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Trial registered on ANZCTR


Registration number
ACTRN12617001649303
Ethics application status
Approved
Date submitted
5/12/2017
Date registered
22/12/2017
Date last updated
22/12/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Methods of tissue preparation after Endoscopic Ultrasound guided fine-needle aspiration without rapid on-site assessment: results of a randomized study.
Scientific title
A study of tissue preparation methods without rapid on-site assessment following Endoscopic Ultrasound guided fine-needle aspiration of patients with upper-gastrointestinal solid mass or lymph nodes.
Secondary ID [1] 293472 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Lesion 305664 0
Condition category
Condition code
Cancer 304886 304886 0 0
Pancreatic
Oral and Gastrointestinal 305050 305050 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The participating subjects underwent standard endoscopic ultrasound (EUS) examination with a linear echo-endoscope (GF180, Olympus, alpha 10, Japan) by an experienced endo-sonographer, who had performed over 5000 EUS procedures. All procedures were performed with anaesthetist-assisted propofol sedation. Once the mass was identified and confirmed to be at least 1cm in size, three passes of EUS FNA were performed without the presence of rapid on-site examination (ROSE). The choice of needle size (25G, 22G or 20G) and type (fine-needle aspiration (FNA) or fine-needle biopsy (FNB)) was at the discretion of the endo-sonographer.
The material derived from each FNA pass was prepared by one of the following 3 tissue preparation techniques:
(i) smearing plus cell-block (CS+CB), where material is divided to either CS or CB;
(ii) cell-block alone (Pure CB); where material is only used in CB;
(iii) direct histology alone (DH).
The order of tissue preparation technique was randomized, which was generated by a computer program. The tissue preparation was performed outside the procedure room to blind the endo-sonographer on which specimen processing technique was used. The specimens were sent to the dedicated GI cytopathologist, where the specimens were processed and examined as outlined below.

Techniques of tissue preparation:
1. Cytological smears:
Using the stylet, 2 drops of specimen from the EUS FNA needle were expelled onto 2 pathology slides (1 drop per slide). The material on the slides was smeared, then fixed with alcohol and air-dried. The smears were done by the investigator who had dedicated training in cytological smearing technique. The remaining material in the FNA needle was expelled in Hank’s solution with 1ml of normal saline for cell-block preparation (see below for description). In the pathology laboratory, the slides were stained using Papanicolaou stain and examined by the dedicated cytopathologist.
2. Cell-block preparation:
This technique involved expulsion of contents from the EUS FNA needle into Hank’s solution with 1ml of normal saline, and the specimen was then sent to the laboratory within 2 hours for processing. The contents were centrifuged, removed and fixed into formalin solution. The specimen was centrifuged again and formalin solution was removed before Agar gel was added. This was then embedded in Paraffin wax and cut at 4 microns to create slides. The slides were examined by the dedicated cytopathologist
3. Direct histology:
This technique involved expressing the EUS FNA contents directly into Formalin and sending to the pathology laboratory for routine histological processing. 4µm sections were cut from paraffin embedded tissue blocks and stained routinely with Haematoxylin and Eosin. Special stains and immunohistochemistry were done when additional tests were required for diagnostic purposes.
Intervention code [1] 299721 0
Diagnosis / Prognosis
Comparator / control treatment
Results are ultimately compared to surgical follow-up via review of the electronic medical record. In cases where there was no positive or malignancy diagnosis, the patients were followed at 6 months after the EUS guided biopsy to ensure the absence of false negatives.
Control group
Active

Outcomes
Primary outcome [1] 304080 0
To compare diagnostic accuracy between the 3 EUS FNA passes in which the expelled tissue was processed by different cell preparation techniques.

Diagnostic accuracy was defined as the percentage of total cases where an accurate cytologic or histologic diagnosis was achieved; accuracy was confirmed by clinical and/or surgical follow-up via review of the electronic medical record.
Timepoint [1] 304080 0
The primary timepoint for analysis was 2 days post-procedure. Patients with a negative diagnosis were also followed-up at 6 months.
Primary outcome [2] 304091 0
Impact of FNA pass order on diangostic yield, defined as the proportion of patients with adequate tissue for diagnosis obtained by EUS FNA. This will be determined via definite histological diagnoses from surgically resected specimens. Trained cytologists and pathologists (who are blinded to the needle type used) will assess the final processed samples from each group.
Timepoint [2] 304091 0
The primary timepoint for analysis was 2 days post-procedure.
Secondary outcome [1] 340935 0
Complications of the EUS FNA procedure in the absence of ROSE, as defined by episodes of pain, pancreatitis, bleeding, perforation. This outcome was assessed by immediate post-procedure monitoring and consulting patient medical records
Given that the use of all devices have already been shown to be a safe method of acquiring pancreatic tissue specimens, this study poses no addition risks to the participants.
Timepoint [1] 340935 0
All participants will also be monitored for safety for up to 7 days post procedure. And by checking medical records over the next 6 months.

Eligibility
Key inclusion criteria
1. Patient referred for EUS-guided FNA of solid mass of lymph nodes in or adjacent to the upper GI tract.

2. The mass lesion had to be at least 1cm in size as measured by EUS.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who were deemed to be at high risk of bleeding from the EUS FNA were excluded (ie. coagulopathy with INR >1.4 and/or platelet count <50 x 109/L).

2. Pregnancy.

3. Those who cannot provide informed consent.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
22/02/2017
Date of last participant enrolment
Anticipated
Actual
1/08/2017
Date of last data collection
Anticipated
1/02/2018
Actual
Sample size
Target
60
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 9469 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 18196 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 298096 0
Hospital
Name [1] 298096 0
Royal Adelaide Hospital
Country [1] 298096 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Department of Gastroenterology and Hepatology,
Port Road, Adelaide,
SA 5000
Country
Australia
Secondary sponsor category [1] 297173 0
None
Name [1] 297173 0
Address [1] 297173 0
Country [1] 297173 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299116 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 299116 0
Ethics committee country [1] 299116 0
Australia
Date submitted for ethics approval [1] 299116 0
Approval date [1] 299116 0
15/02/2017
Ethics approval number [1] 299116 0
HREC/17/RAH/75

Summary
Brief summary
EUS guided fine-needle aspiration (FNA) or fine-needle biopsy (FNB) is a well-established and accurate method of obtaining tissue for the diagnosis of intra-abdominal or mediastinal lesions. Initial findings, have suggested that rapid on-site evaluation (ROSE) using cytological smears (with or without cell block preparation) has the biggest impact with increased diagnostic accuracy and reduced needle passes.
However, newer evidence has brought the value of ROSE into question. Recent reports show conflicting results on whether ROSE actually does influence outcome in EUS FNA. Also a recent meta-analysis suggests that ROSE may not result in higher diagnostic yield, specimen adequacy or pooled sensitivity and specificity.
The utilization of cell blocks or direct histological processing to prepare FNA specimens, involve placing all needle contents into liquid fixative and therefore do not require ROSE. Reports show high diagnostic yield with both, exceeding 89%. These also avoid the need for smear preparation, which requires training and can result in inadvertent loss of diagnostic material.
Prospective randomised data comparing these techniques is lacking and therefore the best method for preparing EUS FNA specimens is unknown.


We hypothesize that without ROSE, direct histology or cell block is the tissue preparation technique of choice, as smearing often has low diagnostic yield and may result in loss of diagnostic material.
The aim of this study is to compare the diagnostic yield of the different methods for EUS FNA/FNB specimen processing in a randomized fashion and to identify the most optimal method of tissue preparation in the absence of ROSE.


All patients who were referred to our unit for EUS guided FNA of a solid mass or lymph nodes in or adjacent to the upper GI tract over an 8-month period were prospectively recruited for the study.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79346 0
Dr Vinh-An Phan
Address 79346 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Port Road, Adelaide, South Australia, Australia 5000.
Country 79346 0
Australia
Phone 79346 0
+61870742189
Fax 79346 0
Email 79346 0
[email protected]
Contact person for public queries
Name 79347 0
Ms Romina Safaeian
Address 79347 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Port Road, Adelaide, South Australia, Australia 5000.
Country 79347 0
Australia
Phone 79347 0
+61870742189
Fax 79347 0
Email 79347 0
[email protected]
Contact person for scientific queries
Name 79348 0
Ms Romina Safaeian
Address 79348 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Port Road, Adelaide, South Australia, Australia 5000.
Country 79348 0
Australia
Phone 79348 0
+61870742189
Fax 79348 0
Email 79348 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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