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.

International cancer seminars: a focus on esophageal squamous cell carcinoma.

The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts.

Incidence of brain metastasis from esophageal cancer.

We investigated whether the incidence of brain metastasis (BM) from primary esophageal and esophagogastric cancer is increasing. A single-institution retrospective review identified 583 patients treated from January 1997 to January 2016 for stages I through IV cancer of the esophagus and esophagogastric junction (follow-up, ≥3 months). Collected data included demographic information, date and staging at primary diagnosis, histologic subtype, treatment regimen for primary lesion, date of BM diagnosis, presence or absence of central nervous system symptoms, presence or absence of extracranial disease, treatment regimen for intracranial lesions, and date of death. The overall cohort included 495 patients (85%) with adenocarcinoma and 82 (14%) with squamous cell carcinoma (492 [84%] were male; median age at diagnosis, 68 years [range: 26-90 years]). BM was identified in 22 patients (3.8%) (median latency after primary diagnosis, 11 months). Among patients with BM, the primary histology was adenocarcinoma in 21 and squamous cell carcinoma in 1 (P = 0.30). BM developed in 12 who were initially treated for locally advanced disease and in 10 stage IV patients who presented with distant metastases. Overall survival (OS) after BM diagnosis was 18% at 1 year (median, 4 months). No difference in OS after BM diagnosis was observed in patients initially treated for localized disease compared to patients who presented with stage IV disease; however, OS was superior for patients who initially had surgical resection compared to patients treated with whole brain radiotherapy or stereotactic radiosurgery alone (1-year OS, 67% vs. 0%; median OS, 13.5 vs. 3 months; P = 0.003). The incidence of BM is low in patients with esophageal cancer. Outcomes were poor overall for patients with BM, but patients who underwent neurosurgical resection had improved survival.

Prospective feasibility study on the use of multiband mucosectomy for endoscopic resection of early squamous neoplasia in the esophagus.

BACKGROUND AND STUDY AIMS: Endoscopic resection for esophageal squamous high-grade intraepithelial neoplasia (HGIN) or intramucosal cancer (esophageal squamous cell carcinoma [ESCC]) with the endoscopic resection cap technique is technically difficult, and requires submucosal lifting and multiple snares for piecemeal resections. Multiband mucosectomy (MBM) is an easy-to-use endoscopic resection technique and may be the modality of choice in China, where ESCC is extremely prevalent. The aim of the current study was to prospectively evaluate MBM for piecemeal endoscopic resection of squamous neoplasia of the esophagus. METHODS: Patients with HGIN/ESCC and no signs of submucosal invasion or metastatic disease were included in the study. Lesions were delineated using electrocoagulation and resected using the MBM technique. Endpoints were procedure time, endoscopic radicality, complications, histology of the endoscopic resection specimens, and absence of HGIN/ESCC at the endoscopic resection scar during follow-up. RESULTS: A total of 41 patients (26 male; mean age 61 years) underwent MBM; all lesions were visible with white light endoscopy (median length 5 cm, interquartile range [IQR] 4 - 6 cm; median circumferential extent 42 %, IQR 25 - 50 %). Median procedure time was 12 minutes (IQR 8 - 24 minutes). Median number of resections was 5 (IQR 3 - 6). Endoscopic complete resection was achieved in all lesions. There was one perforation, which was treated by application of clips. No other complications were observed. The worst histology was ESCC (n = 19), HGIN (n = 17), middle grade intraepithelial neoplasia (n = 4), and normal squamous epithelium (n = 1). Endoscopic follow-up at 3 months showed HGIN at the endoscopic resection scar in two patients, which was effectively treated endoscopically, and showed normal squamous epithelium in all patients at final follow-up (median 15 months, IQR 12 - 24 months). CONCLUSION: This first prospective study on MBM for piecemeal endoscopic resection of early esophageal squamous neoplasia showed that MBM was effective for the complete removal of lesions with short procedure time, few complications, effective histological assessment of resected specimens, and durable treatment effect.

Prevalence of buried Barrett's metaplasia in patients before and after radiofrequency ablation.

BACKGROUND AND STUDY AIM: Radiofrequency ablation (RFA) to treat Barrett's esophagus is increasingly accepted. Description of the etiology, natural history, and prevalence of buried Barrett's metaplasia (BBM) following RFA is limited, although BBM continues to pose a clinical dilemma. We aimed to assess the prevalence, characteristics, and eradication rate of BBM in patients with both dysplastic and nondysplastic Barrett's esophagus, treated with RFA and followed over time. PATIENTS AND METHODS: The presence of Barrett's esophagus, dysplasia, and BBM, before and after RFA, was assessed by two gastrointestinal pathologists in a retrospective chart review of patients who had undergone RFA at our center and had completed appropriate follow-up. RESULTS: We identified 112 patients with completed treatment and no further planned RFA. In 108, no residual Barrett's esophagus was seen after RFA; 4 patients with persistent Barrett's tissue underwent surgery. Regarding BBM, 17/112 patients (15.2%) had evidence of BBM during evaluation. In 12/17 (70.5%) BBM was found during the RFA treatment, with 8 having previously undergone non-RFA therapy and RFA for Barrett's esophagus and 4 having no previous intervention. In 5/17 (29.4%), BBM was seen only after RFA monotherapy. All 17 showed no evidence of BBM at final evaluation and were classified in the complete remission group (108/112). CONCLUSION: Both Barrett's esophagus and BBM were completely eradicated in all patients with long-term follow-up after RFA. Almost half of the patients with BBM had a prior history of non-RFA therapy for Barrett's esophagus compared with 26% the non-BBM cohort. All patients with previously identified Barrett's esophagus and BBM were completely cleared of disease at final follow-up.

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.

Prospective study of outcomes after percutaneous biliary drainage for malignant biliary obstruction.

BACKGROUND: Percutaneous biliary drainage (PBD) is used to relieve malignant bile duct obstruction (MBO) when endoscopic drainage is not feasible. Little is known about the effects of PBD on the quality of life (QoL) in patients with MBO. The aim of this study was to evaluate changes in QoL and pruritus after PBD and to explore the variables that impact these changes. MATERIALS AND METHODS: Eligible patients reported their QoL and pruritus before and after PBD using the Functional Assessment of Cancer Therapy-Hepatobiliary instrument (FACT-HS) and the Visual Analog Scale for Pruritus (VASP). Instruments were completed preprocedure and at 1 and 4 weeks following PBD. RESULTS: A total of 109 (60 male/49 female) patients enrolled; 102 (94%) had unresectable disease. PBD was technically successful (hepatic ducts cannulated at the conclusion of procedure) in all patients. There were 2 procedure-related deaths. All-cause mortality was 10% (N = 11) at 4 weeks and 28% (N = 31) at 8 weeks post-PBD with a median survival of 4.74 months. The mean FACT-HS scores declined significantly (P < .01) over time (101.3, 94.8, 94.7 at baseline, 1 week, 4 weeks, respectively). The VASP scores showed significant improvement at 1 week with continued improvement at 4 weeks (P < .01). CONCLUSIONS: PBD improves pruritus but not QoL in patients with MBO and advanced malignancy. There is high early mortality in this population.

An economic analysis of endoscopic ablative therapy for management of nondysplastic Barrett's esophagus.

BACKGROUND AND AIMS: Advances have occurred in the development of safe and effective ablative therapies for Barrett's esophagus. The aim of the current study was to perform an economic analysis evaluating the cost-effectiveness of endoscopic ablation of nondysplastic Barrett's esophagus. METHODS: A Markov model evaluated three competing strategies in a hypothetical 50-year-old cohort with nondysplastic Barrett's esophagus from a societal perspective. Strategy I -- natural history of Barrett's disease (without surveillance); Strategy II -- surveillance performed according to the American College of Gastroenterology practice guidelines; Strategy III -- endoscopic ablative therapy. The model was biased against ablative therapy with a conservative estimate of complete response and continued standard surveillance even after complete ablation. All potential complications were accounted for, and an incomplete histological response after ablation was presumed to have the same risk of progression as untreated Barrett's. Transitional probabilities, discounted cost, and utility values to estimate quality-adjusted life-years (QALY) were obtained from published information. Direct costs were used in our analysis. RESULTS: In baseline analysis, the ablative strategy yielded the highest QALY and was more cost-effective than endoscopic surveillance. In a Monte Carlo analysis, the relative risk of developing cancer in the strategy based on endoscopic ablation was decreased compared with the other strategies. In threshold analysis, the critical determinants of cost-effectiveness of the ablative strategy were rate of complete response to ablation, total cost of ablation, and risk of progression to dysplasia. CONCLUSIONS: Within the limits of the model, ablation for nondysplastic Barrett's esophagus is more cost-effective than endoscopic surveillance. Clinical trials of ablative therapy in nondysplastic Barrett's esophagus are needed to establish its effectiveness in reducing cancer risk.

Radiofrequency ablation for total Barrett's eradication: a description of the endoscopic technique, its clinical results and future prospects.

Stepwise circumferential and focal radiofrequency ablation using the HALO system is a novel and promising ablative modality for Barrett's esophagus. Primary circumferential ablation is performed using a balloon-based bipolar electrode, while secondary treatment of residual Barrett's epithelium is performed using an endoscope-mounted bipolar electrode on an articulated platform. It has been used as a single-modality treatment or in combination with other therapies. Recent studies suggest that this ablation technique is highly effective in removing Barrett's mucosa and its associated dysplasia without the known drawbacks of photodynamic therapy or argon plasma coagulation, such as esophageal stenosis and subsquamous foci of intestinal metaplasia (also known as "buried Barrett"). [nl]In this review paper we will explain the technical background of radiofrequency ablation using the HALO system, give a summary of its current status, and speculate on possible future applications.

A prospective pilot trial of ablation of Barrett's esophagus with low-grade dysplasia using stepwise circumferential and focal ablation (HALO system).

BACKGROUND AND STUDY AIMS: Yearly surveillance endoscopy is carried out for Barrett's esophagus with low-grade dysplasia (LGD) so that progression to high-grade dysplasia and adenocarcinoma can be detected at the earliest stage. The aim of the study was to assess the long-term safety and effectiveness of circumferential ablation followed by focal ablation (HALO system) for eliminating Barrett's esophagus and LGD. PATIENTS AND METHODS: Patients with 2 - 6 cm of Barrett's esophagus with histology demonstrating LGD on their last two sequential endoscopies over the previous 2 years and confirmed by two pathologists were enrolled in this prospective, single-center trial. Circumferential ablation was carried out at baseline and at 4 months (if residual Barrett's esophagus present). Endoscopy with 4-quadrant biopsies every 1 cm was performed at 1, 3, 6, 12, and 24 months. After 1 year, focal ablation was applied to any visible Barrett's esophagus or irregularity of the squamocolumnar junction. Patients received lansoprazole 30 mg bid. Complete responses for dysplasia (CR-dysplasia) and intestinal metaplasia (CR-IM) at 2-year follow-up, with complete response defined as "all biopsies negative for dysplasia or intestinal metaplasia" were the main outcomes. RESULTS: Ten patients (nine men, mean age 66.9 years, range 48 - 79) with confirmed LGD (median 4.4 cm, range 3 - 6) underwent circumferential ablation with focal ablation after 1 year as necessary. At 2 years, CR-dysplasia was 100 % and CR-IM was 90 %. There were no strictures or buried intestinal metaplasia at follow-up. CONCLUSION: A stepwise regimen of circumferential ablation followed by focal ablation appears to eradicate intestinal metaplasia (90 % CR-IM) and dysplasia (100 % CR-dysplasia) at 2-year follow-up in this trial, without stricture formation or buried intestinal metaplasia.

Patient characteristics, clinical, endoscopic, and histologic findings in adult eosinophilic esophagitis: a case series and systematic review of the medical literature.

The objective of our study is to describe patient characteristics, clinical, endoscopic, and pathologic features and management of adult eosinophilic esophagitis (EE). A retrospective review of adults with EE (20 or more eosinophils per high-power field) diagnosed between 1997 and 2006, and a systematic review of the medical literature was performed. Forty-two patients (31 male; 11 female) had EE. Mean (SD) age at diagnosis was 44 (15.8) years, with highest prevalence (48%) at age 20-39. Predominant symptoms were dysphagia (81%); median duration, 8 years; range, 1-30 years and food impaction (55%). Forty-three percent had allergy or atopy, 36% had asthma, 54% had peripheral eosinophilia, and 10% had a first-degree relative with dysphagia. Endoscopic findings included ringed esophagus (55%), linear furrows (33%), narrow esophagus (10%), normal esophagus (7%), and esophageal strictures (38%). Mean number of dilations was 2 (range, 1-5). There were no perforations, but superficial mucosal tears occurred in 31% of dilations. Nine patients were treated with topical fluticasone with clinical improvement in all four (100%) patients who were seen in follow-up. Pathologic findings included 20 or more eosinophils per high-power field from proximal or mid-esophageal biopsy specimens. A systematic review of 14 studies (11 manuscripts, 2 abstracts, and this case series) with 212 patients showed similar findings. EE should be suspected in young men with unexplained dysphagia or food impaction even in the absence of typical endoscopic findings of rings or corrugations, linear furrows, and narrow esophagus; diagnosis is confirmed by 20 or more eosinophils per high-power field on proximal or mid-esophageal biopsies; EE is associated with allergic or atopic disorders; topical steroids are effective in the management of EE; dilation of esophageal strictures is reasonably safe in EE.

The yield of capsule endoscopy in patients with abdominal pain or diarrhea.

BACKGROUND AND STUDY AIMS: Capsule endoscopy, proven effective for evaluation of obscure gastrointestinal bleeding and suspected Crohn's disease, is increasingly used to investigate other small-intestine disorders, but its yield for other indications is not well known. We sought to evaluate its yield and findings for abdominal pain or diarrhea. PATIENTS AND METHODS: Medical records of patients with abdominal pain or diarrhea (> 6 weeks' duration) who underwent capsule endoscopy between August 2001 and June 2004 were retrospectively reviewed for demographic data, indications, findings, diagnoses, complications, and radiologic studies. All patients had previous endoscopic or radiologic examinations (colonoscopy, enteroscopy, upper endoscopy, small-bowel series, computed tomography enterography, or computed tomography) demonstrating no abnormalities sufficient for diagnosis. RESULTS: 64 patients (26 men; 38 women; mean age, 43 years; age range, 19 - 83 years) who met study criteria had 68 capsule endoscopy studies. Indications were abdominal pain (35 patients), diarrhea (14), or both (15). Complete small-bowel visualization with identification of the cecum was achieved in 81 %; yield of positive findings was 9 % (6 patients). By indications, the yield was 6 % for abdominal pain, 14 % for diarrhea, and 13 % for both. Diagnoses included Crohn's disease (3), enteropathy induced by nonsteroidal anti-inflammatory drugs (2), and submucosal tumor (1). Capsule retention occurred in two patients, requiring surgical removal. CONCLUSIONS: Capsule endoscopy had a low yield for evaluation of abdominal pain or diarrhea and cannot be recommended as a first-line test without further study. Nonetheless, it facilitated diagnosis in 9 % of patients with negative endoscopic and radiologic examinations.

Impaction and fracture of a video capsule in the small bowel requiring laparotomy for removal of the capsule fragments.

Capsule endoscopy has become an important diagnostic tool because of its high sensitivity and specificity for evaluation of the small-bowel mucosa. It is usually a safe procedure. The main complication has been retention of the video capsule in patients with unsuspected obstructive small-bowel disease. We describe a case of a 76-year-old man who underwent capsule endoscopy for the investigation of chronic abdominal pain. The patient returned several months after the procedure with recurrence of his symptoms. Investigations at that time showed that the capsule had been retained in a section of the distal ileum which showed stricture formation and that it had broken up into fragments. This is the first reported case of a fractured video capsule.

Nonvariceal upper gastrointestinal bleeding.

Although the incidence of nonvariceal upper gastrointestinal bleeding (NVUGIB) may be decreasing, the case fatality associated with it remains unchanged. What do the most recent studies tell us about medical and endoscopic therapy? Erythromycin is a potentially useful adjunct to endoscopy, and further data are needed to establish its role in the management of patients with NVUGIB. The use of proton-pump inhibitors in addition to combination endoscopic therapy appears to reduce the rebleeding rate consistently across different studies; the route of administration, dosage, and duration of treatment require further definition. Although two controlled studies suggest improved outcomes with clot removal and endoscopic therapy, the exact role of endoscopic treatment in the setting of overlying clots remains controversial. Hemoclips have not been found, in general, to be superior to the available endoscopic techniques. Currently, other hemostatic techniques such as injection and thermocoagulation - and in particular, combination therapy using both methods - are preferable. No major "breakthrough" endoscopic treatment has emerged. Newer endoscopic therapies such as cryotherapy are interesting, but have not had widespread application. Endoscopic suturing techniques, as used in the treatment of esophageal reflux and obesity, have not been adapted to the management of gastrointestinal bleeding.

Prevalence of gastric precancerous lesions in Ardabil, a high incidence province for gastric adenocarcinoma in the northwest of Iran.

BACKGROUND/AIMS: Ardabil Province, in northwestern Iran, has the highest rate of gastric (predominantly cardia) adenocarcinoma in Iran. This study aimed to investigate the feasibility of endoscopic screening and to look for associated Helicobacter pylori infection and gastric precancerous lesions. METHODS: One thousand one hundred and five adult volunteers, residents of Ardabil and Meshkinshahr, districts, 40 years old and above were selected and invited by a simple random household canvass in rural and urban locations. Informed consents were obtained and upper gastrointestinal video endoscopy was performed to biopsy all visible lesions and standard sites in the antrum, corpus, and cardia. RESULTS: One thousand and eleven of the invited individuals agreed to participate, including 494 men and 517 women, with a mean (SD) age of 53.32 (10.39) years. Endoscopy was well tolerated by all subjects; 96.7% of antral and 80.7% of cardia mucosal biopsies were satisfactory. The urease test or histology for H pylori was positive in at least 89.2% of subjects. Histological evidence of mucosal atrophy was seen in 39.3% of antral and 21.9% of cardia samples. Chronic gastritis with or without activity, reactive atypia of glandular epithelium, intestinal metaplasia, dysplasia, and cancer were found in 95.1%, 38.0%, 8.7%, 0.2%, and 0.3% of antral and 85.3%, 22.9%, 3.8%, 0.3%, and 0.1% of cardiac biopsies, respectively. CONCLUSION: Endoscopic screening for upper gastrointestinal diseases was feasible and well tolerated in Ardabil, Iran. Most subjects showed H pylori infection. Atrophic gastritis, reactive atypia, and intestinal metaplasia were common in antrum, corpus, and cardia subsites.

Endoscopic esophageal cancer survey in the western part of the Caspian Littoral.

After a hiatus of 30 years an attempt is now being made to re-assess the previously reported very high esophageal cancer incidence rates in the Caspian Littoral. The extraordinarily high incidence rates found in the eastern side of the Littoral, were re-confirmed five years ago for the Turkoman region, using esophageal balloon cytology supplemented by esophagoscopy of suspected cases. The focus this time was on the Ardabil province in the western side of the Caspian Littoral, where the rates reported 30 years ago were moderately high. A pilot chromoendoscopic screening program was scheduled for 650 asymptomatic adults from a randomly selected part of the city of Ardabil and adjoining villages, to evaluate the overall patterns of esophageal disease and to establish the utility of endoscopy as an esophageal cancer screening tool. 504 healthy volunteers, giving a compliance rate of 77.5%, submitted to esophagogastroscopy without any mishaps. Contrary to expectation, no dysplasia or esophageal cancer was found in 914 satisfactory biopsy specimens. Total absence of esophageal cancer or precursor dysplastic changes in the surveyed population in the western part of the Caspian Littoral was at variance with the cancer registry findings of three decades ago for the western part of the Littoral. A plausible explanation could be the improved socio-economic conditions and life style changes which have taken place in the recent past all along the Caspian Littoral, except in the Turkoman Plain.