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Background Antimesenteric cutback end‐to‐end isoperistaltic anastomosis (Sasaki‐Watanabe anastomosis; Sasaki‐W anastomosis), which was developed in our department, is a novel hand‐sewn anastomotic technique for Crohn's disease intended to prevent anastomotic stenosis and preserve the peripheral circulation. Aim The aim of the present study is to present the surgical technique of Sasaki‐W anastomosis and to assess the safety and the early results of the surgical anastomotic recurrence of Sasaki‐W anastomosis. Patients and Methods The present study was a single‐center retrospective cohort study. As an early‐period group, 13 patients with Crohn's disease, who were mainly selected from cases considered to be at high risk of recurrence, underwent 15 Sasaki‐W anastomoses from August 2009 to January 2012. As a late‐period group, 36 patients with Crohn's disease, who were selected regardless of risk factors, underwent 37 Sasaki‐W anastomoses from September 2016 to March 2020. The medical data including patient characteristics, surgical records, postoperative details, and surgical recurrences were assessed. Results There were no intraoperative complications. With a median follow‐up of 107 mo, surgical recurrence occurred in one patient at 106 mo after surgery in the early‐period group. The cumulative surgical recurrence‐free rate in the early‐period group was 100% at 5 y and 86% at 10 y after surgery. No patients required reoperation in the late‐period group. Conclusion Sasaki‐W anastomosis is safe and feasible. Although long‐term study is needed, this anastomotic technique can be a reasonable operative option for Crohn's disease., Antimesenteric cutback end‐to‐end isoperistaltic anastomosis (Sasaki‐Watanabe anastomosis; Sasaki‐W anastomosis) is a novel hand‐sewn anastomotic technique for Crohn’s disease intended to prevent anastomotic stenosis and preserve the peripheral circulation. Here we show the surgical technique and early results of surgical anastomotic recurrence.

The prevention of postoperative recurrence is a critical issue in surgery for Crohn’s disease. Prospective randomized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate. We investigated the efficacy of infliximab (IFX) for the prevention of postoperative Crohn’s disease recurrence. We performed a prospective randomized multicenter study. Patients who underwent intestinal resection were assigned to groups treated with or without IFX. Immediately after surgery, patients in the IFX group received IFX at 5 mg/kg at 0, 2, and 6 weeks, followed by every 8 weeks for 2 years. The primary study outcome was the proportion of patients with endoscopic and/or clinical recurrence at 2 years after surgery. Thirty-eight eligible patients participated in this study: 19 in the IFX group and 19 in the non-IFX group. The disease recurrence rate in the IFX group was 52.6% (10/19), which was significantly lower than that in the non-IFX group (94.7% [18/19]). The postoperative use of IFX is effective in preventing Crohn’s disease recurrence for 2 years.

Porous asphalt (PA) pavement has been widely used mainly in national highways and expressways in Japan since the “Drainage Asphalt Pavement Technical Guidelines” was published in 1996. Also, more than 20 years have elapsed since PA pavement began to popularize, and the recycled aggregate due to reconstruction on PA pavement is expected to increase in the future. However, since polymer-modified bitumen with high adhesive strength is used for PA, and since aggregate gradation is largely different from dense graded asphalt (DG) mixture usually used, the recycling method of PA is considered necessary. In this study, the recycled PA pavement which was made of recycled PA mixture and DG mixture, were constructed in 2006 in National Highway No. 408 of Tsukuba City, Japan. And the results of follow-up survey on durability and serviceability for ten years of recycled PA pavement were reported.

Surface protection by hydrophobic impregnation and surface coating are widely used for concrete bridges located at coastal area in Japan. This paper deals with the improvement of adhesion between surface coating and hydrophobic impregnated concrete by different types of silanes and by invastigating surface treatment methods. As a result, adhesion between hydrophobic impregnated concrete and epoxy-based surface coating were improved by applying abrasive paper, portable electric grinder, solvent or diluted hydrochloric acid treatment. Especially, using portable electric grinder gave a remarkable improvement to the adhesive property. Also, hybrid-surface protection system consisting of surface coating and hydrophobic impregnation was discussed to prevent blistering.

In Japan, drainage asphalt pavement (DAP) is widely used especially on the highway and the express way. However, because of the existing porous asphalt materials consist of DAP use polymer modified bitumen, and the aggregate gradation of DAP is differ from conventional mixture, it is difficult to use those porous asphalt materials as the recycled aggregate for reclaimed asphalt pavement. Therefore, the recycling method for recycled DAP which were consisted of recycled porous asphalt materials and virgin aggregates has not been established yet. This paper describes that the recycling method for recycled DAP was considered, and the workability and five years durability was also verified by trial construction of the recycle DAP and new DAP which were consisted of virgin aggregate on the national highway.

Cancer of the intestinal tract (small and large intestine) associated with Crohn's disease has a low incidence but can be fatal if it develops. Thus, the key question is how to deal with this type of cancer. The current study surveyed major medical facilities that treat inflammatory bowel disease (IBD) surgically in Japan in order to examine the clinical features of cancer of the intestinal tract associated with Crohn's disease and explore ways to deal with this cancer in the future.Sixteen major medical facilities that treat IBD surgically were surveyed regarding cancer of the intestinal tract associated with Crohn's disease. The medical facilities had treated 3,454 patients with Crohn's disease, 122 of whom had developed intestinal cancer. The medical facilities were surveyed regarding those 122 patients.The incidence of intestinal cancer associated with Crohn's disease has increased yearly. Cancer most often developed in the left side of the colon and, particularly, in the rectum and anal canal. Seventy-six percent of cases were diagnosed preoperatively, 4% were diagnosed intraoperatively, while the remaining 20% were diagnosed pathologically after surgery. The most prevalent histological type of cancer was mucinous carcinoma (50%). Forty-two percent of cancers were differentiated, with 4% being poorly differentiated. The surgical procedure performed most often (67%) was abdominoperineal resection. The 5-year survival rate by stage was 88% for Stage I, 68% for Stage II, 71% for Stage IIIa, 25% for Stage IIIb and 0% for Stage IV. Overall, the 5-year survival rate was 52%.Gastrointestinal (GI) cancer associated with Crohn's disease had an incidence of 3.5%, but also involved a poor prognosis with a 5-year survival rate of 52%. Early detection through surveillance is crucial to improving the prognosis for patients. However, surveillance of the intestinal tract with endoscopy or contrast studies is technically and diagnostically hampered by Crohn's disease and intestinal strictures. A biopsy of the anal canal, a common site of cancer, can readily be performed and constitutes the first step in surveillance.

Ileal interposition (IT), in which the distal ileum is transposed isoperistaltically into the proximal jejunum, is considered as a procedure for metabolic or antidiabetes surgery. Our aim was to study the effects of IT on glycemic control, fat metabolism, and hormonal changes in obese rats with spontaneous diabetes.Animals were divided into either an IT or a sham (SH) group. They underwent an oral glucose tolerance test (OGTT) before and 4 and 8 weeks after the operation. All animals were killed 10 weeks after operation for analyses of tissue weight (liver, pancreas, epididymal fat, brown fat), immunoblotting of uncoupling protein-1 (UCP1) protein in brown adipose tissue (BAT), and fasting plasma levels of glucose, insulin, glucagon-like peptide (GLP)-1, peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), and leptin.Body weight increased postoperatively in both groups compared with preoperative weight, but it did not differ between the 2 groups. Eight weeks postoperatively, integrated blood glucose levels during the OGTT were decreased in IT compared with SH (P.05). Fasting plasma levels of insulin, GLP-1, and GIP did not differ between the 2 groups, but PYY levels were higher in the IT animals (P.01). The weight of epididymal and BATs, homeostasis model assessment insulin resistance, and fasting plasma leptin levels were decreased in the IT group (P.05). Expression of UCP1 was higher in IT than SH animals (P.05).These results suggest that IT improves glucose and lipid metabolism by decreasing insulin resistance and epididymal fat, and increased expression of UCP1 in BAT might be among the mechanisms responsible.

Interleukin-23 (IL-23) plays an essential role in the mucosal immune system. It has been suggested that IL-23 is able to induce carcinogenesis as well as inflammation and a recent study revealed that IL-23R is expressed in colorectal carcinoma cells. However, neither the differences in the IL-23R expression among the patients nor the concrete functions of IL-23 in colorectal carcinoma cells have been revealed. The aim of the present study was to examine the characteristics of IL-23R expression in colorectal carcinoma and the direct effects of IL-23 on colorectal cancer cells. We examined the IL-23R expression in human colorectal cancer tissue samples by immunohistochemistry. Cell proliferation and invasion assays under IL-23 stimulation were performed using cultured cells derived from colorectal cancer. ELISA and real-time PCR were used to evaluate the transforming growth factor (TGF)-β production due to IL-23 stimulation. All of the TNM stage IV patients were positive for IL-23R. IL-23R expression in the carcinoma tissue was also relatively high at the deepest point of invasion in certain cases. The proliferative and invasive activities and/or TGF-β production of DLD-1 cells increased by IL-23 stimulation, whereas no change was observed in the activities of MIP101 and KM12c cells. IL-23 directly enhanced the malignancy of the colon carcinoma cells. An autocrine mechanism via TGF-β production may underlie these effects. IL-23 is therefore a potential target for cancer immunotherapy. However, the homogeneity in IL-23R expression and the effects of IL-23 on colorectal carcinoma cells should be considered.

A 23-year-old female was referred with constipation that lasted for 2 years. Preoperative examinations revealed multiple submucosal tumors beside the anorectum, along with subcutaneous tumors in the left buttock. The pathological diagnosis was leiomyoma. Low anterior resection of the rectum with regional lymph node dissection, along with the resection of the subcutaneous tumors in the left buttock through the transdermal approach, was performed, since multiple tumor formation indicated a high malignant potential. The tumors were diagnosed as multiple leiomyomas with no malignancy. Disease categories such as intravenous leiomyomatosis, leiomyomatosis peritonealis disseminata, Alport syndrome, and Currarino syndrome have been reported to be associated with leiomyomatosis; however, the current case of "peri-anorectal leiomyomatosis" was not classified into any of these. The patient was monitored with careful checkups, and the postoperative course was satisfactory for over 5 years without any sign of recurrence or metastasis. Although the clinicopathological features of this case are quite rare and no therapeutic guidelines for such a disease have yet been established, radical resection should be considered, and the elucidation of the histogenesis of this disease will help establish future therapeutic guidelines.

Runt-related transcription factor 2 (RUNX2) belongs to the RUNX family of heterodimeric transcription factors, and is mainly associated with osteogenesis. Previous in vitro studies demonstrated that RUNX2 increased the cell proliferation of mouse and rat colon carcinoma cells but the status of RUNX2 has remained unknown in human colon carcinoma. Therefore, we examined clinical significance and biological functions of RUNX2 in colon carcinoma. RUNX2 immunoreactivity was examined in 157 colon carcinoma tissues using immunohistochemistry. RUNX2 immunoreactivity was evaluated as percentage of positive carcinoma cells [i.e., labeling index (LI)]. We used SW480 and DLD-1 human colon carcinoma cells, expressing estrogen receptor-β (ER) in subsequent in vitro studies. RUNX2 immunoreactivity was detected in colon carcinoma cells, and the median value of RUNX2 LI was 67%. RUNX2 LI was significantly associated with Dukes' stage, liver metastasis and ERβ status. In addition, RUNX2 LI was significantly associated with adverse clinical outcome of the colon carcinoma patients, and turned out an independent prognostic factor following multivariate analysis. Results of in vitro studies demonstrated that both SW480 and DLD-1 cells transfected with small interfering RNA against RUNX2 significantly decreased their cell proliferation, migration and invasive properties. In addition, RUNX2 mRNA level was significantly decreased by ER antagonist in these two cells. These findings all suggest that RUNX2 is a potent prognostic factor in human colon carcinoma patients through the promotion of cell proliferation and invasion properties, and is at least partly upregulated by estrogen signals through ERβ of carcinoma cells.

The treatments and prognoses of pelvic organ carcinomas differ, depending on whether the primary tumor originated in the rectum, urinary bladder, prostate, ovary, or uterus; therefore, it is essential to diagnose pathologically the primary origin and stages of these tumors. To establish the panels of immunohistochemical markers for differential diagnosis, we reviewed 91 of the NCBI articles on these topics and found that the results correlated closely with those of the public protein database, the Human Protein Atlas. The results revealed the panels of immunohistochemical markers for the differential diagnosis of rectal adenocarcinoma, in which [+] designates positivity in rectal adenocarcinoma and [-] designates negativity in rectal adenocarcinoma: from bladder adenocarcinoma, CDX2[+], VIL1[+], KRT7[-], THBD[-] and UPK3A[-]; from prostate adenocarcinoma, CDX2[+], VIL1[+], CEACAM5[+], KLK3(PSA)[-], ACPP(PAP)[-] and SLC45A3(prostein)[-]; and from ovarian mucinous adenocarcinoma, CEACAM5[+], VIL1[+], CDX2[+], KRT7[-] and MUC5AC[-]. The panels of markers distinguishing ovarian serous adenocarcinoma, cervical carcinoma, and endometrial adenocarcinoma were also represented. Such a comprehensive review on the differential diagnosis of carcinomas of pelvic organs has not been reported before. Thus, much information has been accumulated in public databases to provide an invaluable resource for clinicians and researchers.

BACKGROUND: Pouchitis is the most common long-term complication after restorative total proctocolectomy and IPAA for ulcerative colitis. OBJECTIVE: We examined the incidence, clinical aspects, and long-term outcome of patients with idiopathic pouchitis. DESIGN: This study was a retrospective review of medical records. PATIENTS: Included in the study were 284 patients with ulcerative colitis who underwent a total proctocolectomy and IPAA. MAIN OUTCOME MEASURES: We evaluated the cumulative risk and long-term outcome of pouchitis including the duration of disease, pattern of relapse, and responsiveness to antibiotic therapy. RESULTS: Sixty-four patients developed idiopathic pouchitis. The cumulative risk was 10.7% at 1 year, 17.2% at 2 years, 24.0% at 5 years, and 38.2% at 10 years. At their first pouchitis episode, 45 patients had acute pouchitis, 19 patients had chronic pouchitis, and all patients received antibiotic therapy with oral ciprofloxacin and/or metronidazole. The efficacy of the therapy was 96.6% initially. Forty-five patients had antibiotic-responsive pouchitis, 17 patients had antibiotic-dependent pouchitis, and 2 patients had antibiotic-refractory pouchitis at their first episode. Whereas 20 of 45 patients (44.4%) with initially acute pouchitis experienced 2 or more relapses, 16 of 19 patients (84.2%) with initially chronic pouchitis had 2 or more relapses. After taking into account the relapses, the number of patients with antibiotic-responsive pouchitis decreased from 45 to 40, the number with antibiotic-dependent pouchitis increased from 17 to 20, and the number with antibiotic-refractory pouchitis increased from 2 to 4. Among the 4 patients with antibiotic-refractory pouchitis, 3 patients had Clostridium difficile-associated pouchitis. LIMITATIONS: This study was retrospective. CONCLUSION: The patients with chronic pouchitis at the first episode tend to have a higher incidence of relapse. In some patients, the responsiveness to antibiotic therapy changes during follow-up. When patients with pouchitis do not respond to standard antibiotic therapy, then the occurrence of C difficile infection should be considered.

今回，我々は家族性大腸腺腫症（familial adenomatous polyposis；以下，FAPと略記）術後に発生したストーマ部の回腸癌を2例経験した．1例目は58歳の男性で，FAPのため31歳時に大腸全摘術，永久回腸ストーマ造設術を施行した．50歳頃からのストーマ部のポリープが直径約5cm大にまで増大した．2例目は65歳の女性で，FAPのため41歳で大腸全摘術，永久回腸ストーマ造設術を施行した．63歳頃からのストーマ部のポリープが直径3～4cm大にまで増大した．いずれの症例に対しても，腫瘤を含む回腸部分切除，回腸ストーマ再造設を行った．病理組織学上はいずれも腺癌であった．癌発生の原因は不明であるが，FAPという遺伝要因に，ストーマ部における物理的・化学的刺激などの環境要因が加わって起こる可能性が推測され，ストーマ造設・ケアにおける注意と定期的なフォローが重要と考えられた．

Background: Previous studies have shown various risk factors for the initial and/or the second operation for Crohn's disease (CD). However, limited data are available with regard to the risk factors for a third operation. We aimed to clarify the risk factors for a third operation for CD. Methods: A total of 200 CD patients who underwent a second intestinal surgery at 13 institutions were examined. We performed univariate and multivariate analyses to examine the influence of independent variables on the cumulative rate of needing a third operation. Results: A total of 95 patients underwent a third operation. The overall 5-year and 10-year cumulative rates for the third operation were 42.2% and 71.0%, respectively. In univariate analysis, the interval between the initial and the second operation (P = 0.0069), postoperative administration of infliximab (P = 0.0030), and the anatomical site of the disease (P = 0.0132) were significant risk factors for the third operation. In multivariate analysis, the interval between the initial and the second operation (P = 0.0287) and postoperative administration of infliximab (P = 0.0297) remained significant risk factors for the third operation. The cumulative 5-year third operation rate was significantly higher in patients with an interval of less than 5 years between the first and second operations than for those with an interval of 5 years or more (47.8% versus 35.2%, P = 0.0232). Conclusions: An interval of less than 5 years between the first and the second operations is a significant risk factor for a third operation in patients with CD. (Inflamm Bowel Dis 2011;)

症例は39歳の女性で，内科的治療に抵抗性の全大腸炎型潰瘍性大腸炎に対し大腸全摘・回腸嚢肛門吻合・回腸瘻造設術を施行した．術後経過は良好で，約4か月後，回腸瘻閉鎖術を行ったが，術後腸閉塞を発症し，術後第10病日よりイレウスチューブ挿入するも改善は乏しかった．第39病日多量の下血が出現，プレショック状態となり，第41病日緊急手術を施行した．術中内視鏡検査にて小腸粘膜に多発するびらんと血液の滲出を認めたが，活動性出血は認めず，びらん部からの生検を行い，手術を終了した．病理組織学的検査所見上，潰瘍性大腸炎類似の小腸病変が示唆され，プレドニゾロンの静注を開始した．また，血管造影検査にて血管外漏出を認めた第2空腸動脈領域に塞栓術を施行した．その後下血は治まり，再手術後第27病日に退院した．これまでの文献を踏まえ，本症例の病態に対する考察を加えて報告する．

症例は69歳の女性で，強皮症の治療中に腹部膨満が出現し，二次性慢性偽性腸閉塞症（chronic intestinal pseudo-obstruction；以下，CIPと略記）および腸管嚢腫様気腫症（pneumatosis cystoides intestinalis；以下，PCIと略記）と診断された．保存的治療により一度は改善したが，その後再増悪した．食事再開とともに発熱などの症状の増悪を繰り返す状態となったため，PCI部の空腸の切除術を施行した．術後経過は良好で，食事量は増加し栄養状態の改善も図れた．CIPに対する外科的治療には議論がある．CIPにPCIを伴い経口摂取が困難な場合，PCI部の切除を考慮する必要があるが，病変が限局的であれば，強皮症のような全身病に合併した場合であっても切除の有効性は高いと思われた．

Background and Aim: Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD. Methods: Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health-related quality of life (HR-QOL) by the SF-36 Japanese version, and patients' compliance to medication was evaluated. Results: Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two-week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR-QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication. Conclusions: Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy.

The apoptosis and antiapoptotic signaling pathways are important for regulating carcinogenesis and cancer progression, and for determining prognosis. Molecules involved in apoptosis represent potential cancer diagnostic markers and therapeutic targets. The inhibitor of apoptosis protein (IAP) family includes several important molecules involved in apoptosis that might represent such targets. Increasing evidence has demonstrated that the IAP family of proteins is integral for antiapoptotic and nuclear factor-κB signal transduction, and enhanced expression of IAPs contributes to colon carcinogenesis and its poor prognosis, as well as to drug resistance of tumors. X-linked IAP, cIAP1, cIAP2, and survivin are prognostic markers of colorectal cancer, and survivin and cIAP2 are also utilized to predict the effect of anticancer treatment in colorectal cancer patients. Novel therapies such as YM155 and LY2181308 targeting survivin, AEG35156 and phenoxodiol targeting X-linked IAP, AT-406 as a Smac mimetic, and survivin peptides are currently being evaluated in clinical trials. This report reviews the involvement of the IAP family in colorectal adenocarcinoma in order to summarize the role of the IAP family members as diagnostic and therapeutic targets, and to provide an overview of the future course of research in this area.

症例は41歳の男性で，前医にて甲状腺癌，多発肺転移の診断で手術を行い，最終診断は濾胞癌の未分化転化であった．当院で頸部への放射線治療を行っていた．腹痛，全身倦怠感を主訴に来院した．左上腹部と臍右に鶏卵大の圧痛を伴う腫瘤を触知し，血液生化学検査では炎症反応の上昇，高度の貧血，凝固線溶系の亢進を認め精査加療目的で入院となった．腹部US，CTで小腸腫瘍による腸重積症の診断となり，腹腔鏡補助下で緊急手術を施行した．術後，経口摂取が一時期可能にはなったが，徐々に全身状態が悪化し，術後第20病日に永眠された．病理組織学的診断は甲状腺未分化癌による小腸転移であった．甲状腺未分化癌が小腸に転移することはまれで，国内外での報告は，自験例を含め5例である．若干の文献的考察を加え報告する．

症例は20歳の女性で，平成21年12月，乗用車運転中に対向車と正面衝突した．精査にて腹腔内出血，肝・膵・脾損傷と右大腿骨骨幹部骨折を認め当院へ入院した．来院時全身状態は安定しており，血管造影検査を行い明らかな造影剤の漏出がないことを確認し，保存的に経過観察とした．受傷後8日に上腹部に限局した腹膜刺激症状が出現しCTを行ったところ，網嚢内に限局した腹水貯留を認めた．胆道損傷を疑い受傷後9日目に緊急手術を行った．肝臓，脾臓からは出血を認めず膵臓は全体に腫大していた．肝十二指腸間膜の検索にて総胆管の完全断裂を認め，胆嚢摘出，術中胆道造影，総胆管空腸吻合術を行った．術後経過は良好で近医へ転院した．鈍的外傷による胆管損傷はまれな病態であり，損傷形態としては総胆管完全離断を来すことが多い．鈍的外傷による複数の臓器損傷から発症初期に胆管損傷を診断することは困難であり注意が必要である．

症例は64歳の男性で，約2年前より肛門部の腫瘍，肛門周囲からの排膿を自覚するも放置．腫瘍の増大，臀部痛のため，座位不能となり受診．精査にて，広範な臀部膿瘍をともなった肛門管癌の診断で，有茎腹直筋皮弁，植皮を付加した腹会陰式直腸切断術を施行した．病理組織学的には中分化型腺癌でAI，N1，H0，P0，Stage IIIaで根治度Aの手術であった．今回，広範な臀部膿瘍をともなった肛門管癌症例を経験したので，文献的考察を加え報告する.

消化管ストーマ造設の標準化を進める上で，適切な分類法に基づいたストーマ合併症の評価が重要である．発症時期別分類としては早期と晩期に分けるのが一般的であるが，早期の定義に関して，過去の報告はストーマ造設術後30日（1カ月）以内とするものと術直後の入院期間中とするものに大別される．術後の入院期間が短縮しつつある昨今，退院直後にストーマ合併症が問題となる症例もみられるので，入院中に限らず術後30日以内を早期と定義するのが良いと考えられる．またストーマ合併症には処置不要なものから緊急手術を要するものまで様々な重症度があるが，重症度別の検討を行った論文は少ない．重症度分類としては有害事象共通用語基準（CTCAE）のストーマ合併症に関するGrade分類が利用可能と考えられるが，用語がストーマケアの現場で使いにくいという問題がある．そこで本稿では用語の修正と追加を行い，ストーマ合併症の重症度分類案として使用可能か検討を行った．

症例は60歳の女性で，腹部膨満を主訴に近医を受診後，胸腹水を伴う卵巣癌の疑いで当院婦人科紹介となった．血液検査にてCA125の異常高値を認め，腹部超音波，腹部造影CT・MRIにて，子宮と接する巨大な多房性嚢胞性腫瘤で，嚢胞内に乳頭状に増殖する充実性部分を認め，卵巣癌（漿液性嚢胞腺癌）が疑われた．開腹所見は両側付属器に異常はなく，空腸から管外に発育する約20cm大の腫瘤を認め，一部は膀胱へ浸潤していたため，合併切除を行った．術後胸腹水の再出現は認めず，第15病日に退院となった．病理組織学的にはc-kit陽性で小腸gastrointestinal stromal tumor（GIST）と診断された．嚢胞性GISTは比較的まれで，CA125の上昇とPseudo-Meigs症候群と同様の機序を呈したきわめて特異な病態であったため術前診断が困難であった．Pseudo-Meigs症候群を来した小腸GISTは本邦では初めての症例である．

Alternative precursor messenger RNA (pre-mRNA) splicing plays an important role in the generation of functional diversity of the genome. The process of pre-mRNA splicing is regulated by cis- and trans-elements, and their deregulations result in aberrantly spliced individual variants and aberrant expression profiles. Accumulating evidence has revealed that aberrant splicing contributes to a number of diseases including human neoplasms. It is well known that germ line mutations in the cis-element of tumor suppressor genes such as mismatch repair (MMR) genes, the adenomatous polyposis coli (APC) gene and the E-cadherin (CDH1) gene are involved in Lynch syndrome, familial adenomatous polyposis and hereditary diffuse gastric cancer, respectively. In addition, somatic mutations in cis-elements also play a role in tumorigenesis. These genetic alterations including nonsense, missense or silent mutations in cis-elements led to aberrant transcripts by exon skipping, retention of the intron or introduction of a new splice site. The majority of erroneous transcripts with a premature termination codon are eliminated through nonsense-mediated mRNA decay. However, it is difficult to accurately predict the resulting transcripts with current in silico strategies. Correct interpretation of genetic alterations and the investigation of aberrant transcripts are crucial for genetic diagnosis of hereditary diseases and elucidation of the molecular characteristics of neoplasms from a clinical point of view. In this review we summarize the current knowledge of the regulatory mechanism underlying alternative pre-mRNA splicing and aberrant splicing, with particular focus on digestive tract malignancies.

5-Fluorouracil (5-FU) is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.

Crohn病に対する外科治療の原則は，健常部をできるだけ温存する病変部の切除である．また，線維性狭窄に対しては各種の狭窄形成術が行われ，病変に応じて消化管の可及的な温存が可能である．ストーマ造設はプアリスク症例や排便機能障害例において適応となる．術後の寛解維持療法については，6～12カ月ごとの内視鏡検査により軽度の病変では5-ASAを，中等度～高度病変に対しては免疫調節薬を加え，さらにInfliximabを用いるアルゴリズムが欧米では提唱されているが，本邦においては，これに成分栄養剤を加えたより丁寧な寛解維持療法が行われている．

Ndc80 has been shown to play an important role in stable microtubule-kinetochore attachment, chromosome alignment, and spindle checkpoint activation in mitosis. It is composed of two heterodimers, CDCA1-KNTC2 and SPC24-SPC25. Overexpression of CDCA1 and KNTC2 is reported to be associated with poor prognosis in non-small cell lung cancers (NSCLC), and siRNA-mediated knockdown against CDCA1 or KNTC2 has been found to inhibit cell proliferation and induction of apoptosis in NSCLC, ovarian cancer, cervical cancer and glioma. Therefore, CDCA1 and KNTC2 can be considered good candidates for molecular target therapy as well as diagnosis in some cancers. However, the role of the Ndc80 complex in colorectal and gastric cancers (CRC and GC) still remains unclear. In the present study, we used qRT-PCR to evaluate the expression levels of CDCA1, KNTC2, SPC24 and SPC25 in CRC and GC and employed siRNA-mediated knockdown to examine cell proliferation and apoptosis. mRNA overexpression of these four genes was observed in CRCs and GCs when compared with the corresponding normal mucosae. Additionally, the expression levels of tumor/normal ratios of CDCA1, KNTC2, SPC24 and SPC25 correlated with each other in CRCs. MTT assays revealed that cell growths after the siRNA-mediated knockdown of either CDCA1 or KNTC2 were significantly suppressed, and flow cytometry analyses revealed significant increases of the subG1 fractions after knockdown against both genes. Our present results suggest that expressional control of component molecules of Ndc80 can be utilized for molecular target therapy of patients with CRC and GC.

PURPOSE: This study aimed to assess the feasibility and safety of undergoing emergency subtotal colectomy with hand-assisted laparoscopic surgery in patients with severe ulcerative colitis. METHODS: We reviewed the medical records of 60 patients who underwent emergency subtotal colectomy with hand-assisted laparoscopic technique (30 cases) or open technique (30 cases) for severe ulcerative colitis. RESULTS: No intraoperative complications occurred in either group. One patient in the laparoscopic group required conversion to open surgery. The median operative time was significantly longer in the laparoscopic group (242 vs. 191 minutes; P < 0.001). The rate of early postoperative complications in the laparoscopic group was significantly less than that in the open group (37 percent vs. 63 percent; P = 0.041). In the open group, four patients required relaparotomy because of peritoneal abscess or strangulation ileus, whereas no patient required relaparotomy in the laparoscopic group (P = 0.040). In the laparoscopic group, the median duration of postoperative food prohibition was significantly shorter (4.8 vs. 5.9 days; P = 0.007), and the median length of hospital stay was significantly shorter (23.0 vs. 33.0 days; P = 0.001). CONCLUSIONS: Although the operative time was elongated in the laparoscopic group, intraoperative safety and postoperative recovery were satisfactory. For severe ulcerative colitis, hand-assisted laparoscopic surgery can be an alternative to conventional open surgery.

Currently 5-fluorouracil (5-FU) plays a central role in the chemotherapeutic regimens for colorectal cancers and thus it is important to understand the mechanisms that determine 5-FU sensitivity. The expression profiles of human colon cancer cell line DLD-1, its 5-FU-resistant subclone DLD-1/FU and a further 21 types of colon cancer cell lines were compared to identify the novel genes defining the sensitivity to 5-FU and to estimate which population of genes is responsible for 5-FU sensitivity. In the hierarchical clustering, DLD-1 and DLD-1/FU were most closely clustered despite over 100 times difference in their 50% inhibitory concentration of 5-FU. In DLD-1/FU, the population of genes differentially expressed compared to DLD-1 was limited to 3.3%, although it ranged from 4.8% to 24.0% in the other 21 cell lines, thus indicating that the difference of 5-FU sensitivity was defined by a limited number of genes. Next, the role of the cellular inhibitor of apoptosis 2 (cIAP2) gene, which was up-regulated in DLD-1/FU, was investigated for 5-FU resistance using RNA interference. The down-regulation of cIAP2 efficiently enhanced 5-FU sensitivity, the activation of caspase 3/7 and apoptosis under exposure to 5-FU. The immunohistochemistry of cIAP2 in cancer and corresponding normal tissues from colorectal cancer patients in stage III revealed that cIAP2 was more frequently expressed in cancer tissues than in normal tissues, and cIAP2-positive patients had a trend toward early recurrence after fluorouracil-based chemotherapy. Although the association between drug sensitivity and the IAP family in colorectal cancer has not yet been discussed, cIAP2 may therefore play an important role as a target therapy in colorectal cancer.

To evaluate the efficacy of early diagnosis and early administration of corticosteroid for peristomal pyoderma gangrenosum, a prospective study was carried out.In April 1998, we began studying a new treatment regimen of peristomal pyoderma gangrenosum in which prednisone at a dose of 20 to 40 mg was administered systemically immediately after diagnosis. Early-stage peristomal pyoderma gangrenosum was treated concurrently with topical cadexomer iodine, and at the granulation stage, treatment with clobetasol ointment was started. Healing of peristomal pyoderma gangrenosum was determined by complete epithelialization of ulcer without pain or exudates. Patients were assigned to group A (n = 7) before April 1998 and group B (n = 10) after April 1998, and historical comparison was done between the 2 groups.In group A, all patients had ulcerative colitis, and in group B, 7 patients had ulcerative colitis, 2 had Crohn's disease, and one had indeterminate colitis. In group B, significantly earlier diagnosis (P = 0.0093), earlier start of treatment (P = 0.0057), higher initial dose of corticosteroid (P = 0.0052), and earlier healing of peristomal pyoderma gangrenosum (P = 0.0023) were observed.Early diagnosis and early corticosteroid administration appeared to be effective for promoting healing of peristomal pyoderma gangrenosum.

慢性膵炎の合併症として膵仮性嚢胞は手術適応のひとつとなりうる．仮性嚢胞内の消化酵素が血管を浸食し，破裂させることが稀にある．嚢胞内出血が腹腔内や消化管内に起こると，大量出血により致命的となる．今回嚢胞内出血が嚢胞外への穿破を逃れ，術前には確定診断がつかず，術中超音波で診断された膵仮性嚢胞内仮性動脈瘤の一例を経験した．症例は56歳の男性．2001年に急性膵炎を発症．保存的加療で軽快したが，大量飲酒を連日続けていた．2007年に上腹部痛出現し，精査したところ，CT上膵仮性嚢胞と慢性膵炎を指摘された．また嚢胞内はわずかに造影効果があったが，全身状態が安定していることと，血管造影が施行できなかったことで嚢胞内出血を断定できなかった．手術施行し，開腹後超音波検索で嚢胞内のジェット流が認められ，嚢胞内出血が確認された．脾動脈を結紮するとジェット流は消失し，脾動脈からの出血と考えられた．その後膵体尾部切除，DuVal式膵空腸吻合術を施行した．標本では嚢胞内に器質化した凝血塊が存在し，そのなかで仮性動脈瘤が形成されていたために腹腔内や消化管内への穿破出血を免れたと考えられた．膵仮性嚢胞内出血が疑われたときは，血管造影を含め慎重な術前評価を行い，術式の決定を行うべきである．

Background Alternative splicing is a molecular mechanism by which different combinations of exons can be alternatively spliced to produce different mRNA isoforms. Recently, several databases have been published to predict the alternative splicing of mRNA; cancer-specific alternative splicing has also been predicted with these databases. Those variants may be potentially useful targets for cancer therapy, however, the accuracy and veracity of these databases have yet to be confirmed. Methods In this study, we analyzed 17 genes by reverse transcriptase-polymerase chain reaction (RT-PCR) that were predicted to have cancer-specific alternative splicing by using the splicing database, the Alternative Splicing Annotation Project (ASAP) by Lee et al, between 38 cancer cell lines from various organs and 9 corresponding normal tissues. By designing 2 types of primer sets for RT-PCR including (1) primers flanking the alternatively spliced exons and (2) primers spanning the exon/exon junctions, cancer-associated splicing variants were investigated. Results The alternatively splicing events were detected in 15 of 17 genes (88%); 35 of 43 variants (81%) were detected successfully with RT-PCR. Among these variants, M-RIP, HYAL2, CDCA1, and MSMB genes showed differential expressions between cancer cell lines and corresponding normal tissues. Furthermore, RT-PCR with surgically resected gastric cancer tissues (diffuse type, 6; intestinal type, 4) confirmed that 2 variants of CDCA1 were upregulated in cancer tissues, whereas both variants of MSMB were expressed predominantly in normal tissues. Conclusion Alternative splicing variants, especially in CDCA1, were detected in this study and may be potentially useful as diagnostic markers and/or novel targets for anticancer therapy.

症例は44歳，女性．2008年7月頃より右腋窩に違和感を感じ外来受診した．可動性良好な腫大したリンパ節を触知し，超音波検査（US）で不整形で一部境界不明瞭な腫大したリンパ節を認めた．リンパ節生検にて低分化型腺癌の転移が疑われ，ER(+)，PgR(+)であったため，転移性乳癌が疑われた．PETにて右腋窩および右乳房の下に高集積を認めた．触診で右乳房下部に皮下腫瘤を触知し，USで11×15mm大の境界不整なlow echoic massを認め，生検にて浸潤性小葉癌の診断であった．右腋窩リンパ節郭清（Level-II）を含む乳房下部腫瘤摘出術を施行し，皮下腫瘤の切除標本内には，小葉と乳管が完備した副乳腺組織が存在するため，副乳腺原発癌と診断した．腋窩リンパ節Level-Iに9/21のリンパ節転移を認め，stageIIのため術後補助化学療法としてCEFを行っている．副乳小葉癌は稀であり，若干の文献的考察を加えて報告する．

腹腔内デスモイド腫瘍に対して薬物療法で良好な経過をたどった1例を経験したので報告する．症例は72歳の男性で，直腸癌術後，異時性肺転移術後の経過観察中に腹腔内腫瘍が出現，直腸癌腹腔内再発と診断し開腹術を施行した．腫瘍は小腸間膜内にあり切除可能であったが，広範な小腸合併切除を要するため切除しなかった．病理組織学的検査でgastrointestinal stromal tumorと診断されメシル酸イマチニブを投与したが，治療抵抗性で有害事象も強かった．永久標本を再検討したところβ-カテニンの核内発現が認められデスモイド腫瘍と診断された．メシル酸イマチニブを中止し高用量タモキシフェン/スリンダク併用療法を開始したところ，2か月後のCTで腫瘍の縮小が認められたが，5か月後には腫瘍径に変化は見られなくなった．手術を勧めたが患者が拒否したため，開始後2年経過した現在も継続中であり，これまでのところデスモイド腫瘍の再増大を認めていない．

短期間で増悪した原発性アミロイドーシスに伴う続発性慢性偽性腸閉塞症（secondary chronic intestinal pseudo-obstruction；以下，Secondary CIP）を経験した．症例は56歳の男性で，2004年より腹部膨満感が出現し近医で特発性CIPと診断された．2005年初めより症状が増悪したため，イレウスチューブを5か月間以上留置するも改善せず，2006年に当科紹介・入院となった．イレウスチューブから連日2,000 ml以上の排液を認め，イレウスチューブの再挿入時に十二指腸穿孔が疑われ緊急手術となった．術中所見では十二指腸損傷は同定できなかったが，Treitz靭帯から回盲弁の口側100 cmまでの小腸の著明な拡張，腸管壁の脆弱化が認められたため，小腸を約300 cm切除し，空腸瘻を作成した．病理組織学的検査所見で原発性アミロイドーシスに続発するCIPの診断となったが，術後半年で原病死した．原発性アミロイドーシスに伴うCIPは予後不良であり，対処療法しかないのが現状である．

A 74-year-old man was hospitalized for the investigation of fever and severe general fatigue. Laboratory examinations revealed severe leukocytosis, with a leukocyte count of 29 500/mm(3). Computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography showed a pancreatic tumor with a diameter of 70 mm. We performed distal pancreatectomy with splenectomy and gastrectomy because there was invasion of the posterior wall of the stomach. The leukocyte count decreased to 16 900/mm(3) immediately following the operation, but it began to increase again a week later, ultimately reaching 213 000/mm(3). We measured the serum granulocyte-colony stimulating factor (G-CSF) concentration and the G-CSF expressions in the resected specimens with immunohistochemistry, the findings of which confirmed the diagnosis of G-CSF-producing pancreatic cancer. G-CSF-producing tumors are considered to be in a category of rare malignant diseases originating in various organs, which carry a poor prognosis. However, G-CSF-producing pancreatic cancer is extremely rare. On postoperative day (POD) 35, an intraabdominal recurrence was detected with marked leukocytosis, and on POD 42 the patient died without receiving postoperative cancer therapy.

In colorectal cancer (CRC) patients, metastasis to the regional lymph node (LN) is an important first step in the dissemination of cancers. To identify the genes possibly involved in LN metastasis of CRC, we analyzed LN metastases in an orthotopic implantation mouse model with 22 CRC cell lines using Matrigel, an extracellular matrix protein derived from mice sarcoma, and combined the data with gene expression profiles of cDNA microarray of those cell lines. With this implantation analysis, the incidence of LN metastasis was 60% in 228 orthotopically implanted mice and varied from 100% to 0% among the cell lines. KM12c and Clone A showed LN metastasis in all orthotopically implanted mice, but DLD-1, HCT-8, and SW948 did not show LN metastases at all. In contrast, the incidence of liver and lung metastasis in 22 CRC cell lines was 13% and 1%, respectively. Combining those data with cDNA microarray in vitro, we isolated 636 genes that were differentially expressed depending on the incidence of LN metastasis. Among those genes, the expression level of ring finger protein 125 (RNF125), previously known as an E3 ubiquitin ligase in T cell activation, was significantly different between primary tumors in Stage III CRC patients with LN metastasis and Stage II patients without LN metastasis. In conclusion, the orthotopic implantation mice model with Matrigel was useful, and we isolated candidate genes such as RNF125 that possibly play an important role in LN metastasis of CRC cells.