ORIGINAL ARTICLE: Clinical Endoscopy
Diagnostic and therapeutic cholangiopancreatoscopy: performance of a new digital cholangioscope Mansour A. Parsi, MD, MPH, Sunguk Jang, MD, Madhusudhan Sanaka, MD, Tyler Stevens, MD, MS, John J. Vargo, MD, MPH Cleveland, Ohio, USA
Background: High-definition cholangioscopes provide excellent images of the pancreatobiliary ductal system and may play a significant role in diagnosis and treatment of various pancreatobiliary disorders. Objective: To assess the performance of a new digital cholangioscope for diagnosis and treatment of pancreatobiliary disorders in clinical practice. Design: Prospective study. Setting: Academic hospital, tertiary-care referral center. Patients: Consecutive patients with suspected pancreatobiliary disorders. Intervention: Diagnostic or therapeutic high-definition digital cholangiopancreatoscopy. Main Outcome Measurements: Satisfactory visualization of the ductal mucosa and lumen and treatment of pancreatobiliary disorders when indicated. Results: A total of 28 cholangioscopy and 4 pancreatoscopy procedures were completed before breakdown of the cholangioscope. Excellent views of the ductal lumen and mucosa were obtained in all patients. In the 18 patients with indeterminate biliary strictures, high-definition cholangioscopy identified all cholangiocarcinomas but labeled as malignant only 1 of 4 strictures caused by pancreatic cancer (sensitivity 73%). All benign strictures were correctly labeled (specificity 100%). Cholangioscopy proved helpful in evaluation of various biliary disorders and lithotripsy of pancreatic stones under direct vision. Limitations: Single center, small number of patients. Conclusion: High-definition cholangioscopy is a useful adjunct to ERCP in the diagnosis and treatment of pancreatobiliary disorders. Although fragility of the cholangioscope remains a problem, the changes made in the construction of this prototype digital cholangioscope have significantly increased its durability. (Gastrointest Endosc 2014;79:936-42.)
Recent years have seen renewed interest in direct visualization of the biliary tree and the pancreatic duct.1 This interest is in large part because of the realization that high-definition images of the biliary or pancreatic ductal mucosa and lumen can provide valuable information for diagnosis of various pancreatobiliary disorders. Such direct
visualization is particularly helpful in biliary disorders that are difficult to diagnose, such as indeterminate strictures, or therapeutic measures in the pancreas, such as lithotripsy of pancreatic duct stones. Currently, high-definition imaging of the ductal epithelium is possible only with the use of video cholangioscopes
Abbreviations: NBI, narrow-band imaging.
Received August 12, 2013. Accepted October 14, 2013.
Disclosure: M. Parsi and T. Stevens are consultants for Boston Scientific. J. Vargo is a consultant for Boston Scientific, Cook Medical, and Olympus America. All other authors disclosed no financial relationships relevant to this publication.
Current affiliations: Center for Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio.
Copyright ª 2014 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2013.10.029
Reprint requests: Mansour A. Parsi, MD, MPH, Head, Center for Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195.
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or through direct insertion of ultraslim upper endoscopes. Direct cholangioscopy is successful in only a fraction of cases mainly because of difficulties in gaining access to the biliary tree.2-5 Direct pancreatoscopy may be even more challenging because of restrictions posed by the diameter of the pancreatic duct. Ductal access by using high-definition cholangioscopes is technically much easier. However, in addition to limited availability, such cholangioscopes are fragile and break easily. We previously reported our experience with a prototype high-definition peroral cholangioscopy system with narrow-band imaging (NBI) for evaluation of biliary disorders.6 That system consisted of a cholangioscope and a dedicated duodenoscope. The dedicated duodenoscope was designed to decrease the stress level exerted on the bending section of the cholangioscope, with the purpose of increasing its lifespan. By using that system, 21 cholangioscopy procedures were completed before the breakdown of the cholangioscope. We found high-definition cholangioscopy with NBI of the biliary system to be extremely useful for diagnosis of various biliary disorders, particularly for classification of indeterminate biliary strictures.6 Since that report, a new prototype high-definition digital cholangioscope has been produced, with special emphasis on durability and with the goal of making it compatible with other duodenoscopes. We sought to evaluate the performance of this newly developed, high-definition digital cholangioscope for diagnosis and treatment of biliary and pancreatic disorders.
METHODS Study design and population This is a prospective cohort study approved by the Cleveland Clinic Institutional Review Board (IRB#11-554). The study population consisted of consecutive patients with biliary or pancreatic disorders who were referred to our center for cholangioscopy or pancreatoscopy as part of their clinical evaluations. The inclusion criteria were suspicion of pancreatobiliary pathology, lack of coagulation disorders, and no suspicion of acute ascending cholangitis or acute pancreatitis.
Cholangioscopy system Cholangioscopy and pancreatoscopy examinations were performed by using a prototype digital cholangioscope (CHF Y0002B; Olympus Medical Systems, Tokyo, Japan). This cholangioscope offers high-resolution images and has NBI capability allowing detailed examination of the biliary and pancreatic ductal mucosa and its vascular pattern. The specifications of the cholangioscope are presented in Table 1. As opposed to its predecessor (CHF Y0002, Olympus Medical Systems, Tokyo, Japan), the new cholangioscope does not have a dedicated duodenoscope and has been www.giejournal.org
Diagnostic and therapeutic cholangiopancreatoscopy
Take-home Message High-definition cholangioscopy and pancreatoscopy can significantly enhance the diagnostic capability of ERCP, especially for classification of indeterminate biliary strictures and therapeutic procedures in the pancreatic duct.
designed to be compatible with most duodenoscopes. The bending section of the cholangioscope has been redesigned to tolerate more stress when passing over the elevator of a duodenoscope. All procedures in this study were performed by using a TJF-180V duodenoscope (Olympus, Center Valley, Pa).
Cholangioscopy and pancreatoscopy procedures All procedures were performed with patients under monitored anesthesia care sedation or general anesthesia with the patients in prone position. Two operators were required for performance of the cholangioscopy procedures. In all cases, the duodenoscope was operated by a single endoscopist (M.A.P.), who also was responsible for cholangioscopy image interpretation. The cholangioscope was operated under his instructions by an advanced endoscopist or an advanced endoscopy fellow. Endoscopic sphincterotomy was performed or had been performed previously before each cholangioscopy or pancreatoscopy. The cholangioscope was advanced through the accessory channel of a duodenoscope. Biliary or pancreatic cannulation was achieved in all cases with a guidewire steering the tip of the cholangioscope into the bile duct or the pancreatic duct. Stricture dilatation was performed as needed to facilitate passage of the cholangioscope across a lesion. Once the cholangioscope was advanced to the target location, the guidewire usually was removed to enhance visualization and to permit use of the working channel. The duct of interest was irrigated through the accessory channel of the cholangioscope with sterile saline solution followed by slow withdrawal of the cholangioscope, allowing systematic inspection of the ductal mucosa. NBI was used in evaluation of biliary strictures to assess the presence or absence of neovascularization. Routine antibiotic prophylaxis was not administered. Cholangioscopic diagnosis of malignant strictures was based on the presence of neovascularization within the stricture or the finding of an intraductal mass protruding into the lumen of the bile duct. Final diagnosis of malignancy was based on tissue diagnosis.
Statistical analysis Descriptive statistics are presented as mean (range) or frequency (percentage). The R version 2.4.1 software (The R Foundation for Statistical Computing, Vienna, Austria) was used to perform all analyses. Volume 79, No. 6 : 2014 GASTROINTESTINAL ENDOSCOPY 937
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TABLE 1. Specifications of the cholangioscope (CHF-Y0002B) Optical system Field of view Direction of view Depth of field Type Narrow-band imaging
90 Forward viewing 1-50–mm Digital Available
Insertion tube Working length
2000 mm
Outer diameter
3.5 mm
Distal end outer diameter
3.4 mm
Instrument channel Inner diameter
1.2 mm
Bending section Angulation range Total length
Figure 1. Cholangioscopic image of a normal left hepatic duct. Note the patent lumen and normal mucosal vascular pattern.
Up 70 , down 70 2300 mm
RESULTS Between September 2011 and October 2012, 31 patients underwent 32 procedures (28 cholangioscopy and 4 pancreatoscopy) with the use of the new cholangioscope. The cholangioscope malfunctioned during the 33rd procedure. In all patients, excellent views of the ductal lumen and mucosa were obtained (Figs. 1 and 2).
Cholangioscopy Fourteen of the 28 patients (50%) who had completed cholangioscopy were male. The median age was 70 years (25th and 75th percentiles; 59 and 74 years). The indications were as follows: evaluation of indeterminate biliary strictures (n Z 18), abnormal cross-sectional imaging study results (n Z 4), further work-up of persistent abnormal liver function test results (n Z 4), assessment of an anastomotic stricture in a patient after liver transplantation (n Z 1), and evaluation of fever of unknown origin attributed to recurrent cholangitis (n Z 1).
Figure 2. Endoluminal view of a tortuous pancreatic duct. Note a dilated side branch at the right upper corner of the image. A guidewire is in place to steer the cholangioscope to a more proximal position.
Among the 18 patients who underwent cholangioscopy for diagnosis of indeterminate biliary strictures, 11 had a final diagnosis of malignancy (7 patients had cholangiocarcinoma, and 4 had pancreatic cancer). Eight of the 11 patients had cholangioscopic findings suggestive of malignancy. Neovascularization and masses were seen in
3 patients, neovascularization alone was seen in 4 patients, and a mass without neovascularization was seen in 1 patient (Figs. 3, 4, and 5). Cholangioscopy correctly diagnosed all patients with cholangiocarcinoma. However, in only 1 of 4 patients with pancreatic cancer was the stricture correctly labeled as malignant by cholangioscopy. In the remaining 3 patients, the biliary mucosa appeared normal at the site of the stricture, suggesting external compression.
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Diagnostic and therapeutic cholangiopancreatoscopy
Figure 5. Cholangioscopic view of a protruding mass into the lumen of the bile duct.
Figure 3. Neovascularization visualized by cholangioscopy with white light at the site of a malignant biliary stricture.
Figure 6. Metallic clips and suture material in the bile duct visualized by high-definition cholangioscopy. Note stones proximal to the foreign bodies. Figure 4. Same stricture as in Figure 3, visualized by cholangioscopy with narrow-band imaging.
Among the 7 patients with a final diagnosis of benign stricture, 2 had primary sclerosing cholangitis, 2 had chronic inflammation because of choledocholithiasis, 1 had chronic pancreatitis, 1 had the surprising finding of suture material and metallic clips in the bile duct (Fig. 6), and 1 patient had a biliary web. All benign strictures were correctly labeled by cholangioscopy.
Overall, the sensitivity and specificity of highdefinition cholangioscopy for diagnosis of indeterminate biliary strictures were 73% and 100%, respectively. Among patients with indeterminate biliary strictures, 5 had biliary stents in place before cholangioscopy. Two of these patients had cholangiocarcinoma, 1 had pancreatic cancer, and 2 had benign strictures. With the exception of the patient with pancreatic cancer, all strictures were diagnosed correctly.
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Cholangioscopy for other indications Ten patients underwent cholangioscopy for indications other than evaluation of indeterminate biliary strictures. Four patients underwent cholangioscopy for evaluation of abnormal liver function test results or fever. All 4 patients already had undergone therapeutic ERCP for stone extraction or treatment of benign biliary strictures 1 to 3 weeks before cholangioscopy. In 3 of these patients, stones were detected by cholangioscopy, which had been missed by ERCP. In all 3 patients, stones were removed, with normalization of the liver function test results. One patient had ERCP 1 week before cholangioscopy for removal of biliary stones and had presented to the emergency department for fever. Because of suspicion for a retained stone, the patient underwent a repeat ERCP with cholangioscopy. Both ERCP and cholangioscopy results were normal. The patient responded well to antibiotic treatment and became afebrile. She has had a follow-up of O1 year without any subsequent problems. In 4 patients, cholangioscopy was performed for evaluation of a biliary abnormality on cross-sectional imaging. Two of these patients were found to have cholesterol stones on cholangioscopy (Fig. 7). One patient with biliary-type pain had biliary dilatation on MRCP. ERCP was suggestive of sphincter stenosis, and cholangioscopy as an adjunct to ERCP showed normal biliary mucosa. The patient was treated with a biliary sphincterotomy, with resolution of the pain. In 1 patient, a presumed biliary filling defect on cross-sectional imaging was later found to be an artifact. The cholangioscopy result was normal in that patient. One patient underwent cholangioscopy for evaluation of fever of unknown origin attributed to recurrent cholangitis. Cholangioscopy showed normal biliary mucosa to the secondary branches without signs of chronic inflammation, suggesting a source other than the biliary system. In a patient who had undergone liver transplantation, cholangioscopy was performed to assess irregularities at the biliary anastomosis and revealed anastomotic hyperplastic tissue. None of the ERCP or cholangioscopy procedures were associated with adverse events.
Pancreatoscopy Three patients underwent 4 pancreatoscopy procedures. One patient with chronic calcific pancreatitis underwent 2 pancreatoscopy procedures for fragmentation of pancreatic duct stones. Electrohydraulic lithotripsy of pancreatic stones was successfully performed under direct visualization (Fig. 8). The other 2 procedures were performed for evaluation of recurrent pancreatitis. Both patients had undergone extensive evaluation in the past without detection of a clear underlying etiology for the recurrence of pancreatitis episodes. In both cases, the pancreatic duct lumen appeared dilated but patent with normal mucosa (Fig. 2). 940 GASTROINTESTINAL ENDOSCOPY Volume 79, No. 6 : 2014
Figure 7. Cholesterol stone in the bile duct.
Figure 8. Pancreatoscopy-guided shockwave lithotripsy of an obstructive pancreatic duct stone. The lithotripsy probe is seen in the left lower corner of the image.
None of the ERCP or pancreatoscopy procedures were associated with adverse events.
DISCUSSION In recent years, cholangioscopy has gained significant interest as a complementary procedure to ERCP for diagnosis and treatment of various biliary disorders, particularly indeterminate biliary strictures. It is well known that the presence of irregularly dilated and tortuous blood vessels (so-called tumor vessels) caused by neovascularization at the site of pancreatic or biliary strictures is www.giejournal.org
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Diagnostic and therapeutic cholangiopancreatoscopy
indicative of malignancy.7-9 Tumor vessels can be detected by direct visualization by using a cholangioscope.7 NBI is an imaging technique especially suited for visualization and characterization of mucosal vascular patterns. Use of cholangioscopes with NBI capability facilitates detection of neovascularization at the site of biliary strictures and thereby diagnosis of malignancy.10 Intraductal nodules or masses also can be indicative of malignancy and can be detected easily by cholangioscopy.8 Studies to assess the value of stricture visualization by cholangioscopy have reported high sensitivity for detection of malignant lesions. In one of the largest cholangioscopic studies to date, diagnostic fiberoptic cholangioscopy by using the Spyglass system (Boston Scientific, Natick, MA) was performed in 226 patients with various biliary disorders. In patients with biliary strictures, the sensitivity for the diagnosis of malignancy was 51% for ERCP impression, 78% for cholangioscopic impression, and 49% for targeted biopsy.11 Smaller studies that used video cholangioscopes with better imaging capability have reported even higher sensitivity for detection of malignancy by visualization of the stricture sites alone.6,10 Overall, the findings of these studies suggest that addition of cholangioscopy enhances the diagnostic performance of ERCP, especially its capability to diagnose indeterminate biliary strictures. In this study, we were able to correctly diagnose all patients with cholangiocarcinoma by visualization of the ductal mucosa alone. However, in patients with pancreatic cancer, cholangioscopic evidence of malignancy could be seen in only 1 of 4 patients. This is not surprising because biliary strictures caused by extraluminal compression, such as those associated with pancreatic cancer, cannot be detected by visualization of the bile duct unless the disease is at later stages when the tumor has infiltrated and penetrated the bile duct wall.1 In these situations, EUS may be a useful adjunct for detecting malignancy. We found cholangioscopy useful for evaluation of patients with abnormal hepatobiliary cross-sectional imaging and for further work-up of patients with suspected stone retention. During ERCP, small stones can be “drowned” in contrast material and missed, and larger stones can block a duct and prevent passage of contrast material and thus evade detection.1 In a study of patients with primary sclerosing cholangitis, stones were not detectable on contrast cholangiography in 7 of 23 patients (30%).12 In a more recent multicenter study, stones were missed in 29% of patients who presented for ERCP for different indications.13 In that study, ERCP was immediately followed by peroral cholangioscopy, which led to detection of the stones. Pancreatoscopy has remained underused. This is mainly because of lack of endoluminal endoscopes with appropriate optics capable of providing high-definition images of the pancreatic duct. Good image quality is important
for both diagnostic and therapeutic purposes in the pancreatic duct because mucosal details aid diagnosis, and adequate views of the lumen assure that therapeutic maneuvers are confined within the lumen. In this study, adequate views of the pancreatic duct lumen ensured that the shock waves were delivered to the stones and not the ductal wall. Digital cholangioscopes are fragile and easily damaged. Most damages occur at the distal end of the cholangioscope as it passes over the elevator of the duodenoscope. Some digital cholangioscopes have a dedicated duodenoscope with a “gentle” elevator to extend their life spans.6 This new cholangioscope has been redesigned to be compatible with various duodenoscopes. The TJF-180V duodenoscope (Olympus, Center Valley, Pa) used in this study has a V-shaped elevator that exerts significant stress on cholangioscopes. Despite using this particular duodenoscope, we were able to complete 32 cholangiopancreatoscopy procedures, indicating significant improvement in the durability of the new-generation digital cholangioscopes compared with earlier generations. As high-definition digital cholangiopancreatoscopes become more durable and readily available, we foresee a more prominent role for cholangiopancreatoscopy for diagnosis and treatment of various pancreatobiliary disorders, particularly diagnosis of indeterminate biliary strictures and treatment of obstructive pancreatic duct stones under the safety of direct vision.
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REFERENCES 1. Parsi MA. Peroral cholangioscopy in the new millennium. World J Gastroenterol 2011;17:1-6. 2. Larghi A, Waxman I. Endoscopic direct cholangioscopy by using an ultra-slim upper endoscope: a feasibility study. Gastrointest Endosc 2006;63:853-7. 3. Choi HJ, Moon JH, Ko BM, et al. Overtube-balloon-assisted direct peroral cholangioscopy by using an ultra-slim upper endoscope (with videos). Gastrointest Endosc 2009;69:935-40. 4. Moon JH, Ko BM, Choi HJ, et al. Intraductal balloon-guided direct peroral cholangioscopy with an ultraslim upper endoscope (with videos). Gastrointest Endosc 2009;70:297-302. 5. Parsi MA, Stevens T, Vargo JJ. Diagnostic and therapeutic direct peroral cholangioscopy using an intraductal anchoring balloon. World J Gastroenterol 2012;18:3992-6. 6. Parsi MA, Stevens T, Collins J, et al. Utility of a prototype peroral video cholangioscopy system with narrow-band imaging for evaluation of biliary disorders (with videos). Gastrointest Endosc 2011;74: 1148-51. 7. Kim HJ, Kim MH, Lee SK, et al. Tumor vessel: a valuable cholangioscopic clue of malignant biliary stricture. Gastrointest Endosc 2000;52:635-8. 8. Seo DW, Lee SK, Yoo KS, et al. Cholangioscopic findings in bile duct tumors. Gastrointest Endosc 2000;52:630-4. 9. Tang D, Nagano H, Yamamoto H, et al. Angiogenesis in cholangiocellular carcinoma: expression of vascular endothelial growth factor, angiopoietin-1/2, thrombospondin-1 and clinicopathological significance. Oncol Rep 2006;15:525-32.
Diagnostic and therapeutic cholangiopancreatoscopy 10. Itoi T, Sofuni A, Itokawa F, et al. Peroral cholangioscopic diagnosis of biliary-tract diseases by using narrow-band imaging (with videos). Gastrointest Endosc 2007;66:730-6. 11. Chen YK, Parsi MA, Binmoeller KF, et al. Single-operator cholangioscopy in patients requiring evaluation of bile duct disease or therapy of biliary stones (with videos). Gastrointest Endosc 2011;74: 805-14.
Parsi et al 12. Awadallah NS, Chen YK, Piraka C, et al. Is there a role for cholangioscopy in patients with primary sclerosing cholangitis? Am J Gastroenterol 2006;101:284-91. 13. Chen YK, Parsi MA, Binmoeller KF, et al. Peroral cholangioscopy (POC) using a disposable steerable single operator catheter for biliary stone therapy and assessment of indeterminate stricturesda multicenter experience using Spyglass [abstract]. Gastrointest Endosc 2009;69:AB264-5.
Registration of Human Clinical Trials Gastrointestinal Endoscopy follows the International Committee of Medical Journal Editors (ICMJE)’s Uniform Requirements for Manuscripts Submitted to Biomedical Journals. All prospective human clinical trials eventually submitted in GIE must have been registered through one of the registries approved by the ICMJE, and proof of that registration must be submitted to GIE along with the article. For further details and explanation of which trials need to be registered as well as a list of ICMJE-acceptable registries, please go to http://www.icmje.org.
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Diagnostic and therapeutic cholangiopancreatoscopy: performance of a new digital cholangioscope Mansour A. Parsi, MD, MPH, Sunguk Jang, MD, Madhusudhan Sanaka, MD, Tyler Stevens, MD, MS, John J. Vargo, MD, MPH Cleveland, Ohio, USA
Background: High-definition cholangioscopes provide excellent images of the pancreatobiliary ductal system and may play a significant role in diagnosis and treatment of various pancreatobiliary disorders. Objective: To assess the performance of a new digital cholangioscope for diagnosis and treatment of pancreatobiliary disorders in clinical practice. Design: Prospective study. Setting: Academic hospital, tertiary-care referral center. Patients: Consecutive patients with suspected pancreatobiliary disorders. Intervention: Diagnostic or therapeutic high-definition digital cholangiopancreatoscopy. Main Outcome Measurements: Satisfactory visualization of the ductal mucosa and lumen and treatment of pancreatobiliary disorders when indicated. Results: A total of 28 cholangioscopy and 4 pancreatoscopy procedures were completed before breakdown of the cholangioscope. Excellent views of the ductal lumen and mucosa were obtained in all patients. In the 18 patients with indeterminate biliary strictures, high-definition cholangioscopy identified all cholangiocarcinomas but labeled as malignant only 1 of 4 strictures caused by pancreatic cancer (sensitivity 73%). All benign strictures were correctly labeled (specificity 100%). Cholangioscopy proved helpful in evaluation of various biliary disorders and lithotripsy of pancreatic stones under direct vision. Limitations: Single center, small number of patients. Conclusion: High-definition cholangioscopy is a useful adjunct to ERCP in the diagnosis and treatment of pancreatobiliary disorders. Although fragility of the cholangioscope remains a problem, the changes made in the construction of this prototype digital cholangioscope have significantly increased its durability. (Gastrointest Endosc 2014;79:936-42.)
Recent years have seen renewed interest in direct visualization of the biliary tree and the pancreatic duct.1 This interest is in large part because of the realization that high-definition images of the biliary or pancreatic ductal mucosa and lumen can provide valuable information for diagnosis of various pancreatobiliary disorders. Such direct
visualization is particularly helpful in biliary disorders that are difficult to diagnose, such as indeterminate strictures, or therapeutic measures in the pancreas, such as lithotripsy of pancreatic duct stones. Currently, high-definition imaging of the ductal epithelium is possible only with the use of video cholangioscopes
Abbreviations: NBI, narrow-band imaging.
Received August 12, 2013. Accepted October 14, 2013.
Disclosure: M. Parsi and T. Stevens are consultants for Boston Scientific. J. Vargo is a consultant for Boston Scientific, Cook Medical, and Olympus America. All other authors disclosed no financial relationships relevant to this publication.
Current affiliations: Center for Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio.
Copyright ª 2014 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2013.10.029
Reprint requests: Mansour A. Parsi, MD, MPH, Head, Center for Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195.
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or through direct insertion of ultraslim upper endoscopes. Direct cholangioscopy is successful in only a fraction of cases mainly because of difficulties in gaining access to the biliary tree.2-5 Direct pancreatoscopy may be even more challenging because of restrictions posed by the diameter of the pancreatic duct. Ductal access by using high-definition cholangioscopes is technically much easier. However, in addition to limited availability, such cholangioscopes are fragile and break easily. We previously reported our experience with a prototype high-definition peroral cholangioscopy system with narrow-band imaging (NBI) for evaluation of biliary disorders.6 That system consisted of a cholangioscope and a dedicated duodenoscope. The dedicated duodenoscope was designed to decrease the stress level exerted on the bending section of the cholangioscope, with the purpose of increasing its lifespan. By using that system, 21 cholangioscopy procedures were completed before the breakdown of the cholangioscope. We found high-definition cholangioscopy with NBI of the biliary system to be extremely useful for diagnosis of various biliary disorders, particularly for classification of indeterminate biliary strictures.6 Since that report, a new prototype high-definition digital cholangioscope has been produced, with special emphasis on durability and with the goal of making it compatible with other duodenoscopes. We sought to evaluate the performance of this newly developed, high-definition digital cholangioscope for diagnosis and treatment of biliary and pancreatic disorders.
METHODS Study design and population This is a prospective cohort study approved by the Cleveland Clinic Institutional Review Board (IRB#11-554). The study population consisted of consecutive patients with biliary or pancreatic disorders who were referred to our center for cholangioscopy or pancreatoscopy as part of their clinical evaluations. The inclusion criteria were suspicion of pancreatobiliary pathology, lack of coagulation disorders, and no suspicion of acute ascending cholangitis or acute pancreatitis.
Cholangioscopy system Cholangioscopy and pancreatoscopy examinations were performed by using a prototype digital cholangioscope (CHF Y0002B; Olympus Medical Systems, Tokyo, Japan). This cholangioscope offers high-resolution images and has NBI capability allowing detailed examination of the biliary and pancreatic ductal mucosa and its vascular pattern. The specifications of the cholangioscope are presented in Table 1. As opposed to its predecessor (CHF Y0002, Olympus Medical Systems, Tokyo, Japan), the new cholangioscope does not have a dedicated duodenoscope and has been www.giejournal.org
Diagnostic and therapeutic cholangiopancreatoscopy
Take-home Message High-definition cholangioscopy and pancreatoscopy can significantly enhance the diagnostic capability of ERCP, especially for classification of indeterminate biliary strictures and therapeutic procedures in the pancreatic duct.
designed to be compatible with most duodenoscopes. The bending section of the cholangioscope has been redesigned to tolerate more stress when passing over the elevator of a duodenoscope. All procedures in this study were performed by using a TJF-180V duodenoscope (Olympus, Center Valley, Pa).
Cholangioscopy and pancreatoscopy procedures All procedures were performed with patients under monitored anesthesia care sedation or general anesthesia with the patients in prone position. Two operators were required for performance of the cholangioscopy procedures. In all cases, the duodenoscope was operated by a single endoscopist (M.A.P.), who also was responsible for cholangioscopy image interpretation. The cholangioscope was operated under his instructions by an advanced endoscopist or an advanced endoscopy fellow. Endoscopic sphincterotomy was performed or had been performed previously before each cholangioscopy or pancreatoscopy. The cholangioscope was advanced through the accessory channel of a duodenoscope. Biliary or pancreatic cannulation was achieved in all cases with a guidewire steering the tip of the cholangioscope into the bile duct or the pancreatic duct. Stricture dilatation was performed as needed to facilitate passage of the cholangioscope across a lesion. Once the cholangioscope was advanced to the target location, the guidewire usually was removed to enhance visualization and to permit use of the working channel. The duct of interest was irrigated through the accessory channel of the cholangioscope with sterile saline solution followed by slow withdrawal of the cholangioscope, allowing systematic inspection of the ductal mucosa. NBI was used in evaluation of biliary strictures to assess the presence or absence of neovascularization. Routine antibiotic prophylaxis was not administered. Cholangioscopic diagnosis of malignant strictures was based on the presence of neovascularization within the stricture or the finding of an intraductal mass protruding into the lumen of the bile duct. Final diagnosis of malignancy was based on tissue diagnosis.
Statistical analysis Descriptive statistics are presented as mean (range) or frequency (percentage). The R version 2.4.1 software (The R Foundation for Statistical Computing, Vienna, Austria) was used to perform all analyses. Volume 79, No. 6 : 2014 GASTROINTESTINAL ENDOSCOPY 937
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TABLE 1. Specifications of the cholangioscope (CHF-Y0002B) Optical system Field of view Direction of view Depth of field Type Narrow-band imaging
90 Forward viewing 1-50–mm Digital Available
Insertion tube Working length
2000 mm
Outer diameter
3.5 mm
Distal end outer diameter
3.4 mm
Instrument channel Inner diameter
1.2 mm
Bending section Angulation range Total length
Figure 1. Cholangioscopic image of a normal left hepatic duct. Note the patent lumen and normal mucosal vascular pattern.
Up 70 , down 70 2300 mm
RESULTS Between September 2011 and October 2012, 31 patients underwent 32 procedures (28 cholangioscopy and 4 pancreatoscopy) with the use of the new cholangioscope. The cholangioscope malfunctioned during the 33rd procedure. In all patients, excellent views of the ductal lumen and mucosa were obtained (Figs. 1 and 2).
Cholangioscopy Fourteen of the 28 patients (50%) who had completed cholangioscopy were male. The median age was 70 years (25th and 75th percentiles; 59 and 74 years). The indications were as follows: evaluation of indeterminate biliary strictures (n Z 18), abnormal cross-sectional imaging study results (n Z 4), further work-up of persistent abnormal liver function test results (n Z 4), assessment of an anastomotic stricture in a patient after liver transplantation (n Z 1), and evaluation of fever of unknown origin attributed to recurrent cholangitis (n Z 1).
Figure 2. Endoluminal view of a tortuous pancreatic duct. Note a dilated side branch at the right upper corner of the image. A guidewire is in place to steer the cholangioscope to a more proximal position.
Among the 18 patients who underwent cholangioscopy for diagnosis of indeterminate biliary strictures, 11 had a final diagnosis of malignancy (7 patients had cholangiocarcinoma, and 4 had pancreatic cancer). Eight of the 11 patients had cholangioscopic findings suggestive of malignancy. Neovascularization and masses were seen in
3 patients, neovascularization alone was seen in 4 patients, and a mass without neovascularization was seen in 1 patient (Figs. 3, 4, and 5). Cholangioscopy correctly diagnosed all patients with cholangiocarcinoma. However, in only 1 of 4 patients with pancreatic cancer was the stricture correctly labeled as malignant by cholangioscopy. In the remaining 3 patients, the biliary mucosa appeared normal at the site of the stricture, suggesting external compression.
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Evaluation of indeterminate biliary strictures
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Diagnostic and therapeutic cholangiopancreatoscopy
Figure 5. Cholangioscopic view of a protruding mass into the lumen of the bile duct.
Figure 3. Neovascularization visualized by cholangioscopy with white light at the site of a malignant biliary stricture.
Figure 6. Metallic clips and suture material in the bile duct visualized by high-definition cholangioscopy. Note stones proximal to the foreign bodies. Figure 4. Same stricture as in Figure 3, visualized by cholangioscopy with narrow-band imaging.
Among the 7 patients with a final diagnosis of benign stricture, 2 had primary sclerosing cholangitis, 2 had chronic inflammation because of choledocholithiasis, 1 had chronic pancreatitis, 1 had the surprising finding of suture material and metallic clips in the bile duct (Fig. 6), and 1 patient had a biliary web. All benign strictures were correctly labeled by cholangioscopy.
Overall, the sensitivity and specificity of highdefinition cholangioscopy for diagnosis of indeterminate biliary strictures were 73% and 100%, respectively. Among patients with indeterminate biliary strictures, 5 had biliary stents in place before cholangioscopy. Two of these patients had cholangiocarcinoma, 1 had pancreatic cancer, and 2 had benign strictures. With the exception of the patient with pancreatic cancer, all strictures were diagnosed correctly.
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Cholangioscopy for other indications Ten patients underwent cholangioscopy for indications other than evaluation of indeterminate biliary strictures. Four patients underwent cholangioscopy for evaluation of abnormal liver function test results or fever. All 4 patients already had undergone therapeutic ERCP for stone extraction or treatment of benign biliary strictures 1 to 3 weeks before cholangioscopy. In 3 of these patients, stones were detected by cholangioscopy, which had been missed by ERCP. In all 3 patients, stones were removed, with normalization of the liver function test results. One patient had ERCP 1 week before cholangioscopy for removal of biliary stones and had presented to the emergency department for fever. Because of suspicion for a retained stone, the patient underwent a repeat ERCP with cholangioscopy. Both ERCP and cholangioscopy results were normal. The patient responded well to antibiotic treatment and became afebrile. She has had a follow-up of O1 year without any subsequent problems. In 4 patients, cholangioscopy was performed for evaluation of a biliary abnormality on cross-sectional imaging. Two of these patients were found to have cholesterol stones on cholangioscopy (Fig. 7). One patient with biliary-type pain had biliary dilatation on MRCP. ERCP was suggestive of sphincter stenosis, and cholangioscopy as an adjunct to ERCP showed normal biliary mucosa. The patient was treated with a biliary sphincterotomy, with resolution of the pain. In 1 patient, a presumed biliary filling defect on cross-sectional imaging was later found to be an artifact. The cholangioscopy result was normal in that patient. One patient underwent cholangioscopy for evaluation of fever of unknown origin attributed to recurrent cholangitis. Cholangioscopy showed normal biliary mucosa to the secondary branches without signs of chronic inflammation, suggesting a source other than the biliary system. In a patient who had undergone liver transplantation, cholangioscopy was performed to assess irregularities at the biliary anastomosis and revealed anastomotic hyperplastic tissue. None of the ERCP or cholangioscopy procedures were associated with adverse events.
Pancreatoscopy Three patients underwent 4 pancreatoscopy procedures. One patient with chronic calcific pancreatitis underwent 2 pancreatoscopy procedures for fragmentation of pancreatic duct stones. Electrohydraulic lithotripsy of pancreatic stones was successfully performed under direct visualization (Fig. 8). The other 2 procedures were performed for evaluation of recurrent pancreatitis. Both patients had undergone extensive evaluation in the past without detection of a clear underlying etiology for the recurrence of pancreatitis episodes. In both cases, the pancreatic duct lumen appeared dilated but patent with normal mucosa (Fig. 2). 940 GASTROINTESTINAL ENDOSCOPY Volume 79, No. 6 : 2014
Figure 7. Cholesterol stone in the bile duct.
Figure 8. Pancreatoscopy-guided shockwave lithotripsy of an obstructive pancreatic duct stone. The lithotripsy probe is seen in the left lower corner of the image.
None of the ERCP or pancreatoscopy procedures were associated with adverse events.
DISCUSSION In recent years, cholangioscopy has gained significant interest as a complementary procedure to ERCP for diagnosis and treatment of various biliary disorders, particularly indeterminate biliary strictures. It is well known that the presence of irregularly dilated and tortuous blood vessels (so-called tumor vessels) caused by neovascularization at the site of pancreatic or biliary strictures is www.giejournal.org
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indicative of malignancy.7-9 Tumor vessels can be detected by direct visualization by using a cholangioscope.7 NBI is an imaging technique especially suited for visualization and characterization of mucosal vascular patterns. Use of cholangioscopes with NBI capability facilitates detection of neovascularization at the site of biliary strictures and thereby diagnosis of malignancy.10 Intraductal nodules or masses also can be indicative of malignancy and can be detected easily by cholangioscopy.8 Studies to assess the value of stricture visualization by cholangioscopy have reported high sensitivity for detection of malignant lesions. In one of the largest cholangioscopic studies to date, diagnostic fiberoptic cholangioscopy by using the Spyglass system (Boston Scientific, Natick, MA) was performed in 226 patients with various biliary disorders. In patients with biliary strictures, the sensitivity for the diagnosis of malignancy was 51% for ERCP impression, 78% for cholangioscopic impression, and 49% for targeted biopsy.11 Smaller studies that used video cholangioscopes with better imaging capability have reported even higher sensitivity for detection of malignancy by visualization of the stricture sites alone.6,10 Overall, the findings of these studies suggest that addition of cholangioscopy enhances the diagnostic performance of ERCP, especially its capability to diagnose indeterminate biliary strictures. In this study, we were able to correctly diagnose all patients with cholangiocarcinoma by visualization of the ductal mucosa alone. However, in patients with pancreatic cancer, cholangioscopic evidence of malignancy could be seen in only 1 of 4 patients. This is not surprising because biliary strictures caused by extraluminal compression, such as those associated with pancreatic cancer, cannot be detected by visualization of the bile duct unless the disease is at later stages when the tumor has infiltrated and penetrated the bile duct wall.1 In these situations, EUS may be a useful adjunct for detecting malignancy. We found cholangioscopy useful for evaluation of patients with abnormal hepatobiliary cross-sectional imaging and for further work-up of patients with suspected stone retention. During ERCP, small stones can be “drowned” in contrast material and missed, and larger stones can block a duct and prevent passage of contrast material and thus evade detection.1 In a study of patients with primary sclerosing cholangitis, stones were not detectable on contrast cholangiography in 7 of 23 patients (30%).12 In a more recent multicenter study, stones were missed in 29% of patients who presented for ERCP for different indications.13 In that study, ERCP was immediately followed by peroral cholangioscopy, which led to detection of the stones. Pancreatoscopy has remained underused. This is mainly because of lack of endoluminal endoscopes with appropriate optics capable of providing high-definition images of the pancreatic duct. Good image quality is important
for both diagnostic and therapeutic purposes in the pancreatic duct because mucosal details aid diagnosis, and adequate views of the lumen assure that therapeutic maneuvers are confined within the lumen. In this study, adequate views of the pancreatic duct lumen ensured that the shock waves were delivered to the stones and not the ductal wall. Digital cholangioscopes are fragile and easily damaged. Most damages occur at the distal end of the cholangioscope as it passes over the elevator of the duodenoscope. Some digital cholangioscopes have a dedicated duodenoscope with a “gentle” elevator to extend their life spans.6 This new cholangioscope has been redesigned to be compatible with various duodenoscopes. The TJF-180V duodenoscope (Olympus, Center Valley, Pa) used in this study has a V-shaped elevator that exerts significant stress on cholangioscopes. Despite using this particular duodenoscope, we were able to complete 32 cholangiopancreatoscopy procedures, indicating significant improvement in the durability of the new-generation digital cholangioscopes compared with earlier generations. As high-definition digital cholangiopancreatoscopes become more durable and readily available, we foresee a more prominent role for cholangiopancreatoscopy for diagnosis and treatment of various pancreatobiliary disorders, particularly diagnosis of indeterminate biliary strictures and treatment of obstructive pancreatic duct stones under the safety of direct vision.
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REFERENCES 1. Parsi MA. Peroral cholangioscopy in the new millennium. World J Gastroenterol 2011;17:1-6. 2. Larghi A, Waxman I. Endoscopic direct cholangioscopy by using an ultra-slim upper endoscope: a feasibility study. Gastrointest Endosc 2006;63:853-7. 3. Choi HJ, Moon JH, Ko BM, et al. Overtube-balloon-assisted direct peroral cholangioscopy by using an ultra-slim upper endoscope (with videos). Gastrointest Endosc 2009;69:935-40. 4. Moon JH, Ko BM, Choi HJ, et al. Intraductal balloon-guided direct peroral cholangioscopy with an ultraslim upper endoscope (with videos). Gastrointest Endosc 2009;70:297-302. 5. Parsi MA, Stevens T, Vargo JJ. Diagnostic and therapeutic direct peroral cholangioscopy using an intraductal anchoring balloon. World J Gastroenterol 2012;18:3992-6. 6. Parsi MA, Stevens T, Collins J, et al. Utility of a prototype peroral video cholangioscopy system with narrow-band imaging for evaluation of biliary disorders (with videos). Gastrointest Endosc 2011;74: 1148-51. 7. Kim HJ, Kim MH, Lee SK, et al. Tumor vessel: a valuable cholangioscopic clue of malignant biliary stricture. Gastrointest Endosc 2000;52:635-8. 8. Seo DW, Lee SK, Yoo KS, et al. Cholangioscopic findings in bile duct tumors. Gastrointest Endosc 2000;52:630-4. 9. Tang D, Nagano H, Yamamoto H, et al. Angiogenesis in cholangiocellular carcinoma: expression of vascular endothelial growth factor, angiopoietin-1/2, thrombospondin-1 and clinicopathological significance. Oncol Rep 2006;15:525-32.
Diagnostic and therapeutic cholangiopancreatoscopy 10. Itoi T, Sofuni A, Itokawa F, et al. Peroral cholangioscopic diagnosis of biliary-tract diseases by using narrow-band imaging (with videos). Gastrointest Endosc 2007;66:730-6. 11. Chen YK, Parsi MA, Binmoeller KF, et al. Single-operator cholangioscopy in patients requiring evaluation of bile duct disease or therapy of biliary stones (with videos). Gastrointest Endosc 2011;74: 805-14.
Parsi et al 12. Awadallah NS, Chen YK, Piraka C, et al. Is there a role for cholangioscopy in patients with primary sclerosing cholangitis? Am J Gastroenterol 2006;101:284-91. 13. Chen YK, Parsi MA, Binmoeller KF, et al. Peroral cholangioscopy (POC) using a disposable steerable single operator catheter for biliary stone therapy and assessment of indeterminate stricturesda multicenter experience using Spyglass [abstract]. Gastrointest Endosc 2009;69:AB264-5.
Registration of Human Clinical Trials Gastrointestinal Endoscopy follows the International Committee of Medical Journal Editors (ICMJE)’s Uniform Requirements for Manuscripts Submitted to Biomedical Journals. All prospective human clinical trials eventually submitted in GIE must have been registered through one of the registries approved by the ICMJE, and proof of that registration must be submitted to GIE along with the article. For further details and explanation of which trials need to be registered as well as a list of ICMJE-acceptable registries, please go to http://www.icmje.org.
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