Biliary strictures or bile duct strictures refer to segments of narrowing of the intrahepatic and/or extrahepatic biliary ductal system. When narrowed, they impede the normal antegrade flow of bile, causing proximal dilatation resulting in clinical and pathological sequelae of biliary obstruction. Patients with chronic biliary strictures present a unique challenge when malignancy is suspected. The diagnosis and management of patients with biliary strictures potentially encompass an interprofessional approach, including endoscopists, surgeons, interventional radiologists, and hepatobiliary specialists.
Bile duct strictures can be congenital or acquired. The later is more common than the congenital strictures. Acquired strictures are further classified as either benign or malignant. There is a wide range of benign acquired conditions causing bile duct strictures and contributing to 30% of biliary strictures. This includes iatrogenic strictures, which comprise the majority of benign biliary strictures. Misidentification of the biliary duct for cystic duct during laparoscopic cholecystectomy leads to bile duct injury, which may be partial or complete. The long term sequelae of these injuries lead to the formation of benign biliary strictures. The incidence of injury may be decreased by obtaining intraoperative cholangiogram, especially in cases of gangrenous cholecystitis or empyema of the gallbladder. Understanding the anatomy of the blood supply to the bile duct is of paramount importance with regards to repair of the bile duct. Similarly, anastomotic biliary strictures are a known complication after orthotopic liver transplantation. Anastomotic strictures are also known to occur after a Whipple procedure (incidence of 4%), performed for pancreatic mass or trauma. This is especially true for small-caliber thin-walled ducts. Though relatively rare, strictures can also result from infections, like tuberculosis. Other benign causes are listed below:
However, the most common etiology for biliary strictures is malignancies. Both pancreatic head cancer and cholangiocarcinoma are attributed to the majority of malignant biliary strictures. Others include periampullary cancer, gallbladder carcinoma, hepatocellular carcinoma, lymphoma, and metastasis to regional solid organs and lymph nodes.
Globally, the incidence of biliary strictures is thought to be on the rise primarily because of the iatrogenic bile duct injuries resulting from the widespread practice of laparoscopic cholecystectomy. Multiple strategies like the critical view of safety have been suggested to minimize bile duct injuries and associated morbidity from bile leaks and strictures. The estimated rate of biliary injuries is about 0.7% after laparoscopic cholecystectomy. Most of these injuries are minor injuries or bile leaks. Biliary strictures are rare in the pediatric age group.
There is no published difference in incidence or prevalence of biliary strictures in males as compared to females though some risk factors like alcoholic chronic pancreatitis are commoner in males.
Biliary strictures are characterized by narrowing of a segment of the bile duct associated with proximal ductal dilatation. Obstruction of bile flow leads to elevation of serum bilirubin levels with clinical and laboratory features of obstructive jaundice. Stasis of bile is a major risk factor for ascending cholangitis.
As observed from magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP), benign strictures have tapered margins with smooth and symmetric borders. On the other hand, malignant strictures have shouldering of the margins with irregular and asymmetric borders. Malignant strictures involve a long segment as opposed to benign, which involves shorter segments. Malignant strictures appear to enhance on contrast-enhanced cross-sectional imaging.
Type E injuries lead to strictures of the hepatic ducts, which are further defined by the proximal extent.
In general, histopathological findings in biliary strictures depend on the etiological agent or mechanism. For example, in the case of primary sclerosing cholangitis, histopathology reveals intrahepatic and/or extrahepatic bile duct inflammation and fibro-obliteration. In the assessment of biliary strictures, histological appraisal with cytology or histopathology is primarily required to rule out malignancy. However, if imaging has confirmed or has high suspicion for malignancy, a positive histological diagnosis is not mandatory preoperatively.
The clinical presentation depends on the location and cause of the stricture. Biliary strictures can be clearly asymptomatic with non-contributory findings on physical examination. Nevertheless, a section of patients with biliary strictures will present with features of obstructive jaundice, which include yellowing of mucosal surfaces and skin, pruritus, pale stools, steatorrhoea, and dark urine.  These may be accompanied by constitutional symptoms, such as weight loss, fever, nausea, vomiting, and malaise. Patients may present with an acute abdomen secondary to cholangitis or hepatic abscess, which can result as a complication of the bile duct stricture.
History of fever and leukocytosis suggest an infective cause or sequelae to the strictures. History of weight loss, abdominal or back pain, worsening performance status should be taken with caution since it could warn towards a possible malignant etiology. 
The previous history of hepatobiliary surgery, autoimmune disease, pancreatitis, cholelithiasis, or chemotherapy should be elicited as it can be pivotal in determining or eliminating the differential diagnosis.
Further efforts should be made during the physical examination to elicit specific clinical signs like Murphy’s and Courvoisier’s signs, as this may also help in narrowing down the diagnosis and/or etiology of jaundice. The presence of hard masses in the abdomen may point towards an advanced malignant process.
Contributory laboratory findings are mainly drawn from a liver function test, a coagulation profile, and a complete blood count. Liver function tests may reveal elevated levels of conjugated bilirubin and liver enzymes (alkaline phosphatase and gamma-glutamyl transferase). Transaminases may be elevated nonspecifically. Immunological studies may be obtained to assess certain autoimmune etiologies of biliary strictures. Apt diagnosis and further management are based on the correlation of laboratory data, imaging findings with epidemiologic and clinical data.
Deranged liver function tests and coagulation profile may help to determine the algorithm of subsequent imaging and minimally invasive studies. Likewise, when present, certain immunological markers help in accurate diagnosis and management. For example, IgG4 associated sclerosing cholangitis presents as hilar or distal common bile duct (CBD) strictures which are associated with autoimmune pancreatitis (IgG4 related). Both these disease entities are responsive to steroid therapy. Antinuclear antibody and rheumatoid arthritis factor may help in support of this diagnosis.
Assay of CA19-9 and carcinoembryonic antigen (CEA) can be obtained in patients with suspected hepatobiliary malignancy as they can help with diagnosis and follow up. Of note, these are not specific to biliary malignancy. endoscopic ultrasound (EUS) guided fine needle aspiration cytology (FNAC) is highly sensitive and specific but not useful to rule out malignancy.
Ductal dilatation is a major feature of imaging for biliary strictures. Imaging of suspected biliary strictures can begin with a trans-abdominal ultrasound, which detects biliary dilatation and is highly sensitive for the detection of biliary obstruction and the level of obstruction. It has a low yield for the detection of strictures, though. Malignant biliary strictures are more likely to cause severe ductal dilation as compared to benign biliary strictures. Endoscopic ultrasound has high sensitivity and accuracy for malignant lesions and has been used as the imaging test of choice in the assessment of distal biliary obstruction.
Computed tomography (CT) scan has higher sensitivity than trans-abdominal ultrasound for biliary malignancy, and its utility can be improved with the use of a multi-detector CT (MDCT) scan and CT-pancreatic protocol in providing more information on tumor vascular encroachment and biliary tree obstruction. It is also able to detect complications from biliary obstruction such as cholangitis and abscesses.
MRCP can provide high-quality cholangiograms, thus establishing the location and extent of biliary strictures. It provides a cross-sectional and three-dimensional reconstruction of the biliary tree. It helps guide endoscopic therapy, especially if ERCP is contraindicated. MRCP also does not have ionizing radiation, thus making it a superior option over a MDCT scan. Its sensitivity and specificity (which can be improved by the use of diffusion-weighted imaging, DWI) are however comparable to that of ERCP.
Evaluation of biliary strictures by ERCP can determine etiology, provide tissue samples for cytology and histology, and facilitate therapeutic interventions like stenting of obstructed segments from strictures. It is, however, associated with post-ERCP pancreatitis and is also being overtaken by newer technologies like confocal laser endomicroscopy (CLE). Other emerging technologies useful in the assessment of the etiology of biliary strictures include fluorescent in-situ hybridization (FISH), Direct peroral cholangioscopy, and intraductal ultrasound.
A hepatobiliary iminodiacetic acid (HIDA) Scan helps to identify the level of bile leaks and bile injuries after cholecystectomy.
Medical management of biliary strictures is largely restricted to addressing complications from biliary obstructions and sometimes treatment of the causative agent. Therefore, analgesics, empiric antibiotics, plus hemodynamic support with intravenous fluids with or without vasopressors and inotropes are often instituted where applicable. Also common are therapies aimed at reducing the effects of increasing bilirubinemia. These efforts are often supportive and in preparation for definitive therapy. Other forms of medical treatment could be aimed at the prevention of further complications like excessive bleeding due to a coagulopathy as well as deep vein thrombosis and sepsis in the early postoperative period.
The goal of the interventions for biliary strictures include reestablishing patency and avoiding additional procedures. There are varying options for operative or interventional management. These options can be accomplished via endoscopy, open surgery, or percutaneously. The etiology and the location of the stricture, as well as the patient’s hemodynamic stability and nutritional status, could determine the timing and type of intervention required. The Bismuth classification can further guide the most appropriate approach since it offers a guide to the determination of the level at which healthy biliary tissue is available for repair and anastomosis. Likewise, the Strasberg classification system, which incorporates the presence of a bile leak and lateral injuries into consideration, can also be useful in some cases in making the choice of the best intervention. Additionally, preoperative determination of malignancy is pivotal in the planning of treatment and avoiding undue exploratory surgery.
In general endoscopic treatment is the first-line treatment of biliary strictures. The treatment of biliary strictures includes options shown below
Common Interventions for Biliary Strictures
Resection and Anastomosis
Image-guided percutaneous transhepatic biliary drainage catheter may be placed for palliation of hyperbilirubinemia in patients with either inoperable disease or until completion of neoadjuvant therapy.
A biliary sphincterotomy involves the division of the biliary sphincter of Oddi and the intraduodenal segment of the common bile duct. It enables removal of stones, placement of stents, and assists endoscopic access for future ERCP. It also facilitates balloon dilatation. 
Novel techniques for management of biliary strictures include magnetic compression anastomosis (MCA), intraductal radiofrequency ablation, and biodegradable stents. Others include large bore catheterization, cutting-balloon dilation, and placement of retrievable covered stents. The magnetic compression anastomosis has specifically been used for biliary recanalization with favorable results.
In the diagnosis and management of biliary strictures, the most valuable and critical distinction that should be made is between benign and malignant etiology. This differentiation presents a major diagnostic and therapeutic challenge. Therefore, elaborate history taking, physical examination, and diagnostic workup should be completed. The addition of other techniques like FISH, Kras/p53 mutation analysis, intraductal biopsies, and CLE may be considered to improve the diagnostic yield.
A diagnosis of choledocholithiasis should also be considered in cases of suspected biliary strictures.
Although generally biliary strictures have a good prognosis, those resulting from malignant and primary sclerosing cholangitis may have unfavorable prognosis as well as strictures arising in patients with immunocompromised states like AIDS.
Biliary strictures can get complicated by chronic low-grade biliary obstruction. This can, in turn, cause recurrent cholangitis, ascending cholangitis, gram-negative septicemia, stone formation, hepatic abscesses, secondary biliary cirrhosis, end-stage liver disease, and cholangiocarcinoma.
Other complications could result from interventional procedures, and they may include pancreatitis, cholangitis, bleeding, and biliary perforation. Additionally, there are reports of distal migration of biliary stents leading to duodenal perforation. Stents can also be complicated by ingrowth or overgrowth by the tumor, rendering them non-functional.
Biliary strictures frequently present a challenge in terms of diagnosis, necessitating interdisciplinary collaboration. Likewise, a significant proportion of patients with benign strictures may have a protracted, complicated course calling for multiple consultations. Therefore, teams caring for patients with biliary strictures may comprise of hepatobiliary surgeons, medical oncologists, diagnostic radiologists, surgical oncologists, endoscopists, gastroenterologists, and interventional radiologists.
Patients drinking alcohol should be counseled against the practice, especially those whose diagnosis is linked to drinking i.e alcoholic chronic pancreatitis. Lastly, the patient and their caregivers should be informed about the prognosis of their disease.
The possibility of bile duct injury and subsequent bile duct stricture formation (although rare) should be discussed in detail with the patients while obtaining consent for laparoscopic cholecystectomy.
Bile duct strictures may present with nonspecific signs and symptoms of obstructive jaundice, abdominal pain, nausea, vomiting, fever, and leukocytosis. The cause of bile duct strictures may be one of the myriads of diagnosis, which includes benign and malignant etiologies. The complexity of this disease process lies in the challenges of its diagnosis and subsequent appropriate management. Inaccurate diagnosis or delay in management can have devastating outcomes for the patient. While the general surgeon is almost always involved in the care of these patients, it may become imperative to consult with an interprofessional team of specialists that include gastroenterologists, interventional radiologists, hepatobiliary surgeons, surgical oncologists, and transplant surgeons.
SAGES offers guidelines for the clinical application of laparoscopic biliary tract surgery. Regarding common bile duct injuries, the guidelines suggest that the factors which have been associated with bile duct injury include surgeon experience, patient age, male sex, and acute cholecystitis (Level II, Grade C). If major bile duct injuries occur, outcomes are improved by early recognition and immediate referral to experienced hepatobiliary specialists for further treatment before any repair is attempted by the primary surgeon, unless the primary surgeon has significant experience in biliary reconstruction. (Level II, Grade A).
Nurses play a vital role during the recovery of such patients. They monitor the patient closely for changes in vital signs and mental status as the patients recuperate. The nurses help in the timely recognition of common postoperative complications such as deep vein thrombosis and anastomotic leaks. The role of the laboratory personnel and pharmacist is critical as well. The pharmacist may be involved in the management of parenteral nutrition for critically ill patients.
|||Management of Biliary Stricture Following Emergent Pancreaticoduodenectomy for Trauma: Report of Two Cases., Israr S,Rubalcava NS,Weinberg JA,Jones M,Gillespie TL,, Cureus, 2018 Jun 18 [PubMed PMID: 30131922]|
|||Primary Endoscopic Closure of Duodenal Perforation Secondary to Biliary Stent Migration: A Case Report and Review of the Literature., Ferm S,Fisher C,Hassam A,Rubin M,Kim SH,Hussain SA,, Journal of investigative medicine high impact case reports, 2018 Jan-Dec [PubMed PMID: 30116760]|
|||Magnetic Anastomosis for Biliojejunostomy: First Prospective Clinical Trial., Liu XM,Yan XP,Zhang HK,Ma F,Guo YG,Fan C,Wang SP,Shi AH,Wang B,Wang HH,Li JH,Zhang XG,Wu R,Zhang XF,Lv Y,, World journal of surgery, 2018 Jun 13 [PubMed PMID: 29947988]|
|||Tubercular biliary hilar stricture: A rare case report., Narayan KS,Kumar M,Padhi S,Jain M,Ashdhir P,Pokharna RK,, The Indian journal of tuberculosis, 2018 Jul [PubMed PMID: 29933873]|
|||Endoscopic management of primary sclerosing cholangitis., Tabibian JH,Baron TH,, Expert review of gastroenterology & hepatology, 2018 Jul [PubMed PMID: 29883229]|
|||Singh A,Gelrud A,Agarwal B, Biliary strictures: diagnostic considerations and approach. Gastroenterology report. 2015 Feb; [PubMed PMID: 25355800]|
|||Moghul F,Kashyap S, Bile Duct Injury . 2020 Jan [PubMed PMID: 31536309]|
|||Mathew G,Kashyap S,Pfeifer C, Gallbladder, Cholecystitis, Clostridial (Gangrenous, Emphysematous) . 2020 Jan [PubMed PMID: 28846291]|
|||Kashyap S,Mathew G,Abdul W,King KC, Gallbladder Empyema . 2020 Jan [PubMed PMID: 29083646]|
|||[PubMed PMID: 30252245]|
|||Shanbhogue AK,Tirumani SH,Prasad SR,Fasih N,McInnes M, Benign biliary strictures: a current comprehensive clinical and imaging review. AJR. American journal of roentgenology. 2011 Aug; [PubMed PMID: 21785056]|
|||Chadha VK,Bhalla BB,Ramesh SB,Gupta J,Nagendra N,Padmesh R,Ahmed J,Srivastava RK,Jaiswal RK,Praseeja P, Tuberculosis diagnostic and treatment practices in private sector: Implementation study in an Indian city. The Indian journal of tuberculosis. 2018 Oct; [PubMed PMID: 30522619]|
|||Paranandi B,Oppong KW, Biliary strictures: endoscopic assessment and management. Frontline gastroenterology. 2017 Apr; [PubMed PMID: 28261440]|
|||[PubMed PMID: 8000648]|
|||Lorenz JM, Management of Malignant Biliary Obstruction. Seminars in interventional radiology. 2016 Dec; [PubMed PMID: 27904244]|
|||Gupta V,Jain G, Safe laparoscopic cholecystectomy: Adoption of universal culture of safety in cholecystectomy. World journal of gastrointestinal surgery. 2019 Feb 27; [PubMed PMID: 30842813]|
|||Chapoy PR,Kendall RS,Fonkalsrud E,Ament ME, Congenital stricture of the common hepatic duct: an unusual case without jaundice. Gastroenterology. 1981 Feb; [PubMed PMID: 7450427]|
|||Ma MX,Jayasekeran V,Chong AK, Benign biliary strictures: prevalence, impact, and management strategies. Clinical and experimental gastroenterology. 2019; [PubMed PMID: 30858721]|
|||Kapoor BS,Mauri G,Lorenz JM, Management of Biliary Strictures: State-of-the-Art Review. Radiology. 2018 Dec; [PubMed PMID: 30351249]|
|||Chun K, Recent classifications of the common bile duct injury. Korean journal of hepato-biliary-pancreatic surgery. 2014 Aug; [PubMed PMID: 26155253]|
|||[PubMed PMID: 29083722]|
|||Pu LZ,Singh R,Loong CK,de Moura EG, Malignant Biliary Obstruction: Evidence for Best Practice. Gastroenterology research and practice. 2016; [PubMed PMID: 26981114]|
|||Costamagna G,Boškoski I, Current treatment of benign biliary strictures. Annals of gastroenterology. 2013; [PubMed PMID: 24714594]|
|||Dadhwal US,Kumar V, Benign bile duct strictures. Medical journal, Armed Forces India. 2012 Jul; [PubMed PMID: 24532893]|
|||Kukar M,Wilkinson N, Surgical Management of Bile Duct Strictures. The Indian journal of surgery. 2015 Apr; [PubMed PMID: 26139967]|
|||Wong MYW,Kaffes AJ, Benign Biliary Strictures: Narrowing the Differences Between Endoscopic and Surgical Treatments. Digestive diseases and sciences. 2018 Oct; [PubMed PMID: 30054841]|
|||Inui K,Yoshino J,Miyoshi H, Differential diagnosis and treatment of biliary strictures. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2009 Nov; [PubMed PMID: 19896104]|