Pankreatisch zystische Neoplasien und das orointestinale Mikrobiom: Evaluierung als Biomarker

by Charlotte Ratei
Doctoral thesis
Date of Examination:2024-09-26
Date of issue:2024-09-24
Advisor:Dr. Dr. Albrecht Prof Neeße
Referee:Dr. Dr. Albrecht Prof Neeße
Referee:PD Dr. Raphael Koch
Persistent Address: http://dx.doi.org/10.53846/goediss-10753

 

 

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Abstract

English

Pancreatic cystic neoplasms (PCN) are mostly benign cystic lesions of the pancreas, which can be a precursor lesion for pancreatic cancer. The risk of malignancy varies widely, depending on the entity of the PCN. Despite known risk factors and several studies, it has not yet been possible to reliably predict which patients with PCN will develop worrisome features or high-grade dysplasia and will therefore benefit from an early operation. Currently, it was revealed the benign pancreatic cysts and the pancreatic cancer harbors an own microbiome, Furthermore, the orointestinal microbiome can be exploited as a predictor for a pancreatic mass dignity. However, there is still a lack of knowledge whether the microbiome can predict the course of PCN. The aim of this prospective study was to investigate the orointestinal microbiome of patients with PCN and the association with the cyst entities, the Dutch-American risk stratification tool (DART-1) score and the presence of worrisome features in branch-duct intraductal papillary mucinous neoplasm (BD-IPMN). Buccal and rectal swab samples were prospectively collected to analyze the microbiome of patients with PCN. The microbiome was assessed by Oxford Nanopore sequencing technology (16S rRNA and metagenomics). Clinical data was collected with a standardized online questionnaire (RedCap). 78 patients have been enrolled in the study between January 2021 and December 2022. Alpha diversity metrics as the Observed Species, Shannon Index and Inverse-Simpson Index were determined and compared between the patients. Furthermore, the relative difference between these groups was shown and calculated using beta diversity distance metrics. The buccal microbiome of patients with BD-IPMN with worrisome features, as defined by the Fukuoka guidelines of 2017, revealed to harbor significantly different species compared to those without worrisome features. The rectal microbiome showed no significant differences between the two groups. In addition, a higher DART-1 score in patients with BD-IPMN was associated with significantly lower alpha diversity. No significant differences in the buccal or rectal microbiome were found between the cyst entities. The present study provides an opportunity to further research the microbiome as a biomarker for the progression of PCN.
Keywords: microbiome; pancreatic cystic neoplasm; worrisome features; Oxford Nanopore Technologies; intraductal papillary mucinous neoplasm