Role of the granuloma in recurrent Crohn's disease.

The clinical significance of sarcoid-like granulomata in recurrent Crohn's disease has been investigated in 90 patients. The recurrence rate for non-granulomatous disease was double that of granulomatous disease. In granulomatous disease, involvement of the mesenteric lymph nodes did not affect the recurrence rate. This suggests that sarcoid-like granulomata reflect the patients' immune response and support the view that excision of the lymphatic drainage en bloc with affected bowel is not indicated.     

CT enterography with polyethylene glycol electrolyte solution for diagnosis of Crohn's disease

This study aimed to assess the diagnostic usefulness of CT enterography (CTE) in Crohn's disease in Japanese patients. A total of 32 cases with bowel symptoms underwent CT enterography with polyethylene glycol electrolyte solution as oral contrast medium, among which 18 were clinically diagnosed as Crohn's disease and 14 were not: ulcerative colitis 1, Be?het disease 1, simple ulcer 1, inflammatory bowel disease without definite diagnosis 5 and bowel symptoms of unknown origin 6. The incidence of bowel wall thickening, mural hyperenhancement, "the comb sign", mesenteric lymph nodes swelling, and stenosis were significantly higher in Crohn's disease than in other disease. Moreover, uneven bowel wall thickening and unilateral mural hyperenhancement on CTE were characteristic features of Crohn's disease, which our original quantitative evaluation with imaging analysis could support. Consequently, CTE is useful in Japanese patients with Crohn's disease.     

Peripheral blood and mesenteric lymph node lymphocytes in Crohn's disease.

Analysis of peripheral blood lymphocytes from 44 patients with Crohn's disease showed no difference in the proportions of T- and B-cells from those in 38 healthy controls. Analysis revealed no disturbances in relation to duration or to activity of disease or to drug treatment. Lymphocytes from 18 patients with rheumatoid arthritis also showed normal proportions of T- and B-cells. Lymphocytes taken from gut lymph nodes were studied in five patients with Crohn's disease. On comparison with peripheral blood lymphocytes, significantly decreased proportions of T-cells and significantly increased proportions of B-cells were found in lymph nodes draining areas of diseased bowel. No differences were seen in the proportions of T- and B-cells from lymph nodes taken from apparently healthy bowel of the Crohn's patients and of four control subjects without inflammatory bowel disease, though these were different from those in the peripheral blood in both the Crohn's patients and control subjects.     

Prevalence and clinical significance of sonographic detection of enlarged regional lymph nodes in Crohn's disease

OBJECTIVE: Reactive regional lymph node enlargement is a frequent ultrasonographic finding in patients with Crohn's disease. However, the prevalence of this condition and its clinical significance are unknown. This study assesses the prevalence of enlarged regional mesenteric lymph nodes and its clinical significance in Crohn's disease, and in particular whether there is a correlation between the sonographic detection of enlarged regional lymph nodes and the degree of clinical or biochemical activity of the disease. MATERIAL AND METHODS: A total of 240 in- and outpatients with Crohn's disease underwent intestinal ultrasound to assess the presence of enlarged regional lymph nodes as well as the thickness and echopattern of the bowel wall, the site and extent of Crohn's disease and the presence of stenosis, fistulas and abscesses. Demographic, clinical and biochemical parameters were also collected for each patient. A multivariate model by means of multiple regression analysis was used to identify independent variables linked to regional lymph node enlargement. RESULTS: Enlarged regional lymph nodes were detected ultrasonographically in 25.4% of Crohn's disease patients. The presence of regional lymph nodes showed a weak correlation with both clinical and biochemical Crohn's disease activity. Regional lymph nodes were found more frequently in young patients (50% of patients < 30 years, 18% of patients between 30 and 50 yrs, and 7% of patients > 50 yrs; p<0.0001) and in patients with a shorter disease duration. Enlarged regional lymph nodes were strongly correlated with internal fistulas and intra-abdominal abscesses. The multiple regression analysis showed that age, duration of disease and presence of internal fistulas were the best independent predictive factors linked to the presence of enlarged mesenteric lymph nodes. CONCLUSIONS: The sonographic detection of enlarged regional lymph nodes is more frequent in young patients, which suggests an earlier phase of Crohn's disease and the presence of septic complications such as fistulas and abscesses, but this is of limited valued in assessing disease activity.     

Bacterial translocation in Crohn disease]

Bacterial translocation is the passage of viable endogenous bacteria from the gastrointestinal tract to mesenteric lymph nodes and other internal organs. The aim of this work was to study bacterial translocation in patients operated on for Crohn's disease. Twenty-eight patients, mean age 29 years, not having received any antibiotics since at least 8 days, presenting with ileal (n = 12), ileo-colonic (n = 14) or colonic (n = 2) Crohn's disease were studied. In 25 out of 28 cases (89%) indication for surgery was strictures inducing an upper small bowel distension in 9 out of 25 patients. Mesenteric lymph nodes and liver biopsies, portal blood samples and peritoneum swabs were harvested after laparotomy and before gut opening. Bacterial translocation, defined as the presence of intestinal bacteria in at least one of the specimens, was present in 8 out of 28 patients. This was found in lymph nodes draining surgical territories in 7 out of 8 cases. Bacterial strains involved in translocation included E. coli (n = 5), Enterococcus (n = 3), Clostridium perfringens (n = 2), Proteus (n = 2), and Bacteroides fragilis (n = 1). The rate of translocation differed neither according to Crohn's disease site nor with perforating or non perforating type of the disease. Five out of 9 patients operated on for strictures with proximal distension had a translocation. In conclusion, bacterial translocation was identified in 29% of patients operated on for Crohn's disease in this series. Distension of the intestine proximal to a digestive stricture could favor the occurrence of bacterial translocation in Crohn's disease.     

The usefulness of MDCT in Crohn's disease]

The usefulness of multidetector-row CT (MDCT) was investigated in 27 patients with Crohn's disease. MDCT depicted characteristic lesions associated with Crohn's disease, including bowel wall thickening, strictures, bowel wall enhancement with contrast, opacity of fatty tissue and mesenteric lymph node enlargement. With respect to delineation of lesion sites, a 76% or higher correlation rate was observed between MDCT and other conventional diagnostic procedures such as colonoscopy, barium enema, small bowel examination, and gastrointestinal endoscopy. The patient were classified as either with active disease or in remission based on the Crohn's disease activity index (CDAI). We then compared MDCT findings in patients with active disease and in remission. A positive correlation (r = 0.70) between CDAI and bowel wall thickening was observed. A comparison of 13 patients with active disease versus 14 patients in remission revealed significant bowel wall thickening, mesenteric lymph node enlargement, and opacity of fatty tissue. MDCT accurately depicted lesions consistent with active Crohn's disease. MDCT is a minimally invasive procedure that is useful in the evaluation of acute active Crohn's disease.     

Seroreactivity of patients with Crohn's disease with lymph nodes of primed nude mice is independent of the tissue used for priming

Athymic nude mice, injected with a cell-free filtrate of intestinal tissue from patients with Crohn's disease, have been shown to express antigens in their lymph nodes to which sera from patients with Crohn's disease contain antibodies. In the present study, immune reactivity was assessed with a histochemical indirect immunoperoxidase assay on paraplast-embedded tissue sections. The reactive lymph node cells were identified as sinus macrophages. We confirmed earlier findings of immunofluorescence studies that the reaction showed some antibody specificity, the proportion of patients with Crohn's disease who were positive (84%) being higher than of patients with ulcerative colitis (29%). However, reactivity of Crohn's disease sera was found to be antigen nonspecific, as it was equally observed with lymph nodes of mice primed with saline or with homogenates from patients with ulcerative colitis, diverticulitis, or volvulus. Hence, this nude mouse model does not seem appropriate to identify a transmissible etiology of Crohn's disease.     

Lymphocyte transformation in the mesenteric lymph nodes of patients with Crohn's disease

The response of lymphocytes from peripheral blood and mesenteric lymph nodes to stimulation with phytohaemagglutinin in vitro has been studied in eight patients suffering from active Crohn's disease. Patients with Crohn's disease exhibited reduced responses when compared with similar studies performed in control subjects. The impaired responses of circulating lymphocytes from these patients were marked on culture in autologous serum and were not improved by culture in homologous AB serum. Lymphocytes from lymph nodes directly draining diseased bowel exhibited lower responses than those from nodes at the root of the mesentery, which in turn were lower than those of circulating lymphocytes.     

An analysis of the reliability of detection and diagnostic value of various pathological features in Crohn's disease and ulcerative colitis

Two pathologists have independently applied 95 separate pathological criteria to 50 cases of inflammatory large bowel disease firmly diagnosed clinically as 25 cases of Crohn's disease and 25 cases of ulcerative colitis.

The observer agreement in the recording of each feature has been calculated and correlations have been made between the pathological features and the final agreed diagnosis in order to obtain an estimate of the value of each feature in differential diagnosis.

The features which have been found to be most accurately observed and useful in the diagnosis of Crohn's disease include confluent linear ulcers, deep fissures, an aggregated inflammatory pattern, and sarcoid-like granulomata. The features which have been shown to be most accurate and valuable in the diagnosis of ulcerative colitis include a `healed granular' mucosa, a continuous inflammatory pattern, an irregular gland pattern, and the absence of fissures.

The authors consider that the use of such accurate and valuable pathological criteria in the examination of inflammatory bowel disease would facilitate retrospective correlation with the clinical findings and help to clarify those intermediate cases which are at present a source of diagnostic difficulty.

     

The sentinel node technique is useful for studies of intestinal immunology in inflammatory bowel disease patients

OBJECTIVE: Mesenteric lymph nodes may play a crucial role in the pathogenesis of human inflammatory bowel disease. We have used the sentinel node technique to analyze mesenteric lymph nodes draining inflammatory lesions sentinel nodes and corresponding site of inflamed bowel in patients with ulcerative colitis or Crohn's disease. METHODS: Thirty-two patients undergoing surgical treatment of inflammatory bowel disease were included. Sentinel nodes were identified intraoperatively. The T cells were harvested from the mesenteric lymph nodes and characterized by flow cytometry. RESULTS: The distribution of CD4CD62L (homing-marked) and CD4CD69 (activated) T cells was studied in mesenteric lymph nodes draining inflammation, nodes draining normal intestine, blood, and mucosa. The turnover of T cells was markedly increased in the lymph nodes connected to inflammatory segments. The immunologic activity of the sentinel lymph nodes correlated with the degree of intestinal inflammation. CONCLUSION: Mesenteric sentinel nodes provide important information about locoregional immunology and pathogenesis in inflammatory bowel disease.     

Newly-formed lymph nodes in the submucosa in chronic inflammatory bowel disease

BACKGROUND AND AIMS: Routine diagnostic work revealed cell aggregates reminiscent of lymph nodes in the bowel submucosa in occasional cases of chronic inflammatory bowel disease. We therefore investigated whether they fulfill criteria for classification as lymph nodes. METHODS: Colon with terminal ileum from a patient with florid Crohn's disease and a colectomy specimen from a patient with ulcerative colitis were investigated. Sections were immunostained with antibodies that recognize endothelial and sinus-lining cells, immune-accessory cells, and lymphoid cells. RESULTS: Circumscribed collections of cells that fulfill all the major criteria for classification as lymph nodes were found in the large and small bowel. They had marginal and intermediate sinuses (positive for BMA 120, CD34, CD31, X-11, and von Willebrand's factor), afferent lymph vessels, T- and B-regions, and a capsule. Small collections composed predominantly of B cells that had only a marginal sinus were also occasionally observed. CONCLUSION: Secondary mucosa-associated lymphoid tissue, typically seen as follicular lymphoid hyperplasia, also appears to occur as secondary submucosal lymph nodes. This phenomenon seems inconsistent with the notion that lymph nodes do not develop after birth. We have also noted secondary development of lymph nodes in lymphangioma and lymphangioleiomyomatosis. It is possible that local lymph vessel proliferation, possibly with chronic lymphedema of the tissue involved, is an important prerequisite for lymph node neogenesis.     

Small intestinal adenocarcinoma in Crohn's disease: a case-control study

BACKGROUND: Small bowel adenocarcinoma is an uncommon complication of Crohn's disease. We sought to describe the clinical features, outcomes, and risk factors of small bowel adenocarcinoma in Crohn's disease. METHODS: A centralized diagnostic index identified all patients with Crohn's disease with small bowel adenocarcinoma evaluated at our institution between 1976 and 2000, and the medical records were abstracted. Two controls with Crohn's disease were selected for each case, matched by gender and age. RESULTS: Nine cases (four males) were identified. The patients presented with abdominal pain (89%), obstruction (89%), and weight loss (78%). Cancer was located in the ileum in 8 patients (89%) and the jejunum in 1 patient (11%). All cases but 1 had either lymph node involvement or metastasis. All cases had surgery, with 1 receiving adjuvant chemotherapy. No significant risk factors were found. The mortality rates at 1 and 2 years were 42% and 61%. CONCLUSIONS: Small bowel adenocarcinoma is a rare complication of Crohn's disease that typically involves the ileum. Affected patients have symptomatic, advanced malignancies upon diagnosis. No significant risk factors were identified.     

Endoscopic ultrasonography in staging rectal cancer

Endoscopic ultrasonography (EUS) was used to stage rectal cancer by assessing depth of invasion through bowel wall layers and/or involvement of lymph nodes. EUS findings were correlated with histopathologic findings to discern the usefulness of this modality in predicting which patients could be candidates for sphinctersaving procedures and the avoidance of abdominoperineal resection. The Olympus EU-M3 endoscopic ultrasound system was used to assess depth of penetration through rectal wall layers and to identify lymph nodes. Comparison of EUS findings to histopathologic findings was possible in 13 patients. EUS agreed with histopathology in 9 of 13 cases (69.3%) ( p = 0.07, kappa statistic). EUS agreed with histopathology as the presence or absence of lymph nodes in 9 of 13 cases (69.3%) (p = 0.07). However, the presence of lymph nodes could not necessarily predict metastatic involvement of these nodes. In one patient, invasion of vaginal cuff was correctly predicted. In nine cases, computed tomographic analysis (CT) was available for comparison to EUS in detection of penetration beyond the bowel wall. CT agreed with histopathology in 3 of 9 (33%), whereas EUS agreed with histopathology in 7 of 9 (78%).     

Seropositivity in Dutch Crohn's disease patients against primed nude mouse lymph nodes, and the difference with lymphocytotoxic antibodies.

Sera from patients with Crohn's disease have been reported to show positive immunofluorescence with lymph nodes of nude mice primed with a filtrate of intestinal tissue affected with Crohn's disease. An indirect immunofluorescence assay was used to test sera of 63 unrelated patients with Crohn's disease, 21 with ulcerative colitis and 36 control subjects against lymph nodes of athymic nude (nu/nu) mice which had been injected with Crohn's disease and ulcerative colitis intestinal tissue filtrates. Forty nine per cent of Crohn's disease patients, 10% of ulcerative colitis patients and 3% of control sera reacted against lymph nodes of mice injected injected with ulcerative colitis intestinal tissue filtrates, 18% of Crohn's disease sera were with intestinal tissue homogenate from Dutch Crohn's patients. With the lymph nodes of mice injected with ulcerative colitis intestinal tissue filtrates, 18% of Crohn's disease sera were positive, whereas all ulcerative colitis and control sera were negative. Lymph nodes from 18 of the 19 mice injected with Crohn's disease tissue filtrates reacted with Crohn's disease sera, whereas only three of these 19 mice reacted with ulcerative colitis sera. A comparative study, carried out in parallel with Crohn's disease filtrate induced hyperplastic lymph nodes from the Bilthoven colony (W2) and from the New York colony (E671) using sera from 54 Crohn's disease patients from Leiden, showed immunoreactivity with 44 and 57% of the Crohn's disease sera against the two hyperplastic lymph nodes. Thirty six of the 54 Crohn's disease sera (67%) reacted with either or both lymph nodes. Only 11% of the Crohn's disease sera which were examined for immunofluorescence and lymphocytotoxic antibodies had lymphocytotoxic antibodies, whereas 40% and 46% of the same sera showed positive immunofluorescence against E671 and W2, respectively. Absorption studies indicated that lymphocytotoxic antibodies activity and the immunofluorescence against the primed nude mouse lymph node are mediated by different serum antibodies in Crohn's disease. The reproducibility of the nude mouse immunofluorescence test system for a preferential immunoreactivity of Crohn's disease sera against Crohn's disease tissue primed murine lymph nodes has been confirmed by the present study. Further studies are necessary to find out whether crossreactive antigen(s) as recognised by some of the Crohn's disease sera in mice injected with ulcerative colitis tissue filtrate is similar to the antigen(s) detected by Crohn's disease sera in mice injected with Crohn's disease tissue filtrates.     

Gastrointestinal Sarcoidosis Resembling Crohn''s Disease

We describe a patient with disseminated sarcoidosis, who had granulomatous enterocolitis with radiological narrowing of the terminal ileum, and was presumed to have Crohn's disease. At autopsy, there were numerous sarcoid-like granulomata throughout the mucosa of the large and small bowel, but no transmural inflammation, lymphoid aggregates, or strictures, thus making Crohn's disease unlikely. It is proposed that a granulomatous enterocolitis resembling Crohn's disease can be a manifestation of disseminated sarcoidosis.     

Can Crohn's disease be diagnosed at laparotomy?

The typical macroscopic features of Crohn's disease have been well described and are widely regarded as sufficient to diagnose the disease at laparotomy. We report six patients undergoing laparotomy for symptomatic Crohn's disease, shown radiologically, who were found to have macroscopically normal small bowel despite careful examination of the bowel by an experienced surgeon. In four cases resection was deferred, but all subsequently deteriorated and required further surgery. Minor abnormalities found by balloon examination of the terminal ileum prompted resection in two further patients. Histology showed an unusually superficial distribution of inflammation, which could explain the negative findings at laparotomy. We conclude that normal laparotomy findings alone do not exclude a diagnosis of clinically important small bowel Crohn's disease. Crohn's disease should be considered in patients with persisting symptoms after negative laparotomy.     

克隆产现与副结核杆菌

分支杆菌、尤其是副结核杆菌长期被疑为克隆病的致病菌。采用聚合酶链反应技术对手术及内镜活检的７４例石蜡包埋组织中的副结核杆菌ＤＮＡ进行检测。扩增的靶ＤＮＡ为副结核杆菌染色体特异重复插入序列ＩＳ９００１上４００ｂｐ的片段。其产笺特异性通过生物素杆主民的副结核杆菌全染色体探针Ｓｏｕｔｈｅｒｎ杂交证实。     

Induction of granulomas in mice by Crohn's disease tissue

Normal and immunodeficient CBA and A2G strain mice were inoculated with crude (100 to 20 to 30 micrometer), cell-free (0.2 micrometer) filtrates of Crohn's or noninflammatory bowel disease tissue homogenates, which were either fresh or frozen to -70 degree C. Mice of each strain developed epithelioid and giant cell granulomas both locally at the site of injection and systemically in response to crude and cell-free filtrates of Crohn's tissues. Control mice did not develop such changes. The granulomas evolved slowly, predominantly between 9 and 27 months. The granuloma-inciting agent has been shown to be present in ileum, colon, and mesenteric lymph nodes of patients with Crohn's disease and it withstands freezing to -70 degree C. The use of Crohn's tissues common to this study and one in rabbits previously reported, suggests that the induction of granulomas by this agent is not strain- or species-specific, and is independent of the immune status of CBA mice.     

Clinical course and magnifying endoscopic findings of fine lesions of the large intestinal mucosa in Crohn's disease

"Worm-eaten" appearance (WEA) is a fine lesion of Crohn's disease observed in apparently normal rectal mucosa by magnifying endoscopy. Magnifying endoscopy has now been performed following application of methylene blue on 37 occasions in 27 patients with Crohn's disease, and the occurrence of WEA was reviewed in relation to the duration and extent of disease. The frequency of WEA was 75% in patients with a history of less than five years and 77% in those who had had the disease for more than five years. In the active stage, the frequency was 85% and 100% respectively, and the degree of WEA also increased. The detection rate of granulomata in regions of WEA was 53% when the clinical history was less than five years and 33% when five years or more. In active disease, granulomata were found in 70% and 67% respectively. The large intestine other than the rectum was reviewed in eight patients with ileitis. WEA and granulomata were observed throughout the large intestine including the cecum, especially when the ileal disease was active.     

Absence of skin sensitivity to oxides of aluminium, silicon, titanium or zirconium in patients with Crohn's disease.

BACKGROUND: Some metallic compounds, especially of zirconium, can cause cell mediated granulomatous inflammation of the skin. Pigment granules containing compounds of aluminium, silicon, and titanium have been observed within macrophages in the wall of the small intestine in health and in Crohn's disease. Zirconium compounds can be ingested in toothpaste. AIM: To determine in a pilot study if granulomatous sensitivity can be detected to compounds of these metals or silicon after injection into the skin of patients with Crohn's disease. SUBJECTS: Eight patients with Crohn's disease known to have had granulomata in the intestine and not currently treated with corticosteroids, and two healthy controls. METHOD: Two intradermal injections each of 0.1 ml of a 0.02% suspension of one of the compounds made in the abdominal wall of each subject. The site was marked and full thickness skin biopsy performed six weeks later. RESULT: A foreign body granuloma was observed on histological examination of two biopsy specimens but no evidence of a cell mediated response in any subject. CONCLUSION: No support was found for the hypothesis that Crohn's disease is due to a specific sensitivity to ingested metallic or silicon compounds.