Chronic pancreatitis (CP)-related common bile duct (CBD) strictures are more difficult to treat endoscopically compared with benign biliary strictures because of their nature, particularly in patients with calcific CP. Before any attempt at treatment, malignancy must be excluded. Single plastic stents can be used for immediate symptom relief and as “bridge to surgery and/or bridge to decision,” but are not suitable for definitive treatment of CP-related CBD strictures because of long-term poor results. Temporary simultaneous placement of multiple plastic stents has a high technical success rate and provides good long-term results.
Key points
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The vast majority of chronic pancreatitis (CP)-related biliary strictures occur as a consequence of progressive fibrosis of pancreatic parenchyma and should be considered as permanent. CP-related biliary strictures are more resistant to endoscopic dilation than other benign biliary strictures.
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Surgical drainage is considered the gold standard for the definitive treatment of CP-related biliary strictures.
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Endoscopic biliary stenting is initially recommended in patients who present with jaundice, especially occurring after an acute exacerbation of pancreatitis, because this may resolve with the resolution of the acute inflammation.
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Endoscopic stenting may be indicated in patients unfit for surgery or in those who refuse surgery.
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Removable, fully covered self-expandable metal stents (FCSEMSs) seem to be a promising alternative for common bile duct strictures related to CP.
Introduction
A stricture of the intrapancreatic common bile duct (CBD) will develop in approximately 3% to 46% of patients with CP and can seriously compromise the clinical course of the disease. Biliary strictures usually complicate a long-lasting disease, as a result of severe fibrosis of the pancreatic head parenchyma, which compresses and narrows the distal CBD. However, CP-related CBD strictures may also be seen in patients with a recently diagnosed disease.
The real incidence of CP-related biliary strictures is unknown. Many patients remain asymptomatic for years before the stricture will cause increasing cholestasis, jaundice, or cholangitis, and this may contribute to underestimate their incidence. Furthermore, many patients with CP have a history of alcohol addiction, being less compliant to medical care and follow-up.
The management of CP-related biliary strictures is still controversial. Traditionally, a surgical bypass, choledochoduodenostomy, choledochojejunostomy, or hepaticojejunostomy, was the only treatment option. Despite the benefits of a definitive solution, because of the morbidity and mortality associated with surgery, alternative drainage techniques have been investigated, especially endoscopic biliary stent placement. Both treatments, endoscopic and surgical, have, as usual, advantages and disadvantages.
Despite some CP-related biliary strictures resolving with time, the vast majority of clinically significant strictures should be considered as permanent. These strictures are usually more resistant to endoscopic dilation than other benign biliary strictures, especially those occurring after biliary surgery or orthotopic liver transplantation. Furthermore, patients with CP have a risk of pancreatic cancer substantially higher than the general population. Cancer usually occurs many years after the clinical onset of CP. Therefore, in certain circumstances, surgery might also be recommended to rule out cancer.
Many patients potentially curable with surgery are not good candidates because of their compromised general status, adverse local conditions (ie, postoperative adhesions, portal vein thrombosis with portal hypertension, consequences of severe necrotizing pancreatitis, and so on) or refusal of surgery. Endoscopic drainage offers a chance to this selected group of patients or may be considered as a bridge to surgery.
The pathogenesis of CP-related biliary strictures, the diagnostic workup, the indication to endoscopic treatment, the results of endotherapy, and the future developments in this field are discussed in this review.
Introduction
A stricture of the intrapancreatic common bile duct (CBD) will develop in approximately 3% to 46% of patients with CP and can seriously compromise the clinical course of the disease. Biliary strictures usually complicate a long-lasting disease, as a result of severe fibrosis of the pancreatic head parenchyma, which compresses and narrows the distal CBD. However, CP-related CBD strictures may also be seen in patients with a recently diagnosed disease.
The real incidence of CP-related biliary strictures is unknown. Many patients remain asymptomatic for years before the stricture will cause increasing cholestasis, jaundice, or cholangitis, and this may contribute to underestimate their incidence. Furthermore, many patients with CP have a history of alcohol addiction, being less compliant to medical care and follow-up.
The management of CP-related biliary strictures is still controversial. Traditionally, a surgical bypass, choledochoduodenostomy, choledochojejunostomy, or hepaticojejunostomy, was the only treatment option. Despite the benefits of a definitive solution, because of the morbidity and mortality associated with surgery, alternative drainage techniques have been investigated, especially endoscopic biliary stent placement. Both treatments, endoscopic and surgical, have, as usual, advantages and disadvantages.
Despite some CP-related biliary strictures resolving with time, the vast majority of clinically significant strictures should be considered as permanent. These strictures are usually more resistant to endoscopic dilation than other benign biliary strictures, especially those occurring after biliary surgery or orthotopic liver transplantation. Furthermore, patients with CP have a risk of pancreatic cancer substantially higher than the general population. Cancer usually occurs many years after the clinical onset of CP. Therefore, in certain circumstances, surgery might also be recommended to rule out cancer.
Many patients potentially curable with surgery are not good candidates because of their compromised general status, adverse local conditions (ie, postoperative adhesions, portal vein thrombosis with portal hypertension, consequences of severe necrotizing pancreatitis, and so on) or refusal of surgery. Endoscopic drainage offers a chance to this selected group of patients or may be considered as a bridge to surgery.
The pathogenesis of CP-related biliary strictures, the diagnostic workup, the indication to endoscopic treatment, the results of endotherapy, and the future developments in this field are discussed in this review.
Pathogenesis
Different mechanisms contribute to the development of biliary strictures in patients with CP. The strictures usually involve the distal third of the CBD, which passes through the pancreatic head before it reaches the papilla of Vater and the duodenum. The intrapancreatic portion of the CBD varies in length from 1.5 to 6 cm, and this accounts for the variability of stricture length seen in clinical practice.
The vast majority of biliary strictures associated with CP occur as a consequence of progressive fibrosis of the pancreatic parenchyma due to recurrent acute or chronic inflammation, which may eventually result in permanent periductal fibrosis. Parenchymal fibrosis in CP is a slow, irreversible process, and these strictures usually occur late in the natural history of the disease. The strictures occurring in patients with calcified pancreatic stones are particularly fibrotic and thus resistant to dilation. CBD strictures can also develop earlier in the course of the disease and be the result of an acute pancreatic inflammation as an exacerbation of the chronic illness: the edema of the pancreatic head compresses the CBD, usually between one to few days after the acute bout. These strictures may resolve spontaneously, few days or weeks after the clinical onset, or, in more severe cases, be persistent and require biliary drainage.
Biliary strictures can also be caused by the extrinsic compression of the CBD from a pancreatic retention cyst, a pseudocyst, or a walled-off pancreatic necrosis. These strictures are usually reversible and are managed by draining the pancreatic fluid collection. However, 2 or more mechanisms may contribute to the development of the biliary stricture; as a consequence, the drainage of the collection might be sufficient to make the jaundice disappear, but subclinical cholestasis may persist and eventually require drainage. Furthermore, the stricture can also be caused by a pancreatic cancer, which can additionally complicate the course of the CP. This danger should always be carefully investigated and excluded when the patient is seen for the first time or in case of a long-lasting disease.
Clinical presentation and diagnosis
Biliary strictures have a broad spectrum of presentation, varying from mildly elevated levels in liver function tests to severe jaundice in case of complete biliary obstruction. Acute cholangitis is uncommon in patients with an intact papilla but may become the predominant symptom in case of prior biliary sphincterotomy.
The “incidental finding” of a CP-related biliary stricture accounts for up to 17% of cases.
Abdominal pain is usually considered the predominant symptom in most patients, but it is doubtful that a biliary stricture per se might be a major contributing factor to pain development. Pain is more likely to be caused by a bout of acute pancreatitis or a stricture of the pancreatic duct than by a biliary stricture.
Jaundice may be present in 30% to 50% of patients at the diagnosis. Transient jaundice is typically seen in patients with exacerbation of the chronic illness, as a result of the edema and acute inflammation of the pancreatic head. In these cases, jaundice will usually recede spontaneously with the resolution of the acute process. Alteration of liver function test results and biochemical markers of cholestasis, including alkaline phosphatase and gamma-glutamyl transferase, may be persistent for some weeks after the normalization of bilirubin levels.
Acute cholangitis may be life threatening and thus becomes a clear indication to an emergency biliary drainage, but it rarely represents the leading symptom at diagnosis.
Jaundice and elevation of alkaline phosphatase level greater than 2-fold lasting for more than 1 month has been advocated as a precise marker of biliary stricture. However, biochemical findings should always be confirmed by radiological imaging, especially before endoscopic drainage.
The demonstration of a dilated CBD at transabdominal ultrasound examination, associated with elevation of levels of biochemical markers of cholestasis, is usually sufficient for the diagnosis. However, a computed tomographic (CT) scan is usually required, especially at the first episode of jaundice, to better clarify the nature of the pancreatic disease, accurately delineate the parenchymal and ductal changes, demonstrate the severity and localization of calcifications, exclude fluid collections, and, importantly, demonstrate suspicious masses. Furthermore, CT scan is fundamental to plan the subsequent treatment of patients. The decision whether to operate or not a patient is also based on the CT scan findings: portal vein thrombosis, a large peripancreatic mass, liver metastases, and cirrhosis are commonly considered contraindications to surgical biliary bypass.
The differentiation between pancreatic cancer and CP is particularly difficult. CT scan offers good visualization of the pancreatic parenchyma, but in the absence of distant metastases, fibrotic and inflammatory masses associated with CP or groove pancreatitis cannot be discriminated with certainty from neoplasms. Cross-sectional imaging by magnetic resonance can provide a better anatomic detail but again often does not permit a definite diagnosis of malignancy. At cholangiography, including magnetic resonance cholangiopancreatography (MRCP), benign biliary strictures appear smooth, tapering and regular, whereas malignant ones are irregular, tightened, and abrupt. However, cholangiographic features are unreliable because of a wide variability of the cholangiographic appearances of the stricture. Endoscopic retrograde cholangiopancreatography (ERCP) is still more accurate than MRCP in delineating the main pancreatic duct and side branches morphology and CBD stricture and may assist in the differential diagnosis ( Fig. 1 ).
Neoplastic biochemical markers are of help for the discrimination between malignant and benign strictures. Markedly increased levels of CA 19-9 (>1000 U/mL) are strongly associated with pancreatic cancer, but this is not a common finding. Unfortunately, moderately increased levels of CA-19.9 are frequently seen also in patients with benign biliary strictures as a result of elevated biliary pressure that causes leakage of CA 19-9 into serum.
Nowadays, a cytologic or histologic confirmation is often advocated to definitely rule out the presence of malignancy. Brush cytology and endobiliary biopsies can be obtained during ERCP, but the sensitivity of the sampling is low for pancreatic cancer and not routinely recommended. Endoscopic ultrasound-guided fine-needle aspiration is becoming the predominant technique to obtain cytologic and histologic sampling from pancreatic masses because of its high safety profile and diagnostic accuracy.
When the suspicion of malignancy is strong, every effort should be made to convince the more reluctant patient to undergo surgery, or at least, the diagnostic test and histologic sampling should be repeated and repeated at short time intervals.
Indications for endoscopic drainage and procedural aspects
Cholangitis is per se a life-threatening complication and an obvious indication for drainage. However, jaundice and subclinical persistent cholestasis usually require drainage too, as they may lead to secondary biliary cirrhosis. Biliary cirrhosis in patients with CBD stenosis secondary to CP has been observed in about 7% of patients, but reports are old and contradictory. Alcohol addiction and “unorthodox” behaviors are common in patients with CP and may be per se the cause of liver cirrhosis. However, Hammel and colleagues found regression of liver fibrosis in patients with CP-related biliary stricture after biliary drainage. Therefore, every biliary stricture that persists for more than 1 month and is associated with increased levels of biochemical markers of cholestasis should be drained by either surgery or endoscopy.
Biliary decompression is also clearly indicated when frequent relapses of biliary obstruction occur, to minimize the risk of secondary biliary cirrhosis and cholangitis. Asymptomatic patients or those with slightly elevated levels of biochemical markers of cholestasis should be treated conservatively with close monitoring of liver functions test results at regular intervals. A conservative approach is also initially recommended for patients who present with jaundice, especially occurring after an acute exacerbation of pancreatitis, because this may resolve with the resolution of the acute inflammation. However, most biliary strictures associated with CP are permanent, and these patients are usually young, with a long life expectancy.
Every biliary stent, whether plastic or metallic, will inevitably occlude over time, leading to recurrent jaundice or cholangitis. Endoscopic bile duct stricture dilation with stent placement has become standard of care for most postoperative biliary strictures. However, CP-related strictures are much more resistant to endoscopic dilation than postoperative strictures, and when successfully dilated, strictures frequently recur, months or years after the end of the stenting period.
Endoscopic biliary stent placement is therefore not recommended as a definitive treatment of CP-related biliary strictures. Surgical drainage is still considered as the gold standard, by either a biliary bypass (ie, hepaticojejunostomy or choledocoduodenostomy) or more complex operations, in patients with pain due to concomitant pancreatic duct obstruction (duodenopancreatectomy or duodenal preserving pancreatectomy, as the Frey or the Beger procedure). However, due to its morbidity and mortality, surgery should be carefully balanced in patients with potentially reversible strictures, which might regress spontaneously or after a short stenting period. Some other patients are not good surgical candidates, because of comorbidities, postoperative adhesions, portal biliopathy, or other anatomic situations that can make surgery more difficult or impossible. Furthermore, some patients with CP refuse surgery and prefer repeated endoscopies to a definitive operation with a potentially complicated postoperative course.
Endoscopic biliary stenting has a high technical success rate and provides short-term resolution of jaundice and cholangitis, but because of the long-term recurrences, it should be proposed as a first-line therapy in a selected group of patients, including (1) symptomatic patients, with jaundice or cholangitis and with a potentially reversible biliary stricture; (2) patients unfit for surgery; (3) patients unwilling to undergo surgery; (4) as a temporary measure, in patients with severe jaundice or in those with acute cholangitis in case of delayed definitive surgery.
Procedural Aspects
From a procedural point of view, biliary stent placement for CP-related CBD strictures does not substantially differ from that for palliation of malignant biliary strictures. After CBD cannulation and cholangiography, a biliary sphincterotomy is performed. Biliary sphincterotomy facilitates stent insertion and future repeat access to the biliary tree and enables placement of single/multiple stents in the course of the treatment. Despite the fibrosis of the pancreatic parenchyma, CP-related biliary strictures are easily traversed with a guidewire and a guiding catheter. Balloon dilation before single stent placement is seldom necessary, and placement of a plastic Amsterdam-type 10F or 11.5F stent over the guiding catheter is usually not technically demanding.
The patency of a large-bore (10–11.5F) biliary plastic stent is 3–4 months, on average. To avoid cholangitis, ERCP is repeated after 3 months, and the stent is removed. The stricture is reevaluated and biopsies or biliary brushing repeated if necessary. The stricture is considered sufficiently dilated when the stricture-waist has disappeared, the ERCP catheter passes through the stricture without resistance, and the contrast agent injected into the bile ducts rapidly flows into the duodenum.
If the stricture persists after 3 months, stenting has to be repeated. The length of treatment should be individualized, according to the patient’s fitness and willingness to undergo surgery. To maximize the dilation of the stricture, some authors recommend the placement of multiple plastic stents, side by side, similarly to that for other benign biliary strictures. Nevertheless, if stricture resolution is not observed after a 1-year treatment, a successful outcome is unlikely and surgery should be again considered ( Fig. 2 ).
Related posts:
Advances in Pancreatic Endoscopy
Effective Endoscopic Management of Pancreatic Diseases
Role of Endoscopic Ultrasonography in the Diagnosis of Acute and Chronic Pancreatitis
Endoscopic Therapy for Acute Recurrent Pancreatitis
Endoscopic Therapy for Chronic Pancreatitis
Endoscopic Ultrasonography–Guided Drainage of the Pancreatic Duct
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