Gastrointestinal Stromal Tumor Clinical Trial
The exact incidence of subepithelial tumors (SETs) in the gastrointestinal (GI) tract is
unknown, but the prevalence of gastric SETs detected during routine
esophagogastroduodenoscopy is 0.36%. GI SETs may include leiomyoma, GI stromal tumor (GIST),
schwannoma, lipoma, cyst, or ectopic pancreas. Surgical resection is the principal diagnostic
and therapeutic method for SETs, especially for large and symptomatic ones. Preoperative
pathological diagnosis of SETs may facilitate clinical decision making, but conventional
endoscopic forceps biopsy does not yield adequate amounts of subepithelial tissue for
definitive diagnosis.
Although endoscopic ultrasonography (EUS) is the best imaging modality for the evaluation of
SETs, it cannot substitute histopathological diagnosis. EUS-guided fine-needle aspiration
(EUS-FNA) may provide adequate amounts of tissue for the diagnosis of SETs, but it does not
always afford adequate samples for immunohistochemical analysis because of the often small
number of cells obtained by aspiration. Since some SETs, especially GI mesenchymal tumors
such as GIST or schwannoma, have varied morphologic appearances, and diagnosis using a small
biopsy is not straightforward, immunohistochemical analysis is strongly advisable, if not
essential. EUS-guided Trucut biopsy (EUS-TNB) may overcome the limitations of EUS-FNA in
procuring sufficient core tissue specimens. Although EUS-TNB is more accurate than EUS-FNA
for diagnosing GI mesenchymal tumors, the rigidity of its 19-gauge (G) caliber and the
mechanical friction of the firing mechanism produced by the torqued echoendoscope limit its
use for SETs located in the gastric antrum and duodenum. Therefore, a needle facilitating
adequate histological core sampling with easy maneuverability needs to be established. A 19G
EUS-guided fine-needle biopsy (EUS-FNB) device with ProCore reverse-bevel technology was
recently introduced. A multicenter study revealed that histological samples could be
successfully obtained using this needle in most patients having GI SETs, with a diagnostic
accuracy of >80%.10 However, because of technical difficulties with this needle in the
gastric antrum and duodenum, the same FNB device was recently developed in a 20 G platform
with coiled sheath. This prospective, multicenter study aimed to evaluate feasibility, yield,
and diagnostic accuracy of a newly developed 20 G ProCore needle with coiled sheath in
patients with GI SETs.
Patients and Methods
Patients with newly diagnosed GI SETs will be prospectively enrolled at 8 university
hospitals in Korea between May and December 2016, if they met the following criteria: having
a hypoechoic mass in the submucosal and/or proper muscle layers on the basis of EUS and tumor
>2 cm in size. Exclusion criteria are: SETs were not located in the submucosal and/or proper
muscle layers on EUS; EUS revealed the characteristic findings of lipoma, cyst, vessel or
extraluminal lesions; the platelet count was <50,000/mm3 and prothrombin time was <50%; or
the patient did not provide consent to undergo the study. This study is approved by the
Institutional Review Board of each hospital and conducted in accordance with the Declaration
of Helsinki and its amendments and the Good Clinical Practice guidelines. All enrolled
patients provide written informed consents to participate in the study.
Technique for EUS-FNB
All procedures are performed by using a linear array echoendoscope (Olympus UCT-140, UCT-240;
Olympus, Tokyo, Japan or PentaxEG-3870UTK; Pentax, Tokyo, Japan) with the patients placed in
the left lateral decubitus position under conscious sedation.
Before the study commenced, all participating endosonographers discuss the procedural steps
in detail. Technical details of the standard tissue-acquisition protocol are as follows.
After the target lesion is endosonographically visualized and the region scanned for SETs
using color or pulsed Doppler, FNB is performed at the esophagus, stomach, duodenum or
rectum, depending on the lesion location. The needle is advanced into the target tissue under
endosonographic guidance.
After penetrating the lesion, the endosonographer moves the needle to-and-fro for more than
10 to 15 times within the lesion while an assistant simultaneously pulled out the stylet
slowly and continuously over 20 s to achieve minimal negative pressure within the needle
(slow-pull technique). Finally, the needle is withdrawn from the lesion. At least three
needle passes are performed using the designated needle, and if a diagnostic or technical
failure is encountered, the patient is switched to the alternative needle according to the
judgment of the endosonographers.
Preparation for histological analysis
Because pathologists are absent during endoscopy, FNB samples are recovered and stored for
subsequent processing by the endosonographers. The specimens are then expressed onto slides
by using a stylet or by flushing with air into the needle assembly, to harvest the core
samples from the needle. The endosonographers then carefully inspect the material on the
slides for the presence of tissue cores defined as whitish pieces of tissue with apparent
bulk, which are measured and then lifted off the slides and placed into a formalin bottle.
The core samples are macroscopically assessed as a definite tissue core; suspicious tissue
core mixed with blood clots; or only blood or scarce sample without any tissue core. The
former two sample types are considered macroscopically optimal core samples.
If tissue cores are obtained, they are fixed in formalin and stained in hematoxylin and eosin
for evaluation by pathologists. Samples with tissue cores are graded as optimal or
suboptimal: optimal, if the material allows satisfactory assessment of histologic
architecture and immunohistochemical evaluation, such as c-kit, CD34, S-100, or smooth muscle
actin, if indicated, and suboptimal, if the histological core is inadequate for the
abovementioned assessments. Because the morphological characteristics of mesenchymal tumors
are nonspecific, a positive diagnosis by EUS-FNB is only considered true positive when
immunohistochemical analysis is conclusive. Conventional cytological analysis is additionally
performed in most cases or if a core sample is unavailable. Cytological material is sent to
the cytologists as a fixed or an air-dried slide. The gold standard is the histopathological
assessment of the resected specimens for patients who underwent endoscopic resection or
surgery, and the assessment of the FNB samples for those who did not.
Outcome parameters
The primary outcome parameter is diagnostic sufficiency. Diagnostic sufficiency is defined as
the proportion of patients in whom the histopathological diagnosis could be established
within three needle passes. The percentage of cases in which the pathologist classified the
quality of the sample as optimal for histological evaluation is also evaluated. The secondary
outcome measures are rates of diagnostic failure, technical failure, and complications.
Diagnostic failure is defined as failure to obtain sufficient core samples even after three
passes, and technical failure is defined as malfunction of the needle before three needle
passes. Complications are defined as any deviation from the clinical course after EUS-guided
sampling, as observed by the endosonographers or recovery suite nurses, or as reported by
patients. Excessive bleeding at the site of puncture, perforation, hypotension, and need for
reversal medication are documented.
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