Advances in lung cancer diagnosis and staging: endobronchial ultrasound

Background:  Endobronchial ultrasound (EBUS) is an accurate and relatively less invasive procedure for the diagnosis of lung lesions and mediastinal lymph node staging for lung cancer. We aimed to evaluate the clinical utility and safety of this new EBUS service established in our hospital.
Methods:  Consecutive patients who underwent EBUS–transbronchial lung biopsy (EBUS–TBLB) for biopsy of peripheral pulmonary lesions or for transbronchial needle aspiration (TBNA) of mediastinal lymph node enlargement were included in this audit. Demographic and clinical data were obtained prospectively. Diagnostic yield from the results of EBUS was compared to other clinical information obtained.
Results:  Thirty-eight patients underwent EBUS over a 10-month period. The yield from EBUS–TBLB was 62%. The average size of the lung lesions biopsied was 3.5 cm and 62% were located in the upper lobes. Malignancy was diagnosed in 14 cases and a benign aetiology in four. The yield from EBUS–TBNA was 88% and the average size of the lymph nodes was 2.3 cm. The lymph nodes were all located in the subcarinal station except for two that were in the lower paratracheal station. Malignancy was diagnosed in 10 cases on TBNA and 4 cases had benign pathology. There was one complication seen (small pneumothorax).
Conclusion:  EBUS is safe and an effective method for both, diagnosis of peripheral pulmonary lesions and staging for lung cancer.     

Ultrasound techniques in the evaluation of the mediastinum,part I: endoscopic ultrasound (EUS), endobronchial ultrasound (EBUS) and transcutaneous mediastinal ultrasound (TMUS), introduction into ultrasound techniques

Ultrasound imaging has gained importance in pulmonary medicine over the last decades including conventional transcutaneous ultrasound (TUS), endoscopic ultrasound (EUS), and endobronchial ultrasound (EBUS). Mediastinal lymph node staging affects the management of patients with both operable and inoperable lung cancer (e.g., surgery vs. combined chemoradiation therapy). Tissue sampling is often indicated for accurate nodal staging. Recent international lung cancer staging guidelines clearly state that endosonography (EUS and EBUS) should be the initial tissue sampling test over surgical staging. Mediastinal nodes can be sampled from the airways [EBUS combined with transbronchial needle aspiration (EBUS-TBNA)] or the esophagus [EUS fine needle aspiration (EUS-FNA)]. EBUS and EUS have a complementary diagnostic yield and in combination virtually all mediastinal lymph nodes can be biopsied. Additionally endosonography has an excellent yield in assessing granulomas in patients suspected of sarcoidosis. The aim of this review, in two integrative parts, is to discuss the current role and future perspectives of all ultrasound techniques available for the evaluation of mediastinal lymphadenopathy and mediastinal staging of lung cancer. A specific emphasis will be on learning mediastinal endosonography. Part I is dealing with an introduction into ultrasound techniques, mediastinal lymph node anatomy and diagnostic reach of ultrasound techniques and part II with the clinical work up of neoplastic and inflammatory mediastinal lymphadenopathy using ultrasound techniques and how to learn mediastinal endosonography.     

Training and proficiency in endobronchial ultrasound‐guided transbronchial needle aspiration: A systematic review

Endobronchial ultrasound (EBUS)‐guided transbronchial needle aspiration (TBNA) is currently the modality of choice for evaluation of mediastinal lymphadenopathy. However, there is still uncertainty regarding the training methodology and the number of procedures required to attain proficiency in EBUS. Herein, we performed a systematic review of studies selected from PubMed, EmBase and Scopus databases describing the training and assessment of proficiency during EBUS, specifically studies investigating various methods for training, its outcome and the number of procedures required to overcome the learning curve for EBUS. Twenty‐seven (simulator‐based learning (n = 8), tools for assessing competence in EBUS‐TBNA (n = 5) and threshold numbers needed to attain proficiency in EBUS‐TBNA (n = 16)) studies were identified. An EBUS simulator accurately stratified individuals based on the level of experience in performing EBUS. Training received on a simulator was comparable with traditional apprentice‐based training. Importantly, skills acquired on a simulator could be transferred to real‐world patients. The number needed to overcome the initial learning curve of EBUS varied from 10 to 100 in individual studies with a mean of 37–44 procedures. Tools such as EBUS‐STAT (EBUS skill and task assessment tool) and EBUSAT (EBUS skill and assessment tool) were effective in evaluating the EBUS trainees. We conclude that an EBUS simulator or EBUS assessment tools can objectively assess the training of an EBUS trainee. Simulator‐based training is a useful modality in EBUS training. The number of procedures needed to overcome the initial learning curve is about 40. Centres involved in EBUS training could incorporate simulator‐based training in their curriculum before allowing operators to perform EBUS on patients.     

Endoscopic ultrasound staging of rectal cancer: diagnostic value before and following chemoradiation

BACKGROUND: Endoscopic ultrasound (EUS) has been shown to be a reliable tool for staging rectal cancer. Nevertheless, the accuracy of EUS after chemoradiation remains unclear; therefore the purpose of the present paper was to compare the accuracy of EUS staging for rectal cancer before and following chemoradiation. METHODS: Patients with rectal cancer undergoing EUS staging were stratified into two groups. Group I consisted of 66 patients who underwent surgery following EUS staging without preoperative chemoradiation. Group II consisted of 25 patients who had EUS evaluation following chemoradiation. The EUS staging was compared to surgical/pathological staging. RESULTS: The accuracy of the T staging for group I was 86% (57/66). Inaccurate staging was mainly associated with overstaging EUS T2 tumors. The accuracy of the N staging for group I was 71% (47/66). The accuracy of EUS for a composite T and N staging relevant to treatment decisions in group I was 91%. In group II, the accuracy of T and N staging was 72% (18/25) and 80% (20/25), respectively. Overstaging EUS T3 tumors accounted for most inaccurate staging. The EUS staging predicted post-chemoradiation T0N0 stage correctly in only 50% of cases. CONCLUSIONS: Preoperative staging of rectal cancer by EUS is a useful modality in determining the need for preoperative chemoradiation. The EUS T staging following chemoradiation appears to be less accurate. Detection of complete response may be insufficient for selecting patients for limited surgical intervention.     

Endoscopic ultrasound for esophageal and gastroesophageal junction cancer: Impact of increased use of primary neoadjuvant therapy on preoperative locoregional staging accuracy

Initial treatment of locally advanced esophageal and gastroesophageal junction (GEJ) malignancies for selected patients at some institutions has recently changed from surgical resection to neoadjuvant therapy. The aim of this study is to evaluate the impact of this change in treatment strategy on both the overall disease profile and locoregional endoscopic ultrasound (EUS) staging accuracy for a cohort of patients managed with primary surgical resection over a 10-year period at our institution. All subjects at our institution who underwent primary esophagectomy from 1993 to 2002 following preoperative EUS for known or suspected esophageal and/or GEJ cancers were identified. Patients with dysplasia alone, prior upper gastrointestinal tract surgery, preoperative neoadjuvant therapy, cancer of the gastric cardia or recurrent malignancy were excluded. EUS findings and staging results were compared to surgical pathology following resection. The impact of the gradually increased use of primary chemoradiation during the second half of the study was assessed. Of the 286 operations performed, 184 subjects were excluded. The remaining 102 underwent primary surgical resection a median of 18 days following EUS staging for adenocarcinoma (88%) or squamous cell carcinoma (12%) of the esophagus (69%) or GEJ (31%). Overall EUS locoregional T and N staging accuracy was 72% and 75% respectively; accuracy for T1, T2, T3 and T4 cancer was 42%, 50%, 88% and 50% respectively. Despite an increased frequency of pathologically confirmed T1 and T2 cancers (P = 0.005) and an insignificant trend toward increased N0 malignancy (P = 0.05) during the second half of the study period, no statistically significant changes in T (P = 0.07) or N (P = 0.82) staging accuracies for EUS or disease characteristics were noted between the first and second half of the study period. Despite both inaccurate radial EUS staging and increased relative use of primary surgery for early cancers, recent increased use of primary neoadjuvant therapy did not change overall disease characteristics and accuracy of locoregional EUS staging of esophageal and GEJ cancers managed with primary surgical resection.     

Lung cancer staging: State of the art in the era of ablative therapies and surgical segmentectomy

Implementation of lung cancer screening and improvements in imaging are expected to increase the proportion of lung cancer diagnosed at an early stage. The standard of care has historically been anatomic lobectomy; however, there is now an array of surgical and non‐surgical approaches for management of local disease either in active use or under investigation. By their nature, these new modalities offer a theoretical trade‐off of reduced morbidity in exchange for reduced efficacy in the setting of advanced disease. It is therefore critical that patients being considered for these approaches (e.g. surgical segmentectomy and SABR) be accurately staged to maximize the potential for definitive treatment. In this article, we will review current approaches to the staging of patients being considered for segmentectomy or ablation. This will serve as a foundation to highlight important questions deserving further investigation.     

Clinical validity of 25-gauge endobronchial ultrasound-guided transbronchial needle in lymph node staging of lung cancer

BackgroundEndobronchial ultrasound-guided transbronchial needle aspiration is recommended for lymph node (LN) staging in lung cancer. Although 22-gauge needles are widely used, they may make some stations difficult to puncture owing to an acute angle. A thinner 25-gauge needle was introduced in Japan at the end of 2016 and offered structural advantages such as improved flexibility and penetrability. We aimed to validate the clinical utility of the 25-gauge needle in LN staging.MethodsPatients who underwent endobronchial ultrasound-guided transbronchial needle aspiration for LN staging of lung cancer using the 25-gauge needle at our institution between November 2016 and March 2019 were included. Patient characteristics, staging procedures, pathology findings, and genetic testing success rates were assessed.ResultsData of 130 patients were included in the analysis. The sampling rate was 87.6% (589/672 lesions). In addition to stations #4R, #7, and #11, which are generally easy to puncture, multiple stations (40.1%) were sampled. The diagnostic accuracy of combined computed tomography and fluorodeoxyglucose positron emission tomography was 82.3% and that of additional endobronchial ultrasound-guided transbronchial needle aspiration was 96.9%. The overall sensitivity, specificity, and positive and negative predictive values validated using resected specimens were 97.1% (34/35), 100% (41/41), 100% (34/34), and 97.6% (41/42), respectively. The success rate of genetic testing was 100% (34/34).ConclusionsThe new 25-gauge needle enabled us to approach a wide range of LNs with a desirable sampling rate and diagnostic accuracy in LN staging using endobronchial ultrasound-guided transbronchial needle aspiration, while providing enough tissue for genetic testing.     

Endobronchial ultrasound-guided transbronchial needle aspiration for lung cancer staging: early experience in Brazil

Objective:

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive, safe and accurate method for collecting samples from mediastinal and hilar lymph nodes. This study focused on the initial results obtained with EBUS-TBNA for lung cancer and lymph node staging at three teaching hospitals in Brazil.

Methods:

This was a retrospective analysis of patients diagnosed with lung cancer and submitted to EBUS-TBNA for mediastinal lymph node staging. The EBUS-TBNA procedures, which involved the use of an EBUS scope, an ultrasound processor, and a compatible, disposable 22 G needle, were performed while the patients were under general anesthesia.

Results:

Between January of 2011 and January of 2014, 149 patients underwent EBUS-TBNA for lymph node staging. The mean age was 66 ± 12 years, and 58% were male. A total of 407 lymph nodes were sampled by EBUS-TBNA. The most common types of lung neoplasm were adenocarcinoma (in 67%) and squamous cell carcinoma (in 24%). For lung cancer staging, EBUS-TBNA was found to have a sensitivity of 96%, a specificity of 100%, and a negative predictive value of 85%.

Conclusions:

We found EBUS-TBNA to be a safe and accurate method for lymph node staging in lung cancer patients.     

Multimodality systematic approach to mediastinal lymph node staging in non‐small cell lung cancer

Establishing an accurate diagnosis and stage for non‐small cell lung cancer has important implications for treatment and prognosis. Ideally, the process should be performed in a way that maximizes the information from each procedure while minimizing the risk to the patient. The concepts of decision analysis and Bayes' theorem form a basis to develop the strategy. In this framework, the pre‐test probability of malignancy is estimated in the lung nodule or mass, the regional lymph nodes and in distant sites. Invasive diagnostic tests are performed in sites with a pre‐test probability greater than the testing threshold, beginning with those sites that would yield the highest stage, if positive. Modalities are chosen that are able to biopsy the suspicious sites and present the least amount of risk to the patient. Following each test, the post‐test probability of malignancy is calculated to determine if it crosses the testing or test‐treatment thresholds. The process continues with further tests until a diagnosis and stage are established.     

Endoscopic ultrasound‐guided fine‐needle aspiration when combined with positron emission tomography improves specificity and overall diagnostic accuracy in unexplained mediastinal lymphadenopathy and staging of non‐small‐cell lung cancer

Background: The aim of this study was to assess the incremental value of endoscopic ultrasound (EUS)‐guided fine‐needle aspiration (FNA) to positron emission tomography (PET) in the diagnosis of unexplained mediastinal lymphadenopathy and staging of non‐small‐cell lung cancer (NSCLC). Methods: Patients who had both EUS‐guided FNA and PET were retrospectively identified from an EUS database at a tertiary hospital. All EUS‐guided FNA were carried out by one endoscopist between August 2002 and April 2005, either for the diagnosis of unexplained mediastinal lymphadenopathy or for the staging of NSCLC. Results of PET and EUS were compared with histology. A true histological positive result was defined as histological involvement in either surgery (mediastinoscopy or resection) or EUS‐guided FNA. A true histological negative result was defined as negative involvement at surgery (mediastinoscopy or resection). Results: Forty‐nine patients who had both PET scanning and EUS‐guided FNA for diagnosis of unexplained mediastinal lymphadenopathy or staging of NSCLC were identified. Of these, 33 (73% males, n = 24, age range = 44–78 years, mean = 62 years) had surgical confirmation of mediastinal lymph node pathology. In these patients, PET alone showed sensitivity, 95%; specificity, 90%; positive predictive value, 87%; negative predictive value, 90% and accuracy, 88%; whereas the addition of EUS‐guided FNA increased the overall specificity and positive predictive value to 100%, with an overall accuracy of 97%. Conclusions: This study suggests that EUS‐guided FNA complements PET by improving the overall specificity and thereby the accuracy for diagnosis of unexplained mediastinal lymphadenopathy. It provides a minimally invasive technique to assess the mediastinum in patients with NSCLC and is particularly valuable in cases in which PET findings are equivocal.     

在B型超声引导下穿刺活检对肺癌检出率的临床研究

目的探讨肺肿瘤患者在B型超声引导下肺穿刺活检对肺癌检出率的研究。方法选择769例肺部肿瘤患者,采用B超引导下穿刺活检,将穿刺吸出物涂片,用10％甲醛液固定,送病理科做细胞学检查。结果769例肺部肿瘤在B超引导下肺活检,确诊为肺癌患者685例,占89．1％,可疑癌14例,占1．8％。肺肿块活检确诊为非肺癌者61例,占7．9％,另有9例,占1．2％的患者肺肿块活检未能确诊。提示B超引导下肺活检对肺癌总检出率为90．9％（699／769）,而肺部疾病部总检出率为98．8％（760/769）。结论B超引导下肺肿瘤活检术,无X线辐射,操作简单,定位准确,并发症少,安全性好;检出率较高,值得临床推广使用。     

Radial endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions: A systematic review and meta‐analysis

Tissue diagnosis of peripheral pulmonary lesions (PPLs) can be challenging. In the past, flexible bronchoscopy was commonly performed for this purpose but its diagnostic yield is suboptimal. This has led to the development of new bronchoscopic modalities such as radial endobronchial ultrasound (R‐EBUS), electromagnetic navigation bronchoscopy (ENB) and virtual bronchoscopy (VB). We performed this meta‐analysis using data from previously published R‐EBUS studies, to determine its diagnostic yield and other performance characteristics. Ovid MEDLINE and PubMed databases were searched for R‐EBUS studies in September 2016. Diagnostic yield was calculated by dividing the number of successful diagnoses by the total number of lesions. Meta‐analysis was performed using MedCalc (Version 16.8). Inverse variance weighting was used to aggregate diagnostic yield proportions across studies. Publication bias was assessed using funnel plot and Duval and Tweedie's test. 57 studies with a total of 7872 lesions were included in the meta‐analysis. These were published between October 2002 and August 2016. Overall weighted diagnostic yield for R‐EBUS was 70.6% (95% CI: 68–73.1%). The diagnostic yield was significantly higher for lesions >2 cm in size, malignant in nature and those associated with a bronchus sign on computerized tomography (CT) scan. Diagnostic yield was also higher when R‐EBUS probe was within the lesion as opposed to being adjacent to it. Overall complication rate was 2.8%. This is the largest meta‐analysis performed to date, assessing the performance of R‐EBUS for diagnosing PPLs. R‐EBUS has a high diagnostic yield (70.6%) with a very low complication rate.     

Role of endoscopic ultrasound‐guided fine‐needle aspiration with flow cytometry to diagnose lymphoma: A single center experience

Background and Aim: The use of endoscopic ultrasound‐guided fine‐needle aspiration (EUS?FNA) ± flow cytometry (FC) for the diagnosis of suspected lymphoma remains controversial. We report our experience and diagnostic yield for EUS ± FC for suspected lymphoma. Methods: Databases were queried for those who underwent EUS?FNA ± FC for suspected lymphoma. Hospital charts were reviewed to confirm the final cytological diagnosis, follow up and FC results if obtained. The final diagnosis was confirmed by the results of EUS?FNA ± FC, other biopsy and/or follow up. Results: In total, 54 patients underwent EUS?FNA of 72 lesions. The final diagnosis of lymphoma was made in 38 of the 54 (70%) patients, and 33 of the 54 (61%) patients relied on EUS?FNA. Cytopathology in 41 patients using EUS?FNA + FC showed lymphoma in 24 patients, atypical lymphoid cells in six and reactive lymph node in 11. In 9 of the 24 with lymphoma by EUS + FC, the diagnosis was confirmed by another diagnostic modality, like surgery, bone marrow biopsy and computed tomography‐guided biopsy. Of the six with atypical lymphoid cells, additional diagnostic methods confirmed lymphoma in three. The remaining 13 of the 54 patients underwent EUS?FNA without FC due to insufficient sample (n = 5) or operator choice (n = 8). Cytopathology in these 13 patients without FC showed lymphoma (9), atypical lymphoid cells (3) and reactive node (1). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS?FNA for lymphoma in all 54 patients ranged from 80% to 87%, 92% to 93%, 97%, 60% to 75% and 83% to 89%, respectively. Conclusions: EUS?FNA is sensitive and specific for the diagnosis of suspected lymphoma. Confirmatory or further testing should be performed when EUS?FNA with or without FC is indeterminate and or non‐diagnostic.