Accuracy for Predicting Deep Submucosal Invasion (NBIBLI)

Diagnostic Accuracy of Deep Submucosal Invasion: White Light Endoscopy vs Invasive Pattern Based on NBI/BLI ± Chromoendoscopy

The main aim of this study is to determine whether the assessment of the invasive pattern based on NBI with dual focus/magnification or BLI with magnification ± chromoendoscopy (NBI+CE) for predicting deep invasion is significantly more accurate than the assessment based on white light endoscopy (WLE), carried out by trained endoscopists.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Colorectal Polyp
• Intervention / Treatment: Diagnostic test: White light endoscopy (WLE); Diagnostic test: NBI/BLI +/- chromoendoscopy (NBIBLI +/- CE)

Detailed Description

A video with the lesion assessment, without any data on the patient, will be recorded in a device connected to the processor provided by the Principal Investigator. The name of the file will be the record ID. All the lesions will be tested by the same endoscopist in vivo and an assistant will fulfill the data collection sheet during the colonoscopy.

First, the lesions will be cleaned and observed in a stable position. Size, location, morphology, demarcated areas, and gross morphological malignant features will be evaluated. Based on these WLE characteristics, a deep invasion prediction will be performed (control test). Second, the lesion will be assessed using NBI with near focus or magnification or BLI with magnification. A second cleaning with pronase (or N-acetylcysteine if pronase is not available) if the surface cannot be clearly observed because of the presence of mucus or if crystal violet is going to be used. Crystal violet 0.05% will be used in case of polyps type 2B in the JNET classification or lesions with a demarcated area. A non-traumatic catheter (or spray catheter) will be used to spray the crystal violet over the lesion. A final prediction of deep invasion will be performed for NBI or BLI ± CE (test evaluated).

The use of a cap to observe the bottom of the lesion, fix the lesion close to the endoscope or to observe the lesion underwater immersion is strongly recommended.

The resection technique will be decided upon according to the local experience. In case of endoscopy resection (cold snare, EMR, ESD, full thickness), lesions will be removed via the anus (not through the endoscopy channel) in order to preserve their integrity. Although EMR is performed, if possible, lesions will be referred to the pathologist well oriented and pinned out on a cork based, as is standard procedure in ESD.

In order to ensure that endoscopic assessment is performed before the histology evaluation, both diagnostic assessments (control test and test evaluated) will be recorded on the REDCap database on the day of the colonoscopy. REDCap records the time and date of all changes in the variables' results. The remaining variables (demographic data, etc.) will be recorded on the data collection sheet and copied later into REDCap.

Videos of the lesion assessments will be sent to the Principal Investigator. Centralized visualization will be conducted to detect protocol violations and to exclude lesions from the study.

A blinded histology assessment will be conducted by the local pathologist and if a carcinoma with submucosal invasion is diagnosed, histology slides will be referred for an additional blinded and centralized histology evaluation at the end of the study.

Pathologists participating in the histological phase will assess all the slides with submucosal invasion and will collect the histological factors associated with lymph node metastasis.

Finally, investigators participating in the translational phase will refer paraffin blocks of 10 lesions of each JNET category (2A, 2B and 3) for genetic tests (sequencing of a panel of 45 genes and analysis of alterations in the number of copies of the genome).

• Study Type: Observational
• Enrollment (Actual): 426

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 104-0045
    • National Cancer Center
• Spain
  • Barcelona, Spain, 08022
    • Centro Medico Teknon
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Aragón
    • Zaragoza, Aragón, Spain, 50009
      • Hospital Clinico Universitario Lozano Blesa
  • Cataluña
    • Badalona, Cataluña, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol (Can Ruti)
    • Barcelona, Cataluña, Spain, 08036
      • Hospital Clinic de Barcelona
    • Barcelona, Cataluña, Spain, 08036
      • Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
    • Manresa, Cataluña, Spain, 08243
      • Althaia. Xarxa Assistencial Universitaria de Manresa
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46009
      • Hospital Universitario y Politecnico de La Fe
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Clínico Universitario Virgen de la Arrixaca
  • Teruel
    • Alcañiz, Teruel, Spain, 44600
      • Hospital Comarcal de Alcañiz
• United States
  • California
    • San Francisco, California, United States, 94121
      • San Francisco Veterans Affairs Medical Center. University of California
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients > 18 years old who undergo a colonoscopy for any reason

Description

Inclusion criteria:

• Non-pedunculated type 0 lesions in Paris classification (not obvious cancers)
• Lesions larger than 10 mm

Exclusion criteria are:

• Lesions assessed as JNET 1 by the endoscopist or serrated by the pathologist
• Previous biopsy or resection attempt
• Previous CT, MR or USE
• Unavailable histology
• Inflammatory bowel disease
• Informed consent not obtained
• Protocol violation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with colorectal polyps; Patients with non-pedunculated type 0 lesions in Paris classification (not obvious cancers) larger than 10 mm

Diagnostic test: White light endoscopy (WLE); Subjective endoscopic assessment of deep submucosal invasion based on the presence of gross morphological malignant features, morphology and size.; Diagnostic test: NBI/BLI +/- chromoendoscopy (NBIBLI +/- CE); Endoscopic assessment of deep submucosal invasion with NBI and dual focus/magnification or BLI and magnification. In the case of demarcated areas or JNET 2B, Kudo pit pattern assessment with crystal violet will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The presence or absence of deep invasion according to the control test (WLE)	Deep invasion will subjectively be diagnosed based on the presence of gross morphological malignant features, morphology and size. No single malignant feature, specific morphology or size is required. The importance given to each criterion and the final diagnosis of deep invasion is based on the personal experience of the endoscopist.	One day
The presence or absence of deep invasion according to the test evaluated (NBI/BLI +/- CE)	Deep invasion will be diagnosed in case of: JNET type 3 or; JNET 2B + Kudo Vn pit pattern or; JNET 2B and Kudo Vi pit pattern fulfilling all the following criteria: severe Kudo Vi pit pattern + presence of a demarcated area + size (demarcated area) >6 mm for PG or 3 mm for NPG.	One day
The presence or absence of deep invasion according to the gold standard (histology)	Deep invasion will be diagnosed if sm invasion ≥1000 μm is measured according to the Japanese guidelines by the central pathologists.	One day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of any genetic mutations	Sequencing of a panel of colorectal cancer genes: the 45 genes will be sequenced frequently mutated in colorectal cancer, through the protocols established in the center Executor: APC, TP53, FBXW7, SOX9, ATM, SMAD4, KRAS, PIK3CA, AMER1, FAT4, ARID1A, BRAF, NRAS, CTNNB1, TCF7L2, ERBB2, MET, EGFR, HRAS, SETD2, DLC1, CDKN2A, PTEN, ARID2, FAT1, POLE, POLD1, NOTCH1, BRCA2, LRP1B, KMT2C, KMT2D, DAPK1, CSMD1, MUC16, ADAMTS15, SYNE1, PCLO, ZFHX4, RYR3, RYR2, RELN, IRS2, GNAS, DMBT1.	one day
Number of genome copies using SNP-arrays	Number of copies using SNP-arrays.	one day

Collaborators and Investigators

• Sponsor: Althaia Xarxa Assistencial Universitària de Manresa
• Collaborators: Hospital Clinic of Barcelona; University of North Carolina, Chapel Hill; Germans Trias i Pujol Hospital; Hospital Universitario Ramon y Cajal; San Francisco Veterans Affairs Medical Center; Hospital Universitario Virgen de la Arrixaca; Hospital Universitario 12 de Octubre; Hospital Universitario La Fe; Centro Medico Teknon; National Cancer Center, Japan; Hospital Clínico Universitario Lozano Blesa; Hospital Comarcal de Alcañiz
• Investigators: Principal Investigator: Ignasi Puig, MD, PhD, Althaia Xarxa Assistencial Universitària de Manresa

Publications and helpful links

General Publications

• Sano Y, Tanaka S, Kudo SE, Saito S, Matsuda T, Wada Y, Fujii T, Ikematsu H, Uraoka T, Kobayashi N, Nakamura H, Hotta K, Horimatsu T, Sakamoto N, Fu KI, Tsuruta O, Kawano H, Kashida H, Takeuchi Y, Machida H, Kusaka T, Yoshida N, Hirata I, Terai T, Yamano HO, Kaneko K, Nakajima T, Sakamoto T, Yamaguchi Y, Tamai N, Nakano N, Hayashi N, Oka S, Iwatate M, Ishikawa H, Murakami Y, Yoshida S, Saito Y. Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team. Dig Endosc. 2016 Jul;28(5):526-33. doi: 10.1111/den.12644. Epub 2016 Apr 20.
• Puig I, Lopez-Ceron M, Arnau A, Rosinol O, Cuatrecasas M, Herreros-de-Tejada A, Ferrandez A, Serra-Burriel M, Nogales O, Vida F, de Castro L, Lopez-Vicente J, Vega P, Alvarez-Gonzalez MA, Gonzalez-Santiago J, Hernandez-Conde M, Diez-Redondo P, Rivero-Sanchez L, Gimeno-Garcia AZ, Burgos A, Garcia-Alonso FJ, Bustamante-Balen M, Martinez-Bauer E, Penas B, Pellise M; EndoCAR group, Spanish Gastroenterological Association and the Spanish Digestive Endoscopy Society. Accuracy of the Narrow-Band Imaging International Colorectal Endoscopic Classification System in Identification of Deep Invasion in Colorectal Polyps. Gastroenterology. 2019 Jan;156(1):75-87. doi: 10.1053/j.gastro.2018.10.004. Epub 2018 Oct 6.
• Backes Y, Moss A, Reitsma JB, Siersema PD, Moons LM. Narrow Band Imaging, Magnifying Chromoendoscopy, and Gross Morphological Features for the Optical Diagnosis of T1 Colorectal Cancer and Deep Submucosal Invasion: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2017 Jan;112(1):54-64. doi: 10.1038/ajg.2016.403. Epub 2016 Sep 20.
• Hayashi N, Tanaka S, Hewett DG, Kaltenbach TR, Sano Y, Ponchon T, Saunders BP, Rex DK, Soetikno RM. Endoscopic prediction of deep submucosal invasive carcinoma: validation of the narrow-band imaging international colorectal endoscopic (NICE) classification. Gastrointest Endosc. 2013 Oct;78(4):625-32. doi: 10.1016/j.gie.2013.04.185. Epub 2013 Jul 30.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): September 28, 2022
• Study Completion (Actual): October 30, 2022

Study Registration Dates

• First Submitted: November 13, 2018
• First Submitted That Met QC Criteria: November 18, 2018
• First Posted (Actual): November 21, 2018

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Endoscopy; Colonoscopy; Polypectomy; NBI; Invasive pattern; BLI; Deep submucosal invasion; JNET; Kudo pit pattern
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CEIC 18/53

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No