H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA. However, the efficacy and ...safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis.
A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared.
According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different.
DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).
Background The technique of endoscopic submucosal dissection (ESD) was introduced to be able to obtain en bloc specimens of large early GI neoplasms. The drawback of ESD is its technical difficulty, ...which, consequently, is associated with a higher rate of complication and which requires advanced endoscopic techniques and a long procedure time. Objective To assess the therapeutic outcome of ESD by expert endoscopists who have at least 3 years' experience of EMR in Korea. Design A retrospective, multicenter study. Patients From January 2006 to June 2007, 1000 early gastric cancers in 952 patients (502 men, 450 women; mean age 62.1 years, range 43-90 years) were treated by using ESD at 6 Korean ESD study group (KESG)–related university hospitals in Korea. Intervention We performed ESD procedures with typical sequences (marking, incision, and submucosal dissection). Main Outcome Measurements The rate of en bloc resection, incidence of complication, and length of procedure. Predetermined factors (various endoscopic and final pathologic features) for these outcomes. Results The rates of en bloc resection, complete en bloc resection, vertical incomplete resection, and piecemeal resection were 95.3%, 87.7%, 1.8%, and 4.1%, respectively. The rates of delayed bleeding, significant bleeding, perforation, and surgery related to complication were 15.6%, 0.6%, 1.2%, and 0.2%, respectively. The mean procedure time was 47.8 ± 38.3 minutes. The rates of en bloc resection differed significantly in relation to the location of the lesions (upper portion vs middle portion vs lower portion of the stomach, 88.6% vs 95.2% vs 96.0%, respectively; P = .02), presence of a scar (no vs yes, 96.0% vs 89.5%, respectively; P = .002), and histologic type (low-grade adenoma vs high-grade adenoma vs differentiated early gastric cancer vs undifferentiated early gastric cancer, 95.8% vs 94.6% vs 96.2% vs 83.8%, respectively; P = .007). The rates of delayed bleeding differed significantly in relation to location (upper portion vs lower portion of the stomach, 28.6% vs 13.8%, respectively; P = .003), the size of the tumor (>40 mm vs <20 mm, 28.6% vs 13.7%, respectively; P = .009), recurrent lesion (29.4% vs 15.1%, respectively; P = .024), and macroscopic type (flat vs elevated, 18.8% vs 12.4%, respectively; P = .047). Factors related to the longer procedure time were location (upper portion vs lower portion of the stomach, 64.8 vs 44.1 minutes, respectively; P < .001), the size of the tumor (>40 mm vs < 20 mm, 67.1 vs 42.0 minutes, respectively; P < .001), the presence of ulcer (54.6 vs 46.8 minutes; P < .045), and the presence of a scar (69.2 vs 45.0 minutes; P < .001). Conclusions ESD is an effective and safe therapy in the management of early gastric neoplasms. Endoscopists have to accept the need for advanced endoscopic techniques for performing ESD in the case of large lesions, scar lesions, undifferentiated cancers, or for the lesions in the upper portion of the stomach. Endoscopists require more experience to decrease complications in patients who have a large or recurrent lesion in the upper portion of the stomach; these lesions also take more time to complete the ESD procedure.
Few studies have compared the long-term outcomes of endoscopic resection and surgery. The aim of this study was to compare the long-term outcomes of endoscopic resection with those of surgery for ...early gastric cancer (EGC).
We reviewed prospectively collected data of patients who had undergone endoscopic resection (1,290 patients) or surgery (1,273 patients) for EGC. To reduce the effect of selection bias, we performed a propensity score-matching analysis between the two groups. The primary outcome was overall survival (OS). The secondary outcomes were disease-specific survival, disease-free survival (DFS), recurrence-free survival (RFS), occurrence of metachronous gastric cancer, treatment-related complications, length of hospital stay, and 30-day outcomes. The study was designed as a non-inferiority study and tested in an intention-to-treat analysis.
In a propensity-matched analysis of 611 pairs, the 10-year OS proportion was 96.7% in the endoscopic resection group and 94.9% in the surgery group (P=0.120) (risk difference -1.8%, 95% confidence interval (CI) -4.04-0.44, Pnon-inferiority=0.014), which met the non-inferiority criterion. In contrast, the 10-year RFS proportion was 93.5% in the endoscopic resection group and 98.2% in the surgery group (P<0.001) (risk difference 4.7%, 95% CI 2.50-6.97, Pnon-inferiority=0.820), which did not meet the non-inferiority criterion, mainly because of metachronous recurrence in the endoscopic resection group. The rate of early complications was higher in the endoscopic resection group than in the surgery group (9.0 vs. 6.6%, P=0.024), whereas the rate of late complications was higher in the surgery group than in the endoscopic resection group (0.5 vs. 2.9%, P<0.001). In the multiple Cox regression analysis, patient's age, the comorbidity index, the performance index, sex, tumor morphology, and depth of invasion were predictors of OS in patients with EGC.
Endoscopic resection might not be inferior to surgery with respect to OS in patients with EGC lesions that meet the absolute or expanded criteria. However, DFS, RFS, and metachronous RFS might be lower after endoscopic resection than after surgery.
Although colorectal cancer (CRC) is considered one of the most preventable cancers, no non-invasive, accurate diagnostic tool to screen CRC exists. We explored the potential of urine nuclear magnetic ...resonance (NMR) metabolomics as a diagnostic tool for early detection of CRC, focusing on advanced adenoma and stage 0 CRC. Urine metabolomics profiles from patients with colorectal neoplasia (CRN; 36 advanced adenomas and 56 CRCs at various stages, n = 92) and healthy controls (normal, n = 156) were analyzed by NMR spectroscopy. Healthy and CRN groups were statistically discriminated using orthogonal projections to latent structure discriminant analysis (OPLS-DA). The class prediction model was validated by three-fold cross-validation. The advanced adenoma and stage 0 CRC were grouped together as pre-invasive CRN. The OPLS-DA score plot showed statistically significant discrimination between pre-invasive CRN as well as advanced CRC and healthy controls with a Q2 value of 0.746. In the prediction validation study, the sensitivity and specificity for diagnosing pre-invasive CRN were 96.2% and 95%, respectively. The grades predicted by the OPLS-DA model showed that the areas under the curve were 0.823 for taurine, 0.783 for alanine, and 0.842 for 3-aminoisobutyrate. In multiple receiver operating characteristics curve analyses, taurine, alanine, and 3-aminoisobutyrate were good discriminators for CRC patients. NMR-based urine metabolomics profiles significantly and accurately discriminate patients with pre-invasive CRN as well as advanced CRC from healthy individuals. Urine-NMR metabolomics has potential as a screening tool for accurate diagnosis of pre-invasive CRN.
Introduction
The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor ...in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea.
Materials and Methods
Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at −80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate.
Results
The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate.
Conclusion
The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.
Despite the benefits from adjuvant chemotherapy or chemoradiotherapy, approximately one-third of stage II gastric cancer (GC) patients developed recurrences. The aim of this study was to develop and ...validate a prognostic algorithm for gastric cancer (GCPS) that can robustly identify high-risk group for recurrence among stage II patients. A multi-step gene expression profiling study was conducted. First, a microarray gene expression profiling of archived paraffin-embedded tumor blocks was used to identify candidate prognostic genes (N=432). Second, a focused gene expression assay including prognostic genes was used to develop a robust clinical assay (GCPS) in stage II patients from the same cohort (N=186). Third, a predefined cut off for the GCPS was validated using an independent stage II cohort (N=216). The GCPS was validated in another set with stage II GC who underwent surgery without adjuvant treatment (N=300). GCPS was developed by summing the product of Cox regression coefficients and normalized expression levels of 8 genes (LAMP5, CDC25B, CDK1, CLIP4, LTB4R2, MATN3, NOX4, TFDP1). A prospectively defined cut-point for GCPS classified 22.7% of validation cohort treated with chemoradiotherapy (N=216) as high-risk group with 5-year recurrence rate of 58.6% compared to 85.4% in the low risk group (hazard ratio for recurrence=3.16, p=0.00004). GCPS also identified high-risk group among stage II patients treated with surgery only (hazard ratio=1.77, p=0.0053).
This nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day ...clarithromycin-containing triple therapy (TT) as first-line treatment for
infection in the Korean population.
Patients with
infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses.
A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms.
The 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.
Endoscopic submucosal dissection (ESD) has been widely accepted for treating superficial esophageal squamous cell carcinoma (SESCC). However, long-term outcomes of ESD and esophagectomy for SESCC ...have not been compared. We compared the clinical outcomes of ESD and esophagectomy in a matched cohort.
Patients who underwent ESD and esophagectomy for SESCC were included. We selected SESCCs without obvious submucosal invasion from the surgical database by reviewing endoscopic images. To minimize the effect of selection bias, propensity score matching was performed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and metachronous RFS were compared between the 2 groups. Adverse event rates were also compared.
In a matched cohort of 120 pairs, OS, DSS, and RFS were comparable between the 2 groups. The 5-year OS, DSS, and RFS rates were 93.9% versus 91.2%, 100% versus 97.4%, and 92.8% versus 95.3% for the ESD and esophagectomy groups, respectively. The metachronous RFS was worse in the ESD group than in the esophagectomy group (P = .004). The 5-year metachronous RFS rates were 90.3% versus 100% for the ESD and esophagectomy groups, respectively. The esophagectomy group showed a higher overall adverse event rate than the ESD group (55.5% vs 18.5%, P < .0001). In each subgroup of mucosal and submucosal cancer, OS, DSS, and RFS were also comparable between the 2 groups.
ESD provides long-term outcomes comparable with esophagectomy in patients with SESCC without endoscopic evidence of obvious submucosal invasion. ESD should be considered as the first-line treatment for these patients.
is the most frequently mutated oncogene in human tumors, and its activating mutations represent important therapeutic targets. The combination of Cas9 and guide RNA from the CRISPR-Cas system ...recognizes a specific DNA sequence and makes a double-strand break, which enables editing of the relevant genes. Here, we harnessed CRISPR to specifically target mutant
alleles in cancer cells. We screened guide RNAs using a reporter system and validated them in cancer cells after lentiviral delivery of Cas9 and guide RNA. The survival, proliferation, and tumorigenicity of cancer cells in vitro and the growth of tumors in vivo were determined after delivery of Cas9 and guide RNA. We identified guide RNAs that efficiently target mutant
without significant alterations of the wild-type allele. Doxycycline-inducible expression of this guide RNA in
-mutant cancer cells transduced with a lentiviral vector encoding Cas9 disrupted the mutant
gene, leading to inhibition of cancer cell proliferation both in vitro and in vivo. Intra-tumoral injection of lentivirus and adeno-associated virus expressing Cas9 and sgRNA suppressed tumor growth in vivo, albeit incompletely, in immunodeficient mice. Expression of Cas9 and the guide RNA in cells containing wild-type
did not alter cell survival or proliferation either in vitro and in vivo. Our study provides a proof-of-concept that CRISPR can be utilized to target driver mutations of cancers in vitro and in vivo.
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