Early gastric cancer of young patients treated by endoscopic submucosal dissection: focusing on the different characteristics and prognosis of elderly patients.

BACKGROUND: A small portion of patients are diagnosed with early gastric cancer (EGC) and undergo endoscopic submucosal dissection (ESD) at a young age. However, their clinical outcomes are rarely known. AIM: We investigated to identify the feasibility and clinical outcomes of ESD for EGC focusing on young patients. METHODS: We analyzed the clinical characteristics and outscomes of patients who had undergone ESD for the treatment of EGC at < 50 years of age. We enrolled patients who had been diagnosed with EGC and had undergone ESD between 2006 and 2020. We divided them by age as follows: ≤ 50 and > 50 years into the young age (YA) and other age (OA) groups, respectively. RESULTS: Altogether, 1681 patients underwent ESD for EGC (YA group: 124 [7.4%], OA group: 1557 [92.6%]). The YA group had less severe atrophy and more undifferentiated (37.1% vs. 13.9%, P < 0.001) and diffuse type (25% vs. 7.7%, P < 0.001) histology. The curative resection rate was not significantly different between the groups. However, among 1075 patients who had achieved curative resection and had been followed-up for > 12 months, the YA group had a lower incidence of MGN (5.2% vs. 17.5%, P = 0.004) and MGC (2.6% vs. 10.9%, P = 0.019) than those exhibited by the OA group. The YA group was a significant negative predictor of MGN (odds ratio [OR]: 2.983, 95% confidence interval [CI] 1.060-8.393, P = 0.038), and marginally negative predictor in MGC (OR: 3.909, 95% CI: 0.939-16.281, P = 0.061). CONCLUSION: ESD is a favorable and effective therapeutic modality for EGC patients aged < 50 years, once curative resection is achieved.

Robot-assisted gastric endoscopic submucosal dissection significantly improves procedure time at challenging dissection locations.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early malignant stomach lesions. However, this procedure is technically demanding and carries a high complication risk. The level of difficulty in performing ESD is influenced by the location of the lesion. In our study, we aimed to investigate and analyze the effectiveness of robot-assisted ESD for lesions situated in challenging locations within the stomach. METHODS: We developed a gastric simulator that could be used to implement various gastric ESD locations. An EndoGel (Sunarrow, Tokyo, Japan) was attached to the simulator for the dissection procedures. Robot-assisted or conventional ESD was performed at challenging or easy locations by two ESD-trainee endoscopists. RESULTS: The procedure time was remarkably shorter for robotic ESD than conventional dissection at challenging locations (6.2 vs. 10.2 min, P < 0.05), mainly due to faster dissection (220.3 vs. 101.9 mm2/min, P < 0.05). The blind dissection rate was significantly lower with robotic ESD than with the conventional method (17.6 vs. 35.2%, P < 0.05) at challenging locations. CONCLUSION: The procedure time was significantly shortened when robot-assisted gastric ESD procedures were performed at challenging locations. Therefore, our robotic device provides simple, effective, and safe multidirectional traction for endoscopic submucosal dissection at challenging locations, thereby reducing difficulty of the procedure.

Development of artificial intelligence system for quality control of photo documentation in esophagogastroduodenoscopy.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is generally a safe procedure, but adverse events often occur. This highlights the necessity of the quality control of EGD. Complete visualization and photo documentation of upper gastrointestinal (UGI) tracts are important measures in quality control of EGD. To evaluate these measures in large scale, we developed an AI-driven quality control system for EGD through convolutional neural networks (CNNs) using archived endoscopic images. METHODS: We retrospectively collected and labeled images from 250 EGD procedures, a total of 2599 images from eight locations of the UGI tract, using the European Society of Gastrointestinal Endoscopy (ESGE) photo documentation methods. The label confirmed by five experts was considered the gold standard. We developed a CNN model for multi-class classification of EGD images to one of the eight locations and binary classification of each EGD procedure based on its completeness. RESULTS: Our CNN model successfully classified the EGD images into one of the eight regions of UGI tracts with 97.58% accuracy, 97.42% sensitivity, 99.66% specificity, 97.50% positive predictive value (PPV), and 99.66% negative predictive value (NPV). Our model classified the completeness of EGD with 89.20% accuracy, 89.20% sensitivity, 100.00% specificity, 100.00% PPV, and 64.94% NPV. We analyzed the credibility of our model using a probability heatmap. CONCLUSIONS: We constructed a CNN model that could be used in the quality control of photo documentation in EGD. Our model needs further validation with a large dataset, and we expect our model to help both endoscopists and patients by improving the quality of EGD procedures.

Colonic stenting as a bridge to surgery for obstructive colon cancer: is it safe in the long term?

BACKGROUND: The placement of a self-expanding metal stent in patients with obstructive colon cancer is used as a bridge to surgery. However, due to a lack of consensus and insufficient data, the long-term oncologic outcomes after colonic SEMS placement remain unclear. We assessed the long-term oncologic outcomes and adverse effects of colonic stenting for malignant colonic obstruction. METHODS: We included 198 patients admitted to Korea University Anam Hospital between 2006 and 2014 for obstructive colon cancer, of whom 98 underwent SEMS placement as a bridge to surgery and 100 underwent direct surgery without stenting. The clinicopathologic characteristics, overall survival, and disease-free survival were compared. RESULTS: There were no significant differences in long-term oncologic outcomes between the two groups. The median follow-up durations were 61.55 and 58.64 months in the SEMS and DS groups, respectively. There were also no significant differences in the 5-year OS (77.4% vs. 74.2%, p = 0.691) and 5-year DFS (61.7% vs. 71.0%, p = 0.194) rates between the groups. However, the DS group had significantly more early postoperative complications (p = 0.002). CONCLUSIONS: Colonic SEMS deployment as a bridge to surgery did not negatively affect long-term oncologic outcomes when compared with DS. In addition, colonic stenting decreased early postoperative complications and reduced the time for patients to return to normal daily activities.

Endoscopic submucosal dissection using a detachable assistant robot: a comparative in vivo feasibility study (with video).

BACKGROUND: Appropriate tissue tension and clear visibility of the dissection area using traction are essential for effective and safe endoscopic submucosal dissection (ESD). We developed a robotic assistive traction device for flexible endoscopy and compared its safety and efficiency in ESD between experienced and novice endoscopists. METHODS: Robotic ESD was performed by experienced and novice endoscopist groups (n = 2, each). The outcomes included time to complete each ESD step, total procedure time, size of the dissected mucosa, rate of en bloc resection, and major adverse events. Furthermore, incision and dissection speeds were compared between groups. RESULTS: Sixteen gastric lesions were resected from nine live pigs. The submucosal incision speed was significantly faster in the expert group than in the novice group (P = 0.002). There was no significant difference in the submucosal dissection speed between the groups (P = 0.365). No complications were reported in either group. CONCLUSIONS: When the robot was assisting in the ESD procedure, the dissection speed improved significantly, especially in the novice surgeons. Our robotic device can provide simple, effective, and safe multidirectional traction during ESD.

Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis.

OBJECTIVE: To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO). DESIGN: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively. CONCLUSION: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms. TRIAL REGISTRATION NUMBER: NCT02388724.

Two-Photon Probe for TNF-α. Assessment of the Transmembrane TNF-α Level in Human Colon Tissue by Two-Photon Microscopy.

We developed Pyr1-infliximab: a two-photon probe for TNF-α. Pyr1-infliximab showed absorption maxima at 280 and 438 nm and an emission maximum at 610 nm in an aqueous buffer and effective two-photon action cross-section values of (520-2830) × 10-50 cm4s/photon in RAW 264.7 cells. After this probe was labeled, it was possible to detect Pyr1-infliximab-transmembrane TNF-α complexes in a live cell and to determine the relative proportion of these complexes in human colon tissues. This proportion among healthy, possibly inflamed, and inflamed tissues of patients with ulcerative colitis was found to be 1.0/4.5/10. This probe may find useful applications for selective detection of transmembrane TNF-α in a live cell or tissue, for quantification of inflammation in human colon tissue or of antidrug antibodies in patients who stop responding to anti-TNF therapy, and for monitoring of the response to this therapy.

Dipeptidyl-peptidase-4 (DPP-4) inhibitor ameliorates 5-flurouracil induced intestinal mucositis.

BACKGROUND: Chemotherapy-induced alimentary mucositis (AM) is difficult to prevent and treatment is rarely effective. Recent study have been showed that glucagon-like peptide (GLP)-1 and GLP-2 has protective in chemotherapy-induced AM. While the DPP-4 enzyme degrades this GLP-1, the DPP-4 inhibitor blocks the degradation process and raises the concentration of GLP-1. This study aimed to assess the role of DPP-4 inhibitor, a well-known hypoglycemic agent, on chemotherapy-induced AM. METHODS: Twenty-four 6-week-old male C57BL/6 mice were divided into 4 groups: control, 5-fluorouracil (5-FU), DPP-4 inhibitor, and saline (DPP-4i), and DPP-4 inhibitor and 5-FU (DPP-4i + 5-FU). Mucositis was induced by intraperitoneal injection of 5-FU (400 mg/kg). DPP-4 inhibitor (50 mg/kg) was administered orally for four days starting the day before 5-FU administration. Post 72 h of 5-FU injection, mice were sacrificed and body weight change, diarrhea score, villus height, villus/crypt ratio, histologic characteristics including goblet cell count, and mRNA expression of inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6, were assessed. RESULTS: Daily body weight change was not statistically significant between the 5-FU and the DPP-4i + 5-FU group (P = 0.571). Diarrhea score was significantly different between these two groups (P = 0.033). In the 5-FU group, the villus height was not maintained well, the epithelial lining was irregular, and inflammatory cell infiltration was observed. Goblet cell count in the DPP-4i + 5-FU group was significantly higher than in the 5-FU group (P = 0.007). However, in the DPP-4i + 5-FU group, the villus height, epithelial lining, and crypt structure were better maintained than in the 5-FU group. Compared with the control group, mRNA expression of TNF-α was significantly up-regulated in the 5-FU group. Moreover, mRNA expression of TNF-α in the DPP-4i + 5-FU group was down-regulated compared to the 5-FU group. However, IL-6 in the 5-FU group was significantly down-regulated compared to the control, there was no significant difference in expression of IL-6 between the 5-FU and DPP4i + 5-FU group. CONCLUSION: DPP-4 inhibitor can improve 5-FU induced AM and, therefore, has potential as an alternative treatment for chemotherapy-induced AM.

A novel technique for repositioning a nasobiliary catheter from the mouth to nostril in endoscopic retrograde cholangiopancreatography.

BACKGROUND: Endoscopic nasobiliary drainage (ENBD) is widely used for biliary decompression in patients with biliary disease. However, it is difficult to reposition a nasobiliary catheter from the mouth to nostril. We developed a new device, which has a curved flexible loop and bar-handle, for repositioning of ENBD catheter. The aim of this study was to evaluate the usefulness of the new loop-device for facilitating the repositioning of an ENBD catheter from the mouth to nostril. METHODS: Between January 2015 and December 2017, a comparative observational study was performed to evaluate the time taken for repositioning a nasobiliary catheter during endoscopic retrograde cholangiopancreatography (ERCP) and compare the results of ENBD procedure between the new loop-device and conventional techniques. In the subgroup analysis, we evaluated the occurrence of oral cavity injury and the time taken to transfer ENBD catheter from the mouth to nostril. RESULTS: In all, 145 ENBD procedures were performed using these two techniques. The procedure time was significantly shorter in the new technique group than in the conventional group. (44 s vs. 194 s, p < 0.001). The total success rate of new device technique was 97.3%. No complication, including oral cavity injury, was observed. CONCLUSIONS: The technique using our new loop-device was useful for repositioning a nasobiliary catheter from the mouth to nostril in ERCP. The new device does not require the removal of the mouthpiece before ENBD positioning, which can help perform the ENBD procedure rapidly and avoid the finger injury of endoscopists.

EUS-guided irreversible electroporation using endoscopic needle-electrode in porcine pancreas.

BACKGROUND: Endoscopic irreversible electroporation (IRE) can be performed using a flexible, thin, needle-shaped electrode for an endoscopic ultrasound (EUS)-guided procedure. This study aimed to evaluate the feasibility and efficacy of performing EUS-guided IRE with endoscopic needle-electrode in porcine pancreas. METHODS: Experimental endoscopic IRE on the pancreas were performed by EUS-guided approach in three pigs and compared with surgical approach in three pigs. The animals were killed after 24 h and their pancreases collected. RESULTS: IRE ablation using endoscopic needle-electrode was successful technically in EUS-guided approaches for the pancreas. Immediately following IRE, the ablated pancreatic tissue showed no gross change except focal hemorrhage. H&E staining presented a well-demarcated ablation site measuring 1.0-1.5 cm in diameter in the pancreas. TUNEL immunohistochemistry showed diffuse cell death along the puncture site 24 h after IRE. No complication was observed in pigs after endoscopic IRE ablation. CONCLUSION: EUS-guided IRE ablation was feasible and effective for pancreas using the newly developed device.

Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells.

BACKGROUND: We investigated the effect of arsenic trioxide (ATO) for inhibition of signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) in gastric cancer cells, and the role of SH2 domain-containing phosphatase-1 (SHP-1) during this process. METHODS: We used AGS cells, which showed minimal SHP-1 expression and constitutive STAT3 expression. After treatment of ATO, cellular migration and invasion were assessed by using wound closure assay, Matrigel invasion assay and 3-D culture invasion assay. To validate the role of SHP-1, pervanadate, a pharmacologic phosphatase inhibitor, and SHP-1 siRNA were used. Xenograft tumors were produced, and ATO or pervanadate were administered via intraperitoneal (IP) route. RESULTS: Treatment of ATO 5 and 10 µM significantly decreased cellular migration and invasion in a dose-dependent manner. Western blot showed that ATO upregulated SHP-1 expression and downregulated STAT3 expression, and immunofluorescence showed upregulation with E-cadherin (epithelial marker) and downregulation of Snail1 (mesenchymal marker) expression by ATO treatment. Anti-migration and invasion effect and modulation of SHP-1/STAT3 axis by ATO were attenuated by pervanadate or SHP-1 siRNA. IP injection of ATO significantly decreased the xenograft tumor volume and upregulated SHP-1 expression, which were attenuated by co-IP injection of pervanadate. CONCLUSION: Our data suggest that ATO inhibits STAT3 activity and EMT process by upregulation of SHP-1 in gastric cancer cells.

Increased heat shock protein 70 expression attenuates pancreatic fibrosis induced by dibutyltin dichloride.

OBJECTIVES: Heat shock protein (HSP) 70 performs a chaperoning function and protects cells against injury. Although the effect of HSPs against acute inflammatory change has been proven, the relationship between HSP70 and chronic pancreatitis remains unclear. This study aimed to investigate the protective effect of increased HSP70 expression induced by thermal stress against pancreatic fibrosis in experimental chronic pancreatitis. MATERIALS AND METHODS: Two experiments to evaluate pancreatic HSP70 expression induced by thermal stress and determine the effect of increased HSP70 expression against pancreatic fibrosis were performed. To investigate HSP70 expression, rats were immersed in a warm bath and sequentially killed, and pancreatic HSP70 expression was measured. To study the effect of increased HSP70 expression, pancreatic fibrosis was induced by intravenous injection of dibutyltin dichloride (DBTC) and analyzed under repeated thermal stress. The severity of pancreatic fibrosis was measured. RESULTS: Thermal stress significantly increased HSP70 expression in the pancreas. HSP70 expression peaked at 6-12 h after warm bathing, and the increased HSP70 expression was associated with the attenuation of pancreatic fibrosis. Although pancreatic fibrosis was induced by DBTC injection, HSP70 expression induced by repeated thermal stress diminished the severity of atrophy and fibrosis. On western blot analysis, collagen type 1 expression was diminished in the increased HSP70 expression group, but not α-smooth muscle actin expression. CONCLUSIONS: Thermal stress could increase pancreatic HSP70 expression, and induced HSP70 expression showed a protective effect against pancreatic fibrosis. Modulation of HSP70 expression could be a potential therapeutic target in the treatment of chronic pancreatitis.

A randomized controlled trial comparing the efficacy of 1-L polyethylene glycol solution with ascorbic acid plus prucalopride versus 2-L polyethylene glycol solution with ascorbic acid for bowel preparation.

OBJECTIVES: Bowel cleansing is a major patient complaint during colonoscopy. Adding laxatives to the bowel preparation is effective in replacing a portion of bowel preparation solution and reducing its volume. Prucalopride is a serotonin receptor agonist that stimulates gastrointestinal motility and provides propulsive force for defecation. This study aimed to compare 1 L polyethylene glycol (PEG) with ascorbic acid (Asc) plus 2 mg prucalopride (1LP/AP) and 2 L PEG with Asc (2LP/A) for colonoscopy preparation with respect to bowel-cleansing quality and side effects. METHODS: A single-center, randomized, prospective study was conducted with 260 outpatients administered either 1LP/AP or 2LP/A. The primary endpoint was bowel preparation quality, which was evaluated using the Boston Bowel Preparation Scale and Aronchick Bowel Preparation Scale, and the secondary endpoints were patient tolerability and acceptability, assessed by a questionnaire-based survey. RESULTS: The adequate bowel preparation rates were 88.5% and 83.1% in the 2LP/A and 1LP/AP groups, respectively, and the efficacy of 1LP/AP was equivalent to the control regimen (p=.216). Other colonoscopic variables including adenoma detection rate were similar in both groups. Patient tolerability and acceptability were not significantly different, but patients in the 1LP/AP group were more willing to repeat the same regimen (p=.039). CONCLUSIONS: Bowel preparation quality with 1LP/AP was equivalent to that with 2LP/A, which did not increase the occurrence of side effects, but it reduced the volume of the solution ingested, and increased patient satisfaction.

Additional Benefits of Routine Drugs on Gastrointestinal Cancer: Statins, Metformin, and Proton Pump Inhibitors.

BACKGROUND: Commonly used medications including statins, metformin, and proton pump inhibitors (PPIs) effectively reduce the risk of esophageal, gastric, and colorectal cancer (CRC). SUMMARY: A number of observational studies and meta-analyses have shown that long-term statin use significantly reduces the incidence of gastrointestinal (GI) cancer. Moreover, statin use after GI cancer diagnosis has been significantly associated with better prognosis in large-scale cohort studies. Metformin was rigorously evaluated in a population-based study and meta-analysis, and was found to have an unexpected benefit in the prevention and prolonged survival of CRC patients with type 2 diabetes mellitus. In contrast, few studies have demonstrated the chemopreventive effect of metformin for esophageal and gastric cancer. Recent observational studies have demonstrated that PPIs effectively reduce the progression of nondysplastic Barrett's esophagus into esophageal adenocarcinoma in a dose-dependent manner. However, the association between chronic PPI use and CRC or gastric cancer risk is still controversial. It was expected that these 3 routinely used medicines would show a synergistic effect with conventional systemic chemotherapy in advanced GI cancers. However, recent phase III studies failed to show significantly better outcomes. Key Messages: Further studies are needed to identify "additional" anticancer effects of these commonly used medicines.

Two-Photon Probes for pH: Detection of Human Colon Cancer using Two-Photon Microscopy.

We have developed two-photon (TP) pH-sensitive probes (BH-2 and BHEt-1) that exhibit absorption and emission maxima at 370 and 466 nm, and TP absorption cross-section values of 51 and 61 GM (1 GM = 10-50cm4s/photon), respectively, at 750 nm and pH 3.0 in a universal buffer (0.1 M citric acid, 0.1 M KH2PO4, 0.1 M Na2B4O7, 0.1 M Tris, 0.1 M KCl)/1,4-dioxane (7/3) solution. The TPM images of CCD-18co (a normal colon cell line) and HCT116 cells (a colon cancer cell line) labeled with BH-2 were too dim to be distinguished. When the same cells were labeled with BHEt-1, however, the TPM image of the HCT116 cells was much brighter than that of CCD-18co cells, and the relative proportion of the acidic vesicles (Pacid) of the former was 5-fold larger than that of latter. BHEt-1 could also differentiate HepG2 cells (a human liver cancer cell line) from LX-2 cells (a human hepatic stellate cell line) with a 6-fold larger Pacid value. Human colon cancer tissues labeled with BHEt-1 showed similar results, demonstrating much brighter TPM images and 6-fold larger Pacid values compared to normal tissue. These results suggest the potential utility of BHEt-1 for detecting colon cancer in human tissues using TPM.

Comparison of a split-dose bowel preparation with 2 liters of polyethylene glycol plus ascorbic acid and 1 liter of polyethylene glycol plus ascorbic acid and bisacodyl before colonoscopy.

BACKGROUND AND AIMS: Recently, a low-volume polyethylene glycol formulation containing ascorbic acid (PEG-Asc) has proven as safe and effective as traditional 4-L PEG solutions for colonoscopy preparation. However, currently available aqueous purgative formulations are poorly tolerated. The aim of this study was to compare a split-dose 2-L PEG-Asc formulation and a 1-L PEG-Asc formulation with bisacodyl (10 mg) to determine the quality of bowel cleansing and patient tolerability. METHODS: A single-center, randomized, observer-blinded study was performed between May 2015 and September 2015. Two hundred outpatients referred for colonoscopy were prospectively enrolled and assigned to either the split-dose 2-L PEG-Asc group or the 1-L PEG-Asc with bisacodyl 10-mg group. The Boston Bowel Preparation Scale (BBPS) and Aronchick Bowel Preparation Scale (ABPS) were used to evaluate bowel cleansing. The tolerability of the regimens and satisfaction of patients was determined based on a questionnaire. RESULTS: Two hundred patients received either 2-L PEG-Asc or 1-L PEG-Asc with bisacodyl. Regarding colon cleansing outcome (BBPS and ABPS), the 1-L PEG-Asc with bisacodyl group showed similar but non-inferior results compared with the 2-L PEG-Asc group on both BBPS (6.92 ± 1.63 vs 6.57 ± 1.37; P = .103) and ABPS (96% vs 95%; P = 1.000) scales. Tolerability was similar for both 1-L PEG-Asc with bisacodyl and 2-L PEG-Asc. CONCLUSIONS: 1-L PEG-Asc is a suitable alternative to low-volume bowel preparation for colonoscopy. Our study showed that the 1-L PEG-Asc plus bisacodyl preparation has comparable tolerability and results in adequate colon cleansing. Bowel preparation with bisacodyl and 1-L PEG-Asc is a suitable alternative to low-volume bowel preparation for colonoscopy. (Clinical trial registration number: NCT02980562.).

Selenium Administration Attenuates 5-Flurouracil-Induced Intestinal Mucositis.

Chemotherapy-induced mucositis is mediated by the release of proinflammatory cytokines and reactive oxygen species. Selenium has several metabolic functions, including the protection of membrane lipids and macromolecules against oxidative damage. However, to date, there is little evidence on the effect of trace elements on intestinal mucositis after chemotherapy. This study investigated the protective effect of selenium against chemotherapy-induced mucositis in rats. Twenty-four 9-wk-old female Wistar rats were randomized to 4 groups: control, selenium, 5-fluorouracil (5-FU), and 5-FU plus selenium. Mucositis was induced by a single dose of 5-FU (400 mg/kg BW) via intraperitoneal injection, and selenium was administered by a single intraperitoneal dose of sodium selenite (0.2 mg/kg BW). Diarrhea and weight loss after 5-FU administration were attenuated by selenium treatment. The mean villus height in the 5-FU plus selenium group was significantly taller than rats administered with 5-FU alone, but not significantly different compared to the control group. Interleukin (IL)-1ß and tumor necrosis factor (TNF)-α mRNA expression were significantly lower in the 5-FU plus selenium group than in the 5-FU only group (IL-1ß, P < 0.01; TNF-α, P < 0.05). These findings indicate that selenium protects the mucosa during chemotherapy via its anti-inflammatory effects and its suppression of cytotoxic cytokine production.

Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations.

BACKGROUND AND AIM: In a recent study, microsatellite variations (GCA tandem repeats) in the promoter region of the (kidney-type) glutaminase gene were associated with the development of hepatic encephalopathy (HE) in Spanish patients with cirrhosis. The objective of this study was to validate the relation between microsatellite variations in the glutaminase promoter region and the development of overt HE in Korean patients with liver cirrhosis. METHODS: We performed a prospective cohort study of 154 cirrhotic patients who underwent a glutaminase microsatellite study without previous overt HE history at baseline. The primary end point was the first episode of overt HE. The microsatellite length was categorized into three groups based on its repeated number, with a cutoff value of 14; 65 (42.2%), 70 (45.5%), and 19 (12.3%) patients had the short-short, short-long, and long-long alleles, respectively. RESULTS: Over a median 3.5 years of follow-up (range = 0.1-4.4), overt HE developed in 28 patients (18.2%). The 3-year cumulative incidence of overt HE was 18.4%. Multivariate Cox model indicated that past hepatocellular carcinoma history, alcoholic etiology for cirrhosis, higher Model for End-Stage Liver Disease scores and their deterioration, and serum ammonium levels were independently associated with HE development. However, microsatellite length was not associated with the development of overt HE. CONCLUSIONS: In Korean patients with cirrhosis, microsatellite variations in the glutaminase promoter region were not associated with development of overt HE. Thus, additional studies are needed to identify other genetic factors related to glutaminase activity in Asians with overt HE.

Successful access to the ampulla for endoscopic retrograde cholangiopancreatography in patients with situs inversus totalis: a case report.

BACKGROUND: Although various endoscopic techniques in situs inversus have been reported, endoscopic retrograde cholangiopancreatography (ERCP) in patients with situs inversus is always challenging even for an experienced endoscopist. We performed ERCP using two different techniques, and compare the merits of each technique. CASE PRESENTATION: A 74-year-old woman presented with epigastric pain and jaundice for 3 days. Computed tomography revealed diffuse dilatation of the biliary tree, with multiple intrahepatic duct and common bile duct (CBD) stones, in addition to situs inversus totalis. ERCP was performed twice for CBD stone to remove the CBD stones using two techniques. For the first technique used, the patient was placed in a prone position with the endoscopist on the right side of the table. First, the endoscope was rotated 180° counterclockwise in the stomach, and was then shortened by turning 180° the counterclockwise again in the duodenum. For the second technique, we assessed the second portion of the duodenum by following the lesser curvature, while slowly turning the endoscope clockwise. CONCLUSION: We present an unusual case of biliary stones in a patient with situs inversus who was treated using modified ERCP techniques.

Epigenetic regulation and anti-tumorigenic effects of SH2-containing protein tyrosine phosphatase 1 (SHP1) in human gastric cancer cells.

SH2-containing protein tyrosine phosphatase 1 (SHP1) is an important negative regulator in cytokine-mediated signal transduction and cell cycling. Recent studies have demonstrated that SHP1 promoter methylation is frequently observed in gastric adenocarcinoma tissues. In this in vitro study, we attempted to reveal promoter hypermethylation and to investigate effects of SHP1 in gastric carcinoma cell lines. We observed that both gene and protein expression of SHP1 were negative in 8 of 10 gastric cancer cell lines (SNU-1, SNU-5, SNU-16, SNU-638, SNU-719, MKN-28, MKN-45, AGS). Methylation-specific PCR (MSP) showed a methylation-specific band only in the 10 gastric cancer lines. Bisulfite pyrosequencing in AGS, MKN-28, and SNU-719 cells indicated that methylation frequency was as high as 94.4, 92.6, and 94.5 %, respectively, in the three cell lines. Treatment of SNU-719, MKN-28, and AGS cells with 5-Aza-2'-deoxycytidine (5-Aza-dc) led to re-expression of SHP1 in these cells. Introduction of exogenous SHP1 in SNU-719 and MKN-28 cells by transient transfection substantially downregulated protein expression of constitutive phosphor-Janus kinase 2 (JAK2) (tyrosine 1007/1008) and phosphor-signal transducers and activators of transcription 3 (STAT3) (tyrosine 705), which in turn decreased expression of STAT3 target genes including those encoding cyclin D1, MMP-9, VEGF-1, and survivin. Induction of SHP1 significantly inhibited cell proliferation, migration and invasion in SNU-719 and MKN-28 cells. Taken together, epigenetic silencing of SHP1 is frequently caused by promoter hypermethylation in gastric carcinoma cells. Overexpression of SHP1 downregulates the JAK2/STAT3 pathway to modulate various target genes and inhibit cell proliferation, migration, and invasion in gastric cancer cells.