Exploring the Landscape of Injury and Repair in the Human Oesophagus
Characterising the Genomic and Phenotypic Changes That Define Injury and Repair in the Context of Early Carcinogenesis in the Human Oesophagus.
The goal of this study limited to working with human tissue samples is to delineate the mechanisms defining appropriate oesophageal injury and repair and to use this information to understand how these rules are dysregulated and result in cancer formation in adult patients undergoing endoluminal vacuum therapy (EVT therapy) for the treatment of perforations to the oesophagus.
The main question[s] it aims to answer are:
- to gain a deeper understanding of the processes underlying tissue regeneration and repair in the oesophagus and upper gastro-intestinal tract following physical injury
- to identify the similarities in the processes of regeneration and early carcinogenesis
Participants will take part in the study during their usual EVT therapy schedule. Tissue brushings and pinch biopsies will also be taken.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Tissue injury activates a number of cellular responses to initiate wound healing, resulting in the formation of new tissue within a short span of time and in a controlled fashion. In contrast, cancer results when a tissue mass forms in an unregulated process. Understanding the molecular mechanisms behind appropriate wound healing enables us to delineate how this process goes askew in the context of cancer. The goal is to delineate the mechanisms defining appropriate oesophageal injury and repair, and to use this information to understand how these rules are dysregulated and result in cancer formation.
In this study, the researchers wish to recruit adult patients undergoing endoluminal vacuum therapy (EVT therapy) for the treatment of perforations to the oesophagus in order to collect the discarded EVT sponge, biopsies from endoscopies, resected surgical specimens and additional blood samples. The researchers will request consent for access to archived tissue samples from any previous related surgery and some associated clinical metadata. The samples and associated clinical metadata will then be pseudonymised and sent to the Wellcome Sanger Institute.
Once samples are received at the Wellcome Sanger Institute, they will undergo a number of procedures including but not limited to genome sequencing, this will enable the researchers to gain a better understanding of the wound healing process, specifically how it can sometimes go wrong and lead to the development of cancer.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Locations
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Cambridge, United Kingdom
- Wellcome Sanger Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Male and Female patients 18 years old and over who are having elective upper gastro-intestinal surgery where a leak is a recognised complication (but has not occurred)
- Male and Female patients 18 years and over who present acutely with an upper gastro-intestinal leak.
Exclusion Criteria:
- patients who do not have a good understanding of the English Language
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
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Group 1
Group 1 will include patients who are having elective upper gastro-intestinal surgery where a leak is a recognised complication (but has not occurred).
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Sample collection: EVT sponges, tissue brushings and pinch biopsies
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Group 2
Group 2 will include patients who present acutely with an upper gastro-intestinal leak.
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Sample collection: EVT sponges, tissue brushings and pinch biopsies
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Genetic changes in regenerating oesophageal tissue
Time Frame: approximately 52 months
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To develop a detailed description of the genetic changes in regenerating oesophageal tissue in cancerous vs. non-cancerous oesophageal tissue
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approximately 52 months
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Characterising germline mutations
Time Frame: approximately 52 months
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blood samples will be used to characterise the 'germline mutations' or inherited mutations present in all of the participants cells.
The samples will be processed to separate the white blood cells which will then undergo processes to look at individual genes, collections of genes, exomes, whole exomes and whole genome sequencing (WGS)
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approximately 52 months
|
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DNA sequencing
Time Frame: approximately 52 months
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DNA from microdissected and in vitro cultured tissues will be extracted and sequenced using state-of-the-art sequencing methods to look at individual genes, collections of genes, exomes, whole exomes and whole genomes.
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approximately 52 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: AYESHA NOORANI, PhD MRCS, Genome Research Limited operating as The Wellcome Sanger Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 293952
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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