BACKGROUND: Although change in the birth cohort effect on cancer mortality rates is known to be highly associated with the decreasing rates of age-standardized cancer mortality rates in Japan, the differences in the trends of cohort effect for representative cancer types among the prefectures remain unknown. This study aimed to investigate the differences in the decreasing rate of cohort effects among the prefectures for representative cancer types using age-period-cohort (APC) analysis. METHODS: Data on stomach, colorectal, liver, and lung cancer mortality for each prefecture and the population data from 1999 to 2018 were obtained from the Vital Statistics in Japan. Mortality data for individuals aged 50 to 79 years grouped in 5-year increments were used, and corresponding birth cohorts born 1920-1924 through 1964-1978 were used for analysis. We estimated the effects of age, period, and cohort on each type of mortality rate for each prefecture by sex. Then, we calculated the decreasing rates of cohort effects for each prefecture. We also calculated the mortality rate ratio of each prefecture compared with all of Japan for cohorts using the estimates. RESULTS: As a result of APC analysis, we found that the decreasing rates of period effects were small and that there was a little difference in the decreasing rates among prefectures for all types of cancer among both sexes. On the other hand, there was a large difference in the decreasing rates of cohort effects for stomach and liver cancer mortality rates among prefectures, particularly for men. For men, the decreasing rates of cohort effects in cohorts born between 1920-1924 and 1964-1978 varied among prefectures, ranging from 4.1 to 84.0% for stomach cancer and from 20.2 to 92.4% for liver cancers, respectively. On the other hand, the differences in the decreasing rates of cohort effects among prefectures for colorectal and lung cancer were relatively smaller. CONCLUSIONS The decreasing rates of cohort effects for stomach and liver cancer varied widely among prefectures. It is possible that this will influence cancer mortality rates in each prefecture in the future.
Aged ; Cohort Studies ; Colorectal Neoplasms/mortality* ; Female ; Humans ; Japan/epidemiology* ; Liver Neoplasms/mortality* ; Lung Neoplasms/mortality* ; Male ; Middle Aged ; Risk Factors ; Stomach Neoplasms/mortality*

OBJECTIVE: To investigate the differentially expressed genes between gastric cancer and normal gastric mucosa by bioinformatics analysis, identify the important gene participating in the occurrence and progression of gastric cancer, and predict the functions of these genes. METHODS: The gene expression microarray data GSE100935 (including 18 gastric cancer samples and normal gastric mucosal tissues) downloaded from the GEO expression profile database were analyzed using Morpheus to obtain the differentially expressed genes in gastric cancer, and a cluster analysis heat map was constructed. The online database UALCAN was used to obtain the expression levels of these differentially expressed genes in gastric cancer and normal gastric mucosa. The prognostic value of the differentially expressed genes in gastric cancer was evaluated with Kaplan-Meier survival analysis. GO functional enrichment analysis was performed using Fun-Rich software, and the STRING database was exploited to establish a PPI network for the differentially expressed genes. RESULTS: A total of 45119 differentially expressed genes were identified from GSE100935 microarray data. Analysis with UALCAN showed an obvious high expression of EXD3 gene in gastric cancer, and survival analysis suggested that a high expression level of EXD3 was associated with a poorer prognosis of the patients with gastric cancer. GO functional enrichment analysis found that the differentially expressed genes in gastric cancer were involved mainly in the regulation of nucleotide metabolism and the activity of transcription factors in the cancer cells. CONCLUSIONS EXD3 may be a potential oncogene in gastric cancer possibly in relation to DNA damage repair. The up-regulation of EXD3 plays an important role in the development and prognosis of gastric cancer, and may serve as an important indicator for prognostic evaluation of the patients.
Computational Biology ; Databases, Genetic ; Exonucleases ; genetics ; Gastric Mucosa ; chemistry ; enzymology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins ; genetics ; Prognosis ; Stomach Neoplasms ; enzymology ; genetics ; mortality

OBJECTIVE: To investigate the prognostic value of tumor deposits(TD)in N0 stage gastric cancer. METHODS: A retrospective case-control study was performed on clinicopathological data of 751 N0 stage gastric cancer patients who underwent subsequent R0 gastrectomy from January 2011 to February 2013 at Zhengzhou University Affiliated Tumor Hospital. Patients were divided into TD-negative group (688 cases) and TD-positive group (63 cases). Propensity score matching was used to balance the covariances between the two groups, such as age, gender, differentiation degree, tumor location, T stage, perineural invasion, lymphovascular invasion, extent of resection, tumor size, surgical procedure,and chemotherapy. Matching was performed by the minimal adjacent method of 1:2 pairing. The survival analysis was carried out using Kaplan-Meier method,and differences between the curves were detected by log-rank test. Cox proportional hazard model was used to perform univariate analysis and multivariate analysis. RESULTS: After matching,56 patients were allocated into the TD-positive group and 112 patients into the TD-negative group, and the baseline of clinicopathological data of 2 groups matched well (all P>0.05). The median follow-up time was 55.2 (12.0-83.2) months, and 3 patients were lost to follow-up (died of other diseases). In TD-positive group, 38 patients died of gastric cancer and 1 died of other disease. In TD-negative group, 52 patients died of gastric cancer and 2 died of other diseases. The TD-positive group had lower 5-year survival rate than TD-negative group (31.0% vs. 52.9%,χ²=6.230, P=0.014). Subgroup analysis showed that the 5-year survival rate of T1-2 stage TD-positive patients was significantly lower than that of T1-2 stage TD-negative patients (47.1% vs. 92.6%, χ²=11.433,P<0.001),while the difference between two groups with T3-4 stage (23.8% vs. 40.0%, χ²=2.995,P=0.084)was not significant. In patients receiving chemotherapy, the 5-year survival rate of TD-positive group was significantly lower than that of TD-negative group(34.1% vs. 54.8%, χ²=4.122, P=0.042). Further subgroup analysis showed that patients receiving postoperative chemotherapy of TD-positive group both in T1-2 stage (63.6% vs. 100%, χ²=3.830,P=0.048) and in T3-4 stage (24.2% vs. 48.4%, χ²=4.740,P=0.029) had significantly lower 5-year survival rates than those of TD-negative group. However,T1-2 stage TD-positive patients receiving chemotherapy had significantly higher 5-year survival rate as compared to those without receiving chemotherapy(63.6% vs. 16.7%, χ²=5.474,P=0.019).Univariate analysis revealed T stage (HR=1.829, 95%CI:1.490-2.245, P<0.001),perineural invasion (HR=2.620, 95%CI:1.617-4.246,P<0.001),tumor size (HR=1.646, 95%CI:1.078-2.512, P=0.021),TD(HR=1.691,95%CI:1.112-2.572,P=0.014) were associated with the prognosis of patients with gastric cancer. Multivariate analysis showed TD-positive (HR=2.035, 95%CI:1.325-3.126, P=0.001), later T stage (HR=1.812, 95%CI: 1.419-2.313,P<0.001), perineural invasion (HR=1.782,95%CI:1.058-3.002,P=0.030) were independent risk factors for the prognosis of gastric cancer. CONCLUSIONS TD is an independent risk factor for N0 stage gastric cancer,and may be closely related to T stage. Patients with TD-positive stage T1-2 should receive chemotherapy, but the prognosis of TD-positive patients undergoing adjuvant chemotherapy is poorer as compared to TD-negative patients. Therefore, more individualized treatments should be administrated.
Antineoplastic Agents ; therapeutic use ; Case-Control Studies ; Chemotherapy, Adjuvant ; Gastrectomy ; Humans ; Neoplasm Staging ; Prognosis ; Propensity Score ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; mortality ; pathology ; surgery ; Survival Analysis ; Survival Rate

OBJECTIVE: To compare the clinicopathological features and the prognosis between patients with adenocarcinoma of esophagogastric junction (AEG) and with adenocarcinoma of gastric antrum (AGA), and to investigate the prognostic factors of AEG and AGA. METHODS: A retrospective cohort study was performed on clinicopathological data of 239 AEG patients (AEG group) and 313 AGA patients selected simultaneously (AGA group) undergoing operation at Harbin Medical University Cancer Hospital from January 2001 to December 2012. INCLUSION CRITERIA: (1) receiving radical surgery (R0 resection); (2) AEG or AGA confirmed by pathological examination of postoperative tissue specimens; (3) without preoperative neoadjuvant radiotherapy or chemotherapy; (4) complete clinicopathological and follow-up data; (5) patients who died of non-tumor-related causes were excluded. Chi-square test and independent samples t-test were used to determine differences in clinicopathological factors between two groups. The overall survival (OS) of patients was compared by Kaplan-Meier method and Log-rank test. Multivariate prognosis analysis was performed using Cox proportional hazards regression model. RESULTS: As compared to AGA group, AEG group had higher proportion of male [82.0%(196/239) vs. 65.2%(204/313),χ²=19.243,P<0.001], older age [(60±10) years vs. (55±12) years, t=4.895, P<0.001], larger tumor diameter [(5.6±2.4) cm vs. (5.0±3.3) cm, t=2.480,P=0.013], more T4 stage[64.8%(155/239) vs. 55.6%(174/313),Z=-3.998, P<0.001], and more advanced tumor stage [stage III:60.7%(145/239) vs. 55.6%(174/313),Z=-2.564,P=0.010]. There were no statistically significant differences in serum albumin or hemoglobin between two groups (all P>0.05). The 5-year OS rate was 33.5% and 56.9% in AEG group and AGA group respectively and the median OS was 60.0(3.0-60.0) months and 33.6(3.0-60.0) months respectively; the difference was statistically significant (P<0.001). In AEG group, univariate analysis showed that differences of hemoglobin level (5-year OS rate: 24.0% for <130 g/L, 39.9% for ≥130 g/L, P=0.006), tumor diameter (5-year OS rate: 41.9% for <5 cm,28.8% for ≥5 cm, P=0.014), N stage (5-year OS rate: 42.2% for N0, 40.9% for N1, 31.7% for N2, 15.8% for N3a, 9.0% for N3b, P<0.001) and TNM stage (5-year OS rate: 56.2% for stage I, 38.5% for stage II, 28.3% for stage III,P=0.017) were statistically significant (all P<0.05); multivariate analysis revealed that the worse N stage was an independent risk factor of prognosis survival for AEG patients(HR=1.404,95%CI:1.164-1.693, P<0.001), and serum hemoglobin level ≥130 g/L was an independent protective factor of prognosis survival for AEG patients (HR=0.689,95%CI:0.501-0.946,P=0.021). In AGA group, univariate analysis showed that differences of serum albumin (5-year OS rate: 49.1% for <40 g/L, 61.1% for ≥ 40 g/L, P=0.021), tumor diameter (5-year OS rate: 74.2% for <5 cm, 39.9% for ≥ 5 cm, P<0.001), T stage (5-year OS rate: 98.3% for T1,83.3% for T2,50.0% for T3,36.8% for T4, P<0.001), N stage (5-year OS rate: 89.0% for N0, 62.3% for N1, 50.0% for N2, 33.9% for N3a, 10.3% for N3b, P<0.001) and TNM stage (5-year OS rate: 97.3% for stage I, 75.8% for stage II, 32.8% for stage III, P<0.001) were statistically significant (all P<0.05); multivariate analysis revealed that the worse T stage (HR=1.516,95%CI:1.060-2.167,P=0.023) and the worse N stage (HR=1.453,95%CI:1.209-1.747,P<0.001) were independent risk factors for prognosis of AGA patients. CONCLUSIONS As compared to AGA, AEG presents have poorer prognosis,and is easier to present with later pathological stage and larger tumor diameter. N stage and hemoglobin level are independent factors associated with the OS of AEG patients. T stage and N stage are independent factors associated with the OS of AGA patients.
Adenocarcinoma ; mortality ; pathology ; surgery ; Adult ; Aged ; Esophagogastric Junction ; pathology ; surgery ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Pyloric Antrum ; pathology ; surgery ; Retrospective Studies ; Stomach Neoplasms ; mortality ; pathology ; surgery

OBJECTIVE: To compare the long-term survival outcomes of Siewert II adenocarcinoma of esophagogastric junction (AEG) between transthoracic (TT) approach and transabdominal (TA) approach. METHODS: The databases of Gastrointestinal Surgery Department and Thoracic Surgery Department in West China Hospital of Sichuan University from 2006 to 2014 were integrated. Patients of Siewert II AEG who underwent resection were retrospectively collected. INCLUSION CRITERIA: (1) adenocarcinoma confirmed by gastroscopy and biopsy; (2) tumor involvement in the esophagogastric junction line; (3) tumor locating from lower 5 cm to upper 5 cm of the esophagogastric junction line, and tumor center locating from upper 1 cm to lower 2 cm of esophagogastric junction line; (4)resection performed at thoracic surgery department or gastrointestinal surgery department; (5) complete follow-up data. Patients at thoracic surgery department received trans-left thoracic, trans-right thoracic, or transabdominothoracic approach; underwent lower esophagus resection plus proximal subtotal gastrectomy; selected two-field or three-field lymph node dissection; underwent digestive tract reconstruction with esophagus-remnant stomach or esophagus-tubular remnant stomach anastomosis above or below aortic arch using hand-sewn or stapler instrument to perform anastomosis. Patients at gastrointestinal surgery department received transabdominal(transhiatal approach), or transabdominothoracic approach; underwent total gastrectomy or proximal subtotal gastrectomy; selected D1, D2 or D2 lymph node dissection; underwent digestive tract reconstruction with esophagus-single tube jejunum or esophagus-jejunal pouch Roux-en-Y anastomosis, or esophagus-remnant stomach or esophagus-tubular remnant stomach anastomosis; completed all the anastomoses with stapler instruments. The follow-up ended in January 2018. The TNM stage system of the 8th edition UICC was used for esophageal cancer staging; survival table method was applied to calculate 3-year overall survival rate and 95% cofidence interval(CI); log-rank test was used to perform survival analysis; Cox regression was applied to analyze risk factors and calculate hazard ratio (HR) and 95%CI. RESULTS: A total of 443 cases of Siewert II AEG were enrolled, including 89 cases in TT group (with 3 cases of transabdominothoracic approach) and 354 cases in TA group. Median follow-up time was 50.0 months (quartiles:26.4-70.2). The baseline data in TT and TA groups were comparable, except the length of esophageal invasion [for length <3 cm, TA group had 354 cases(100%), TT group had 44 cases (49.4%), χ²=199.23,P<0.001]. The number of harvested lymph node in thoracic surgery department and gastrointestinal surgery department were 12.0(quartiles:9.0-17.0) and 24.0(quartiles:18.0-32.5) respectively with significant difference (Z=11.29,P<0.001). The 3-year overall survival rate of TA and TT groups was 69.2%(95%CI:64.1%-73.7%) and 55.8% (95%CI:44.8%-65.4%) respectively, which was not significantly different by log-rank test (P=0.059). However, the stage III subgroup analysis showed that the survival of TA group was better [the 3-year overall survival in TA group and TT group was 78.1%(95%CI:70.5-84.0) and 46.3%(95%CI:31.0-60.3) resepectively(P=0.001)]. Multivariate Cox regression analysis revealed that the TT group had poor survival outcome (HR=2.45,95%CI:1.30-4.64, P=0.006). CONCLUSION The overall survival outcomes in the TA group are better, especially in stage III patients, which may be associated with the higher metastatic rate of abdominal lymph node and the more complete lymphadenectomy via TA approach.
Adenocarcinoma ; classification ; mortality ; pathology ; surgery ; China ; Databases, Factual ; Esophageal Neoplasms ; classification ; pathology ; surgery ; Esophagectomy ; methods ; Esophagogastric Junction ; pathology ; surgery ; Gastrectomy ; methods ; Humans ; Laparotomy ; Lymph Node Excision ; methods ; Neoplasm Staging ; Retrospective Studies ; Stomach Neoplasms ; classification ; mortality ; pathology ; surgery ; Survival Analysis ; Thoracic Surgical Procedures

PURPOSE: Half of the world's gastric cancer cases and the highest gastric cancer mortality rates are observed in Eastern Asia. Although several genome-wide association studies (GWASs) have revealed susceptibility genes associated with gastric cancer, no GWASs have been conducted in the Korean population, which has the highest incidence of gastric cancer. MATERIALS AND METHODS: We performed genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and 3,693 healthy controls. RESULTS: We showed that the rs2976394 in the prostate stem cell antigen (PSCA) gene is a gastriccancer-susceptibility gene in a Korean population, with genome-wide significance and an odds ratio (OR) of 0.70 (95% confidence interval [CI], 0.64 to 0.77). A strong linkage disequilibrium with rs2294008 was also found, indicating an association with susceptibility. Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold lower risk of gastric cancer compared to those with the TT genotype (OR, 0.47; 95% CI, 0.39 to 0.57). The effect of the PSCA gene on gastric cancer was more prominent in the female population and for diffuse type gastric cancer. CONCLUSION: Our result confirmed that the PSCA gene may be the most important susceptibility gene for gastric cancer risk in a Korean population.
Exome ; Far East ; Female ; Genetic Variation ; Genome ; Genome-Wide Association Study ; Genotype ; Humans ; Incidence ; Linkage Disequilibrium ; Mortality ; Odds Ratio ; Prostate ; Stem Cells ; Stomach Neoplasms

PURPOSE: Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival. MATERIALS AND METHODS: The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models. RESULTS: After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival. CONCLUSION: Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.
Breast ; Cohort Studies ; Colorectal Neoplasms ; Electronic Health Records ; Humans ; Insulin ; Lung ; Metformin ; Mortality ; Proportional Hazards Models ; Stomach Neoplasms

BACKGROUND/AIMS: The risk of peritoneal seeding following perforation after endoscopic resection in patients with early gastric cancer is unclear. The purpose of this study was to investigate long-term clinical outcomes including peritoneal seeding and overall survival rate following gastric perforation during endoscopic submucosal dissection (ESD). METHODS: Between January 2002 and March 2015, 556 patients were diagnosed with early gastric cancer and underwent ESD. Among them, 34 patients (6.1%) experienced gastric perforation during ESD. Clinicopathological data of these patients were reviewed to determine the clinical outcome and evidence of peritoneal seeding. RESULTS: Among 34 patients with perforation, macroperforations occurred during ESD in 17 cases (50%), and microperforation was identified in the remaining 17 cases (50%). All patients except one who underwent emergency surgery due to severe panperitonitis were managed successfully by endoscopic clipping (n=27) or conservative medical treatment (n=6). No evidence of peritoneal seeding after perforation associated with ESD was found in our cohort. Cumulative survival rates did not differ between the perforation and non-perforation groups (p=0.691). Furthermore, mortality was not associated with perforation. In addition, multivariate analysis showed that tumor size and achievement of curative resection were related to cancer recurrence. Perforation was not associated with cancer recurrence and survival. CONCLUSIONS: Perforation associated with ESD does not lead to worse clinical outcomes such as peritoneal seeding or cumulative survival rate. Therefore, periodic follow-up might be possible if curative resection was achieved even if perforation occurred during ESD.
Cohort Studies ; Emergencies ; Follow-Up Studies ; Humans ; Mortality ; Multivariate Analysis ; Recurrence ; Stomach Neoplasms ; Survival Rate

Gastric intestinal metaplasia (GIM) is a known premalignant condition of the human stomach along the pathway to gastric cancer (GC). Histologically, GIM represents the replacement of normal gastric mucosa by mucin-secreting intestinal mucosa. Helicobacter pylori infection is the most common etiologic agent of GIM development worldwide. The prevalence of GIM is heterogeneous among different regions of the world and correlates with the population endemicity of H. pylori carriage, among other environmental factors. GC remains the third leading cause of cancer-related mortality globally. GIM is usually diagnosed by upper endoscopy with biopsy, and histologic scoring systems have been developed to risk-stratify patients at highest risk for progression to GC. Several recent endoscopic imaging modalities may improve the optical detection of GIM and early GC. Appropriate surveillance of GIM may be cost effective and represents an opportunity for the early diagnosis and therapy of GC. Certain East Asian nations have established population-level programs for the screening and surveillance of GIM; guidelines regarding GIM surveillance have also recently been published in Europe. By contrast, few data exist regarding the appropriateness of surveillance of GIM in the United States. In this review, we discuss the pathogenesis, epidemiology, diagnosis, and management of GIM with an emphasis on the role of appropriate endoscopic surveillance.
Asian Continental Ancestry Group ; Biopsy ; Diagnosis ; Early Diagnosis ; Endoscopy ; Epidemiology ; Europe ; Gastric Mucosa ; Helicobacter pylori ; Humans ; Intestinal Mucosa ; Mass Screening ; Metaplasia ; Mortality ; Prevalence ; Stomach ; Stomach Neoplasms ; United States

Despite its declining incidence, gastric cancer is globally, still, the third most common cause of cancer-related mortality. Gastric cancer is a heterogeneous disease with diverse pathogenesis and molecular backgrounds. Therefore several systems have been proposed to aid in the classification of gastric adenocarcinoma based on the macroscopic, microscopic and anatomical features of the tumor. However, these classifications did not reflect the pathogenesis of the disease. Recently, genomic analysis has identified several subtypes of gastric adenocarcinoma and a detailed understanding of the molecular biology behind the neoplastic phenotype is possible to develop of more effective therapies. We will describe the existing various classification of gastric cancer and the recently introduced molecular biology and immunological classification.
Adenocarcinoma ; Classification ; Incidence ; Molecular Biology ; Mortality ; Phenotype ; Stomach Neoplasms