Endoscopic Diagnosis and Management of Gastrointestinal Malignancy
Endoscopic Diagnosis and Management of Gastrointestinal Malignancy
The endoscopic diagnosis, staging, and management of gastrointestinal
(GI) malignancies is a rapidly advancing field. We have chosen
to address these topics by summarizing recent advances
in the diagnosis and management of GI malignancies, using the
esophagus as a paradigm. The esophagus is the prototype for the
endoscopic management of GI malignancies, and thus, the methods
and principles described for diagnosing and treating esophageal
cancers can be applied to most areas of the GI tract. In subsequent
sections, we explore the application of endoscopic techniques
to the diagnosis of the most common cancers in each portion of
the GI tract, as well as accepted and potentially useful endoscopic
treatments for these malignant lesions. (A full discussion of
the endoscopic management of the less common cancers and premalignant
lesions, with their associated controversies, is beyond the scope
of this paper.)
The advent of various new diagnostic techniques has led to progress
in lesion recognition.
In the esophagus, 2.5% Lugol's solution stains the glycogen of
normal squamous cells greenish-brown. This technique, also known
as chromoscopy, allows one to target the nonstaining areas for
biopsy. Indigo-carmine dye (2.5% ) enhances the architecture of
the glandular mucosa, and thus, is helpful in the columnar-cell
lined esophagus and stomach. These two methods can be combined
to facilitate the identification of squamous and columnar cells.
A recently described clinical application involves dye spraying
and magnification endoscopy for the recognition of Barrett's epithelium
Laser-Induced Fluorescence Microscopy
In the future, recognition of dysplastic mucosa may be facilitated
by laser-induced fluorescence microscopy. This technique, still
in the developmental stage, exploits characteristic differences
in the spectra of emitted light from normal and dysplastic tissue
when these tissues are excited by an endoscopically directed laser
One recent study used a tuned dye laser to distinguish malignant
from benign tissue in 91 patients. The technique correctly identified
tissue samples from the 74 normal subjects and 17 patients with
esophageal carcinoma . With further development, this technology
may have important roles in the guidance of endoscopic biopsies
and surveillance of potentially dysplastic epithelium.
Biopsies are obtained under direct vision by passing a forceps
through a working endoscope channel. A greater number of biopsies
from a suspected malignancy increases the diagnostic yield .
Biopsy forceps are available in various sizes, with the largest
(jumbo) forceps fitting through the channels of adult endoscopes
and yielding tissue samples up to 8 mm in size. In addition, forceps
have been developed with a needle positioned in their center;
this needle can impale a second piece of tissue, allowing multiple
samples to be obtained during a single pass. Sessile and pedunculated
polyps can be removed completely using an electrocautery snare,
laser, or a nonthermal excisional technique.
Specialized Biopsy Techniques
Specialized biopsy methods have been developed to obtain significantly
larger and deeper samples of tissue.
The well technique involves taking multiple samples from
the same site, which permits deep tissue sampling. Even larger
tissue samples can be obtained using a snare alone or in combination
with a biopsy forceps passed through a dual-channel endoscope.
Core Biopsy Needles--Recently, the development of endoscopic
core biopsy needles has increased the ability to obtain tissue,
but the yield and safety of this technique have not been fully
Strip Biopsy Technique--Large mucosally based lesions may
be removed in their entirety using the strip biopsy technique,
in which normal saline or 50% dextrose is injected submucosally
in order to raise a bleb. The raised area is then grasped with
an electrocautery snare and removed . Recently, a combination
of the strip and well biopsy techniques has been advocated for
use in submucosal tumors that remain undiagnosed despite the use
of jumbo forceps .
Tissue samples obtained by standard endoscopic biopsy techniques
have been adequate for the performance of flow cytometry. Studies
comparing specialized biopsy techniques with standard techniques
have demonstrated no increase in the incidence of complications
with the former.
Endoscopy-Guided Fine-Needle Aspiration
Fine-needle aspiration (FNA) of submucosal lesions, bile duct
strictures, and thickened mucosal folds may be performed under
direct vision through the endoscope, preferably with a cytology
team present to assess the yield. More recently, FNA, under endosonographic
guidance, has been used to biopsy submucosal lesions, extraluminal
masses, the pancreas, and mediastinal lymph nodes . This technique,
performed at specialized tertiary centers, involves the identification
of a mass or lymph node by endosonography and the subsequent passage
of a specialized cytology needle through the working channel of
the echoendoscope. At present, these needles are approved by the
FDA only for use in submucosal lesions; however, they are under
study and should be approved in the future for FNA of extraluminal
masses and lymph nodes.
Since its clinical introduction in the late 1980s, endoscopic
ultrasound (EUS) has become an important addition to surgical
evaluation. Endoscopic ultrasound was initially developed to circumvent
difficulties encountered with conventional transabdominal ultrasound.
This goal was achieved and endosonography has burgeoned into a
modality that enables the endoscopist to accurately (1) determine
the T and N stages of tumors preoperatively, (2) assess wall layer
structural integrity in intramural disease, and (3) image extraluminal
abnormalities that are in proximity to the GI lumen.
EUS vs Transabdominal Ultrasound
Typically, EUS images are obtained at 5 to 12 MHz, whereas conventional
transabdominal ultrasound images are usually obtained at 3.5 to
5 MHz or less. The higher frequency of the EUS image increases
resolution but sacrifices depth of penetration. This trade-off
makes EUS suboptimal for establishing M stage in most instances.
Consequently, EUS is considered as a complementary study to cross-sectional
imaging modalities for complete preoperative staging.
The high frequency of EUS imaging allows the endoscopist to clearly
delineate the layers of the GI tract into a five-layer pattern,
demonstrating the superficial and deep mucosa, submucosa, muscularis
propria, and serosa. (Figures 1A and 1B). This permits depth of
invasion and intramural tumors to be easily evaluated.
Recently, through-the-scope ultrasound probes (12 to 20 Mhz) have
been developed. Their clinical utility is unclear, however.
The most well-established indications for EUS include the following:
(1) staging of GI malignancies, (2) evaluation of submucosal lesions,
and (3) imaging of islet-cell tumors. Endoscopic ultrasound also
is being used clinically on a routine basis for a host of other
indications related to both malignant and nonmalignant disorders,
and additional indications are being investigated.
Staging--Endoscopic ultrasound has been shown to be highly
reliable in the preoperative T-staging of esophageal, gastric,
pancreatic, colonic, and rectal neoplasms. When compared with
other imaging modalities, EUS is clearly superior for T- and N-staging
(Table 1) [8-11].
Evaluation of GI Endocrine Tumors--In addition, EUS detected
82% of pancreatic endocrine tumors that were negative on extracorporeal
ultrasound and CT. These difficult-to-detect tumors also eluded
angiographic detection in 78% of cases . Moreover, EUS proved
more accurate than somatostatin-receptor scintigraphy for localizing
neuroendocrine tumors of the GI tract .
EUS-Guided Biopsies and Cytology
Despite the many advances made in endosonography, and the fact
that typical internal endosonographic characteristics of specific
lesions have been recognized and studied, a precise histologic
diagnosis can still be made only by histopathologic examination
of tissue. Biopsies or cytology must be done to establish a definitive
diagnosis. Endosonographic characteristics alone cannot determine
histology, although when EUS is combined with guided biopsies
or cytology, these techniques have the greatest diagnostic yield.
Endosonographic-guided biopsy techniques are currently being refined,
and outcome trials involving EUS are currently underway.