Inflammatory bowel diseases (IBDs), such as Crohn's disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in vivo, and to identify the genes involved in colitis-associated cancer. We found that TNF-α (50 ng/mL) inhibited the proliferation, migration, and invasion of HCT8 and COLO205 colon cancer cell lines and that anti TNF-α Ab neutralized TNF-α inhibition in vitro. The effects of anti TNF-α Ab, infliximab (10 mg/kg) were investigated in mouse models of colitis-associated cancer induced by intraperitoneally injected azoxymethane (AOM: 10 mg/kg)/orally administered dextran sodium sulfate (DSS: 2.5%) (AOM/DSS) in vivo. Infliximab significantly attenuated the development of colon cancer in these mice. Microarray analyses and RT-qPCR revealed that mast cell protease 1, mast cell protease 2, and chymase 1 were up-regulated in cancer tissue of AOM/DSS mice; however, those mast cell related genes were downregulated in cancer tissue of AOM/DSS mice with infliximab. These results suggested that mast cells play a pivotal role in the development of cancer associated with colitis in AOM/DSS mice.

Objectives: The possible effects and benefits of oral rehydration solution (ORS) on chronic dehydration after total proctocolectomy. Methods: To evaluate the effect of ORS on the renin-angiotensin system after remnant proctocolectomy in patients with ulcerative colitis (UC), we selected 20 patients after remnant proctocolectomy, ileal J pouch-anal anastomosis, and construction of a diverting ileostomy for UC. Patients were randomly divided into two groups, A (n=9) or B (n=11), 2 weeks after the surgery. In group A, ORS (1000 mL/day) was given for the first 7 days and mineral water (1000 mL/day) for the next 7 days. In group B, mineral water (1000 mL/day) was given for the first 7 days and ORS (1000 mL/day) for next 7 days. Plasma levels of renin, aldosterone and excretion of sodium in urine were evaluated at days 0, 7, and 14. We defined day 0 as the day of beginning this study. Results: Mean plasma renin levels on day 0 were six to eight times greater than the upper normal limit. In group A, ORS lowered plasma renin levels. In group B, plasma levels of renin and aldosterone after ORS were lower than those at days 0 and 7. Conclusions: ORS corrected increased plasma levels of renin and aldosterone to within the normal range in patients after proctocolectomy.

We report a resected case of cancer at the ileum of the blind loop. An 81-year-old male underwent an appendectomy for acute appendicitis and an ileotransverse colostomy for postoperative obstruction when he was 14 years old. He underwent radiation therapy for prostate cancer when he was 75 years old. Six years later, enhanced computed tomography revealed a 7 cm mass in the ileum of the blind loop. Colonoscopy showed wall thickening at the ileum of the blind loop, and biopsy revealed an adenocarcinoma. We performed partial resection of the ileum. The patient was discharged 17 days after surgery. Cancer at the ileum of the blind loop after an ileotransverse colostomy has rarely been reported.

Although surgery is commonly used to treat parastomal hernia, it is very difficult and has shown poor results. Recently, repair with prosthetic materials has been thought to be a more promising method.

Laparoscopic transabdominal preperitoneal inguinal hernia repair (TAPP) is technically difficult and not infrequently followed by postoperative complications and pain, especially when performed by inexperienced surgeons. To simplify TAPP and reduce postoperative pain, we devised a novel procedure whereby TAPP is carried out after the inguinal preperitoneal infiltration of diluted lidocaine and epinephrine saline solution and carbon dioxide gas (tumescent TAPP). This report introduces the concept of tumescent TAPP and summarizes its operative results.About 120 ml of diluted lidocaine and epinephrine solution and 60 ml of CO2 gas were infiltrated into the inguinal preperitoneal space through a transabdominal needle before TAPP. Tumescent TAPP was performed for 400 patients (355 men, 45 women; mean age, 63.2 years).Using tumescent TAPP, we found it easier to confirm the inguinal anatomy and dissect the preperitoneal layer and inguinal floor, with less bleeding. The mean operation time was 101.9 min and there were few perioperative complications and minimal pain.Tumescent TAPP makes conventional TAPP easier and safer; however, this procedure should be verified by a comparative study with conventional TAPP.

BACKGROUND:5-Fluorouracil (5-FU), a core anticancer agent for malignancies, induces gastrointestinal (GI) toxicities. Despite recent advances in tumor immunology, it still remains unknown how GI toxicities affect antitumor immunity. S-1 is a tegafur-based oral 5-FU prodrug which has been widely introduced in Japan and other countries. The alternate-day S-1 administration has been proposed to minimize its GI and other toxicities without reducing its anticancer efficacy.METHODS:In this study, two S-1 administration regimens were compared in mice to evaluate their impact of GI toxicities on immunity. In the daily group as a standard administration model, S-1 was administered for 14 days on and 14 days off, and in the alternate-day group as a non-GI toxicity model, S-1 was administered every other day for 28 days. As well as physical findings, regulatory T cells, Th1 cells and other cells in murine lymphoid tissues were analyzed with flow cytometry.RESULTS:Only the daily group exhibited body weight loss and GI toxicities. In the daily group, a proportion of regulatory T cells in the intestinal lymphoid tissue were demonstrated to be six-fold higher than in the control without S-1, and the proportion of Th1 cells showed a decreasing trend. However, the alternate-day group exhibited almost no change in T-cell subsets.CONCLUSION:GI toxicities of 5-FU may have a negative influence on antitumor immunity due to increased proportions of regulatory T cells and decreased proportions of Th1 cells. The alternate-day S-1 administration may be a useful regimen with its minimal influence on T-cell subsets.

Background A clinical trial of S-1 with leucovorin (S-1/LV) in metastatic colorectal cancer (CRC) patients demonstrated promising efficacy; however, the gastrointestinal toxicities were so severe that it has not been applied in the clinical setting. On the other hand, alternate-day administration of S-1 has been proposed to attenuate the adverse events without reducing its anticancer activity. Our present study was conducted to confirm the feasibility of alternate-day administration of S-1/LV in in vivo xenograft tumor models. Methods Mice were treated with S-1/LV in a daily group (2 weeks of administration followed by 2 weeks of withdrawal) or an alternate-day group (administration on alternate days for 4 weeks), then the mice were killed and the xenograft tumors were resected. We compared body weight changes, condition of feces, mucosal injury and myelosuppression and assessed adverse reactions, tumor volume, tumor growth inhibition (TGI) and expression of Ki67, TUNEL, cIAP2 and XIAP to evaluate the antitumor activity and tumor apoptosis. Results Severe weight loss, diarrhea, mucosal injury and myelosuppression were observed only in the daily group; however, some myelosuppression was also observed in the alternate-day group. The TGI in the alternate-day group was better than in the daily group, possibly resulting from apoptosis due to the suppression of cIAP2 but not XIAP. Conclusion Our findings suggest that alternate-day administration of S-1/LV for CRC treatment can achieve high antitumor activity without severe adverse reactions, and we propose that clinical trials with this regimen should be conducted in CRC patients.

症例は88歳，男性．血便を主訴に近医を受診し，潰瘍性大腸炎の疑いで入院となった．ステロイド治療を開始したが，改善せず，精査加療目的に当院へ転院となった．転院後，左側大腸炎，中等症の潰瘍性大腸炎の診断にて，ステロイドパルス療法を施行したが，治療抵抗性で，画像診断で口側進展が認められたことから，前医入院から20日後に手術となった．初回手術は用手補助腹腔鏡下に大腸亜全摘を施行し，術後第28病日に退院となった．6ヵ月後に残存直腸切除術を施行し，術後合併症なく退院し，外来にて経過観察中である．医学中央雑誌にて，「高齢者」「潰瘍性大腸炎」で検索したところ，報告されている手術例の中で，本症例が最高齢であった．高齢者潰瘍性大腸炎では，重症化した場合，全身感染症，心肺合併症併発による生命予後が不良であるため，内科治療にて改善がみられない場合，早期に手術を決断する必要があると考えられた．

目的：今回，我々は胃癌手術症例に対して，術前controlling nutritional status（以下，CONUTと略記）法による栄養評価と術後合併症について検討を行ったので報告する．方法：当科にて胃癌の診断で手術療法を実施した178例のうち，術前にCONUT法により栄養評価を行った174例を対象とし，CONUT値3点以下をA群152例，4点以上をB群22例として2群に分け検討を行った．結果：手術時年齢はA群65.2±11.3歳，B群が71.6±6.7歳で，B群が高齢であった（P=0.009）．進行度についてはstage IA・IBがA群109例に対し，B群は5例であった（P<0.0001）．術後合併症は，A群で22例（14%），B群では9例（41%）に認められた（P=0.002）．術後合併症のうち，遠隔臓器感染症はA群では4例（2.7%）に認められたのに対し，B群は4例（22.2%）であり（P=0.001），多変量解析では，危険因子として術前CONUT値と，臨床病期が抽出された．結語：胃癌手術症例において，術前のCONUT値が4以上の栄養障害を認める症例は合併症，特に遠隔臓器感染が多く認められた．

INTRODUCTION:Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is a rare overlap syndrome that includes features characteristic of both Behçet's disease (BD) and relapsing polychondritis (RP).CASE DESCRIPTION:A 30-year-old female complained of lower abdominal pain and bloody stools during medical treatment for RP. Total colonoscopy revealed oval-shaped deep ulcers on the terminal ileum similar to those of intestinal BD. After performing the ileocecal resection, both RP and gastrointestinal lesions relapsed, but improved with infliximab treatment.DISCUSSION AND EVALUATION:During medical treatment for RP, we experienced a rare case with ileocecal ulcers similar to intestinal BD. Although our case did not meet the diagnosis criteria of intestinal BD because of the lack of BD's major clinical symptoms, intestinal lesions shared quite similar features with intestinal BD. Our case could possibly be a rare subtype of MAGIC syndrome that had the features characteristic of both intestinal BD and RP.CONCLUSIONS:We described a rare case of ileocecal ulcers without any BD symptoms but accompanied by RP, possibly be a subtype of MAGIC syndrome.

The clinicopathological features of neuroendocrine tumor (NET) of the rectum were retrospectively analyzed in 25 patients( 17 men and 8 women; mean age, 57 years[ 30-78 years]) at Tohoku University Hospital from January 1998 to December 2012. The average diameter of 25 tumors was 15 mm (5-70 mm). Local resections and rectal resections with lymph node dissection were performed in 16 and 9 tumors, respectively. Three of the 9 tumors had lymph node metastases (33%), including 2 tumors with a diameter of 10 mm. In a median follow-up of 48 months, tumor recurrence was observed in 3 of 25 patients( 12%); local recurrence was observed in 1 patient; and liver metastasis was observed in 2 patients. Of the 2 patients with liver metastasis, liver metastasis recurred in a patient whose primary tumor, with a diameter of 10 mm, had been locally resected 40 months ago. According to histopathological analysis, 3 primary tumors with local recurrence or liver metastasis were categorized as G2 or G3 according to the World Health Organization (WHO) classification. Tumors with a diameter of ≥10 mm, in principle, may be removed by rectal resection with lymph node dissection. However, histopathological findings such as a proliferation of tumor cells should also be taken into consideration when deciding the treatment strategy for rectal NET.

BACKGROUND/AIMS:The frequent occurrence of bile gastritis and esophagitis associated with dehiscence of 'uncut' jejunal portion was of concern for "uncut" Roux-en-Y reconstruction after distal gastrectomy. Our aim was to study if our technique of a modified, uncut Roux-en-Y procedure would decrease this dehiscence.METHODOLOGY:Ten patients with gastric cancer underwent distal gastrectomy with a modified, uncut Roux-en-Y reconstruction. Transmural silk stitches were added around the staples at the "uncut" portion in attempt to prevent dehiscence of the staple line. Dehiscence of the jejunum at the enterically closed site was investigated endoscopically or fluoroscopically.RESULTS:Mean operative time and intraoperative blood loss were 246 minutes and 381 mL, respectively. Morbidity occurred in three patients. No dehiscence was observed in any of the patients examined.CONCLUSIONS:These results suggest the possibility that our technique of a modified, uncut Roux-en-Y reconstruction after distal gastrectomy decreases dehiscence of enterically closed portion.

AIM:The purpose of the present study was to examine the possible relation between anorectal carcinoma and infliximab therapy for Crohn's disease.PATIENTS AND METHODS:This study reviewed the medical records of patients with perianal Crohn's disease, who have required surgical intervention at the Tohoku University Hospital since May 2002, when infliximab was approved as a remedy for Crohn's disease in Japan.RESULTS:Ninety-two patients underwent surgery due to perianal Crohn's disease between May 2002 and December 2011. Four out of 92 patients were diagnosed as having anorectal carcinoma associated with perianal fistula. All four patients had advanced carcinoma, and received infliximab before the diagnosis of cancer was made. Infliximab was administered due to an exacerbated anal lesion in three patients.CONCLUSION:Careful inspection and obtaining of a biopsy sample under anesthesia is recommended for patients with Crohn's disease who have long-standing anal fistulas, especially before infliximab administration due to a possible exacerbation of anal symptoms.

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.