Clinical approach to indeterminate biliary strictures: Clinical presentation, diagnosis, and workup

Table 1 Etiologies of biliary strictures

Benign	Malignant
Postoperative or iatrogenic strictures: After cholecystectomy, liver transplantation or surgical procedures involving pancreas. Local cancer treatment including radiation therapy, chemoembolization, and microwave ablation	Pancreatic adenocarcinoma
Chronic pancreatitis	Cholangiocarcinoma
Primary sclerosing cholangitis	Gallbladder malignancy
Trauma	Hepatocellular carcinoma
Infection: Recurrent pyogenic cholangitis, AIDS cholangiopathy	Ampullary carcinoma
Autoimmune: IgG4 related sclerosing cholangitis, sarcoidosis	Metastatic tumors or perihilar malignant nodes (colon cancer, breast cancer, renal cell cancer, squamous cell carcinoma)
Vascular: Ischemia, portal hypertensive biliopathy	Less common: Lymphomas or neuroendocrine tumors
Primary biliary cirrhosis
Rarely COVID-19 cholangiopathy, gallstones, inflammatory bowel disease or medications

IgG4: Immunoglobulin G4; AIDS: Acquired immunodeficiency syndrome; COVID-19: Coronavirus disease 2019.

Table 2 Tissue sampling techniques in evaluation of indeterminate biliary strictures

Tissue acquisition technique	Advantages	Disadvantages	Comments
ERCP-guided techniques
Intraductal biopsy	Direct sampling of larger tissue samples	Risk of bleeding, perforation, pancreatitis	Used in conjunction to other techniques to maximize yield
Brush cytology	Less invasive. Can be used in cases of advanced liver or pancreatic disease	Smaller tissues sample. Low diagnostic yield	Used in conjunction to other techniques to maximize yield
FISH	Can detect genetic abnormalities associated with malignancy	Requires specialized equipment for analysis. Limited sensitivity and specificity	Used in conjunction with biopsies or brushings to improve diagnostic yield
Flow cytometry	Can detect abnormal cellular DNA associated with malignancy	Requires specialized equipment for analysis. Limited sensitivity and specificity	Used in conjunction with other techniques
Cholangioscopy with biopsy	Direct visualization of stricture and targeted biopsies	Requires specialized equipment and expertise. Associated with higher risk of complications such as cholangitis, pancreatitis, and bleeding. More expensive than conventional ERCP	Can perform interventions under direct visualization
Intraductal ultrasound	High-resolution imaging of the biliary tract and surrounding structures, can detect structural abnormalities associated with malignancy	Invasive, requires specialized equipment and expertise	Not available in every institution
Risks associated with ERCP - bleeding, perforation, pancreatitis, infection
EUS guided sampling
EUS with FNA	High diagnostic yield, ability to sample adjacent lymph nodes or lesions	Invasive, risk of bleeding and infection, requires expertise	Can be used as a complementary technique to ERCP or alone. Should be used with ROSE if available and if malignancy suspected
EUS with FNB	High diagnostic yield, ability to sample lymph nodes, larger tissue	Invasive, risk of bleeding and infection, requires expertise	Can be used as a complementary technique to ERCP or alone
EUS/ERCP combination	Ability to obtain tissue samples and perform therapeutic interventions in the same encounter	Invasive, requires specialized equipment and expertise	Used in complex cases and in cases where biliary drainage is needed
Confocal laser endomicroscopy	Real-time in vivo imaging of biliary tissue at the cellular level	Limited availability and expertise, expensive	Can be used to improve diagnostic accuracy and guide targeted biopsies
Optical coherence tomography	High-resolution imaging of biliary tissue, can detect structural abnormalities associated with malignancy	Limited availability and expertise, expensive	Can be useful in cases where other techniques have failed or when precise localization of the stricture is necessary

ERCP: Endoscopic retrograde cholangiopancreatography; EUS: Endoscopic ultrasound; FNA: Fine-needle aspiration; FNB: Fine-needle biopsy; ROSE: Rapid onsite evaluation; FISH: Fluorescent in situ hybridization.