Charles P. Theuer

The role of oral contrast administration immediately prior to the computed tomographic evaluation of the blunt trauma victim

BACKGROUND It is unclear whether the administration of oral contrast followed by immediate computerised tomographic (CT) scanning presents a significant risk of aspiration and whether it is useful in the diagnosis of hollow viscus injury. OBJECTIVE Determine the number of intestinal perforations diagnosed by oral contrast enhanced CT scans for blunt trauma and identify those who developed aspiration pneumonitis causally related to oral contrast administration. METHODS We analysed a database of consecutive blunt trauma admissions over a 2-year period. The majority received oral contrast immediately prior to CT scanning. We determined the number of intestinal perforations identified by abdominal CT confirmed at laparatomy and the number of cases of aspiration pneumonia. RESULTS Nine (1%) of the 1173 CT scans identified enteric perforations. Oral contrast enhanced CT scans demonstrated pneumoperitoneum (3), extraluminal contrast extravasation (2), and the presence of free fluid with small bowel wall thickening (8). In this same cohort, eight (0.7%) cases of aspiration pneumonia were diagnosed within 48 h of admission in patients with a mean GCS of 4.25; only one (0.1%) was temporally related to oral contrast administration. In a prospective study, none of the 65 consecutive patients who received oral contrast had witnessed aspiration. CONCLUSIONS Oral contrast administration given immediately prior to CT scanning does not increase the risk of clinically significant aspiration and assists in the detection of enteric perforation.

Endoglin expression on cancer-associated fibroblasts regulates invasion and stimulates colorectal cancer metastasis

Purpose: Cancer-associated fibroblasts (CAF) are a major component of the colorectal cancer tumor microenvironment. CAFs play an important role in tumor progression and metastasis, partly through TGF-β signaling pathway. We investigated whether the TGF-β family coreceptor endoglin is involved in CAF-mediated invasion and metastasis. Experimental Design: CAF-specific endoglin expression was studied in colorectal cancer resection specimens using IHC and related to metastases-free survival. Endoglin-mediated invasion was assessed in vitro by transwell invasion, using primary colorectal cancer–derived CAFs. Effects of CAF-specific endoglin expression on tumor cell invasion were investigated in a colorectal cancer zebrafish model, whereas liver metastases were assessed in a mouse model. Results: CAFs specifically at invasive borders of colorectal cancer express endoglin and increased expression intensity correlated with increased disease stage. Endoglin-expressing CAFs were also detected in lymph node and liver metastases, suggesting a role in colorectal cancer metastasis formation. In stage II colorectal cancer, CAF-specific endoglin expression at invasive borders correlated with poor metastasis-free survival. In vitro experiments revealed that endoglin is indispensable for bone morphogenetic protein (BMP)-9–induced signaling and CAF survival. Targeting endoglin using the neutralizing antibody TRC105 inhibited CAF invasion in vitro. In zebrafish, endoglin-expressing fibroblasts enhanced colorectal tumor cell infiltration into the liver and decreased survival. Finally, CAF-specific endoglin targeting with TRC105 decreased metastatic spread of colorectal cancer cells to the mouse liver. Conclusions: Endoglin-expressing CAFs contribute to colorectal cancer progression and metastasis. TRC105 treatment inhibits CAF invasion and tumor metastasis, indicating an additional target beyond the angiogenic endothelium, possibly contributing to beneficial effects reported during clinical evaluations. See related commentary by Becker and LeBleu, p. 6110.