Technetium Tc 99m hexamethyl propylene amine oxine leukocyte scintigraphy in patients with ulcerative colitis: correlation with clinical, biologic, endoscopic, and pathologic intensity, and local release of interleukin 8.

BACKGROUND: Technetium Tc 99m hexamethyl propylene amine oxine (99mTc-HMPAO) has been used to radiolabel leukocytes with promising results for its clinical use in inflammatory bowel disease. During active ulcerative colitis, colonoscopy is indicated to determine the extent and the intensity of the disease for proper management. The aim of this prospective study was to determine whether 99mTc-HMPAO-labeled leukocyte scintigraphy can give information similar to that obtained with colonoscopy during acute attacks of ulcerative colitis. METHODS: Thirty-three consecutive patients with 50 acute episodes of ulcerative colitis underwent 99mTc-HMPAO scintigraphy and colonoscopy with biopsies. Scintigraphic determination of disease extent and intensity were compared with those obtained by colonoscopy with biopsies and clinicobiologic markers. RESULTS: The scintigraphic index of disease intensity was correlated with endoscopic index, Truelove index, biologic markers, and local release of interleukin-8. The extent measured by scintigraphy was well correlated to the endoscopic and histologic extent. CONCLUSIONS: 99mTc-HMPAO scintigraphy accurately determines the extent and the intensity of acute ulcerative colitis lesions. This noninvasive method can specify the extent and the intensity of an acute attack in patients with previously known ulcerative colitis.

Network of inflammatory cytokines and correlation with disease activity in ulcerative colitis.

OBJECTIVE: The inflammatory component of most human inflammatory chronic diseases implicates the production of proinflammatory cytokines. Tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL1beta) seem to play an important role in ulcerative colitis (UC) in relevant experimental models. Moreover, antiTNF therapy seems promising experimentally and clinically. However, these cytokines, and TNFalpha more particularly, are hardly seen in vivo in such patients. The mediators of choice, correlated with disease activities or drug efficacy, remain unclear. To characterize in vivo the network of colonic cytokines in patients with UC, and the contribution of the various cytokines to disease activity we performed this study, using the colonic perfusion method. METHODS: A 20-cm colon length was perfused. Perfusate samples were collected for cytokine determination by enzyme-linked immnoassays. Nineteen perfusions were performed in mild to moderate UC, including two successive perfusions in four patients. Six healthy control patients and four having Crohn's disease (CD) with rectal involvement were studied. Endoscopic score, leukocyte scintigraphy, and systemic markers of inflammation were simultaneously quantified. RESULTS: Large amounts of IL1beta, TNFalpha, IL6, and IL8 were produced in UC patients with a highly significant correlation between TNFalpha, IL1beta and IL8 two by two. Multivariate factorial analysis indicated that IL1beta showed the best correlation with disease activity. Locally produced IL6 was strongly associated with circulating platelet counts. Moreover, production of inflammatory cytokines was associated with similar variations of disease activity in the four patients with two successive perfusions performed. The level of inflammatory cytokines in CD was lower than in UC; TNFalpha, IL1beta, and IL6 were not found in any control patients. CONCLUSION: UC appears to be a chronic inflammatory disease characterized by high production of all four proinflammatory cytokines (IL1beta, TNFalpha, IL6, and IL8). These results suggest that colonic perfusion may be a suitable method to evaluate the local anticytokine properties of new drugs, in correlation with disease activity and systemic markers of inflammation.

Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course.

The pleiotropic cytokine leukemia inhibitory factor (LIF) possesses proinflammatory properties in common with tumor necrosis factor (TNF-alpha), interleukine (IL) -1 and -6, such as the induction of acute phase protein synthesis. LIF may have chemotactic activity through the induction of IL-8 production. LIF is produced by normal and tumoral cells and appears to facilitate in vivo rat colon carcinoma cells growth. Inflammatory bowel diseases, ulcerative colitis (UC) in particular, are histologically characterized by the infiltration of the colonic mucosa with activated neutrophils, macrophages and lymphocytes. Cytokines with their inflammatory as well as their regulatory activities may play a role in the perpetuation and possibly the initiation of inflammation in this disease and its local and/or systemic complications. Moreover, colorectal cancer is a late well identified complication in patients with long standing inflammatory bowel disease, UC in particular. Taken together, these results suggest that LIF could be involved in tumorigenic and/or metastatic processes of colorectal cells in UC patients. The aims of the present study was to quantify and to compare the colonic and systemic productions of LIF in UC patients. We showed for the first time in patients with UC, a high local production of LIF well correlated with IL-8 production. We also analyzed the effect of LIF on a human colon carcinoma cell line HT29. We demonstrated that LIF stimulated HT29 cell growth in a dose dependent-manner. These results suggest that LIF may play a critical role in the susceptibility of colonic host cells to tumor growth in patients with UC.

Risk factors of oesophageal perforation during pneumatic dilatation for achalasia.

BACKGROUND/AIMS: Pneumatic dilatation of the oesophagus is a well established treatment for achalasia. Oesophageal perforation is the most serious complication that occurs in 2% to 6% of cases. The aim of this retrospective survey was to identify predictive risk factors for perforation in a consecutive series of 218 patients with achalasia. METHODS: Between 1983 and 1993, 270 pneumatic dilatations were performed in 218 patients. A Witzel dilator was used in 58 cases and a Rigiflex dilator in 212. Eight oesophageal perforations occurred (3%). The clinical, radiological, endoscopic, manometric, and technical data for the eight perforated patients were compared with those of 30 patients randomly sampled among those without perforation. RESULTS: All perforations occurred during the first dilatation. Perforations were fewer during dilatations with the Rigiflex dilator than with the Witzel dilator (2.4% v 5.2%). Perforations were all located above the cardia, on the left side of the oesophagus. In a multivariate analysis, a small weight loss and a high amplitude of oesophageal contractions in the group of patients with perforations were predictive of complications (respectively, p = 0.001 and p = 0.026). A contraction amplitude higher than 70 cm H2O in the lower part of the oesophagus was observed in three of eight patients with perforations but was not seen in any of the 30 patients without perforation (p < 0.01). CONCLUSIONS: This identification of risk factors should facilitate the choice between pneumatic dilatation or a surgical approach.