Upgrade of Lesions Initially Diagnosed as Low-Grade Gastric Dysplasia upon Forceps Biopsy Following Endoscopic Resection

Background/Aims

Gastric dysplasia is generally accepted to be the precursor lesion of gastric carcinoma. Approximately 25% to 35% of histological diagnoses based on endoscopic forcep biopsies for gastric dysplastic lesions change following endoscopic resection (ER). The aim of this study was to determine the predictive endoscopic features of high-grade gastric dysplasia (HGD) or early gastric cancer (EGC) following ER for lesions initially diagnosed as low-grade dysplasia (LGD) by a forceps biopsy.

Methods

To determine predictive variables for upgraded histology (LGD to HGD or EGC). The lesion size, gross endoscopic appearance, location, and surface nodularity or redness as well as the presence of a depressed portion, Helicobacter pylori infection, and intestinal metaplasia were retrospectively investigated.

Results

Among 251 LGDs diagnosed by an initial forceps biopsy, the diagnoses of 100 lesions (39.8%) changed following the ER; 56 of 251 LGDs (22.3%) were diagnosed as HGD, 39 (15.5%) as adenocarcinoma, and 5 (2.0%) as chronic gastritis. In a univariate analysis, large lesions (>15 mm), those with a depressed portion, and those with surface nodularity were significantly correlated with a upgraded histology classification following ER. In a multivariate analysis, a large size (>15 mm; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.46 to 5.43) and a depressed portion in the lesion (OR, 2.7; 95% CI, 1.44 to 5.03) were predictive factors for upgraded histology following ER.

Conclusions

Our study shows that a substantial proportion of diagnoses of low-grade gastric dysplasias based on forceps biopsies were not representative of the entire lesion. We recommend ER for lesions with a depressed portion and for those larger than 15 mm.     

LINE-1 Hypomethylation is Associated with the Risk of Coronary Heart Disease in Chinese Population

Background

Global methylation level in blood leukocyte DNA has been associated with the risk of coronary heart disease (CHD), with inconsistent results in various populations. Similar data are lacking in Chinese population where different genetic, lifestyle and environmental factors may affect DNA methylation and its risk relationship with CHD.

Objectives

To examine whether global methylation is associated with the risk of CHD in Chinese population.

Methods

A total of 334 cases with CHD and 788 healthy controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing LINE-1 repeats using bisulfite pyrosequencing.

Results

In an initial analysis restricted to control subjects, LINE-1 level reduced significantly with aging, elevated total cholesterol, and diagnosis of diabetes. In the case-control analysis, reduced LINE-1 methylation was associated with increased risk of CHD; analysis by quartile revealed odds ratios (95%CI) of 0.9 (0.6-1.4), 1.9 (1.3-2.9) and 2.3 (1.6-3.5) for the third, second and first (lowest) quartile (P_trend < 0.001), respectively, compared to the fourth (highest) quartile. Lower (<median) LINE-1 methylation was associated with a 2.2-fold (95%CI = 1.7-3.0) increased risk of CHD. The lower LINE-1-related CHD risk estimates tended to be stronger among subjects with the highest tertile of homocysteine (P_interaction = 0.042) and those with diagnosis of hypertension (P_interaction = 0.012).

Conclusion

LINE-1 hypomethylation is associated with the risk of CHD in Chinese population. Potential CHD risk factors such as older age, elevated total cholesterol, and diagnosis of diabetes may have impact on global DNA methylation, whereby exerting their effect on CHD risk.     

An Inverse Relationship between the Expression of the Gastric Tumor Suppressor RUNX3 and Infection with Helicobacter pylori in Gastric Epithelial Dysplasia

Background/Aims

This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions.

Methods

We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction.

Results

The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08).

Conclusions

Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.     

Dysplasia at the surgical margin is associated with recurrence after resection of non-invasive intraductal papillary mucinous neoplasms

Background

The significance of a positive margin in resected non-invasive pancreatic intraductal papillary mucinous neoplasms (IPMN) remains controversial. The aim of this study was to determine recurrence rates when dysplasia was present at the final surgical margin.

Methods

A prospectively maintained database identified 192 patients undergoing resection of non-invasive IPMN. Pathological, peri-operative and recurrence data were analysed.

Results

Ductal dysplasia was identified at the final surgical margin in 86 patients (45%) and defined as IPMN or Pancreatic Intraepithelial Neoplasia PanIN in 38 (20%) and 54 (28%) patients, respectively. At a median follow-up of 46 months, 40 (21%) patients recurred with 31 developing radiographical evidence of new cysts, 6 re-resected for IPMN and 3 diagnosed with pancreatic cancer within the remnant. Of those with margin dysplasia, 31% developed recurrent disease compared with 13% in those without dysplasia (P = 0.002). On multivariate analysis, margin dysplasia was associated with a three-fold increased risk of recurrence (P = 0.02). No relationship between dysplasia and development of pancreatic cancer was found.

Discussion

In this study, dysplasia at the margin after a pancreatectomy for non-invasive IPMN was associated with recurrence in the remnant gland, but not at the resection margin. While this finding may warrant closer follow-up, it does not identify a gland at higher risk for the subsequent development of invasive disease.     

Is Endoscopic Mucosal Resection a Sufficient Treatment for Low-Grade Gastric Epithelial Dysplasia?

Background/Aims

The rate of diagnosis of gastric adenoma has increased because esophagogastroduodenoscopy is being performed at an increasingly greater frequency. However, there are no treatment guidelines for low-grade dysplasia (LGD). To determine the appropriate treatment for LGD, we evaluated the risk factors associated with the categorical upgrade from LGD to high grade dysplasia (HGD)/early gastric cancer (EGC) and the risk factors for recurrence after endoscopic treatment.

Methods

We compared the complication rates, recurrence rates, and remnant lesions in 196 and 56 patients treated with endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR), respectively, by histologically confi rming low-grade gastric epithelial dysplasia.

Results

The en bloc resection rate was significantly lower in the EMR group (31.1%) compared with the ESD group (75.0%) (p<0.001). However, no significant difference was observed in the prevalence of remnant lesions or recurrence rate (p=0.911) of gastric adenoma. The progression of LGD to HGD or EGC caused an increase in the incidence of tumor lesions >1 cm with surface redness and depressions.

Conclusions

For the treatment of LGD, EMR resulted in a higher incidence of uncertain resection margins and a lower en bloc resection rate than ESD. However, there was no signifi cant difference in recurrence rate.     

Risk Factors for Metachronous Gastric Neoplasms in Patients Who Underwent Endoscopic Resection of a Gastric Neoplasm

Background/Aims

To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm.

Methods

We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms.

Results

A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 high-grade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020).

Conclusions

In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms.     

Helicobacter pylori infection and markers of gastric cancer risk in Alaska Native persons: A retrospective case-control study

BACKGROUND:

Alaska Native persons experience gastric cancer incidence and mortality rates that are three to four times higher than in the general United States population.

OBJECTIVE:

To evaluate pepsinogen I, pepsinogen I/II ratio, anti-Helicobacter pylori and cytotoxin-associated gene A (CagA) antibody levels, and blood group for their associations with gastric cancer development in Alaska Native people.

METHODS:

The present analysis was a retrospective case-control study that matched gastric cancers reported to the Alaska Native Tumor Registry from 1969 to 2008 to three controls on known demographic risk factors for H pylori infection, using sera from the Alaska Area Specimen Bank. Conditional logistic regression evaluated associations between serum markers and gastric cancer.

RESULTS:

A total of 122 gastric cancer cases were included, with sera predating cancer diagnosis (mean = 13 years) and 346 matched controls. One hundred twelve cases (91.8%) and 285 controls (82.4%) had evidence of previous or ongoing H pylori infection as measured by anti-H pylori antibody levels. Gastric cancer cases had a 2.63-fold increased odds of having positive anti-H pylori antibodies compared with their matched controls (P=0.01). In a multivariate model, non-cardia gastric cancer (n=94) was associated with anti-H pylori antibodies (adjusted OR 3.92; P=0.004) and low pepsinogen I level (adjusted OR 6.04; P=0.04). No association between gastric cancer and blood group, anti-CagA antibodies or pepsinogen I/II ratio was found.

CONCLUSION:

Alaska Native people with gastric cancer had increased odds of previous H pylori infection. Low pepsinogen I level may function as a precancer marker for noncardia cancer.     

Treatment of gastric epithelial tumours by endoscopic submucosal dissection using an insulated-tip diathermic knife

BACKGROUND:

Endoscopic submucosal dissection (ESD) is a promising technique for the treatment of large, pre- and early malignant gastrointestinal lesions.

OBJECTIVE:

To assess the rates of en bloc resection, incidence of complications, procedure times and therapeutic outcomes of ESD using an insulated-tip diathermic knife; and to investigate predictors of these outcomes based on the final pathological features of biopsy specimens.

METHODS:

One hundred twenty patients with endoscopically suspected gastric epithelial tumours who were treated with ESD from January 2006 to December 2009 were evaluated.

RESULTS:

The mean diameter of the gastric epithelial tumours in the present cohort was 1.88 cm. The mean diameter of the resected specimens was 3.33 cm. The en bloc resection rate was 90% (108 of 120). The median length of the operation was 64.6 min. The bleeding and perforation complication rates were 5.0% (six of 120) and 2.5% (three of 120), respectively. Of 10 gastric tumours initially diagnosed as adenocarcinoma on biopsy, four were found to be low-grade dysplasia and six were found to be high-grade dysplasia after resection and final pathological examination. A total of 112 (93.33%) patients underwent curative treatment, eight patients (6.67%) underwent noncurative treatment with ESD, and two patients (1.67%) experienced local recurrence and subsequently underwent surgery.

CONCLUSIONS:

ESD is a promising local curative treatment option for gastric epithelial tumours, but still carries the risks of bleeding and/or perforation. Differences in the interpretation of histological results among different pathologists and/or between biopsy specimens before ESD and the en bloc tissue specimens after ESD will result in discrepancies.     

Clinicopathological features associated with lymph node metastasis in early gastric cancer: Analysis of a single-institution experience in China

BACKGROUND:

An accurate assessment of potential lymph node metastasis is an important issue for the appropriate treatment of early gastric cancer. Minimizing the number of invasive procedures used in cancer therapy is critical for improving the patient’s quality of life.

OBJECTIVE:

To evaluate the clinicopathological features associated with lymph node metastasis of early gastric cancer in patients from a single institution in China.

METHODS:

A retrospective review of data from 410 patients surgically treated for early gastric cancer at the First Affiliated Hospital (Nanjing, China) between 1998 and 2007, was conducted. The clinicopathological variables associated with lymph node metastasis were evaluated.

RESULTS:

Lymph node metastasis was observed in 12.20% of patients. The macroscopic type, tumour size, location in the stomach, depth of gastric carcinoma infiltration, and presence of vascular or lymphatic invasion showed a positive correlation with the incidence of lymph node metastasis by univariate analysis. Multivariate analyses revealed histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion to be significantly and independently related to lymph node metastasis. The depth of gastric carcinoma infiltration was the strongest predictive factor for lymph node metastasis. For intramucosal cancer, tumour size was the unique risk factor for lymph node metastasis. For submucosal cancer, histological classification and tumour size were independent risk factors for lymph node metastasis.

CONCLUSIONS:

Histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion are independent risk factors for lymph node metastasis in patients with early gastric cancer in China. Minimal invasive treatment, such as endoscopic mucosal resection, may be possible for highly selected cancers.     

Effects of oxidative stress on mitochondrial content and integrity of human anastomotic colorectal dehiscence: a preliminary DNA study

BACKGROUND:

Anastomotic dehiscence is one of the most severe complications of colorectal surgery. Gaining insight into the molecular mechanisms responsible for the development of anastomotic dehiscence following colorectal surgery is important for the reduction of postoperative complications.

OBJECTIVE:

Based on the close relationship between surgical stress and oxidative stress, the present study aimed to determine whether a correlation exists between increased levels of reactive oxygen species and colorectal anastomotic dehiscence.

METHODS:

Patients who underwent surgical resection for colorectal cancer were divided into three groups: patients with anastomotic dehiscence (group 1); patients without dehiscence who underwent neoadjuvant radiochemotherapy (group 2); and patients without anastomotic dehiscence who did not undergo neoadjuvant radiochemotherapy (group 3). Quantitative polymerase chain reaction and real-time polymerase chain reaction assays were performed to measure nuclear DNA and mitochondrial DNA (mtDNA) content, and possible oxidative damage to nonmalignant colon and rectal tissues adjacent to the anastomoses.

RESULTS:

mtDNA content was reduced in the colon tissue of patients in groups 1 and 2. Rectal mtDNA was found to be more damaged than colonic mtDNAs in all groups. The 4977 bp common deletion was observed in the mtDNA of tissues from both the colon and rectum of all patients.

DISCUSSION:

Patients in groups 1 and 2 were more similar to one another than to group 3, probably due to higher levels of reactive oxygen species in the mitochondria; the greater damage found in the rectum suggests that dehiscence originates primarily from the rectal area.

CONCLUSIONS:

The present study of mtDNA analyses of normal human colon and rectal tissues from patients with colorectal cancer is among the first of its kind.     

Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women

Background

Gastric cancer incidence rates are consistently lower in women than men in both high and low‐risk regions worldwide. Sex hormones, such as progesterone and estrogen, may protect women against gastric cancer.

Objective

To investigate the association of menstrual and reproductive factors and gastric cancer risk.

Methods

These associations were prospectively investigated in 73 442 Shanghai women. After 419 260 person‐years of follow‐up, 154 women were diagnosed with gastric cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for age, body mass index, education, income, and cigarette use.

Results

No associations were observed between gastric cancer risk and age of menarche, number of children, breast feeding, or oral contraceptive use. In contrast, associations were observed with age of menopause (HR 0.80 per five‐year increase in menopausal age, 95% CI 0.66–0.97), years of fertility (participants with less than 30 years of fertility were at increased risk compared with those with 30–36 years of fertility, HR 1.90, 95% CI 1.25–2.90), years since menopause (HR 1.26 per five years, 95% CI 1.03–1.53), and intrauterine device use (HR for users 1.61, 95% CI 1.08–2.39).

Conclusions

These results support the hypothesis that female hormones play a protective role in gastric cancer risk.     

Endoscopy-Guided Balloon Dilation of Benign Anastomotic Strictures after Radical Gastrectomy for Gastric Cancer

Background/Aims

The aim of this study was to evaluate the outcome of endoscopic dilation for benign anastomotic stricture after radical gastrectomy in gastric cancer patients.

Methods

Gastric cancer patients who underwent endoscopic balloon dilation for benign anastomosis stricture after radical gastrectomy during a 6-year period were reviewed retrospectively.

Results

Twenty-one patients developed benign strictures at the site of anastomosis. The majority of strictures occurred within 1 year after surgery (95.2%). The median duration to stenosis after surgery was 1.70 months (range, 0.17 to 23.97 months). The success rate of the first endoscopic dilation was 61.9%. Between the restenosis group (n=8) and the no restenosis group (n=13), there were no significant differences in the body mass index (22.82 kg/m² vs 22.46 kg/m²), interval to symptom onset (73.9 days vs 109.3 days), interval to treatment (84.6 days vs 115.6 days), maximal balloon diameter (14.12 mm vs 15.62 mm), number of balloon dilation sessions (1.75 vs 1.31), location of gastric cancer or type of surgery. One patient required surgery because of stricture refractory to repeated dilation.

Conclusions

Endoscopic dilation is a highly effective treatment for benign anastomotic strictures after radical gastrectomy for gastric cancer and should be considered a primary intervention prior to proceeding with surgical revision.     

Differential Expression and Significance of Endoplasmic Reticulum Golgi Intermediate Compartment 1 in Precancerous Gastric Lesions and Gastric Cancer

Background

We investigated the expression of endoplasmic reticulum Golgi intermediate compartment 1 (ERGIC1) in precancerous gastric lesions and gastric cancer and the function of ERGIC in human gastric cancer cell lines.

Clinical implications of DNA methylation in hepatocellular carcinoma

Background

Epigenetics is a rapidly evolving field of genetic study applicable to nearly every aspect of genome-related research. The importance of epigenetics has been recognised in human hepatocellular carcinoma (HCC). Changes in DNA methylation patterns, including global hypomethylation and promoter hypermethylation, are thought to be early events in hepatocarcinogenesis.

Objectives

This review aimed to summarise the role of epigenetics in HCC, to describe the mechanisms of epigenetic changes in HCC and to examine the clinical relevance of epigenetics in HCC.

Methods

This review examines the role of CpG-rich regions and DNA methylation, and describes an epigenetic model of cancer, tumour type-specific methylation, the relationships among methylation, cirrhosis and hepatocarcinogenesis, and the role of DNA methylation in HCC. The clinical implications of epigenetics in HCC are discussed.

Results

A multivariate predictor model based on traditional clinical factors and DNA methylation profile may have important applications in the early detection of neoplastic transformation in populations at high risk for HCC. CpG methylation may be valuable in HCC prognostics. DNA methylation profiles may enable clinical prediction in pre-therapy patient biopsies, paraffin-embedded samples or plasma DNA.

Conclusions

Epigenetic changes and profiles may correlate to the biological behaviour of tumours and clinical outcome of HCC patients. The use of DNA methylation profiles as a surrogate biomarker remains an active area of clinical cancer research.     

Relationship between the Extent of DNA Damage and Gastritis in Normal and Helicobacter pylori-Infected Patients

Background/Aims

The role of Helicobacter pylori in gastric carcinogenesis is unclear, but H. pylori infection is thought to predispose carriers to gastric cancer. The aim of this study was to investigate the relationship between the extent of DNA damage in normal gastric epithelial cells and H. pylori-positive and -negative gastritis according to histological diagnosis. We also compared the percentage of cometed cells on the surface of the gastric epithelial cells to the percentage beneath the gastric mucosal cells using serial incubations times.

Methods

The comet assay is a rapid, efficient and reproducible measure of DNA damage in single cell and it was used in this study. DNA damage was evaluated in 52 cases using alkaline single cell gel electrophoresis (comet assay). Comparisons were made between 19 normal individuals, 19 patients with H. pylori-positive and -negative gastritis and 14 mixed cases with different histology gradings to determine if there was a relationship between histological diagnosis and DNA damage (comet percentage).

Results

The comet percentages in specimens from cases with normal histology were significantly higher than the comet percentages in specimens from cases with H. pylori-positive gastritis. In addition, there was a significant increase in the percentage of cometed cells on the surface of gastric epithelial cells in both normal and H. pylori-infected cells compared to the subsequent gastric cell layers of the same specimen.

Conclusions

A relationship between the comet percentage and the histological diagnosis was observed.     

AEG-1 Is a Target of Perifosine and Is Over-Expressed in Gastric Dysplasia and Cancers

Background

Perifosine, an alkylphospholipid, is an Akt inhibitor which inhibits the growth of diverse cancer cells. We have reported its inhibitory effects on the growth of gastric cancer cells recently, but its molecular mechanisms are still largely unknown.

Aims

The purpose of this study was to investigate the effect and regulatory mechanism of perifosine in gastric cancer.

Methods

Cell viability was determined by sulforhodamine B assay after transiently transfected with AEG-1 specific siRNAs. qRT-PCR and western blot assay were used to determine the mRNA expression and proteins levels of cell signaling molecules examined. Immunohistochemistry was used to detect the AEG-1 expression in 87 gastric carcinomas, 60 dysplasia, and 47 normal gastric mucosa.

Results

Perifosine decreased AEG-1 gene expression along with inhibition of Akt/GSK3β/C-MYC signaling pathway. Knockdown of AEG-1 using siRNA led to significant down-regulation of cyclin D1 expression at both mRNA level and protein level, and inhibited the growth of gastric cancer cells. AEG-1 expression was elevated in gastric dysplasia and cancer tissues compared to normal gastric mucosa (P < 0.01). AEG-1 over-expression correlated with diffuse type of gastric cancer and advanced tumor stages.

Conclusions

Perifosine inhibits the growth of gastric cancer cells possibly through inhibition of the Akt/GSK3β/C-MYC signaling pathway—mediated down-regulation of AEG-1 that subsequently down-regulated cyclin D1. AEG-1 may play an important role in the carcinogenesis and progression of gastric cancer and could be a therapeutic target of perifosine.     

Interleukin-4 receptor -3223T→C polymorphism is associated with increased gastric adenocarcinoma risk

BACKGROUND:

Gastric cancer remains one of the most common types of cancer worldwide, with a large geographical variation in incidence and mortality rates. Cytokine polymorphisms are the most studied host polymorphisms and are associated with an increased risk of stomach cancer in many regions, but have not been studied extensively in Eastern European populations.

OBJECTIVE:

To investigate the potential association between five cytokine promoter polymorphisms (interleukin [IL] 1β −511C→T [rs16944], IL-4 receptor [IL-4R] −3223C→T [rs2057768], IL-8 −251T→A [rs4073], IL-10 −1082A→G [rs1800896] and tumour necrosis factor-alpha −308G→A [rs1800629]) and susceptibility to gastric adenocarcinoma in a Romanian population.

METHODS:

A total of 347 subjects, consisting of 105 patients with gastric adenocarcinoma and 242 controls, were included. All cytokine polymorphisms were genotyped using allele-specific, commercially available probes. Hardy-Weinberg equilibrium in both groups was analyzed using the χ² test, and the relationship between targeted polymorphisms and the risk of gastric cancer was estimated using OR and 95% CI.

RESULTS:

A significant association between the IL-4R −3223C→T polymorphism and risk of gastric cancer was found. Carriers of the IL-4R −3223TT genotype were at a 2.5-fold increased risk for gastric cancer (OR 2.51 [95% CI 1.08 to 5.84]; P=0.041). Moreover, the presence of the IL-4R −3223TT genotype was associated with an increased risk of noncardia gastric adenocarcinoma (OR 3.08 [95% CI 1.25 to 7.58]; P=0.023). No associations were found among the other polymorphisms.

CONCLUSION:

The results suggest that the IL-4R −3223C→T polymorphism may increase the risk of gastric adenocarcinoma, mainly for the noncardia type, in the Romanian population.     

Methylated APC and RASSF1A in multiple specimens contribute to the differential diagnosis of patients with undetermined solitary pulmonary nodules

Background

Inactivation of tumor-suppressor gene (TSG) by promoter hypermethylation has been reported in many tumor types, including lung cancer. This study was designed to determine the methylated APC and RASSF1A genes in tumor tissue, serum and plasma of patients with early stage lung cancer.

Methods

Eighty-nine patients with undetermined solitary pulmonary nodules detected upon CT-scan were recruited in this study. DNA samples were extracted from biopsy tissues, serum and plasma and QMSP of APC and RASSF1A was carried out after bisulfite conversion. The 89 patients consist of 58 stage I lung cancer patients and 31 benign lung disease according to pathological report. Twenty-six cancer patients had matched biopsy tumor tissue, serum and plasma samples.

Results

The methylation rates of APC and RASSF1A were 59.0% and 66.1% in biopsy tissues, 42.5% and 52.5% in serum, and 24.1% and 43.1% in plasma of cancer patients. For RASSF1A, different samples all showed a significant difference between cancer group and benign group (P<0.05). However, APC gene only explored the P value less than 0.05 in plasma result. Towards the 26 lung cancer patients with three matched samples, methylation rate in each sample type was more than 50.0% and displayed no difference.

Conclusions

Evaluation of APC and RASSF1A promoter methylation by using QMSP appears to be very useful for the differential diagnosis of patients with undetermined solitary pulmonary nodules. Our results also suggested that plasma might be the best sample for clinical detection of early stage lung.     

Glomus tumor of the stomach: a clinicopathologic analysis of 10 cases and review of the literature

Background/Aims

Gastric glomus tumors are extremely rare, and presurgical confirmation is often impossible. The identification of clinical and radiologic characteristics of this tumor type is important for preoperative diagnosis and treatment planning.

Methods

In this study, we analyzed 10 cases of gastric glomus tumors resected at a single institute over 9 years.

Results

Eight of the patients were men and 2 were women, with a mean age of 49 years. Five patients presented with abdominal discomfort or pain, 1 presented with anemia, and the remaining 4 cases were found incidentally during endoscopic examinations. The most common location of the tumor was the antrum (n=7), followed by the low (n=2) and high body (n=1). Although the endoscopic ultrasonography findings were variable, contrast-enhanced computed tomography generally showed a strong homogeneous enhancement. The resected tumors were well-demarcated solid masses with sizes ranging from 1.0 to 3.6 cm. Microscopically, the masses were composed of abundant vascular channels with clusters of uniform and round glomus cells. There was no evidence of recurrence after complete surgical resection.

Conclusions

Gastric glomus tumors are unusual, distinct lesions that should be considered in the differential diagnosis of a gastric submucosal mass. Unlike their deep soft tissue counterparts, most glomus tumors in the stomach are benign.     

Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

Background/Aims

The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A₂ (cPLA₂), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model.

Methods

The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA₂, and 5-LOX.

Results

All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA₂ and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups.

Conclusions

SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.