Multicenter study on the diagnostic performance of multiframe volumetric laser endomicroscopy targets for Barrett's esophagus neoplasia with histopathology correlation.

Volumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett's esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs. In total, 191 ROIs (120 nondysplastic and 71 neoplastic) from 50 BE patients were evaluated in a random order using a web-based module. All ROIs contained histopathology correlations enabled by VLE laser marking. Assessors were blinded to endoscopic BE images and histology. ROIs were first scored as nondysplastic or neoplastic. Level of confidence was assigned to the predicted diagnosis. Outcome measures were: (i) diagnostic performance of VLE assessors for identification of BE neoplasia in all VLE ROIs, defined as accuracy, sensitivity, and specificity; (ii) diagnostic performance of VLE assessors for only high level of confidence predictions; and (iii) interobserver agreement. Accuracy, sensitivity, and specificity for BE neoplasia identification were 79% (confidence interval [CI], 75-83), 75% (CI, 71-79), and 81% (CI, 76-86), respectively. When neoplasia was identified with a high level of confidence, accuracy, sensitivity, and specificity were 88%, 83%, and 90%, respectively. The overall strength of interobserver agreement was fair (k = 0.29). VLE assessors can identify BE neoplasia with reasonable diagnostic accuracy in histopathology-correlated VLE ROIs, and accuracy is enhanced when BE neoplasia is identified with high level of confidence. Future work should focus on renewed VLE image reviewing criteria and real-time automatic assessment of VLE scans.

Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer.

Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study is to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal adenocarcinoma. This study includes patients with esophageal adenocarcinoma who had failed or were not candidates for conventional therapy enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from 11 academic and community practices. Endoscopic spray cryotherapy was performed until biopsy proven local tumor eradication or until treatment was halted due to progression of disease, patient withdrawal or comorbidities. Eighty-eight patients with esophageal adenocarcinoma (median age 76, 80.7% male, mean length 5.1 cm) underwent 359 treatments (mean 4.4 per patient). Tumor stages included 39 with T1a, 25 with T1b, 9 with unspecified T1, and 15 with T2. Eighty-six patients completed treatment with complete response of intraluminal disease in 55.8%, including complete response in 76.3% for T1a, 45.8% for T1b, 66.2% for all T1, and 6.7% for T2. Mean follow-up was 18.4 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 12 of 88 patients (13.6%) but were present before spray cryotherapy in 3 of 12. This study suggests that endoscopic spray cryotherapy is a safe, well-tolerated, and effective treatment option for early esophageal adenocarcinoma.

Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.

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.

The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract.

BACKGROUND: Confocal laser endomicroscopy (CLE) is rapidly emerging as a valuable tool for gastrointestinal endoscopic imaging. Fluorescent contrast agents are used to optimize imaging with CLE, and intravenous fluorescein is the most widely used contrast agent. Fluorescein is FDA-cleared for diagnostic angiography of the retina. For these indications, the safety profile of fluorescein has been well-documented; however, to date, fluorescein is not cleared for use with CLE. AIMS: To estimate the rate of serious and total adverse events attributable to intravenous fluorescein when used for gastrointestinal CLE. METHODS: We performed a cross sectional survey of 16 International Academic Medical Centres with active research protocols in CLE that involved intravenous fluorescein. Centres using i.v. fluorescein for CLE who were actively monitored for adverse events were included. RESULTS: Sixteen centres performed 2272 gastrointestinal CLE procedures. The most common dose of contrast agent was 2.5-5 mL of 10% sodium fluorescein. No serious adverse events were reported. Mild adverse events occurred in 1.4% of individuals, including nausea/vomiting, transient hypotension without shock, injection site erythema, diffuse rash and mild epigastric pain. The limitation is that only immediate post procedure events were actively monitored. CONCLUSIONS: Use of intravenous fluorescein for gastrointestinal CLE appears to be safe with few acute complications.

Depth of resection using two different endoscopic mucosal resection techniques.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) has been carried out for high-grade dysplasia (HGD) and intramucosal carcinoma (IMCA) in Barrett's esophagus using two different cap-assisted techniques, the "inject, suck, and cut" and the "band and snare." Previous work has demonstrated comparable specimen diameters. However, the two techniques have not been previously compared with respect to depth of resection. PATIENTS AND METHODS: From a database of patients with Barrett's esophagus, we identified 40 consecutive specimens removed using EMR from patients with HGD or IMCA, 20 each from the "inject, suck, and cut" and the "band and snare" techniques. Specimens were evaluated and measured separately by two pathologists for greatest diameter and depth, and for the presence of submucosa and muscularis propria at the deepest margin of resection. Follow-up data were collected regarding clinical outcome and stricture formation. RESULTS: The mean depth of the specimens from the two techniques was not significantly different (0.51 cm vs. 0.50 cm, P = 0.76). All specimens contained substantial submucosa, allowing accurate staging of the neoplastic lesions resected. Muscularis propria was identified at the base of 65% of the "band and snare" and 50% of the "inject, suck, and cut" specimens (P = 0.52). CONCLUSIONS: The "inject, suck, and cut" and "band and snare" techniques both yield equivalent adequate depth of histological specimens from Barrett's esophagus with HGD or IMCA, and both provide accurate pathological staging.

Long-term follow-up of complete Barrett's eradication endoscopic mucosal resection (CBE-EMR) for the treatment of high grade dysplasia and intramucosal carcinoma.

BACKGROUND AND STUDY AIMS: In patients with Barrett's esophagus (BE), targeted endoscopic mucosal resection (EMR) of visible lesions of high grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) is effective, but carries the risk of leaving in place synchronous lesions and Barrett's epithelium with the potential for recurrent disease. We evaluated the safety and long-term efficacy of complete Barrett's eradication EMR (CBE-EMR) for the treatment of patients with HGD or IMC, independently of the presence of macroscopically visible lesions or surgical risk. PATIENTS AND METHODS: 26 consecutive patients with BE and HGD or IMC underwent CBE-EMRs, which were performed with the endoscopic cap suction method and/or a 2.3-mm monofilament mucosectomy snare. Endoscopic follow up after completion of resection was carried out to assess the rate of residual or recurrent BE with or without HGD or IMC. RESULTS: 24 patients completed the study. They underwent a total of 44 EMR sessions with a median of 3 pieces (range 1-8) removed per session. Two patients with immediate bleeding were successfully managed endoscopically. Three patients developed an early esophageal stricture that was completely resolved with a single endoscopic dilation. After a median follow-up of 28 months (range 15-51 months), persistent endoscopic and histologic eradication of BE was demonstrated in 21 patients (87.5 %). In two patients, Barrett's epithelium was detected beneath the neosquamous epithelium 3 months after completion of the resection. In the remaining patient, IMC was found in a nodule seen and removed by EMR at 12-month surveillance endoscopy. CONCLUSIONS: CBE-EMR is a safe and highly effective long-term treatment that should be offered to all patients with Barrett's esophagus with HGD and IMC.

Prospective evaluation of balloon-sheathed catheter US system.

BACKGROUND: Catheter US probes must rely on luminal water to create images because they do not incorporate a water-filled balloon such as that used with a designated echoendoscope. The purpose of this study is to determine the effectiveness and safety of a balloon sheath for the US catheter system. METHODS: Catheter EUS was performed on 50 patients by using a 2.3 mm 12 MHz or 20 MHz catheter probe. Catheter EUS was used in 47 cases, and a newly developed water-filled balloon sheath was used in 41 cases. Both devices were used in 39 cases. Procedure time, depth of ultrasound penetration, and a subjective assessment of image quality and ease of use were recorded, along with TMN stage as applicable. Catheter EUS findings were confirmed with a standard radial scanning echoendoscopy (S-EUS) in 18 cases. RESULTS: Catheter probe EUS (C-EUS) and catheter probe plus balloon (CB-EUS) imaging was obtained of 25 esophageal, 8 gastric, 4 rectal, 1 biliary, and 1 duodenal lesion. Time required for the ultrasound portion of the examination was identical with C-EUS and CB-EUS. Depth of penetration increased with CB-EUS with both the 12 MHz and 20 MHz probes (p < 0.05). Subjective assessment of image clarity improved when CB-EUS was used in the esophagus. C-EUS failed to identify 2 esophageal cancers and 2 sets of paraesophageal lymph nodes, and understaged 1 esophageal cancer. The remaining 14 cancers were staged identically by both modalities. The catheter probes with and without the balloon sheath were easy to use, even in markedly narrow esophageal strictures. CB-EUS did not significantly improve resolution in the stomach or rectum. S-EUS confirmed findings of CB-EUS in all 18 cases in which both instruments were used. There were no procedure-related complications. CONCLUSIONS: For esophageal lesions, CB-EUS improves images compared with C-EUS, and enhances depth of penetration without prolonging or encumbering the examination. CB-EUS offers no advantage over C-EUS in organs other than the esophagus. S-EUS, when possible, remains the preferred imaging modality for esophageal cancers because of the ability to image the celiac axis and other deep structures.

1999 ASGE endoscopic ultrasound survey. ASGE Ad Hoc Endoscopic Ultrasound Committee.

BACKGROUND: Gastrointestinal endoscopic ultrasound (EUS) has become an important imaging modality for the diagnosis and staging of gastrointestinal disorders. This study assessed current EUS practice, training, coding, and reimbursement in the United States. METHODS: A direct mail survey was sent to members of the American Society for Gastrointestinal Endoscopy. RESULTS: There were 115 American respondents. The median age was 39 years, 57% were in academic practice, and 84% performed endoscopic retrograde cholangiopancreatography. The median number of EUS procedures performed was 200. In the preceding year, the median number of upper EUS was 60, lower EUS 10, and EUS/fine-needle aspiration 3. The most common indication was evaluation of esophageal or gastric lesions. Forty-six (40%) trained an average of 0.4 advanced fellows in EUS during the prior year. Of endosonographers involved in training, 53% thought formal training was necessary, for a median of 6 months and 100 procedures; 82% did not know whether they were reimbursed for EUS. There was great variation in the use of current procedural terminology (CPT) codes for lower EUS and upper EUS/fine-needle aspiration. CONCLUSIONS: EUS in the United States in 1999 is performed mostly by young, academic, interventional endoscopists. Diagnostic upper EUS is most commonly performed. Few new endosonographers are being trained. There is great variability in CPT coding of lower EUS and EUS/fine-needle aspiration procedures.

Role of photodynamic therapy in the management of advanced esophageal cancer.

Esophageal cancer usually presents at an advanced stage with dysphagia, and palliative therapy often is appropriate. Expandable metal stents are used for palliation because of their ease of insertion, but long-term complications remain common. Photodynamic therapy has been shown to be an effective ablative treatment for obstructing esophageal cancer, overall easier to use, and longer lasting than Nd:YAG laser ablation. Photodynamic therapy may be particularly useful in areas where stents may be problematic, such as in the upper esophagus, at the esophagogastric junction (where adenocarcinomas are increasing in frequency), and following radiation and chemotherapy.

A multicenter U.S. experience with EUS-guided fine-needle aspiration using the Olympus GF-UM30P echoendoscope: safety and effectiveness.

BACKGROUND: The aim of this study was to determine the safety, efficacy, and accuracy of endoscopic ultrasound (EUS)-guided fine-needle aspiration using the GF-UM30P echoendoscope. METHODS: GF-UM30P-guided EUS-guided fine-needle aspiration results from 3 EUS referral centers were prospectively recorded. Successful sampling required that the needle tip be seen within the lesion on at least 1 pass. Aspirates were considered adequate if they were diagnostic for cancer, contained suspicious or atypical cells, or were adequately cellular for interpretation but nondiagnostic. RESULTS: EUS-guided fine-needle aspiration was attempted on 162 lesions in 152 patients with no complications. Sampling was successful in 150 of 162 (93%) attempts (mean lesion size 2.5 +/- 1.2 cm (range 0.7 to 6.0 cm). Aspirates were adequately cellular in 138 of 162 (85%) attempts (43% diagnostic, 15% suspicious and/or atypical cells, 27% adequate cellularity but nondiagnostic). Sampling failed in 12 of 162 (7%) attempts. Ten of 12 (83%) failures and 11 of 12 (92%) inadequate aspirates occurred when lesions measured less than 2 cm. The sensitivity for malignancy was 93% if only successfully sampled lesions with surgically confirmed negative results were included. However, it was 68% if all attempts were included and when unconfirmed high/moderate suspicion negative results were counted as false negatives and low suspicion negative results as true negatives. CONCLUSIONS: The GF-UM30P may be clinically useful for EUS-guided fine-needle aspiration if a curved linear array instrument is unavailable.

Clinical implications of endoluminal ultrasonography using through-the-scope catheter probes.

BACKGROUND: Ultrasound catheter probe-assisted endosonography is a relatively new technique. The aim of this prospective multicenter study was to determine its potential clinical impact by assessing changes in diagnostic and therapeutic management affected by catheter probes compared with ultrasound endoscopes. METHODS: Endosonographers at three centers selected theoretic diagnostic and therapeutic plans that would be followed if neither catheter probes nor ultrasound endoscopes were available. Patients with suitable lesions underwent endosonography with catheter probes followed by an ultrasound endoscope. Diagnostic and therapeutic plans were noted after each examination. RESULTS: Sixty-six patients, of whom 15 had a stenotic esophageal cancer, 39 had a mucosal or submucosal lesion, and 12 had a stricture of the pancreaticobiliary system or the gastrointestinal tract, were enrolled. If neither form of endosonography were available, invasive or surgical diagnostic procedures would have been performed on 23 (35%) patients and surgical therapy would have been planned in 31 (47%) patients. Catheter probe-assisted ultrasonography and endoscopic ultrasonography led to a less invasive diagnostic plan in 11 (16%) and 12 (18%) patients and a less invasive therapeutic plan in 10 (15%) and 14 (21%) patients, respectively (p > 0.1 for differences). CONCLUSIONS: Catheter probe-assisted endosonography has a modest effect on diagnostic and therapeutic management, comparable with endoscopic ultrasonography in the same patients. The vast majority of effected changes are toward less invasive management.