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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.

Background and Aims: Optical coherence tomography (OCT) is an imaging technique that produces high-resolution cross-sectional images in vivo. The aim of this study was to establish the sensitivity and specificity of OCT for diagnosing specialized intestinal metaplasia (SIM)., Methods: OCT was used to image the stomach and esophagus of 121 patients. A total of 288 biopsy-correlated OCT images were acquired. OCT criteria for SIM were formulated by analyzing 75 images of SIM. The SIM image criteria were retrospectively tested by applying them to images of gastric, squamous, SIM, and cardiac epithelium. The criteria were then tested prospectively to determine the sensitivity and specificity of OCT for diagnosing SIM., Results: OCT images of SIM are characterized by (1) absence of the layered structure of normal squamous epithelium and the vertical "pit and crypt" morphology of gastric mucosa, (2) disorganized architecture with inhomogeneous tissue contrast and an irregular mucosal surface, and (3) presence of submucosal glands. These criteria were 100% sensitive and 93% specific for SIM when applied retrospectively and 97% sensitive and 92% specific when tested prospectively., Conclusions: OCT is highly sensitive and specific for SIM and may aid in the diagnosis and surveillance of this preneoplastic lesion.

Ultraviolet laser-induced fluorescence was examined in vivo to determine whether the technique can reliably distinguish between hyperplastic and adenomatous polyps of the colon. Spectra from 86 normal colonic sites, 35 hyperplastic polyps, and 49 adenomatous polyps were recorded in vivo. Polyp type was independently determined by two senior pathologists who were unaware of the fluorescence measurement. A multivariate linear regression analysis was used to differentiate spectra from hyperplastic and adenomatous polyps and resulted in a sensitivity, specificity, predictive value positive, and predictive value negative for identifying adenomatous polyps of 86%, 80%, 86%, and 80%, respectively. These values were not significantly different from the accuracy of routine clinical pathology. Thus, ultraviolet laser-induced fluorescence appears to show promise as a means for distinguishing tissue types. However, further experience is needed before its routine clinical use can be recommended. Significant changes in the fluorescence spectra occurred postmortem, suggesting that future studies of laser-induced fluorescence of colonic tissue must use data acquired in vivo.

Experimental work has established that the Candela (Candela Laser Corporation, Wayland, MA) flashlamp excited dye laser (wavelength, 504 nm) is a highly effective method for fragmenting biliary stones and has minimal potential for injuring the bile duct wall. This technique was evaluated in 25 complex patients whose stones, usually because of large size, did not respond to standard nonoperative treatment. The laser imaging was applied through a quartz fiber and aimed either under direct vision with choledochoscopes passed percutaneously or through a special "mother" duodenoscope or under fluoroscopic guidance at standard duodenoscopy. Laser treatment resulted in some fragmentation of stones in 23 cases. Subsequently, it proved that it was possible to clear the bile duct of stones in 20 patients, 12 of them receiving successful treatment during the same endoscopic procedure. There were no significant complications. This endoscopic technique seems to be a useful new alternative to surgery in patients with large and difficult bile duct stones.

The application of lasers in gastrointestinal endoscopy is rapidly expanding. Because of the tubular configuration of the gastrointestinal tract, endoscopists often deliver laser energy at large angles of incidence. As incident angle affects the fraction of radiation reflected from the tissue surface, we measured the transmittance and reflectance of laser light from in vitro esophagus as a function of incident angle, using integrating sphere and goniometric techniques. At a wavelength of 633 nm and angles of incidence less than 50 degrees, the total transmittance of the esophagus is approximately 25% and the total reflectance is approximately 45%; both are isotropically distributed. At larger angles of incidence, a specularly reflected component becomes evident and the total reflectance increases. The absorbed light per unit area illuminated decreases with increasing angle, because the area illuminated by the laser beam is proportional to the secant of the incident angle. The data suggest that during endoscopic laser procedures the incident laser beam should be directed within 50 degrees of normal for optimal performance and safety.

Previous studies have demonstrated that brief pulses of selectively absorbed optical radiation can be used to confine thermal injury to pigmented targets within tissues. We performed studies in rabbits to assess the usefulness of this technique for selectively coagulating the colonic vasculature. By measuring the optical absorbance of rabbit colon with a spectrophotometer, it was determined that hemoglobin exhibits strong absorption relative to the rabbit colon at a wavelength of 577 nm. Because light must be absorbed to affect tissue, it was hypothesized that laser pulses of this wavelength would selectively damage blood vessels. This hypothesis was tested by examining the effect of 300-microseconds-long 577-nm laser pulses on rabbit colon in vivo. For delivered radiant exposures between 4 and 8 J/cm2, selective coagulation of the colonic vasculature could be produced without damage to the surrounding colon. At greater radiant exposures, vessel hemorrhage was occasionally noted but no transmural thermal injury was produced with delivered radiant exposures as high as 22 J/cm2. This technique may form the basis of a safe and simple treatment of vascular lesions of the colon such as angiodysplasia.

A pulsed holmium laser (wavelength 2.1 microns, pulse duration 250 microseconds) was used to ablate rabbit liver, stomach, and colon in vivo. Microscopic examination of the tissues revealed zones of thermal damage extending 0.5-1.0 mm from ablation sites. In addition, ablation rates were measured using a mass loss technique and found to increase linearly with delivered radiant exposure. The threshold radiant exposure for ablation was calculated to be 50 J/cm2 with a heat of ablation of 7000 J/cm3. Because the holmium laser produces less thermal necrosis than current endoscopic laser systems, such as the continuous-wave neodymium:YAG laser, and because the ablation rate can be precisely controlled, the holmium laser shows promise as an alternative method for endoscopic removal of tissue.

The feasibility of using lasers to fragment biliary calculi was examined in vitro. Flashlamp-pumped tunable dye lasers were coupled to small-diameter flexible quartz fibers that were placed in direct contact with biliary calculi. The minimum laser energy necessary to damage a calculus was measured for wavelengths between 450 and 700 nm and for pulse durations between 0.8 and 360 microseconds. This threshold energy increased with increasing wavelength but was not significantly affected by pulse duration. Cholesterol stones had uniformly higher thresholds than pigmented ones. When a repetitively pulsed laser was used, complete fragmentation required fewer than 500 pulses and fragments were predominantly less than 2 mm. The pulsed dye laser can effectively fragment biliary calculi when transmitted through a small-diameter quartz fiber and may be useful as a tool for fragmenting retained common duct stones.