Costochondral calcification, osteophytic degeneration, and occult first rib fractures in patients with venous thoracic outlet syndrome.

OBJECTIVE: Subclavian vein (SCV) compression in venous thoracic outlet syndrome (TOS) has been attributed to various anatomic factors, but a potential role for costochondral degeneration in the underlying first rib has not been previously examined. The purpose of this study was to examine the frequency of costochondral calcification (CC), osteophytic degeneration (OD), and occult first rib fractures (FRFx) in patients with venous TOS. METHODS: Thirty-seven patients (21 male, 16 female) were referred for surgical treatment of venous TOS during a 12-month period, with a mean age of 30.7 ± 1.8 year (range, 12-55). Thirteen (35%) had acute SCV effort thrombosis and 24 (65%) had chronic symptoms (>14 days). Twenty (54%) had undergone SCV thrombolysis, 11 (30%) had persistent SCV occlusion, and 10 (27%) had concomitant symptoms of neurogenic TOS. All patients underwent paraclavicular thoracic outlet decompression with complete resection of the first rib to the sternum, with 20 (54%) having concomitant SCV reconstruction. The presence or absence of CC, OD, and FRFx was determined by direct visual examination of the rib at operation and following debridement of the excised specimen. RESULTS: One patient had a cervical rib but there were none with radiographic first rib abnormalities. In contrast, FRFx were observed at surgical resection in 16 of 37 patients (43%). All FRFx were small, nondisplaced, linear lesions located within an area of CC in the anterior rib, typically in association with OD and perivenous soft tissue thickening. The mean age of patients with FRFx was higher than those with a normal first rib (38.1 ± 1.5 years vs 25.0 ± 2.3 years; P < .0001), and FRFx were present in 16 of 21 (76%) patients ≥ 30 years of age but in no patients younger than 30 (P < .0001). CONCLUSIONS: A high proportion (43%) of patients with venous TOS exhibited CC, OD, and a previously undetected FRFx, including 76% of those over the age of 30. These lesions occur in the cartilaginous anterior rib where they are clinically occult and undetected by standard radiographic imaging. We postulate that age-related CC may predispose to OD and stress-induced FRFx, and that inflammation, fibrosis, and anatomic distortion in the surrounding soft tissues may contribute to SCV compression.

Roles of myofibroblasts in prostaglandin E2-stimulated intestinal epithelial proliferation and angiogenesis.

Prostaglandins (PG) are produced throughout the gastrointestinal tract and are critical mediators for a complex array of physiologic and pathophysiologic processes in the intestine. Intestinal myofibroblasts, which express cyclooxygenase (COX) and generate PGE(2), play important roles in intestinal epithelial proliferation, differentiation, inflammation, and neoplasia through secreting growth factors and cytokines. Here, we show that PGE(2) activated human intestinal subepithelial myofibroblasts (18Co) through Gs protein-coupled E-prostanoid receptors and the cyclic AMP/protein kinase A pathway. 18Co cells and primary colonic myofibroblast isolates expressed a number of growth factors; several of them were dramatically regulated by PGE(2). An epidermal growth factor-like growth factor, amphiregulin (AR), which was not expressed by untreated cells, was strongly induced by PGE(2). Expression of vascular endothelial growth factor A (VEGFA) was rapidly increased by PGE(2) exposure. Hepatocyte growth factor (HGF) was elevated in PGE(2)-treated myofibroblasts at both mRNA and protein levels. Thus, PGE(2)-activated myofibroblasts promoted the proliferation and migration of intestinal epithelial cells, which were attenuated by neutralizing antibodies to AR and HGF, respectively. Moreover, in the presence of PGE(2), myofibroblasts strongly stimulated the migration and tubular formation of vascular endothelial cells. Neutralizing antibody to VEGFA inhibited the observed stimulation of migration. These results suggest that myofibroblast-generated growth factors are important mediators for PGE(2)-induced intestinal epithelial proliferation and angiogenesis, which play critical roles in intestinal homeostasis, inflammation, and neoplasia.