Improving patient selection towards personalized treatment decisions in esophageal cancer

Om de overleving van patiënten met een lokaal gevorderd slokdarmcarcinoom te verbeteren worden patiënten behandeld met chemoradiotherapie alvorens geopereerd te worden. Echter, niet iedereen heeft baat bij deze neoadjuvante chemoradiotherapie (nCRT). Het doel van dit promotieonderzoek was om de selectie en behandeling van patiënten met slokdarmkanker te verbeteren en zo toe te werken naar een gepersonaliseerde behandeling. In dit proefschrift werd aangetoond dat endoechografie de behandeling in 29% van de patiënten beïnvloedde na stadiering met een 18F-FDG PET/CT-scan. Echter, zelfs na stadiëring met deze beeldvormende technieken bleek de beoordeling van lymfekliermetastasen vaak inaccuraat. Re-stadiëring na nCRT en vóór de slokdarmoperatie met CT-scans bleek nuttig, maar matig effectief, waarbij op basis van literatuuronderzoek een prominentere rol blijkt te zijn weggelegd voor 18F-FDG PET/CT-scans. In een gepersonaliseerde behandeling is naast een adequate stadiëring, een goede inschatting welke patiënt baat heeft bij nCRT onmisbaar. Hoewel uitbreiding van traditionele inclusiecriteria voor nCRT niet tot een toename van bijwerkingen en mortaliteit leidde, was de overleving wel significant lager. Daarnaast veranderde nCRT de prognostische waarde van een vrije circumferentiële resectie marge op de overleving. Patiënten met een pathologisch complete respons (pCR: 25-42%) zouden in de toekomst mogelijk voordeel hebben bij een ‘wait-and-see’ beleid. In dit proefschrift werd aangetoond dat textural features, verkregen uit PET/PET-CT-scans, waardevol zijn in de predictie van pCR. Tot slot bleek in een pilotstudie dat diffusie gewogen magnetic resonance imaging (DW-MRI) van additionele waarde was op de standaard 18F-FDG PET/CT-scan in de detectie van pCR

Mass-Forming Portal Biliopathy Presenting as Extreme Wall-Thickening of the Common Bile Duct

Portal biliopathy refers to biliary tree abnormalities in patients with peribiliary collateral vessels and non-neoplastic extrahepatic portal vein occlusion. These biliary abnormalities are caused by vascular compression and ischemic damage of the biliary tree, which can result in bile duct compression, stenosis, fibrotic strictures, bile duct dilation, and thickening of the bile duct wall. Portal biliopathy is difficult to distinguish from cholangiocarcinoma, IgG4-related disease, and sclerosing cholangitis. Although most patients are asymptomatic, portal biliopathy can lead to serious complications, such as recurrent cholangitis. This case illustrates the importance of including portal biliopathy in the differential diagnosis at an early stage, especially in patients with portal hypertension. With early recognition, the need for additional invasive diagnostic procedures such as biopsies is minimized. Pathogenesis, clinical presentation, diagnostics, and treatment options of portal biliopathy are described in the article

Motor Network Degeneration in Amyotrophic Lateral Sclerosis: A Structural and Functional Connectivity Study

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by motor neuron degeneration. How this disease affects the central motor network is largely unknown. Here, we combined for the first time structural and functional imaging measures on the motor network in patients with ALS and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Structural measures included whole brain cortical thickness and diffusion tensor imaging (DTI) of crucial motor tracts. These structural measures were combined with functional connectivity analysis of the motor network based on resting state fMRI. Focal cortical thinning was observed in the primary motor area in patients with ALS compared to controls and was found to correlate with disease progression. DTI revealed reduced FA values in the corpus callosum and in the rostral part of the corticospinal tract. Overall functional organisation of the motor network was unchanged in patients with ALS compared to healthy controls, however the level of functional connectedness was significantly correlated with disease progression rate. Patients with increased connectedness appear to have a more progressive disease course. CONCLUSIONS/SIGNIFICANCE: We demonstrate structural motor network deterioration in ALS with preserved functional connectivity measures. The positive correlation between functional connectedness of the motor network and disease progression rate could suggest spread of disease along functional connections of the motor network

Effect of Extending the Original CROSS Criteria on Tumor Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients:A National Multicenter Cohort Analysis

BACKGROUND: Extending the original criteria of the Chemoradiotherapy for Oesophageal Cancer followed by Surgery Study (CROSS) in daily practice may increase the treatment outcome of esophageal cancer (EC) patients. This retrospective national cohort study assessed the impact on the pathologic complete response (pCR) rate and surgical outcome. PATIENTS AND METHODS: Data from EC patients treated between 2009 and 2017 were collected from the national Dutch Upper Gastrointestinal Cancer Audit database. Patients had locally advanced EC (cT1/N+ or cT2-4a/N0-3/M0) and were treated according to the CROSS regimen. CROSS (n = 1942) and the extended CROSS (e-CROSS; n = 1359) represent patients fulfilling the original or extended CROSS criteria, respectively. The primary outcome was total pCR (ypT0N0), while secondary outcomes were local esophageal pCR (ypT0), surgical radicality, and postoperative morbidity and mortality. RESULTS: Overall, CROSS and e-CROSS did not differ in total or local pCR rate, although a trend was observed (23.2% vs. 20.4%, p = 0.052; and 26.7% vs. 23.8%, p = 0.061). When stratifying by histology, the pCR rate was higher in the CROSS group compared with e-CROSS in squamous cell carcinomas (48.2% vs. 33.3%, p = 0.000) but not in adenocarcinomas (16.8% vs. 16.9%, p = 0.908). Surgical radicality did not differ between groups. Postoperative mortality (3.2% vs. 4.6%, p = 0.037) and morbidity (58.3% vs. 61.8%, p = 0.048) were higher in e-CROSS. CONCLUSION: Extending the CROSS inclusion criteria for neoadjuvant chemoradiotherapy in routine clinical practice of EC patients had no impact on the pCR rate and on radicality, but was associated with increased postoperative mortality and morbidity. Importantly, effects differed between histological subtypes. Hence, in future studies, we should carefully reconsider who will benefit most in the real-world setting

Magnetic resonance imaging of the coronary arteries: clinical results from three dimensional evaluation of a respiratory gated technique

BACKGROUND: Magnetic resonance coronary angiography is challenging because of the motion of the vessels during cardiac contraction and respiration. Additional challenges are the small calibre of the arteries and their complex three dimensional course. Respiratory gating, turboflash acquisition, and volume rendering techniques may meet the necessary requirements for appropriate visualisation. OBJECTIVE: To determine the diagnostic accuracy of respiratory gated magnetic resonance imaging (MRI) for the detection of significant coronary artery stenoses evaluated with three dimensional postprocessing software. METHODS: 32 patients referred for elective coronary angiography were studied with a retrospective respiratory gated three dimensional gradient echo MRI technique. Resolution was 1.9 x 1.25 x 2 mm. After manual segmentation three dimensional evaluation was performed with a volume rendering technique. RESULTS: Overall 74% (range 50% to 90%) of the proximal and mid coronary artery segments were visualised with an image quality suitable for further analysis. Sensitivity and specificity for the detection of significant stenoses were 50% and 91%, respectively. CONCLUSIONS: Volume rendering of respiratory gated MRI techniques allows adequate visualisation of the coronary arteries in patients with a regular breathing pattern. Significant lesions in the major coronary artery branches can be identified with a moderate sensitivity and a high specificity

MR coronary angiography with breath-hold targeted volumes: preliminary clinical results

PURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. MATERIALS AND METHODS: Thirty-eight patients referred for elective coronary angiography were included. The coronary arteries were localized during single-breath-hold, three-dimensional imaging of the entire heart. MR coronary angiography was then performed along the major coronary branches with a double-oblique, three-dimensional, gradient-echo sequence. Conventional coronary angiography was the reference-standard method. RESULTS: Adequate visualization was achieved with MR coronary angiography in 85%-91% of the proximal coronary arterial branches and in 38%-76% of the middle and distal branches. Overall, 187 (69%) of 272 segments were suitable for comparison between conventional and MR coronary angiography. The diagnostic accuracy of MR coronary angiography for the detection of hemodynamically significant stenoses was 92%; sensitivity, 68%; and specificity, 97%. The sensitivity in individual segments was 50%-77%, whereas the specificity was 94%-100%. CONCLUSION: Adequate visualization of the major coronary arterial branches was possible in the majority of patients. The observed accuracy of MR coronary angiography for detection of hemodynamically significant coronary arterial stenosis is promising, but it needs to be higher before this modality can be used reliably in a clinical setting