Faculty Bibliography

BACKGROUND AND AIMS/OBJECTIVE:Palliation of dysphagia associated with advanced esophageal cancer is challenging. Previous studies suggest liquid-nitrogen spray cryotherapy (LNSC) is effective to palliate obstructive esophageal cancer. We sought to prospectively examine the utility, safety, and efficacy of serial applications of repeated palliative LNSC in this population. METHODS:We performed a prospective cohort trial of LNSC for persistent esophageal cancer without the possibility of resection for palliation of obstructive symptoms. We used repeated measures and competing risks analyses to study the course of patients treated over two years. Efficacy of treatment was assessed using quality-of-life scores 14 days after treatment, using general cancer (QLQ-C30) and esophageal cancer-specific (QLQ-OES18) quality-of-life questionnaires, as well as ordinal dysphagia scores. Complications were assessed using structured interviews and classified according to Common Terminology Criteria. RESULTS:On repeated treatments, each participant (N = 49) improved their QLQ-C30 score by a mean 1.7 (95% confidence interval (CI) 0.1 - 3.3) and improved their QLQ-OES18 score by a mean 1.8 (95% CI 0.4-3.3). For each subsequent round of treatment, the effect improved 0.1 (95% CI 0.3-0.4) for the QLQ-C30 score and worsened -0.2 (95% CI -0.5 - 0.2) for QLQ-OES18 score. There was no signifcant improvement in the ordinal dysphagia score. 19 (39.6%) of 48 participants with a feedng tube at baseline required a feeding tube or stent at a mean of 8 months. While unrelated serious adverse events were common (38.8%), only two patients had events possibly related to LNSC (4.1%, melena and dysphagia). CONCLUSIONS:Spray cryotherapy had a durable and repeatable benefit for palliation of obstructive symptoms of esophageal cancer and quality of life in the majority of patients, without the need for feeding tube or esophageal stent placement. Treatments were generally well-tolerated.

BACKGROUND:The diagnosis of Barrett's esophagus (BE) requires identification of goblet cells in esophageal columnar-lined epithelium. Forceps biopsies (FB) may miss goblet cells due to sampling error. Additionally, pathologists may misidentify distended pseudo-goblet cells as true goblet cells. CDX2 and MUC2 are molecules involved in BE pathogenesis. AIM/OBJECTIVE:To assess the utility of CDX2 and MUC2 immunohistochemistry in the diagnosis of BE. METHODS:We performed a prospective, community-based registry study of GERD patients undergoing endoscopy for BE screening. All patients underwent both FB and WATS3D. CDX2 and MUC2 immunohistochemistry were performed on WATS3D samples. We assessed concordance between CDX2 and MUC2 staining and goblet cells, on both WATS3D and FB. Operating characteristics of FB for diagnosing BE were calculated using MUC2 positivity and goblet cells on WATS3D as the gold standard. RESULTS:Of 35,265 patients enrolled, 11,040 (31.3%) met endoscopic criteria for BE. Of these, 8,464 (76.7%) were CDX2+ and 3,563 (32.3%) were MUC2+. Whereas there was almost perfect concordance between MUC2 positivity and goblet cells on WATS3D, only 65.4% of patients with goblet cells on FB were MUC2+ on WATS3D. When using MUC2+ and goblet cells on WATS3D as the reference standard, FB diagnosed BE with sensitivity of 46.3%, specificity 88.3%, PPV 65.4%, and NPV 77.5%. CONCLUSIONS:MUC2 immunohistochemistry may be more sensitive and specific for diagnosing BE than goblet cells by FB. FB misses approximately half of BE when using MUC2/WATS3D as an alternative gold standard. The addition of MUC2 immunohistochemistry may aid in the recognition of BE.

INTRODUCTION/BACKGROUND:Patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy for Barrett's esophagus (BE) frequently demonstrate columnar-lined epithelium, with forceps biopsies (FBs) failing to yield intestinal metaplasia (IM). Repeat endoscopy is then often necessary to confirm a BE diagnosis. The aim of this study was to assess the yield of IM leading to a diagnosis of BE by the addition of wide-area transepithelial sampling (WATS-3D) to FB in the screening of patients with GERD. METHODS:We performed a prospective registry study of patients with GERD undergoing screening upper endoscopy. Patients had both WATS-3D and FB. Patients were classified by their Z line appearance: regular, irregular (<1 cm columnar-lined epithelium), possible short-segment BE (1 to <3 cm), and possible long-segment BE (≥3 cm). Demographics, IM yield, and dysplasia yield were calculated. Adjunctive yield was defined as cases identified by WATS-3D not detected by FB, divided by cases detected by FB. Clinicians were asked if WATS-3D results affected patient management. RESULTS:Of 23,933 patients, 6,829 (28.5%) met endoscopic criteria for BE. Of these, 2,878 (42.1%) had IM identified by either FB or WATS-3D. Among patients fulfilling endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and absolute yield was 18.1%. One thousand three hundred seventeen patients (19.3%) who fulfilled endoscopic BE criteria had IM detected solely by WATS-3D. Of 240 patients with dysplasia, 107 (44.6%) were found solely by WATS-3D. Among patients with positive WATS-3D but negative FB, the care plan changed in 90.7%. DISCUSSION/CONCLUSIONS:The addition of WATS-3D to FB in patients with GERD being screened for BE resulted in confirmation of BE in an additional one-fifth of patients. Furthermore, dysplasia diagnoses approximately doubled.

INTRODUCTION/BACKGROUND:Studies have shown that dysplasia in Barrett's esophagus (BE) has a predilection for the right hemisphere. There is limited information on the longitudinal distribution. The aim was to determine both the longitudinal and circumferential distributions of dysplasia and early neoplasia from 3 prospective studies. METHODS:This is a pooled analysis from 3 prospective studies of patients with treatment-naive BE. Both circumferential and longitudinal locations (for BE segments greater than 1 cm) of dysplastic and early neoplastic lesions were recorded. RESULTS:A total of 177 dysplastic and early neoplastic lesions from 91 patients were included in the pooled analysis; of which 59.3% (n = 105) were seen on high-definition white light endoscopy, 29.4% (n = 52) on advanced imaging, and 11.2% (n = 20) with random biopsies. The average Prague score was C3M5. Of 157 lesions within BE segments greater than 1 cm, 49 (34.8%) lesions were in the proximal half, whereas 92 lesions (65.2%) were in the distal half (P < 0.001). The right hemisphere of the esophagus contained 55% (86/157) of the total lesions compared with 45% (71/157) for the left hemisphere (P = 0.02). This was because of the presence of high-grade dysplasia being concentrated in the right hemisphere compared with the left hemisphere (60% vs 40%, P = 0.002). DISCUSSION/CONCLUSIONS:In this pooled analysis of prospective studies, both low-grade dysplasia and high-grade dysplasia are more frequently found in the distal half of the Barrett's segment. This study confirms that the right hemisphere is a hot spot for high-grade dysplasia. Careful attention to these locations is important during surveillance endoscopy.

Choking remains a leading cause of accidental death and morbidity worldwide. Currently, there is no device to assist in the resuscitation of a choking victim when standard maneuvers fail. A novel portable non-powered suction device (LifeVac; LifeVac LLC, Nesconset, NY) has been developed and may have potential use in patients with oropharyngeal dysphagia who are at increased risk of choking. The device is FDA registered and distributed worldwide. This case series provides a summary of self-reported data regarding the use of the suction device in adult patients with oropharyngeal dysphagia during real-world choking emergencies recorded between January 2014 and July 2020. Over a 6-year monitoring period the device has been reported to be successful in the resuscitation of 38 out of 39 patients with oropharyngeal dysphagia during choking emergencies. Although the obstruction was removed with the device from the 39^th patient, resuscitation was not successful and he succumbed to his injuries. This portable, non-powered suction device may be useful in resuscitating patients with oropharyngeal dysphagia who are choking. The reported cases describe successful use of the device in real-world settings with minimal risk. Resuscitating patients with oropharyngeal dysphagia using this device may be a viable option when abdominal thrusts or back blows fail to resolve a choking emergency.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

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.
METHOD(S): 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.
RESULT(S): 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(S): 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

Background and aims/UNASSIGNED:Mutational load (ML) has been shown to help risk-stratify those that may progress from non-dysplastic Barrett's oesophagus (BE) to dysplastic disease. Management of patients with BE and indefinite for dysplasia (BE-IND) is challenging and risk stratification tools are lacking. The aim of this pilot study is to evaluate the utility of ML for risk stratification in patients with BE-IND. Methods/UNASSIGNED:This is a single-centre, retrospective pilot study evaluating ML quantification in patients with BE-IND. Histology at follow-up endoscopy at least 1 year after the baseline endoscopy was used to determine if a patient progressed to low or high dysplasia. The ML levels were then compared among patients who progressed to dysplasia versus those who did not. Results/UNASSIGNED:Thirty-five patients who met the inclusion criteria were identified, and seven met the exclusion criteria. Twenty-eight patients were analysed, of whom eight progressed to low-grade dysplasia (6) and high-grade dysplasia (2). Seven of these eight patients had some level of genomic instability detected in their IND biopsy (ML ≥0.5). Ten of the 20 (50%) who did not progress had no ML level. At an ML cut-off above 1.5, the risk of progression to high-grade dysplasia was 33% vs 0% (p=0.005), with a sensitivity of 100% and a specificity of 85%. Conclusion/UNASSIGNED:These results indicate that ML may be able to risk-stratify progression to high-grade dysplasia in BE-IND. Larger studies are needed to confirm these findings.