Endoscopic features predictive of gastric cancer in superficial lesions with biopsy-proven high grade intraepithelial neoplasia

AIM:To investigate the macroscopic and clinicopathologic features of gastric cancer in patients with biopsy-suggested high grade intraepithelial neoplasia. METHODS:Patients with biopsy-confirmed gastric high grade intraepithelial neoplasia were reviewed from January 2001 to March 2008.Pathologic sections were re-evaluated by two senior pathologists. Patients with an en-bloc resection of the lesion within two months after the diagnosis of high grade intraepithelial neoplasia were enrolled in the study. Clinical manifestations,endoscopic features,biopsy and surgical pathology of all patients were collected and analyzed.The data acquired were subjected to univariate and multivariate analysis. RESULTS:Seventy-two superficial gastric lesions with a pathologic diagnosis of high grade intraepithelial neoplasia based on biopsy specimens were enrolled. True high grade intraepithelial neoplasia was finally proved in 16 lesions and gastric cancer in the rest 56 lesions,most of which(96.4%)were differentiated carcinomas.The result of univariate analysis indicatedthat the size and the presence of marked ulcer plaque or scar in a superficial lesion were independently associated with gastric cancer(P<0.05),when high grade intraepithelial neoplasia was diagnosed by biopsy pathology.The results of multivariate analysis revealed the size greater than 1.5 cm[odds ratio(OR)18.400,P<0.001]and the presence of 5-odd mm ulcer plaque or scar(OR 10.000,P=0.044)were associated with gastric cancer.Accordingly,the sensitivity,specificity and negative predictive value of multivariate analysis for predicting"true high grade intraepithelial neoplasia" was 87.5%,89.3%and 96.2%,respectively. CONCLUSION:Macroscopic findings are of value in differentiation between high grade intraepithelial neoplasia and superficial gastric cancer.This may simplify patient work-up and save costs for patients and healthcare system.

Idiopathic mesenteric phlebosclerosis associated with long-term use of medical liquor:Two case reports and literature review

A 62-year-old woman was admitted to our hospital in2011 because of recurrent abdominal pain,nausea and constipation for six months.Computed tomography enterography(CTE)showed tortuous thread-like calcifications in the ileocolic vein and right colic vein,while colonoscopy revealed purple-blue mucosa extending from the cecum to the splenic flexure.Based on the results of these tests,the patient was diagnosed with idiopathic mesenteric phlebosclerosis(IMP).She had a history of Chinese medical liquor intake for one and a half years and her symptoms subsided after conservative treatment.In 2013,a 63-year-old male patient who presented with recurrent lower right abdominal pain,bloating,melena and diarrhea for fifteen months was admitted to our institution.Colonoscopy and CTE led to the diagnosis of IMP.He also used Chinese medical liquor for approximately 12 years.The patient underwent total colectomy and the postoperative course was uneventful.We searched for previously published reports on similar cases and analyzed the clinical data of 50 cases identified in PubMed.As some of these patients admitted use of Chinese medicines,we hypothesize that Chinese medicines may play a role in the pathogenesis of IMP.

Advances in pancreatic cancer research: Moving towards early detection

Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients(nearly80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC.However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide cluesfor its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

A randomized,double-blind,placebo-controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation

AIM: To evaluate the efficacy and safety of tegaserod, 6 mg twice daily (b.i.d.), in men and women with chronic constipation (CC) from China. METHODS: This was a multicenter, double-blind, placebo-controlled study. Following a 2-wk treatment-free baseline period, patients were randomized to receive either tegaserod (6 mg b.i.d.) or placebo (b.i.d.) for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements (CSBMs) during the 4-wk treatment period. Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients’ daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events (AEs).RESULTS: A total of 607 patients were randomized to receive either tegaserod (n = 304) or placebo (n = 303). Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo (1.39 vs 0.91, P = 0.0002). A statistically significant difference in favor of tegaserod was also observed for a mean increase ≥ 1 CSBM/wk over wk 1-4 (47.7% vs 35.0%, tegaserod vs placebo, respectively, P = 0.0018) and for the absolute number of ≥ 3 CSBMs/wk over wk 1-4 (25.0% vs 14.5%, tegaserod vs placebo, respectively, P = 0.0021). Improvements in other symptoms of CC were also seen in the tegaserod group, including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod (3.6%) compared with placebo (1.7%).CONCLUSION: Tegaserod treatment improved multiple symptoms of CC and was associated with a favorable safety profile.

High dose glargine alters the expression profiles of microRNAs in pancreatic cancer cells

AIM: To investigate the effect of high dose glargine on the expression profiles of microRNAs in human pancreatic cancer cells. METHODS: Real-time polymerase chain reaction array (RT-PCR) was applied to investigate miRNAs differentially expressed in Sw1990 cells treated with or without 100 IU/L glargine. Stem-loop RT-PCR was used to confirm the results of the array assay in Sw1990 and Panc-1 cells. The effects of miR-95 on cell growth, apoptosis, invasion and migration abilities were respectively examined by CCK8 assay, apoptosis assay, Matrigel invasion and migration assay in Sw1990 and Panc-1 cells. Nude mice xenograft models with Sw1990 cells were built to investigate pancreatic cancer growth in vivo after transfection by the lentivirus pGLV3-GFP-miR-95. RESULTS: Ten miRNAs were significantly up-regulated and 2 miRNAs down-regulated in glargine treated Sw1990 cells when compared with non-treated cells (2.48-fold changes on average, P < 0.01). miR-95, miR-134 and miR-34c-3p are the top three miRNAs regulated by glargine (3.65-fold, 2.67-fold and 2.60-fold changes respectively, P < 0.01) in Sw1990 cells. Stem-loop RT-PCR confirmed that high dose glargine up-regulated the expression of miR-95 and miR-134 in both Sw1990 and Panc-1 cells. The most obvious change is the apparent increase of miR-95. Forced expression of miR-95 significantly increased cell proliferation (Sw1990: 2.510 ± 0.129 vs 2.305 ± 0.187, P < 0.05; Panc-1: 2.439 ± 0.211 vs 2.264 ± 0.117, P < 0.05), invasion (Sw1990: 67.90 ± 12.33 vs 47.30 ± 5.89, P < 0.01; Panc-1: 37.80 ± 8.93 vs 30.20 ± 5.14, P < 0.01), migration (Sw1990: 101 ± 6.00 vs 51.20 ± 8.34, P < 0.01; Panc-1: 91.80 ± 9.22 vs 81.50 ± 7.47, P < 0.01) and inhibited cell apoptosis (Sw1990: 22.05% ± 1.92% vs 40.32% ± 1.93%, P < 0.05; Panc-1: 20.17% ± 0.85% vs 45.60% ± 1.43%, P < 0.05) when compared with paired negative controls, whereas knockdown of miR-95 obtained the opposite effect. Nude mice xenograft models confirmed that miR-95 promoted the growth of pancreatic cancer in vivo when compared with negative control (tumor volume: 373.82 ± 23.67 mLvs 219.69 ± 17.82 mL,P < 0.05). CONCLUSION: These observations suggested that mod- ulation of miRNA expression may be an important mechanism underlying the biological effects of glargine.