Spontaneous biloma due to an intrahepatic cholangiocarcinoma: An extremely rare case report with long term survival and literature review.

Cholangiocarcinomas are tumors that arise from the ductal epithelium of the intrahepatic or extra-hepatic bile ducts. Patients are usually asymptomatic or may present with weight loss, fatigue, loss of appetite and abdominal pain (intrahepatic cholangiocarcinomas) or jaundice (extra-hepatic cholangiocarcinomas). Subcapsular bile vessel rupture, due to intrahepatic cholangiocarcinoma, is an extremely rare clinical presentation, which is an emergent and potentially life-threatening complication. We report the case of a 79-year-old female patient suffering from an intrahepatic cholangiocarcinoma that completely obliterated the left main hepatic duct. This obstruction in intrahepatic bile flow had resulted in intraperitoneal rupture of subcapsular bile vessels (not infiltrated by the tumor) of the left liver lobe and formation of spontaneous biloma. The patient was admitted for acute abdominal pain. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) revealed the tumor and an upper abdominal fluid collection. Since the patient was hemodynamically stable and afebrile, a CT-guided percutaneous aspiration of the collection was undertaken, showing a biloma. A left hepatectomy was performed two weeks later and today, sixty months since the incident, the patient enjoys good health, with no signs of local recurrence or distant metastases. Intraperitoneal rupture of bile ducts and subsequent spontaneous biloma formation, due to an intrahepatic cholangiocarcinoma which completely obstructed the left main hepatic duct, is a unique situation and this is the first time to be reported. Prompt surgical management can lead to successful treatment of this rare and difficult entity.

Cholangiocarcinoma

Intrahepatic Cholangiocarcinoma

Aspartate Aminotransferase

Alanine Transaminase

Total Bilirubin

Gamma-glutamyltransferase

Alkaline Phosphatase

Carcinoembryonic Antigen

Alpha Fetoprotein

Carbohydrate Antigen or Cancer Antigen 19-9

α-Amylase

Endoscopic Retrograde Cholangiopancreatography

Introduction

Cholangiocarcinoma (CCA) is a rare malignant neoplasm of the biliary tree, accounting for about 10% of all primary liver tumors [1], [2]. Based on its location, CCA is classified as intrahepatic and extra-hepatic (perihilar or distal) [3]. As for intrahepatic CCA (IH-CCA), progression is usually silent and most patients are diagnosed at an advanced stage, leaving no place for curative treatment, but to only about one third of patients [4]. Five-year survival after R0 resection (no macroscopic or microscopic evidence of tumor infiltration at the resection margins; curative resection) is in the range of 23–42% [3], [5].

Biloma is an encapsulated bile collection outside the biliary tree [6]. The majority of bilomas are caused by trauma or iatrogenic injury. Spontaneous bilomas are very rare.

We report the unique case of a patient who presented with the clinical picture of acute abdomen, as a result of intraperitoneal rupture of subcapsular bile vessels of the left liver lobe, caused by an IH-CCA which had obstructed the left main hepatic duct, leading to spontaneous biloma formation. The work has been reported in line with the SCARE criteria [7].

Presentation of case

A 79-year-old female patient presented to her local hospital due to a dull epigastric pain and nausea for the last 3 days. Her past medical history included arterial hypertension, dyslipidemia, mild gastro-esophageal reflux disease and left knee osteoarthritis. Upon admission, her clinical examination was unremarkable and laboratory investigation was normal, except for elevated liver function tests (AST: 57 IU/L, ALT: 97 IU/L, TBIL: 1,3 mg/dL, γ-GT: 267 IU/L, ALP: 307 IU/L). During the next days her clinical condition deteriorated (she developed abdominal guarding and rebound tenderness at the epigastrium). Abdominal ultrasonography (U/S) and computed tomography (CT) imaging revealed a left liver lobe mass, with focal dilatation of the intrahepatic bile ducts around the lesion, findings suggestive of the presence of an intrahepatic cholangiocarcinoma. A sub-diaphragmatic fluid collection was also detected, as well as a large complex cystic-solid left adnexal mass lesion, measuring 86 × 73 mm. There was no evidence of metastatic disease.

The patient was subsequently referred to our hospital for further investigation and treatment. Anti-echinococcus antibodies and tumor markers (CEA: 1.7 ng/mL - normal upper range <5, AFP: 4.1 ng/mL - normal upper range <9) were negative and CA 19-9 was slightly elevated at 51 U/mL (normal upper range <35). Abdominal magnetic resonance imaging (MRI) revealed the presence of an ill-defined mass, of 53 mm in maximal diameter at liver segment IV, while segmental dilatation of the left intrahepatic bile ducts was seen on magnetic resonance cholangiopancreatography (MRCP), due to the presence of an intraductal polypoid mass. Two separate fluid collections under the left liver lobe that spanned towards the omentum were also detected (Fig. 1). Percutaneous drainage under CT-guidance defined the fluid as bile (BIL: 27.9 mg/dL, aAMS: 30 IU) and a drainage tube was left in place, resulting in clinical improvement. Due to the ongoing bile leak, an ERCP and stent insertion was attempted with no success, since the left bile duct was totally obstructed by the tumor. Laparotomy was decided.

Fig. 1

Findings on Magnetic Resonance Cholangiopancreatography (MRCP): complete left main duct obliteration and peripheral bile duct dilatation, typical for cholangiocarcinoma (red arrow) and site of subcapsular bile duct rupture (blue arrow), with subsequent bile leak, leading to two distinct bilomas (the small one depicted with *, the greatest with **). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

At theater, after a bilateral subcostal incision with small vertical extension (‘Mercedes-Benz’) a left liver lobe tumor was discovered (segment IVb), with dilation and rupture of the subscapular bile ducts in segment III, which caused the biloma (Fig. 2). Typical left hepatectomy was performed. Pathological examination showed an intrahepatic cholangiocarcinoma of the mixed mass-forming/periductal-infiltrating type: the tumor had a mixed pattern of development, i.e. in part it exhibited a longitudinal growth pattern along the course of the left main hepatic duct (at a distance of 3.5 cm), and in part it expanded radially in the liver parenchyma as a well-defined mass at segment IVb (sizing 5.8 × 3.6 × 3.1 cm), extending up to the liver capsule. The site of bile leak due to capsular rupture was located at segment III. Resection margins (left hepatic duct, left portal vein and left hepatic artery) were free of invasion (R0) and lymph nodes were free of invasion (pT4N0). The ovary was found to carry a mucinous cystadenoma (cystic component) combined with a fibroma (solid component).

Fig. 2

Intraoperative photo, highlighting the dilated subcapsular bile ducts. The site of spontaneous rupture is just above, covered by the omentum that is attached to it.

The patient received no adjuvant chemotherapy and today, sixty months after the procedure, she enjoys good health with no signs of local recurrence or distant metastases at routine oncological follow-up (Table 1).

Table 1

Timeline representation of the case report.

Timeline	Event	Result
Day 0	Onset of epigastric pain	No action
Day 3	Admission to local hospital	Typical workup inconclusive
Day 6	Symptoms of acute abdomen	US + CT performedPotential diagnosis: CCA
Day 7	Referral to tertiary center	Additional workup (tumor markers, MRI, MRCP)
Day 8	No laparotomy yet decided (patient stable, afebrile)	CT-guided percutaneous drainage
Day 12	Ongoing bile leak through drains	ERCP decided
Day 13	ERCP unsuccessful (left hepatic duct obstructed)	Laparotomy decided
Day 14	Exploratory laprotomy (left hepatectomy + oophorectomy)	Patient's uneventful recovery
Day 40	Pathological report obtained	IH-CCA
Month 60	Oncologic follow-up (clinical examination, liver tests, tumors markers, CT Chest, abdomen every 6 months)	No locoregional or distant metastases discovered

Discussion

Cholangiocarcinomas (CCAs) are tumors that arise from the ductal epithelium of the intrahepatic or extrahepatic bile ducts [4]. They comprise the second most common primary liver tumor, accounting for 10–15% of all non-metastatic hepatic malignancies [3], [4], [8]. Histologically, the great majority of these tumors (around 90%) are adenocarcinomas, but other variants such as squamous cell carcinomas and clear cell carcinomas have also been described [9].

Although spontaneous rupture of the mass itself can be seen with primary liver tumors such as hepatic adenomas or hepatocellular carcinomas, it is extremely rare for IH-CCAs [10]. Only a few cases have been reported to date. In the study by Chong et al., a peripheral CCA was found to be the cause of hemoperitoneum in a 45 year-old female patient, suffering from HBV infection and cirrhosis [10]. Watanabe et al. described the simultaneous presence of CCA and hepatocellular carcinoma, with intraperitoneal bleeding discovered at autopsy [11]. In the case presented by Akatsu et al., the patient had intra-abdominal bleeding and hypovolemic shock, as a result of ruptured CCA [12]. Transcatheter arterial embolization was successfully employed to control the hemorrhage and the patient received definite surgical treatment 3 weeks later.

The term biloma describes an encapsulated extrahepatic collection of bile. It was first introduced by Gould and Patel in 1979 [6]. Bilomas are usually formed after operations in the biliary system, after ERCP or trauma. The majority of the collections are subphrenic or subhepatic. Subcapsular bilomas are less common and the main causes are surgery and trauma. Bilomas that are not caused by trauma or an operation or intervention are called spontaneous bilomas. The most common cause of spontaneous biloma is obstruction of the extrahepatic biliary tract due to choledocholithiasis [13]. Hepatic subcapsular spontaneous bilomas are very rare. The exact mechanism of spontaneous biloma formation is unclear. It seems that the main factor is the raised intraductal pressure, secondary to biliary tree obstruction by stone, stricture or tumor. Mushtaque et al. report three cases of spontaneous hepatic subcapsular biloma formation [14]. In two cases the cause was choledocholithiasis and in one case it was caused by a distal cholangiocarcinoma. Also, Rodriguez et al., report an interesting case of a patient with spontaneous rupture of right bile vessels due to a head of pancreas tumor, leading to a right pleural and retroperitoneal biloma. He was managed initially with percutaneous and internal-external biliary drainage and underwent a Whipple procedure in a second stage [15].

Chung et al. report bile leak as a result of spontaneous rupture of intrahepatic bile ducts, following portal vein embolization, in a patient with perihilar cholangiocarcinoma [16]. In their study, percutaneous drainage of the bilomas was initially performed, followed by right hepatectomy, caudate lobectomy and resection of extrahepatic bile ducts involved; however no follow-up data of the patient are provided. Finally, Ranjeev et al. report a case of iatrogenic intrahepatic biloma formation during endoscopic treatment of CCA [17].

Our patient had an intrahepatic cholangiocarcinoma of the left liver lobe that was completely obstructing the left main duct. Subsequent dilatation of the left liver lobe bile ducts resulted in spontaneous rupture of segment III bile ducts and biloma formation. Choloperitoneum was avoided since the omentum had isolated the fluid collection leading to biloma formation. We decided not to perform urgent laparotomy, since the clinical condition of the patient was stable. Percutaneous drainage helped in establishing the diagnosis, but was unsuccessful in controlling the ongoing bile leak and endoscopic stenting of the left main duct (through ERCP) was impossible, since the left duct was completely obliterated by the tumor. We felt that percutaneous biliary drainage prior to liver resection would not be beneficial as the patient was not jaundiced. It seems that the CCA originated as an intra-ductal growing tumor and eventually developed as an intrahepatic mass towards the periphery of liver parenchyma.

Conclusion

In conclusion, we report the unique situation of spontaneous rupture of peripheral bile ducts due to obstructing intrahepatic CCA that eventually resulted in biloma formation. To our knowledge, this appears to be the first case of intrahepatic CCA presenting with spontaneous bile leak which treated with a left hepatectomy resulting in long term (60 months) disease-free survival. Although spontaneous bilomas due to cholangiocarcinomas are extremely rare, it should be considered in the differential diagnosis of patients presented with epigastric pain, hepatic tumor and peri-hepatic fluid collection. Aggressive surgical management can offer long term survival.

Ethical approval

None.

Sources of funding

None.

Conflict of interest statement

None declared.

Author contribution

Georgios K. Georgiou, Michalis Fatouros and Georgios Glantzounis conceived and designed the study. Georgios K. Georgiou, Athina Tsili, Anna Batistatou, Alexandra Papoudou-Bai, Georgios Papadopoulos and Georgios Glantzounis participated in the acquisition of data, analysis and interpretation of data. Georgios K. Georgiou and Georgios Glantzounis drafted the article and revised it critically for important intellectual content. All authors approved the final version of the manuscript to be submitted.

Guarantor

Dr Georgios Glantzounis – MD, PhD, FEBS.

Associate Professor of Surgery and Transplantation, Department of Surgery.

Medical School University of Ioannina, 45 110 Ioannina, Greece.

Tel: 00302651099695, 00306984189292 fax: 00302651099890.

e-mail: gglantzounis@uoi.grgglantzounis@gmail.com.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.