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Comparison of the diagnostic accuracy of peroral video-cholangioscopic visual findings and cholangioscopy-guided forceps biopsy findings for indeterminate biliary lesions: a prospective study
ORIGINAL ARTICLE: Clinical Endoscopy
Comparison of the diagnostic accuracy of peroral videocholangioscopic visual findings and cholangioscopy-guided forceps biopsy findings for indeterminate biliary lesions: a prospective study Takao Nishikawa, MD,1 Toshio Tsuyuguchi, MD, PhD,1 Yuji Sakai, MD, PhD,1 Harutoshi Sugiyama, MD, PhD,1 Masaru Miyazaki, MD, PhD,2 Osamu Yokosuka, MD, PhD1 Chiba, Japan
Background: The diagnostic accuracy of peroral video-cholangioscopy for indeterminate biliary lesions has not been determined in a prospective study. Objective: To evaluate and compare the diagnostic accuracy of the peroral video-cholangioscopic visual findings for indeterminate biliary lesions with that of the cholangioscopy-guided forceps biopsy findings. Design: Prospective cohort study. Setting: Tertiary-care referral center. Patients: Patients who showed indeterminate biliary lesions on endoscopic retrograde cholangiography underwent peroral video-cholangioscopy for diagnosis. Intervention: Each patient underwent peroral video-cholangioscopy with cholangioscopy-guided forceps biopsy. Main Outcome Measurements: The accuracy of diagnosis by the peroral video-cholangioscopic visual findings and cholangioscopy-guided forceps biopsy findings compared with that of the final diagnosis by other methods (malignant or benign). Results: Thirty-three patients were enrolled, and the final diagnoses revealed that the lesions were malignant in 21 patients. All procedures were technically successful, and fine views were obtained in all patients. Procedurerelated complications occurred in 2 patients (6.1%), but these complications were mild. The sensitivity, specificity, and accuracy were 100%, 91.7%, and 97.0%, respectively, for the peroral video-cholangioscopic visual findings and 38.1%, 100%, and 60.6%, respectively, for the cholangioscopy-guided forceps biopsy findings, and a significant difference was observed in the accuracy (P ⫽ .0018). Limitations: This was not a blinded study. No comparison was made with other diagnostic modalities involving tissue sampling. Conclusion: The diagnostic accuracy of the peroral video-cholangioscopic visual findings for indeterminate biliary lesions was excellent and significantly higher than that of the cholangioscopy-guided forceps biopsy findings. The accuracy of the cholangioscopy-guided forceps biopsy was insufficient, but the technique had an excellent specificity. (Gastrointest Endosc 2013;77:219-26.)
Accurate diagnosis of indeterminate biliary lesions is essential in therapeutic planning to avoid unnecessary surgery for lesions that are benign. Despite the advances
in biliary diagnostic techniques, such as endoscopic retrograde cholangiography (ERC), EUS, and those involving tissue sampling, the diagnostic accuracy necessary for dis-
Abbreviations: ERC, endoscopic retrograde cholangiography; PVCS, peroral video-cholangioscopy.
Received August 1, 2012. Accepted October 5, 2012.
DISCLOSURE: All authors disclosed no financial relationships relevant to this publication.
Current affiliations: Department of Medicine and Clinical Oncology (1), Department of General Surgery (2), Graduate School of Medicine, Chiba University, Chiba, Japan.
Copyright © 2013 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2012.10.011
Reprint requests: Toshio Tsuyuguchi, MD, PhD, Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
www.giejournal.org
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Take-home Message ●
●
The diagnostic accuracy of peroral video-cholangioscopic visual findings for indeterminate biliary lesions was 97% and was significantly higher than that of cholangioscopyguided forceps biopsy findings. The accuracy of cholangioscopy-guided forceps biopsy findings was insufficient, but the technique had an excellent specificity.
that of the PVCS-guided forceps biopsy findings in patients with indeterminate biliary lesions.
METHODS Study design This was a prospective, single-center, cohort study of patients with indeterminate biliary lesions who were referred to Chiba University Hospital for diagnosis by using PVCS. The present study was approved by the institutional review board of Chiba University and was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000004711. Written informed consent was obtained from all patients. None of the authors have financial conflicts of interest to disclose.
Patients Figure 1. Peroral video-cholangioscopic view showing a malignant biliary lesion. A, Irregularly dilated and tortuous vessels. B, Easy oozing of blood.
tinguishing malignant biliary lesions from benign biliary lesions is insufficient.1,2 A previous study showed that the addition of peroral fiberoptic cholangioscopy to ERC/tissue sampling improved the diagnostic accuracy up to 94.8% for biliary lesions.3 Peroral video-cholangioscopy (PVCS) has higher image resolution and permits a clearer view than fiberoptic-cholangioscopy; therefore, the addition of PVCS to ERC/tissue sampling was shown to improve the diagnostic accuracy to ⬎98%.4,5 Another advantage of cholangioscopy is that it allows biopsy of the lesions under direct visualization, but the cup diameter of the forceps used in this technique is smaller than that of standard forceps used with fluoroscopic guidance. To our knowledge, there has been no prospective study of the diagnostic accuracy of pure PVCS visual findings and pure PVCS-guided forceps biopsy findings for indeterminate biliary lesions. This prospective study aimed to evaluate and compare the diagnostic accuracy of the PVCS visual findings with 220 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 2 : 2013
Patients who showed indeterminate biliary lesions on ERC and other imaging modalities, with no pathologic evidence of malignancy, were considered for this study. Exclusion criteria included age younger than 20 years, medical unsuitability for PVCS, and inability to provide informed consent.
Intervention Each patient with an indeterminate biliary lesion underwent PVCS with cholangioscopy-guided forceps biopsy during the same session.
Procedure All procedures were performed by using side-viewing duodenoscopes (Olympus TJF-240/260V; Olympus Medical Systems, Tokyo, Japan). Endoscopic sphincterotomy was performed for the patients who had not undergone the procedure previously. If necessary, extension of the previous sphincterotomy or additional balloon dilation was performed for the passage of a cholangioscope across the papilla. PVCS was performed with duodenoscopic assistance by using Olympus CHF-B260 (diameter, 3.4 mm; Olympus Medical Systems). To clearly observe the biliary lesions, we irrigated the bile duct with sterile saline solution through the working channel (diameter, 1.2 mm), as described elsewhere.3-5 FB-44U-1 with a cup (diameter, www.giejournal.org
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Peroral video-cholangioscopy
Figure 2. A, Cholangiogram showing an indeterminate hilar stricture (arrows) and filling defect in the left hepatic duct (arrowheads). B, Cholangioscopic view showing an irregular papillary epithelium with irregularly dilated vessels. C, D, Photomicrograph of a cholangioscopy-guided forceps biopsy specimen showing papillary adenocarcinoma (H&E, orig. mag. C, ⫻100, D, ⫻200).
1.15 mm; Olympus Medical Systems) was used for direct visualization during PVCS-guided forceps biopsy. ERC was previously performed by one of two therapeutic endoscopists (Y.S., H.S., with a combined experience of ⬎1000 ERC procedures). All procedures in this study were performed by another therapeutic endoscopist (T.T.) with an experience of ⬎500 peroral cholangioscopies, and he evaluated the visual findings of PVCS. The decision (malignant or benign) on indeterminate biliary lesions was made on the basis of PVCS visual findings and was prospectively recorded into the computer database, before the results of PVCS-guided forceps biopsy and final diagnosis were confirmed. Biopsy specimens were evaluated by experienced pathologists who were blinded to the fact that the specimens www.giejournal.org
were part of a study evaluation but who interpreted the results with full knowledge of the clinical data.
Outcomes and definitions The primary study outcome measure was the accuracy of diagnosis by the PVCS visual findings and PVCS-guided forceps biopsy findings compared with that of the final diagnosis by other methods (malignant or benign). We evaluated the indeterminate biliary lesions on the basis of the cholangioscopic findings described in previous studies.3-7 Biliary lesions were defined as malignant on the basis of the following visual findings: (1) irregularly dilated and tortuous vessels (tumor vessels), (2) easy oozing of blood, and (3) irregular surface (or papillary projections) (Figs. 1 and 2). Easy oozing of blood was defined Volume 77, No. 2 : 2013 GASTROINTESTINAL ENDOSCOPY 221
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RESULTS Patient characteristics
Figure 3. Peroral video-cholangioscopic view showing petechial hemorrhage of biliary mucosa because of stent placement.
as continuous bleeding and was distinguished from petechial hemorrhage of biliary mucosa due to stent placement or contact with a cholangioscope (Fig. 3). Biliary lesions were defined as benign on the basis of the following visual findings: (1) smooth mucosal surface without definite neovascularization and (2) lower homogeneous papillogranular mucosa without a primary mass (Fig. 4). The final diagnosis was made on the basis of pathologic evaluation of tissue specimens obtained at surgery or by using other tissue sampling modalities and uneventful clinical course in patients with benign lesions. Secondary outcomes included procedural technical success, complications, and the diagnostic values, such as the sensitivity, specificity, positive predictive value, and negative predictive value for the PVCS visual findings and PVCS-guided forceps biopsy findings. The 2010 American Society for Gastrointestinal Endoscopy consensus criteria were used to define and grade complications.8
Statistical analysis Sample size was estimated on the basis of statistical analysis of the diagnostic accuracy of cholangioscopic findings and endobiliary forceps biopsy findings. Previous reported data indicated that the accuracy of peroral cholangioscopy was ⬎90%3,5 and that of conventional endobiliary forceps biopsy was approximately 60%.1 As a result, 33 patients would be required to detect a significant difference between the PVCS visual findings and PVCSguided forceps biopsy findings with a P value of .05 and power of 0.8. A McNemar exact test was used to assess the comparison of the diagnostic accuracy between the PVCS visual findings and PVCS-guided forceps biopsy findings. Continuous variables were calculated as mean and standard deviation (SD). SAS version 9.2 (SAS Institute, Cary, NC) was used to perform all statistical analyses. The significant level was set to P ⬍ .05. 222 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 2 : 2013
Sixty-three patients underwent ERC for the diagnosis of indeterminate biliary lesions during the study period (Fig. 5). Thirty-three patients (23 men and 10 women; mean age 67.52 [SD ⫾ 8.00] years) who showed indeterminate biliary lesions on ERC with no pathologic evidence of malignancy were recruited for this study between December 2010 and March 2012. All patients underwent PVCS and PVCSguided forceps biopsy during the same session. The patient characteristics and procedural details are summarized in Table 1. According to the final diagnoses, the lesions were malignant in 21 patients and benign in 12 patients (Table 2). The final diagnosis of a malignant biliary lesion was established on the basis of surgical resection specimens in 20 patients and PVCS-guided forceps biopsy specimens in 1 patient. The final diagnosis of a benign biliary lesion was established on the basis of surgical resection specimens in 5 patients and clinical follow-up in 7 patients. Five of the 7 patients had uneventful clinical courses of at least 12 months, and 2 of the 7 patients showed disappearance of the biliary lesions accompanied by improvement of bile duct inflammation after 3 or 6 months.
Outcomes All procedures were technically successful, and fine views were obtained in all patients. Procedure-related complications occurred in only 2 patients (6.1%). Mild cholangitis occurred in 1 patient (3.0%), and mild pancreatitis occurred in 1 patient (3.0%). No other morbidities or mortalities were observed. In all 21 patients, lesions that were malignant as per the final diagnosis were also deemed malignant after the visual evaluation of the PVCS findings. Among the benign lesions of 12 patients, as confirmed by the final diagnosis, lesions in 1 patient were considered malignant and those in 11 patients were considered benign after the visual evaluation of the PVCS findings. The PVCS findings showed tumor vessels in 1 and 20 patients with benign and malignant lesions, respectively, as per the final diagnosis. Easy oozing of blood was observed in 1 and 18 patients with benign and malignant lesions, respectively. An irregular surface (or papillary projection) was observed in 20 patients with malignant lesions (Table 3). There was one false-positive diagnosis based on the results of the PVCS visual findings, in which the patient showed tortuous dilated vessels and easy oozing of blood in the right hepatic duct stricture. The PVCS-guided forceps biopsy specimens of this patient gave a negative result, and the lesions were finally diagnosed as benign by clinical follow-up, including repeated performance of PVCS. The previous PVCS visual findings of malignancy disappeared, and the surface of the lesions became smooth, which was www.giejournal.org
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Figure 4. A, Cholangiogram showing an indeterminate stricture in the origin of the cystic duct (arrows). B, Cholangioscopic view showing smooth papillary epithelium without dilated vessels. Photomicrograph of a cholangioscopy-guided forceps biopsy specimen showing chronic inflammatory change with inflammatory cellular infiltration into the stroma, fibroedematous change, hyperemia, and no cancer cells (H&E, orig. mag. C, ⫻100, D, ⫻200).
decided on the basis of an inflammatory change with biliary stricture and hepatolithiasis. On pathologic evaluation of the PVCS-guided forceps biopsy specimens, none of the patients had inadequate specimens for histology. Of 21 patients with a final malignant diagnosis, biopsy specimens showed malignant and benign changes on histology in 8 and 13 patients, respectively. Of all 12 patients with a final diagnosis of benign lesions, biopsy specimens showed benign changes on histology (Table 3). Table 4 shows the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the PVCS visual findings and PVCS-guided forceps biopsy findings. The accuracy of the PVCS visual findings was significantly higher than that of PVCS-guided forceps biwww.giejournal.org
opsy (97.0% vs 60.6%; P ⫽ .0018). The PVCS visual findings had a sensitivity and negative predictive value of 100% and a specificity and positive predictive value of ⬎90%. The PVCS-guided forceps biopsy had a specificity and positive predictive value of 100% but a sensitivity and negative predictive value of ⬍50%.
DISCUSSION Cholangioscopy permits direct visualization and tissue sampling of indeterminate biliary lesions. Severe and fatal complications are more frequently associated with percutaneous transhepatic cholangioscopy9,10; therefore, peroral cholangioscopy has become a popular technique for diagnosing indeterminate biliary lesions. The diagnostic Volume 77, No. 2 : 2013 GASTROINTESTINAL ENDOSCOPY 223
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Figure 5. Flow chart showing the recruitment of patients in the study. ERC, Endoscopic retrograde cholangiography; PVCS, peroral video-cholangioscopy. *Fluoroscopy-guided brushing cytology and/or forceps biopsy.
accuracy of pure peroral fiberoptic-cholangioscopy (SpyGlass; Boston Scientific Japan, Tokyo, Japan) visual findings for indeterminate biliary lesions was between 80% and 89%.11-13 In this study, we determined the diagnostic accuracy of pure PVCS visual findings and pure PVCSguided forceps biopsy findings for indeterminate biliary lesions. The diagnostic accuracy of the PVCS visual findings was 97.0%, and that of the PVCS-guided forceps biopsy findings was 60.0%, and the difference was significant. Furthermore, the largest clinical trial on SpyGlass peroral cholangioscopy indicated that cholangioscopic impression of malignant biliary lesions has higher sensitivity than targeted biopsy.13 No studies have directly compared the diagnostic accuracy of videocholangioscopy and fiberoptic cholangioscopy for indeterminate biliary lesions, but video-cholangioscopy has higher image resolution and permits a clearer view than fiberoptic cholangioscopy.3-5,11-13 It was reported that detection of neoplasia in biliary strictures was better with large-capacity forceps than with standard forceps.14 In this study, despite small-capacity forceps, the accuracy of PVCS-guided forceps biopsy was comparable to that of conventional fluoroscopy-guided forceps biopsy because of the direct visualization of indeterminate biliary lesions. Then again, despite the interpre224 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 2 : 2013
tation of the clinical data that included the PVCS visual findings of pathologists, the accuracy of PVCS-guided forceps biopsy was significantly lower. The accuracy of the PVCS (CHF-B260) visual findings is very high, but it requires difficult maneuverability for the mother-baby system and 2-way deflected steering of the tip and has only one channel. When the biopsy forceps are inserted into the channel, the view of PVCS becomes worse because of insufficient irrigation in the bile duct, even with a water pump connected to a Y-connector. Therefore, sampling errors are liable to occur in PVCS-guided forceps biopsy. Moreover, once PVCS-guided forceps biopsy is performed, the view becomes much worse because of oozing, and the number of tissue samples is limited. In fact, the number of tissue samples obtained for each patient was different in this study, and the lower sensitivity also may be a result of limited tissue sampling. On the other hand, the SpyGlass single-operator peroral cholangioscopy system overcomes these limitations. In brief, it permits 4-way deflected steering and has one working channel and two detached irrigation channels.11 The diagnostic accuracy of SpyGlass-guided forceps biopsy for indeterminate biliary lesions was between 75% and 90%.11-13,15 Because of improved maneuverability and sufficient irrigation in the bile duct, sampling errors do not occur easily www.giejournal.org
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TABLE 1. Baseline patient characteristics and procedural details Age, mean (⫾ SD), range, y
TABLE 3. Results of PVCS visual findings and PVCSguided forceps biopsy findings
67.52 (⫾ 8.00), 50-80
Sex, male/female
Final diagnosis
23/10
Malignant
Benign
Visual findings
Location of lesions, no. Intrahepatic
3
Malignant
21
1
Hilar
17
Tumor vessels
20
1
Middle bile duct (including cystic duct)
8
Easy oozing of blood
18
1 0
5
Irregular surface (or papillary projection)
20
Low bile duct
Benign
0
11
Malignant
8
0
Benign
13
12
Type of biliary lesion, no. Biliary stricture
30
Biliary nodule
3
Forceps biopsy findings
Procedure for major duodenal papilla, no.
PVCS, Peroral video-cholangioscopy.
Sphincterotomy
0
Additional balloon dilation
6
Biopsy sampling, mean (⫾ SD), range, no.
2.39 (⫾ 1.14), 1-5
TABLE 4. Diagnostic values of PVCS visual findings and PVCS-guided forceps biopsy
SD, Standard deviation.
TABLE 2. Final diagnosis* Malignant biliary lesion (n ⫽ 21), no. Cholangiocarcinoma
21
Benign biliary lesion (n ⫽ 12), no. Calculi-induced inflammatory change*
10
Primary sclerosing cholangitis with benign stricture
1
IgG4-related sclerosing cholangitis with benign stricture
1
IgG4, Immunoglobulin G4. *Calculi-induced inflammatory changes included hepatolithiasis (n ⫽ 4), Mirizzi syndrome (n ⫽ 3), and benign biliary stricture accompanying cholelithiasis (n ⫽ 3).
in SpyGlass-guided forceps biopsy. To perform accurate tissue sampling, improved PVCS that is maneuverable, has a working channel with a larger diameter for largecapacity forceps, and enables sufficient irrigation in the bile duct is required. We diagnosed one inflammatory benign stricture induced by calculi as malignant on PVCS visual findings of tortuous dilated vessels and easy oozing of blood. It was also reported that tortuous dilated vessels and the irregular surface were observed in benign strictures because of www.giejournal.org
Visual findings
Forceps biopsy findings
Sensitivity
100%
38.1%
Specificity
91.7%
100%
Positive predictive value
95.5%
100%
Negative predictive value
100%
48.0%
Accuracy
97.0%
60.6%
P value
.0018
—
PVCS, Peroral video-cholangioscopy.
immunoglobulin G4 –related sclerosing cholangitis.16,17 Even if benign biliary lesions, tortuous dilated vessels, easy oozing of blood, or the irregular surface are attended during an intensely active phase of inflammation, overdiagnosis may occur. It was suggested that PVCS observations by narrow-band imaging could identify surface structures and mucosal vessels of biliary lesions better than those by white-light imaging.18 In recent years, the use of narrow-band imaging with magnification for diagnosis of digestive tract lesions has given good results,19-21 and it may resolve issues of overdiagnosis. For the accurate diagnosis of indeterminate biliary lesions, it is important to develop peroral magnifying cholangioscopy. The limitations of this study are that it was not a multicenter study, and there may have been biases related to patient selection and the fact that the PVCS operator was not blinded to the clinical data. To perform PVCS safely Volume 77, No. 2 : 2013 GASTROINTESTINAL ENDOSCOPY 225
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and to investigate indeterminate biliary lesions accurately, it was necessary for the PVCS operator to have information regarding biliary lesions and patients conditions. In addition, PVCS with forceps biopsy was not compared directly with other diagnostic modalities, such as EUS with tissue sampling and SpyGlass peroral fiberoptic cholangioscopy with forceps biopsy. Although we did not evaluate the accuracy of PVCS observations by narrow-band imaging, a prospective multicenter study reported that the accuracy of PVCS plus narrow-band imaging combined with fluoroscopy-guided or cholangioscopy-guided biopsy distinguished malignant from benign biliary lesions in all 91 cases.22 A study with a large number of patients is needed to develop a classification system of narrow-band imaging in biliary lesions, such as surface patterns and vascular patterns in digestive tract lesions.19-21 In conclusion, the diagnostic accuracy of PVCS visual findings for indeterminate biliary lesions is excellent and significantly higher than that of PVCS-guided forceps biopsy findings. The PVCS-guided forceps biopsy has an excellent positive predictive value, but sampling errors often occur. Further improvement of PVCS is required to perform accurate tissue sampling. ACKNOWLEDGMENT The authors would like to thank Enago (www.enago.jp) for the English language review. REFERENCES 1. De Bellis M, Sherman S, Fogel EL, et al. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 2). Gastrointest Endosc 2002;56: 720-30. 2. Rösch T, Hofrichter K, Frimberger E, et al. ERCP or EUS for tissue diagnosis of biliary strictures? A prospective comparative study. Gastrointest Endosc 2004;60:390-6. 3. Fukuda Y, Tsuyuguchi T, Sakai Y, et al. Diagnostic utility of peroral cholangioscopy for various bile-duct lesions. Gastrointest Endosc 2005; 62:374-82. 4. Kawakami H, Kuwatani M, Etoh K, et al. Endoscopic retrograde cholangiography versus peroral cholangioscopy to evaluate intraepithelial tumor spread in biliary cancer. Endoscopy 2009;41:959-64. 5. Itoi T, Osanai M, Igarashi Y, et al. Diagnostic peroral video cholangioscopy is an accurate diagnostic tool for patients with bile duct lesions. Clin Gastroenterol Hepatol 2010;8:934-8. 6. Kim HJ, Kim MH, Lee SK, et al. Tumor vessel: a valuable cholangioscopic clue of malignant biliary stricture. Gastrointest Endosc 2000;52:635-8.
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7. Seo DW, Lee SK, Yoo KS, et al. Cholangioscopic findings in bile duct tumors. Gastrointest Endosc 2000;52:630-4. 8. Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010;71:446-54. 9. Nimura Y, Shionoya S, Hayakawa N, et al. Value of percutaneous transhepatic cholangioscopy (PTCS). Surg Endosc 1988;2:213-9. 10. Oh HC, Lee SK, Lee TY, et al. Analysis of percutaneous transhepatic cholangioscopy-related complications and the risk factors for those complications. Endoscopy 2007;39:731-6. 11. Chen YK, Pleskow DK. SpyGlass single-operator peroral cholangiopancreatoscopy system for the diagnosis and therapy of bile-duct disorders: a clinical feasibility study (with video). Gastrointest Endosc 2007; 65:832-41. 12. Ramchandani M, Reddy DN, Gupta R, et al. Role of single-operator peroral cholangioscopy in the diagnosis of indeterminate biliary lesions: a single-center, prospective study. Gastrointest Endosc 2011;74:511-9. 13. 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. 14. Ikeda M, Maetani I, Terada K, et al. Usefulness of endoscopic retrograde biliary biopsy using large-capacity forceps for extrahepatic biliary strictures: a prospective randomized study. Endoscopy 2010;42:837-41. 15. Draganov PV, Chauhan S, Wagh MS, et al. Diagnostic accuracy of conventional and cholangioscopy-guided sampling of indeterminate biliary lesions at the time of ERCP: a prospective, long-term follow-up study. Gastrointest Endosc 2012;75:347-53. 16. Yasuda I, Nakashima M, Moriwaki H. Cholangioscopic view of IgG4related sclerosing cholangitis. J Hepatobiliary Pancreat Sci 2011;18: 122-4. 17. Okano N, Igarashi Y, Kishimoto Y, et al. Case of immunoglobulin G4related cholangitis accompanying autoimmune pancreatitis: diagnosis by peroral cholangioscopy and treatment by endoscopic biliary stenting. Dig Endosc 2012;24(suppl 1):62-6. 18. 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. 19. Silva FB, Dinis-Ribeiro M, Vieth M, et al. Endoscopic assessment and grading of Barrett’s esophagus using magnification endoscopy and narrow-band imaging: accuracy and interobserver agreement of different classification systems (with videos). Gastrointest Endosc 2011; 73:7-14. 20. Kato M, Kaise M, Yonezawa J, et al. Magnifying endoscopy with narrowband imaging achieves superior accuracy in the differential diagnosis of superficial gastric lesions identified with white-light endoscopy: a prospective study. Gastrointest Endosc 2010;72:523-9. 21. Kanao H, Tanaka S, Oka S, et al. Narrow-band imaging magnification predicts the histology and invasion depth of colorectal tumors. Gastrointest Endosc 2009;69:631-6. 22. Osanai M, Igarashi Y, Itoi T, et al. Diagnostic peroral videocholangioscopy using narrow band imaging for the bile duct lesions: a prospective multicenter clinical trial [abstract]. Gastrointest Endosc 2011;73:AB113.
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Comparison of the diagnostic accuracy of peroral videocholangioscopic visual findings and cholangioscopy-guided forceps biopsy findings for indeterminate biliary lesions: a prospective study Takao Nishikawa, MD,1 Toshio Tsuyuguchi, MD, PhD,1 Yuji Sakai, MD, PhD,1 Harutoshi Sugiyama, MD, PhD,1 Masaru Miyazaki, MD, PhD,2 Osamu Yokosuka, MD, PhD1 Chiba, Japan
Background: The diagnostic accuracy of peroral video-cholangioscopy for indeterminate biliary lesions has not been determined in a prospective study. Objective: To evaluate and compare the diagnostic accuracy of the peroral video-cholangioscopic visual findings for indeterminate biliary lesions with that of the cholangioscopy-guided forceps biopsy findings. Design: Prospective cohort study. Setting: Tertiary-care referral center. Patients: Patients who showed indeterminate biliary lesions on endoscopic retrograde cholangiography underwent peroral video-cholangioscopy for diagnosis. Intervention: Each patient underwent peroral video-cholangioscopy with cholangioscopy-guided forceps biopsy. Main Outcome Measurements: The accuracy of diagnosis by the peroral video-cholangioscopic visual findings and cholangioscopy-guided forceps biopsy findings compared with that of the final diagnosis by other methods (malignant or benign). Results: Thirty-three patients were enrolled, and the final diagnoses revealed that the lesions were malignant in 21 patients. All procedures were technically successful, and fine views were obtained in all patients. Procedurerelated complications occurred in 2 patients (6.1%), but these complications were mild. The sensitivity, specificity, and accuracy were 100%, 91.7%, and 97.0%, respectively, for the peroral video-cholangioscopic visual findings and 38.1%, 100%, and 60.6%, respectively, for the cholangioscopy-guided forceps biopsy findings, and a significant difference was observed in the accuracy (P ⫽ .0018). Limitations: This was not a blinded study. No comparison was made with other diagnostic modalities involving tissue sampling. Conclusion: The diagnostic accuracy of the peroral video-cholangioscopic visual findings for indeterminate biliary lesions was excellent and significantly higher than that of the cholangioscopy-guided forceps biopsy findings. The accuracy of the cholangioscopy-guided forceps biopsy was insufficient, but the technique had an excellent specificity. (Gastrointest Endosc 2013;77:219-26.)
Accurate diagnosis of indeterminate biliary lesions is essential in therapeutic planning to avoid unnecessary surgery for lesions that are benign. Despite the advances
in biliary diagnostic techniques, such as endoscopic retrograde cholangiography (ERC), EUS, and those involving tissue sampling, the diagnostic accuracy necessary for dis-
Abbreviations: ERC, endoscopic retrograde cholangiography; PVCS, peroral video-cholangioscopy.
Received August 1, 2012. Accepted October 5, 2012.
DISCLOSURE: All authors disclosed no financial relationships relevant to this publication.
Current affiliations: Department of Medicine and Clinical Oncology (1), Department of General Surgery (2), Graduate School of Medicine, Chiba University, Chiba, Japan.
Copyright © 2013 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2012.10.011
Reprint requests: Toshio Tsuyuguchi, MD, PhD, Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
www.giejournal.org
Volume 77, No. 2 : 2013 GASTROINTESTINAL ENDOSCOPY 219
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Take-home Message ●
●
The diagnostic accuracy of peroral video-cholangioscopic visual findings for indeterminate biliary lesions was 97% and was significantly higher than that of cholangioscopyguided forceps biopsy findings. The accuracy of cholangioscopy-guided forceps biopsy findings was insufficient, but the technique had an excellent specificity.
that of the PVCS-guided forceps biopsy findings in patients with indeterminate biliary lesions.
METHODS Study design This was a prospective, single-center, cohort study of patients with indeterminate biliary lesions who were referred to Chiba University Hospital for diagnosis by using PVCS. The present study was approved by the institutional review board of Chiba University and was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000004711. Written informed consent was obtained from all patients. None of the authors have financial conflicts of interest to disclose.
Patients Figure 1. Peroral video-cholangioscopic view showing a malignant biliary lesion. A, Irregularly dilated and tortuous vessels. B, Easy oozing of blood.
tinguishing malignant biliary lesions from benign biliary lesions is insufficient.1,2 A previous study showed that the addition of peroral fiberoptic cholangioscopy to ERC/tissue sampling improved the diagnostic accuracy up to 94.8% for biliary lesions.3 Peroral video-cholangioscopy (PVCS) has higher image resolution and permits a clearer view than fiberoptic-cholangioscopy; therefore, the addition of PVCS to ERC/tissue sampling was shown to improve the diagnostic accuracy to ⬎98%.4,5 Another advantage of cholangioscopy is that it allows biopsy of the lesions under direct visualization, but the cup diameter of the forceps used in this technique is smaller than that of standard forceps used with fluoroscopic guidance. To our knowledge, there has been no prospective study of the diagnostic accuracy of pure PVCS visual findings and pure PVCS-guided forceps biopsy findings for indeterminate biliary lesions. This prospective study aimed to evaluate and compare the diagnostic accuracy of the PVCS visual findings with 220 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 2 : 2013
Patients who showed indeterminate biliary lesions on ERC and other imaging modalities, with no pathologic evidence of malignancy, were considered for this study. Exclusion criteria included age younger than 20 years, medical unsuitability for PVCS, and inability to provide informed consent.
Intervention Each patient with an indeterminate biliary lesion underwent PVCS with cholangioscopy-guided forceps biopsy during the same session.
Procedure All procedures were performed by using side-viewing duodenoscopes (Olympus TJF-240/260V; Olympus Medical Systems, Tokyo, Japan). Endoscopic sphincterotomy was performed for the patients who had not undergone the procedure previously. If necessary, extension of the previous sphincterotomy or additional balloon dilation was performed for the passage of a cholangioscope across the papilla. PVCS was performed with duodenoscopic assistance by using Olympus CHF-B260 (diameter, 3.4 mm; Olympus Medical Systems). To clearly observe the biliary lesions, we irrigated the bile duct with sterile saline solution through the working channel (diameter, 1.2 mm), as described elsewhere.3-5 FB-44U-1 with a cup (diameter, www.giejournal.org
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Figure 2. A, Cholangiogram showing an indeterminate hilar stricture (arrows) and filling defect in the left hepatic duct (arrowheads). B, Cholangioscopic view showing an irregular papillary epithelium with irregularly dilated vessels. C, D, Photomicrograph of a cholangioscopy-guided forceps biopsy specimen showing papillary adenocarcinoma (H&E, orig. mag. C, ⫻100, D, ⫻200).
1.15 mm; Olympus Medical Systems) was used for direct visualization during PVCS-guided forceps biopsy. ERC was previously performed by one of two therapeutic endoscopists (Y.S., H.S., with a combined experience of ⬎1000 ERC procedures). All procedures in this study were performed by another therapeutic endoscopist (T.T.) with an experience of ⬎500 peroral cholangioscopies, and he evaluated the visual findings of PVCS. The decision (malignant or benign) on indeterminate biliary lesions was made on the basis of PVCS visual findings and was prospectively recorded into the computer database, before the results of PVCS-guided forceps biopsy and final diagnosis were confirmed. Biopsy specimens were evaluated by experienced pathologists who were blinded to the fact that the specimens www.giejournal.org
were part of a study evaluation but who interpreted the results with full knowledge of the clinical data.
Outcomes and definitions The primary study outcome measure was the accuracy of diagnosis by the PVCS visual findings and PVCS-guided forceps biopsy findings compared with that of the final diagnosis by other methods (malignant or benign). We evaluated the indeterminate biliary lesions on the basis of the cholangioscopic findings described in previous studies.3-7 Biliary lesions were defined as malignant on the basis of the following visual findings: (1) irregularly dilated and tortuous vessels (tumor vessels), (2) easy oozing of blood, and (3) irregular surface (or papillary projections) (Figs. 1 and 2). Easy oozing of blood was defined Volume 77, No. 2 : 2013 GASTROINTESTINAL ENDOSCOPY 221
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RESULTS Patient characteristics
Figure 3. Peroral video-cholangioscopic view showing petechial hemorrhage of biliary mucosa because of stent placement.
as continuous bleeding and was distinguished from petechial hemorrhage of biliary mucosa due to stent placement or contact with a cholangioscope (Fig. 3). Biliary lesions were defined as benign on the basis of the following visual findings: (1) smooth mucosal surface without definite neovascularization and (2) lower homogeneous papillogranular mucosa without a primary mass (Fig. 4). The final diagnosis was made on the basis of pathologic evaluation of tissue specimens obtained at surgery or by using other tissue sampling modalities and uneventful clinical course in patients with benign lesions. Secondary outcomes included procedural technical success, complications, and the diagnostic values, such as the sensitivity, specificity, positive predictive value, and negative predictive value for the PVCS visual findings and PVCS-guided forceps biopsy findings. The 2010 American Society for Gastrointestinal Endoscopy consensus criteria were used to define and grade complications.8
Statistical analysis Sample size was estimated on the basis of statistical analysis of the diagnostic accuracy of cholangioscopic findings and endobiliary forceps biopsy findings. Previous reported data indicated that the accuracy of peroral cholangioscopy was ⬎90%3,5 and that of conventional endobiliary forceps biopsy was approximately 60%.1 As a result, 33 patients would be required to detect a significant difference between the PVCS visual findings and PVCSguided forceps biopsy findings with a P value of .05 and power of 0.8. A McNemar exact test was used to assess the comparison of the diagnostic accuracy between the PVCS visual findings and PVCS-guided forceps biopsy findings. Continuous variables were calculated as mean and standard deviation (SD). SAS version 9.2 (SAS Institute, Cary, NC) was used to perform all statistical analyses. The significant level was set to P ⬍ .05. 222 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 2 : 2013
Sixty-three patients underwent ERC for the diagnosis of indeterminate biliary lesions during the study period (Fig. 5). Thirty-three patients (23 men and 10 women; mean age 67.52 [SD ⫾ 8.00] years) who showed indeterminate biliary lesions on ERC with no pathologic evidence of malignancy were recruited for this study between December 2010 and March 2012. All patients underwent PVCS and PVCSguided forceps biopsy during the same session. The patient characteristics and procedural details are summarized in Table 1. According to the final diagnoses, the lesions were malignant in 21 patients and benign in 12 patients (Table 2). The final diagnosis of a malignant biliary lesion was established on the basis of surgical resection specimens in 20 patients and PVCS-guided forceps biopsy specimens in 1 patient. The final diagnosis of a benign biliary lesion was established on the basis of surgical resection specimens in 5 patients and clinical follow-up in 7 patients. Five of the 7 patients had uneventful clinical courses of at least 12 months, and 2 of the 7 patients showed disappearance of the biliary lesions accompanied by improvement of bile duct inflammation after 3 or 6 months.
Outcomes All procedures were technically successful, and fine views were obtained in all patients. Procedure-related complications occurred in only 2 patients (6.1%). Mild cholangitis occurred in 1 patient (3.0%), and mild pancreatitis occurred in 1 patient (3.0%). No other morbidities or mortalities were observed. In all 21 patients, lesions that were malignant as per the final diagnosis were also deemed malignant after the visual evaluation of the PVCS findings. Among the benign lesions of 12 patients, as confirmed by the final diagnosis, lesions in 1 patient were considered malignant and those in 11 patients were considered benign after the visual evaluation of the PVCS findings. The PVCS findings showed tumor vessels in 1 and 20 patients with benign and malignant lesions, respectively, as per the final diagnosis. Easy oozing of blood was observed in 1 and 18 patients with benign and malignant lesions, respectively. An irregular surface (or papillary projection) was observed in 20 patients with malignant lesions (Table 3). There was one false-positive diagnosis based on the results of the PVCS visual findings, in which the patient showed tortuous dilated vessels and easy oozing of blood in the right hepatic duct stricture. The PVCS-guided forceps biopsy specimens of this patient gave a negative result, and the lesions were finally diagnosed as benign by clinical follow-up, including repeated performance of PVCS. The previous PVCS visual findings of malignancy disappeared, and the surface of the lesions became smooth, which was www.giejournal.org
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Figure 4. A, Cholangiogram showing an indeterminate stricture in the origin of the cystic duct (arrows). B, Cholangioscopic view showing smooth papillary epithelium without dilated vessels. Photomicrograph of a cholangioscopy-guided forceps biopsy specimen showing chronic inflammatory change with inflammatory cellular infiltration into the stroma, fibroedematous change, hyperemia, and no cancer cells (H&E, orig. mag. C, ⫻100, D, ⫻200).
decided on the basis of an inflammatory change with biliary stricture and hepatolithiasis. On pathologic evaluation of the PVCS-guided forceps biopsy specimens, none of the patients had inadequate specimens for histology. Of 21 patients with a final malignant diagnosis, biopsy specimens showed malignant and benign changes on histology in 8 and 13 patients, respectively. Of all 12 patients with a final diagnosis of benign lesions, biopsy specimens showed benign changes on histology (Table 3). Table 4 shows the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the PVCS visual findings and PVCS-guided forceps biopsy findings. The accuracy of the PVCS visual findings was significantly higher than that of PVCS-guided forceps biwww.giejournal.org
opsy (97.0% vs 60.6%; P ⫽ .0018). The PVCS visual findings had a sensitivity and negative predictive value of 100% and a specificity and positive predictive value of ⬎90%. The PVCS-guided forceps biopsy had a specificity and positive predictive value of 100% but a sensitivity and negative predictive value of ⬍50%.
DISCUSSION Cholangioscopy permits direct visualization and tissue sampling of indeterminate biliary lesions. Severe and fatal complications are more frequently associated with percutaneous transhepatic cholangioscopy9,10; therefore, peroral cholangioscopy has become a popular technique for diagnosing indeterminate biliary lesions. The diagnostic Volume 77, No. 2 : 2013 GASTROINTESTINAL ENDOSCOPY 223
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Figure 5. Flow chart showing the recruitment of patients in the study. ERC, Endoscopic retrograde cholangiography; PVCS, peroral video-cholangioscopy. *Fluoroscopy-guided brushing cytology and/or forceps biopsy.
accuracy of pure peroral fiberoptic-cholangioscopy (SpyGlass; Boston Scientific Japan, Tokyo, Japan) visual findings for indeterminate biliary lesions was between 80% and 89%.11-13 In this study, we determined the diagnostic accuracy of pure PVCS visual findings and pure PVCSguided forceps biopsy findings for indeterminate biliary lesions. The diagnostic accuracy of the PVCS visual findings was 97.0%, and that of the PVCS-guided forceps biopsy findings was 60.0%, and the difference was significant. Furthermore, the largest clinical trial on SpyGlass peroral cholangioscopy indicated that cholangioscopic impression of malignant biliary lesions has higher sensitivity than targeted biopsy.13 No studies have directly compared the diagnostic accuracy of videocholangioscopy and fiberoptic cholangioscopy for indeterminate biliary lesions, but video-cholangioscopy has higher image resolution and permits a clearer view than fiberoptic cholangioscopy.3-5,11-13 It was reported that detection of neoplasia in biliary strictures was better with large-capacity forceps than with standard forceps.14 In this study, despite small-capacity forceps, the accuracy of PVCS-guided forceps biopsy was comparable to that of conventional fluoroscopy-guided forceps biopsy because of the direct visualization of indeterminate biliary lesions. Then again, despite the interpre224 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 2 : 2013
tation of the clinical data that included the PVCS visual findings of pathologists, the accuracy of PVCS-guided forceps biopsy was significantly lower. The accuracy of the PVCS (CHF-B260) visual findings is very high, but it requires difficult maneuverability for the mother-baby system and 2-way deflected steering of the tip and has only one channel. When the biopsy forceps are inserted into the channel, the view of PVCS becomes worse because of insufficient irrigation in the bile duct, even with a water pump connected to a Y-connector. Therefore, sampling errors are liable to occur in PVCS-guided forceps biopsy. Moreover, once PVCS-guided forceps biopsy is performed, the view becomes much worse because of oozing, and the number of tissue samples is limited. In fact, the number of tissue samples obtained for each patient was different in this study, and the lower sensitivity also may be a result of limited tissue sampling. On the other hand, the SpyGlass single-operator peroral cholangioscopy system overcomes these limitations. In brief, it permits 4-way deflected steering and has one working channel and two detached irrigation channels.11 The diagnostic accuracy of SpyGlass-guided forceps biopsy for indeterminate biliary lesions was between 75% and 90%.11-13,15 Because of improved maneuverability and sufficient irrigation in the bile duct, sampling errors do not occur easily www.giejournal.org
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TABLE 1. Baseline patient characteristics and procedural details Age, mean (⫾ SD), range, y
TABLE 3. Results of PVCS visual findings and PVCSguided forceps biopsy findings
67.52 (⫾ 8.00), 50-80
Sex, male/female
Final diagnosis
23/10
Malignant
Benign
Visual findings
Location of lesions, no. Intrahepatic
3
Malignant
21
1
Hilar
17
Tumor vessels
20
1
Middle bile duct (including cystic duct)
8
Easy oozing of blood
18
1 0
5
Irregular surface (or papillary projection)
20
Low bile duct
Benign
0
11
Malignant
8
0
Benign
13
12
Type of biliary lesion, no. Biliary stricture
30
Biliary nodule
3
Forceps biopsy findings
Procedure for major duodenal papilla, no.
PVCS, Peroral video-cholangioscopy.
Sphincterotomy
0
Additional balloon dilation
6
Biopsy sampling, mean (⫾ SD), range, no.
2.39 (⫾ 1.14), 1-5
TABLE 4. Diagnostic values of PVCS visual findings and PVCS-guided forceps biopsy
SD, Standard deviation.
TABLE 2. Final diagnosis* Malignant biliary lesion (n ⫽ 21), no. Cholangiocarcinoma
21
Benign biliary lesion (n ⫽ 12), no. Calculi-induced inflammatory change*
10
Primary sclerosing cholangitis with benign stricture
1
IgG4-related sclerosing cholangitis with benign stricture
1
IgG4, Immunoglobulin G4. *Calculi-induced inflammatory changes included hepatolithiasis (n ⫽ 4), Mirizzi syndrome (n ⫽ 3), and benign biliary stricture accompanying cholelithiasis (n ⫽ 3).
in SpyGlass-guided forceps biopsy. To perform accurate tissue sampling, improved PVCS that is maneuverable, has a working channel with a larger diameter for largecapacity forceps, and enables sufficient irrigation in the bile duct is required. We diagnosed one inflammatory benign stricture induced by calculi as malignant on PVCS visual findings of tortuous dilated vessels and easy oozing of blood. It was also reported that tortuous dilated vessels and the irregular surface were observed in benign strictures because of www.giejournal.org
Visual findings
Forceps biopsy findings
Sensitivity
100%
38.1%
Specificity
91.7%
100%
Positive predictive value
95.5%
100%
Negative predictive value
100%
48.0%
Accuracy
97.0%
60.6%
P value
.0018
—
PVCS, Peroral video-cholangioscopy.
immunoglobulin G4 –related sclerosing cholangitis.16,17 Even if benign biliary lesions, tortuous dilated vessels, easy oozing of blood, or the irregular surface are attended during an intensely active phase of inflammation, overdiagnosis may occur. It was suggested that PVCS observations by narrow-band imaging could identify surface structures and mucosal vessels of biliary lesions better than those by white-light imaging.18 In recent years, the use of narrow-band imaging with magnification for diagnosis of digestive tract lesions has given good results,19-21 and it may resolve issues of overdiagnosis. For the accurate diagnosis of indeterminate biliary lesions, it is important to develop peroral magnifying cholangioscopy. The limitations of this study are that it was not a multicenter study, and there may have been biases related to patient selection and the fact that the PVCS operator was not blinded to the clinical data. To perform PVCS safely Volume 77, No. 2 : 2013 GASTROINTESTINAL ENDOSCOPY 225
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and to investigate indeterminate biliary lesions accurately, it was necessary for the PVCS operator to have information regarding biliary lesions and patients conditions. In addition, PVCS with forceps biopsy was not compared directly with other diagnostic modalities, such as EUS with tissue sampling and SpyGlass peroral fiberoptic cholangioscopy with forceps biopsy. Although we did not evaluate the accuracy of PVCS observations by narrow-band imaging, a prospective multicenter study reported that the accuracy of PVCS plus narrow-band imaging combined with fluoroscopy-guided or cholangioscopy-guided biopsy distinguished malignant from benign biliary lesions in all 91 cases.22 A study with a large number of patients is needed to develop a classification system of narrow-band imaging in biliary lesions, such as surface patterns and vascular patterns in digestive tract lesions.19-21 In conclusion, the diagnostic accuracy of PVCS visual findings for indeterminate biliary lesions is excellent and significantly higher than that of PVCS-guided forceps biopsy findings. The PVCS-guided forceps biopsy has an excellent positive predictive value, but sampling errors often occur. Further improvement of PVCS is required to perform accurate tissue sampling. ACKNOWLEDGMENT The authors would like to thank Enago (www.enago.jp) for the English language review. REFERENCES 1. De Bellis M, Sherman S, Fogel EL, et al. Tissue sampling at ERCP in suspected malignant biliary strictures (Part 2). Gastrointest Endosc 2002;56: 720-30. 2. Rösch T, Hofrichter K, Frimberger E, et al. ERCP or EUS for tissue diagnosis of biliary strictures? A prospective comparative study. Gastrointest Endosc 2004;60:390-6. 3. Fukuda Y, Tsuyuguchi T, Sakai Y, et al. Diagnostic utility of peroral cholangioscopy for various bile-duct lesions. Gastrointest Endosc 2005; 62:374-82. 4. Kawakami H, Kuwatani M, Etoh K, et al. Endoscopic retrograde cholangiography versus peroral cholangioscopy to evaluate intraepithelial tumor spread in biliary cancer. Endoscopy 2009;41:959-64. 5. Itoi T, Osanai M, Igarashi Y, et al. Diagnostic peroral video cholangioscopy is an accurate diagnostic tool for patients with bile duct lesions. Clin Gastroenterol Hepatol 2010;8:934-8. 6. Kim HJ, Kim MH, Lee SK, et al. Tumor vessel: a valuable cholangioscopic clue of malignant biliary stricture. Gastrointest Endosc 2000;52:635-8.
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7. Seo DW, Lee SK, Yoo KS, et al. Cholangioscopic findings in bile duct tumors. Gastrointest Endosc 2000;52:630-4. 8. Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010;71:446-54. 9. Nimura Y, Shionoya S, Hayakawa N, et al. Value of percutaneous transhepatic cholangioscopy (PTCS). Surg Endosc 1988;2:213-9. 10. Oh HC, Lee SK, Lee TY, et al. Analysis of percutaneous transhepatic cholangioscopy-related complications and the risk factors for those complications. Endoscopy 2007;39:731-6. 11. Chen YK, Pleskow DK. SpyGlass single-operator peroral cholangiopancreatoscopy system for the diagnosis and therapy of bile-duct disorders: a clinical feasibility study (with video). Gastrointest Endosc 2007; 65:832-41. 12. Ramchandani M, Reddy DN, Gupta R, et al. Role of single-operator peroral cholangioscopy in the diagnosis of indeterminate biliary lesions: a single-center, prospective study. Gastrointest Endosc 2011;74:511-9. 13. 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. 14. Ikeda M, Maetani I, Terada K, et al. Usefulness of endoscopic retrograde biliary biopsy using large-capacity forceps for extrahepatic biliary strictures: a prospective randomized study. Endoscopy 2010;42:837-41. 15. Draganov PV, Chauhan S, Wagh MS, et al. Diagnostic accuracy of conventional and cholangioscopy-guided sampling of indeterminate biliary lesions at the time of ERCP: a prospective, long-term follow-up study. Gastrointest Endosc 2012;75:347-53. 16. Yasuda I, Nakashima M, Moriwaki H. Cholangioscopic view of IgG4related sclerosing cholangitis. J Hepatobiliary Pancreat Sci 2011;18: 122-4. 17. Okano N, Igarashi Y, Kishimoto Y, et al. Case of immunoglobulin G4related cholangitis accompanying autoimmune pancreatitis: diagnosis by peroral cholangioscopy and treatment by endoscopic biliary stenting. Dig Endosc 2012;24(suppl 1):62-6. 18. 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. 19. Silva FB, Dinis-Ribeiro M, Vieth M, et al. Endoscopic assessment and grading of Barrett’s esophagus using magnification endoscopy and narrow-band imaging: accuracy and interobserver agreement of different classification systems (with videos). Gastrointest Endosc 2011; 73:7-14. 20. Kato M, Kaise M, Yonezawa J, et al. Magnifying endoscopy with narrowband imaging achieves superior accuracy in the differential diagnosis of superficial gastric lesions identified with white-light endoscopy: a prospective study. Gastrointest Endosc 2010;72:523-9. 21. Kanao H, Tanaka S, Oka S, et al. Narrow-band imaging magnification predicts the histology and invasion depth of colorectal tumors. Gastrointest Endosc 2009;69:631-6. 22. Osanai M, Igarashi Y, Itoi T, et al. Diagnostic peroral videocholangioscopy using narrow band imaging for the bile duct lesions: a prospective multicenter clinical trial [abstract]. Gastrointest Endosc 2011;73:AB113.
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