Christine Hartmann | Search PubMed

PubMed2002

Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor.

The low-density lipoprotein receptor-related protein (Lrp)-5 functions as a Wnt coreceptor. Here we show that mice with a targeted disruption of Lrp5 develop a low bone mass phenotype. In vivo and in vitro analyses indicate that this phenotype becomes evident postnatally, and demonstrate that it is secondary to decreased osteoblast proliferation and function in a Cbfa1-independent manner. Lrp5 is expressed in osteoblasts and is required for optimal Wnt signaling in osteoblasts. In addition, Lrp5-deficient mice display persistent embryonic eye vascularization due to a failure of macrophage-induced endothelial cell apoptosis. These results implicate Wnt proteins in the postnatal control of vascular regression and bone formation, two functions affected in many diseases. Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome, caused by LRP5 inactivation.

Animals↗

PubMed2002

Prospective comparison of endoscopy, endosonography and computed tomography for staging of tumours of the oesophagus and gastric cardia.

BACKGROUND: Local and multimodal therapeutic strategies for tumours of the oesophagus and gastric cardia, require precise preoperative staging. Endosonography is considered the most accurate staging method, while computed tomography (CT) has limitations especially in the evaluation of local infiltration. Macroscopic endoscopic evaluation was reported to be accurate in selected series, but no study has yet compared all three staging modalities. METHODS: One hundred and seventeen unselected patients with tumours of the oesophagus and gastric cardia were prospectively staged first by the endoscopic macroscopic appearance and then by endosonography. All patients had preoperative CT scans, however, only the 36 patients receiving the scans at our institution were included in the study. The preoperative staging results were then compared to postoperative histology which was available as the gold standard in all included patients. Kappa statistics were used to exclude chance agreement of the clinical staging results with the pathohistological findings. Differences between the resulting kappa values for the different staging modalities were analysed with a jack-knife test. RESULTS: Endoscopic macroscopic staging and endosonography (accuracy 67 and 69%, weighted kappa 0.78 and 0.84) were significantly more accurate than CT (accuracy 33%, weighted kappa 0.44) for determination of the T category (p = 0.006 and p = 0.001). After exclusion of tumours of the cardia (n = 33), the accuracy of macroscopic and endosonographic staging (accuracy 72 and 75%, weighted kappa 0.86 and 0.88) increased and remained more accurate than CT (accuracy 50%, weighted kappa 0.62). The main pitfall in our series in staging the T category was the overestimation of T2 tumours in the cardia as T3 or even as T4 tumours due to the inability to visualise the serosa. The accuracy of predicting lymph node metastasis was 68% for macroscopic endoscopic, 79% for endosonographic, and 67% for CT staging. Only endosonographic staging was significantly different from chance agreement with histology (weighted kappa = 0.56). Endosonographic staging was significantly more accurate than endoscopic macroscopic and CT staging (p = 0.03). CONCLUSIONS: Endosonography is the most accurate staging modality for overall preoperative staging of oesophageal and cardial tumours. Endoscopic macroscopic staging allows a reasonably accurate assessment of the T category.

Biopsy↗