R Girometti, MD, G Brondani, MD, L Cereser, MD, G Como, MD, M Del Pin, MD, M Bazzocchi, MD, and C Zuiani, MD
Post-cholecystectomy syndrome (PCS) is defined as a complex of heterogeneous symptoms, consisting of upper abdominal pain and dyspepsia, which recur and/or persist after cholecystectomy. Nevertheless, this term is inaccurate, as it encompasses biliary and non-biliary disorders, possibly unrelated to cholecystectomy. Biliary manifestations of PCS may occur early in the post-operative period, usually because of incomplete surgery (retained calculi in the cystic duct remnant or in the common bile duct) or operative complications, such as bile duct injury and/or bile leakage. A later onset is commonly caused by inflammatory scarring strictures involving the sphincter of Oddi or the common bile duct, recurrent calculi or biliary dyskinesia. The traditional imaging approach for PCS has involved ultrasound and/or CT followed by direct cholangiography, whereas manometry of the sphincter of Oddi and biliary scintigraphy have been reserved for cases of biliary dyskinesia. Because of its capability to provide non-invasive high-quality visualisation of the biliary tract, magnetic resonance cholangiopancreatography (MRCP) has been advocated as a reliable imaging tool for assessing patients with suspected PCS and for guiding management decisions. This paper illustrates the rationale for using MRCP, together with the main MRCP biliary findings and diagnostic pitfalls.
Post-cholecystectomy syndrome (PCS) consists of a group of abdominal symptoms that recur and/or persist after cholecystectomy [1, 2]. It is defined as early if occurring in the post-operative period and late if it manifests after months or years.
Although this term is used widely, it is not completely accurate, as it includes a large number of disorders, both biliary (Table 1) and extra-biliary (Table 2) in origin, that may be unrelated to cholecystectomy [1, 2]. It has been reported that ∼50% of these patients suffer from organic pancreaticobiliary and/or gastrointestinal disorders, whereas the remaining patients are affected by psychosomatic or extra-intestinal diseases. Moreover, in 5% of patients who undergo laparoscopic cholecystectomy, the reason for chronic abdominal pain remains unknown . Probably because of the uncertainty in nosographic definition, the reported prevalence of PCS ranges from very low  to 47% . Symptoms include biliary or non-biliary-like abdominal pain, dyspepsia, vomiting, gastrointestinal disorders and jaundice, with or without fever and cholangitis [1, 2]. Severe symptoms are more likely to represent a complication of cholecystectomy if they occur early or to express a definite treatable cause when compared with non-specific, dyspeptic or mild symptoms. A non-biliary aetiology of PCS should be suspected if no calculi or gallbladder abnormalities are found at cholecystectomy and symptoms are similar to those suffered pre-operatively . Treatment for PCS is tailored to the specific cause and includes medication, sphincterotomy, biliary stenting, percutaneous drainage of bilomas and surgical revision for severe strictures [1–4].
|Retained stones in the cystic duct stump and/or common bile duct|
|Bile duct injury/ligature during surgery|
|Recurrent stones in the common bile duct|
|Bile duct strictures|
|Cystic duct remnant harbouring stones and/or inflammation|
|Gallbladder remnant harbouring stones and/or inflammation|
|Gastrointestinal causes||Extra-intestinal causes|
|Acute/chronic pancreatitis (and complications)||Psychiatric and/or neurological disorders|
|Pancreatic tumours||Coronary artery disease|
|Pancreas divisum||Intercostal neuritis|
|Oesophageal diseases||Unexplained pain syndromes|
|Peptic ulcer disease|
|Organic or motor intestinal disorders|
The traditional imaging approach to PCS includes ultrasonography and/or CT, followed by direct cholangiography, as the gold standard . Biliary scintigraphy has been advocated as a reliable non-invasive tool to evaluate sphincter of Oddi activity. Nevertheless, it has limited diagnostic accuracy compared with sphincter of Oddi manometry (SOM), which represents the gold standard for assessing functional forms of PCS . Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive and reliable alternative to direct cholangiography for the evaluation of the biliary tract. This has led to an increasing demand for MRCP to be used in patients with suspected PCS, despite the fact that its role in patient management has been assessed only briefly [1, 2]. The main advantages of using MRCP are its non-invasiveness and its capability to provide a road-map for interventional treatments [1–4]. Heavily T2weighted images with a high bile duct-to-background contrast may be obtained either with a set of single breath-hold, single-shot turbo spin-echo projective thick slabs or by using a respiratory-triggered three-dimensional (3D) turbo spin-echo sequence for a detailed representation of the biliary tree, together with multiplanar reformations and volumetric reconstructions [2–4]. Alternatives to the standard MRCP techniques include the use of fat-saturated 3D spoiled gradient-echo sequences in conjunction with intravenous contrast agents excreted (to a varying degree) via the biliary system, such as mangafodipir trisodium, gadobenate dimeglumine or gadoxetic acid. Advantages over fluid-based techniques include biliary function assessment, background suppression of ascites and bowel fluid, and identification of biliary leaks following cholecystectomy, with a reported sensitivity and specificity of 86% and 83%, respectively (Figure 1) .
Calculi in the common bile duct (CBD) or cystic duct remnant are the most common cause of PCS. Calculi are traditionally classified as “retained” or “recurrent”, if found before or after two years following surgery, respectively. The former are likely to have been present at the time of intervention; the latter are usually “secondary calculi”, which form as a result of biliary stasis (often caused by co-associated strictures, papillary stenosis or biliary dyskinesia) .
MRCP has a sensitivity of 95–100% and a specificity of 88–89% for detecting CBD calculi . They appear as smoothly marginated filling defects within the CBD or cystic duct remnant, usually in the dependent position, surrounded by a thin rim of hyperintense bile (Figure 2). If a multislice technique is used, the analysis of maximum intensity projection reconstructions should be associated with a careful scrolling of source thin-slice images in order to avoid overlooking calculi, especially the smallest ones (Figure 3) . When calculi are impacted in the intramural portion of the CBD, with minimal surrounding fluid, they may be not detectable on MRCP . Repeated single-slice acquisitions of the biliary tree are useful to differentiate impacted calculus from the “pseudo-calculus” effect resulting from a prominent or spasmodic papillary sphincter (Figure 4). Dynamic scanning is also helpful in avoiding false-negative cases, as calculi are better appreciated on images obtained during sphincter relaxation .
Bile duct injury and biliary leaks
The rate of bile duct injuries is slightly higher using laparoscopic surgery than open surgery (0.5% and 0.15%, respectively) . In general, a laparoscopic approach allows less complete traction of the gallbladder and cystic duct than open surgery. This can lead to incomplete isolation of anatomical structures and/or traction injury. The main causes of ductal injury are erroneous cutting of bile ducts, inadvertently placed clips or ligatures, periductal bile leakage resulting in fibrosis and thermal injury owing to electrocautery . Common sites of biliary leaks include injured ducts, the cystic duct stump and the gallbladder stump. Fluid collections in the gallbladder bed occur in up to 14% of patients following cholecystectomy and tend to resolve spontaneously; collections persisting for more than a week or fluid outside the gallbladder bed raise the suspicion of a biliary leak and/or injury .
Bile duct injury manifests as a leak, stricture or transection . Strictures and transection appear as a focal narrowing or abrupt interruption of the bile duct, respectively, with or without biliary dilatation upstream (Figure 5). The distinction between biliary stricture and transection is often impossible. Nevertheless, a complete lack of visualisation on source and projection images is highly suspicious for duct disruption . Injuries derived from laparoscopic cholecystectomy are usually more extensive than those following an open surgical approach; they may involve major intrahepatic bile ducts and are more frequent in patients with anatomic variants [3, 10]. Evolution of duct injury is towards duct stricture formation and fibrosis/atrophy of the obstructed liver segment .
A hilar and/or subhepatic fluid collection close to the CBD or strictured ducts, or in the right side of the abdomen, is suspicious of a biliary origin, particularly if a thin hyperintense connection to the biliary tree is demonstrated (Figure 6). Nevertheless, biloma is often indistinguishable from post-operative collections or haemorrhage, unless direct cholangiography is performed to demonstrate contrast leak .
Strictures occur in up to 0.6% of cases after cholecystectomy. If not involving previously injured anatomical variants, strictures usually occur because the CBD is injured during clamping or ligation of the cystic duct close to its insertion . Strictures are the most common late complication of biliary surgery, developing a few months to years after cholecystectomy.
On MRCP, they appear as a narrowing of the luminal signal and are usually short with smooth regular margins (Figure 7). The typical locations of strictures are in the CBD, near the insertion of the cystic duct, or at the hepatic confluence . Defining the site and extent of a stricture (according to the Bismuth classification shown in Figure 8) is of crucial importance, particularly when bilio-digestive reconstruction is planned. MRCP tends to overestimate the length (and the extent) of the stricture, especially when the duct immediately distal to the stricture is collapsed (but not strictured). This can lead to misinterpretation of the position of the distal end of the stenosis . The use of the multislice technique, with a careful analysis of source images, helps to reduce the risk of overestimating the stricture length .
Biliary dyskinesia and papillary stenosis
The term “biliary dyskinesia” has traditionally been used to refer to primarily motor forms of sphincter of Oddi dysfunction (SOD) (Table 3). It occurs more frequently years after cholecystectomy, and is diagnosed in 9–11% of patients with abdominal pain . Papillary stenosis has been described as an organic variant of SOD related to a fibrotic narrowing of the sphincter in response to inflammatory processes from pancreatitis or gallstone migration through the papilla . The causes of abdominal pain in these patients are thought to be impeded flow, resulting in ductal hypertension, distension and inflammation. SOM remains the gold standard with which to diagnose SOD and to stratify therapy. Nevertheless, abnormal SOM findings are not frequent in SOD Types II and III (Table 3) and do not differ reliably between primary motor and stenotic forms . The role of MRCP in diagnosing SOD is still undefined, as correlation with endoscopic retrograde cholangiopancreatography or biliary manometry has been poorly investigated, and differentiation between stenotic or spasmotic papilla is difficult. State-of-the-art MRCP techniques may serve as a first-line non-invasive tool with which to demonstrate biliary abnormalities in patients with possible SOD .
|Type||Clinical criteria||Prevalence of abnormal SOM (%)||Treatment of choice|
|I||Typical biliary-like pain||65–86||Sphincterotomy|
|Liver function tests elevated by two-fold|
|Dilated CBD (diameter ≥12 mm) on ERCP|
|Delayed drainage of contrast medium in duodenum on ERCP (>45 min)|
|II||Typical biliary-like pain||50||Sphincterotomy in patients. with altered SOM|
|One or more (but not all) additional criteria|
|III||Typical biliary-like pain only||28||Medication|
SOM, sphincter of Oddi manometry; CBD, common bile duct; ERCP, endoscopic retrograde cholangiopancreatography.
On MRCP, narrowing of the papilla ranges from a mild, progressive and smoothly marginated stricture to a lack of visualisation of the sphincteric segment (Figure 9), with no clear cause of extrinsic compression. The stricture may extend to the distal aspect of the CBD or main pancreatic duct, and can be associated with a variable degree of biliary and/or pancreatic proximal ductal dilatation. A dynamic evaluation with repeated single thick slices is mandatory to verify whether stenosis is temporary and due to physiological contraction. According to Van Hoe et al [8, 12], a spasmodic sphincter shows no morphological variations and appears either as a prolonged lack of visualisation of the sphincter (Figure 10) or as a thin rim of signal entrapped in a asymmetrically narrowed sphincter (Figure 11).
Other biliary findings
The presence of a gallbladder remnant after subtotal cholecystectomy (performed inadvertently or as a surgical option) is very rare. The remnant becomes symptomatic if harbouring gallstones or chronic inflammation. MRCP depicts the remnant filled with bile at the extremity of the cystic duct . Further rare causes of PCS include biliary ascariasis (frequent in tropical and subtropical countries), choledochocele and neuromas and/or granuloma of the cystic duct stump .
MRCP techniques are reliable for identifying biliary causes of PCS. Accurate assessment of the site and type of biliary abnormality provides a road-map for interventional procedures, and is crucial for tailoring patients’ therapy.
The main limitation of MRCP in evaluating PCS is the evaluation of SOD. As main pancreatic duct dilatation is commonly found in patients with SOD and flow obstruction, secretin-enhanced MRCP has been advocated as a potential non-invasive diagnostic tool able to improve MRCP diagnostic performance . Secretin is a polypeptide hormone that induces stimulation of pancreatic secretion of bicarbonate-rich fluid and a transient increase in the tone of the sphincter of Oddi. To date, the evaluation of main pancreatic duct dilation (degree and timing pre and post stimulation) and duodenal filling before and after stimulation in patients with suspected SOD has been limited, and data regarding its ability to predict SOD are controversial . A general consideration could be that secretin-enhanced MRCP represents an initial non-invasive tool for evaluating patients with PCS to exclude organic underlying disorders such as chronic pancreatitis.