Comparison of electromagnetic navigation bronchoscopy and transthoracic needle biopsy for diagnosing bronchus sign-positive pulmonary lesions.

OBJECTIVES: Electromagnetic navigation bronchoscopy (ENB) is an advanced technique for diagnosing peripheral pulmonary lesions, and the bronchus sign is a well-established factor for improving the diagnostic performance. However, ENB is a novel technology compared to the commonly adopted transthoracic needle biopsy (TTNB). There are limited data on the comparison of these techniques for diagnosing bronchus sign-positive lesions. Therefore, we aimed to compare the diagnostic yield and complication rates of ENB and TTNB for diagnosing lung cancer in bronchus sign-positive pulmonary lesions. MATERIALS AND METHODS: We assessed 2,258 individuals who underwent either of the techniques for initial biopsy between September 2016 and May 2022 at a tertiary center in South Korea and analyzed 1,248 participants (153 ENB and 1,095 TTNB cases) with a positive bronchus sign. We performed multivariable logistic regression analyses to evaluate the factors associated with the diagnostic yield, sensitivity for malignancy, and procedure-related complications. In addition, the outcomes were compared between the two techniques after a 1:2 propensity score-matching to control for pre-procedural factors. RESULTS: After adjustments for clinical/radiological factors, performing TTNB over ENB was not significantly associated with a higher diagnostic yield but with a higher risk of pneumothorax (OR = 9.69, 95% CI = 4.15-22.59). Propensity score-matching resulted in 459 participants (153 ENB and 306 TTNB cases) with balanced pre-procedural characteristics. The overall diagnostic yield did not differ significantly between ENB and TTNB (85.0% vs. 89.9%, p = 0.124). The diagnostic yield (86.7% vs. 90.3%, p = 0.280) and sensitivity for malignancy (85.3% vs. 88.8%, p = 0.361) were comparable among patients with a class 2 bronchus sign. However, TTNB demonstrated a significantly higher complication rate of pneumothorax (28.8% vs. 3.9%, p < 0.001) and pneumothorax requiring tube drainage (6.5% vs. 2.0%, p = 0.034) than ENB. CONCLUSION: ENB demonstrated a diagnostic yield comparable with that of TTNB for diagnosing bronchus sign-positive peripheral pulmonary lesions with significantly lower complication rates.

Mutant p53 promotes ovarian cancer cell adhesion to mesothelial cells via integrin ß4 and Akt signals.

Missense mutations in the TP53 gene resulting in the accumulation of mutant proteins are extremely common in advanced ovarian cancer, which is characterised by peritoneal metastasis. Attachment of cancer cells to the peritoneal mesothelium is regarded as an initial, key step for the metastatic spread of ovarian cancer. In the present study, we investigated the possible role of a p53 mutant in the mesothelial adhesion of ovarian cancer cells. We found that OVCAR-3 cells with the R248 TP53 mutation (p53(R248)) were more adhesive to mesothelial Met5A cells than were A2780 cells expressing wild-type p53. In addition, ectopic expression of p53(R248) in p53-null SKOV-3 cells significantly increased adhesion to Met5A cells. Knockdown of mutant p53 significantly compromised p53(R248)-induced cell adhesion to Met5A cells. Microarray analysis revealed that several adhesion-related genes, including integrin ß4, were markedly up-regulated, and certain signalling pathways, including PI3K/Akt, were activated in p53(R248) transfectants of SKOV-3 cells. Inhibition of integrin ß4 and Akt signalling using blocking antibody and the inhibitor LY294002, respectively, significantly attenuated p53(R248)-mediated ovarian cancer-mesothelial adhesion. These data suggest that the p53(R248) mutant endows ovarian cancer cells with increased adhesiveness and that integrin ß4 and Akt signalling are associated with the mutation-enhanced ovarian cancer-mesothelial cell adhesion.