Biomedical subjects

K Geboes

Publications and source records attributed to K Geboes.

At least 91 records · Page 5Linked to original sources

PubMed2000

Early vascular changes in Crohn's disease: an endoscopic fluorescence study.

BACKGROUND AND STUDY AIMS: Early recurrent lesions occurring after surgery in Crohn's disease may be the result of localized vasculitis. The aim of this study was use fluorescence endoscopy to evaluate the mucosal microcirculation of the neoterminal ileum in relation to endoscopic recurrence in patients who had undergone ileocolonic resection for Crohn's disease. PATIENTS AND METHODS: Ten patients were prospectively enrolled in an endoscopic follow-up study one year after surgery. Recurrence was assessed using routine and fluorescence endoscopy. Biopsies were taken from fluorescent and nonfluorescent sites to look for inflammation and mucosal vascular lesions using standard histological and immunohistochemical methods. RESULTS: Endoscopic recurrence was found in eight patients. At fluorescence endoscopy, the mucosa displayed a heterogeneous pattern, with fluorescent areas corresponding to aphthoid ulcerations; fluorescent rims surrounding dark zones, corresponding to stellar deep ulcers; and small bright spots distributed singly in the mucosa, which appeared normal on routine endoscopy. Histology revealed inflammatory changes with evidence of vascular involvement in 79% of the biopsies taken from the fluorescent spots. CONCLUSIONS: Endoscopic recurrence in Crohn's disease is associated with fluorescent aspects that may reflect vasodilation associated with inflammation, or genuine microvascular lesions. Correlation with the histological findings suggests that these early vascular lesions were secondary to the inflammatory process.

Adult↗

PubMed2000

IOIBD questionnaire on the clinical use of azathioprine, 6-mercaptopurine, cyclosporin A and methotrexate in the treatment of inflammatory bowel diseases.

OBJECTIVE: To obtain information on the clinical experience with azathioprine (AZA), 6-mercaptopurine (6-MP), cyclosporin A (CyA) and methotrexate (MTX) in the treatment of patients with inflammatory bowel disease (IBD) by gastroenterologists and internists in different countries. DESIGN: A questionnaire designed by the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) was mailed to 300 gastroenterologists, living in North America (n = 76) and Europe (n = 224) (12 countries), to obtain information on clinical experience. PARTICIPANTS: More than half of the respondents (168/298; 56.4%) worked in university hospitals and 58/298 (19.5%) in general (non-university) hospitals. Two-thirds (65%) had more than 10 years' experience in gastroenterology. RESULTS: The respondents had personal experience with AZA (88.4%), 6-MP (33.3%), CyA (48.7%) and MTX (36.3%). AZA was prescribed more frequently in Europe (92.6%) than in North America (74.2%) (P = 0.0002), 6-MP less frequently by the European than the North American respondents (23.8 and 53.3% respectively, P = 0.0001). Two-thirds (69.7%) usually prescribed AZA together with steroids to Crohn's disease patients; 62.4% of the respondents prescribed AZA for periods longer than 24 months. For ulcerative colitis, 77.9% had experience with AZA (Europe > North America, P = 0.0001). AZA had been prescribed by 69 respondents to pregnant patients, without apparent toxicity. Acute pancreatitis had been observed after AZA by 56.7% respondents; 25 malignancies were mentioned (six lymphoma, three leukaemia, three colon cancer, four renal carcinoma, nine others). CyA had been prescribed in acute ulcerative colitis by 140/291 respondents (North America 45.1%, Europe 49.1 %); of all respondents 63.9% treated < 5 patients with CyA, 36.1% 6-20 cases. CyA results were considered good in 29.5%, acceptable but with recurrences in 58.6%, and poor in 14.3%. MTX was prescribed in North America by 47.8% of the respondents, and by 33.9% in Europe (not significant). Several significant differences were observed between the prescription behaviour of respondents working at university hospitals and non-university hospitals, in particular in relation to participation in clinical trials. CONCLUSIONS: Considerable experience exists in the use of immunosuppressive therapy in IBD; however, differential prescription behaviour exists in the choice of immunosuppressives between North America and Europe. These IOIBD study results may contribute to a better insight in the daily use of immunosuppressive agents in IBD by gastroenterologists and other specialists.

Azathioprine↗

PubMed2000

Crohn's disease and intestinal endometriosis: an intriguing co-existence.

OBJECTIVES: We present a series of eight female patients who came to surgery for complicated Crohn's disease of the terminal ileum (n = 7) or colon (n = 1). Indications for surgery were medically intractable disease in three, steroid dependence in four and ileal perforation in one. RESULTS: Histological examination using routine haematoxylin-eosin stained sections revealed the presence of intestinal endometriosis of the ileum (n = 6), colon (n = 1) or ileum and rectum (n = 1) in addition to the typical features of Crohn's disease. In particular, chronic transmural inflammation was observed in locations other than the endometriotic deposits, which were confined to the serosa in three, the muscularis propria in two, both the serosa and the muscularis propria in one and the serosa, muscularis propria and submucosa in two. In none of these patients had the diagnosis of intestinal endometriosis been suspected pre-operatively based on clinical (gynaecological) or radiological tests. CONCLUSION: Intestinal endometriosis and Crohn's disease can occur simultaneously. The diagnosis is often only made after surgical resection of the diseased segment. In Crohn's disease, endometriosis of the terminal ileum seems more common.

Adolescent↗

PubMed2000

Expression of gelatinase B in trachomatous conjunctivitis.

BACKGROUND/AIMS: Gelatinase B is a matrix metalloproteinase involved in extracellular matrix (ECM) breakdown often associated with scarring and other pathological disorders. It was investigated whether gelatinase B is involved in the pathogenesis of ECM degradation associated with trachomatous conjunctivitis. METHODS: Conjunctival biopsy specimens obtained from six patients with active trachoma, six patients with active vernal keratoconjunctivitis (VKC), and seven control subjects were studied. Immunohistochemical techniques and a specific monoclonal antibody against human gelatinase B were used, and a monoclonal antibody against macrophage CD68 to identify mononuclear cells with gelatinase B immunoreactivity. In addition, quantitative zymography was used to compare the activity of gelatinase B in conjunctival biopsy specimens from seven patients with active trachoma and seven control subjects. RESULTS: Gelatinase B was detected by immunohistochemistry only in polymorphonuclear cells located in the vascular lumens in three normal conjunctival biopsy specimens. In all trachoma specimens and in five VKC specimens, gelatinase B was localised in monocyte/macrophage cells, positive for the CD68 marker, and in polymorphonuclear cells. The majority of the latter cell type was located in intravascular spaces. Compared with VKC specimens, trachoma specimens showed significantly more immunoreactive gelatinase B monocyte/macrophage cells (52.3 (21.9) v 8.2 (6.4); p <0.001) and polymorphonuclear cells (23.2 (14.2) v 6.3 (5.4); p = 0. 013). Activated macrophages with giant cell morphology clearly stained with the gelatinase B specific monoclonal antibody were observed in trachoma specimens. Zymography revealed that gelatinase B levels in trachoma specimens were significantly higher than the levels found in normal conjunctiva (1739.6 (1078.3) v 609.3 (395.9) scanning units; p = 0.0127). CONCLUSIONS: The increased activity of gelatinase B and numbers of inflammatory cells containing gelatinase B in trachoma specimens suggest that this enzyme plays a part in the pathogenesis of conjunctival scarring in trachoma.

Acute Disease↗

PubMed2000

Chemokines in the limbal form of vernal keratoconjunctivitis.

BACKGROUND/AIMS: Chemokines are a family of low molecular weight cytokines that attract and activate leucocytes. The CC chemokines act on eosinophils, basophils, monocytes, and lymphocytes, suggesting that they play an important part in allergic diseases. The aims of this study were to investigate the expression of the CC chemokines, RANTES, eotaxin, monocyte chemotactic protein (MCP) 1, MCP-2, and MCP-3 in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and to determine the cellular source of these chemokines. METHODS: Conjunctival biopsy specimens from nine subjects with active VKC, and six control subjects were studied by immunohistochemical techniques using a panel of monoclonal and polyclonal antibodies directed against RANTES, eotaxin, MCP-1, MCP-2, and MCP-3. The phenotype of inflammatory cells expressing chemokines was examined by sequential double immunohistochemistry. RESULTS: In the normal conjunctiva, superficial epithelial cells showed a constitutive, weak cytoplasmic expression of eotaxin. Few inflammatory cells in the perivascular areas expressed RANTES, MCP-1, MCP-2, and MCP-3. In VKC specimens, the epithelium showed intense cytoplasmic eotaxin staining in all cells, and cytoplasmic RANTES staining mainly in the superficial layers. Furthermore, RANTES and eotaxin were expressed on the vascular endothelium mainly in the upper substantia propria. Compared with normal controls, VKC specimens showed significantly more inflammatory cells expressing RANTES, eotaxin, MCP-1, and MCP-3 (p<0.001, 0.0028, 0.0092, and <0. 001, respectively). In VKC specimens, the numbers of inflammatory cells expressing RANTES were significantly higher than the numbers of inflammatory cells expressing eotaxin, MCP-1, and MCP-2 (all p values <0.001). Colocalisation studies revealed that the majority of inflammatory cells expressing chemokines were CD68 positive monocytes/macrophages. CONCLUSIONS: These results demonstrate an increase in the expression of RANTES, eotaxin, MCP-1, and MCP-3 in the conjunctiva of patients with VKC compared with control subjects. These data suggest a potential role for these chemokines in the pathogenesis of VKC. Antagonists of chemokine receptors may provide new therapeutic modalities in VKC.

Adolescent↗

PubMed2000

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

Adenoma↗

PubMed2000

A reproducible grading scale for histological assessment of inflammation in ulcerative colitis.

BACKGROUND: Evaluation of histological activity in ulcerative colitis needs to be reproducible but has rarely been tested. This could be useful both clinically and in clinical trials. AIM: To develop reproducible criteria which are valid in the assessment of acute inflammation (activity) and chronicity, and to evaluate these features in an interobserver variability study. METHODS: A six grade classification system for inflammation was developed which could also be fine tuned within each grade. The grades were: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin sections from endoscopically inflamed and non-inflamed mucosa from patients with distal ulcerative colitis were assessed in two separate readings by three pathologists independently and without knowledge of the clinical status. Interobserver agreement was compared pairwise using kappa statistics. RESULTS: Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which are too low to be of value. Following development of a semiquantitative pictorial scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For activity defined by neutrophils between epithelial cells, kappa values were 0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils in epithelium correlated with the presence of crypt destruction and ulceration. CONCLUSION: A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.

Biopsy↗

PubMed1999

Hyperexpression of CD40 ligand (CD154) in inflammatory bowel disease and its contribution to pathogenic cytokine production.

CD40 ligand (CD40L or CD154), a type II membrane protein with homology to TNF, is transiently expressed on activated T cells and known to be important for B cell Ig production and for activation and differentiation of monocytes and dendritic cells. Both Crohn's disease and ulcerative colitis are characterized by local production of cytokines such as TNF and by an influx of activated lymphocytes into inflamed mucosa. Herein, we investigated whether CD40L signaling participates in immune responses in these diseases. Our results demonstrated that CD40L was expressed on freshly isolated lamina propria T cells from these patients and was functional to induce IL-12 and TNF production by normal monocytes, especially after IFN-gamma priming. The inclusion of a blocking mAb to CD40L or CD40 in such cocultures significantly decreased monocyte IL-12 and TNF production. Moreover, lamina propria and peripheral blood T cells from these patients, after in vitro activation with anti-CD3, showed increased and prolonged expression of CD40L as compared with controls. Immunohistochemical analyses indicated that the number of CD40+ and CD40L+ cells was significantly increased in inflamed mucosa, being B cells/macrophages and CD4+ T cells, respectively. These findings suggest that CD40L up-regulation is involved in pathogenic cytokine production in inflammatory bowel disease and that blockade of CD40-CD40L interactions may have therapeutic effects for these patients.

Adult↗

PubMed1999

The effect of preoperative radiation therapy on glucose utilization and cell kinetics in patients with primary rectal carcinoma.

BACKGROUND: Proliferating cells in neoplasms usually show rapid cell cycle times and high rates of glycolysis. Tumor glucose utilization (TuGluc), potential cell doubling time (Tpot), and the effect of radiotherapy (RT) were evaluated in patients with primary rectal carcinoma. METHODS: 2-[18F]-fluoro-2-deoxy-glucose (18F-FDG) was administered and dynamic positron emission tomography (PET) performed to determine TuGluc. Cell kinetics were measured with flow cytometry after labeling with iodo-deoxy-uridine. Two groups of patients were investigated prospectively: 1) those patients undergoing surgery only and 2) those patients undergoing surgery after receiving 30 gray of RT. Twenty consecutive patients with a cT3-NX-M0 tumor and age > 50 years were selected and randomized. One patient was excluded because of unexpected liver metastases and another had incomplete data. RESULTS: At baseline, the TuGluc for Group 1 was 222+/-104 nmol/mL/minute (mean +/- 1 standard deviation), and was 215+/-126 nmol/mL/minute for Group 2 (P > 0.8). After RT TuGluc decreased to 77+/-39 nmol/mL/minute (P = 0.008). Tpot was 3.4+/-1.2 days for Group 1 and 2.6+/-2.0 days for Group 2 at baseline (P > 0.2). Two weeks after RT, Tpot slowed to 5.7+/-3.6 days (P = 0.04). A weak negative correlation (correlation coefficient = -0.36) was found between TuGluc and Tpot. After RT, the proportion of labeled cells had not changed from baseline levels (P > 0.2), suggesting undisturbed proliferation, but the DNA synthesis time had increased. The significant decrease of TuGluc indicated cell loss. CONCLUSIONS: Tumor FDG uptake and cell kinetics are not correlated strongly in rectal carcinoma. Preoperative RT results in an overall loss of tumor cells (tumor reduction) and an increase in Tpot, although proliferation of the viable cell fraction is maintained.

Cell Cycle↗

PubMed1999

Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.

The incidence of adenocarcinoma of the esophagus has been increasing in developing countries over the last three decades and probably reflects a genuine increase in the incidence of its recognized precursor lesion, Barrett's metaplasia. Despite advances in multimodality therapy, the prognosis for invasive esophageal adenocarcinoma is poor. An improved understanding of the molecular biology of this disease may allow improved diagnosis, therapy, and prognosis. We focus on recent developments in the molecular and cell biology of Barrett's metaplasia, a heterogeneous lesion affecting the transitional zone of the gastro-esophageal junction whose associated molecular alterations may vary both in nature and temporally. Early premalignant clones produce biological and genetic heterogeneity as seen by multiple p53 mutations, p16 mutations, aneuploidy, and abnormal methylation resulting in stepwise changes in differentiation, proliferation, and apoptosis, allowing disease progression under selective pressure. Abnormalities in expression of growth factors of the epidermal growth factor family and cell adhesion molecules, especially cadherin/catenin complexes, may occur early in invasion. Exploitation of these molecular events may lead to a more appropriate diagnosis and understanding of these lesions in the future.

Adenocarcinoma↗

PubMed1999

Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial.

BACKGROUND & AIMS: Tumor necrosis factor (TNF) is a pivotal cytokine in intestinal inflammation. Controlled trials using a chimeric anti-TNF antibody (infliximab) have shown its efficacy in refractory Crohn's disease. METHODS: Endoscopic and histological response to infliximab was investigated in a multicenter, randomized, double-blind, and placebo-controlled trial including 30 patients with active Crohn's disease undergoing ileocolonoscopy before and 4 weeks after intravenous administration of 5, 10, or 20 mg/kg of infliximab or placebo as a single infusion. Lesions were scored by means of the validated Crohn's Disease Endoscopic Index of Severity (CDEIS). Endoscopic biopsy specimens were taken during both procedures from 9 of 30 patients and scored by a single gastrointestinal pathologist. RESULTS: CDEIS scores decreased significantly in most infliximab-treated patients without an apparent dose response. No endoscopic improvement was observed in the placebo group. The changes in CDEIS correlated highly with those of the Crohn's Disease Activity Index. At a histological level, disappearance of the inflammatory infiltrate was observed in infliximab-treated patients but not in placebo-treated ones; however, architectural changes persisted in most patients. Strictures developed in several patients. CONCLUSIONS: Clinical improvement after infliximab therapy in active Crohn's disease is accompanied by significant healing of endoscopic lesions and disappearance of the mucosal inflammatory infiltrate.

Adult↗

PubMed1999

Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis.

BACKGROUND & AIMS: Anti-tumor necrosis factor alpha monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohn's disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohn's ileocolitis were studied. METHODS: Thirteen patients with steroid-refractory Crohn's disease were treated with a single infusion of infliximab (5-20 mg/kg), and 5 were treated with placebo. Ileal and colonic biopsy specimens of all patients were collected before and 4 weeks after therapy. Severity of inflammation was assessed by a histological score. Immunohistochemical stainings with antibodies against HLA-DR, CD68, tumor necrosis factor alpha, intercellular adhesion molecule 1, lymphocyte function-associated antigen, CD4, CD8, and interleukin 4 were performed. RESULTS: Total histological activity score was reduced significantly in both ileitis and colitis after infliximab. This is caused by a virtual disappearance of the neutrophils and a reduction of mononuclear cells. Mucosal architecture returned to normal in 4 patients at 4 weeks. The number of lamina propria mononuclear cells decreased because of a global reduction of CD4(+) and CD8(+) T lymphocytes and CD68(+) monocytes. Aberrant colonic epithelial HLA-DR expression completely disappeared. The percentage of intercellular adhesion molecule 1 and lymphocyte function-associated antigen 1-expressing and interleukin 4- and tumor necrosis factor-positive lamina propria mononuclear cells sharply decreased. CONCLUSIONS: Infliximab dramatically decreases histological disease activity in Crohn's ileocolitis. Signs of active inflammation nearly disappear accompanied by a profound down-regulation of mucosal inflammatory mediators.

Adult↗

PubMed1999

Inflammatory alterations in mesenteric adipose tissue in Crohn's disease.

BACKGROUND & AIMS: Abnormalities of fat in the mesentery including adipose tissue hypertrophy and fat wrapping have been long recognized on surgical specimens as characteristic features of Crohn's disease. However, the importance, origin, and significance of the mesenteric fat hypertrophy in this chronic inflammatory disease are unknown. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a crucial factor involved in the homeostasis of adipose tissue, a major source of biologically active mediators. METHODS: Intra-abdominal fat accumulation was quantified using a magnetic resonance imaging method in patients with Crohn's disease and controls. PPARgamma and inflammatory cytokines synthesized by mesenteric adipose tissues were assessed by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. RESULTS: In vivo, patients with Crohn's disease have an important accumulation of intra-abdominal fat. This mesenteric obesity, present from the onset of the disease, is associated with overexpression of PPARgamma and tumor necrosis factor (TNF)-alpha, synthesized, at least in part, by adipocytes. CONCLUSIONS: These results suggest that confined increased PPARgamma mesenteric concentrations could lead to the mesenteric fat hypertrophy, which could actively participate through the synthesis of TNF-alpha in the inflammatory response.

Abdomen↗

PubMed1999

Endoscopic and histologic healing of Crohn's (ileo-) colitis with azathioprine.

BACKGROUND: The correlation between disease activity and endoscopic findings in Crohn's disease is poor. Corticosteroids induce symptom relief without consistent improvement of endoscopic lesions. Our aim was to examine the effect of azathioprine therapy on healing of inflammatory lesions in patients with severe Crohn's disease. METHODS: The study included 20 consecutive patients with Crohn's colitis or ileocolitis in clinical remission while taking azathioprine for at least 9 months and no corticosteroids for at least 3 months who had had an ileocolonoscopy less than 1 year before the start of azathioprine. All 20 patients underwent a new ileocolonoscopy with biopsies. RESULTS: The duration of azathioprine therapy was 24.4 +/- 13.7 months. In the colon, we observed complete healing in 14 of 20 patients (70%), near-complete healing in 2 of 20 (10%), partial healing in 3 of 20 (15%), and no healing in 1 of 20 (5%). In the ileum complete healing was seen in 7 of 13 (54%) patients with ileitis, near-complete healing in 2 of 13 (15%), partial healing in 1 of 13 (8%), and no healing in 2 of 13 (15%); the ileum was not reached in 1 patient. Histologic examination revealed disappearance of the inflammatory infiltrate, with a certain degree of architectural disturbance remaining. CONCLUSIONS: Successful azathioprine therapy is accompanied by mucosal healing and disappearance of the inflammatory infiltrate.

Adult↗

PubMed1999

Primary diffuse large B cell lymphoma of the stomach: analysis of somatic mutations in the rearranged immunoglobulin heavy chain variable genes indicates antigen selection.

Gastric low grade MALT lymphomas show a pattern of somatic mutations in their rearranged immunoglobulin genes, indicative of antigen selection. This provides evidence for antigen stimulation in the lymphomagenesis. Gastric diffuse large B cell lymphomas develop secondary to low grade MALT lymphoma or de novo. To study whether antigen-selection is also a feature of primary diffuse large B cell lymphomas, we analysed somatic mutations in the rearranged immunoglobulin heavy chain (IgH) variable genes (VH). The rearranged VH genes of six cases of gastric primary diffuse large B cell lymphoma were amplified from genomic or complementary DNA by a VH gene family-specific polymerase chain reaction method. The PCR products were directly sequenced and were compared to published germline sequences to analyse somatic mutations. Similarly to low grade MALT lymphomas 5/6 primary diffuse large B cell lymphomas show a pattern of somatic mutation in their rearranged VH genes, indicative of antigen selection and suggesting a role for antigens in lymphomagenesis. One case showed bi-allelic VH gene rearrangements, which were non-functional due to extensive deletions. Antigen selection could not be demonstrated or excluded. Antigen selection is a common feature in most analysed primary diffuse large B cell lymphomas, although some heterogeneity in the mechanisms involved in the lymphomagenesis of gastric primary diffuse large B cell lymphomas has not been excluded entirely (case 4).

Aged↗

PubMed1999

Local and systemic effects of intraoperative whole-colon washout with 5 per cent povidone-iodine.

BACKGROUND: Segmental intraluminal instillation of several tumoricidal agents including povidone-iodine has been advocated to prevent anastomotic recurrence after colonic resection for colorectal cancer. The local and systemic effects of on-table whole-colon washout using 5 per cent povidone-iodine were assessed in patients undergoing elective surgery for colorectal cancer. METHODS: The local effect of 5 per cent povidone-iodine on the colonic mucosa and the effect of colonic mucosal damage by povidone-iodine on tumour take was first investigated in Fischer 344 rats. In 12 euthyroid non-allergic patients, on-table whole-colon lavage via the appendix was performed. Systemic (thyroid function) and local (mucosal damage assessed by repeat biopsies) effects were studied, as well as the in vitro tumoricidal effect of the final anal effluent on tumour cell suspensions. RESULTS: After 30 min of contact with povidone-iodine the rat colonic mucosa was severely injured, with detachment of the epithelial cell layer. Povidone-iodine-induced 'colitis' did not result in tumour development after inoculation of 10(6) Mtln3 carcinoma cells in ten rats. Epithelial desquamation was also observed, in all but one patient, 1 and 4 h after colonic lavage. However, epithelial restitution started within 1 day and no abnormality was revealed after 3-7 days. Urinary iodine excretion increased markedly and was not within normal values after 1 week. Levels of thyroid hormones decreased significantly but became normal within 1 week. The anal effluent containing povidone-iodine was found to be tumoricidal in vitro on a human colonic carcinoma cell line and on a tumour cell suspension produced from the patient's tumour. CONCLUSION: On-table whole-colon washout using 5 per cent povidone-iodine seems clinically feasible. This technique deserves further study as a substitute for preoperative bowel preparation and may help to prevent recurrent cancer due to implantation of viable exfoliated tumour cells.

Adult↗

PubMed1999

Is calcifying fibrous pseudotumor a late sclerosing stage of inflammatory myofibroblastic tumor?

Calcifying fibrous pseudotumor is a recently described distinctive lesion, characterized by the presence of abundant hyalinized collagen with psammomatous or dystrophic calcifications and a lymphoplasmacytic infiltrate. The cause and pathogenesis are unclear, but a possible relationship with other pseudotumors, like nodular fasciitis or inflammatory myofibroblastic tumor, has been proposed by some authors. However, cases with overlapping histologic features have not been reported. A 17-year-old girl with multiple peritoneal calcifying fibrous pseudotumors and inflammatory myofibroblastic tumors (inflammatory pseudotumors) is described. Some multinodular lesions showed calcifying fibrous pseudotumors next to inflammatory myofibroblastic tumors. Transitional stages between calcifying fibrous pseudotumor and inflammatory myofibroblastic tumor were also present. This case clearly illustrates a histogenetic relationship between calcifying fibrous pseudotumor and inflammatory myofibroblastic tumor, and it suggests that calcifying fibrous pseudotumor is a late sclerosing stage of inflammatory myofibroblastic tumor, at least in some cases.

Adolescent↗

PubMed1999

Abnormalities in mucin gene expression in Crohn's disease.

Alterations in the structure and/or quantity of mucins could alter the barrier function of mucus and play a role in initiating and maintaining mucosal inflammation in Crohn's disease. To investigate the hypothesis of a mucin gene defect in Crohn's disease, we analyzed the expression of the different mucin genes in the ileal mucosa of patients with Crohn's disease and controls. mRNA expression levels were assessed by a quantitative dot blot analysis and compared (i) between healthy and involved ileal mucosa of patients with Crohn's disease and (ii) between healthy mucosa of patients with Crohn's disease and controls. Expression of the different mucin genes was heterogeneous among controls and patients with Crohn's disease, except for MUC6 in controls. Nevertheless, MUC1 mRNA expression was significantly decreased in the involved ileal mucosa of patients with Crohn's disease when compared to the healthy mucosa (p = 0.02). Moreover, the expression levels of MUC3, MUC4, and MUC5B were significantly lower in both healthy and involved ileal mucosa of patients with Crohn's disease compared to controls (p < or = 0.05). The decrease of expression levels of some mucin genes (more particularly MUC3, MUC4, and MUC5B) in both healthy and involved ileal mucosa suggests a primary or very early mucosal defect of these genes in CD.

Adolescent↗