Lung Cancer Surgery in Octogenarians: Implications and Advantages of Artificial Intelligence in the Preoperative Assessment.

The general world population is aging and patients are often diagnosed with early-stage lung cancer at an advanced age. Several studies have shown that age is not itself a contraindication for lung cancer surgery, and therefore, more and more octogenarians with early-stage lung cancer are undergoing surgery with curative intent. However, octogenarians present some peculiarities that make surgical treatment more challenging, so an accurate preoperative selection is mandatory. In recent years, new artificial intelligence techniques have spread worldwide in the diagnosis, treatment, and therapy of lung cancer, with increasing clinical applications. However, there is still no evidence coming out from trials specifically designed to assess the potential of artificial intelligence in the preoperative evaluation of octogenarian patients. The aim of this narrative review is to investigate, through the analysis of the available international literature, the advantages and implications that these tools may have in the preoperative assessment of this particular category of frail patients. In fact, these tools could represent an important support in the decision-making process, especially in octogenarian patients in whom the diagnostic and therapeutic options are often questionable. However, these technologies are still developing, and a strict human-led process is mandatory.

Xanthoma of rib: a case report and review of the literature.

BACKGROUND: Xanthomas are well-circumscribed benign proliferative lesions seen mainly in soft tissues. Usually, they are found in hyperlipidemia and familial hyperlipoproteinemia. Histologically, are characterized by macrophage-like mononuclear cells, multinucleated giant cells and abundant foam cells. The bone involvement, however, is notoriously rare and rib localization is extremely rare. CASE PRESENTATION: A 55-year-old man performed a chest X-ray and a subsequent chest Computed Tomography scan showing a rib lesion that was surgically removed and a diagnosis of rib xanthoma was made. The patient presented an unknown condition of hyperlipidemia. CONCLUSION: Rib xanthoma can be discovered accidentally and can be helpful in identifying an unrecognized condition of hyperlipidemia.

Lung Transplantation for Primary Ciliary Dyskinesia and Kartagener Syndrome: A Multicenter Study.

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population.

Non-Intubated Thoracic Surgery: Standpoints and Perspectives.

Non-intubated video-assisted thoracic surgery (NI-VATS) combines the advantages of a non-intubated surgery with the benefits of a minimally invasive approach. First, NI-VATS is performed in the case of fragile patients when general anesthesia and/or orotracheal intubation can be foreseen as inconvenient. However, NI-VATS indications have been increasingly extended to different patient conditions, considering the increasingly assessed safety and feasibility of the procedure. Currently, the NI-VATS approach is used worldwide for different thoracic surgery procedures, including the management of malignant pleural effusion, surgical treatment of empyema, anatomical and non-anatomical lung resection, and other indications. In fact, this approach has shown to be less impactful than VATS under general anesthesia, allowing for shortened hospitalization and faster recovery after surgery. Besides, NI-VATS is associated with fewer pulmonary complications, less respiratory distress, and a mild systemic inflammatory reaction. For these reasons, this approach should be considered not only in patients with poor cardiac or respiratory function (general functional reserve), but also in other eligible conditions. We explored the anesthetic and surgical aspects of such an approach, including the management of analgesia, cough reflex, depth of sedation, and intraoperative technical issues to put this approach in perspective.

Coaxial Drainage versus Standard Chest Tube after Pulmonary Lobectomy: A Randomized Controlled Study.

Chest tubes are routinely inserted after thoracic surgery procedures in different sizes and numbers. The aim of this study is to assess the efficacy of Smart Drain Coaxial drainage compared with two standard chest tubes in patients undergoing thoracotomy for pulmonary lobectomy. Ninety-eight patients (57 males and 41 females, mean age 68.3 ± 7.4 years) with lung cancer undergoing open pulmonary lobectomy were randomized in two groups: 50 received one upper 28-Fr and one lower 32-Fr standard chest tube (ST group) and 48 received one 28-Fr Smart Drain Coaxial tube (SDC group). Hospitalization, quantity of fluid output, air leaks, radiograph findings, pain control and costs were assessed. SDC group showed shorter hospitalization (7.3 vs. 6.1 days, p = 0.02), lower pain in postoperative day-1 (p = 0.02) and a lower use of analgesic drugs (p = 0.04). Pleural effusion drainage was lower in SDC group in the first postoperative day (median 400.0 ± 200.0 mL vs. 450.0 ± 193.8 mL, p = 0.04) and as a mean of first three PODs (median 325.0 ± 137.5 mL vs. 362.5 ± 96.7 mL, p = 0.01). No difference in terms of fluid retention, residual pleural space, subcutaneous emphysema and complications after chest tubes removal was found. In conclusion, Smart Drain Coaxial chest tube seems a feasible option after thoracotomy for pulmonary lobectomy. The SDC group showed a shorter hospitalization and decreased analgesic drugs use and, thus, a reduction of costs.

Role of radiomics in predicting lung cancer spread through air spaces in a heterogeneous dataset.

Background: Spread through air spaces (STAS) has been reported as a negative prognostic factor in patients with lung cancer undergoing sublobar resection. Radiomics has been recently proposed to predict STAS using preoperative computed tomography (CT). However, limitations of previous studies included the strict selection of imaging acquisition protocols, leading to results hardly applicable to daily clinical practice. The aim of this study is to test a radiomics-based prediction model of STAS in a practice-based dataset. Methods: A training cohort of 99 consecutive patients (65 STAS+ and 34 STAS-) with resected lung adenocarcinoma (ADC) was retrospectively collected. Preoperative CT images were collected from different centers regardless model and scanner manufacture, acquisition and reconstruction protocol, contrast phase and pixel size. Radiomics features were selected according to separation power and P value stability within different preprocessing setups and bootstrapping resampling. A prospective cohort of 50 patients (33 STAS+ and 17 STAS-) was enrolled for the external validation. Results: Only the five features with the highest stability were considered for the prediction model building. Radiomics, radiological and mixed radiomics-radiological prediction models were created, showing an accuracy of 0.66±0.02 after internal validation and reaching an accuracy of 0.78 in the external validation. Conclusions: Radiomics-based prediction models of STAS may be useful to properly plan surgical treatment and avoid oncological ineffective sublobar resections. This study supports a possible application of radiomics-based models on data with high variance in acquisition, reconstruction and preprocessing, opening a new chance for the use of radiomics in the prediction of STAS. Trial Registration: ClinicalTrials.gov identifier: NCT04893200.

Adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers as prognostic factors of early-stage large-cell neuroendocrine carcinoma.

BACKGROUND: We investigated whether adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers affected survival of patients with the early stage of large-cell neuroendocrine cancer. METHODS: This was a retrospective multicenter study including consecutive patients undergoing resection of node negative large-cell neuroendocrine carcinoma. Five-year survival and disease-free survival rate were evaluated by the Kaplan-Meier method and the log-rank test in relation to adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers (synaptophysin, chromogranin A, and neuron-specific enolase). RESULTS: Our study population included 117 patients; 47 (40%) of these received adjuvant chemotherapy. Patients treated with adjuvant chemotherapy had better survival (74% vs. 45%, p = 0.002) and disease-free survival (79% vs. 40%, p = 0.001) in all cases except patients with tumor <20 mm (79.5% vs. 57.4%, p = 0.43). Lobectomy compared to sublobar resection was associated with better survival (67% vs. 0.1%, p < 0.0001) and disease-free survival (65% vs. 0.1%, p < 0.0001) also in patients with tumor <20 mm (79% vs. 28%, p = 0.001). Patients with triple-positive neuroendocrine markers had better survival (79% vs. 35%, p = 0.0001) and disease-free survival (69% vs. 42%, p = 0.0008). Regression analysis showed that tumor size <20 mm, lobectomy, adjuvant chemotherapy, and triple-positive immunistochemical neuroendocrine markers were significant favorable prognostic factors for survival outcomes. CONCLUSIONS: Lobectomy seems to be the management of choice in patients with large-cell neuroendocrine cancer <20 mm while adjuvant chemotherapy should be administered only in patients with tumor >20 mm.

Prognostic impact of spread through air spaces in lung adenocarcinoma.

OBJECTIVE: Spread through air spaces (STAS) is a pattern of invasion present in some adenocarcinomas (ADC). The goal of this study was to assess the impact of STAS in patients treated with different types of surgical resections and on the clinical outcome in patients with ADC of different diameters and with different degrees of nodal involvement. METHODS: A total of 109 patients were reviewed. Complete surgical resection with systematic nodal dissection was achieved in all patients. The median follow-up was 65 months (3-90 months). RESULTS: STAS was observed in 70 cases (64.2%); 13 patients (18.5%) had lymph node involvement (N1 and N2). Overall survival and progression-free survival were higher in patients without STAS (P = 0.042; P = 0.027). The presence of STAS in tumours ≤2 cm was a predictor of worse progression-free survival following sublobar resection compared to major resections (P = 0.011). Sublobar resection of N0 STAS-positive tumours was associated with worse long-term survival compared to a major resection (P = 0.04). Statistical analyses showed that age >70 years and recurrence were independent variables for survival; smoking pack-years >20, sublobar resection and nodal involvement were independent variables for recurrence; and smoking pack-years >20 were independent variables for a history of cancer and pleural invasion for local recurrence. CONCLUSIONS: STAS seems to play a role in long-term survival, particularly for patients with N0 and tumours smaller than 2 cm. Further studies are necessary to validate this hypothesis.

Genome-wide expression of the residual lung reacting to experimental Pneumonectomy.

BACKGROUND: Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lung, after 60 post-operative completely uneventful days, underwent genome-wide bulk RNA-Sequencing (RNA-Seq). RESULTS: Histological analysis showed dilation of air spaces and rupture of interalveolar septa. In addition, mild inflammation, no fibrosis, radial stretch of the bronchus, strong enlargement of airspaces and thinning of the blood supply were observed. Bioinformatic analyses of bulk RNA-Seq data identified 553 Differentially Expressed Genes (DEGs) at adjusted P-value below 0.001, between pre- and post-pneumonectomy. The top 10 up-regulated DEGs were Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated DEGs were Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Leveraging digital cytometry tools, no difference in cellular abundance was found between the two experimental groups, while the analysis of cell type-specific gene expression patterns highlighted a striking predominance of macrophage-specific genes among the DEGs. DAVID-based gene ontology analysis showed a significant enrichment of "Extrinsic apoptotic signaling pathway" (FDR q = 7.60 × 10- 3) and "Response to insulin" (FDR q = 7.60 × 10- 3) genes, along with an enrichment of genes involved as "Negative regulators of DDX58/IFIH1 signaling" (FDR q = 7.50 × 10- 4) found by querying the REACTOME pathway database. Gene network analyses indicated a general dysregulation of gene inter-connections. CONCLUSION: This translational genomics study highlighted the existence both of individual genes, mostly dysregulated in certain cellular populations (e.g., macrophages), and gene-networks involved in pulmonary reaction after left pneumonectomy. Their involvement in lung homeostasis is largely supported by previous studies, carried out both in humans and in other animal models (under homeostatic or disease-related conditions), that adopted candidate-gene approaches. Overall, the present findings represent a preliminary assessment for future, more focused, studies on compensatory lung adaptation, pulmonary regeneration and functional reload.

Left uniportal VATS for lung decortication after chemical pleurodesis under spontaneous breathing in patient with lymphangiomyomatosis.

Pneumothorax can be the first symptom of lymphangioleiomyomatosis. Patients with lymphangioleiomyomatosis have a higher risk of recurrence of pneumothorax. Chemical pleurodesis is a viable option to treat the recurrence, but in rare cases, it is not the solution. We present the case of a patient with lymphangioleiomyomatosis undergoing a talc poudrage via video-assisted thoracoscopic surgery for pneumothorax that failed to reexpand the lung. We proposed to the patient a surgical approach to debride the lung parenchyma with the patient under deep sedation with spontaneous breathing. The patient was discharged on the 5th postoperative day. The chest computed tomography scan showed complete lung reexpansion.    We advocate that video-assisted thoracoscopic surgery in patients who are awake is a feasible surgical option that permits the restoration of physiological lung expansion in selected patients who underwent chemical pleurodesis and minimizes the risk of one-lung ventilation.

METTL3-dependent MALAT1 delocalization drives c-Myc induction in thymic epithelial tumors.

BACKGROUND: Thymic epithelial tumors (TETs) are rare neoplasms, originating from epithelial thymic cells. The oncogenic potential of these rare neoplasms is still largely undefined, and a deeper molecular characterization could result in a relevant advance in their management, greatly improving diagnosis, prognosis and treatment choice. Deregulation of N6-methyladenosine (m6A) RNA modification, catalyzed by the METTL3/METTL14 methyltransferase complex, is emerging as a relevant event in cell differentiation and carcinogenesis. Various studies have reported that altered expression of METTL3 is associated with an aggressive malignant phenotype and favors migration and invasiveness, but its role in Thymic Tumors remains unknown. RESULTS: In this study, we characterized that METTL3 contributes to Thymic Epithelial Tumor phenotype. We evidenced that METTL3 is overexpressed in tumor tissue compared to normal counterpart. Silencing of METTL3 expression in thymic carcinoma cells results in reduced cell proliferation and overall translation rate. Of note, METTL3 is responsible for the induction of c-MYC expression in TET cells. Specifically, high expression of c-MYC protein is enabled by lncRNA MALAT1, which is methylated and delocalized by METTL3. Interestingly, blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death. CONCLUSION: This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET.

Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study.

PURPOSE: Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. METHODS: It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development RESULTS: Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p < 0.0001) were the significant risk factors for lung cancer. CONCLUSION: PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.

A multidisciplinary approach for the differential diagnosis between multiple primary lung adenocarcinomas and intrapulmonary metastases.

PURPOSE: The distinction between multiple primary lung cancers (MPLCs) and intrapulmonary metastases has a significant impact on tumor staging and therapeutic choices. Several criteria have been proposed to solve this diagnostic issue, but a definitive consensus is still missing. We tested the efficacy of a combined clinical, histopathological and molecular ("real world") approach for the correct classification of multiple lung tumors in a selected cohort of patients. METHODS: 24 multiple lung tumors with a diagnosis of adenocarcinoma from 10 patients were retrospectively reviewed. Radiological, pathological and clinical information, including follow-up, were integrated with molecular profiling via a routine multigene panel sequencing. RESULTS: Comprehensive histologic assessment revealed readily distinguishable histologic patterns between multiple tumors suggesting unrelated lesions in 7 cases, in agreement with clinical, radiological and molecular data, thus leading to final diagnosis of MPLCs. In the remaining 3 cases, the differential diagnosis between MPLCs and intrapulmonary metastases was challenging, since the histologic features of the lesions were similar or identical. The final interpretation (2 MPLCs and 1 most likely intrapulmonary metastases) was reached thanks to the integration of all available data, and was confirmed by follow-up. CONCLUSIONS: A multidisciplinary approach including a routinely affordable multigene panel sequencing is a useful tool to discriminate MPLCs from intrapulmonary metastases in multiple lung nodules sharing the adenocarcinoma histotype.

LINC00174 is a novel prognostic factor in thymic epithelial tumors involved in cell migration and lipid metabolism.

Long non-coding RNAs are emerging as new molecular players involved in many biological processes, such as proliferation, apoptosis, cell cycle, migration, and differentiation. Their aberrant expression has been reported in variety of diseases. The aim of this study is the identification and functional characterization of clinically relevant lncRNAs responsible for the inhibition of miR-145-5p, a key tumor suppressor in thymic epithelial tumors (TETs). Starting from gene expression analysis by microarray in a cohort of fresh frozen thymic tumors and normal tissues, we identified LINC00174 as upregulated in TET. Interestingly, LINC00174 expression is positively correlated with a 5-genes signature in TETs. Survival analyses, performed on the TCGA dataset, showed that LINC00174 and its associated 5-genes signature are prognostic in TETs. Specifically, we show that LINC00174 favors the expression of SYBU, FEM1B, and SCD5 genes by sponging miR-145-5p, a well-known tumor suppressor microRNA downregulated in a variety of tumors, included TETs. Functionally, LINC00174 impacts on cell migration and lipid metabolism. Specifically, SCD5, one of the LINC00174-associated genes, is implicated in the control of lipid metabolism and promotes thymic cancer cells migration. Our study highlights that LINC00174 and its associated gene signature are relevant prognostic indicators in TETs. Of note, we here show that a key controller of lipid metabolism, SCD5, augments the migration ability of TET cells, creating a link between lipids and motility, and highlighting these pathways as relevant targets for the development of novel therapeutic approaches for TET.

Bedside Transcervical-Transtracheal Postintubation Injury Repair in a COVID-19 Patient.

Severe acute respiratory syndrome coronavirus 2 disease 2019 (COVID-19) has rapidly spread worldwide since December 2019. An acute respiratory distress syndrome develops in a relevant rate of patients, who require hospitalization. Among them, a nonnegligible rate of 9.8% to 15.2% of patients requires tracheal intubation for invasive ventilation. We report the case of a pneumomediastinum and subcutaneous emphysema developing in a COVID-19 patient secondary to postintubation tracheal injury. The management of COVID-19 patients can be challenging due to the risk of disease transmission to caregivers and epidemic spread. We performed a bedside tracheal injury surgical repair, after failure of conservative management, with resolution of pneumomediastinum and subcutaneous emphysema and improvement of the patient's conditions.

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study).

BACKGROUND: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. METHODS: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. RESULTS: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). CONCLUSIONS: The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival.