Atopic dermatitis is associated with the clinical course of inflammatory bowel disease.

OBJECTIVES: There are a few studies about the relationship between inflammatory bowel disease (IBD) and atopic dermatitis (AD). It is implied that both diseases have common pathophysiologic mechanisms and can affect each other. However, little information is available on the effect of AD on the clinical course of patients with IBD. METHODS: This is a multi-center, retrospective, observational study. We define AD as a chronic eczematoid dermatosis diagnosed by dermatologists. Patients with concurrent IBD and AD were defined as a case group. Age, gender, and IBD subtype-matched patients without AD were included as a reference group. RESULTS: The numbers of patients in the case and reference groups were 61 and 122 respectively. There was a significantly shorter biologics-free survival in the case group than that in the reference group according to the multivariable-adjusted Cox regression analysis with the onset age, disease duration, smoking status, use of steroid, use of immunomodulator, initial C-reactive protein, initial erythrocyte sedimentation rate, presence of other allergic diseases and initial disease severity [hazard ratio (HR) 1.828, 95% confidence interval (CI) 1.022-3.271, p = .042]. The trend was consistent in the subgroup analysis with ulcerative colitis (HR 3.498, 95% CI 1.066-11.481, p = .039), but not with Crohn's disease (HR 1.542, 95% CI 0.720-3.301, p = .265). CONCLUSIONS: AD showed a significant effect on the biologics-free survival of patients with IBD and especially the UC subtype. Further mechanistic research is required to elucidate the pathogenesis of AD on the clinical course of IBD.

Composite scoring system and optimal tumor budding cut-off number for estimating lymph node metastasis in submucosal colorectal cancer.

BACKGROUND: Tumor budding is associated with lymph node (LN) metastasis in submucosal colorectal cancer (CRC). However, the rate of LN metastasis associated with the number of tumor buds is unknown. Here, we determined the optimal tumor budding cut-off number and developed a composite scoring system (CSS) for estimating LN metastasis of submucosal CRC. METHODS: In total, 395 patients with histologically confirmed T1N0-2M0 CRC were evaluated. The clinicopathological characteristics were subjected to univariate and multivariate analyses. The Akaike information criterion (AIC) values of the multivariate models were evaluated to identify the optimal cut-off number. A CSS for LN metastasis was developed using independent risk factors. RESULTS: The prevalence of LN metastasis was 13.2%. Histological differentiation, lymphatic or venous invasion, and tumor budding were associated with LN metastasis in univariate analyses. In multivariate models adjusted for histological differentiation and lymphatic or venous invasion, the AIC value was lowest for five tumor buds. Unfavorable differentiation (odds ratio [OR], 8.16; 95% confidence interval [CI], 1.80-36.89), lymphatic or venous invasion (OR, 5.91; 95% CI, 2.91-11.97), and five or more tumor buds (OR, 3.01; 95% CI, 1.21-7.69) were independent risk factors. In a CSS using these three risk factors, the rates of LN metastasis were 5.6%, 15.5%, 31.0%, and 52.4% for total composite scores of 0, 1, 2, and ≥ 3, respectively. CONCLUSIONS: For the estimation of LN metastasis in submucosal CRC, the optimal tumor budding cut-off number was five. Our CSS can be utilized to estimate LN metastasis.

Occult Blood in Feces Is Associated with Increased Risk of Psoriasis.

BACKGROUND: The fecal immunochemistry test (FIT) has been proposed as a surrogate marker of intestinal inflammation. Psoriasis is a chronic inflammatory skin disease that is linked to underlying systemic inflammatory conditions, including inflammatory bowel disease. METHODS: We investigated the association between occult blood in feces and the risk of psoriasis using data from the National Health Insurance System. This study was conducted involving 1,395,147 individuals who underwent health examinations from January 2009 to December 2012 and were followed up until the end of 2017. RESULTS: The incidence of psoriasis (per 1,000 person-years) was 3.76 versus 4.14 (FIT-negative versus FIT-positive group) during a median follow-up of 6.68 years. In the multivariable-adjusted model, the hazard ratios for psoriasis were 1.03 for one positive FIT result, 1.12 for two positive FIT results, and 1.34 for three positive FIT results compared with negative FIT results. CONCLUSION: The risk of psoriasis was significantly increased in patients with positive FIT results compared to the FIT-negative population.

Incidence of Psoriasis in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Matched Cohort Study.

BACKGROUND: Emerging data suggest that inflammatory bowel disease (IBD) and psoriasis are associated, sharing common genetic predispositions and immunological mechanisms. However, concrete data on psoriasis risk in IBD patients compared to the general population are limited. OBJECTIVE: We investigated the risk of developing psoriasis in IBD patients compared to controls without IBD. METHODS: Using the Korean National Health Insurance Database, patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2005 and 2008 were age- and sex-matched 1:4 to non-IBD subjects from 2003 to 2018. IBD patients were defined by combining the International Classification of Diseases 10th revision code and at least one prescription of IBD-specific medications. Disease phenotypes, including psoriasis severity and psoriatic arthritis, were also identified. We investigated newly diagnosed psoriasis from 2009 to 2018. Incidence rates and risk of psoriasis were assessed with multivariate Cox regression models. Subgroup analyses for age and sex, and sensitivity analysis involving tumor necrosis factor (TNF) inhibitor-naïve patients were performed. RESULTS: During nearly a decade of follow-up, 20,152 IBD patients were identified (14,619 [72.54%] UC and 5,533 [27.46%] CD). Among them, 439 patients were newly diagnosed with psoriasis (incidence rate of 217.68 per 100,000 person-years and 228.62 per 100,000 person-years for UC and CD, respectively). The psoriasis risk was higher in IBD patients than in the matched controls (adjusted hazard ratio, aHR, 2.95, 95% confidence interval, CI, 2.60-3.33). Moreover, IBD patients aged <30 years were at an increased risk (aHR 3.35, 95% CI 2.58-4.35), a trend that was unchanged across all psoriasis phenotypes. Sensitivity analysis of TNF inhibitor-naïve patients revealed consistent results. CONCLUSIONS: IBD patients were more likely to develop psoriasis compared to non-IBD subjects, including younger patients at an elevated risk regardless of TNF inhibitor use. This advocates the interplay between IBD and psoriasis; thus, inspection of cutaneous manifestation and dermatological consultation may be helpful in IBD patients at risk.

Clinical Course of COVID-19 in Patients with Inflammatory Bowel Disease in Korea: a KASID Multicenter Study.

In 2020, the novel coronavirus disease 2019 (COVID-19) began to spread worldwide and remains an ongoing medical challenge. This case series reports on the clinical features and characteristics of patients with inflammatory bowel disease (IBD) and confirmed COVID-19 infection. From February 2020 to March 2021, nine patients with IBD had confirmed COVID-19 across four hospitals in Korea. The median age at COVID-19 diagnosis was 42 years. Six patients were male, and seven patients had ulcerative colitis (UC). No patients required oxygen therapy, intensive care unit hospitalizations, or died. The most common symptom was fever, and gastrointestinal (GI) symptoms developed as diarrhea in five patients with UC. Oral steroids were used to combat UC aggravation in two patients. In this case series of nine IBD patients diagnosed with COVID-19 in Korea, the clinical presentation was predominately a mild respiratory tract infection. Most patients with UC developed new GI symptoms including diarrhea.

Bidirectional relationship between atopic dermatitis and inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: Recently, atopic dermatitis has been suggested as a systemic inflammatory disorder that can accompany other inflammatory diseases, including inflammatory bowel disease. However, comprehensive reviews that specifically focus on the association between inflammatory bowel disease and atopic dermatitis are lacking. OBJECTIVE: To determine the association between inflammatory bowel disease and atopic dermatitis. METHODS: We searched for relevant studies from MEDLINE, EMBASE, and the Cochrane Library from inception to November 22, 2019. Considering a potential bidirectional relationship, studies reporting inflammatory bowel disease in patients with atopic dermatitis and atopic dermatitis in patients with inflammatory bowel disease were evaluated separately. RESULTS: We included 10 studies with 95,291,110 patients (4 studies on the prevalence of atopic dermatitis in inflammatory bowel disease, 2 on the prevalence and incidence of inflammatory bowel disease in atopic dermatitis, and 4 on either the prevalence or incidence of inflammatory bowel disease in atopic dermatitis). Meta-analyses revealed a statistically significant association between inflammatory bowel disease and atopic dermatitis in both directions (4 studies on atopic dermatitis prevalence in inflammatory bowel disease, odds ratio 1.39, 95% confidence interval 1.28-1.50; 5 on inflammatory bowel disease prevalence in atopic dermatitis, odds ratio 1.35, 95% confidence interval 1.05-1.73; and 3 studies on inflammatory bowel disease incidence in atopic dermatitis, relative risk 1.46, 95% confidence interval 0.98-2.17). LIMITATIONS: A small number of observational studies were reviewed. CONCLUSION: Published literature suggests a bidirectional relationship between inflammatory bowel disease and atopic dermatitis.

Matricellular protein periostin promotes colitis-associated colon tumorigenesis in mice.

Periostin is expressed in inflamed colonic mucosa and colon cancer tissue; however, its role in the development of colitis-associated colon cancer (CAC) remains unclear. Wild-type and periostin-deficient (Postn-/-) mice were given a single intraperitoneal injection of azoxymethane at 12.5 mg/kg on day 0. Seven days later, 2% dextran sulfate sodium (DSS) was administered via drinking water for 5 days, followed by untreated, free water consumption for 16 days. This cycle was repeated three times. In vitro assays were performed using COLO205 and HCT116 cells. Small interfering RNA was used to inhibit Postn gene translation. Periostin expression was determined using colon samples from patients with CAC. Postn-/- mice exhibited lower tumor burden compared with wild-type mice. Exposure to azoxymethane/DSS resulted in extensive epithelial apoptosis in Postn-/- mice compared with that in wild-type mice. In addition, immunoreactivity for IκB kinase, ß-catenin and COX2 was markedly reduced in Postn-/- mice. Expression of interleukin (IL)-1ß and tumor necrosis factor α (TNF-α) significantly decreased, whereas that of IL-10 and transforming growth factor ß (TGF-ß) increased in peritoneal macrophages isolated from Postn-/- mice. Silencing of the Postn gene resulted in reduced cell viability, which was associated with caspase-3 activation, and this was reversed by treatment with recombinant periostin. Knockdown of Postn downregulated bcl-2, cIAP1, cFLIP-L, VEGF, Axin 2 and cyclin D1, and upregulated bak expression. Periostin expression was significantly increased in patients with CAC. Periostin aggravates CAC development, which suggests that periostin is a potential therapeutic target for the prevention of CAC in patients with inflammatory bowel disease.

Intermittent hypoxia promotes carcinogenesis in azoxymethane and dextran sodium sulfate-induced colon cancer model.

Intermittent hypoxia (IH), a characteristic of obstructive sleep apnea, is known to promote cancer progression and aggressiveness in mouse models. However, little is known regarding the effect of IH on cancer initiation. Here, the effect of IH on carcinogenesis was explored in azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon cancer models with three different protocols. In the first protocol, two other application time points (early or late initiation of IH) were applied. In the second protocol, mice were divided into only two groups, and then exposed to either N or IH conditions for 14 days. In the third protocol, a pharmacological inhibition study for anti-inflammation (5-aminosalicylate) or anti-oxidative stress (N-acetylcysteine [NAC]) was performed. The number of tumors was significantly higher in the IH-1 than in the N or IH-2 groups. 8-oxo-2'-deoxyguanosine (8-OHdG) levels were higher in tumors of the IH-1 group than in that of the N and IH-2 groups. Gene expression related to reactive oxygen species production was higher in the IH-1 group than in the N and IH-2 groups, and it showed a positive correlation with 8-OHdG levels. Prior to cancer development 8-OHdG levels were already elevated in colonic epithelial regions in the IH group, possibly due to an imbalance between oxidative stress and antioxidant systems. NAC treatment resulted in a significant reduction in the number of tumors in mice exposed to IH. In conclusion, IH promotes carcinogenesis in a chemically-induced colon cancer model where elevated 8-OHdG may contribute to the increased tumor induction.

Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice.

PURPOSE: Walnuts (Juglans regia) are known to have anti-cancer and immunomodulatory effects. However, little information is available on the effects of walnut phenolic extract (WPE) on intestinal inflammation and colitis-associated colon cancer. METHODS: COLO205 cells were pretreated with WPE and then stimulated with tumor necrosis factor (TNF)-α. In the acute colitis model, wild type mice (C57BL/6) were administered 4% dextran sulfate sodium (DSS) for 5 days. In the chronic colitis model, interleukin (IL)-10-/- mice were administered with either the vehicle or WPE (20 mg/kg) by oral gavage daily for 2 weeks. In an inflammation-associated tumor model, wild type mice were administered a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. RESULTS: WPE significantly inhibited IL-8 and IL-1α expression in COLO205 cells. WPE attenuated both the TNF-α-induced IκB phosphorylation/degradation and NF-κB DNA binding activity. The administration of oral WPE significantly reduced the severity of colitis in both acute and chronic colitis models, including the IL-10-/- mice. In immunohistochemical staining, WPE attenuated NF-κB signaling in the colons of both colitis models. Finally, WPE also significantly reduced tumor development in a murine model of colitis-associated colon cancer (CAC). CONCLUSIONS: WPE ameliorates acute and chronic colitis and CAC in mice, suggesting that WPE may have potentials for the treatment of inflammatory bowel disease.

Tauroursodeoxycholic acid attenuates colitis-associated colon cancer by inhibiting nuclear factor kappaB signaling.

BACKGROUND AND AIM: Inflammatory bowel diseases is associated with an increased risk for the development of colorectal cancer. However, the mechanism of immune signaling pathways linked to colitis-associated cancer (CAC) has not been fully elucidated. Tauroursodeoxycholic acid (TUDCA) exhibits anti-inflammatory and anti-cancer activities. The aim of this study is to investigate the role of TUDCA in the pathogenesis of CAC. METHODS: Colitis-associated cancer was induced in mice using azoxymethane and dextran sodium sulfate administration, and TUDCA's effect on tumor development was evaluated. HCT 116 and COLO 205 were treated with TUDCA or vehicle and then stimulated with tumor necrosis factor-α (TNF-α). Expression of interleukin (IL)-8 was determined by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, and IκBα phosphorylation and degradation was evaluated by immunoblot assay. The DNA-binding activity of NF-κB was assessed by electrophoretic mobility shift assay. Cell viability assay and real-time reverse transcription-polymerase chain reaction of bcl-xL, MCL1, c-FLIP-L, and VEGF were performed. RESULTS: Tauroursodeoxycholic acid significantly attenuated the development of CAC in mice. Exposure to TUDCA resulted in extensive epithelial apoptosis and reduced levels of phospho-IκB kinase in the colon. In HCT 116 cells stimulated with TNF-α, TUDCA significantly inhibited IL-8 and IL-1α expression and suppressed TNF-α-induced IκBα phosphorylation/degradation and DNA-binding activity of NF-κB. Furthermore, in both HCT 116 and COLO 205 cells, TUDCA reduced cell viability and downregulated the expression of bcl-xL, MCL1, c-FLIP-L, and VEGF. CONCLUSION: These results demonstrated that TUDCA suppresses NF-κB signaling and ameliorates colitis-associated tumorigenesis, suggesting that TUDCA could be a potential treatment for CAC.

Complications of percutaneous endoscopic and radiologic gastrostomy tube insertion: a KASID (Korean Association for the Study of Intestinal Diseases) study.

BACKGROUND: Gastrostomy tube insertion is beneficial to selected patients, and percutaneous endoscopic gastrostomy (PEG) and percutaneous radiological gastrostomy (PRG) are two of the frequently used methods in gastrostomy. This study aimed to investigate the indications and complications of both PEG and PRG. METHODS: This was a retrospective multicenter cohort study. Patients who underwent initial PEG or PRG tube insertion for nutritional purpose between January 2010 and December 2015 at five university hospitals were included in the study. We analyzed the indications and all complications related to gastrostomy, which were divided into the major (systemic or life-threatening) and minor (local and non-life-threatening) categories. RESULTS: A total of 418 patients who underwent PEG (n = 324) and PRG (n = 94) were reviewed. The indications for gastrostomy tube insertion were different and included mainly neurological disease (n = 240, 74.1%) such as cerebrovascular accident in the PEG group (n = 119, 36.7%) and mainly surgical disease (n = 28, 29.8%) such as head and neck cancer (n = 16, 17.0%) in the PRG group (p = 0.05). There were no differences in the minor (16.4% vs. 19.1%, p = 0.52) and major (12.3% vs. 14.9%, p = 0.51) complication rates between the PEG and PRG groups. The risk factors for complications were age [yearly increments; odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.06], tube diameter (1-Fr increments; OR 1.26, 95% CI 1.01-1.58), insertion time (1-min increments; OR 1.07, 95% CI 1.01-1.13), and neurological disease as the gastrostomy indication (vs. surgical disease; OR 4.61 95% CI 1.47-14.42). CONCLUSIONS: In our study, both PEG and PRG provided a safe route for nutrition delivery despite their different indications. Our data suggest that PEG might be the procedure of choice for patients with medical or neurological disease and PRG for patients with surgical disease in whom PEG is technically difficult or contraindicated.

Imiquimod-applied Interleukin-10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state.

Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison with previous models. IL-10 deficient and wild-type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15. For earlier time point data, either imiquimod or vehicle cream was applied for 2 days, and the mice were sacrificed on day 3. Imiquimod-applied IL-10 deficient mice showed more persistent psoriasis-like inflammation and higher severity index than did WT between day 8 and 15. Histopathologically, they demonstrated significantly thicker epidermis and larger number of CD45+, myeloperoxidase+ and IL-17+ cell counts on day 15. Quantitative reverse transcription-polymerase chain reaction with skin tissue revealed significantly higher imiquimod-induced IL-23p19 expression in imiquimod-applied IL-10 deficient mice on day 15. IL-10 deficient mice also showed significantly higher serum levels of imiquimod-induced IL-17A and tumor necrosis factor-α by enzyme-linked immunosorbent assay on day 15. Furthermore, IL-10 deficient mice showed more prominent increase of spleen weight and decrease of body weight in response to imiquimod application on day 3 and 15. In conclusion, IL-10 deficient mice model with imiquimod application may better reflect severe and persistent psoriasis with systemic inflammatory state.

Obstructive sleep apnea is associated with an increased risk of colorectal neoplasia.

BACKGROUND AND AIMS: A recent meta-analysis showed that obstructive sleep apnea (OSA) is associated with a higher prevalence of cancer and cancer-related mortality; however, little information is available on the association between OSA and colorectal neoplasia. METHODS: We identified consecutive patients who underwent overnight polysomnography (PSG) and subsequent colonoscopy. We compared the prevalence of colorectal neoplasia between patients with or without OSA according to the results of PSG. For each patient with OSA, 1 or 2 controls matched for age (±5 years), sex, body mass index (BMI), and smoking who had undergone first-time screening colonoscopy were selected. RESULTS: Of the 163 patients, 111 patients were diagnosed with OSA and 52 patients were within the normal range of the Apnea-Hypopnea Index. Of the 111 patients with OSA, 18 patients (16.2%) had advanced colorectal neoplasia, including 4 (3.6%) colorectal cancers. In the multivariate analyses, OSA was associated with an increased risk of advanced colorectal neoplasia after adjusting for factors including age and sex (mild: odds ratio [OR], 14.09; 95% confidence interval [CI], 1.55-127.83; P = .019; moderate or severe: OR, 14.12; 95% CI, 1.52-131.25; P = .020). Our case-control study revealed that the odds of detecting advanced colorectal neoplasia among patients with OSA were approximately 3.03 times greater than in the controls matched for age, sex, BMI, and smoking (OR, 3.03; 95% CI, 1.44-6.34; P = .002). CONCLUSION: Physicians should be aware of the association between OSA and the development of colorectal neoplasia and explain the need for colonoscopy to patients with OSA.

Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

BACKGROUND/AIMS: Although sarcopenia is associated with an increased risk for mortality after the curative resection of colorectal cancer, its influence on the development of advanced colonic neoplasia remains unclear. METHODS: This study included 1270 subjects aged 40 years or older evaluated with first-time screening colonoscopy at Seoul National University Boramae Health Care Center from January 2010 to February 2015. Skeletal muscle mass was measured with a body composition analyzer (direct segmental multifrequency bioelectrical impedance analysis method). Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with advanced colorectal neoplasia. RESULTS: Of 1270 subjects, 139 (10.9%) were categorized into the sarcopenia group and 1131 (89.1%) into the non-sarcopenia group. In the non-sarcopenia group, 55 subjects (4.9%) had advanced colorectal neoplasia. However, in the sarcopenia group, 19 subjects (13.7%) had advanced colorectal neoplasia, including 1 subject with invasive colorectal cancer (0.7%). In addition, subjects with sarcopenia had a higher prevalence of advanced adenoma (P < 0.001) than those without sarcopenia. According to the multiple logistic regression analysis adjusted for variable confounders, age (odds ratio 1.062, 95% confidence interval 1.032-1.093; P < 0.001), male sex (odds ratio 1.749, 95% confidence interval 1.008-3.036; P = 0.047), and sarcopenia (odds ratio 2.347, 95% confidence interval 1.311-4.202; P = 0.004) were associated with an advanced colorectal neoplasia. CONCLUSION: Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

Alcoholic Liver Disease Is Associated with an Increased Risk of Gastric Cancer.

BACKGROUND: Little information is available regarding the relationship between alcoholic liver diseases (ALD) and the development of gastric neoplasia. AIM: The aim of this study was to examine whether ALD is associated with the increased risk of gastric neoplasia. METHODS: We reviewed the medical records 514 patients diagnosed with ALD at Seoul Metropolitan Government Boramae Hospital between January 2000 and December 2011. Control subjects were selected by using propensity score matching (age, sex, and body mass index) from 8190 members of the general population who underwent EGD for screening for gastric neoplasia at Boramae Health Promotion Center during the study period. We compared the frequency of gastric neoplasia between the two groups and evaluated the risk factors for the development of gastric cancer in patients with ALD. In addition, we compared the frequency of gastric cancer between patients with ALD and those with nonalcoholic steatohepatitis (NASH). RESULTS: Of the 514 patients with ALD, 16 patients (3.1 %) had gastric neoplasia, including 14 gastric cancers (2.7 %). The odds of detecting a gastric cancer in ALD patients were approximately 4.77 times greater than in healthy controls [odds ratio (OR) 4.77; 95 % confidence interval (CI) 1.36-16.69; P = 0.007]. ALD (OR 5.32, 95 % CI 1.51-18.68, P = 0.009) was found to be an independent risk factor by multivariate logistic analysis. However, there were no significant differences in the prevalence of gastric adenoma and gastric cancer between patients with ALD and those with NASH. CONCLUSIONS: The rate of gastric cancer was significantly higher in patients with ALD than in healthy controls, suggesting that strict endoscopic surveillance is warranted in patients with ALD.

Long-Term Clinical Outcomes of Rectal Neuroendocrine Tumors According to the Pathologic Status After Initial Endoscopic Resection: A KASID Multicenter Study.

OBJECTIVES: With advances in diagnostic endoscopy, the detection of rectal neuroendocrine tumors (NETs) has increased. However, clinical outcomes, especially after endoscopic treatment, are still unclear. The aim of this study was to determine the long-term clinical outcomes of endoscopically resected rectal NETs according to the pathologic status after initial resection. METHODS: In this large, multicenter, retrospective cohort study, we analyzed the medical records of patients who underwent endoscopic resection of rectal NETs and were followed for ≥24 months at 16 university hospitals. The outcomes of interest were local or distant recurrence and metachronous lesions. RESULTS: On the pathologic assessment of 407 patients, the resection margin status was positive in 76 (18.7%) and indeterminate in 72 (17.7%) patients. Patients whose rectal NETs were diagnosed or suspected as NETs before resection showed a much higher complete resection rate than those whose tumors were resected as polyps and then diagnosed (P<0.001). Fourteen patients received salvage treatment at 1.9±2.8 months after initial treatment. During a median follow-up period of 45.0 months, local recurrence occurred in 3 (0.74%) patients, but there was no recurrence in the lymph nodes or distant organs. Metachronous rectal NETs were diagnosed in 3 (0.74%) patients. According to the pathologic status after initial resection, local recurrence and metachronous lesions occurred in 1 (0.4%) and 2 (0.8%) patients, respectively, in the pathologic tumor-free group, whereas they occurred in 2 (1.4%) and 1 (0.7%) patients, respectively, in the indeterminate group. CONCLUSIONS: Considering the long-term prognosis including that for recurrences or metachronous lesions, endoscopic resection is an efficient and a safe modality for the treatment of rectal NETs. This treatment may result in favorable clinical outcomes in patients with tumors of indeterminate pathology, as well as in pathologic tumor-free cases after initial resection.

The Effect of Probiotics on Gut Microbiota during the Helicobacter pylori Eradication: Randomized Controlled Trial.

BACKGROUND: Helicobacter pylori causes chronic gastritis, gastroduodenal ulcers, and gastric cancer, and has been treated with two antibiotics (amoxicillin and clarithromycin) and proton-pump inhibitors (PPIs). However, antibiotic treatment alters the indigenous gut microbiota to cause side effects. Therefore, the effects of probiotic supplementation on therapy have been studied. Although several studies have covered the probiotics' effects, details about the gut microbiota changes after H. pylori eradication have not been evaluated. Therefore, we analyzed the influences of antibiotics and their combination with probiotics on the composition of the gut microbiota using high-throughput sequencing. METHODS: Subjects were divided into two groups. The antibiotics group was treated with general therapy, and the probiotics group with general therapy and probiotic supplementation. Fecal samples were collected from all subjects during treatments, and the influences on gut microbiota were analyzed by 16S rRNA gene-pyrosequencing. RESULTS: Three phyla, Firmicutes, Bacteroidetes, and Proteobacteria, were predominant in the gut microbiota of all subjects. After treatment, the relative abundances of Firmicutes were reduced, whereas those of Proteobacteria were increased in both groups. However, the changed proportions of the gut microbiota in the antibiotics group were higher than those in the probiotics group. In addition, the increase in the levels of antibiotic-resistant bacteria was higher in the antibiotics group than in the probiotics one. CONCLUSION: Probiotic supplementation can reduce the antibiotic-induced alteration and imbalance of the gut microbiota composition. This effect may restrict the growth of antibiotic-resistant bacteria in the gut and improve the H. pylori eradication success rate.

Patients with perianal Crohn's disease have poor disease outcomes after primary bowel resection.

BACKGROUND AND AIM: The presence of perianal disease in Crohn's disease patients is one of the factors of postoperative recurrence. The aim of this study is to evaluate long-term prognosis of perianal Crohn's disease patients in Asian. METHODS: Patients with Crohn's disease who had undergone surgical bowel resection were divided into two groups according to the presence of perianal lesion. We monitored the occurrences of abdominal and/or perianal reoperation and readmission due to disease flare-up. RESULTS: The 132 patients included in the study were divided into 2 groups, those with perianal disease (45 patients, 34.1%) and those without perianal disease (87 patients, 65.9%). Patients with perianal disease was younger in age (33.8 years versus 39.8 years, p = 0.015) and had been diagnosed as CD at a younger age (21.9 years versus 28.6 years, p = 0.005) than patients without perianal disease. Patients with perianal disease showed more extra-intestinal manifestation than patients without perianal disease (8 versus 3, p = 0.008). Reoperation was required in 46 (44.8%) patients during the follow-up period. The presence of perianal disease independently increased the risk of reoperation [hazard ratio (HR), 3.112; confidence interval (CI), 1.707-5.675]. Furthermore, patients with perianal disease had increasing risks of abdominal reoperation (HR 1.978; 95% CI, 1.034-3.784). CONCLUSIONS: Patients with Crohn's disease and perianal lesions had a higher risk of reoperation. Considering these findings, physicians should consider aggressive and early top down therapy for patients with perianal Crohn's disease.

Fexofenadine regulates nuclear factor-κB signaling and endoplasmic reticulum stress in intestinal epithelial cells and ameliorates acute and chronic colitis in mice.

The aim of this study was to evaluate the effect of fexofenadine on intestinal inflammation. HCT116 and COLO205 cells were pretreated with fexofenadine and then stimulated with tumor necrosis factor (TNF)-α. Interleukin (IL)-8 expression was determined by real-time reverse-transcription polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. DNA-binding activity of nuclear factor-κB was assessed by electrophoretic mobility shift assay. The molecular markers of endoplasmic reticulum (ER) stress were evaluated by Western blot analysis and PCR. In the acute colitis model, mice were given 4% dextran sulfate sodium (DSS) for 5 days with or without fexofenadine. IL-10(-/-) mice were used to evaluate the effect of fexofenadine on chronic colitis. Fexofenadine significantly inhibited the upregulated expression of IL-8 in HCT116 and COLO205 cells stimulated with TNF-α. Fexofenadine suppressed nuclear factor-κB DNA-binding activity. C/EBP homologous protein mRNA expression was enhanced in the presence of TNF-α, and it was dampened by pretreatment of fexofenadine. In addition, the induction of ER stress markers caspase-12 and p-eukaryotic initiation factor 2 (eIF2)-α was significantly suppressed by the pretreatment of fexofenadine. Administration of fexofenadine significantly reduced the severity of DSS-induced murine colitis, as assessed by the disease activity index, colon length, and histology. In addition, the DSS-induced phospho-IκB kinase activation was significantly decreased in fexofenadine-pretreated mice. Finally, fexofenadine significantly reduced the severity of colitis and the immunoreactivity of caspase-12 and p-eIF2-α in IL-10(-/-) mice as compared with controls. These results suggest that fexofenadine is a potential therapeutic agent for the treatment of inflammatory bowel disease.