Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study.

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

Dynamic magnetic resonance imaging to quantify pelvic organ prolapse: reliability of assessment and correlation with clinical findings and pelvic floor symptoms.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the interobserver agreement of magnetic resonance imaging (MRI)-based staging of pelvic organ prolapse (POP) and to quantify associations between MRI-based POP staging, findings at pelvic examination, and pelvic floor symptoms. METHODS: This was a cross-sectional study of ten symptomatic POP patients, ten symptomatic patients without POP, and ten nulliparous asymptomatic women. Three different observers performed MRI-based POP staging using the pubococcygeal line (PCL), midpubic line (MPL), perineal line, and H line as references. RESULTS: The interobserver agreement of MRI-based staging of the anterior and middle compartment was good to excellent. In symptomatic women without prolapse, MRI-based and pelvic-examination-based POP staging were poorly correlated. In none of the women were MRI-based POP Quantification (POP-Q) staging and pelvic floor symptoms strongly associated. CONCLUSION: The interobserver agreement of MRI-based POP staging is excellent, but the added clinical value of such staging is questionable due to poor association with clinical findings and pelvic floor symptoms.

Coordinate reduction in cell proliferation and cell death in mouse olfactory epithelium from birth to maturity.

We investigated cell proliferation and cell death in the olfactory epithelium (OE) of mice from birth to maturity using bromodeoxyuridine and terminal deoxynucleotidyl transferase nick end labeling. We show that cell death events and proliferative activity diminish concomitantly with age in the OE. Thus, the age-dependent and coordinate diminution in cell proliferative activity and cell death events may serve to maintain the thickness of the OE as mice mature and age.

The cellular and molecular biology of medulloblastoma.

Medulloblastomas are prototypical of primitive neuroectodermal tumors which are some of the most frequent malignant brain tumors of childhood. The cell biology of medulloblastomas is still poorly understood, but recent studies of the expression of trophic factors and their receptors in medulloblastomas and the development of animal models of primitive neuroectodermal tumors may provide clues as to the induction or progression of these tumors. For example, they could clarify mechanisms that regulate cell death, proliferation and differentiation in these tumors.

Integrins and extracellular matrix-proteins in the different components of the Wilms' tumour.

The Wilms' tumour (WT) is composed of blastema, epithelium and mesenchyme; the epithelium and possibly also the mesenchyme develop from the blastema, parallel to embryonal development. Since interactions between cell adhesion receptors and extracellular matrix (ECM) proteins play an important role in tissue maturation, we examined the expression of the integrin subunits alpha 1-alpha 6, beta 1 and beta 4, and of the ECM proteins fibronectin, laminin and collagen I and IV, in 20 frozen WT samples and in 5 fetal and 2 adult kidneys. The integrin and ECM protein distribution in tumour epithelium and mesenchyme showed strong similarities to that in their fetal counterparts, whereas the tumour blastema differed strongly from the fetal blastema. In the WT blastema different components were recognized. Undifferentiated blastema, characterized by expression of alpha 3 and alpha 6 and the virtual absence of ECM proteins. Blastema with epithelial commitment, showing increased expression of alpha 3 and alpha 6 and the appearance of alpha 2 and, as a very early phenomenon, production of laminin. Blastema with mesenchymal commitment, with loss of alpha 3 and alpha 6 and expression of alpha 1, alpha 4 and alpha 5 and presence of ECM proteins. It is speculated that the inability of the (undifferentiated) blastema to produce ECM proteins is related to its relatively high metastatic potential when compared with epithelium and mesenchyme.