Continuing Education Activity

A biloma is defined as an abnormal, well-circumscribed, extra-biliary collection of bile. Most bilomas present secondary to iatrogenic or traumatic disruption of the biliary tree. While uncommon, bilomas are associated with significant morbidity and mortality, especially when infected or impinging on surrounding structures. Bilomas may present with varied and subtle symptoms and signs, and therefore physicians must recognize their etiology and presentation to allow prompt diagnosis. This article will review the etiology, pathophysiology, diagnosis, and role of the interprofessional team in managing bilomas.

Objectives:

• Describe the etiology of hepatic bilomas.
• Outline the typical presentation of hepatic bilomas.
• Describe the typical imaging findings of hepatic bilomas.
• Summarize the management options for hepatic bilomas.

Introduction

Gould and Patel coined the term “biloma” in 1979 to describe an encapsulated collection of extrahepatic bile secondary to bile leakage into the peritoneal cavity.[1] However, the term “biloma” has evolved to describe any well-circumscribed intra-abdominal bile collection external to the biliary tree. Disruption of the biliary tree can result in either intrahepatic or extrahepatic biloma formation. The current definition of a biloma does not require it to be encapsulated, although many are.[2] 

The well-circumscribed margins of the biloma differentiate it from ongoing bile leaks or intraperitoneal free bile. “Choleperitoneum” and “bile ascites” are other terms used to describe free bile in the peritoneum; however, some of the literature uses this term and “biloma” interchangeably.[3][4] 

Iatrogenic injury and abdominal trauma causing damage to the biliary tree resulting in a bile leak are the most common causes of biloma formation. Bilomas are associated with infection, ongoing bile leakage, and mass effect on surrounding structures. While uncommon, bilomas are associated with significant morbidity and mortality if not promptly diagnosed and appropriately managed.[2] 

Radiological investigation utilizing ultrasound (US), computed tomography (CT), magnetic resonance (MR) imaging, magnetic resonance cholangiopancreatography (MRCP), or hepatobiliary cholescintigraphy can be used to form a diagnosis and allow planning of accurate minimally invasive management where possible.[5][6][7]

Etiology

Bilomas are most commonly secondary to disruption of the biliary tree by either an iatrogenic or traumatic cause. Iatrogenic causes of biloma formation include laparoscopic cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP), radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), liver transplant, resection, and biopsy.[8][9][10][11][10] While exceedingly rare, spontaneous rupture of the biliary tree and biloma formation has been recognized in the literature.[12]

The increased utilization of laparoscopic cholecystectomy over the past 3 decades has been linked with increased rates of disruption to the biliary tree. Laparoscopic cholecystectomy is associated with bile duct injuries in 0.6 to 1.5% of cases compared with 0.2 to 0.3% of open operations.[13] Biliary leaks following laparoscopic cholecystectomy can be attributed to damage of the common bile duct (CBD), unsuccessful cystic duct ligation, or anatomical variation leading to damaged or leaking accessory ducts.[14] The ducts of Luschka, small ducts draining into the biliary system, are found in the gallbladder fossa in up to 25 to 35% of patients and are vulnerable to damage during laparoscopic cholecystectomy.[15] Fluid collection, including bile leakage, is more common following cholecystectomy than many physicians realize. In 1986, small volume bile leakage was shown to occur in up to 44% of laparoscopic cholecystectomies. However, 95% of these did not require any further management.[16] 

In 1991, Kang et al. showed that 53% of patients who had a US scan 24 hours following laparoscopic cholecystectomy showed small volume fluid collections. However, they determined that a routine postoperative US scan did not change management and was unwarranted.[17] While it has been shown that small fluid collections are common postoperatively, these leaks are mostly small, asymptomatic, and often resolve without treatment. It is thought that many small leaks are never identified. However, significant bile leaks and biloma formation must remain a key differential diagnosis in patients with a complicated recovery following laparoscopic cholecystectomy.[4]

Biloma has been demonstrated following perforation of the common bile duct during ERCP.[18][19] A prospective multicentre study of 5461 patients showed CBD perforation occurred in 0.4% of patients undergoing ERCP. Risk factors identified for perforation of the biliary tree included the precut access to the common bile duct and the presence of malignancy.[19]

Biloma formation was identified in 3.3% of 3284 patients undergoing RFA of hepatocellular carcinoma. However, biloma formation in the context of RFA is a minor complication. Chang et al. examined 109 bilomas following RFA for hepatocellular carcinoma, with only one patient requiring percutaneous drainage of the biloma for infection.[20] Thermal ablation of hepatocellular carcinoma is also associated with biloma formation, with bile leaks identified in 0.1 to 12% of cases. Previous TACE procedures and reduced distance from the biliary tree were both associated with increased risk of bile leak and biloma formation in patients undergoing thermal ablation.[9] TACE procedures for hepatocellular carcinoma are also associated with biloma formation. Zhang et al. demonstrated an incidence of 1.04% in 4695 patients undergoing TACE in 2017.[21]

Liver transplantation is known to be associated with biloma formation. Biloma forms part of a spectrum of post-transplant cholangiopathies. Post-transplant cholangiopathy is one of the most challenging complications following a liver transplant. The pathophysiology of post-transplant cholangiopathy is likely to involve ischemia-reperfusion injury, bile salt toxicity, or immune-mediated injury. Biloma formation after liver transplant can be associated with both anastomotic leakage and non-anastomotic strictures with associated bile duct necrosis and resulting intraparenchymal bile leakage.[11] Liver resection is also associated with biloma formation due to disruption of intrahepatic bile ducts.[22]

Abdominal trauma has been associated with biloma formation. In most cases, this involves blunt trauma to the upper abdomen. Post-traumatic biloma can take 1 to 2 days to appear.[23][24] Spontaneous rupture of the biliary tree is very rare; however, it has been associated with underlying weaknesses in the walls of the bile ducts caused by cholelithiasis, cholangiocarcinoma, hepatic abscess, or tuberculosis infection.[25] Spontaneous rupture of the biliary tree is often a diagnosis of exclusion.[26] Biloma formation is also linked to sickle cell disease, with the likely cause being hepatic infarction.[27] Bile leakage can occur without disrupting the biliary tree, for example, in leakage from the duodenal stump following Billroth II surgery.

Epidemiology

There is little epidemiological data with regards to biloma formation. Most bilomas are secondary to iatrogenic disruption of the biliary tree, and therefore the incidence of bilomas depends on the frequency of interventions. Biloma typically presents in patients aged 60 to 70 years old. This likely reflects the underlying etiological factors requiring invasive intervention rather than a predisposition to complications resulting in biloma formation. There has been no difference shown in the incidence of biloma formation between male and female patients.[28] 

Spontaneous biloma formation is exceedingly rare, with all literature on the subject in the form of case reports. In 2007, Ahktar et al. noted that 27 cases of spontaneous biloma had been reported since 1979.[29]

Pathophysiology

Disruption of the biliary tree and subsequent bile leakage is the cause of most bilomas. Encapsulation of the bile leak is thought to be via two mechanisms, depending on the rate of bile leakage. Most commonly, slow bile leakage causes mild inflammation in the surrounding abdominal tissues or liver parenchyma, resulting in fibrosis and encapsulation. Bile acids produce low-grade inflammation in surrounding tissues because of their detergent and tissue destroying properties.[30] 

Biliary peritonitis can be present in large volume, rapid bile leaks. This may present with encapsulation; however, patients may present acutely before encapsulation has occurred. Intraperitoneally, the omentum and mesentery can form inflammatory adhesions aiding encapsulation.[2] Biloma size and location depend on the mechanism of biliary tree disruption, rate of bile leakage, and reabsorption of bile by surrounding liver parenchyma or peritoneum.[24] 

Extravasated bile follows abdominal anatomy with its shape often demarcated by the diaphragm, liver margins, mesentery, and transverse mesocolon. It is not uncommon for patients to have multiple bilomas. Extrahepatic bilomas predominantly form in the right upper quadrant of the abdomen. However, in about 40% of cases, bile migrates over the anterior part of the liver to the left subphrenic or left subhepatic spaces.[2][29] 

Biloma content is typically greenish-yellow bile. However, they can contain blood or exudate, especially in the context of infection. Secondary infection can lead to a systemic inflammatory response, sepsis, and abscess formation. The natural history of abdominal bile collections from injured bile ducts is the progression from sterile bile collection to infection.[4]

History and Physical

Bilomas typically present with upper abdominal fullness and right upper quadrant discomfort following iatrogenic or traumatic disruption to the biliary tree. Nausea, vomiting, and fever are recognized symptoms, especially in cases of infected biloma. Jaundice may be present in cases of extrinsic compression of the bile duct. Key aspects required from the history include previous surgical or endoscopic interventions or abdominal trauma that may have caused biliary tree disruption. A history of hepatobiliary surgery or diseases of the biliary tree also increases the risk of bile leak and biloma formation.[2]

While patients may present acutely unwell with septic shock from bilomas, and many may be asymptomatic. The large variation in presenting symptoms makes the diagnosis of biloma difficult. Bile peritonitis is a recognized presentation of bile leak and large biloma. However, Lee et al. showed that this presentation is unusual, and most patients present with more subtle symptoms. They describe delayed diagnosis in 77% of 179 patients with abdominal bile collections and bile leaks following laparoscopic cholecystectomy. Significant abdominal pain and tenderness were only seen in 21% of patients. Initial peritonitis does not predict the severity of the disease, with many subtly symptomatic patients developing serious complications.[4] 

Following iatrogenic intervention or traumatic injury, physicians should be alert to persistent abdominal distention, bloating, or anorexia as early signs of bile leak and biloma. Physicians should be aware that any delay in recovery from hepatobiliary surgery, especially laparoscopic cholecystectomy, is a possible early symptom of bile leak and biloma formation. Biloma remains an uncommon diagnosis, and other gastroenterological and hepatobiliary diagnoses should be considered for patients presenting with upper abdominal fullness and discomfort. However, in patients who have recently experienced surgical or endoscopic interventions in the region of the biliary tree, bile leak and biloma are essential differential diagnoses to exclude as they can present subtly and have significant morbidity and mortality.[2][4]

Evaluation

Initial laboratory testing may reveal a systemic inflammatory response to the presence of a biloma. Blood tests may demonstrate raised inflammatory markers such as leucocytosis, neutrophilia, and raised C-reactive protein (CRP). However, many patients with bilomas have no abnormalities in laboratory tests. Vazquez et al. demonstrated normal blood results in 40% of 21 patients presenting with bilomas.[24] 

Liver function tests may be deranged in cases with bile duct compression. In cases of infected biloma, blood cultures may reveal gram-negative bacteremia. Wurstle et al. showed positive blood cultures in 93% of 32 bilomas following iatrogenic injury to the biliary tree. The most common organisms found in a laboratory culture of biloma fluid were Enterobacteriaceae, followed by Enterococcus species. They demonstrated multi-drug resistant bacteria in 25% of biloma cultures.[31] 

The variable and often subtle presentation of bilomas make radiological investigation the mainstay of diagnosis. US, CT, MR imaging, and HIDA are the main radiological modalities used when investigating bilomas. US imaging of the abdomen is often the first investigation due to the frequency of presentation with right upper quadrant discomfort. US imaging can frequently identify a cystic lesion. It can also demonstrate debris or blood clots within the biloma. The US may reveal a wide range of findings from well-circumscribed collections in the liver parenchyma to large loculated fluid collections throughout the abdomen. Heavily loculated bilomas seen on US imaging have been associated with an infection. Although US imaging is effective for identifying a cystic mass, further imaging is usually required to make a diagnosis.[2][32]

CT imaging typically shows bilomas as a well-circumscribed collection with clear margins. However, a well-defined capsule is not always present.[2] Bilomas are typically hypoechoic, hypo-attenuated collections that have a density of less than 20 Hounsfield units on CT.[24][33] CT imaging has the benefit of precisely localizing the biloma and imaging the surrounding structures. While CT can provide a more detailed picture of bilomas, it cannot definitively differentiate between differential diagnoses such as postoperative seroma, hematoma, abscess, lymphocele, liver cyst, and pseudocyst.[34] Therefore, further imaging using MR imaging or hepatobiliary cholescintigraphy is often required alongside a direct sampling of the biloma to confirm the diagnosis.[2]

MR imaging, alongside MRCP in some cases, can further define the characteristics of a biloma. Biloma typically produces a low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. While contrast rarely permeates into the biloma, rim-enhancement is sometimes present due to reactive inflammation. Enhancing septations are often observed in superimposed infection. MRCP, particularly thin slab sequences, may demonstrate the source of a biliary leak.[35]

Hepatobiliary cholescintigraphy is an extremely effective non-invasive imaging modality when diagnosing and planning treatment for bilomas. Cholescintigraphy utilizes a radiotracer called Tc-99m iminodiacetic acid and therefore is known as hepatobiliary iminodiacetic acid (HIDA) imaging. HIDA is very sensitive when looking for a bile leak. However, it does not provide detailed imaging of the surrounding anatomy. Single positron emission computed tomography (SPECT) can provide more detailed imaging of the location of possible leaks and can be more useful when planning percutaneous image-guided drains. Invasive imaging techniques such as ERCP and Percutaneous transhepatic cholangiogram (PTC) can provide further guidance on endoscopic, percutaneous, or surgical management.[2][26]

US or CT-guided sampling of the biloma, followed by laboratory analysis, is sometimes required to confirm the diagnosis when prior imaging and clinical findings are not conclusive.[2]

Treatment / Management

Management varies depending on the clinical presentation, laboratory results, and radiological findings of the biloma. The three main options are percutaneous or endoscopic drainage, surgical drainage, or close monitoring. Ongoing bile leak, size, and position of the biloma, alongside superimposed infection and patient fitness, will determine which management strategy is most appropriate.[2] Small, asymptomatic fluid collections may be reabsorbed and not require any intervention. However, Lee et al. demonstrated that collections larger than 4cm were rarely reabsorbed, and it was hard to predict whether patients would become symptomatic.[4]

Most bilomas can be managed successfully with radiologically guided percutaneous drainage. Fixation of the underlying disruption of the biliary tree is often unnecessary.[22][33] The US or CT-guided aspiration by an interventional radiologist is the preferred method. Due to the lack of radiation and real-time imaging, US is preferred over CT in most cases. Spectral Doppler and real-time color allow avoidance of vascular structures. Interventional radiologists may access extrahepatic bilomas via the liver if there is no other clear window. Other methods of drainage include endoscopic ultrasound (EUS) guided drainage. For example, Shami et al. described, in 2008, successful management of bilomas adjacent to bowel with EUS guided drainage.[36] Tonozuka et al. described, in 2015, successful management of hepatic abscess and infected bilomas with EUS guided metal stents.[37] Most bilomas, without ongoing bile leaks and managed with percutaneous drainage, will not recur and have a good prognosis.

Ongoing bile leaks may require further management, with either surgical fixation or endoscopic stent placement. However, Lee et al. recommend drainage of the biloma post-laparoscopic cholecystectomy in the first case, especially in the acutely unwell or symptomatic patient.[4] PTC or Percutaneous transhepatic biliary drainage (PTBD) are sometimes required to further image the biliary tree or decompress the gallbladder when there is an ongoing bile leak.[2]

Surgical management of biloma is sometimes indicated in failed percutaneous drainage, some multiloculated lesions, and in cases with ongoing bile leaks. Cases of bile leak identified intraoperatively during laparoscopic cholecystectomy or requiring surgical management for ongoing bile leak are best managed in specialist tertiary centers.[38]

The rarity of biloma formation means there is little reliable evidence beyond case reports and case series describing management strategies. However, percutaneous drainage has successfully managed biloma, and biloma patients have a very good prognosis.

Differential Diagnosis

Due to biloma formation being an uncommon occurrence, it is important to consider the possible differential diagnoses. Right upper quadrant discomfort and abdominal fullness are non-specific symptoms that have a wide variety of possible causes. Biloma should enter the differential where patients present secondary to an iatrogenic or traumatic event that could disrupt the biliary tree. Following this, appropriate imaging should be undertaken.

Differential diagnoses following radiological investigation include hepatic abscess, cyst, pseudocyst, and lymphocele. As most bilomas form post-operatively or post-endoscopic investigation, seroma and hematoma are key differential diagnoses to consider. It is important to correctly identify bilomas as they often require drainage, while many differential diagnoses such as hematoma do not routinely require drainage.[2][4]

Prognosis

Biloma prognosis varies depending on site, size, and etiology. However, uncomplicated bilomas without underlying ongoing bile leaks have a good prognosis. Small, asymptomatic bilomas with no ongoing bile leak are often treated conservatively to good effect.[2] 

In patients with symptomatic bilomas, drainage via interventional radiology is an effective strategy, and patients have a good prognosis.[2][22] Lee et al. have shown that prompt drainage of symptomatic bilomas significantly improves patient morbidity and mortality while reducing chances of secondary infection and complications.[4] Most bilomas, having been managed with percutaneous drainage, will not recur and have a good prognosis. However, massive bile leaks into the peritoneum are associated with significant morbidity, often requiring urgent and invasive intervention to avoid deterioration.[4]

Complications

Complications of biloma include infection, septic shock, abscess formation, and cholestasis through impingement on the biliary tree. Lee et al. also describe pancreatitis, respiratory failure, and trans-diaphragmatic bile fistulation in patients with abdominal bile collections.[4] Risks of percutaneous drainage of bilomas include bleeding, infection, damage to surrounding structures, and failure to drain the biloma. Ongoing bile leaks may require further endoscopic or surgical management.[2]

Deterrence and Patient Education

While bilomas mostly occur following iatrogenic or traumatic disruption of the biliary tree, and patients should be counseled regarding the symptoms and signs that may indicate biloma formation following possible traumatic or iatrogenic damage to the biliary tree. Both patients and physicians should be aware of the possibility of biloma formation in any patients presenting with non-specific abdominal symptoms following trauma or procedures involving the biliary tree. This should include any delay to the expected recovery following procedures such as laparoscopic cholecystectomy. Prompt investigation and management of bilomas improve patient morbidity and mortality.

Enhancing Healthcare Team Outcomes

The rarity of biloma presentation means there is little evidence from large trials to guide diagnosis and management. Most evidence is in the form of case series and case reports. However, there is a consensus in the literature that bilomas, when diagnosed early and managed appropriately with percutaneous drainage or, in certain cases, surgical intervention, have a good prognosis. As there is little evidence to guide clinicians, expert opinion should be sought from gastroenterological surgeons, clinicians, and radiologists to undertake prompt and accurate diagnosis and effective management of bilomas. [Level 5]

The interprofessional team, including medical, nursing, and perioperative care practitioners, should be aware of biloma formation that can result from hepatobiliary surgical or endoscopic interventions.

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Disclosure: James Balfour declares no relevant financial relationships with ineligible companies.

Disclosure: Anne Ewing declares no relevant financial relationships with ineligible companies.