Wang, Kenneth K.

INTRODUCTION: It is assumed that screening risk factors for Barrett's esophagus (BE) and prevalent esophageal adenocarcinoma (EAC) are the same. METHODS: A matched case-control study comparing risk factors between EAC and BE was performed. RESULTS: In 1,356 patients (678 with EAC and 678 with BE), heartburn (52.7%), diabetes, hyperlipidemia, hypertension, nonalcoholic steatohepatitis, and metabolic syndrome were less common in EAC (52.7, 29.2, 45.7, 48.2, 12, and 28.5%, resp.) compared with BE (84.5, 37.6, 82.2, 64.6, 18.4, and 44.1%, P < 0.01). Mean alanine aminotransferase and HgA1c levels were also significantly lower in EAC compared with BE. DISCUSSION: Optimal strategies for screening for prevalent EAC may be different than that for BE.

INTRODUCTION: Nonendoscopic Barrett's esophagus (BE) screening may help improve esophageal adenocarcinoma outcomes. We previously demonstrated promising accuracy of methylated DNA markers (MDMs) for the nonendoscopic diagnosis of BE using samples obtained from a capsule sponge-on-string (SOS) device. We aimed to assess the accuracy of these MDMs in an independent cohort using a commercial grade assay. METHODS: BE cases had ≥ 1 cm of circumferential BE with intestinal metaplasia; controls had no endoscopic evidence of BE. The SOS device was withdrawn 8 minutes after swallowing, followed by endoscopy (the criterion standard). Highest performing MDMs from a previous study were blindly assessed on extracted bisulfite-converted DNA by target enrichment long-probe quantitative amplified signal (TELQAS) assays. Optimal MDM combinations were selected and analyzed using random forest modeling with in silico cross-validation. RESULTS: Of 295 patients consented, 268 (91%) swallowed the SOS device; 112 cases and 89 controls met the pre-established inclusion criteria. The median BE length was 6 cm (interquartile range 4–9), and 50% had no dysplasia. The cross-validated sensitivity and specificity of a 5 MDM random forest model were 92% (95% confidence interval 85%–96%) and 94% (95% confidence interval 87%–98%), respectively. Model performance was not affected by age, gender, or smoking history but was influenced by the BE segment length. SOS administration was well tolerated (median [interquartile range] tolerability 2 [0, 4] on 10 scale grading), and 95% preferred SOS over endoscopy. DISCUSSION: Using a minimally invasive molecular approach, MDMs assayed from SOS samples show promise as a safe and accurate nonendoscopic test for BE prediction.

AbstractThe clinical application of photodynamic therapy (PDT) for gastrointestinal (GI) neoplastic lesions has been developed with appreciation for the great efforts and kind support of Dr. Tom Dougherty and his followers’ contributions. There are several published studies on clinical PDT in the field of GI oncology. Esophageal cancer was one of the first clinical indications for PDT that was approved as an endoscopic procedure in both the United States and Japan. PDT was initially used as a palliative local treatment for patients with obstructive esophageal cancer. PDT is also indicated for eradicative therapy for dysplastic Barret’s esophagus, which is the precursor state of esophageal adenocarcinoma, with the support of level one evidence. In Japan, PDT was approved as a curative treatment for superficial esophageal carcinoma lesions, which are difficult to treat with endoscopic resection. Further, PDT using second‐generation photosensitizers is approved for early local failure after radiotherapy, for which treatment with other modalities is difficult. PDT has also been assessed in other GI cancers, including gastric cancer, biliary cancer and pancreatic cancer. In this review, we overview the history and state of PDT for GI cancer.

INTRODUCTION: Non-variceal upper gastrointestinal hemorrhage is traditionally managed with mechanical devices, thermal coagulation, or injection therapy. However, due to specific lesion characteristics, certain cases may not be easily or effectively managed by these methods, in which case either a novel therapy or repurposing of an existing technique could be considered. Here, we present a case of gastric antral vascular ectasia (GAVE) addressed with cryotherapy. CASE DESCRIPTION/METHODS: An 82 year old man with CAD s/p CABG, AS s/p AVR, symptomatic AVB s/p PPM, HTN, and BPH presented to his primary care provider Clinic with chronic, symptomatic, transfusion-dependent iron-deficiency anemia with a hemoglobin nadir of 6.7 g/dL from 12.2 g/dL four months prior. The patient also reported possible melena, though stool appearance was obscured by oral iron supplementation. He underwent diagnostic EGD, which identified severe GAVE with mild associated bleeding throughout the entire stomach. This was therapeutically managed with APC, but given the severity and diffuse nature of the GAVE (Figure 1), the patient was referred for cryotherapy. Medically, the patient was recommended to initiate PPI therapy and continue iron supplementation. Three sessions occurring at 1 month intervals were completed, followed by one session 3 months out. By the third session, the patient no longer required transfusional support to maintain appropriate hemoglobin levels. On endoscopic follow-up 6 months out (one year from initial EGD), the GAVE had improved in severity (Figure 2). DISCUSSION: The current treatment of GAVE primarily involves argon plasma coagulation, which is limited by its inability to treat large areas of mucosa in an efficient manner. However, data supporting the use of cryotherapy as a safe and effective treatment for GAVE are emerging. Patients with diffuse, extensive mucosal gastrointestinal lesions should be referred to a tertiary care center to assess cryotherapy candidacy.

INTRODUCTION: Epidermal metaplasia is a histological correlate to a white patch on the surface of a mucous membrane that cannot be rubbed off, known as leukoplakia. It is a common finding in oral mucosa, however rare in esophageal mucosa. Etiology of this condition in the esophagus is unclear, thought to be associated with esophageal tobacco and alcohol exposure or possibly an unusual response to chronic acid reflux. In contrast to oral leukoplakia there is a female predominance. Although generally asymptomatic, symptom presentation can include dysphagia. Endoscopic features include slightly elevated whitish surface, which can be translucent or cobblestone-like in appearance. The natural history is unknown though there is concern for an increased risk of squamous cell cancer. Due to paucity of published studies about this condition, we aim to report a case treated with endoscopic submucosal dissection (ESD). CASE DESCRIPTION/METHODS: A 64-year-old Caucasian man with a history of tobacco use and stable weight, presented to Gastroenterology clinic due to an 11-month history of solid food esophageal dysphagia. Physical examination was unremarkable. Upper endoscopy demonstrated white plaques at the gastroesophageal junction (Figure 1A and B). Biopsies obtained from this abnormality showed esophageal epidermoid metaplasia consistent with leukoplakia and mild patchy active chronic inflammation. GMS stain for fungal organisms was negative. An ESD procedure was planned, due to lesion size to ensure complete removal. Chromoscopy with methylene blue was used to mark the borders of the lesion and ESD was accomplished without adverse events (Figure 1C). Histologic examination confirmed hyperplastic squamous esophageal mucosa with marked hyperkeratosis without dysplasia and negative margins. During 2 year follow up, patient reported complete resolution of his dysphagia. DISCUSSION: The management strategy for esophageal leukoplakia is not well defined though reports suggest that endoscopic resection and surveillance are warranted. Here we represent a case where symptoms resolved and the lesion was completely removed by ESD.

INTRODUCTION: Volumetric laser endomicroscopy (VLE) is a high-resolution imaging modality used in Barrett’s esophagus (BE) surveillance. Established VLE scoring systems use a combination of features to guide BE dysplasia diagnosis but it remains unclear whether these features are sufficient to reach optimal VLE diagnostic performance. This study explores an exhaustive list of VLE features using one-to-one imaging to pathology correlation to develop optimal VLE diagnostic models for BE dysplasia. METHODS: In this prospective, multi-center (5 sites) study, patients with dysplastic BE underwent VLE with laser targeted regions of interest (ROIs), followed by standard surveillance endoscopy and biopsy directed to laser-marked sites. Histology was reviewed by two GI pathologists (MV, RO) who achieved a consensus diagnosis (gold-standard). ROIs were dysplastic if low-grade dysplasia (LGD), high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) was present. Two VLE experts (CLL, GJT) reviewed ROIs and corresponding endoscopic images to identify and define a set of VLE features associated with BE dysplasia. A multi-variable logistic regression model based on least absolute shrinkage and selection operator (LASSO) method was developed to determine the optimal diagnostic performance of these features. A decision tree model with high clinical usability also was developed to evaluate VLE diagnostic performance for real-time image interpretation. RESULTS: A total of 461 VLE ROIs with matching histology were obtained from 150 patients (Table 1). A final dataset of 55 neoplastic (LGD, 12; HGD, 24; IMC, 19) and 56 randomly selected non-dysplastic ROIs were reviewed. Twenty-eight VLE features were identified describing layering, signal intensity, surface topography, and glandular characteristics. LASSO logistic regression modeling identified 5 VLE features which when utilized optimized diagnostic performance with an area under the curve (AUC) for BE dysplasia of 0.95 (Figure 1). To improve clinical usability, a decision tree model was optimized to three levels with an AUC of 0.90 (Figure 2). CONCLUSION: This study represents the most comprehensive review of VLE features associated with BE dysplasia to date. The proposed high-performing diagnostic models suggest that VLE can be used efficiently and effectively to enhance BE surveillance by identifying ROIs for targeted biopsy. Further validation of the proposed VLE models will determine their clinical utility.