DIAGNOSIS AND CLINICAL COURSE OF ULCERATIVE GASTRODUODENAL LESION ASSOCIATED WITH ULCERATIVE COLITIS: POSSIBLE RELATIONSHIP WITH POUCHITIS

Background and Aim: Ulcerative colitis (UC) is not only characterized by pathological lesions localized to colonic mucosa, but also to various complications involving other organs, including postoperative pouchitis. Among these complications, diffuse gastroduodenitis with lesions resembling colonic lesions has been reported, albeit rarely. The aim of the present study was to attempt to characterize the lesions of the upper gastrointestinal tract occurring as a complication of UC, and to assess the frequency and clinical course of these lesions. Methods: A total of 322 UC patients who had undergone upper gastrointestinal endoscopy were retrospectively analyzed. We assessed the frequency of endoscopic findings, including diffuse gastroduodenal lesions resembling colonic lesions. Ulcerative gastroduodenal lesion (UGDL) associated with UC was diagnosed if lesions satisfied the following criteria: (i) improvement of the lesions with treatment of UC; and/or (ii) resemblance to UC in pathological findings. Results: UGDL satisfying the aforementioned criteria was found in 15 (4.7%) of 322 patients. All the 15 patients had UGDL accompanied by pancolitis or after proctocolectomy. Frequency in 146 patients with pancolitis was 6.2% (nine patients) and that in 81 patients who had undergone proctocolectomy was 7.4% (six patients). Four patients with diffuse ulcerative upper‐gastrointestinal mucosal inflammation (DUMI) had pouchitis. In all patients except one, the lesions resolved easily with medical treatment. Conclusions: In more than half of the post‐proctocolectomy patients, UGDL was related to the occurrence of pouchitis. The existence of characteristic UGDL must be taken into account in the diagnosis and treatment of UC, and UGDL is possibly related to the occurrence of pouchitis.     

PSEUDOMEMBRANOUS COLITIS COMPLICATING ULCERATIVE COLITIS

Clostridium difficile toxin (CD toxin) causes antibiotic‐associated colitis, or pseudomembranous colitis (PMC). Although CD toxin is sometimes found in the stools of patients with ulcerative colitis (UC), UC is rarely complicated by PMC. We report herein a case of PMC complicating UC, and present a review of the literature. A 71‐year‐old woman was diagnosed as having UC of the left colon, and treated with prednisolone and mesalazine. Later, however, lumbar spinal stenosis was also detected. After surgery for lumbar spinal stenosis, she suffered postoperative infection of the lumbar region. After 3‐week treatment with antibiotics, she developed diarrhea, bloody stools, and abdominal pain. Colonoscopy revealed PMC of the cecum, ascending colon, sigmoid colon, and rectum. Stools were positive for CD toxin. As cefotiam hydrochloride, levofloxacin hydrate (LVFX), and prednisolone were suspected as the causative agents, she was treated with 1.5 g vancomycin (VCM) daily for 2 weeks without ceasing LVFX. Her symptoms improved, and colonoscopy confirmed resolution of PMC. The possibility of PMC should be considered in UC patients treated with antibiotics, immunosuppressive agents or corticosteroids who complain of gastrointestinal symptoms. These patients should be thoroughly investigated by several modalities, including colonoscopy and CD toxin testing.     

POTENTIAL OF AUTOFLUORESCENCE COLONOSCOPY FOR PATIENTS WITH ULCERATIVE COLITIS

The aim of the present paper was to determine the efficacy and potential of autofluorescence imaging (AFI) colonoscopy for patients with ulcerative colitis. Fifteen biopsy specimens were taken from endoscopic remission colonic mucosa. Eight specimens were AFI positive and seven specimens were AFI negative. While most of the histological activity findings for AFI‐positive samples were moderate active (6/8, 75.0%), most of the findings for AFI‐negative specimens were mild active (6/7, 85.7%). AFI findings for colitis‐associated cancer or dysplasia are still unclear. Further prospective studies are needed to investigate the relationship of autofluorescence findings and recurrence rate.     

NASAL MUCOSAL INVOLVEMENT IN ULCERATIVE COLITIS

Abstract: :A patient with ulcerative colitis, sclerosing cholangitis, and mouth ulceration, developed an unusual lesion involving the nasal mucosa. This was thought to represent another extra-intestinal manifestation of inflammatory bowel disease.     

SURVEILLANCE BY MAGNIFYING ENDOSCOPY IN PATIENTS WITH ULCERATIVE COLITIS

Background: Patients with total or left‐sided ulcerative colitis (UC) for more than 10 years have an increased risk of colon cancer. We studied usefulness of magnifying chromoendoscopy for the surveillance of dysplasia and colitic cancer associated with UC. Methods: From April 2003 through February 2004, 39 patients who had total or left‐sided UC for at least 7 years were prospectively enrolled in an endoscopic surveillance program, including target biopsy. All patients were examined by chromoendoscopy and magnifying endoscopy. Sites showing abnormal mucosal surface patterns or pit patterns suggestive of dysplasia underwent biopsy. Results: Of the 39 patients, 26 had total UC and 13 left‐sided UC. The mean time elapsed since the onset of UC was 16.2 ± 5.9 years. Disease activity at examination was remission in 22 patients, mild in 15, and moderate in two. Dysplasia was diagnosed in two patients (three lesions), dysplastic changes were suspected in two (two lesions), and sporadic adenoma was diagnosed in four (five lesions). On endoscopic examination, dysplasia appeared as flat elevated lesions with types IIIl and IV pit patterns. Resected specimens showed low‐to‐high‐grade dysplasia. The four patients presenting with a type III to IV mucosal pit pattern during remission were evaluated as sporadic adenoma on pathological findings. Conclusions: A combination of chromoendoscopy and magnifying endoscopy is useful for the detection of dysplasia and colitic cancer in patients with UC.     

TOLERABILITY AND USEFULNESS OF MERCAPTOPURINE IN AZATHIOPRINE‐INTOLERANT JAPANESE PATIENTS WITH ULCERATIVE COLITIS

Background and Aim: Azathioprine (AZA) and mercaptopurine (6‐MP) are established as effective therapeutic drugs for the induction and maintenance of remission in patients with ulcerative colitis (UC). However, AZA is often intolerable due to adverse effects. Evidence regarding the approach of switching from AZA to 6‐MP in patients of Asian ethnicity is lacking. We assessed the tolerability and usefulness of 6‐MP in Japanese UC patients who had shown intolerance to AZA. Methods: One‐hundred and ten UC patients who had been treated with AZA and/or 6‐MP from January 1985 to October 2008 were examined retrospectively. Results: Among 110 patients, 107 were treated first with AZA; only three were treated first with 6‐MP. Thirty‐five (33%) of the 107 patients were intolerant of AZA, with adverse effects including myelosuppression (8/35, 23%), hepatotoxicity (8/35, 23%), and abdominal symptoms (6/35, 17%). Among 35 AZA‐intolerant patients, 23 were switched to 6‐MP treatment. The cumulative probability of colectomy was significantly higher in patients not treated with 6‐MP than in patients treated with 6‐MP (log–rank test, P = 0.0002). Among the 26 patients (23 AZA‐intolerant and three AZA‐untreated) treated with 6‐MP, 22 (85%) could tolerate the therapy. Adverse effects due to 6‐MP were abdominal symptoms (2/4), myelosuppression (1/4), and rash (1/4). The median initial dose of 6‐MP was 20 mg/day, and the median final dose was 30 mg/day. Conclusions: 6‐MP was tolerated in 83% of AZA‐intolerant patients, and it was effective for maintenance therapy of UC patients. 6‐MP treatment should be considered in AZA‐intolerant patients.     

MAGNIFYING COLONOSCOPY FOR THE DIAGNOSIS OF INFLAMMATORY CHANGES IN ULCERATIVE COLITIS

Background: Endoscopic observation is the most effective method for the evaluation of staging in ulcerative colitis (UC). However, in cases with very mild inflammatory activity, histopathological diagnosis may also be required. Unfortunately, biopsy‐related accidents are not uncommon. As an alternative, we have used a magnifying colonoscope commonly used for tumor diagnosis to examine in detail the colon mucosa of UC patients in clinical remission, and then compared these findings relative to conventional endoscopy using histopathological diagnosis. Subjects and Methods: Among UC cases examined by colonoscopy between April 2000 and April 2005, 27 cases without hematochezia for at least 1 month were enrolled in this study. Following observations of inflammatory changes using conventional colonoscopy, magnifying observation and biopsies at a total of 144 sites were evaluated. Using histopathological standards, acute‐phase inflammation was indicated by the presence of neutrophil infiltration, whereas chronic‐phase inflammation was indicated by infiltration of lymphocytes, plasma cells and eosinophils. Results: Indicators of significant inflammation by conventional observation was erosion. Under magnification, inflammation appears as superficial defects in mucosa and small whitish spots. When the presence of infiltrating neutrophils was used as a positive histological marker for inflammation, there was no difference in the accuracy of diagnosis by conventional observation (95.1%) versus magnifying observation (97.2%). In contrast, when lymphocyte infiltration was used as a marker, the accuracy of diagnosis increased significantly (88.2%) using magnifying observation relative to conventional observation (61.1%). Conclusions: Magnifying endoscopy can be used effectively in the evaluation of minute mucosal changes in cases of UC remission.     

SURVEILLANCE FOR DYSPLASIA AND COLITIC CANCER BY MAGNIFYING COLONOSCOPY IN PATIENTS WITH ULCERATIVE COLITIS

The aim of this study was to evaluate the macroscopic appearance and pit pattern of colitic cancer and dysplasia associated with ulcerative colitis (UC) by conventional and magnifying colonoscopy. Twelve lesions of dysplasia in nine patients and five colitic cancers in four patients were observed by magnifying colonoscopy. On conventional colonoscopy, most colitic cancers and dysplasias were protruded lesions. However, flat lesions were observed only in dysplasia, not in colitic cancer. All colitic cancers and 83% (10/12 lesions) of dysplasias presented reddish surface. On magnifying colonoscopy, most lesions of colitic cancer and dysplasia showed III_S to III_L or III_L to IV or IV type pit patterns. Tumorous pits associated with colitic cancers and dysplasias were similar to those seen in sporadic colorectal cancers and adenomas. Magnifying colonoscopy is expected to facilitate the qualitative diagnosis of colitic cancer and dysplasia associated with ulcerative colitis and to improve the efficiency of targeted biopsy.     

REFRACTORY DIVERTICULAR COLITIS WITH PROGRESSIVE ULCERATIVE COLITIS‐LIKE CHANGES EXTENDING TO THE RECTUM

A 68‐year‐old man visited our department because of diarrhea and bloody stools. Colonoscopy revealed diverticula scattered in the sigmoid colon with localized mucosal edema and reddening. The mucosa became somewhat rough 9 months later, and had an erosive, ulcerative colitis (UC)‐like appearance after a further 6 months, with these changes extending to the rectum. These findings led to a diagnosis of diverticular colitis (DC) with UC‐like changes. The condition was refractory to treatment including drug therapy and was thus surgically treated. No cases of DC have been reported in Japan, and a refractory case of DC with progressive UC‐like changes extending to the rectum is rare even in Europe and the USA.     

VALIDITY OF ACTIVITY INDICES IN ULCERATIVE COLITIS: COMPARISON OF CLINICAL AND ENDOSCOPIC INDICES

Aim: Various different clinical indices (CI) and endoscopic indices (El) have been used to evaluate the clinical disease activity of ulcerative colitis (UC). However, no standardized CI or El of UC has been established. The aim of the present study was to determine whether or not any of the CI and/or EI for assessing the disease activity of UC could be established as a standard. Methods: The most frequently used CI and EI were identified from 100 published clinical trials dealing with UC, and representative CI and El were selected. Seventy‐four patients were enrolled in this study and their CI and El were assessed prior to treatment and at 2, 4 and 8 weeks after treatment. Furthermore, changes over time and relationships among the indices were analyzed. In this study, the clinical activity index (CAI), the disease activity index (DAI), the Lichtiger index (LI) and the Seo index were selected as the representative CI, and the Baron score and the Rachmilewitz endoscopic index (REI) were selected as the representative EI. Results: A significant decrease in all the CI and El was observed after treatment, as compared with the baseline values. Moreover, there were positive relationships among the CI and between the CI and El. Conclusion: Our results demonstrated that all the CI and El examined were almost equally useful for evaluating disease activity in UC patients. Further studies may help to determine which of the indices is the most suitable for use in UC clinical trials.     

AUTOFLUORESCENCE IMAGING COLONOSCOPY IN ULCERATIVE COLITIS: COMPARISON WITH CONVENTIONAL AND NARROW‐BAND IMAGING COLONOSCOPY

Autofluorescence imaging (AFI) endoscopy is a procedure to demonstrate gastrointestinal neoplasia and inflammation as colored areas distinct from the surrounding normal tissue. In the present pilot study AFI colonoscopy findings in patients with ulcerative colitis (UC) were analyzed. Ten patients with UC were examined using conventional colonoscopy, followed by AFI colonoscopy and narrow band imaging (NBI) colonoscopy. Images under AFI colonoscopy were classified into high AF (green or white) and low AF (magenta). NBI colonoscopy determined vasculature, either into regular, irregular or obscure mucosal vascular pattern. A total of 48 colorectal segments were assessed with the three modes of colonoscopy. The AF was high in 100% of the segments with normal mucosa or with quiescent disease and in 44% of the segments with active mucosa (P < 0.001). Mucosal vascular pattern under NBI was obscure more frequently in low‐AF segments than in high‐AF segments (P < 0.001). Inflammatory infiltrate was more severe and crypt distortion was more frequent in the latter than in the former (P < 0.001). There were trends towards more frequent obscure vascular pattern and more severe inflammation in active segments with low AF than in those with high AF mucosa. These findings suggest that AF status determined by AFI colonoscopy may be a clue for subclassification of active UC.     

A CASE OF INDETERMINATE COLITIS UNDERGOING SUBTOTAL COLECTOMY

The nomenclature inflammatory bowel disease (IBD) generally defines ulcerative colitis (UC) and Crohn's disease (CD). However, we sometimes find patients who cannot be diagnosed as UC or CD, because of the presence of both characteristics. These cases have been reported as indeterminate colitis (IC) since the first report in 1978. In our department, we have experienced IBD since 1993 (366 cases of CD), but only three cases were diagnosed as IC. Of the three, we report here the clinical and pathological features of a patient who was followed up since the diagnosis. The case was a 19‐year‐old Japanese woman without any particular past history. In December 1997, she was admitted to our hospital complaining of abdominal pain, high fever, diarrhea and fresh blood in the stool. Based on the findings of various tests, we made a diagnosis of IC, and started to treat her with prednisolone intravenous injection (i.v) at a dose of 40 mg per day. Because symptoms and signs of inflammation relapsed frequently, it was judged that there was a relative indication for surgical operation. She underwent subtotal colectomy with end‐to‐end ileorectal anastomosis on 6 January 2002. On the histopathological examination of surgical specimens, several characteristics of both UC and CD were observed. Therefore, we finally diagnosed this case as IC. After operation, she has not experienced a relapse so far and maintained fair physical condition.     

AUTOFLUORESCENCE IMAGING IS USEFUL TO ASSESS ACTIVITY OF ULCERATIVE COLITIS

The efficacy of autofluorescence imaging (AFI) for assessing ulcerative colitis (UC) activity was reviewed. AFI images of UC lesions could be classified into four categories: green; green with purple spots; purple with green spots; and purple. The strength of purple in AFI images of UC lesions is related to histologic severity, thus this classification is helpful to assess the activity of UC. The autofluorescence of AFI images was also quantified using color analysis software. Active lesions had significantly low autofluorescence/reflex ratio than inactive areas in UC patients. The ratio is inversely proportional to histologic severity. When the cut‐off is 0.9, the accuracy to predict histologic activity by AFI is 92%.     

RECURRENT POLYARTHRITIS IN A YOUNG WOMAN WITH AN ILEOANAL POUCH FOR ULCERATIVE COLITIS

We describe a patient who, following the construction of anileoanal pouch developed a seronegative polyarthritis. KEY WORDS: Ileoanal pouch, Perianal sepsis, Arthritis     

ENDOSCOPIC QUANTIFICATION OF MUCOSAL SURFACE ROUGHNESS FOR GRADING SEVERITY OF ULCERATIVE COLITIS

Background: Mucosal surface roughness is the element of Matts grading system for endoscopic severity of ulcerative colitis. The aims of the present study were to develop an image‐processing method for quantifying mucosal surface roughness and to evaluate performance of this method by comparison with visually assessed surface roughness. Methods: A total of 139 digitized colonoscopic pictures from 69 randomly selected patients with ulcerative colitis were used. The red frame of the endoscopic picture was processed for the mean spatial gradient reflecting the surface roughness. Three endoscopists (E1, E2, E3), unaware of the study design were asked to assess the surface roughness by using a visual analog scale (VAS) from 0 to 1. A total of three sessions for surface roughness were performed by each endoscopist on different days. Results: The overall mean gradient was 28.9 ± 10.9. The mean VAS did not significantly differ among endoscopists (0.42 ± 0.23 for E1, 0.45 ± 0.19 for E2 and 0.43 ± 0.28, P > 0.05). The correlation coefficient of VAS between E1 and E2, between E2 and E3, and between E3 and E1 was 0.957 (P < 0.0001), 0.914 (P < 0.0001) and 0.950 (P < 0.0001), respectively. The mean gradient correlated with the averaged VAS for each endoscopist (r = 0.711 for E1, P < 0.0001; 0.672 for E2, P < 0.0001; 0.826 for E3, P < 0.0001). Conclusion: This method may provide a means for mucosal surface roughness as a pictorial parameter, regardless of the organ studied.     

MINUTE FINDINGS DETECTED BY MAGNIFYING COLONOSCOPY IN ULCERATIVE COLITIS

In order to detect flat‐type dysplastic and cancerous lesions associated with longstanding ulcerative colitis, it is important to understand the minute findings detected by magnifying colonoscopy in active and quiescent stage of ulcerative colitis. The severity of mucosal findings by magnifying colonoscopy could be categorized as follows: polypoid mucosal tag which has severe ulceration and hemorrhage; coral‐reef‐like appearance which has coarse or nodular mucosa with ulcerations; minute defect of epithelia which has minute or shallow depressions surrounded by edematous mucosa; small yellowish spots which has minute whitish or yellowish coats; villi‐like appearance which has shaggy appearance like small intestinal villi; and regularly arranged crypt opening which has round shaped and regularly arranged crypt.     

SUPERFICIAL TYPE SERRATED ADENOMA IN ULCERATIVE COLITIS RESECTED BY ENDOSCOPIC SUBMUCOSAL DISSECTION

A female patient with a 17‐year history of an entire type of ulcerative colitis (UC) showed a superficial elevated lesion in the rectum on surveillance colonoscopy. A standard colonoscopic picture showed a slightly red lesion in the background reticular mucosa in the remission stage of UC after a longstanding chronic inflammation. A chromoendoscopic picture using indigo carmine dye‐spraying showed a distinct superficial elevated lesion with slight marginal elevation of 12 mm in diameter. A magnified view showed a slightly irregular type II pit pattern (Kudo & Tsuruta's classification). Ultrasonographic view using a high frequency ultrasound probe (20 MHz) showed that this lesion was confined to the intramucosal layer. As submucosal fibrosis due to previous repeated inflammations made it difficult to perform strip biopsy, an endoscopic submucosal dissection (ESD) method using a Hook knife was undertaken. A completely resected histological specimen showed a serrated adenoma.     

RELATIONSHIP BETWEEN ENDOSCOPIC FINDINGS OF THE POUCH AND BOWEL FREQUENCY AFTER RESTORATIVE PROCTOCOLECTOMY IN ULCERATIVE COLITIS

Background and aim: Pouchitis is one of the late complications of restorative proctocolectomy in ulcerative colitis (UC) and is associated with increased bowel frequency. The present study aimed to clarify the endoscopic findings that are associated with bowel frequency. Patients and methods: The macroscopic and microscopic features in the ileum proximal to the pouch, the pouch, and the remnant short rectum in 100 endoscopies on 63 patients were studied retrospectively. Results: Four of 28 (14%) patients had inflammatory changes in the proximal ileum. Sixty‐seven percent of patients showed an abnormal appearance of the pouch. Granularity, friability, presence of mucus, erythema, and erosions were significantly related to bowel frequency. ‘Endoscopic pouch activity index’ (EPAI), which is the number of positive findings of diffuse erythema, mucus, friability, ulcer, erosion, and granularity, was strongly associated with bowel frequency (P < 0.0001). Patients without macroscopic inflammation in the rectum had significantly lower bowel frequency than those with mild or moderately active inflammation (P = 0.0294 and 0.0183, respectively). Multivariate analysis revealed that ‘endoscopic pouch activity index’ and histological grade of pouch inflammation were significant factors (P = 0.0004 and P = 0.0429, respectively) influencing bowel frequency. Time–course study demonstrated that changes in EPAI and macroscopic grade of the rectum were significantly related to alteration in bowel frequency (P = 0.0120 and 0.0244, respectively). Conclusion: Erythema, mucus discharge and granularity were significantly related to bowel frequency. EPAI may be useful to evaluate endoscopic pouch inflammation.