Trial Information

Randomized Controlled Study Comparing Endoscopic Ultrasonography Guided Fine Needle Aspiration Using Free Stylet 22g and 25 g Needles in Solid Lesions

1. Objectives

PRIMARY To compare diagnostic yield of stylet-free, solid lesion EUS-FNA using the 22 G FNA
vs the 25 G FNA needle, in consecutive patients referred to EUS-FNA.

SECONDARY

To investigate:

1. specimen adequacy,

2. number of FNA passes,

3. ease of puncture,

4. failure of the FNA needle and

5. complications

3. Methods

3.1. Design: prospective randomized trial.

3.2. Inclusion: Consecutive patients referred for EUS-FNA of a solid lesion will be
considered for inclusion.

3.3. Exclusion: Age < 18 years, patients with suspected diagnosis of lymphoma, GIST,
sarcoidosis or other lesions in which a large amount of tissue will be required for
diagnosis, significant coagulopathy (INR > 1.5, platelets < 50000/mm3, use of low molecular
weight heparin, use of clopidogrel within 7 days of EUS), cystic lesions, or inability or
refusal to sign the informed consent.

3.4. Endoscopic procedures: Informed consent will be obtained before each procedure by one
of the researchers. Patients will not receive economic compensation or reimbursement of
their expenses for coming to the exploration, since it is a procedure previously indicated.
Then, potential candidates will be randomized to 22 G or 25 G FNA using a computer generated
random sequence. There will be block randomization for a) pancreatic masses, 2) lymph nodes,
or 3) all other lesions.

All examinations will be performed by two experienced endosonographers with a lineal
echoendoscope (AS and SP). EUS procedures will be carried out with the patient, in left
lateral position under conscious sedation using midazolam (2.5-5 mg) plus meperidine (50-100
mg) and droperidol (2.5-5 mg). Before performing the EUS-FNA biopsy, a complete examination
of the pancreas, liver as well as other vicinity organs will be performed.

EUS-FNA passes will be performed without stylet until sample adequacy or until a maximum of
5 FNA passes in pancreatic lesions or 3 FNA passes in other lesions. In case of inadequate
sample after 3 passes, or needle failure, cross over to the other type of needle is allowed.
Ease of puncture will be scored qualitatively as poor (scored 1), good (scored 2) or
excellent (scored 3).[14] FNA failure will be also reported. All procedures will be
digitally videotaped. The examinations will be reviewed by a endosonographer blinded to the
type of needle used and visibility of the needle will be scored (score 1 "poor", score 2
"good", score 3 "excellent").[14] After the procedure, patients will be monitored in the
recovery room at least 60 minutes before discharge. Immediate complications will be assessed
and recorded by nurses and/or physicians during and after the procedure while the patient
was recovering from sedation.

3.5. Cytological analysis: All passes will be read by one experienced cytopathologist
on-site utilizing microscopic evaluation of air-dried slides stained with Diff-Quik
(International Reagents Co., Ltd., Kobe, Japan). The cytopathologist will be blinded to the
type of needle used. The final cytological diagnosis was made using a standard Papanicolaou
stain. For each lesion, the cytologist assessed sample adequacy: cellularity (score 1
"poor", score 2 "good", score 3 "excellent"),[14] and bloodiness (score 1 "minimal", score 2
"moderate", score 3 "significant")[21] and the presence or absence of malignancy
("positive"/"negative"/"suspicious"/ inconclusive).

3.6. Follow up Lesions will be considered malignant in the following cases: positive
cytological diagnosis, positive histological diagnosis and clinical or radiological
progression in the next 6 months. In case of negative results in the cytological diagnosis
absence of clinical worsening and radiologic progression at least in the following 6 months
after FNA will be required.

3.7. Data collection Clinical data will be prospectively collected and saved in a database
including: demographic information (age and gender), size and location of the target lesion
(pancreas, lymph node, liver, adrenal gland, others) and technical and procedure variables:
FNA path (esophagus, stomach, duodenum), number of needle passes, needle visibility, ease to
puncture, needle failure, cellularity, bloodiness, cytological diagnosis, final diagnosis,
immediate complications.

4. Statistical analysis Results for continuous variables will be expressed as means and
standard deviations. Categorical variables will be expressed as frequencies and percentages.
Chi-square test will be used to compare proportions. Continuous variables will be compared
using Student´s t test. A two-tailed P values of less than 0.05 will be considered
statistically significant. Data were analyzed with the Statistical Package for Social
Sciences v. 15.0 (SPSS Inc., Chicago, IL, USA). The diagnostic yield of 15 G and 22 G needle
will be evaluated by four criteria: sensitivity, specificity, positive predictive value and
negative predictive value.

Sample size An expected rate of diagnostic yield from EUS guided FNA by using 22G needle of
85% will be considered. By using a power of 80% and an α value of 0.05 would be necessary
120 patients per group to detect a 15% difference in the rate of diagnostic yield.