Endoscopic submucosal dissection (ESD) of early gastric cancer is a minimally invasive procedure. However, the risk for metachronous cancers after successful cancer treatment remains high and the ...risk factors for metachronous cancers have not been elucidated.
To evaluate the risk factors for metachronous gastric cancers after ESD with a long-term follow-up.
A total of 155 consecutive patients (119 men, 36 women, mean age 68.9 years) were treated with ESD between September 2000 and September 2009. Biopsy specimens were obtained from the greater curvature of the antrum and middle corpus to evaluate gastric mucosal status, including Helicobacter pylori, intestinal metaplasia (IM) and neutrophil infiltration (NI) before ESD. Follow-up endoscopy after ESD was scheduled at two and six months, one year and annually thereafter. H pylori eradication was recommended when possible.
The median follow-up period was 4.2 years. Metachronous gastric cancers were found in 23 of 155 patients (3.5% per year). No local recurrences were observed. The cumulative incidence of metachronous gastric cancer was significantly high in IM and NI in the corpus (P=0.0093 and P=0.0025, respectively log-rank test). The ORs for IM and NI in the corpus were 2.65 and 3.06, respectively, according to the Cox proportional hazards model (P=0.024 and P=0.0091, respectively).
The presence of IM and NI in the corpus was closely related to the development of metachronous gastric cancer after ESD.
Abstract The third-line treatment regimen for Helicobacter pylori after failure of clarithromycin- and metronidazole-based therapies is not yet established. Sitafloxacin (STX) is a quinolone that ...possesses potent in vitro activity against H. pylori. In this study, the susceptibility of H. pylori isolates to STX was examined and the efficacy of STX-based triple therapy as a third-line regimen was evaluated. STX showed minimum inhibitory concentrations (MICs) of ≤1 μg/mL against all 100 H. pylori isolates, and the MIC90 (MIC for 90% of the organisms) of STX was 5 log2 dilutions lower than that of levofloxacin (LVX). The MIC50 (MIC for 50% of the organisms) of STX against gyrA mutants was 0.12 μg/mL and was significantly lower than that of LVX (8 μg/mL). The activity of STX at pH 5.5 was significantly less than that at pH 7.0. In the clinical trial, 28 patients with two eradication failures were treated with STX-based triple therapy rabeprazole 10 mg twice daily (b.i.d.), amoxicillin 750 mg b.i.d. and STX 100 mg b.i.d. for 7 days. The eradication rate was 75% using intention-to-treat analysis and 80% using per-protocol analysis. Two gyrA mutant strains were eradicated. Amongst participants, a low pepsinogen I/II ratio was associated with successful eradication. These results suggest that STX could be active against most clinical H. pylori isolates and that STX-based triple therapy is a promising and safe third-line therapy.
Helicobacter pylori infection is the most important risk factor for gastric cancer, for which eradication therapy is commonly performed. However, gastric cancer is sometimes discovered after ...successful eradication of H. pylori. Much evidence indicates that diabetes mellitus (DM) is a risk factor for gastric cancer. The incidence and characteristics of gastric cancer diagnosed after H. pylori eradication in DM patients remain to be determined.
We followed the clinical course of patients who underwent H. pylori eradication therapy at our institution. Endoscopy was performed before and after eradication. We compared the incidence and clinical characteristics of gastric cancer arising in DM and non-DM patients.
In total, 965 patients who underwent successful eradication (518 DM and 447 non-DM patients) were followed-up for an average of 4.5 years. During the follow-up period, 21 gastric cancers were diagnosed (12 in DM patients and 9 in non-DM patients). The incidence of gastric cancer after eradication was not significantly different between DM and non-DM patients (0.485 and 0.482 %/year, respectively). There was no significant difference in the pathology, diameter, depth, location, or treatment of gastric cancer between patients with and without DM.
The incidence and characteristics of gastric cancer occurring after H. pylori eradication were comparable between DM and non-DM patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background and study aims
The repair costs of gastrointestinal endoscopes account for a significant proportion of the total budget of an endoscopy unit. This study evaluated the repair ...costs of small-caliber endoscopes and conventional endoscopes used in esophagogastroduodenoscopy (EGD).
Patients and methods
A retrospective analysis of upper gastrointestinal endoscope damage and repair costs between April 2012 and May 2019 was performed at the Toyoshima Endoscopy Clinic. Conventional endoscopes (GIF-H260, GIF-HQ290, and GIF-H290Z) were used for transoral EGD while small-caliber endoscopes (GIF-XP260N and GIF-XP290N) were used for transnasal or transoral EGD.
Results
Three small-caliber endoscopes and five conventional endoscopes were used for 1,031 procedures and 31,192 procedures, respectively. The number of procedures/damage incidence for small-caliber endoscope and conventional endoscopes was 344 and 1950, respectively. Damage incidence for small-caliber endoscopes was significantly higher than for conventional endoscopes (
P
= 0.014). Repair costs/procedure were $ 5.95 ± $132 for small-caliber endoscopes and $2.41 ± $115 for conventional endoscopes. Repair costs/procedure for small-caliber endoscopes were more than twice those for conventional endoscopes.
Conclusions
Small-caliber endoscopes are more fragile than conventional endoscopes.
INTRODUCTION:
Cigarette smoking is regarded as a weak or moderate risk factor of gastroesophageal reflux disease (GERD), and smoking cessation may reduce GERD symptoms. However, the evidence for ...these associations is limited. This study aimed to investigate the effects of cigarette smoking or smoking cessation on the development of GERD by using endoscopic findings and the Gastrointestinal Symptom Rating Scale (GSRS).
METHODS:
The subjects were 848 patients who received upper endoscopy and answered the GSRS questionnaire as health checkup at our hospital in Japan. The patients were divided into three groups; non-smoking, smoking-cessation, and current-smoking group (322, 371 and 155 patients, respectively). Endoscopic findings of GERD were graded by the Los Angeles classification, and grade B or more were defined as severe GERD. The GSRS questionnaire is an interview-based seven-graded rating scale including the questions on heart burn and acid regurgitation. The prevalence of patients with positive GSRS scores (i.e. 2 or more) was compared between three groups. Data were analyzed statistically using the Kruskal-Wallis, Mann-Whitney U, or chi-square test.
RESULTS:
The overall prevalence of endoscopic GERD and positive GSRS scores on heart burn and acid regurgitation was 19.2, 14.5, and 19.7%, respectively. The prevalence of patients with severe endoscopic GERD in smoking group was significantly higher than that in non-smoking group (OR: 4.64; 95% CI: 1.47-14.67;
P
= 0.007). In contrast, the prevalence of patients with positive GSRS scores on heart burn in smoking group was significantly lower than that in non-smoking group (OR: 0.46; 95% CI: 0.26-0.80;
P
= 0.006). As for smoking cessation, there was no significant difference in the prevalence of patients with severe endoscopic GERD between smoking-cessation and current-smoking group (OR: 0.37; 95% CI: 0.11-1.18;
P
= 0.149). Also, there was no significant difference in positive GSRS scores between smoking-cessation and current-smoking group (heart burn;
P
= 0.077, and acid regurgitation;
P
= 0.871).
CONCLUSION:
Cigarette smoking increases risk of developing endoscopic GERD severity, while not developing GERD symptoms. Upper endoscopy may be useful for Japanese using cigarette even if they have no GERD symptoms. Although smoking cessation is not associated with improvement of endoscopic GERD severity in this study, prospective studies should be performed to evaluate the effects of smoking cessation on GERD.
The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1+ stem ...cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.
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•Quiescent Mist1+ stem cells reside in the corpus isthmus•Mist1+ stem cells are a cellular origin of gastric cancers•Cxcl12/Cxcr4 perivascular niche supports isthmus stem cells•Wnt5a from Cxcr4+ ILCs promotes diffuse cancer development
Hayakawa et al. show that Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs) form a perivascular niche to support diffuse-type gastric cancer (DGC) development from Mist1-expressing gastric stem cells through Wnt5a produced by ILCs. Targeting ILCs, Cxcr4, or Wnt5a inhibits DGC development.
Abstract
Within the gastrointestine, nerves help to regulate both normal and neoplastic stem cell dynamics. Several previous studies suggested that cholinergic nerve signaling plays an important role ...in gastrointestinal cancer development, but the exact underlying mechanism has not been clarified. In this study, we examined the role of muscarinic acetylcholine receptor subtype 3 (M3R) in gastric homeostasis and cancer development by using mouse models and human cancer cell lines. In situ hybridization revealed M3R expression in gastric stem cell zone, and its expression was markedly upregulated in gastric cancer cells. We knocked out M3R in Lgr5+ gastric stem cells in Lgr5-CreERT; M3Rflox/flox mice, and found that deletion of M3R inhibited clonal expansion of Lgr5+ cells in regenerative states. In a gastric tumor model of Mist1-CreERT; Apcflox/flox mice, knockout of M3R dramatically suppressed tumor growth. RNA sequencing analysis of these tumors revealed that several important pathways were significantly inhibited in M3R knockout samples, including YAP/TAZ pathway. We established M3R-expressing gastric cancer cell lines, and western blotting, luciferase assay, and RT-PCR analysis confirmed that acetylcholine (ACh) agonist activates YAP pathway through M3R. YAP is upregulated in approximately half of gastric cancer patients, and its expression is significantly associated with disease stage and histological form. This M3R-YAP axis activates the gastric stem cell niche and offers a compelling target for tumor treatment and prevention.
Note: This abstract was not presented at the meeting.
Citation Format: Yoku Hayakawa, Mitsuru Konishi, Kosuke Sakitani, Kazuhiko Koike, Timothy Wang. Muscarinic acetylcholine receptor subtype 3 regulates gastric stem cell expansion and gastric cancer progression by controlling YAP activation abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3339. doi:10.1158/1538-7445.AM2017-3339
To clarify the role of serum anti-
(
) antibody titers in gastric cancer.
In this cross-sectional study, the effect of patients' baseline characteristics and endoscopic findings on their serum ...antibody titers were assessed. We evaluated consecutive patients who underwent esophagogastroduodenoscopy and their first evaluation for
infection using a serum antibody test. We excluded patients with a history of eradication therapy. The participants were divided into four groups according to their E-plate serum antibody titer. Patients with serum antibody titers < 3, 3-9.9, 10-49.9, and ≥ 50 U/mL were classified into groups A, B, C, and D, respectively.
In total, 874 participants were analyzed with 70%, 16%, 8.7%, and 5.1% of them in the groups A, B, C, and D, respectively. Patients in group C were older than patients in groups A and B. Gastric open-type atrophy, intestinal metaplasia, enlarged folds, diffuse redness, and duodenal ulcers were associated with a high titer. Regular arrangements of collecting venules, fundic gland polyps, superficial gastritis, and gastroesophageal reflux disease were related to a low titer. Multivariate analysis revealed that nodularity (
= 0.0094), atrophy (
= 0.0076), and age 40-59 years (
age ≥ 60 years,
= 0.0090) were correlated with a high serum antibody titer in
-infected patients. Intestinal metaplasia and atrophy were related to age ≥ 60 years in group C and D.
Serum antibody titer changes with age, reflects gastric mucosal inflammation, and is useful in predicting the risk of gastric cancer.
BACKGROUNDAccurate diagnosis of colorectal premalignant polyps, including adenomas, is vital in clinical practice. AIMTo investigate the diagnostic yields of novel findings of brown slits for ...adenomas. METHODSPatients who underwent colonoscopy at the Toyoshima Endoscopy Clinic were enrolled. Polyps sized ≥ 5 mm suspected of adenomas or clinically significant serrated polyps were included in the study. We defined the surface structures of colorectal polyps, which were brown curves inside and along the tubular glands identified using a combination of a new X1 system (Olympus Corporation) and a conventional magnifying colonoscope with non-staining narrow band imaging (NBI), as brown slits. The brown slits corresponded to slit-like lumens on endocytoscopy and histological crypt openings of an adenoma. We evaluated the diagnostic performance of brown slits for adenoma. RESULTSA total of 108 Lesions from 62 patients were eligible. The average age was 60.4 years and 41.9% were male. The mean polyp size was 7.45 ± 2.83 mm. Fifty-seven lesions were positive for brown slits. Histopathological diagnosis comprised 59 low-grade tubular adenomas, 16 sessile serrated lesions, and 33 hyperplastic polyps. Among 59 adenomas, 56 (94.9%) were positive for brown slits. Among 16 sessile serrated lesions, 0 (0%) was positive for brown slits. Among 33 hyperplastic polyps, 1 (3.0%) was positive for brown slits. The sensitivity, specificity, and accuracy of brown slits for adenoma were 94.9%, 98.0%, and 96.3%, respectively. The positive predictive value and negative predictive value of brown slits for adenoma were also excellent for 98.2%, and 94.1%, respectively. CONCLUSIONBrown slits on conventional magnifying endoscopy with non-staining NBI using the X1 system were useful for diagnosing colorectal adenoma. The new endoscopy system could be examined using new standards.
Histopathological changes of the gastric mucosa after Helicobacter pylori infection, such as atrophy, metaplasia, and dysplasia, are considered to be precursors of gastric cancer, yet the mechanisms ...of histological progression are unknown. The aim of this study was to analyze the histopathological features of the gastric mucosa in mice infected with H. pylori strain PMSS1 in relation to gastric stem cell marker expression. C57BL/6J mice infected with PMSS1 were examined for histopathological changes, levels of proinflammatory cytokines, and expression of stem cell markers. Histopathological gastritis scores, such as atrophy and metaplasia, and levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), were increased after PMSS1 infection. Expression levels of the cell proliferation and stem cell markers CD44 and SOX9 were also significantly increased in PMSS1-infected mice. Importantly, almost all metaplastic cells induced by PMSS1 infection expressed SOX9. When IL-1 receptor (IL-1R) knockout mice were infected with PMSS1, metaplastic changes and expression levels of stem cell markers were significantly decreased compared with those in wild-type (WT) mice. In conclusion, H. pylori infection induced the expression of cytokines and stem cell markers and histopathological metaplasia in the mouse gastric mucosa. SOX9 expression, in particular, was strongly associated with metaplastic changes, and these changes were dependent on IL-1 signaling. The results suggested the importance of SOX9 in gastric carcinogenesis.
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