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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. [ABSTRACT FROM AUTHOR]

Background and Aim: Colorectal cancer (CRC) remains the second most frequent cause of cancer deaths in the United States. Blood tests using tumor-related antigens aid in diagnosing CRC. However, higher sensitivity and specificity are needed before an acceptable tumor antigen blood test for CRC is clinically useful. This study describes the diagnostic accuracy of an enzyme-linked immunosorbent assay for the CA11-19 serologic tumor antigen for the detection of CRC., Methods: Serum specimens were obtained from 522 colonoscopy-confirmed subjects in institutional review board-approved studies. Specimens were blind coded. CA11-19 levels were determined by using enzyme-linked immunosorbent assay analysis. The results were tabulated for categories of normal, hyperplastic polyps, benign GI, adenomatous polyps, and CRC based on their final diagnosis., Results: When a cutoff of 6.4 units/mL for normal is used, the CA11-19 level was elevated in 128 of 131 of CRC subjects, for an observed sensitivity of 98% (95% confidence interval, 93.1%-99.5%). Normal levels were found in 87% of normal subjects (90/103) and 83% of those with benign GI diseases (185/223). When combined, this yields an observed specificity of 84% (95% confidence interval, 80.0%-87.9%)., Conclusion: CA11-19 is a serologic tumor marker for the diagnosis of CRC with a sensitivity of 98% and specificity of 84%. This high sensitivity means that this test will detect 43 of 44 cases of CRC presented. For those older than 50 years of age, it has a positive predictive value of 3.6% and a negative predictive value of 99.98%. Additional prospective studies are needed to further clarify the use of CA11-19 as an aid in the diagnosis of CRC., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA)., Objective: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE., Design: The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE., Patients: Patients enrolled with BE., Interventions: RFA., Main Outcome Measurements: We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, and number of treatments to CEIM by sex and race and/or ethnicity., Results: Among 5521 patients (4052 men; 5126 white, 137 Hispanic, 82 African American, 40 Asian, 136 heritage not identified), women were younger (60.0 vs 62.1 years) and had shorter BE segments (3.2 vs 4.4 cm) and less dysplasia (37% vs 57%) than did men. Women were almost twice as likely to stricture (odds ratio 1.7; 95% confidence interval, 1.2-2.3). Although white patients were predominantly male, about half of African Americans and Asians with BE were female. African Americans and Asians had less dysplasia than white patients. Asians and African Americans had more strictures than did white patients. There were no sex or race differences in efficacy., Limitations: Observational study with non-mandated paradigms, no central laboratory for reinterpretation of pathology., Conclusion: In the U.S. RFA patient registry, women had shorter BE segments and less-aggressive histology. The usual tendency toward BE in men was absent in African Americans and Asians. Posttreatment stricture was more common among women and Asians. RFA efficacy did not differ by sex or race., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: After endoscopic radiofrequency ablation (RFA) of dysplastic Barrett's esophagus (BE), endoscopic biopsy samples are obtained to assess response to therapy. Whether these biopsies are of adequate depth to assess efficacy is unknown., Objective: To compare the depth of endoscopic biopsy samples after RFA with those of untreated controls and to determine the prevalence of subepithelial structures in endoscopic biopsy fragments., Design: Secondary analysis of the AIM Dysplasia Trial, a multicenter, randomized, sham-controlled study., Setting: Nineteen treatment centers., Patients: Subjects with dysplastic BE, either status post RFA or ablation naïve (sham)., Main Outcome Measurements: The proportion of biopsy samples demonstrating subepithelial structures, stratified by tissue type (columnar vs squamous) in sham- and RFA-treated subjects., Results: A total of 5648 biopsy fragments were analyzed from 113 subjects (78 RFA, 35 sham; mean 50.0 fragments per subject). Most fragments (4653, 82.4%) contained subepithelium. Squamous biopsy samples from RFA and sham subjects demonstrated subepithelium at similar rates (78.4% vs 79.1%, respectively, P = not significant [NS]). Columnar biopsy samples from RFA and sham subjects also included subepithelium at similar rates (99.0% vs 98.8%, respectively, P = NS). Regardless of treatment assignment, more columnar than squamous biopsy samples demonstrated subepithelium (98.8% vs 78.5%, P < .001)., Limitations: Biopsy samples were not individually mounted., Conclusions: In both squamous and columnar tissue, endoscopic biopsy samples after RFA were as likely to demonstrate subepithelium as untreated controls. Almost 80% of all biopsy samples were adequate to evaluate for subsquamous intestinal metaplasia. The primary determinant of biopsy depth is the type of epithelium that underwent biopsy, with squamous less likely to yield subepithelium than columnar. Biopsy samples after RFA appear to be of adequate depth to assess response to therapy. (Clinical trial registration number NCT00282672.)., (Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

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.

Background: The management strategies for Barrett's esophagus (BE) that contains high-grade dysplasia (HGD) include intensive endoscopic surveillance, photodynamic therapy, thermal ablation, EMR, and esophagectomy., Objective: To assess the safety and effectiveness of endoscopic circumferential balloon-based ablation by using radiofrequency energy for treating BE HGD., Design: Multicenter U.S. registry., Setting: Sixteen academic and community centers; treatment period from September 2004 to March 2007., Patients: Patients with histologic evidence of intestinal metaplasia (IM) that contained HGD confirmed by at least 2 expert pathologists. A prior EMR was permitted, provided that residual HGD remained in the BE region for ablation., Intervention: Endoscopic circumferential ablation with follow-up esophageal biopsies to assess the histologic response to treatment., Outcomes: Histologic complete response (CR) end points: (1) all biopsy specimen fragments obtained at the last biopsy session were negative for HGD (CR-HGD), (2) all biopsy specimens were negative for any dysplasia (CR-D), and (3) all biopsy specimens were negative for IM (CR-IM)., Results: A total of 142 patients (median age 66 years, interquartile range [IQR] 59-75 years) who had BE HGD (median length 6 cm, IQR 3-8 cm) underwent circumferential ablation (median 1 session, IQR 1-2). No serious adverse events were reported. There was 1 asymptomatic stricture and no buried glands. Ninety-two patients had at least 1 follow-up biopsy session (median follow-up 12 months, IQR 8-15 months). A CR-HGD was achieved in 90.2% of patients, CR-D in 80.4%, and CR-IM in 54.3%., Limitations: A nonrandomized study design, without a control arm, a lack of centralized pathology review, ablation and biopsy technique not standardized, and a relatively short-term follow-up., Conclusions: Endoscopic circumferential ablation is a promising modality for the treatment of BE that contains HGD. In this multicenter registry, the intervention safely achieved a CR for HGD in 90.2% of patients at a median of 12 months of follow-up.

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.

Background: Photodynamic therapy (PDT) may be used to ablate high-grade dysplasia/early stage cancer (HGD/T1) in patients with Barrett's esophagus. PDT may result in esophageal stricture. This nonrandomized, unblinded, dose de-escalation study in consecutive patients was designed to determine the lowest light dose effective for ablation of HGD/T1 while reducing the incidence of stricture., Methods: A total of 113 patients received an injection of porfimer sodium (2 mg/kg). Three days later, 630 nm light was delivered by using a 20-mm-diameter PDT balloon at doses of 115 J/cm (n=59), 105 J/cm (n=18), 95 J/cm (n=17), or 85 J/cm (n=19). Treatment efficacy was determined by obtaining biopsy specimens of the treated area 3 months later. The incidence of stricture was determined by the need for esophageal dilation to treat dysphagia. A stricture was considered severe if 6 or more dilations were required., Results: The incidence of severe stricture was related to the light dose. At 115 J/cm, 15.3% of patients developed severe strictures compared with 5.3% to 5.6% of those treated with the lower doses. At a light dose of 115 J/cm, 17.0% of patients had residual HGD/T1. Light doses of 105 J/cm, 95 J/cm, and 85 J/cm resulted in residual HGD/T1 in 33.3%, 29.4%, and 31.6% of patients, respectively. None of the observations were statistically significant., Conclusions: Decreasing the light dose below 115 J/cm appeared to result in a reduced incidence rate of severe stricture but higher relative frequencies of residual HGD/T1 in Barrett's esophagus.

Background: Perforation as a complication of colonoscopy is estimated to occur in 0.01% to 0.3% of procedures, but the frequency in ambulatory settings is unknown. This study determined the number of perforations occurring within a network of endoscopic ambulatory surgery centers., Methods: A total of 116,000 colonoscopies were performed within one network of 45 endoscopic ambulatory surgery centers in the United States during 1999. All identified perforations were reported to the network clinical director and reviewed by a panel of 3 gastroenterologists., Results: There were 37 (0.03%) perforations; 27 in women and 10 in men. Median patient age was 75 years (range 39-87 years); 18 patients (49%) had diverticular disease and 20 (54%) had a history of pelvic or colonic surgery. Twenty-four (65%) procedures were diagnostic, and 13 (35%) were therapeutic. The most common site of perforation was the sigmoid colon (62%); followed by the ascending colon (16%); cecum, transverse colon, and splenic flexure (11%); and rectum, anastomotic, or unknown (11%). The time to diagnosis ranged from immediate to 72 hours (29 <1 hour, 8 >1 hour). All patients were hospitalized; 35 (95%) underwent exploratory laparotomy, and 2 (5%) were treated conservatively. No patient died., Conclusions: Reported perforations for procedures performed in endoscopic ambulatory surgery centers occurred most frequently during diagnostic colonoscopy in older woman with a history of surgery or diverticular disease. Reported perforations in endoscopic ambulatory surgery centers were uncommon.

Background: Photodynamic therapy has been shown to eliminate Barrett's dysplasia. This report presents long-term follow-up data after photodynamic therapy of Barrett's esophagus with high-grade dysplasia, low-grade dysplasia, or early stage carcinoma., Methods: Porfimer-photodynamic therapy was performed in 103 patients. The Nd:YAG laser was used to photoablate small areas of residual or untreated Barrett's mucosa. Acid suppression was maintained in all patients (omeprazole, 20 mg twice a day)., Results: Mean follow-up was 50.65 (SD 20.57) months (range 2-122 months). For the 82 patients not lost to follow-up, mean follow-up was 58.5 (12.89) months (range 41-132 months). After photodynamic therapy, the length of Barrett's mucosa decreased by a mean of 6.92 cm (range 1-22 cm). Of the 65 patients with high-grade dysplasia, 60 (94%) had elimination of high-grade dysplasia. Three (4.6%) patients developed subsquamous adenocarcinoma. Subsquamous, nondysplastic, metaplastic epithelium was found in 4 patients (4.9%). Strictures occurred in 18% with one session of photodynamic therapy, and 50% with two treatments, 30% overall. For the 103 patients, intention-to-treat success rates were 92.9%, 77.5%, and 44.4% for, respectively, low-grade dysplasia, high-grade dysplasia, and early stage carcinoma groups., Conclusion: Porfimer-photodynamic therapy with supplemental Nd:YAG photoablation and continuous treatment with omeprazole reduces the length of Barrett's mucosa, eliminates high-grade dysplasia, and, by comparison with historical data, may reduce the expected frequency of carcinoma.

Background: This report presents clinical results of photodynamic therapy in patients with Barrett's esophagus and dysplasia or superficial esophageal cancer., Methods: One hundred patients including 13 with superficial cancers were treated. Light (630 nm) was endoscopically delivered to the esophageal mucosa by a diffuser or a windowed esophageal centering balloon. Nd:YAG laser was required to ablate small residual areas of Barrett's mucosa during-long-term follow-up. Patients were maintained on omeprazole and were followed for 4 to 84 months (mean 19 months)., Results: Conversion of approximately 75% to 80% of treated Barrett's mucosa to normal squamous epithelium was found in all patients; complete elimination of Barrett's mucosa was noted in 43 patients. Dysplasia was eliminated in 78 patients. Dysplasia developed during follow-up in 11 of 48 patients in untreated Barrett's mucosa requiring additional therapy. Ten of the 13 malignancies were ablated. Esophageal strictures occurred in 34%. Use of longer centering balloons reduced the incidence of strictures., Conclusion: Photodynamic therapy alone or with Nd:YAG laser thermal ablation combined with long-term acid inhibition provides an effective endoscopic therapy to (1) eliminate Barrett's mucosal dysplasia and superficial esophageal cancer and (2) reduce the extent of and, in some cases, eliminate Barrett's mucosa.

Background: Photodynamic therapy (PDT) is a different type of laser treatment from Nd:YAG thermal ablation for palliation of dysphagia from esophageal cancer., Methods: In this prospective, multicenter study, patients with advanced esophageal cancer were randomized to receive PDT with porfimer sodium and argon-pumped dye laser or Nd:YAG laser therapy., Results: Two hundred thirty-six patients were randomized and 218 treated (PDT 110, Nd:YAG 108) at 24 centers. Improvement in dysphagia was equivalent between the two treatment groups. Objective tumor response was also equivalent at week 1, but at month 1 was 32% after PDT and 20% after Nd:YAG (p < 0.05). Nine complete tumor responses occurred after PDT and two after Nd:YAG. Trends for improved responses for PDT were seen in tumors located in the upper and lower third of the esophagus, in long tumors, and in patients who had prior therapy. More mild to moderate complications followed PDT, including sunburn in 19% of patients. Perforations from laser treatments or associated dilations occurred after PDT in 1%, Nd:YAG 7% (p < 0.05). Termination of laser sessions due to adverse events occurred in 3% with PDT and in 19% with Nd:YAG (p < 0.05)., Conclusions: Photodynamic therapy with porfimer sodium has overall equal efficacy to Nd:YAG laser thermal ablation for palliation of dysphagia in esophageal cancer, and equal or better objective tumor response rate. Temporary photosensitivity is a limitation, but PDT is carried out with greater ease and is associated with fewer acute perforations than Nd:YAG laser therapy.

Laser-induced fluorescence spectroscopy was used to measure fluorescence emission of normal and malignant tissue during endoscopy in patients with esophageal cancer and volunteers with normal esophagus. The spectroscopy system consisted of a nitrogen-pumped dye-laser tuned at 410 nm for excitation source, an optical multichannel analyzer for spectrum analysis, and a fiberoptic probe designed for both the delivery of excitation light and the collection of fluorescence emission from tissue. The fluorescence lineshape of each spectrum was determined and sampled at 15-nm intervals from 430 to 716 nm. A calibration set of spectra from normal and malignant spectra was selected. Using stepwise discriminate analysis, significant wavelengths that separated normal from malignant spectra were selected. The intensities at these wavelengths were used to formulate a classification model using linear discriminate analysis. The model was then used to classify additional tissue spectra from 26 malignant and 108 normal sites into either normal or malignant spectra. A sensitivity of 100% and specificity of 98% were obtained.

Delivery of uniform circumferential light is desirable during photodynamic therapy of early or advanced esophageal cancer in human beings. Studies were performed in the canine esophagus to investigate whether use of a centering balloon would improve circumferential illumination of esophageal mucosa for photodynamic therapy of esophageal cancer. When the centering balloon was used, photodynamic therapy produced uniform and circumferential injury. With the cylindrical diffuser used in human studies, non-uniform and focal esophageal injury occurred. Placement of isotropic probes on the balloon wall allowed measurement and verification of relatively uniform light doses delivered to esophageal mucosa during balloon photodynamic therapy. The centering balloon has a potential role in improving light dosimetry during esophageal photodynamic therapy.

Primary panendoscopy is defined as a limited-consultative, diagnostic, UGI endoscopic examination that provides, in non-critically ill patients with dyspeptic symptoms, an accurate and cost-effective alternative to the standard UGI x-ray examination. The procedure was instituted at St. Mary's Medical Center's hospital in February 1985. During the first 12 months, a total of 321 patients were examined: 212 inpatients and 109 outpatients. In those patients with complete information, primary panendoscopy changed the diagnosis in 67% and the treatment in 52%. As expected, the number of esophagogastroduodenoscopies decreased during this time, but the combined numbers of primary panendoscopies and esophagogastroduodenoscopies exceeded the projected increase of esophagogastroduodenoscopies. Similarly, the number of UGI x-ray examinations fell sharply. With a physician fee of $150.00 and a facility fee of $50.00, theoretical savings of some $117,000.00 to the patients were estimated. The authors conclude that primary panendoscopy provides a cost-effective and beneficial patient service that warrants broad consideration by gastroenterologists as they face the cost constraints being imposed within the health care system of the 1980s.