scholarly journals Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L. Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Xiaoguang Sun ◽  
...  

Abstract Rationale Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. Conclusion These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

2020 ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Kenneth S. Knox ◽  
...  

Abstract Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures.Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis).Methods: Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways.Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level.Conclusion: These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.


2020 ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Kenneth S. Knox ◽  
...  

Abstract Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods: Transcriptomic profiles of immune-related gene from micro-dissected lungs and mediastinal lymph nodes sarcoidosis granulomas was compared to infectious granulomas. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers, excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, CXCL2, FABP4 . Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. Conclusion : These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in two commonly affected tissue in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.


2020 ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Kenneth S. Knox ◽  
...  

Abstract Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures.Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods: Transcriptomic profiles of immune-related gene from micro-dissected lungs and mediastinal lymph nodes sarcoidosis granulomas was compared to infectious granulomas. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers, excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, CXCL2, FABP4. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level.Conclusion: These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in two commonly affected tissue in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.


Author(s):  
Mitsuhiro Kamiyoshihara ◽  
Hitoshi Igai ◽  
Takashi Ibe ◽  
Natsuko Kawatani ◽  
Yoichi Ohtaki ◽  
...  

Objective This study investigated the use of a new bipolar sealing device (BSD) in right superior mediastinal lymph node dissection during thoracoscopic surgery. Methods The study population consisted of 42 consecutive patients undergoing lobectomy with right superior mediastinal lymph node dissection for primary lung cancer. Operative results were compared with those of conventional surgery in 42 background-matched controls. The primary endpoint for the present analysis was the success of right superior mediastinal lymph node dissection during thoracoscopic surgery using a BSD. The secondary endpoints included the duration of the operation, number of dissected lymph nodes, chest drainage volume and duration, postoperative hospital stay, morbidity, and mortality. Results The BSD was used successfully in 42 patients. No significant difference in duration of lymph node dissection, chest drainage volume, drainage duration, or number of dissected lymph nodes was observed between the study group and the controls. Because of a learning curve, the procedure initially took more than 20 minutes to complete, but surgical time was reduced to approximately 15 minutes after the procedure was performed in 15 patients. Conclusions Our method is safe and in no way inferior to the conventional procedure. The tendency of the learning curve suggests that a significantly shorter duration of lymph node dissection is possible using this method.


2020 ◽  
pp. 1-8
Author(s):  
Kazuo Koyanagi ◽  
Kazuo Koyanagi ◽  
Kentaro Yatabe ◽  
Miho Yamamoto ◽  
Soji Ozawa ◽  
...  

Objective: We reviewed the surgical outcomes of minimally invasive esophagectomy (MIE), especially the number of lymph nodes retrieved, for the patients with esophageal cancer to clarify the surgical benefits of MIE in patients with esophageal cancer. Material and Methods: A systematic literature search was performed, and articles that fully described the surgical results of MIE were selected. Parameters such as operative time, blood loss, the number of lymph nodes retrieved, and postoperative complications were compared among patients undergoing minimally invasive esophagectomy (MIE) in the left lateral decubitus position (MIE-LP), MIE in the prone position (MIE-PP), and open thoracic esophagectomy (OE). Results: The conversion rate from MIE to OE was very low. MIE-PP was associated with lower blood loss than OE and MIE-LP. Results of a multicenter randomized controlled trial demonstrated that pneumonia and recurrent laryngeal nerve paralysis in MIE-PP significantly reduced compared with OE. Although postoperative complications were not different between MIE-PP and MIE-LP, the number of lymph nodes retrieved in MIE-PP was higher than that in MIE-LP. Conclusion: MIE-PP has potential benefits in terms of less surgical invasiveness and improvement of mediastinal lymph node dissection. A prospective randomized control trial using a large number of cases and long-term follow-up is recommended for analyses of appropriate mediastinal lymph node dissection and its impact on oncological benefit.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yichun Wang ◽  
Dongmei Ye ◽  
Mei Kang ◽  
Liyang Zhu ◽  
Mingwei Yang ◽  
...  

BackgroundThe lower neck and upper mediastinum are the major regions for postoperative radiotherapy (PORT) in thoracic esophageal squamous cell carcinoma (TESCC). However, there is no uniform standard regarding the delineation of nodal clinical target volume (CTVnd). This study aimed to map the recurrent lymph nodes in the cervical and upper mediastinal regions and explore a reasonable CTVnd for PORT in TESCC.MethodsWe retrospectively reviewed patients in our hospital with first cervical and/or upper mediastinal lymph node recurrence (LNR) after upfront esophagectomy. All of these recurrent lymph nodes were plotted on template computed tomography (CT) images with reference to surrounding structures. The recurrence frequency at different stations was investigated and the anatomic distribution of recurrent lymph nodes was analyzed.ResultsA total of 119 patients with 215 recurrent lymph nodes were identified. There were 47 (39.5%) patients with cervical LNR and 102 (85.7%) patients with upper mediastinal LNR. The high-risk regions were station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. LNR in the external group of station 104L/R was not common, and LNR was not found in the narrow spaces where the trachea was in close contact with the innominate artery, aortic arch and mediastinal pleura. LNR below the level of the cephalic margin of the superior vena cava was also not common for upper TESCC.ConclusionsThe CTVnd of PORT in the cervical and upper mediastinal regions should cover station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. Based on our results, we proposed a useful atlas for guiding the delineation of CTVnd in TESCC.


2020 ◽  
Author(s):  
Tuan Pham

<div>Lung cancer causes the most cancer deaths worldwide and has one of the lowest five-year survival rates of all cancer types. It is reported that more than half of patients with lung cancer die within one year of being diagnosed. Because mediastinal lymph node status is the most important factor for the treatment and prognosis of lung cancer, the aim of this study is to improve the predictive value in assessing the computed tomography (CT) of mediastinal lymph-node malignancy in patients with primary lung cancer. This paper introduces a new method for creating pseudo-labeled images of CT regions of mediastinal lymph nodes by using the concept of recurrence analysis in nonlinear dynamics for the transfer learning. Pseudo-labeled images of original CT images are used as input into deep-learning models. Three popular pretrained convolutional neural networks (AlexNet, SqueezeNet, and DenseNet-201) were used for the implementation of the proposed concept for the classification of benign and malignant mediastinal lymph nodes using a public CT database. In comparison with the use of the original CT data, the results show the high performance of the transformed images for the task of classification. The proposed method has the potential for differentiating benign from malignant mediastinal lymph nodes on CT, and may provide a new way for studying lung cancer using radiology imaging. </div><div><br></div>


2020 ◽  
Vol 48 (8) ◽  
pp. 1017-1024
Author(s):  
Sophie Nelissen ◽  
Ronnie Chamanza

Two similar benign, nonneoplastic vascular lesions have been described in the lymph nodes of humans and animals: angiomyomatous hamartoma (AMH), which is characterized by the replacement of lymphoid tissue by blood vessels, smooth muscle, and fibrous tissue, and vascular transformation of sinuses (VTS), which is considered a reactive transformation of lymph node sinuses into capillary-like vascular channels. We hereby report a lesion with features common to both lesions in the mediastinal lymph nodes of a 1-year-old beagle dog in a 1-month toxicity study. Grossly, enlargement and red discoloration were observed, while microscopically, the lesion was characterized by effacement of the lymph node parenchyma with replacement by mature blood vessels, smooth muscle, and fibrous tissue, associated with lymphoid atrophy, which is consistent with AMH. However, multifocal areas of anastomosing or plexiform capillary-like channels lined by normal to slightly plump endothelium, similar to those described for VTS, were also present. Immunohistochemistry analysis revealed abundant positive staining for smooth muscle actin and endothelial cells (von Willebrand factor/factor VIII) and the absence of proliferation (Ki67). In conclusion, these lesions most likely represent a mixture of both AMH and VTS.


2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Ercan Kurtipek ◽  
Meryem İlkay Eren Karanis ◽  
Nuri Düzgün ◽  
Hıdır Esme ◽  
Mustafa Çaycı

Chylothorax is characterized by fluid accumulation in the pleural cavity containing chylomicrons due to disruption of lymphatic drainage in the thoracic ductus and development of chylothorax. A 60-year-old male patient presented to our clinic with shortness of breath and displayed bilateral pleural effusion and diffuse mediastinal lymph nodes in his computed chest tomography images. There were no thickening and nodular formation on the pleural surfaces. PET-CT showed no pathological FDG uptake. Thoracentesis showed a chylous effusion. Drainage reduced during monitoring could not be stopped; therefore, surgical intervention was considered. The patient underwent right thoracotomy. There were no pathological findings in the parietal and visceral pleura during the surgery. Initially lymphoma was considered. Perioperative samples were collected from the mediastinal lymph node. The pathology analysis reported metastasis of malignant mesothelioma. Evaluation of a repeated chest computed tomography showed nodular formations on the pleural surfaces. Mediastinal lymph nodes compressed the ductus thoracicus, resulting with chylothorax. The present case, with malignant mesothelioma, bilateral chylothorax, and mediastinal lymph node without any pleural involvement during initial diagnosis, is rare and will hence contribute to the literature.


2000 ◽  
pp. 623-627 ◽  
Author(s):  
F Arturi ◽  
D Russo ◽  
D Giuffrida ◽  
M Schlumberger ◽  
S Filetti

OBJECTIVE: To investigate the molecular mechanisms underlying the influence of alteration of iodine trapping on the prognosis of metastatic papillary thyroid carcinomas, focusing on the expression of the Na+/I(-) symporter (NIS). DESIGN: We evaluated the expression of the NIS gene in a series of 11 enlarged neck lymph-node metastases of papillary thyroid carcinomas, including four patients in whom an enlarged lymph node represented the first sign of the tumoral disease. Nine lymph nodes, either reactive or metastatic for non-thyroid tumors, were also investigated. METHODS: Expression of the NIS gene was evaluated by RT-PCR in material obtained by fine-needle aspiration biopsy. RESULTS: The NIS gene was expressed in eight (73%) of 11 differentiated thyroid cancer metastatic lymph nodes examined. Five of these metastatic lymph nodes were positive at the post-treatment total-body iodine-131 scan; in the other three, the total-body scan showed no uptake in the metastatic tissues, indicating an alteration downstream to the NIS mRNA synthesis causing the loss of iodide uptake. As expected, when the NIS mRNA expression was absent, total-body (131)I scan showed no uptake in the metastatic lymph nodes. CONCLUSIONS: Our study demonstrates that NIS gene expression may be absent in metastatic differentiated thyroid carcinomas and that different mechanisms, other than loss of NIS transcription, may also be involved in the loss of iodide uptake in metastatic thyroid cells. Study of NIS gene expression in the metastatic lymph nodes, therefore, may provide useful information in the management of patients with thyroid carcinoma.


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