Nonoperative Imaging Techniques in Suspected Biliary Tract Obstruction

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provided by Elsevier - Publisher Connector HPB, 2006; 8: 409425

REVIEW ARTICLE

Nonoperative imaging techniques in suspected biliary tract obstruction

FRANCES TSE1, JEFFREY S. BARKUN2, JOSEPH ROMAGNUOLO3, GAD FRIEDMAN4, JEFFREY D. BORNSTEIN5 & ALAN N BARKUN2

1Division of Gastroenterology, McMaster University Medical Centre, McMaster University, Hamilton, Ontario, Canada, 2Division of Gastroenterology, Montreal General Hospital and Royal Victoria Hospital Sites, McGill University Health Centre, Montreal, Quebec, Canada, 3Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC, USA, 4Division of Gastroenterology, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada and 5Division of Gastroenterology, Duke University Medical Centre, Durham, NC, USA

Abstract Evaluation of suspected biliary tract obstruction is a common clinical problem. Clinical data such as history, physical examination, and laboratory tests can accurately identify up to 90% of patients whose jaundice is caused by extrahepatic obstruction. However, complete assessment of extrahepatic obstruction often requires the use of various imaging modalities to confirm the presence, level, and cause of obstruction, and to aid in treatment plan. In the present summary, the literature on competing technologies including endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiopancreatography (PTC), endoscopic ultrasound (EUS), intraductal ultrasonography (IDUS), magnetic resonance cholangiopancreatography (MRCP), helical CT (hCT) and helical CT cholangiography (hCTC) with regards to diagnostic performance characteristics, technical success, safety, and cost-effectiveness is reviewed. Patients with obstructive jaundice secondary to choledocholithiasis or pancreaticobiliary malignancies are the primary focus of this review. Algorithms for the management of suspected obstructive jaundice are put forward based on current evidence. Published data suggest an increasing role for EUS and other noninvasive imaging techniques such as MRCP, and hCT following an initial transabdominal ultrasound in the assessment of patients with suspected biliary obstruction to select candidates for surgery or therapeutic ERCP. The management of patients with a suspected pancreaticobiliary condition ultimately is dependent on local expertise, availability, cost, and the multidisciplinary collaboration between radiologists, surgeons, and gastroenterologists.

Key Words: jaundice, cholestasis, choledocholithiasis, common bile duct neoplasms, cholangiocarcinoma, cholangiopancreatography, cholangiography, endosonography, magnetic resonance angiography, magnetic resonance imaging, CT, spiral CT, ultrasonography, costs and cost analysis

Introduction rately identify up to 90% of patients whose jaundice is caused by extrahepatic obstruction [121]. However, Evaluation of obstructive jaundice is a common clinical problem. Often, the initial problem is to complete assessment of extrahepatic obstruction often distinguish between intrahepatic and extrahepatic requires the use of various imaging modalities to biliary obstruction. Choledocholithiasis and pancrea- confirm the presence, level, and cause of obstruction, ticobiliary malignancies (pancreatic head cancer, and to aid in treatment planning. Current technolo- ampullary cancer, and cholangiocarcinoma) are the gies include transabdominal ultrasound (US), endo- most common causes of extrahepatic obstruction. scopic retrograde cholangiopancreatography (ERCP), Less common causes include benign strictures, transhepatic cholangiopancreatography (PTC), endo- chronic pancreatitis, metastatic nodes to the porta scopic ultrasound (EUS), magnetic resonance cho- hepatis, and primary sclerosing cholangitis. Many langiopancreatography (MRCP), helical CT (hCT), studies have shown that clinical data such as history, and helical CT cholangiography (hCTC). With the physical examination, and laboratory tests can accu- rapid advancement in imaging technology, there is

Correspondence: Dr Frances Tse, 4W8, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario, Canada, L8N 3Z5. Tel: /1905 521 2100, ext. 76732. Fax: /1 905 521 4958. E-mail: [email protected]

ISSN 1365-182X print/ISSN 1477-2574 online # 2006 Taylor & Francis DOI: 10.1080/13651820600746867 410 F. Tse et al. little consensus in the literature as to which imaging where appropriate. Where appropriate, although be- modality is most appropriate for a given clinical yond the scope of this narrative review, pertinent situation. This can lead to duplication of testing issues relating to tissue diagnosis and therapy (since with the possibility of increasing costs and delaying some of the techniques described may be both diagnosis. Furthermore, newer modalities are often diagnostic and therapeutic) are briefly discussed. being incorporated into practice before accurate Finally, based on the results of the literature search, assessment of their cost-effectiveness has been com- clinically relevant algorithms were constructed to pleted. highlight the possible roles of new technologies in The purpose of this article is to review competing the work-up of patients with suspected CBD stones or technologies in the evaluation of suspected extrahe- pancreaticobiliary malignancies. patic obstruction with regard to diagnostic performance characteristics, technical success, safety, and cost-effectiveness. Patients with obstructive jaundice Current imaging technologies secondary to common bile duct (CBD) stones or Direct versus indirect imaging pancreaticobiliary malignancies are the primary focus The various imaging modalities can be classified into of this review. The work-up of patients with suspected either direct or indirect techniques [22]. The former intrahepatic cholestasis will not be addressed. Algo- rithms for the management of suspected obstructive are more invasive, and include ERCP and PTC. They jaundice due to CBD stones and pancreaticobiliary carry a higher associated risk, but have the added malignancies are provided. ability to sample tissue and perform therapeutic maneuvers, such as biliary drainage with stenting or stone removal. The main concern with these techni- Methods ques is the risk of pancreatitis and cholangitis as a A systematic search was performed for relevant arti- result of opacification of an obstructed biliary tree cles published in English language using MEDLINE that cannot be drained, with rare complications such and PUBMED from 1966 to December 2003. The as perforation, bleeding or bile leak [2326]. Also, search strategy included the key terms: cholestasis, direct techniques are limited to the evaluation of the choledocholithiasis, pancreatic neoplasms, biliary tract intrinsic biliary tract and cannot define the presence neoplasms, cholangiocarcinoma, ampulla of vater, cho- of extrinsic compression of the biliary tree by langiography, endoscopic, intravenous, laparoscopic, in- surrounding structures. Indirect techniques offer tra-operative, ultrasonography, magnetic resonance lower procedural risk and may allow staging of imaging, computed tomography, spiral computed tomo- malignancies. New indirect modalities, such as graphy, surgery, complications, decision support techni- MRCP (with solid organ MR), EUS, and hCTC ques, costs and cost analysis, cost-benefit analysis, (with hCT) offer improved imaging quality, while at sensitivity and specificity, comparative study, and pro- the same time maintaining a low risk profile. EUS has spective studies. Information was collected on test some therapeutic potential in addition to the oppor- performance characteristics (sensitivity, specificity, tunity for biopsy and cytology, but because it requires negative and positive predictive values), with regards conscious sedation, it is the most invasive of the to identifying the presence, level, and cause of biliary indirect group of imaging technologies. Table I obstruction. The technical success, safety and costs of summarizes the advantages and disadvantages of the the various imaging modalities were also examined main techniques discussed.

Table I. Comparison of advantages and disadvantages of the main biliary imaging techniques.

Indirect Direct

Imaging modality US hCTC* MRCP$ EUS ERCP PTC

Portability /// / / // / / Safety /// // /// // / / Operator dependence /// / // /// // // Low cost /// / / / / // Staging of malignancy / /// /// /// / / Tissue sampling / / / /// /// // Therapy / / / / /// ///

US, transabdominal ultrasound; hCTC, helical CT cholangiography; MRCP, magnetic resonance cholangiopancreatography; EUS, endoscopic ultrasound; ERCP, endoscopic retrograde cholangiopancreatography; PTC, transhepatic cholangiopancreatography. *hCTC includes cholangiography that requires intravenous contrast administration that is excreted into the biliary tract. $Includes abdominal MR. Nonoperative imaging techniques in suspected biliary tract obstruction 411 Transabdominal ultrasonography (US) strate the cause of biliary obstruction, and helps in making a diagnosis based on the morphology of the Transabdominal US (US) remains the initial imaging biliary and pancreatic ducts. In the evaluation of CBD test of choice in the evaluation of suspected biliary stones, Frey et al. [61] noted that ERCP had a obstruction because it is noninvasive, inexpensive, sensitivity of 90%, a specificity of 98%, and an and readily available [9,2734]. Dilated ducts are accuracy of 96%. Standard procedures, such as usually taken as indirect evidence of biliary obstruc- sphincterotomy (ES) and balloon or basket stone tion [9,32,33,3538]. The presence of normal ducts, extraction, are successful in clearing CBD stones in however, does not exclude obstruction [9,32,33,35 8590% of cases [6267]. For those patients in 38]. This is mainly because, in certain cases, biliary whom standard techniques are unsuccessful, mechan- obstruction may not be accompanied by dilatation of ical lithotripsy will increase the success rate to more the CBD. Conversely, the CBD increases in diameter than 90% [68,69], while the insertion of a biliary stent in response to cholecystectomy and aging [3945]. is reserved for rare high-risk cases [7072]. Despite these exceptions, ductal dilatation remains ERCP also plays an important role in the diagnosis an excellent clue to biliary obstruction. Specifically, and palliation of pancreaticobiliary tumors. Radio- US has been shown to be highly accurate (7898%) graphic findings may be suggestive of malignancy, but for detecting extrahepatic obstruction [9,27,32,33, a definitive diagnosis requires tissue sampling. 36,46]. In conjunction with a concordant clinical Although many patients are managed without histo- evaluation, US allows an accurate differentiation logical confirmation, confirmation allows accurate between liver parenchymal disease and extrahepatic decision making with respect to patient management obstruction (sensitivity 65%, specificity 92%, PPV options, including surgery, endoscopic stenting, che- 92%, NPV 98%) [8,47]. However, US is less motherapy, or radiotherapy [73]. Common methods discriminating with respect to the level and cause of endoscopic tissue sampling including brush cytol- of obstruction, with reported accuracies ranging ogy, endoscopic fine-needle aspiration (FNA), and between 2795% and 2388%, respectively [2932, forceps biopsy have relatively low to moderate sensi- 34,35,46,4850]. Also, the test performance of US is tivity (2060%) but almost 100% specificity [7476]. variable in differentiating malignant from benign Cancer detection rate may be increased by combining causes of obstruction with an overall accuracy ranging at least two sampling methods [74,77]. Tissue sam- from 47% to 90% [2931,34,35,46,4851]]. In the pling sensitivity also varies according to the type of diagnosis of CBD stones, US exhibits poor test tumor. Brush cytology and forceps biopsy have a performance at detecting CBD stones with sensitiv- higher sensitivity for cholangiocarcinoma (44100%) ities in the range of 2558% and specificities of than for pancreatic cancer (3065%) [73,74,7784]. 6891% [27,36,46,48,52,53]. Variable results are Forceps biopsy is the single best technique for the also seen in the setting of pancreaticobiliary malig- diagnosis of ampullary tumors, with a cancer detec- nancies, with sensitivities ranging from 5% for tion rate of 7788% [74]. More recently, a number of ampullary to 6781% for pancreaticobiliary malig- newer technologies have been proposed [76]. Pallia- nancies [5459]. These data demonstrate that the tion of malignant obstruction can be achieved by major limitation of US is in its inability to reliably ERCP with biliary stent insertion (plastic or metal). diagnose the level and cause of obstruction. Other Randomized controlled trials have shown endoscopic drawbacks of US are operator dependency and stent placement to be cost-effective compared with suboptimal imaging of retroperitoneal structures due surgery, and to enhance quality of life [8589]. to overlying bowel gas or obesity [60]. ERCP combines the advantage of diagnosis of biliary obstruction with possible therapeutic intervention. Because of the ability to perform therapeutic Endoscopic retrograde cholangio-pancreatogragraphy maneuvers, ERCP has become the intervention of (ERCP) choice in the management of patients with CBD Endoscopic retrograde cholangio-pancreatography stones, and in the palliative treatment of patients (ERCP) is performed using a side-viewing duodeno- with malignant biliary obstruction [9092]. The scope, which allows an en face view of the ampulla. drawbacks to ERCP include equipment cost, need An instrument channel in the duodenoscope enables for conscious sedation, and high operator depen- cannulation of the papilla and injection of contrast dency. Failure rate increases substantially for patients into the biliary and pancreatic ducts to obtain with altered anatomy such as Billroth II gastrectomy diagnostic images. Therapeutic interventions such as [9396]. Limitations of ERCP include reduced sphincterotomy, stone extraction, stricture dilatation, sensitivity with small stones in a dilated bile duct, stent insertion, and tissue sampling can be performed failure to visualize stones because of inadequate at the same time. opacification of the biliary tree with contrast, and ERCP has traditionally been considered the gold difficulty in differentiating stones from air bubbles standard for imaging the biliary system, particularly [97,98]. These limitations may lead to increases in if therapeutic intervention is planned. It can demon- procedure time, unnecessary sphincterotomy, and 412 F. Tse et al. unnecessary instrumentation of the bile duct with failed or when altered anatomy (gastroenterostomy) balloon catheters and basket. Visualization of the precludes accessing the ampulla [116]. It has also biliary tree proximal to an obstructing lesion can be been used as a therapeutic drainage procedure in difficult, and contrast injection above the site of patients with unresectable hilar tumors or hepato- obstruction usually mandates biliary stent insertion lithiasis [117121]. because of the risk of cholangitis [92]. Also, the low yield of ERCP for cytology in malignant obstruction Endoscopic ultrasonography (EUS) often results in additional procedures (EUS-FNA, CT-FNA, or operation) to make a tissue diagnosis of EUS combines endoscopy and ultrasound to provide cancer [73,74,7784,99]. Furthermore, staging in- high-resolution images of the pancreaticobiliary sys- formation for pancreaticobiliary malignancies is very tem transgastrically or transduodenally using a water- difficult to obtain by ERCP [100,101]. Large pro- filled balloon system for acoustic coupling [122,123]. spective series have found overall complication rates Echoendoscopes have frequencies in the 7.512 MHz of 510% and mortality rates of 0.020.5% after range, which gives a depth of penetration of 810 cm. diagnostic and therapeutic ERCP [2326]. The most Tissue sampling in the form of EUS-guided fine- common complication is acute pancreatitis, occurring needle aspirate (EUS-FNA) can also be performed. in 5% of cases, and being moderate to severe in about EUS is very accurate in determining the cause of 1% [2326,102]. Complication rates appear to have extrahepatic obstruction with a sensitivity of 97% and decreased more recently owing to a more careful a specificity of 88% compared with the combined gold selection of patients (at lower risk for complications), standard of ERCP, intraoperative cholangiography and perhaps, the increased use of guidewires for (IOC), and clinical-follow-up [124]. In particular, selective cannulation [103,104]. Because of its atten- EUS is very accurate in diagnosing CBD stones, with dant risks, and the availability of safer noninvasive a sensitivity of 95%, specificity of 98%, and an cholangiographic methods with comparable diagnos- accuracy of 96% [17,22,57,122,123,125131]. These tic abilities, ERCP is evolving into a predominantly results are far superior to US (sensitivity 63%) and therapeutic procedure [105]. CT (sensitivity 71%) [127], and are equivalent if not superior to those of ERCP or MRCP [132]. EUS is especially more accurate in detecting small stones or Percutaneous transhepatic cholangiography (PTC) stones within small caliber CBDs [127,133]. EUS has PTC involves puncture of the liver with a 22-gauge also been shown to be excellent in distinguishing needle under fluoroscopic guidance to enter the among different types of malignant obstruction peripheral intrahepatic bile duct system above the [57,99,134136]. The reported accuracies for EUS- common hepatic duct [106108]. Contrast is then FNA of pancreaticobiliary masses are over 80%, with injected to opacify the biliary tree and to identify results better for pancreatic masses than for biliary obstruction. The biliary tree can be successfully tumors [137144]. Many prospective studies have visualized in close to 100% of patients with dilated shown EUS to be more sensitive (93100%) than all ducts, and in 6080% of patients with nondilated other imaging modalities including CT (5377%), ducts [106108]. PTC is considered, along with US (5067%), MRI (5067%), and ERCP (90%) ERCP, the gold standard by which all other imaging in the detection of pancreatic tumors [5456,136, modalities of the biliary tree are evaluated. It is 145153]. The superiority of EUS becomes even excellent at determining the level and cause of biliary more evident for tumors B/3 cm [54,55,145, obstruction, as well as distinguishing benign from 149,150,152]. This is clinically relevant as patients malignant lesions, while being less costly than ERCP with small tumors are most likely to benefit from [109,110]. It can also be applied therapeutically for surgical resection. Once a pancreatic mass is identi- external drainage of obstructed ducts. fied, accurate staging is crucial to identify patients

The overall rate for major complications is B/5%, with locoregional disease that is amenable to surgical with a mortality rate of 0.1% [107,111]. Complica- resection, and to prevent unnecessary surgical ex- tions include bile leaks, bile peritonitis, hemobilia, ploration. EUS is highly accurate in determining the sepsis, intraperitoneal hemorrhage, intrahepatic fistu- T (6994%) and N staging (5480%) of pancreatic las, gallbladder puncture, pneumothorax, subphrenic/ tumors [54,136,147,148,148,154]. It is more accu- subhepatic abscess, pseudoaneurysms, arteriovenous rate (8795%) than CT (4175%) and angiography shunts, and allergic reactions to contrast material (7579%) for detecting invasion of the portal vein, [106,112114]. In a randomized controlled trial splenic vein, and confluence of the portal vein and comparing ERCP to PTC in the management of superior mesenteric vein [55,155160]. It is not as patients with malignant biliary obstruction, ERCP accurate, however, for detecting involvement of the was found to be superior to PTC because of a higher superior mesenteric vein and major arterial vessels success rate, and lower complication rate and mortal- [156,159,160]. For the detection of ampullary tu- ity [115]. Currently, indications for PTC are few; it is mors, many prospective studies have shown EUS performed primarily in patients in whom ERCP has (95100%) to be equivalent to ERCP, but more Nonoperative imaging techniques in suspected biliary tract obstruction 413 sensitive than CT (568%) and US (524%) ERCP-guided bile duct biopsy fails to demonstrate [57,57,59,158,161169]. Also, locoregional tumor malignancy, the presence of certain IDUS sono- staging was more accurately assessed by EUS (72 graphic criteria such as a sessile tumor, tumor size

82% for T stage, 4771% for N stage) than with any /10 mm, and an interrupted wall structure can more other imaging modalities [57,57,59,158,161169]. favor a diagnosis of malignancy [184]. In a prospec- The improved staging ability of EUS may allow tive study by Menzel et al., IDUS was more accurate selection of patients with ampullary tumors who can than EUS for determination of the nature of bile duct undergo local resection instead of pancreaticoduode- strictures (89% vs 76%) and for T staging (78% vs nectomy [157,165]. With respect to cholangiocarci- 54%), particularly for tumors located at the bifurca- noma, EUS has not been proven to offer more tion and mid-bile duct [185]. However, N staging information than other imaging modalities. with IDUS was inferior [185]. For the diagnosis and There are many features that make EUS an T staging of ampullary tumors, IDUS was found to be attractive procedure. It is less invasive than ERCP superior to EUS (100% and 88.9%, 59.3% and [170], and is able to diagnose most causes of 56.3%, respectively) in a prospective study using obstructive jaundice such as pancreaticobiliary malig- histopathology as gold standard [191]. For the nancies and CBD stones [17,122,123,125131] with diagnosis of pancreatic cancer, preliminary studies the same or better accuracy than ERCP. This tech- suggest that IDUS may be useful in detecting nology does not expose the patient to radiation or carcinoma in situ and small tumors and in assessing contrast material. EUS-FNA can also provide a tissue parenchymal invasion and the intraductal spread of diagnosis and important staging information for the tumor [150,192,193]. However, the tortuosity of pancreaticobiliary malignancies. The limitations of the pancreatic duct often precludes passage of the EUS include the high operator dependency with a probe to the proximal duct [194]. For the diagnosis of steep learning curve, equipment cost, unit availability, CBD stones, IDUS seems to be more accurate than the inability to provide an immediate therapeutic ERCP in the detection of small stones within a dilated solution, the need for conscious sedation, and a 2% duct and can differentiate stones from air bubbles failure rate [126]. Visualization is limited to the [195198]. nearest 810 cm depth from the probe, and imaging IDUS has several advantages over EUS of the bile can be obscured by pneumobilia, stents, surgical clips, duct, including higher resolution and the ability to calcifying pancreatitis, or a duodenal diverticulum image the proximal bile ducts. Complications are [171]. rare [176,194]. The drawbacks of IDUS include high equipment cost, fragility of the probe, low depth of penetration, and operator expertise. IDUS Intraductal ultrasonography (IDUS) is of limited value in assessing lymph nodes, IDUS is a relatively new technology and is not and cannot provide a histopathological diagnosis. available at most centers. IDUS of the bile duct Stent-related changes of the bile duct wall may is performed with a highly flexible, thin-caliber reduce the diagnostic utility of IDUS [199201].

(/2 mm), non-optic US probe that can be passed More studies are therefore needed to clearly define through the working channel of a standard duodeno- the role, utility, and cost-effectiveness of IDUS in scope and introduced into the biliary and pancreatic the evaluation of patients with selected pancreatico- ducts during ERCP. Acoustic coupling is optimized biliary diseases. Depending on local availability, by filling both ducts with fluid. IDUS images at higher expertise, and competing technologies, IDUS may frequencies (1230 MHz) than standard EUS and be considered in the work-up of patients with biliary therefore provides higher resolution (0.070.18 mm), obstruction. A combination approach, using infor- but the depth of penetration is consequently reduced mation from IDUS, EUS, and ERCP may prove to (23 cm) [172]. Compared to standard EUS, IDUS be ideal. provides a better evaluation of the proximal biliary system and surrounding structures such as the right Magnetic resonance cholangio-pancreatography (MRCP) hepatic artery, portal vein, and contents of the hepatoduodenal ligament [172176]. Use of wire- Magnetic resonance cholangio-pancreatography guided IDUS probes allows biliary cannulation in (MRCP) is performed with high resolution heavily nearly 100% of patients without sphincterotomy T2-weighted sequences to enhance the signal of [177,178]. However, it may be necessary to dilate stationary fluids in the biliary and pancreatic ducts severely stenotic lesions to facilitate passage of the without the use of contrast material or ionizing probe [177,178]. radiation [202205]. Multiple images are generated In the evaluation of biliary obstruction, IDUS as an and reconstructed by a computer providing a three- adjunct to ERCP and tissue sampling has been shown dimensional image of the bile ducts. Current techni- to improve the ability to distinguish malignant from ques permit imaging of the entire biliary tract in benign strictures with a high degree of accuracy a single breath-hold of 20 s or less and provide

(/90%) [173176,178190]. Furthermore, when high spatial resolution so that structures such as 414 F. Tse et al. fourth-order intrahepatic bile ducts are easily visua- ability, lack of an immediate therapy that can be lized in many cases [206208]. provided for duct obstruction, claustrophobia, and A recent authoritative meta-analysis [209] of 67 the inability to evaluate patients with pacemakers or published controlled trials showed that MRCP has ferromagnetic implants [228]. Causes of possible excellent overall sensitivity (95%: 95% CI (75,99)) artifacts include pneumobilia, normal vessels, flow and specificity (97%: 95% CI (86,99)) for demon- artifacts, and duodenal diverticulum [229231]. A strating the level and presence of biliary obstruction. stone impacted at the ampulla may be missed [232]. However, MRCP is less sensitive for detecting stones As well, low insertion of the cystic duct may be (91%: 95% CI (73,97)) [209]. Moreover, the sensi- mistaken for a dilated CBD [226], and clips in the tivity for detecting stones seems to decrease accord- abdomen from previous surgery may distort images ing to stone size: 67100% for stones /10 mm [233]. in size, 8994% for stones measuring 610 mm, and 3371% for bile duct stones B/6 mm in size [210213]. Therefore, there may still be a need Helical CT (hCT) and helical CT cholangiography for additional non-invasive or invasive imaging (hCTC) methods when choledocholithiasis is suspected. Also, MRCP is not reliable for differentiating malig- hCTC uses slip ring technology with oral or intrave- nant from benign obstruction (88%: 95% CI nous contrast to acquire volumetric data in a single (70,96)) [209]. breath-hold for high-quality three-dimensional recon- MRCP is very useful in the diagnosis of cholan- structions of the acquired image [2,4,203,234240]. giocarcinoma by identifying the exact location, It has the ability to opacify up to third-order intrahe- extent, and severity of the obstruction [214218]. patic bile ducts, and evaluate extra-ductal structures Complete staging information of tumor size, bile in different phases (arterial, portal, parenchymal) duct involvement, and vascular invasion can be [241,242]. obtained when MRCP is combined with conven- The accuracy of conventional CT in determining tional MRI and MR angiography (MRA) [215]. In the presence and level of obstruction has been 81 so doing, MRCP can evaluate the appropriateness of 94% and 8892%, respectively [9,29,46,242245]. curative surgical resection versus palliative drainage In the majority of cases, conventional CT can also procedures, and help determine whether PTC or determine the cause of obstruction with a high degree ERCP constitutes the most appropriate therapeutic of accuracy (7094%) [4,29,53,234,244]. There are intervention [215,218,219]. For pancreatic cancer, a only a few studies published on the use of hCTC large prospective controlled study found MRCP to [24,214,235]. In a prospective study involving 131 be as sensitive (84%) as ERCP in detecting pan- patients with suspected biliary obstruction, hCTC creatic cancer associated with ductal dilatation had an overall diagnostic accuracy of 93% in differ- [220]. However, the detection of pancreatic cancer entiating benign from malignant causes of biliary by MRCP alone without ductal dilatation is difficult obstruction [214]. For the diagnosis of CBD stones, [221225]. Ampullary lesions may be missed be- hCTC achieved a sensitivity of 87% (95% CI cause of the poor performance of MRCP at or near (84,90)), a specificity of 97% (95% CI (95,98)), the duodenal wall as a result of interference from and an overall accuracy of 95% (95% CI (94,97)) for intraluminal gas [226]. Also, MRCP does not the diagnosis of CBD stones compared to direct provide adequate information on staging and resect- imaging such as ERCP or IOC [3,4,235,237 ability. The combinations of MRCP with conven- 242,246]. For the diagnosis and determination of tional MRI and MRA may provide sufficient ductal, resectability of pancreatic cancer, a recent meta- parenchymal, and vascular information for the analysis of 68 controlled trials showed that hCT has diagnosis and resectability of pancreatic cancers significantly higher accuracy (sensitivity 91% and [221225]. specificity 81%) than conventional US (sensitivity The major advantage of MRCP is the noninvasive 82% and specificity 75%), or MRI (sensitivity 84% nature of the procedure. It does not require conscious and specificity 76%) [247]. For the diagnosis and sedation, intravenous contrast, or radiation exposure. locoregional staging of peri-ampullary tumors, many Diagnostic images can be obtained in the vast prospective studies have shown CT to be unreliable majority of patients including those who have com- (detection rates of 2229%) and less accurate than plex bilio-enteric anastomoses [227]. As well, MRCP EUS [59,157,158,162,166,167,191]. With regards can demonstrate the biliary tree above and below a to the diagnosis of cholangiocarcinoma, hCT has complete obstruction [203]. In cholangiocarcinoma, been shown to display accuracies up to 100% in the main advantage of MRCP is that it can noninva- hepatic arterial dominant phase and 86% in portal sively provide a three-dimensional understanding of vein dominant phase scans [248]. However, hCT the biliary tree, which can help in planning treatment is inaccurate for assessing resectability (6086%), [218]. The major disadvantages of MRCP compared because of its limitations in detecting small perito- with ERCP are lower spatial resolution, unit avail- neal implants, small hepatic metastasis, lymph node Nonoperative imaging techniques in suspected biliary tract obstruction 415 metastasis in normal sized nodes, and the intraductal Algorithmic approach to patients with suspected extent of tumor [248250]. biliary obstruction The major advantages of hCTC over ERCP or None of the aforementioned technologies are ideal, EUS include its low level of invasiveness, operator and each exhibits advantages and disadvantages. independence, and low technical failure rate (1%), as The optimal method of biliary imaging for the well as, in contrast to ERCP, a three-dimensional diagnosis and management of patients with biliary understanding of the biliary tree. Although noninva- obstruction depends on the clinical situation. sive, hCTC gives a relatively high dose of radiation Although every patient is different, general guide- to patients. The major drawback of hCTC is a risk lines, based on diagnostic test performance of the of adverse reaction to the iodinated contrast agents different imaging modalities, may be put forward in (1%). Major reactions include hepatorenal toxicity, the form of management algorithms. It must be cardiopulmonary symptoms, hypotension, severe emphasized, however, that any final management skin reactions, and anaphylaxis [113]. Minor reac- decisions for a given patient must be based on the tions have been reported in up to 24% of patients pre-test probability of a given condition (based on [113]. These include urticaria, pruritus, and gastro- history, physical examination, and laboratory data), intestinal symptoms. The overall mortality rate is patient preferences, local availability of equipment, 1 in 30005000 examinations [113]. Its main limita- and expertise. We attempt below to provide broad tion is in patients with high-grade obstruction guidelines in the work-up of patients with suspected and impaired hepatic function with high serum biliary obstruction. bilirubin levels (/35 mmol/L) because contrast is The initial imaging test in patients with suspected not eliminated sufficiently into the biliary tree biliary obstruction should be a transabdominal [237,238]. The artifacts produced by a patient’s ultrasound. It is inexpensive, easy to perform, movement or respiration might also limit the diag- readily available, and noninvasive. It has been nostic value of this test. shown to be excellent for determining the presence

Suspected CBD stones

Likelihood of CBD stone based on history, physical examination, lab data, and US

Low Intermediate High

Laparoscopic cholecystectomy Preoperative ERCP No bile duct imaging (in certain cases OR* postoperative ERCP)

Laparoscopic Preoperative ERCP* or intraoperative EUS* or cholangiography MRCP*

Positive

OR*

Laparoscopic CBD exploration Postoperative ERCP

Figure 1. A proposed algorithm for the management of patients with suspected common bile duct (CBD) stones undergoing laparoscopic cholecystectomy. ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; MRCP, magnetic resonance cholangiopancreatography; US, transabdominal ultrasound. *Depending on costs, availability, and local expertise. 416 F. Tse et al. or absence of bile duct obstruction, although it is laparoscopic cholecystectomy should be performed not as good for determining the level or the cause with no cholangiography. ERCP remains the pre- of the obstruction. Ultrasound results will help ferred procedure (either preoperatively or postopera- determine the next imaging study to perform, if tively) for patients at high risk of CBD stones. For any. patients at intermediate risk of CBD stones, the optimal approach seems to be intraoperative cholan- giogram followed, if positive, by laparoscopic CBD Biliary obstruction suspected CBD stones exploration or postoperative ERCP depending on Proper selection of patients for further biliary imaging local expertise. Alternatively, a strategy that involves to exclude CBD stones is crucial in order to minimize preoperative ERCP, EUS, or MRCP may be consid- patient morbidity and institutional costs. Many deci- ered for patients at intermediate risk, depending on sion models have confirmed that an optimal approach local availability, expertise, and cost issues. A pro- to the management of these patients is dependent on posed algorithm for the management of patients with the pre-test probability of having CBD stones, as well suspected CBD stones undergoing laparoscopic cho- as local availability and expertise [1,1021]. A full lecystectomy is shown in Figure 1 [22]. In the discussion of all predictive models is beyond the scope postoperative setting, the optimal approach is again of this review. For patients at low risk of CBD stones, dependent on the pre-test probability of CBD stones.

Suspected pancreaticobiliary malignancy based on history, physical examination, lab data, and US

Suspected level of obstruction based on US

Level Upper third of Middle third of Lower third indeterminate CBD CBD of CBD

Diagnosis MRCP* or MRCP* EUS* or EUS *or and staging EUS* or or hCTC* MRCP* or ERCP* modalities hCTC* or hCTC* ERCP*

No specific cause Specific cause determined

Surgical candidate and Re-evaluate lesion appears resectable Further imaging

Yes No

Surgery EUS-FNA*

Palliative treatment that may include ERCP with stenting

Figure 2. A proposed algorithm for the management of patients with suspected pancreaticobiliary malignancy. CBD, common bile duct; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; FNA, ﬁne-needle aspiration; hCTC, helical CT cholangiography; MRCP, magnetic resonance cholangiopancreatography; US, ultrasound. *Depending on costs, availability, and local expertise. Nonoperative imaging techniques in suspected biliary tract obstruction 417 PTC can be used as an alternative to surgery in the need for further diagnostic tests while influencing patients with failed ERCP who require urgent biliary clinical decisions [256259]. drainage, such as in undrained cholangitis. hCTC Real-life results, however, may be different from cannot be recommended in the routine work-up and what could be anticipated on the basis of test management of patients with suspected CBD stones performance characteristics or decision modeling. because of its risks and limited performance char- For example, coincident with the marked increase in acteristics in patients with high grade obstruction. the number of MRCPs performed for biliary obstruction at the Hopital Erasme in Brussels from 1995 to 1997, there was only a minor reduction in the total Biliary obstruction suspected pancreaticobiliary number of ERCPs (about one diagnostic or thera- malignancy peutic ERCP less for every four additional MRCPs) If pancreaticobiliary malignancy is suspected on the [260]. Preliminary data from a prospective rando- basis of clinical and US findings, further imaging mized trial [261] from our group comparing ERCP must be performed to obtain a diagnosis, stage the with MRCP, whose study population was mainly extent of the malignant process for resectability, and composed of patients with suspected choledocho- evaluate the need for possible palliative treatment. lithiasis, suggested a high rate of subsequent ERCPs Identification of the level of obstruction is of great in the MRCP arm (51%), with no differences between importance since the differential diagnosis and ther- the groups in terms of rate of subsequent complica- apeutic implications are different for each level. A tions or overall duration of hospital stay. In a distal CBD obstruction may be amenable to an prospective study, performing EUS-FNA as the first endoscopic or surgical drainage procedure whereas a endoscopic procedure in patients suspected to have more proximal one may require a more complex biliary obstruction obviated the need for about 50% of intrahepatic anastomosis or percutaneous drainage. ERCPs, helped direct subsequent therapeutic ERCP, The optimal approach to patients with malignant and substantially reduced costs by $3513 per patient biliary obstruction must take into account the perfor- [262]. Similarly, in a selected cohort of 44 patients mance characteristics of the different imaging mod- with pancreatic cancer, EUS-FNA may have avoided alities, the level and cause of the obstruction, the risk unnecessary surgery in 27% and further diagnostic of cholangitis when opacifying an obstructed biliary testing in 57% for a saving of $3300 per patient [140]. tree, and the potential for curative versus palliative More true outcome trials are therefore needed to therapy. Recent data suggest that noninvasive biliary better assess the impact on clinical decision-making or imaging may greatly assist endoscopic drainage and patient outcomes of these new diagnostic methods. diminish septic complications that occur when there is a failed attempt at unilateral or bilateral drainage Conclusion [215,216,218,251,252]. A proposed algorithm for the management of patients with suspected pancreatico- In summary, published data suggest an increasing role biliary malignancy is shown in Figure 2, and presents for EUS and other noninvasive imaging techniques many similarities to that recently proposed by the such as MRCP and hCT following an initial US in the ASGE [253]. assessment of patients with suspected biliary obstruction to select candidates for surgery or therapeutic ERCP. Ultimately, the management of patients with a Decision models, cost-effectiveness and suspected pancreaticobiliary condition is dependent outcome studies on local expertise, availability, cost, and collegial The literature with respect to cost-effectiveness of the multidisciplinary collaboration between radiologists, new biliary imaging technologies is unfortunately surgeons, and gastroenterologists. limited. 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