A Randomized Prospective trial of the A Randomized Prospective trial of the Utility of Utility of Rapid On-Site Evaluation Rapid On-Site Evaluation of of

Transbronchial Needle Aspirate Transbronchial Needle Aspirate SpecimensSpecimens

J Bronchol Intervent Pulmonol 2011;18:121-127

Lonny Yarmus, DO,FCCP, Thomas Van der Kloot, MD, Noah Lechzin, MD, Mark Napier,MD, Douglas Dressel, MD, and David Feller-kopman,MD,FCCP

Background:Background: Previous studies have Previous studies have suggested an increased diagnostik yield for suggested an increased diagnostik yield for flexible bronchoscopic (FB) transbronchial flexible bronchoscopic (FB) transbronchial needle aspirate (TBNA) specimens from needle aspirate (TBNA) specimens from lymph nodes when using rapid on-site lymph nodes when using rapid on-site evaluation (ROSE) by cytophatologyevaluation (ROSE) by cytophatology

Objective: Objective: to determine the effect of ROSE to determine the effect of ROSE on the diagnostic power of TBNA.on the diagnostic power of TBNA.

Methods:Methods: The study is a prospective The study is a prospective randomized controlled trial.randomized controlled trial.

FB is the most common modality used to FB is the most common modality used to diagnose lung cancerdiagnose lung cancer

TBNA biopsy is a biopsy technique used during TBNA biopsy is a biopsy technique used during bronchoscopy which involves passing a bronchoscopy which involves passing a catheter containing a needle through the catheter containing a needle through the trachea or bronchial wall into the lymph nodes trachea or bronchial wall into the lymph nodes or masses to obtain samples for Cytopathologic or masses to obtain samples for Cytopathologic assesment.assesment.

Conventional TBNA is a blind procedure in that Conventional TBNA is a blind procedure in that the structures external to the bronchial wall are the structures external to the bronchial wall are not direcly visualized. To addres this concern , not direcly visualized. To addres this concern , ROSE of spesimens has been carried out.ROSE of spesimens has been carried out.

. .

Introduction

With ROSE biopsy material is prepared and With ROSE biopsy material is prepared and stained during the bronchoscopystained during the bronchoscopy

If the cytopathologist determine that the biopsy If the cytopathologist determine that the biopsy was unuccessful, futher TBNA passed can was unuccessful, futher TBNA passed can be made during the same procedure, be made during the same procedure, potentially sparing the patient repeated or potentially sparing the patient repeated or alternative invasive procedure and their alternative invasive procedure and their associated risk of complication.associated risk of complication.

Introduction

This single centre study used a randomized This single centre study used a randomized control designs. The protocol was approved control designs. The protocol was approved by the Maine Medical Center Institutional.by the Maine Medical Center Institutional.

All patients (> 18 years) referred for All patients (> 18 years) referred for evaluation of mediastinal or hilar adenopathy evaluation of mediastinal or hilar adenopathy and scheduled to undergo FB with TBNA. and scheduled to undergo FB with TBNA. Eligible patients including those with no Eligible patients including those with no mediastinal or hilar adenopathy (short axis,> mediastinal or hilar adenopathy (short axis,> 1cm) confirmed in the Scan computer 1cm) confirmed in the Scan computer tomography of the chest.tomography of the chest.

Sixty-eight patients screened were enrolled.Sixty-eight patients screened were enrolled.

Patient & methods

Patients were randomized at the time of Patients were randomized at the time of bronchoscopy into the ROSE or the no-ROSE bronchoscopy into the ROSE or the no-ROSE groupgroup

Before the procedure a subjective pretest Before the procedure a subjective pretest clinical probability of malignancy was clinical probability of malignancy was determined based on the bronchoscopist”s determined based on the bronchoscopist”s clinical suspicion ( Patient age, tobacco clinical suspicion ( Patient age, tobacco history, medical history, & radiographic history, medical history, & radiographic imaging)imaging)

The location of TBNA, number of needle The location of TBNA, number of needle passes size of needle (19 gauge or 22 gauge), passes size of needle (19 gauge or 22 gauge), duration of procedure,effect of on-site duration of procedure,effect of on-site assessment, amount of sedative and topical assessment, amount of sedative and topical anasthetic medication used were recorded anasthetic medication used were recorded using a standardized data collection sheet.using a standardized data collection sheet.

Patient & methods

The ROSE group had ROSE of TBNA with the The ROSE group had ROSE of TBNA with the same cytopathologist present during each same cytopathologist present during each procedure with TBNA specimens procedure by procedure with TBNA specimens procedure by a dry smear technique & minimum 3 passes a dry smear technique & minimum 3 passes were made at the highest potential ATS nodal were made at the highest potential ATS nodal station, if no diagnosis, additional passes were station, if no diagnosis, additional passes were allowed & additional procedure could be allowed & additional procedure could be peformed (brushing, washing& transbrochial peformed (brushing, washing& transbrochial biopsy)biopsy)

The no-ROSE: TBNA sample were collected in The no-ROSE: TBNA sample were collected in liquid media and later prepared by liquid media and later prepared by cytopathologist & minimum 3 passes maximum cytopathologist & minimum 3 passes maximum 7 passes were made at each ATS nodal 7 passes were made at each ATS nodal station.station.

Then Both ROSE & no ROSE cytopathologic Then Both ROSE & no ROSE cytopathologic specimen were reviewed by the same specimen were reviewed by the same attending cytopathologist who was blinded for attending cytopathologist who was blinded for the final review for all casesthe final review for all cases

Patient & methods

Total of 68 patients with median age of 68 years Total of 68 patients with median age of 68 years (range: 32 to 88 years old) were randomized for (range: 32 to 88 years old) were randomized for the study between February 2005 and July 2006the study between February 2005 and July 2006

ROSE NO-ROSE

Patient (n) 34 34

Age (y) 70,5 65,5

Male (%) 65 53

Tobacco use (%) 94 91

Median pack years 50 40

High CPM (%) 77 65

Intermediate CPM (%)

12 9

Low CPM (%) 12 27

CPM = clinical probability of malignancy

Result

Table 1: Baseline characteristic patient

ATS Nodal Station

ROSE NO-ROSE

2 1 1

4 12 16

7 23 24

10 4 3

11 0 0

Mass 4 2

ATS=american thoracic society; TBNA: Transbroncial needle aspiration

Table 2: TBNA Anatomic site locations

Table 3: Main Results

ROSE NO-ROSE

P

TBNA Diagnostic Yield (%)

56 53 1,0

TBNA diagnosis of lung neoplasma (%)

59 59 1,0

TBNA diagnosis of any neoplasma (%)

65 59 0,80

TBNA adequacy (%) 94 88 0,67

Table 4: Procedural Data

ROSE NON-ROSE

Aspirates/Site 4,47 4,14

Time(min) 29,5 27,6

Midazolam(mg) 4,38 5,60

Fentanyl(mcg) 107 111

Lidocaine 1% (mL)

22,3 22,8

Histology needle (19 gauge) (%)

38 41

Table 5: Number of Transbronchial Biopsies Performed

ROSE NON-ROSE

Transbronchial biopsies performed

8 15

No transbronchial biopsies performed

26 19

Both group were followed up for period of Both group were followed up for period of up to 2 years after the initial bronchoscopy up to 2 years after the initial bronchoscopy was performedwas performed

There are no significant statistical There are no significant statistical differences in final TBNA diagnosis, final differences in final TBNA diagnosis, final tissue diagnosis, and typed of neoplasma tissue diagnosis, and typed of neoplasma or benign disease diagnosed between the or benign disease diagnosed between the 2 group2 group

Tabel 6: final diagnosis

Final Diagnosis

ROSE TBNA

Other Diagnostic Testing

NON-ROSE

Other Diagnostic Testing

NSCLC 11 5 (T2, B1, BB1, TT1)

12 4 (BB1, V3)

SCLC 3 1 (E1) 4 0

Sarcoid 3 3 (T1,M2) 2 4 (T1, M3)

Melanoma 1 0 0 0

Lymphoma

1 0 0 0

AFB 0 1(V1) 0 0

True Negative

- 6 (M2, V2, C2) - 8 (M2,C6)

DISCUSSIONDISCUSSION TBNA has become very valuable for the TBNA has become very valuable for the

diagnosis and staging of mediastinal use. From diagnosis and staging of mediastinal use. From ROSE during bronchoscopy has previously ROSE during bronchoscopy has previously been reported to result in improved diagnostic been reported to result in improved diagnostic results for TBNA.results for TBNA.

In a randomized controlled trial comparing In a randomized controlled trial comparing prospective ROSE without on-site assessment prospective ROSE without on-site assessment of Cytopathology (no-ROSE), we found no of Cytopathology (no-ROSE), we found no benefit on the adequacy of the diagnostic results benefit on the adequacy of the diagnostic results or related to use of the ROSE specimensor related to use of the ROSE specimens

However, there are chances of decresing However, there are chances of decresing number of transbronchial biopsy is needed in number of transbronchial biopsy is needed in the group ROSE.the group ROSE.

DISCUSSIONDISCUSSION

In this study, the use of ROSE was not In this study, the use of ROSE was not associated with an improved diagnostic associated with an improved diagnostic yield or specimen adequacy, reduced or yield or specimen adequacy, reduced or increased procedure time, or with increased procedure time, or with amount of sedation /topical anasthesia amount of sedation /topical anasthesia required and there no difference in required and there no difference in malignancy rates between the ROSE malignancy rates between the ROSE and no-ROSE procedure. Its suggesting and no-ROSE procedure. Its suggesting than randomization may have than randomization may have prevented a preferential use of ROSE in prevented a preferential use of ROSE in patients with malignant versus benign patients with malignant versus benign lymadenopathylymadenopathy

ConclusionConclusion

The ROSE procedure should be The ROSE procedure should be used on a case by case basis.used on a case by case basis.

Larger studies investigating the Larger studies investigating the utility of ROSE on EBUS-TBNA and utility of ROSE on EBUS-TBNA and the incremental yield of EBUS-the incremental yield of EBUS-TBNA over standard TBNA when TBNA over standard TBNA when performed by experienced providers performed by experienced providers are neededare needed

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