An optimized method for IgE-mediated degranulation of human lung mast cells.

Background: Mast cells are critically involved in IgE-mediated diseases, e.g., allergies and asthma. Human mast cells are heterogeneous, and mast cells from different anatomical sites have been shown to respond differently to certain stimuli and drugs. The origin of the mast cells is therefore of importance when setting up a model system, and human lung mast cells are highly relevant cells to study in the context of asthma. We therefore set out to optimize a protocol of IgE-mediated activation of human lung mast cells. Methods: Human lung mast cells were extracted from lung tissue obtained from patients undergoing pulmonary resection by enzyme digestion and mechanical disruption followed by CD117 magnetic-activated cell sorting (MACS) enrichment. Different culturing media and conditions for the IgE-mediated degranulation were tested to obtain an optimized method. Results: IgE crosslinking of human lung mast cells cultured in serum-free media gave a stronger response compared to cells cultured with 10% serum. The addition of stem cell factor (SCF) did not enhance the degranulation. However, when the cells were put in fresh serum-free media 30 minutes prior to the addition of anti-IgE antibodies, the cells responded more vigorously. Maximum degranulation was reached 10 minutes after the addition of anti-IgE. Both CD63 and CD164 were identified as stable markers for the detection of degranulated mast cells over time, while the staining with anti-CD107a and avidin started to decline 10 minutes after activation. The levels of CD203c and CD13 did not change in activated cells and therefore cannot be used as degranulation markers of human lung mast cells. Conclusions: For an optimal degranulation response, human lung mast cells should be cultured and activated in serum-free media. With this method, a very strong and consistent degranulation response with a low donor-to-donor variation is obtained. Therefore, this model is useful for further investigations of IgE-mediated mast cell activation and exploring drugs that target human lung mast cells, for instance, in the context of asthma.

Uniportal video-assisted thoracic surgery: segmentectomy versus lobectomy-early outcomes.

OBJECTIVES: To assess the feasibility and safety of uniportal video-assisted thoracoscopic pulmonary segmentectomy compared with lobectomy by studying early postoperative outcomes. METHODS: We included all patients who underwent uniportal segmentectomy and lobectomy between 2017 and 2022 at Karolinska University Hospital. Early clinical outcomes were compared between the uniportal segmentectomy and lobectomy groups. Differences in baseline characteristics were addressed using inverse probability of treatment weighting. RESULTS: A total of 833 patients (232 segmentectomy, 601 lobectomy) were included. The number of uniportal operations increased during the study period. Patients in the segmentectomy and lobectomy groups, respectively, had stage I lung cancer in 65% and 43% of the cases; 97% and 94% had no postoperative complications, the median number of lymph node stations sampled was 4 vs 5, and non-radical microscopic resection occurred in 1.7% vs 1.8%. The drains were removed on postoperative day 1 in 75% vs 72% of the patients following segmentectomy and lobectomy, respectively, and 90% vs 89% were discharged directly home. CONCLUSIONS: Uniportal video-assisted segmentectomy was performed with similar early postoperative clinical results compared with uniportal lobectomy in patients with benign, metastatic or early-stage lung cancer.

Sex and Survival After Surgery for Lung Cancer: A Swedish Nationwide Cohort.

BACKGROUND: Prior reports on a possible female survival advantage in both surgical and nonsurgical cohorts of patients with lung cancer are conflicting. Previously reported differences in survival after lung cancer surgery could be the result of insufficient control for disparities in risk factor profiles in men and women. RESEARCH QUESTION: Do women who undergo pulmonary resections for lung cancer have a better prognosis than men when taking a wide range of prognostic factors into account? STUDY DESIGN AND METHODS: We performed a nationwide population-based observational cohort study analyzing sex-specific survival after pulmonary resections for lung cancer. We identified 6356 patients from the Swedish National Quality Register for General Thoracic Surgery and performed individual-level record linkage to other national health-data registers to acquire detailed information regarding comorbidity, socioeconomic status, and vital status. Inverse probability of treatment weighting was used to account for differences in baseline characteristics. The association between female sex and all-cause mortality was assessed with Cox regression models, and flexible parametric survival models were used to estimate the absolute survival differences with 95% CIs. We also estimated the difference in restricted mean survival time. RESULTS: We observed a lower risk of death in women compared with men (hazard ratio, 0.73; 95% CI, 0.67-0.79). The absolute survival difference at 1, 5, and 10 years was 3.0% (95% CI, 2.2%-3.8%), 10% (95% CI, 7.0%-12%), and 12% (95% CI, 8.5%-15%), respectively. The restricted mean survival time difference at 10 years was 0.84 year (95% CI, 0.61-1.07 years). The findings were consistent across several subgroups. INTERPRETATION: Women who underwent pulmonary resections for lung cancer had a significantly better prognosis than men. The survival advantage was evident regardless of age, common comorbidities, socioeconomic status, lifestyle factors, physical performance, type and extent of surgery, tumor characteristics, and stage of disease. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03567538; URL: www.clinicaltrials.gov.

Household disposable income and long-term survival after pulmonary resections for lung cancer.

INTRODUCTION: Socioeconomic disparities have been linked to survival differences in patients with lung cancer. Swedish healthcare is tax-funded and provides equal access to care, therefore, survival following lung cancer surgery should be unrelated to household income. The aim of this study was to investigate the association between household disposable income and survival following surgery for lung cancer in Sweden. METHODS: We conducted a nationwide population-based cohort study including all patients who underwent pulmonary resections for lung cancer in Sweden 2008-2017. Individual-level record linkages between national quality and health-data registers were performed to acquire information regarding socioeconomic status and medical history. Cox regression by quintiles of household disposable income was used to estimate the adjusted risk for all-cause mortality. RESULTS: We included 5500 patients and the age-adjusted and sex-adjusted incidence rate of death per 100 person-years was 15 and 9.4 in the lowest and highest income quintile, respectively (mean follow-up time 3.2 years). Deprived patients were older, had more comorbidities and were less likely to have preoperative positron emission tomography or minimally invasive surgery, compared with patients with higher income. The adjusted HR for death was 0.77 (95% CI: 0.62 to 0.96) for the highest income quintile compared with the lowest. CONCLUSIONS: We found an association between household disposable income and survival in patients who underwent surgery for lung cancer in Sweden, despite tax-funded universal health coverage. The association remained after adjustment for differences in baseline characteristics.

Uniportal versus multiportal video-assisted thoracic surgery for lung cancer.

BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy is the recommended surgical approach for patients with stage I lung cancer. Whether a multiportal or a uniportal approach is preferable remains unclear. The aim of this study was to evaluate the safety of implementing uniportal VATS lobectomy into the treatment program of lung cancer patients. METHODS: We used the national quality register for general thoracic surgery in Sweden and included all patients who underwent VATS lobectomy for lung cancer at the Karolinska University Hospital between 2016-2018. Early postoperative complications were compared in patients undergoing uniportal (n=122) and multiportal (n=211) VATS lobectomy for lung cancer. Inverse probability of treatment weighting and standardized mean differences were used to limit differences in baseline characteristics and to assess balance after weighting. RESULTS: The proportion of uniportal VATS lobectomies increased during the study period and the conversion rates declined significantly. Baseline characteristics were similar in the two groups with the exception of a higher percentage of patients without any comorbidity in the uniportal group (59.8% vs. 44.5%, P=0.010). After inverse probability of treatment weighting the groups were well balanced. Postoperative complications were rare regardless of surgical approach, 94% in both groups had no complications. The 30-day mortality and overall survival at 1 year was 0% and 97% in the uniportal group, and 0.5% and 98% in the multiportal group (P=0.71). Patients undergoing uniportal VATS lobectomy were discharged directly to home to a higher extent than multiportal VATS patients (76.2% vs. 62.1%, P=0.008). CONCLUSIONS: We found that uniportal VATS lobectomy was feasible and safe, and might entail advantages in terms of a faster recovery after surgery as compared to multiportal VATS lobectomy in patients with lung cancer.