The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non-small cell lung cancer (NSCLC). However, therapies against TAFs are limited due to a lack of understanding in the subtype-specific mechanisms underlying their accumulation. Here, the mechanical (i.e., matrix rigidity) and soluble mitogenic cues that drive the accumulation of TAFs from major NSCLC subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were dissected. Fibroblasts were cultured on substrata engineered to exhibit normal-or tumor-like stiffnesses at different serum concentrations, and critical regulatory processes were elucidated. In control fibroblasts from nonmalignant tissue, matrix stiffening alone increased fibroblast accumulation, and this mechanical effect was dominant or comparable with that of soluble growth factors up to 0.5% serum. The stimulatory cues of matrix rigidity were driven by b1 integrin mechanosensing through FAK (pY397), and were associated with a posttranscriptionally driven rise in b1 integrin expression. The latter mechano-regulatory circuit was also observed in TAFs but in a subtype-specific fashion, because SCC-TAFs exhibited higher FAK (pY397), b1 expression, and ERK1/2 (pT202/Y204) than ADCTAFs. Moreover, matrix stiffening induced a larger TAF accumulation in SCC-TAFs (>50%) compared with ADC-TAFs (10%-20%). In contrast, SCC-TAFs were largely serum desensitized, whereas ADC-TAFs responded to high serum concentration only. These findings provide the first evidence of subtype-specific regulation of NSCLC-TAF accumulation. Furthermore, these data support that therapies aiming to restore normal lung elasticity and/or b1 integrin-dependent mechano regulation may be effective against SCC-TAFs, whereas inhibiting stromal growth factor signaling may be effective against ADC-TAFs.Implications: This study reveals distinct mechanisms underlying the abnormal accumulation of tumor-supporting fibroblasts in two major subtypes of lung cancer, which will assist the development of personalized therapies against these cells.

Mediastinal staging of NSCLC by FDG-PET/CT showed a considerable incidence of FNs. NPV is lower than previously reported and the preoperative mediastinal staging by 18FDG-PET/CT may jeopardise the accurate treatment for early stage NSCLC patients.

The fissureless technique appears to be a superior approach for fused fissures in terms of both preventing persistent air leak and reducing the length of hospitalisation. This technique can be performed safely at no additional cost and without adverse consequences.

In our study, we did not find significant differences between the use of one or two drains after lobectomy or bilobectomy in relation to early postoperative outcome. However, the use of only one drain is more economical and is less painful for patients, without any additional adverse consequences.

Conservative treatment for TBI is effective regardless of the mechanism of production, length, or site of the injury. Conservative treatment should be carefully assessed in patients who meet strict selection criteria. Membranous injuries can be treated more often with a conservative approach, however, cartilaginous injuries should be treated surgically if major symptoms are detected.

No abstract

Composite results for non-invasive mediastinal staging (CT scan, PET-CT) showed 11% of FNs in cI stage (7.6% in non-central cIA and 14.8% in cIB). In tumours≤1 cm, NPV makes surgical staging unnecessary. In women with adenocarcinoma and non-central cIB, however, the high FN rate makes invasive staging necessary, particularly in pT2b to decrease the incidence of unexpected pN2 in thoracotomy.

Parenchyma-sparing procedures can reduce the PN rate to less than 10%. A PN:SL index lower than 1:1.5 as a quality standard in a specialised thoracic unit should encourage the use of broncho-angioplastic procedures and improve patient outcomes. Long-term survival, QoL, postoperative lung function test and tolerance of adjuvant therapies are significantly better after SL than PN intervention.