Cholangioscopy is a noninvasive endoscopic method used for both direct visual diagnostic evaluation and simultaneous therapeutic intervention of the bile ducts. Peroral cholangioscopy overcomes some of the limitations of endoscopic retrograde cholangiopancreatography (ERCP). Pancreatoscopy is the direct visual evaluation of the pancreatic ducts.
Cholangioscopy has recently matured as a noninvasive technique, although it has been in limited use since the 1950s. In the 1970s, Rosch et al  and Urakami  independently described two different endoscopic methods for peroral cholangioscopy. Since that time, peroral cholangioscopy has been refined largely due to advances in endoscopic technique, scope design, and functionality. However, widespread adoption of peroral cholangioscopy was hampered by technologic hurdles until recently. 
Early cholangioscopes [1, 2, 4] 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.  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 have overcome many of the limitations posed by these earlier cholangioscopes.
With the introduction of a sophisticated spyglass cholangioscope system for cholangiopancreatoscopy, most experts believe that peroral cholangioscopy will soon become a universally adopted technique for the evaluation and treatment of biliary tract diseases. Indeed, the Spyglass cholangiopancreatoscopy showed promising results in a multicenter international study  and was approved by the U.S. Food and Drug Administration in 2009 for diagnostic and therapeutic applications during endoscopic procedures in the pancreaticobiliary system. [6, 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. 
Direct cholangioscopy (DC) using ultraslim gastroscopes was recently 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. [9, 10]
In addition, Itoi et al  have tested a novel multibending prototype peroral direct cholangioscope (PDCS). This study showed that a cholangioscope passed over a guidewire 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  have shown that short-access mother baby scope (SAMBA) is better than DC with regard to intraductal stability and accessibility of the intrahepatic bile ducts. Mori et al  suggested duodenal balloon-assisted cholangioscopy as an alternative technique in cases of failure with conventional endoscopic retrograde cholangiopancreatography (ERCP). A digital version of a spyglass cholangioscope is currently being developed. 
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.  PCLE provides microscopic information in real time, incorporating dynamic information such as blood flow, cellular architecture, contrast uptake, and leakage. Initial observational studies have reported a good sensitivity and negative predictive value of the PCLE findings in diagnosing malignancy. However, evaluation in prospective, randomized studies is needed. 
Diagnostic applications are as follows:
Virtual or optic chromoscopy 
Confocal laser endomicroscopy
Precise mapping and delineation of intraductal tumor spread before resection
Therapeutic applications are as follows  :
Endoscopic tumor ablation therapy
Migrating stent removal
Endoscopic biliary drainage
Endoscopic nasobiliary drainage
Plastic stent placement
Itoi et al evaluated the efficacy of cholangioscopy in IgG4-related sclerosing cholangitis (IgG4 SC).  Their results suggested 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 have shown peroral cholangioscopy is useful as a preoperative examination modality for assessing tumor extension in cholangiocarcinoma patients. 
Biopsy of indeterminate strictures in patients without primary sclerosing cholangitis
Exclusion of malignant stricture in primary sclerosing cholangitis by providing visual-guided biopsy
Indeterminate filling defect of bile ducts seen on imaging or ERCP
Nondiagnostic ERCP findings for biopsy
Precise preoperative location of biliary and pancreatic intraductal tumors
Visual evaluation and biopsy to evaluate posttransplantation biliary issues, intraductal mucinous neoplasm, and eosinophilic cholangitis
Evaluation for cytomegalovirus, fungal, and parasitic infections
Therapeutic indications for cholangiopancreatoscopy in biliary disease include the following:
Cystic duct stent placement
Photodynamic therapy of cholangiocarcinoma (potential indication)
Argon photocoagulation of intraductal mucinous neoplasm (potential indication)
Alternate to surgery in patients with Mirizzi syndrome type II (potential indication)
Biliary stone extraction and dissolution using mechanical, electrohydraulic, or laser lithotripsy (see 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:
Pancreatic duct tumors
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  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  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  has shown that cholangioscopy significantly improves the ability to differentiate between benign and malignant biliary stenosis in patients with primary sclerosing cholangitis.
Siddique et al  reported additional unexpected diagnostic information was provided by cholangioscopy for 18 of 61 patients. In 7 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  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  has reported 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  reported improved ability to diagnose intraductal papillary mucinous neoplasms of the pancreas by pancreatic cytology using mother-baby cholangioscopes. Importantly, 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. [3, 19, 20] In one series, cholangioscopy-guided bile duct biopsies could be successfully performed in 89% of cases. Importantly, 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  have been able to diagnose at least 29% of ERCP-missed biliary stones by subsequent cholangioscopy, leading them to conclude 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  have reported excellent success with lithotripsy with electrohydraulic or laser using ultraslim cholangioscopes.
In patients with difficult-to-treat stones, Arya et al  described peroral cholangioscopy with electrohydraulic lithotripsy in 94 patients reporting a 96% fragmentation rate and 90% ﬁnal stone clearance rate. Moreover, Hui et al  demonstrated significantly less cholangitis and a decreased mortality rate with peroral cholangioscopy-guided lithotripsy compared to 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 for cholangioscopy include the following  :
Any condition that precludes patients from undergoing endoscopy
Acute pancreatitis excluding due to biliary stones
Uncorrected coagulopathy with a high bleeding risk
Altered upper gastrointestinal anatomy precluding access to the second portion of duodenum (eg, Roux-en-Y)
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.
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.
Caution has to taken to confirm coagulation parameters are normal before the procedure to prevent bleeding risk.
Aggressive irrigation should be avoided when obstruction is visualized within the biliary duct to prevent cholangitis.
Patient Education/Informed Consent
Patients should be instructed to fast overnight before the procedure.
Elements of Informed Consent
Informed consent has to be obtained from the patient. The procedure to be performed and risks involved with the anesthesia and the procedure should be explained.
The procedure should be explained to the assisting staff.
All required equipment should be checked before the procedure begins.
Prophylactic antibiotics are usually administered 30 minutes before the procedure.
Two-Operator Systems: Mother-Baby Scopes and Miniscopes
These endoscopes use a large “mother” scope for duodenoscopy and then introduce a smaller “baby” scope to cannulate biliary ducts. When it was introduced, it was a revolutionary technology that provided successful visualization of bile ducts and pancreatic ducts. It also offered excellent diagnostic and therapeutic potential in the management of biliary disorders.
However, these systems are limited. They are fragile and cumbersome; require two endoscopists; are limited to two-way endoscopic steering; lack adequate working channels, widespread availability, and expertise; and have high maintenance costs.
Miniscopes were then developed. They were introduced into bile ducts through standard duodenoscopes. Earlier versions were fragile, did not have tip deflection, and lacked working channels.
Larger miniscopes were later developed to overcome the limitations of earlier, smaller miniscopes. Advantages include therapeutic capability from the instrumentation channel, but they were limited by the absence of separate air and water channels.
Single-Operator System: Spyglass Cholangiopancreatoscopy
The initial clinical feasibility study for the Spyglass cholangioscopy system (developed by Boston Scientific) was described by Chen et al in 2007.  This system is considered a major breakthrough in cholangioscope technology and overcame many limitations of earlier versions.
The Spyglass cholangioscopy system uses single-endoscopist operation. It has 4-way tip deflection, separate irrigation and working (instrumentation) channels, and a 4-lumen single catheter. It allows for significantly decreased time under fluoroscopy and thus decreased radiation exposure. Multicenter international trials have shown promising results in the diagnosis and treatment of many biliary and pancreatic diseases.
Capital components include the following:
Component cart and three-joint arm
Light source and cable (300-W high intensity white light)
Camera and camera head (autoshutter camera with color image sensor)
Ocular–optical coupler that interfaces with the probe and camera head
Power cable pack
Regarding consumable devices, the system makes use of a disposable access and delivery catheter (10-F outer diameter), a reusable optical probe, and disposable biopsy forceps.
The Spyscope access and delivery catheter is a single-operator, disposable catheter used for introducing the spyglass system into the biliary system. It has a length of 230 cm and an outer diameter of 10 F. It consists of 4 lumens: one for the spyglass optical probe, one lumen for the Spybite forceps, and electrohydraulic lithotripsy or laser probes. Two irrigation channels exit at the end of the catheter for irrigation of ducts. It is unique because it has a 4-way tip deflection to help with navigation and better visualization of the biliary ducts.
The Spyglass fiberoptic probe is a multiple-use device with a length of 231 cm that conducts light to biliary ducts and captures fiberoptic endoscopic images. It consists of a 6000-pixel image bundle surrounded by an approximately 225-light transmission bundle. A lens connected at the distal end of the image bundle captures a 70-degree field of view. Images captured are inferior to those captured by video cholangioscopes.
The Spybite forceps are a single-use device that has a 286-cm working length. The forceps are introduced through the 1.2-mm working channel of the Spyscope catheter. The forceps jaw is designed with a central spike and has an outer diameter of 1 mm for obtaining small target biopsies under direct visualization.
The Spyglass system is compatible with a few electrohydraulic lithotripsy and laser probe devices introduced through the working channel of Spyscope catheter.
Direct cholangioscopy has superior image quality. The following equipment has been used: Olympus Gastroscope GIF-Q 180 with a diameter of 8.8 mm preloaded with an 11.5-F balloon and an Olympus Ultraslim upper endoscope GIF-XP 160 with a diameter of 5.9 mm with an instrument channel of 2 mm.
Cholangioscopy is a time-consuming and labor-intensive procedure. Deep sedation with parenteral midazolam/fentanyl by an anesthesiologist during the procedure is preferred. In few cases, general anesthesia may be required to perform the procedure. Protection of airway is an important concern during a prolonged procedure such as cholangioscopy, which further emphasizes the need for an anesthesiologist.
The patient should be under continuous monitoring of blood pressure, heart rate, heart rhythm, respiratory rate, and pulse oximetry during the procedure.
Patients are generally placed in a prone position during cholangioscopy.
The potential complications associated with cholangioscopy are numerous and range from relatively mild sequelae to life-threatening conditions, including the following:
Cholangitis (most common complication)
Perforation of bile duct (from the guide wire)
Elevated amylase and lipase without clinical pancreatitis
Cholangioscopy using the Spyglass cholangioscopy system [26, 44, 49] can be performed by a single endoscopist. The Spyscope access and delivery catheter is attached to duodenoscope by a silastic band below the working channel of duodenoscope. The duodenoscope along with the Spyglass cholangioscopy system is held by one hand of endoscopist. The other hand of the endoscopist is used for operating the deflection wheels of the duodenoscope and Spyglass system. The procedure is always performed in conjunction with ERCP.
The spyglass direct visualization probe is inserted into the optical channel of the spyglass catheter.
Under direct vision, the duodenoscope is passed through the oral cavity and pharynx. Then the esophagus is intubated and the duodenoscope is passed through the esophagus and stomach to reach the second portion of the duodenum to visualize ampulla of Vater and the papillae.
A selective and deep cannulation of the biliary tree is performed. A guide wire is then introduced and positioned in the bile duct (or pancreatic duct) under fluoroscopy.
Sphincterotomy is usually performed for better access of the biliary tree.
The Spyscope catheter, along with the optical probe, are introduced into the duodenoscope together as a unit and advanced into the biliary ducts for direct visualization. Once inside the common bile duct, the Spyglass catheter is slowly advanced under fluoroscopy. Once the Spyscope catheter is positioned in the common bile duct, the guide wire is removed.
The optical probe is then advanced beyond the tip of Spyglass catheter. Direct visualization of biliary ducts is performed by repeated advancing and withdrawal of Spyscope catheter in the biliary duct. Four-way tip deflection of the Spyscope catheter aids in better visualization of the biliary ducts.
If a suspicious lesion is found in the biliary ducts, the Spybite forceps are introduced through the operating channel for obtaining targeted small biopsies. If biliary stones are found, Spyglass-directed electrohydraulic or laser lithotripsy is performed.
Irrigation of the biliary ducts is performed through the two irrigation ports built within the Spyscope catheter that exit at the tip of the catheter. This clears the debris in the bile ducts and provides better visual images throughout the procedure. Lack of a suction port is a drawback of this system, but manual suction can be achieved by attaching a syringe to the operating channel.
After completion of the procedure, patients are generally kept to nothing per orem until the next day.
Cholangioscopy using a mother duodenoscope and baby cholangioscope requires two experienced endoscopists working together to complete the procedure. 
The procedure starts as a regular ERCP, with the introduction of duodenoscope under direct visualization through the mouth. It is advanced to the second portion of duodenum to visualize the ampulla of Vater.
Selective cannulation of the common bile duct is performed. A sphincterotomy is usually performed.
Cholangiography is then performed and a guide wire is placed in the biliary system.
The cholangioscope is introduced into the working channel of duodenoscope to cannulate the common bile duct. Under fluoroscopy, cholangioscope is slowly advanced over the guide wire to the common bile duct.
Once the cholangioscope is within the common bile duct, the guide wire may be removed. The working channel available in the cholangioscopes is used for diagnostic and therapeutic interventions. Targeted small biopsies can be obtained by introducing forceps through the working channel of the cholangioscope.
Electrohydraulic or laser lithotripsy also may be performed through the working channel of the cholangioscope.
Direct cholangioscopy is a relatively new technique with limited available data. [50, 45, 46] It is a technically difficult procedure that needs a larger sphincterotomy and dilated bile duct, but the image quality is superior.
This procedure can be performed by either wire-guided or balloon-assisted procedure.
A standard therapeutic duodenoscope is advanced to the second portion of the duodenum, similar to earlier mentioned methods for cholangioscopy.
A guide wire is then introduced into the bile ducts under fluoroscopy.
The duodenoscope is removed, leaving the guide wire in the bile ducts.
An ultraslim endoscope is then back loaded over the guide wire using a standard ERCP cannula.
Under fluoroscopic guidance, an ultraslim endoscope is advanced into the bile ducts.
If a balloon-assisted method is used, a balloon is introduced and inflated in the common hepatic duct. This is used as an anchor to advance the ultraslim endoscope into the bile ducts.