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 evaluated.
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.
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