The emergence of infliximab was an epochal event in the treatment of inflammatory bowel disease (IBD). Because colitis-associated cancers arose in the setting of chronic inflammation, during which "inflammation-dysplasia-carcinoma sequence" prevails and anti-inflammatory agents can prevent carcinogenesis, we hypothesized whether infliximab can prevent colitic cancer in animal models for which C57BL/6 mice were exposed to 15 cycles of dextran sulfate sodium (DSS), with each cycle consisting of 0.7% DSS for 1 week followed by sterilized water for 10 days. Infliximab (4 mg/kg i.v.) was given on the 1st, 3rd, and 7th weeks or 25th, 27th, and 31st weeks of cycle according to "step-up" versus "top-down" strategy. Molecular change about inflammation and carcinogenesis was compared between groups. Multiple colorectal tumors developed in 75% to 80% of control mice, whereas only 16.7% of mice treated with infliximab on the 1st, 3rd, and 7th weeks developed colon tumors. Significant decreases in tumor necrosis factor-α level, mast cell number, and the expression of inflammatory cytokines were observed in top-down strategy using infliximab. The expression and activity of matrix metalloproteinase-9 (MMP-9) and MMP-11 were significantly decreased in mice treated with infliximab accompanied with attenuated numbers of "β-catenin-accumulated crypts." In animal group where infliximab was administered at later stage of 25th, 27th, and 31st weeks, no reduction in tumorigenesis was noted. These biological effects of infliximab were further explored in in vitro experiment using Raw264.7 and Jurkat T cells. Conclusively, earlier and intensive therapy with infliximab should be considered for either mitigating clinical course or preventing ultimate development of colitic cancer in high-risk IBD patients. Cancer Prev Res; 3(10); 1314-33. ©2010 AACR.

Fournier's gangrene is a gas-forming, necrotising soft tissue infection affecting the perineum. It spreads rapidly along the deep fascial planes and is associated with a high mortality rate. With a growing elderly population with comorbidities, the frequency of severe cases of Fournier's gangrene is expected to increase. We retrospectively reviewed 20 patients diagnosed with Fournier's gangrene at our institution from 2003 to 2014 and analysed data. Thirteen patients had diabetes mellitus, two had been diagnosed with liver cirrhosis, and four were chronic alcoholics. Of 15 patients admitted to an intensive care unit, 11 underwent colostomy, and 4 required skin grafts for wound healing. The wide wounds of two patients were healed using vacuum-assisted closure (VAC ) dressing without additional surgery. The mortality rate was 25%, and the patients whose Fournier's gangrene severity index (FGSI) score was higher than 9 points or whose blood urea nitrogen (BUN) level was higher than 50 mg/dl had a poor prognosis. In order to treat Fournier's gangrene, aggressive surgical treatment, including wide debridement and stoma creation, should be considered as soon as possible to improve survival rates. Additionally, VAC dressing is helpful in healing the wide debridement wound without additional reconstructive surgery.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a rapidly progressive, fatal lung disease that affects older adults. One of the detrimental natural histories of IPF is acute exacerbation of IPF (AE-IPF), of which bacterial infection is reported to play an important role. However, the mechanism by which bacterial infection modulates the fibrotic response remains unclear.ObjectivesAltered glucose metabolism has been implicated in the pathogenesis of fibrotic lung diseases. We have previously demonstrated that glucose transporter 1 (GLUT1)-dependent glycolysis regulates fibrogenesis in a murine fibrosis model. To expand on these findings, we hypothesised that GLUT1-dependent glycolysis regulates acute exacerbation of lung fibrogenesis during bacterial infection via AIM2 inflammasome activation.ResultsIn our current study, using a murine model of Streptococcus pneumoniae (S. pneumoniae) infection, we investigated the potential role of GLUT1 on mediating fibrotic responses to an acute exacerbation during bleomycin-induced fibrosis. The results of our current study illustrate that GLUT1 deficiency ameliorates S. pneumoniae-mediated exacerbation of lung fibrosis (wild type (WT)/phosphate buffered saline (PBS), n=3; WT/S. pneumoniae, n=3; WT/Bleomycin, n=5 ; WT/Bleomycin+S. pneumoniae, n=7; LysM-Cre-Glut1fl/f/PBS, n=3; LysM-Cre-Glut1fl/fl/S. pneumoniae, n=3; LysM-Cre-Glut1fl/fl/Bleomycin, n=6; LysM-Cre-Glut1fl/fl/Bleomycin+S. pneumoniae, n=9, p=0.041). Further, the AIM2 inflammasome, a multiprotein complex essential for sensing cytosolic bacterial DNA as a danger signal, is an important regulator of this GLUT1-mediated fibrosis and genetic deficiency of AIM2 reduced bleomycin-induced fibrosis after S. pneumoniae infection (WT/PBS, n=6; WT/Bleomycin+S. pneumoniae, n=15; Aim2−/−/PBS, n=6, Aim2−/−/Bleomycin+S. pneumoniae, n=11, p=0.034). GLUT1 deficiency reduced expression and function of the AIM2 inflammasome, and AIM2-deficient mice showed substantial reduction of lung fibrosis after S. pneumoniae infection.ConclusionOur results demonstrate that GLUT1-dependent glycolysis promotes exacerbation of lung fibrogenesis during S. pneumoniae infection via AIM2 inflammasome activation.

Helicobacter pylori infection has been reported to be very common in patients with chronic liver diseases, including cirrhosis. To elucidate the pathological effect of H. pylori infection on the progression of hepatic fibrosis, C57BL/6 mice and Sprague-Dawley rats were orally inoculated with H. pylori, and hepatic fibrosis was induced with carbon tetrachloride (CCl 4 ) administration. We observed the histopathological changes and the presence of H. pylori genes by PCR in the liver. Significant increase in the fibrotic score as well as in serum alanine aminotransferase and aspartate aminotransferase levels was shown in the CCl 4 þ H. pylori group compared with that in the CCl 4 -treated group. Compared with the CCl 4 -treated group, a-smooth muscle actin and transforming growth factor-b1 were enhanced; however, senescence marker protein-30, a multifunctional protein protecting hepatocytes against oxidative stress and apoptosis, was suppressed in the CCl 4 þ H. pylori group. The 16S rRNA (400 bp) was demonstrated by PCR for H. pylori genes from genomic DNA extracted from the liver, and H. pylori-infected mice showed 93.8% (15 of 16) seropositivity by contrast with seronegativity in all H. pylori-noninfected mice. In addition, immunohistochemical study against H. pylori showed positive antigen fragments in the liver of the infected groups. Consequently, our data suggest that H. pylori infection could be an important contributing infectious factor to the development of liver cirrhosis.

Colitis-associated cancers arise in the setting of chronic inflammation wherein an "inflammationdysplasia-carcinoma" sequence prevails. Based on our previous findings in which the proton pump inhibitor could impose significant levels of anti-inflammatory, antiangiogenic, and selective apoptosis induction beyond gastric acid suppression, we investigated whether omeprazole could prevent the development of colitis-associated cancer in a mouse model induced by repeated bouts of colitis. Omeprazole, 10 mg/kg, was given i.p. all through the experimental periods for colitis-associated carcinogenesis. Molecular changes regarding inflammation and carcinogenesis were compared between control groups and colitis-associated cancer groups treated with omeprazole in addition to chemopreventive outcome. Nine of 12 (75.0%) mice in the control group developed multiple colorectal tumors, whereas tumors were noted in only 3 of 12 (25.0%) mice treated with daily injections of omeprazole. The cancer-preventive results of omeprazole treatment was based on significant decreases in the levels of nitric oxide, thiobarbituric acid-reactive substance, and interleukin-6 accompanied with attenuated expressions of tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2. The expressions of matrix metalloproteinase (MMP)-9, MMP-11, and MT1-MMMP were significantly decreased in mice treated with omeprazole in accordance with significant decreases in the number of β-catenin-accumulated crypts. A significant induction of apoptosis was observed in tumor tissue treated with omeprazole. Omeprazole could block the trophic effect of gastrin in colon epithelial cells. The significant anti-inflammatory, antioxidative, and antimutagenic activities of omeprazole played a cancer-preventive role against colitisinduced carcinogenesis, and our novel in vivo evidence is suggestive of chemopreventive action independent of gastric acid suppression. Cancer Prev Res; 3(8); 963-74. ©2010 AACR.

PurposeIn recent years, many psychological problems in patients with stomas have been addressed in a number of studies. But there are only a few studies that use objective measures to take into account self-appraisal by patients with permanent or temporary stomas. The aim of this study is to compare the psychological attitude of patients with permanent and temporary stomas and to determine the most appropriate psychological supportive care.MethodsSixty-five patients, who received a stoma between January 2009 and March 2012, were classified into two groups with either permanent or temporary stomas and were observed prospectively. We developed a questionnaire with the aid of a psychiatrist to analyze the grade of psychological attitude of self-appraisal of patients. The questionnaire was categorized into three parts; body image scale, self-esteem scale, and depression scale. Patients responded to the questionnaire 4 weeks after the operation and the answers of each group were compared.ResultsOut of 65 patients, 42 received temporary stomas and 23 received permanent stomas. There was no significant mean difference between permanent and temporary stoma patients in the body image scale, the self-esteem scale, and the depression scale. However, patients with a permanent stoma tended to have a worse body image and lower self-esteem on some specific items within the questionnaires.ConclusionPatients with stomas have negative attitudes toward themselves and some meaningful differences were found between different types of stoma applied. Surgeons should be concerned about postoperative psychological support for patients with stomas.

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