INTRODUCTION:Recent studies have shown that combined use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and cryobiopsy provides a higher diagnostic yield for mediastinal lesions as compared with EBUS-TBNA alone. Currently, cryoprobes with diameters of 1.1mm and 1.7mm have been reported to be used for mediastinal cryobiopsy. METHODS:We conducted a randomized controlled trial to evaluate and compare the diagnostic safety and efficacy profile the two cryoprobes in mediastinal disease. Consecutive patients with mediastinal lesions (≥1cm in the short axis) were prospectively enrolled. After four passes of needle aspiration, participants underwent mediastinal cryobiopsy with 1.1-mm and 1.7-mm cryoprobes in a randomized order. The main endpoints included procedural success rate, diagnostic yield, and safety. RESULTS:A total of 137 patients were recruited and randomized. Both 1.1-mm and 1.7-mm probe cryobiopsies added diagnostic value to EBUS-TBNA. (94.2% vs 75.9%; p<0.001; 92.0% vs 75.9%; p<0.001; respectively). Supplementing EBUS-TBNA with either 1.1-mm or 1.7-mm probe-cryobiopsy resulted in no differences in overall diagnostic yield (94.2% vs 92.0%; p=0.48). Nevertheless, direct comparison revealed a significantly improved overall diagnostic yield with 1.1-mm cryoprobe relative to 1.7-mm cryoprobe, primarily due to technical failures associated with the latter (88.3% vs 79.6%; p=0.048). Additionally, 1.1-mm and 1.7-mm cryoprobes yielded mediastinal specimens of similar size. Both approaches were safe, with no serious adverse events reported. CONCLUSIONS:1.1-mm cryoprobe demonstrates better performance in transbronchial mediastinal cryobiopsy vs 1.7-mm cryoprobe, making it a viable adjunct to traditional needle biopsy.

Objective To elucidate the effects of miR-616 on the malignant biological processes of osteosarcoma and to preliminarily explore its potential mechanisms.Methods In situ hybridization(ISH)was employed to analyze miR-616 expression in 11 paraffin-embedded osteosarcoma specimens collected in our department during January 2018 to December 2019.Quantitative real-time PCR(qRT-PCR)was used to compare the mRNA expression level of miR-616 in the osteoblast cell line hFOB1.19 and osteosarcoma cell lines 143B and HOS.Stable cell lines with miR-616 knockdown or overexpression were established via lentiviral transfection in 143B and HOS cells.Cell proliferation and apoptosis were detected by flow cytometry,while cell invasion and migration were assessed using Transwell and colony formation assays,respectively.To evaluate the effect of miR-616 on tumor growth in vivo,10 female nude mice(4 weeks old,weighing 18～20 g)were randomized into a control group and a miR-616 overexpression group.After the xenograft tumor model was constructed,the growth of subcutaneous tumors was monitored.Finally,next-generation sequencing and a dual-luciferase reporter assay were performed to identify the target genes of miR-616.Results ISH results showed that miR-616 expression was up-regulated in osteosarcoma tissues than adjacent tissues,and primarily localized in the cytoplasm.qRT-PCR confirmed that miR-616 level was significantly higher in 143B and HOS cells than hFOB1.19 cells(P<0.05).In vitro experiments revealed that miR-616 overexpression enhanced the proliferation,migration and invasion,while suppressing apoptosis in 143B and HOS cells(P<0.01).Conversely,miR-616 knockdown weakened these malignant phenotypes(P<0.05),with miR-616-3p showing a stronger effect on apoptosis than miR-616-5p.Animal experiments demonstrated that the tumor weight in the miR-616 overexpression group was significantly greater than that of the control group(98.00±17.22 vs 33.60±8.08 mg,P<0.01).Furthermore,KLF2 was identified and confirmed as a direct target of miR-616.Conclusion MiR-616 promotes malignant biological behaviors in osteosarcoma,and its expression level indicates that it may serve as a potential therapeutic target.

Fibrosing mediastinitis is a rare benign disease frequently complicated by pulmonary hypertension. A definitive diagnosis for fibrosing mediastinitis-associated pulmonary hypertension (FM-PH) and its etiologies necessitates mediastinal biopsy and subsequent pathological assessment. Endobronchial ultrasound (EBUS)-guided transbronchial mediastinal cryobiopsy is a recently developed technique that provides diagnostic advantages over standard needle biopsy, particularly in benign mediastinal disorders. Nevertheless, their safety and efficacy in diagnosing FM-PH remain elusive. We retrospectively studied patients with mediastinal lesion and pulmonary vascular compression who underwent both transbronchial needle aspiration and mediastinal cryobiopsy with EBUS guidance. Diagnostic yields of FM-PH and its etiologies, along with procedure-related adverse events, were analyzed. Immunohistochemical study was conducted to identify immunological properties of FM-PH. Of the 529 patients with mediastinal lesions, 80 exhibited pulmonary vessel compression, including 10 who were ultimately diagnosed with FM-PH following mediastinal biopsy and right heart catheterization. Cryobiopsy showed a higher diagnostic yield for FM-PH compared to needle aspiration (100

Introduction Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the standard approach for lung cancer staging. However, its diagnostic utility for other mediastinal diseases might be hampered by the limited tissue retrieved. Recent evidence suggests the novel sampling strategies of forceps biopsy and cryobiopsy as auxiliary techniques to EBUS-TBNA, considering their capacity for larger diagnostic samples.Methods This study determined the added value of forceps biopsy and cryobiopsy for the diagnosis of mediastinal diseases. Consecutive patients with mediastinal lesions of 1 cm or more in the short axis were enrolled. Following completion of needle aspiration, three forceps biopsies and one cryobiopsy were performed in a randomised pattern. Primary endpoints included diagnostic yield defined as the percentage of patients for whom mediastinal biopsy led to a definite diagnosis, and procedure-related complications.Results In total, 155 patients were recruited and randomly assigned. Supplementing EBUS-TBNA with either forceps biopsy or cryobiopsy increased diagnostic yield, with no significant difference between EBUS-TBNA plus forceps biopsy and EBUS-TBNA plus cryobiopsy (85.7 % versus 91.6 %, P = 0.106). Yet, samples obtained by additional cryobiopsies were more qualified for lung cancer molecular testing than those from forceps biopsies (100.0 % versus 89.5 %, P = 0.036). When compared directly, the overall diagnostic yield of cryobiopsy was superior to forceps biopsy (85.7 % versus 70.8 %, P = 0.001). Cryobiopsies produced greater samples in shorter procedural time than forceps biopsies. Two (1.3 %) cases of postprocedural pneumothorax were detected.Conclusions Transbronchial mediastinal cryobiopsy might be a promising complementary tool to supplement traditional needle biopsy for increased diagnostic yield and tissue harvesting.Trial registration ChiCTR2000030373

Background Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. Methods Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. Results Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. Conclusions Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Introduction: Fibrosing mediastinitis is a benign but fatal disorder characterized by the proliferation of fibrous tissue in the mediastinum, causing encasement of mediastinal organs and extrinsic compression of adjacent bronchovascular structures. FM-associated pulmonary hypertension (FM-PH) is a serious complication of FM, resulting from the external compression of lung vessels. Pathologic assessment is important for etiologic diagnosis and effective treatment of this disease. Case Presentation: A 59-year-old male patient presented at our hospital and was diagnosed with FM-PH. He declined surgical biopsy that is the reference standard for pathologic assessment, in consideration of the potential risks. Therefore, an endobronchial ultrasound examination was performed, which identified the subcarinal lesion. Under ultrasound guidance, four needle aspirations were carried out, followed by one cryobiopsy. Histopathological examination of transbronchial needle aspiration specimens was inconclusive, while samples from cryobiopsy suggested a diagnosis of idiopathic FM. Further immunophenotyping demonstrated the infiltration of lymphocytes, macrophages, and FOXP3-positive cells in FM-PH. Conclusion: Mediastinal cryobiopsy might be a novel and safe option for FM-PH patients who are unwilling or unsuitable for surgical procedure.

Lung cancer is the leading cause of deaths from malignant neoplasms worldwide, and a satisfactory biopsy that allows for histological and other analyses is critical for its diagnosis. Guidelines have recommended endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as the reference standard for the staging of lung cancer. However, the relatively limited sample volume retrieved by needle aspiration might restrict the diagnostic capacity of EBUS-TBNA in other uncommon thoracic tumors. Transbronchial mediastinal cryobiopsy is a recently developed sampling strategy for mediastinal lesions, which demonstrates added diagnostic value to conventional needle aspiration. Here, we present a case of thoracic SMARCA4-deficient undifferentiated tumor successfully diagnosed by mediastinal cryobiopsy additional to EBUS-TBNA.

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the most widely-accepted approach for mediastinal disease; however, its diagnostic utility could be limited by the insufficiency of intact samples. We and others have priorly shown that additional transbronchial forceps biopsy and cryobiopsy, which can offer larger amounts of intact mediastinal tissues, improve the overall diagnostic yield of EBUS-TBNA. Aims and Objectives: We aimed to compare the added value of cryobiopsy with forceps biopsy for the diagnosis of mediastinal lesion. Methods: Patients with at least 1 mediastinal lesion were enrolled. After 4 passes of TBNA, 3 forceps biopsies and 1 cryobiopsy were conducted in a randomised order. Efficacy and safety were assessed. Results: 154 patients (106 males and 48 females; mean age 57 years) were included in this prospective, randomised trial. The overall diagnostic yield of EBUS-TBNA plus cryobiopsy was 91.6%, which was similar with that of EBUS-TBNA plus forceps biopsy (85.7%, p=0.11). Both forceps biopsy and cryobiopsy were able to establish a diagnosis in 106 (70.1%) patients. 26 additional cases nondiagnostic by forceps biopsy were successfully diagnosed by cryobiopsy, whereas in 3 patients, the diagnosis were only established by forceps biopsy, resulting in a overall diagnostic yield of 70.8% for forceps biopsy and 85.7% for cryobiopsy (p=0.001). The time needed for 1 cryobiopsy was significantly shorter than that of 3 forceps biopsies. We observed 2 cases of pneumothorax. Conclusions: Transbronchial mediastinal cryobiopsy might be an ideal complementary biopsy tool to standard needle aspiration.

Background:The aortic bulge sign possibly indicates an arterial aneurysm, pseudoaneurysm, aortic dissection, or aortic diverticulum. The aortic diverticulum is a congenital abnormality of the aorta, mainly known as an aneurysmal remnant of the dorsal fourth aortic arch or ductus arteriosus. However, the diverticulum of another part of the aorta has rarely been reported.Case summary:We report a case of a 24-year-old male with a history of oral ulcer presented with recurrent hyperpyrexia and chest pain. Echocardiography and computed tomography showed the anomalous origin of the coronary arteries, aortic valve vegetations, and a bulge at the aortic root. The patient then received a Bentall procedure. The aorta and aortic valves were replaced by a valved conduit. The bulge with a normal arterial wall at the aortic root was considered to be a diverticulum. The infective endocarditis was verified as a secondary oral-derived streptococcal infection. The patient was discharged 15 days after surgery. Post-operative echocardiography had no positive findings.Conclusion:Our case report highlights the role of multimodal cardiovascular imaging for the diagnostic workup of rare disorders, such as the presence of a diverticulum in the aortic root in a patient with endocarditis and anomalous origin of the right coronary artery.

Transbronchial mediastinal cryobiopsy is a novel sampling strategy that shows improved diagnostic utility for mediastinal lesions, particularly in rare tumors and benign disorders, as compared to standard endobronchial ultrasound-guided transbronchial needle aspiration. During this procedure, electrocautery incision is frequently needed to advance the cryoprobe through the airway into the mediastinal lesion, which however results in increased operative difficulty and prolonged procedural time. Here we present a case of mediastinal large B-cell lymphoma successfully diagnosed by transbronchial mediastinal cryobiopsy without cautery-induced airway incision.

BACKGROUND:Transbronchial mediastinal cryobiopsy is a novel sampling technique for mediastinal disease. Despite the possibility of lung cancer misdiagnosis, the improved diagnostic yield of this approach for non-lung-cancer lesions compared with standard endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) highlights its diagnostic potential as a complementary technique to conventional biopsy. We aimed to evaluate the safety profile and added value of the combined use of transbronchial mediastinal cryobiopsy and standard EBUS-TBNA for the diagnosis of mediastinal diseases. METHODS:We conducted an open-label, randomised trial at three hospital sites in Europe and Asia. Eligible patients were aged 15 years or older, with at least one mediastinal lesion of 1 cm or longer in the short axis that required diagnostic bronchoscopy. Participants were randomly assigned (1:1) using a block randomisation scheme generated by a computer (block size of four participants based on a random table from an independent statistician) to the combined use of EBUS-TBNA and transbronchial mediastinal cryobiopsy (combined group) or EBUS-TBNA alone (control group). Because of the nature of the intervention, neither participants nor investigators were masked to group assignment. The coprimary outcomes were differences in procedure-related complications and diagnostic yield (defined as the proportion of participants for whom mediastinal biopsy led to a definitive diagnosis), assessed in the full analysis set, including all the patients who met the eligibility criteria and had a biopsy. A fully paired, intraindividual diagnostic analysis in participants who had both needle aspiration and mediastinal cryobiopsy was conducted, in addition to interindividual comparisons. This trial is now complete and is registered with ClinicalTrials.gov, NCT04572984. FINDINGS:Between Oct 12, 2020, and Sept 9, 2021, 297 consecutive patients were assessed for eligibility and 271 were enrolled and randomly assigned to the combined group (n=136) or the control group (n=135). The addition of cryobiopsy to standard sampling significantly increased the overall diagnostic yield for mediastinal lesions, as shown by both interindividual (126 [93%] of 136 participants in the combined group vs 109 [81%] of 135 in the control group; risk ratio [RR] 1·15 [95% CI 1·04-1·26]; p=0·0039) and intraindividual (126 [94%] of 134 vs 110 [82%] of 134; RR 1·15 [95% CI 1·05-1·25]; p=0·0026) analyses. In subgroup analyses in the intraindividual population, diagnostic yields were similar for mediastinal metastasis (68 [99%] of 69 participants in the combined group vs 68 [99%] of 69 in the control group; RR 1·00 [95% CI 0·96-1·04]; p=1·00), whereas the combined approach was more sensitive than standard needle aspiration in benign disorders (45 [94%] of 48 vs 32 [67%] of 48; RR 1·41 [95% CI 1·14-1·74]; p=0·0009). The combined approach also resulted in an improved suitability of tissue samples for molecular and immunological analyses of non-small-cell lung cancer. The incidence of adverse events related to the biopsy procedure did not differ between trial groups, as grade 3-4 airway bleeding occurred in three (2%) patients in the combined group and two (1%) in the control group (RR 0·67 [95% CI 0·11-3·96]; p=1·00). There were no severe complications causing death or disability. INTERPRETATION:The addition of mediastinal cryobiopsy to standard EBUS-TBNA resulted in a significant improvement in diagnostic yield for mediastinal lesions, with a good safety profile. These data suggest that this combined approach is a valid first-line diagnostic tool for mediastinal diseases. FUNDING:National Natural Science Foundation of China.

Objective:Screening the causative genes of nonspecific interstitial pneumonia (NSIP) by bioinformatics and provide targets for further research.Method:By downloading the gene chip datasets GSE110147, GSE21369, GSE40839 from the GEO database, and using the limma package analysis tool to screen out the differentially expressed genes between normal tissues and NSIP. The clusterProfiler package was used to perform GO analysis and KEGG pathway enrichment analysis on the differentially expressed genes to find the biological functions of the differentially expressed genes and their concentrated signaling pathways in the pathogenesis of NSIP. To study the relationship between differentially expressed genes and proteins, the STRING database and CYTOSCAPE software were used to construct the protein-protein interaction (PPI) network, and the MCODE software was used to extract the sub-network modules in the protein interaction network.Result:Veen plots result suggested three common significantly differentially expressed genes were found. GO enrichment analysis showed that up-regulated differentially expressed genes in NSIP mainly affected biological processes related to RNA splicing, antiviral infection, and cellular responses to peptides. The enriched molecules are mainly involved in the synthesis, secretion, and splicing complexes of cellular components, and the enriched molecular function are mainly involved in ATPase activity, receptor ligand activity and DNA-binding transcription activator activity. The down-regulated proteins in NSIP are mainly involved in biological processes regulated by transferase activity. KEGG pathway analysis showed that the up-regulated differentially expressed genes in NSIP were mainly involved in signaling pathways such as PI3K-Akt pathways, human papilloma virus infection pathways and MAPK pathways.Conclusion:The differentially expressed genes screened by bioinformatics may be new targets for the pathogenesis of NSIP, which is significant for the future clinical diagnosis and treatment of NSIP.

Objective To screen a key molecule, leucine-rich glioma inactivated protein 4 (LGI4), which participates in endothelial cell-mediated osteosarcoma metastasis, and to further analyze its function and molecular mechanism in osteosarcoma metastasis. Methods A co-culture model of human umbilical vein endothelial cells (HUVECs)-osteosarcoma cells was established, and the genes with significant fold change were screened by whole transcriptome sequencing in combination with relevant literature. After, the candidate target gene, LGI4 was verified with real-time quantitative PCR (RT-qPCR) and Western blotting, the expression of LGI4 at mRNA and protein levels was also determined. Osteosarcoma cell line 143B and MTF LGI4 were transfected with the overexpression plasmid of LGI4 to construct the cells with stable overexpression of LGI4. Then the experiments included 5 groups of osteosarcoma cells, including negative control group (normally cultured), co-culture group (co-cultured with HUVECs), co-culture medium group (treated with the HUVECs medium), vector control group (transfected with control plasmid) and LGI4 group (overexpression of LGI4). Transwell assay and wound healing test were used to detect the migration and invasion abilities of osteosarcoma cells. A tumor metastasis model in nude mice was used to verify the effect of LGI4 overexpressed osteosarcoma cells on distant metastasis in vivo. Bioinformatics analysis was applied to analyze the potential downstream target signaling pathways of LGI4, and recovery experiments were performed with related inhibitors to clarify the role of target signaling pathways in the regulation of osteosarcoma metastasis by LGI4. Results The expression levels of LGI4 were markedly decreased in 143B and MTF cells after co-culture with HUVECs (P < 0.05). Compared with the negative control group, the cell migration and invasion abilities of the co-culture group and co-medium group were significantly enhanced, whereas the cell migration and invasion rates of the LGI4 overexpression group were significantly lower than that of the vector control group (P < 0.05). The nude mice metastasis model revealed that the metastasis ability of osteosarcoma cells was suppressed with LGI4 overexpression. Further analysis revealed that NOTCH4 signaling pathway was the downstream target signaling pathway of LGI4, and functional recovery experiments confirmed that LGI4 resulted in osteosarcoma metastasis by inhibiting NOTCH4 signaling pathway (P < 0.05). Conclusion Endothelial cells activate NOTCH4 signaling pathway and thus promote tumor metastasis by inhibiting the expression of LGI4 in osteosarcoma cells.

Spontaneous rupture of testicular rhabdomyosarcoma is very rare. We report a case of spontaneous testicular rupture that was pathologically confirmed as rhabdomyosarcoma with unilateral blepharoptosis. The patient, a 19-year-old male, and his father had weakness of the left eyelid muscle. The patient was suspected to have a right inguinal hernia by a family doctor but was not treated further. 2 days later, there was skin itching in the right inguinal area, accompanied by redness, swelling and discomfort of the right scrotum, and the patient went to the local hospital again. Ultrasound examination showed that a contusion of the right testis may have been complicated with orchitis. Oral levofloxacin was ineffective. In addition, the swelling of scrotal increased significantly. He came to the emergency room of our hospital and also was treated with levofloxacin, but the pain was still not relieved. CT and ultrasound examination could not identify the cause of the disease. Exploration of the right scrotum was performed under general anesthesia and confirmed that the right testis had spontaneously ruptured. The pathological diagnosis was rhabdomyosarcoma of the right testis. Testicular rhabdomyosarcoma is clinically rare, and spontaneous rupture is even rarer. The pathogenesis of the disease needs to be further studied, and the diagnosis should be made on a case-by-case basis. Overall, the prognosis of testicular rhabdomyosarcoma is poor. As seen in this case, further study is required to determine whether there is some association between testicular rhabdomyosarcoma and ptosis. Unfortunately, the patient's family rejected a genetic examination because of financial difficulty. We only report a single case of this rare phenomenon here.

BackgroundPulmonary fibroleiomyomatous hamartomas (PFLH) is an extremely rare benign leision, characterized by most patients have no respiratory symptoms and pulmonary nodules is found during rutine chest imaging. It’s completely different from fibrochondrolipoma (ie.chondrogenic pulmonary hamartoma, FCL), Herein, we report three unusual cases of PFLH in a 48-year-old male patient, a 63-year-old male patient and a 63-year-old female patient,respectively and discuss their morphological characteristics and differential diagnoses including fibrochondrolipoma (FCL), pulmonary fibroadenoma (PFA), primary pulmonary leiomyoma (PPL), bronchioloalveolar adenoma (BAA), solitary fibrous tumor (SFT) and pulmonary metastatic leiomyoma (PML) in female patients.Case presentationThree cases showed singler and multiple nodules in the pulmonary parenchyma,the boundary of these nodules was clear. it showed swelling growth and lobulated in larger tumors. it consisted of the mesenchymal rich in spindle cells and the glandular epithelium tissue. the spindle cells form smooth muscle tissue and fibrous tissue, the glandular epithelium with invagination showed glandular ducts or fissures, disorder of composition. Immunohistochemical staining showed Desmin, SMA,H-caldesmon-positive in the all spindle cells; H-caldesmon-positive, SMA-weak positive and desmin-negative in the long spindle cells; TTF-1,CK7 were positive in glandular epithelium and P63,CK5/6 were expressed in basal cells; HMB45,S-100,CD34, ER,PR were negative in all cells. Additionally, Ki-67 VPI was low and less than 1%. The immunohistochemical analysis combined with the morphological results supported the diagnosis of solitary PFLH (SPFLH) or multiple PFLH (M PFLH). There was no recurrence in SPFLH and recurrence in MFLH in the group.ConclusionsPFLH is a rare benign leision .It originated from the small bronchus or smooth muscle cells of vascular wall which implanted into the lung parenchyma and overgrowth into nodules or mass, the messenchymal component of PFLH is the most important for accurate pathological diagnosis, PFLH is easy to be confused with PFA and PPL when there are not enough immune marker such as SMA,desmin, H-caldesmon to mark the mesenchymal components. Therefore, Diagnosis of PFLH mainly depends on pathological examination, females patients have to exclude PML.

Background: Tuberculous pleural effusion (TPE) is one of the most prevalent causes of exudative pleural effusion. As it is curable, early diagnosis is essential. Nevertheless, direct examination is not so sensitive while thoracoscopy is invasive and resource-demanding. Objective: To seek a less-invasive but also cost-effective substitute for medical thoracoscopy to identify TPE. Methods: We retrospectively collected 662 patients with pleural effusions who have undergone thoracoscopy as the training cohort, developed a predictive model and then validated it in another independent cohort. Independent predictor was screened by univariate analysis, feature selection and multivariate logistic regression. A predictive nomogram model was then established and evaluated by calibration, discrimination and clinical values. A standard model with a pleural adenosine deaminase (plADA) cut-off value at 40 IU/L was applied for comparison. Results: A lower plADA threshold at 24.5 IU/L was identified to discriminate TPE from other etiologies. Furthermore, serum tumor marker CA153 and Cyfra21.1, pleural lactic acid dehydrogenase and pleural interstitial cells were also identified as independent predictors (p<0.05) in multivariate logistic regression. The multivariate nomogram model presented good calibration, discrimination and clinical values, superior to the standard model. Excellent discrimination was demonstrated by the Harrell’s concordance index of 0.993 in the training cohort and 0.968 in the validation cohort. Furthermore, decision curve analysis demonstrated that the multivariate nomogram model added more benefit to patients with TPE. Conclusion: A multivariate nomogram model involved biochemical examinations and thoracentesis performed well in TPE clinical diagnosis among undetermined pleural effusions with approximate efficacy to medical thoracoscopy.

Guidelines have recommended endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine-needle aspiration biopsy as initial sampling approaches of mediastinal lymph nodes for lung cancer staging. However, the small sample volume might restrict the diagnostic utility of needle aspiration in certain mediastinal diseases. We have recently shown that transbronchial mediastinal cryobiopsy, which is capable of providing larger amounts of intact tissue, improves diagnostic yield in rare tumors and benign diseases compared to EBUS-TBNA. Here, we present a case of mediastinal nodular lymphocyte predominant Hodgkin lymphoma successfully diagnosed by endoscopic transesophageal cryobiopsy.

Mediastinal biopsy is essential for the clinical diagnosis of mediastinal disease. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established approach for obtaining diagnostic samples from mediastinal masses or enlarged lymph nodes which is proven to be minimally invasive and effective. However, the insufficiency of intact samples acquired might restrict the diagnostic efficacy of EBUS-TBNA for mediastinal lesions such as rare malignancy and granulomatous disorder. We here present an EBUS-guided approach for the cryobiopsy of mediastinal diseases that is capable of providing larger amounts of intact tissue with few observed complications.

BACKGROUND:Castleman's disease (CD) is an uncommon type of benign proliferation of the lymphoid tissue, characterized by local or systemic lymphadenopathy that most frequently appears in the mediastinum; involvement of the kidney is uncommon, and proliferation originating from the kidney is extremely rare. Herein, we report a rare case of hyaline vascular Castleman's disease (HV-CD) in a 56-year-old male patient and discuss its morphological characteristics and differential diagnoses including mantle cell lymphoma (MCL), follicular lymphoma (FL), and nodal marginal zone lymphoma (NMZL). CASE PRESENTATION:A right upper-middle renal mass was detected after physical examination in a 56-year-old man without any clinical symptoms and a previous partial resection of the right kidney. Microscopically, the lymphoid follicles were increased in number and had expanded mantle zones and atrophic germinal centers. Vascular proliferation and hyalinization in the interfollicular zones were observed. Immunohistochemical staining showed CD20-positive cells in the mantle zones; CD21 and CD35 were expressed in the dendritic cells, CD3 was positive in a small number of T cells, and CD38 and CD138 were positive in the plasma cells. Additionally, Ki-67 expression was positive in the follicle centers. In contrast, staining for Bcl-2 in the germinal centers and cyclin D1 were negative. The immunohistochemical analysis combined with the morphological results supported the diagnosis of HV-CD. The patient recovered well after surgery. CONCLUSIONS:Primarily renal HV-CD without lymph node hyperplasia or clinical symptoms is extraordinarily rare and different from the multicentric-type CD (MCD) with kidney involvement. Therefore, it is extremely important to improve the awareness of this diagnosis. Attention should be paid to the difference between HV-CD and common lymph node reactive hyperplasia, MCL, FL, NMZL, and so on. To avoid misdiagnosis as a renal malignant tumor requiring radical resection, distinguishing these diseases is crucial.