EUS-CNB Versus EUS-SINK for Diagnosis of Upper Gastrointestinal (UGI) Subepithelial Tumors

Study Overview
=================
Brief Summary
-----------------
This is a single-blinded randomized control trial trying to compare the effectiveness of diagnosis between two techniques employed in tissue sampling for subepithelial tumors (SETs) of the gastrointestinal tract. Over 2 years, patients having SET will be randomized to either get the EUS-guided core needle biopsy (EUS-CNB) or EUS-guided single-incision with needle knife (SINK) technique. This is of grave importance because the diagnosis of the myriad types of SETs is made histologically requiring a good sample.

Detailed Description
-----------------
Upper gastrointestinal (GI) subepithelial tumors (SETs) are tumors arising from subepithelial layers of esophageal, gastric or duodenal wall, mostly from the submucosa and muscular layer. The incidence of SETs on routine endoscopy is 0.36% The differential diagnosis of SETs include, though are not limited to: lipoma, leiomyoma, aberrant pancreas, varices, carcinoid, gastrointestinal stromal tumors (GISTs), and lymphomas . Therefore, a correct diagnosis of these tumors is important to guide subsequent management. These lesions are often not accurately diagnosed on cross-sectional imaging . Endoscopic ultrasound (EUS) aids in narrowing the differential diagnosis of the lesion as it is often able to establish the layer of origin . However, an accurate diagnosis and targeted therapy is not made solely on the morphological features but on histologic type and at times mitotic index. Thus the need for techniques to obtain histology is beneficial in guiding management. Since standard endoscopy with pinch biopsies of the overlying mucosa often fails to provide an adequate sample for analysis, multiple other modalities to sample the lesion have been utilized: EUS-guided fine needle aspiration (EUS-FNA), EUS-guided core needle biopsy (EUS-CNB), bite-on-bite forceps biopsies, EUS-guided single-incision with needle knife (SINK) and endoscopic resection. EUS-FNA is now considered to be the usual method of sampling; however, the diagnostic yield is low: 38% to 82% . Moreover, EUS-FNA often provides insufficient specimens which may not allow for immunohistochemistry that is often essential for diagnosis . Thus EUS-CNB has been assessed for the purpose of obtaining a core sample which allows for histological assessment. Published data reveals a diagnostic (though not histologic) yield using EUS-CNB of 75% In 2011, the SINK technique for sampling was presented with a reported diagnostic accuracy of 92.8% [8]. The technique utilizes a conventional needle-knife connected to an electrosurgical unit. A 6 to 12-mm mucosal incision is made over the lesion. Then conventional biopsy forceps are introduced to obtain 3-5 samples. Subsequently, the incision is closed with 2 to 3 endoclips. The purpose of this study is to prospectively compare the efficacy and safety of EUS-CNB with SINK in patients with upper GI SETs. The investigators hypothesis is that the SINK technique will be superior to the EUS-CNB in obtaining a histological specimen. The results of the study would provide data which may improve the diagnostic ability for SETs. This in turn will guide appropriate surveillance or management (surgical or endoscopic) for patients with these lesions.

Official Title
-----------------
EUS-guided Core Needle Biopsy (EUS-CNB) Versus EUS-guided Single-incision With Needle Knife (SINK) for the Diagnosis of Upper Gastrointestinal Subepithelial Lesions - a Multicenter Randomized Controlled Trial

Conditions
-----------------
Esophageal Subepithelial Lesions

Intervention / Treatment
-----------------
* Device: 22-gauge Procore needle (ProCore, Cook Medical Inc., Winston-Salem, NC)
* Device: conventional needle-knife sphincterotome (Microknife XL; Boston Scientific Inc, Natick, Mass)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients referred for EUS evaluation of upper GI SETs measuring an estimated 15mm or greater in maximal diameter. Location of SET: esophagus, stomach, duodenum Age >18 years and older Patient consent obtained Exclusion Criteria: Endoscopically non bulging lesion Upper GI SETs <15 mm in size as measured during study EUS Lesions not necessitating tissue acquisition: i.e. lipomas, varices Cystic lesion Patients < 18 years of age Uncorrectable Coagulopathy (INR >1,5, platelets <100,000) Patients with stigmata of portal hypertension Patients with post-surgical UGI anatomy (Roux-en-Y gastric bypass, esophagectomy etc) Uncooperative patients Pregnant women (women of childbearing age will undergo urine pregnancy testing, which is routine for all endoscopic procedures) Refusal to consent form

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EUS-CNB<br>Using a linear EUS with color and pulsed Doppler to scan the area for vessels, the lesion was then sampled with a 22-gauge beveled needle (using the slow capillary suction and fanning techniques with 5 to 15 to-and-fro movements with each pass). A total of 4 passes were performed and after that the procedure terminated. | Device: 22-gauge Procore needle (ProCore, Cook Medical Inc., Winston-Salem, NC)<br>* Using a linear EUS with color and pulsed Doppler to scan the area for vessels, the lesion was then sampled with a 22-gauge beveled needle (using the slow capillary suction and fanning techniques with 5 to 15 to-and-fro movements with each pass). A total of 4 passes were performed and after that, the procedure terminated.<br>|
| Active Comparator: SINK<br>Using a conventional needle-knife sphincterotome connected to an electrosurgical unit, and under direct endoscopic vision, a 6-12mm linear incision was made from the periphery of the lesion to its highest convexity zone. A conventional biopsy forceps was then deeply introduced through the hole, and 2 bites were obtained per pass. A total of 4 passes were performed by passing the biopsy forceps through the incision on each occasion. The mucosal incision was then closed with endoclips whenever possible. | Device: conventional needle-knife sphincterotome (Microknife XL; Boston Scientific Inc, Natick, Mass)<br>* Using a conventional needle-knife sphincterotome connected to an electrosurgical unit, and under direct endoscopic vision, a 6-12mm linear incision was made from the periphery of the lesion to its highest convexity zone. A conventional biopsy forceps was then deeply introduced through the hole, and 2 bites were obtained per pass. A total of 4 passes were performed by passing the biopsy forceps through the incision on each occasion. The mucosal incision was then closed with endoclips whenever possible.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic Accuracy | Diagnostic accuracy is defined as the percentage of true positive and true negative biopsy specimens combined divided by total number of specimens | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological Yield | This will be assessed by the percentage of patients whose samples were adequate for histopathological evaluation | 30 days | 
| Technical Failure Rate | Percentage of procedures in whom sampling technique failed to take biopsy specimens | 1 day | 
| Time of the Procedure | Time from the beginning of the incision or needle insertion, to completion of tissue acquisition by the techniques defined in the protocol. | Tissue sampling procedure, up to 60 minutes | 
| Percent Sample Contribution to Immunohistochemistry Diagnosis | Percentage of all samples from participants in whom biopsy specimen was adequate enough to contribute to immunohistochemistry diagnosis | 30 days |