Mark Krasnik

Real-time endobronchial ultrasound guided transbronchial needle aspiration for sampling mediastinal lymph nodes

Background: Transbronchial needle aspiration (TBNA) is an established method for sampling mediastinal lymph nodes to aid in diagnosing lymphadenopathy and in staging lung cancers. Real-time endobronchial ultrasound (EBUS) guidance is a new method of TBNA that may increase the ability to sample these nodes and hence to determine a diagnosis. A descriptive study was conducted to test this new method. Methods: Consecutive patients referred for TBNA of mediastinal lymph nodes were included in the trial. When a node was detected, a puncture was performed under real-time ultrasound control. The primary end point was the number of successful biopsy specimens. Diagnostic results from the biopsies were compared with operative findings. Lymph node stations were classified according to the recently adopted American Thoracic Society scheme. Results: From 502 patients (316 men) of mean age 59 years (range 24–82), 572 lymph nodes were punctured and 535 (94%) resulted in a diagnosis. Biopsy specimens were taken from lymph nodes in region 2L (40 nodes), 2R (53 nodes), 3 (35 nodes), 4R (86 nodes), 4L (77 nodes), 7 (127 nodes), 10R (38 nodes), 10L (43 nodes), 11R (40 nodes) and 11L (33 nodes). The mean (SD) diameter of the nodes was 1.6 (0.36) cm and the range was 0.8–3.2 cm (SD range 0.8–4.3). Sensitivity was 94%, specificity 100%, and the positive predictive value was 100% calculated per patient. No complications occurred. Conclusion: EBUS-TBNA is a promising new method for sampling mediastinal lymph nodes. It appears to permit more and smaller nodes to be sampled than conventional TBNA, and it is safe.

The IASLC Lung Cancer Staging Project: Validation of the Proposals for Revision of the T, N, and M Descriptors and Consequent Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours

Introduction: In 1996, the International Association for the Study of Lung Cancer (IASLC) launched a worldwide TNM staging project to inform the next edition (seventh) of the TNM lung cancer staging system. In this article, we describe the methods and validation approaches used and discuss the internal and external validity of the recommended changes. Methods: The International Staging Committee agreed on a number of general principles that guided the decision-making process. Internal validity was addressed by visually assessing the consistency of Kaplan-Meier curves across database types, geographic regions and addressing external validity, by assessing the similarity of curves generated using the population-based Surveillance Epidemiology and End Results cancer registry data to those generated using the project database. Cox proportional hazards regression was used to calculate hazard ratios between the proposed stage groupings with adjustment for cell type, sex, age, and region. Results: Calls for data by the International Staging Committee resulted in the creation of an international database containing information on more than 100,000 cases. The present work is based on analyses of the 67,725 cases of non-small cell lung cancer. Validation checks were robust, demonstrating that the suggested staging changes are stable within the data sources used and externally. For example, suggested changes based on tumor size were well supported, with statistically significant hazard ratios ranging from 1.14 to 1.51 between adjacent pairs in the Surveillance Epidemiology and End Results data. Conclusions: Lung cancer stage definitions have never been subjected to such an intense validation process. We do accept, however, that this work is limited in ways that can only be addressed by a prospective database, which we intend to develop. In the meantime, we think that this new system will greatly improve the usefulness of TNM lung staging across all of its purposes.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration of Lymph Nodes in the Radiologically and Positron Emission Tomography-Normal Mediastinum in Patients With Lung Cancer

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can reliably sample enlarged mediastinal lymph nodes in patients with non-small cell lung cancer (NSCLC), and in practice is mostly used to sample nodes visible on CT or positron emission tomography (PET). Few data are available on the use of endoscopic procedures to stage the mediastinum in clinical stage 1 lung cancer. The aim of the present study was to determine the results of EBUS-TBNA in sampling mediastinal lymph nodes in patients with lung cancer and a radiographically normal mediastinum and no PET activity. From January 2004 to May 2007, patients highly suspicious for NSCLC with CT scans showing no enlarged lymph nodes (no node > 1 cm) and a negative PET finding of the mediastinum underwent EBUS-TBNA. Identifiable lymph nodes at locations 2r, 2L, 4r, 4L, 7, 10r, 10L, 11r, and 11L were aspirated. All patients underwent subsequent surgical staging. Diagnoses based on aspiration results were compared with those based on surgical results. One hundred patients (mean age, 52.4 years; 59 men) were included. After surgery, 97 patients (mean age, 52.9 years; 57 men) had NSCLC confirmed and were included in the analysis. In this group, 156 lymph nodes ranging 5 to 10 mm in size were detected and sampled. Malignancy was detected in nine patients but missed in one patient. Mean diameter of the punctured lymph nodes was 7.9 mm. The sensitivity of EBUS-TBNA for detecting malignancy was 89%, specificity was 100%, and the negative predictive value was 98.9%. No complications occurred. In conclusion, EBUS-TBNA can be used to accurately sample and stage patients with clinical stage 1 lung cancer and no evidence of mediastinal involvement on CT and PET. Potentially operable patients with no signs of mediastinal involvement may benefit from presurgical staging with EBUS-TBNA.

Diagnosis of Mediastinal Adenopathy—Real-Time Endobronchial Ultrasound Guided Needle Aspiration versus Mediastinoscopy

Background: Real-time endobronchial ultrasound has increased the accuracy of conventional transbronchial needle aspiration biopsy in sampling mediastinal lymph nodes. Nevertheless, direct comparisons with mediastinoscopy are not available to determine the role of endobronchial ultrasound in pathologic staging. Objectives: To compare the diagnostic yield of endobronchial ultrasound against cervical mediastinoscopy in the diagnosis and staging of radiologically enlarged mediastinal lymph nodes stations accessible by both modalities in patients with suspected nonsmall cell lung cancer. Methods: Prospective, crossover trial with surgical lymph node dissection used as the accepted standard. Biopsy results of paratracheal and subcarinal lymph nodes were compared. Results: Sixty-six patients with a mean age 60 ± 10 years were studied. The prevalence of malignancy was 89% (59/66 cases). Endobronchial ultrasound had a higher overall diagnostic yield (91%) compared with mediastinoscopy (78%; p = 0.007) in the per lymph node analysis. There was disagreement in the yield between the two procedures in the subcarinal lymph nodes (24%; p = 0.011). There were no significant differences in the yield at other lymph node stations. The sensitivity, specificity, and negative predictive value of endobronchial ultrasound were 87, 100, and 78%, respectively. The sensitivity, specificity, and negative predictive value of mediastinoscopy were 68, 100, and 59%, respectively. No significant differences were found between endobronchial ultrasound (93%) and mediastinoscopy (82%; p = 0.083) in determining true pathologic N stage (per patient analysis). Conclusions: In suspected nonsmall cell lung cancer, endobronchial ultrasound may be preferred in the histologic sampling of paratracheal and subcarinal mediastinal adenopathy because the diagnostic yield can surpass mediastinoscopy.

Endobronchial Ultrasound With Transbronchial Needle Aspiration for Restaging the Mediastinum in Lung Cancer

PURPOSE To investigate the sensitivity and accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for restaging the mediastinum after induction chemotherapy in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS One hundred twenty-four consecutive patients with tissue-proven stage IIIA-N2 disease who were treated with induction chemotherapy and who had undergone mediastinal restaging by EBUS-TBNA were reviewed. On the basis of computed tomography, 58 patients were classified as having stable disease and 66 were judged to have had a partial response. All patients subsequently underwent thoracotomy with attempted curative resection and a lymph node dissection regardless of EBUS-TBNA findings. RESULTS Persistent nodal metastases were detected by using EBUS-TBNA in 89 patients (72%). Of the 35 patients in whom no metastases were assessed by EBUS-TBNA, 28 were found to have residual stage IIIA-N2 disease at thoracotomy. The majority (91%) of these false negative results were due to nodal sampling error rather than detection error. Overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of EBUS-TBNA for mediastinal restaging after induction chemotherapy were 76%, 100%, 100%, 20%, and 77%, respectively. CONCLUSION EBUS-TBNA is a sensitive, specific, accurate, and minimally invasive test for mediastinal restaging of patients with NSCLC. However, because of the low negative predictive value, tumor-negative findings should be confirmed by surgical staging before thoracotomy.

Combined endoscopic-endobronchial ultrasound-guided fine-needle aspiration of mediastinal lymph nodes through a single bronchoscope in 150 patients with suspected lung cancer.

BACKGROUND For mediastinal lymph nodes, biopsies must often be performed to accurately stage lung cancer. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) allows real-time guidance in sampling paratracheal, subcarinal, and hilar lymph nodes, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can sample mediastinal lymph nodes located adjacent to the esophagus. Nodes can be sampled and staged more completely by combining these procedures, but to date use of two different endoscopes has been required. We examined whether both procedures could be performed with a single endobronchial ultrasound bronchoscope. METHODS Consecutive patients with a presumptive diagnosis of non-small cell lung cancer (NSCLC) underwent endoscopic staging by EBUS-TBNA and EUS-FNA through a single linear ultrasound bronchoscope. Surgical confirmation and clinical follow-up was used as the reference standard. RESULTS Among 150 evaluated patients, 139 (91%; 83 men, 56 women; mean age 57.6 years) were diagnosed with NSCLC. In these 139 patients, 619 nodes were endoscopically biopsied: 229 by EUS-FNA and 390 by EBUS-TBNA. Sensitivity was 89% for EUS-FNA and 92% for EBUS-TBNA. The combined approach had a sensitivity of 96% and a negative predictive value of 95%, values higher than either approach alone. No complications occurred. CONCLUSIONS The two procedures can easily be performed with a dedicated linear endobronchial ultrasound bronchoscope in one setting and by one operator. They are complementary and provide better diagnostic accuracy than either one alone. The combination may be able to replace more invasive methods as a primary staging method for patients with lung cancer.

Preliminary experience with a new method of endoscopic transbronchial real time ultrasound guided biopsy for diagnosis of mediastinal and hilar lesions

Background: The aim of the present study was to gain experience with a new method of endoscopic transbronchial ultrasonography with direct, real time guided fine needle aspiration biopsy (EBUS-FNA). Methods: EBUS-FNA was performed in 11 patients. Selection of the patients for EBUS-FNA was based on computed tomographic (CT) scanning in 10 patients and on positron emission tomography in one. The ultrasonic bronchoscope used was a prototype with an outer diameter of 6.9 mm. The instrument has a small curved array transducer located in front of a 30° oblique forward viewing optic lens and a biopsy channel of 2 mm. The procedures were performed under general anaesthesia. EBUS-FNA was performed by direct transducer contact with the trachea or main bronchi with a prototype 22 gauge needle. Results: A total of 15 lesions were punctured. No complications were experienced. Four lesions were targeted in region 10L, four in region 10R, one in region 4L, three in region 4R, one in region 1, one in region 7, and one in region 2R. The size of the lesions ranged from 7 mm to 80 mm. EBUS-FNA identified malignant cells in 13 lesions and benign cells in two. Conclusions: EBUS-FNA is a promising technique for lymph node staging of lung cancer as well as for the primary diagnosis of solid lesions located adjacent to the trachea and main bronchi and not accessible by other methods apart from surgical intervention.

Endoscopic ultrasound guided biopsy of mediastinal lesions has a major impact on patient management

Background: A study was undertaken to evaluate the clinical impact of endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) in patients with mediastinal masses suspected of malignancy. Methods: From April 1993 to December 1999, 84 patients were referred for EUS-FNA. In all patients CT scanning had shown a lesion of the mediastinum suspected of malignancy located adjacent to the oesophagus. In order to evaluate the clinical impact of EUS-FNA, the history of each patient up to referral for EUS-FNA was reviewed. A board of thoracic specialists was asked to decide the further course of the patient if EUS-FNA had not been available, and this diagnostic strategy was compared with the actual clinical course after EUS-FNA. Results: For the 79 patients in whom sufficient verification was obtained, EUS-FNA had a sensitivity of 92%, specificity of 100%, PPV of 100%, NPV of 80%, and an accuracy of 94% for cancer of the mediastinum. In 18 of 37 patients (49%) a thoracotomy/thoracoscopy was avoided as a result of EUS-FNA, and in 28 of 41 patients (68%) a mediastinoscopy was avoided. The direct result of the cytological diagnosis obtained by EUS-FNA was that a final diagnosis of small cell lung cancer was made in eight patients resulting in referral for chemotherapy, and in another three patients with benign disease specific treatment could be initiated (sarcoidosis, mediastinal abscess, and leiomyoma of the oesophagus). Conclusions: EUS-FNA is a safe and sensitive minimally invasive method for evaluating patients with a solid lesion of the mediastinum suspected by CT scanning. EUS-FNA has a significant impact on patient management and should be considered for diagnosing the spread of cancer to the mediastinum in patients with lung cancer considered for surgery, as well as for the primary diagnosis of solid lesions located in the mediastinum adjacent to the oesophagus.

High Procedure Volume Is Strongly Associated With Improved Survival After Lung Cancer Surgery

PURPOSE Studies have reported an association between hospital volume and survival for non-small-cell lung cancer (NSCLC). We explored this association in England, accounting for case mix and propensity to resect. METHODS We analyzed data on 134,293 patients with NSCLC diagnosed in England between 2004 and 2008, of whom 12,862 (9.6%) underwent surgical resection. Hospital volume was defined according to number of patients with resected lung cancer in each hospital in each year of diagnosis. We calculated hazard ratios (HRs) for death in three predefined periods according to hospital volume, sex, age, socioeconomic deprivation, comorbidity, and propensity to resect. RESULTS There was increased survival in hospitals performing > 150 surgical resections compared with those carrying out < 70 (HR, 0.78; 95% CI, 0.67 to 0.90; Ptrend < .01). The association between hospital volume and survival was present in all three periods of follow-up, but the magnitude of association was greatest in the early postoperative period. CONCLUSION High-volume hospitals have higher resection rates and perform surgery among patients who are older, have lower socioeconomic status, and have more comorbidities; despite this, they achieve better survival, most notably in the early postoperative period.

The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer

ABSTRACT This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part‐solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS). We also propose that MIA be classified as T1mi. Furthermore, the use of the invasive size for T descriptor size follows a recommendation made in three editions of the Union for International Cancer Control tumor, node, and metastasis supplement since 2003. For tumor size, the greatest dimension should be reported both clinically and pathologically. In nonmucinous lung adenocarcinomas, the computed tomography (CT) findings of ground glass versus solid opacities tend to correspond respectively to lepidic versus invasive patterns seen pathologically. However, this correlation is not absolute; so when CT features suggest nonmucinous AIS, MIA, and lepidic predominant adenocarcinoma, the suspected diagnosis and clinical staging should be regarded as a preliminary assessment that is subject to revision after pathologic evaluation of resected specimens. The ability to predict invasive versus noninvasive size on the basis of solid versus ground glass components is not applicable to mucinous AIS, MIA, or invasive mucinous adenocarcinomas because they generally show solid nodules or consolidation on CT.