Detection of Early Adenocarcinoma of the Esophagogastric Junction by Spraying an Enzyme-Activatable Fluorescent Probe Targeting Dipeptidyl Peptidase-IV

Abstract Background: It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). Methods: Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. Results: Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7%, 85.7%, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. Conclusions: Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.

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Detection of Early Adenocarcinoma of the Esophagogastric Junction by Spraying an Enzyme-Activatable Fluorescent Probe Targeting Dipeptidyl Peptidase-IV

10.21203/rs.2.14772/v1 ◽

2019 ◽

Author(s):

Keiko Yamamoto ◽

Shunsuke Ohnishi ◽

Takeshi Mizushima ◽

Junichi Kodaira ◽

Masayoshi Ono ◽

...

Keyword(s):

Intestinal Metaplasia ◽

Fluorescent Probe ◽

Fluorescence Imaging ◽

Esophagogastric Junction ◽

Dipeptidyl Peptidase ◽

Clinical Samples ◽

Specific Sequence ◽

Dpp Iv ◽

Early Adenocarcinoma ◽

Sensitivity Specificity

Abstract Background: It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). Methods: Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. Results: Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7%, 85.7%, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. Conclusions: Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.

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Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV

BMC Cancer ◽

10.1186/s12885-020-6537-9 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Keiko Yamamoto ◽

Shunsuke Ohnishi ◽

Takeshi Mizushima ◽

Junichi Kodaira ◽

Masayoshi Ono ◽

...

Keyword(s):

Fluorescent Probe ◽

Esophagogastric Junction ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Early Adenocarcinoma

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Confocal Laser Endomicroscopy vs Biopsies in the Assessment of Persistent or Recurrent Intestinal Metaplasia/Neoplasia after Endoscopic Treatment of Barrett’s Esophagus related Neoplasia

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld-2467 ◽

2020 ◽

Vol 29 (3) ◽

pp. 305-312

Author(s):

Jana Krajciova ◽

Marek Kollar ◽

Jana Maluskova ◽

Martin Janicko ◽

Zuzana Vackova ◽

...

Keyword(s):

Intestinal Metaplasia ◽

Barrett’S Esophagus ◽

Endoscopic Treatment ◽

Barrett's Esophagus ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Low Grade ◽

Predictive Values ◽

Early Adenocarcinoma ◽

Sensitivity Specificity

Background and Aims: Patients after endoscopic treatment of Barrett‘s esophagus (BE) related neoplasia (BORN) should enter endoscopic surveillance with biopsies to detect persistent or recurrent neoplasia or intestinal metaplasia (IM). Probe-based confocal laser endomicroscopy (pCLE) serves as a virtual biopsy and could replace standard biopsies. However, the role of pCLE in patients after endoscopic treatment of BORN has not been systematically assessed. The aim of this study was to compare pCLE with biopsies in detecting persistent/recurrent IM/neoplasia. Methods: A single center, prospective and pathologist-blinded study was performed. Patients after endoscopic treatment of BORN (endoscopic resection or dissection, radiofrequency ablation) underwent surveillance endoscopy with pCLE followed by biopsies. Results: A total of 56 patients were enrolled: initial diagnoses were low-grade dysplasia (LGD) in 24 patients (43%), high-grade dysplasia (HGD) in 12 patients (21%) and early adenocarcinoma (EAC) in 20 patients (36%). Only one patient (2%) experienced recurrent neoplasia (LGD), which was diagnosed by pCLE only. Twenty patients (35.7%) experienced persistent/recurrent IM, diagnosed by both pCLE and biopsies in 17 patients (17/30, 85%) and by pCLE only in 3 pts (3/30, 15%). Sensitivity, specificity, positive and negative predictive values to diagnose recurrent/persistent IM did not differ significantly between pCLE and biopsies; diagnostic accuracy was 100% (95%CI 93.6-100) for pCLE and 94.6 (95%CI 85.1-98.9%) for biopsies, p=0.25. In patients with IM detected by both tested methods, pCLE detected significantly more goblet cells (median 43 per patient) than biopsies (median 12 per patient), p=0.01. Conclusion: pCLE is at least as effective as standard biopsies in the detection of persistent/recurrent IM after endoscopic treatment of BORN.

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Tu1939 FLUORESCENCE IMAGING OF EARLY ADENOCARCINOMA OF THE ESOPHAGOGASTRIC JUNCTION BY TOPICALLY SPRAYING PROBE TARGETING DIPEPTIDYLPEPTIDASE-IV

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2019.03.1083 ◽

2019 ◽

Vol 89 (6) ◽

pp. AB624

Author(s):

Keiko Yamamoto ◽

Shunsuke Ohnishi ◽

Takeshi Mizushima ◽

Junichi Kodaira ◽

Masayoshi Ono ◽

...

Keyword(s):

Fluorescence Imaging ◽

Esophagogastric Junction ◽

Dipeptidylpeptidase Iv ◽

Early Adenocarcinoma

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Dipeptidyl Peptidase IV Inhibitors for Nonalcoholic Fatty Liver Disease – Systematic Review and Metanalysis

Current Diabetes Reviews ◽

10.2174/1573399816999201110195634 ◽

2020 ◽

Vol 16 ◽

Author(s):

Lucas Ribeiro dos Santos ◽

Marcio Luis Duarte ◽

Maria Stella Peccin ◽

Antônio Ricardo de Toledo Gagliardi ◽

Tamara Melnik

Keyword(s):

Hepatic Steatosis ◽

Grey Literature ◽

Specific Treatment ◽

Reducing Power ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Cochrane Library ◽

Vast Number ◽

Dpp Iv ◽

Dipeptidyl Peptidase Iv Inhibitors

Introduction:: Hepatic steatosis is a frequent condition, that afflicts, especially, obese and insulin resistant patients; diagnosis is made, usually, through imaging tests. Despite the high prevalence and risk of complications, there is no specific treatment approved, though a vast number of medications have been tested. Objective:: To determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP-IV) in the treatment of NAFLD. Methods:: We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE and LILACS, as well as reference lists of the included studies and grey literature; 9 studies were selected for inclusion. Results:: 7 studies were used for metanalysis, for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83 [95% CI 35.23 to 13.57] at 3 months and MD -9.27 [95% CI 10.92 to -7.62] at 6 months of intervention, as well as reduction of hepatic steatosis via MRI of SMD 0.10 [95% CI 0.31 to 0.50]; the overall incidence of adverse events was very low. The studies were considered of low and very low quality by the GRADE evaluation. Conclusion:: Because of the poor overall quality of the studies and heterogeneity of the population analyzed, i DPP-IV did not show efficacy on inflammatory markers or fibrosis in patients with NAFLD.

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512 Confirmatory Factor Analysis of the Sleep Inertia Questionnaire in a Clinical Sample with Sleep Disorders

SLEEP ◽

10.1093/sleep/zsab072.511 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A201-A202

Author(s):

Kristina Puzino ◽

Susan Calhoun ◽

Allison Harvey ◽

Julio Fernandez-Mendoza

Keyword(s):

Factor Analysis ◽

Confirmatory Factor Analysis ◽

Construct Validity ◽

Sleep Disorders ◽

Goodness Of Fit ◽

Criterion Validity ◽

Clinical Samples ◽

Sleep Inertia ◽

Confirmatory Factor ◽

Sensitivity Specificity

Abstract Introduction The Sleep Inertia Questionnaire (SIQ) was developed and validated in patients with mood disorders to evaluate difficulties with becoming fully awake after nighttime sleep or daytime naps in a multidimensional manner. However, few data are available regarding its psychometric properties in clinical samples with sleep disorders. Methods 211 patients (43.0±16.4 years old, 68% female, 17% minority) evaluated at the Behavioral Sleep Medicine (BSM) program of Penn State Health Sleep Research & Treatment Center completed the SIQ. All patients were diagnosed using ICSD-3 criteria, with 111 receiving a diagnosis of chronic insomnia disorder (CID), 48 of a central disorder of hypersomnolence (CDH), and 52 of other sleep disorders (OSD). Structural equation modelling was used to conduct confirmatory factor analysis (CFA) of the SIQ. Results CFA supported four SIQ dimensions of “physiological”, “cognitive”, “emotional” and “response to” (RSI) sleep inertia with adequate goodness-of-fit (TLI=0.90, CFI=0.91, GFI=0.85, RMSEA=0.08). Internal consistency was high (α=0.94), including that of its dimensions (physiological α=0.89, cognitive α=0.94, emotional α=0.67, RSI α=0.78). Dimension inter-correlations were moderate to high (r=0.42–0.93, p<0.01), indicating good construct validity. Convergent validity showed moderate correlations with Epworth sleepiness scale (ESS) scores (r=0.38) and large correlations with Flinders fatigue scale (FFS) scores (r=0.65). Criterion validity showed significantly (p<0.01) higher scores in subjects with CDH (69.0±16.6) as compared to those with CID (54.4±18.3) or OSD (58.5±20.0). A SIQ cut-off score ≥57.5 provided a sensitivity/specificity of 0.77/0.65, while a cut-off score ≥61.5 provided a sensitivity/specificity of 0.71/0.70 to identify CDH vs. ESS<10 (AUC=0.76). Conclusion The SIQ shows satisfactory indices of reliability and construct validity in a clinically-diverse sleep disorders sample. Its criterion validity is supported by its divergent association with hypersomnia vs. insomnia disorders, as well as its adequate sensitivity/specificity to identify patients with CDH. The SIQ can help clinicians easily assess the complex dimensionality of sleep inertia and target behavioral sleep treatments. Future studies should confirm the best SIQ cut-off score by including good sleeping controls, while clinical studies should determine its minimal clinically important difference after pharmacological or behavioral treatments. Support (if any):

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