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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2020; 26(1): 70-85
Published online Jan 7, 2020. doi: 10.3748/wjg.v26.i1.70
Risk of gastrointestinal cancer in a symptomatic cohort after a complete colonoscopy: Role of faecal immunochemical test
Noel Pin-Vieito, María J Iglesias, David Remedios, Lorena Rodríguez-Alonso, Francisco Rodriguez-Moranta, Victoria Álvarez-Sánchez, Fernando Fernández-Bañares, Jaume Boadas, Eva Martínez-Bauer, Rafael Campo, Luis Bujanda, Ángel Ferrandez, Virginia Piñol, Daniel Rodríguez-Alcalde, Jordi Guardiola, Joaquín Cubiella, on behalf of the COLONPREDICT study investigators
Noel Pin-Vieito, María J Iglesias, David Remedios, Joaquín Cubiella, Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Ourense 32005, Spain
Noel Pin-Vieito, María J Iglesias, David Remedios, Instituto de Investigación Biomedica Galicia Sur, Ourense 32005, Spain
Noel Pin-Vieito, Department of Biochemistry, Genetics and Immunology, Faculty of Biology, University of Vigo, Vigo 36200, Spain
Lorena Rodríguez-Alonso, Francisco Rodriguez-Moranta, Jordi Guardiola, Department of Gastroenterology and Hepatology, University Hospital of Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08907, Spain. Ciber de Epidemiología y Salud Pública (CIBERESP), Spain
Victoria Álvarez-Sánchez, Gastroenterology Department, Complejo Hospitalario de Pontevedra, Pontevedra 36001, Spain
Fernando Fernández-Bañares, Gastroenterology Department, Hospital Universitari Mútua de Terrassa, CIBERehd, Terrassa 08221, Spain
Jaume Boadas, Gastroenterology Department, Consorci Sanitari de Terrassa, Terrassa 08221, Spain
Eva Martínez-Bauer, Rafael Campo, Gastroenterology Department, Hospital de Sabadell, Corporació Sanitària i Universitària Parc Taulí, Sabadell 08208, Spain
Luis Bujanda, Donostia Hospital, Biodonostia Institute, University of the Basque Country UPV/EHU, CIBERehd, San Sebastian 20010, Spain
Ángel Ferrandez, Servicio de Aparato Digestivo, Hospital Clínico Universitario, IIS Aragón, University of Zaragoza, CIBERehd, Zaragoza 50009, Spain.
Virginia Piñol, Gastroenterology Department, Hospital Dr. Josep Trueta, Girona 17007, Spain
Daniel Rodríguez-Alcalde, Digestive Disease Section, Hospital Universitario de Móstoles, Madrid 28935, Spain
Author contributions: Pin-Vieito N and Cubiella J designed the analysis, Pin-Vieito N, Iglesias M, Remedios D, Álvarez-Sánchez V, Fernández-Bañares F, Rodríguez-Alonso L, Rodríguez-Moranta F, Boadas J, Martínez-Bauer E, Campo R, Bujada L, Ferrández A, Piñol V, Rodríguez-Alcalde D and Guardiola J were involved in acquisition of data; Pin-Vieito N and Cubiella J analysed and prepared manuscript drafts; all authors contributed to writing of the paper. All authors had full access to all the data, tables and statistical reports in the study and take responsibility for integrity of the data and accuracy of the data analysis; Cubiella J and Pin-Vieito N acted as full guarantors of the research.
Supported by Instituto de Salud Carlos III through the project PI17/00837 (Co-funded by European Regional Development Fund/European Social Fund "A way to make Europe"/"Investing in your future").
Institutional review board statement: This is a post hoc cohort analysis performed within two prospective diagnostic test studies. The protocols of both studies conform to the ethical guidelines of the 1975 Declaration of Helsinki. COLONPREDICT study was approved by the Clinical Research Ethics Committee of Galicia (Code 2011/038) under resolution dated 11 April, 2012. The study of Rodríguez-Alonso et al. was approved by Bellvitge Hospital Clinical Research Ethics Committee (Code 21/11) on 1 December, 2011.
Informed consent statement: Patients of both studies provided written informed consent before inclusion.
Conflict-of-interest statement: Dr. Pin-Vieito reports non-financial support from ABBVIE, non-financial support from GILEAD SCIENCES, outside the submitted work; Dr. Cubiella reports grants from Instituto de Investigación Sanitaria Galicia Sur, grants from Fondo de Investigaciones Sanitarias (FIS), during the conduct of the study; personal fees from NORGINE, personal fees from IMC, outside the submitted work; Dr. Rodríguez-Alcalde reports non-financial support from SALVAT, outside the submitted work; all other authors have no conflict of interest related to the manuscript to declare.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at noel.pin.vieito@sergas.es.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Noel Pin-Vieito, MD, Staff Physician, Statistician, Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, C/ Ramón Puga 52-54, Ourense 32005, Spain. noel.pin.vieito@sergas.es
Received: September 20, 2019
Peer-review started: September 20, 2019
First decision: November 22, 2019
Revised: December 11, 2019
Accepted: December 21, 2019
Article in press: December 22, 2019
Published online: January 7, 2020
ARTICLE HIGHLIGHTS
Research background
Faecal immunochemical test for haemoglobin (FIT) is more specific and appears to be equal to or more sensitive than guaiac-based tests when used for colorectal cancer (CRC) screening. FIT reacts with human globin, so it should have greater specificity to detect lower gastrointestinal tract (GIT) lesions than guaiac-based tests. However, a previous systematic review led to the conclusion that there is insufficient evidence to recommend for or against routine esophagogastroduodenoscopy in asymptomatic patients with a positive faecal occult blood test followed by negative colonoscopy.
Research motivation
Out of a screening setting, several approaches have been developed to improve the suitability of referrals for investigation of symptoms suggestive of CRC and reduce delays in diagnosis and some include using FIT. Therefore, it will be increasingly common for clinicians to face the uncertainty of a patient with non-specific digestive symptoms, a positive FIT result and normal colonoscopy.
Research objectives
We aim to assess the risk of gastrointestinal cancer (GIC) detection and related death in symptomatic patients with a positive determination of FIT (threshold 10 μg Hb/g faeces) without CRC at baseline quality colonoscopy.
Research methods
We performed a post hoc cohort analysis within two prospective diagnostic test studies evaluating the diagnostic accuracy of FIT for CRC detection. Outpatients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare were divided into two groups (positive and negative FIT) using the threshold of 10 μg Hb/g of faeces and data from follow-up were retrieved from their electronic medical records. We determined the cumulative risk of GIC, CRC and upper GIC. Hazard rate was calculated adjusted by age, sex and presence of significant colonic lesion on basal colonoscopy.
Research results
This study revealed high neoplasia and death rates in our cohort (n = 2709) of people consulting with a physician for non-acute symptoms suggestive of lower gastrointestinal tract disorders. FIT-positive patients have higher incidence of GIC during follow-up. However, this did not result in a statistically significant increase in the risk of upper GIC development after multivariate adjustment. Moreover, we found that this cohort of patients only has an increased risk of related CRC and death when compared to the cohort with a negative FIT result.
Research conclusions
This study suggests that FIT positivity using the threshold of 10 μg Hb/g of faeces is not enough to differentiate which patients would benefit from continuing workup to rule out a GIC out of screening setting. Nevertheless, small amounts of f-Hb may originate in the upper GI tract or the small bowel and this possibility must be considered along with other false-positive risk factors when interpreting FIT requested to rule out CRC or another significant colonic lesion.
Research perspectives
We hypothesize that benign lesions (i.e. due to non-steroid anti-inflammatory drugs) are much more prevalent than GIC in the upper tract regardless of symptoms. Thus, it is much more likely that a small amount of detectable (unmetabolized) haemoglobin, originally from any kind of lesion located in the upper tract or the small bowel will be unrelated to a GIC. However, the study design is not suitable to prove this hypothesis. A large prospective follow-up study which takes competitive FIT positive causes and other risk factors into consideration would provide a predictive model to guide decision-making.
