Sanren Lin

Three aromatic amino acids in gastric juice as potential biomarkers for gastric malignancies

For screening early-stage gastric malignancies, the existing serum biomarkers have limited sensitivity and specificity. Gastric juice biomarkers are scarce and require further investigation. We divided this study on searching potential biomarkers into four parts: (1) detection of differential fluorescence spectrum and peaks in the gastric juice from patients using fluorescence spectroscopy and HPLC, (2) identification and validation of differential peaks using LC/MS and NMR, (3) quantification of potential biomarkers, and (4) establishment of diagnostic detection. The fluorescence intensity (FI), tyrosine, phenylalanine, tryptophan and total protein content were significantly higher in the gastric juice of patients with gastric malignancies (all P<0.01). With all P<0.001, the areas under the receiver operating characteristic curves of the biomarkers were tyrosine, 0.838; phenylalanine, 0.856; and tryptophan, 0.816. At a specificity of 79.4%, the sensitivity for gastric malignancy detection with phenylalanine was 87.9% only. Aromatic amino acids in gastric juices could be used as potential diagnostic biomarkers to screen gastric malignancies. It is a less-invasive and economical method compared to gastric biopsy.

High Levels of Aromatic Amino Acids in Gastric Juice during the Early Stages of Gastric Cancer Progression

Background Early-stage gastric cancer is mostly asymptomatic and can easily be missed easily by conventional gastroscopy. Currently, there are no useful biomarkers for the early detection of gastric cancer, and their identification of biomarkers is urgently needed. Methods Gastric juice was obtained from 185 subjects that were divided into three groups: non-neoplastic gastric disease (NGD), advanced gastric cancer and early gastric cancer (EGC). The levels of aromatic amino acids in the gastric juice were quantitated using high-performance liquid chromatography. Results The median values (25th to 75th percentile) of tyrosine, phenylalanine and tryptophan in the gastric juice were 3.8 (1.7–7.5) µg/ml, 5.3 (2.3–9.9) µg/ml and 1.0 (0.4–2.8) µg/ml in NGD; 19.4 (5.8–72.4) µg/ml, 24.6 (11.5–73.7) µg/ml and 8.3 (2.1–28.0) µg/ml in EGC. Higher levels of tyrosine, phenylalanine and tryptophan in the gastric juice were observed in individuals of EGC groups compared those of the NGD group (NGD vs. EGC, P<0.0001). For the detection of EGC, the areas under the receiver operating characteristic curves (AUCs) of each biomarker were as follows: tyrosine, 0.790 [95% confidence interval (CI), 0.703–0.877]; phenylalanine, 0.831 (95% CI, 0.750–0.911); and tryptophan, 0.819 (95% CI, 0.739–0.900). The sensitivity and specificity of phenylalanine were 75.5% and 81.4%, respectively, for detection of EGC. A multiple logistic regression analysis showed that high levels of aromatic amino acids in the gastric juice were associated with gastric cancer (adjusted β coefficients ranged from 1.801 to 4.414, P<0.001). Conclusion Increased levels of tyrosine, phenylalanine and tryptophan in the gastric juice samples were detected in the early phase of gastric carcinogenesis. Thus, tyrosine, phenylalanine and tryptophan in gastric juice could be used as biomarkers for the early detection of gastric cancer. A gastric juice analysis is an efficient, economical and convenient method for screening early gastric cancer development in the general population.

The feasibility of light microscopic measurements of intercellular spaces in squamous epithelium in the lower-esophagus of GERD patients

The study aims to determine whether light microscopy can be used to accurately measure the diameters of intercellular spaces between squamous epithelial cells in the lower esophagus, and whether changes in this outcome measure can be used as a diagnostic marker for gastroesophageal reflux disease (GERD). The study has two parts. Part 1 involves 42 asymptomatic controls and 119 patients with typical symptoms of GERD, including 58 with erosive esophagitis (EE), and 61 patients with nonerosive gastroesophageal reflux disease (NERD). All biopsies were taken from the lower esophagus. All samples were observed using an immersion objective, after which diameters were measured by computer-assisted morphometry. Part 2 involves 61 individuals who were randomly selected from part 1, including 19 controls, 13 with NERD and 29 with EE. Diameter measurements using both light microscopy and transmission electron microscopy (TEM) were performed for samples of 61 individuals. Samples from a total of 61 individuals (31 male, 30 female, mean age 44.3 ± 16.0 years) were observed using both light microscopy and TEM. Both methods showed significant differences between control and disease groups; the outcomes from the two methods had a certain correlation (r = 0.605, P = 0.000). Morphometric analysis of all 161 individuals (83 males, 78 females, mean age 41.4 ± 15.7) showed mean diameters from light microscopy to be 0.58 ± 0.16 µm for controls, 1.07 ± 0.30 µm for NERD, and 1.29 ± 0.20 µm for EE; differences between control and disease groups were significant (P<0.05). The optimal cut-off value from receiver operator characteristic analysis was 0.85 µm. Diagnoses were validated using the combination of symptoms of GERD, endoscopy, and 24 h ambulatory pH monitoring as the gold standard. At the optimal cutoff, sensitivity was 93.3% and specificity was 100%. The diameters of the intercellular spaces in squamous epithelium of lower esophagus from controls and in patients with GERD can be quantitatively measured using light microscopy. Dilated diameters can serve as a sensitive, specific, and objective indicator for diagnosis of GERD.

Therapeutic Effect of Esophageal Foreign Body Extraction Management: Flexible versus Rigid Endoscopy in 216 Adults of Beijing

Background The aim of this study was to assess the effectiveness and complications of rigid endoscopy (RE) and flexible endoscopy (FE) for the extraction of esophageal foreign bodies (FB) in adults. Material/Methods A retrospective analysis was conducted on the medical records of 216 adult patients with esophageal FB impaction treated at Peking University Third Hospital, Beijing, China, between January 2008 and December 2012. Results The success rate of FB extraction was 100% (142/142) in patients treated with RE compared to 97.3% (72/74) in those treated with FE (P=0.045). The total incidence of complications in RE-treated patients was lower than that in FE-treated patients (28.2% vs. 45.9%, P=0.009), but the perforation rate was higher (5.6% vs. 1.4%, P=0.135). The incidences of total complications and perforation were associated with the duration of FB impaction in patients who underwent RE (both P<0.05) but not in patients who underwent FE. RE was more frequently used in extraction of FBs located in the upper esophagus (88.7%, 126/142) compared to FE (60.8%, 45/74) (P<0.05). The size of extracted FB was significantly larger in patients treated with FE compared to those treated with RE (P<0.05). Conclusions Both RE and FE were effective in the extraction of esophageal FB. However, the perforation rate and the need for general anesthesia were higher in RE-associated extraction. FE may be the preferred endoscopic treatment for the extraction of esophageal FB, except possibly for those impacted in the upper esophagus. FB extraction may produce better outcomes if endoscopy is employed early.

Diagnostic value of dilated intercellular space and histopathologic scores in gastroesophageal reflux disease

The aim of this paper is to investigate the diagnostic value of histopathologic score and the dilated intercellular space (DIS) in patients with gastroesophageal reflux disease (GERD) and functional heartburn (FH). Participants with GERD symptoms including reflux esophagitis, non-erosive reflux disease (NERD), Barretts esophagus (BE), functional heartburn (FH), along with a control group with atypical GERD-like symptom (Sym-C), and asymptomatic healthy volunteers (H-C) were administered GERD questionnaire, and subjected to endoscopy and biopsies, as well as 24-hour pH-impedance monitoring. Biopsies were evaluated using standards from the 2011 Esohisto Project after Hematoxylin-Eosin staining. DIS was measured quantitatively under light microscopy. Among the total of 565 participants with qualified biopsy specimens, the mean DIS of the reflux esophagitis (RE) group was significantly wider compared with the other five groups. DIS in patients with GERD-like symptoms was significantly wider compared with the H-C. No significant differences were observed between NERD and FH. Results from 24-hour pH-impedance monitoring indicated that only the DIS of patients with acid reflux or the amount of acid reflux episodes in patients with DIS was significantly wider compared with patients with nonacid reflux or patients without DIS (P < 0.001). With DIS = 0.9 μm as the cutoff value, the sensitivity and specificity were 62.6% and 54.1%, respectively. Using the total histopathologic score > 3 as the diagnostic criterion, the sensitivity and specificity were 71.7% and 47.4%. DIS is closely associated with GERD and acid reflux. The diagnostic value of histological scores in lower esophagus in GERD is very similar to that of the quantitative measurement of DIS.

The Diagnostic Value of Combining DNA Promoter Hypermethylation With Autofluroscene Spectrum Analysis of Gastric Juice in Gastric Cancer

Gastric cancer is one of the most common neoplasms, ranking as the second leading cause of cancer-related deaths worldwide. The predominant factor associated to gastric cancer is Helicobacter pylori infection, which leads to a chronic inflammatory response and subsequent oxyntic atrophy. Parietal cell loss result in two types of metaplasia, the intestinal metaplasia (IM) characterized by the presence of cells with goblet cell morphology and spasmolytic polypeptide-expressing metaplasia (SPEM) that shows morphological characteristics of the deep antral glands and express trefoil factor 2 (spasmolytic polypeptide). Although metaplastic lesions are considered neoplastic precursors, their direct association to cancer is still in debate. Similar to other cancers, gastric cancers are marked by global gene expression alterations. MicroRNAs (miRNAs) are small noncoding RNAs involved in the post-transcriptional regulation of gene expression and an increasing number of studies has been showing their aberrant expression in cancer. In order to identify miRNAs involved in the early stages of gastric cancer we performed a miRNA profiling on laser capture micro-dissected IM and SPEM cells from patient lesions. Using a qRT-PCR approach for quantitation of 754 human miRNAs, we identified 77 miRNAs differentially expressed in the metaplastic samples (greater than two-fold) in comparison to normal chief cells. The highest number of dysregulated miRNAs was observed in IM,which showed 45 up-regulated and 25 down-regulatedmiRNAs. In SPEM, 28 miRNAs were found up-regulated (21 of them also up-regulated in IM), whereas no down-regulation was detected. Some of the up-regulated miRNAs have already been associated to cancer in general (miR-26-a, miR-191, miR-155), as well as specifically to gastric cancer (miR-18b, miR-196b and miR-106a). However, the regulation of some of the top up-regulated miRNAs revealed here including miR-802, miR-922 and miR-622 are still poorly characterized in cancer. In a comparison with a previous mRNA profiling study performed on a similar group of samples, we observed that 108 out of the 568 mRNAs found up-regulated in IM are predicted targets of the 26 microRNAs down-regulated in IM, revealing a potential mechanism for the regulation of those genes in gastric metaplasia. Particularly interesting are 4 members of the miR-30 family, with 31 predicted mRNA targets amongst those up-regulated in IM. Although miR-30 family members have been described as down-regulated in gastric cancer, no data on their targets in this neoplasia is currently available. An extended characterization of the microRNAs identified here will provide a better understanding of their function in gastric metaplasia and progression to neoplasia, as well as might reveal useful early stage biomarkers or therapeutic targets.