Mediastinal Lymph Nodes In Patients Research Articles

Expression of PD-1/PD-L1 axis in mediastinal lymph nodes and lung tissue of human and experimental lung fibrosis indicates a potential therapeutic target for idiopathic pulmonary fibrosis

BackgroundMediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking.MethodsProgrammed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1) expression in mediastinal lymph nodes and lung tissues was analyzed. PD-1, PD-L1 mRNA expression was measured in tracheobronchial lymph nodes of mice following bleomycin-induced injury on day 14. Finally, the effect of the PD-1 inhibitor, pembrolizumab, in bleomycin-induced pulmonary fibrosis was investigated.ResultsWe analyzed mediastinal lymph nodes of thirty-three patients (n = 33, IPF: n = 14, lung cancer: n = 10, concomitant IPF and lung cancer: n = 9) and lung tissues of two hundred nineteen patients (n = 219, IPF: 123, controls: 96). PD-1 expression was increased, while PD-L1 expression was decreased, in mediastinal lymph nodes of patients with IPF compared to lung cancer and in IPF lungs compared to control lungs. Tracheobronchial lymph nodes isolated on day 14 from bleomycin-treated mice exhibited increased size and higher PD-1, PD-L1 mRNA levels compared to saline-treated animals. Pembrolizumab blunted bleomycin-induced lung fibrosis, as indicated by reduction in Ashcroft score and improvement in respiratory mechanics.ConclusionsMediastinal lymph nodes of patients with IPF exhibit differential expression profiles than those of patients with lung cancer indicating distinct immune-mediated pathways regulating fibrogenesis and carcinogenesis. PD-1 expression in mediastinal lymph nodes is in line with lung tissue expression. Lower doses of pembrolizumab might exert antifibrotic effects. Clinical trials aiming to endotype patients based on mediastinal lymph node profiling and accordingly implement targeted therapies such as PD-1 inhibitors are greatly anticipated.

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.

Radioisotope-Guided Excision of Mediastinal Lymph Nodes in Patients with Non-Small Cell Lung Carcinoma: Feasibility and Clinical Impact.

Intraoperative localisation of nodal disease in non-small cell lung cancer (NSCLC) can be challenging. Lymph node localisation via radiopharmaceuticals is used in many conditions; we tested the feasibility of this approach in NSCLC. NSCLC patients were prospectively recruited. Intraoperative peri-tumoral injections of [99mTc]Tc-albumin nanocolloids were performed, followed by removing the tumour and locoregional lymph nodes. These were examined ex vivo with a gamma probe and labelled sentinel lymph nodes (SLNs) if they showed any activity or non-sentinel lymph nodes (nSLNs) if they did not. Thereafter, the surgical field was scanned with the probe; any further radioactive lymph node was removed and labelled as "extra" SLNs (eSLNs). All specimens were sent to histology, and metastatic status was recorded. 48 patients were enrolled, and 290 nodal stations were identified: 179 SLNs, 87 nSLNs, and 24 eSLNs. A total of 44 nodal metastases were identified in 22 patients, with 36 of them (82%) located within SLNs. Patients with nSLNs metastases had at least a co-existing positive SLN. No metastases were found in eSLNs. The technique shows high sensitivity for intraoperative nodal metastases identification. This information could allow selective lymphadenectomies in low-risk patients or more aggressive approaches in high-risk patients.

Association between Parenchymal B-Cell Follicles and CT-Proven Enlarged Mediastinal Lymph Nodes in Patients with Pulmonary Fibrosis

Background: Mediastinal lymph node enlargement (MLNE) is a finding described in a subset of patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs) and is associated with accelerated disease progression and increased mortality. The cause of MLNE is still not known. Our hypothesis is that there is an association between MLNE and B-cell follicles in lung tissue, another aspect detectable in the lung tissue of patients with IPF and other ILDs. Objectives: The aim of this study was to assess if there is an association between MLNE and B-cell follicles in lung tissue in patients with IPF and other ILDs. Method: Patients having transbronchial cryobiopsies performed as part of an investigation for ILD were included in this prospective observational study. MLNE (smallest diameter ≥10 mm) were assessed in station 7, 4R, and 4L on high-resolution computed tomography scans. B-cell follicles were assessed on haematoxylin-eosin-stained specimens. Lung function, 6-minute walk test, acute exacerbation, and mortality were registered after 2 years. In addition, we investigated if the finding of B-cell follicles was consistent in patients who underwent both surgical lung biopsies (SLBs) and cryobiopsies. Results: In total, 93 patients were included for analysis (46% diagnosed with IPF, 54% diagnosed with other ILDs). MLNE was found in 26 (60%) of the IPF patients and in 23 (46%) of the non-IPF patients (p = 0.164). Diffusing capacity for carbon monoxide was significantly lower (p = 0.03) in patients with MLNE compared to patients without MLNE. B-cell follicles were found in 11 (26%) of the IPF patients and in 22 (44%) of the non-IPF patients (p = 0.064). Germinal centres were not seen in any of the patients. There was no association between MLNE and B-cell follicles (p = 0.057). No significant difference in change of pulmonary function test was seen at 2-year follow-up when comparing the patients with and without MLNE or B-cell follicles. In 13 patients, both SLBs and cryobiopsies were performed. The presence of B-cell follicles was not consistent when comparing the two different methods. Conclusion: MLNE is evident in a substantial part of patients with ILD and is associated with lower DLCO at inclusion. We could not demonstrate an association between histological B-cell follicles in biopsies and MLNE. A possible explanation for this is that the cryobiopsies might not have captured the changes we sought.

Positron emission tomography - Computed tomography for staging of mediastinal lymph nodes in patients with non-small cell lung cancer.

The tumor involvement of lymph nodes (LN) in N2 station is a very important factor for the further therapy decision and the prognosis of lung cancer patients. Today, integrated positron emission tomography-computed tomography (PET-CT) is considered to be the new standard in the staging of bronchial carcinoma. The aim of this study is to investigate the correctness of the clinical staging of the mediastinal LNs in operated patients and to investigate the sensitivity and specificity of the PET-CT examination for mediastinal LNs. In the years 2010-2014, 359 patients underwent surgery for bronchial carcinoma. The histological examination of all mediastinal and hilar LNs was used as a reference to the data from the PET-CT examinations. The correctness of the PET staging, overestimation, and underestimation for the N stage was analyzed. In addition, the "sensitivity," "specificity," and "overall accuracy" of the PET-CT examination with regard to the N2 LNs were calculated. It was found that in 8.9% the staging of the mediastinal N2/N3 LN stations was rated too high by the PET and in 11.2% too low. The study showed a sensitivity of 47.37%, a specificity of 90.07%, and an accuracy of 81.01% for the mediastinal LNs. Our study confirms the limited ability of integrated PET-CT in staging the mediastinal LNs. We, therefore, recommend a histological examination of the LNs in patients with PET-positive N2 LNs to avoid false-positive results and to initiate correct therapy.

CT texture analysis and node-RADS CT score of mediastinal lymph nodes - diagnostic performance in lung cancer patients

BackgroundTexture analysis derived from computed tomography (CT) can provide clinically relevant imaging biomarkers. Node-RADS is a recently proposed classification to categorize lymph nodes in radiological images. The present study sought to investigate the diagnostic abilities of CT texture analysis and Node-RADS to discriminate benign from malignant mediastinal lymph nodes in patients with lung cancer.MethodsNinety-one patients (n = 32 females, 35%) with a mean age of 64.8 ± 10.8 years were included in this retrospective study. Texture analysis was performed using the free available Mazda software. All lymph nodes were scored accordingly to the Node-RADS classification. All primary tumors and all investigated mediastinal lymph nodes were histopathologically confirmed during clinical workup.ResultsIn discrimination analysis, Node-RADS score showed statistically significant differences between N0 and N1-3 (p < 0.001). Multiple texture features were different between benign and malignant lymph nodes: S(1,0)AngScMom, S(1,0)SumEntrp, S(1,0)Entropy, S(0,1)SumAverg. Correlation analysis revealed positive associations between the texture features with Node-RADS score: S(4,0)Entropy (r = 0.72, p < 0.001), S(3,0) Entropy (r = 0.72, p < 0.001), S(2,2)Entropy (r = 0.72, p < 0.001).ConclusionsSeveral texture features and Node-RADS derived from CT were associated with the malignancy of mediastinal lymph nodes and might therefore be helpful for discrimination purposes. Both of the two quantitative assessments could be translated and used in clinical routine.

Potential application of cryobiopsy for histo-molecular characterization of mediastinal lymph nodes in patients with thoracic malignancies: a case presentation series and implications for future developments

BackgroundThe management of non-small cell lung cancer (NSCLC) has become increasingly complex due to the evolution of personalized medicine approaches. Such approaches are characterized by the necessity of adequate tumor samples; hence, improved biopsy techniques are needed. Transbronchial lung cryobiopsy is a novel endoscopic procedure designed to collect peripheral pulmonary tissue, and it is currently employed in interstitial lung diseases. The use of this technique in oncology might result in improved mediastinum staging and molecular characterizations; however, available data involving the use of a cryoprobe on mediastinal lymph nodes are still limited.Case presentationHere we present a series of five consecutive patients who underwent endoscopic assessment of mediastinal lymph nodes for oncologic reasons. All patients were subjected both to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) and cryobiopsy of mediastinal lymph nodes during the same procedure, and no complications were observed. In three of the reported cases, both cryobiopsy and cell block from EBUS TBNA were positive, while in one case cryobiopsy was not diagnostic and EBUS TBNA was negative; moreover, one case showed discordance between the procedures, as cryobiopsy was negative and cell block obtained from multiple stations was diagnostic for small cell lung cancer. In one case involving a patient treated for lymphoma, cryobiopsy provided more complete histologic characterization, and in another case involving a patient affected by NSCLC cryobiopsy provided more material for molecular analyses.ConclusionThis case presentation series suggests that cryobiopsy, which has been generally used on peripheral lung lesions so far, is a feasible and safe approach for diagnosis and staging of mediastinal lymph nodal involvement, especially when station 7 is involved. Compared to EBUS TBNA, cryobiopsy might provide more adequate histological samples, with a possible impact on molecular characterizations and, therefore, therapeutic decisions. However, the learning curve of the procedure has not to be understated and optimal protocols for implementing this technique are needed. In our opinion, further studies designed to integrate the routine use of cryobiopsy in current practice for solid and eventually hematologic tumors with mediastinal lymph node involvement are warranted.

LOBE-SPECIFIC METASTASIS IN NON-SMALL CELL LUNG CANCER

Aim: to identify the pathways of lymph node metastases in non-small cell lung cancer (NSCLC).Material and Methods. The frequency of mediastinal lymph node metastases and treatment outcomes were analyzed in 327 patients with stage I–III non-small cell lung carcinoma (NSCLC), who underwent lung resection with systematic lymph node dissection (SLND) between 2007 and 2011.Results. In cases with tumor location in any lobe of the right lung, metastasis occurred in the superior and inferior mediastinal lymph nodes. In left-side tumors, the main pathways of lymphatic spread of tumors were superior and inferior mediastinal nodes as well as aortic lymph nodes. Left lower lobe tumors metastasized most often to inferior mediastinal lymph nodes. Skip metastases were observed at any location of the tumor. Routine examination of all ipsilateral mediastinal lymph nodes overstaged NSCLC in 19.5 % of cases. The overall 5-and 10-year survival rates in patients with stage I–III NSCLC with SND were 61.5 % and 49.2 %, respectively. The median survival time was 103 months.Conclusion. Despite typical metastatic patterns of mediastinal lymph nodes in patients with NSCLC, non-specific metastasis was observed at any location of the tumor, which required mandatory systematic nodal dissection.

Prevalence and Significance of FDG-avid Mediastinal Lymph Nodes in Patients with Colorectal Cancer in a Tuberculosis-endemic Area

Objective: To find prevalence and causes of fluorodeoxyglucose (FDG)-avid mediastinal lymph nodes in patients with colorectal cancer in a tuberculosis-endemic area.Material and Methods: For this study we enrolled patients with colorectal cancer who underwent Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT). Then, PET/CT images were reviewed by a nuclear medicine physician to find mediastinal lymph nodes with FDG uptake beyond the lung background defined as FDG-avid node. The degree of FDG uptake was graded and measured, and associated factors for presence of FDG-avid nodes were evaluated. The causes of FDG-avid nodes were also determined.Results: A total of 109 patients (64 males; mean age 61.2 years) were studied. Seventy-five patients had FDG-avid mediastinal nodes; accounting for a prevalence of 68.8% (95% CI: 59.2-77.3%). Most of the patients had multiple and bilateral nodes; with the zones of hilar and interlobar being the most common location. Age ≥50 years was the only associated factor for FDG-avid nodes (OR of 3.16, p-value=0.035). Only one out of the 32 patients (with fulfilled followup criteria) had a metastatic node.Conclusion: The prevalence of FDG-avid mediastinal nodes in colorectal cancer patients in a tuberculosis-endemic area was significantly high. Most of the lesions were benign in nature; thus, interpretation of these findings should be considered carefully to avoid false-positive results.

Comparison of Local Recurrence Patterns of Postoperative Radiotherapy with Surgery Alone for Esophageal Carcinoma Patients

<strong>Background:</strong> We analyzed local regional recurrence patterns of thoracic esophageal carcinoma after three-field lymph node dissection (3-FLD) with and without postoperative radiotherapy, and assessed the postoperative radiation value for local control. <strong>Methods:</strong> The study reviewed 239 local recurrences of esophageal squamous cell carcinoma after 3-FLD from 2010 to 2018 in our hospital, retrospectively, and compared local regional recurrence patterns between surgery followed by radiotherapy (S+RT) and surgery alone (SA). <strong>Results:</strong> In 239 thoracic esophageal carcinomas that underwent curative surgery, the lymph node recurrence was the most common type of local recurrence for patients in both groups. The sequence of lymph node recurrence rate in both groups from highest to lowest was mediastinal, cervical, and abdominal. The recurrence rate of superior mediastinal lymph node in patients without radiotherapy was significantly higher than that in patients with radiotherapy (67.72% vs. 47.54%, x² = 7.615, P = 0.006). The recurrence rate of abdominal lymph node in the upper TEC was significantly lower than that in the middle and lower TEC (x² = 9.452, P = 0.009). The abdominal lymph node recurrence rate in patients with preoperative abdominal LNM was very significantly higher than that in patients without preoperative abdominal LNM (43.63% vs. 6.66%, P &lt; 0.001). <strong>Conclusions:</strong> The dangerous lymph node recurrence regions included superior, middle mediastinum, and neck. Postoperative radiotherapy shows great value for patients in reducing superior mediastinal lymph node recurrence rate. The lower segment of thoracic esophageal carcinoma and preoperative abdominal lymph node metastasis, especially para-aortic lymph node metastasis, may be risk factors for abdominal lymph node recurrence.

Prediction of mediastinal lymph node metastasis based on 18F-FDG PET/CT imaging using support vector machine in non-small cell lung cancer.

The purpose of this study was to develop a classification method based on support vector machine (SVM) to improve the diagnostic performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to detect the lymph node (LN) metastasis in non-small cell lung cancer (NSCLC). Two hundred nineteen lymph nodes (37 metastatic) from 71 patients were evaluated in this study. SVM models were developed with 7 LN features. The area under the curve (AUC) and accuracy of 9 models were compared to select the best model. The best SVM model was simplified on the basis of the feature weights and value distribution to further suit the clinical application. The maximum, minimum, and mean accuracy of the best model was 91.89% (68/74, 95% CI 83.11~96.54%), 66.22% (49/74, 95% CI 54.85~75.98%), and 80.09% (59,266/74,000, 95% CI 70.27~89.19%), respectively, with an AUC of 0.94, 0.66, and 0.81, respectively. The best SVM model was finally simplified into a score rule: LNs with scores more than 3.0 were considered as malignant ones, whereas LNs with scores less than 1.5 tended to be benign ones. For the LNs with scores within a range of 1.5-3.0, metastasis was suspected. An SVM model based on 18F-FDG PET/CT images was able to predict the metastatic LNs for patients with NSCLC. The ratio of the maximum of standard uptake value of LNs to aortic arch played a major role in the model. After simplification, the model could be transferred into a scoring method which may partly help clinicians determine the clinical staging of patients with NSCLC relatively easier. • The SVM model based on 18F-FDG PET/CT features may help clinicians to make a decision for metastatic mediastinal lymph nodes in patients with NSCLC. • The SURblood plays a major role in the SVM model. • The score rule based on the SVM model simplified the complexity of the model and may partly help clinicians determine the clinical staging of patients with NSCLC relatively easier.

Risk factor of mediastinal lymph node metastasis of Siewert type I and II esophagogastric junction carcinomas.

Incidence of esophagogastric junction (EGJ) carcinoma has been increasing worldwide. Several studies revealed that the distance from the EGJ to the proximal edge of the primary tumor (esophageal invasion: EI) may be a significant indicator of metastasis in the mediastinal lymph nodes in patients with Siewert type II carcinomas. However, few studies have been conducted in patients with carcinomas located at Siewert type II sequentially to upper carcinomas (Siewert type I) for mediastinal metastasis regardless of histological types. This was a single-center retrospective cohort study. EGJ carcinomas located at Siewert type I and II regions including both squamous cell carcinoma (SCC) and adenocarcinoma were analyzed in terms of lymph node metastasis patterns. We included 121 patients in this study. Thirty-three (27.3%) patients had SCC. In multivariate analysis, the distance of EI (> 20 mm) was an independent risk factor (OR 11.80, p = 0.005) for lower mediastinal lymph node metastasis. In terms of above the middle mediastinal metastasis, the distance of EI (> 30 m), histological type (SCC), and tumor size (> 40 mm) were risk factors in univariate analysis. Furthermore, EI was significant (OR 13.50, p = 0.026) in multivariate analysis. The distance of EI was the independent risk factor for mediastinal lymph node metastasis, especially > 20 mm related with a higher risk for mediastinal lymph node metastasis. Furthermore, EGJ carcinoma patients who have EI > 30 mm, large SCC carcinoma, and multiple lymph node metastasis might be considered the middle-upper mediastinal lymph node dissection by transthoracic approach.

Toll-like receptors 2 expression in mediastinal lymph node of patients with sarcoidosis.

BackgroundToll-like receptors (TLRs) play a vital role as a first defense mechanism linking the innate with the adaptive immune system. Prior studies showed that TLR2 participated in immune responses of sarcoidosis. However, the role of TLR2 in the progression of mediastinal lymph nodes associated with sarcoidosis is still unknown. The current study aims to investigate the expression of Toll-like receptors 2 (TLR2) in mediastinal lymph nodes of patients with sarcoidosis.MethodsMediastinal lymph nodes biopsy specimens were collected from 10 patients with sarcoidosis and 11 normal controls. The expression of TLR2 in mediastinal lymph nodes was detected by immunohistochemistry.ResultsIn mediastinal lymph nodes specimens, immunohistochemical examination revealed that expression of TLR2 could be detected in sarcoidosis patients, while it was scarcely detected in the mediastinal lymph nodes of control. The mean optical density of TLR2 in mediastinal lymph nodes of sarcoidosis was significantly higher than controls (124.9±24.3 vs. 92.6±35.2, P=0.026). Among patients with sarcoidosis, correlation analysis showed that the mean optical density of TLR2 in mediastinal lymph nodes positively correlated with the level of 24-hour urinary calcium (R=0.781, P=0.038).ConclusionsThe expression of TLR2 was upregulated in mediastinal lymph nodes of sarcoidosis patients. The expression of TLR2 in mediastinal lymph nodes was associated with the level of 24-hour urinary calcium, suggesting that TLR2 might become another predictor of disease activity.

Video-assisted mediastinoscopic lymphadenectomy (VAMLA) for staging & treatment of non-small cell lung cancer (NSCLC).

Precise preoperative staging and restaging of mediastinal lymph nodes in patients with potentially resectable non-small cell lung cancer (NSCLC) is of supreme importance. Over the last years, algorithms on preoperative mediastinal staging incorporating imaging, endoscopic and surgical techniques have been widely published, offering more evidence concerning different mediastinal staging techniques. Current guidelines well define when and how to receive tissue confirmation in case of computed tomography (CT)-enlarged or positron emission tomography (PET)-positive mediastinal lymph nodes. Endosonography [(endoscopic bronchial ultrasonography/oesophageal ultrasonography (EBUS/EUS)] with fine needle aspiration still is the first choice (when accessible) since it is minimally invasive and has a high sensitivity to confirm mediastinal nodal disease. If negative, surgical staging with nodal dissection or biopsy is indicated. Video-assisted mediastinoscopic lymphadenectomy (VAMLA) and transcervical extended mediastinal lymphadenectomy (TEMLA) are preferred over conventional mediastinoscopy if a mediastinal R0-resection can be achieved. The mutual use of endoscopic and surgical staging effects highest accuracy. Straight surgical resection of tumors ≤3 cm (located within the external third of the lung) with systematic nodal dissection is justified as soon as there are no enlarged lymph nodes on CT-scan and once there is no nodal uptake on PET-CT. In case of central tumors and enlarged or FDG avid nodes regardless of cytological result, preoperative invasive mediastinal staging is indicated to rule out mediastinal nodal spread. However, accuracy needed in preoperative nodal staging has been under continuous debate ever since and with the advent of immunotherapy is right now intensely revived. During the last two decades VAMLA has been growing up from being a merely staging tool to an expert-recognized therapeutic tool in the context of minimal invasive lung cancer resection.

P2.13-11 Predicting Micrometastasis in Mediastinal Lymph Nodes in Patients with Non-Small Cell Lung Cancer

Non-small-cell lung cancer staging is the most important factor affecting both the potential treatment and the prognosis. The evaluation of non-small cell lung carcinoma staging uses the TNM classification (tumor, node, metastasis). The N factor plays a more critical role in staging than T and M factors, because of its unpredictability. We know that undiagnosed micrometastatic nodal disease has a poor prognosis. Detecting micrometastasis is expensive and time consuming, so that’s why we aimed to investigate the factors predicting micrometastatic mediastinal disease. We collected all the lymph nodes from the patients that we operated between July 2012 and July 2013. We excluded all the patients who had an induction treatment and preoperatively diagnosed with mediastinal metastasis. We studied the expressions of three biomarkers; EpCAM, CEACAM5 and KRT19 using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in lymph nodes and compared the expressions with healthy controls. If all three of them are positive, we have accepted it as micrometastasis. We compared the presence of micrometastasis with the pathological data to identify possible predictive factors. We analyzed 86 lymph nodes from 32 patients. Twenty seven out of 86 lymph nodes (%31.4) were positive for micrometastasis. Eighteen out of 32 patients (%56.3) became micrometastatic and 16 out of 32 patients are upstaged. Four of them are upstaged from N1 to N2 and 12 of them are upstaged from N0 to N2. Micrometastatic patients tend to have poorer survival compared to non-micrometastatic patients but without an statistical significance. However micrometastasis was found significantly higher in tumors with less than 2 cm (p: 0.03) and lower in tumors without lymphovasculary invasion (p: 0.03). In our study tumors with smaller than 2cm in diameter and without lymphovascular invasion have significantly higher micrometastatic potential. In order to validate these parameters as predictive markers this experiment should be performed in a larger cohort with increased control population.

Statistical approach to mediastinal staging in NSCLC with M.E.S.S.i.a. software.

The exclusion of pathological involvement of mediastinal lymph nodes in patients affected by NSCLC plays a central role in assessing their prognosis and operability. Ceron et al. developed a software - called M.E.S.S.i.a (Mediastinal Evaluation with Statistical Support; instan approach) - that allows the calculation of the residual probability of lymph node involvement after a certain number of tests has been done, by integrating every test result with the pre-test prevalence. M.E.S.S.i.a. bridges a gap of current American College of Chest Physicians (ACCP) guidelines, providing probability values of mediastinal metastasis for a correct clinical decision. We conducted a preliminary retrospective study in a series of 108 patients affected by non small cell lung cancer (NSCLC). Pathological staging was compared to the probability of nodal involvement calculated by M.E.S.S.i.a. software. Forty-two out of 108 subjects (39%) had a calculated post-test probability <8%; none of these had proven N2/N3 metastasis at surgical staging (negative predictive value, NPV: 100%). In 12/41 cases M.E.S.S.i.a. was able to avoid invasive procedures. The remaining 66 (61%) patients did not reach the surgical threshold; among these, 11 displayed N2 positivity at pathological staging. Receiving operator curve (ROC) analysis produced an area under curve (AUC) value of 0.773 (p<0.001). These preliminary data show high accuracy of M.E.S.S.i.a. software in excluding N2/N3 lymph node involvement in NSCLC. We have therefore promoted a prospective multicenter study in order to to get a validation of the calculator at different levels of probability of lymph node involvement. The recruitable subjects are potentially operable NSCLC patients; the gold standard for detection of mediastinal disease is the surgical lymph node dissection.

Value of LSR and ADCs in differential diagnosis of hilar and mediastinal lymph nodes in lung cancer

Objective: To evaluate the value of minimum ADC(ADC(min))and mean ADC(ADC(mean)), lesion to spinal cord signal intensity ratio (LSR) in diagnosis of metastatic hilar and mediastinal lymph nodes in patients with lung cancer. Methods: A total of 34 patients (89 lymph nodes) pathologically diagnosed as lung cancer were enrolled into this study who were examined in the Second Affiliated Hospital of Nantong University from January 2016 to June 2017. All patients underwent MRI scan 1 week before surgery or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The short-axis diameter, ADC(mean) and ADC(min) of lymph nodes were measured and recorded respectively by two radiologists.The signal intensity of lymph nodes and spinal cord was also measured on DWI images (b=800 s/mm(2)). According to pathological findings, all lymph nodes were divided into metastasis group (58 lymph nodes) and non-metastasis group(31 lymph nodes). An independent sample t-test was used to compare the differences between the two groups of short-axis diameter, LSR, ADC(mean) and ADC(min) between two groups.The diagnostic performance of short-axis diameter, LSR, ADC(mean) and ADC(min) was analyzed by ROC curves. Results: There were significant differences in short-axis diameter, ADC(mean), ADC(min) and LSR values between two groups (all P<0.01). The short-axis diameter and LSR of the metastatic group were higher than that in non-metastasis group, while ADC(mean) and ADC(min) in metastatic group were lower than that in non-metastasis group.The ROC curve analysis showed that ADC(mean), ADC(min) and LSR achieved excellent but comparable diagnostic performance with an AUC of 0.977, 0.972 and 0.941, respectively (P<0.05). While the short-axis diameter of lymph nodes demonstrated poor diagnosis performance with an AUC of 0.798 (P<0.05). The thresholds of short-axis diameter, ADC(mean), ADC(min) and LSR were 9.86 mm, 1.88×10(-3) mm(2)/s, 1.57×10(-3) mm(2)/s and 0.80, respectively.Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for ADC(mean) were 96.6%, 90.3%, 94.9%, 93.3% and 94.4%, respectively, and those for ADC(min) were 98.3%, 90.3%, 95.0%, 96.6% and 94.4%, respectively, those for LSR were 91.4%, 90.3%, 94.6%, 84.8% and 89.9%, respectively, while those for short-axis diameter were 79.3%, 71.0%, 83.6%, 64.7% and 76.4%, respectively.There were significant differences in the area under the ROC curve between short-axis diameter and LSR, short-axis diameter and ADC(mean), short-axis diameter and ADC(min) (P<0.05). But there was no significant difference in the area under ROC curve between LSR and ADC(mean), LSR and ADC(min), ADC(mean) and ADC(min) (P>0.05). Conclusion: LSR, ADC(min) and ADC(mean) are the reliable parameters for the differentiation of metastatic and non-metastatic lymph nodes in lung cancer patients, and have good performance.

Prevalence and echo features of mediastinal lymph nodes in EUS for non-malignant indications: a prospective study in a Southern European Population.

Background and study aims Significant heterogeneity in geographic distribution regarding the prevalence of mediastinal lymph nodes (MLN) has been documented in autopsy and computed tomography (CT) studies. Awareness of the local prevalence and characteristics of lymph nodes will be relevant when performing endoscopic ultrasonography (EUS) for staging of malignant neoplasias. The aims of this study were to document the prevalence and echo features of MLN in patients undergoing EUS for non-malignant extrathoracic disease and to identify predictive factors for the presence of MLN. Patients and methods A prospective single-center study was performed over 6 months. Mediastinal stations 9, 8, 7, 6, 5, 4 L and 2 were systematically evaluated using a linear echoendoscope in all patients undergoing EUS due to benign extrathoracic pathology and without history of oncologic disease. Demographic, clinical and EUS features of the lymph nodes were analysed. Results Seventy-five patients were included: male/female 32/43; mean age, 63 years. The majority of patients (72 %) had lymph nodes in at least one mediastinal station and 88 % of these were found in stations 7 or 4 L. Overall, 133 MLN were identified: 19 % were hypoechogenic, 6 % had a short-axis diameter > 10 mm, and 6 % were round. The prevalence of lymph nodes was higher in smokers (83 % vs 64 %, P = 0.024), with a higher average number of lymph nodes per patient in this group (2.1 vs 1.6; P = 0.017). By logistic regression analysis, none of the variables analyzed were independently associated with the presence of MLN. Conclusion This prospective Portuguese study documented a higher prevalence of MLN than previously reported in Northern Europe, in patients with no evidence of oncologic disease. This higher prevalence may negatively influence the specificity and positive predictive value for malignancy of MLN (N) staging by EUS.

Macroelement and microelement composition of mediastinal lymph nodes of patients with sarcoidosis

This study was aimed at measuring concentrations and investigation of relationships between macro- and microelements in mediastinal lymph nodes of patients with sarcoidosis. Methods. The study involved 28 patients (50% were males; median age, 42.5 (23; 53) years) with confirmed diagnosis of sarcoidosis. Autopsy samples from 13 individuals died from occasional causes (41.2% were males; median age, 43 (38.7; 61.3) years) were used for comparison. The groups did not differ in age and gender. Neutron activation analysis was used to investigate chemical elements in mediastinal lymph node tissue samples. Results. Concentrations of Ca, Cr, Fe, Co, Zn, Rb, Sb, Cs, Ba, Eu, Lu, Yb, Hf, Th, and U in the lymph node tissue of patients with sarcoidosis were increased, and concentration of zinc was decreased compared to control samples. Concentrations of Sm, Au, Sr, Nd, As, Br, Ag, Tb, Sc, Ta, Na, and La did not differ between the groups. Direct relationships were found in element groups Fe-Cr-Sb-Ca, Fe-U-Th, Co-U-Th, U-Cr, Th-Br, Sc-Zn, Eu-La, and Ce-Lu.

Texture Analysis and Synthesis of Malignant and Benign Mediastinal Lymph Nodes in Patients with Lung Cancer on Computed Tomography

Texture analysis of computed tomography (CT) imaging has been found useful to distinguish subtle differences, which are in- visible to human eyes, between malignant and benign tissues in cancer patients. This study implemented two complementary methods of texture analysis, known as the gray-level co-occurrence matrix (GLCM) and the experimental semivariogram (SV) with an aim to improve the predictive value of evaluating mediastinal lymph nodes in lung cancer. The GLCM was explored with the use of a rich set of its derived features, whereas the SV feature was extracted on real and synthesized CT samples of benign and malignant lymph nodes. A distinct advantage of the computer methodology presented herein is the alleviation of the need for an automated precise segmentation of the lymph nodes. Using the logistic regression model, a sensitivity of 75%, specificity of 90%, and area under curve of 0.89 were obtained in the test population. A tenfold cross-validation of 70% accuracy of classifying between benign and malignant lymph nodes was obtained using the support vector machines as a pattern classifier. These results are higher than those recently reported in literature with similar studies.