Toshiki Mimura

Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis

Background: Ten to 15% of patients with pouchitis experience refractory or recurrent disease. The aim of this study was to evaluate the effectiveness of a single daily high dose probiotic preparation (VSL#3) in maintaining antibiotic induced remission, and quality of life (QOL), for one year in such patients. Methods: Patients with pouchitis at least twice in the previous year or requiring continuous antibiotics, associated with a pouchitis disease activity index (PDAI) ⩾7 (0 = perfect; 18 = worst), in whom remission was induced by four weeks of combined metronidazole and ciprofloxacin, were randomised to receive VSL#3 6 g or placebo once daily for one year or until relapse. Symptomatic, endoscopic, and histological evaluations were made before, and two and 12 months after randomisation or at the time of relapse. Remission was defined as a clinical PDAI ⩽2 and endoscopic PDAI ⩽1. Relapse was defined as an increased clinical PDAI score ⩾2 and increased endoscopic PDAI score ⩾3. QOL was assessed using the inflammatory bowel disease questionnaire (IBDQ). Results: Thirty six patients were randomised: 20 to VSL#3 and 16 to placebo. Remission was maintained at one year in 17 patients (85%) on VSL#3 and in one patient (6%) on placebo (p<0.0001). The IBDQ score remained high in the VSL#3 group (p = 0.3) but deteriorated in the placebo group (p = 0.0005). Conclusion: The once daily high dose probiotic VSL#3 is effective in maintaining antibiotic introduced remission for at least a year in patients with recurrent or refractory pouchitis. This is associated with a high level of quality of life.

Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis

Background: The intestinal microbiota plays a critical role in the pathophysiology of pouchitis, a major complication after ileal pouch anal anastomosis in patients with ulcerative colitis. Recently, controlled trials have demonstrated that probiotics are effective in maintenance of remission in pouchitis patients. However, the mechanism by which therapy with probiotics works remains elusive. This study explores the role of the bacterial and fungal flora in a controlled trial for maintenance of remission in pouchitis patients with the probiotic VSL#3 compound. Methods: The mucosa associated pouch microbiota was investigated before and after therapy with VSL#3 by analysis of endoscopic biopsies using ribosomal DNA/RNA based community fingerprint analysis, clone libraries, real time polymerase chain reaction (PCR), and fluorescence in situ hybridisation. Patients were recruited from a placebo controlled remission maintenance trial with VSL#3. Results: Patients who developed pouchitis while treated with placebo had low bacterial and high fungal diversity. Bacterial diversity was increased and fungal diversity was reduced in patients in remission maintained with VSL#3 (p = 0.001). Real time PCR experiments demonstrated that VSL#3 increased the total number of bacterial cells (p = 0.002) and modified the spectrum of bacteria towards anaerobic species. Taxa specific clone libraries for Lactobacilli and Bifidobacteria showed that the richness and spectrum of these bacteria were altered under probiotic therapy. Conclusions: Probiotic therapy with VSL#3 increases the total number of intestinal bacterial cells as well as the richness and diversity of the bacterial microbiota, especially the anaerobic flora. The diversity of the fungal flora is repressed. Restoration of the integrity of a “protective” intestinal mucosa related microbiota could therefore be a potential mechanism of probiotic bacteria in inflammatory barrier diseases of the lower gastrointestinal tract.

Four-week open-label trial of metronidazole and ciprofloxacin for the treatment of recurrent or refractory pouchitis

Preliminary data suggest that short‐term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis. However, some patients are resistant to treatment.

Treatment of impaired defecation associated with rectocele by behavioral retraining (biofeedback)

PURPOSE: Large rectoceles have been associated with symptoms of impaired rectal evacuation, often leading to rectocele repair. However, these symptoms, or the anatomic abnormality, may be caused, at least in part, by a primary disturbance of rectoanal coordination. This study aimed to determine the efficacy of biofeedback therapy in such patients. METHODS: Thirty-two female patients (median age, 52 years) complaining of impaired rectal evacuation and with a rectocele greater than 2 cm at proctography were evaluated by structured questionnaire before, immediately after treatment, and at follow-up. Physiologic and proctographic findings were related to outcome. RESULTS: Immediate results were available in 32 patients and medium-term follow-up (median, 10; range, 2–30 months) in 25 patients. At follow-up 14 (56 percent) patients felt a little and 4 (16 percent) patients felt major improvement in symptoms, including 3 (12 percent) with complete symptom relief. Immediately after biofeedback there was a modest reduction in need to strain (from 72 to 50 percent), feeling of incomplete evacuation (from 78 to 59 percent), need to assist defecation digitally (from 84 to 63 percent), and need to use an evacuant (from 47 to 28 percent), and this was maintained at follow-up. Bowel frequency was significantly normalized at follow-up (P=0.02). Pretreatment presence of symptoms of digitally assisting defecation, pelvic floor incoordination, and proctographic rectocele size and contrast trapping, did not predict outcome. CONCLUSIONS: Behavioral therapy, including biofeedback, leads to major symptom relief in a minority, and partial symptom relief in a majority, of patients with a feeling of impaired defecation and the presence of a large rectocele. Residual symptoms are common. Biofeedback may be a reasonable first-line treatment for such patients.

Up-Regulation of Collagen and Tissue Inhibitors of Matrix Metalloproteinase in Colonic Diverticular Disease

PURPOSEThickening of the muscularis propria is a key pathologic feature of colonic diverticulosis but its cause is unknown. This study was designed to investigate the role of collagens, matrix metalloproteinases, and tissue inhibitor of metalloproteinases in colonic diverticulosis.METHODSCollagen content was determined by Sircol Collagen Assay and standard van Gieson staining. Messenger-RNA expression for matrix metalloproteinases and tissue inhibitor of metalloproteinase was analyzed by quantitative competitive reverse transcription polymerase chain reaction. Immunohistochemical staining was performed to localize tissue inhibitor of metalloproteinases in sections.RESULTSIn mucosa and submucosal layer, complicated diverticular disease samples had a higher collagen content than uncomplicated disease, which in turn had higher levels than controls. There was an 18-fold increase in tissue inhibitor of metalloproteinase-1 mRNA, and a threefold increase in tissue inhibitor of metalloproteinase-2 mRNA in complicated diverticulosis compared with controls. In the muscularis propria, the amount of total soluble collagen also was higher in both uncomplicated and complicated diverticulosis samples than in the controls. Tissue inhibitor of metalloproteinase-1 and metalloproteinase-2 mRNA was significantly increased in diverticulosis compared with controls. Macrophage-like and fibroblast-like cells stained strongly positive for tissue inhibitor of metalloproteinases in the submucosa, serosa, and muscularis propria and in areas around the blood vessels.CONCLUSIONSColonic diverticulosis is associated with altered collagen content and tissue inhibitor of metalloproteinases expression. These factors may play a role in remodeling the gut wall in this condition.

Diagnostic evaluation of patients with faecal incontinence at a specialist institution.

Background: Evaluation of the anorectal function, clinically, structurally, and functionally, in patients with faecal incontinence should ensure appropriate and individual treatment. Methods: Two hundred and twenty-six patients with faecal incontinence were reviewed regarding disease history and results of anorectal physiological tests and anal ultrasonography. Results: The mean age was 54 years, and 191 patients (85%) were female. Sixty-two patients had passive faecal incontinence only, 49 had urge faecal incontinence only, and 115 had both passive and urge faecal incontinence. Patients with passive faecal incontinence only had a significantly higher voluntary contraction pressure and less external sphincter abnormalities than patients with urge faecal incontinence or both passive and urge faecal incontinence. The structural abnormalities of the internal and external anal sphincters identified on anal ultrasonography were significantly associated with a low maximum resting pressure and with a low voluntary contraction pressure, respectively. The causes identified for this faecal incontinence were: in 90 patients idiopathic, in 76 obstetric injury, in 36 internal anal sphincter degeneration, in 20 anal surgical injury, in 6 rectal prolapse, and in 9 patients miscellaneous. Conclusions: The anal sphincter structure as demonstrated by ultrasonography was closely related to the anorectal function, as determined by anorectal physiological tests, and the observations from these were reflected in the range of patient-reported symptoms. Anal ultrasonography and anorectal physiological tests are useful tools, enabling us to identify the mechanisms and causes of faecal incontinence in at least 60% of the patients.

Peutz-Jeghers syndrome manifesting complete intussusception of the appendix and associated with a focal cancer of the duodenum and a cystadenocarcinoma of the pancreas : Report of a case

The unusual occurrence of an “inside-out” appendix reported here is a case of complete intussusception of the appendix of a 45-year-old woman with Peutz-Jeghers syndrome in whom the diagnosis of intussusception was made preoperatively. At laparotomy, the lead point of intussusceptum was revealed to be a Peutz-Jeghers syndrome polyp of the appendix. There was also a cystic lesion in the pancreas, and subsequent distal pancreatectomy revealed a cystadenocarcinoma of the pancreas. Two jejunal Peutz-Jeghers syndrome polyps and two duodenal Peutz-Jeghers syndrome polyps were foundvia intraoperative endoscopies. The duodenal polyps were endoscopically removed, whereas a jejunal wedge resection was performed for the adjoining jejunal polyps. One of the two duodenal polyps possessed an adenocarcinoma focus. To our knowledge, this is the first report of complete intussusception of the appendix caused by a Peutz-Jeghers syndrome polyp.

Leiomyosarcoma Originating in Meckel's Diverticulum: Report of a Case and a Review of 59 Cases in the English Literature

A 49-year-old woman was referred to our hospital with complaints of epigastric colicky pain and high fever. Abdominal computed tomography and ultrasonography showed a solid tumor in the lower abdomen. Laparotomy revealed a neoplastic mass arising in Meckels diverticulum; therefore, a segment of the ileum, including the tumor-possessing diverticulum, was resected with a lymph node dissection. A histologic examination confirmed the lesion to be leiomyosarcoma. In the English literature, 59 cases of leiomyosarcoma in Meckels diverticulum were reported from 1941 to 1994. The majority of patients were in their 4th decade of life, with both sexes equally affected. The most frequent symptoms associated with this disease were abdominal pain with nausea, vomiting, and melena. The majority were larger than egg-size. Although Meckels diverticulum is difficult to diagnose preoperatively, mesenteric arteriography may at times prove useful. The standard management of this particular tumor is wide segmental resection, including the tumor and diverticulum with lymph node dissection.

Familial adenomatous polyposis: a case report and histologic mucin study.

Adenocarcinoma arising at an ileostomy is uncommon, and only 29 cases have been reported in the literature. The case of a 54-year-old man who developed an adenocarcinoma at a Brooke ileostomy is reported. The ileostomy had been fashioned 21 years earlier after proctocolectomy for familial adenomatous polyposis (FAP). A wide local excision of the stoma was performed, and a new Brooke ileostomy was fashioned on the opposite side of the abdomen. Histopathologic examination revealed a well-differentiated adenocarcinoma with early invasion of the submucosa. On hematoxylin and eosin staining, the ileal mucosa adjacent to the tumor showed signs of colonic metaplasia, including loss of villous architecture and a reduced number of Paneth cells. Mucin staining using the high iron diamine-alcian blue stain demonstrated a mixture of sulfomucin and sialomucin in the ileal mucosa near the tumor, confirming colonic metaplasia. Ileostomy site carcinogenesis can be attributed to both the colonic metaplasia and the inherent nature of FAP or ulcerative colitis (UC), where colonic mucosa is susceptible to adenoma formation or dysplasia. Longstanding ileostomies in patients with FAP or UC should be followed to exclude the development of adenoma, dysplasia, or cancer.

Flat cancers do develop in the polyp-free large intestine.

PURPOSE AND BACKGROUND: Qualitative and quantitative analysis of many flat early cancers that have been discovered during the last decade led us to recognize that a flat route of cancer developmentde novois as important a route as the polypoid one. We aim to prove through a longitudinal study that these flat early cancers indeed develop in flat mucosa and not in an adenomatous polyp. METHODS: From January 1, 1990, to July 31, 1994, 554 patients underwent at least two colonoscopies. These patients consisted of 364 males, and average age was 59 years. We searched for flat early cancers developing in polyp-free colorectal mucosa on or after a second colonoscopy. Polyp-free mucosa here means an intestinal segment proved to possess no adenomatous polyp during the preceding colonoscopies, irrespective of the presence of polyps else-where. RESULTS: Four flat early cancers were found developing in polyp-free colonic mucosa in four patients. Average age of the patients was 67 years. Locations of the cancers were the transverse (3) and descending colons (1). The shapes were all depressed, and average size of the lesions was 11 mm. Two lesions were endoscopically resected, and two by surgery. CONCLUSION: These four depressed cancers developing in polyp-free mucosa show that flat early colorectal cancers do arisede novoand not from an adenomatous polyp having collapsed on itself.