[Malignant gastrointestinal lymphoma with cicatricial stenosis after complete response to chemotherapy].

A 75-year-old woman presented complaining of anorexia. A malignant gastrointestinal lymphoma was diagnosed, and chemotherapy was initiated. After 2 months, she developed vomiting. Computed tomography (CT) revealed thickening of the jejunal wall and dilatation of the intestine proximal to that area. Positron emission tomography-CT showed no uptake. Small bowel stenosis due to cicatricial stenosis after chemotherapy was suspected. Laparoscopic partial resection of the stenotic small bowel segment was performed. Histopathologically, only granulation tissue was seen with no evidence of tumor. Occasionally, cicatricial stenosis can develop after chemotherapy for malignant gastrointestinal lymphoma. Therefore, this condition must be considered an important complication of treatment for this disease.

Cytomegalovirus infection in ulcerative colitis assessed by quantitative polymerase chain reaction: risk factors and effects of immunosuppressants.

We investigated the risk factors of and appropriate treatment for cytomegalovirus colitis in patients with ulcerative colitis, using quantitative polymerase chain reaction analysis to detect cytomegalovirus in the colonic mucosa. Between February 2013 and January 2017, patients with exacerbated ulcerative colitis who were admitted to our hospital were consecutively enrolled in this retrospective, single-center study. Patients were evaluated for cytomegalovirus using serology (antigenemia) and quantitative polymerase chain reaction analyses of the colonic mucosa, which were sampled during colonoscopy. Of 86 patients, 26 (30.2%) had positive quantitative polymerase chain reaction results for cytomegalovirus; only 4 were also positive for antigenemia. The ages of the cytomegalovirus DNA-positive patients were significantly higher than those of negative patients (p = 0.002). The mean endoscopic score of cytomegalovirus DNA-positive patients was significantly higher than that of cytomegalovirus DNA-negative patients. Treatment with combined immunosuppressants was associated with an increased risk of cytomegalovirus. Fourteen of 15 (93.3%) cytomegalovirus DNA-positive patients who were negative for antigenemia showed a clinical response to treatment with additional oral tacrolimus, without ganciclovir. cytomegalovirus reactivation in active ulcerative colitis is associated with age and combined immunosuppressant therapy. Because additional treatment with tacrolimus was effective, patients who are negative for antigenemia and cytomegalovirus DNA-positive colonic mucosa may recover without antiviral therapy.

Augmented O-GlcNAcylation alleviates inflammation-mediated colon carcinogenesis via suppression of acute inflammation.

Colon cancer prevalence is high worldwide. O-GlcNAcylation has been associated with tumor growth in various tissues, including the colon; however, its link to carcinogenesis is not fully understood. We investigated the association of O-GlcNAcylation with colon carcinogenesis using a 1,2-dimethylhydrazine/dextran sodium sulfate-induced colon carcinogenesis model in wild type and O-GlcNAc transferase-transgenic (Ogt-Tg) mice. The incidence of colon cancer was significantly lower in Ogt-Tg than in wild type mice. The colonic length was not shortened in Ogt-Tg mice, and NF-κB p65 phosphorylation was strongly suppressed, indicating that reduction of inflammation might be related to the alleviation of colon carcinogenesis. Dextran sodium sulfate-induced acute colitis mice were used to evaluate the effect of O-GlcNAcylation on inflammation at the maximal inflammation period. In Ogt-Tg mice, NF-κB p65 phosphorylation and interleukin-1ß mRNA expression were suppressed. Histochemical staining demonstrated shedding of colon epithelial cells in wild type mice a few days after dextran sodium sulfate treatment, whereas they remained essentially intact in Ogt-Tg mice. There were no significant differences on histochemical staining in the remaining epithelia between groups. These data suggest that O-GlcNAcylation could prevent colon carcinogenesis through reducing acute maximum inflammation, suggesting modulation of O-GlcNAcylation as a novel therapeutic option.

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, suppresses CXCL5 and SDF-1 and does not accelerate intestinal neoplasia formation in ApcMin/+ mice fed a high-fat diet.

The relationship between type 2 diabetes mellitus and intestinal neoplasia has been shown epidemiologically. A high-fat diet (HFD) is also known to promote insulin resistance, which is a risk factor for intestinal neoplasia. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used in the clinic for the treatment of type 2 diabetes and also to prolong the effects of glucagon-like peptide-1 (GLP-1). However, since the intestinotrophic hormone GLP-2 and chemokines, such as CXCL5 and stromal cell-derived factor-1 (SDF-1), are also substrates of DPP-4, DPP-4 inhibitors may increase the risk of intestinal carcinogenesis. In this study, we evaluated the impact of a DPP-4 inhibitor on intestinal tumorigenesis in ApcMin/+ mice fed a HFD. Six-week-old male ApcMin/+ mice were randomized to either a normal diet (10 kcal% fat) group, a HFD (60 kcal% fat) group, or a HFD group treated with sitagliptin (STG). The mice were euthanized nine weeks after the start of treatment. Daily treatment with STG did not increase number of intestinal tumors in the HFD group; however, this increase was not statistically significant. The mucosal concentration of total GLP-2 was significantly increased in the HFD group. The chemokine protein array showed elevated plasma concentrations of CXCL5 and SDF-1 in the HFD group. The administration of STG significantly suppressed the levels of plasma CXCL5 and SDF-1 in mice fed a HFD. Since CXCL5 expression is increased in patients with type 2 diabetes, and GLP-2, CXCL5 and SDF-1 are associated with tumor progression, DPP-4 inhibition may have potential as an agent for decreasing the risk of cancer in obese or diabetic patients.

Reocclusion after Self-Expandable Metallic Stent Placement for Relieving Malignant Colorectal Obstruction as a Palliative Treatment.

Self-expandable metallic stent (SEMS) placement has been practiced in several hospitals in Japan, including ours, since January 2012. Here, we report the case of an 82-year-old Japanese man who presented to the hospital with a 1-week history of right hypochondrial pain. Computed tomography (CT) findings indicated colorectal cancer. The laboratory findings on admission indicated severe anemia (red blood cell count, 426 × 104/µL; hemoglobin, 7.9 g/dL). We performed SEMS placement because the patient refused to undergo surgery. He did not attend any of the scheduled follow-up visits after SEMS placement. However, a year and a half after the SEMS placement, the patient attended the hospital because of difficulty in passing stool. A plain abdominal CT scan showed bowel reobstruction due to the ascending colon cancer after SEMS placement. We performed an emergency operation, ascending colostomy, on the same day. Colorectal stent placement may be a good treatment option for patients who refuse to undergo conventional therapeutic treatments or in those with unresectable colorectal cancer. Patients should be carefully followed up every few months after SEMS placement because of the risk of reocclusion.

[A case of ruptured giant splenic artery aneurysm].

A 68-year-old woman presented with general malaise. Her vital signs were unstable, and abdominal computed tomography revealed giant (10 cm) splenic artery aneurysm with evidence of rupture. We first occluded the root of the splenic artery using a balloon catheter. Next, we resected the distal pancreas and spleen because of the aneurysm size and destruction of the related vasculature. After surgery, the patient's condition improved, and she was discharged from the hospital on postoperative day 18. Because ruptured giant splenic artery aneurysms are very rare, we report this case with a review of the literature.

Celecoxib, a cyclooxygenase-2 inhibitor, improved upper gastrointestinal lesions in rheumatoid arthritis patients as assessed by endoscopic evaluation.

We prospectively evaluated the effects of celecoxib (CEL) on the gastrointestinal (GI) tract of rheumatoid arthritis (RA) patients with endoscopically identified GI mucosal injury after therapeutic switching from the long-term use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Upper GI endoscopy was performed on RA patients who had been treated with NSAIDs for ≥3 months. GI mucosal injury was evaluated according to the modified LANZA score. Patients with mucosal injury without ulcers were switched from NSAIDs to CEL, while those with ulcers were switched to CEL with famotidine after ulcer healing. At week 16 of treatment, GI mucosal injury was endoscopically revaluated. An efficacy analysis was performed before therapeutic switching and at 8 and 16 weeks post-switching. Endoscopic analysis revealed GI mucosal injury, including six ulcers, in 45 of the 82 patients (54.9%). Sixteen weeks after switching to CEL, LANZA scores were significantly improved [2.1 ± 0.8 (pre-switching) vs. 1.6 ± 1.3, P = 0.0073] in patients with LANZA scores of 1, 2, or 3 (n = 35). The Disease Activity Score using 28 joint counts (DAS28) [erythrocyte sedimentation rate item score (ESR4) (P = 0.0257) and C-reactive protein item score (CRP4) (P = 0.0031)] was also significantly improved by week 16. Based on these results, we conclude that preexisting NSAID-induced upper GI injury is improved following therapeutic switching to CEL without any reduction in analgesic efficacy.