Takanori Fujiki

Quantitative analysis for human glucocorticoid receptor α/β mRNA in IBD ☆

We have previously reported that in peripheral blood mononuclear cells (PBMC), the augmented expression of the β isoform of the human glucocorticoid receptor (hGRβ), as a putative dominant negative regulator of glucocorticoid action, is associated with glucocorticoid (GC) unresponsiveness of UC patients. In this study, we quantified the levels and serial changes of hGR transcripts in PBMC of IBD patients by a real-time fluorescence monitoring of PCR. As results, relative hGRβ mRNA expression was significantly higher in the active stage of UC than in inactive periods of UC or CD patients. Longitudinal analysis revealed that hGRβ mRNA expression in UC was increased after the relapse of inflammation, suggesting that the overproduction of cytokines during inflammation may be responsible. In in vitro culture experiments of human lymphoid cell (CEM) and human PBMC, IL-7, and IL-18 increased hGRβ mRNA expression in these cells but GC itself did not. Through these analyses, it is indicated that the inflammatory cytokines altered the splicing condition of the primary transcript of hGR gene in IBD patients.

7122 Can endoscopic retrograde ileography alone assess the disease activity in crohn's disease ?

Background: The ileum is frequently affected site of the small intestine in Crohns disease (CD). However, precise evaluation of disease activity is sometimes difficult by small bowel enteroclysis (SBE) because of multiple overlapping loops. We have reported the usefulness of balloon occluded endoscopic retrograde ileography (ERIG) that is a combination of colonoscopic and radiological ileal examination for the evaluation of the disease activity not only in the colon but also in the distal ileum at one procedure (Taruishi M. et al. Radiology; in press). Aim: To evaluate weather ERIG alone can represent the disease activity of the whole small intestine without SBE information. Patients and Methods: Between May 1990 and May 1999, 50 times of both ERIG and SBE were performed within two weeks in 33 cases of known CD. Three cases were colitis, 12 were ileocolitis and 18 were ileitis type of CD. Written informed consent was obtained. Briefly, ERIG procedures were as follows. Total colonoscopy was performed, followed by intubation to the ileum. After a guide wire was introduced through the forceps channel into the ileum, only colonoscope was removed. Silicon balloon tube was inserted into the terminal ileum and fixed by the expanded balloon. After barium surfate and air was injected followed by several turning of position, double contrasted radiography was obtained. Disease activity was diagnosed independently on ERIG and SBE.We compared the disease activity assessed by ERIG with that by SBE. Results: Of 50 procedures, both ERIG and SBE revealed identical CD activity; active disease in 25 procedures and remission in 9. On the other hand, in 10 procedures ERIG showed active disease but SBE did not, and SBE showed active disease but ERIG did not in 6 procedures. ERIG could represent and evaluate the disease activity of whole small bowel in 44 (88%) of 50 procedures. The reasons to fail in evaluating the disease activity by ERIG alone were visualization of only short part of the distal ileum (less than about 100 cm) in 4 procedures, severe stricture in 1 procedure and active disease affected only in the jejunum and remission in the ileum in 1 procedure. Conclusion: Because most CD affected distal ileum, ERIG could represent the disease activity of CD not only in the colon but also in the whole small bowel, and assess it at one procedure without SBE.

6962 High frequency ultrasound probes for curative endoscopic mucosal resection for colorectal submucosal cancers.

Background: In the treatment of colorectal submucosal (sm) cancers, endoscopic mucosal resection (EMR) is limited to focally extended submucosal (sm1) cancers in which lymphnode metastasis is extremely rare. According to the retrospective study using resected specimens, risk factors of lymphnode metastasis in sm cancers were (1) invasion more than 1.5 mm into the sm layer from the muscularis mucosae (Mm), (2) vessel permeation, and (3) poorly differentiated adenocarcinoma in the deepest invasive portion (Tanaka S. et al.Gastrointest Endosc 1998, 47:AB105). However, colonoscopy is unable to evaluate the cancer-invasion distance to the sm layer even using chromoendoscopy. High Frequency Ultrasound Probe (HFUP) can precisely delineate the extension degree to submucosa in colorectal sm cancers. Aim: To evaluate whether HFUP could yield an objective invasiondistance to the sm layer; 1.5 mm of invasion distance into the sm layer that is critical for the lymphnode metastasis in sm cancers. Methods: HFUP and chromoendoscopy were performed in 35 cases of sm colorectal cancers. Invasion depth diagnosis (sm1, 2 and 3) was made and the invasion distance to the sm layer from Mm was measured on HFUP images. All the lesions were resected either by EMR (6 cases) or surgery (29 cases). Invasion distance evaluated by HFUP was compared with the microscopically determined invasion distance in the histological specimens. Results: In 35 sm cancers, 4 lesions were sessile (Is), 11 were flat elevated (IIa), 3 were slightly depressed (IIc) and 17 were flat elevated with depression (IIa+IIc). As for invasion depth, 8 lesions were sm1, 10 were sm2 and 17 were sm3. In histological specimens, average distances of cancer invasion in sm1, 2 and 3 were 0.4 mm, 2.9 mm and 4.0 mm, respectively. HFUP could delineate the cancer invasion into the sm layer in 30 (85.7%) of 35 sm cancers and sm invasion distance of those 30 cases was histologically 0.7 mm or more. The cancer-invasion distance to the sm layer evaluated by HFUP correlated well with the histologically measured distance (correlation coefficient; 0.91). HFUP correctly differentiated sm cancers with more than 1.5 mm cancer-invasion from those with 1.5 mm or less in 34 (97.1%) of 35 lesions. Conclusions: HFUP proved to provide a highly reliable cancer-invasion distance to the sm layer and to be capable of differentiating sm cancers in terms of the choice of therapy in sm cancers.

4478 Endoscopic prediction of early postsurgical recurrence in patients with crohn's disease.

Background/Aim: High relapse rate of re-stenosis at the site of intestinal anastomosis in postsurgical patients with Crohns disease is reported from several study groups. These studies revealed that appearance of endoscopic changes at the site of anastomosis frequently preceded to production of typical symptoms. However, it is still unclear when endoscopic observation should be performed, or how we can detect risky patients of earlier recurrence of anastomotic re-stenosis. To find out the predictive markers for earlier recurrence, we have prospectively observed the sequential changes of endoscopic features appeared at the site of anastomosis, from immediately after surgery to recurrence of typical stenotic lesions. Patients/Methods: Twenty-nine patients with Crohns disease who underwent intestinal/colonic resection in Asahikawa Medical College Hospital from 1990 to 1999 were subjected in this study. All the patients had ileocolonic or colo-colonic anastomosis, which were accessible by colonoscopy. Endoscopic observation and combined endoscopic retrograde ileography (ERIG) were performed at 1,6, and 12 months after surgery. One year after surgery, these observations were repeated at once a year. Results: At 1 month after surgery, 24.9% (7/29) patients already had small aphthous ulcer(s) at the site of anastomosis. These lesions were not disappeared, then incidence of relapsing these lesions were increased ( 6 months; 48.3% (14/29) 12 months; 65.5% (19/29)). Stenotic lesions due to multiple or longitudinal ulceration of anastomosis were detected from 2 years after surgery, in the patients of ulcer(+) at 12 months (31.6% (6/19)). However, no patients developed stenotic lesions within 5 years after surgery among 10 patients of ulcer (-) at 12 months. Significant statistical correlation in Logrank test was detected between ulcer (+) at 12 months and development of stenosis, or requirement of re-operation. Other factors such as disease duration, administration of 5-ASA, nocternal nutritional supprement with elemental diet, or methods of anastomosis did not correlate with postsurgical relapse rate in our patients. Conclusion: Developement of aphthous or small ulcer(s) within a year after surgery at the site of anastomosis is a risk factor of earlier re-stenosis or re-operation. Endoscopic evaluation of anastomotic areas at 12 months after surgery is necessary in management for postsurgical CD patients.