***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Because the clinics in a multiclinic r and omized clinical trial represent neither fixed stratification effects nor r and om classificatory effects , the appropriate analysis of data from such a trial has been the subject of controversy and debate . The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed . Is it ever valid to ignore the effects of clinics in the analysis ? Is it ever valid to drop clinics from the analysis ? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor ? Assuming that clinics will be taken account of in the analysis , should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments ? How should the data be analyzed if there is evidence of treatment-by-clinic interaction CONTEXT Up to 40 % of thoracotomies performed for non-small cell lung cancer are unnecessary , predominantly due to inaccurate preoperative detection of lymph node metastases and mediastinal tumor invasion ( T4 ) . Mediastinoscopy and the novel , minimally invasive technique of transesophageal ultrasound-guided fine-needle aspiration ( EUS-FNA ) target different mediastinal lymph node stations . In addition , EUS can identify tumor invasion in neighboring organs if tumors are located adjacent to the esophagus . OBJECTIVE To investigate the additional value of EUS-FNA to mediastinoscopy in the preoperative staging of patients with non-small cell lung cancer . DESIGN , SETTING , AND PATIENTS Prospect i ve , nonr and omized multicenter trial performed in 1 referral and 5 general hospitals in the Netherl and s. During a 3-year period ( 2000 - 2003 ) , 107 consecutive patients with potential resectable non-small cell lung cancer underwent preoperative staging by both EUS-FNA and mediastinoscopy . Patients underwent thoracotomy with tumor resection if mediastinoscopy was negative . Surgical-pathological staging was compared with preoperative findings and the added benefit of the combined strategy was assessed . INTERVENTION The EUS-FNA examination was performed as an additional staging test to mediastinoscopy in all patients . MAIN OUTCOME MEASURE Detection of mediastinal tumor invasion ( T4 ) and lymph node metastases ( N2/N3 ) comparing the combined staging by both EUS-FNA and mediastinoscopy with staging by mediastinoscopy alone . RESULTS The combination of EUS-FNA and mediastinoscopy identified more patients with tumor invasion or lymph node metastases ( 36 % ; 95 % confidence interval [ CI ] , 27%-46 % ) compared with either mediastinoscopy alone ( 20 % ; 95 % CI , 13%-29 % ) or EUS-FNA ( 28 % ; 95 % CI , 19%-38 % ) alone . This indicated that 16 % of thoracotomies could have been avoided by using EUS-FNA in addition to mediastinoscopy . However , 2 % of the EUS-FNA findings were false-positive . CONCLUSION These preliminary findings suggest that EUS-FNA , when added to mediastinoscopy , improves the preoperative staging of lung cancer due to the complementary reach of EUS-FNA in detecting mediastinal lymph node metastases and the ability to assess mediastinal tumor invasion CONTEXT Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer ( NSCLC ) .  Surgical staging has limitations , which results in the performance of unnecessary thoracotomies . Current guidelines acknowledge minimally invasive endosonography followed by surgical staging ( if no nodal metastases are found by endosonography ) as an alternative to immediate surgical staging . OBJECTIVE To compare the 2 recommended lung cancer staging strategies . DESIGN , SETTING , AND PATIENTS R and omized controlled multicenter trial ( Ghent , Leiden , Leuven , Papworth ) conducted between February 2007 and April 2009 in 241 patients with resectable ( suspected ) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography . INTERVENTION Either surgical staging or endosonography ( combined transesophageal and endobronchial ultrasound [ EUS-FNA and EBUS-TBNA ] ) followed by surgical staging in case no nodal metastases were found at endosonography . Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread . MAIN OUTCOME MEASURES The primary outcome was sensitivity for mediastinal nodal ( N2/N3 ) metastases . The reference st and ard was surgical pathological staging . Secondary outcomes were rates of unnecessary thoracotomy and complications . RESULTS Two hundred forty-one patients were r and omized , 118 to surgical staging and 123 to endosonography  , of whom 65 also underwent surgical staging .  Nodal metastases were found in 41 patients ( 35 % ; 95 % confidence interval [ CI ] , 27%-44 % ) by surgical staging vs 56 patients ( 46 % ; 95 % CI , 37%-54 % ) by endosonography ( P = .11 ) and in 62 patients ( 50 % ; 95 % CI , 42%-59 % ) by endosonography followed by surgical staging ( P = .02 ) . This corresponded to sensitivities of 79 % ( 41/52 ; 95 % CI , 66%-88 % ) vs 85 % ( 56/66 ; 95 % CI , 74%-92 % ) ( P = .47 ) and 94 % ( 62/66 ; 95 % CI , 85%-98 % ) ( P = .02 ) . Thoracotomy was unnecessary in 21 patients ( 18 % ; 95 % CI , 12%-26 % ) in the mediastinoscopy group vs 9 ( 7 % ; 95 % CI , 4%-13 % ) in the endosonography group ( P = .02 ) . The complication rate was similar in both groups . CONCLUSIONS Among patients with ( suspected ) NSCLC , a staging strategy combining endosonography and surgical staging compared with surgical staging alone result ed in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00432640 Introduction : Correct mediastinal staging is critical for determination of the most appropriate management strategy in patients with non – small-cell lung cancer ( NSCLC ) . The purpose of this study was to compare the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration ( EBUS-TBNA ) with that of mediastinoscopy in patients with NSCLC . Methods : A prospect i ve trial was conducted in a tertiary referral center in Korea . Patients with histologically proven NSCLC and suspicion for N1 , N2 , or N3 metastasis were enrolled . Each patient underwent EBUS-TBNA followed by mediastinoscopy . Surgical resection and complete lymph node dissection were conducted in patients for whom no evidence of mediastinal metastasis was apparent after mediastinoscopy . Results : In total , 138 patients underwent EBUS-TBNA and 127 completed both EBUS-TBNA and mediastinoscopy . N2/N3 disease was confirmed in 59.1 % of the patients . The diagnostic sensitivity , specificity , accuracy , positive predictive value , and negative predictive value ( NPV ) of EBUS-TBNA on a per-person analysis were 88.0 % , 100 % , 92.9 % , 100 % , and 85.2 % , respectively . The diagnostic sensitivity , specificity , accuracy , positive predictive value , and NPV of mediastinoscopy on a per-person analysis were 81.3 % , 100 % , 89.0 % , 100 % , and 78.8 % , respectively . Significant differences in the sensitivity , accuracy , and NPV were evident between EBUS-TBNA and mediastinoscopy ( p < 0.005 ) . Conclusions : EBUS-TBNA was superior to mediastinoscopy in terms of its diagnostic performance for mediastinal staging of cN1–3 NSCLC . Because EBUS-TBNA is both less invasive and affords superior diagnostic sensitivity , it should be the first-line procedure performed in patients with NSCLC BACKGROUND Exact mediastinal evaluation of patients with non-small-cell lung cancer ( NSCLC ) is m and atory to improve selection of resectable and curable patients for surgery . Mediastinoscopy ( MS ) and endoscopic ultrasound guided fine needle aspiration biopsy ( EUS-FNA ) are considered complementary , MS covering the anterior- and EUS-FNA the posterior mediastinum . Both methods can reach the paratracheal- and subcarinal-regions , but little is known about which method is most accurate , when compared in patients having both procedures performed . The aim of this study was to assess and compare the diagnostic value of  MS  and  EUS-FNA  with regard to mediastinal malignancy in the paratracheal- and subcarinal-regions . METHODS Sixty patients considered to be potential c and i date s for resection of verified or suspected NSCLC underwent MS and EUS-FNA . The EUS-FNA diagnoses were confirmed either by open thoracotomy , MS or clinical follow-up . RESULTS MS and EUS-FNA were conclusive for paratracheal or subcarinal mediastinal disease in 6 and 24 patients , respectively . Two patients with N2 disease diagnosed by EUS-FNA were upstaged to N3 by MS . The sensitivity for lymph node metastases in the right paratracheal region ( 2/4R ) was 67 % for EUS-FNA versus 33 % for MS ( p=0.69 ) . In the left paratracheal region ( 2/4L ) the sensitivity of EUS-FNA was 80 % versus 33 % for MS ( p=0.06 ) . In the subcarinal region ( 7 ) the sensitivity of EUS-FNA was 100 % versus 7 % for MS ( p<0.01 ) . The sensitivity for lymph node metastases in region 2/4L and /or 2/4R and /or 7 was 96 % for EUS-FNA versus 24 % for MS ( p<0.01 ) . CONCLUSION In our h and s EUS-FNA was superior to MS in the examination of paratracheal- and subcarinal-regions of patients considered for resection of lung cancer RATIONALE Data about the influence of the type of sedation on yield , complications , and tolerance of endobronchial  ultrasound-guided transbronchial needle aspiration ( EBUS-TBNA ) are based mostly on retrospective studies and are largely inconsistent . OBJECTIVES To determine whether the type of sedation influences the diagnostic yield of EBUS-TBNA , its complication rates , and patient tolerance . METHODS Patients referred for EBUS-TBNA were r and omized ( 1:1 ) to undergo this procedure under general anesthesia ( GA ) or moderate sedation ( MS ) .  Pathologists were blinded to group allocation . MEASUREMENTS AND MAIN RESULTS The main outcome was " diagnostic yield , " defined as the percentage of patients for whom EBUS-TBNA rendered a specific diagnosis . One hundred and forty-nine patients underwent EBUS-TBNA , 75 under GA and 74 under MS .  Demographic and baseline clinical characteristics were well balanced . Two hundred and thirty-six lymph nodes ( LNs ) and six masses were sample d in the GA group ( average , 3.2 ± 1.9 sites/patient ) , and 200 LNs and six masses in the MS group ( average , 2.8 ± 1.5 sites/patient ) ( P = 0.199 ) . The diagnostic yield was 70.7 % ( 53 of 75 ) and 68.9 % ( 51 of 74 ) for the GA group and MS group , respectively ( P = 0.816 ) . The sensitivity was 98.2 % in the GA group ( confidence interval , 97 - 100 % ) and 98.1 % in the MS group ( confidence interval , 97 - 100 % ) ( P = 0.979 ) . EBUS was completed in all patients in the GA group , and in 69 patients ( 93.3 % ) in the MS group ( P = 0.028 ) . There were no major complications or escalation of care in either group . Minor complications were more common in the MS group ( 29.6 vs. 5.3 % ) ( P < 0.001 ) . Most patients stated they " definitely would " undergo this procedure again in both groups ( P = 0.355 ) . CONCLUSIONS EBUS-TBNA performed under MS results in comparable diagnostic yield , rate of major complications , and patient tolerance as under GA . Future prospect i ve multicenter studies are required to corroborate our findings . Clinical trial registered with www . clinical trials.gov ( NCT 01430962 ) BACKGROUND It is unclear whether endoscopic mediastinal lymph node ( LN ) staging techniques are equivalent to surgical mediastinal staging ( SMS ) techniques in patients with potentially operable non-small cell lung cancer ( NSCLC ) . METHODS A total of 166 patients with confirmed or suspected NSCLC who required SMS based on current guidelines were enrolled 
    Output:
    
The complication rate was significantly lower with endosonographic procedures .
Endoscopic ultrasound-guided fine needle aspiration/endobronchial ultrasound-guided transbronchial needle aspiration was found to have similar yield but lower complication rate compared to mediastinoscopy in the initial mediastinal staging of non-small cell lung cancer