Emily J. Lloyd

Sep70/Pepsin expression in hypopharynx combined with hypopharyngeal multichannel intraluminal impedance increases diagnostic sensitivity of laryngopharyngeal reflux

BackgroundImproved methods of diagnosis of laryngopharyngeal reflux (LPR) would enable surgeons to better identify patients who may benefit from antireflux surgery (ARS). The objective of the present study was to assess if hypopharyngeal Pepsin and Sep70 expression combined with hypopharyngeal multichannel intraluminal impedance (HMII) has the potential to increase diagnostic sensitivity of LPR.MethodsThis study was performed on patients who underwent unsedated transnasal endoscopy with hypopharyngeal biopsy and 24-h HMII to determine abnormal proximal exposure (APE) and DeMeester score (DMS) from 2013 to 2016. Pepsin and Sep70 protein expression was assessed by Western blots of biopsy specimens. The outcomes of ARS were assessed using reflux symptom index (RSI). HMII APE classification, Sep 70, and Pepsin protein levels were compared in normative and symptomatic LPR patients and further analyzed alongside quality of life changes following ARS.ResultsOf 30 subjects enrolled, 23 were excluded for abnormal HMII results or endoscopic evidence of esophagitis. Seven subjects and 105 patients were included in the normative and symptomatic groups, respectively. Compared to the normative group, only Pepsin expression was significantly higher in the symptomatic group [APE+/LPR+ (p = 0.000), APE+/LPR− (p = 0.001), and APE− (p = 0.047)]. Further, the ratio of Sep70/Pepsin was significantly lower in the symptomatic group [APE+/LPR+ (p = 0.008), APE+/LPR− (p = 0.000), and APE− (p = 0.050)], and a cutoff ratio for a diagnosis of LPR was established as < 158. Of 105 symptomatic patients, 48 patients underwent ARS. Of these, 17 patients had complete pre- and post-RSI questionnaires. LPR symptoms improved in 15 (88%), of whom 2 were APE− but met criteria for a diagnosis of LPR based on the Sep70/Pepsin cutoff.ConclusionsThe identified Sep70/Pepsin ratio may serve as a reliable biomarker for the diagnosis of LPR. As a result, this may help identify additional patients who have a false-negative HMII result due to the 24-h testing window.

223 Evaluation of Post-Transoral Endoscopic Circumferential Resection Esophageal Biopsies With p53 Staining

(16.2%) showed low TSR (<0.50). There was significant inverse association (P = .020) between TSR and tumor grade. Low TSR value was found in 3.5% (3/86) of the non-invasive tumors and 35.7% (5/14) of invasive tumors. A highly significant inverse relation was found between TSR and bladder muscle invasion (P < .001). Conclusions: Low TSR was found to be significantly associated with high-grade tumors and muscle invasion, thus, making this a parameter of poor prognostic value.

High yield reproducible rat model recapitulating human Barrett's carcinogenesis

AIM To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma (EAC) using the modified Levrat model of end-to-side esophagojejunostomy. METHODS End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10 (n = 6), 17 (n = 8), 24 (n = 9), 31 (n = 6), 38 (n = 6), and 40 (n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation was completed to determine respective rates of carcinogenic development. Quantitative reverse transcription-polymerase chain reaction was performed to determine gene expression levels of MUC2, CK19, and CK20, and results were compared to determine significant differences throughout disease progression stages. RESULTS The overall study mortality was 15%. Causes of mortality included anastomotic leak, gastrointestinal hemorrhage, stomach ulcer perforation, respiratory infection secondary to aspiration, and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery, 100% of animals presented with esophagitis. Barrett’s esophagus (BE) was first observed at 10 wk, and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk, and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition, two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine, respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC. CONCLUSION Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden, which may facilitate broader adoption to study EAC development, progression, and therapeutics.