9 cases were analyzed (3-10).

Differential diagnosis and the extent of the disease can be measured by biopsy of IPMN lesions and exfoliative cytology of biliary irrigation fluid using SpyGlass under direct visual observation, which is more accurate compared to the conventional endoscopic retrograde cholangiopancreatography (ERCP) in diagnosis. In addition, the results of SpyGlass examination can provide important information for making treatment plans. For instance, the SpyGlass results in this case showed diffuse intrahepatic and extrahepatic bile ducts involvement and indicated liver transplantation rather than partial hepatectomy. Even though there is no consensus on the differentiation of benign and malignant features of biliary and pancreatic duct diseases under direct vision of SpyGlass examination, obvious masses or dilated and twisted vessels often indicate malignant lesions (13). The sensitivity and accuracy of direct observation under SpyGlass were 78% and 80% to 96.7% respectively, which were higher than those of ERCP and biopsy under SpyGlass (14). Robles-Medranda et al. recently proposed a new diagram to differentiate benign and malignant lesions, benign lesions are generally micronodular or villous avascular while malignant lesions can be manifested as flat, elevated, ulcerative or honeycomb, with irregular or distorted vascular formation (15). However, the malignant lesions need to be further differentiated from lesions of biliopancreatic stent removal and traumatic ulcers. The “fish-egg uplift” sign of bile duct feature under SpyGlass examination is not unique to IPMN. Nagayoshi et al. reported that fibroplasia after stent implantation may also show papillary hyperplasia (16). Therefore, it is difficult to differentiate benign and malignant lesions in patients who received stent implantation or biopsy based on just direct visual observation.

The large amount of mucus secreted in IPMN-B can block bile duct and impede biliary drainage. Among all 9 IPMN-B cases we reviewed, 8 (88.9%) developed abdominal pian and 5 (55.6%) developed jaundice. For IPMN-B patients who complicated with fistula formation, although mucus can drain from the fistula, it remains inadequate and cannot completely eliminate clinical symptoms. Fistula formation is not unique to malignant IPMN-B, it can also occur in benign IPMN-B, though through a different a mechanism. In benign IPMN-B, the major pathogenesis for fistula formation is due to the increased pancreatic duct pressure caused by massive mucus secretion and inflammation while direct invasion of cancer cells also plays an important role in forming the fistula in malignant cases (3-9,11,12). IPMN-B could form fistula with surrounding organs, and the commonly involved organs were duodenum (5/9, 55.6%), stomach (5/9, 55.6%) and pancreatic duct (1/9, 11.1%). Single fistula formation was more common while 22.2% (2/9) patients had multiple fistula formation. Even though IPMN-B can originate from any part of the intrahepatic and extrahepatic bile ducts, it more likely to be originated from left intrahepatic bile duct therefore fistula formation in the left intrahepatic bile duct is also more commonly observed (6/9, 66.7%).

IPMN-B is a precancerous disease and surgery is the first-line treatment. The 5-year survival rate of IPMN-B patients who received surgery for respectable tumor is more than 80% (2,17,18). Even though choledochoduodenal fistula may drain mucus and bile but is not sufficient to prevent the blockade of bile duct. In this case we reported, prolonged cholestasis led to cholestasis, hepatic cirrhosis and hepatic insufficiency. The patient we reported here had repeated retrograde biliary infection and died 10 months later due to hepatic failure. Therefor for IPMN-B patients with fistula formation, surgical removement of IPMN-B lesion and fistula should be considered first. For patients who cannot tolerate surgery or are unwilling to undergo surgery, external drainage treatments such as ENBD and percutaneous transhepatic cholangial drainage (PTCD) should be considered rather than internal drainage since drainage devices are often blocked by thick mucus. If the catheter is blocked, external suction can be performed. Bile duct stent placement under endoscope, endoscopic ultrasonography (EUS) guided drainage and other drainage methods may also be considered.

Limitations of this study: (I) the medical history of the patient in this case was incomplete and some data were missing; (II) only 1 case was reported; (III) not all diagnoses reviewed in this report were confirmed by pathology.

Conclusions

SpyGlass can allow direct visualization of lesion morphology and define the extent of the lesion. Endoscopic intervention relieves biliary obstruction to some extent in patients with high operative risk or reluctance to undergo surgery.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-54/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-54/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-54/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s son for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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