支气管内超声引导针吸活检术（EBUS-TBNA）临床应用的初步体会

目的探讨支气管内超声引导针吸活检术（endobronchial ultrasound-guided transbronchial needle aspiration,EBUS-TBNA）在明确纵隔和肺门肿大淋巴结定性诊断中的应用价值。方法2009年9~11月,对25例胸部CT检查提示纵隔和（或）肺门淋巴结肿大（短径〉1 cm）进行EBUS-TBNA检查,阴性者进一步接受纵隔镜检查或胸腔镜、开胸手术加以确证。结果本组25例共穿刺32组淋巴结。EBUS-TBNA明确淋巴结恶性转移者15例;EBUS-TBNA阴性者10例,其中1例开胸术后证实隆突下淋巴结转移。EBUS-TBNA在纵隔和肺门肿大淋巴结良恶性鉴别诊断中的敏感性、特异性和准确性分别为94%（15/16）,100%（9/9）和96%（24/25）。所有患者检查耐受良好,无任何相关并发症发生。结论EBUS-TBNA是评价纵隔及肺门淋巴结安全有效的方法。     

The Role of Mediastinoscopy for Diagnosis of Isolated Mediastinal Lymphadenopathy

To determine the role of mediastinoscopy (MDS) in the histological diagnosis of isolated mediastinal lymphadenopathy in a centre where more sophisticated investigations, like positron emitting tomography (PET) scan and endobronchial ultrasound guided trans-bronchial needle aspiration (EBUS-TBNA) is not available. This is a retrospective study. From January 2006 to December 2009, 31 patients with isolated mediastinal lymphadenopathy underwent MDS to establish a histological diagnosis. The mean age was 36.3 years. Among the patients, 19 were males and 12 were females. The most common symptom was dry cough in 18 (58%) patients. The diagnostic yield was 96.8%, with sarcoidosis being the commonest diagnosis. It was concluded that MDS was vital in establishing a histological diagnosis in patients with isolated mediastinal lymphadenopathy.     

The value of mediastinal staging with endobronchial ultrasound-guided transbronchial needle aspiration in patients with lung cancer

Objective: To evaluate the diagnostic yield, the learning curve and the safety of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in mediastinal staging of patients with lung cancer. Methods: Mediastinal staging was performed with EBUS-TBNA according to the Danish national guidelines in patients fulfilling one or more of the following criteria: (1) central tumour; (2) enlarged (>10 mm) mediastinal lymph nodes on computed tomography; or (3) positron emission tomography (PET)-positive mediastinal lymph nodes. The study period began in January 2006 when EBUS-TBNA was introduced in the department and ended in December 2007. All records were reviewed retrospectively. None of the four examiners had any previous experience with EBUS-TBNA or ultrasound when the study began. All examinations were performed under general anaesthesia. Patients without useful cytological material from the EBUS-TBNA were subjected to a supplementary standard cervical mediastinoscopy if the mediastinal lymph nodes were found to be enlarged (>10 mm), PET positive or if the examiner was insecure of the result of the EBUS-TBNA. Patients with mediastinal lymph node involvement, detected by EBUS-TBNA or standard cervical mediastinoscopy, were referred to oncological treatment, while those without mediastinal lymph node involvement underwent – if they were otherwise eligible for surgery – resection and systematic lymph node sampling either by thoracotomy or by video-assisted thoracoscopy. Final mediastinal staging was defined as positive if mediastinal lymph node involvement was detected by EBUS-TBNA, standard cervical mediastinoscopy or surgery, or defined as negative otherwise. Results: A total of 157 patients were included in the study. N2/N3 disease was found in 67 patients (42.6%). EBUS-TBNA missed the mediastinal spread in 10 patients. Five of the ten patients had lymph node metastases in station 5, 6 or 8 – out of reach of EBUS-TBNA or standard cervical mediastinoscopy. EBUS-TBNA had a sensitivity of 0.85 (0.74–0.93) and a negative predictive value of 0.90 (0.82–0.95). No complications occurred from EBUS-TBNA. The number of supplementary standard cervical mediastinoscopies decreased significantly in the study period. Conclusion: The results of this study suggest that staging of the mediastinum with EBUS-TBNA is safe and easy to learn – even without previous experience with ultrasound. The diagnostic yield of EBUS-TBNA is in accordance with the yield of standard cervical mediastinoscopy reported in the literature. We do not find any indications in the present study of the recommended necessity for mediastinoscopy in all EBUS-TBNA-negative patients.     

Endobronchial ultrasound in the diagnosis and staging of lung cancer and other thoracic tumors

Bronchoscopy has been in clinical use for a long time with an excellent safety record. Unfortunately, the yield of bronchoscopic procedures for staging mediastinal lymph nodes as well as for the biopsy of peripheral lesions with conventional techniques has been disappointing. Transbronchial biopsy as well as transbronchial needle aspiration are generally performed without direct visualization, which partially explains this problem. The advent of endobronchial ultrasound has dramatically changed the environment, and, if used for guidance of transbronchial biopsy, lymph nodes can be reliable samples challenging the notion that mediastinoscopy should be the mediastinal staging procedure of choice. This article reviews technological background, application, and results of endobronchial ultrasound added to diagnostic bronchoscopy in the diagnosis and staging of patients with lung cancer.     

Diagnosis and staging of "other bronchial tumors"

Unusual bronchial tumors represent 4% to 6% of all lung tumors. These lesions include hamartomas, bronchial carcinoids, adenoid cystic carcinoma, mucoepidermoid carcinoma, and other more rare tumors. In the majority of patients these lesions are diagnosed using transthoracic FNA and different bronchoscopic biopsy techniques such as bronchial lavage, bronchial brushing, endobronchial biopsy, transbronchial biopsy, and transbronchial needle aspiration. Thoracoscopic wedge biopsy is diagnostic in the remainder of cases. Occasionally, because of tumor location, thoracoscopically-guided FNA or thoracoscopic ultrasound are helpful in obtaining a diagnosis. Staging of these lesions is assessed after proper resection; however, mediastinoscopy should be performed if preoperative mediastinal adenopathy is appreciated.     

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration of Undiagnosed Chest Tumors

Background  

A number of patients with radiologically suspicious chest tumors remain undiagnosed despite bronchoscopy or CT-guided fine-needle aspiration (CT-FNA). Such patients are often referred for mediastinoscopy, which is an invasive surgical procedure that poses a small but significant risk to the patient. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS) is a well-established method for mediastinal staging of lung cancer but may also be used as a diagnostic tool in patients with undiagnosed intrathoracic lesions.     

Changes in diagnostic strategies for hilar-type castleman’s disease: Report of two cases

Castleman’s disease (CD) is rare and difficult to diagnose preoperatively. We report two similar cases of hyaline vascular type CD diagnosed preoperatively using different modalities. In the first case, a biopsy specimen taken during diagnostic thoracoscopy revealed lymphatic structure suggestive of CD. In the second case, endobronchial ultrasound-guided transbronchial needle aspiration enabled sampling of histological cores for histological diagnosis. In both cases, the final diagnosis was established by surgical resection.     

支气管内超声引导针吸活检术在肺癌分期中的应用

目的 探讨支气管内超声引导针吸活检术(EBUS-TBNA)在肺癌分期中的应用价值.方法 回顾性总结2009年9月至2010年2月,52例胸部CT均发现纵隔淋巴结肿大≥1.0 cm肺癌病人经EBUS-TBNA检查的临床资料.结果 经EBUS-TBNA检查证实纵隔淋巴结转移(阳性)者41例,未见纵隔淋巴结转移(阴性)者11例.阳性者放弃手术,予以化疗.阴性者接受胸腔镜或开胸手术,行肺叶切除或肺楔形切除加纵隔淋巴结清扫.术后病理证实,9例纵隔淋巴结确实末见转移,2例纵隔淋巴结可见癌转移,即EBUS-TBNA检查假阴性.EBUS-TBNA的敏感性、特异性、准确性、阳性预测价值及阴性预测价值分别为95.3%、100%、96.2%、100%及81.8%.该检查耐受良好,无任何相关并发症发生.结论 EBUS-TBNA是一种安全、有效的肺癌分期方法.

Abstract：

Objective To determine the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging of lung cancer. Methods The study was retrospective, a total of 52 patients underwent EBUSTBNA for known or suspected lung cancer. All patients were detected enlarged mediastinal lymph nodes on CT scan ( ≥ 1.0cm). Results Of the 52 patients, 41 patients were found with N2 or N3 disease on EBUS-TBNA. 11 patients with negative EBUS-TBNA underwent thoracoscopy or thoracotomy for pulmonary resection and mediastinal lymph node dissection, 9 patients were confirmed N0 by pathology, whereas 2 patients had metastatic lymph node. The diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive value of EBUS-TBNA for the mediastinal staging of lung cancer were 95.3%, 100%, 96.2%, 100%, and 81.8%, respectively. The procedure was uneventful, and there were no postoperative complications. Conclusion EBUS-TBNA is an effective and safe technique for mediastinal staging in lung cancer patients.     

Preclinical feasibility of bronchoscopic fluorescence-guided lung sentinel lymph node mapping

ObjectiveLung sentinel lymph node mapping, where peritumorally injected material is tracked through the lymphatics, aims to find the first potential sites of nodal metastasis. We sought to evaluate the preclinical feasibility of bronchoscopic fluorescence-guided sentinel lymph node mapping.MethodsHealthy Yorkshire pigs were used; sentinel lymph node mapping was performed with indocyanine green. The primary fluorescence imaging method was an ultrathin composite fiberscope placed in the bronchoscope working channel. Secondary methods used a fluorescence thoracoscope placed in the trachea (rigid bronchoscopy) and pretracheal fascial plane (mediastinoscopy) to validate ultrathin composite fiberscope settings for sentinel lymph node detection. A tracheostomy was created, and the pig was placed in a lateral decubitus position. Transbronchial intraparenchymal indocyanine green injection was performed primarily in the right lower lobe. Ultrathin composite fiberscope and rigid bronchoscopy were performed with (n = 6) or without (n = 2) mediastinoscopy, with the former group guiding dose and ultrathin composite fiberscope optimization. Fluorescent targets were interrogated by endobronchial ultrasound before ultrathin composite fiberscope–guided transbronchial needle aspiration. Specimen fluorescence was documented before creating cytological smears. Pigs were killed postprocedure for nodal dissection.ResultsA total of 100 μL of 10 mg/mL indocyanine green generated strong transbronchial fluorescence with low risk of indocyanine green contamination. Fluorescence was detectable by 10 minutes postinjection. There was concordance among ultrathin composite fiberscope, rigid bronchoscopy, and mediastinoscopy. Except for 1 pig with airway contamination, ultrathin composite fiberscope–guided endobronchial ultrasound transbronchial needle aspiration obtained fluorescent material in all pigs. Specimen fluorescence was associated with specimen adequacy.ConclusionsBronchoscopic fluorescence-guided sentinel lymph node mapping was feasible, with specimen fluorescence providing real-time feedback on sentinel lymph node biopsy success. If translated to clinical practice, attention must be paid to minimizing indocyanine green leakage.     

Linear Endobronchial Ultrasound as the Initial Diagnostic Tool in Patients With Indications of Mediastinal Disease

IntroductionLinear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven useful for sampling mediastinal masses and nodes and staging lung cancer. The aim of this study was to assess the usefulness of this diagnostic tool in patients with indications of mediastinal disease that could not be diagnosed by noninvasive methods or white light bronchoscopy.Patients and MethodsAll patients undergoing linear EBUS-TBNA for the diagnosis of mediastinal masses and/or adenopathy at our endoscopy unit were included in the study. Diagnoses obtained by linear EBUSTBNA or any surgical technique performed after a nondiagnostic EBUS-TBNA were considered as final.ResultsIn the study population of 128 patients with a mean (SD) age of 62.0 (11.2) years, a total of 294 TBNAs were performed on 12 masses and 282 nodes. Satisfactory samples were obtained in 11 cases (91.7%) from masses and in 233 cases (82.6%) from nodes. Linear EBUS-TBNA was diagnostic, obviating the need for mediastinoscopy in 115 patients (diagnostic sensitivity, 89.8%). The technique confirmed the diagnosis in 85 of the 94 patients with cancer (90.4%), in 8 of the 10 patients with tuberculosis (80.0%), and in the 5 with sarcoidosis.ConclusionsLinear EBUS-TBNA is a useful diagnostic tool in patients with mediastinal disease for whom a pathologic diagnosis is not achieved by noninvasive methods or white light bronchoscopy.     

Clinical Utility and Economic Impact of Conventional Transbronchial Needle Aspiration of Mediastinal Lymphadenopathies in Bronchogenic Carcinoma

ObjectivesTo analyse the clinical utility and economic impact of conventional transbronchial needle aspiration (TBNA) in patients with diagnosis of bronchogenic carcinoma (BC) and mediastinal lymphadenopathies in thoracic computed tomography (CT). To assess the predictive factors of valid aspirations.Patients and methodsRetrospective observational study between 2006 and 2011 of all TBNA performed in patients with final diagnosis of BC and accessible hilar or mediastinal lymphadenopathies on thoracic CT.ResultsWe performed TBNA on 267 lymphadenopathies of 192 patients. In 34.9% of patients, two or more lymph nodes were biopsied. Valid aspirations were obtained in 153 patients (79.7%) that were diagnostic in 124 patients (64.6%). Multivariate analysis showed that factors associated with valid or diagnostic results are the diameter of the lymph node and the number of lymph nodes explored. TBNA was the only endoscopic technique that provided the diagnosis of BC in 54 patients (28.1%). Staging mediastinoscopy was avoided in 67.6% of patients. The prevalence of mediastinal lymph node involvement was 74.4%, sensitivity of TBNA was 86.2% and negative predictive value was 63.6%. Including mediastinoscopy and other avoided diagnostic techniques, TBNA saved 451.57 € per patient.ConclusionsTBNA is a clinically useful, cost-effective technique in patients with BC and mediastinal or hilar lymphadenopathies. It should therefore be performed on a regular basis during diagnostic bronchoscopy of these patients.     

Summary of the British Thoracic Society guidelines for advanced diagnostic and therapeutic flexible bronchoscopy in adults

This new guideline covers the rapidly advancing field of interventional bronchoscopy using flexible bronchoscopy. It includes the use of more complex diagnostic procedures such as endobronchial ultrasound, interventions for the relief of central airway obstruction due to malignancy and the recent development of endobronchial therapies for chronic obstructive pulmonary disease and asthma. The guideline aims to help all those who undertake flexible bronchoscopy to understand more about this important area. It also aims to inform respiratory physicians and other specialists dealing with lung cancer of the procedures possible in the management and palliation of central airway obstruction. The guideline covers transbronchial needle aspiration and endobronchial ultrasound-guided transbronchial needle aspiration, electrocautery/diathermy, argon plasma coagulation and thermal laser, cryotherapy, cryoextraction, photodynamic therapy, brachytherapy, tracheobronchial stenting, electromagnetic navigation bronchoscopy, endobronchial valves for emphysema and bronchial thermoplasty for asthma.     

ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer.

Accurate preoperative staging and restaging of mediastinal lymph nodes in patients with non-small cell lung cancer (NSCLC) is of paramount importance. It will guide choices of treatment and determine prognosis and outcome. Over the last years, different techniques have become available. They vary in accuracy and procedure-related morbidity. The Council of the ESTS initiated a workshop on preoperative mediastinal lymph node staging. This resulted in guidelines for primary staging and restaging. For primary staging, mediastinoscopy remains the gold standard for the superior mediastinal lymph nodes. Invasive procedures can be omitted in patients with peripheral tumors and negative mediastinal positron emission tomography (PET) images. However, in case of central tumors, PET hilar N1 disease, low fluorodeoxyglucose uptake of the primary tumor and LNs > or = 16 mm on CT scan, invasive staging remains indicated. PET positive mediastinal findings should always be cyto-histologically confirmed. Transbronchial needle aspiration (TBNA), ultrasound-guided bronchoscopy with fine needle aspiration (EBUS-FNA) and endoscopic esophageal ultrasound-guided fine needle aspiration (EUS-FNA) are new techniques that provide cyto-histological diagnosis and are minimally invasive. Their specificity is high but the negative predictive value is low. Because of this, if they yield negative results, an invasive surgical technique is indicated. However, if fine needle aspiration is positive, this result may be valid as proof for N2 or N3 disease. For restaging, invasive techniques providing cyto-histological information are advisable despite the encouraging results supported with the use of PET/CT imaging. Both endoscopic techniques and surgical procedures are available. If they yield a positive result, non-surgical treatment is indicated in most patients.     

Diagnostic Algorithm in Patients with Superior Vena Cava Syndrome and Efficacy of Cervical Mediastinoscopy

Background: Superior vena cava syndrome (SVCS) is the result of the direct obstruction of the superior vena cava by malignancy and/or mediastinal lymphadenopathy. Our aim is to propose a diagnostic algorithm for undiagnosed superior vena cava syndrome patients and compare the diagnostic value, mortality and morbidity rates in patients diagnosed by mediastinoscopy.

Methods: Ninety-seven patients with SVCS underwent diagnostic management starting with the least invasive technique and proceeding to more advanced and invasive methods between January 2000 and June 2013. Seventy one (73%) patients received histopathologic diagnosis using local biopsy, endobronchial biopsy by fiberoptic bronchoscopy and/or endobronchial ultrasound (EBUS) and CT-guided fine needle aspiration biopsy. Twenty six patients out of 97 patients who had superior vena cava syndrome underwent cervical mediastinoscopy for definitive diagnosis. Four patients (three male and one female) received histopathologic diagnosis using EBUS with the use of this method in our institution after 2010.

Results: Of 26 patients who underwent cervical mediastinoscopy, 11 had small cell lung carcinoma, six had squamous cell lung carcinoma, three had adenocarcinoma, two had lymphoma, one had thymoma, one had tuberculosis, one had seminoma and one had chronic fibrous mediastinitis. Definitive tissue diagnosis was obtained in all patients. No peri-operative mortality was recorded. One patient had minor bleeding which was controlled without additional surgical intervention.

Conclusions: We propose a diagnostic algorithm in undiagnosed patients with superior vena cava syndrome. We conclude that cervical mediastinoscopy is a safe, fast and effective technique to establish pathologic diagnosis, and directs the physicians to apply the appropriate treatment in clinically diagnosed superior vena cava syndrome when less invasive techniques have been unsuccessful.     

Cost-effectiveness of mediastinal lymph node staging in non–small cell lung cancer

Objective

To assess the cost-effectiveness of various modes of mediastinal staging in non–small cell lung cancer (NSCLC) in a single-payer health care system.

Intrapulmonary Schwannoma Diagnosed With Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: Case Report

A 47-year-old woman was referred to our hospital for further examination of a lung tumor. CT of the chest revealed a round, well-defined 2.4-cm nodule in S2, adjacent to right superior lobe bronchus. Endobronchial ultrasonography showed a well-defined, hypoechoic tumor with echogenic capsule and posterior acoustic enhancement. Diagnosis of schwannoma was confirmed from the specimen obtained by endobronchial ultrasound-guided transbronchial needle aspiration. She underwent tumorectomy due to the possibility of obstructive pneumonia. Pathology diagnosis from the surgical specimen was also schwannoma. Endobronchial ultrasound-guided transbronchial needle aspiration and findings with endobronchial ultrasonography might be helpful in the diagnosis of intrapulmonary schwannoma.     

Current status and perspective of EBUS-TBNA

In 2002, a new bronchoscope equipped with a convex type ultrasound probe on the tip was introduced into clinical practice. This convex probe endobronchial ultrasound (CP-EBUS) provides a long axis image of surrounding structures of the major airway. The CP-EBUS combined with a dedicated biopsy needle allows real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of mediastinal and hilar lymph nodes. Samples obtained from EBUS-TBNA can be used for pathological diagnosis including immunohistochemistry. EBUS-TBNA is now being performed worldwide for several indications including mediastinal staging, mediastinal pathology and for benign diseases. For mediastinal staging in lung cancer, the diagnostic yield of EBUS-TBNA is comparable to surgical staging in patients with enlarged lymph nodes. In addition, EBUS-TBNA can be used for molecular analysis of tumor cells obtained during the procedure. DNA mutation testing using EBUS-TBNA samples was first reported in 2007 for a chondrosarcoma case. Also, isolated DNA from EBUS-TBNA samples was applied for epidermal growth factor receptor mutation testing and aberrant methylation analysis in patients with lung cancer. RNA was also isolated from properly stored EBUS-TBNA samples and used for gene expression research and aberrant fusion gene detection in lung cancer patients. Optimization of tissue banking methods of EBUS-TBNA specimens was also investigated. Currently, EBUS-TBNA samples can be used for comprehensive mRNA and miRNA expression analysis. EBUS-TBNA will become an important modality for bronchoscopists in the era of personalized medicine in lung cancer.     

Endobronchial ultrasonography in a patient with a mediastinal thoracic duct cyst

Mediastinal thoracic duct cysts are rare clinical findings. We report the case of a symptomatic 58-year-old woman in whom a thoracic duct cyst was successfully treated with surgical resection. Preoperative endobronchial ultrasonography revealed an oval-shaped hypoechoic area with a distinct, thick pedicle, gradual intermittent flux of the fluid content within the lesion, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) revealed lymphocyte predominant serous fluid without malignancy, which is consistent with features of a mediastinal thoracic duct cyst. We postulate that EBUS-TBNA can be used as a preoperative diagnostic tool for patients with possible mediastinal thoracic duct cysts.     

EBUS-TBNA在纵隔气管周围病变诊断中的应用

目的 探讨支气管内超声引导针吸活检术(EBUS-TBNA)在纵隔气管周围病变诊断中的应用价值。方法 回顾性总结2009年9月至2010年7月,34例不明原因的纵隔淋巴结肿大或纵隔肿物患者经EBUS-TBNA检查的临床资料。对EBUS-TBNA仍未能明确诊断者,进一步接受外科手术活检或至少6个月以上的临床及影像学随诊。结果 经EBUS-TBNA检查后28例获得明确诊断,其中恶性病变10例,良性病变18例,确诊率82.4％。EBUS-TBNA在纵隔病变良、恶性诊断和鉴别诊断方面的敏感性、特异性和准确性分别为90.9％、100％和97.1％。所有受检者耐受良好,无任何相关并发症发生。结论 对于纵隔气管周围病变,EBUS-TBNA是一种安全、有效的诊断方法。     

支气管内超声引导针吸活检术在纵隔淋巴结CT阳性肺癌分期中的价值

目的 评价支气管内超声引导下针吸活检术(EBUS-TBNA)在纵隔淋巴结CT阳性肺癌病例分期中的应用价值.方法 2009年9月至12月共对28例胸部CT纵隔淋巴结阳性(短径≥1 cm)的肺癌病人行EBUS-TBNA检查.总结穿刺结果,评价该方法的诊断价值和安全性.结果 28例共穿刺淋巴结40组,淋巴结穿刺取材满意率96.3%(27/28例),无任何相关并发症.EBUS-TBNA阳性(取得恶性细胞病理学证据)20例,阴性(未取得恶性细胞病理学证据)8例;阴性者接受进一步外科手术,术后证实纵隔淋巴结转移2例(EBUS-TBNA假阴性).EBUS-TBNA检查准确率92.9%(26/28例),灵敏度90.9%(20/22例),特异度100%(6/6例),阳性预测值100%(20/20例),阴性预测值75%(6/8例).结论 EBUS-TBNA是评价纵隔淋巴结CT阳性肺癌分期的安全有效方法.