Mediastinal lymph node removal modulates natural killer cell exhaustion in patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death globally. In this study, the effect of complete removal of mediastinal lymph nodes by video-assisted mediastinoscopic lymphadenectomy (VAMLA) on natural killer (NK) cell phenotype and functions in patients with NSCLC was evaluated. The study included 21 NSCLC patients (cIA-IVA) undergoing VAMLA staging and 33 healthy controls. Mononuclear cells were isolated from peripheral blood of all participants and mediastinal lymph nodes of the patients. NK cells were analyzed by flow cytometry to define NK subsets, expressions of PD-1, CTLA-4, activating/inhibitory receptors, granzyme A, and CD107a. The plasma levels of soluble PD-1, PDL-1, and CTLA-4 were measured by ELISA. Mediastinal lymph nodes of NSCLC patients had increased ratios of exhausted NK cells, increased expression of PD-1 and IL-10, and impaired cytotoxicity. Mediastinal lymph nodes removal increased CD56dimCD16bright cytotoxic effector phenotype and reduced exhausted NK cells. PD-1+ NK cells were significantly more abundant in patients' blood, and VAMLA significantly reduced their ratio as well. The ratio of IL-10 secreting regulatory NK cells was also reduced after VAMLA. Blood NK cells had increased cytotoxic functions and spontaneous IFN-γ secretion, and these NK cell functions were also recovered by VAMLA. Mediastinal lymph node removal reversed NK cell exhaustion, reduced regulatory NK cells, and improved antitumoral functions of NK cells. Tumor-draining lymph nodes may contribute to tumor evasion from antitumoral immune responses. The role of their removal needs to be further studied both to better understand this mechanism and as a potential immunotherapeutic approach.

Mediastinal lymph node removal ameliorates cytotoxic T-lymphocyte functions in patients with non-small cell lung cancer.

INTRODUCTION: Mediastinal lymph node (MLN) removal by video-assisted mediastinoscopic lymphadenectomy (VAMLA) for preoperative cancer staging was reported to be associated with increased survival. The aim of this study was to evaluate the immunologic effects of complete MLN removal by VAMLA on cytotoxic T lymphocyte (CTL) phenotype and function. METHODS: Seventeen patients with non-small cell lung cancer (NSCLC) (stage cT1-4N0-3M0-1A) and 20 healthy participants were included in this study. Blood samples were collected before and 4 weeks after the procedure. Lymphocytes were isolated from the removed MLNs. CTL phenotypes and functions were evaluated by flow cytometry. Plasma levels of soluble programmed cell death protein 1 (sPD-1), soluble programmed cell death protein 1 ligand, and soluble CTL antigen 4 (sCTLA-4) were measured with enzyme-linked immunosorbent assay. RESULTS: The ratio of the immunosenescent CTLs (CD3+CD8+CD28-) was increased in peripheral blood and MLNs of the patients with NSCLC compared to controls (p = 0.037), and MLN removal did not change this ratio. PD-1 and CTL antigen 4 expressions were significantly reduced in peripheral blood CTLs after MLN removal by VAMLA (p = 0.01 and p = 0.01, respectively). Granzyme A expression was significantly reduced in the peripheral blood CTLs of the patients compared to controls (p = 0.006) and MLN removal by VAMLA significantly improved Granzyme A expression in CTLs (p = 0.003). Plasma concentrations of sPD-1 and sCTLA-4 remained unchanged after VAMLA. CONCLUSION: CTLs in the MLNs and peripheral blood of the patients with NSCLC had an immunosenescent phenotype, increased immune checkpoint receptor expression, and impaired cytotoxicity. MLN removal by VAMLA improved these phenotypic and functional characteristics of CTLs. These changes may explain the potential contribution of VAMLA to improved survival.

The prognostic effect of lymph node dissection in secondary lung tumor metastasectomies.

Background: In this study, we aimed to investigate the prognostic effect of lymph node dissection in secondary lung tumor metastasectomies. Methods: Between January 2001 and December 2015, a total of 201 patients (122 males, 79 females; mean age: of 41.4±19.2 years; range, 3 to 79 years) who had pulmonary metastasectomy due to colorectal carcinoma, renal cell carcinoma, and soft tissue - skeletal sarcomas were retrospectively analyzed. The clinicopathological features of the patients, overall survival, and complication rates according to the presence of lymph node dissection were evaluated. Results: The most common histopathological subtype was a sarcoma in 118 (58.7%) patients, followed by colorectal carcinoma in 63 (31.3%) patients, and renal cell carcinoma in 20 (10%) patients. A total of 88 (43.7%) patients underwent systematic lymph node dissection with pulmonary metastasectomy. The mean overall survival of patients with and without lymph node dissection were 49±5.9 (95% confidence interval 37.3-60.6) and 26±4.4 (95% confidence interval 17.2-34.7) months, respectively (p=0.003). The five-year survival rates in colorectal carcinoma, renal cell carcinoma, and sarcoma were 52%, 30%, and 23%, respectively (p=0.002). Locoregional recurrences occurred in 15 (35.7%) patients in the lymph node dissection group and in 23 (60.5%) patients in the non-lymph node dissection group (p=0.026). Lymph node dissection did not show a significant relationship regarding to postoperative complications (p=0.09). Conclusion: Lymph node dissection following pulmonary metastasectomy may improve the overall survival and reduce locoregional recurrence, without any increase in morbidity and mortality.

Videothoracoscopic excision of a diaphragmatic bronchogenic cyst appearing as a pulmonary lesion.

Diaphragmatic bronchogenic cysts are rare, and very few cases have been reported in the literature to date. Herein, we present a 42-year-old male patient who had a diaphragmatic bronchogenic cyst with the radiologic appearance of an intrapulmonary lesion as the 32nd case in the English literature. We performed a videothoracoscopic excision of the cyst, which was later found to be originated from the diaphragm. Pathologic examination confirmed the diagnosis of the bronchogenic cyst. Diaphragmatic bronchogenic cysts may present as intrapulmonary lesions radiologically. Videothoracoscopic excision is a feasible treatment method for these lesions.

Predictors of malignancy in patients with solitary pulmonary nodules undergoing pulmonary resection.

BACKGROUND: The management of a solitary pulmonary nodule is a challenging issue in pulmonary disease. Although many factors have been defined as predictors for malignancy in solitary pulmonary nodules, the accurate diagnosis can only be established with the permanent histological diagnosis. OBJECTIVE: We tried to clarify the possible predictors of malignancy in solitary pulmonary nodules in patients who had definitive histological diagnosis. METHODS: We made a retrospective study to collect the data of patients with solitary pulmonary nodules who had histological diagnosis either before or after surgery. We made a statistical analysis of both the clinic and radiological features of these nodules with respect to malignancy both in contingency tables and with logistic regression analysis. RESULTS: We had a total of 223 patients with a radiological diagnosis of solitary pulmonary nodule. Age, smoking status and pack years of smoking, maximum standardized uptake value (SUVmax), and radiological features such as solid component, spiculation, pleural tag, lobulation, calcification, and higher density were significant predictors of malignancy in contingency tables. Age, smoking status and smoking (pack/year), SUVmax, and radiological features including spiculation, pleural tag, lobulation, calcification, and higher density were the significant predictors in univariate analysis. However, multivariate analysis revealed only SUVmax greater than 2.5 (p < 0.0001), spiculation (p = 0.009), and age older than 61 years (p = 0.015) as the significant predictors for malignancy. CONCLUSION: Age, SUVmax, and spiculation are the independent predictors of malignancy in patients with solitary pulmonary nodules.

Religious and Cultural Aspects of Organ Donation in the Turkish Population.

OBJECTIVE: Organ donation is becoming more important with increasing organ transplantation possibilities. We aimed to determine the knowledge, sociocultural view, and influences of religious belief regarding opinions on organ donation. MATERIAL AND METHOD: This study was based on a self-administered survey questionnaire distributed via the Internet. The study sample was sent to Internet communication groups. RESULTS: Three hundred and seventeen participants completed the survey: 39.4% of respondents said that they would definitely donate their organs; 6.9% would only give via live donation; 51.4% were undetermined; and 2.2% absolutely refused to donate. Muslim respondents favored organ donation (36.5%) and linked it to religious reasons (6.3%). Only 4 (1.3%) of the 6 (1.9%) Muslim respondents who said they would definitely not donate did so because they felt that organ donation was religiously inappropriate. Of 22 Muslim participants (7.3%), 5 (1.6%) attributed the idea of living donation to religious reasons and 11 (3.6%) did not have enough information. The atheist respondents believed that the reason for organ donation was to do someone else a favor (88.8%). The deist and agnostic believers also ascribed to this view. In order to evaluate the effects of cultural causes, we examined regional responses and found that 85 of the 196 participants in the Marmara Region would definitely donate organs, 18 would do so only for live donations, and 5 would definitely not donate. CONCLUSION: Religious and cultural factors affect people's decision to donate their organs. In the survey we conducted on Turkish responders, we saw that religious causes are particularly effective in organ donation.