Clutch cutter is a safe device for performing endoscopic submucosal dissection of superficial esophageal neoplasms: a western experience.

Although the endoscopic submucosal dissection (ESD) has been established to be more efficacious in the treatment of superficial gastrointestinal neoplasia than the piecemeal resection, its use is still limited due to the concern about serious adverse events particularly in the west. Newer ESD knives have been developed that have been said to be safer than the first-generation devices. We aimed to report a Western single center experience regarding the initial safety and performance of ESD for superficial esophageal neoplasia treated with the Clutch Cutter (DP2618DT; Fujifilm Corporation, Tokyo, Japan). Our main outcome was safety in terms of bleeding or perforation. Secondary outcomes included en bloc resection and the R0 resection. Fourteen patients with superficial esophageal neoplasia underwent 15 ESDs using the Clutch Cutter. The mean age was 65 ± 16.7 years and 10 (71.4%) males. Eight (57%) patients had esophageal adenocarcinoma, 3 (21.4%) had high-grade dysplasia, 1 (7%) had nodular low-grade dysplasia, and 2 (14.3%) had squamous cell carcinoma. Mild anticipated intraprocedural bleeding was present with most procedures. However, no significant postoperative bleeding or perforation was encountered. One patient had mild chest pain postprocedure. En bloc resection was achieved in all lesions 100%. Histological R0 was achieved in 5/12 lesions (41.6%). The mean length of the resected area was 24.8 ± 13 mm (IQR: 17-30 mm). All patients were safely discharged home after overnight observation. In conclusion, this is the largest series of esophageal ESD using the multimodal Clutch Cutter in the United States; we found that the device effectively achieved en bloc resection of superficial esophageal neoplasia without significant adverse events. The use of the Clutch Cutter should be considered as one option to minimize adverse events during ESD in the Western population.

Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma.

Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

Predictive biomarkers for Barrett's esophagus: so near and yet so far.

Barrett's esophagus (BE) is the strongest risk factor for the development of esophageal adenocarcinoma. However, the risk of cancer progression is difficult to ascertain in individuals, as a significant number of patients with BE do not necessarily progress to esophageal adenocarcinoma. There are several issues with the current strategy of using dysplasia as a marker of disease progression. It is subject to sampling error during biopsy acquisition and interobserver variability among gastrointestinal pathologists. Ideal biomarkers with high sensitivity and specificity are needed to accurately detect high-risk BE patients for early intervention and appropriate cost-effective surveillance. To date, there are no available molecular tests in routine clinical practice despite known genetic and epigenetic aberrations in the Barrett's epithelium. In this review, we present potential biomarkers for the prediction of malignant progression in BE. These include markers of genomic instability, tumor suppressor loci abnormalities, epigenetic changes, proliferation markers, cell cycle predictors, and immunohistochemical markers. Further work in translating biomarkers for routine clinical use may eventually lead to accurate risk stratification.

Endoscopic ablative therapy for Barrett's esophagus: a potential cause of eosinophilic esophagitis.

Markedly increased esophageal eosinophils are associated with allergy- or reflux-based eosinophilic esophagitis. Other known disorders that cause this entity are unusual. To characterize the clinical, endoscopic, and histological findings of patients who develop marked esophageal eosinophilic infiltration after ablative therapy for Barrett's dysplasia. All patients who underwent endoscopic ablation of Barrett's esophagus between 1991 and 2009 with photodynamic therapy or radio frequency were screened for a pathologic descriptor of 'eosinophils' on biopsy. Patients whose biopsies demonstrated >15 eosinophils per high power (HPF) field in squamous epithelium after ablation were reviewed and included in the study group. Thirteen of 385 (3.4%) patients underwent ablation for Barrett's esophagus and subsequently had large numbers of intraepithelial eosinophils. All patients had long segment Barrett's (mean 8.0 cm) with low- or high-grade dysplasia or adenocarcinoma. All had undergone photodynamic therapy as their form of ablation. No patients had typical symptoms or endoscopic findings of eosinophilic esophagitis. Eleven patients were on proton pump inhibitors. The time between ablation and onset of esophageal eosinophilia ranged from 83 to 692 days. Intraepithelial eosinophil counts ranged from 30 to 150/HPF (mean 90). The majority of cases showed eosinophilic degranulation, spongiosis, increased papillary height, and basal zone thickening. The natural history of esophageal eosinophilia was variable after ablation, persisting consistently or sporadically on biopsy for up to 6 years. Ablation for Barrett's dysplasia can be followed rarely by eosinophil infiltrates with a histological resemblance to allergy-based eosinophilic esophagitis, but lacking dysphagia. The pathophysiology is unknown.

Medical and endoscopic management of high-grade dysplasia in Barrett's esophagus.

The management of high-grade dysplasia in Barrett's esophagus has clearly changed over recent years. The risk of cancer development is still substantial, with about one in three patients developing cancer, but a number of patients do not develop cancer. The nature of high-grade dysplasia has also been genetically elucidated with more evidence of chromosomal instability being present at this stage than previously thought. Therapy of the condition has evolved more toward endoscopic therapy, given the good results of radio-frequency ablation and photodynamic therapy in eliminating dysplasia and decreasing cancer development in randomized controlled trial. The best candidates for treatment include compliant patients that have relatively short segments of Barrett's esophagus, an anatomically straight segment, lack of nodularity, and an intact p16. However, even with excellent long-term results similar to surgical resection, the risk of recurrence is present in over 14% of patients, which indicates that there will be a need to continue surveillance endoscopy in these patients.

Photodynamic therapy for Barrett's esophagus: does light still have a role?

Photodynamic therapy was the first treatment to have been shown to significantly decrease high-grade dysplasia and cancer in patients with Barrett's esophagus. However, its use has been limited, primarily because of the side effects, which include esophageal strictures, cutaneous photosensitivity, chest pain, and nausea and vomiting. The tolerability aspects of photodynamic therapy, as well as the dosimetry, though, can be improved with existing technologies to further develop this therapy into truly a widely applicable therapy. Studies have recently been done to help identify patients more likely to suffer stricture after photodynamic therapy. In addition there has been evidence to suggest that the efficacy of photodynamic therapy also can be limited by genetic abnormalities in the mucosa. By combining knowledge of tissue biology, optical properties of the tissue, and dosimetry issues with ablation, photodynamic therapy can still have a potentially bright future.

Contribution of intraoperative enteroscopy in the management of obscure gastrointestinal bleeding.

Obscure gastrointestinal bleeding remains a significant diagnostic challenge. Our aims were (1) to determine the efficacy of intraoperative enteroscopy (IOE) in identifying lesions responsible for obscure gastrointestinal bleeding and (2) to determine the outcome of patients after treatment of these lesions. We retrospectively reviewed all patients who underwent IOE for obscure gastrointestinal bleeding from 1992 to 1998. Patients were divided into those with overt and those with occult gastrointestinal bleeding. Follow-up was complete in 67 patients (96%), with a median of 32 months (range 1 to 91 months). Seventy patients (52 overt and 18 occult) underwent IOE after extensive preoperative evaluation. Median duration of bleeding was 12 months, requiring a median of 14 blood transfusions. Risk factors for bleeding were identified in 46 patients (61%). A lesion was identified and treated in 52 patients (74%)-39 in the overt group and 13 in the occult group. Lesions identified were vascular (54%), ulcerations (31%), tumors (11%), and small bowel diverticula (4%). Overall, 35 patients (52%) were found to have one or more lesions at IOE that were treated surgically and had no further bleeding. IOE, through a mid-small bowel enterotomy, has low morbidity and is effective in that it identified a treatable lesion in 74% of patients, which led to cure of bleeding in 52%.

Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett's esophagus.

BACKGROUND: Endoscopic mucosal resection (EMR) and photodynamic therapy have been proposed as treatments for early stage cancers. EMR is limited by its focal nature whereas photodynamic therapy is dependent on precise staging. The combination of EMR and photodynamic therapy were studied in the treatment of superficial cancer in patients with Barrett's esophagus. METHODS: Seventeen consecutive nonsurgical patients with superficial cancers underwent EMR followed by photodynamic therapy with a porphyrin photosensitizer. Photoradiation was performed at 630 nm for a total dose of 200 J/cm of diffuser. RESULTS: Seventeen patients (15 men; mean age 69 +/- 13 years) underwent EMR. The mean diameter of mucosal resection was 1 cm. The margins were involved by cancer in 3 cases. EMR improved staging in 8 patients (47%). Sixteen (94%) patients remained in remission (median follow-up 13 months). Complications included minor bleeding after EMR in 1 patient (6%), stricture in 5 (30%), cutaneous phototoxicity in 2 (12%), and supraventricular tachycardia in 1 patient (6%). CONCLUSIONS: Combined EMR and photodynamic therapy appears to be an effective and safe therapy for superficial esophageal cancer within Barrett's esophagus. This combination improves cancer staging, removes the superficial cancer, and eliminates remaining mucosa at risk for cancer development.

Persistent genetic abnormalities in Barrett's esophagus after photodynamic therapy.

BACKGROUND & AIMS: Photodynamic therapy (PDT) is a technique for nonsurgical treatment of patients with dysplasia in Barrett's esophagus. The primary endpoint for PDT has been resolution of dysplasia. We studied the effect of PDT at the genetic level. METHODS: Archival material from 3 patients who had initial improvement in dysplasia after PDT but occurrence of high-grade dysplasia during follow-up was used. Biopsy specimens were analyzed for increased proliferation, aneuploidy, p53 protein overexpression, p53 mutations, and p16 promoter hypermethylation. RESULTS: Patients developed high-grade dysplasia 16, 28, and 37 months after PDT. In all cases, one or more genetic markers were positive after PDT treatment, whereas histology was downstaged consistently after therapy. Increasing genetic abnormalities were noted by the end of follow-up. CONCLUSIONS: Genetic abnormalities may persist after PDT despite phenotypical improvement of dysplasia. These patients may progress to high-grade dysplasia or develop adenocarcinoma. Histologic improvement in dysplasia is an inadequate endpoint for PDT in patients with Barrett's esophagus.

Extent of high-grade dysplasia in Barrett's esophagus correlates with risk of adenocarcinoma.

BACKGROUND & AIMS: The identification of any high-grade dysplasia (HGD) in Barrett's esophagus has been considered to be an indication for esophagectomy because of the increased risk of cancer. The aim of this study was to determine if a limited extent of HGD has the same potential for cancer as diffuse HGD. METHODS: A retrospective cohort study was performed to assess the risk of developing adenocarcinoma in relationship to the extent of HGD found on endoscopic surveillance. The extent of HGD was defined as focal if cytologic and/or architectural changes of HGD were limited to a single focus of 5 or fewer crypts and diffuse if more than 5 crypts were involved in a single biopsy specimen or if HGD involved more than one biopsy fragment. The relative risk of cancer was assessed using a Cox proportional hazard model, and cancer-free survival was determined using survival curves. RESULTS: Sixty-seven patients with diffuse HGD and 33 with focal HGD satisfied selection criteria. Cancer-free survival rates at 1 and 3 years were 93% and 86% for focal HGD compared with 62% and 44% for diffuse HGD (P < 0.001). On univariate analysis, extent of HGD (relative risk, 5.36; 95% confidence interval, 1.84-15.56), nodularity on endoscopy (relative risk, 3.98; 95% confidence interval, 1.97-8.04), and lack of acid suppression (relative risk, 2.48; 95% confidence interval, 1.16-5.28) were associated with an increased risk of esophageal adenocarcinoma. Diffuse HGD had a 3.7-fold increase in the risk of esophageal cancer compared with focal HGD (P = 0.02) on multivariate analysis. CONCLUSIONS: Patients with focal HGD are less likely to have cancer during the first year after diagnosis or on subsequent follow-up compared with diffuse HGD.