Percutaneous computed tomography‐guided lung biopsy and pleural dissemination

Abstract

Objective Connective tissue growth factor (CTGF; CCN2) is overexpressed in systemic sclerosis (SSc) and has been hypothesized to be a key mediator of the pulmonary fibrosis frequently observed in this disease. CTGF is induced by transforming growth factor β (TGFβ) and is a mediator of some profibrotic effects of TGFβ in vitro. This study was undertaken to investigate the role of CTGF in enhanced expression of type I collagen in bleomycin‐induced lung fibrosis, and to delineate the mechanisms of action underlying the effects of CTGF on Col1a2 (collagen gene type I α2) in this mouse model and in human pulmonary fibroblasts. Methods Transgenic mice that were carrying luciferase and β‐galactosidase reporter genes driven by the Col1a2 enhancer/promoter and the CTGF promoter, respectively, were injected with bleomycin to induce lung fibrosis (or saline as control), and the extracted pulmonary fibroblasts were incubated with CTGF blocking agents. In vitro, transient transfection, promoter/reporter constructs, and electrophoretic mobility shift assays were used to determine the mechanisms of action of CTGF in pulmonary fibroblasts. Results In the mouse lung tissue, CTGF expression and promoter activity peaked 1 week after bleomycin challenge, whereas type I collagen expression and Col1a2 promoter activity peaked 2 weeks postchallenge. Fibroblasts isolated from the mouse lungs 14 days after bleomycin treatment retained a profibrotic expression pattern, characterized by greatly elevated levels of type I collagen and CTGF protein and increased promoter activity. In vitro, inhibition of CTGF by specific small interfering RNA and neutralizing antibodies reduced the collagen protein expression and Col1a2 promoter activity. Moreover, in vivo, anti‐CTGF antibodies applied after bleomycin challenge significantly reduced the Col1a2 promoter activity by ∼25%. The enhanced Col1a2 promoter activity in fibroblasts from bleomycin‐treated lungs was partly dependent on Smad signaling, whereas CTGF acted on the Col1a2 promoter by a mechanism that was independent of the Smad binding site, but was, instead, dependent on the ERK‐1/2 and JNK MAPK pathways. The CTGF effect was mapped to the proximal promoter region surrounding the inverted CCAAT box, possibly involving CREB and c‐Jun. In human lung fibroblasts, the human COL1A2 promoter responded in a similar manner, and the mechanisms of action also involved ERK‐1/2 and JNK signaling. Conclusion Our results clearly define a direct profibrotic effect of CTGF and demonstrate its contribution to lung fibrosis through transcriptional activation of Col1a2. Blocking strategies revealed the signaling mechanisms involved. These findings show CTGF to be a rational target for therapy in fibrotic diseases such as SSc.

Micropapillary and/or Solid Histologic Subtype Based on Pre-Treatment Biopsy Predicts Local Recurrence After Thermal Ablation of Lung Adenocarcinoma

“…However, there is some concern that biopsy may result in tumor seeding and possibly contribute to recurrences. At least in the surgery literature, the evidence seems to support no needle dissemination from CT-guided lung biopsies(33). Moreover, the overall rate of local recurrence in our cohort of biopsied patients was similar to published rates including studies where not all patients were biopsied.…”

Risks of Transthoracic Needle Biopsy

“…Sano et al 29 have attempted to address this concern with a prospective study. They performed intraoperative pleural lavage on 412 patients undergoing resection of a lung cancer, 171 of whom had undergone transthoracic needle biopsy prior to surgery.…”

Recurrence risk after preoperative biopsy in patients with resected early-stage non-small-cell lung cancer: a retrospective study

“… 12 , 13 , 15 However, Sano et al reported that preoperative percutaneous CT-guided needle biopsy did not lead to pleural dissemination, as determined by intraoperative pleural lavage cytology in patients with lung cancer. 27 Recent studies also demonstrated that PNB was not associated with increased pleural recurrence or impaired survival outcomes in NSCLC patients. 14 , 16 , 28 Importantly, a recent meta-analysis, including these related observational studies revealed that PNB did not increase the risk of pleural recurrence compared with non-percutaneous transthoracic needle biopsy strategies in early-stage lung cancer patients.…”