High-frequency ultrasonographic imaging of the gastrointestinal wall.

The gastrointestinal (GI) tract, with its layered structure, can be imaged by ultrasound using a transabdominal approach or intraluminal high-frequency probes. New ultrasound technology can be used to characterize tissue hardness, study motility in real-time, direct diagnostic and therapeutic intervention, evaluate GI wall perfusion and tissue viability, and perform 3D imaging. Ultrasound is a safe imaging modality, and development of smaller devices has improved its application as a flexible clinical tool, which also can be used bedside. Recently, microbubbles have been injected into the blood stream loaded with contrast agents, or other diagnostic and therapeutic agents. Such bubbles can be destroyed by ultrasound waves, thus releasing their content at a given area of interest. In this article, we present a review of the GI wall anatomy and discuss currently available ultrasound technology for diagnosis and treatment of GI wall disorders.

Prospective study of the progression of low-grade dysplasia in ulcerative colitis using current cancer surveillance guidelines.

BACKGROUND: The goal of this study was to assess the natural history of low-grade dysplasia (LGD) and its risk of progression in ulcerative colitis (UC) patients by prospective endoscopic surveillance. METHODS: Forty-two UC patients with LGD were followed prospectively using a uniform approach to surveillance colonoscopy with an average of 43 biopsies per exam. The interval between colonoscopies ranged from 3-12 months. Progression was defined as development of high-grade dysplasia (HGD) or cancer at subsequent colonoscopy or at colectomy. Univariate and multivariate analysis were performed to identify risk factors associated with progression. RESULTS: Patients were followed for an average of 3.9 years (range 1-13). Over that period 19% (8/42) of patients progressed to advanced neoplasia (two cancer, six HGD) while 17% (7/42) had persistent LGD and 64% (27/42) had indefinite dysplasia or no dysplasia at the end of follow-up. Multivariate analysis demonstrated that the number of biopsies with LGD at baseline was associated with an increased risk of progression to advanced neoplasia (relative risk [RR] 5.8, 95% confidence interval [CI]: (1.29-26.04). Among the 15 patients who underwent colectomy, four were found to have higher-grade neoplasia on their colectomy specimen than their preoperative colonoscopy, and these patients were more likely to be nonadherent with recommendations for colectomy. CONCLUSIONS: The majority (81%) of UC patients with LGD did not progress to higher grades of dysplasia during a 4-year follow-up. Patients with three or more biopsies demonstrating LGD at a single colonoscopy were at increased risk for progression to advanced neoplasia.

Durability of radiofrequency ablation in Barrett's esophagus with dysplasia.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett's esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE. METHODS: We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events. RESULTS: After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years). CONCLUSIONS: In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.

Imaging of subsquamous Barrett's epithelium with ultrahigh-resolution optical coherence tomography: a histologic correlation study.

BACKGROUND: Optical coherence tomography (OCT) is being developed as a potentially valuable method for high-resolution cross-sectional imaging of the esophageal mucosal and submucosal layers. One potential application of OCT imaging is to identify subsquamous Barrett's epithelium in patients who have undergone ablative therapy, which is not visible on standard endoscopic examination. However, histologic correlation confirming the ability of OCT to image subsquamous Barrett's epithelium has yet to be performed. DESIGN: Histologic correlation study. OBJECTIVE: To perform histologic correlation of ultrahigh-resolution optical coherence tomography (UHR-OCT) imaging for identification of subsquamous Barrett's epithelium. SETTING: Academic Medical Center (University of Washington, Seattle, WA). PATIENTS: Fourteen patients with pathologic biopsy specimens, proven to be high-grade dysplasia or adenocarcinoma underwent esophagectomy. INTERVENTIONS: UHR-OCT imaging was performed on ex vivo esophagectomy specimens immediately after resection. MAIN OUTCOME MEASUREMENTS: Correlation of UHR-OCT images with histologic images. RESULTS: Subsquamous Barrett's epithelium was clearly identified by using UHR-OCT images and was confirmed by corresponding histology. LIMITATIONS: Difficulty distinguishing some subsquamous Barrett's glands from blood vessels in ex vivo tissue (because of the lack of blood flow) in some cases. Imaging was performed with a bench-top system. CONCLUSIONS: Results from this study demonstrate that UHR-OCT imaging is capable of identifying subsquamous Barrett's epithelium.

Serious complications within 30 days of screening and surveillance colonoscopy are uncommon.

BACKGROUND & AIMS: The risk of serious complications after colonoscopy has important implications for the overall benefits of colorectal cancer screening programs. We evaluated the incidence of serious complications within 30 days after screening or surveillance colonoscopies in diverse clinical settings and sought to identify potential risk factors for complications. METHODS: Patients age 40 and over undergoing colonoscopy for screening, surveillance, or evaluation based an abnormal result from another screening test were enrolled through the National Endoscopic Database (CORI). Patients completed a standardized telephone interview approximately 7 and 30 days after their colonoscopy. We estimated the incidence of serious complications within 30 days of colonoscopy and identified risk factors associated with complications using logistic regression analyses. RESULTS: We enrolled 21,375 patients. Gastrointestinal bleeding requiring hospitalization occurred in 34 patients (incidence 1.59/1000 exams; 95% confidence interval [CI], 1.10-2.22). Perforations occurred in 4 patients (0.19/1000 exams; 95% CI, 0.05-0.48), diverticulitis requiring hospitalization in 5 patients (0.23/1000 exams; 95% CI, 0.08-0.54), and postpolypectomy syndrome in 2 patients (0.09/1000 exams; 95% CI, 0.02-0.30). The overall incidence of complications directly related to colonoscopy was 2.01 per 1000 exams (95% CI, 1.46-2.71). Two of the 4 perforations occurred without biopsy or polypectomy. The risk of complications increased with preprocedure warfarin use and performance of polypectomy with cautery. CONCLUSIONS: Complications after screening or surveillance colonoscopy are uncommon. Risk factors for complications include warfarin use and polypectomy with cautery.

Radiofrequency ablation in Barrett's esophagus with dysplasia.

BACKGROUND: Barrett's esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barrett's esophagus and decrease the rate of neoplastic progression. METHODS: In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barrett's esophagus in a 2:1 ratio to receive either radiofrequency ablation (ablation group) or a sham procedure (control group). Randomization was stratified according to the grade of dysplasia and the length of Barrett's esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia. RESULTS: In the intention-to-treat analyses, among patients with low-grade dysplasia, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (P<0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19.0% of those in the control group (P<0.001). Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the control group (P<0.001). Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045). Patients reported having more chest pain after the ablation procedure than after the sham procedure. In the ablation group, one patient had upper gastrointestinal hemorrhage, and five patients (6.0%) had esophageal stricture. CONCLUSIONS: In patients with dysplastic Barrett's esophagus, radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression. (ClinicalTrials.gov number, NCT00282672.)

Squamous overgrowth is not a safety concern for photodynamic therapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND & AIMS: Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. METHODS: Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n=138) or 20 mg omeprazole twice daily (n=70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. RESULTS: Histologic assessment of 33,658 biopsies showed no significant difference (P> .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. CONCLUSIONS: No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.

Scanning single fiber endoscopy: a new platform technology for integrated laser imaging, diagnosis, and future therapies.

Remote optical imaging of human tissue in vivo has been the foundation for the growth of minimally invasive medicine. This article describes a new type of endoscopic imaging that has been developed and applied to the human esophagus, pig bile duct, and mouse colon. The technology is based on a single optical fiber that is scanned at the distal tip of an ultrathin and flexible shaft that projects red, green, and blue laser light onto tissue in a spiral pattern. The resulting images are high-quality color video that is expected to produce future endoscopes that are thinner, longer, more flexible, and able to directly integrate the many recent advances of laser diagnostics and therapies.

Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up.

BACKGROUND: For patients with Barrett's esophagus (BE), life-long surveillance endoscopy is recommended because of an elevated risk for developing dysplasia and esophageal adenocarcinoma. Various endoscopic therapies have been used to eradicate BE. Recently circumferential radiofrequency ablation has been used with encouraging short-term results. OBJECTIVE: To provide longer follow-up and to assess the long-term safety and efficacy of step-wise circumferential ablation with the addition of focal ablation for BE. DESIGN: Prospective, multicenter clinical trial (NCT00489268). SETTING: Eight U.S. centers, between May 2004 and February 2007. PATIENTS: Seventy subjects with 2 to 6 cm of BE and histologic evidence of intestinal metaplasia (IM). INTERVENTIONS: Circumferential ablation was performed at baseline and repeated at 4 months if there was residual IM. Follow-up biopsy specimens were obtained at 1, 3, 6, 12, and 30 months. Specimens were reviewed by a central pathology board. Focal ablation was performed after the 12-month follow-up for histological evidence of IM at the 12-month biopsy (absolute indication) or endoscopic appearance suggestive of columnar-lined esophagus (relative indication). Subjects received esomeprazole for control of esophageal reflux. MAIN OUTCOME MEASUREMENTS: Complete absence of IM per patient from biopsy specimens obtained at 12 and 30 months, defined as complete remission-IM (CR-IM). RESULTS: At 12 months, CR-IM was achieved in 48 of 69 available patients (70% per protocol [PP], 69% intention to treat [ITT]). At 30 months after additional focal ablative therapy, CR-IM was achieved in 60 of 61 available patients (98% PP, 97% ITT). There were no strictures or buried glandular mucosa detected by the standardized biopsy protocol at 12 or 30 months, and there were no serious adverse events. LIMITATIONS: This was an uncontrolled clinical trial with 2.5-year follow-up. CONCLUSION: Stepwise circumferential and focal ablation resulted in complete eradication of IM in 98% of patients at 2.5-year follow-up.

Tethered capsule endoscopy, a low-cost and high-performance alternative technology for the screening of esophageal cancer and Barrett's esophagus.

Esophageal cancer is currently the fastest growing cancer in the United States. To help combat the recent rise in morbidity, our laboratory has developed a low-cost tethered capsule endoscope system (TCE) aimed at improving early detection of esophageal cancer. The TCE contains a resonant fiberoptic laser scanner (1.6 mm O.D.) which fits into 6.4-mm easy-to-swallow capsule at the distal tip. The tethered portion contains a single mode optical fiber multiplexed to three laser diodes at the proximal end. This design offers two main advantages over current endoscope technology. First, because of its small size, the TCE can be swallowed with minimal patient discomfort, thereby obviating sedation. Second, by imaging via directed laser light, the TCE is strategically positioned to employ several burgeoning laser-based diagnostic technologies, such as narrow-band, hyperspectral, and fluorescence imaging. It is believed that the combination of such imaging techniques with novel biomarkers of dysplasia will greatly assist in identifying precancerous conditions such as Barrett's esophagus (BE). As the probe is swallowed, the fiber scanner captures high resolution, wide-field color images of the gastroesophageal junction (500 lines at 0.05-mm resolution) currently at 15-Hz frame rate. Video images are recorded as the capsule is slowly retracted by its tether. Accompanying software generates panoramic images from the video output by mosaicing individual frames to aid in pattern recognition. This initial report describes the rationale for the unique TCE system design, results from preliminary testing in vitro and in vivo, and discussion on the merits of this new platform technology as a basis for developing a low-cost screening program for esophageal cancer.

Complications after ERCP in patients with primary sclerosing cholangitis.

BACKGROUND: There are conflicting data regarding the role of ERCP in patients with primary sclerosing cholangitis (PSC) and the risk of procedure-related complications. OBJECTIVE: We compared the complication rate after ERCP in a consecutive series of patients with PSC compared with control patients with biliary strictures who did not have PSC. DESIGN: Retrospective cross-sectional study. SETTING: A tertiary referral academic hospital. MAIN OUTCOME MEASUREMENTS: Incidence of complications after ERCP. PATIENTS AND RESULTS: A total of 85 ERCPs among 30 patients with PSC and 70 ERCPs among 45 control patients were reviewed. There was no significant difference in the overall complication rates between patients with and without PSC (11/85 [12.9%] vs 6/70 [8.6%], P = .45). Complications in PSC were more likely to occur after ERCP done to evaluate an acute sign or symptom than in elective cases (7/24 [29.2%] vs 4/61 [6.6%], P = .01). Patients with PSC who had complications had more total and acute ERCPs than did those without complications. There was no significant difference in the rate of complications in diagnostic versus therapeutic ERCPs nor between stent placement and dilation-only therapeutic ERCPs in the PSC population. LIMITATIONS: Retrospective study design and limited power related to the small sample sizes. CONCLUSIONS: Elective ERCP is safe and carries a modest risk in patients with PSC; however, ERCP for acute indications greatly increases the probability of postprocedure complications. The overall complication rate after therapeutic ERCP in patients with PSC is similar to that in patients without PSC.

Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett's high-grade dysplasia.

BACKGROUND: Barrett's esophagus (BE) with high-grade dysplasia (HGD) is a risk factor for development of esophageal carcinoma. Photodynamic therapy (PDT) with Photofrin (PHO) has been used to eliminate HGD in BE. OBJECTIVE: Our purpose was to compare PHOPDT plus omeprazole with omeprazole only (OM). DESIGN: Five-year follow-up of a randomized, multicenter, multinational, pathology-blinded HGD trial. SETTING: 30 sites in 4 countries. PATIENTS: 208. INTERVENTIONS: Patients with BE and HGD were randomized (2:1) to PHOPDT (n=138) or OM (n=70) into a 2-year trial followed up for 3 more years. PHOPDT patients received 2 mg/kg PHO intravenously followed by endoscopic laser light exposure of Barrett's mucosa at a wavelength of 630 nm within 40 to 50 hours to a maximum of 3 courses at least 90 days apart. Both groups received 20 mg of OM twice daily. Pathologists at one center assessed biopsy specimens in a blinded fashion. MAIN OUTCOME MEASUREMENT: HGD ablation status over 5 years of follow-up. RESULTS: At 5 years PHOPDT was significantly more effective than OM in eliminating HGD (77% [106/138] vs 39% [27/70], P<.0001). A secondary outcome measure preventing progression to cancer showed a significant difference (P=.027) with about half the likelihood of cancer occurring in PHOPDT (21/138 [15%]) compared with OM (20/70 [29%]), with a significantly (P=.004) longer time to progression to cancer favoring PHOPDT. LIMITATIONS: Not all patients were available for follow-up. CONCLUSIONS: This 5-year randomized trial of BE patients with HGD demonstrates that PHOPDT is a clinically and statistically effective therapy in producing long-term ablation of HGD and reducing the potential impact of cancer compared with OM.

Interobserver agreement for EUS findings in familial pancreatic-cancer kindreds.

BACKGROUND: EUS is a promising modality for pancreatic-cancer screening in high-risk persons, including familial pancreatic-cancer (FPC) kindreds. OBJECTIVE: To assess interobserver agreement for interpretation of EUS in persons at high risk for pancreatic cancer. DESIGN: Seventeen expert endosonographers blinded to patients' clinical history rated a "training set" of pancreatic EUS video clips for the presence of a normal examination, masses, cysts, and features of chronic pancreatitis. Clips included high-risk persons and controls (normal and various pancreatic diseases). The endosonographers then participated in a workshop on EUS findings in high-risk persons and drafted a consensus statement. Three months later, they blindly rated a "test set" composed of the same video clips. MAIN OUTCOME MEASUREMENTS: Interobserver agreement at baseline (training set) and after a consensus process (test set). RESULTS: For the training set, interobserver agreement was good (kappa>or=0.4) for the presence of cysts and was fair to poor for all other rated EUS features and diagnosis of normal. There was no overall improvement in the test set. In both the training and test sets, agreement was worse for clips from FPC kindreds (kappa>or=0.4 for cysts and <0.4 for all other features) than for controls (kappa>or=0.4 for normal, cysts, masses, echogenic strands, and lobularity). LIMITATIONS: Video clips were not of identical image quality and duration as a clinical EUS examination. CONCLUSIONS: There was fair to poor interobserver agreement for the interpretation of pancreatic EUS video clips from members of FPC kindreds. Agreement was not improved by a consensus process.

Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett's esophagus: 1-year follow-up of 100 patients.

OBJECTIVE: To assess the dose-response, safety, and efficacy of circumferential endoscopic ablation of Barrett's esophagus (BE) by using an endoscopic balloon-based ablation device (HALO360 System). DESIGN: This study was conducted in 2 serial phases (dosimetry phase and effectiveness phase) to evaluate a balloon-based ablation device that delivers a pre-set amount of energy density (J/cm2) to BE tissue. The dosimetry phase evaluated the dose-response and the safety of delivering 6 to 12 J/cm2. The effectiveness phase used 10 J/cm2 (delivered twice [x2]) for all patients, followed by EGD with biopsies at 1, 3, 6, and 12 months. A second ablation procedure was performed if BE was present at 1 or 3 months. Patients received esomeprazole 40 mg twice a day for 1 month after ablation, and 40 mg every day thereafter. Postablation symptoms were quantified by using a 14-day symptom diary (scale, 0-100). A complete response (CR) was defined as all biopsy specimens negative for BE at 12 months. SETTING: Eight U.S. centers, between September 2003 and September 2005. PATIENTS: Patients were 18 to 75 years of age, with a diagnosis of BE (without dysplasia), with histopathology reconfirmation of the diagnosis within 6 months of enrollment. RESULTS: In the dosimetry phase, 32 patients (29 men; mean age, 56.8 years) were enrolled. Median symptom scores returned to a score of 0 of 100 by day 3. There were no dose-related serious adverse events, and the outcomes at 1 and 3 months permitted the selection of 10 J/cm2 (x2) for the subsequent effectiveness phase of the study. In the effectiveness phase, 70 patients (52 men, 18 women; mean age, 55.7 years) were enrolled. Median symptom scores returned to a score of 0 of 100 by day 4. At 12 months (n = 69; mean, 1.5 sessions), a CR for BE was achieved in 70% of patients. There were no strictures and no buried glandular mucosa in either study phase (4306 biopsy fragments evaluated). CONCLUSIONS: Circumferential ablation of nondysplastic BE by using this balloon-based ablation device can be performed with no subsequent strictures or buried glands and with complete elimination of BE in 70% of patients at 1-year follow-up.

Incidence of minor complications and time lost from normal activities after screening or surveillance colonoscopy.

BACKGROUND: Few studies address the development of minor complications after screening or surveillance colonoscopy. OBJECTIVES: Our purpose was to examine in previously asymptomatic people the incidence of new symptoms after colonoscopy, risk factors for symptoms, and patients' perceptions of this examination. DESIGN: Prospective cohort study. Patients completed a standardized interview at 7 and 30 days after colonoscopy. PATIENTS: A total of 502 patients aged 40 years and older undergoing colonoscopy for colorectal cancer screening, surveillance, or follow-up of another abnormal screening test result. Patients were excluded if they had a history of inflammatory bowel disease, visible GI bleeding, or anemia. MAIN OUTCOME MEASURES: Incidence of minor complications and patient perceptions about colonoscopy. RESULTS: Minor complications occurred in 162 subjects (34%) before day 7 and in 29 subjects (6%) between day 7 and day 30, most commonly bloating (25%) and abdominal pain (11%). Six subjects had unexpected emergency department visits or hospitalizations within 30 days, including 2 with postpolypectomy bleeding. On multivariate analysis, minor complications were more common in women (odds ratio 1.78, 95% CI 1.21-2.62) and when the procedure lasted 20 minutes or longer. Bowel preparation was rated the most difficult part of the examination for 77%. Most subjects (94%) lost 2 or fewer days from normal activities for the colonoscopy itself, preparation, or recovery. CONCLUSIONS: Minor complications were common after screening and surveillance colonoscopy. The bowel preparation was the most difficult part of the examination for most patients. Most subjects lost 2 or fewer days from normal activities because of colonoscopy.

American Gastroenterological Association Institute technical review on the management of gastric subepithelial masses.

This literature review and the recommendations therein were prepared for the American Gastroenterological Association Institute Clinical Practice and Economics Committee. The paper was approved by the Committee on January 19, 2006, and by the AGA Institute Governing Board on April 20, 2006.

A prospective study comparing endoscopy and EUS in the evaluation of GI subepithelial masses.

BACKGROUND: The purpose of this study is to prospectively evaluate the performance characteristics of endoscopy and EUS in the diagnosis of GI subepithelial masses. METHODS: A total of 100 consecutive patients referred for the evaluation of a suspected GI subepithelial lesion were prospectively studied with endoscopy followed by EUS. Size, color, mobility, location (intramural or extramural), consistency (solid, cystic, or vascular), and presumptive diagnosis were recorded at the time of endoscopy. EUS then was performed, and size, echogenicity, location, and presumptive diagnosis were determined. RESULTS: A total of 100 subepithelial lesions were evaluated. Endoscopy had 98% sensitivity and 64% specificity in identifying intramural lesions. Size measurement by endoscopy correlated with size measurement by EUS (r = 0.88). Histology was obtained in 23 cases, with the presumptive EUS diagnosis correct in only 48% of cases. Most incorrect EUS diagnoses occurred with hypoechoic 3rd and 4th layer masses. CONCLUSIONS: Endoscopy has high sensitivity but low specificity in identifying the location (intramural or extramural) of subepithelial lesions. In addition, EUS imaging alone is insufficient to accurately diagnose 3rd and 4th layer hypoechoic masses, and histologic confirmation should be obtained whenever possible.

Optical coherence tomography imaging of the pancreas: a needle-based approach.

A novel, high-resolution, needle-based optical coherence tomography (OCT) device for improving the ability to detect early epithelial dysplasia in solid tissues/organs in vivo is currently in development. An instrument capable of real-time imaging of tissue microstructures in vivo could improve the ability to detect pathologic conditions such as dysplasia, and consequently improve patient outcomes. OCT is an emerging technology that can perform real-time cross-sectional imaging of tissue structures at micron-scale resolution in vivo. OCT has been shown to be effective in the imaging of luminal epithelium, capable of detecting epithelial dysplasia in Barrett's esophagus, and colonic polyps. However, OCT imaging depth with conventional probes is limited to the luminal surface (approximately 1-2 mm). The development of a technology and device that enables high-resolution, real-time imaging of solid tissues beyond 1- to 2-mm deep at or near the cellular level in vivo could improve the diagnosis of diseases of the pancreas and other solid organs.

Vascular effects induced by combined 1-MHz ultrasound and microbubble contrast agent treatments in vivo.

Previous in vivo studies have demonstrated that microvessel hemorrhages and alterations of endothelial permeability can be produced in tissues containing microbubble-based ultrasound contrast agents when those tissues are exposed to MHz-frequency pulsed ultrasound of sufficient pressure amplitudes. The general hypothesis guiding this research was that acoustic (viz., inertial) cavitation, rather than thermal insult, is the dominant mechanism by which such effects arise. We report the results of testing five specific hypotheses in an in vivo rabbit auricular blood vessel model: (1) acoustic cavitation nucleated by microbubble contrast agent can damage the endothelia of veins at relatively low spatial-peak temporal-average intensities, (2) such damage will be proportional to the peak negative pressure amplitude of the insonifying pulses, (3) damage will be confined largely to the intimal surface, with sparing of perivascular tissues, (4) greater damage will occur to the endothelial cells on the side of the vessel distal to the source transducer than on the proximal side and (5) ultrasound/contrast agent-induced endothelial damage can be inherently thrombogenic, or can aid sclerotherapeutic thrombogenesis through the application of otherwise subtherapeutic doses of thrombogenic drugs. Auricular vessels were exposed to 1-MHz focused ultrasound of variable peak pressure amplitude using low duty factor, fixed pulse parameters, with or without infusion of a shelled microbubble contrast agent. Extravasation of Evans blue dye and erythrocytes was assessed at the macroscopic level. Endothelial damage was assessed via scanning electron microscopy (SEM) image analysis. The hypotheses were supported by the data. We discuss potential therapeutic applications of vessel occlusion, e.g., occlusion of at-risk gastric varices.

Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents.

Gold nanocages of <40 nm in dimension have been synthesized using the galvanic replacement reaction between Ag nanocubes and HAuCl4 in an aqueous solution. By controlling the molar ratio between Ag and HAuCl4, the gold nanocages could be tuned to display surface plasmon resonance peaks around 800 nm, a wavelength commonly used in optical coherence tomography (OCT) imaging. OCT measurements on phantom samples indicate that these gold nanocages have a moderate scattering cross-section of approximately 8.10 x 10(-16) m2 but a very large absorption cross-section of approximately 7.26 x 10(-15) m2, suggesting their potential use as a new class of contrast agents for optical imaging. When bioconjugated with antibodies, the gold nanocages have also been demonstrated for specific targeting of breast cancer cells.