PhD Defence Danique Heuvelings

Keywords: Anastomotic leakage, fluorescence imaging, colorectal surgery complication, peritoneal metastases
 

"Transforming Outcomes in Colorectal Surgery"

The first part of this thesis focuses on the reporting of AL after CRC surgery. Chapter 2 is a systematic review that focuses on the use of different AL definitions in high-level evidence literature (randomized controlled trials, systematic reviews, and meta-analyses) and additional reported elements that are related to AL. In this chapter, we also highlight the importance of standardized reporting of AL. Subsequently, Chapter 3 reflects an international consensus project, in which the overview of current evidence regarding colorectal AL is presented, followed by a reporting framework to standardize reporting of colorectal AL after oncological surgery. As radiological assessment of AL plays a key role in the diagnostic phase, Chapter 4 displays a study protocol for the development of a radiological scoring system that can be used to assess AL on CT-scans and to radiologically report its assessment in a standardized way.  

Part II of this thesis provides insights into bowel perfusion assessment to reduce the risk of AL. Chapter 5 is a feasibility study in a porcine model which evaluates a new imaging system that is able to visualize both MB and ICG. This study illustrates the use of MB for both ureter visualization and bowel perfusion assessment. Subsequently, Chapter 6 is a quantification analysis in which MB and ICG are compared in a porcine model using ischemic bowel loops. Chapter 7 highlights the clinical implications of LSCI by performing a porcine experiment on anastomotic site selection. In this study, we demonstrate how LSCI can provide valuable real-time feedback on intestinal tissue perfusion during surgery. Chapter 8 is a preclinical validation of LSCI for bowel perfusion assessment in a porcine model. In this quantification study, we perform a correlation analysis between laser speckle units and local lactate levels in ischemic bowel loops and assess inter-observer variability. In addition,  

The third part of this thesis gives insights into the patients’ perspective on AL after CRC surgery. Chapter 9 is a systematic review that provides an overview of current literature on the impact on the QoL of patients after AL. In this chapter, we also give additional recommendations on how to improve future AL research in relation to QoL. In Chapter 10, a qualitative interview study provides an insight into patients’ experiences after developing an AL. In addition to summarizing the identified interview themes, we emphasize the key factors highlighted by patients that can directly enhance clinical practice and improve patient outcomes. 

Part IV of this thesis describes potentials to reduce the risk of developing PM by considering prophylactic interventions in patients who are at risk. Chapter 11 provides an overview of current knowledge on specific biomarkers in the primary colorectal tumor that could serve as a prediction tool to estimate the risk of distant peritoneal spread. Chapter 12 is an explorative study in which primary colorectal tumor samples are analyzed to identify specific DNA and/or RNA that may predict metachronous PM after curative resection. As intraperitoneal administration of cytostatic loaded hydrogels is a promising preventive strategy for patients who have a high risk of developing metachronous PM, we evaluate the safety of a certain intervention in Chapter 13. This evaluation describes the effect of an intraperitoneal mitomycin-loaded hydrogel on anastomotic healing in a rodent model, based AL scores, adhesion scores and microscopic evaluation. 

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