The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn's disease patients: a pilot open-labeled prospective study

Purpose

Crohn's disease (CD) commonly recurs after surgery, and a number of patients need repeated surgery, especially smokers and those with repeated surgeries or penetrating disease. Whether infliximab prevents postsurgical recurrence in high-risk CD remains unknown. In the present pilot open-labeled study, we investigated the safety and efficacy of scheduled infliximab, which was started early after surgery, in maintaining remission of CD patients who have undergone multiple surgeries due to penetrating disease.

Methods

Eleven patients (nine male, two female; age range, 26–48?years) who had undergone repeated surgeries (median, 4; range, 2–5) for penetrating disease were enrolled. Two to 4?weeks after surgery, the patients were started on intravenous infliximab (5?mg/kg) at an 8-week interval. The primary end points were the proportion of patients in clinical remission at the end of the study, the rate of endoscopic/radiologic remission at 24?months, and the rate of adverse effects.

Results

One patient dropped out due to non-compliance, and ten patients were eligible for analysis. Clinical remission was maintained in six of ten patients (60.0%) at the end of the study. At 24?months, four out of ten patients were in endoscopic or radiological remission (40.0%). Two patients experienced adverse effects (18.2%), one of whom elected to withdraw from the study.

Conclusion

The findings of no major safety concern and possible clinical benefit in our study suggest that further investigation of infliximab as a treatment for prevention of postsurgical recurrence in high-risk CD is warranted.     

A case of fulminant amoebic colitis with an abscess in the abdominal cavity rescued by conservative management

A 75-year-old man was admitted because of watery diarrhea, hematochezia and right lower abdominal pain. Many deep undermining colonic ulcers were found by colonoscopy, and we detected trophozoite amoeba pathologically. Metronidazole was administered orally from 3 days after admission. However, since CT demonstrated a huge abscess in the abdominal cavity, we performed percutaneous drainage from 17 days after admission. On day 157, the patient was discharged, because the colonic ulcers had almost healed, and trophozoite amoebas were not recognized pathologically.     

Immobilization-induced hypersensitivity associated with spinal cord sensitization during cast immobilization and after cast removal in rats

This study examined mechanical and thermal hypersensitivity in the rat hind paw during cast immobilization of the hind limbs for 4 or 8 weeks and following cast removal. Blood flow, skin temperature, and volume of the rat hind paw were assessed in order to determine peripheral circulation of the hind limbs. Sensitization was analyzed by measuring the expression of the calcitonin gene-related peptide (CGRP) in the spinal dorsal horn following cast immobilization. Two weeks post immobilization, mechanical and thermal sensitivities increased significantly in all rats; however, peripheral circulation was not affected by immobilization. Cast immobilization for 8 weeks induced more serious hypersensitivity compared to cast immobilization for 4 weeks. Moreover, CGRP expression in the deeper lamina layer of the spinal dorsal horn increased in the rats immobilized for 8 weeks but not in those immobilized for 4 weeks. These findings suggest that immobilization-induced hypersensitivity develops during the immobilization period without affecting peripheral circulation. Our results also highlight the possibility that prolonged immobilization induces central sensitization in the spinal cord.     

A Case of Carcinoma Ex Pleomorphic Adenoma in the Buccal Mucosa: Review of the Literature

We present a case of carcinoma ex pleomorphic adenoma on the right buccal mucosa in a 52-year-old Japanese woman. Based on the histopathology, the excised tumor was the non-invasive type, but the majority of the tumor consisted of poorly-differentiated adenocarcinoma cells. We performed proton radiation after the surgery. The patient was well, without evidence of disease, 48 months after surgery. Carcinoma ex pleomorphic adenoma in the buccal mucosa has been reported in only four cases during the past twenty years. Therefore, our case was comparatively rare.     

Safety measures for gastrointestinal endoscopy in patients receiving antithrombotic therapy

Aim: Owing to carelessness of endoscopists, invasive procedures, such as biopsy, are sometimes carried out inadvertently in patients receiving antithrombotic therapy. The aim of the present study was to retrospectively evaluate the actual status of such careless mistakes and the efficacy of new safety measures. Methods: A questionnaire survey was conducted in 34 endoscopists at Toranomon Hospital about experiences of careless mistakes and experiences of anxiety before and after the procedure. ‘Anxiety before procedure’ was defined as the experience of discontinuing a given procedure because endoscopists remembered that the patient was receiving antithrombotic therapy, and ‘anxiety after procedure’ was defined as the experience of feeling anxious about the status of medication after the invasive procedure. A new measure was introduced at Health Management Center in August 2009. In this measure, endoscopists directly interview each patient about the status of medication just before examination, and attach forceps valves of one of two colors depending on the status of medication. A blue forceps valve is attached for patients undergoing antithrombotic therapy, and a conventional black forceps valve is attached for patients not undergoing antithrombotic therapy. Six months after introduction, a questionnaire survey was conducted in 10 endoscopists in this center. Results: Approximately half of endoscopists (18/34) experienced such careless mistakes. ‘Anxiety’ had been experienced by approximately 80%. After introduction, there was no report of careless mistakes and frequency of ‘anxiety’ evaluated by visual analog scale score decreased significantly. Conclusion: This new safety measure is expected to facilitate safer gastrointestinal endoscopy in patients receiving antithrombotic therapy.     

Attenuation of indomethacin-induced gastric mucosal injury by prophylactic administration of sake yeast-derived thioredoxin

Background

Indomethacin is one of the group of nonsteroidal anti-inflammatory drugs, which often cause gastric mucosal injury as a side effect. Infiltration and activation of inflammatory cells, production of proinflammatory cytokines and chemokines, generation of reactive oxygen species, and activation of apoptotic signaling are involved in the pathogenesis of indomethacin-induced gastric injury. We examined whether sake yeast-derived thioredoxin (a small redox-active protein with anti-oxidative activity and various redox-regulating functions) reduced indomethacin-induced gastric injury.

Methods

Gastric injury was produced by the intraperitoneal administration of indomethacin (40?mg/kg body weight) to C57BL/6 mice. Prior to the administration of indomethacin, the mice were offered food pellets containing non-genetically modified sake yeast-derived thioredoxin (thioredoxin 200?μg/g) for 3?days. Histological examinations, assessment of myeloperoxidase activity, and analysis of the gene expressions of proinflammatory cytokines and a chemokine (interleukin [IL]-1β, IL-6, and CXCL1) were statistically evaluated. Indomethacin cytotoxicity was determined by lactate dehydrogenase release from murine gastric epithelial GSM06 cells induced by 24-h treatment with 200 and 400?μM indomethacin after 1-h preincubation with 100?μg/ml sake yeast-derived thioredoxin.

Results

Macroscopic (edema, hemorrhage, and ulcers) and histological (necrosis, submucosal edema, neutrophil infiltration) findings induced by indomethacin were significantly reduced by pretreatment with food pellets containing thioredoxin. Gastric myeloperoxidase activity and the gene expressions of proinflammatory cytokines (IL-1β and IL-6) were also significantly reduced by this pretreatment compared with findings in the mice not pretreated with thioredoxin-containing food pellets. The administration of sake yeast-derived thioredoxin significantly reduced indomethacin-induced cytotoxicity in GSM06 cells.

Conclusions

We conclude that oral administration of sake yeast-derived thioredoxin reduces indomethacin-induced gastric injury. Sake yeast-derived thioredoxin may have therapeutic potential against indomethacin-induced gastric injury.