For years, pancreatic cancer had a dismal prognosis with a long term survival of around 5%. Since the centralization of pancreatic cancer surgery and the introduction of systemic chemotherapy... Show moreFor years, pancreatic cancer had a dismal prognosis with a long term survival of around 5%. Since the centralization of pancreatic cancer surgery and the introduction of systemic chemotherapy with FOLFIRINOX, the median overall survival increased to around 20%. Radical tumor-margin free resection provides the patient with the best potential chance for cure. However, due to late onset of symptoms, the majority of patients present with inoperable disease. These patients can benefit from neoadjuvant therapy, or palliative chemotherapy. During clinical practice, this means that decision-making before and during surgery is critical to select the most optimal primary treatment modality. Currently, conventional imaging modalities lack sensitivity to detect small metastatic lesions, and are unable to visualize treatment response on neoadjuvant therapy. Tumor-specific molecular imaging in the form of fluorescence and photoacoustic imaging aids the surgeon to accurately recognize and resect malignant tissues in real-time during surgery. This thesis focuses on the challenges a surgeon faces during pancreatic cancer treatment, and the potential improvements that could be achieved by the use of tumor-specific imaging. In addition, the regulatory aspects of clinical translation of tumor-specific optical imaging agents are addressed. Show less
Surgery is the cornerstone of curative treatment of many malignancies. However, incomplete resections and avoidable iatrogenic damage during surgery increase morbidity and mortality rates in... Show moreSurgery is the cornerstone of curative treatment of many malignancies. However, incomplete resections and avoidable iatrogenic damage during surgery increase morbidity and mortality rates in patients. Although advances in preoperative imaging modalities have improved adequate patient selection and surgical planning, during procedures surgeons rely mainly on inspection and palpation. It is often very difficult to distinguish between fibrotic, inflamed, or malignant tissues [1]. Inspection and palpation are highly subjective and have low sensitivity for detecting cancer, especially for subcentimeter lesions [2].Near-infrared fluorescence (NIRF) imaging is a technique that enhances contrast of certain structures during surgery and thereby improves their detectability [3, 4]. It uses targeted and non-targeted fluorescent tracers in combination with dedicated NIRF imaging systems. These tracers consist of fluorophores; molecules that emit fluorescence with a certain wavelength upon excitation by an external light source. These fluorescence signals can be captured by an imaging system optimized for that specific wavelength. Especially near-infrared wavelengths (i.e. 700-900 nm) have excellent characteristics, including relatively high tissue penetration capacity and low tissue autofluorescence, and are therefore preferably used for clinical applications [5]. NIRF imaging can identify targets covered by up to 10 mm tissue.Non-targeted fluorescent tracers such as indocyanine green (ICG; emission peak 830 nm) and methylene blue (emission peak 700 nm) have been available for several decades, albeit for different indications. Their off-label use is safe and cheap, which contributed significantly to clinical experience and enabled NIRF imaging research to get momentum (chapter 2 and 3). NIRF imaging systems could be developed simultaneously with improved fluorophores. In general, NIRF-guided surgery has the potential to increase radical resection rates, while reducing avoidable iatrogenic damage. Both non-targeted as well as targeted tracers will be discussed, followed by the future perspectives of NIRF imaging.Non-specific Show less
