PMN-elastase in assessment of patients with inflammatory bowel disease

PMN-elastase is a proteinase released by activated neutrophils. PMN-elastase was determined in two independent populations with inflammatory bowel disease. In an unselected population of 70 consecutive patients with Crohn's disease and 24 patients with ulcerative colitis with different degrees of disease activity plasma PMN-elastase levels were statistically significantly higher in patients with active than in patients with inactive disease [Crohn's disease: 80.5±33.2 ng/ml vs 60.1±24.6 ng/ml (means±sd),P=0.0017; ulcerative colitis: 98.2±54.9 ng/ml vs 59.2±16.8 ng/ml,P=0.026]. PMN-elastase levels in feces were also higher in patients with active Crohn's disease (23.6±15.3 ng/g vs 13.6±12.5 ng/g,P=0.0021) and active ulcerative colitis (46.5±60.5 ng/g vs 20.2±25.0 ng/g,P=0.46), but the difference reached significance only in Crohn's disease. Correlation of disease activity and PMN-elastase in individual patients showed a statistically significant correlation between plasma and fecal elastase concentrations and disease activity in ulcerative colitis (plasma:r=0.72,P<0.001; feces:r=0.423,P<0.001) but not fecal elastase concentrations (r=0.0083,P=0.485) correlated significantly with disease activity. Plasma PMN-elastase correlated weakly with fecal PMN-elastase levels in Crohn's disease (r=0.431,P<0.01) and in ulcerative colitis (r=0.515,P=0.05). In 28 patients with highly active Crohn's disease [median severity activity index (SAI) 203] and 11 patients with highly active ulcerative colitis [median Rachmilewitz index (RI) 14] studied before and four weeks after steroid therapy, treatment lowered the median SAI to 140 and the median RI to 4.5. Mean plasma elastase concentrations decreased concomitantly from 83±44.9 ng/ml to 61.8±25.8 (P=0.0035) in patients with Crohn's disease and from 110±49.5 to 71.6±28.8 ng/ml (P=0.0069) in patients with ulcerative colitis. In conclusion, there is a release of PMN-elastase in active IBD, which can be detected in plasma as well as in feces. Plasma elastase levels reflect disease activity in patients with IBD. The variation of the data and the large overlap between different groups, however, strongly reduce the clinical value.This research was supported by the SFB 154 of the Deutsche Forschungsgemeinschaft. V. Gross is supported by a Heisenberg-Stipendium of the Deutsche Forschungsgemeinschaft.     

Mucosal glucosamine synthetase activity in inflammatory bowel disease

Abnormalities in colonic glycoprotein synthesis have been implicated in the pathogenesis of ulcerative colitis and Crohn's disease. Glucosamine synthetase is the rate-limiting step in the biosynthesis of gastrointestinal glycoprotein and has been measured in control subjects (N=23) and patients with ulcerative colitis (N=26) or Crohn's disease of the colon (N=20) classified according to the macroscopic status of the rectum. Glucosamine synthetase activity was relatively constant around the normal colon but lower levels were found in the terminal ileum. In ulcerative colitis, glucosamine synthetase activity was similar to controls (24.0±1.9) mmol/g wet (wt/hr) irrespective of disease activity (quiescent:N=13, =27.3±1.9; activeN=16, =26.2±2.3). Rectal glucosamine synthetase activity was normal in the presence of active Crohn's proctocolitis (29.4±3.1) but raised in patients with Crohn's colitis and rectal sparing (37.2±4.9P<0.02). Glucosamine synthetase activity was strongly influence by the degree of epithelial preservation.     

Influence of Disease Site and Activity on Peripheral Neutrophil Function in Inflammatory Bowel Disease

Reactive oxygen species, released by phagocytes, are involved in tissue injury in inflammatory bowel diseases. The aim of our study was to evaluate peripheral neutrophil function in patients with ulcerative colitis (N = 66) and Crohn's disease (N = 62) with respect to disease activity and extent, using chemiluminometry after three stimuli. Twenty-seven healthy subjects were enrolled as controls. Neutrophils from ulcerative colitis and Crohn's disease patients had a significantly higher response than those from controls following phorbol myristate acetate (86.6 ± 6.5, 173.8 ± 11.9, 167.5 ± 12.2 mV, P < 0.0001), formyl-methionyl-leucyl-phenylalanine (39.5 ± 3.4, 41.3 ± 2.7, 58.6 ± 4.7 mV, P < 0.001), and zymosan (142.6 ± 10.4, 223.7 ± 8.9, 231.2 ± 9.5 mV, P < 0.0001) administration. The increased response was observed during both active disease and remission. The highest chemiluminescence values were found in patients with active ulcerative pancolitis and ileal Crohn's disease. The activation of circulating neutrophils may indicate persistent intestinal inflammation or may be triggered by luminal factors even in the absence of symptoms.     

Fecal short chain fatty acids in South African Urban Africans and whites

Diminished levels for fecal short chain fatty acids (SCFAs) have been linked to occurrence of ulcerative colitis, colorectal polyps, and colon cancer, diseases that are rare or uncommon in African populations. PURPOSE: The aim of this study was to determine fecal SCFA concentrations and fecal pH values in groups of black South Africans (African) and white South Africans (white) subjects. METHODS: Twenty healthy Africans (all women; mean age, 35 years) and 17 healthy whites (7 women; 10 men; mean age, 32 years) were tested. RESULTS: Mean total concentrations of SCFAs in the two groups were 142.1 (±53.9) and 69.2 (±26.0) mmol/kg wet feces, respectively (P=0.0001). Mean values for Africans were significantly higher in all subfractions except butyrate. There was a significant inverse correlation between fecal pH value and total fecal SCFA concentration (r=0.704;P=0.001). CONCLUSION: High concentrations of fecal SCFAs in the African group could protect against chronic bowel diseases.Abstract presented at the annual meeting of the South African Gastroenterology Society, October 1 to 5, 1993.Supported by the National Cancer Association of South Africa, Kellogg's South Africa, the Anglo-American and De Beers Chairman's Fund, Medical Faculty Research Endowment Fund, University of Witwatersrand, Johannesburg, South Africa.     

Cholelithiasis in inflammatory bowel disease

Cholelithiasis is considered an extraintestinal manifestation of Crohn's ileitis but has not been associated with ulcerative colitis. To evaluate if an increased risk of cholelithiasis exists in patients with ulcerative colitis, biliary ultrasonography was performed on 159 patients with inflammatory bowel disease, 114 patients with ulcerative colitis, and 45 patients with Crohn's disease. A control population of 2453 residents of the town near the authors' institute was also studied. An echographic survey of gallstones was performed on the control subjects, who participated in the Multicentrica Italiana Colelitiasi (MICOL). Seventeen patients with inflammatory bowel disease had gallstones (10.7 percent), 11 patients with ulcerative colitis had gallstones (9.6 percent), and 6 patients with Crohn's disease had gallstones (13.3 percent). In the control population, diagnosis of cholelithiasis was made in 239 subjects (9.7 percent). An estimate of the relative risk (odds ratio) of gallstones in ulcerative colitis and Crohn's disease and also in 4 subgroups formed on the basis of the extent of disease (total ulcerative colitis, partial ulcerative colitis, Crohn's disease with ileitis, Crohn's disease without ileitis) with respect to the general population was calculated using logistic regression with gallstones, sex, age, and body mass index as independent variables and inflammatory bowel disease as a dependent variable. The author's findings show an increased risk of gallstones in both patients with Crohn's disease (odds ratio = 3.6; 95 percent confidence limits = 1.2 - 10.4; P = 0.02) and patients with ulcerative colitis (odds ratio = 2.5; 95 percent confidence limits = 1.2 - 5.2; P = 0.01). The risk was highest in patients with Crohn's disease involving the distal ileum (odds ratio = 4.5; 95 percent confidence limits = 1.5 - 14.1; P = 0.009) and in patients with total ulcerative colitis extending to the cecum (odds ratio = 3.3; 95 percent confidence limits = 1.3 - 8.6; P = 0.01). These results confirm that there is an increased risk of gallstones in Crohn's ileitis but they show that there also exists an increased risk in patients with total ulcerative colitis.     

Total abdominal colectomy and ileorectal anastomosis for inflammatory bowel disease

PURPOSE: This retrospective study assesses the results of total colectomy and ileorectostomy for inflammatory bowel disease. METHODS: Between January 1974 and December 1990, 90 patients underwent total colectomy and ileorectal anastomosis for chronic ulcerative colitis (n=48) or Crohn's colitis (n=42) at the Mayo Clinic. Patients' records were reviewed retrospectively. Long-term results were assessed by chart reviews and postal questionnaires. Conversion to a permanent ileostomy, with or without proctectomy, was considered a failure of the procedure. The Kaplan-Meier method was used to estimate survivorship free of failure. The log-rank test was used to compare survivorship curves. Ninety-five percent confidence intervals were calculated at selected time points.P values<0.05 were considered to be statistically significant. RESULTS: The main indication for surgery was refractory chronic disease. There were no immediate postoperative deaths. The anastomotic leakage rate was 4.4 percent, and small-bowel obstruction occurred in 15.6 percent. At the time of follow-up (mean, 6.5±4.8 years), 46 patients (58.9 percent) had recurrence or exacerbation of the disease. This was the most common indication for subsequent proctectomy/permanent ileostomy in the follow-up period. There were 8 failures in 48 patients with ulcerative colitis (16.7 percent) and 11 failures in 42 patients with Crohn's disease (26.2 percent), although this difference was not statistically significant. Cumulative probability of having a functioning ileorectal anastomosis at five years was 84.2 percent (95 percent confidence interval, 71–95.9 percent) for ulcerative colitis and 73.8 percent (95 percent confidence interval, 58.6–88.6 percent) for Crohn's disease. In the latter group, females showed a significantly lower cumulative probability of having a functioning ileorectal anastomosis (females, 634 percent; males, 92.3 percent;P =0.04). Crohn's patients 36 years of age or younger also showed a lower probability of success (patients 36 years, 57 percent; patients >36 years, 93.8 percent;P =0.03). In the group with chronic ulcerative colitis, younger patients also seemed to require additional surgery more frequently; however, this difference was not statistically significant. Previous duration of symptoms, with mild or moderate disease in a distensible rectum, had no effect on results in either disease group. Functional results were acceptable in 63.6 and 87.5 percent of patients with Crohn's and ulcerative colitis, respectively. Eighty-four percent of ulcerative colitis patients and 91 percent of Crohn's disease patients reported an improvement in their quality of life, and overall, more than 90 percent considered their health status to be better than before surgery. One patient with ulcerative colitis developed carcinoma of the rectal stump 11.5 years after the colectomy and ileorectal anastomosis (cumulative probability of remaining free of cancer, 85.7 percent at 12 years; 95 percent confidence interval, 57.7–100 percent). CONCLUSIONS: These results demonstrate that, in selected patients with a relatively spared rectum and without severe perineal disease, total colectomy and ileorectal anastomosis still remains a viable option to total proctocolectomy with extensive Crohn's colitis. In addition, ileorectal anastomosis, as a sphincter-saving procedure, continues to have a place in the surgical treatment of chronic ulcerative colitis for high-risk or older patients who are not good candidates for ileal pouch-anal anastomosis, when the latter procedure cannot be done because of technical reasons and in the presence of advanced carcinoma concomitant with colitis, when life expectancy is limited.     

Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis

Eosinophil and mast cell counts were done in 44 patients with active ulcerative colitis, 10 patients with ulcerative colitis in remission, and 44 matched subjects with functional bowel disorder. Mean (±sd) rectal eosinophil counts (EC) per unit area were significantly high (P<0.01) in active ulcerative colitis (5.80±5.49) as compared with inactive disease (2.81±2.19) or controls (3.01±1.67). Eosinophil count was not significantly different in the acute stage between responder (6.36±5.95) and nonresponders (5.1±5.84) to medical treatment and was thus of little discriminatory and prognostic value. Mean (±sd) EC was reduced from 6.36±5.95 to 3.91±3.19 in responders after four weeks of medical treatment. There was little change in the EC with treatment in nonresponders. No correlation was seen between tissue eosinophils and clinical severity of ulcerative colitis. Mast cell count was not significantly different between patients with active ulcerative colitis, inactive disease, and controls and thus had little diagnostic or prognostic value. It can be concluded therefore, that EC in the rectal mucosa indicated activity but not severity of ulcerative colitis. A reduction in EC possibly indicated remission. Rectal EC, however, cannot correctly prognosticate the treatment response and outcome of the disease.     

Effect of 4G-β-D-galactosylsucrose (lactosucrose) on fecal microflora in patients with chronic inflammatory bowel disease

Metabolic interaction between the intestinal microflora and the host has been suggested to play a role in the pathogenesis of chronic inflammatory bowel disease. Elemental or low-fat, low-residual diets in patients with Crohn's disease or ulcerative colitis are reported to decrease anaerobic bacteria and to change the composition of the intestinal microflora. We examined the effect of an indigestible agent, 4^G--d-galactosylsucrose (lactosucrose), which is selectively utilized by intestinalBifidobacterium, on the composition of the intestinal microflora. After the administration of lactosucrose to two patients with Crohn's disease and five patients with ulcerative colitis for 2 weeks, significant induction of the growth ofBifidobacterium was observed, and significant reduction in the population level of Bacteroidaceae was seen. Bowel movements improved in four patients. The intestinal environment, estimated by measuring fecal pH, fecal levels of short-chain fatty acids and putrid products, and the urinary secretion of indican, also improved in these patients. These results suggest that lactosucrose may be useful for patients with chronic inflammatory bowel disease.     

Muramidase (lysozyme) in Crohn's disease and in ulcerative colitis

Estimation of lysozyme (LZM) activity in the serum was suggested as a valuable test to distinguish between Crohn's disease and ulcerative colitis. Subsequently several reports either supported or denied the original observation. Selection of patients and methodological differences were suggested as an explanation for the controversy. We estimated serum LZM in a large group of patients using the lysoplate method and human LZM as a standard. The conditions of the assay were strictly standardized. In 90 patients with Crohn's disease the LZM level was 8.3±2.1 (sd) g/ml, in 57 patients with ulcerative colitis it was 7.4±2.0 (sd) g/ml, and in 40 healthy individuals it was 7.0±1.2 (sd) g/ml. Although the difference between the mean LZM levels in Crohn's disease and in ulcerative colitis was statistically significant, there was a definite overlapping of values between these two diseases. No significant correlation of LZM level to the duration or extent of the disease, activity, or treatment was found in Crohn's disease. In ulcerative colitis the LZM level was often a little higher in severe disease, especially when the whole colon was involved.Supported in part by grant-in-aid from the Medical Research Council of Canada.     

Evolutionary changes in the pathologic diagnosis after the ileoanal pouch procedure

PURPOSE: Inadequate initial differentiation between ulcerative colitis and Crohn's disease may lead to a diagnosis of indeterminate colitis. Construction of an ileoanal pouch in these patients may result in significant morbidity and pouch failure when the ultimate diagnosis is Crohn's disease. METHOD: We prospectively studied 543 patients with idiopathic inflammatory bowel disease to determine whether a patient's pathologic diagnosis changed with time and how it affected outcome. RESULTS: Preoperative diagnosis was ulcerative colitis in 499 patients, indeterminate colitis in 42 patients, and Crohn's disease in 2 patients. Prior colectomy was performed in 58 percent of patients with ulcerative colitis and in all patients with indeterminate colitis and Crohn's disease. Postoperatively, the diagnosis changed in 20 patients with ulcerative colitis (13 to indeterminate colitis, 7 to Crohn's disease). Another two patients with indeterminate colitis showed evidence of Crohn's disease in the resected rectal specimen. As patients were followed up, an additional 13 patients were found to have Crohn's disease (5 indeterminate colitis, 8 ulcerative colitis). With the current diagnosis, perineal complications and pouch failure occurred, respectively, in 23 and in 2 percent of patients with ulcerative colitis, in 44 and in 12 percent of patients with indeterminate colitis, and in 63 and in 37 percent of patients with Crohn's disease. Pathologic diagnosis was altered in 35 patients (6 percent) overall, with a 12-fold increase in the diagnosis of Crohn's disease. Only 3 percent of patients with ulcerative colitis compared with 13 percent of patients with indeterminate colitis had a change in diagnosis to Crohn's disease (P =0.006; Fisher's exact test). CONCLUSION: Pouch-related complications, eventual pouch failure, and discovery of underlying Crohn's disease occurred in a significant number of patients with a diagnosis of indeterminate colitis. Until more accurate diagnostic differentiation is available, caution is advised in recommending the ileoanal pouch procedure to patients with indeterminate colitis.Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

Prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease

Recent investigations suggest that microthrombi formation in bowel capillaries could be a determinant factor in inflammatory bowel disease (IBD) pathogenesis. To evaluate the implication of the hemostatic system during these thrombotic events, we analyzed plasmatic values of prothrombotic state markers, physiologic inhibitors of coagulation, and endothelial lesion markers in 112 IBD patients. We found an increase in thrombin-antithrombin complexes and a decrease in antithrombin III, probably due to consumption, demonstrating an increase in thrombin generation. High levels ofd-dimer reflect increased fibrin formation, but there is no correlation between thrombin generation markers andd-dimer, possibly suggesting the presence of inadequate fibrinolysis. Levels of tissue factor pathway inhibitor were higher in patients than in controls. Nine patients with Crohn's disease (35% of our sample) had levels of this marker under 70% (range 37–69%). Von Willebrand factor values were increased and those of thrombomodulin only in active patients. Most of the changes were detected in patients with inflammatory activity, and there were no differences between ulcerative colitis and Crohn's disease. In conclusion, these results support the hypothesis that there is an endothelial lesion with sustained coagulation activation in IBD patients.     

Fecal Lysozyme in Assessment of Disease Activity in Inflammatory Bowel Disease

This study was undertaken to determine whethermeasurement of fecal lysozyme is helpful in determiningdisease activity in inflammatory bowel disease. In 112patients with Crohn's disease, 46 patients with ulcerative colitis, and 40 controls, fecallysozyme concentration was measured. Results werecorrelated with CDAI and AI in Crohn's disease and withTruelove and Witts' grading in ulcerative colitis. Fecal lysozyme concentration (mean ± SEM) wassignificantly (P < 0.001) higher in Crohn's disease(75 ± 14 mug/g) and ulcerative colitis (238± 33 mug/g) than in controls (6 ± 1g/g). There was only a weak correlation between fecal lysozymeconcentration and CDAI (r = 0.32; P = 0.001) and AI (r= 0.38; P < 0.0005) in patients with Crohn's diseaseand with Truelove and Witts' grading (r = 0.47; P =0.001) in ulcerative colitis. When CDAI 150 or AI 100were used as the standard for active disease, fecallysozyme concentration was elevated in 78% of patientswith active colonic Crohn's disease. In ulcerative colitis fecal lysozyme concentration wasincreased in active disease (95% in grade II and 94% ingrade III) as compared 33% in grade I. Measurement offecal lysozyme is of little help in diagnosing and determining disease activity of inflammatorybowel disease as whole, but it may be of help fordiagnosis and assessment of activity of colonicIBD.     

Ascorbic acid absorption in Crohn's disease

Total body pool and intestinal absorption of ascorbic acid were studied in 12 patients undergoing operation for Crohn's disease (six with fistulae and six without) and in six control patients undergoing operation for reasons other than Crohn's disease.l-[caxboxyl-¹⁴C]Ascorbic acid, 0.19–0.40 megabecquerels (MBq), was given orally. After a period of equilibration, the labeled ascorbic acid was flushed out of the patient's body tissues using large doses of unlabeled ascorbic acid. Intestinal absorption of ascorbic acid, assessed from the total cumulative urinary¹⁴C recovery, was found to be similar in patients with fistulizing Crohn's disease (73.9±8.45%), those without fistulas (72.8±11.53%), and in controls (80.3±8.11%). Total body pools of ascorbic acid, calculated using the plasma¹⁴C decay curves, were similar in patients with Crohn's disease with fistulas (17.1±5.91 mg/kg), patients without fistulas (9.6±3.58 mg/kg), and in controls (13.3±4.28 mg/kg). The results indicate that ascorbic acid absorption is normal in patients with both fistulizing and nonfistulizing Crohn's disease. The results suggest that routine supplements of vitamin C are not necessary unless oral ascorbic acid intake is low.The authors thank Hoffmann La Roche for performing the ascorbic acid analyses. The study was supported by grants from the Sheila Dawber Fund, the North Western Regional Health Authority and Hoffmann La Roche.     

NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene polymorphisms in Turkish patients with inflammatory bowel disease

Purpose The genetic susceptibility of people with certain NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene variants to inflammatory bowel disease is still under investigation. The aim of this study was to investigate polymorphisms in the NOD2/CARD15 (R702W, G908R, and 3020insC), NOD1/CARD4 (E266K, D372N), and ICAM-1 (G241R, K469E) genes, which are known to be associated with inflammation, in Turkish patients with inflammatory bowel disease and healthy control groups. Methods The genotypes of 70 patients with endoscopically and histopathologically diagnosed Crohn's disease (38 men, 32 women; mean age, 38.8 ± 1.3), 120 patients with ulcerative colitis (67 men, 53 women; mean age, 41.7 ± 1.3) and 106 healthy control subjects (37 men, 69 women; mean age, 35.7 ± 1.4), who stated that they had never had any prior bowel disease history, were compared. A polymerase chain reaction-restriction fragment length polymorphism analysis was performed for two variants of the ICAM-1 gene, the three main variants of the NOD2/CARD15 gene, and the E266K variant of the NOD1/CARD4 gene, and DNA sequencing was used for the D372N polymorphism of the NOD1/CARD4 gene. Results In this study, the three previously described Crohn's disease-predisposing variants of the NOD2/CARD15 gene and the polymorphisms examined in the NOD1/CARD4 and ICAM-1 genes were not found to be associated with ulcerative colitis or Crohn's disease. Conclusions These findings suggest that the polymorphisms observed in the NOD2/CARD15, NOD1/CARD4, and ICAM-1 genes are not genetic susceptibility factors for Crohn's disease or ulcerative colitis in Turkey.     

Alteration in intestinal permeability after ileal pouch-anal anastomosis

PPURPOSE: The physiologic changes that occur when the small bowel is used as a reservoir, as in the ileal pouchanal anastomosis, are poorly understood. Alterations in bowel permeability, which may lead to bacterial translocation that could result in illness or dysfunction of the pouch, may be one such consequence of the pouch procedure. METHODS: Whole-bowel permeability was evaluated in patients with and without the pouch through the use of an orally consumed nonmetabolizable sugar clearance technique. Patients in whom the ileal pouchanal anastomosis was performed for ulcerative colitis (17 patients) and patients with familial polyposis (7 patients) were compared with normal healthy volunteers (10 patients) and patients with ulcerative colitis with and without curative colectomy and ileostomy (6 and 5 patients, respectively). RESULTS: Measured by this technique, no differences were noted in bowel permeability between the volunteers and patients with ulcerative colitis, even after colectomy and ileostomy (1.7±0.4 in normal healthy volunteers, 1.8±0.5 in patients with ulcerative colitis without stoma, and 1.4±0.2 in patients with ulcerative colitis with ileostomy). The group of patients with an ileal reservoir, however, had a significantly increased index of measured bowel permeability (3.5±0.5 in patients with ulcerative colitis and 5.1±0.7 in patients with familial polyposis; P<0.05 by analysis of variance compared with normal healthy volunteers and patients with ulcerative colitis with or without ileostomy). CONCLUSION: The exact site, cause, and consequence of this possible alteration of bowel permeability are unclear but appear to be related to the presence of the pouch and are not caused by the underlying pathologic diagnosis.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991. Winner of the New Jersey Society of Colon and Rectal Surgeons Award, 1991.     

Long-term results of ileal pouch-anal anastomosis in patients with Crohn's disease

PURPOSE: Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for most patients with chronic ulcerative colitis. Crohn's disease is, however, a contraindication. Because distinction between UC and Crohn's disease can be difficult, some patients with Crohn's disease inadvertently undergo IPAA. The aim of this study was to determine the long-term outcome of patients with Crohn's disease who have undergone IPAA. METHODS: A total of 37 patients (20 men) were studied. Each had undergone mucosectomy with handsewn IPAA (J-pouch, n=35; S-pouch, n=1; W-pouch, n=1). Histologic examination of the resected specimen at time of IPAA showed features of ulcerative colitis (n=22), indeterminate colitis (n=9), or Crohn's disease (n=6). The stoma was closed in all patients. RESULTS: A total of 11 of 37 patients developed complex fistulas (pouch-cutaneous (n=6), pouch-vaginal (n=4), or pouch-vesical (n=1). Crohn's disease has recurred in the pouch (n=20), anal canal (n=4), pouch and anal canal (n=10), and elsewhere (n=3). After ten years (range, 3–14), the pouch remains in situ in 20 patients in whom frequency of bowel movement is seven times (3–10)/24 hours,in situ but defunctioned in seven patients, and excised in ten patients (failure rate, 45 percent). CONCLUSIONS: Inadvertent IPAA for Crohn's disease is associated with a high rate of failure (45 percent) but an acceptable long-term functional result if the pouch can be kept in situ.Read at the meeting of the Association of Surgeons of Great Britain and Ireland, Glasgow, United Kingdom, May 22 to 24, 1996.     

Increased permeability of macroscopically normal small bowel in Crohn's disease

To investigate permeability alterations of the macroscopically normal jejunum in Crohn's disease, the permeation of two probes was measured during perfusion of an isolated jejunal segment. The data were compared with the results obtained by the standard per oral test in the same patients. Test probes were PEG-400 and [⁵¹Cr]EDTA. Ten normal individuals, 12 patients with Crohn's ileitis or ileocolitis, and seven patients with isolated Crohn's colitis all with normal jejunum on x-ray series were studied. Upon perfusion of the proximal small bowel, the 3-hr [⁵¹Cr]EDTA excretion was significantly increased in ileitis patients (P=0.023) as compared to normals. The excretion exceeded the highest value of normals in eight of 12 ileitis patients. The excretion in Crohn's colitis patients was not significantly increased (P=0.24) and abnormal excretion was found only in one of the Crohn's colitis patients. PEG-400 permeation during perfusion did not differentiate between the groups, but five of the seven patients with isolated Crohn's colitis had PEG-400 excretion exceeding the highest value in normals. Overall, 13 of the 19 patients had increased permeation of one of the two probes through jejunal mucosa during perfusion. These data suggest that the permeability is increased in the majority of patients even in segments that seem normal on x-ray.This study has been supported by grant 3.0061.92, FWGO, Brussels.     

Clinical applicability of shortenedd-Xylose breath test for diagnosis of intestinal malabsorption

Urinary and/or plasmaticd-xylose tests are broadly used in clinical practice for the diagnosis of intestinal malabsorption. A 5-hr hydrogen breath test (H₂ BT) has also proven useful. Our goal was to determine whether a shorter, hence more efficient, 3-hr test would perform as well as the 5-hr test. We studied 33 patients with proven malabsorption, 44 patients with irritable bowel syndrome (IBS), and 27 healthy subjects. Each individual ingested 25 g ofd-xylose, and alveolar breath samples were obtained thereafter at 30 min intervals for 5 hr. Breath samples were analyzed for H₂ by gas chromatography. Individual peak delta changes and area under the curve (AUC) were calculated. Simultaneously, the 5-hr cumulative urinary excretion ofd-xylose was measured by colorimetry. Results of 5-hr tests were compared with those of the first 3 hrs. In the malabsorption group, the 5-hr test showed a markedly enhanced production of H₂ relative to healthy controls (delta: 60.7±6.4 vs 7.7±1.5 and AUC: 8465.0±985.4 vs 393.2±232.6,P<0.001 for both) and a reduced urinary excretion ofd-xylose (2.8±0.3 g/5 hr vs 6.3±0.2,P<0.001). Results in IBS patients did not differ from those in healthy controls. Three-hour analysis also reflected an enhanced production of H₂ in the malabsorption group (delta: 45.4±6.4 and AUC: 3700.0±545.6,P<0.001 vs healthy controls). Correlation between 3-hr and 5-hr tests was significant in healthy controls (r=0.9), IBS (r=0.9), and malabsorption (r=0.8). The sensitivity of the 3-hr test was lower than of the 5-hr test (0.72 vs 0.91). The loss of sensitivity of the 3-hr test was attributed to a delayed appearance of the delta peak in the malabsorption group. In conclusion, the H₂ breath test withd-xylose is a useful test for the diagnosis of the intestinal malabsorption, but requires a 5-hr monitoring period to be reliable.     

Significance of anergy to dinitrochlorobenzene (DNCB) in inflammatory bowel disease: family and postoperative studies.

To evaluate the pathogenetic significance of impaired cellular immunity in inflammatory bowel disease (IBD), we have measured the cutaneous responsiveness to dinitrochlorobenzene (DNCB) among 58 patients with IBD, 33 with Crohn's disease and 25 with ulcerative colitis, 63 of their clinically normal relatives, 24 additional ileitis and colitis patients who had undergone resection of all visibly diseased bowel, and 23 control subjects. Cutaneous anergy to DNCB was demonstrated among 70% of the patients with CD and 48% of those with UC, as against only 9% of the controls (p less than 0.001). There was no increased incidence of anergy among either 44 first-degree relatives (7%) or 19 spouses (3%), nor was there any special proclivity toward anergy among six pairs of patients with familial inflammatory bowel disease. In Crohn's disease, anergy was still present after bowel resection in six of 10 patients (60%), while in ulcerative colitis anergy was found after colectomy in only two of 14 patients (14%). Our data suggest that the immune defect in patients with inflammatory bowel disease may be a secondary phenomenon. In ulcerative colitis, the defect appears to reverse after colectomy, but in Crohn's disease it persists despite resection. This finding is consistent with the observed tendency of Crohn's disease, but not ulcerative colitis, to inexorable postoperative recurrence.     

Inflammatory bowel disease and leukemia

In a review of a large number of patients with inflammatory bowel disease, leukemia was observed in five patients with chronic ulcerative colitis and in two patients with Crohn's disease. In ulcerative colitis patients, there were three cases of acute myelocytic leukemia and one case each of acute lymphoblastic leukemia and chronic granulocytic leukemia. In Crohn's disease patients, there was one case each of chronic granulocytic leukemia and chronic lymphocytic leukemia associated with thrombocythemia. Sixteen other cases of leukemia have been reported to date in inflammatory bowel disease. All types of leukemia, but particularly acute myelocytic leukemia, have been described. There has been no single common feature as to type (whether ulcerative colitis or Crohn's disease), extent and course, or medical and surgical treatment of the bowel disease. The relative risk of leukemia in patients with ulcerative colitis was 5.3 [95% confidence interval 1.7 to 12.3 (P<0.01)] and of acute myelocytic leukemia 11.4 [95% confidence interval 2.3 to 24.9 (P<0.01)]. Our data on patients with Crohn's disease were not sufficient to assess the statistical significance of leukemia in this disease. This study suggests that there may be an increased risk of leukemia, particularly acute myelocytic leukemia, in ulcerative colitis. The causal relationship, if any, remains undetermined.