Disclosure: None of the authors have any disclosures to make.
Conflicts of interest: None.
Kei Ito, Department of Gastroenterology, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-ku, Sendai, Miyagi 983-0824, Japan. Email: firstname.lastname@example.org
The causes of benign biliary stricture include chronic pancreatitis, primary/immunoglobulin G4-related sclerosing cholangitis and complications of surgical procedures. Biliary stricture due to fibrosis as a result of inflammation is sometimes encountered in patients with chronic pancreatitis. Frey's procedure, which can provide pancreatic duct drainage with decompression of biliary stricture, can be an initial treatment for chronic pancreatitis with pancreatic and bile duct strictures with upstream dilation. When patients are high-risk surgical candidates or hesitate to undergo surgery, endoscopic treatment appears to be a potential second-line therapy. Placement of multiple plastic stents is currently considered to be the best choice as endoscopic treatment for biliary stricture due to chronic pancreatitis. Temporary placement with a fully covered metal stent has become an attractive option due to the lesser number of endoscopic retrograde cholangiopancreatography (ERCP) sessions and its large diameter. Further clinical trials comparing multiple placement of plastic stents with placement of a covered metal stent for biliary stricture secondary to chronic pancreatitis are awaited.
Benign biliary strictures occur due to various etiologies such as chronic pancreatitis, primary/immunoglobulin (Ig)G4-related sclerosing cholangitis and complications of surgical procedures. Biliary stricture may lead to pain, jaundice, cholangitis and secondary biliary cirrhosis.1 The majority of patients with benign biliary stricture can be correctly diagnosed based on a past/present history, clinical course, cholangiography or histological evaluation. Some benign biliary strictures, however, mimic malignant ones. The exclusion of malignant biliary stricture is crucial before making a therapeutic decision. Current status regarding endoscopic treatment for biliary stricture due to chronic pancreatitis are discussed in this review article.
DIAGNOSIS OF BENIGN BILIARY STRICTURE
Benign biliary strictures are associated with a broad spectrum of signs and symptoms, ranging from subclinical disease with mild elevation of hepatobiliary enzymes to complete obstruction with jaundice, pruritus, cholangitis and biliary cirrhosis.1 Numerous modalities such as transabdominal ultrasonography (US), multidetector row computed tomography (MDCT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS), endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage and so forth are available for the differential diagnosis of biliary strictures. Because some modalities have a risk of complications, an efficient diagnostic strategy for lessening patient burden should be established. Figure 1 shows the diagnostic flow chart for biliary stricture at our institution. MRI/MDCT should be performed for benign biliary stricture in order to rule out the existence of distant metastases. Although EUS can provide detailed images of the pancreatobiliary system, the diagnosis of benign biliary stricture based only on EUS is often difficult. Because EUS cannot always depict the whole hilar portion of the bile duct, it can be omitted when magnetic resonance cholangiopancreatography/MDCT findings suggest a hilar or intrahepatic biliary stricture.
The causes of benign biliary stricture include chronic pancreatitis, primary/IgG4-related sclerosing cholangitis and complications of surgical procedures. As mentioned above, the exclusion of malignant biliary stricture is always indispensable.
ERCP cannot only provide a direct cholangiogram but also enable biliary decompression. Because each etiology of biliary stricture has typical cholangiographic findings, the endoscopists who attempt ERCP should be familiar with such findings. Although bile cytology is commonly performed in cases of biliary stricture, its sensitivity and accuracy have not been satisfactory. Moreover, a negative result of cytology cannot rule out malignancy. Its results, therefore, should carefully be dealt with. Biopsy of the bile duct should be attempted in patients with biliary stricture if possible. The accuracy of biopsy for bile duct cancer has been reported to be 84%.2 Multiple biopsies from the stenotic site can help achieving accuracy of nearly 100% for biliary cancer. The inflammatory change of the bile duct after biliary drainage makes differential diagnosis between malignancy and benignity difficulty.3 Therefore, biopsy should be performed before biliary drainage. Histological evaluation with special stains such as p53 and Ki-67 often provide useful information for differential diagnosis.
Peroral cholangioscopy (POCS) has been reported to be useful for the diagnosis of lateral spread in patients with bile duct cancer.4 The typical findings of malignant biliary stricture consist of a nodular/papillary tumor and dilated/torturous vessels in its surface. However, differential diagnosis of benign biliary stricture by POCS alone has not yet been established.
Intraductal ultrasonography (IDUS) is an examination using a thin-caliber ultrasonic probe, yielding real-time, high-quality cross-sectional images due to the use of high frequency ultrasound. The over-the-wire model has enabled insertion of the probe into the bile duct via the papilla without endoscopic sphincterotomy.5 IDUS has been reported to be useful in the differential diagnosis between malignant and benign biliary strictures.6,7 However, typical findings of benign biliary strictures have not been elucidated.
ENDOSCOPIC TREATMENT FOR CHRONIC PANCREATITIS
The bile duct traverses the pancreatic head in up to 85% of humans and runs posteriorly adjacent to it in the remainder. Biliary stricture due to fibrosis as a result of inflammation or compression by a pseudocyst is sometimes encountered in patients with chronic pancreatitis, whose typical cholangiographic finding is a smooth, tapering stenosis at the lower bile duct. Because it is difficult to rule out malignancy based only on cholangiographic findings, histological evaluations such as cytology and biopsy are indispensable.
Chronic pancreatitis with biliary stricture is quite frequently associated with pancreatic duct strictures at the pancreatic head and upstream dilation. Because long-term clinical resolution of endoscopic treatment for biliary stricture due to chronic pancreatitis has not been satisfactory, surgical treatment is generally the treatment of choice. Frey's procedure was developed for chronic pancreatitis with pancreatic duct strictures and stones.8 This procedure includes coring out the diseased portion of the pancreatic head and lateral pancreaticojejunostomy. Because Frey's procedure contributes to decompression of the intrapancreatic portion of the bile duct, choledochojejunostomy is often unnecessary. Therefore, this procedure is the treatment of choice for chronic pancreatitis with bile and pancreatic duct strictures with upstream dilation.
Many endoscopic approaches have been developed as useful treatment options alternative to surgery in the field of pancreatobiliary diseases. Endoscopic management for biliary stricture secondary to chronic pancreatitis typically consists of dilation of the stricture and insertion of one or more plastic stents followed by elective stent exchange every several months to avoid cholangitis caused by stent clogging. Because a metal stent (MS) has a longer stent patency than a plastic stent due to its large diameter, MS is widely used for patients with malignant biliary stricture.9 The use of non-covered MS for benign biliary stricture, however, is not recommended because a placed MS cannot be removed as hyperplastic change or granulation growth occurs through the mesh of MS.10 The membrane-covered MS contributes to prevention of such occlusion and allows its removal several months after deployment.
Considering the reported technical success rate, clinical response rate and risks of complications, placement of multiple plastic stents is currently the endoscopic treatment of choice for biliary stricture due to chronic pancreatitis. These results, however, were mainly based on case series studies with relatively small patient numbers.11–13 Furthermore, a major problem of temporary plastic stenting is the high number of ERCP sessions required for stent exchange. The use of a fully covered metal stent (FCMS) for biliary stricture due to chronic pancreatitis has been reported.14–16 Temporary placement of an FCMS is an attractive option because of the following reasons: (i) theoretically, only two ERCP sessions are required compared to five sessions for plastic stent exchange every 3 months in 1 year post-procedure; and (ii) a dilation diameter similar to that obtained with simultaneous placement of four plastic stents is achieved. Further clinical trials comparing CMS with multiple plastic stents in this particular condition are awaited.
THERAPEUTIC STRATEGY FOR BILIARY STRICTURE SECONDARY TO CHRONIC PANCREATITIS
There have been no studies comparing endoscopic treatment with surgical treatment for biliary stricture due to chronic pancreatitis. As mentioned above, such patients quite frequently have pancreatic duct strictures/stones and upstream dilation. Treatment of chronic pancreatitis should aim at not only control of clinical symptoms but also prevention of disease progression. Therefore, achievement of both biliary and pancreatic duct drainage should be weighed while making therapeutic decisions. Figure 2 shows the therapeutic strategy for biliary stricture secondary to chronic pancreatitis.
Two randomized controlled trials (RCT) have been reported in chronic pancreatitis with pancreatic duct strictures/stones and upstream dilation (Table 1).17,18 Dite et al.17 reported an RCT comparing surgery with endoscopic treatment in 72 patients with chronic pancreatitis. Although an additional 68 patients who refused the clinical trial confused the results of the study, they concluded that surgical treatment is better. Cahen et al.18 conducted an RCT to compare surgical and endoscopic drainage in 39 patients with chronic pancreatitis. In terms of technical success rate and clinical response rate, surgical treatment was superior to endoscopic treatment. Frey's procedure, which can enable both bile and pancreatic duct drainage, is now considered to be the best treatment for chronic pancreatitis with pancreatic and bile duct stricture. Endoscopic treatment for such patients is performed as a bridge to surgery or to assess potential response to surgical treatment (Fig. 3).
Table 1. Endoscopic vs surgical therapy for chronic pancreatitis with pancreatic duct strictures and stones
Although these two studies showed the clinical usefulness of surgical treatment for chronic pancreatitis, this procedure is not always a feasible treatment due to patient comorbidities or preferences. If patients are high-risk surgical candidates, endoscopic treatment appears to be a potential option.
For biliary stricture due to chronic pancreatitis with neither pancreatic duct strictures nor upstream dilation, endoscopic treatment with multiple plastic stents or CMS should be considered as an initial therapy. Surgical treatment such as choledochojejunostomy is a second-line therapy if endoscopic treatment fails.
Frey's procedure, which can achieve both pancreatic and bile duct drainage, is the treatment of choice for chronic pancreatitis with pancreatic and bile duct strictures with upstream dilation. When patients are at high risk of surgical treatment or hesitate to undergo surgery, endoscopic treatment is a potential second-line therapy.
Placement of multiple plastic stents is currently the endoscopic treatment of choice for biliary stricture due to chronic pancreatitis. Temporary placement with an FCMS has become an attractive option due to lessening the number of ERCP sessions and its large diameter. Further clinical trials comparing CMS with multiple plastic stents for biliary stricture are awaited.
The authors are indebted to Mr Thomas Mandeville for his English review of this manuscript.