• The Korea Journal of Herbology
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• v.36 no.3
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• pp.1-8
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• 2021

Objective : Reflux esophagitis (RE), one of gastroesophageal reflux disease (GERD), is a disease that causes inflammation due to reflux of stomach contents such as stomach acid and pepsin due to the unstable gastroesophageal sphincter, and is currently increasing worldwide. The currently used treatment for reflux esophagitis has various side effects. Therefore, in this study the effect of Toosendan Fructus extract on chronic acid reflux esophagitis in rats was evaluated in order to find a new treatment material for reflux treatment. Methods : After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks; Normal rats (Normal, n=8), chronic acid reflux esophagitis rats (Control, n=8), Toosendan Fructus 200 mg/kg body weight/day-treated chronic acid reflux esophagitis rats (TF, n=8). After, we were taken esophageal tissue and esophageal mucosa damage was identified, and analyzed the expression of NADPH oxidase, AP-1/MAPK-related proteins, and tight junction proteins by western blot in esophageal tissue. Results : Toosendan Fructus administration significantly protected the esophageal mucosal damage of reflux esophagitis. Also, Toosendan Fructus significantly reduced the expression of NADPH oxidases (NOX2 and p22^phox) and AP-1/MAPK-related proteins (c-Fos, c-Jun, p-p38, p-ERK, and p-JNK). In addition, it significantly increased the expression of tight junction proteins (Occludin, Claudin-3, and Claudin-4). Conclusions : These results suggest that Toosendan Fructus reduced damage to the esophageal mucosa by protecting the esophageal mucosa by upregulating tight junctions proteins as well as inhibiting the AP-1/MAPK pathway through reducing NADPH oxidases expression.

• Journal of Medicine and Life Science
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• v.21 no.2
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• pp.49-52
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• 2024

Massive gastric mucosal ruptures during upper gastrointestinal endoscopy in patients with esophageal hiatal hernias are rare. However, tearing of the gastric mucosa alone, without tearing of the gastroesophageal junction, is even rarer. This study reports a case of a large mucosal rupture that occurred on the posterior wall of the upper body of the stomach during upper gastrointestinal endoscopy in an 83-year-old woman with an esophageal hiatal hernia while sedated. The patient was treated with endoclips for the rupture.

• Journal of Gastric Cancer
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• v.23 no.2
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• pp.289-302
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• 2023

Purpose: Liver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM-) LM at baseline. Materials and Methods: Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM-: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM-: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan-Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM- subgroups was analyzed using the Cox regression model with reported interaction P-values. Results: The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM- (OS HR, 0.71 [LM+] vs. 0.88 [LM-]; PFS HR, 0.47 [LM+] vs. 0.76 [LM-]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05). Conclusions: RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.

• Herbal Formula Science
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• v.31 no.4
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• pp.389-413
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• 2023

Objectives : This study aimed to review the current trends in experimental studies on the use of natural products for treatment of gastroesophageal reflux disease (GERD). Methods : Experimental studies assessing the efficacy of natural products against GERD were searched on PubMed. Articles were selected based on predefined inclusion and exclusion criteria and then analyzed for experimental methods, interventions, and result analysis techniques. Results : A total 37 studies were included in this review. Predominantly, in vivo experiments were conducted to induce GERD through surgery, involving the ligation of the pylorus and the transitional junction between the corpus and the forestomach using 7-week-old male Sprague-Dawley rats. The acute induction model, sacrificing animals after a single administration following GERD induction, was mainly used.The utilization of cell experiments was relatively infrequent, with a focus on assessing antioxidant and anti-inflammatory effects via the treatment of the RAW 264.7 cell line with lipopolysaccharides treatment. Glycyrrhizae Radix et Rhizoma, Pinelliae Tuber, Ginseng Radix and Zingiberis Rhizoma were used as single ingredients, and herbal formula, STW-5 (iberogast), Rikkunshito (六君子湯), Banhasasim-tang (半夏瀉心湯), and Hewei Jiangni granule (和胃降逆湯) were used. Outcome analysis methods encompassed Macroscopic evaluation, esophageal function assessment, blood biomarker analysis, histological examination, protein analysis, gene expression analysis, and gastric juice analysis. Proton pump inhibitors were predominantly employed as positive controls. Conclusions : This study revealed the current trends in non-clinical research evaluating natural products for GERD. Based on the results of this study, we expect that non-clinical research on clinically effective natural products will be revitalized.

• Journal of Chest Surgery
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• v.34 no.10
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• pp.763-768
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• 2001

Background: The high pressure zone(HPZ) at the gastroesophageal junction is an important barrier for prevention of gastroesophageal reflux. Smooth muscle layers in the lower esophageal sphincter mainly contributes to HPZ at the throacoabdominal junction. The purpose of this study was to investigate the manometric characteristics of the thora-coabdominal junction in patients after surgical removal of the lower esophageal sphincter. Material and Method: Twenty two patients with prior esophagogastrectomy(10 Ivor-Lewis method and 12 left thoracotomy) and 30 normal adults(control group) were studied manometrically. Result: Esophageal manometry showed a HPZ and pressure inversion points distal to the anastomosis in 12 of 22 patients(2 of 10 patients with Ivor-Lewis method and 10 of 12 patients with left thoracotomy) and a HPZ in 30 of 30 normal adults. The location of HPZ front nostril was not significant different between the two groups(42.5$\pm$0.9cm in patients and 43.9$\pm$2.1cm in the control), while the length of HPZ was shorter in patients than in the control(2.13$\pm$0.6cm vs 2.83$\pm$0.59cm). By SPT and RPT, pressures of HPZ at rest were lower in patients(13.78$\pm$1.63mmHg, 28.58$\pm$6.06mmHg) than in control(20.3$\pm$4.95mmHg, 42.80$\pm$15.91mmHg). The HPZ relaxed partially in response to deglutition(84.4% in patient, 90.5% in control group) and contracted in response to increased intra- abdominal pressure induced by leg lifts(HPZ/ Intra-abdominal pressure= 1.81$\pm$0.23 in patient, 2.13$\pm$ 0.58 in control group).

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.349-359
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• 2020

Gastroesophageal reflux disease (GERD) is a disease that stomach contents continually refluxing, and is currently on the rise worldwide. The purpose of this study is to find natural materials that can reduce side effects and effectively treat chronic acid reflux esophagitis (CARE), one of GERD. First, the antioxidant activity was confirmed by varying the mixing ratio of Coptidis Rhizoma and Evodiae Fructus, which are effective against chronic reflux esophagitis. After, animal experiments were conducted using a 1:1 (CE) and 1:2 (CEE) combination ratio of Coptidis Rhizoma and Evodiae Fructus, which had the best antioxidant efficacy. Gross lesion of esophageal mucosa after CE or CEE treatment showed a superior enhancement compared with that of CARE control rats. Additionally, its inhibited MAPK phosphorylation and led NF-κB inactivation through the suppression of IκBα phosporylation by regulating Nrf2/Keap-1, and NF-κB inactivation induced reduced protein expressions including inflammatory mediators and cytokines. Moreover, its improved esophageal barrier function through upregulating protein expressions of tight junction protein, whereas downregulating protein expressions of MMPs. Taken together, a mixture of Coptidis Rhizoma and Evodiae Fructus can attenuate the esophageal mucosal ulcer by inhibiting MAPK and NF-κB pathway, and upregulating proteins associated with tight junction.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.3
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• pp.209-213
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• 2018

Most solitary gastrointestinal (GI) polyps in children are either inflammatory or hamartomatous. Solitary hyperplastic polyp, sentinel polyp and solitary adenomatous polyp have been occasionally diagnosed in adults, but very rarely reported in Korean children. We recently came across a case with adenomatous polyp in the colon, a case with hyperplastic polyp beneath the gastroesophageal junction, a case with hyperplastic polyp in the prepyloric area, and a case with sentinel polyp in the distal esophagus, which are unusual pathologic types in children. These mucosal lesions were diagnosed incidentally during elective endoscopic examinations for GI symptoms. Most polyps do not cause significant symptoms, so the diagnosis might be delayed, especially in children, in whom GI endoscopy is not commonly performed for screening purpose as in the adults.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.143-148
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• 2004

Purpose: To determine the clinical value of the Siewert classification for gastic-cancer patients in Korea, we evaluated and compared the clinicopathologic factors of type II and type III cancer. Materials and Methods: The medical records of 89 consecutive patients who had undergone surgery for an adenocarcinoma of the gastroesophageal junction (GEJ) at the Department of Surgery, Hanyang University Hospital, between Jun. 1992 and Dec. 2003 were reviewed retrospectively. Results: There were one patient with type I, 12 pateints with type II and 77 patients with type III. During the same period, 1,341 patients underwent surgery for a gastric carcinoma, so proportion of GEJ cancer being $6.6\%$. The median followup duration was 31 months (range: $2\∼135$ months), and the follow-up rate was $100\%$. Between type II and type III cancers, there were no significant differences in the clinicopathologic variables including age, sex, gross appearance, histologic type, depth of invasion, and pathologic stage. The longest diameter of the tumor was larger in type III ($6.1\pm2.1$ cm) than in type II ($3.9\pm1.1$ cm)(P=0.001). A total gastrectomy with Roux-en-Y esophagojejunostomy was done most frequently, while jejunal interposition was done in 3 cases of type II and 2 cases of type III. More than a D2 lymphadenectomy was done all cases. The numbers of dissected lymph nodes and metastatic lymph nodes in type II were 43.8 and 5.8 respectively, while they were 49.8 and 8.1 in type III, but the difference between the two groups were not statistically significant. The mean length of the proximal resection margin was $15\pm5$ mm in type II and $21\pm13$ mm in type III, but this difference was not statistically significanct. The time to recurrence after operation was 19.3 months in type II and 16.9 months in type III. The five-year survival rates of type II and III were $68.8\%\;and\;52.7\%$ respectively, but difference was not significant. Conclusion: There were no significant differences in the clinicopathologic variables, including survival rate, between type II and type III cancers in Korean patients According to these findings, it appears to be reasonable to classify type III cancer as a cardia cancer in a broad sense.

• Journal of Gastric Cancer
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• v.17 no.2
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• Journal of Gastric Cancer
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• v.24 no.3
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• pp.267-279
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• 2024

Purpose: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. Materials and Methods: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. Results: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients. All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients. Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. Conclusions: Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.