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Shu Kojima,1 Satohiro Matsumoto,1 Yudai Koito,1 Takaya Miura,1 Masanari Sekine,1 Takeshi Uehara,1 Takeharu Asano,1 Yasuhiro Yamaguchi,2 Hirosato Mashima1 1Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Japan; 2Department of Respiratory Medicine, Jichi Medical University Saitama Medical Center, Saitama, JapanCorrespondence: Shu Kojima, Department of Gastroenterology, Jichi Medical University Saitama Medical Center, 1-847 Amanuma, Omiya, Saitama, 330-8503, Japan, Tel +81 48 647 2111, Fax +81 48 648 5188, Email s.kojima@jichi.ac.jpAbstract: A 51-year-old Japanese man was diagnosed with left-sided ulcerative colitis (UC) at age 41. He was treated with mesalazine and azathioprine and maintained remission. At age 51, the patient developed bloody stools, abdominal pain, scleritis, arthritis, cough, bloody sputum, and pericardial effusion. Considering that pericardial effusion is an atypical extraintestinal complication of UC, and the patient met the diagnostic criteria for relapsing polychondritis (RP), a diagnosis of RP complicating a relapse of UC was made. Steroid therapy was administered, and both diseases improved. Golimumab, an anti-tumor necrosis factor-α inhibitor, was introduced as maintenance therapy for UC. All symptoms, including pericardial effusion, improved. Subsequently, no relapse of UC or RP was observed. As only a few cases of RP overlapping with UC have been reported and no treatment protocol has been established, we considered this case valuable and worthy of publication.Keywords: ulcerative colitis, relapsing polychondritis, anti-tumor necrosis factor-α inhibitor, golimumab

Hitomi Kashima, Satohiro Matsumoto, Shu Kojima, Yudai Koito, Takaya Miura, Takehiro Ishii, Hirosato Mashima Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, JapanCorrespondence: Satohiro MatsumotoDepartment of Gastroenterology, Jichi Medical University Saitama Medical Center, 1-847 Amanuma, Omiya, Saitama, Saitama, 330-8503, Japan, Tel +81 48 647 2111, Fax +81 48 648 5188, Email s.w.himananon@ac.auone-net.jpAbstract: A 55-year-old man presented with recurrent ulcers and an enterocutaneous fistula at the anastomotic site after surgery for an ileovesical fistula and was diagnosed with intestinal Behçet’s disease after undergoing surgery for enterocutaneous fistulae twice. The patient was transferred to our hospital because of recurrent enterocutaneous fistulae. He had a history of recurrent oral aphthous ulcers, folliculitis, and epididymitis and met the diagnostic/classification criteria for incomplete Behçet’s disease and thus was diagnosed as having intestinal Behçet’s disease. Remission induction therapy with steroids was administered for an ileal ulcer and an enterocutaneous fistula, and adalimumab was initiated for maintenance therapy. The fistula was closed, and the clinical course was favorable. Two months after initiating adalimumab, a subcutaneous abscess was detected at the site of the enterocutaneous fistula scar, and relapse of intestinal Behçet’s disease was suspected. Steroids were re-administered for remission induction, followed by maintenance therapy, for which adalimumab was switched to infliximab. No relapse was detected after steroid withdrawal. No therapeutic strategies have been established for intestinal Behçet’s disease. Moreover, there have been very few reports on therapeutic strategies and postoperative maintenance therapy for enterocutaneous fistulae. We thus consider this case valuable.Keywords: intestinal Behçet’s disease, adalimumab, infliximab, enterocutaneous fistulae

Tatsuya Yoshida,1 Takuya Miura,1 Tomoh Matsumiya,2 Hidemi Yoshida,2 Hajime Morohashi,1 Yoshiyuki Sakamoto,1 Akira Kurose,3 Tadaatsu Imaizumi,2 Kenichi Hakamada1 1Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan; 2Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan; 3Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, JapanCorrespondence: Kenichi HakamadaDepartment of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, JapanTel +81 172 39 5079Fax +81 172 39 5080Email hakamada@hirosaki-u.ac.jpPurpose: Colorectal cancer (CRC) often recurs after curative resection. Identification of major risk factors for CRC recurrence is important for effective prevention and treatment. In this study, we examined the potential relationship between CRC and TLR3 as this remains unclear.Patients and Methods: Correlations between TLR3 immunostaining and clinicopathological factors and prognosis were examined in 50 samples that were randomly extracted from 264 patients with CRC from January 2010 to December 2011. Chemokines induced by TLR3 agonist stimulation were also examined using TLR3-positive human CRC cell lines. Furthermore, the association between TLR3 and chemokine expression was assessed by analyzing the immunohistochemistry of surgical specimens.Results: Of the 50 patients, 14 (28%) were TLR3-negative. In the comparison of clinicopathological factors between the TLR3-negative and -positive groups, there were more lymph node metastasis-positive cases in the TLR3-negative group, and this difference was significant. Furthermore, there was no difference in overall survival rates between the two groups, but the 5-year recurrence-free survival (RFS) was significantly lower in the TLR3-negative group (46.2%) than in the TLR3-positive group (78.1%). Analysis of 5-year RFS using factors thought to be related to recurrence identified a high tumor budding and a TLR3-negative status as independent risk factors for recurrence. TLR3 activation of CRC cell lines induced expression of C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 5 (CCL5), and interleukin-8. The expressions of CCL2, CCL5, and IL-8 were observed in the TLR3-positive tumor cells of surgical specimens.Conclusion: Non-expression of TLR3 in CRC cells was associated with lymph node metastasis and was an independent risk factor for recurrence. These results suggest that TLR3 may not only be used as a prognostic factor and a risk factor for recurrence, but further studies on the involvement of TLR3 with tumor growth may provide new therapeutic strategies.Keywords: colorectal cancer, toll-like receptor 3, recurrence, CCL2, CCL5, IL-8

We investigated the role of Bruton's tyrosine kinase (Btk) in FcepsilonRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcepsilonRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcepsilonRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcepsilonRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcepsilonRI signal transduction in mast cells.