Search

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. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.)

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.

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., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: The AIM-II Trial included patients with nondysplastic Barrett's esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up., Patients and Methods: Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barrett's esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA., Results: Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12)., Conclusions: In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA., (© Georg Thieme Verlag KG Stuttgart · New York.)

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., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (.)

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.), (2009 Massachusetts Medical Society)

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.

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.

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.

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.

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.

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.

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.

We determined the incidence of severe bleeding from gastric antral vascular ectasia (GAVE) after myeloablative hematopoietic cell transplant and the outcomes after treatment with endoscopic neodymium:YAG laser photocoagulation. From 1992 to 2005, the incidence of severe bleeding from GAVE was 6/4491 (0.13%). All patients had received oral busulfan and four had sinusoidal obstruction syndrome. Gastrointestinal bleeding began a median of 53 days after transplant (range 15-2952). After GAVE was diagnosed by endoscopic and histologic findings, a median of three (range 2-7) sessions of laser therapy were required to control the bleeding with a median of 2737 J (range 1117-6160 J) per session. A median of 16 units (range 4-44) had been transfused prior to laser therapy and a median of four additional units (range 0-113) were transfused until bleeding was controlled. All patients were followed for at least 70 days after the last laser therapy session, with no further episodes of bleeding. Complications were mild and included abdominal pain and asymptomatic ulceration; however, one patient required gastrectomy due to gastric necrosis following transarterial embolizations. In summary, severe bleeding from GAVE is rare following hematopoietic cell transplant. Treatment with endoscopic therapy using the Nd:YAG laser is safe and effective.

Acute colonic pseudo-obstruction is the clinical syndrome of acute large bowel dilatation without mechanical obstruction that is an important cause of morbidity and mortality. Acute colonic pseudo-obstruction occurs in hospitalized or institutionalized patients with serious underlying medical and surgical conditions. The pathogenesis of acute colonic pseudo-obstruction is not completely understood but likely results from an imbalance in the autonomic regulation of colonic motor function. Metabolic or pharmacological factors, as well as spinal or retroperitoneal trauma, may alter the autonomic regulation of colonic function, leading to excessive parasympathetic suppression or sympathetic stimulation. This imbalance results in colonic atony and dilatation. Early recognition and appropriate management are critical to minimizing morbidity and mortality. The mortality rate is estimated at 40% when ischaemia or perforation occurs. The best-studied treatment of acute colonic pseudo-obstruction is intravenous neostigmine, which leads to prompt colon decompression in the majority of patients after a single infusion. In patients failing or having contraindications to neostigmine, colonoscopic decompression is the active intervention of choice. Surgery is reserved for those with peritonitis or perforation.

Biliary complications are important causes of early and late postoperative morbidity and mortality after liver transplantation and are seen in 10-20 % of the patients. The common biliary complications include bile leaks, stones or debris, and anastomotic strictures. Less common complications are hilar strictures, intrahepatic strictures, and papillary stenosis/dysfunction. The complications are similar in living-donor and cadaveric liver transplantations, except for a higher incidence of bile leaks among living-donor transplant recipients. The clinical presentation of post-liver transplant bile duct complications is often subtle, and noninvasive imaging studies may sometimes fail to detect mild but clinically significant stenoses or small leaks. Early recognition and prompt treatment of biliary complications following liver transplantation reduces the morbidity and improves long-term graft and patient survival. In this report, we discuss the role of endoscopy in the diagnosis, treatment options, and the outcome for patients with biliary complications following liver transplantation.

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.

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 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.

Aspirin is a very useful medication for the prevention of cardiovascular thrombotic events in patients with or those at risk for cardiovascular disease (CVD). Aspirin, however, carries an increased risk for gastrointestinal (GI) injury (e.g., ulceration) and its complications (e.g., hemorrhage), which may be caused by its antiplatelet and gastric mucosal effects. In those with established CVD, aspirin use has been documented to decrease the risk of a first myocardial infarction (MI). Its effects on stroke and vascular death are less conclusive. The use of aspirin in these individuals is recommended only for those whose risk for cardiovascular events (based on coronary risk assessment tools) is sufficiently high that it outweighs the risk for GI complications. Secondary prevention refers to the use of aspirin to prevent cardiovascular events in patients with established CVD such as an MI, stroke, or angina. The use of aspirin in these individuals is recommended based on a documented decrease in future cardiovascular events and mortality. The risk for GI events with aspirin is at least additive to the risk for these events in those who also are receiving therapy with a nonsteroidal anti-inflammatory drug. Patients being treated with aspirin, even at 81 mg/day for cardioprotection, should be assessed for factors that increase the risk for GI injury. Studies have confirmed that co-therapy with a proton pump inhibitor (PPI) or misoprostol decreases the risk for GI injury and complications. Although both classes of such gastroprotective agents are effective, treatment with a PPI is tolerated better, with fewer patients discontinuing the drug because of side effects such as diarrhea.

Background: The aim of this study was to determine the frequency and the severity of pancreatitis after EUS-guided FNA of solid pancreatic masses. A survey of centers that offer training in EUS in the United States was conducted., Methods: A list of centers in which training in EUS is offered was obtained from the Web site of the American Society for Gastrointestinal Endoscopy. Designated program directors were contacted via e-mail. The information requested included the number of EUS-guided FNA procedures performed for solid pancreatic masses, the number of cases of post-procedure pancreatitis, and the method for tracking complications. For each episode of pancreatitis, technical details were obtained about the procedure, including the location of the mass, the type of fine needle used, the number of needle passes, and the nature of the lesion., Results: Nineteen of the 27 programs contacted returned the questionnaire (70%). In total, 4909 EUS-guided FNAs of solid pancreatic masses were performed in these 19 centers over a mean of 4 years (range 11 months to 9 years). Pancreatitis occurred after 14 (0.29%): 95% CI[0.16, 0.48] procedures. At two centers in which data on complications were prospectively collected, the frequency of acute pancreatitis was 0.64%, suggesting that the frequency of pancreatitis in the retrospective cohort (0.26%) was under-reported (p=0.22). The odds that cases of pancreatitis would be reported were 2.45 greater for the prospective compared with the retrospective cohort (95% CI[0.55, 10.98]). The median duration of hospitalization for treatment of pancreatitis was 3 days (range 1-21 days). The pancreatitis was classified as mild in 10 cases, moderate in 3, and severe in one; one death (proximate cause, pulmonary embolism) occurred after the development of pancreatitis in a patient with multiple comorbid conditions., Conclusions: EUS-guided FNA of solid pancreatic masses is infrequently associated with acute pancreatitis. The procedure appears to be safe when performed by experienced endosonographers. The frequency of post EUS-guided FNA pancreatitis may be underestimated by retrospective analysis.

We developed a miniature endoscope that is capable of rapid lateral scanning and is suitable for real-time forward-imaging optical coherence tomography (OCT). The endoscope has an outer diameter of 2.4 mm, consisting of a miniature tubular lead zirconate titanate (PZT) actuator, a single-mode fiber-optic cantilever, and a graded-index lens. Rapid lateral scanning at 2.8 kHz is achieved when the fiber-optic cantilever is resonated with the PZT actuator. This allows OCT imaging to be performed by fast lateral beam scanning followed by slow depth scanning, which is different from the conventional OCT imaging sequence. Real-time OCT imaging with the endoscope operated in the new image acquisition sequence at 6 frames/s is demonstrated.

Background & Aims: Ibuprofen is a well-tolerated nonsteroidal anti-inflammatory drug (NSAID), particularly at over-the-counter (OTC) doses. Cyclooxygenase 2 (COX-2)-selective inhibitors cause less ulceration than prescription-dose nonselective NSAIDs. We compared endoscopic injury related to nonprescription ibuprofen doses with celecoxib, also comparing prescription doses of naproxen with placebo as a positive control., Methods: The study was a randomized, placebo-controlled, double blind, double-dummy endoscopic evaluation with concealed allocation. A 2-way crossover with a 4-5-week washout period was used. Participants were healthy adults with normal baseline findings from endoscopy. Ninety-five subjects were randomly assigned, and 79 subjects completed both study phases. Age distribution was reflective of the target population of the OTC agent. Twenty percent were infected with Helicobacter pylori, and 79% and 67% had a current or past medical problem, respectively. Qualifying subjects, stratified by the presence or absence of H. pylori infection (n = 20), were randomly assigned to 1 of the 4 sequences (phase I/II) as follows: ibuprofen/celecoxib; celecoxib/ibuprofen, naproxen/placebo, or placebo/naproxen. Primary end points were the frequency of endoscopic ulcers and erosions in the groups administered: (1) celecoxib vs. ibuprofen and (2) naproxen vs. placebo., Results: In celecoxib-treated subjects, 2.6% developed ulcers compared with 17.9% of those treated with ibuprofen (P = 0.056). Naproxen treatment was associated with a significantly greater ulceration rate compared with placebo., Conclusions: Short-term use of the nonselective COX inhibitors ibuprofen and naproxen is associated with a greater risk for endoscopic mucosal injury compared with the COX-2-selective inhibitor celecoxib or placebo. A prospective analysis appropriately powered to address the incidence of clinically significant gastroduodenal ulceration associated with the short-term use of these agents would be required to further define the clinical relevance of these findings.

Patients with unresectable or metastatic rectal cancer may have symptoms of obstruction, bleeding, pain, or tenesmus. Insertion of a self-expandable metal stent is the most durable nonsurgical method for relieving obstruction and has been reviewed in the previous article. Other endoscopic methods of palliating obstruction have been largely replaced by expandable metal stent placement. However, laser ablation is still a useful therapy for some patients, particularly when the predominant symptom is rectal bleeding. The indications and results of endoscopic laser therapy along with other endoscopic treatments for the palliation of rectal cancer will be reviewed here.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used classes of medications in the USA, annually accounting for over 100 million prescriptions. Gastrointestinal complications associated with NSAIDs are common, and result in a substantial amount of morbidity and mortality, despite the advent of the cyclooxygenase-2 selective inhibitors or 'coxibs'. Emerging clinical and economic data suggest that, depending on the baseline risk to patients, the use of a traditional NSAID alone or in combination with a proton pump inhibitor are effective and well tolerated alternatives to coxibs. The optimal therapeutic strategy for NSAID selection and use of co-therapy should be guided by a consideration of each patient's risk of having an adverse event arising from the NSAID. Patients at the highest risk for gastrointestinal complications with traditional NSAIDs are those with a history of an ulcer or ulcer complication, those of advanced age (greater than 65 years), and those receiving concurrent aspirin, anticoagulants or corticosteroid therapy. Proton pump inhibitor co-therapy is highly effective in reducing NSAID-related dyspeptic symptoms, healing the injured mucosa even in those who continue to ingest NSAIDs, and preventing gastrointestinal complications. In addition to their selective use in patients who experience NSAID-related dyspepsia and other symptoms, proton pump inhibitor co-therapy should be considered in those at high risk (with coxib or traditional NSAID therapy) and is necessary in high-risk patients receiving aspirin, with or without NSAID therapy.

We present a design of a miniature fiber-optic probe capable of rapid lateral scanning. The miniature probe permits forward-looking optical coherence tomography (OCT) imaging of internal organs in real time. Fast lateral scanning also enables a new real-time image acquisition sequence, potentially permitting real-time focus tracking. To perform sensitive heterodyne detection, a sufficient Doppler frequency is achieved by using an electro-optic (EO) phase modulator. In this paper we describe an effective approach to compensate the dispersion induced by the EO crystal up to the third order. We show that an optimal axial resolution offered by the light source can be recovered through the dispersion management. Preliminary results of real-time OCT imaging of biological tissues with the lateral-priority scanning probe are presented.

Background: High-intensity focused US has been shown to achieve hemostasis in lacerated large veins and arteries. High-intensity focused US was studied as a potential endoscopic treatment for GI bleeding., Methods: A segment of the auricular vein of the rabbit was lacerated longitudinally and then treated with a high-intensity focused US transducer driven at 3.9 MHz (focal intensity of 750 W/cm(2)) in 15 animals until hemostasis was achieved. Sham treatment was delivered to 3 vessels. Rabbits were euthanized on days 0, 2, 7, 14, and 28 to allow for histologic evaluation of the response to treatment., Results: Hemostasis was achieved in all treated vessels and in none of the sham treatments. Mean treatment time was 13 seconds. Histology initially demonstrated acute thermal injury with subsequent thrombus formation and chronic inflammation leading to replacement of the vessel by fibrous scar tissue., Conclusions: High-intensity focused US causes hemostasis in acutely bleeding veins and results in occlusion of treated vessel with subsequent granulation tissue formation.

Background: The aim of this study was to evaluate the degree of agreement among endosonographers for EUS diagnosis of neoplastic versus non-neoplastic pancreatic cystic lesions and the specific type of cystic lesion., Methods: Videotapes of EUS procedures from 31 consecutive cases of a range of histopathologically proven lesions, including mucinous cystic neoplasm, serous cystadenoma, neuroendocrine tumor, intraductal papillary mucinous tumor, and pseudocyst, were used to make a study videotape, which was reviewed by 8 experienced endosonographers. The reviewers, blinded to clinical and surgical histopathology results, reviewed each case for the presence or absence of the following features: abnormality of pancreatic duct and parenchyma, margins, solid component, debris, and septations. They were asked to identify each lesion as neoplastic or non-neoplastic and to give a specific diagnosis for each lesion., Results: There was fair agreement between endosonographers for diagnosis of neoplastic versus non-neoplastic lesions (kappa = 0.24). Agreement for individual types of lesions was moderately good for serous cystadenomas (kappa = 0.46) but fair for the remainder. Agreement was moderately good for presence or absence of solid component (kappa = 0.43); fair for presence or absence of abnormal pancreatic duct (kappa = 0.29), debris (kappa = 0.21), and septations (kappa = 0.30); and slight for presence or absence of margins (kappa = 0.01) and abnormal pancreatic parenchyma (kappa = 0.01). Accuracy rates of EUS for the diagnosis of neoplastic versus non-neoplastic lesions ranged from 40% to 93%., Conclusions: There is little more than chance interobserver agreement among experienced endosonographers for diagnosis of neoplastic versus non-neoplastic, specific type, and EUS features of pancreatic cystic lesions.

Although initial studies suggest a limited role for EUS in the detection of BE and the diagnosis and staging of dysplasia, a defined role in several specific situations is emerging. EUS is useful in selecting appropriate candidates for nonoperative therapies by excluding patients with submucosal cancers and those with malignant lymph nodes. EUS may also help in the selection of patients for EMR, either alone or in combination with ablative therapies.

Background: Endoscopic screening of families predisposed to pancreatic cancer is increasingly used, but the cost-effectiveness of screening is unknown., Methods: A decision analysis was used to compare one-time screening for pancreatic dysplasia with EUS to no screening in a hypothetical cohort of 100 members of familial pancreatic cancer kindreds. Abnormal EUS findings are confirmed with ERCP and patients with abnormal findings are candidates for total pancreatectomy. Lifetime medical care costs and life expectancy were modeled, and the main analysis was conducted from the third-party payer perspective. The base-case analysis assumed a 20% prevalence of pancreatic dysplasia and 90% sensitivity of EUS and ERCP., Results: Endoscopic screening was cost-effective, with an incremental cost-effectiveness ratio of $16,885/life-year saved. Screening was more cost-effective as the probability of dysplasia increased and as the sensitivity of EUS and ERCP increased. Screening remained cost-effective if the prevalence of dysplasia was greater than 16% or if the sensitivity of EUS was greater than 84%. Procedure costs had a limited impact on cost-effectiveness., Conclusions: Endoscopic screening of carefully selected members of familial pancreatic cancer kindreds appears to increase patient life expectancy in a cost-effective manner. Screening should be performed in centers that have experience with endoscopic screening for pancreatic dysplasia. The cost-effectiveness of repeated screening remains to be determined.

Acute colonic pseudo-obstruction is a syndrome of massive dilation of the colon without mechanical obstruction that develops in hospitalized patients with serious underlying medical and surgical conditions. Increasing age, cecal diameter, delay in decompression, and status of the bowel significantly influence mortality, which is approximately 40% when ischemia or perforation is present. Evaluation of the markedly distended colon in the intensive care unit setting involves excluding mechanical obstruction and other causes of toxic megacolon such as Clostridium difficile infection, and assessing for signs of ischemia and perforation. The risk of colonic perforation in acute colonic pseudo-obstruction increases when cecal diameter exceeds 12 cm and when the distention has been present for greater than 6 days. Appropriate management includes supportive therapy and selective use of neostigmine and colonoscopy for decompression. Early recognition and management are critical in minimizing complications.

Pancreatic cancer is the fifth leading cause of cancer death in the United States. Nearly every person diagnosed with pancreatic cancer will die from it, usually in <6 mo. Familial clustering of pancreatic cancers is commonly recognized, with an autosomal dominant inheritance pattern in approximately 10% of all cases. However, the late age at disease onset and rapid demise of affected individuals markedly hamper collection of biological samples. We report a genetic linkage scan of family X with an autosomal dominant pancreatic cancer with early onset and high penetrance. For the study of this family, we have developed an endoscopic surveillance program that allows the early detection of cancer and its precursor, before family members have died of the disease. In a genomewide screening of 373 microsatellite markers, we found significant linkage (maximum LOD score 4.56 in two-point analysis and 5.36 in three-point analysis) on chromosome 4q32-34, providing evidence for a major locus for pancreatic cancer.

Understanding the pathology of familial pancreatic carcinoma may provide important insights into pancreatic tumorigenesis. We now describe in detail the pancreatic pathology of an autosomal dominant pancreatic carcinoma kindred with distinct clinical, genetic, and pathologic manifestations differing from all other reported forms of sporadic or familial pancreatic neoplasia. Affected individuals develop a prodrome of diabetes mellitus, pancreatic exocrine insufficiency, and characteristic pancreatic imaging abnormalities. Eleven family members have undergone total pancreatectomy, revealing a unique and characteristic fibrocystic, lobulocentric pancreatic atrophy. This was patchy to diffuse in distribution and was invariably associated with a nesidioblastosis-like endocrine cell hyperplasia. All but one resected pancreas demonstrated glandular epithelial dysplasia: 10 had low-grade dysplasia (pancreatic intraductal neoplasia grade II of III or PanIN II) and seven also had high-grade dysplasia (pancreatic intraductal neoplasia grade III of III or PanIN III). Dysplasia was multifocal in small-to medium-sized duct-like structures within areas of acinar atrophy, microcystic change, and mucinous hyperplasia. Two pancreata had carcinomas of multiple and unusual histologic subtypes, including small cell undifferentiated carcinoma and giant cell anaplastic carcinoma. The findings in this kindred yield important information on a distinctive and previously unrecognized pancreatic cancer precursor. Recognition of this entity may help identify additional kindreds and perhaps the underlying genetic defect. As is the case for other familial cancers, the as yet unknown specific genetic defect may have wider implications for pancreatic cancer in general.

Background: Patients with ulcerative colitis and primary sclerosing cholangitis are at high risk for colonic dysplasia and cancer. This risk approaches 50% after 25 years of colitis. Ursodiol has been shown to protect against development of colorectal neoplasia in animal models., Objective: To assess the relationship between ursodiol use and colonic dysplasia, the precursor to colon cancer, in patients with ulcerative colitis and primary sclerosing cholangitis., Design: Cross-sectional study., Setting: University medical center., Patients: 59 patients with ulcerative colitis and primary sclerosing cholangitis who were undergoing colonoscopic surveillance for colonic dysplasia., Measurements: Use of ursodiol was assessed in all patients. The presence or absence of colonic dysplasia was evaluated by colonoscopic surveillance. Other variables assessed were age at onset and duration of ulcerative colitis; duration of primary sclerosing cholangitis; Child-Pugh classification; and use of sulfasalazine, other 5-aminosalicylic acid preparations, prednisone, cyclosporine, azathioprine, and methotrexate., Results: Ursodiol use was strongly associated with decreased prevalence of colonic dysplasia (odds ratio, 0.18 [95% CI, 0.05 to 0.61]; P = 0.005). The association between dysplasia and ursodiol use remained after adjustment for sex, age at onset of colitis, duration of colitis, duration of sclerosing cholangitis, severity of liver disease, and sulfasalazine use (adjusted odds ratio, 0.14 [CI, 0.03 to 0.64]; P = 0.01). Younger age at onset of colitis was associated with an increased risk for dysplasia., Conclusions: Ursodiol use appears to be associated with a lower frequency of colonic dysplasia in patients with ulcerative colitis and primary sclerosing cholangitis. A randomized trial investigating the chemoprotective effect of ursodiol in patients with ulcerative colitis may be warranted.

Chronic ingestion of NSAIDs increases the risk for gastrointestinal complications, which range from dyspepsia to gastrointestinal bleeding, obstruction, and perforation. Among patients using NSAIDs, 0.1 to 2.0% per year suffer serious gastrointestinal complications. Patients who require analgesic therapy should be carefully assessed for the lowest possible dosage and shortest duration of NSAID use and for the potential of treatment with a non-NSAID pain reliever. These patients should also be assessed for factors that increase their risk of gastrointestinal complications, including increased age, concomitant anticoagulant or corticosteroid use, and past history of NSAID-associated gastrointestinal complications. The exact association between Helicobacter pylori infection and NSAID-related ulcer disease is unclear, and the routine testing and treatment of all NSAID using patients for H. pylori infection is not recommended at this time. NSAID-using patients who suffer from dyspepsia should have NSAIDs discontinued, the dosage changed, or be changed to a different class of NSAID. If NSAIDs cannot be discontinued, then an antisecretory agent should be initiated. Misoprostol prevents NSAID-associated gastrointestinal complications. Proton pump inhibitors are the most effective at healing NSAID-associated ulcers among patients who cannot discontinue NSAID therapy.

Background: Pancreatic cancer, the fourth most common cause of cancer death in the United States, is hereditary in an estimated 10% of cases. Surveillance of patients with a familial predisposition for pancreatic cancer has not been systematically evaluated., Objective: To develop a surveillance program that can identify and treat patients who have precancerous conditions of the pancreas and a family history of pancreatic cancer., Design: Prospective cohort study., Setting: University medical center., Patients: 14 patients from three kindreds with a history of pancreatic cancer., Interventions: Endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), spiral computed tomography, and serum carcinoembryonic antigen and CA19-9 analysis were performed in all patients. Four affected patients were tested for the K-ras mutation., Main Outcome Measurement: Pancreatic dysplasia was determined by histologic evaluation., Results: Seven of the 14 patients were believed to have dysplasia on the basis of clinical history and abnormalities on endoscopic ultrasonography and ERCP and were referred for pancreatectomy. All 7 patients had histologic evidence of dysplasia in pancreatectomy specimens. Findings on endoscopic ultrasonography were subtle, nonspecific, and similar to those seen in patients with chronic pancreatitis. Findings on ERCP ranged from mild and focal side-branch duct irregularities and small sacculations to main-duct strictures and grapelike clusters of saccules. Some of these changes are typical of chronic pancreatitis, but others are more distinctive. Spiral computed tomography and serum tumor markers had low sensitivity in the detection of pancreatic dysplasia. Analysis for the K-ras mutation yielded positive results in 3 of 4 patients with dysplasia., Conclusions: Thorough screening of patients with a family history of pancreatic cancer is feasible. Clinical data combined with imaging studies (endoscopic ultrasonography and ERCP) can be used to identify high-risk patients who have dysplasia. The role of molecular genetic testing is uncertain at this time.