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Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.
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Background@#/Aim: Endoscopic retrograde cholangiopancreatography (ERCP) is one of the useful treatment for treating diseases that cause pancreatic duct stenosis. However, if the stenosis is severe, accessories other than the guide wire cannot pass through. This makes the ERCP procedure difficult. At this time, cystotome, a type of diathermic dilator seems to be an option. In this paper, we would like to discuss the experience of treatment procedures using cystotome. @*Methods@#Patients who underwent ERCP at a single tertiary hospital from November 2019 to October 2022 were analyzed retrospectively. Among them, cystotome was used in eight procedures in seven patients who passed the guide wire but failed to pass the stenosis. @*Results@#Technical success was achieved in all eight times. All the balloon catheter smoothly passed through the stenosis after cystotome was performed. In the second ERCP, it was a functional success for the balloon catheter to pass through stenosis without further treatment. This was achieved in 6 out of 8 (75.0%). In the case of complications, only one of the total successful procedures developed mild pancreatitis, which led to additional hospitalization for about two days after the procedure, and improved after conservative treatment. @*Conclusions@#Based on this, cystotome seems to be a good option as an alternative treatment to severe stenosis of the pancreatic duct.
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Cholangiocarcinoma (CCA) is one of the cancers with the worst prognosis. Its incidence and mortality have increased in recent years, but treatment options are limited. Although various clinical trials have been conducted, there is no effective therapeutic agent yet. As molecular genetic profiling is progressing in CCA, the interest in targeted therapies is growing. To realize targeted therapy in practice, various clinical requirements must be met. A molecular biological test should be performed on a patient’s tissue or blood, a target should be determined using an appropriate analysis method, and there should be a targeted agent. Regarding CCA, genetic variation occupies an intermediate level. Accordingly, many new agents have been recently developed for molecular biological targets. The most common genetic aberrations show almost similar patterns in intrahepatic and extrahepatic CCA. However, HER2 gene amplification is more often observed in extrahepatic CCA, and FGFR2 fusion, IDH1 mutation, and RAS-RAF-MEK-ERK signaling system mutations are more frequently found in intrahepatic CCA. Phase 2 or 3 clinical trials are being conducted with zanidatamab for HER2 amplification, pemigatinib/infigratinib for FGFR fusion, ivosidenib for IDH1 mutation, and dabrafenib for BRAFV600E mutation. In addition, clinical trials for agents targeting the NTRK, BRCA, and ARID1A gene mutations are ongoing. These targeted therapies are expected to have a bright future as a new treatment for CCA.
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Purpose@#Resectable pancreatic ductal adenocarcinoma (PDAC) has a high risk of recurrence after curative resection; despite this, the preoperative risk factors for predicting early recurrence remain unclear. This study therefore aimed to identify preoperative inflammation and nutrition factors associated with early recurrence of resectable PDAC. @*Methods@#From March 2021 to November 2021, a total of 20 patients who underwent curative resection for PDAC were enrolled in this study. We evaluated the risk factors for early recurrence within 1 year by univariate and multivariate analyses using Cox hazard proportional regression. The cutoff values for predicting recurrence were examined using receiver operating characteristic (ROC) curves. @*Results@#In our univariate and multivariate analyses, C-reactive protein (CRP), CRP-albumin ratio, and CRP-prealbumin ratio, as well as sex and age, were significant independent prognostic factors for early recurrence in PDAC. However, known inflammatory factors (neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios), nutritional factors (albumin, prealbumin, ferritin, vitamin D), and inflammatory-nutritional factors (Glasgow Prognostic Score, modified Glasgow Prognostic Score, albumin-bilirubin) showed no association with early recurrence. In addition, using cutoff values by ROC curve analysis, a high preoperative CRP level of >5 mg/L, as well as high CRP-to-albumin (>5.3) and CRP-to-prealbumin (>1.3) ratios showed no prognostic value. @*Conclusion@#Our results showed that inflammatory and perioperative nutritional factors, especially CRP-to-prealbumin ratio, have significant associations with early recurrence after curative resection in resectable PDAC. Therefore, for such patients, a cautious approach is needed when inflammation and poor nutritional status are present.
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Background/Aims@#The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS. @*Methods@#In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively. @*Results@#Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001) and TPG (87 days [52.5 to 121.5] vs 130 [97.0 to 162.9], p<0.001). Patients with an MBO located within 2 cm from the AOV in both groups had a higher percentage of duodenal invasion (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001) than patients with an MBO located more than 2 cm from the AOV. @*Conclusions@#The SPG and TPG showed similar results in terms of stent patency and rate of adverse events. However, patients with an MBO located within 2 cm from the AOV had a higher percentage of duodenal invasion with shorter stent patency than those with an MBO located more than 2 cm from the AOV, regardless of stent position.
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Percutaneous balloon dilation with or without placement of an external biliary drain is a nonoperative alternative method for treating benign bilioenteric anastomotic strictures. Although this procedure has a high technical success rate, outcomes are less optimal when attempting to dilate refractory tight strictures. For the stricture, cutting balloon can be an option. We present four patients with benign bilioenteric anastomotic strictures refractory to conventional balloon dilation. To the patients, a peripheral cutting balloon over-the-wire system was inflated, following subsequent conventional non-compliant balloon dilation. After the balloon dilation treatment, an external drainage catheter was placed through the stricture site and maintained for up to 30 days. Technical and end-treatment success was achieved in all four patients. In conclusion, the use of cutting balloon dilation may appear to be a safe and effective alternative method of treatment in patients with benign bilioenteric anastomotic strictures refractory to conventional balloon dilation.
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Purpose@#Although there are many studies on prealbumin in individual diseases such as malignant or inflammatory diseases, there are few comparative studies. This study aimed to compare the clinical differences between prealbumin levels in cholecystitis and pancreaticobiliary malignancies and investigate the clinical impact of low prealbumin levels in pancreaticobiliary malignancies. @*Methods@#From June 2021 to September 2021, 61 patients who had undergone surgery for various pancreaticobiliary diseases were enrolled in this study, and their clinicopathological data were retrospectively analyzed. @*Results@#Many elderly patients with malignant diseases had poor American Society of Anesthesiologists (ASA) scores, significantly lower albumin and prealbumin levels, and higher systemic immune inflammation indices. The low prealbumin group was older; had poorer ASA scores; and had significantly lower body mass index and hemoglobin and albumin levels and higher systemic immune inflammation indices than the normal prealbumin group. In malignant diseases, the low prealbumin group had significantly lower body mass index and hemoglobin levels and a tendency toward more advanced disease (lymph node and distant metastasis). @*Conclusion@#Preoperative low prealbumin levels had an area under the receiver operator characteristic curve of 0.69, suggesting that it may be useful for predicting pancreaticobiliary malignancies. Prealbumin levels were lower in malignant diseases, possibly related to poor nutritional status and systemic immune inflammation. Low prealbumin levels may predict the risk of more advanced disease.
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Purpose@#Pancreatic enzyme reflux into the biliary tract is associated with chronic inflammation and increased cellular proliferation in the biliary epithelium, leading to biliary carcinoma. We evaluated the relationship between high bile juice amylase levels and biliary microflora in patients with malignant gallbladder lesions. @*Methods@#In this retrospective study, 25 gallbladder specimens were obtained from patients with gallbladder cancer to evaluate amylase levels and perform bacterial culture. The samples were divided into high and low amylase groups and culture-positive and negative groups for analysis. Bile juice amylase 3 times higher than the normal serum amylase level (36–128 IU/L) was considered high. @*Results@#The number of positive cultures was higher in the high amylase group than in the low amylase group, but the difference was insignificant. There were no differences in other clinicopathological factors. Sixteen patients showed positive culture results; Escherichia coli and Klebsiella spp. were the most common gram-negative bacteria, whereas Enterococcus and Streptococcus spp. were the most common gram-positive bacteria. Age and bile juice amylase levels were significantly higher in the culture-positive group than in the culture-negative group. The incidence of bacterial resistance to cephalosporins was 6.25%–35.29%, and this incidence was particularly high for lower-generation cephalosporins. @*Conclusion@#Bacteria in gallbladder were identified more frequently when the amylase level was high. High amylase levels in the gallbladder can be associated with caused chronic bacterial infections with occult pancreaticobiliary reflux, potentially triggering gallbladder cancer
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Objective@#: People are living longer and the elderly population continues to increase. The incidence of degenerative spinal diseases (DSDs) in the elderly population is quite high. Therefore, we are facing more cases of DSD and offering more surgical solutions in geriatric patients. Understanding the significance and association of frailty and central sarcopenia as risk factors for spinal surgery in elderly patients will be helpful in improving surgical outcomes. We conducted a retrospective cohort analysis of prospectively collected data to assess the impact of preoperative central sarcopenia, frailty, and comorbidity on surgical outcome in elderly patients with DSD. @*Methods@#: We conducted a retrospective analysis of patients who underwent elective spinal surgery performed from January 1, 2019 to September 30, 2020 at our hospital. We included patients aged 65 and over who underwent surgery on the thoracic or lumbar spine and were diagnosed as DSD. Central sarcopenia was measured by the 50th percentile of psoas : L4 vertebral index (PLVI) using the cross-sectional area of the psoas muscle. We used the Korean version of the fatigue, resistance, ambulation, illnesses, and loss of weight (K-FRAIL) scale to measure frailty. Comorbidity was confirmed and scored using the Charlson Comorbidity Index (CCI). As a tool for measuring surgical outcome, we used the Clavien-Dindo (CD) classification for postoperative complications and the length of stay (LOS). @*Results@#: This study included 85 patients (35 males and 50 females). The mean age was 74.05±6.47 years. Using the K-FRAIL scale, four patients were scored as robust, 44 patients were pre-frail and 37 patients were frail. The mean PLVI was 0.61±0.19. According to the CD classification, 50 patients were classified as grade 1, 19 as grade 2, and four as grade 4. The mean LOS was 12.35±8.17 days. Multivariate stepwise regression analysis showed that postoperative complication was significantly associated with surgical invasiveness and K-FRAIL scale. LOS was significantly associated with surgical invasiveness and CCI. K-FRAIL scale showed a significant correlation with CCI and PLVI. @*Conclusion@#: The present study demonstrates that frailty, comorbidity, and surgical invasiveness are important risk factors for postoperative complications and LOS in elderly patients with DSD. Preoperative recognition of these factors may be useful for perioperative optimization, risk stratification, and patient counseling.
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Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)‒positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) ‘biological process’ terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including ‘cell cycle’ (cdc2, rik1, pas1, and leo1), ‘signaling’ (sck2, oga1, and cki3), and ‘vesicle-mediated transport’ (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the ‘signaling’ GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.
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Background/Aims@#Real-world, clinical practice data are lacking about sofosbuvir/ ribavirin (SOF/RBV) treatment of Korean patients with hepatitis C virus genotype 2 (HCV GT2) infection. This study investigated the efficacy and safety of SOF/RBV in Korean patients with HCV GT2 infection and clinical factors predicting sustained virological response 12 weeks (SVR12) after the end of SOF/RBV treatment. @*Methods@#A total of 181 patients with HCV GT2 with/without cirrhosis were treated with SOF/RBV for 16/12 weeks. Rapid virological response (RVR) was defined as non-detectable HCV RNA at 4 weeks. @*Results@#The RVR rate was 80.7% (146/181), the end of treatment response rate was 97.8% (177/181) and the SVR12 rate was 92.8% (168/181). Of eight patients with relapse, four did not achieve RVR. Three patients had a history of hepatocellular carcinoma (HCC). Multivariable analysis showed that RVR (p = 0.015) and no previous history of HCC (p = 0.007) were associated with SVR12. Factors significantly contributing to RVR included cirrhosis, creatinine concentration, and pre-treatment HCV RNA level. SVR12 rate was significantly higher in RVR (+) than RVR (–) patients (95.2% vs. 82.9%, p = 0.011) and also significantly higher in patients without than with a history of HCC (94.1% vs. 72.7%, p = 0.008). During treatment, 80/181 patients (44.2%) experienced mild to moderate adverse events, with 32 (17.7%) requiring RBV dose reductions due to anemia. @*Conclusions@#SOF/RBV treatment was effective and tolerable in HCV GT2 patients. RVR and no previous history of HCC were positive predictors of SVR12.
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Background/Aims@#Glecaprevir/pibrentasvir (G/P) is a combination of direct-acting antiviral agents that is an approved treatment for chronic infections by all six hepatitis C virus (HCV) genotypes. However, there are limited data on the effect of G/P in Korean patients in actual real-world settings. We evaluated the real-life effectiveness and safety of G/P at a single institution in Korea. @*Methods@#This retrospective, observational, cohort study used sustained virologic response at 12 weeks after treatment completion (SVR12) as the primary effectiveness endpoint. Safety and tolerability were also determined. @*Results@#We examined 267 individuals who received G/P for chronic HCV infections. There were 148 females (55.4%), and the overall median age was 63.0 years (range, 25 to 87 years). Eightythree patients (31.1%) had HCV genotype-1 and 182 (68.2%) had HCV-2. A total of 212 patients (79.4%) were HCV treatment-naïve, 200 (74.9%) received the 8-week treatment, 13 (4.9%) had received prior treatment for hepatocellular carcinoma, 37 (13.7%) had chronic kidney disease stage 3 or higher, and 10 (3.7%) were receiving dialysis. Intention to treat (ITT) analysis indicated that 256 (95.9%) achieved SVR12. A modified ITT analysis indicated that SVR12 was 97.7% (256/262). Six patients failed therapy because of posttreatment relapse. SVR12 was significantly lower in those who received prior sofosbuvir treatment (p=0.002) and those with detectable HCV RNA at week 4 (p=0.027). Seventy patients (26.2%) experienced one or more adverse events, and most of them were mild. @*Conclusions@#These real-life data indicated that G/P treatment was highly effective and well tolerated, regardless of viral genotype or patient comorbidities.
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Background/Aims@#Real-world, clinical practice data are lacking about sofosbuvir/ ribavirin (SOF/RBV) treatment of Korean patients with hepatitis C virus genotype 2 (HCV GT2) infection. This study investigated the efficacy and safety of SOF/RBV in Korean patients with HCV GT2 infection and clinical factors predicting sustained virological response 12 weeks (SVR12) after the end of SOF/RBV treatment. @*Methods@#A total of 181 patients with HCV GT2 with/without cirrhosis were treated with SOF/RBV for 16/12 weeks. Rapid virological response (RVR) was defined as non-detectable HCV RNA at 4 weeks. @*Results@#The RVR rate was 80.7% (146/181), the end of treatment response rate was 97.8% (177/181) and the SVR12 rate was 92.8% (168/181). Of eight patients with relapse, four did not achieve RVR. Three patients had a history of hepatocellular carcinoma (HCC). Multivariable analysis showed that RVR (p = 0.015) and no previous history of HCC (p = 0.007) were associated with SVR12. Factors significantly contributing to RVR included cirrhosis, creatinine concentration, and pre-treatment HCV RNA level. SVR12 rate was significantly higher in RVR (+) than RVR (–) patients (95.2% vs. 82.9%, p = 0.011) and also significantly higher in patients without than with a history of HCC (94.1% vs. 72.7%, p = 0.008). During treatment, 80/181 patients (44.2%) experienced mild to moderate adverse events, with 32 (17.7%) requiring RBV dose reductions due to anemia. @*Conclusions@#SOF/RBV treatment was effective and tolerable in HCV GT2 patients. RVR and no previous history of HCC were positive predictors of SVR12.
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We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.
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Background/Aims@#Glecaprevir/pibrentasvir (G/P) is a combination of direct-acting antiviral agents that is an approved treatment for chronic infections by all six hepatitis C virus (HCV) genotypes. However, there are limited data on the effect of G/P in Korean patients in actual real-world settings. We evaluated the real-life effectiveness and safety of G/P at a single institution in Korea. @*Methods@#This retrospective, observational, cohort study used sustained virologic response at 12 weeks after treatment completion (SVR12) as the primary effectiveness endpoint. Safety and tolerability were also determined. @*Results@#We examined 267 individuals who received G/P for chronic HCV infections. There were 148 females (55.4%), and the overall median age was 63.0 years (range, 25 to 87 years). Eightythree patients (31.1%) had HCV genotype-1 and 182 (68.2%) had HCV-2. A total of 212 patients (79.4%) were HCV treatment-naïve, 200 (74.9%) received the 8-week treatment, 13 (4.9%) had received prior treatment for hepatocellular carcinoma, 37 (13.7%) had chronic kidney disease stage 3 or higher, and 10 (3.7%) were receiving dialysis. Intention to treat (ITT) analysis indicated that 256 (95.9%) achieved SVR12. A modified ITT analysis indicated that SVR12 was 97.7% (256/262). Six patients failed therapy because of posttreatment relapse. SVR12 was significantly lower in those who received prior sofosbuvir treatment (p=0.002) and those with detectable HCV RNA at week 4 (p=0.027). Seventy patients (26.2%) experienced one or more adverse events, and most of them were mild. @*Conclusions@#These real-life data indicated that G/P treatment was highly effective and well tolerated, regardless of viral genotype or patient comorbidities.
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Background@#/Aim: Percutaneous transhepatic cholangioscopy (PTCS) has been widely used for the diagnosis and treatment. PTCS-related complications (hemobilia, cholangitis, biliary tract perforations) are not infrequent. However, data on the risk factors for PTCS-related complications are limited. Therefore, we aimed to identify the risk factors for PTCS-related complications. @*Methods@#Two hundred thirty-three patients who underwent PTCS at a single tertiary center between January 2006 and October 2014 were enrolled. After retrospectively analyzing the patients’ medical records, 212 patients were enrolled and classified into two groups: 1) a complication group and 2) a non-complication group. @*Results@#The study population comprised 112 men and 100 women, with a median age of 64.5 years. Of the 212 patients, 32 (15.1%) developed complications: 14 (6.7%) developed cholangitis, six (2.8%) developed bile duct injury, and two (0.9%) developed hemobilia. In the univariate analyses, older age, a small number of tract dilatation sessions, and computed tomography (CT) findings of liver cirrhosis and a non-dilated intrahepatic duct were risk factors for PTCS-related complications. In the multivariate analysis, older age, a small number of tract dilatation sessions, and the CT finding of a non-dilated intrahepatic duct were independent factors for predicting PTCS-related complications. Serial tract dilatations (≥2 sessions) were performed in 95 patients (44.8%), but this did not affect the complication rate. In this subgroup of patients, a short interval between sessions (≤3 days) was associated with PTCSrelated complications. @*Conclusions@#Elderly patients and those with non-dilated intrahepatic ducts on CT need to be managed carefully. Stepwise tract dilatations and a long interval between sessions (>3 days) can help decrease PTCS-related complications.
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Purpose@#Gastric delta cells (D-cells), which are somatostatin-secreting cells, are the main paracrine inhibitor of acid secretion. The number of D-cells was studied in children presenting with upper gastrointestinal (UGI) disease. @*Methods@#We retrospectively investigated the number of D-cells in the gastric body and antrum through immunofluorescence examinations according to symptoms, endoscopic findings, and Helicobacter pylori infection in 75 children who visited Hanyang University Hospital Pediatrics. @*Results@#The mean patient age was 12.2±3.3 years. The male-to-female ratio was 1:1.4. The mean D-cell number per high-power field in the antrum and body was 20.5 and 12 in children with substernal pain, 18.3 and 10.3 in vomiting, 22.3 and 6 in diarrhea, and 9.3 and 6 in abdominal pain, respectively (p>0.05). According to endoscopic findings, the mean D-cell number in the antrum and body was 14.3 and 6 with gastritis, 14 and 9.3 with reflux esophagitis, 16.7 and 8.7 with duodeno-gastric reflux, 19.3 and 12.7 with gastric ulcer, 16 and 13.7 with duodenitis, and 12.3 and 4 with duodenal ulcer, respectively (p>0.05). The D-cell number in the gastric body was 2.7 and 8.7 in children with current H. pylori infection and non-infected children, respectively (p=0.01), while those in the antrum were 15.5 and 14, respectively, with no statistical significance. @*Conclusion@#The D-cell number was lower in the gastric body of children with current H. pylori infection. Further studies concerning peptide-secreting cells with a control group would provide information about the pathogenic pathways of UGI disorder.
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Econazole, a potent broad-spectrum antifungal agent and a Ca2+ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.
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BACKGROUND/AIMS: Proton pump inhibitors are widely used to prevent gastric endoscopic submucosal dissection (ESD)-related bleeding, but no standard administration regimens have been established. We aimed to prospectively compare the effects of continuous infusion and intermittent dosing with pantoprazole on preventing gastric ESD-related bleeding. Additionally, we analyzed the risk factors for bleeding. METHODS: From April 2012 to May 2013, patients with a gastric epithelial neoplasm scheduled for ESD in the Pusan National University Hospital were randomly assigned to one of two groups according to the pantoprazole administration regimen (continuous infusion or intermittent dosing). The primary outcomes measured were intra- and postprocedural bleeding events. RESULTS: The final analysis included 401 patients. The rate of significant intraprocedural bleeding was 25.4% in the C group and 24.0% in the I group, with no significant difference (p=0.419). In addition, there was no significant difference in the postprocedural bleeding rate between the C and I groups (11.7% vs 10.2%, p=0.374). Multivariate analysis showed that intraprocedural bleeding was associated with the proximal tumor location, the presence of fibrosis, and the size of the resected specimen, whereas postprocedural bleeding was associated with the size of the resected specimen and the procedure/coagulation time. CONCLUSIONS: Intermittent dosing with pantoprazole is sufficient and cost-effective for the prevention of gastric ESD-related bleeding. Operators should consider tumor characteristics when planning ESD to minimize the risk of intraprocedural bleeding, and patients with large iatrogenic ulcers should be carefully monitored for postprocedural bleeding.
Subject(s)
Humans , Fibrosis , Gastrointestinal Hemorrhage , Hemorrhage , Multivariate Analysis , Neoplasms, Glandular and Epithelial , Prospective Studies , Proton Pump Inhibitors , Risk Factors , Stomach Neoplasms , UlcerABSTRACT
BACKGROUND/AIMS: Cooperation of patients plays an essential role during gastric endoscopic submucosal dissection (ESD) for successful outcomes. We aimed to assess the efficacy and safety of a patient-positioning device (EZ-FIX®) during ESD for gastric epithelial neoplasm.MATERIALS AND METHODS: In this prospective study, 86 consecutive patients with gastric epithelial neoplasm scheduled for ESD at the Pusan National University Hospital were included and randomly assigned to the EZ-FIX® (n=44) or non-EZ-FIX® (n=42) groups. The primary outcomes measured were endoscopist satisfaction profiles and contribution level of EZ-FIX® to the procedure.RESULTS: No significant differences were observed between the two groups regarding patients' clinicopathologic characteristics, though the mean procedure time was longer in the EZ-FIX® group (P=0.044). In the EZ-FIX® group, 16 patients (36.4%) were categorized as a contribution group. Subgroup analysis between the contribution and non-contribution groups revealed that the contribution group had a larger lesion size (P=0.043) and a longer procedure time (P=0.037) and showed a higher patient's movement score (P < 0.001) with a higher dosage of propofol (P=0.004) and pethidine (P=0.001) required. Endoscopist satisfaction scores on sedation (P < 0.001) and overall procedure (P=0.010) were lower in the contribution group.CONCLUSIONS: Thus, EZ-FIX® might be helpful especially for patients who are expected to exhibit uncooperative sedation or those with a large lesion size, which would necessitate a longer procedure time.