The objective of the PoCoMiMo study is to compare the abundance, and hepatic clearance of microbiota-derived molecules in the portal venous circulation between patients suffering from a primary hepatic malignancy versus those with pancreatic cancer…
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameter is the intestinal uptake of microbiome-derived
metabolites as defined by their enrichment between arterial (pre-intestinal)
and post-intestinal (portal venous) blood samples.
Secondary outcome
Secondary outcomes are the association between intestinal uptake of metabolites
with microbial features determined by metagenomic sequencing, and - in the
subset of patients undergoing partial liver resection - the rate of hepatic
clearance of microbial metabolites between pre-hepatic (portal venous) and
post-hepatic (hepatic venous) blood samples in relation to hepatic gene
expression of phase I and phase II biotransformation enzymes in a research
liver biopsy.
Background summary
Changes to the composition of the intestinal microbiome are associated with a
variety of human cancers and the outcome of cancer treatment, yet the
mechanisms via which microbial dysbiosis can contribute to pathogenesis remain
poorly defined. Since gut bacteria generally stay confined to the lumen of the
intestine, it is assumed that their extra-intestinal effects must be mediated
to a large extent by bacteria-derived products that gain access to the host by
crossing the epithelial barrier of the gut. Following their absorption from the
intestine, microbially-derived metabolites enter the portal venous circulation
and hence must pass the liver before entering the systemic circulation. This
direct delivery to the liver is significant, since the liver functions as a
metabolic and immunological hub that orchestrates whole-body physiology. The
liver is furthermore responsible for detoxifying foreign chemical compounds,
which may result in the hepatic clearance of particular microbial metabolites
before ever reaching the systemic circulation (first-pass effect).
Consequently, in-depth analysis of pre-hepatic, portal venous blood samples can
improve our understanding of the molecular mechanisms that integrate gut
microbiota and extra-intestinal human physiology.
Study objective
The objective of the PoCoMiMo study is to compare the abundance, and hepatic
clearance of microbiota-derived molecules in the portal venous circulation
between patients suffering from a primary hepatic malignancy versus those with
pancreatic cancer versus living liver donors (healthy controls).
Study design
This is an exploratory, single-centre, case-control study.
Study burden and risks
Participating patients will be asked for a one-time stool collection and a
1-day dietary recall questionnaire, and to consent to the perioperative
sampling of 5 ml of portal vein blood and 5 ml arterial blood and - in patients
undergoing partial liver resection - 5 ml post-hepatic venous blood and a
surgical biopsy from the resected liver tissue.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
Adult patients undergoing any of the following surgical interventions:
• Partial hepatic resection for an underlying hepatic malignancy
• Pancreaticoduodenectomy for a pancreatic malignancy
• Living donor liver transplantation
Exclusion criteria
Exclusion criteria are as follows:
• Patients who are known to suffer from an active viral infection (e.g.
hepatitis B or C)
• Patients with severe portal hypertension
• Patients who cannot provide informed consent due to cognitive impairment or
language barrier
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL77185.042.21 |