This thesis focused on risk factors and outcomes based on colorectal cancer auditing and aimed to provide new insights into outcome indicators, treatment modalities, and outcomes in high-risk... Show moreThis thesis focused on risk factors and outcomes based on colorectal cancer auditing and aimed to provide new insights into outcome indicators, treatment modalities, and outcomes in high-risk patients, and to monitor outcomes after implementation of minimally invasive surgery. Nationwide population-based studies with data of the Dutch ColoRectal Audit (DCRA) were used to provide information regarding colorectal cancer care on different levels (hospital, national, and international level) and in specific high-risk subpopulations. Show less
The studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS)... Show moreThe studies in this thesis contribute to more accurate risk assessment and prognosis prediction for DCIS and to better response evaluation of IBC treatment.For the Ductal Carcinoma In Situ (DCIS) studies, unbiased cohorts were used within the international Grand Challenge PRECISION consortium, funded by Cancer Research UK and KWF Dutch Cancer Society. DCIS is graded as low-, intermediate-, or high-grade depending on how abnormal the DCIS-cells look like. However, we showed that pathologists often disagree on grade. To overcome this limitation, we found that almost all DCIS scored as non-high-grade by the majority of pathologists express the estrogen receptor (ER) and are negative for the growth factor receptor HER2, whereas high-grade DCIS is mixed in expression for ER and HER2. We also provided insights in the recurrence risks of DCIS after treatment. See also https://cancergrandchallenges.org/teams/precision.The studies on Invasive Breast Cancer (IBC) were performed on a hospital-based cohort. We found for example substantial variation in tumour response evaluation for HER2-positive IBC after pre-operative chemotherapy due to different guidelines used. For accurate outcome analysis, reducing such variation is mandatory. Therefore, we are working on reaching international consensus of response evaluation. Show less
As with all cancer screening programmes, the expected reduction in cancer cases and deaths must be weighed against the burden of screening and possible side effects. The aim of this thesis is to... Show moreAs with all cancer screening programmes, the expected reduction in cancer cases and deaths must be weighed against the burden of screening and possible side effects. The aim of this thesis is to provide insights in consequences of colorectal cancer screening participation from a surgical perspective. We investigated potential harm in terms of serious morbidity from colonoscopy, additional findings on imaging, and psychological impacts following a positive faecal immunochemical test (FIT) result. Second, studies were performed to gain more in-depth insight into surgical referral patterns for benign colorectal lesions and CRC lesions with only submucosal invasion (pT1), thereby contributing to the understanding of whether early diagnosis following CRC screening results in better surgical outcomes. Third, surgical outcomes of screen-detected patients were compared with symptomatic patients. Show less
This thesis focus on the quality assurance in the surgical treatment of gastric cancer. This has been investigated using data of the CRITICS trial. In this randomized clinical patients underwent... Show moreThis thesis focus on the quality assurance in the surgical treatment of gastric cancer. This has been investigated using data of the CRITICS trial. In this randomized clinical patients underwent preoperative chemotherapy, followed by surgery, followed by adjuvant chemotherapy or chemoradiotherapy. Surgical quality in the CRITICS trial was investigated and was excellent (PART I). Furthermore, the influence of hospital volume on surgical quality and survival was analyzed using data of the CRITICS trial (PART II). Surgery performed in hospitals with high hospital volume was associated with better surgical quality and better survival. In part III of this thesis analyses were performed to analyze treatment strategy and survival in patients with resectable gastric cancer and in patients with metastatic gastric cancer. Show less
Bone metastases of the long bones can cause pain and pathologic fractures. Local treatment consists of radiotherapy or surgical stabilisation. The most appropriate treatment depends on many factors... Show moreBone metastases of the long bones can cause pain and pathologic fractures. Local treatment consists of radiotherapy or surgical stabilisation. The most appropriate treatment depends on many factors, including the symptoms, the location and extent of the lesion, the wishes and expectations of the patient, and the expected remaining survival. Survival estimation of patients with symptomatic long bone metastases is crucial to prevent over- and undertreatment. This thesis aimed to develop a prognostic model for estimating survival in patients with cancer and symptomatic metastases of the long bones, evaluate current (surgical) treatment modalities and trends, and provide rationale for future prospective randomized trials. As a result, the OPTIModel was developed: an easy-to-use prognostic model that categorises patients into four clinically relevant survival categories based on only three variables (tumour type, Karnofsky Performance Score, visceral/brain metastases). To enable easy use of the model, an app was created (OPTIModel). Futhermore, this thesis shows that almost all treatments of pathologic fractures are based on expert opinion and small, retrospective cohorts, as opposed to large, prospective (randomized) trials, which is interesting in an era of evidence based medicine. This confirms the need of a prospective, multicenter cohort, which was designed and implemented accordingly. Show less
Intraoperative imaging using near-infrared (NIR) fluorescence is a fast developing imaging modality as it provides real-time visual information during surgery (Chapter 1). The ability to detect... Show moreIntraoperative imaging using near-infrared (NIR) fluorescence is a fast developing imaging modality as it provides real-time visual information during surgery (Chapter 1). The ability to detect lymph nodes and tumours that need to be resected can assist the surgeon to improve surgery by reducing time of the procedure, reducing iatrogenic damage, and improve the number of radical resections. This thesis focuses on the introduction of NIR fluorescence imaging into the clinic. Part 1 of this thesis describes the optimization of NIR fluorescence imaging for sentinel lymph node (SLN) biopsy using the clinically available NIR tracer Indocyanine green (ICG) in various cancer types. Moreover, these studies show both the limitations as the clinical benefit of NIR fluorescence for SLN biopsy. Part 2 describes the use of NIR light for tumour detection. Tissue absorption and scattering in the NIR light spectrum was used for neoadjunvant treatment response monitoring in breast cancer patients. Moreover, NIR fluorescence imaging using NIR contrast agents was used for the intraoperative detection of otherwise difficult to localize liver metastases of colorectal cancer. Show less
Fluorescence-guided surgery (FGS) is an intraoperative imaging technique already introduced and validated in the clinic for sentinel lymph node mapping and biliary imaging. Conjugating a NIR... Show moreFluorescence-guided surgery (FGS) is an intraoperative imaging technique already introduced and validated in the clinic for sentinel lymph node mapping and biliary imaging. Conjugating a NIR-dye to a specific tumor-targeting vehicle dramatically enhances the specificity of this technique. Hence, a powerful synergy can be achieved when fluorescent imaging is combined with nuclear imaging. The (NIR) fluorescent signal aids the surgeon to accurately recognize and resect malignant tissues and detect (nearby) vital structures in real-time during surgery, while its nuclear counterpart can be used to preoperative assess tumor spread and aid in the surgical planning and guidance. Patients may benefit directly from better tumor detection as the surgical status (R0 or R1) is one of the most import parameters for morbidity and patient survival. This thesis focus on the evaluation of potential targets for image-guided surgery applications and describes the preclinical evaluation of novel tracers for (hybrid) image-guided surgery. Show less
This thesis shows that quality of colorectal cancer care is irrevocably associated with hospital costs. Although surgical auditing is a cost and time-consuming exercise, it has a strong potential... Show moreThis thesis shows that quality of colorectal cancer care is irrevocably associated with hospital costs. Although surgical auditing is a cost and time-consuming exercise, it has a strong potential to improve outcomes in healthcare and simultaneously reduce hospital costs. Comparing hospital performances on both quality and costs makes identification of ‘best practice’ hospitals possible. Moreover, providing combined quality-cost outcomes of frail patients or operation techniques provides valuable insights where to start quality improvement initiatives. Finally, rewarding healthcare providers based on operative risk could be a first step in developing powerful reimbursement systems. This all might catalyze the continuous improvement of value leading to a more sustainable healthcare system in the future. Show less
The work described in this thesis shows how intraoperative lesion identification can be improved via the introduction of (hybrid) tracers and optimised (hybrid) imaging modalities capable... Show more The work described in this thesis shows how intraoperative lesion identification can be improved via the introduction of (hybrid) tracers and optimised (hybrid) imaging modalities capable of detecting this tracers. In part one, the reader is introduced to the concept of fluorescence image-guided surgery and the evolution thereof. Furthermore the hybrid approach for image-guided surgical guidance is presented. Part two describes the clinical evaluation of the hybrid approach using the hybrid tracer indocyanine green-technetium 99m-nanocolloid. To further refine the hybrid approach for surgical guidance, part three of this thesis describes the development and evaluation of different types of (hybrid) imaging modalities. Show less
