Associations of Serum Lipid Level with Gastric Cancer Risk, Pathology, and Prognosis.

PURPOSE: The association of serum lipids with gastric cancer is controversial. We clarified the role of serum lipids in the development, progression, and prognosis of gastric cancer. MATERIALS AND METHODS: In total, 412 patients diagnosed with gastric cancer were prospectively recruited, and 2,934 control subjects who underwent screening endoscopy were enrolled from December 2013 to March 2017 to conduct a case-control study in a tertiary center. Serum lipid profiles, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (apoA-I), and apolipoprotein B, and clinicopathologic characteristics were analyzed. RESULTS: The gastric cancer group showed significantly lower HDL-C, higher LDL-C, and lower apoA-I level than the control group. In multivariate analysis, old age (odds ratio [OR], 1.051; p < 0.001), smoking (OR, 1.337; p < 0.001), a family history of gastric cancer (OR, 2.038; p < 0.001), Helicobacter pylori seropositivity (OR, 4.240; p < 0.001), lower HDL-C (OR, 0.712; p=0.020), and higher LDL-C (p=0.002) were significant risk factors for gastric cancer. Lower HDL-C and higher LDL-C remained significant after adjustments for covariates, including age and sex. In a subgroup analysis of the gastric cancer group, lower TG levels were associated with undifferentiated histology. No serum lipids were associated with overall survival. CONCLUSION: Lower HDL-C and higher LDL-C were associated with the risk of gastric cancer, even after adjusting for age, sex, and other factors. In the gastric cancer group, undifferentiated histology was associated with lower TG levels.

Novel Endoscopic Criteria for Predicting Tumor Invasion Depth in Superficial Esophageal Squamous Carcinoma.

BACKGROUND: Accurate prediction of tumor invasion depth in superficial esophageal squamous carcinoma (SESC) is essential for deciding the appropriate treatment strategy. We proposed novel endoscopic criteria to differentiate between mucosal and submucosal esophageal cancers and to evaluate the diagnostic accuracy and usefulness of the criteria. METHODS: A total of 352 patients who underwent endoscopic or surgical resection for SESC between 1991 and 2010 were included. First, the novel endoscopic criteria were created based on the endoscopic features of 60 randomly selected patients as follows: for T1m cancers, I. flat or slightly elevated or depressed lesion with smooth/even surface of any size, II. slightly elevated lesion of ≤ 1 cm with granular or uneven surface, III. hyperemic flat lesion of ≤ 3 cm with granular or uneven surface, IV. slightly depressed lesion of ≤ 2 cm with uneven surface and for T1sm cancers, I. irregularly (unevenly) nodular or protruded lesion of any size, II. slightly elevated lesion of > 1 cm with granular or uneven surface, III. hyperemic flat lesion of > 3 cm with granular or uneven surface, IV. irregularly (unevenly) depressed lesion of > 2 cm, and V. ulcerative lesion of any size. Next, the endoscopic findings of the remaining 292 patients were reviewed according to the criteria. RESULTS: The accuracy of novel endoscopic criteria was 79.5% (232/292). The sensitivity and specificity of mucosal cancers were 78.4% and 81.0%, respectively, whereas those for submucosal cancers were 81.0% and 78.4%, respectively. The accuracy for mucosal cancers was high (97.3%, 72/74) when the lesions were flat or slightly elevated/depressed with smooth/even surface regardless of size, whereas that for submucosal cancers was high (85.7%, 18/21) when the lesions were irregular/nodular protrusions regardless of size. In multivariate analysis, macroscopic type IIb lesion was identified as an independent factor affecting accuracy (P < 0.05). The difference in recurrence-free survival rates between endoscopically mucosal and submucosal cancers was significant (P = 0.026). CONCLUSION: The novel endoscopic criteria appear to be accurate and useful in predicting invasion depth in SESC. Our criteria might help not only to decide the treatment strategy between surgery and endoscopic resection but also to predict the outcomes of SESC.

Progression of pancreatic cystic lesions without any risk features is associated with initial cyst size and obesity.

BACKGROUND AND AIM: The clinical significance of incidental pancreatic cystic lesions (PCLs) remains unclear in those that are not accompanied by worrisome features or high-risk stigmata. We aimed to investigate the natural course of PCLs without any risk features and examine the clinical factors associated with their progression. METHODS: We conducted a retrospective cohort study of 427 patients with PCLs, which were incidentally detected by computed tomography between January 2003 and December 2012. Progression of PCLs without any risk features and the clinical factors associated with their progression were investigated. The length of time to significant growth was also evaluated. RESULTS: Ninety-four (22.0%) of the 427 patients had asymptomatic PCLs that showed significant growth after a median surveillance period of 5.3 years; approximately 27.7% of the patients showed significant size changes in the first 5 years, while the remaining 72.3% showed significant changes after 5 years. The cumulative rate of patients with significant growth was associated with initial cyst size and high body mass index. In the growth group, additional treatments were required for 12 patients, one of whom developed malignancy. Four patients in the stable group underwent additional treatment and showed no malignant change. CONCLUSIONS: One-fifth of the asymptomatic PCLs significantly increased in size after a long-term follow-up period, which was associated with initial cyst size and obesity. The size of PCLs mostly increased after 5 years; although the malignancy risk of PCLs was low, it was still a concern.

Characteristics of non-cardia gastric cancer with a high serum anti-Helicobacter pylori IgG titer and its association with diffuse-type histology.

BACKGROUND: Data on implications of a high positive titer of serum anti-Helicobacter pylori antibody on gastric cancer (GC) is limited. This study aimed to investigate the characteristics of GC with a high serum anti-H. pylori IgG (Hp-IgG) titer, and its association with diffuse-type GC. METHODS: We analyzed clinical and histological characteristics of 917 non-cardia GC patients who underwent gastrectomy. H. pylori infection was determined serologically by measuring Hp-IgG titer with immunoassay. Seropositive patients were divided into three groups (low-positive, mid-positive, and high-positive) according to the Hp-IgG titer value. Tumors were classified according to the Lauren criteria as diffuse or intestinal types. RESULTS: The median age of the patients was 59.0 years, and 33.8% were female. The patents were grouped as follows: seronegative, 188 (20.5%); low-positive, 288 (31.4%); mid-positive, 290 (31.6%); and high-positive 151 (16.5%). The high-positive group was significantly younger (median age, 55.0 years), with a higher proportion of female (45.0%) and non-smokers (58.9%). The proportion of diffuse-type GC increased in the order low-, mid-, and high-positive groups (p<0.001). In univariate analysis, the factors associated with diffuse-type GC were younger age, female sex, non-smokers, and a high-positive Hp-IgG titer. Younger age, female sex, and non-smokers remained significant on multivariate analysis whereas the high-positive Hp-IgG titer showed only a tendency toward the association (p = 0.078). CONCLUSIONS: Non-cardia GC patients with a high Hp-IgG titer have distinct clinicopathologic characteristics. A high-positive Hp-IgG titer should be interpreted together with patients' age, sex, and smoking status.

The effect of eradication of Helicobacter pylori on gastric cancer prevention in healthy asymptomatic populations.

BACKGROUND: Although many epidemiologic studies have evaluated the effect of Helicobacter pylori eradication on gastric cancer, the effect is still uncertain in general populations. We evaluated whether H. pylori eradication would affect the incidence of gastric cancer in healthy asymptomatic populations. MATERIALS AND METHODS: We performed a retrospective cohort study in 38 984 asymptomatic individuals, who underwent health screening examinations more than twice between 2005 and 2016. We investigated the incidence of gastric cancer among 3 groups: those without H. pylori infection (Hp-negative group), those with H. pylori eradication (eradication group), and those without H. pylori eradication (non-eradication group). RESULTS: The cumulative incidence of gastric cancer was 54.5 cases per 100 000 person-years during a median of 6.4 years. In a multivariate analysis using the Cox proportional hazard model, the cumulative incidence of gastric cancer in the non-eradication group was significantly higher than those in the Hp-negative (hazard ratio [HR] 4.12, P < .001) and eradication groups (HR 2.73, P = .001). However, the cumulative incidence of gastric cancer was not significantly different between the eradication and Hp-negative groups. Other risk factors for gastric cancer occurrence were age, smoking, family history of gastric cancer, and gastric atrophy. The standardized incidence ratios of the age groups above 40 and below 70 in the eradication group were all significantly decreased. CONCLUSIONS: Helicobacter pylori eradication reduced the cumulative incidence of gastric cancer in healthy asymptomatic population, and the effect of H. pylori eradication on the prevention of gastric cancer was observed in all ages.

The Characteristics and Prognosis of Diffuse-Type Early Gastric Cancer Diagnosed during Health Check-Ups.

BACKGROUND/AIMS: Because of the poor prognosis of diffuse-type gastric cancer, early detection is important. We investigated the clinical characteristics and prognosis of diffuse-type early gastric cancer (EGC) diagnosed in subjects during health check-ups. METHODS: Among 121,111 subjects who underwent gastroscopy during a routine health check-up, we identified 282 patients with 286 EGC lesions and reviewed their clinical and tumor-specific parameters. RESULTS: Patients with diffuse-type EGC were younger, and 48.1% of them were female. Serum anti-Helicobacter pylori IgG (Hp-IgG) was positive in 90.7% of diffuse-type EGC patients (vs 75.9% of intestinal-type EGC, p=0.002), and the proportion of diffuse-type EGC cases increased significantly with increasing Hp-IgG serum titers (p<0.001). Diffuse-type EGC had pale discolorations on the tumor surface (26.4% vs 4.0% in intestinal-type EGC, p<0.001) and were often located in the middle third of the stomach. Submucosal invasion or regional nodal metastasis was observed more commonly in patients with diffuse-type EGC. However, during the median follow-up period of 50 months, 5-year disease-free survival rates did not differ between the groups. CONCLUSIONS: Diffuse-type EGC shows different clinical and endoscopic characteristics. Diffuse-type EGC is more closely associated with Hp-IgG seropositivity and a higher serum titer. Early detection results in excellent prognosis.

Atrophic and Metaplastic Progression in the Background Mucosa of Patients with Gastric Adenoma.

BACKGROUND: In patients with adenoma, assessing premalignant changes in the surrounding mucosa is important for surveillance. This study evaluated atrophic and metaplastic progression in the background mucosa of adenoma or early gastric cancer (EGC) cases. METHODS: Among 146 consecutive patients who underwent endoscopic resection for intestinal-type gastric neoplasia, the adenoma group included 56 patients with low-grade dysplasia and the ECG group included 90 patients with high-grade dysplasia or invasive carcinoma. For histology, 3 paired biopsies were obtained from the antrum, corpus lesser curvature (CLC), and corpus greater curvature (CGC). Serological atrophy was determined based on pepsinogen A (PGA), progastricsin (PGC), gastrin-17, and total ghrelin levels. Topographic progression of atrophy and/or metaplasia was staged using the operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia assessment (OLGIM) systems. RESULTS: Rates of moderate-to-marked histological atrophy/metaplasia in patients with adenoma were 52.7%/78.2% at the antrum (vs. 58.8%/76.4% in EGC group), 63.5%/75.0% at the CLC (vs. 60.2%/69.7% in EGC group), and 10.9%/17.9% at the CGC (vs. 5.6%/7.8% in EGC group). Serological atrophy indicated by PGA and PGC occurred in 23.2% and 15.6% of cases in the adenoma and ECG groups, respectively (p = 0.25). Mean serum gastrin-17 concentrations of the adenoma group and EGC group were 10.4 and 9.0 pmol/L, respectively (p = 0.54). Mean serum total ghrelin levels were 216.6 and 209.5 pg/mL, respectively (p = 0.71). Additionally, between group rates of stage III-IV OLGA and OLGIM were similar (25.9% vs. 25.0%, p = 0.90; 41.8% vs. 44.9%, p = 0.71, respectively). CONCLUSIONS: Atrophic and metaplastic progression is extensive and severe in gastric adenoma patients. A surveillance strategy for metachronous tumors should be applied similarly for patients with adenoma or EGC.

Method evaluation of pepsinogen I/II assay based on chemiluminescent immunoassays and comparison with other test methods.

BACKGROUND: Serum pepsinogen (PG) I and the PG I/PG II ratio have been used for atrophic gastritis (AG) diagnosis for decades. Low levels of PG I and/or PG I/PG II are closely related to AG and predict the risk of gastric cancer. We evaluated the performance of the chemiluminescent immunoassay-based Architect Pepsinogen I/II assay. METHODS: The evaluation consisted of determination of the precision, linearity, limit of blank (LoB), limit of detection (LoD) and method comparison with Eiken and Biohit assays. RESULTS: The total CVs were below 5% for both PG I and PG II. Acceptable linearity was observed for PG I and PG II in their respective reportable ranges. The PG I LoB was 0.317ng/mL and the PG II LoB was 0.418ng/mL, and LoDs were 0.412ng/mL and 0.497ng/mL, respectively. Correlation analysis indicated that results of the Architect assay were comparable to those of the Eiken and Biohit assays, but the three methods lead to different estimations of the cancer risk. CONCLUSION: The overall analytical performance of Architect Pepsinogen I/II assay is acceptable for the detection of patients with suspected AG. The categorization results of gastric cancer risk showed some difference among test methods suggesting the need for harmonization among the methods from vendors.

Risk factors of lymph node metastasis in patients with gastric neuroendocrine tumor with normal serum gastrin level.

BACKGROUND/AIMS: Locoregional gastric carcinoids with normal serum gastrin level have been recommended radical resection regardless of tumor size or depth of invasion. However, there have been some reports which showed small sporadic gastric carcinoids could be treated with local resection. The aim of this study was to elucidate risk factors of lymph node metastasis in patients with gastric carcinoids with normal serum gastrin level and determine the indications for limited resection such as endoscopic treatment. METHODOLOGY: We performed clinicopathologic reviews of thirty gastric carcinoids with normal serum gastrin level from January 1996 to December 2010. RESULTS: One case show distant metastasis and two cases showed lymph node metastasis at the time of diagnosis. For twenty seven cases which showed no regional lymph node or distant metastasis initially no additional lymph node or distant metastasis were diagnosed throughout the follow up period. Large tumor size (>10 mm), proper muscle infiltration, WHO classification grade 2 and lymphovascular invasion was noted risk factor of lymph node metastasis by univariate logistic regression analysis. CONCLUSIONS: Small (≤10 mm) gastric carcinoids with normal serum gastrin level confined to submucosa can be treated with endoscopic or local resection unless lymphovascular invasion.

Effect of Helicobacter pylori eradication on metachronous recurrence after endoscopic resection of gastric neoplasm.

OBJECTIVES: Although many epidemiologic studies have shown that Helicobacter pylori (H. pylori) eradication has prophylactic effects on gastric cancer, their results are less clear in high-risk populations. We conducted this study to examine whether H. pylori eradication would affect the occurrence of metachronous gastric cancer after endoscopic resection in patients with early gastric cancer. METHODS: We retrospectively analyzed 2,089 adults who underwent endoscopic resection of gastric low-grade neoplasia, high-grade neoplasia, or differentiated invasive neoplasia from 2004 to 2008 at Asan Medical Center. Of these, a total of 1,007 patients with early gastric cancer were enrolled in this study. We evaluated the demographic data, the pathology, and the incidence of metachronous recurrence by dividing them into three groups: those without active H. pylori infection (Hp negative group, n=340), those who successfully underwent H. pylori eradication (eradicated group, n=485), and those who failed or did not undergo H. pylori eradication (noneradicated group, n=182). RESULTS: Metachronous recurrence was diagnosed in 75 patients, including 17 in the Hp, 34 in the eradicated, and 24 in the noneradicated groups. Median time to metachronous recurrence was 18 months (range, 7-75 months). The incidence of metachronous gastric cancer was 10.9 cases per 1,000 person-years in the Hp negative group, 14.7 cases per 1,000 person-years in the eradicated group, and 29.7 cases per 1,000 person-years in the noneradicated group. The hazard ratios in the noneradicated group compared with the Hp negative and eradicated groups were 2.5 (P<0.01) and 1.9 (P=0.02), respectively. H. pylori eradication reduced metachronous recurrence of gastric neoplasm, which was also shown in the secondary analysis of 1,487 patients with low-grade neoplasia and early gastric cancer. CONCLUSIONS: Successful H. pylori eradication may reduce the occurrence of metachronous gastric cancer after endoscopic resection in patients with early gastric cancer.

A Comparison of 2 L of Polyethylene Glycol and 45 mL of Sodium Phosphate versus 4 L of Polyethylene Glycol for Bowel Cleansing: A Prospective Randomized Trial.

BACKGROUND/AIMS: Polyethylene glycol (PEG)-based gut lavage solutions are safe and effective, but require the intake of large volumes of fluid. The use of 2 L PEG plus 45 mL sodium phosphate (PEG2 plus NaP) was compared with 4 L PEG (PEG4) for bowel cleansing before colonoscopy. METHODS: Patients were randomized to the PEG2 plus NaP group or PEG4 group between January 1, 2009 and March 31, 2010. One hundred and thirty patients were included in the PEG2 plus NaP group, and 141 patients in the PEG4 group. RESULTS: The qualities of the bowel preparation, based on the Ottawa scale were not significantly different between the groups (4.8±2.25 for the PEG2 plus NaP group vs. 5.11±2.26 for the PEG4). In addition, there were no significant differences in side effects. Laboratory findings after bowel preparation, including electrolyte, phosphorus and creatinine levels, were within the normal ranges in both groups. CONCLUSIONS: PEG2 plus NaP provides good cleansing that is similar to PEG4, but with a lower volume. However, because PEG2 plus NaP can cause serious side effects such as calcium deposition in the kidneys (i.e., nephrocalcinosis), this solution might be considered for the outpatients who cannot tolerate PEG4.

Seroconversion rates of Helicobacter pylori infection in Korean adults.

BACKGROUND: Studies on seroconversion and its reversion rate in Korean adults with Helicobacter pylori infection are very rare. The purpose of this study was to evaluate the overall seroprevalence, seroconversion rate, and seroreversion rate of H. pylori infection in an adult population. MATERIALS AND METHODS: We performed this retrospective cohort study on healthy adults who had visited our health screening center at Asan Medical Center more than twice between January 2000 and December 2010. We reviewed the anti- H. pylori Ab IgG profiles of the enrolled people and their family members and the results of esophagogastroduodenoscopies and a self-reported questionnaire. RESULTS: A total of 67,212 people were enrolled in this study. The mean follow-up duration was 4.6 years, and each participant visited the center for a mean of 3.8 visits. The overall proportions of participants demonstrating persistent seropositivity, persistent seronegativity, seroconversion, and seroreversion were 53.1%, 32.5%, 4.3%, and 10.1%, respectively. The annual seroconversion rate was 2.79%. The annual crude and spontaneous seroreversion rates of the entire study population were 3.64% and 2.42%, respectively. According to multivariate logistic regression, old age (HR = 1.015), smoking (HR = 1.216), alcohol consumption more than four times per week (HR = 1.263), marriage (HR = 2.735), and living with H. pylori-infected family members (HR = 1.525) were identified as statistically significant risk factors associated with seroconversion. CONCLUSION: The annual seroconversion rate was 2.79% in our study population. Marriage and living with H. pylori-infected family members were important risk factors affecting seroconversion in our adult population.

[The effect of aspirin alone or aspirin plus additional antiplatelets therapy on upper gastrointestinal hemorrhage].

BACKGROUND/AIMS: The increasing incidence of cardiovascular disease has led to an increase in the frequency of upper gastrointestinal (GI) hemorrhage due to the use of antiplatelet agents. This study examined the clinical characteristics of patients with upper GI hemorrhage who were administered aspirin alone or a combination treatment of antiplatelet agents. METHODS: A 656 patients who underwent drug-eluting coronary stenting at Ewha Mokdong Hospital in 2008 were divided into three groups according to the antiplatetlet agents used after the intervention; groups of aspirin alone, aspirin plus clopidogrel, and aspirin, and clopidogrel plus another antiplatelet agent, respectively. Patients admitted with GI hemorrhage in the same period without a medication history of antiplatelet or nonsteroidal anti-inflammatory drugs were used as the control hemorrhage group. The medical records were reviewed. RESULTS: Significant GI symptoms were observed in 21.1% of total patients, of whom 48.2% had ulcers. The upper GI hemorrhage rate was 3.8%. There was no significant difference in the hemorrhage rate between three groups. Compared to the control hemorrhage group, the endoscopic variables of the antiplatelet-related hemorrhage group were not significantly different. However, the Helicobacter pylori infection rate was lower, the admission period was longer, and the mortality rate was higher in the antiplatelet-related hemorrhage group (p<0.05, respectively). There was no direct association between restarting or discontinuance of antiplatelets after the hemorrhage event and mortality. CONCLUSIONS: Adding other antiplatelet agents to aspirin did not increase the hemorrhage rate. However, active diagnostic and therapeutic efforts are recommended in patients with GI symptoms during antiplatelet therapy.