• biliary fibrosis
• cholangiopathy
• etiology
• mechanism
• therapeutic strategy

• CECT
• ERCP
• MRCP
• MRI
• biliary stricture
• cholangiocarcinoma (CCA)

• biliary tree disorders
• cholangiocarcinoma
• cholangioscopy
• endoscopic retrograde cholangiopancreatography
• endoscopic ultrasound
• indeterminate strictures

The diagnosis of biliary strictures in clinical practice can be challenging. Discriminating between benign and malignant biliary strictures is important to prevent the morbidity and mortality associated with incorrect diagnoses. Missing a malignant biliary stricture may delay surgery, resulting in poor prognostic outcomes. Conversely, it has been demonstrated that approximately 20% of patients who undergo surgery for suspected biliary malignancies have a benign etiology on histopathology. Traditional tissue sampling using endoscopic retrograde cholangiography does not always produce a definitive diagnosis, with a considerable proportion of cases remaining as indeterminate biliary strictures. Recent advances in endoscopic techniques have the potential to improve the diagnostic and prognostic accuracy of biliary strictures.

• Bile ducts
• Biliary tract neoplasm
• Cholestasis
• Endoscopy
• Pathologic constriction

• ERCP
• EUS
• EUS-FNA
• biliary strictures
• cholangioscopy
• confocal laser endomicroscopy
• endoscopic retrograde cholangiopancreatography
• endoscopic ultrasound

In suspected malignant biliary strictures (MBSs), the diagnostic yield of endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling is limited. Transpapillary forceps biopsy (TPB) under intraductal ultrasonography (IDUS) guidance is expected to improve the diagnostic accuracy in patients with indeterminate biliary strictures. We evaluated the usefulness of IDUS-guided TPB in patients with suspected MBS.

Consecutive patients with suspected MBS were prospectively enrolled in the study. ERCP with IDUS was performed in all patients. Both conventional TPB and IDUS-guided TPB on fluoroscopy were performed in each patient. The primary outcome was the diagnostic accuracy of conventional TPB and IDUS-guided TPB.

The technical success rate of IDUS-guided TPB was 97.0% (65/67 patients). Of these 65 patients, the final diagnosis was malignancy in 61 patients (93.8%). On IDUS, the most common finding of IDUS was an intraductal infiltrating lesion in 29 patients (47.5%). The overall diagnostic accuracy was significantly higher using IDUS-guided TPB than that using conventional TPB (90.8% vs 76.9%, p=0.027). According to the subgroup analysis based on the tumor morphology, IDUS-guided TPB had a significantly higher cancer detection rate than conventional TPB for intraductal infiltrating lesions (89.6% vs 65.5%, p=0.028).

IDUS-guided TPB appears to improve the accuracy of histological diagnosis in patients with MBS.

• Biopsy
• Cholangiopancreatography, endoscopic retrograde
• Intraductal ultrasonography
• Malignant biliary stricture

Patients with esophageal stricture who have normal mucosa and whose endoscopic biopsies are inconclusive pose a difficult diagnostic dilemma. We prospectively assessed high-frequency miniprobe endoscopic ultrasonography (EUS) for the evaluation of indeterminate esophageal strictures.

Over a period of 3 years, 19 patients (14 male; mean age: 58.9±11.6 years) with indeterminate esophageal strictures were studied using high-frequency miniprobe EUS. The final diagnosis was based on definitive cytopathology, surgical pathology or clinical follow up for more than 6 months.

The etiology of the esophageal stricture was benign in 10 patients (peptic 2, tubercular 2, drug-induced 2, idiopathic 1, post-pancreatitis 1, post-surgical 1, and IgG4-related sclerosing esophagitis 1), and malignant in 9 patients (squamous cell carcinoma 5, and adenocarcinoma 4). The esophageal stricture was located in the upper, mid and lower esophagus in 1, 9 and 9 patients respectively. The mean length of benign and malignant esophageal strictures was 2.4±1.1 cm and 5.3±1.6 cm, respectively (P=0.0003). EUS was performed successfully without dilatation in all patients. Wall stratification was lost in all patients with malignant strictures and in 3/10 (30%) patients with benign strictures (P=0.03). The mean esophageal wall thickness in malignant and benign strictures was 11.7±2.5 mm and 7.1±2.2 mm, respectively (P=0.0005). A wall thickness ≥9 mm had a sensitivity, specificity, and accuracy of 78%, 80%, and 79%, respectively, for the diagnosis of malignancy.

High-frequency miniprobe EUS provides important diagnostic information about esophageal strictures. Thicker esophageal walls and a loss of wall stratification are more common in malignant strictures.

• Endosonography
• corrosive
• malignancy
• stricture
• tuberculosis

Primary sclerosing cholangitis (PSC) is a disease of the biliary tract, which has been documented in the literature since 1867. This disease has a strong predilection for affecting men and can be seen in individuals as young as 2 years of age. PSC has a strong associated with inflammatory bowel disease, more commonly with ulcerative colitis, and is also part of the clinical spectrum of IgG4-related diseases. Small-duct PSC, a variant of PSC, also has an association with inflammatory bowel disease. The exact pathogenesis of PSC is not well understood at present, however, is likely a combination of a genetic predisposition with alteration of the molecular structure of the gut. Abnormal serum liver chemistry and presence of certain autoimmune markers are usually the first indicators leading to a diagnosis of PCS, however, these may often be normal in early stages of this disease. The diagnosis is made by cholangiography, which is now considered the gold standard. PSC is a known pre-malignant condition. Such patients have an increased risk of developing cholangiocarcinoma, gallbladder neoplasia, and colon cancer. Many new treatment modalities have emerged in the recent past, including anti-tumor necrosis factor- α and anti-integrins; however, liver transplantation is the only known cure for PSC. Despite past and present research, PSC remains an enigmatic biliary disease with few viable treatment options.

• Primary sclerosing cholangitis
• Cholestasis
• Inflammatory bowel disease
• Autoimmune
• Gallbladder neoplasia
• Cholangiocarcinoma
• IgG4 related disease
• Colon cancer
• Liver transplant

• Animals
• Autoimmune Diseases/complications
• Autoimmune Diseases/immunology
• Cholangitis, Sclerosing/etiology
• Cholangitis, Sclerosing/genetics
• Cholangitis, Sclerosing/immunology
• Cholangitis, Sclerosing/therapy
• Genetic Predisposition to Disease
• Humans
• Inflammation Mediators/immunology
• Inflammation Mediators/metabolism
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/immunology
• Intestinal Mucosa/metabolism
• Intestines/immunology
• Phenotype
• Predictive Value of Tests
• Prognosis
• Risk Factors

• BILIARY ENDOSCOPY
• BILIARY STRICTURES
• CHOLANGIOCARCINOMA
• ENDOSCOPIC RETROGRADE PANCREATOGRAPHY
• ENDOSCOPIC ULTRASONOGRAPHY

Endoscopic evaluation of indeterminate biliary strictures (IDBSs) has evolved considerably since the development of flexible fiberoptic endoscopes over 50 years ago. Endoscopic retrograde cholangiography pancreatography (ERCP) was introduced nearly a decade later and has since become the mainstay of therapy for relieving obstruction of the biliary tract. However, longstanding methods of ERCP-guided tissue acquisition (i.e., biliary brushings for cytology and intraductal forceps biopsy for histology) have demonstrated disappointing performance characteristics in distinguishing malignant from benign etiologies of IDBSs. The limitations of these methods have thus helped drive the search for novel techniques to enhance the evaluation of IDBSs and thereby improve diagnosis and clinical care. These modalities include, but are not limited to, endoscopic ultrasound, intraductal ultrasound, cholangioscopy, confocal endomicroscopy, and optical coherence tomography. In this review, we discuss established and emerging options in the evaluation of IDBSs.

• Cholangiocarcinoma
• Bile duct diseases
• Cholangiopathies
• Gastrointestinal endoscopy
• Pancreatic adenocarcinoma

• brush cytology
• cholangiocarcinoma
• endoscopic retrograde cholangiopancreatography
• fluorescence in situ hybridization
• forceps biopsy

• biliary disease
• hydatid disease
• intraductal ultrasound

Hilar cholangiocarcinoma (HC) is a rare tumor that causes devastating disease. In the late stages, this carcinoma primarily invades the portal vein and metastasizes to the hepatic lobes; it is associated with a poor prognosis. HC is diagnosed by its clinical manifestation and results of imaging techniques such as ultrasound, computed tomography, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography. Preoperative hepatic bile drainage can improve symptoms associated with insufficient liver and kidney function, coagulopathy, and jaundice. Surgical margin-negative (R0) resection, including major liver resection, is the most effective and potentially curative treatment for HC. If the tumor is not resected, then liver transplantation with adjuvant management can improve survival. We conducted a systematic review of developments in imaging studies and major surgical hepatectomy for HC with positive outcomes regarding quality of life.

Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient’s outcome. Early and accurate diagnosis of malignancy impacts not only a patient’s candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.

• Indeterminate stricture
• Bile duct
• Single operator cholangioscope
• Cholangioscopy
• Endoscopic ultrasound
• Endoscopic retrograde cholangiopancreatography
• Bile duct stricture
• Indeterminate biliary stricture
• Confocal microscopy
• Transpapillary biopsy
• Cholangiocarcinoma
• Primary sclerosing cholangitis
• Spyglass

• Acute pancreatitis
• Bile duct stones
• Chronic pancreatitis
• Contrast harmonic endoscopic ultrasound
• Duct drainage
• Endoscopic ultrasound
• Fine needle aspiration
• Pancreatic cysts
• Pancreatic tumors

• Bile Duct Diseases/diagnosis
• Bile Duct Diseases/diagnostic imaging
• Biliary Tract/diagnostic imaging
• Endosonography/methods
• Endosonography/standards
• Endosonography/trends
• Humans
• Outcome Assessment, Health Care
• Pancreas/diagnostic imaging
• Pancreatic Cyst/diagnosis
• Pancreatic Cyst/diagnostic imaging
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatitis/diagnosis
• Pancreatitis/diagnostic imaging
• Sensitivity and Specificity

The accurate diagnosis of extrahepatic bile duct carcinoma is difficult, even now. When ultrasonography (US) shows dilatation of the bile duct, magnetic resonance cholangiopancreatography followed by endoscopic US (EUS) is the next step. When US or EUS shows localized bile duct wall thickening, endoscopic retrograde cholangiopancreatography should be conducted with intraductal US (IDUS) and forceps biopsy. Fluorescence in situ hybridization increases the sensitivity of brush cytology with similar specificity. In patients with papillary type bile duct carcinoma, three biopsies are sufficient. In patients with nodular or infiltrating-type bile duct carcinoma, multiple biopsies are warranted, and IDUS can compensate for the limitations of biopsies. In preoperative staging, the combination of dynamic multi-detector low computed tomography (MDCT) and IDUS is useful for evaluating vascular invasion and cancer depth infiltration. However, assessment of lymph nodes metastases is difficult. In resectable cases, assessment of longitudinal cancer spread is important. The combination of IDUS and MDCT is useful for revealing submucosal cancer extension, which is common in hilar cholangiocarcinoma. To estimate the mucosal extension, which is common in extrahepatic bile duct carcinoma, the combination of IDUS and cholangioscopy is required. The utility of current peroral cholangioscopy is limited by the maneuverability of the “baby scope”. A new baby scope (10 Fr), called “SpyGlass” has potential, if the image quality can be improved. Since extrahepatic bile duct carcinoma is common in the Far East, many researchers in Japan and Korea contributed these studies, especially, in the evaluation of longitudinal cancer extension.

• Bile duct cancer
• Bile duct carcinoma
• Cholangiocarcinoma
• Endoscopic retrograde cholangiopancreatography
• Intraductal ultrasonography

AIM: To assess the diagnostic ability of endoscopic ultrasonography (EUS) for evaluating causes of distal biliary strictures shown on endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP), even without identifiable mass on computed tomography (CT).

METHODS: The diagnostic ability of EUS was retrospectively analyzed and compared with that of routine cytology (RC) and tumor markers in 34 patients with distal biliary strictures detected by ERCP or MRCP at Dokkyo Medical School Hospital from December 2005 to December 2008, without any adjacent mass or eccentric thickening of the bile duct on CT that could cause biliary strictures. Findings considered as benign strictures on EUS included preservation of the normal sonographic layers of the bile duct wall, irrespective of the presence of a mass lesion. Other strictures were considered malignant. Final diagnosis of underlying diseases was made by pathological examination in 18 cases after surgical removal of the samples, and by clinical follow-up for > 10 mo in 16 cases.

RESULTS: Seventeen patients (50%) were finally diagnosed with benign conditions, including 6 “normal” subjects, while 17 patients (50%) were diagnosed with malignant disease. In terms of diagnostic ability, EUS showed 94.1% sensitivity, 82.3% specificity, 84.2% positive predictive value, 93.3% negative predictive value (NPV) and 88.2% accuracy for identifying malignant and benign strictures. EUS was more sensitive than RC (94.1% vs 62.5%, P = 0.039). NPV was also better for EUS than for RC (93.3% vs 57.5%, P = 0.035). In addition, EUS provided significantly higher sensitivity than tumor markers using 100 U/mL as the cutoff level of carbohydrate antigen 19-9 (94.1% vs 53%, P = 0.017). On EUS, biliary stricture that was finally diagnosed as malignant showed as a hypoechoic, irregular mass, with obstruction of the biliary duct and invasion to surrounding tissues.

CONCLUSION: EUS can diagnose biliary strictures caused by malignant tumors that are undetectable on CT. Earlier detection by EUS would provide more therapeutic options for patients with early-stage pancreaticobiliary cancer.

• Computed tomography
• Cytology
• Endoscopic retrograde cholangiopancreatography
• Endoscopic ultrasound
• Indeterminate biliary stricture
• Magnetic resonance cholangiopancreatography
• Tumor marker

Several advances in diagnosis, treatment and palliation of cholangiocarcinoma (CC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. CC is a relatively rare tumor and the main risk factors are: chronic inflammation, genetic predisposition and congenital abnormalities of the biliary tree. While the incidence of intra-hepatic CC is increasing, the incidence of extra-hepatic CC is trending down. The only curative treatment for CC is surgical resection with negative margins. Liver transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation therapy. Magnetic resonance imaging/magnetic resonance cholangiopancreatography, positron emission tomography scan, endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging. Adjuvant therapy, palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable CC. For most of these patients biliary stenting provides effective palliation. Photodynamic therapy is an emerging palliative treatment that seems to provide pain relief, improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization, hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.

• Cholangiocarcinoma
• Epidemiology
• Diagnosis
• Therapy
• Palliation
• Systematic review

• Biopsy, Fine-Needle/methods
• Contrast Media
• Endosonography/methods
• Humans
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/pathology
• Mediastinum/diagnostic imaging
• Mediastinum/pathology
• Neoplasm Staging/methods
• Pancreatic Cyst/diagnostic imaging
• Pancreatic Cyst/pathology
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/pathology

• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Bile Duct Neoplasms/diagnosis
• Bile Duct Neoplasms/epidemiology
• Bile Duct Neoplasms/etiology
• Bile Duct Neoplasms/metabolism
• Bile Duct Neoplasms/therapy
• Bile Ducts, Intrahepatic
• Biomarkers, Tumor/metabolism
• Cholangiocarcinoma/diagnosis
• Cholangiocarcinoma/epidemiology
• Cholangiocarcinoma/etiology
• Cholangiocarcinoma/metabolism
• Cholangiocarcinoma/therapy
• Cholangitis, Sclerosing/complications
• Diagnosis, Differential
• Humans
• Neoplasm Staging

• Ampulla of Vater
• Cholestasis/diagnostic imaging
• Common Bile Duct Neoplasms/diagnostic imaging
• Endoscopes, Gastrointestinal
• Endoscopy, Gastrointestinal
• Gallbladder Diseases/diagnostic imaging
• Gallstones/diagnostic imaging
• Humans
• Ultrasonography