Microbiome Analysis in esoPhageal, PancreatIc and Colorectal CaNcer Patients Undergoing Gastrointestinal Surgery (MA-PPING)

The MA-PPING is a multicenter prospective observational study that includes patients undergoing surgery for gastrointestinal cancer.

The study aims to map the oral and gut microbiome of patients diagnosed with pancreatic, esophageal or colorectal cancer during their surgical patient journey from the moment of diagnosis until full recovery (three months after surgery).

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Pancreatic Cancer; Esophageal Cancer; Esophageal Neoplasms; Anastomotic Leak; Colonic Neoplasms; Pancreatic Ductal Adenocarcinoma; Gastrointestinal Cancer; Microbiota; Gastrointestinal Microbiome; Rectum Neoplasm

Detailed Description

Rationale: The gut microbiome is the composition of micro-organisms that reside in the gastrointestinal tract. Under normal circumstances, the microbiome is balanced and has a beneficial effect on gut function. However, when the microbiome is stressed i.e. by an operation, patients' health or medication, the composition of the microbiome may change rapidly and the virulence of its micro-organisms can increase fast. Surgery, in particular gastrointestinal surgery, has a disruptive effect on the mucosal gut barrier and may lead to shifts in microbial composition. Also, the underlying surgical disease itself can be characterized by changes in the microbiome. Gastrointestinal cancer is associated with specified alterations of the microbiome, and the presence of certain microbiota is related with carcinogenesis and lymph node involvement.

Anastomotic leakage is a severe complication after gastrointestinal surgery and several animal studies linked microbial shifts to the development of anastomotic leakage. Only a few, small and explorative, human studies investigated the microbiome during surgery and correlated their findings with the development of postoperative complications. However, the majority of these studies only sampled the microbiome intraoperatively. Surgery-related microbial shifts manifest also in the pre- and postoperative phase, therefore, sampling in these phases is crucial. To further understand the changes of the microbiome composition due to gastrointestinal surgery and the relation with postoperative infectious complications, samples should be collected on several time points; before, during, and after surgery. With this study we aim to map the oral and gut microbiome of patients diagnosed with pancreatic, esophageal or colorectal cancer in a time frame ranging from the work-up for an operation until the postoperative phase to assess the changing composition of the microbiome during a surgical patient journey.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All adult patients who are presented/present at the participating hospitals with a proven gastrointestinal malignancy and scheduled for surgery.

Description

Inclusion Criteria:

• Patients with proven malignancy of the distal esophagus, pancreatic head/corpus, colon or rectum
• Patients undergoing primary elective surgery with construction of an anastomosis of the gastrointestinal tract
• Adult patients above age 18 years
• Written informed consent

Exclusion Criteria:

• History of chronic gastro-intestinal disease e.g. Crohns disease and ulcerative colitis
• Presence of acute gastrointestinal infection
• Chronic use of oral antibiotics (3 months or longer)
• Patients undergoing gastrointestinal surgery for gastrointestinal cancer in acute setting
• Patients undergoing construction of an end/loop colostomy or ileostomy (following primary resection)
• Patients undergoing colon and/ or rectal resection without construction of an anastomosis
• Patients who have insufficient knowledge of the Dutch language
• Patients who are not able to give reliable answers to the questionnaires due to a (mental) disease or (cognitive) condition
• Patients who are not able to collect microbiome samples due to a physical or mental condition

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compositional changes of the oral and gut microbiome, assessed by alpha-diversity using 16S rRNA (ribosomal ribonucleic acid) sequencing, described in a surgical patient journey from moment of diagnosis until full recovery	Changes of the microbiome composition during the surgical treatment quantified as alpha-diversity by 16S rRNA sequencing. Samples will be collected on 7 moments, starting one month before surgery until three months after surgery.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compositional changes of the oral and gut microbiome, assessed by beta-diversity using 16S rRNA sequencing, correlated with neo-adjuvant therapy	The effect of neo-adjuvant therapy on microbiome composition quantified as beta-diversity by 16S rRNA sequencing	1 month
Compositional changes of the oral and gut microbiome, assessed by beta-diversity using 16S rRNA sequencing, correlated with antibiotic prophylaxis	The effect of (preoperative) antibiotic prophylaxis on microbiome composition quantified as beta-diversity by 16S rRNA sequencing	1 week
Compositional changes of the oral and gut microbiome, assessed by beta-diversity using 16S rRNA sequencing, correlated with bowel preparation	The effect of preoperative bowel preparation on microbiome composition quantified as beta-diversity by 16S rRNA sequencing	1 week
Compositional changes of the oral and gut microbiome, assessed by beta-diversity using 16S rRNA sequencing, correlated with selective decontamination of the digestive tract (SDD)	The effect of selective decontamination of the digestive tract (SDD) on microbiome composition quantified as beta-diversity by 16S rRNA sequencing	1 week
Compositional changes of the oral and gut microbiome, assessed by beta-diversity using 16S rRNA sequencing, correlated to the development of infectious complications (30-day)	The effect of infectious complications (such as anastomotic leakage, sepsis, wound infection, pneumonia and urinary tract infection) on microbiome composition quantified as beta-diversity by 16S rRNA sequencing	1 month

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Stefan AW Bouwense, MD PhD, Radboud University Medical Center Nijmegen; Principal Investigator: Martijn WJ Stommel, MD PhD, Radboud University Medical Center Nijmegen; Principal Investigator: Harry van Goor, MD PhD, Radboud University Medical Center Nijmegen

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): December 6, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Site; Postoperative Complications; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Esophageal Diseases; Neoplasms; Colorectal Neoplasms; Rectal Neoplasms; Gastrointestinal Neoplasms; Anastomotic Leak; Esophageal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: 2019-5859

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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