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The immunomodulatory and anti-inflammatory effects of thalidomide are associated with inhibition of TNF-α levels. However, the mechanism by which thalidomide reduces TNF-α production remains elusive. NF-κB is known to play a central role in regulating inflammatory responses in patients with inflammatory bowel disease (IBD). We tested whether thalidomide acts through inhibiting NF-κB activity. HT-29 cells were stimulated with LPS (1 ug/ml) alone, or after pretreatment with thalidomide (100 pg/ml), and NF-κB activity was determined by gel mobility shift assays. RT-PCR was used to measure expression of the proinflammatory cytokine genes TNF-α, IL-ip and IL-8. The level of TNF-α mRNA was also analyzed by real-time quantitative RT-PCR, and TNF-α protein was measured by ELISA. Thalidomide pretreatment did not affect NF-κB activity in HT-29 cells stimulated with LPS but production of TNF-α was depressed. Thalidomide was found to accelerate the degradation of TNF-α mRNA, but had little effect on IL-1β or IL-8. These observations suggest that the immunomodulatory effect of thalidomide in colonic epithelial cells is associated with inhibition of TNF-α. However, it does not act by inhibiting NF-κB but rather by inducing degradation of TNF-α mRNA. [ABSTRACT FROM AUTHOR]

Discusses a study which examined the outcome of patients with low-grade gastric mucosa-associated lymphoid tissue lymphoma. Patients and methods; Results; Conclusions.

Endoscopic ultrasonography (EUS) has been a useful method for the accurate staging of esophageal cancer. This study aimed to compare the diagnostic performance of EUS, positron emission tomography (PET), and computed tomography (CT) in the locoregional staging of resectable esophageal cancer. A total of 109 patients with resectable esophageal cancer were prospectively enrolled and retrospectively reviewed for evaluation of preoperative EUS, PET, and CT. The sensitivity, specificity, and accuracy of tumor depth (T) staging and regional lymph nodal (N) staging for each test were compared with the postoperative histopathologic stage as the gold standard. The overall accuracy of EUS for T staging was 72%, and it was the only method for delineating the layers of the esophageal wall. The sensitivities for N staging were 42% for EUS, 49% for PET, and 35% for CT, and their specificities were, respectively, 91, 87, and 93%. The accuracy for N staging was 66% for EUS, 68% for PET, and 63% for CT, and it did not differ significantly across the three tests. Preoperative EUS for the locoregional staging of esophageal cancer provides excellent T staging accuracy and similar accuracy for N staging compared with PET and CT. Especially in T staging, EUS could play an important role in the choice of candidates for esophageal cancer surgery. [ABSTRACT FROM AUTHOR]

Early gastric cancer (EGC) with undifferentiated histology has not been generally accepted as an indication for endoscopic treatment. This study was designed to evaluate the outcomes and clinicopathological factors associated with the complete resection of undifferentiated EGC using endoscopic submucosal dissection (ESD). A retrospective analysis of prospectively collected data was performed on consecutive patients who underwent ESD. Among the 456 EGCs treated using ESD at the Seoul National University Hospital, Seoul, Korea, between April 2005 and June 2008, 60 lesions (13.2%) were diagnosed as undifferentiated gastric cancer (poorly differentiated adenocarcinoma or signet ring cell carcinoma). En bloc resection was performed in all lesions without significant complications. The size discrepancy between the pretreatment endoscopy and the resected specimen was significantly higher in undifferentiated EGCs than differentiated EGCs ( p = 0.002). The complete resection rate was significantly lower for undifferentiated EGC (55%) cases than differentiated EGC cases (84.1%; p < 0.001). Independent risk factors for incomplete resection of undifferentiated EGC included tumor size >20 mm, submucosal invasion, and presence of ulceration. During a mean observation time of 16 months, no recurrence developed in any of the patients with undifferentiated EGCs thought to be completely resected by ESD. ESD might be considered an alternative treatment modality in carefully selected cases of undifferentiated EGC. [ABSTRACT FROM AUTHOR]

Depressed-type early gastric cancer (EGC) is known to repeat improvement and exacerbation of ulceration during its natural course, forming a “malignant cycle.” However, it is difficult to observe the malignant cycle of EGC in clinical practice, and little is known about the clinicopathologic factors associated with this cycle. This study aimed to evaluate the malignant cycle of EGC and to determine the clinicopathologic factors associated with the time-dependent morphologic change of EGC. The medical records of EGC patients treated at the Seoul National University Hospital were retrospectively reviewed with two or more comparable endoscopic photos taken between March 1999 and December 2005. The ulcer stages in EGC were classified by the gastric ulcer stage system and evaluated for time-dependent morphologic changes according to the relevant factors. In this study, 231 cases of depressed-type EGC were evaluated. At the follow-up endoscopy after a median interval of 23 days, a change in ulcer stage was observed in 66 patients (29%), with improvement in 45 patients (20%) and exacerbation in 21 patients (9%). Of the 177 patients who demonstrated an active or healing stage, 45 (25%) showed improvement and 10 (6%) exhibited exacerbation. The multivariate analysis showed that the usage of antisecretory medications, mucosal cancer, and a longer interval between the two endoscopic examinations were the factors that had a significant association with improvement of the ulcer stage. The malignant cycle was frequently observed in depressed-type EGC. The improvement of ulceration in EGC was time dependent and associated with the usage of antisecretory medication and the depth of invasion. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a medical case of cytomegalovirus-associated multiple gastric ulcers in ulcerative colitis.

A response from Hae Yeon Kang and colleagues to a letter to the editor on their article about endoscopic resection for undifferentiated early gastric cancer, in a previous issue is presented.

Background: Endoscopic resection as curative treatment of early gastric cancer (EGC) requires accurate staging for depth of invasion (T) before therapy. This study aimed to compare T staging of EGC using a miniprobe with that of conventional endoscopy (CE). Methods: A total of 388 patients with suspected of EGC by CE were prospectively enrolled in the study. After miniprobe staging by an experienced endosonographer, CE staging was performed by another endoscopist who was blinded to the miniprobe assessment. Patients underwent either endoscopic resection ( n = 325) or surgery (=63) according to staging results. Results of each method were compared with the histology of the resected specimen. Clinicopathological factors affecting accuracy of each test were also evaluated. Results: Overall accuracy of miniprobe and CE staging was 78.9% (306/388) and 81.4% (316/388), respectively ( p = 0.052). Sensitivity for T1m was more than 95% (miniprobe 98.7%, CE 97.7%), whereas sensitivity for T1sm was lower at 6.6% for miniprobe and 23.7% for CE ( p = 0.002). Among nine lesions identically considered submucosal invasion by both methods, three were T1sm cancer. Diagnostic accuracy of the miniprobe was lower than that of CE with respect to lesions located in the lower third of the stomach, differentiated histology, or massive submucosal invasion. Conclusions: Overall accuracy of the miniprobe and CE for T staging in EGC was approximately 80% with no significant difference. Accurate prediction of both techniques for submucosal invasion was poor, even by using a combination of the two methods. The use of the miniprobe may not increase the positive predictive value for T staging over the use of CE alone. [ABSTRACT FROM AUTHOR]

The p53 gene has been referred to as 'the guardian of the genome' because it controls apoptosis and cell cycle arrest. The purpose of this study was to evaluate the association of p53 codon 72 genetic polymorphism and the p53 immunohistochemistry with Helicobacter pylori-associated gastroduodenal diseases, including gastric cancer. This study included 1,852 subjects: controls and patients with gastric cancer, dysplasia, benign gastric ulcers, and duodenal ulcers (DU). Biallelic polymorphism was genotyped by restriction fragment length polymorphism. Immunohistochemical analysis for the detection of mutant type p53 expression was performed. The frequency of the Pro/Pro allele of the p53 codon 72 was higher in the patients with H. pylori-positive dysplasia than in controls (OR: 2.3, 95% CI: 1.3-4.3), but it was less frequent among patients with a H. pylori-positive DU (OR: 0.5, 95% CI: 0.3-0.8). However, there was no significant association with gastric cancer, including the location, stage, or histological type of gastric cancer. Expression of a mutant type of p53 protein was detected in 6.3% of dysplastic tissues and 26.5% of cancerous tissues compared 0% in the controls. Positive expression was higher in the intestinal type of cancer (34.9%) than in the diffuse type (15.0%; P = 0.001). These results suggest that genetic polymorphism of p53 codon 72 played a role in the determination of H. pylori-associated gastroduodenal diseases, but p53 immunostaining did not correlate with those of the p53 genetic polymorphism analysis. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Colorectal adenoma is known to be associated with obesity, but the association between colorectal adenoma and visceral adipose tissue (VAT) area measured by abdominal computed tomography (CT) has not been documented clearly. In addition, the relationship between insulin resistance and colorectal adenomas, which underlies the mechanism that links obesity and colorectal adenoma, has not been studied extensively. The aim of this study was to examine VAT area and insulin resistance as risk factors of colorectal adenoma.METHODS:A cross-sectional, case–control study was conducted in Koreans that presented for health check-ups. Subjects underwent various laboratory tests, abdominal CT, and colonoscopy. VAT, subcutaneous adipose tissue (SAT), and homeostatic metabolic assessment (HOMA) index were evaluated as potential risk factors of colorectal adenoma in 2,244 age- and sex-matched subjects.RESULTS:According to univariate analysis, the prevalences of smoking, hypertension, metabolic syndrome, and family history of colorectal cancer were higher in the adenoma group than in the normal control group. In addition, body mass index, waist circumference, triglyceride, high-density lipoprotein cholesterol, and VAT and SAT areas were significantly different in the two groups. According to the multivariate analysis adjusted for multiple confounders, VAT area was independently associated with the risk of colorectal adenoma (odds ratio (OR)=3.09, 95% confidence interval (CI): 2.19–4.36, highest quintile vs. lowest quintile). Mean HOMA index was higher in the adenoma group than in the control group (OR=1.99, 95% CI: 1.35–2.92, highest vs. lowest quintile).CONCLUSIONS:Visceral obesity was found to be an independent risk factor of colorectal adenoma, and insulin resistance was associated with the presence of colorectal adenoma. [ABSTRACT FROM AUTHOR]

Cochinchina momordica seed extract (SKMS10), which is composed of the major compounds momordica saponins, has been evaluated for its gastroprotective effects in rat models of acute gastric mucosal damage. Ethanol and water immersion restraint stress (WRS) induced gastric damage, including hemorrhages and edema, was significantly attenuated by pretreatment with SK-MS10. In addition, SK-MS10 reduced increases of mucosal myeloperoxidase (MPO), IL-1β, and TNFα levels and the expression of cPLA(2), and 5-LOX induced by ethanol or WRS. SK-MS10 also increased hexosamine, adherent mucus, and the expression of MUC5AC. Furthermore, SK-MS10 enhanced the mucosal expression of the CGRP gene and its serum levels.N(G)-methyl L-arginine (L-NMMA) or capsaicin desensitization reversed the SK-MS10-induced gastroprotection effect. These results suggest that SK-MS10 is a gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, downregulating cPLA(2), 5-LOX, and increasing the synthesis of mucus. Furthermore, CGRP-NO pathway was found to play an important role in these gastroprotective effects of SK-MS10. [ABSTRACT FROM AUTHOR]