Coffee and caffeine intake reduces risk of ulcerative colitis: a case-control study in Japan.

BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.

Palliative stenting for malignant colorectal stenosis in the elderly.

Objectives: Self-expandable metal stents are widely used for the treatment of malignant colorectal stenosis (MCS). In elderly individuals with MCS, self-expandable metal stents are often used as a palliative treatment, but prophylactic stent placement is not recommended. We investigated the efficacy and safety of self-expandable metal stents for the elderly in a palliative setting, specifically in a prophylactic setting. Methods: Elderly patients with MCS who received a palliative stent (the stent group) or palliative stoma (the stoma group) were retrospectively enrolled between April 2017 and June 2022, and the prognosis and complication rates were assessed. Additionally, patients in the stent group were divided into symptomatic and asymptomatic subgroups, and prognosis, stent patency, and complication rates were evaluated. Results: During the study period, 31 patients with a mean age of 85.4 years and 12 patients with a mean age of 82.0 years were enrolled in the stent and stoma groups, respectively. While overall survival and complication rates were comparable, the length of hospital stay was significantly shorter in the stent group. Of the 31 patients in the stent group, 16 asymptomatic patients received prophylactic stenting, which was not associated with increased complication rates. Conclusions: Palliative stents for MCS appear to be effective and safe even in the elderly, and thus, prophylactic stents can be considered for asymptomatic patients.

IL12B rs6887695 polymorphism and interaction with alcohol intake in the risk of ulcerative colitis in Japan.

BACKGROUND: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. METHODS: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008). CONCLUSIONS: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.

[Fecal microbiota transplantation for refractory Clostridioides difficile infection with Crohn's disease in an allogeneic bone marrow transplant recipient].

We report a case of a 15-year-old girl who developed refractory Clostridioides difficile infection (CDI) after allogeneic bone marrow transplantation (BMT). She was treated successfully with fecal microbiota transplantation (FMT). The patient who had aplastic anemia underwent allogeneic BMT from an HLA 1-locus-mismatched unrelated donor. Four months later, she developed gastrointestinal graft-versus-host disease (GVHD), and immunosuppressive treatment improved the GVHD. However, she developed CDI 5 months after BMT and experienced recurrence after that. Fifteen months after transplant, CDI relapsed despite discontinuation of immunosuppressive treatment; thus, she underwent FMT. Colonoscopy at the time of FMT revealed round aphthae, mainly in the ileocecum, and colonic biopsy revealed inflammatory cell infiltration and noncaseating epithelioid granuloma, which fulfilled the diagnostic criteria for Crohn's disease. Following FMT for CDI, she was treated with enteric budesonide and intravenous methotrexate for Crohn's disease. These interventions resulted in a marked improvement in both CDI and Crohn's disease. Twenty-eight months after FMT, both CDI and Crohn's disease remained in remission with oral mesalamine monotherapy.

Active and passive smoking and risk of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

Dietary intake of vegetables, fruit, and antioxidants and risk of ulcerative colitis: A case-control study in Japan.

OBJECTIVES: Oxidative stress is considered one of the etiologic factors involved in ulcerative colitis (UC), yet there is limited epidemiologic information regarding the relationship between antioxidant intake and the risk of UC. The aim of the present case-control study in Japan was to examine the association between intake of green and yellow vegetables, other vegetables, fruit, vitamin C, vitamin E, retinol, alpha-carotene, beta-carotene, and cryptoxanthin and UC risk. METHODS: A total of 384 cases within 4 y of diagnosis with UC and 665 controls were included in the study. Data on dietary intake and confounders were obtained using a self-reported questionnaire. Information on dietary factors was collected using a 169-item semiquantitative food-frequency questionnaire. Adjustment was made for sex, age, pack-y of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Higher intake levels of other vegetables, vitamin C, and retinol were independently associated with a reduced risk of UC. The adjusted odds ratio between extreme quartiles was 0.51 (95% confidence interval [CI], 0.34-0.76; P for trend ≤ 0.001) for other vegetables, 0.45 (95% CI, 0.30-0.69, P for trend ≤ 0.001) for vitamin C, and 0.64 (95% CI, 0.43-0.95, P for trend = 0.04) for retinol. There were no associations between intake of green and yellow vegetables, fruit, vitamin E, alpha-carotene, beta-carotene, or cryptoxanthin and UC risk (P for trend = 0.29, 0.56, 0.89, 0.20, 0.69, and 0.22, respectively). CONCLUSIONS: Intake of other vegetables, vitamin C, and retinol was inversely associated with UC risk.

The efficacy of fecal microbiota transplantation for patients with chronic pouchitis: A case series.

Pouchitis is one of the most common complications that develop after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Single fecal microbiota transplantation (FMT) by colonoscopy was performed safely on three patients with pouchitis. However, the efficacy of FMT on pouchitis was limited.

Successful treatment by fecal microbiota transplantation for Japanese patients with refractory Clostridium difficile infection: A prospective case series.

We prospectively enrolled four Japanese patients with refractory Clostridium difficile infection (CDI) and were treated with a single fecal microbiota transplantation (FMT). The average age of the patients was 83.7 years. All patients had a successful clinical course for up to 3 months without any adverse events.

Efficacy and safety of cold forceps polypectomy utilizing the jumbo cup: a prospective study.

BACKGROUND/AIMS: There are few prospective studies on cold forceps polypectomy (CFP) using jumbo cup forceps. Therefore, we examined patients with diminutive polyps (5 mm or smaller) treated with CFP using jumbo cup forceps to achieve an adenoma-free colon and also assessed the safety of the procedure and the recurrence rate of missed or residual polyp after CFP by performing follow-up colonoscopy 1 year later. METHODS: We included patients with up to 5 adenomas removed at initial colonoscopy and analyzed data from a total of 361 patients with 573 adenomas. One-year follow-up colonoscopy was performed in 165 patients, at which 251 lesions were confirmed. RESULTS: The one-bite resection rate with CFP was highest for lesions 3 mm or smaller and decreased significantly with increasing lesion size. Post-procedural hemorrhage was observed in 1 of 573 lesions (0.17%). No perforation was noted. The definite recurrence rate was 0.8% (2/251 lesions). The probable recurrence rate, which was defined as recurrence in the same colorectal segment, was 17%. Adenoma-free colon was achieved in 55% of patients at initial resection. Multivariate analysis revealed that achievement of an adenoma-free colon was significantly associated with number of adenomas and years of endoscopic experience. CONCLUSIONS: CFP using jumbo biopsy forceps was safe and showed a high one-bite resection rate for diminutive lesions of 3 mm or smaller. The low definite recurrence rate confirms the reliability of CFP using jumbo biopsy forceps. Number of adenomas and years of endoscopic experience were key factors in achieving an adenoma-free colon.

Expression of Interleukin-26 is upregulated in inflammatory bowel disease.

AIM: To investigate interleukin (IL)-26 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and the function of IL-26. METHODS: Human colonic subepithelial myofibroblasts (SEMFs) were isolated from colon tissue surgically resected. The expression of IL-26 protein and its receptor complex was analyzed by immunohistochemistry. The gene expression induced by IL-26 was evaluated by real-time polymerase chain reaction. Intracellular signaling pathways were evaluated by immunoblotting and specific small interfering (si) RNA transfection. RESULTS: The mRNA and protein expression of IL-26 were significantly enhanced in the inflamed mucosa of patients with IBD. IL-26 receptor complex was expressed in colonic SEMFs in vivo and in vitro. IL-26 stimulated the mRNA expression of IL-6 and IL-8 in colonic SEMFs. The inhibitors of mitogen-activated protein kinases and phosphoinositide 3-kinase, and siRNAs for signal transducers and activator of transcription 1/3, nuclear factor-kappa B and activator protein-1 significantly reduced the mRNA expression of IL-6 and IL-8 induced by IL-26. CONCLUSION: These results suggest that IL-26 plays a role in the pathophysiology of IBD through induction of inflammatory mediators.

Application of novel magnified single balloon enteroscopy for a patient with Cronkhite-Canada syndrome.

We present a case of Cronkhite-Canada syndrome (CCS) in which the entire intestine was observed using a prototype of magnifying single-balloon enteroscope (SIF Y-0007, Olympus). CCS is a rare, non-familial gastrointestinal polyposis with ectodermal abnormalities. To our knowledge, this is the first report showing magnified intestinal lesions of CCS. A 73-year-old female visited our hospital with complaints of diarrhea and dysgeusia. The blood test showed mild anemia and hypoalbuminemia. The esophagogastroduodenoscopy and colonoscopy revealed diffuse and reddened sessile to semi-pedunculated polyps, resulting in the diagnosis of CCS. In addition to the findings of conventional balloon-assisted enteroscopy or capsule endoscopy, magnifying observation revealed tiny granular structures, non-uniformity of the villus, irregular caliber of the loop-like capillaries, scattered white spots in the villous tip, and patchy redness of the villus. Histologically, the scattered white spots and patchy redness of the villus reflect lymphangiectasia and bleeding to interstitium, respectively.

Sarcopenia is a predictive factor for intestinal resection in admitted patients with Crohn's disease.

The relationship between skeletal muscle volume and the prognosis of patients with inflammatory bowel disease (IBD) remains undetermined. We conducted a retrospective study of 72 IBD patients who were admitted to the hospital due to disease exacerbation. We enrolled IBD patients who had undergone abdominal computed tomography and assessed the nutritional indices, such as the Onodera's prognostic nutritional index (O-PNI) and the controlling nutritional status (CONUT) index. The L3 skeletal muscle index (SMI), which is the ratio of the cross-sectional area of skeletal muscles at the level of the third lumbar (L3) vertebra to the height squared, was used to identify sarcopenia. Sarcopenia, defined as a low SMI, was observed in 42% of all IBD patients (37% with Crohn's disease (CD) and 48% with ulcerative colitis (UC)). In UC patients, the O-PNI and CONUT values, height, and albumin levels were significantly lower than in CD patients. The SMI strongly correlated with sex, body weight, albumin level, and O-PNI in IBD patients. Multivariate analysis using the Cox regression model demonstrated that the presence of sarcopenia (P = 0.015) and disease type (CD or UC) (P = 0.007) were significant factors predicting intestinal resection. The cumulative operation-free survival rate was significantly lower for sarcopenic patients than in all IBD patients (P = 0.003) and a stratified analysis of CD patients (P = 0.001) using the Kaplan-Meier method and log-rank test. The L3 skeletal muscle area is a prognostic factor for intestinal resection in patients with CD.

Efficacy and safety of single fecal microbiota transplantation for Japanese patients with mild to moderately active ulcerative colitis.

BACKGROUND: The clinical utility of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC) is still controversial. We investigated the efficacy and safety of single FMT for patients with mild to moderately active UC in a Japanese population. METHODS: Fifty-seven patients were evaluated for eligibility, and 16 patients were excluded. Forty-one patients with UC refractory to standard medical therapy were treated with single FMT by colonoscopic administration. Changes in the fecal microbiota were assessed by 16S ribosomal DNA based terminal restriction fragment length polymorphism analysis. RESULTS: At 8 weeks after FMT, no patient achieved clinical remission, and 11 of 41 patients (26.8 %) showed clinical response. The full Mayo score and the Mayo clinical score significantly decreased at week 8 [full Mayo score 5.5 ± 2.4 (mean ± standard deviation) at initiation and 4.6 ± 2.2 at week 8, P < 0.004; Mayo clinical score 4.0 ± 2.0 at initiation and 3.0 ± 1.9 at week 8, P < 0.001], but there were no statistically significant effects on the Mayo endoscopic score. No adverse events occurred after FMT or during the follow-up period of 8 weeks. The proportion of Bifidobacterium was significantly higher in the donor feces used for responders than in the donor feces used for nonresponders. The proportion of Lactobacillales and Clostridium cluster IV were significantly higher in the donor feces used for nonresponders. CONCLUSIONS: Single FMT by colonoscopy was performed safely in all patients, but sufficient clinical efficacy and microbial restoration were not confirmed in patients with mild to moderately active UC.

Association between serum adalimumab concentrations and endoscopic disease activity in patients with Crohn's disease.

BACKGROUND AND AIMS: The serum trough level of adalimumab (ADA) associated with mucosal healing (MH) remains unclear. Our objective was to determine the association between ADA trough levels and the endoscopic activity in Crohn's disease. MATERIALS AND METHODS: This was a cross-sectional study including 42 patients with Crohn's disease. Endoscopic activity was assessed using the modified Rutgeerts scoring system. The primary outcome was mucosal healing, and the secondary outcomes were serum levels of C-reactive protein and albumin. RESULTS: Endoscopic disease activity negatively correlated with serum ADA trough levels (Spearman's rank correlation coefficient (ρ) = -0.42, P < 0.01). MH was achieved in 14 of 42 patients (33.3%). Serum ADA trough levels were significantly higher in the MH group than in the no-MH group (ADA mean trough level, 11.7 vs 7.5 µg/mL). The proportion of patients with ADA as the first biologic was significantly higher in the MH group than in the no-MH group (85.7% vs 53.5%, P = 0.04). The ADA trough levels that were best associated with normal C-reactive protein and albumin levels were 5.57 µg/mL (odds ratio [OR] 16.0, specificity 0.80) and 6.95 µg/mL (OR 9.2, specificity 0.81), respectively. The ADA trough level that was best associated with MH was 7.9 µg/mL (OR 13.5, specificity 0.86). The endoscopic disease activity was significantly higher in the patients with ADA as the second biologic as compared with those with ADA as the first biologic (P < 0.05). CONCLUSION: Mucosal healing requires higher ADA trough levels, compared with those required to normalization of routine clinical markers.

Prediction of clinical and endoscopic responses to anti-tumor necrosis factor-α antibodies in ulcerative colitis.

Objective In patients with ulcerative colitis (UC), the relationship between the initial endoscopic findings and the response to anti-tumor necrosis factor (TNF)-α antibodies remains unclear. We herein evaluated the potential of endoscopic assessment using the ulcerative colitis endoscopic index of severity (UCEIS) to predict the response to anti-TNF-α antibodies. Methods We enrolled 64 patients with UC undergoing anti-TNF-α maintenance therapy with infliximab (IFX) or adalimumab (ADA) between April 2010 and March 2015. Anti-TNF-α trough levels were determined by ELISA. Endoscopic disease activity was assessed using the UCEIS. Results The clinical response rate at 8 weeks was 77.4% for IFX and 66.7% for ADA. Serum albumin levels were significantly higher and the UCEIS bleeding descriptor before treatment was significantly lower in the responders than in the non-responders (p < 0.05 each). The CRP levels at 2 weeks were significantly lower in the responders (p < 0.001). The serum albumin levels before treatment were significantly higher and the UCEIS erosions and ulcers descriptor was significantly lower in the mucosal healing group than in the non-mucosal healing group (p < 0.05 each). A significant and negative correlation between the trough levels of anti-TNF-α antibodies and the UCEIS descriptors was observed. The trough levels of anti-TNF-α antibodies to achieve mucosal healing were 2.7 µg/mL for IFX and 10.3 µg/mL for ADA. Conclusions The UCEIS score, as well as some clinical markers (serum albumin and CRP levels), is useful for the prediction of the treatment outcome of UC patients in response to anti-TNF-α antibodies.

Reduced Abundance of Butyrate-Producing Bacteria Species in the Fecal Microbial Community in Crohn's Disease.

BACKGROUND: The global alteration of the gut microbial community (dysbiosis) plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). However, bacterial species that characterize dysbiosis in IBD remain unclear. In this study, we assessed the alteration of the fecal microbiota profile in patients with Crohn's disease (CD) using 16S rRNA sequencing. SUMMARY: Fecal samples from 10 inactive CD patients and 10 healthy individuals were subjected to 16S rRNA sequencing. The V3-V4 hypervariable regions of 16S rRNA were sequenced by the Illumina MiSeq™II system. The average of 62,201 reads per CD sample was significantly lower than the average of 73,716 reads per control sample. The genera Bacteroides, Eubacterium, Faecalibacterium and Ruminococcus significantly decreased in CD patients as compared to healthy controls. In contrast, the genera Actinomyces and Bifidobacterium significantly increased in CD patients. At the species level, butyrate-producing bacterial species, such as Blautia faecis, Roseburia inulinivorans, Ruminococcus torques, Clostridium lavalense, Bacteroides uniformis and Faecalibacterium prausnitzii were significantly reduced in CD patients as compared to healthy individuals (p < 0.05). These results of 16S rRNA sequencing were confirmed in additional CD patients (n = 68) and in healthy controls (n = 46) using quantitative PCR. The abundance of Roseburia inulinivorans and Ruminococcus torques was significantly lower in C-reactive protein (CRP)-positive CD patients as compared to CRP-negative CD patients (p < 0.05). KEY MESSAGE: The dysbiosis of CD patients is characterized by reduced abundance of multiple butyrate-producing bacteria species.

Interleukin (IL)-1ß Is a Strong Inducer of IL-36γ Expression in Human Colonic Myofibroblasts.

BACKGROUNDS AND AIMS: Interleukin (IL)-36 cytokines are members of the IL-1 cytokine family. In this study, we investigated the expression of IL-36γ in human colonic myofibroblasts to explore the molecular mechanisms underlying IL-36γ induction. MATERIALS AND METHODS: IL-36 mRNA was analyzed by real-time PCR method. Secretion of IL-36γ protein was evaluated by Western blot and ELISA analyses. Molecular mechanism of IL-36γ induction was evaluated by siRNA analyses and immunofluorescence experiments. RESULTS: IL-36γ mRNA expression was scarcely detected in the cells without stimulation. IL-1ß induced a marked increase of IL-36γ mRNA expression. TNF-α markedly enhanced IL-1ß-induced IL-36γ mRNA expression. These responses were confirmed at the protein levels. The inhibitors for ERK1/2 (PD98059 and U0216) and a p38 MAPK (SB203580) significantly reduced the IL-1ß-induced IL-36γ mRNA expression. In addition, the siRNAs specific for NF-κB p65 and AP-1 (c-Jun) significantly reduced the expression of IL-1ß-induced IL-36γ mRNA. CONCLUSIONS: Colonic myofibroblasts are cellular source of IL-36γ in the intestine. IL-36γ expression was induced by the combination of IL-1ß and TNF-α via activation of MAPKs and transcription factors, NF-κB and AP-1.

[Cases of Three Patients with Gastric Cancer and Metastasis to the Skeletal Muscle].

Metastasis to the skeletal muscle from gastric cancer is relatively rare. We report cases of 3 patients undergoing chemotherapy for gastric cancer with metastasis to the skeletal muscle. Case 1: A man in his 70s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the lung, brain, lymph node, and iliopsoas muscle. Case 2: A man in his 60s was diagnosed with advanced gastric cancer (cT3N3M1P0, stage IV), with metastasis to the brain, lung, lymph node, and iliopsoas muscle. Case 3: A man in his 50s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the urinary duct, lymph node, back muscle, and iliopsoas muscle. All 3 patients died within 7-8 months after the diagnosis due to progressive disease despite chemotherapy. The prognosis of these 3 patients was significantly poorer than that of patients in our hospital with metastasis not involving the skeletal muscle (p<0.01). Accordingly, metastasis to the skeletal muscle may be an adverse prognostic factor in gastric cancer.

Interleukin(IL)-36α and IL-36γ Induce Proinflammatory Mediators from Human Colonic Subepithelial Myofibroblasts.

BACKGROUND: Interleukin (IL)-36 cytokines are recently reported member of the IL-1 cytokine family. However, there is little information regarding the association between IL-36 cytokines and gut inflammation. In the present study, we investigated the biological activity of IL-36α and IL-36γ using human colonic subepithelial myofibroblasts (SEMFs). METHODS: The mRNA expression and the protein expression of target molecules in SEMFs were evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The intracellular signaling of IL-36 cytokines was analyzed using Western blot analysis and small interfering RNAs (siRNAs) specific for MyD88 adaptor proteins (MyD88 and IRAK1) and NF-κB p65. RESULTS: IL-36α and IL-36γ significantly enhanced the secretion of IL-6 and CXC chemokines (CXCL1, CXCL2, and CXCL8) by SEMFs. The combination of IL-36α/γ and IL-17A or of IL-36α/γ and tumor necrosis factor-α showed a synergistic effect on the induction of IL-6 and CXC chemokines. The mRNA expression of proinflammatory mediators induced by IL-36α and/or IL-36γ was significantly suppressed by transfection of siRNA for MyD88 or IRAK1. Both inhibitors of mitogen activated protein kinases and siRNAs specific for NF-κBp65 significantly reduced the expression of IL-6 and CXC chemokines induced by IL-36α and/or IL-36γ. CONCLUSION: These results suggest that IL-36α and IL-36γ contribute to gut inflammation through the induction of proinflammatory mediators.

Familial and multiple gastrointestinal stromal tumors with fair response to a half-dose of imatinib.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Since our first report in 1998, approximately 30 families with multiple GISTs due to a germline gain-of-function mutation of c-kit have been reported. We herein present a case of a family with multiple GISTs that have a germline c-kit mutation in exon 11 (Del-Val560) in two siblings. One of the patients showed a fair response to treatment with a half-dose of imatinib (200 mg/day). There are few reports describing the response to imatinib in familial GISTs and this drug appears to be a promising therapeutic option.