Hepatobiliary Oncologic Emergencies: Imaging Appearances and Therapeutic Options

Hepatobiliary Oncologic Emergencies: Imaging Appearances and Therapeutic Options Matthew J. Kogut, MD,a,b Sarah Bastawrous, DO,a,b Siddharth Padia, MD,a and Puneet Bhargava, MBBS, DNBa,b

During the course of their disease, many patients with cancer may require urgent care related to hepatobiliary disease. Cross-sectional imaging of these patients is usually performed initially, and the radiologist plays a pivotal role in the initial diagnosis. In this article, we discuss the commonly seen hepatobiliary oncologic emergencies, briefly review imaging diagnosis, and discuss in detail the management options for these conditions. The radiologist’s awareness and prompt diagnosis aid in formulating a management plan to decrease morbidity and mortality in these potentially lethal conditions.

Patients with cancer are at an increased risk for life-threatening complications because of disease progression, treatment-related complications, and altered immune response. In particular, disorders of the liver, gallbladder, and pancreas can present with vague clinical symptoms, including abdominal pain, nausea, vomiting, and fever. The radiologist plays an important role in the multidisciplinary approach to cancer management and the recognition of emergent imaging findings that are essential to initiate appropriate medical, interventional, or surgical management. In this article, we present the key imaging appearances and associated image-guided management of commonly encountered hepatobiliary emergencies in patients with cancer.

From the aDepartment of Radiology, University of Washington School of Medicine, Seattle, WA; and bVA Puget Sound Health Care System, Seattle, WA. Reprint requests: Matthew J. Kogut MD, VA Puget Sound Health Care System, 1660 S Columbia Way, S-114/Radiology, Seattle, WA 98108. E-mail: [email protected]. Curr Probl Diagn Radiol 2013;42:113–126. Published by Mosby, Inc. 0363-0188/$36.00 + 0 http://dx.doi.org/10.1067/j.cpradiol.2012.08.003

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Biliary Obstruction Local invasion of the primary tumor or metastases can result in obstruction of the biliary system, which is a significant cause of morbidity in patients with malignancy. Malignant biliary obstruction occurs most frequently due to adenocarcinoma of the pancreatic head, periampullary neoplasms, cholangiocarcinoma (CCA), and metastatic lymphadenopathy in the hepatoduodenal ligament.1 Pancreatic adenocarcinoma is the fourth leading cause of death from cancer in the United States. It carries a poor prognosis for which surgical resection is the only definitive cure. Typically, the tumor is hypovascular compared with the briskly enhancing surrounding pancreatic parenchyma. Secondary signs, such as pancreatic and biliary ductal dilatation, help in tumor localization (Fig 1). Approximately 10% of pancreatic adenocarcinomas are isodense to the pancreatic parenchyma, and in these difficult cases, these secondary signs are extremely valuable in making an accurate diagnosis. The double duct sign, in which both the common bile duct and pancreatic ducts are dilated, is not specific for pancreatic adenocarcinoma; however, it is reliably associated with an obstructing lesion in the periampullary region.2 CCA is an adenocarcinoma arising from the bile duct epithelium and is classified as intrahepatic, hilar, or extrahepatic. Approximately 60%-70% of the tumors originate at the bifurcation of the hepatic ducts (Klatskin tumor), and 20%-30% originate in the distal common bile ducts (Fig 2). Both intrahepatic and extrahepatic CCAs are commonly diagnosed at advanced stages because specific symptoms, physical examination findings, and laboratory abnormalities are typically absent early in the disease process.3 CCAs often present once the tumor obstructs the biliary drainage system, causing painless jaundice. The typical computed tomographic (CT) features of

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FIG 1. Pancreatic adenocarcinoma presenting as acute pancreatitis. Axial contrast-enhanced CT image shows an ill-defined mass in the pancreatic body (arrowheads) with surrounding peripancreatic inflammation. There is dilatation of the main pancreatic duct in the pancreatic body or tail (arrow). The patient was treated with supportive care.

intrahepatic CCA include a homogeneous or lowattenuation mass demonstrating irregular peripheral enhancement with gradual centripetal enhancement. Capsular retraction and focal dilatation of intrahepatic ducts around the tumor may also be present. Infiltrating hilar CCA is the most common type of hilar CCA and on contrast-enhanced CT, appears as a focally thickened ductal wall with obliteration of the lumen. The majority of these tumors are hyperattenuating relative to liver parenchyma. Often, central intrahepatic ductal dilatation with a normal common bile duct and absence of a well-marginated mass can be the presentation.4 Secondary sclerosing cholangitis can present secondary to local malignant infiltration and has been reported with the use of intrahepatic arterial infusion of fluoxouridine.5,6 Radiation-induced biliary strictures have also been reported. This condition is morphologically, clinically, and radiologically similar to the more common primary sclerosing cholangitis. In the early phase, patients can be asymptomatic with only elevated serum alkaline phosphatase and gammaglutamyltransferase. In patients who are symptomatic, jaundice, pruritus, and abdominal pain are the common signs and symptoms. Secondary sclerosing cholangitis is a progressive disease characterized by fibrosis, cirrhosis, and ultimately liver failure; patients are not at a higher risk of developing CCA or hepatocellular carcinoma (HCC). Diffuse multifocal strictures with interposed segments of normal and ectatic bile ducts are seen on a cholangiogram. Typically, these findings are limited to the intrahepatic and

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FIG 2. Klatskin Tumor. (A) Percutaneous transhepatic cholangiogram via a peripheral right-sided duct shows an extensive intrahepatic biliary dilation with an abrupt cutoff at the confluence of the hepatic ducts (arrows). Note the associated long stricture (arrowheads) related to cholangiocarcinoma. (B) The stenotic hepatic duct has been crossed, and an internal-external drainage catheter now extends into the duodenum where a pigtail has been formed (arrow). Side-holes (arrowheads) extend across the stenotic area. The patient was treated with chemotherapy and long-term drainage.

proximal extrahepatic bile ducts, but rarely the cystic duct and the main pancreatic duct may be involved as well. Small diverticulum-like outpouchings may also

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be seen. Magnetic resonance cholangiopancreatography is an excellent modality to diagnose this condition and offers better visualization upstream of tight strictures that are not well visualized in endoscopic retrograde cholangiopancreatography. Magnetic resonance cholangiopancreatography avoids the risk of radiation, pancreatitis, and conscious sedation but does not allow interventions or procedures such as brush biopsy, balloon dilatation, or stenting. Liver biopsies are not required for the diagnosis of this entity and do not change the clinical management in majority of patients. Therapeutic options are limited, and the prognosis is worse compared with primary sclerosing cholangitis.6 Overall prognosis of malignancy causing biliary obstruction is very poor, and palliative treatments are often the only option. Malignant biliary strictures can be managed endoscopically or through percutaneous methods. Drainage of the obstructed biliary system becomes an emergency in the setting of infection, obstructive cholangitis. Patients who have undergone endoscopic instrumentation or have a pre-existing sphincterotomy or bilioenteric bypass are at an increased risk for superimposed infection. The presence of biliary dilation or hyperbilirubinemia alone is not an indication for drainage. Symptoms from hyperbilirubinemia, such as pruritus, and cholangitis are the common indications of drainage. Drainage may also be required to lower a patient’s bilirubin to allow administration of certain chemotherapeutic agents.7 Lower biliary obstruction is often amenable to endoscopic stent placement and drainage. In contrast, endoscopic drainage of obstruction at the level of the common hepatic duct or higher is extremely technically challenging, and this patient population is often managed with a percutaneous approach. Planning the percutaneous approach with cross-sectional imaging is strongly encouraged with the particular attention to levels of obstruction and presence of anatomical variants. The liver can be drained by a right- or leftsided approach, and occasionally both sides need drainage. If both sides are dilated, most operators prefer a right-sided approach for technical reasons; however, this may be more uncomfortable for the patients as it is performed from a lateral intercostal approach. If the portal vein is occluded in only one lobe, draining this lobe does not typically improve liver function. Drainage can be performed with fluoroscopic guidance alone or with the addition of ultrasound (US). The bile ducts are entered as

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peripheral as possible to reduce complications and aid in the technical success of crossing the occluded segment. Once access has been obtained to the biliary system, there are a few options for treatment: placement of drainage catheter for external drainage vs crossing the occluded or narrowed segment with primary placement of a metallic stent or an internalexternal drainage catheter. In infected or unstable patients, an external drainage catheter should be placed with future plans for more definitive treatment. In the absence of infection, significant hemorrhage, stones, or intraductal tumor, primary stent placement can be considered.8 Metallic stents are typically reserved for patients with proven malignancy, as the patency rates are approximately 4-9 months.7,9 Biopsies can be obtained through biliary access when necessary.10 When a metallic stent is placed, an external drainage catheter is often left behind temporarily until stent function is confirmed.8 Metallic stents are larger in caliber than the plastic stents typically placed endoscopically, which is the reason for superior patency rates, 4-9 months vs 2-6 months, respectively.9,11 Stents are associated with a higher quality of life as opposed to the presence of an external catheter.9 Technical success is greater than 90% with clinical success ranging from 77%-98%.11 In patients without a diagnosis or in the presence of intraductal tumor or debris, placement of an internalexternal drainage catheter is desirable. Unlike an external drainage catheter, this catheter has side-holes spanning from above the obstruction to the duodenum. This allows capping of the external portion of the tube, improving quality of life. It also facilitates physiological drainage of bile, preventing electrolyte abnormalities, and possible metabolic alkalosis associated with prolonged external drainage. Complications from percutaneous biliary intervention include cholangitis, bile leak, extrahepatic hemorrhage, abscess, pneumothorax, and hemobilia.10 One late complication of stenting is stent occlusion (Fig 3). This is reported to occur in 5%-25% of patients after metallic stent placement.11 However, the majority of these patients can be treated with another stent or placement of an internal-external drainage catheter.

Infectious and Inflammatory Emergencies Cholecystitis in patients with cancer may occur secondary to cholelithiasis, due to transient obstruction

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FIG 3. Occluded stent secondary to cholangiocarcinoma. (A) Axial contrast-enhanced CT reveals a self-expandable metal stent in the right hepatic duct (arrowhead), extending into the common hepatic duct. Moderate intrahepatic biliary ductal dilatation is present; arrow indicates a dilated left hepatic duct. (B) Coronal reformatted CT image shows internal low-density material occluding the stent (arrows), related to tumor in growth and debris. Residual contrast is within the stent from recent endoscopic retrograde cholangiopancreatography. (C) The occluded stent has been crossed, and an internal-external drainage is in place. Note the contrast in the gallbladder and dilated left-sided ducts. The patient was treated with palliative drainage and supportive care.

of the cystic duct. Patients with cancer may also develop cholecystitis as a complication of locoregional treatment of hepatic neoplasms, such as chemoembolization, or may occur following biliary stent placement.12,13 Additionally, patients with cancer frequently encounter immunosuppression, malnutrition, and other factors that can predispose them to acalculous cholecystitis. Right upper quadrant pain is the typical presenting symptom, but sometimes the clinical picture can be confusing and imaging is indicated early. US is an initial imaging choice for the assessment of cholecystitis as it is highly sensitive and specific for the detection of gallstones and biliary dilatation. It is also safe, relatively inexpensive, and readily accessible for the evaluation of acutely ill patients.14 The most sensitive US findings for acute cholecystitis include the combination of gallstones

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with right upper quadrant tenderness on transducer compression directly over the gallbladder (the sonographic Murphy sign) and gallstones plus a thickened gallbladder wall (43 mm). Pericholecystic fluid is a secondary finding that is neither sensitive nor specific for acute cholecystitis.15 CT can also allow for the diagnosis of acute cholecystitis and is useful when US results are equivocal. CT typically reveals a distended gallbladder with mucosal hyperenhancement and wall thickening, pericholecystic fluid, adjacent inflammatory stranding, and possible increased enhancement in adjacent liver parenchyma during the arterial phase. However, CT does not allow for the assessment of the Murphy sign, and noncalcified gallstones are not reliably seen by CT.14,16 Complications of acute cholecystitis include gangrenous and emphysematous cholecystitis, as well as gallbladder perforation; the latter of

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which is discussed subsequently. Gangrenous changes can typically occur in the setting of advanced cholecystitis, complicating 2%-38% of cases.17 Gangrenous cholecystitis carries a higher patient morbidity and mortality than uncomplicated acute cholecystitis; therefore, prompt diagnosis and treatment are crucial. Sonographic imaging features of these 2 entities may overlap, and finding suggesting gangrenous changes includes floating internal membranes, gas within the gallbladder wall or lumen, and wall disruption.14,17 Emphysematous cholecystitis is a rare condition associated with gas within the gallbladder wall or lumen in the setting of acute cholecystitis. The etiology is thought to be secondary to underlying vascular insufficiency and ischemia of the gallbladder wall, which allows gas-forming bacteria to proliferate. Elderly men are typically affected in the setting of underlying diabetes mellitus or other debilitating diseases. US findings can show curvilinear nondependent hyperechoic foci in the lumen representing air, which may move with the patient’s position. CT can be obtained to confirm gas in the gallbladder wall or lumen (Fig 4).17 Percutaneous cholecystostomy is used to treat both calculous and acalculous cholecystitis as a temporizing measure bridging to surgery or occasionally as definitive therapy. In high-risk patients, mortality related to immediate cholecystectomy is as high as 18%, whereas it is only 2% for percutaneous cholecystostomy. All patients need medical management, which typically includes antibiotics and any necessary hemodynamic

FIG 4. Emphysematous cholecystitis. Axial contrast-enhanced CT revealed shows foci of air (arrowheads) within the gallbladder lumen. Gallstones are also present. The patient was treated with emergent cholecystostomy.

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support. Bile cultures are positive in nearly half of the patients undergoing cholecystostomy, revealing a variety of pathogens. However, neither positive cultures nor specific organisms appear to affect overall clinical outcomes.18 A large amount of ascites is a contraindication to cholecystostomy, given that they often develop leaking of ascites and are at significant risk for bacterial or bile peritonitis.19 Percutaneous cholecystostomy is usually performed with combined US and fluoroscopic guidance. Although it can be performed with CT guidance, this is usually not necessary and this resource is not always readily available for interventional procedures. The drainage catheters are typically placed using the Seldinger technique and can be placed from a transhepatic or transperitoneal approach. The classical teaching was to place from a transhepatic approach; however, many operators now prefer a transperitoneal approach. In 1 large case series, there was no statistical difference in outcomes between either approach; however, all cases of bile leak and hemobilia were from the transhepatic approach.18 Longterm outcome is improved in patients who ultimately undergo cholecystectomy.18 This may reflect selection bias, in that the sicker patients with multiple comorbidities are deemed unfit for surgical intervention. When used as a bridge to surgery, the cholecystostomy catheter is typically left in place until cholecystectomy. In patients unfit for surgery, options include percutaneous stone retrieval, leaving the catheter in place for life, or removing the catheter, which carries a risk of up to 30% recurrence.19 Perforation of the gallbladder is a serious complication of primarily acute cholecystitis and may occur in up to 11% of patients, with an associated mortality rate of 19%-24%.14,19 Rarely, perforation can be associated with primary malignancy or metastases of the gallbladder.20 Signs and symptoms can be indistinguishable from those of uncomplicated acute cholecystitis; therefore, prompt radiologic diagnosis is imperative. The clinical presentation of gallbladder perforation may vary from an acute generalized peritonitis to nonspecific abdominal and right upper quadrant symptoms. Differentiation between gallbladder perforation and cholecystitis can be difficult because the bile leak from a ruptured gallbladder might be contained in the extraperitoneal gallbladder fossa and may not produce symptoms of peritonitis immediately.21 Gallbladder perforation is classified into 3 clinical categories by Niemeier: type 1 is a perforation into the

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peritoneal cavity with the resulting bile peritonitis, type 2 is a localized perforation with adjacent abscess, and type 3 is a perforation into adjacent organs, usually the duodenum, resulting in cholecysto-enteric fistula formation. Most perforations are subacute in nature, representing 60% of all cases.14 The pathogenesis of gallbladder perforation is not completely understood. Ultimately, the sequence of events that leads to perforation is thought to result from cystic duct occlusion, resulting in retention of intraluminal secretions. This occurs most often in patients with gallstone disease. However, perforation is also associated with acalculous cholecystitis, systemic diseases causing vascular insufficiency, and immunosuppression. Perforation typically occurs at the gallbladder fundus because anatomically it is the least vascularized area of the organ.22 Perforation may occur due to direct invasion of the gallbladder wall or secondarily, as a complication of underlying cholecystitis (Fig 5). Some authors have also suggested that malignancy aids in the development of acalculous cholecystitis and gallbladder perforation by its immunosuppressive effects. It has been reported that 11.6% of patients in a series with gallbladder malignancy had simultaneous perforation. Gallbladder perforation remains a rare event, which can occur in the setting of primary gallbladder adenocarcinoma, duodenal ampullary carcinoma, or gallbladder metastases.20,23,24

FIG 5. Gallbladder perforation secondary to acute cholecystitis. Axial contrast-enhanced CT image shows a distended gallbladder with indistinct borders and surrounding pericholecystic inflammation. Curvilinear hypoattenuating areas adjacent to the gallbladder fossa (arrowheads) represent small pericholecystic abscesses due to gallbladder perforation. The patient was treated with emergent cholecystostomy tube placement.

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The mortality and morbidity surrounding cholecystitis with associated perforation are increased, as described previously. However, percutaneous drainage as a temporizing measure before cholecystectomy lowers mortality rates.25 This typically includes a cholecystostomy tube described in the previous section as well as percutaneous image-guided drainage of the associated fluid collection related to the perforation. Pyogenic liver abscesses (PLAs) usually develop following hematogenous spread of either gastrointestinal tract infection via the portal vein or disseminated sepsis via the hepatic artery. Abscesses can also develop in the setting of ascending cholangitis or superinfection of necrotic tissue.26 The etiology of PLA formation has shifted over the years. Previously, appendicitis was the most common underlying pathology, but that has shifted to biliary disease, including obstructive tumors, and diverticular disease.27,28 In 1 institutional experience, 88% of the patients presenting with PLA had an underlying malignancy.29 Additionally, PLA is a known complication of the treatment modalities used for hepatobiliary malignancies, specifically transarterial hepatic artery embolization and hepatic radiofrequency ablation. The typical clinical manifestations of PLA are nonspecific, including fever, abdominal pain, rigors, and weight loss, making early diagnosis a challenge. Abscesses may be solitary or multiple lesions ranging in size from a few millimeters to several centimeters. At US, hepatic abscesses vary in echogenicity, containing variable material and debris. Gas-containing abscesses may appear as echogenic masses with acoustic shadowing or reverberation artifacts.26 CT is a reliable modality for the detection of greater than 90% of PLA. CT findings of PLA typically include smoothly marginated hypoattenuating masses, which may or may not exhibit rim enhancement (Fig 6). Internal septations may also be present with surrounding perilesional edema. The presence of gas is relatively uncommon.30 Early diagnosis and percutaneous drainage have markedly reduced both the mortality rates and the need for surgery in patients with PLA. Although open surgical drainage or resection is still performed, it is typically considered second-line therapy after percutaneous drainage.28,29 All patients are treated with broad-spectrum antibiotics as well, which can be tailored based on samples taken during drainage catheter placement. Occasionally, PLA can be treated with antibiotics alone; however, drainage is usually

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when there is a history of alcohol abuse, providing an alternative cause for pancreatitis.

Acute Vascular Complications

FIG 6. Intrahepatic abscess. Axial contrast-enhanced CT shows a large multiloculated abscess (arrows) in the right hepatic lobe with enhancing internal septations (arrowheads). The patient was treated with a percutaneous drainage catheter.

necessary for abscesses greater than 3 cm.27 Drainage catheters can be placed by the Seldinger technique typically with combined US and fluoroscopic guidance or CT guidance. Given that most PLAs contain a variable amount of debris, many advocate 12-French or larger catheters to facilitate drainage. The drains must be flushed on a routine basis to maintain patency. Drainage typically takes much longer for PLA when compared to intra-abdominal or soft-tissue abscess. Factors that may be associated with clinical failure after percutaneous drainage are the presence of yeast, communication with the biliary tree, and increased hepatic abscess complexity.29,31 Pancreatitis can often occur following the administration of chemotherapeutic agents, such as L-asparginase, ifosfamide, paclitaxel, cisplatin, vinorelbine, cytarabine, tretinoin, sunitinib, and sorafenib. Combined therapy of erlotinib and sunitinib in patients with metastatic non–small cell lung cancer can cause necrotizing pancreatitis. Intraperitoneal chemotherapy in patients with pseudomyxoma peritonei can also produce pancreatitis.5 CT features are similar to pancreatitis from any other etiology, and findings include peripancreatic edema, fat stranding, and fluid collections. Clinical correlation and awareness that these agents cause pancreatitis help make the correct diagnosis. Pancreatic carcinoma may also present as acute pancreatitis and in up to 13.8% of patients. The diagnosis in these patients may also be delayed, especially when gallstones are incidentally noted or

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Portal vein thrombosis (PVT) is seen in up to 0.5% of people in autopsy studies, and cancer has long been recognized as a risk factor.32,33 Hypercoagulability is common in patients with cancer because tumor cells produce substances with procoagulant activity. Venous thromboembolism has been reported with a variety of chemotherapeutic agents, such as gemictabine, thalidomide, lenalidomide, semaxibin, and prinomastat. It is postulated that chemotherapy may induce apoptosis of the vascular endothelium cells, with subsequent exposure of the basement membrane and activation of clotting cascade leading to thrombosis.5 Additionally, chemotherapeutic agents can decrease levels of naturally occurring anticoagulant proteins.1 Risk factors for PVT include malignancy, cirrhosis, hypercoaguable states, and liver transplant.32-34 Up to 25% of patients have an associated myeloproliferative neoplasm, and other prothrombotic states predispose patients to PVT. Patients may present with sudden abdominal pain, which may be out of proportion to examination findings and can be associated with a systemic inflammatory response. Complications from PVT include intestinal infarction in 2%-28% of patients with mortality up to 60%.32,33 It can also lead to portal hypertension and variceal bleeding with a mortality up to 37%.32 On cross-sectional imaging, low-density, expansile, and enhancing intrahepatic portal venous thrombus is strongly suggestive of tumor thrombus. On early arterial phase images, tumor thrombus related to HCC can show thread-like contrast enhancement and also suggests portal vein invasion.35 A bland thrombus tends not to expand the portal vein as much and typically does not enhance.36 Thrombus in the mesenteric veins can be confirmed by CT and shows venous enlargement with central filling defect (Fig 7).37 Immediate anticoagulation is usually recommended to prevent propagation of thrombus. However, in patients with cirrhosis, the decision to anticoagulate must be weighed against the risk of bleeding complications.38 Worsening of abdominal pain, gastrointestinal tract hemorrhage, ascites, or acidosis should raise concern for the propagation of thrombus and bowel infarction. In patients who do not progress,

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FIG 7. Superior mesenteric vein thrombosis. Axial (A) and coronal (B) contrast-enhanced CT images show low-density thrombus in the superior mesenteric vein, which extends into the main portal vein (arrows). The patient was treated with intra-arterial thrombolysis with resolution of thrombus.

anticoagulation is typically continued for 3-6 months. This has been shown to result in partial recanalization of the portal vein in 39% of patients as well as recanalization of the superior mesenteric vein in 73% and the splenic vein in 80% of patients. Complete recanalization of the portal vein after anticoagulation is seen in only14%.33,34 Some advocate for thrombolysis of portal and mesenteric vein thrombosis. However, most of the literature on catheter-directed thrombolysis is limited to small case series.32,34 Patients who worsen clinically have continued propagation of thrombus, or signs of bowel ischemia may be considered for catheter-directed thrombolysis. Standard techniques are yet to be developed. Routes of administration include a direct approach to the portal vein from the percutaneous transhepatic approach or a transjugular approach, as used in transjugular portosystemic shunt (TIPS) placement. Another option is infusion of

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thrombolytics through the superior mesenteric artery (Fig 8). Although this may seem attractive technically, there is concern that the thrombolytic is shunted through the remaining patent veins and does not penetrate the thrombus. Rates of recanalization of the portal vein are reported to be 41% and 45% for complete and partial recanalization, respectively.34 Yet, the concern for major complication must be weighed against the patient’s clinical status. Major complications have been reported at up to 60%, most of which are hemorrhagic.32,34 The Budd-Chiari syndrome (BCS) is a group of disorders characterized by obstruction of hepatic venous outflow, leading to increased hepatic sinusoidal pressure and portal hypertension. Acute or chronic forms can occur, and symptoms vary from mild to fulminant acute liver failure in chronic disease. Direct primary tumor or metastatic invasion of the hepatic veins, inferior vena cava (IVC), or right atrium, or both can lead to BCS.39 Additionally, in patients with cancer, this rare complication can be caused by treatment with oxaliplatin for metastatic colorectal carcinoma. It can also occur as a complication of cytoreductive therapy in stem cell transplantation or following intensive chemotherapy in patients with hematologic malignancies.5 Other hematologic diseases, including myeloproliferative disorders, can also cause BCS. The cross-sectional imaging characteristics of BCS vary depending on chronicity. In the acute phase, the liver is diffusely enlarged with lower attenuation on CT images, and ascites may be present. Differential contrast enhancement of hepatic parenchyma can also be seen at CT with decreased peripheral enhancement and strong central enhancement. Increased enhancement is seen in areas of venous drainage that are less affected, such as the caudate lobe, which eventually leads to hypertrophy, given its separate drainage pattern. The edematous and congested peripheral regions demonstrate diminished contrast enhancement (Fig 9). In chronic BCS, there is atrophy of the affected portions of the liver with fibrosis and regenerative nodules. Intrahepatic and subcapsular collateral veins develop in the chronic phase and are easily seen in contrast-enhanced CT.39 Digital subtraction angiography can accurately evaluate the hepatic veins and IVC in BCS by demonstrating the level of obstruction, presence of an occluding membrane, thrombus, or tumor. Intrahepatic and extrahepatic collaterals, such as prevertebral hemiazygous and azygous veins, can also be seen at

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beta-blockers and diuretics. The incidence of heparininduced thrombocytopenia is increased in this population, so platelet counts should be monitored.33 If the BCS is related to a hepatic vein or IVC stenosis, angioplasty or stenting should be considered. Unfortunately, this is seen in the minority of patients. In patients who fail medical treatment and do not have an identifiable stenosis, TIPS is the treatment of choice.42 TIPS insertion involves creation of a low-resistance channel between the hepatic vein and the portal vein, thereby decreasing the portal-systemic pressure gradient. TIPS placement in BCS is technically challenging, which is secondary to the difficulty in accessing hepatic veins and hepatomegaly. If access cannot be achieved to the hepatic vein, the portal vein can be accessed directly from the IVC. Technical success is reported at greater than 90% in experienced operators.42 Secondary to hepatomegaly, the transhepatic tract is often longer than typical and multiple stents may be required to create the shunt. Although traversal of the liver capsule during attempts to enter the portal vein is relatively common, the development of clinically obvious hemoperitoneum is relatively rare. This can be confirmed by high-density fluid on CT or US. Another important complication is the inadvertent creation of a fistula between the shunt and the hepatic artery or bile ducts. The clinical consequences depend on the specific structures involved. As an example, the inadvertent creation of a TIPS-biliary fistula can cause hemobilia. Liver transplantation is the remaining option for patients who develop liver failure after TIPS or when TIPS is contraindicated or unsuccessful. FIG 8. Portal vein thrombolysis. (A) Transjugular access with a vascular sheath in the central hepatic vein and catheter extending into the portal system (arrowheads). Venography demonstrates the nearly occlusive thrombus at the portosplenic confluence (arrows). Thrombolysis was initiated. (B) Portal venous phase of a splenic artery angiogram shows nearly occlusive thrombus (arrows) protruding into the splenic vein. Arrowheads show the subtraction artifact of the splenic artery catheter. Initial attempt at thrombolysis via the superior mesenteric artery was unsuccessful, but the thrombus resolved with thrombolysis via the transjugular route.

angiography. Intrahepatic venous collateral vessels classically show a spiderweb appearance on venography.40,41 BCS can result in portal hypertension, variceal bleeding, refractory ascites, and liver failure. Initial management for BCS includes anticoagulation, and management of medical management portal hypertension includes

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Tumor-Associated Hemorrhage Spontaneous hepatic bleeding is rare in the absence of trauma or anticoagulation therapy. The most common cause of atraumatic hemorrhage within the liver is hypervascular neoplasm, such as HCC and hepatic adenoma.43 Rupture of HCC is associated with a high mortality rate, and therefore, early diagnosis and management are essential. HCC commonly occurs in the setting of cirrhosis or chronic hepatic inflammation and is the most prevalent malignant disease in the world, killing up to 1.25 million persons annually. Over the past 30 years, its prevalence has increased 2-fold in the United States.44 Spontaneous rupture has been reported at 3%-15% and is the third leading cause of death after liver failure and

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FIG 9. Budd-Chiari syndrome. Contrast-enhanced axial CT (A) shows heterogeneous and decreased peripheral enhancement of the liver parenchyma with surrounding ascites. Note the thrombosed hypoattenuating hepatic veins (arrows). Venography of the middle hepatic vein (B) shows a spiderweb pattern of collateral vessels, pathognomonic for Budd-Chiari. (C) A covered TIPS has been placed, and 2 stents were needed given the long track secondary to hepatomegaly. Arrows indicate the radiopaque rings that mark the covered portion of each stent graft. The patients liver function improved after TIPS.

tumor progression.45 However, ruptured HCC is less common in the Western world when compared to Asia, which may be related to smaller tumor size at diagnosis. The likelihood of rupture is higher in patients with concomitant cirrhosis and HCC.43,46 The clinical diagnosis of ruptured HCC may prove difficult, given the lack of specific symptoms. Some patients may report a history of minor abdominal trauma; however, symptoms often overlap with those of uncomplicated HCC. Subcapsular hematomas may present as a sudden onset of epigastric or right upper quadrant pain due to rapid distention or tearing of Gilson’s capsule. Shock is present in the majority of patients at admission, and 60%-100% of patients have signs of peritonitis and abdominal distention.47

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The exact mechanisms for spontaneous rupture of HCC have not been established, and some theories have been proposed. For example, bleeding may occur from rupture of a parasitic feeding artery or draining vein. Other investigators believe hemorrhage may arise secondary to tumor laceration, as a result of minor trauma, or as a result of repeated respiratory movement. Additionally, bleeding and rupture may occur due to an increased intratumoral pressure related to associated hepatic vein occlusion. Subcapsular tumors are at higher risk for rupture than tumors that are entirely surrounded by hepatic parenchyma. Ascites in the space between the liver and parietal peritoneum may cause separation, leading to tearing of adherent surfaces or rupture of an

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adjacent artery.47,48 Rupture on the surface of the liver results in hemoperitoneum, whereas rupture of an intraparenchymal tumor may manifest as pain with controlled bleeding secondary to tamponade from the liver parenchyma rather than significant blood loss, when a tumor ruptures into the peritoneum. A wide spectrum of imaging appearances are seen with ruptured HCC, from minor intrahepatic hemorrhage to extensive subcapsular hemorrhage with rupture through the capsule into the peritoneum. CT is useful in detecting HCC rupture by demonstrating the tumor and delineating the extent and age of hemorrhage by showing serial density changes. Acute hemorrhage is hyperattenuating and progressively decreases in attenuation with the development of a pseudocapsule by 10-30 days. On nonenhanced CT, high-attenuating areas near the ruptured tumor represent clotted blood, also known as the sentinel clot sign. Subcapsular hemorrhage appears as highattenuation peritoneal fluid around the liver and spleen (Fig 10). The CT appearance during the arterial phase may show a nonenhancing, low-attenuatinglesion with focal discontinuity and peripheral rim enhancement.47,49 In the US, the diagnosis of a hemorrhagic HCC is suggested by a hyperechoic mass or a mass containing mixed hyperechoic areas. An intralesional high T1-weighted signal on magnetic resonance imaging can suggest the diagnosis of hemorrhagic HCC. However, one-third of HCCs have increased signal intensity on T1-weighted images, and this appearance can be due to steatosis, intracellular glycogen, or copper deposition in addition to hemorrhage.43 Although some patients can be managed expectantly, many require either surgery or catheter-based therapy. Some advocate surgery for treatment as it may allow for definitive treatment.45,50 However, though some patients have an anatomically resectable disease amenable to surgery, patients with bilobar or multifocal disease should be treated with transarterial embolization. Unfortunately, many patients may not have the liver functional reserve to tolerate surgery nor embolization.45,51 Yet, transarterial embolization is usually performed as a life-saving measure, even though the patient may ultimately die from related progressive liver failure. Transarterial embolization is 94% effective at initial hemostasis.51 Embolization can be performed at the level of a lobar artery. Yet, if clear active bleeding is identified at angiography, many operators attempt more selective embolization to preserve as much liver function as possible.

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Embolization can be performed with gelfoam or permanent embolic particles. Some advocate gelfoam, which may preserve vasculature for chemoembolic or radioembolic treatment if the patient survives. Even if the patient tolerates embolization, prognosis after peritoneal rupture remains poor as peritoneal metastasis is seen in 20% of these patients.51 Hepatocellular adenomas are benign tumors of the liver. These tumors are associated with oral contraceptive use and estrogen steroid therapy, and the incidence is increasing. Hepatic adenomas can also occur spontaneously or associated with underlying

FIG 10. Ruptured HCC. Axial contrast-enhanced CT (A) shows a focal disruption in the liver capsule (arrow) at the site of tumor rupture, and hyperattenuating sentinel clot (arrowheads) extends along the liver surface. (B) Celiac angiogram shows displacement of the liver from the body wall (arrowheads) secondary to hematoma. Arrow indicates an area of active hemorrhage. The patient was treated with selective gelfoam embolization. The patient stabilized after embolization, however, had widespread peritoneal metastases at follow-up.

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metabolic diseases, such as type 1 glycogen storage disease.47 They are most often found in women of childbearing age who have a history of prolonged oral contraceptive use. Although there is risk of malignant transformation, the risk of spontaneous rupture and bleeding is more common.52 Adenomas are hypervascular masses and are predisposed to hemorrhage and spontaneous rupture due to their underlying tumor architecture. Adenomas consist of well-differentiated hepatocytes separated by blood-filled, dilated sinusoids and lack a connective tissue support. Also, because the tumor capsule is usually incomplete, hemorrhage may spread into the liver or abdominal cavity.47,53 Identification of hepatic adenomas is important because of the associated risk of life-threatening hemorrhage. Large adenomas are more prone to spontaneous hemorrhage. US shows hemorrhagic adenomas as echogenic or heterogeneous mass containing cystic areas, likely representing areas of old hemorrhage. The diagnosis is highly suggested on nonenhanced CT, as a hepatic tumor containing hyperattenuating areas with adjacent subcapsular hematoma, in a woman taking oral contraceptives. On magnetic resonance imaging, hepatic adenomas may appear heterogeneous and hyperintense on T1-weighted and T2-weighted images due to underlying hemorrhage.47 In contrast to patients with HCC, this patient population is often younger and healthier. This makes them more likely to respond to conservative medical management. Patients who do not respond to medical management can proceed to embolization or resection, which should be well tolerated in most of these patients given preserved liver function.52 Much less common than HCC are hepatic angiosarcomas. These are hypervascular hepatic tumors that can also undergo spontaneous hemorrhage.46 Intrahepatic metastases can also undergo spontaneous rupture; however, this is very uncommon. Hepatic metastases from lung carcinoma, renal carcinoma, and melanoma are the most frequent types to cause hemorrhage. Spontaneous rupture of hepatic metastases is a rare event, and the hemoperitoneum is most frequently associated with primary liver tumors, which have greater vascularity than metastatic lesions.47 Rupture is also extremely uncommon in CCA due to the low vascularity and abundant fibrous stroma of these tumors.53 Transarterial chemoembolization (TACE) has become the accepted treatment for people with

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unresectable HCC with adequate liver reserve and acceptable performance status. Although chemoembolization is a relatively safe procedure, major complications can arise in up to 5% of patients.54 Complications from TACE can be categorized as vascular (secondary to catheter or wire manipulation) or hepatic related. Abscess formation is also seen postembolization, and treatment has been discussed in previous sections. Biloma formation is often detected on follow-up cross-sectional imaging after TACE. The majority of bilomas are asymptomatic and do not require treatment.54 However, the presence of bilomas may preclude future catheter-based therapies. If a biloma causes obstruction or infection, it is treated with percutaneous drainage as previously described. Liver failure is a rare complication of TACE, occurring in 2%-3% of patients. Although several risk factors increase the likelihood of liver failure, the presence of baseline liver dysfunction is the most significant factor. In patients with acute liver failure following TACE, cross-sectional imaging is often unremarkable. Radioembolization with yttrium-90 microspheres has emerged as a safe and efficacious treatment modality for liver malignancies, showing efficacy in both primary and metastatic liver tumors. The most common and serious liver-related complication is radiation-induced liver disease, which can occur in up to 5% of patients. This is clinically manifested by liver dysfunction, and veno-occlusive disease is detected on pathology. Baseline underlying liver dysfunction, higher radiation doses (in excess of 150 Gy), and exposure to prior chemotherapy or intra-arterial therapies are the risk factors.55 The sequelae of nontarget embolization can be seen as cholecystitis or bowel ulceration.

Conclusion The clinical manifestations of hepatobiliary malignant disease are often nonspecific, and imaging plays a significant role in the diagnosis and prompt management of hepatobiliary oncologic emergencies. These emergencies can cause significant morbidity and mortality when not accurately identified and timely addressed. Additionally, the number of patients with cancer continues to increase, many with complex and multisystem diseases. The radiologist’s awareness of the imaging findings and associated interventions of hepatobiliary emergencies will aid in the timely diagnosis and management of these patients.

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