Impact of Silicone Stent Placement in Symptomatic Airway Obstruction due to Non-Small Cell Lung Cancer - A French Multicenter Randomized Controlled Study: The SPOC Trial.

BACKGROUND: Therapeutic bronchoscopy (TB) is an accepted strategy for the symptomatic management of central airway malignant obstruction. Stent insertion is recommended in case of extrinsic compression, but its value in preventing airway re-obstruction after endobronchial treatment without extrinsic compression is unknown. OBJECTIVE: Silicone stent Placement in symptomatic airway Obstruction due to non-small cell lung Cancer (SPOC) is the first randomized controlled trial investigating the potential benefit of silicone stent insertion after successful TB in symptomatic malignant airway obstruction without extrinsic compression. METHOD: We planned an inclusion of 170 patients in each group (stent or no stent) over a period of 3 years with 1-year follow-up. The 1-year survival rate without symptomatic local recurrence was the main endpoint. Recurrence rate, survival, quality of life, and stent tolerance were secondary endpoints. During 1-year follow-up, clinical events were monitored by flexible bronchoscopies and were evaluated by an independent expert committee. RESULTS: Seventy-eight patients (mean age 65 years) were randomized into 2 arms: stents (n = 40) or no stents (n = 38) after IB. Consequently, our main endpoint could not be statistically answered. Improvement of dyspnea symptoms is noticeable in each group but lasts longer in the stent group. Stents do not change the survival curve but reduce unattended bronchoscopies. In the no stent group, 19 new TB were performed with 16 stents inserted contrasting with 10 rigid bronchoscopies and 3 stents placed in the stent group. In a subgroup analysis according to the oncologic management protocol following TB (first-line treatment and other lines or palliation), the beneficial effect of stenting on obstruction recurrence was highly significant (p < 0.002), but was not observed in the naïve group, free from first-line chemotherapy. CONCLUSION: Silicone stent placement maintains the benefit of TB after 1 year on dyspnea score, obstruction's recurrence, and the need for new TB. Stenting does not affect the quality of life and is suggested for patients after failure of first-line chemotherapy. It is not suggested in patients without previous oncologic treatment.

Modulation of the responses of human osteoblast-like cells to physiologic mechanical strains by biomaterial surfaces.

In a previous study we demonstrated that MG-63 cells cultured on Ti-6Al-4V discs covered by alumina ceramic and submitted to intermittent mechanical strain (IMS) presented morphological alteration associated with enhanced differentiation. Here we examine how the mechanical response of osteoblasts can be modulated by the nature of the substrate. MG-63 cells were cultured on four materials: polystyrene and Ti-6Al-4V (average roughness = 0.48 microm) as smooth substrates; Ti-6Al-4V (average roughness = 5.76 microm) and Ti-6Al-4V covered with alumina (average roughness = 5.21 microm) as rough substrates. Mechanical strains were applied for 15 min, three times a day for 1-5 days with a 600 microstrains magnitude and a 0.25 Hz frequency. IMS stimulated alkaline phosphatase activity by 25-35% on all substrates and had no effect on cell growth on either substrate. Fibronectin (FN) was chosen as representative of cell-matrix interaction. FN production was increased by 60% after 1 day of stretching only on alumina-coated discs. FN organization examined on smooth substrates was affected by 5 days of IMS, showing a thickening of the fibres. The same modifications induced by IMS were previously observed on alumina-covered discs. Vinculin expression was not affected by IMS whatever the substrate. Cell-cell interactions were determined by N-cadherin immunoblotting. N-cadherin expression was increased by IMS specifically on rough substrates. Our results suggest that the nature of the surface did not influence the up-regulation of alkaline phosphatase activity induced by IMS, but modulates specifically cell-substrate as well as cell-cell interactions in response to IMS.

Physiological strains remodel extracellular matrix and cell-cell adhesion in osteoblastic cells cultured on alumina-coated titanium alloy.

The effects of mechanical strains on cellular activities were assessed in an in vitro model using human osteoblastic MG-63 cells grown on titanium alloy discs coated with porous alumina and exposed to chronic intermittent loading. Strain was applied with a Dynacell device for three 15-min sequences per day for several days with a magnitude of 600 microepsilon strain and a frequency of 0.25 Hz. We have previously demonstrated that this regimen increased alkaline phosphatase activity in confluent cultures on ceramic coated titanium (alumina and hydroxyapatite) (Biomaterials 24 (2003) 3139). In this study, we analysed the production of bone matrix proteins. Osteocalcin secretion quantified by ELISA between day 5 and 11 was not affected by mechanical strain. Strain had even no quantifiable effect on collagen production from day 1 to 5 as measured by carboxy terminal collagen type I propeptide release. On the other hand, stress stimulation resulted in increased expression of fibronectin (FN) measured by Western blot after 1 day stretching. This upregulation of FN production was followed by reorganisation of the FN network after 5 days stretching observed by immunostaining. The receptors for collagen and FN, alpha2beta1, alpha5beta1 and beta1 integrins were not quantitatively affected by the strains as measured by flow cytometry. A modification of cell morphology was seen after 5 days of loading that appeared to increase cell spreading, implying consequences on intercellular contacts. For this reason, N, C11 and E-adherins were examined. We noted a selective effect characterised by increased expression of N-cadherin using both RT-PCR and Western blot analyses. We concluded that reinforcement of cell-cell adhesion and remodelling of the FN network are important adaptive responses to physiological strains for human osteoblasts grown on alumina-coated biomaterials.