XCR1 expression distinguishes human conventional dendritic cell type 1 with full effector functions from their immediate precursors.

Dendritic cells (DCs) are major regulators of innate and adaptive immune responses. DCs can be classified into plasmacytoid DCs and conventional DCs (cDCs) type 1 and 2. Murine and human cDC1 share the mRNA expression of XCR1. Murine studies indicated a specific role of the XCR1-XCL1 axis in the induction of immune responses. Here, we describe that human cDC1 can be distinguished into XCR1- and XCR1+ cDC1 in lymphoid as well as nonlymphoid tissues. Steady-state XCR1+ cDC1 display a preactivated phenotype compared to XCR1- cDC1. Upon stimulation, XCR1+ cDC1, but not XCR1- cDC1, secreted high levels of inflammatory cytokines as well as chemokines. This was associated with enhanced activation of NK cells mediated by XCR1+ cDC1. Moreover, XCR1+ cDC1 excelled in inhibiting replication of Influenza A virus. Further, under DC differentiation conditions, XCR1- cDC1 developed into XCR1+ cDC1. After acquisition of XCR1 expression, XCR1- cDC1 secreted comparable level of inflammatory cytokines. Thus, XCR1 is a marker of terminally differentiated cDC1 that licenses the antiviral effector functions of human cDC1, while XCR1- cDC1 seem to represent a late immediate precursor of cDC1.

Managing One-Lung Ventilation in Tracheostomized Patients: A 6-Year Retrospective Analysis.

BACKGROUND: To ensure safe and optimal surgical conditions in thoracic surgery, one-lung ventilation is crucial. Various techniques exist to achieve one-lung ventilation. Tracheotomized patients who require one-lung ventilation represent a unique and rare subgroup that demands specialized knowledge and skills. The very limited literature has discussed alternative methods, no randomized controlled trials have addressed this issue yet. METHODS: We performed a retrospective analysis of patients who underwent one-lung ventilation in the Department of Thoracic Surgery of a German University Hospital between 2016 and 2021. The study assessed patient demographics, airway management techniques, ventilation parameters, and adverse events. RESULTS: In 3,197 anesthesia procedures during the observation period, 152 patients had an existing tracheostomy, of which 56 required one-lung ventilation. Among others in 42 cases, a tracheostomy tube was combined with a bronchial blocker, and in 10 cases, a double-lumen tracheostomy tube was used. There were no severe complications. Intraoperative dislocations that required repositioning of the device occurred in six patients (13.3%) with bronchial blockers and one patient with double-lumen tracheostomy tube (10%). CONCLUSION: The management of one-lung ventilation in tracheotomized patients presents unique challenges. While double-lumen tracheostomy tubes have specific advantages, we recommend considering their use carefully. For most tracheotomized patients, bronchial blockers in conjunction with a tracheostomy tube are used, which offers safety and practicality, irrespective of the tracheostomy's age or type. Further research and randomized controlled trials are warranted to establish best practices for one-lung ventilation in this unique patient population.

Spread through Air Spaces (STAS) in Solitary Pulmonary Metastases from Colorectal Cancer (CRC).

BACKGROUND: Spread through air spaces (STAS) is a recently described route of tumor invasion associated with poor prognosis in primary lung cancer. Aim of this study was to investigate the presence of STAS and to assess its prognostic significance in patients undergoing pulmonary metastasectomy (PM) for solitary metastases from colorectal cancer (CRC). MATERIALS AND METHODS: All 49 CRC patients (30 male and 19 female, median age 66 years) who underwent PM between January 2008 and December 2015 were retrospectively analyzed. RESULTS: STAS was identified in 26.5% (n = 13) of resected specimens. Location of pulmonary lesions (central vs. peripheral) was assessed based on the available computed tomography imaging (n = 47, 96%). STAS was detected in all five patients with central metastases (100%) versus 7 of 42 (17%) with peripheral metastases (p = 0.0001). Locoregional recurrence occurred in STAS-positive patients (n = 4 of 13 vs. n = 0 of 36), all STAS-negative patients remained recurrence-free (p = 0.003). Median number of alveoli with STAS involvement was four (range from 2 to 9). There was statistically positive relationship between the number of alveoli invaded with STAS and locoregional recurrence of metastases (p = 0.0001). The presence of STAS is not a factor affecting the 5-year overall survival rate (p = 0.6651). CONCLUSION: We identified STAS as a frequent finding in resected CRC lung metastases and found insignificant association with outcome.

Gene Expression in Solitary Fibrous Tumors (SFTs) Correlates with Anatomic Localization and NAB2-STAT6 Gene Fusion Variants.

Solitary fibrous tumors (SFTs) harbor recurrent NAB2-STAT6 gene fusions, promoting constitutional up-regulation of oncogenic early growth response 1 (EGR1)-dependent gene expression. SFTs with the most common canonical NAB2 exon 4-STAT6 exon 2 fusion variant are often located in the thorax (pleuropulmonary) and are less cellular with abundant collagen. In contrast, SFTs with NAB2 exon 6-STAT6 exon 16/17 fusion variants typically display a cellular round to ovoid cell morphology and are often located in the deep soft tissue of the retroperitoneum and intra-abdominal pelvic region or in the meninges. Here, we employed next-generation sequencing-based gene expression profiling to identify significant differences in gene expression associated with anatomic localization and NAB2-STAT6 gene fusion variants. SFTs with the NAB2 exon 4-STAT6 exon 2 fusion variant showed a transcriptional signature enriched for genes involved in DNA binding, gene transcription, and nuclear localization, whereas SFTs with the NAB2 exon 6-STAT6 exon 16/17 fusion variants were enriched for genes involved in tyrosine kinase signaling, cell proliferation, and cytoplasmic localization. Specific transcription factor binding motifs were enriched among differentially expressed genes in SFTs with different fusion variants, implicating co-transcription factors in the modification of chimeric NGFI-A binding protein 2 (NAB2)-STAT6-dependent deregulation of EGR1-dependent gene expression. In summary, this study establishes a potential molecular biologic basis for clinicopathologic differences in SFTs with distinct NAB2-STAT6 gene fusion variants.

Survival and Prognostic Analysis after Pulmonary Metastasectomy for Head and Neck Cancer.

BACKGROUND: There is no consensus on the value of pulmonary metastasectomy (PM) for head and neck cancer (HNC). The aim of our single-institution study was to evaluate outcomes and to examine factors influencing 5-year survival of patients undergoing resections for HNC lung metastases. METHODS: All HNC patients undergoing curative-intent PM between January 2008 and December 2018 were retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on patient survival was evaluated using the univariable Cox proportional hazard model. Cutoff values of continuous variables were determined by a receiver operating characteristic analysis. RESULTS: In total, 44 patients (32 males and 12 females, with a median age of 65 years) underwent PM for metastatic HNC. There was one perioperative death, and major complications occurred in 2 (4.5%) patients. The median interval between the treatment of primary tumor and PM was 19.4 months (range: 0-151 months). Median size of the largest resected pulmonary lesion was 1.3 cm (range: 0.3-6.9 cm). Mean follow-up was 21 months (range: 0-123 months), and 5-year overall survival (OS) rate after the first PM was 41%. Resection was complete (R0) in all patients. Larger size of pulmonary metastasis (≥1.4 cm; hazard ratio: 4.49; 95% confidence interval: 1.79-11.27) was a significantly negative prognostic factor. CONCLUSION: Despite the lack of randomized controlled trials, PM for HNC is a reasonable therapeutic option with favorable survival in a selected population. In patients with larger pulmonary lesions, shorter OS after PM is to be expected.

Surgery for Pulmonary Metastases: Long-Term Survival in 281 Patients.

BACKGROUND: Despite weak evidence, pulmonary metastasectomy (PM) is widely performed with intent to improve patient survival. Our single-institution analysis aims to evaluate outcomes and to identify factors influencing survival of patients undergoing PM for metastases from wide range of primary tumors. MATERIALS AND METHODS: All patients undergoing curative-intent PM between 2008 and 2018 were retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on overall survival (OS) was evaluated using univariable and multivariable Cox proportional hazard models. Cutoff values of continuous variables were determined by a receiver operating characteristic analysis. RESULTS: In this study, 281 patients (178 male, median age 61 years) underwent PM. Two (0.7%) perioperative deaths and 23 (8.2%) major complications occurred. Median interval between the treatment of primary tumor and PM was 21 months. Median size of largest metastasis was 1.4 cm. After the median follow-up of 29 months, 134 patients (47.7%) had died. Five-year OS rate after first PM was 47.1%. Complete resection was achieved in 274 (97.5%) patients. Multivariable analysis identified genitourinary origin (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.15-0.60, p = 0.0008) as independent positive survival prognosticator; incomplete resection (HR: 3.53, 95% CI: 1.40-8.91, p = 0.0077) and age at PM of ≥66 years (HR: 1.97, 95% CI: 1.36-2.85, p = 0.0003) were negative prognosticators. CONCLUSION: The use of PM as a part of multimodal treatment is in selected population justified. Our analysis identified age, primary tumor origin, and completeness of resection as independent survival prognosticators.

Major Pathologic Response after Induction Therapy Has a Long-Term Impact on Survival and Tumor Recurrence in Stage IIIA/B Locally Advanced NSCLC.

BACKGROUND: Major pathologic response (MPR) determines favorable outcome in locally advanced non-small cell lung cancer after induction therapy (IT) followed by lung resection. The aim of this retrospective study was to identify the prognostic relevance of MPR in long-term interval. METHODS: In 55 patients, the survival rate according to MPR and non-MPR was estimated by Kaplan-Meier method and compared using log-rank, Breslow, and Tarone-Ware tests. RESULTS: The IT included chemoradiation with 50.4 Gy (range: 45-56.4 Gy) combined with platinum-based chemotherapy in 52 patients (94.5%) and platinum-based chemotherapy in 3 patients (5.5%). Perioperative morbidity and 30-day mortality were 36 and 3.6%, respectively. The estimated 5-year postoperative and progressive-free survivals were statistically significantly improved in MPR versus non-MPR with 53.5 versus 18% and 49.4 versus 18.5%, respectively. According to the log-rank, Breslow, and Tarone-Ware tests, the MPR demonstrates prognostic significance in early, long-term, and whole postoperative interval. CONCLUSION: MPR is associated with a robust correlation to long-term postoperative and recurrence-free survival improvement, and can potentially simplify the multidisciplinary debate and allow further stratification of adjuvant treatment in multimodality therapy.

Increased expression of the immunosuppressive interleukin-35 in patients with non-small cell lung cancer.

BACKGROUND: The immunosuppressive role of the cytokine IL-35 in patients with non-small cell lung cancer (NSCLC) is poorly understood. In this study, we analysed the localisation and regulation of IL-35 in the lung of patients with non-small cell lung cancer (NSCLC) to further elucidate the immune-escape of cancer cells in perioperative course of disease. METHODS: Interleukin 35 (IL-35) was measured by ELISA in postoperative serum from 7 patients with NSCLC as well as 8 samples from healthy controls. Immunohistochemistry, FACS analysis, real-time PCR, as well as western blot from samples of the control (CTR), peri-tumoural (PT) and the tumoural (TU) region of the lung derived from patients with NSCLC and 10 controls were performed. RESULTS: Here we found elevated levels of IL-35 in the TU region as well as postoperative serum from patients with lung adenocarcinoma. Consistently, we found an increased expression of IL-35+Foxp-3+ cells, which associated with ARG1 mRNA expression and decreased TNFA in the TU region of the lung of patients with NSCLC as compared to their CTR region. Furthermore, in the CTR region of the lung of patients with NSCLC, CD68+ macrophages were induced and correlated with IL-35+ cells. Finally, IL-35 positively correlated with TTF-1+PD-L1+ cells in the TU region of NSCLC patients. CONCLUSIONS: Induced IL-35+Foxp3+ cell numbers in the TU region of the lung of patients with NSCLC associated with ARG1 mRNA expression and with TTF-1+PD-L1+ cells. In the tumour-free CTR area, IL-35 correlated with CD68+ macrophages. Thus inhibitors to IL-35 would probably succeed in combination with antibodies against immune checkpoints like PD-L1 and PD-1 currently used against NSCLC because they would inhibit immunosuppressive macrophages and T regulatory cells while promoting T cell-mediated anti-tumoural immune responses in the microenvironment as well as the TU region of NSCLC patients.

[Impact of Selective Quality of Life Analysis in Patients with Local Hyperhidrosis after Sympathicus Clipping]. / Bedeutung der selektiven Lebensqualitätsanalyse nach Sympathikus-Clipping bei Patienten mit lokaler Hyperhidrose.

INTRODUCTION: Hyperhidrosis (HH) is associated with physical and psychological restrictions. The treatment includes both conservative and surgical methods and aims to permanently improve the quality of life (QoL) of those affected. Endoscopic sympathetic blockade (ESB) is an established surgical therapeutic method and is considered effective when conservative treatment options fail. The aim of our study was to comprehensively analyse the QoL alteration and patient satisfaction after ESB and to identify the corresponding influencing factors. METHODS: From July 2008 to April 2016, 105 patients were operated for treatment-refractory HH. In all cases, an ESB was performed according to the HH form and the STS expert consensus (STS: Society of Thoracic Surgeons). QoL and hyperhidrosis status were selectively analysed pre- and postoperatively and evaluated using detailed questionnaires (a self-developed questionnaire, SF36, DLQI, Hyperhidrosis LQ (HidroQoL)). Statistical processing was performed with SPSS Statistics version 21.0.0.2 for Windows (Armonk, NY: IBM Corp.). Descriptive statistical analysis and nonparametric tests were used. RESULTS: 105 patients who underwent bilateral ESB between July 2008 and April 2016 were evaluated: 73 women (69.5%) and 31 men (29.5%) with median age of 26 years (range: 16 - 64 years). Of the 105 patients who underwent bilateral ESB, 12 patients had focal Hyperhidrosis palmar and axillar (12.4%), 20 had Hyperhidrosis palmo-plantar (19.0%), 47 had Hyperhidrosis palmoplantar and axillar (44.8%), 11 had Hyperhidrosis axillar (10.5%), and 14 had Hyperhidrosis facial (13.3%). HydroQoL scores showed improvement in all forms of HH. All patient groups demonstrated improvement in DLQI, while the LQ analysis of SF36 showed an improvement in social functioning and mental well-being in all forms of HH other than HA. 86.7% of patients (n = 91) were satisfied with their postoperative outcome. Compensatory sweating (CS) was observed in 76.2% of cases (n = 80), without a clear LQ impact. No significant correlation between CS and the hyperhidrosis form was found. CONCLUSIONS: ESB is associated with a long-time improvement in social functioning, psychological well-being, and high patient satisfaction. The onset of CS has no clear correlation to QoL and patient satisfaction.

Long-Term Survival after Salvage Surgery for Local Failure after Definitive Chemoradiation Therapy for Locally Advanced Non-small Cell Lung Cancer.

BACKGROUND: The incidence of local failure and residual tumor after definitive chemoradiation therapy (dCRT) for locally advanced non-small-cell lung cancer remains high, irrespective of applied radiation dose (>59 Gy). So-called salvage surgery has been suggested as a feasible treatment option after failure of definitive chemoradiation for locally advanced non-small cell lung cancer (NSCLC). Experience with salvage lung surgery (SLS) is limited, and long-term survival is rarely reported. Patient selection criteria for surgical lung salvage are not defined. The aim of this study was to assess postoperative survival and perioperative morbidity/mortality to identify prognostic factors and to define patient selection criteria. PATIENTS AND METHODS: Records of 13 consecutive patients with locally advanced NSCLC, who underwent SLS at a single institution between March 2011 and November 2016, were reviewed. Descriptive statistics were applied for patient characteristics and surgical and oncological outcome. Survival rates were calculated using the Kaplan-Meier method and were compared with the long-rank test. RESULTS: All patients initially received curative-intent definitive chemoradiation with median radiation doses of 66 Gy (range 59.4-72) and concurrent platinum-based chemotherapy. Clinical tumor stage before definitive chemoradiation was IIIA in 9, IIIB in 3, IV in 1 patients. Median interval between definitive chemoradiation and salvage surgery was 6.7 months. Perioperative morbidity and 30-days-mortality was 38% and 7.7%, respectively. The median postoperative survival and estimated 5-year survival rate were 29.7 months and 46%, respectively. CONCLUSION: SLS in patients with locally advanced non-small cell lung surgery following dCRT is feasible, prolongs long-term survival and allows local tumor control. Selection criteria remain undefined and patients should be considered surgical candidates during multidisciplinary team conference.

[Videothoracoscopic Sympathetic Clipping in a Patient With Azygos Lobe. Intraoperative Management to Avoid Potential Complications]. / Videothorakoskopisches Sympathikus-Clipping bei einem Patienten mit Lobus venae azygos. Intraoperatives Management zur Vermeidung von potenziellen Komplikationen.

INTRODUCTION: Sympathetic clipping in the presence of an azygos lobe is a rare combination. Anatomical relations between the sympathetic trunk and the mesoazygos impede surgical handling and can be associated with potential complications. INDICATION: We report the case of a 25-year old woman with grade III palmoplantar and axillary hyperhidrosis with azygos lobe incidentally found on preoperative chest X-ray. METHOD: Our intraoperative video shows a step-by-step approach to the sympathetic trunk in the presence of the azygos lobe, involving thoracoscopic looping and precise clip application onto the sympathetic trunk. Video-assisted reposition and expansion of the accessory lobe to avoid potential complications have been demonstrated. CONCLUSION: Videothoracoscopic sympathetic clipping in patients with lobus azygos is technically challenging. Potential complications can be avoided by coordinated surgical management.

[Lung Resection after Definitive and Neo-Adjuvant Chemoradiation for Stage IIIA/B Locally Advanced Non-Small Cell Lung Cancer: a Retrospective Analysis]. / Lungenresektion nach definitiver und neoadjuvanter Radiochemotherapie im Stadium IIIA/B des lokal fortgeschrittenen nicht kleinzelligen Lungenkarzinoms: eine retrospektive Analyse.

BACKGROUND: The outcomes of so called "salvage" resections after definitive chemoradiation vs. curative resections after neoadjuvant chemoradiation therapy (IT-resection) in patients with stage IIIA/B locally advanced non-small cell lung cancer have rarely been compared. The aim of our study was to compare perioperative results, postoperative and recurrence-free survival and to identify relevant prognostic survival factors for both therapy strategies. PATIENTS AND METHODS: Between June 2008 and May 2017, 43 patients underwent pulmonary resection following induction therapy (group 1) and 14 patients underwent salvage resection after definitive chemoradiation (group 2). Retrospective analysis was performed of demographic factors, tumour stage and location, initial therapy, preoperative regression status, perioperative morbidity and mortality, postoperative and recurrence-free survival. RESULTS: In group 2, significantly higher radiation dose was applied (p < 0.001) and the interval between chemoradiation and lung resection was significantly longer (p = 0.02). In addition, significantly higher perioperative blood loss and more frequent blood transfusions were noted (p = 0.003 and 0.005, respectively). Perioperative morbidity and mortality were statistically comparable in the two groups (p = 0.72 and 0.395, respectively). Postoperative 5 year survival in group 1 was 55%, in group 2 48% (log-rank p = 0.353). Five year recurrence-free survival in group 1 was 53%, in group 2 42% (log-rank p = 0.180). Diffuse metastasis occurred mostly in group 2, whereas in group 1 oligometastasis was more frequently noted. CONCLUSION: Postoperative outcome after salvage resection seems statistically comparable to results following curative resection after induction therapy. Diffuse distant metastasis is frequently noted. Careful patient selection is required.

Interleukin-10-regulated tumour tolerance in non-small cell lung cancer.

BACKGROUND: Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape. METHODS: Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer. RESULTS: Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide. IL-10 and IL-10R were found induced in cells surrounding the lung tumour cells, and IL-10R was mainly expressed on the surface of Foxp-3+ T-regulatory lymphocytes infiltrating the tumour of these patients where its expression inversely correlated with programmed cell death 1. These findings were confirmed in translational studies. In a human lung adenocarcinoma cell line, IL-10R was found induced under metabolic restrictions present during tumour growth, whereby IL-10 inhibited PDL1 and tumour cell apoptosis. CONCLUSIONS: These new findings suggest that IL-10 counteracts IFN-γ effects on PD1/PDL1 pathway, resulting in possible resistance of the tumour to anti-PD1/PDL1 immunotherapy.

Forty-Two Years' Experience with Pulmonary Resections of Metastases from Colorectal Cancer.

Background Pulmonary metastasectomy is a commonly performed surgery in patients with controlled metastatic colorectal cancer (CRC). We reviewed our long-term single institution experience with lung resections for colorectal metastases to assess the factors influencing patient survival. Materials and Methods A cohort of 220 patients (138 men and 82 women; median age, 59 years) who underwent complete pulmonary metastasectomy for CRC with curative intent between 1972 and 2014 was retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on patient survival was assessed. Results Two postoperative inhospital deaths occurred. The median interoperative interval was 26 months. The overall 5-year survival rate after pulmonary metastasectomy was 49.4%. In univariable analysis, bilateral pulmonary metastases (log rank p = 0.02), multiple metastases (log rank p = 0.005), and stage IV UICC (the International Union Against Cancer) CRC at the time of initial presentation (log rank p = 0.008) were significantly associated with poor outcome. Multivariable Cox analysis demonstrated that stage IV CRC (p = 0.02) and multiple metastases (p = 0.0019) were statistically significant predictors of survival after the pulmonary metastasectomy. There was no significant difference in survival between patients with high versus low preoperative carcinoembryonic antigen serum level (p = 0.149), high versus low preoperative carbohydrate antigen 19-9 serum level (p = 0.291), and primary tumor location in rectum versus colon (p = 0.845). Conclusion Patients with unilateral metastasis and stages I to III primary tumor benefited most from pulmonary metastasectomy for CRC.

Impaired T-bet-pSTAT1α and perforin-mediated immune responses in the tumoral region of lung adenocarcinoma.

BACKGROUND: In spite of modern therapies for non-small-cell lung cancer (NSCLC), prognosis for many patients is still poor and survival rates are low. Immunotherapy is the possibility to improve the lung immune response surrounding the tumour. However, this approach requires detailed understanding of the local immune-responses of NSCLC patients. METHODS: We analysed samples from three different regions within the lungs of NSCLC patients, whereas we distinguished between patients suffering from adenocarcinoma and squamous cell carcinoma. Expression of type 1 T helper (Th1)/type 1 cytotoxic (Tc1) factors was assessed by quantitative real-time PCR, western blot analyses or immunohistochemistry. Cytotoxic cell activity of CD8(+) T cells was determined via co-culture with autologous tumour cells and apoptosis assay. RESULTS: We found decreased levels of the transcription factor T-box expressed in T cells (T-bet or Tbx21) and of the downstream activated IFN-γ-dependent pSTAT1α isoform in the lung tumour areas of patients with NSCLC as compared with tumour-free control regions. In these patients, reduced T-bet and pSTAT1α levels were found associated with increased immunosuppressive markers like cytotoxic T lymphocyte-associated protein 4, programmed cell death 1 and with a suppression of the Th1 cell cytokine production and Tc1 cell activity. CONCLUSIONS: These findings confirm a central role of T-bet in targeted immunotherapy for patients with NSCLC.

Solitary fibrous tumors/hemangiopericytomas with different variants of the NAB2-STAT6 gene fusion are characterized by specific histomorphology and distinct clinicopathological features.

Recurrent somatic fusions of the two genes, NGFI-A-binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been recently identified to be presumable tumor-initiating events in solitary fibrous tumors (SFT). Herein, we evaluated a cohort of 52 SFTs/hemangiopericytomas (HPCs) by whole-exome sequencing (one case) and multiplex RT-PCR (all 52 cases), and identified 12 different NAB2-STAT6 fusion variants in 48 cases (92%). All 52 cases showed strong and diffuse nuclear positivity for STAT6 by IHC. We categorized the fusion variants according to their potential functional effects within the predicted fusion protein and found strong correlations with relevant clinicopathological features. Tumors with the most common fusion variant, NAB2ex4-STAT6ex2/3, corresponded to classic pleuropulmonary SFTs with diffuse fibrosis and mostly benign behavior and occurred in older patients (median age, 69 years). In contrast, tumors with the second most common fusion variant, NAB2ex6-STAT6ex16/17, were found in much younger patients (median age, 47 years) and represented typical HPCs from deep soft tissue with a more aggressive phenotype and clinical behavior. In summary, these molecular genetic findings support the concept that classic pleuropulmonary SFT and deep-seated HPC are separate entities that share common features but correlate to different clinical outcome.

Video double-lumen tube for one lung ventilation: implementation and experience in 343 cases of routine clinical use during the first 20 months of the SARS-CoV-2 pandemic.

BACKGROUND: Double-lumen tubes (DLTs) are the preferred device for lung isolation. Conventional DLTs (cDLT) need a bronchoscopic position control. Visualisation of correct DLT positioning could be facilitated by the use of a video double-lumen tube (vDLT). During the SARS-CoV-2-pandemic, avoiding aerosol-generation was suggesting using this device. In a large retrospective series, we report both general and pandemic related experiences with the device. METHODS: All anesthesia records from patients aged 18 years or older undergoing surgery from April 1st, 2020 to December 31st, 2021 in the department of thoracic surgery requiring intraoperative lung isolation were analyzed retrospectively. RESULTS: During the investigation period 343 left-sided vDLTs (77.4%) and 100 left-sided cDLTs (22.6%) were used for one lung ventilation. In the vDLT group bronchoscopy could be reduced by 85.4% related to the cDLT group. Additional bronchoscopy to reach or maintain correct position was needed in 11% of the cases. Other bronchoscopy indications occured in 3.6% of the cases. With cDLT, in 1% bronchoscopy for other indications than conforming position was observed. CONCLUSIONS: The Ambu® VivaSight™ vDLT is an efficient, easy-to-use and safe airway device for the generation of one lung ventilation in patients undergoing thoracic surgery. The vDLT implementation was achieved easily with full interchangeability to the left-sided cDLT. Using the vDLT can reduce the need for aerosol-generating bronchoscopic interventions by 85.4%. Continuous video view to the carina enabling position monitoring of the DLT without need for bronchoscopy might be beneficial for both employee's and patient's safety.

Short-chain fatty acids induced lung tumor cell death and increased peripheral blood CD4+ T cells in NSCLC and control patients ex vivo.

Background: Despite therapy advances, one of the leading causes of cancer deaths still remains lung cancer. To improve current treatments or prevent non-small cell lung cancer (NSCLC), the role of the nutrition in cancer onset and progression needs to be understood in more detail. While in colorectal cancer, the influence of local microbiota derived SCFAs have been well investigated, the influence of SCFA on lung cancer cells via peripheral blood immune system should be investigated more deeply. In this respect, nutrients absorbed via the gut might affect the tumor microenvironment (TME) and thus play an important role in tumor cell growth. Objective: This study focuses on the impact of the short-chain fatty acid (SCFA) Sodium Butyrate (SB), on lung cancer cell survival. We previously described a pro-tumoral role of glucose on A549 lung adenocarcinoma cell line. In this study, we wanted to know if SB would counteract the effect of glucose and thus cultured A549 and H520 in vitro with and without SB in the presence or absence of glucose and investigated how the treatment with SB affects the survival of lung cancer cells and its influence on immune cells fighting against lung cancer. Methods: In this study, we performed cell culture experiments with A549, H520 and NSCLC-patient-derived epithelial cells under different SB levels. To investigate the influence on the immune system, we performed in vitro culture of peripheral mononuclear blood cells (PBMC) from control, smoker and lung cancer patients with increasing SB concentrations. Results: To investigate the effect of SB on lung tumor cells, we first analyzed the effect of 6 different concentrations of SB on A549 cells at 48 and 72 hours cell culture. Here we found that, SB treatment reduced lung cancer cell survival in a concentration dependent manner. We next focused our deeper analysis on the two concentrations, which caused the maximal reduction in cell survival. Here, we observed that SB led to cell cycle arrest and induced early apoptosis in A549 lung cancer cells. The expression of cell cycle regulatory proteins and A549 lung cancer stem cell markers (CD90) was induced. Additionally, this study explored the role of interferon-gamma (IFN-γ) and its receptor (IFN-γ-R1) in combination with SB treatment, revealing that, although IFN-γ-R1 expression was increased, IFN-γ did not affect the efficacy of SB in reducing tumor cell viability. Furthermore, we examined the effects of SB on immune cells, specifically CD8+ T cells and natural killer (NK) cells from healthy individuals, smokers, and NSCLC patients. SB treatment resulted in a decreased production of IFN-γ and granzyme B in CD8+ T cells and NK cells. Moreover, SB induced IFN-γ-R1 in NK cells and CD4+ T cells in the absence of glucose both in PBMCs from controls and NSCLC subjects. Conclusion: Overall, this study highlights the potential of SB in inhibiting lung cancer cell growth, triggering apoptosis, inducing cell cycle arrest, and modulating immune responses by activating peripheral blood CD4+ T cells while selectively inducing IFN-γ-R1 in NK cells in peripheral blood and inhibiting peripheral blood CD8+ T cells and NK cells. Thus, understanding the mechanisms of action of SB in the TME and its influence on the immune system provide valuable insights of potentially considering SB as a candidate for adjunctive therapies in NSCLC.

Interdisciplinary Treatment of Malignant Chest Wall Tumors.

BACKGROUND: Chest wall resections for malignant chest wall tumors (MCWTs), particularly those with full-thickness chest wall involvement requiring reconstruction, present a therapeutic challenge for thoracic and plastic reconstructive surgeons. The purpose of this study was to review our experience with chest wall resection for primary and metastatic MCWTs, with a focus on perioperative outcomes and postoperative overall survival (OS). METHODS: All patients who underwent surgical resection for primary and secondary MCWTs at our single institution between 2000 and 2019 were retrospectively analyzed. RESULTS: A total of 42 patients (25 male, median age 60 years) operated upon with curative (n = 37, 88.1%) or palliative (n = 5, 11.9%) intent were reviewed. Some 33 (78%) MCWTs were of secondary origin. Chest wall reconstruction was required in 40 (95%) cases. A total of 13 (31%) patients had postoperative complications and one (2.3%) died perioperatively. The 5-year postoperative overall survival rate was 51.9%. The postoperative 5-year survival rate of 42.6% in patients with secondary MCWTs was significantly lower compared to the figure of 87.5% in patients with primary MCWTs. CONCLUSIONS: In well-selected patients, chest wall resections for primary and secondary MCWTs are feasible and associated with good perioperative outcomes. For secondary MCWTs, surgery can also be performed with palliative intent.