Background
Cholangioscopy is a noninvasive endoscopic method used for both direct visual diagnostic evaluation and simultaneous therapeutic intervention of the bile ducts. [1] Peroral cholangioscopy overcomes some of the limitations of endoscopic retrograde cholangiopancreatography (ERCP). Pancreatoscopy is the direct visual evaluation of the pancreatic ducts.
Although cholangioscopy has been in limited use since the 1950s, it has only comapratively recently matured as a noninvasive technique. In the 1970s, Rosch et al [2] and Urakami [3] independently described two different endoscopic methods for peroral cholangioscopy. Since that time, peroral cholangioscopy has been refined largely through advances in endoscopic technique, scope design, and functionality. However, widespread adoption of peroral cholangioscopy was hampered by technologic hurdles until relatively recently. [4]
Early cholangioscopes [2, 3, 5] had several limitations: they were very fragile and could break up; required two endoscopists; had only a two-way steering mechanism, which severely limited negotiation of ducts; and lacked working channels and irrigation ports. [6] Thus, in the absence of more modern endoscopic technologies, this procedure was restricted to a few specialized centers worldwide for very specific indications. However, the SpyGlass cholangioscopes (Boston Scientific, Marlborough, MA) overcame many of the limitations posed by these earlier cholangioscopes.
The introduction of a sophisticated cholangioscope system for cholangiopancreatoscopy has led many experts to believe that peroral cholangioscopy will become a universally adopted technique for the evaluation and treatment of biliary tract diseases. Indeed, SpyGlass cholangiopancreatoscopy showed promising results in a multicenter international study [4] and was approved by the US Food and Drug Administration for diagnostic and therapeutic applications during endoscopic procedures in the pancreaticobiliary system. [7]
Cholangioscopy has been shown to be an effective diagnostic and therapeutic tool. Studies have evaluated clinical efficacy of peroral cholangioscopy in characterizing benign versus malignant natures of biliary strictures, diagnosing intraductal tumors, better defining unknown biliary pathologies, and treating biliary stones. [8, 9, 10, 11, 12]
Direct cholangioscopy (DC) using ultraslim gastroscopes was developed as an alternative to mother-and-baby cholangioscopes. DC provides superior imaging, achieves shorter total procedure time, and has a wider working channel for adequate tissue sampling. [13, 14]
In addition, Itoi et al [15] tested a novel multibending prototype peroral direct cholangioscope (PDCS). This study showed that a cholangioscope passed over a guide wire or anchoring balloon had a high diagnostic and therapeutic success rate. However, results were not appealing with the free-hand insertion technique.
Pohl et al [16] showed that a short-access mother-and-baby scope (SAMBA) is better than DC with regard to intraductal stability and accessibility of the intrahepatic bile ducts. Mori et al [17] suggested duodenal balloon-assisted cholangioscopy as an alternative technique in cases of failure with conventional ERCP. A digital version of a SpyGlass cholangioscope is being developed and evaluated. [13, 18]
Image enhancement of endoscopically visualized tissue can be performed by dye, autofluorescence, narrowband image, or probe-based confocal fluorescence (PCLE) microscopy. Cholangioscopy, with the addition of these enhancing methods, helps to distinguish benign from malignant biliary strictures. [19] PCLE provides microscopic information in real time, incorporating dynamic information such as blood flow, cellular architecture, contrast uptake, and leakage. Initial observational studies reported a good sensitivity and negative predictive value of the PCLE findings in diagnosing malignancy. However, evaluation in prospective, randomized studies is needed. [20]
Diagnostic applications are as follows:
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Virtual or optic chromoscopy [13]
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Confocal laser endomicroscopy
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Precise mapping and delineation of intraductal tumor spread before resection
Therapeutic applications are as follows [13] :
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Endoscopic tumor ablation therapy
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Migrating stent removal
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Endoscopic biliary drainage
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Endoscopic nasobiliary drainage
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Plastic stent placement
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Endoscopic resection
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Hot biopsy
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Snare resection
Itoi et al evaluated the efficacy of cholangioscopy in IgG4-related sclerosing cholangitis (IgG4 SC). [21] Their results suggested that cholangioscopy was effective in differentiating IgG4-SC from primary sclerosing cholangitis. Proliferative vessels on cholangioscopy was suggested to be useful to differentiating IgG4-SC from cholangiocarcinoma. Moreover, Suyigama et al showed peroral cholangioscopy to be useful as a preoperative examination modality for assessing tumor extension in cholangiocarcinoma patients. [22, 9, 10]
Indications
Indications for cholangiopancreatoscopy in biliary disease include the following [23, 4, 6, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43] :
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Biopsy of indeterminate strictures [44] in patients without primary sclerosing cholangitis
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Exclusion of malignant stricture in primary sclerosing cholangitis by providing visual-guided biopsy [45]
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Diagnosing cholangiocarcinoma
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Indeterminate filling defect of bile ducts seen on imaging or ERCP
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Nondiagnostic ERCP findings for biopsy
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Precise preoperative location of biliary and pancreatic intraductal tumors
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Visual evaluation and biopsy to evaluate posttransplantation biliary issues, intraductal mucinous neoplasm, and eosinophilic cholangitis
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Evaluation for cytomegalovirus, fungal, and parasitic infections
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Hemobilia
Therapeutic indications for cholangiopancreatoscopy in biliary disease include the following:
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Cystic duct stent placement
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Photodynamic therapy of cholangiocarcinoma (potential indication)
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Argon photocoagulation of intraductal mucinous neoplasm (potential indication)
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Alternative to surgery in patients with Mirizzi syndrome type II (potential indication)
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Biliary stone extraction [46] and dissolution using mechanical, electrohydraulic, or laser lithotripsy (see the image below)
Cholangioscopic view of (A) bile duct stone and (B) electrohydraulic lithotripsylithotripsy.
Diagnostic and therapeutic indications for cholangiopancreatoscopy in pancreatic disease include the following:
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Pancreatic stones
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Pancreatic duct tumors
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Potential role in autoimmune pancreatitis
Some studies have demonstrated the efficacy of peroral cholangioscopy in comparison to ERCP for evaluating many biliary disorders. Kawakami et al [47] showed that ERCP diagnosed intraepithelial tumor spread in only 22% of cases, whereas peroral cholangioscopy was successful in 77% of cases. Further, peroral cholangioscopy with concomitant biopsy accurately diagnosed 100% of cases.
A study by Fukuda et al [48] showed that the sensitivity of combined ERCP/peroral cholangioscopy in diagnosing biliary lesions was 93% compared with only 58% for ERCP alone. The same study showed the superiority of cholangioscopy with biopsy in differentiating benign from malignant lesions with an accuracy of 100%.
Additionally, cholangioscopy was useful in evaluating indeterminate filling defects seen on ERCP. A study by Tischendorf et al [49] showed that cholangioscopy significantly improves the ability to differentiate between benign and malignant biliary stenosis in patients with primary sclerosing cholangitis.
Siddique et al [50] reported additional unexpected diagnostic information was provided by cholangioscopy for 18 of 61 patients. In seven of 61 patients, cholangioscopy revealed normal results when standard cholangiography suggested abnormal findings. This study also showed a role for cholangioscopy in biliary strictures in patients after liver transplantation and patients with hemobilia. (See the image below.)
A study by Awadallah et al [51] reported that peroral cholangioscopy-guided biopsy was able to exclude malignancy in 31 patients with primary sclerosing cholangitis who had a prior finding of a dominant biliary stricture. A study by Itoi et al [52] found that cholangioscopy with biopsy can diagnose benign and malignant lesions with a sensitivity of 99% and specificity of 95.8%.
Peroral cholangioscopy has also been evaluated as an effective tool for evaluation of pancreatic ducts. A study by Yamaguchi et al [24] reported improved ability to diagnose intraductal papillary mucinous neoplasms of the pancreas by pancreatic cytology using mother-baby cholangioscopes. This study also concluded that there is no diagnostic value with pancreatic juice cytology in diagnosing pancreatic carcinoma.
Studies evaluating the efficacy of the SpyGlass cholangioscopy system have reported that direct visualization improves the accuracy of cholangiographic findings and has good positive predictive value in evaluating patients with biliary obstructive symptoms of indeterminate origin. [4, 25, 26] In one series, cholangioscopy-guided bile duct biopsies could be successfully performed in 89% of cases. Notably, the sensitivity of this technique for diagnosing intrinsic malignant strictures was higher than the transpapillary route.
An unanticipated benefit of the high sensitivity of cholangioscopy is that it has revealed previously unappreciated weaknesses in ERCP-mediated evaluation and diagnosis of biliary stones.
Parsi et al [25] were able to diagnose at least 29% of ERCP-missed biliary stones by subsequent cholangioscopy, subsequently concluding that rates of missed stones on ERCP may be higher than previously thought. The same study reported a success rate of 92% in treatment of biliary stones using electrohydraulic or laser lithotripsy. Moon et al [27] reported excellent success with lithotripsy with electrohydraulic or laser using ultraslim cholangioscopes.
In patients with difficult-to-treat stones, Arya et al [28] described peroral cholangioscopy with electrohydraulic lithotripsy in 94 patients reporting a 96% fragmentation rate and 90% final stone clearance rate. Moreover, Hui et al [29] demonstrated significantly less cholangitis and a decreased mortality with peroral cholangioscopy-guided lithotripsy as compared with biliary stenting alone in elderly patients.
Multiple other studies reported similar success rates in treatment of biliary stones using peroral cholangioscopy and electrohydraulic or laser therapy. Thus, when performed by experienced and well-trained personnel, peroral cholangioscopy can be a safe and highly effective technique for the management of difficult-to-treat biliary stones.
Contraindications
Contraindications for cholangioscopy include the following [53] :
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Any condition that precludes patients from undergoing endoscopy
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Acute pancreatitis excluding due to biliary stones
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Uncorrected coagulopathy with a high bleeding risk
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Altered upper gastrointestinal anatomy precluding access to the second portion of duodenum (eg, Roux-en-Y)
Technical Considerations
Procedural planning
Early communication has to be established with the institutional pathology department to alert them of a possible small biopsy specimen arrival from cholangioscopy. As the quantity of tissue sample acquired during cholangioscopy is very small, this communication will ensure optimal processing of the precious specimens.
Complication prevention
Cholangioscopy involves significant manipulation of the biliary ducts. Antibiotic prophylaxis is generally given before the procedure, with levaquin, ampicillin, and gentamicin being the most commonly used antibiotics.
Care must be taken to confirm that coagulation parameters are normal before the procedure so as to minimize bleeding risk.
Aggressive irrigation should be avoided when obstruction is visualized within the biliary duct so as to prevent cholangitis.
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Spyglass System and images from the biliary system.
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Cholangioscopic view of (A) bile duct stone and (B) electrohydraulic lithotripsylithotripsy.
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Cholangioscopic view of normal intrahepatic biliary mucosa.
