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1.
Gut Liver ; 18(1): 10-26, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37850251

ABSTRACT

With an aging population, the number of patients with difficulty swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. Long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach, aided endoscopically, which may be an alternative to a nasogastric tube when enteral nutritional is required for 4 weeks or more. This paper is the first Korean clinical guideline for PEG. It was developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tubes removal for PEG based on the currently available clinical evidence.


Subject(s)
Gastrostomy , Quality of Life , Humans , Aged , Enteral Nutrition , Intubation, Gastrointestinal , Endoscopy, Gastrointestinal
2.
World J Clin Cases ; 11(26): 6194-6199, 2023 Sep 16.
Article in English | MEDLINE | ID: mdl-37731566

ABSTRACT

BACKGROUND: Since fat does not transmit electrical energy well, delayed perforation and post-polypectomy syndrome due to electrical thermal injury are concerns in the endoscopic removal of colonic lipoma. The endoscopic submucosal dissection (ESD) technique concentrates electrical energy conducts to the submucosa, not the adipose tissue. This helps to minimize electrical thermal injury, especially in the case of large colonic lipomas. In rare cases, such as colonic lipomas accompanied by mucosal lesions, it is difficult for endoscopists to decide how to safely remove them. CASE SUMMARY: A 78-year-old man underwent colonoscopy for colorectal cancer screening. During colonoscopy, a yellowish submucosal tumor with positive cushion sign was observed in the ascending colon measuring about 4.5 cm. A nodular mucosal lesion of about 2.5 cm was observed on the mucosal surface of the lipoma. The lipoma was so large that it occupied much of the inside of the colon, making it difficult to see the entire laterally spreading tumor (LST) at once. The LST was confined to the surface of the lipoma, which had a semipedunculated shape with a wide neck. The margin of the LST was not observed at the neck of the lipoma. ESD was performed and the colonic lipoma with the LST was successfully removed without complications. After 3 d of hospitalization, the patient was discharged without any symptoms. The final pathology report showed that the lesion consisted of submucosal lipoma and tubulovillous adenoma with low-grade dysplasia. CONCLUSION: ESD is effective and safe for treating a large colonic lipoma with an LST by minimizing electrical thermal injury.

3.
Korean J Gastroenterol ; 82(3): 107-121, 2023 Sep 25.
Article in Korean | MEDLINE | ID: mdl-37743809

ABSTRACT

With an aging population, the number of patients with difficulty in swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. However, the long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach that is aided endoscopically and may be an alternative to a nasogastric tube when enteral nutritional is required for four weeks or more. This paper is the first Korean clinical guideline for PEG developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tubes removal for PEG based on the currently available clinical evidence.

4.
Clin Endosc ; 56(4): 391-408, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37430395

ABSTRACT

With an aging population, the number of patients with difficulty in swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. However, the long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach that is aided endoscopically and may be an alternative to a nasogastric tube when enteral nutritional is required for four weeks or more. This paper is the first Korean clinical guideline for PEG developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tube removal for PEG based on the currently available clinical evidence.

5.
Intest Res ; 21(1): 20-42, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36751043

ABSTRACT

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: adenoma ≥10 mm in size; 3 to 5 (or more) adenomas; tubulovillous or villous adenoma; adenoma containing high-grade dysplasia; traditional serrated adenoma; sessile serrated lesion containing any grade of dysplasia; serrated polyp of at least 10 mm in size; and 3 to 5 (or more) sessile serrated lesions. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.

6.
Clin Endosc ; 55(6): 703-725, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36225130

ABSTRACT

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for the management of advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: (1) adenoma ≥10 mm in size; (2) 3 to 5 (or more) adenomas; (3) tubulovillous or villous adenoma; (4) adenoma containing high-grade dysplasia; (5) traditional serrated adenoma; (6) sessile serrated lesion (SSL) containing any grade of dysplasia; (7) serrated polyp of at least 10 mm in size; and (8) 3 to 5 (or more) SSLs. More studies are needed to fully comprehend the patients most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.

7.
Korean J Gastroenterol ; 80(3): 115-134, 2022 09 25.
Article in Korean | MEDLINE | ID: mdl-36156035

ABSTRACT

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: 1) adenoma ≥10 mm in size; 2) 3-5 (or more) adenomas; 3) tubulovillous or villous adenoma; 4) adenoma containing high-grade dysplasia; 5) traditional serrated adenoma; 6) sessile serrated lesion (SSL) containing any grade of dysplasia; 7) serrated polyp of at least 10 mm in size; and 8) 3-5 (or more) SSLs. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.


Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Adenoma/diagnosis , Adenoma/pathology , Adenoma/surgery , Colonic Polyps/diagnosis , Colonic Polyps/epidemiology , Colonic Polyps/surgery , Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/surgery , Humans , Republic of Korea , Risk Factors
8.
Dig Dis Sci ; 67(7): 3158-3165, 2022 07.
Article in English | MEDLINE | ID: mdl-34383200

ABSTRACT

BACKGROUND AND AIM: Although colonoscopy has been widely performed in patients with end-stage renal disease (ESRD), studies on the safety of routine colonoscopy, including bowel preparation and sedation, in these patients are limited. This study aimed to investigate the safety of colonoscopy in patients with ESRD who underwent peritoneal dialysis (PD) or hemodialysis (HD). METHODS: We retrospectively reviewed 538 patients with ESRD who underwent colonoscopy between 2010 and 2020. We compared the incidence of adverse events (AEs) between the ESRD group and a propensity score-matched control group of healthy adults. Cardiovascular/pulmonary and procedure-related AEs were analyzed. We also compared the rates of AEs between patients who underwent PD or HD. RESULTS: The overall rate of AEs was 5.7% in patients with ESRD, which was significantly higher than that in healthy adults (0.6%, P < 0.001). All AEs were cardiovascular/pulmonary in nature, but no perforation or bleeding occurred. Most AEs were not severe and resolved with medical treatment. The incidence of AEs was higher in the HD group than in the PD group, but the difference was not significant (6.1% vs. 3.5%, respectively, P = 0.451). In the HD group, patients with AEs were significantly older than those without AEs (P = 0.009). CONCLUSIONS: The rate of colonoscopy-related AEs in patients with ESRD on dialysis was higher than that in healthy adults, but most AEs were not severe. Routine colonoscopy may be safely performed in patients with ESRD regardless of the method of dialysis, but more carefully in older patients on HD.


Subject(s)
Kidney Failure, Chronic , Peritoneal Dialysis , Adult , Aged , Colonoscopy/adverse effects , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Renal Dialysis/adverse effects , Retrospective Studies
9.
Melanoma Res ; 32(1): 1-10, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34939980

ABSTRACT

Macrophage inhibitory cytokine-1 (MIC-1) has been reported to be elevated in various human cancers including melanoma; however, the function of MIC-1 in cancer remains unclear. In this study, we attempt to clarify the role of MIC-1 in tumor pathogenesis by employing the orthotopic B16F1 melanoma mouse model in which serum MIC-1 levels are positively correlated with tumor size. By stably transfecting a MIC-1 expression construct into B16F1 melanoma cells, we increased the expression and secretion levels of MIC-1. This increase in MIC-1 expression significantly enhanced the growth of tumors derived from B16F1 cells in vivo, despite not affecting in vitro cell growth. The elevated MIC-1 expression in B16F1 cells also resulted in lymph node metastasis in B16F1 tumor-bearing mice, significantly increasing mortality. Interestingly, among small melanoma tumors of similar size, tumors derived from the MIC-1-transfected B16F1 cells exhibited enhanced blood vessel formation compared with those of mock transfectant cells. Also, more MIC-1 was found in well-vascularized tumor regions than in poorly vascularized tumor regions. Moreover, conditioned medium (CM) of the MIC-1-transfected melanoma cells enhanced the angiogenic properties of endothelial cells more than CM of mock transfectant cells. Notably, hypoxic culture conditions forced parental B16F1 cells to secrete more endothelial cell-stimulating factors, among which the function of MIC-1 was confirmed by blocking the effects with an anti-MIC-1 antibody. Taken together, these results suggest that the MIC-1 produced by melanoma cells in response to oxygen deprivation promotes tumor vascularization during melanoma development in vivo, leading to enhanced tumor growth and metastasis.


Subject(s)
Growth Differentiation Factor 15/metabolism , Melanoma/genetics , Skin Neoplasms/genetics , Animals , Cell Line, Tumor , Cell Proliferation , Female , Humans , Melanoma/pathology , Mice , Neoplasm Metastasis , Neovascularization, Pathologic , Skin Neoplasms/pathology , Transfection
10.
Korean J Intern Med ; 36(5): 1063-1073, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34098714

ABSTRACT

BACKGROUND/AIMS: Although second-look endoscopy (SLE) is frequently performed after gastric endoscopic submucosal dissection (ESD) to prevent bleeding, no studies have reported SLE findings after colorectal ESD. This study aimed to investigate SLE findings and their role in preventing delayed bleeding after colorectal ESD. METHODS: Post-ESD ulcer appearances were divided into coagulation (with or without remnant minor vessels) and clip closure groups. SLE findings were categorized according to the Forrest classification (high-risk ulcer stigma [type I and IIa] and low-risk ulcer stigma [type IIb, IIc, III, or clip closure]), and risk factors for high-risk ulcer stigma were analyzed. RESULTS: Among the 375 cases investigated, SLEs were performed in 171 (45.6%) patients. The incidences of high-risk ulcer stigma and low-risk stigma were 5.3% (9/171) and 94.7% (162/171), respectively. During SLE, endoscopic hemostasis was performed more frequently in the high-risk ulcer stigma group than in the lowrisk ulcer stigma group (44.4% [4/9] vs. 1.9% [3/162], respectively; p < 0.001), but most of the endoscopic hemostasis in the high-risk ulcer stigma group (3/4, 75.0%) were prophylactic hemostasis. Post-ESD delayed bleeding occurred in three (0.8%) patients belonging to the SLE group, of which, one patient was from the high-risk stigma group and two were from the low-risk stigma group. CONCLUSION: The incidence of high-risk ulcer stigma during SLE was low, and delayed bleeding occurred in, both, high-risk and low-risk groups of SLE. SLEs performed after colorectal ESD may not be effective in preventing delayed bleeding, and further prospective studies are needed to evaluate the efficacy of SLE in post-colorectal ESD.


Subject(s)
Colorectal Neoplasms , Endoscopic Mucosal Resection , Neoplasms, Glandular and Epithelial , Stomach Neoplasms , Colorectal Neoplasms/surgery , Endoscopic Mucosal Resection/adverse effects , Gastric Mucosa , Gastroscopy , Humans , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/prevention & control , Retrospective Studies
11.
J Cell Physiol ; 236(5): 4008-4023, 2021 05.
Article in English | MEDLINE | ID: mdl-33151561

ABSTRACT

Macrophage inhibitory cytokine-1 (MIC-1) is a cytokine with pleotropic actions and its expression is markedly increased by inflammation and cardiac injury and in cancers. In particular, MIC-1 production after cardiac ischemia injury is associated with enhanced cardiac angiogenesis as well as myocardial protection. However, it remains uncertain whether MIC-1 itself has proangiogenic activity. In this study, we tried to determine the precise role of MIC-1 in physiological and pathological angiogenesis. Human microvessel endothelial cells responded to MIC-1 with enhanced angiogenic behaviors. Employing various angiogenesis assays, MIC-1 was found to promote vessel formation and development with a potency similar to that of vascular endothelial growth factor (VEGF). MIC-1 transgenic (Tg) mice also displayed enhanced neovascularization in both developing embryos and neonatal mouse retinas, compared with wild-type mice. Furthermore, endothelial cells (ECs) isolated from MIC-1 Tg mouse lung exhibited higher angiogenic potential than ECs from wild-type lung. MIC-1-induced angiogenesis was also observed in the recovery or healing processes of injuries such as hindlimb ischemia and skin wounds in mice. However, unlike VEGF, MIC-1 induced neither endothelial inflammation nor increased vascular permeability. In ECs, the MIC-1 signal exerted proangiogenic actions via the MEK/extracellular signal-regulated kinase- and phosphatidylinositol 3-kinase/Akt-dependent pathways. Notably, these MIC-1 signaling events in ECs were abrogated by small interfering RNA-mediated knockdown of GFRAL, suggesting that GFRAL is an EC receptor for MIC-1. In summary, we here show a novel role of MIC-1 as a potent EC activator, which promotes both normal and injury-related angiogenesis.


Subject(s)
Glial Cell Line-Derived Neurotrophic Factor Receptors/metabolism , Growth Differentiation Factor 15/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Neovascularization, Physiologic , Signal Transduction , Animals , Embryo, Mammalian/metabolism , Hindlimb/blood supply , Hindlimb/pathology , Humans , Inflammation/pathology , Ischemia/pathology , MAP Kinase Signaling System , Mice, Inbred C57BL , Mice, Transgenic , Microvessels/cytology , Permeability , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Regeneration/physiology , Retina/metabolism , Skin/pathology , Wound Healing
12.
Scand J Gastroenterol ; 54(8): 1058-1063, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31430183

ABSTRACT

Background: The benefits of narrow band imaging (NBI) for improving the detection rate of colorectal polyps remain unclear. New generation NBI using the 290 system (290-NBI) provides an at least two-fold brighter image than that of the previous version. We aimed to compare polyp miss rates between 290-NBI colonoscopy and high-definition white light endoscopy (HDWL). Methods: In total, 117 patients were randomized to undergo either 290-NBI or HDWL from June 2015 to February 2017. In the HDWL group, we performed HDWL as an initial inspection, followed by a second inspection with NBI. In the 290-NBI group, NBI was performed as the initial inspection, followed by a second inspection with HDWL. We compared polyp and adenoma detection rates and polyp miss rates (PMR) between the two groups and analyzed the factors associated with the PMR. Results: In total, 127 polyps were detected in the 117 patients. No differences in adenoma or polyp detection rates were observed between the two groups. The PMR for 290-NBI was 20.6% and that for HDWL was 33.9% (p = .068). However, the non-adenomatous PMR for 290-NBI was significantly lower than that of HDWL (11.5% vs. 52.2%, p = .002). Furthermore, the miss rates of polyps on the left side of the colon, flat-type polyps, and non-adenomatous polyps were significantly lower in the 290-NBI than HDWL. Conclusions: New generation NBI may reduce PMR, especially of flat-type and non-adenomatous polyps and those on the left side of the colon. (UMIN000025505).


Subject(s)
Adenoma/diagnosis , Colonic Polyps/diagnosis , Colonoscopy/methods , Narrow Band Imaging , Adenoma/pathology , Colonic Polyps/pathology , Colonoscopy/instrumentation , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Missed Diagnosis/prevention & control , Missed Diagnosis/statistics & numerical data , Precancerous Conditions/pathology , Prospective Studies , Republic of Korea , Tertiary Care Centers
13.
Prostate ; 79(12): 1400-1411, 2019 09.
Article in English | MEDLINE | ID: mdl-31212375

ABSTRACT

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) is closely associated with cancer invasion and metastasis. Since the transforming growth factor ß (TGF-ß) and Wnt signals induce EMT in various epithelial cell types, we examined whether and how the CD82/KAI1 metastasis suppressor affects the TGF-ß and Wnt signal-dependent EMT in human prostate cancer cells. METHODS: The invasiveness of cancer cells was evaluated by examining their ability to pass through the basement membrane matrigel. The subcellular localizations of Smad4 and ß-catenin proteins were respectively examined by confocal microscopy following immunofluorescence antibody staining and immunoblotting analysis following subcellular fractionation. The transcriptional activities of the TGF-ß1 -responsive TRE and Wnt-responsive Tcf/Lef promoters were determined by a luciferase reporter assay following transfection of the recombinant reporter vector into the cell. RESULTS: TGF-ß1 and Wnt3a treatments of human prostate cancer cells without CD82 expression resulted in not only increased invasiveness but also EMT involving the development of motile structures, downregulation of E-cadherin, and upregulation of the mesenchymal proteins. However, in the cells with high levels of CD82, the TGF-ß1 and Wnt3a stimulations neither elevated invasiveness nor induced EMT. Furthermore, the TGF-ß1 signaling events occurring in the CD82-deficient cells, such as phosphorylation of Smad2, nuclear translocation of Smad4, and transactivation of the TRE promoter, did not take place in the high CD82-expressing cells. Further, high CD82 expression interfered with the Wnt signal-dependent alterations in the phosphorylation pattern of glycogen synthase kinase 3ß (GSK-3ß) in prostate cancer cells, which allowed GSK-3ß to continue phosphorylating ß-catenin, thereby attenuating the Wnt signaling effects on the nuclear translocation of ß-catenin and subsequent transactivation of the Tcf/Lef promoter. CONCLUSIONS: The results of the present study suggest that CD82/KAI1 functions in suppressing TGF-ß1 - and Wnt-induced EMT in prostate cancer cells by inhibiting the TGF-ß1 /Smad and Wnt/ß-catenin pathways. Therefore, loss or decrease of CD82 expression is likely to render prostate cancer cells prone to respond to the TGF-ß1 and Wnt signals with EMT, resulting in the development of a motile and invasive mesenchymal phenotype related to the initiation of the metastatic cascade.


Subject(s)
Epithelial-Mesenchymal Transition/physiology , Kangai-1 Protein/metabolism , Prostate/pathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Transforming Growth Factor beta1/metabolism , Animals , Cell Line, Tumor , Humans , Male , Mice , Neoplasm Invasiveness , Neoplasm Metastasis , Prostate/metabolism , Smad2 Protein/metabolism , Wnt Signaling Pathway
14.
Dig Dis Sci ; 64(9): 2607-2613, 2019 09.
Article in English | MEDLINE | ID: mdl-30977077

ABSTRACT

BACKGROUND: Colonic bubbles obscure the colonic mucosa during colonoscopy following bowel preparation with polyethylene glycol plus ascorbic acid (PEG-Asc). Simethicone is used to enhance visualization during colonoscopy. We aimed to determine the optimal timing of simethicone addition to improve bowel preparation using PEG-Asc. METHODS: This prospective, randomized study enrolled patients undergoing elective colonoscopy from April 2017 to January 2018. They were randomly assigned to one of the following three groups: PEG-Asc only (control) or simethicone addition in the morning on the day of colonoscopy (PEG-S1) or in the evening of the day prior to colonoscopy (PEG-S2). The primary outcome was the quality of colon cleansing, and the secondary outcomes were the adenoma detection rate (ADR), polyp detection rate (PDR), and diminutive (≤ 5 mm) ADR. RESULTS: In total, 240 patients were randomly allocated to the three groups; six patients were withdrawn. Of the 234 patients evaluated, 78, 79, and 77 were allocated to the control, PEG-S1, and PEG-S2 groups, respectively. The bubble scores of all colonic segments were lowest in the PEG-S2 group. There was no significant difference in ADR or PDR among the three groups. However, the diminutive ADR was significantly higher in the PEG-S2 group compared to the other two groups (control 5.1% vs. PEG-S1 8.9% vs. PEG-S2 20.8%; P = 0.009). CONCLUSION: Addition of simethicone to PEG-Asc at the optimal time prevents the formation of air bubbles and so improves the quality of bowel preparation, especially enhancing diminutive ADR.


Subject(s)
Adenoma/diagnostic imaging , Antifoaming Agents/administration & dosage , Colonic Polyps/diagnostic imaging , Colonoscopy , Colorectal Neoplasms/diagnostic imaging , Simethicone/administration & dosage , Adenoma/pathology , Adult , Aged , Ascorbic Acid , Cathartics , Colorectal Neoplasms/pathology , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Polyethylene Glycols , Prospective Studies
15.
Cell Signal ; 52: 83-94, 2018 12.
Article in English | MEDLINE | ID: mdl-30189244

ABSTRACT

Tetraspanin membrane proteins form physical complexes with signaling molecules and have been suggested to influence the signaling events of associated molecules. Of the tetraspanin proteins, CD82 has been shown to promote homotypic cell-cell adhesion, which partially accounts for its role in suppressing cancer invasion and metastasis. We found here that CD82-induced cell-cell adhesion is attributed to increased E-cadherin expression through CD82-mediated downregulation of the E-cadherin repressor Snail. The Snail repression by CD82 resulted from the reduced binding of the Sp1 transcription factor to the Snail gene promoter. Notably, high CD82 expression did not allow the fibronectin matrix to induce Sp1 phosphorylation, implicating CD82 inhibition of the fibronectin-integrin signaling-dependent Sp1 activation. Meanwhile, E-cadherin upregulated by CD82 pulled ß-catenin up to the membrane region, and consequently reduced the amount of cytoplasmic ß-catenin that was able to move into to the nucleus. The Wnt signal-induced nuclear translocation of ß-catenin was also inhibited by the CD82 function of upregulating E-cadherin. Overall, high CD82 expression was likely to suppress fibronectin adhesion-induced Sp1 activation signaling for Snail expression, resulting in continuous E-cadherin expression, which contributed not only to the maintenance of strong cell-cell adhesion but also to the blockage of nuclear ß-catenin signaling.


Subject(s)
Antigens, CD/metabolism , Cadherins/metabolism , Cell Adhesion , Kangai-1 Protein/physiology , Prostatic Neoplasms/metabolism , Snail Family Transcription Factors/metabolism , Sp1 Transcription Factor/metabolism , beta Catenin/metabolism , Cell Line, Tumor , Fibronectins/metabolism , Humans , Integrins/metabolism , Male , Wnt Signaling Pathway
16.
J Dig Dis ; 19(5): 279-287, 2018 May.
Article in English | MEDLINE | ID: mdl-29696804

ABSTRACT

OBJECTIVE: Limited evidence is available on rebleeding due to nonsteroidal anti-inflammatory drugs (NSAIDs)-induced enteropathy. Previous studies have primarily analyzed endoscopic findings. Therefore, there is a need to evaluate their clinical implications for patients. This study aimed to evaluate the rebleeding rate and its related risk factors in patients with NSAIDs-induced enteropathy. METHODS: Of 402 patients with obscure gastrointestinal bleeding who were evaluated with capsule endoscopy, 49 were diagnosed with NSAIDs-induced enteropathy. The clinical characteristics of the patients were retrospectively analyzed. The Charlson comorbidity index was used to stratify the comorbidities. For patients who used additional drugs that influenced their tendency to bleeding, the odds ratio was calculated and used for a quantitative comparison. RESULTS: The rebleeding rate in patients with NSAIDs-induced enteropathy was 20.4%, within a mean duration of 23.4 months. Age ≥65 years (hazard ratio [HR] 8.628, 95% confidence interval [CI] 1.152-64.625), no additional use of mucoprotective agents (HR 11.712, 95% CI 1.278-76.098) and the continuation of NSAIDs after the first bleeding episode (HR 9.861, 95% CI 1.395-98.344) were independently related to rebleeding due to NSAIDs-induced enteropathy. The underlying comorbidities, drug-related rebleeding risk scores and therapeutic use of proton pump inhibitors were not significantly different (P = 0.209, 0.212 and 0.720, respectively). CONCLUSIONS: Approximately one-fifth of patients with NSAIDs-induced enteropathy showed rebleeding within 2 years. A careful long-term follow-up should be offered to elderly patients with NSAIDs-induced enteropathy who need continuous NSAID treatment without the additional use of mucoprotective medications.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Gastrointestinal Hemorrhage/epidemiology , Intestinal Diseases/chemically induced , Aged , Aged, 80 and over , Capsule Endoscopy , Female , Gastrointestinal Hemorrhage/therapy , Humans , Intestinal Diseases/therapy , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors
17.
Intest Res ; 15(4): 467-474, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29142514

ABSTRACT

BACKGROUND/AIMS: Although the role of capsule endoscopy (CE) in Crohn's disease (CD) has expanded, CE is not used routinely for diagnosing and evaluating CD in Korea. We aimed to investigate current patterns of practice and evaluate the clinical significance of the use of CE in CD in Korean patients. METHODS: Among 651 CE procedures performed for various indications, we retrospectively analyzed the medical records of patients who underwent CE in 57 cases of suspected CD (sCD) and 14 cases of established CD (eCD). RESULTS: In the sCD group, CE was most commonly used for the initial diagnosis of CD (54.4%). Capsule retention was found in only 1 patient in the eCD group (1/71, 1.4%). In the sCD group, 28.1% of patients were diagnosed with CD on the basis of CE findings; other diseases diagnosed included tuberculous enteritis (7.0%), non-steroidal anti-inflammatory drug-induced enteropathy (5.3%), and other enteritis (17.5%). Only 11.5% of patients with eCD (14/122) underwent CE. The indication for CE in the 14 patients with eCD was to assess disease extent and activity. The overall diagnostic yield of CE was 59.7%. Therapeutic strategies were changed in 70.2% of patients in the sCD group and 50% of those in the eCD group based on CE findings. CONCLUSIONS: In clinical practice, CE was most commonly indicated for the initial diagnosis of CD and was not generally performed in patients with eCD. CE appears to be an effective diagnostic modality for evaluating sCD and is useful for determining therapeutic strategies for patients with sCD and those with eCD.

18.
World J Gastroenterol ; 23(19): 3530-3537, 2017 May 21.
Article in English | MEDLINE | ID: mdl-28596689

ABSTRACT

AIM: To evaluate the short health scale (SHS), a new, simple, four-part visual analogue scale questionnaire that is designed to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQOL), in Korean-speaking patients with IBD. METHODS: The SHS was completed by 256 patients with Crohn's disease (CD) and ulcerative colitis (UC). Individual SHS items were correlated with inflammatory bowel disease questionnaire (IBDQ) dimensions and with disease activity to assess validity. Test-retest reliability, responsiveness and patient or disease characteristics with probable association with high SHS scores were analyzed. RESULTS: Of 256 patients with IBD, 139 (54.3%) had UC and 117 (45.7%) had CD. The correlation coefficients between SHS questions about "symptom burden", "activities of daily living", and "disease-related worry" and their corresponding dimensions in the IBDQ ranged from 0.62 to 0.71, compared with correlation coefficients ranging from -0.45 to -0.61 for their non-corresponding dimensions. There was a stepwise increase in SHS scores, with increasing disease activity in both CD and UC (all P values < 0.001). Reliability was confirmed with test-retest correlations ranging from 0.68 to 0.90 (all P values < 0.001). Responsiveness was confirmed with the patients who remained in remission. Their SHS scores remained unchanged, except for the SHS dimension "disease-related worry". In the multivariate analysis, female sex was associated with worse "general well-being" (OR = 2.28, 95%CI: 1.02-5.08) along with worse disease activity. CONCLUSION: The SHS is a valid and reliable measure of HRQOL in Korean-speaking patients with IBD.


Subject(s)
Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/psychology , Quality of Life , Severity of Illness Index , Activities of Daily Living , Adolescent , Adult , Aged , Anxiety , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/psychology , Crohn Disease/diagnosis , Crohn Disease/psychology , Female , Health Status , Humans , Language , Male , Middle Aged , Pain Measurement , Prospective Studies , Remission Induction , Reproducibility of Results , Republic of Korea , Surveys and Questionnaires , Young Adult
19.
Oncotarget ; 8(1): 1641-1654, 2017 Jan 03.
Article in English | MEDLINE | ID: mdl-27926483

ABSTRACT

The transmembrane protein CD82/KAI1 suppresses the metastatic potential of various cancer cell types. Moreover, decrease or loss of CD82 expression is closely associated with malignancy and poor prognosis in many human cancers including prostate cancer. Despite intense scrutiny, the mechanisms underlying the metastasis-suppressing role of CD82 are still not fully understood. Here, we found that a fibronectin matrix induced mesenchymal phenotypes in human prostate cancer cells with no or low CD82 expression levels. However, high CD82 expression rendered prostate cancer cells to have intensified epithelial characteristics upon fibronectin engagement, along with decreased cell motility and invasiveness. The CD82 function of inhibiting fibronectin-induced epithelial-to-mesenchymal transition (EMT) was dependent not only on CD82 interactions with fibronectin-binding α3ß1/α5ß1 integrins but also on the integrin-mediated intracellular signaling events. Notably, CD82 attenuated the FAK-Src and ILK pathways downstream of the fibronectin-receptor integrins. Immunofluorescence staining of human prostate cancer tissue specimens illustrated a negative association of CD82 with EMT-related gene expression as well as prostate malignancy. Altogether, these results suggest that CD82 suppresses EMT in prostate cancer cells adhered to the fibronectin matrix by repressing adhesion signaling through lateral interactions with the associated α3ß1 and α5ß1 integrins, leading to reduced cell migration and invasive capacities.


Subject(s)
Epithelial-Mesenchymal Transition/physiology , Fibronectins/antagonists & inhibitors , Integrin alpha3beta1/metabolism , Integrin alpha5beta1/metabolism , Kangai-1 Protein/metabolism , Prostatic Neoplasms/pathology , Signal Transduction/physiology , Cadherins/biosynthesis , Cell Line, Tumor , Cell Movement/genetics , Epithelial-Mesenchymal Transition/genetics , Focal Adhesion Kinase 1/antagonists & inhibitors , Humans , Kangai-1 Protein/genetics , Male , Neoplasm Metastasis/pathology , Prostate/pathology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Signal Transduction/genetics , Snail Family Transcription Factors/biosynthesis , src-Family Kinases/antagonists & inhibitors
20.
Gastric Cancer ; 20(1): 200-206, 2017 Jan.
Article in English | MEDLINE | ID: mdl-26661593

ABSTRACT

BACKGROUND: In ulcerative early gastric cancer, improvement and exacerbation of ulceration repeat as a malignant cycle. Moreover, early gastric cancer combined with ulcer is associated with a low curative resection rate and high risk of adverse events. The aim of this study was to investigate the ulcer healing rate and clinical outcomes with the administration of a proton pump inhibitor before endoscopic submucosal dissection for differentiated early gastric cancer with ulcer. METHODS: A total of 136 patients with differentiated early gastric cancer with ulcer who met the expanded indications for endoscopic submucosal dissection were reviewed between June 2005 and June 2014. Eighty-one patients were given PPI before endoscopic submucosal dissection and 55 patients were not given PPI. RESULTS: The complete ulcer healing rate was significantly different between the two groups (59.3 % vs. 23.6 %, P < 0.001). The procedure time was 38.1 ± 35.7 and 50.8 ± 50.2 min (P = 0.047). However, no significant differences were detected in the en bloc resection rate, complete resection rate, and adverse events including bleeding and perforation. Multivariate analysis showed that administration of PPI (OR = 10.83, P < 0.001) and mucosal invasion (OR = 24.43, P < 0.001) were independent factors that predicted complete healing of ulceration. The calculated accuracy for whether complete healing of the ulcer after PPI administration can differentiate mucosal from submucosal invasion was 75.3 %. CONCLUSIONS: Administration of PPI before ESD in differentiated EGC meeting the expanded criteria is effective to heal the ulcer lesion and reduce the mean procedure time. Complete healing of the ulcer after PPI administration suggests mucosal cancer.


Subject(s)
Gastric Mucosa/drug effects , Gastrointestinal Hemorrhage/prevention & control , Proton Pump Inhibitors/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Ulcer/drug therapy , Aged , Case-Control Studies , Endoscopic Mucosal Resection , Female , Follow-Up Studies , Gastrointestinal Hemorrhage/etiology , Gastroscopy , Humans , Male , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/complications , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Stomach Ulcer/complications , Stomach Ulcer/pathology , Stomach Ulcer/surgery
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