Spread Through Air Spaces in Stage I to III Resected Lung Adenocarcinomas: Should the Presence of Spread Through Air Spaces Lead to an Upstaging?

In recent years, the concept of spread through air spaces (STAS) has been discussed as an adverse prognostic factor for lung cancer. The aim of our study is to clarify the prognostic role of STAS in relation to the main recognized prognostic factors in a retrospective cohort of 330 European patients who underwent stages I to III lung adenocarcinoma resection. On univariate analysis, the presence of STAS was related to progression-free survival (PFS; hazard ratio [HR]: 1.48; 95% CI: 1.02-2.19; P = 0.038) and overall survival (OS; HR: 1.61; 95% CI: 1.03-2.52; P = 0.50). On multivariate analysis, STAS was related to PFS (HR: 1.51; 95% CI: 1.00-2.17; P = 0.050) and to OS (HR: 1.67; 95% CI: 1.00-2.81; P = 0.050). We showed that the presence of STAS was associated with lower PFS, equivalent to the next pathologic T stage, especially the median PFS of T3 stages without STAS was at 62.8 months while the median PFS of T3 stages with STAS was at 15.7 months, closer to the median PFS of 17.4 months in T4 stages. To conclude, STAS is an independent prognostic factor of PFS in this European cohort and is close to significance for OS. We suggest that the presence of STAS might lead to an upstaging of lung adenocarcinoma.

Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial.

Rationale: Management of first episodes of primary spontaneous pneumothorax remains the subject of debate. Objectives: To determine whether first-line simple aspiration is noninferior to first-line chest tube drainage for lung expansion in patients with complete primary spontaneous pneumothorax. Methods: We conducted a prospective, open-label, randomized noninferiority trial. Adults aged 18-50 years with complete primary spontaneous pneumothorax (total separation of the lung from the chest wall), recruited at 31 French hospitals from 2009 to 2015, received simple aspiration (n = 200) or chest tube drainage (n = 202) as first-line treatment. The primary outcome was pulmonary expansion 24 hours after the procedure. Secondary outcomes were tolerance of treatment, occurrence of adverse events, and recurrence of pneumothorax within 1 year. Substantial discordance in the numerical inputs used for trial planning and the actual trial rates of the primary outcome resulted in a reevaluation of the trial analysis plan. Measurement and Main Results: Treatment failure occurred in 29% in the aspiration group and 18% in the chest tube drainage group (difference in failure rate, 0.113; 95% confidence interval [CI], 0.026-0.200). The aspiration group experienced less pain overall (mean difference, -1.4; 95% CI, -1.89, -0.91), less pain limiting breathing (frequency difference, -0.18; 95% CI, -0.27, -0.09), and less kinking of the device (frequency difference, -0.05; 95% CI, -0.09, -0.01). Recurrence of pneumothorax was 20% in this group versus 27% in the drainage group (frequency difference, -0.07; 95% CI, -0.16, +0.02). Conclusions: First-line management of complete primary spontaneous pneumothorax with simple aspiration had a higher failure rate than chest tube drainage but was better tolerated with fewer adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT01008228).

Value of immunohistochemistry in crushed areas of pulmonary neuroendocrine carcinoma.

Immunohistochemical demonstration of neuroendocrine differentiation is often performed in routine diagnostic practice for lung neuroendocrine carcinoma. However, these carcinomas are often crushed, especially on small specimens. The value of immunohistochemistry on crushed areas is not known. We aimed to assess the value of immunohistochemical markers in crushed areas. We performed a retrospective study of 299 patients with a diagnosis of pulmonary neuroendocrine carcinoma. We showed that the markers TTF-1, synaptophysin, chromogranin A, CD56, and INSM1 were more often negative in crushed areas compared with well-preserved areas. The proliferation index with anti-Ki67 was decreased but remained on average around 90%. For all markers, the percentage of labeled cells was lower than in the preserved areas. Finally, we show that cases without labeling in the crushed areas and maintained labeling in the non-crushed areas have a lower percentage of labeling than cases without this labeling mismatch. Finally, there were no false positives of these stains. Neuroendocrine markers are valid in crushed areas when positive. However, the percentage of labeled cells may be lower than on preserved areas and lead to false negatives. Finally, the proliferation index, although decreased, remains close to that on preserved areas.

Prognostic role of immune microenvironment in pleural metastases from breast and lung adenocarcinomas.

Background: Pleural metastatic disease is a common disease with dismal prognosis. The immune microenvironment of metastatic pleural tissue remains largely unknown. Thus, we aimed to investigate the presence of different immune cell populations, and to compare them with clinical characteristics. Methods: We included 70 patients with lung and breast adenocarcinoma (ADC) diagnosed with pleural metastasis during a 2-year period with the primary endpoint to investigate if the main immune cell populations are present in pleural metastases and if they have any prognostic role. Secondary endpoints were to detect any differences in their presence between lung and breast primaries and to search for any correlation with the macroscopic (thoracoscopic) findings. We used immunohistochemical techniques for the detection of CD4+, CD8+, CD20+, CD163+ and S100+ cells in whole tissue pleural biopsies of lung and breast metastases. Results: Primary endpoint: all these populations are present in the biopsies from lung and higher stromal and intratumoral CD4 counts, as well as higher stromal CD20 cells were positive prognostic factors for lung cancer metastases, while higher S100 intratumoral counts were positive prognostic factors in lung and marginally breast cancer metastases. Secondary endpoints: significant higher values for the stromal CD163 group (P=0.04) and for the intratumoral S100 group (P=0.006) were seen in lung compared to breast metastases. Interesting correlations were also noted between thoracoscopic findings (nodules, masses, pachypleuritis) and the different factors studied. Conclusions: Our data show that the immune microenvironment may be important in this advanced tumoral setting and that possible targets of the nowadays numerous treatment strategies implicating the immune system may merit further exploration in this poor prognosis disease.

Spread Through Air Spaces (STAS) Is an Independent Prognostic Factor in Resected Lung Squamous Cell Carcinoma.

Objective: There is no histoprognostic grading for lung squamous cell carcinoma (LUSC). Different prognostic factors have been described in the recent literature and are not always studied in parallel. Our objective was to search for morphological histopathological prognostic factors in LUSC. Materials and Methods: In this single-center retrospective study of 241 patients, all patients with LUSC who underwent surgical excision over a 12-year period were included. The primary endpoint was 5-year overall survival. Results: STAS was present in 86 (35.7%) patients. The presence of Spread Through Air Spaces (STAS) was correlated with tumor location (p < 0.001), pathological stage (p = 0.039), tumor differentiation (p = 0.029), percentage of necrosis (p = 0.004), presence of vascular and/or lymphatic emboli, budding (p = 0.02), single cell invasion (p = 0.002) and tumor nest size (p = 0.005). The percentage of tumor necrosis was correlated with the overall survival at 5 years: 44.6% of patients were alive when the percentage of necrosis was ≥50%, whereas 68.5% were alive at 5 years when the necrosis was <30% (p < 0.001). When vasculolymphatic emboli were present, the percentage of survival at 5 years was 42.5% compared to 65.5% when they were absent (p = 0.002). The presence of isolated cell invasion was correlated with a lower 5-year survival rate: 51.1% in the case of presence, versus 66% in the case of absence (p = 0.02). In univariate analysis, performance status, pathological stage pT or pN, pleural invasion, histopathological subtype, percentage of tumor necrosis, vasculolymphatic invasion, single-cell invasion, budding and tumor nest size correlated with the percentage of survival at 5 years. On multivariate analysis, only STAS > 3 alveoli (HR, 2.74; 95% CI, 1.18−6.33) was related to overall survival. Conclusion: In conclusion, extensive STAS is an independent factor of poor prognosis in LUSC. STAS is correlated with the presence of other poor prognostic factors such as emboli and pleural invasion and would reflect greater tumor aggressiveness.

Preventive tract embolization with gelatin sponge slurry is safe and considerably reduces pneumothorax after CT-guided lung biopsy with use of large 16-18 coaxial needles.

OBJECTIVE: To evaluate the clinical impact of the tract embolization technique using gelatin sponge slurry after percutaneous CT-guided lung biopsy. METHODS: We retrospectively compared coaxial needle CT-guided lung biopsies performed without embolization (100 patients) and with the tract embolization technique using a mixture of iodine and gelatin sponge slurry (105 patients) between June 2012 and July 2020. Uni- and multivariate analyses were performed between groups to determine risk factors of pneumothorax. RESULTS: Patients with gelatin sponge slurry tract embolization had statistically lower rates of pneumothorax ((17.1% vs 39%, p < 0.001). In univariate analysis, tract embolization (OR = 0.32, CI = 0.17-0.61 p<0.001) and nodule size >2 cm (OR = 0.33 CI = 0.14-0.8 p = 0.013) had a protective effect on pneumothorax. The puncture path lengths > 2-20 mm and >20 mm were risk factors for pneumothorax (OR = 3.35 IC = 1.44-8.21 p = 0.006 and OR = 4.36 CI = 1.98-10.29 p<0.001, respectively). In multivariate regression analysis, tract embolization had a protective effect of pneumothorax (OR = 0.25, CI = 0.12-0.51, p < 0.001). The puncture path lengths > 2-20 mm and >20 mm were risk factors for pneumothorax (p = 0.030 and p = 0.002, respectively). CONCLUSIONS: The tract embolization technique using iodinated gelatin sponge slurry is safe and considerably reduces pneumothorax after percutaneous CT-guided lung biopsy. Our results suggest that it could be use in clinical routine. ADVANCES IN KNOWLEDGE: The systemic use of gelatin sponge slurry is safe and reduces considerably the rate of pneumothorax upon needle removal when CT-guided core biopsies are performed using large 16-18G coaxial needles.

Superior vena cava graft infection in thoracic surgery: a retrospective study of the French EPITHOR database.

OBJECTIVES: To report our experience on the management of superior vena cava graft infection. METHODS: Between 2001 and 2018, patients with superior vena cava synthetic graft or patch reconstruction after resection of intrathoracic tumours or benign disease were selected retrospectively from the French EPITHOR database and participating thoracic centres. Our study population includes patients with superior vena cava graft infection, defined according to the MAGIC consensus. Superior vena cava synthetic grafts in an empyema or mediastinitis were considered as infected. RESULTS: Of 111 eligible patients, superior vena cava graft infection occurred in 12 (11.9%) patients with a polytetrafluoroethylene graft secondary to contiguous contamination. Management consisted of either conservative treatment with chest tube drainage and antibiotics (n = 3) or a surgical graft-sparing strategy (n = 9). Recurrence of infection appears in 6 patients. Graft removal was performed in 2 patients among the 5 reoperated patients. The operative mortality rate was 25%. CONCLUSIONS: Superior vena cava graft infection may develop as a surgical site infection secondary to early mediastinitis or empyema. Graft removal is not always mandatory but should be considered in late or recurrent graft infection or in infections caused by aggressive microorganisms (virulent or multidrug resistant bacteria or fungi).

Adjuvant chemotherapy for completely resected IIA-IIIA non-small cell lung cancer: compliance to guidelines, safety and efficacy in real-life practice.

Background: Since randomised clinical trials demonstrated a survival benefit of adjuvant chemotherapy (AC) following curative-intent lung surgery, AC has been implemented as a standard therapeutic strategy for patients with a completely resected IIA-IIIA non-small cell lung cancer (NSCLC). Regarding the moderate benefit of AC and the lack of literature on AC use in real-life practice, we aimed to evaluate compliance to guidelines, AC safety and efficacy in a less selected population. Methods: Between January 2009 and December 2014, we retrospectively analysed 210 patients with theoretical indication of AC following curative-intent lung surgery for a completely resected IIA-IIIA NSCLC. The primary objective of this retrospective study was to evaluate compliance to AC guidelines. Secondary objectives included safety and efficacy of AC in real-life practice. Results: Among 210 patients with a theoretical indication of AC, chemotherapy administration was validated in multidisciplinary team (MDT) for 62.4% of them and 117 patients (55.7%) finally received AC. Patient's clinical conditions were the main reasons advanced in MDT for no respect to AC guidelines. Most of the patients received cisplatin-vinorelbine (86.3%) and AC was initiated within 8 weeks following lung surgery for 73.5% of patients. One-half of patients who received AC experienced side effects leading to either dose-intensity modification or treatment interruption. In real-life practice, AC was found to provide a survival benefit over surgery alone. Factors related to daily-life practice such as delayed AC initiation or incomplete AC planned dose received were not associated with an inferior survival. Conclusions: Although AC use might differ from guidelines in real-life practice, this retrospective study highlights that AC can be used safely and remains efficient among a less selected population. In the context of immunotherapy and targeted therapies development in peri-operative treatment strategies, the place of AC has to be precised in the future.

Histopathological and molecular profiling of lung adenocarcinoma skin metastases reveals specific features.

AIMS: Little is known regarding the histopathological and molecular features of lung adenocarcinoma skin metastases. Our study is the largest, to our knowledge, to comprehensively explore these to date. METHODS AND RESULTS: We performed a retrospective cohort study analysing 42 lung adenocarcinoma skin metastasis samples obtained from a database of 2659 lung adenocarcinomas collected between 2010 and 2020. EGFR exon 19 deletion was detected in one patient and KRAS mutations were detected in 12 (33.3%) patients. The programmed cell death ligand 1 (PD-L1) tumour proportion score was <1% in 27 patients, ≥1% and <50% in eight patients, ≥50% in six patients and not assessable in one patient. We showed that the predominant histopathological subtype is different from that at other metastatic sites (P = 0.024). Thyroid transcription factor I (TTF-1) was more often negative in skin metastases compared to other sites (P < 0.001). The EGFR mutation rate tended to be lower for skin metastases compared to other sites (P = 0.079). Skin metastases were associated with a high rate of PD-L1-negative cases (P = 0.022). CONCLUSION: Our work shows that the skin metastases of lung adenocarcinoma have a specific histopathological profile.

Histopathological typing in diffuse malignant epithelioid mesothelioma: implication for prognosis and molecular basis.

The prognostic impact of tumour grading, cytological and architectural patterns and stromal features in diffuse pleural malignant epithelioid mesothelioma (MEM) has been partly studied but not correlated to molecular features. We performed a retrospective study on 92 MEM in our department in order to assess the prognostic role of architectural and stromal patterns, especially tumour to stroma ratio. Secondly, based on The Cancer Genome Atlas (TCGA) database, we analysed the differentially expressed genes in prognostic groups of interest. Our results showed that tumour grading, tumour to stroma ratio and predominant pattern were related to overall survival, p≤0.001, p=0.01 and p=0.001, respectively. In univariate analysis, for high grade tumours hazard ratio (HR) was 4.75 (2.47-9.16), for stroma poor tumours HR=0.016, for predominant tubular or tubulopapillary pattern HR=0.044. In multivariate analysis, high grade tumours were related to overall survival [HR=3.09 (1.50-6.35), p=0.002] and predominant tubular or tubulopapillary pattern [HR=0.56 (0.32-0.99), p=0.045]. In TCGA analysis, after grading of diagnostic slides, we showed that KRTDAP and CXRCR1 expression was higher in low grade tumours, unlike PDZD7 and GPR176 expression which was higher in high grade tumours. FAM81B had a higher expression in stroma poor tumours. We did not find any differentially expressed genes in the architectural patterns group. Our work suggests that tumour grading is an important parameter in MEM with an underlying genomic basis. The role of tumour to stroma ratio needs to be investigated and might also have a genomic basis.

Heterogeneity of PD-L1 expression in lung adenocarcinoma metastasis is related to histopathological subtypes.

OBJECTIVES: The heterogeneity of PD-L1 expression and its relationship with histopathological subtype has recently been shown on primary tumor but has not been evaluated on metastases. The aim of our work is to analyze PD-L1 expression within each histopathological pattern on resected metastases. MATERIAL AND METHODS: 136 patients were included in this retrospective study. Immunohistochemistry was performed with 22C3 laboratory-developed test. The Tumor Proportion Score was evaluated on each subtype. RESULTS: The most frequent major histopathological subtype was solid (n = 69, 50.7 %), followed by acinar (n = 37, 27.2 %), micropapillary (n = 14, 10.3 %) and papillary (n = 10, 7.3 %). Mean percentage of PD-L1 expression for each subtype was at 28+/-4.8 % for solid subtype, 5.3+/-1.9 % for acinar subtype, 5+/-1.9 % for papillary subtype and 23.6+/-4.1 % for micropapillary subtype. Mean percentage of PD-L1 expression was different between solid pattern and acinar pattern (p < 0.001), solid pattern and papillary pattern (p = 0.007), micropapillary pattern and acinar pattern (p < 0.001) and micropapillary pattern and papillary pattern (p = 0.015). CONCLUSION: To conclude, we have showed firstly that several patterns are present in metastases of lung adenocarcinoma, secondly that the evaluation of patterns and PD-L1 stain on different patterns is reproducible, thirdly that pattern heterogeneity is related to PD-L1 staining, fourthly that in metastatic lung adenocarcinoma with at least two patterns, solid and micropapillary subtypes have higher levels of PD-L staining, fifthly that PD-L1 heterogeneity between different patterns is not a rare event. These results might explain discrepancies of PD-L1 results between biopsies and surgical samples and the fact that some patients might respond to checkpoint inhibitors even though PD-L1 expression is low or absent.

Use of adjuvant chemotherapy in resected non-small cell lung cancer in real-life practice: a systematic review of literature.

BACKGROUND: Adjuvant chemotherapy (AC) is recommended since 2004 for patients with a completely resected non-small cell lung cancer (NSCLC). Indeed, several randomized clinical trials have demonstrated an improved survival for patients treated with adjuvant cisplatin-based regimen than surgery alone. In these large clinical trials, patients were well selected and fit to receive AC. As the benefit of AC was estimated at 5.4% of 5-year overall survival (OS), it seems important to evaluate AC use in a less selected population. In particular, elderly patients were underrepresented in large randomized clinical trials. Furthermore, other confounding factors might limit AC efficacy in real-life practice such as the delay of chemotherapy initiation following lung surgery or the number of AC cycles received. Therefore, the aim of this systematic review is to summarize the state of the literature on AC use in current clinical practice. METHODS: A systematic assessment of literature articles and reviews on AC use in real-life practice was performed by searching in several relevant database including Medline, Google Scholar and Cochrane Library following PICOS (i.e., Population, Intervention, Comparison, Outcomes, Study design) eligibility criteria and PRISMA guidelines. Among the 1,957 results obtained with the request formulated on these research database, 56 relevant articles on AC use in non-trial setting were selected and included in the results section. RESULTS: This systematic literature review highlights the lack of literature on AC use in real-life practice as most of these studies were retrospective. Interestingly, a delayed AC-mostly due to postoperative complications-was better than surgery alone. Furthermore, AC was less purposed to elderly patients, despite retrospective studies outlined that this therapeutic option could be benefit in this specific population as for younger patients. In real-life practice, AC was also often incomplete due to adverse events, but dose reduction or omission was not always associated with an inferior survival. In non-trial setting, number of AC cycles delivered, dose reduction or omission is quite similar to randomized clinical trials. DISCUSSION: Nowadays, AC is part of the therapeutic strategy used in completely resected NSCLC. In a population of less selected patients, this systematic literature review shows that AC can be used safely and efficiently, especially in elderly patients. As well, delayed AC seems effective. Finally, the place of immunotherapy and targeted therapies have to be precised in the future as well as biomarkers to better select patients that would response to chemotherapy.

Clinical long-term outcome of non-specific pleuritis (NSP) after surgical or medical thoracoscopy.

BACKGROUND: Thoracoscopy, either "medical" or "surgical", is the gold standard to reveal the cause of pleural effusion by taking large biopsies. However, in some cases, the histology of pleural biopsies is inconclusive for a specific cause, describing a variable process of inflammation, encompassing for non-specific pleuritis (NSP). Questions are raised whether the surgical (or video-assisted thoracoscopic surgery, VATS) is doing better than the medical thoracoscopy (MT or pleuroscopy), but no direct comparison between the two techniques exist in the current bibliography. The aim of our retrospective study was to compare these two techniques to find whether there is any difference in the false negative cases of NSP. METHODS: We included in our study 295 patients with NSP, 179 patients who underwent VATS comparing to 116 patients who underwent MT for pleural effusion of initially undetermined cause, having a follow-up of at least one year. Analysis of patients' files, history, clinical examinations, further tests, and follow-up were recorded. RESULTS: The mean age of our patients was 58.5±19.1 and M/F gender was 216/79; no difference was observed between the two groups. The mean follow-up period was 47.3±20.7 months. After VATS, only one patient (0.55%) was finally diagnosed with pleural malignancy (false negative) while after MT 2 patients (1.7%). Negative predictive value for pleura-related malignancy for VATS was 0.994 and for MT 0.982. CONCLUSIONS: In patients with histological diagnosis of NSP both VATS and MT showed similar and excellent results of false negative cases and negative predictive value in excluding malignant pleural disease.

Airway complications after lung transplantation: benefit of a conservative bronchoscopy strategy.

BACKGROUND: After lung transplantation (LT), between 2% and 25% of bronchial anastomoses develop complications requiring therapeutic intervention. The status of healing of both bronchial anastomoses and downhill airways are well described by the French consensual MDS standardized grading system (Macroscopic, Diameter, Suture). We analyzed risks factors for airway complications (AC) after transplantation and the way we managed them. We report here our challenging method of early rigid bronchoscopic intervention with airway stenting on bronchial healing. METHODS: All single center consecutives LTs were retrospectively analyzed between 2010-2016. Patient-level data (demographic, peri-operative data) and anastomosis-level data (surgical parameters, bronchoscopy findings) were monitored. The incidence and contributive factors of ACs are reported. We also reported modalities of the conservative treatment and outcome. RESULTS: A total of 121 LTs were performed, 39 single-lung and 82 bilateral sequential LT. Main indication for LT were cystic fibrosis (45%) and emphysema (25%) and 58 were male patients (n=70). After a waiting period of healing, 28 patients presented AC on 41 anastomoses (prevalence: 23%). A multivariate analysis found as contributive factors of ACs, post-operative infection by Aspergillus [odds ratio (OR) 2.7, 95% confidence interval (CI): 1.08-6.75; P=0.033] at the patient level, and at the anastomosis level, emphysema (OR 2.4, 95% CI: 1.02-5.6; P=0.045), early dehiscence (OR 11.2, 95% CI: 1.7-76; P=0.01) and cold ischemia time >264 min (OR 2.45, 95% CI: 1.08-5.6; P=0.03). All the 41 ACs were managed conservatively with rigid bronchoscopy (range, 1-10), 41 stents (21 in silicone and 20 fully-covered Silicone Expandable Metallic Stents) without major complication. Two AC were still under regular bronchoscopic care and silicone stenting for long left bronchus reason. No surgical intervention was needed. The 2-years overall survival rate where not different between AC group and controls, respectively 85% and 81%. CONCLUSIONS: Airway healing after transplantation remains a scalable process and the French consensual MDS classification helped us for therapeutic decisions. Rigid bronchoscopy and safety use of current stenting devices may have the pivotal role in the conservative management of ACs, avoiding perilous situation of surgery for AC. Despite a high rate of AC, their favorable evolution may be explained by the cautious care of airway healing and maybe by the use of the Celsior antioxidant solution.

Histopathological subtyping is a prognostic factor in stage IV lung adenocarcinoma.

Lung adenocarcinoma is a heterogeneous tumor made of different architectural patterns. These tumors are classified into subtypes according to the predominant pattern in the primary tumor because the predominant pattern is related to overall survival. The prognostic role of these subtypes in stage IV disease is not well known, and most lung adenocarcinomas are diagnosed at the stage of metastatic disease. We aimed to evaluate the prognostic role of histopathological subtypes in lung adenocarcinoma metastases in a retrospective study of 253 patients with clinical, histopathological and molecular data. The presence of the solid subtype was related to overall survival (p = 0.045); the median overall survival was 6.8 months (95 % confidence interval (95 %CI) 4.4-9.1) when present and 11.1 months (95 %CI 8.6-21.3) when absent. Thyroid transcription factor 1 (TTF-1) immunohistochemistry was related to overall survival (p < 0.001); the median overall survival was 11.2 months (95 %CI 8.4-17.7) when positive and 4 months (95 %CI 2.3-5.7) when negative. On multivariate analysis, the presence of the solid subtype (p = 0.0036, hazard ratio (HR) 1.55, 95 %CI 1.03-2.34), TTF-1 positivity (p = 0.044, HR 0.64, 95 %CI 0.42-0.98), age <60 years at the time of resection (p = 0.017, HR 1.89; 95 %CI 1.12-3.21), performance status <2 (p = 0.017, HR 0.57; 95 %CI 0.36-0.91), treatment by chemotherapy (p = 0.033, HR 0.54, 95 %CI 0.31-0.95), and treatment by tyrosine kinase inhibitor or immunotherapy (p = 0.013, HR 0.36, 95 %CI 0.17-0.81) were related to overall survival. The evaluation of architectural pattern in metastases in stage IV patients provides further information for physicians about patient prognosis. This information might be included in clinical trials in patients with stage IV lung adenocarcinoma.

Immune Escape Is an Early Event in Pre-Invasive Lesions of Lung Squamous Cell Carcinoma.

Bronchial dysplasia is the pre-neoplastic lesion recognized for invasive squamous cell carcinoma. The mechanisms leading to invasive squamous cell carcinoma for this lesion are not fully known. Programmed Death-Ligand 1 (PD-L1) expression by the bronchial dysplasia neoplastic epithelium might suggest a response to immunotherapy. The objective of this work is to further characterize PD-L1 and CD8 expression in bronchial dysplasia and bronchial metaplasia compared to normal bronchial epithelium. Immunohistochemical analysis of PD-L1 and CD8 staining were characterized in bronchial dysplasia of 24 patients and correlated with clinical data. We also compared PD-L1 expression in dysplasia samples to 30 normal epithelium and 20 samples with squamous bronchial metaplasia. PD-L1 was never expressed in normal epithelium and in metaplastic epithelium whereas 37.5% of patients with bronchial dysplasia were stained by PD-L1 (p < 0.001). PD-L1 expression was not related to the degree of dysplasia or a medical history of invasive squamous cell carcinoma, while CD8 expression and its localization were related to medical history of squamous cell carcinoma (p = 0.044). Our results show that PD-L1 is expressed in roughly one third of patients with bronchial dysplasia and is not expressed in normal and metaplastic epithelium. This suggests that PD-L1 is expressed in preneoplastic lesions of squamous cell carcinoma.

Histopathological and molecular study for synchronous lung adenocarcinoma staging.

The presence of multiple synchronous lung cancer with the same histopathological type for a patient is a common situation and an issue for staging. Pathological criteria exist to distinguish multiple primaries from intra-pulmonary metastases of the same tumor, but they lack standardization. We wondered how molecular analysis with a limited Next Generation Sequencing panel could bring further information for tumor staging in this setting. We analyzed 24 patients with a total of 50 tumor nodules (22 pairs, two triplets). We compared histopathological examination with molecular analysis. A total of 50 tumors were molecularly tested. Nucleoli size was associated with molecular analysis concordance (p = 0.047). The presence of lepidic component in any of the two larger tumors was associated with molecular analysis concordance (p = 0.012). For molecular analysis, the proportion of progression-free patients was at the limits of significance (p = 0.054) whereas the presence of lepidic component, architectural concordance, and the concordance of comprehensive histologic assessments was not related to progression-free survival. For two patients with a discordant TTF-1 immunohistochemistry, molecular analysis showed a different mutation. Our results show that a limited NGS panel brings supplementary data to classify synchronous lung adenocarcinoma in most patients. We show that molecular staging seems in accordance with progression-free survival. Histopathological examination alone might not be accurate enough to assess a correct staging for synchronous tumors. We also suggest that TTF-1 immunohistochemistry, for the rare discrepant cases, might be a surrogate to molecular analysis.

Utility of radiation-free imaging for initial evaluation of pectus excavatum.

OBJECTIVES: The OrtenBodyOne scanner is a radiation-free, 3-dimensional imaging system recently developed for evaluation of the severity of pectus excavatum (PE). The goal of this study was to evaluate the utility of this new imaging system compared with that of computed tomography (CT) for the evaluation of the severity of PE. METHODS: Patients treated for PE from April 2015 to January 2017 with available CT and OrtenBodyOne data were included. Correlations between indexes calculated from CT and from OrtenBodyOne were determined by applying the non-parametric Spearman correlation procedure with a Bonferroni correction to adjust for multiple comparisons. RESULTS: Forty men (90.9%) and 4 women (9.1%), 20 with symmetrical (45.5%) and 24 with asymmetrical PE (54.5%), were included. The median age was 16.1 years (range 4.3-63.5 years). The following measures and indexes acquired using OrtenBodyOne and CT were significantly correlated: pectus depth (r = 0.84; P = 0.002), anthropometric index (r = 0.81; P = 0.002) and asymmetry index (r = 0.67; P = 0.002). The correlation between the CT Haller index and the external Haller index was only significant for symmetrical PE (r = 0.57; P = 0.008). CONCLUSIONS: The OrtenBodyOne imaging system can be used to evaluate the severity of symmetrical PE using the external Haller index. Asymmetry and anthropometric indexes are more reliable for the evaluation of asymmetrical PE. Measures can be repeated throughout treatment while avoiding unnecessary irradiation.