Prognostic Impact of Mediastinal Lymph Nodes in Interstitial Lung Diseases: Is Environmental Exposure the Offender?
Ontology highlight
ABSTRACT:
SUBMITTER: Khamis W
PROVIDER: S-EPMC6467302 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description: Not available
| S-EPMC6467315 | biostudies-literature
Project description:Background: Lymph node metastasis (LNM) status is critical to the treatment. Fewer studies has focused on LNM in patients with small-size non-small cell lung cancer (NSCLC). This study aims to investigate clinicopathological characteristics associated with skip N2 (SN2) and non-skip N2 (NSN2) metastasis, and their metastatic patterns in NSCLC with tumor size of 1-2 cm. Methods: We reviewed the records of NSCLC patients with tumor size of 1-2 cm who underwent lobectomy with systematic lymph node dissection (LND) between January 2013 and June 2019. Clinical, radiographical, and pathological characteristics were compared among N1, SN2, and NSN2 groups. Metastatic patterns of mediastinal lymph node were analyzed based on final pathology. Results: A total of 63 NSCLC patients with tumor size of 1-2 cm were staged as pN2, including 25 (39.7%) SN2 and 38 (60.3%) NSN2. The incidence rates of SN2 and NSN2 were 2.8% (25/884) and 4.3% (38/884), respectively. For all clinicopathological characteristics, no significant difference was observed among the groups of N1, SN2, and NSN2. For the tumor located in each lobe, specific nodal drainage stations were identified: 2R/4R for right upper lobe; 2R/4R and subcarinal node (#7) for right middle lobe and right lower lobe; 4L and subaortic node (#5) for left upper lobe; #7 for left lower lobe. However, there were still a few patients (10.9%, 5/46) had the involvement of lower zone for tumors of upper lobe and the involvement of upper zone for lower lobe. Conclusions: SN2 occurs frequently in patients with small-size NSCLC. Whether lobe-specific selective LND is suitable for all small-size patients deserves more studies to confirm. Surgeons should be more careful when performing selective LND for tumors located in the lower and upper lobes.
| S-EPMC7536402 | biostudies-literature
Project description:It is important to detect mediastinal lymph node metastases in patients with lung cancer to improve outcomes, and it is possible that activatable fluorescence imaging with indocyanine green (ICG) can help visualize metastatic lymph nodes. Therefore, we investigated the feasibility of applying this method to mediastinal lymph node metastases in an epidermal growth factor receptor (EGFR)-positive squamous cell carcinoma of the lung. Tumors were formed by injecting H226 (EGFR-positive) and H520 (EGFR-negative) cell lines directly in the lung parenchyma of five mice each. When computed tomography revealed tumors exceeding 8 mm at their longest or atelectasis that occupied more than half of lateral lung fields, a panitumumab (Pan)-ICG conjugate was injected in the tail vein (50 ?g/100 ?L). The mice were then sacrificed 48 hours after injection and their chests were opened for fluorescent imaging acquisition. Lymph node metastases with the five highest fluorescent signal intensities per mouse were chosen for statistical analysis of the average signal ratios against the liver. Regarding the quenching capacity, the Pan-ICG conjugate had almost no fluorescence in phosphate-buffered saline, but there was an approximate 61.8-fold increase in vitro after treatment with 1% sodium dodecyl sulfate. Both the fluorescent microscopy and the flow cytometry showed specific binding between the conjugate and H226, but almost no specific binding with H520. The EGFR-positive mediastinal lymph node metastases showed significantly higher average fluorescence signal ratios than the EGFR-negative ones (n = 25 per group) 48 hours after conjugate administration (70.1% ± 4.5% vs. 13.3% ± 1.8%; p < 0.05). Thus, activatable fluorescence imaging using the Pan-ICG conjugate detected EGFR-positive mediastinal lymph node metastases with high specificity.
| S-EPMC5983456 | biostudies-literature
Project description:AimsThis study evaluated the safety and efficacy of stereotactic radiation therapy (SRT) for the treatment of patients with oligometastases or oligorecurrence within mediastinal lymph nodes (MLNs) originating from different tumors.MethodsBetween October 2006 and May 2015, patients with MLN oligometastases or oligorecurrence were enrolled and treated with SRT at our hospital. The primary endpoint was MLN local control (LC). Secondary endpoints were time to symptom alleviation, overall survival (OS) after SRT, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0).ResultsEighty-five patients with 98 MLN oligometastases or oligorecurrences were treated with SRT. For the entire cohort, the 1-year and 5-year actuarial LC rates were 97% and 77%, respectively. Of 53 symptomatic patients, symptom alleviation was observed in 47 (89%) after a median of 5 days (range, 3-30 days). The median OS was 27.2 months for all patients. For patients with non-small cell lung cancer, univariate and multivariate analyses revealed that a shorter interval between diagnosis of primary tumors and SRT and larger MLN SRT volume were associated with worse OS. CTCAE v4.0 ? Grade 3 toxicities occurred in six patients (7%), with Grade 5 in three patients (all with RT history to MLN station 7).ConclusionsSRT is a safe and efficacious treatment modality for patients with oligometastases or oligorecurrence to MLNs originating from different tumors, except for patients who received radiotherapy to MLN station 7. Further investigation is warranted to identify the patients who benefit most from this treatment modality.
| S-EPMC4951277 | biostudies-literature
Project description:A balance between tumor invasion and immune defence system is widely investigated. Objective. The aim of this study was to evaluate lymphocyte phenotype in lymph nodes (LNs) of patients with lung cancer in relation to the presence of metastases. Methods. We investigated 364 LNs resected by transcervical extended mediastinal lymphadenectomy (TEMLA) of 49 patients with squamous cell carcinoma (SCC) or adenocarcinoma (AD) with (A) and without metastases (B). Expression of CD4, CD8, CD25, CTLA-4, and Foxp3 was assessed by immunohistochemical staining. Results. We observed a strong nuclear staining for Foxp3 in lymphocytes and cancer cells and strong membranous/cytoplasmatic reaction for CD4 and CD8, but low for CD25 and CTLA-4. There were significantly higher proportions of CD8+ cells in AD (B) versus AD (A) LNs (80% versus 52.5%, p < 0.05). The Foxp3/CD8 ratio was higher in AD (A) versus AD (B) LNs (0.4 versus 0.25, p < 0.05). No significant differences in the cell markers expression in SCC LNs were found. Conclusion. Significant differences in lymphocyte phenotype in AD may indicate an exceptional biology of this type of lung cancer. TEMLA resected LNs may serve as valuable samples for evaluation of immune status in lung cancer patients.
| S-EPMC5558641 | biostudies-other
Project description:Background/aimPatients with stage IIIA (N2) non-small cell lung cancer (NSCLC) with no progression after induction chemotherapy are usually selected for surgery. Nowadays, response to chemotherapy is not predictable. We aimed to identify genomic predictive markers for response to induction chemotherapy in stage IIIA (N2) NSCLC patients.Patients and methodsWhole-exome sequencing (WES) was performed on samples from 11 patients with no response after induction chemotherapy and 6 patients with documented pathological response, admitted to the Hotel Dieu Hospital, Paris or Allegemeines Krakenhaus University, Vienna.ResultsA higher alternative allele frequency was found on SENP5, rs63736860, rs1602 and NCBP2, rs553783 in the non-responder group, and on RGP1, rs1570248, SLFN12L, rs2304968, rs9905892, and GBA2, rs3833700 in the responder group.ConclusionThese polymorphisms contribute to inter-individual sensibility to chemotherapy response. Interrogation of these genetic variations may have potential applicability when deciding the treatment strategy for patients with stage III NSCLC (N2).
| S-EPMC7472447 | biostudies-literature
Project description:RationaleMediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking.ObjectivesWe aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD.MethodsMLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity-related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts.Measurements and main resultsChest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (≥10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12-2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17-1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15-2.53; P = 0.008, respectively) when compared with subjects with MLN <10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration >45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21-14.68; P = 0.024). Independent analysis of external datasets confirmed these findings.ConclusionsMLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.
| S-EPMC6423102 | biostudies-literature
Project description:The regulation of lymphocyte adhesion and migration plays crucial roles in lymphocyte trafficking during immunosurveillance. However, our understanding of the intracellular signalling that regulates these processes is still limited. Here, we show that the Ste20-like kinase Mst1 plays crucial roles in lymphocyte trafficking in vivo. Mst1(-/-) lymphocytes exhibited an impairment of firm adhesion to high endothelial venules, resulting in an inefficient homing capacity. In vitro lymphocyte adhesion cascade assays under physiological shear flow revealed that the stopping time of Mst1(-/-) lymphocytes on endothelium was markedly reduced, whereas their L-selectin-dependent rolling/tethering and transition to LFA-1-mediated arrest were not affected. Mst1(-/-) lymphocytes were also defective in the stabilization of adhesion through alpha4 integrins. Consequently, Mst1(-/-) mice had hypotrophic peripheral lymphoid tissues and reduced marginal zone B cells and dendritic cells in the spleen, and defective emigration of single positive thymocytes. Furthermore, Mst1(-/-) lymphocytes had impaired motility over lymph node-derived stromal cells and within lymph nodes. Thus, our data indicate that Mst1 is a key enzyme involved in lymphocyte entry and interstitial migration.
| S-EPMC2683056 | biostudies-literature
Project description:Air pollution exposure is a well-established risk factor for several adverse respiratory outcomes, including airways diseases and lung cancer. Few studies have investigated the relationship between air pollution and interstitial lung disease (ILD) despite many forms of ILD arising from environmental exposures. There are potential mechanisms by which air pollution could cause, exacerbate, or accelerate the progression of certain forms of ILD via pulmonary and systemic inflammation as well as oxidative stress. This article will review the current epidemiologic and translational data supporting the plausibility of this relationship and propose a new conceptual framework for characterizing novel environmental risk factors for these forms of lung disease.
| S-EPMC4388120 | biostudies-other
Project description:Pandemic live attenuated influenza vaccines (pLAIV) prime subjects for a robust neutralizing antibody response upon subsequent administration of a pandemic inactivated subunit vaccine (pISV). However, a difference was not detected in H5-specific memory B cells in the peripheral blood between pLAIV-primed and unprimed subjects prior to pISV boost. To investigate the mechanism underlying pLAIV priming, we vaccinated groups of 12 African green monkeys (AGMs) with H5N1 pISV or pLAIV alone or H5N1 pLAIV followed by pISV and examined immunity systemically and in local draining lymph nodes (LN). The AGM model recapitulated the serologic observations from clinical studies. Interestingly, H5N1 pLAIV induced robust germinal center B cell responses in the mediastinal LN (MLN). Subsequent boosting with H5N1 pISV drove increases in H5-specific B cells in the axillary LN, spleen, and circulation in H5N1 pLAIV-primed animals. Thus, H5N1 pLAIV primes localized B cell responses in the MLN that are recalled systemically following pISV boost. These data provide mechanistic insights for the generation of robust humoral responses via prime-boost vaccination.IMPORTANCE We have previously shown that pandemic live attenuated influenza vaccines (pLAIV) prime for a rapid and robust antibody response on subsequent administration of inactivated subunit vaccine (pISV). This is observed even in individuals who had undetectable antibody (Ab) responses following the initial vaccination. To define the mechanistic basis of pLAIV priming, we turned to a nonhuman primate model and performed a detailed analysis of B cell responses in systemic and local lymphoid tissues following prime-boost vaccination with pLAIV and pISV. We show that the nonhuman primate model recapitulates the serologic observations from clinical studies. Further, we found that pLAIVs induced robust germinal center B cell responses in the mediastinal lymph node. Subsequent boosting with pISV in pLAIV-primed animals resulted in detection of B cells in the axillary lymph nodes, spleen, and peripheral blood. We demonstrate that intranasally administered pLAIV elicits a highly localized germinal center B cell response in the mediastinal lymph node that is rapidly recalled following pISV boost into germinal center reactions at numerous distant immune sites.
| S-EPMC5899203 | biostudies-literature