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- Al-Ameri, Mamdoh
(författare)
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Pulmonary resection for malignant tumors
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Resection of malignant tumors in the lung represents greater than 70% of thoracic surgeries. The continuous evolution of new surgical techniques and management of malignant diseases have improved the clinical outcomes of survival and quality of life. The aim of this thesis is to review important clinical aspects of the surgical resection of malignant tumors in the lung. Study I A prospective population-based cohort assessment of the relation between preoperative baseline self-reported SF-36 questionnaire data and long-term survival after thoracic procedures. The study included 249 patients planned for thoracic surgery at Karolinska University Hospital, Stockholm, Sweden, between 2006 and 2008. During an 8.0-year (median) follow-up, 48% of patients died. Patients with a physical component summary score less than the reference experienced significantly higher mortality rates compared with those of patients with lower mental component summary scores (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.34–3.06, p = 0.001) and (HR, 1.32; 95% CI, 0.84–3.06, p = 0.233), respectively. Study II A population-based cohort study of 184 patients who underwent pulmonary metastasectomy for colorectal cancer at Karolinska University Hospital between January 1, 2004, and December 31, 2015. The median follow-up was 3.2 years, and 36% (66/184) of patients died. Five-year overall survival was 60% (95% CI, 50%–68%), and carcinoembryonic antigen levels were the only statistically significant prognostic factor of mortality (age- and sex-adjusted, [HR, 2.46; 95% CI, 1.15–5.26, p = 0.020]). Study III A nationwide cohort study to investigate overall survival after surgical resection of pulmonary metastases of colorectal cancer in Sweden and to assess the discriminatory power of a recently suggested risk-prediction model. This study, which used the Swedish national quality register for thoracic surgery (ThoR), included 756 patients who underwent surgery between 2009 and 2015. Five-year overall survival was 56%, and the median follow-up was 2.9 years. Study IV Evaluation of early and late clinical outcomes after video-assisted thoracic surgery (VATS) and thoracotomy-lobectomy for non-small cell lung cancer of a cohort of patients in Sweden. The study used the ThoR register and included patients (n = 285) who underwent VATS lobectomy at Karolinska University Hospital and patients (n = 1316) who underwent thoracotomy lobectomy at other hospitals in Sweden between 2012 and 2015. Study V A study of a nationwide cohort conducted in Sweden to determine if the weekday of surgery influenced the long-term survival of patients listed in the ThoR register who underwent surgery for lung cancer between 2009 and 2015.
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| 2. |
- Ravindran, Avinash, et al.
(författare)
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An Optimized Protocol for the Isolation and Functional Analysis of Human Lung Mast Cells
- 2018
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mast cells are tissue-resident inflammatory cells defined by their high granularity and surface expression of the high-affinity IgE receptor, Fc + RI, and CD117/KIT, the receptor for stem cell factor (SCF). There is a considerable heterogeneity among mast cells, both phenotypically and functionally. Human mast cells are generally divided into two main subtypes based on their protease content; the mucosa-associated MCT (tryptase positive and chymase negative mast cell) and the connective tissue associated-residing MCTC (tryptase and chymase positive mast cell). Human lung mast cells exhibit heterogeneity in terms of cellular size, expression of cell surface receptors, and secreted mediators. However, knowledge about human lung mast cell heterogeneity is restricted to studies using immunohistochemistry or purified mast cells. Whereas the former is limited by the number of cellular markers that can be analyzed simultaneously, the latter suffers from issues related to cell yield.Aim: To develop a protocol that enables isolation of human lung mast cells at high yields for analysis of functional properties and detailed analysis using single-cell based analyses of protein (flow cytometry) or RNA (RNA-sequencing) expression.Methods: Mast cells were isolated from human lung tissue by a sequential combination of washing, enzymatic digestion, mechanical disruption, and density centrifugation using Percoll (WEMP). As a comparison, we also isolated mast cells using a conventional enzyme-based protocol. The isolated cells were analyzed by flow cytometry.Results: We observed a significant increase in the yield of total human lung CD45(+) immune cells and an even more pronounced increase in the yield of CD117(+) mast cells with the WEMP protocol in comparison to the conventional protocols. In contrast, the frequency of the rare lymphocyte subset innate lymphoid cells group 2 (ILC2) did not differ between the two methods.Conclusion: The described WEMP protocol results in a significant increase in the yield of human lung mast cells compared to a conventional protocol. Additionally, the WEMP protocol enables simultaneous isolation of different immune cell populations such as lymphocytes, monocytes, and granulocytes while retaining their surface marker expression that can be used for advanced single-cell analyses including multi-color flow cytometry and RNA-sequencing.
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