Int J Colorectal Dis DOI 10.1007/s00384-015-2230-x
ORIGINAL ARTICLE
Next-generation narrow band imaging system for colonic polyp detection: a prospective multicenter randomized trial Takahiro Horimatsu 1,2 & Yasushi Sano 3 & Shinji Tanaka 4 & Takuji Kawamura 5 & Shoichi Saito 6 & Mineo Iwatate 3 & Shiro Oka 4 & Koji Uno 5 & Kenichi Yoshimura 7 & Hideki Ishikawa 8 & Manabu Muto 1 & Hisao Tajiri 9
Accepted: 21 April 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose Previous studies have yielded conflicting results on the colonic polyp detection rate with narrow-band imaging (NBI) compared with white-light imaging (WLI). We compared the mean number of colonic polyps detected per patient for NBI versus WLI using a next-generation NBI system (EVIS LUCERA ELITE; Olympus Medical Systems) used with standard-definition (SD) colonoscopy and wide-angle (WA) colonoscopy. Methods Design: this study is a 2×2 factorial, prospective, multicenter randomized controlled trial. Setting: this study
* Takahiro Horimatsu [email protected] 1
Department of Therapeutic Oncology, Kyoto University Hospital, 54 Kawahara-cho, Shogoin Sakyo, Kyoto 606-8507, Japan
2
Department of Experimental Therapeutics, Institute for Advancement of Clinical and Translational Science (iACT), Kyoto University Hospital, Kyoto, Japan
3
Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Kobe, Japan
4
Department of Endoscopy, Hiroshima University, Hiroshima, Japan
5
Department of Gastroenterology, Kyoto Second Red Cross Hospital, Kyoto, Japan
6
Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
7
Center for Clinical Research, Kobe University Hospital, Kobe, Japan
8
Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan
9
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
was conducted at five academic centers in Japan. Interventions: patients were allocated to one of four groups: (1) WLI with SD colonoscopy (H260AZI), (2) NBI with SD colonoscopy (H260AZI), (3) WLI with WA colonoscopy (CF-HQ290), and (4) NBI with WA colonoscopy (CF-HQ290). Main outcome: the mean numbers of polyps detected per patient were compared between the four groups: WLI with/without WA colonoscopy and NBI with/without WA colonoscopy. Results Of the 454 patients recruited, 431 patients were enrolled. The total numbers of polyps detected by WLI with SD, NBI with SD, WLI with WA, and NBI with WA were 164, 176, 188, and 241, respectively. The mean number of polyps detected per patient was significantly higher in the NBI group than in the WLI group (2.01 vs 1.56; P=0.032). The rate was not higher in the WA group than in the SD group (1.97 vs 1.61; P=0.089). Conclusions Although WA colonoscopy did not improve the polyp detection, next-generation NBI colonoscopy represents a significant improvement in the detection of colonic polyps. Keywords Colonoscopy . Number of polyps detected per patient . Narrow band imaging (NBI) . Wide-angle colonoscopy
Introduction Most colorectal cancers (CRCs) arise from preexisting adenomas, and the adenoma–carcinoma sequence offers an opportunity for the screening and prevention of CRC [1]. Colonoscopy with adenoma resection can reduce the incidence of CRC by as much as 80 % [2] and the mortality of CRC by 50 % [3]. However, these benefits of colonoscopy are contingent upon the early detection and resection of adenomas.
Int J Colorectal Dis
The role of colonoscopy in CRC prevention is limited by the risk of missing polyps. A systematic review of six tandem colonoscopy studies of 465 patients reported a pooled adenoma miss rate of 22 %. As might be expected, the miss rate was higher (26 %) for small adenomas (1–5 mm) compared with those >10 mm (2.1 %) in size [4]. To overcome the limitations of standard colonoscopy in detecting adenomas, there has been a recent trend toward the use of advanced endoscopic techniques, including high-definition colonoscopy, dye-assisted chromoendoscopy, third-eye colonoscopy, cap-fitted colonoscopy, and narrow-band imaging (NBI). Although dye-assisted chromoendoscopy has been established as superior to WLE for the detection of colonic adenomas, the procedure is both cumbersome and time-consuming. NBI is an innovative imaging technology that uses narrowbandwidth filters [5]. Muto et al. reported on the efficacy of NBI for the early detection of superficial cancer in the head and neck region and the esophagus [6]. In the colorectal region, this modality was expected to enable early detection of neoplastic lesions; however, both positive [7, 8] and negative [9–14] results have been reported, and several meta-analyses have concluded that NBI does not improve the neoplastic detection rate compared with white-light imaging (WLI) [15–18]. The reason for the differences in findings might be because the mucosa appears as a darker color when visualized using NBI compared with WLI. The wider colorectal lumen compared with the esophageal lumen can also contribute to the dark appearance of the mucosa when visualized using NBI [10–12]. To overcome these limitations, a next-generation NBI system (EVIS LUCERA ELITE; Olympus Medical Systems, Tokyo, Japan) with a dedicated xenon lamp has been developed. This next-generation NBI system might allow the early detection of colonic polyps. We conducted a prospective, randomized, controlled trial to compare the mean number of colonic polyps detected per patient with NBI versus that with WLI using the Olympus next-generation NBI system with standard-definition (SD) colonoscopy or wide-angle (WA) colonoscopy.
Patients/material and methods Study design and participants This randomized, controlled, open-label, multicenter trial was conducted at five academic centers in Japan. This study was conducted according to the Standards for the Reporting of Diagnostic Accuracy Studies (STARD) initiative and the Declaration of Helsinki. We enrolled patients aged 20 years or older who were referred for colonoscopy for CRC screening including fecal occult blood testing (FOBT) positive,
surveillance of colorectal polyps, and diagnosis workup for colonic symptoms. Patients undergoing total colonoscopy with the next-generation NBI system were considered eligible if they met the inclusion criteria in this study. Patients were excluded if (1) they had a history of colectomy; (2) they had an inflammatory bowel disease; (3) they had familial adenomatous polyposis, hereditary nonpolyposis CRC, or serrated polyposis syndrome; (4) the colonoscopist judged that they could not obtain a clean colon; or (5) the colonoscopist judged that they could not accept random allocation. Written informed consent was obtained, and the institutional review board of each participating hospital approved the study. This study was registered in the University Hospital Medical Network Clinical Trials Registry (UMIN000007150). All authors had access to the study data and reviewed and approved the final manuscript. After insertion of the colonoscope into the cecum, screening was performed using colonoscopy according to the method of the specific allocated group. To avoid bias, the colonoscopists were blinded to the diagnosis of any previously detected lesions. Patients with an incomplete total colonoscopy, poor bowel preparation, melanosis coli, or multiple polyps that were unresectable in a single endoscopic examination were excluded. The target lesions for this study were all polyps except for rectosigmoid lesions ≤5 mm in size that were diagnosed as hyperplastic lesions endoscopically. The diameter of each lesion was estimated in relation to the size of the biopsy forceps. Randomization and masking A 2×2 factorial design was used to compare the detection rates between the four groups. There are two comparisons; one is WLI vs NBI and the other is WA vs SD. The patients were assigned randomly by an investigator using a computeraided system on the Medical Research Support Web site (Kyoto, Japan). A minimization algorithm was used to balance the selection of the primary examination according to the following five stratification variables: institution, age (5000 colonoscopies in 9 years of NBI use, 9 experienced colonoscopists who had performed >3000 colonoscopies in 4–6 years of NBI use, and 13 trainees who had performed 1 polyp Mean insertion time (s) Mean withdrawal time (s)
WLI N=218
NBI N=213
335 1.54 (1.28–1.79)
425 2.00 (1.66–2.33)
150 446 507
159 473 572
WLI. To overcome these limitations, the EVIS LUCERA ELITE next-generation NBI system was developed. Leung et al. described that 190-NBI colonoscopy using EXERA ELITE system was superior to the conventional HD-WL using LUCERA ELITE system in detecting colorectal adenomas or polyps. However, this study is using another systems. To our knowledge, our study is the first randomized controlled trial in a multicenter setting to use this next-generation NBI system to compare the mean number of polyps detected per patient between NBI and WLI with SD or WA colonoscopy using EVIS LUCERA ELITE System. We demonstrated greater efficacy of NBI for detecting colorectal polyps compared with WLI. In Western countries, surveillance intervals are determined according to the number of adenomas in addition to the detected polyp size, the degree of dysplasia, and the presence of villous architecture [19]. Therefore, accurate detection of colorectal polyp is very important. A systematic review of six tandem colonoscopy studies with a total of 465 patients reported a pooled adenoma miss rate of 22 % [4]. The reasons for missing polyps were
Fig. 3 Mean number of polyps detected per patient in each group
P value
SD N=219
WA N=212
P value
0.031
347 1.58 (1.32–1.85)
413 1.95 (1.62–2.27)
0.087
0.178 0.352 0.001
151 479 537
158 439 541
0.199 0.178 0.836
considered to be the quality of bowel preparation, lesion characteristics (location, number, morphology, and size), the endoscopists’ level of experience, and the endoscopists’ insertion and withdrawal times [20, 21]. We found no significant difference in the quality of bowel preparation, endoscopists’ level of experience (number of previous colonoscopies and years of NBI use), or insertion time between the groups. Because most previous analyses were performed only by expert colonoscopists, we included 13 trainees who had performed NBI for
ORIGINAL ARTICLE
Next-generation narrow band imaging system for colonic polyp detection: a prospective multicenter randomized trial Takahiro Horimatsu 1,2 & Yasushi Sano 3 & Shinji Tanaka 4 & Takuji Kawamura 5 & Shoichi Saito 6 & Mineo Iwatate 3 & Shiro Oka 4 & Koji Uno 5 & Kenichi Yoshimura 7 & Hideki Ishikawa 8 & Manabu Muto 1 & Hisao Tajiri 9
Accepted: 21 April 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose Previous studies have yielded conflicting results on the colonic polyp detection rate with narrow-band imaging (NBI) compared with white-light imaging (WLI). We compared the mean number of colonic polyps detected per patient for NBI versus WLI using a next-generation NBI system (EVIS LUCERA ELITE; Olympus Medical Systems) used with standard-definition (SD) colonoscopy and wide-angle (WA) colonoscopy. Methods Design: this study is a 2×2 factorial, prospective, multicenter randomized controlled trial. Setting: this study
* Takahiro Horimatsu [email protected] 1
Department of Therapeutic Oncology, Kyoto University Hospital, 54 Kawahara-cho, Shogoin Sakyo, Kyoto 606-8507, Japan
2
Department of Experimental Therapeutics, Institute for Advancement of Clinical and Translational Science (iACT), Kyoto University Hospital, Kyoto, Japan
3
Gastrointestinal Center and Institute of Minimally Invasive Endoscopic Care (iMEC), Sano Hospital, Kobe, Japan
4
Department of Endoscopy, Hiroshima University, Hiroshima, Japan
5
Department of Gastroenterology, Kyoto Second Red Cross Hospital, Kyoto, Japan
6
Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
7
Center for Clinical Research, Kobe University Hospital, Kobe, Japan
8
Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan
9
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
was conducted at five academic centers in Japan. Interventions: patients were allocated to one of four groups: (1) WLI with SD colonoscopy (H260AZI), (2) NBI with SD colonoscopy (H260AZI), (3) WLI with WA colonoscopy (CF-HQ290), and (4) NBI with WA colonoscopy (CF-HQ290). Main outcome: the mean numbers of polyps detected per patient were compared between the four groups: WLI with/without WA colonoscopy and NBI with/without WA colonoscopy. Results Of the 454 patients recruited, 431 patients were enrolled. The total numbers of polyps detected by WLI with SD, NBI with SD, WLI with WA, and NBI with WA were 164, 176, 188, and 241, respectively. The mean number of polyps detected per patient was significantly higher in the NBI group than in the WLI group (2.01 vs 1.56; P=0.032). The rate was not higher in the WA group than in the SD group (1.97 vs 1.61; P=0.089). Conclusions Although WA colonoscopy did not improve the polyp detection, next-generation NBI colonoscopy represents a significant improvement in the detection of colonic polyps. Keywords Colonoscopy . Number of polyps detected per patient . Narrow band imaging (NBI) . Wide-angle colonoscopy
Introduction Most colorectal cancers (CRCs) arise from preexisting adenomas, and the adenoma–carcinoma sequence offers an opportunity for the screening and prevention of CRC [1]. Colonoscopy with adenoma resection can reduce the incidence of CRC by as much as 80 % [2] and the mortality of CRC by 50 % [3]. However, these benefits of colonoscopy are contingent upon the early detection and resection of adenomas.
Int J Colorectal Dis
The role of colonoscopy in CRC prevention is limited by the risk of missing polyps. A systematic review of six tandem colonoscopy studies of 465 patients reported a pooled adenoma miss rate of 22 %. As might be expected, the miss rate was higher (26 %) for small adenomas (1–5 mm) compared with those >10 mm (2.1 %) in size [4]. To overcome the limitations of standard colonoscopy in detecting adenomas, there has been a recent trend toward the use of advanced endoscopic techniques, including high-definition colonoscopy, dye-assisted chromoendoscopy, third-eye colonoscopy, cap-fitted colonoscopy, and narrow-band imaging (NBI). Although dye-assisted chromoendoscopy has been established as superior to WLE for the detection of colonic adenomas, the procedure is both cumbersome and time-consuming. NBI is an innovative imaging technology that uses narrowbandwidth filters [5]. Muto et al. reported on the efficacy of NBI for the early detection of superficial cancer in the head and neck region and the esophagus [6]. In the colorectal region, this modality was expected to enable early detection of neoplastic lesions; however, both positive [7, 8] and negative [9–14] results have been reported, and several meta-analyses have concluded that NBI does not improve the neoplastic detection rate compared with white-light imaging (WLI) [15–18]. The reason for the differences in findings might be because the mucosa appears as a darker color when visualized using NBI compared with WLI. The wider colorectal lumen compared with the esophageal lumen can also contribute to the dark appearance of the mucosa when visualized using NBI [10–12]. To overcome these limitations, a next-generation NBI system (EVIS LUCERA ELITE; Olympus Medical Systems, Tokyo, Japan) with a dedicated xenon lamp has been developed. This next-generation NBI system might allow the early detection of colonic polyps. We conducted a prospective, randomized, controlled trial to compare the mean number of colonic polyps detected per patient with NBI versus that with WLI using the Olympus next-generation NBI system with standard-definition (SD) colonoscopy or wide-angle (WA) colonoscopy.
Patients/material and methods Study design and participants This randomized, controlled, open-label, multicenter trial was conducted at five academic centers in Japan. This study was conducted according to the Standards for the Reporting of Diagnostic Accuracy Studies (STARD) initiative and the Declaration of Helsinki. We enrolled patients aged 20 years or older who were referred for colonoscopy for CRC screening including fecal occult blood testing (FOBT) positive,
surveillance of colorectal polyps, and diagnosis workup for colonic symptoms. Patients undergoing total colonoscopy with the next-generation NBI system were considered eligible if they met the inclusion criteria in this study. Patients were excluded if (1) they had a history of colectomy; (2) they had an inflammatory bowel disease; (3) they had familial adenomatous polyposis, hereditary nonpolyposis CRC, or serrated polyposis syndrome; (4) the colonoscopist judged that they could not obtain a clean colon; or (5) the colonoscopist judged that they could not accept random allocation. Written informed consent was obtained, and the institutional review board of each participating hospital approved the study. This study was registered in the University Hospital Medical Network Clinical Trials Registry (UMIN000007150). All authors had access to the study data and reviewed and approved the final manuscript. After insertion of the colonoscope into the cecum, screening was performed using colonoscopy according to the method of the specific allocated group. To avoid bias, the colonoscopists were blinded to the diagnosis of any previously detected lesions. Patients with an incomplete total colonoscopy, poor bowel preparation, melanosis coli, or multiple polyps that were unresectable in a single endoscopic examination were excluded. The target lesions for this study were all polyps except for rectosigmoid lesions ≤5 mm in size that were diagnosed as hyperplastic lesions endoscopically. The diameter of each lesion was estimated in relation to the size of the biopsy forceps. Randomization and masking A 2×2 factorial design was used to compare the detection rates between the four groups. There are two comparisons; one is WLI vs NBI and the other is WA vs SD. The patients were assigned randomly by an investigator using a computeraided system on the Medical Research Support Web site (Kyoto, Japan). A minimization algorithm was used to balance the selection of the primary examination according to the following five stratification variables: institution, age (5000 colonoscopies in 9 years of NBI use, 9 experienced colonoscopists who had performed >3000 colonoscopies in 4–6 years of NBI use, and 13 trainees who had performed 1 polyp Mean insertion time (s) Mean withdrawal time (s)
WLI N=218
NBI N=213
335 1.54 (1.28–1.79)
425 2.00 (1.66–2.33)
150 446 507
159 473 572
WLI. To overcome these limitations, the EVIS LUCERA ELITE next-generation NBI system was developed. Leung et al. described that 190-NBI colonoscopy using EXERA ELITE system was superior to the conventional HD-WL using LUCERA ELITE system in detecting colorectal adenomas or polyps. However, this study is using another systems. To our knowledge, our study is the first randomized controlled trial in a multicenter setting to use this next-generation NBI system to compare the mean number of polyps detected per patient between NBI and WLI with SD or WA colonoscopy using EVIS LUCERA ELITE System. We demonstrated greater efficacy of NBI for detecting colorectal polyps compared with WLI. In Western countries, surveillance intervals are determined according to the number of adenomas in addition to the detected polyp size, the degree of dysplasia, and the presence of villous architecture [19]. Therefore, accurate detection of colorectal polyp is very important. A systematic review of six tandem colonoscopy studies with a total of 465 patients reported a pooled adenoma miss rate of 22 % [4]. The reasons for missing polyps were
Fig. 3 Mean number of polyps detected per patient in each group
P value
SD N=219
WA N=212
P value
0.031
347 1.58 (1.32–1.85)
413 1.95 (1.62–2.27)
0.087
0.178 0.352 0.001
151 479 537
158 439 541
0.199 0.178 0.836
considered to be the quality of bowel preparation, lesion characteristics (location, number, morphology, and size), the endoscopists’ level of experience, and the endoscopists’ insertion and withdrawal times [20, 21]. We found no significant difference in the quality of bowel preparation, endoscopists’ level of experience (number of previous colonoscopies and years of NBI use), or insertion time between the groups. Because most previous analyses were performed only by expert colonoscopists, we included 13 trainees who had performed NBI for
