Potentialities of ultrasound and computed tomography in the diagnosis of metastases of lung cancer in the mediastinal lymph nodes]

The results of routine roentgenotomography, CT and USI in the diagnosis of intrathoracic metastases of lung cancer were compared in 69 patients (central type--52, peripheral--17). These results were compared with operative findings in 45 patients. The sensitivity of USI in the diagnosis of enlarged paravasal lymph nodes exceeded that of roentgenotomography and was slightly inferior to CT. CT was informative for all mediastinal lymph nodes whereas tomography and USI were informative in certain areas only. The authors recommend to combine the use of routine and ultrasound tomography to assess the spreading of lung cancer to the mediastinum. The information obtained increases the accuracy of staging and specifying a process, slightly yielding CT results.     

Measurement of primary tumor volume by PET–CT to evaluate risk of mediastinal nodal involvement in NSCLC patients with clinically negative N2 lymph nodes

Aim

The study aimed to determine a prognostic value of primary tumor volume measured on the basis of integrated positron emission tomography–computerized tomography (PET–CT) in terms of mediastinal nodal metastases (N2) prediction in non-small-cell lung cancer (NSCLC) patients with PET–CT N2 negative lymph nodes.

Methods

The records of 70 potentially operable NSCLC patients treated with surgical resection were analyzed. All patients underwent diagnostic, preoperative PET–CT, which was the basis for tumor volume calculations as well as the evaluation of N2 nodes status. The logistic regression analysis was employed to determine correlation between mediastinal nodal involvement and volume of primary tumor (izoSUV2.5 volume), that is the volume of primary tumor inside SUV 2.5 line, tumor histology, location (peripheral vs. central), hilar node status.

Results

A statistically significant correlation between mediastinal node involvement and izoSUV2.5 volume, tumor histology, locations peripheral vs. central and hilar node status was found. The risk of mediastinal lymph node metastasis is 24% for tumor volume of 100 cm³ and increases up to 40% for tumor volume of 360 cm³. An increase of tumor volume by 1 cm³ increases the risk of lymph node disease by 0.3%. Tumor histology adenocarcinoma vs. squamous cell carcinoma increases the risk of mediastinal lymph node involvement by 195%, location central vs. peripheral by 68% and hilar node involvement by 166%.

Conclusions

The study demonstrates that izoSUV2.5 volume of primary tumor may be considered as a prognostic factor in NSCLC patients, since it strongly correlates with mediastinal lymph node pathological status. This correlation is modified by primary tumor location, histology and hilar node involvement.     

Model for mediastinal lymph node metastasis produced by orthotopic intrapulmonary implantation of lung cancer cells in mice

This study is designed to establish a pulmonary tumor model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma cell (LLC) suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 sec per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph nodes metastasis were observed in all mice that were succeeded to form a lung nodule after intrapulmonary implantation. The size of tumor nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21 +/- 2 days (range; 19-24 days). Histopathological analysis revealed that no metastatic tumor was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary implantation is due to the release of tumor cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of CDDP on day 1 after tumor implantation tended to suppress the primary tumor nodule and significantly inhibited the lymph node metastasis. Thus, a solitary pulmonary tumor nodule model with lymph node metastasis approximates clinical lung cancer, and may provide a useful basis for lung cancer research.     

Topography of lymphatic collectors and regional lymph nodes of the canine heart and their morphological characteristics

In 40 dogs lymphatic vessels and regional lymph nodes of the heart have been prepared. Morphology of the regional lymph nodes have been studied by means of various histological techniques. Lymph outflow from the canine ventricles is realized by three (less often), or by two (more often) collectors. In very rare cases one collector is formed. From the right atrium lymph flows out in two collectors (cranial and left). Lymphatic vessels of the left atrium get into the left collector of the ventricles, or into the tracheobronchial lymph nodes. Into the same nodes gets the lymphatic vessel, forming at the border of the left and right atrii. Cranial, medial, caudal mediastinal nodes (lymphatic mediastinal system) and right, middle and left tracheobronchial lymph nodes (tracheobronchial system) are regional lymph nodes of the canine heart. In the lymph nodes of the tracheobronchial system of puppies older than one month presence of exogenic pigment and signs of fibrous degeneration of parenchyma are noted.     

电视纵隔镜与CT 对胸部疾病诊断的运用研究

目的:探讨电视纵隔镜与CT对胸部疾病诊断中的运用.方法:对我院收治的59例胸部疑难疾病患者采用CT以及电视纵隔镜检查,并对两种方法对肺癌纵膈淋巴转移的诊断效果进行比较.结果:所有患者采用纵隔镜检查其确诊率为100％,CT诊断诊断符合率为525％;CT对肺癌纵隔淋巴结转移的灵敏度为55.26％、真实性为57.89％、特异度为60.53％、阳性预测值为44.74％以及阴性预测值为81.58％,而电视纵隔镜其分别为94.74％、97.37％、100.00％、100.00％、97.37％.电视纵隔镜在诊断肺癌纵膈淋巴结转移的各项指标中均优于CT.结论:电视纵隔镜对胸部疑难疾病具有较好的诊断效果,而且其具有并发症少等特点.     

Caractérisation des adénopathies médiastinales en TEP/TDM au 18F-FDG

The mediastinum is a complex anatomical region located at the junction of the cervical, thoracic and abdominal regions. It is an important lymphatic gateway that has an impact in many pathologies with nodal involvement and for which ¹⁸F-FDG PET/CT is a central examination. In this review article, we propose to recall the normal and pathological lymphatic drainage, mediastinum anatomy, the International Association for the Study of Lung Cancer (IASLC) lymph node classification and its implications in lung cancer. Then we will detail the morphological and metabolic characteristics, principal etiologies and the procedures to access mediastinal lymph nodes.     

Patterns of lymphatic drainage to individual thoracic and cervical lymph nodes in the rat

Colloidal carbon was used as tracer material to determine the lymphatic drainage to the cervical and thoracic lymph nodes from various regions of the respiratory tract in the F344 rat. While the lung region may be drained mainly to the posterior mediastinal lymph nodes, the tracheal wall drains primarily to the internal jugular and posterior cervical nodes.     

Specific route mapping visualized with GFP of single‐file streaming contralateral and systemic metastasis of Lewis lung carcinoma cells beginning within hours of orthotopic implantion

In this study, we visualized the origin of Lewis lung carcinoma metastasis after transducing tumor cells with green fluorescent protein (GFP) and transplanting them orthotopically in the middle lobe of the right lung of nude mice. Metastasis was visualized in live tissue at single cell resolution by GFP‐expression as early as 18 h post‐tumor transplant. At this time, single‐file streaming lung carcinoma cells already had invaded inferiorly via a tubular lymphatic structure crossing the lower lobes of the lung to the ipsilateral diaphragmatic surface. By post‐implantation day 2, the ipsilateral lower lobes of the lung were involved with metastatic cells. By post‐implantation day 3, the ipsilateral lower lobes of the lung and the ipsilateral diaphragmatic surface were highly involved with streaming metastatic cells trafficking in single file. By day 4 post‐implantation, cancer cells invaded across the diaphragm to the contralateral diaphragmatic surface. Metastatic cells then invaded superiorly through a lymphatic vessel to involve the contralateral mediastinal lymph nodes. In this model of lung cancer, the origin of metastasis was an inferior invasion from the implanted tumor via a lymphatic duct to the ipsilateral diaphragmatic surface. The cancer cells from this site invaded on the surface of the diaphragm to the contralateral diaphragmatic surface and proceeded superiorly through a lymphatic duct to contralateral lymph nodes. Other organs such as the kidneys and the adrenal glands later became involved with metastasis with the contralateral mediastinal lymph nodes as the source. The use of GFP and the highly metastatic orthotopic lung cancer model allowed the visualization of the origin of metastasis at the single‐cell level and demonstrated the critical role of lymphatic ducts and the diaphragmatic surface as the path to the contralateral side. J. Cell. Biochem. 114: 1738–1743, 2013. © 2013 Wiley Periodicals, Inc.     

Stereotactic radiotherapy for oligometastases in the lymph nodes

Even though systemic therapy is standard treatment for lymph node metastases, metastasis-directed stereotactic radiotherapy (SRT ) seems to be a valid option in oligometastatic patients with a low disease burden.Positron emission tomography-computed tomography (PET-CT ) is the gold standard for assessing metastases to the lymph nodes; co-registration of PET-CT images and planning CT images are the basis for gross tumor volume (GTV ) delineation. Appropriate techniques are needed to overcome target motion. SRT schedules depend on the irradiation site, target volume and dose constraints to the organs at risk (OARs) of toxicity. Although several fractionation schemes were reported, total doses of 48–60 Gy in 4–8 fractions were proposed for mediastinal lymph node SRT, with the spinal cord, esophagus, heart and proximal bronchial tree being the dose limiting OAR s. Total doses ranged from 30 to 45 Gy, with daily fractions of 7–12 Gy for abdominal lymph nodes, with dose limiting OARs being the liver, kidneys, bowel and bladder. SRT on lymph node metastases is safe; late side effects, particularly severe, are rare.     

Comparison of local and systemic responsiveness of lymphocytes in vitro to Bovicola ovis antigen and Concanavalin A in B. ovis-infested and naive lambs

The in vitro proliferation assay was used to determine lymphocyte responsiveness to soluble antigen of B. ovis and to Concanavalin A (Con A) in peripheral blood, spleen and various lymph nodes from B. ovis-infested and naive lambs. From March to July, an assay of monthly blood samples showed generally higher proliferative responses to antigen and Con A in B. ovis-infested than naive lambs. The proliferative response of cells from the skin-draining prescapular lymph nodes to B. ovis antigen was significantly higher in B. ovis-infested than naive lambs. Responses of cells from the medial iliac, mediastinal and mesenteric lymph nodes (which do not receive lymph from the skin) and spleen showed no significant differences between groups. Within the B. ovis-infested lambs, the response of cells from the prescapular lymph node was significantly higher than that from any other lymphoid organ examined. Responsiveness of the prescapular, medial iliac and mesenteric lymph node and spleen cells to Con A was not significantly different between groups, while mediastinal lymph node cells showed a significantly higher response in B. ovis-infested lambs. The data indicate that the antigen-specific cellular immune response is operating mainly locally, at the level of the skin and draining lymph nodes. Responses to the T cell mitogen Con A did not support non-specific immunodepression as reported in other ectoparasite/host systems.     

Pan and sentinel lymph node visualization using a near-infrared fluorescent probe

A number of different types of agents have been employed to aid in the visualization of lymph nodes, particularly the sentinel lymph node, and to decrease the tissue destruction associated with the diagnosis of nodal metastases. The current study was performed to see if a novel macromolecular near-infrared fluorescent (NIRF) probe could be used to visualize lymph nodes after intravenous administration (pan-node visualization) or subcutaneous administration (sentinel node visualization), and serve as method for guiding dissection with interventional radiologic and surgical procedures. Cy5.5-PGC, the near-infrared dye Cy5.5 coupled to a protected graft copolymer (PGC), was injected (i.v. or s.c.) into nude mice. Twenty-four hours later white light and NIRF images were obtained on (i) the live animal, (ii) a partially dissected animal, and (iii) tissue specimens. With Cy5.5-PGC administered intravenously, axillary nodes were visualized from outside a living mouse. With partial dissection, iliac and aortic nodes were visible as concentrated foci of high-intensity NIRF signals. With subcutaneous injection in the front extremity, axillary and brachial nodes draining the injection site were easily visualized. NIRF imaging provides a nonradioactive method of visualizing lymph nodes through layers of tissue that can be employed with intravenous or subcutaneous injection.     

Endobronchial ultrasound-guided transbronchial needle aspiration cytology: a state of the art review

S. E. H. Cameron, R.S. Andrade and S.E. Pambuccian
Endobronchial ultrasound-guided transbronchial needle aspiration cytology: a state of the art review
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a recently developed, accurate, safe and cost-effective technique that allows sampling of mediastinal lymph nodes and peribronchial lesions including pulmonary and mediastinal lesions. Its major indications are the nodal staging of non-small cell carcinomas of the lung, their restaging after chemotherapy and/or radiation, the diagnosis of sarcoidosis and of metastases from extrathoracic malignancies, and the diagnosis of mediastinal lymphadenopathy and masses of unknown aetiology. From our experience at the University of Minnesota and a comprehensive review of the literature, we discuss technical aspects of the procedure, its advantages and limitations in comparison with other methods of sampling mediastinal lymph nodes, focusing on the role of the cytopathologist in ensuring the effectiveness of the procedure. An algorithmic approach to the cytological diagnosis, starting with the determination of the adequacy of the sample, is also presented.     

Kinetics of T- and B-lymphocytes in the lymph nodes of human fetuses

Investigations of the lymph nodes embryogenesis had mainly an anatomo-histological character. At the present time a new approach is necessary: elucidation of main immunological characteristics of lymphoid elements, occupying lymph nodes already at early stages of ontogenesis. The aim of the investigation was to study marker composition of lymphocytes, occupying the lymph nodes of various regional groups, that are in anatomical and functional connection with the thymus, Waldeyer-Pirogov lympho-epithelial pharyngeal ring, appendix and Peyer's patches. The anterior, mediastinal, ileocecal and deep cervical lymph nodes have been studied in 23 human fetuses 17-28-week-old. Immunological and morphological peculiarities of development have been followed in the groups of the lymph nodes mentioned. According to the expression of superficial markers the character of heterogeneity in T- and B-cell systems and their kinetics during embryogenesis has been stated to be characteristic for each regional group. In all lymph nodes the number of T-lymphocytes predominate, their greatest content is noted in the ileocecal lymph nodes. The B-lymphatic system in the lymph nodes is presented poorly with its predominance among immunoglobulin-positive lymphocytes of Ig M(+)-cells.     

Diagnostic value of EBUS-TBNA for lung cancer with non-enlarged lymph nodes: a study in a tuberculosis-endemic country

Background

In tuberculosis (TB)-endemic areas, contrast-enhanced computed tomography (CT) and positron emission tomography (PET) findings of lung cancer patients with non-enlarged lymph nodes are frequently discrepant. Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) enables real-time nodal sampling, and thereby improves nodal diagnosis accuracy. This study aimed to compare the accuracy of nodal diagnosis by using EBUS-TBNA, and PET.

Methods

We studied 43 lung cancer patients with CT-defined non-enlarged mediastinal and hilar lymph nodes and examined 78 lymph nodes using EBUS-TBNA.

Results

The sensitivity, specificity, positive predictive value, and negative predictive value of EBUS-TBNA were 80.6%, 100%, 100%, and 85.7%, respectively. PET had low specificity (18.9%) and a low positive predictive value (44.4%). The diagnostic accuracy of EBUS-TBNA was higher than that of PET (91% vs. 47.4%; p<0.001). Compared to CT-based nodal assessment, PET yielded a positive diagnostic impact in 36.9% nodes, a negative diagnostic impact in 46.2% nodes, and no diagnostic impact in 16.9% nodes. Patients with lymph nodes showing negative PET diagnostic impact had a high incidence of previous pulmonary TB. Multivariate analysis indicated that detection of hilar nodes on PET was an independent predictor of negative diagnostic impact of PET.

Conclusion

In a TB-endemic area with a condition of CT-defined non-enlarged lymph node, the negative diagnostic impact of PET limits its clinical usefulness for nodal staging; therefore, EBUS-TBNA, which facilitates direct diagnosis, is preferred.     

Gene expression profiling of endobronchial ultrasound (EBUS)‐derived cytological fine needle aspirates from hilar and mediastinal lymph nodes in non‐small cell lung cancer

R. Lee, D. J. Cousins, E. Ortiz‐Zapater, R. Breen, E. McLean and G. Santis
Gene expression profiling of endobronchial ultrasound (EBUS)‐derived cytological fine needle aspirates from hilar and mediastinal lymph nodes in non‐small cell lung cancer Objective: Endobronchial ultrasound (EBUS) allows minimally invasive sampling of hilar and mediastinal lymph nodes and has an established role in non‐small cell lung cancer (NSCLC) diagnosis and staging. Molecular biomarkers are being explored increasingly in lung cancer research. Gene expression profiling (GEP) is a microarray‐based technology that comprehensively assesses genome‐wide changes in gene expression that can provide tumour‐specific molecular signatures with the potential to predict prognosis and treatment responsiveness. We assessed the feasibility of using EBUS‐derived aspirates from benign and tumour‐infiltrated lymph nodes for GEP. Methods: RNA was extracted from EBUS‐directed transbronchial fine needle aspiration samples in routine clinical practice. GEP was subsequently performed in six patients with NSCLC, three of whom had tumour‐infiltrated nodes and three who had benign lymph nodes; the differences in gene expression were then compared. Results: RNA was successfully extracted in 29 of 32 patients, 12 of whom were diagnosed with NSCLC. RNA yield (median, 12.1 μg) and RNA integrity (median, 6.3) were sufficient after amplification for GEP. Benign and malignant nodes in adenocarcinoma were discriminated by principal component analysis and hierarchical clustering with different expression patterns between malignant and benign nodes. Conclusion: We have demonstrated the feasibility of RNA extraction and GEP on EBUS‐derived transbronchial fine needle aspirates from benign and tumour‐infiltrated lymph nodes in patients with known NSCLC in routine clinical practice. Further studies on larger patient cohorts are required to identify expression profiles that robustly differentiate benign from malignant lymph nodes in NSCLC.     

Cellular immune responses of mice to influenza virus infection

Mice infected with influenza virus develop cytotoxic T lymphocytes (CTL) specific for viral antigens prior to the appearance of virus-specific antibody-forming cells (AFCs). Effector T cells were detected at a time coincident with a precipitous decline in pulmonary virus titer. CTLs of draining lymph nodes and spleen were found to be cross-reactive among H-2 compatible cells infected with influenza type A virus subtypes. AFCs were observed to be primarily hemagglutinin specific. Virus-specific IgA-secreting AFCs were detected in mediastinal lymph nodes of infected mice.     

MRI of the heart, mediastinum and great vessels

MRI permits to study the anatomical structures of the heart and great vessels without cardiac catheterization or contrast injections. It aims to differentiate trachea and bronchia from the mediastinal lymph nodes. In mediastinal tumours, MRI supplies essential information for the planning of therapy. Only in the area of the structures adjacent to the diaphragm, an improvement of the images by means of additional respiratory gating is desirable.     

Distribution of primed T cells and antigen-loaded antigen presenting cells following intranasal immunization in mice

Priming of T cells is a key event in vaccination, since it bears a decisive influence on the type and magnitude of the immune response. T-cell priming after mucosal immunization via the nasal route was studied by investigating the distribution of antigen-loaded antigen presenting cells (APCs) and primed antigen-specific T cells. Nasal immunization studies were conducted using the model protein antigen ovalbumin (OVA) plus CpG oligodeoxynucleotide adjuvant. Trafficking of antigen-specific primed T cells was analyzed in vivo after adoptive transfer of OVA-specific transgenic T cells in the presence or absence of fingolimod, a drug that causes lymphocytes sequestration within lymph nodes. Antigen-loaded APCs were observed in mediastinal lymph nodes, draining the respiratory tract, but not in distal lymph nodes. Antigen-specific proliferating T cells were first observed within draining lymph nodes, and later in distal iliac and mesenteric lymph nodes and in the spleen. The presence at distal sites was due to migration of locally primed T cells as shown by fingolimod treatment that caused a drastic reduction of proliferated T cells in non-draining lymph nodes and an accumulation of extensively divided T cells within draining lymph nodes. Homing of nasally primed T cells in distal iliac lymph nodes was CD62L-dependent, while entry into mesenteric lymph nodes depended on both CD62L and α4β7, as shown by in vivo antibody-mediated inhibition of T-cell trafficking. These data, elucidating the trafficking of antigen-specific primed T cells to non-draining peripheral and mucosa-associated lymph nodes following nasal immunization, provide relevant insights for the design of vaccination strategies based on mucosal priming.