Pancreatic cancer is an aggressive cancer associated with a poor prognosis as a large proportion of these patients have locally advanced disease or metastases at the time of diagnosis. Currently... Show morePancreatic cancer is an aggressive cancer associated with a poor prognosis as a large proportion of these patients have locally advanced disease or metastases at the time of diagnosis. Currently onlypatients with localized pancreatic tumors can undergo surgery, which is the cornerstone in thetreatment of pancreatic cancer, whether or not preceded by neoadjuvant (chemo/radio)therapy. To establish the diagnosis, imaging techniques are used, tumor tissue must be obtained, and certain tumor markers can be determined in the blood. During surgery, the tumor must be removed in its entirety to prevent early recurrence. This thesis describes the potential role of tumor markers, which can be determined in the blood, and several experimental optical imaging techniques applied to pancreatic cancer. Show less
This thesis includes studies on how to measure and improve the quality of care for hip fracture patients in The Netherlands. Several determinants of quality of care such as treatment and outcomes... Show moreThis thesis includes studies on how to measure and improve the quality of care for hip fracture patients in The Netherlands. Several determinants of quality of care such as treatment and outcomes are studied, as well as the maturation of the Dutch Hip Fracture Audit (DHFA); a quality of care registry including all adult patients suffering a hip fracture in The Netherlands. Show less
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 ageing of the world’s population requires new methods to prevent adverse outcomes such as delirium in older patients after surgery. Delirium is an expression of depleted reserves, which in turn... Show moreThe ageing of the world’s population requires new methods to prevent adverse outcomes such as delirium in older patients after surgery. Delirium is an expression of depleted reserves, which in turn decreases a patient’s resilience and makes a patient more frail. It may be triggered due to precipitating risk factors that shift the balance and overflow a patient’s resilience. A systematic review and meta-analysis demonstrated that delirium can be prevented by implementing multicomponent interventions. Therefore, a new multicomponent prehabilitation intervention was designed. The incidence of delirium was successfully reduced by implementing this prehabilitation program, however no effects were seen on all other short-term outcomes. On the long term, postoperative delirium increases the risk of 1-year mortality over 4 times and is associated with decreased functional outcomes after 6 and 12 months. Moreover, surgery and subsequent delirium affect the quality of life of patients and caregivers and may lead to depressive symptoms. Faster return to preoperative functioning may therefore be key to a faster return to preoperative quality of life. Future perioperative care pathways focusing on delirium prevention, optimisation and fast return to baseline functioning after surgery, should begin prior to hospital admission and end long after discharge. 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
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
In the last two decades, treatment of rectal cancer has considerably improved in Europe. Although this applies to most solid malignancies, improvements in the diagnosis and treatment of rectal... Show moreIn the last two decades, treatment of rectal cancer has considerably improved in Europe. Although this applies to most solid malignancies, improvements in the diagnosis and treatment of rectal cancer surpass virtually all others. In the early 1990s, outcome after rectal cancer treatment was poor, with survival and recurrence rates of approximately 45%.1 Nowadays, survival after rectal cancer is sometimes even better than after colon cancer.2 While radiotherapy and chemoradiotherapy play an important role in the current, multidisciplinary treatment of rectal cancer, surgery remains the inevitable cornerstone for cure. For each and every improvement in surgical techniques, (neo)adjuvant treatment schedules, imaging and pathology, clinical trials and population-based audit registrations have played a crucial role. The aim of this thesis is to contribute to further improvements in rectal cancer treatment by investigating the multidisciplinary treatment forms, quality control and European collaboration. Show less
In the first part an update of a guideline for the physiotherapy treatment of patients with hip and knee OA is described. Then a set of quality indicators for the physiotherapy management is... Show moreIn the first part an update of a guideline for the physiotherapy treatment of patients with hip and knee OA is described. Then a set of quality indicators for the physiotherapy management is developed to be used as an instrument to measure guideline adherence. Subsequently the effect of educational strategies to enhance their uptake by physiotherapists in daily clinical practice is investigated. An interactive approach with patient colaboration and following a proces of clinical reasoning has shown to be the most effective strategy. The second part describes the extent of the provision of physiotherapy before and after joint replacement surgery from the physiotherapists__ and patients__ perspective. Results showed a large variation in provided interventions before and after surgery, although evidence for physiotherapy before joint replacement surgery is lacking. This indicates that more research is necessary focussing on effectiveness for specific groups of patients. In addition it was concluded that the presence of severe back pain in THA and dizziness in THA and TKA, should maybe ascertained before surgery and if present be treated if possible in order to decrease the chance of unfavourable outcome, although the predictive value of dizziness should be confirmed in a study with a prospective design. Show less
Data from clinical audits such as the Dutch Surgical Colorectal Audit, can be used for valid and meaningful feedback information, which may support improvement of quality of care. First, we showed... Show moreData from clinical audits such as the Dutch Surgical Colorectal Audit, can be used for valid and meaningful feedback information, which may support improvement of quality of care. First, we showed that the continuous feedback cycle of clinical auditing has an autonomous, positive effect on the quality of surgical care. Second, we describe how data from clinical audits can be used to monitor and improve national practice and performance in colorectal cancer care, especially for high-risk patients. Third, we describe how clinical auditing can be used for the evaluation and monitoring of the implementation of new techniques, such as laparoscopic surgery, on a national level. We demonstrate that, although there is a large hospital variation in the use of laparoscopic surgery, this does not explain the variation in outcome. Last, we investigate how data can be used to evaluate quality of care and give transparency to all stakeholders. As the various aspects of quality of care can be strongly interrelated, quality of care may best be represented using composite-measures. These composite measures can be used by all stakeholders to evaluate quality of care as a whole. The methodologies described in this thesis may be used in many other clinical audits. Show less
This thesis focus on preclinical validation of novel fluorescent contrast agents for solid tumor imaging (Part I), the clinical introduction of NIR fluorescence sentinel lymph node imaging in... Show moreThis thesis focus on preclinical validation of novel fluorescent contrast agents for solid tumor imaging (Part I), the clinical introduction of NIR fluorescence sentinel lymph node imaging in several cancer types using indocyanine green (Part II) and the clinical translation of NIR fluorescence imaging using clinically available fluorescent contrast agents for solid tumor imaging (Part III) Show less
Colorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain.... Show moreColorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain. For example among certain subgroups of patients, such as elderly patients and patients with comorbidities. Besides, inequalities in the quality of care between European countries remain. Quality control on surgery, radiotherapy, and pathology have been introduced in trials, followed by incorporation in the general care. Another option to incorporate improved quality of care is via an audit structure in which hospitals and clinicians can improve their results by learning from their own outcome statistics and those from colleagues treating a similar patient group. Although all these audit structures have achieved excellent results within countries, differences in outcome between European countries remain. A next step will b e to combine these national audits. The combined audit structure will provide a network in which __best practices__ can be compared and identified, including for certain subgroups, which has been initiated as European Registration of Cancer Care (EURECCA). To achieve optimal care for all patients, multidisciplinary care is the only way. By comparing multidisciplinary audit structures across countries, optimal treatment strategies within subgroups can be identified Show less
Quality of care- and of surgical oncology in particular- is gaining momentum. In this thesis the scientific bases of minimal volume standards and quality indicators are evaluated. Also the impact... Show moreQuality of care- and of surgical oncology in particular- is gaining momentum. In this thesis the scientific bases of minimal volume standards and quality indicators are evaluated. Also the impact of centralization of pancreatic surgery is investigated as is the influence of comorbidity on patient outcomes after colorectal surgery Show less
Pati_nten met een degeneratieve ruptuur van de rotatorcuff vormen een uitdagend probleem voor de behandeld specialist in de besluitvorming met betrekking tot in de behandelstrategie. De opzet van... Show morePati_nten met een degeneratieve ruptuur van de rotatorcuff vormen een uitdagend probleem voor de behandeld specialist in de besluitvorming met betrekking tot in de behandelstrategie. De opzet van dit proefschrift was om beter inzicht te cre_ren in de evaluatie, klinische uitkomst en chirurgische behandeling van degeneratieve rotatorcuffrupturen. In Hoofdstuk 3 wordt de overeenstemming in de beoordeling van de Geometrische Classificatie van cuffrupturen door ervaren beoordelaars onderzocht met behulp van MR beeldvorming met artrografie. In Hoofdstuk 4 wordt een nieuwe methode ge_ntroduceerd om pati_nten met een symptomatische cuffruptuur te onderscheiden van mensen met een asymptomatisch ruptuur middels de kwalificatie van de adductor co-activatie tijdens schouderabductie. In Hoofdstuk 5 werd de associatie onderzocht van de ernst van de ziekte activiteit van reumatoide arthritis en kraakbeenschade, rotatorcuffrupturen en opwaartse migratie van de schouderkop. In Hoofdstuk 6 werd een gerandomiseerde studie uitgevoerd naar de klinische resultaten van een volledig artroscopische versus mini-open behandeling van rotatorcuffrupturen bij 100 pati_nten. In Hoofdstuk 7 werden de klinische uitkomsten en structurele integriteit op postoperatieve MRI onderzocht van volledig artroscopische behandeling van subscapularispeesr upturen. Het doel van Hoofdstuk 8 was de introductie en evaluatie van een nieuwe artroscopische techniek voor de behandeling van massieve cuffrupturen. In Hoofdstuk 9 werd de grootste serie uit de orthopaedische literatuur beschreven van teres major peestransposities. Show less
Surgery always concerns the balance of risk and benefit. Both risk and benefit can vary immensely among patients. Outcome and prognosis are determined by several patient, tumour and treatment... Show moreSurgery always concerns the balance of risk and benefit. Both risk and benefit can vary immensely among patients. Outcome and prognosis are determined by several patient, tumour and treatment characteristics. In order to achieve the best possible outcomes for colorectal cancer patients, detailed and objective information on risk profiles is indispensible. For the individual patient it should guide clinical judgment and the administration of tailored care. On a hospital or population level knowledge of risk factors can lead to adjusted (better tailored) treatment protocols and better information on case mix influences adding to an improved care for colorectal cancer patients. Show less
The aim of this thesis is to evaluate the effect of doxycycline on the proteolytic and inflammatory processes in abdominal aneurysms. This data is essential for the development of pharmaceutical... Show moreThe aim of this thesis is to evaluate the effect of doxycycline on the proteolytic and inflammatory processes in abdominal aneurysms. This data is essential for the development of pharmaceutical strategies for the stabilization of an AAA. Such an approach could reduce the need for elective surgery and endovascular repair. It has repeatedly been shown that AAA progression and rupture is related to the failure of collagen in the aortic wall. Yet the exact mechanism underlying this failure remains unknown. Furthermore, the precise mechanism of activation of collagenases and their inflammatory mediators that are responsible for the collagen turnover of AAA are unknown. In this thesis we attempt to determine how collagen metabolism is balanced in aneurysmal diseases and contribute to the knowledge which collagenases and inflammatory mediators are involved in the destruction of the collagen network in AAA disease. Moreover, we evaluate some of the effects of doxycycline on the proteases and inflammatory mediators in AAA. Analyses showed that doxycycline inhibits specific MMPs and inflammatory pathways that are involved in the collagen balance and aneurysm growth. Together, these observations provide a rationale for a randomized clinical trial studying the effect of doxycycline on aneurysm growth. Show less
This thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to... Show moreThis thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to achieve improved surgical options and to assess tumor response. We also demonstrated that overexpression of the breast cancer stem cell marker aldehyde dehydrogenase-1 in early stage breast cancer patients is inversely associated with age and is of prognostic importance. In part II, we have demonstrated proof-of-principle of intraoperative tumor detection and image-guided tumor resection by using the novel technique of near-infrared fluorescence imaging. We have performed two clinical trials to optimize the use of indocyanine green as a near-infrared fluorescence lymphatic tracer for the sentinel lymph node procedure in breast cancer patients. Show less
This thesis evaluates, using various methods, two important surgical procedures currently used in heart failure patients: surgical ventricular restoration and restrictive mitral annuloplasty. The... Show moreThis thesis evaluates, using various methods, two important surgical procedures currently used in heart failure patients: surgical ventricular restoration and restrictive mitral annuloplasty. The conductance catheter was used to analyze the hemodynamic effects of heart failure surgery invasively. It demonstrated improvement in systolic function of the left ventricle for both procedures at long term follow-up. Diastolic function demonstrated signs of impairment, although the functional effect remained limited, regarding limited or no increase in left ventricular end-diastolic pressure for SVR and RMA, respectively. Furthermore, assessment of left ventricular volumes demonstrated persistent reverse remodeling at follow-up. Clinical performance demonstrated significant improvement for both surgical procedures. The hemodynamic results together with the positive clinical outcome for both surgical procedures supports the use of these procedures in end-stage heart failure patients. Regarding the fact that using the conductance catheter is time consuming and can be burdensome for patients, a demand for less invasive methods was generated. Evaluation of alternative methods demonstrated that heart failure surgery can also be evaluated by single-beat analysis, a simplified method of the conventional conductance catheter method avoiding load interventions by temporary vena cava occlusions. Furthermore, echocardiography and to a certain extent, serum biomarker analysis can also be used. Show less
