Digestive Endoscopy 2014; 26: 335–336
Editorial
Seeing is believing
T
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HE DIAGNOSIS AND management of biliary tract disease remains challenging. While the spectrum of diagnostic tests for such disease has continued to expand, a specific diagnosis for some lesions, especially cholangiocarcinoma, remains difficult. Great strides have been made in non-invasive imaging of the biliary tree, specifically by magnetic resonance cholangiopancreatography (MRCP). Such studies now better define the character and location of a lesion, thus suggesting the likely cause; however, a tissue diagnosis remains essential for the diagnosis of cancer. The only modest sensitivity of biliary brushings for malignant lesions is well recognized and problematic. More recently, the use of endoscopic ultrasonography with fine-needle aspiration has significantly improved the ability to diagnose distal cholangiocarcinoma, may identify hilar lesions not seen on imaging, and assist in tumor staging.1 Intuitively, direct visualization of a lesion is likely to provide inherent benefit as has been witnessed for other disorders throughout the luminal gastrointestinal tract. Direct endoscopic examination of the biliary tree – termed cholangioscopy – has been difficult to achieve.2 Previously, the use of a fiberoptic or video-assisted mother-baby cholangioscope provided direct visualization and potential for tissue acquisition and therapy of the bile duct, but this system was difficult to use as it required two endoscopists; the endoscope was small, very fragile with a limited range of motion, and the working channel was small. A singleoperator system was recently marketed and termed the SpyGlass® system (Boston Scientific, Natick, MA, USA). With this system, direct targeting of lesions for endoscopic therapy, as well as biopsy, can be achieved and while an improvement over the mother-baby scope system, the images are still inferior to standard video endoscopic systems and the system is somewhat cumbersome to use. Most recently, the use of an ultrathin upper endoscope typically used for transnasal endoscopy has provided the quality of images we have grown accustomed to. With such an endoscope, we now have a larger working channel (2 mm) to provide larger biopsy specimens giving potential for endoscopic therapy as well as superior imaging quality.3 A number of studies now demonstrate the benefit of cholangioscopy using these newer systems. One of the initial benefits of cholangioscopy was direct inspection of the biliary mucosa most commonly to exclude carcinoma in a
stricture or intraluminal filling defect seen at endoscopic retrograde cholangiography (ERC). With the availability of a sufficiently sized working channel, cholangioscopy becomes not only diagnostic but therapeutic. One of the first therapeutic uses reported for cholangioscopy was electrohydraulic lithotripsy of large bile duct stones. Emerging diagnostic uses include evaluation for immunoglobulin (Ig)G4-related cholangiopathy and evaluation of ductal strictures and ischemia after liver transplantation. The utility of direct cholangioscopy for better targeted biopsies to evaluate indeterminate biliary stricture is now well established.4 Other potential therapeutic uses include ablative therapies for tumors such as photodynamic therapy and radiofrequency ablation as well as assisting in selective guidewire placement. One could foresee many uses for biliary therapy which obviously would depend on the available technology and tools compatible with the current working channel. With that as a background, in this issue of the Journal, Nishikawa and colleagues5 further expand the potential utility of peroral video cholangioscopy (PVCS) to the management of biliary tract disease. The hypothesis of this prospective single-center study was that PVCS would be useful for determining the longitudinal extension of cholangiocarcinoma to better define planned surgical therapy. A 3.4-mm video endoscope was passed through the working channel of a therapeutic duodenoscope into the bile duct. The bile duct was irrigated with saline and a guidewire was placed into the desired segment confirmed fluoroscopically. The primary outcome measure was the diagnostic accuracy of PVCS in the preoperative assessment of longitudinal extension. The cholangioscopic appearance (benign vs malignant) was determined based on prior observations (dilated irregular tumor blood vessels, friability, papillary projections, luminal narrowing). Diagnostic accuracy was determined by comparing the results of the endoscopic appearance with those of the histopathological analysis of surgical specimens. The accuracy of PVCS for diagnosing longitudinal extension to the secondary biliary radicals in the contralateral lobe in perihilar cholangiocarcinoma was 82% whereas longitudinal extension to the confluence in patients with distal cholangiocarcinoma was 92%. Distal extension into the intrapancreatic common bile duct was similarly accurate at over 90%. Findings were similar with white light or narrow-band imaging. Use of PVCS-guided targeted biopsies did not
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
335
336
Editorial
improve the overall diagnostic accuracy of cholangioscopy. When comparing longitudinal extension of PVCS to ERC, PVCS was more accurate whereas ERC tended to underestimate extension both to the intrahepatic system as well as distally. Incremental gain of PVCS over ERC was 17% for involvement of the secondary radicals for hilar tumors but was equivalent for extension to the intrapancreatic common bile duct. For distal tumors, improvement by PVCS was seen in 23% for proximal extension and in 28% for extension into the intrapancreatic bile duct; PVCS did ‘overcall’ proximal extension in one patient (7%) with distal cancer. However, all longitudinal extensions detected by ERC were likewise detected by PVCS. In one-third of patients, the cholangioscope could not be passed through the stricture. The procedure was safe with only one patient developing cholangitis. These results are encouraging, confirm prior observations, and provide an exciting additional role for direct cholangioscopy, although several caveats deserve mention. First, the primary endoscopist carrying out cholangioscopy was highly experienced in the technique. Also, while a significant advancement over the old mother-baby scopes, the same principal applies for this system in that two endoscopists are needed. Second, the cholangioscopic appearance of tumor was as reliable as a biopsy. Nevertheless, in some cases, there was underestimation based on the surgical specimen. Third, there were no patients in this study with primary sclerosing cholangitis which is a disease process with high potential for malignant transformation and where we anticipate great utility for direct visualization methods. Last, significant luminal narrowing may preclude examination proximally. So where do we go from here? Based upon this data from Nishikawa and colleagues,4 coupled with the emerging literature on cholangioscopy, this technique is here to stay. New devices and accessories must be developed to allow easier access to the bile duct and greater stability for the use of an ultraslim endoscope especially where biopsies or additional therapy are required. Improved evaluation of patients with sclerosing cholangitis in whom cholangiocarcinoma is
Digestive Endoscopy 2014; 26: 335–336
tricky to diagnose could pay significant dividends. In addition, further technological advances may open other avenues for additional therapy delivered via cholangioscopy. This technique should be more widely applied. While these data suggest that the visual appearance of the lesion is an accurate means of confirming tumor, many oncologists will still insist on a histological diagnosis to provide chemotherapy and are not yet ready to say ‘seeing is believing’. We feel surgeons, however, would welcome such visual aids to guide resection with potential to improve both short-term and long-term outcomes. Authors declare no conflict of interests for this article. C. Mel Wilcox, Jayapal Ramesh and Klaus Mönkemüller Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, USA doi: 10.1111/den.12184
REFERENCES 1 Mohamadnejad M, DeWitt JM, Sherman S et al. Role of EUS for preoperative evaluation of cholangiocarcinoma: A large singlecenter experience. Gastrointest. Endosc. 2011; 73: 71–8. 2 Moon JH, Terheggan G, Choi HJ, Neuhaus H. Peroral cholangioscopy: diagnostic and therapeutic applications. Gastroenterology 2013; 144: 276–82. 3 Meves V, Ell C, Pohl J. Efficacy and safety of direct transnasal cholangioscopy with standard ultraslim endoscopes: results of a large cohort study. Gastrointest. Endosc. Published online: 9 Jul 2013; DOI: 10.1016/j.gie.2013.05.032 4 Nishikawa T, Tsuyuguchi T, Sakai Y, Suglyama H, Miyazaki M, Yokosuka O. Comparison of the diagnostic accuracy of peroral video-cholangioscopic visual findings and cholangioscopyguided forceps biopsy findings for indeterminate biliary lesions: a prospective study. Gastrointest. Endosc. 2013; 77: 219–26. 5 Nishikawa T, Tsuyuguchi T, Sakai Y et al. Preoperative assessment of longitudinal extension of cholangiocarcinoma with peroral video-cholangioscopy: A prospective study. Dig. Endosc. 2014; 26: 450–7.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Editorial
Seeing is believing
T
bs_bs_banner
HE DIAGNOSIS AND management of biliary tract disease remains challenging. While the spectrum of diagnostic tests for such disease has continued to expand, a specific diagnosis for some lesions, especially cholangiocarcinoma, remains difficult. Great strides have been made in non-invasive imaging of the biliary tree, specifically by magnetic resonance cholangiopancreatography (MRCP). Such studies now better define the character and location of a lesion, thus suggesting the likely cause; however, a tissue diagnosis remains essential for the diagnosis of cancer. The only modest sensitivity of biliary brushings for malignant lesions is well recognized and problematic. More recently, the use of endoscopic ultrasonography with fine-needle aspiration has significantly improved the ability to diagnose distal cholangiocarcinoma, may identify hilar lesions not seen on imaging, and assist in tumor staging.1 Intuitively, direct visualization of a lesion is likely to provide inherent benefit as has been witnessed for other disorders throughout the luminal gastrointestinal tract. Direct endoscopic examination of the biliary tree – termed cholangioscopy – has been difficult to achieve.2 Previously, the use of a fiberoptic or video-assisted mother-baby cholangioscope provided direct visualization and potential for tissue acquisition and therapy of the bile duct, but this system was difficult to use as it required two endoscopists; the endoscope was small, very fragile with a limited range of motion, and the working channel was small. A singleoperator system was recently marketed and termed the SpyGlass® system (Boston Scientific, Natick, MA, USA). With this system, direct targeting of lesions for endoscopic therapy, as well as biopsy, can be achieved and while an improvement over the mother-baby scope system, the images are still inferior to standard video endoscopic systems and the system is somewhat cumbersome to use. Most recently, the use of an ultrathin upper endoscope typically used for transnasal endoscopy has provided the quality of images we have grown accustomed to. With such an endoscope, we now have a larger working channel (2 mm) to provide larger biopsy specimens giving potential for endoscopic therapy as well as superior imaging quality.3 A number of studies now demonstrate the benefit of cholangioscopy using these newer systems. One of the initial benefits of cholangioscopy was direct inspection of the biliary mucosa most commonly to exclude carcinoma in a
stricture or intraluminal filling defect seen at endoscopic retrograde cholangiography (ERC). With the availability of a sufficiently sized working channel, cholangioscopy becomes not only diagnostic but therapeutic. One of the first therapeutic uses reported for cholangioscopy was electrohydraulic lithotripsy of large bile duct stones. Emerging diagnostic uses include evaluation for immunoglobulin (Ig)G4-related cholangiopathy and evaluation of ductal strictures and ischemia after liver transplantation. The utility of direct cholangioscopy for better targeted biopsies to evaluate indeterminate biliary stricture is now well established.4 Other potential therapeutic uses include ablative therapies for tumors such as photodynamic therapy and radiofrequency ablation as well as assisting in selective guidewire placement. One could foresee many uses for biliary therapy which obviously would depend on the available technology and tools compatible with the current working channel. With that as a background, in this issue of the Journal, Nishikawa and colleagues5 further expand the potential utility of peroral video cholangioscopy (PVCS) to the management of biliary tract disease. The hypothesis of this prospective single-center study was that PVCS would be useful for determining the longitudinal extension of cholangiocarcinoma to better define planned surgical therapy. A 3.4-mm video endoscope was passed through the working channel of a therapeutic duodenoscope into the bile duct. The bile duct was irrigated with saline and a guidewire was placed into the desired segment confirmed fluoroscopically. The primary outcome measure was the diagnostic accuracy of PVCS in the preoperative assessment of longitudinal extension. The cholangioscopic appearance (benign vs malignant) was determined based on prior observations (dilated irregular tumor blood vessels, friability, papillary projections, luminal narrowing). Diagnostic accuracy was determined by comparing the results of the endoscopic appearance with those of the histopathological analysis of surgical specimens. The accuracy of PVCS for diagnosing longitudinal extension to the secondary biliary radicals in the contralateral lobe in perihilar cholangiocarcinoma was 82% whereas longitudinal extension to the confluence in patients with distal cholangiocarcinoma was 92%. Distal extension into the intrapancreatic common bile duct was similarly accurate at over 90%. Findings were similar with white light or narrow-band imaging. Use of PVCS-guided targeted biopsies did not
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
335
336
Editorial
improve the overall diagnostic accuracy of cholangioscopy. When comparing longitudinal extension of PVCS to ERC, PVCS was more accurate whereas ERC tended to underestimate extension both to the intrahepatic system as well as distally. Incremental gain of PVCS over ERC was 17% for involvement of the secondary radicals for hilar tumors but was equivalent for extension to the intrapancreatic common bile duct. For distal tumors, improvement by PVCS was seen in 23% for proximal extension and in 28% for extension into the intrapancreatic bile duct; PVCS did ‘overcall’ proximal extension in one patient (7%) with distal cancer. However, all longitudinal extensions detected by ERC were likewise detected by PVCS. In one-third of patients, the cholangioscope could not be passed through the stricture. The procedure was safe with only one patient developing cholangitis. These results are encouraging, confirm prior observations, and provide an exciting additional role for direct cholangioscopy, although several caveats deserve mention. First, the primary endoscopist carrying out cholangioscopy was highly experienced in the technique. Also, while a significant advancement over the old mother-baby scopes, the same principal applies for this system in that two endoscopists are needed. Second, the cholangioscopic appearance of tumor was as reliable as a biopsy. Nevertheless, in some cases, there was underestimation based on the surgical specimen. Third, there were no patients in this study with primary sclerosing cholangitis which is a disease process with high potential for malignant transformation and where we anticipate great utility for direct visualization methods. Last, significant luminal narrowing may preclude examination proximally. So where do we go from here? Based upon this data from Nishikawa and colleagues,4 coupled with the emerging literature on cholangioscopy, this technique is here to stay. New devices and accessories must be developed to allow easier access to the bile duct and greater stability for the use of an ultraslim endoscope especially where biopsies or additional therapy are required. Improved evaluation of patients with sclerosing cholangitis in whom cholangiocarcinoma is
Digestive Endoscopy 2014; 26: 335–336
tricky to diagnose could pay significant dividends. In addition, further technological advances may open other avenues for additional therapy delivered via cholangioscopy. This technique should be more widely applied. While these data suggest that the visual appearance of the lesion is an accurate means of confirming tumor, many oncologists will still insist on a histological diagnosis to provide chemotherapy and are not yet ready to say ‘seeing is believing’. We feel surgeons, however, would welcome such visual aids to guide resection with potential to improve both short-term and long-term outcomes. Authors declare no conflict of interests for this article. C. Mel Wilcox, Jayapal Ramesh and Klaus Mönkemüller Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, USA doi: 10.1111/den.12184
REFERENCES 1 Mohamadnejad M, DeWitt JM, Sherman S et al. Role of EUS for preoperative evaluation of cholangiocarcinoma: A large singlecenter experience. Gastrointest. Endosc. 2011; 73: 71–8. 2 Moon JH, Terheggan G, Choi HJ, Neuhaus H. Peroral cholangioscopy: diagnostic and therapeutic applications. Gastroenterology 2013; 144: 276–82. 3 Meves V, Ell C, Pohl J. Efficacy and safety of direct transnasal cholangioscopy with standard ultraslim endoscopes: results of a large cohort study. Gastrointest. Endosc. Published online: 9 Jul 2013; DOI: 10.1016/j.gie.2013.05.032 4 Nishikawa T, Tsuyuguchi T, Sakai Y, Suglyama H, Miyazaki M, Yokosuka O. Comparison of the diagnostic accuracy of peroral video-cholangioscopic visual findings and cholangioscopyguided forceps biopsy findings for indeterminate biliary lesions: a prospective study. Gastrointest. Endosc. 2013; 77: 219–26. 5 Nishikawa T, Tsuyuguchi T, Sakai Y et al. Preoperative assessment of longitudinal extension of cholangiocarcinoma with peroral video-cholangioscopy: A prospective study. Dig. Endosc. 2014; 26: 450–7.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
