Near-infrared fluorescence-guided surgery : pre-clinical validation and clinical translation

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 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)UBL - phd migration 201

Chronic limb-threatening ischemia: when is enough enough?

Vascular Surger

Inaccurate risk assessment by the ACS NSQIP risk calculator in aortic surgery

Objectives: The aim of this retrospective study was to assess the predictive performance of the American College of Surgeons (ACS) risk calculator for aortic aneurysm repair for the patient population of a Dutch tertiary referral hospital. Methods: This retrospective study included all patients who underwent elective endovascular or open aortic aneurysm repair at our institution between the years 2013 and 2019. Preoperative patient demographics and postoperative complication data were collected, and individual risk assessments were generated using five different current procedural terminology (CPT) codes. Receiver operating characteristic (ROC) curves, calibration plots, Brier scores, and Index of Prediction Accuracy (IPA) values were generated to evaluate the predictive performance of the ACS risk calculator in terms of discrimination and calibration. Results: Two hundred thirty-four patients who underwent elective endovascular or open aortic aneurysm repair were identified. Only five out of thirteen risk predictions were found to be sufficiently discriminative. Furthermore, the ACS risk calculator showed a structurally insufficient calibration. Most Brier scores were close to 0; however, comparison to a null model though IPA-scores showed the predictions generated by the ACS risk calculator to be inaccurate. Overall, the ACS risk calculator showed a consistent underestimation of the risk of complications. Conclusions: The ACS risk calculator proved to be inaccurate within the framework of endovascular and open aortic aneurysm repair in our medical center. To minimize the effects of patient selection and cultural differences, multicenter collaboration is necessary to assess the performance of the ACS risk calculator in aortic surgery.Vascular Surger

Stent graft sizing for endovascular abdominal aneurysm repair using open source image processing software

Introduction: An important step to reach a favorable outcome of abdominal endovascular aneurysm repair (EVAR) is preoperative sizing of the stent graft using computed tomography angiography (CTA) images of the abdominal aorta. A variety of costly image processing software options is available to obtain the necessary aortic measurements. A package that can be used for EVAR sizing is OsiriX Lite (R)-an open source, freely downloadable image processing option. This study assesses the concurrent validity of OsiriX Lite (R) when compared with commercially available 3Mensio Vascular (R) and Siemens Syngo.via (R).Methods: CTA scans of 20 patients that underwent EVAR for abdominal aneurysm were selected, 10 elective and 10 ruptured. For each scan, 6 observers determined 20 parameters needed for proper stent graft sizing, 2 using Osirix Lite (R), 3 using 3Mensio Vascular (R), and 1 using Siemens Syngo.via (R). For each parameter, an intraclass correlation coefficient (ICC) and a P-value were calculated. Interrater agreement was interpreted using the Koo and Li Guidelines. Time needed to perform EVAR planning was compared.Results: Overall interrater agreement between the 3 sizing options was found to be either "good" or "moderate" for 16 out of 20 parameters (80%). Time needed to perform EVAR planning was not significantly different for Osirix Lite (R) (568 sec) when compared with 3Mensio Vascular (R) (603 sec) or Siemens Syngo.via (R) (659 sec) with a P-value of 0.88.Conclusions: The authors conclude that Osirix Lite (R) is an accurate and time-effective image processing option for preoperative sizing of an EVAR stent graft when matched to 3Mensio Vascular (R) and Siemens Syngo.via (R).Development and application of statistical models for medical scientific researc

Risk assessment in aortic aneurysm repair by medical specialists versus the American College of Surgeons National Surgical Quality Improvement Program risk calculator outcomes

Objective: The aim of this online clinical vignette-based survey study was to compare risk assessments by vascular surgeons, anaesthesiologists and interventional radiologists involved in treating patients with aortic aneurysms in the Netherlands with the NSQIP risk calculator outcomes.Methods: Participants, recruited using purposive sampling, provided their estimation of the likelihood of postoperative complications and events following aortic surgery in five fictional cases. These cases were subsequently scored using the NSQIP calculator. The risk assessments were statistically analysed using the ANOVA and student t-test.Results: All participating specialists i.e. twelve vascular surgeons, ten interventional radiologists and ten anaesthesiologists completed the survey. In the vast majority of outcomes and vignettes, no significant differences were found between various specialists, whereas significant differences were found between the NSQIP risk calculator outcomes and the combined risk assessments of the specialists. Overall, specialist risk assessments differ from the NSQIP, but neither particularly higher nor lower compared to the risk calculator.Conclusions: Risk assessment by vascular surgeons, anaesthesiologists and interventional radiologists differs significantly with NSQIP risk calculator outcomes, within the framework of both endovascular and open aortic aneurysm repair. Based on these results, implementing the NSQIP risk calculator in preoperative workup could be of added value in both patient planning as well as adequately informing patients for obtaining consent.Cardiovascular Aspects of Radiolog

Functional performance after complex endovascular aortic repair: a single-center retrospective cohort study

Purpose Complex endovascular aortic repair (EVAR) procedures provide a treatment option for patients with aortic aneurysms involving visceral branches. Good technical results and short-term outcomes have been reported. Whether complex EVAR provides acceptable functional outcomes is not clear. The current study aims to describe postoperative functional outcomes in complex EVAR patients-an older and relatively frail patient group. Materials and Methods A single-center retrospective cohort study was performed, using data from a computerized database of consecutive patients who underwent complex EVAR in the Leiden University Medical Center (LUMC, The Netherlands) between July 2013 and September 2020. As of May 2017, patients scheduled for complex EVAR were referred to a geriatric care pathway to determine (Instrumental) Activities of Daily Living ((I)ADL) scores at baseline and, if informed consent was given, after 12 months. For the total patient group, adverse functional performance outcomes were: discharge to a nursing home and 12-month mortality. For the patients included in geriatric follow-up, the additional outcome was the incidence of functional decline (defined by a >= 2 point increase in (I)ADL-score) at 12-month follow-up Results Eighty-two patients underwent complex EVAR, of which 68 (82.9%) were male. Mean age was 73.3 years (SD=6.3). Within 30 days postsurgery, 6 patients (7.3%) died. Mortality within 12 months for the total patient group was 14.6% (n=12). After surgery, no patients had to be discharged to a nursing home. Fifteen patients (18.3%) were discharged to a rehabilitation center. Twenty-three patients gave informed consent and were included in geriatric follow-up. Five patients (21.7%) presented functional decline 12 months postsurgery and 4 patients had died (17.4%) by that time. This means that 39.1% of the patients in the care pathway suffered an adverse outcome. Conclusion To our knowledge, this is the only study that examined functional performance after complex EVAR, using a prospectively maintained database. No patients were newly discharged to a nursing home and functional performance results at 12 months are promising. Future multidisciplinary research should focus on determining which patients are most prone to deterioration of function, so that efforts can be directed toward preventing postoperative functional decline.Cardiovascular Aspects of Radiolog

Perfusion patterns in patients with chronic limb-threatening ischemia versus control patients using near-infrared fluorescence imaging with indocyanine green

In assessing the severity of lower extremity arterial disease (LEAD), physicians rely on clinical judgements supported by conventional measurements of macrovascular blood flow. However, current diagnostic techniques provide no information about regional tissue perfusion and are of limited value in patients with chronic limb-threatening ischemia (CLTI). Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has been used extensively in perfusion studies and is a possible modality for tissue perfusion measurement in patients with CLTI. In this prospective cohort study, ICG NIR fluorescence imaging was performed in patients with CLTI and control patients using the Quest Spectrum Platform(R) (Middenmeer, The Netherlands). The time-intensity curves were analyzed using the Quest Research Framework. Fourteen parameters were extracted. Successful ICG NIR fluorescence imaging was performed in 19 patients with CLTI and in 16 control patients. The time to maximum intensity (seconds) was lower for CLTI patients (90.5 vs. 143.3, p = 0.002). For the inflow parameters, the maximum slope, the normalized maximum slope and the ingress rate were all significantly higher in the CLTI group. The inflow parameters observed in patients with CLTI were superior to the control group. Possible explanations for the increased inflow include damage to the regulatory mechanisms of the microcirculation, arterial stiffness, and transcapillary leakage.Cardiovascular Aspects of Radiolog

Perfusion parameters in near-infrared fluorescence imaging with indocyanine green: a systematic review of the literature

(1) Background: Near-infrared fluorescence imaging is a technique capable of assessing tissue perfusion and has been adopted in various fields including plastic surgery, vascular surgery, coronary arterial disease, and gastrointestinal surgery. While the usefulness of this technique has been broadly explored, there is a large variety in the calculation of perfusion parameters. In this systematic review, we aim to provide a detailed overview of current perfusion parameters, and determine the perfusion parameters with the most potential for application in near-infrared fluorescence imaging. (2) Methods: A comprehensive search of the literature was performed in Pubmed, Embase, Medline, and Cochrane Review. We included all clinical studies referencing near-infrared perfusion parameters. (3) Results: A total of 1511 articles were found, of which, 113 were suitable for review, with a final selection of 59 articles. Near-infrared fluorescence imaging parameters are heterogeneous in their correlation to perfusion. Time-related parameters appear superior to absolute intensity parameters in a clinical setting. (4) Conclusions: This literature review demonstrates the variety of parameters selected for the quantification of perfusion in near-infrared fluorescence imaging.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Cell-based tracers as Trojan horses for image-guided surgery

Surgeons rely almost completely on their own vision and palpation to recognize affected tissues during surgery. Consequently, they are often unable to distinguish between different cells and tissue types. This makes accurate and complete resection cumbersome. Targeted image-guided surgery (IGS) provides a solution by enabling real-time tissue recognition. Most current targeting agents (tracers) consist of antibodies or peptides equipped with a radiolabel for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), magnetic resonance imaging (MRI) labels, or a near-infrared fluorescent (NIRF) dye. These tracers are preoperatively administered to patients, home in on targeted cells or tissues, and are visualized in the operating room via dedicated imaging systems. Instead of using these ‘passive’ tracers, there are other, more ‘active’ approaches of probe delivery conceivable by using living cells (macrophages/monocytes, neutrophils, T cells, mesenchymal stromal cells), cell(-derived) fragments (platelets, extracellular vesicles (exosomes)), and microorganisms (bacteria, viruses) or, alternatively, ‘humanized’ nanoparticles. Compared with current tracers, these active contrast agents might be more efficient for the specific targeting of tumors or other pathological tissues (e.g., atherosclerotic plaques). This review provides an overview of the arsenal of possibilities applicable for the concept of cell-based tracers for IGS

Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts