Endoscopic Resection For Gastric Cancer Research Articles

Long-term cardiovascular risk reduction after gastric cancer surgery: a nationwide cohort study.

Gastrectomy for gastric cancer is associated with postoperative changes in cardiovascular risk factors, however, the impact of gastrectomy on cardiovascular events remains unclear. We assessed the incidence of cardiovascular events between patients undergoing gastrectomy or endoscopic resection for gastric cancer, and the general population. This retrospective nationwide cohort study included patients with gastric cancer undergoing gastrectomy(n=37,698), endoscopic resection(n=2,773), and matched control population(n=161,887) between 2004 and 2013. We included patients without a history of cancer other than gastric cancer, myocardial infarction, or ischemic stroke. The primary outcome was the incidence of major adverse cardiovascular events (MACE) such as acute myocardial infarction, revascularization, or acute ischemic stroke, in patients with gastric cancer. Among patients who underwent gastrectomy for gastric cancer, 2.9% (4.69 per 1000 person-years) developed novel MACE within the seven-year follow-up period. The gastrectomy group demonstrated a significantly decreased risk for MACE than the control population (hazard ratio[HR], 0.65; 95% confidence interval[CI], 0.61-0.69; P <0.001). Among the patients undergoing endoscopic resection for gastric cancer, 5.4% (8.21 per 1000 person-years) developed novel MACE within the seven-year follow-up period. The risk for MACE in the endoscopic resection group was not significantly different from the control population. Patients with gastric cancer who have undergone gastrectomy exhibit a reduced risk of cardiovascular diseases in comparison to the general population. In contrast, the risk for cardiovascular diseases in patients with gastric cancer who underwent endoscopic resection did not demonstrate a significant difference in cardiovascular risk in comparison to the general population.

Risk of tuberculosis after endoscopic resection and gastrectomy in gastric cancer: nationwide population-based matched cohort study.

This study aimed to investigate the association between gastrectomy and endoscopic resection for gastric cancer and the subsequent tuberculosis incidence. We conducted a nationwide matched cohort study using data from the Korea National Health Insurance Service from 2013 to 2019. We created two cohorts: patients who underwent gastrectomy and those who had endoscopic resection. Each patient was matched 1:1 with an unexposed individual based on index year, age, sex, income, and various comorbidities. The primary outcome was the incidence of tuberculosis during the follow-up period. Our study comprised 90,886 gastrectomy patients and 46,759 endoscopic resection patients. The tuberculosis incidence was significantly higher in the gastrectomy group compared to its matched non-gastrectomy group (IRR 1.69, 95% CI 1.43-1.99, p < .001). In contrast, there was no significant difference in tuberculosis incidence between the endoscopic resection group and its matched non-resection group (IRR 0.95, 95% CI 0.75-1.19, p = 0.627). The Kaplan-Meier cumulative incidence also did not differ between the two groups. However, tuberculosis incidence significantly increased in the first year after endoscopic resection. Gastrectomy for gastric cancer is associated with a higher incidence of subsequent tuberculosis, while no significant association was observed for endoscopic resection. However, tuberculosis incidence increases significantly during the first year after endoscopic resection.

Factors influencing occurrence of metachronous gastric cancer after endoscopic resection: a systematic review and meta-analysis

Background/Aims: Metachronous gastric cancer (MGC) can occur after endoscopic resection for gastric cancer. Further studies on factors other than &lt;i&gt;Helicobacter pylori&lt;/i&gt; infection are needed. This systematic review and meta-analysis aimed to evaluate risk factors for metachronous recurrence of endoscopically resected gastric cancer.Methods: We searched medical literature published by February 2023 and identified patients with MGC after endoscopic resection for gastric cancer. The occurrence of MGC and the presence of intestinal metaplasia (IM), severe atrophic gastritis (AG), and &lt;i&gt;H. pylori&lt;/i&gt; infection were quantitatively analyzed.Results: We identified 2,755 patients from nine cohort studies who underwent endoscopic resection for gastric cancer by 2018. Those with severe AG or presence of IM had a significantly higher incidence of MGC than those without (RR 2.00, 95% CI 1.35–2.98, I&lt;sup&gt;2&lt;/sup&gt; = 52% for severe atrophy on antrum; RR 7.08, 95% CI 3.63–13.80, I&lt;sup&gt;2&lt;/sup&gt; = 0% for antral IM). Absolute risk difference of MGC occurrence was 7.1% in those with severe AG and 9.2% in those with IM. The difference in incidence rate per 1,000 person-years was 17.5 person-years for those with severe AG and 24.7 person-years for those with IM. However, &lt;i&gt;H. pylori&lt;/i&gt; eradication did not significantly affect the occurrence of MGC (RR 1.18, 95% CI 0.88–1.59, I&lt;sup&gt;2&lt;/sup&gt; = 10%).Conclusions: Gastric cancer patients with severe AG or presence of IM had a 2.0-fold or 7.0-fold higher risk of MGC occurrence after endoscopic resection than those without, respectively. They need more stringent follow-up to monitor MGC occurrences (CRD42023410940).

Comparative Risk of Type 2 Diabetes after Gastrectomy and Endoscopic Resection for Gastric Cancer: A Nationwide Cohort Study.

Patients with gastric cancer (GC) experience 2 characteristic treatment modalities (gastrectomy or endoscopic resection), which may induce heterogeneity in the risk of post-cancer treatment type 2 diabetes (T2D). We investigated differences in the risk for T2D development in survivors of GC according to the 2 treatment methods. This retrospective nationwide population-based cohort study included 14,646 patients with GC who underwent gastrectomy (n = 12,918) or endoscopic resection (n = 1,728). We enrolled patients who survived for at least 5 years after gastrectomy or endoscopic resection, had no history of diabetes, and had not received adjuvant chemotherapy. T2D risk was evaluated using Cox regression for the gastrectomy group and compared to that of the endoscopic resection group. Because of the competing risks of incident T2D and death, a competing risk regression was performed. After a median follow-up duration of 8.1 years, the incidence rates of T2D in the endoscopic resection group and gastrectomy group were 7.58 and 6.98 per 1,000 person-years, respectively. Patients undergoing gastrectomy showed a significantly higher risk for developing T2D than patients undergoing endoscopic resection (hazard ratio [HR], 1.37; 95% CI 1.18 to 1.58; p < 0.0001). In subgroup analyses, gastrectomy was associated with increased T2D risk in female patients (HR, 1.72; 95% CI 1.22 to 2.43; p = 0.030 for interaction). Among GC survivors, patients undergoing gastrectomy showed a 37% increased risk of T2D development compared to patients undergoing endoscopic resection. Subgroup analyses showed that T2D risk increased by up to 72% in female patients. These results provide insights for establishing screening and preventive strategies for GC survivors to prevent T2D according to different treatment modalities.

Abstract 738: Long-term survivorship between gastrectomy and endoscopic resection for gastric cancer using a nationwide real-world database: 15 years of follow-up

Abstract Introduction: Nutritional deficiency and weight loss after gastrectomy are important detrimental factors for gastric cancer survivorship, which is avoided by endoscopic resection (ER). On the other hand, chronic metabolic or cardiovascular diseases in long term survivors may require appropriate weight reduction. The purpose of this study is to evaluate long term survival, cumulative incidence, and medical expenses of chronic diseases between gastric cancer survivors who underwent gastrectomy and ER using the Korean National Health Insurance (KNHI) database. Methods: Big data of patients treated by either gastrectomy or ER for gastric cancer were restructured from 2008 to 2015 through the KNHI database which covers the entire Korean population. Those who had other primary cancer within 3 years before the treatment, received chemotherapy or radiotherapy, or had gastric cancer as the cause of death in death certificates were excluded. After 2:1 propensity score matching by age, sex, Charlson Comorbidity Index, insurance premium quartiles, and year of treatment, gastrectomy and ER groups were compared for 15-year survival, and incidence of new chronic diseases including major adverse cardiovascular events (MACE). MACE-3 was defined as first occurrence of all-cause mortality, ischemic heart disease, and cerebrovascular events, and MACE-6 as MACE-3 plus heart failure, nephropathy, and atrial fibrillation. Results: After matching, 49,578 survivors for the gastrectomy group and 24,789 for the ER group were analyzed. The gastrectomy group showed significantly higher risk of death by respiratory diseases (HR 1.37, 95% CI 1.18 - 1.35, P &amp;lt; 0.0001) including pneumonia (HR 1.62, 95% CI 1.32 - 2.00, P &amp;lt; 0.0001), and external causes such as trauma (HR 1.38, 95% CI 1.16 - 1.63, P &amp;lt; 0.0001), but lower risk of death caused by other cancers (HR 0.85, 95% CI 0.77 - 0.95, P &amp;lt; 0.0001) especially obesity-related cancers including liver, bile duct, gallbladder, and pancreatic cancer. There was no difference in risk of death by other ICD-10 diseases between the two groups. Gastrectomy group showed significantly lower incidence of hypertension (HR 0.65), ischemic heart disease (HR 0.84), heart failure (HR 0.80), and cerebrovascular diseases (HR 0.79) than the ER group. The gastrectomy group had lower risk of MACE-3 (HR 0.86, 95% CI 0.83 - 0.89, P &amp;lt; 0.0001) and MACE-6 (HR 0.86, 95% CI 0.83 - 0.89, P &amp;lt; 0.0001). Conclusion: The gastrectomy group showed lower risk of MACE and obesity-related cancers with less medical care expenses for diabetes or hypertension, but had higher risk of death by pneumonia or external causes than the ER group in Korea. Citation Format: Hyeong-taek Woo, So Hyun Kang, Ji Yoon Baek, Mira Yoo, Duyeong Hwang, Eunju Lee, Young Suk Park, Sang-Hoon Ahn, Nayoung Kim, Dong Ho Lee, Hyung-Ho Kim, Aesun Shin, Yun-Suhk Suh. Long-term survivorship between gastrectomy and endoscopic resection for gastric cancer using a nationwide real-world database: 15 years of follow-up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 738.

Effects of activation of an alcohol metabolic gene, cigarette smoking, and alcohol intake on the incidence of metachronous gastric cancer in patients who underwent endoscopic resection for gastric cancer: A multicenter retrospective pilot study.

Metachronous gastric cancer (GC) frequently occurs in patients who have undergone endoscopic resection (ER) for GC. We evaluated the risk for development of metachronous GC following ER for GC based on genetic polymorphisms for alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2), as well as alcohol consumption and smoking habits. We studied 77 patients who underwent ER for GC (median follow-up of 84 months). Genotyping of ADH1B/ALDH2 was performed using saliva sampling. Histories of alcohol consumption and smoking before and after ER and Helicobacter pylori eradication were documented. Multivariate analyses revealed that homozygous slow-metabolizing ADH1B (hazard ratio [HR] = 2.38, P < 0.13), heavy smoking (HR = 2.36, P < 0.09), and cigarette smoking after ER (HR = 2.47, P < 0.10) were not independently associated with the risk of secondary GC development. We analyzed the cessation status of the 38 patients who were classified as heavy smokers before ER based on their smoking habits after the ER and divided them into a cessation group (n = 27, non-smokers after ER) and a non-cessation group (n = 11). Cumulative incidence curves of secondary GC in the cessation and non-cessation groups revealed 5-year incidence rates of 19.0% and 45.0%, respectively (P = 0.02). Continued cigarette smoking, at a high level, may be an important risk factor for the development of metachronous GC. Advice for smoking cessation should be given.

The role of lymph node metastasis in early gastritis Individuals following noncurative endoscopic Resection: a systematic review and meta-analysis.

Recent studies suggest that individuals who underwent noncurative endoscopic resection for gastric cancer may require additional surgery. We conducted a comprehensive systematic review and meta-analysis to investigate the risk of lymph node metastasis in these cases. We comprehensively examined relevant literature by extensively reviewing electronic databases such as PubMed, Cochrane Library, and Google Scholar. Subsequently, we analyzed clinicopathological outcomes and calculated pooled odds ratios and 95 percent confidence intervals using diverse effects models. This analysis included 12 papers with 4808 individuals who underwent additional surgery after noncurative endoscopic resection for early gastric cancer. The results indicated significant associations between lymph node metastasis and submucosal invasion (Odd ratio 2.04, 95% (CI): 1.58-2.63, I 2 = 88.7%; p<0.001), vertical margin (Odd ratio 6.11, 95% (CI): 1.94-19.23, I 2 = 0%; p<0.001), lymphatic invasion (Odd ratio 10.02, 95% (CI): 7.57-13.27, I 2 = 92%; p<0.000), and vascular invasion (Odd ratio 7.11, 95% (CI): 5.49-9.22, I 2=92%; p<0.000). When choosing factors for surgical treatment, it is essential to thoroughly consider the invasion of lymph nodes, vascular system, submucosa, and positive vertical margin.

Long-term Survival After Endoscopic Resection For Gastric Cancer: Real-world Evidence From a Multicenter Prospective Cohort

We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study. We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C). Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS. ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Use of Antibiotics and Probiotics Reduces the Risk of Metachronous Gastric Cancer after Endoscopic Resection.

Simple SummaryHelicobacter pylori is the most important cause of gastric cancer, and its eradication reduces the incidence of gastric cancer after endoscopic resection. However, incidence of metachronous gastric cancer is still high. More studies are needed to identify other chemopreventive drugs that may reduce the incidence of this disease. In this study, we focused on the alteration of the intragastric microbiome and examined the association between the use of antibiotics and probiotic drugs and risk of metachronous gastric cancer. Our findings suggest that the gut microbiome is associated with metachronous gastric cancer development.Metachronous gastric cancer often occurs after endoscopic resection. Appropriate management, including chemoprevention, is required after the procedure. This study was performed to evaluate the association between medication use and the incidence of metachronous gastric cancer after endoscopic resection. This multicenter retrospective cohort study was conducted with data from nine hospital databases on patients who underwent endoscopic resection for gastric cancer between 2014 and 2019. The primary outcome was the incidence of metachronous gastric cancer. We evaluated the associations of metachronous gastric cancer occurrence with medication use and clinical factors. Hazard ratios were adjusted by age and Charlson comorbidity index scores, with and without consideration of sex, smoking status, and receipt of Helicobacter pylori eradication therapy during the study period. During a mean follow-up period of 2.55 years, 10.39% (140/1347) of all patients developed metachronous gastric cancer. The use of antibiotics other than those used for H. pylori eradication was associated with a lower incidence of metachronous gastric cancer than was non-use (adjusted hazard ratio (aHR) 0.56, 95% confidence interval (CI) 0.38–0.85, p = 0.006). Probiotic drug use was also associated with a lower incidence of metachronous gastric cancer compared with non-use (aHR 0.29, 95% CI 0.091–0.91, p = 0.034). In conclusion, the use of antibiotics and probiotic drugs was associated with a decreased risk of metachronous gastric cancer. These findings suggest that the gut microbiome is associated with metachronous gastric cancer development.

White-Light Endoscopy Versus Magnifying Narrow-Band Imaging for Diagnosis of the Histological Subtype of Gastric Cancer

Background: Distinguishing gastric cancer from non-cancer using endoscopy has already been validated. However, distinguishing undifferentiated-type (diffuse-type) from differentiated-type (intestinal-type) cancer is also crucial for determining the indication of endoscopic resection for gastric cancer. This study aimed to evaluate on-site diagnostic performance of conventional white-light endoscopy (WLE) and magnifying narrow-band imaging (M-NBI) in determining the subtype of gastric cancer. Methods: We conducted a multicenter prospective single-arm trial. This study was registered with UMIN Clinical Trials Registry, number UMI32151. Patients who planned to undergo treatment for histologically proven cT1 gastric cancer were recruited from six tertiary care institutions. The primary and key secondary endpoints were diagnostic accuracy and specificity, respectively. The diagnostic algorithm of WLE was based on lesion color. The M-NBI algorithm was based on the microsurface and microvascular patterns. Findings: A total of 208 patients were enrolled. After protocol endoscopy, 167 gastric cancers were included in the analysis. The accuracy, sensitivity, specificity, and positive likelihood ratio of WLE for undifferentiated-type cancer were 80% (95% CI 73%–86%), 69% (53%–82%), 84% (77%–90%), and 4·4 (2·8–7·0), respectively. Those of M-NBI were 82% (75%–88%), 53% (38%–68%), 93% (87%–97%), and 7·2 (3·6–14·4), respectively. There was no significant difference in accuracy between WLE and M-NBI (p = 0·755), but specificity was significantly higher with M-NBI than with WLE (p = 0·041). Those of M-NBI combined with WLE were 81% (74%–87%), 38% (24%–54%), 97% (92%–99%), and 11·5 (4·1–32·4), respectively. Interpretation: M-NBI is more specific than WLE in distinguishing undifferentiated-type from differentiated-type gastric cancer. M-NBI combined with WLE is highly reliable (positive likelihood ratio >10) for diagnosing the subtype of gastric cancer, and optical biopsy may be introduced to determine the indication for endoscopic resection of gastric cancer. Trial Registration: UMIN Clinical Trials Registry, number UMI32151 Funding: The Yasuda Medical Foundation. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This multicenter, prospective, single-arm, phase II trial was conducted in accordance with the Declaration of Helsinki and Ethical Guidelines for Medical and Health Research Involving Human Subjects. The study protocol was approved by the Institutional Review Board of Osaka International Cancer Institute on December 22, 2017 (approval number: 1712226191) and each participating institution. All participants provided written informed consent.

Clinical prediction of solitary pulmonary nodule after a curative resection for gastric cancer.

Gastric cancer metastasis to the lung can rarely manifest as solitary pulmonary nodule. The surgical strategies are different between metastasis from gastric cancer and primary lung cancer; therefore, the clinical prediction of solitary pulmonary nodule is important. Between September 2006 and September 2016, 38 patients with a history of curative resection for gastric cancer who subsequently underwent lung resection for solitary pulmonary nodule at our institution were evaluated. We retrospectively reviewed clinical characteristics in order to investigate clinical predictors for diagnosis and appropriate operative strategies. Nodules were shown to be 9 metastasis from gastric cancer, 26 primary lung cancer and 3 benign tumors. Between metastasis from gastric cancer and primary lung cancer, there was a significant difference in age (P = 0.013), surgical procedure used for gastrectomy (P = 0.018) and pathological stage of gastric cancer (P = 0.031). All eight patients who had undergone endoscopic resection for gastric cancer and all 10 patients whose pulmonary nodules were detected more than 5 years after gastrectomy were diagnosed as primary lung cancer. Regarding the prognosis after lung resection, at a median follow-up of 29.3 months, the median survival time in patients with metastasis from gastric cancer was 19.7 months (range, 10.2-63.7 months), whereas that was not reached in patients with primary lung cancer. Solitary pulmonary nodule in patients with a history of pathological stage I gastric cancer may be suspected as primary lung cancer, and an anatomical lung resection should be considered positively. In the case of solitary pulmonary nodule suspected metastasis from gastric cancer from clinical characteristics, a limited resection may be considered, and metastasectomy can potentially result in long-term survival.

Factors Affecting Endoscopic Curative Resection of Gastric Cancer in the Population-Based Screening Era.

Background/AimsSince population-based screening for gastric cancer in Korea was implemented, endoscopic treatment of early gastric cancer has become increasingly popular. This study investigates factors affecting endoscopic curative resection of early gastric cancer in population-based screening for gastric cancer. MethodsWe retrospectively reviewed data of patients with newly diagnosed gastric cancer who underwent treatment at Seoul St. Mary’s Hospital. All patients completed questionnaires about clinical information, including interval between surveillance tests for gastric cancer. ResultsOf 469 gastric cancer patients, 147 (31.3%) had undergone curative endoscopic resection, 260 (55.4%) had undergone curative surgical resection, and 62 (13.3%) underwent non-curative resection or were in an inoperable state. Patients with curative endoscopic resection had fewer alarm symptoms/signs than other groups. In multivariate analysis, regular surveillance endoscopy was the only factor predicting curative endoscopic resection (odds ratio [OR], 6.099; 95% confidence interval [CI], 2.532–14.933). In addition, patients undergoing gastric cancer screening had a significantly higher rate of endoscopic curative resection compared with subjects who had never been screened. (1-year interval: OR, 49.969; 95% CI, 6.340–393.827, 2-year interval: OR, 15.283; 95% CI, 1.833–127.406, over 2-year interval: OR, 10.651; 95% CI, 1.248–90.871). Shorter screening test intervals were associated with higher rates of endoscopic curative resection. ConclusionsRegular surveillance testing was the independent factor predicting curative endoscopic resection of gastric cancer.

Clinical efficacy of endoscopic ultrasonography for decision of treatment strategy of gastric cancer

Accurate preoperative tumor staging of gastric cancer is indispensable with expansion of indications for laparoscopic surgery and endoscopic resection. It is important to distinguish mucosal cancer (T1a) in smaller lesion and differentiate early gastric cancer (EGC) in larger lesion considering endoscopic resection indication and laparoscopic surgery indication. We evaluated the clinical outcomes of endoscopic ultrasonography (EUS) for the decision of treatment strategy of gastric cancer compared with pathological staging. The patients who underwent EUS and surgical or endoscopic resection for gastric cancer were retrospectively reviewed between September 2005 and February 2016. The depth of tumor invasion (T staging) by EUS was compared with the pathological staging after endoscopic or surgical resection. A total of 6084 patients were finally analyzed. The accuracy rates for T1a and EGC were 75.0 and 89.4%, respectively. The overall accuracy of T staging by EUS was 66.3% when divided by T1a, T1b, and over T2. The accuracy of EUS prior to endoscopic resection was 75.1% in absolute indication and 73.1% in expanded criteria, respectively. The accuracy rates for T1a with lesion ≤ 2cm in miniprobe EUS and EGC with lesion > 2cm in conventional EUS were 84.6 and 83.2%, respectively. In multivariate analysis, presence of ulcer, large tumor size, and radial EUS were associated with overestimation, and small tumor size and miniprobe were associated with underestimation in T staging. EUS showed the high accuracy of 84.6% for T1a in lesion ≤ 2cm in miniprobe EUS and 83.2% for EGC in lesion > 2cm in conventional EUS, respectively. EUS can be a complementary diagnostic method to determine endoscopic or surgical treatment modality.

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Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis

Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of benefit of H pylori eradication in populations with different levels of gastric cancer risk and in different clinical scenarios is unclear. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies to investigate the effects of H pylori eradication on the incidence of gastric cancer. We searched PubMed, Cochrane Library, and ClinicalTrials.gov, reviewing titles and abstracts of studies of the effects of eradication of H pylori infection on risk of gastric cancer, through May 2015. We also searched bibliographies of included studies, related reviews, and abstracts presented at Digestive Disease Week. Twenty-four eligible studies (22 research manuscripts and 2 abstracts) were included in our meta-analysis (715 incident gastric cancers among a total of 48,064 individuals/340,255 person-years). We assessed the effects, as well as their modification by baseline gastric cancer incidence, study design (randomized trial vs observational study), clinical scenario (asymptomatic infected individuals vs individuals after endoscopic resection of early gastric cancer), demographic characteristics of patients (age and sex), and duration of follow-up. After adjustment for baseline gastric cancer incidence, individuals with eradication of H pylori infection had a lower incidence of gastric cancer than those who did not receive eradication therapy (pooled incidence rate ratio= 0.53; 95% confidence interval: 0.44-0.64). There was little heterogeneity among studies. Baseline gastric cancer incidence modified the benefit of H pylori eradication (P= .037 for interaction); the incidence rate ratio of gastric cancer decreased in a nonlinear fashion with increasing baseline incidence of gastric cancer (P= .018, in comparison with the linear model). The benefit also modestly increased with age (P= .023 for interaction), but this might be due to correlation between age and baseline gastric cancer incidence. Eradication provided significant benefit for asymptomatic infected individuals (pooled incidence rate ratio, 0.62; 95% CI: 0.49-0.79) and individuals after endoscopic resection of gastric cancers (pooled incidence rate ratio, 0.46; 95% CI: 0.35-0.60). The benefits of H pylori eradication did not differ with study design, sex, or follow-up period. In a systematic review and meta-analysis, we associated eradication of H pylori infection with a reduced incidence of gastric cancer. The benefits of eradication vary with baseline gastric cancer incidence, but apply to all levels of baseline risk.

Gastric cancer development after the successful eradication of Helicobacter pylori.

Gastric cancer (GC) develops as a result of inflammation-associated carcinogenesis due to Helicobacter pylori (H. pylori) infection and subsequent defects in genetic/epigenetic events. Although the indication for eradication therapy has become widespread, clinical studies have revealed its limited effects in decreasing the incidence of GC. Moreover, research on biopsy specimens obtained by conventional endoscopy has demonstrated the feasibility of the restoration of some genetic/epigenetic alterations in the gastric mucosa. Practically, the number of sporadic cases of primary/metachronous GC that emerge after successful eradication has increased, while on-going guidelines recommend eradication therapy for patients with chronic gastritis and those with background mucosa after endoscopic resection for GC. Accordingly, regular surveillance of numerous individuals who have received eradication therapy is recommended despite the lack of biomarkers. Recently, the focus has been on functional reversibility after successful eradication as another cue to elucidate the mechanisms of restoration as well as those of carcinogenesis in the gastric mucosa after H. pylori eradication. We demonstrated that Congo-red chromoendoscopy enabled the identification of the multi-focal distribution of functionally irreversible mucosa compared with that of restored mucosa after successful eradication in individuals at extremely high risk for GC. Further research that uses functional imaging may provide new insights into the mechanisms of regeneration and carcinogenesis in the gastric mucosa post-eradication and may allow for the development of useful biomarkers.

Heat shock protein A4 controls cell migration and gastric ulcer healing.

Heat shock protein A4 (HSPA4, also called Apg-2), a member of the HSP110 family, regulates the immune response in the gut. Here, we assessed the involvement of HSPA4 in gastric ulcer healing by using fibroblasts from wild-type and HSPA4-deficient mice, a murine gastric ulcer model, and samples from 65 patients with gastric cancer. HSPA4 expression was inversely correlated with gastric ulcer healing following endoscopic resection of gastric cancer. In the human gastric mucosa, the expression of HSPA4 was inversely correlated with the expression of stromal cell-derived factor 1 (SDF-1), its cognate receptor CXC chemokine receptor 4 (CXCR4), the stromal cell marker vimentin, and the epithelial-mesenchymal transition regulator Twist. HSPA4 was overexpressed in stromal cells as well as in human gastric cancer cells. HSPA4 deficiency increased the expression of SDF-1 and CXCR4, as well as the number of fibroblast-specific protein 1-positive cells, leading to accelerated ulcer healing in the murine gastric ulcer model. Deletion of HSPA4 promoted cell migration in mouse fibroblasts through increased expression of SDF-1 and Twist. HSPA4 regulates the expression of SDF-1 and Twist in fibroblasts, thereby controlling gastric ulcer healing.

Prediction of Helicobacter pylori Status by Conventional Endoscopy, Narrow‐Band Imaging Magnifying Endoscopy in Stomach after Endoscopic Resection of Gastric Cancer

To reduce the incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer, Helicobacter pylori eradication therapy has been endorsed. It is not unusual for such patients to be H. pylori negative after eradication or for other reasons. If it were possible to predict H. pylori status using endoscopy alone, it would be very useful in clinical practice. To clarify the accuracy of endoscopic judgment of H. pylori status, we evaluated it in the stomach after endoscopic submucosal dissection (ESD) of gastric cancer. Fifty-six patients treated by ESD were enrolled. The diagnostic criteria for H. pylori status by conventional endoscopy and narrow-band imaging (NBI)-magnifying endoscopy were decided, and H. pylori status was judged by two endoscopists. Based on the H. pylori stool antigen test as a diagnostic gold standard, conventional endoscopy and NBI-magnifying endoscopy were compared for their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Interobserver agreement was assessed in terms of κ value. Interobserver agreement was moderate (0.56) for conventional endoscopy and substantial (0.77) for NBI-magnifying endoscopy. The sensitivity, specificity, PPV, and NPV were 0.79, 0.52, 0.70, and 0.63 for conventional endoscopy and 0.91, 0.83, 0.88, and 0.86 for NBI-magnifying endoscopy, respectively. Prediction of H. pylori status using NBI-magnifying endoscopy is practical, and interobserver agreement is substantial.

Surgical Outcomes and Clinicopathological Characteristics of Patients Who Underwent Potentially Noncurative Endoscopic Resection for Gastric Cancer: A Report of a Single-Center Experience

Background. Standard treatment of early gastric cancer (EGC) after endoscopic resection with risk factors of nodal metastases and incomplete resection is controversial. We investigated optimal management for the patients with potentially noncurative EGC after endoscopic resection. Methods. We retrospectively examined clinicopathological data and surgical outcomes of all patients with clinically solitary gastric adenocarcinoma who underwent curative surgery after a single peroral endoscopic resection at the Digestive Disease Center of Showa University Northern Yokohama Hospital between April 2001 and December 2012. Fisher's exact test was used for univariate analysis. For multivariate analysis, stepwise multiple linear regression was used to identify independent predictors related to lymph node metastasis and remnant of primary tumor. Results. A total of 41 patients were studied. Four patients (9.8%) had lymph node metastases. Primary tumors remained in 6 patients (14.6%). Only venous invasion was statistically significant to lymph node metastasis (P = 0.017). With respect to remnant of the primary tumor, pT1b2 tumor invasion (P = 0.015) and horizontal margin (P = 0.013) were statistically significant. Conclusions. Surgery with limited lymphadenectomy is recommended for tumors with venous invasion or pT1b2 tumor invasion, and additional endoscopic resection may be allowed for tumors with horizontal involvement.

Enfermedades relacionadas con la infección por Helicobacter pylori

This article summarizes the main conclusions drawn from the studies presented in Digestive Disease Week in 2012 on Helicobacter pylori infection. In developed countries, the prevalence of this infection has decreased, although it continues to be high. The prevalence in Spain is high (50%) and does not seem to be decreasing. There is an increase in antibiotic resistance, which is correlated with the frequency of prior antibiotic prescription. H. pylori eradication improves the symptoms of “epigastric pain syndrome” in functional dyspepsia. The frequency of idiopathic peptic ulcers seems to be increasing. To prevent the development of gastric cancer, eradication therapy should be administered early (before intestinal metaplasia develops). H. pylori eradication in patients undergoing early endoscopic resection of gastric cancer reduces the incidence of metachronous tumors, although endoscopic follow-up should be performed periodically. H. pylori eradication induces MALT lymphoma regression in most patients and tumoral recurrence in the long term is exceptional; radiotherapy is an excellent second-line option; a watch and wait approach to histologic recurrence after initial MALT lymphoma remission is a reasonable alternative. Idiopathic thrombocytopenic purpura is an indication for eradication therapy in children as well as adults. There are several diagnostic innovations, such as high-resolution endoscopy, narrow-band imaging, a method based on the electrochemical properties of H. pylori, and the cytosponge. Quadruple therapy with bismuth is at least as effective as standard triple therapy. The superiority of “sequential” therapy over standard triple therapy should be confirmed in distinct settings. The efficacy of “concomitant” therapy is similar –or even better– than that of “sequential” therapy, but has the advantage of being simpler. A hybrid sequential-concomitant therapy is highly effective. In patients allergic to beta-lactams, the efficacy of treatment with a proton pump inhibitor-clarithromycin-metronidazole is insufficient. When standard triple therapy fails, the second-line option of a 10-day course of levofloxacin is effective and is simpler and better tolerated than quadruple therapy. Triple therapy with levofloxacin is also a promising alternative after failure of “sequential” and “concomitant” therapy. New-generation quinolones, such as moxifloxacin and sitafloxacin, could be useful as eradication therapy, especially as rescue therapy. When two eradication therapies have failed, empirical administration of a third (e.g. levofloxacin) is a valid option. Even after three eradication therapies have failed, an empirical rescue therapy (with rifabutin) can be effective. H. pylori reinfection is highly frequent in developing countries, probably due to intrafamilial transmission.