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Endoscopic biopsy technique for acquiring larger mucosal samples.

Biopsies of the esophagus, stomach, and intestine are most often obtained using the traditional advance-and-close method with flexible endoscopes by extending an open forceps several millimeters beyond the endoscope tip to sample the mucosa, all under direct vision. We developed an alternative "turn-and-suction" endoscopic biopsy technique that permits the acquisition of larger mucosal samples. The biopsy forceps is advanced into the lumen, opened, and withdrawn backward until it is flush with the endoscope tip. Next, the endoscope tip is turned gently into the wall while air is suctioned from the lumen, and the biopsy forceps is very slightly advanced and then closed, usually without direct visualization. After straightening the endoscope tip, the biopsy is obtained by withdrawing the forceps and avulsing a superficial mucosal sample. By using this new method, we have safely taken over 10,000 biopsies without complications in endoscopic surveillance research protocols in patients at risk for gastrointestinal cancer. To compare the sizes of biopsies obtained with these two techniques, histologic sections of 341 mucosal samples from 12 patients with chronic ulcerative colitis were studied retrospectively. The mean greatest length of biopsy sections using the traditional technique was 4.72 mm, and using our new technique was 7.35 mm (56% longer). The turn-and-suction endoscopic biopsy method is best applied when flat mucosa is randomly sampled to seek microscopic pathologic changes that are not visible endoscopically, and may be advantageous for various non-histologic research analyses of gastrointestinal mucosa which are limited by tissue quantity.

Adult↗

Effect of preinduction of heat shock proteins on acetic acid-induced colitis in rats.

In order to study the cytoprotective function of heat shock proteins (HSPs) in vivo, the effect of preinduction of HSPs by hyperthermia on acetic acid-induced colitis was investigated. Expression of 60-kDa, 72-kDa, and 90-kDa heat shock proteins (HSP60, HSP72, and HSP90, respectively) in rat colonic mucosa was investigated by Western blot analysis and immunohistochemical study before and after hyperthermia. Following pretreatment with or without hyperthermia, the rats received intrarectal infusion of various doses of acetic acid. The colonic mucosal damage was evaluated by macroscopic and microscopic assessments 24 hr after the intrarectal infusion of acetic acid. Expression of HSPs was significantly increased by hyperthermia in rat colonic mucosa. Immunohistochemical study also showed the increments of HSPs in the colonic mucosal cells after hyperthermia. Acetic acid-induced colitis was dramatically prevented by pretreatment with hyperthermia when HSP72 and HSP90 were preinduced. On the other hand, induction of HSP60 did not correlate with mucosal protection. Our findings suggest that HSP72 and HSP90 may have cytoprotective function against acetic acid-induced mucosal damage. These results may be important for understanding the mechanism of "adaptive cytoprotection" mediated by HSPs.

Acetic Acid↗

Diversion colitis and involution of the defunctioned anorectum.

To measure the effects of defunction in the anorectum, 12 patients (seven men and five women aged 59 (44-81) years) were studied after the Hartmann operation. The operation was for septic complications of diverticular disease in nine and sigmoid carcinoma in three patients. Physiology studies were undertaken 1 and 3 months after surgery, and diversion colitis was assessed endoscopically and by mucosal biopsy at 3 months. There was no change in anal sphincter function by three months. Proctometrogram studies, however, showed an appreciable decrease in rectal volume in all cases, by a mean of 35% of the 1 month volume. The maximum tolerable volume at 1 month was 157 (111-210) ml and at 3 months 87 (71-145) ml; p < 0.01. There was no change in rectal sensation or compliance. Erythema and granularity without gross erosions or ulceration were found at endoscopy. Histology showed abnormalities in all cases by 3 months. The characteristic features were of a chronic inflammatory cell infiltrate with surface exudate, microscopic erosions, and lymphoid follicular hyperplasia. Crypt abscesses were not a feature at this stage and there was no distortion of crypt architecture. After defunction the previously normal rectum is affected by diversion colitis which, at 3 months, is mild but has characteristics that distinguish the changes from those of inflammatory bowel disease. It is associated with progressive rectal stump involution.

Adult↗

Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat.

OBJECTIVES: Inulin stimulates intracolonic generation of butyrate and growth of lactic acid bacteria. This study investigated whether inulin protects against colitis. METHODS: Rats with dextran sodium sulfate colitis received inulin either orally (1% in drinking water, or 400 mg/day) or by enema. Matched groups received vehicle. In addition, fecal water obtained from inulin-fed rats was administered by enema to rats with colitis and compared with fecal water from control rats. Finally, rats with colitis received daily enemas of either butyrate (at 40 or 80 mmol/L) or vehicle. Inflammation was assessed by eicosanoid asssay in rectal dialysates and MPO activity in colonic tissue. Mucosal lesions were blindly scored by microscopic examination. Luminal pH was measured from cecum to rectum by a surface microelectrode. RESULTS: Oral inulin prevented inflammation, as evidenced by lower lesion scores (p < 0.05), decreased release of mediators (p < 0.05), and lower tissue MPO (p < 0.05) as compared with controls. Inulin induced acidic environment (pH <7.0) from cecum to left colon and increased counts of lactobacilli. Fecal water from inulin-fed rats also reduced scores (p < 0.05) and inflammation (p < 0.05). However, inulin or butyrate enemas had no effect. CONCLUSIONS: Oral inulin reduces the severity of dextran sodium sulfate colitis. The effect seems to be mediated by modification of the intracolonic milieu.

Animals↗

Protective function of extrinsic sensory neurons in acute rabbit experimental colitis.

BACKGROUND/AIMS: Sensory nerves appear to have a protective effect against acute injury in the gastric mucosa. Their function in the intestine is unclear. METHODS: In this study an immune-complex model of colitis was used to induce inflammation in the distal colon with and without functional ablation of sensory neurons by capsaicin pretreatment. RESULTS: Colitis was more severe in the capsaicin-pretreated group than in the vehicle group 48 and 96 hours after induction of colitis. Neutrophil infiltration, expressed as inflammatory index, was significantly increased to 4.25 +/- 0.4 vs. 1.83 +/- 0.5 at 48 hours and to 2.66 +/- 0.6 vs. 1.65 +/- 0.3 at 96 hours in the capsaicin group and the vehicle group, respectively. The microscopic ulcer index also was significantly increased in the capsaicin-pretreated group compared with the vehicle group (63.3 +/- 10.6 vs. 3.3 +/- 2.4 at 48 hours, 20.0 +/- 8.4 vs. 1.5 +/- 1.1 at 96 hours). Immunoreactive substance P (SP) and calcitonin gene-related peptide (CGRP) contents were decreased in extracts of inflamed compared with uninflamed colon. CONCLUSIONS: These data suggest that sensory neurons have a protective role in an acute rabbit model of experimental colitis by release of sensory neuropeptides (SP, CGRP), which may modulate vascular tone and mucosal blood flow.

Animals↗

The pathology of experimental Corynebacterium equi infection in foals following intragastric challenge.

The intragastric inoculation of a suspension of Corynebacterium equi on five consecutive days induced severe ulcerative colitis, typhlitis, and lymphadenitis of colonic and cecal nodes in two ponies necropsied three weeks after infection. No gross lesions were observed in two ponies necropsied ten days after infection. A single inoculum of equivalent size failed to induce gross lesions in four ponies killed at ten or 20 days after infection. Microscopic lesions consistent with early C. equi infection of Peyer's patches were seen in two of the ponies killed ten days after infection. Only one small pulmonary abscess occurred in one foal, suggesting that intestinal lesions are not likely the usual precursor of pulmonary disease in naturally infected foals. The gross and microscopic lesions in the experimentally infected ponies were typical of the intestinal form of naturally occurring C. equi associated disease in foals.

Animals↗

[Value of omeprazole in the treatment of collagenous colitis].

The authors report the case of a patient suffering from collagen colitis in whom the administration of omeprazole achieved the rapid and total abolition of the clinical signs and a significant reduction of the collagen band (measurements determined over 10 cryptic spaces using a graduated micrometric ocular microscope). Although the outcome of this disorder is variable, with the possibility of spontaneous recovery or, more frequently, of remission, the authors consider, in their conclusions, that omeprazole may have a beneficial effect in this disorder even though the mechanism for this has not been established.

Administration, Oral↗

Vulvar lichen planus associated with ulcerative colitis. A case report.

BACKGROUND: Lichen planus (LP) is a common inflammatory dermatosis the diagnosis of which can be very complex when it affects the female genital area exclusively. The condition should be managed by both dermatologists and gynecologists because the association between vulvar LP and other immune-mediated disorders occurs frequently. CASE: Vulvar LP was diagnosed in 37-year-old woman whose past history was significant for ulcerative colitis (UC) since the age of 21. The oral mucosa and skin were completely unaffected, but whitish papules and plaques were seen diffusely on the whole vulvar region, which had become sclerotic and edematous. Microscopic examination of lesional tissue confirmed the diagnosis, showing classic histologic features in spite of the mixed and hypertrophic clinical variant. Oral therapy with cyclosporin at an initial dose of 250 mg/d led to complete remission within 3 months. CONCLUSION: This case is reported on for the rarity of isolated vulvar involvement by LP and for the excellent response to treatment.

Adult↗

Bacterial hemorrhagic enterocolitis.

Bacterial diarrhea can be classified into two clinical entities, noninflammatory diarrhea and inflammatory diarrhea syndromes. The latter type of diarrhea is characterized by bloody and puruloid mucus stool, and is often accompanied by fever, tenesmus, and severe abdominal pain. Pathogenic bacteria causing the inflammatory diarrhea syndrome include Salmonella, Vibrio, Shigella, enteroinvasive and enterohemorrhagic Escherichia coli, Campylobacter, Yersinia, Chlamydia, and Clostridium difficile. The pathologic changes in the inflammatory diarrhea syndrome range from a superficial exudative enterocolitis to a transmural enterocolitis with overt ulceration. This syndrome is also designated as bacterial hemorrhagic enterocolitis because of its usual manifestation by bloody diarrhea. The diagnostic approach needs information on the patient's age, travel history, epidemiological associations, sexual practice, and medical history, including usage of antibiotics. Bacterial information can be obtained by microscopic study, culture, and the identification of specific bacterial toxins. Flexible colonoscopy with biopsy is useful for the differentiation of bacterial hemorrhagic enterocolitis from idiopathic ulcerative colitis and ischemic colitis. Physicians should be familiar with the diagnostic modalities used to detect the specific pathogens causing hemorrhagic bacterial enterocolitis; namely, bacterial culture, serology, histology, and nucleic acid technologies.

Bacterial Infections↗

Induction of inflammatory bowel disease accelerates adenoma formation in Min +/- mice.

BACKGROUND: The accelerated incidence of colorectal carcinoma in individuals with inflammatory bowel disease suggests that cellular perturbation triggered by chronic inflammation is linked to the development of dysplasia and neoplastic transformation. To test the mechanistic links between these processes, we employed the following murine strains: (1) multiple intestinal neoplasia (Min) +/- mice, bearing a mutation in the adenomatous polyposis coli (APC) gene; (2) mice deficient in interleukin 10 (IL-10), which normally develop enterocolitis; and (3) Min +/-/IL-10 null mice, first developed in our laboratory. METHODS: Mice with either parental strain or the cross were sacrificed at time points ranging from 10 to 30 weeks of age. The small bowel and colon of 170 IL-10 null mice, 31 Min +/- mice, and 120 Min +/-/IL-10 null mice were examined microscopically. RESULTS: The number of flat adenomas was increased in the colons of the Min +/-/IL-10-/- mice, compared with the Min +/- mice (P = .0005). Neither colitis-type dysplasia nor carcinoma was increased in the Min +/-/IL-10 -/-, compared with the IL-10 null mice (P = .18). Mice deficient in IL-10 developed colitic-type dysplasia (P = .0001) or carcinoma (P = .0001) correlated with increasing inflammation. CONCLUSIONS: Breeding the Min +/- genotype into the IL-10 -/- background increased the incidence of colonic adenomas. Our studies demonstrate that acceleration of dysplasia and progression to invasion were associated with the degree of the inflammatory response in mice deficient in IL-10. These findings provide a novel system to dissect the pathways by which inflammatory mechanisms accelerate adenoma formation.

Adenoma↗

[Light and electron microscopic studies of relationship between colon carcinoma and schistosomiasis].

The light and electron microscopic observations were carried out in 50 cases of colon specimens. No remarkable morphologic differences were found between the epithelial cells of the mucosa with schistosomiasis, colitis and the normal specimens. Cells of the colon carcinoma also showed no significant difference from those of the colon carcinoma associated with schistosomiasis. Atypical changes in the epithelial cells were not seen in the areas both adjacent to and remote from the carcinoma and in the egg deposit areas. Under LM, changes were manifested in various degrees in degeneration and disassociation of mucosal cells in colitis (1), schistosomiasis (1) and carcinoma associated with schistosomiasis (8). Under EM, changes in mucosal muscle cells were seen in colon carcinoma (2) and carcinoma associated with schistosomiasis (5). Proliferation of fibroblasts and hyperchromasia of the nuclei were noted in 3 cases of carcinoma associated with schistosomiasis. The pathological changes mentioned above were more prominent in cases of carcinoma associated with schistosomiasis than in those of colon carcinoma alone. The authors believed that the cause was non-specific changes induced by the toxin of the egg mechanical effects rather than a direct carcinogenic action of the eggs, and that the non-specific changes implied no direct relationship between the development of colon carcinoma and schistosomiasis.

Adenocarcinoma↗

[Surgical treatment of Crohn's disease--recurrence and prognosis in operated cases].

We have experienced 40 cases of Crohn's disease from 1970 to 1984 and surgical treatments were performed in 22 cases. Ileocolitis was found in 10, ileitis in 6, colitis in 5 and appendix was involved in 1 case. Postoperative follow-up is accomplished in all cases. Recurrences are confirmed in 7 cases (35%). Microscopic findings at the resected stump showed no significant difference in recurrent rate. Recurrence was found in 2 of 6 inflammatory positive cases (33%). And 5 were recurred in 13 negative cases (38%). Mean recurred time, however, is shorter in positive cases (1 Yr 10 mos) compared with negative cases (4 yrs 7 mos). We have performed intraoperative endoscopy for the decision of the scope of resection in recent 7 cases, of which 2 cases recurred (follow-up time: 6 years). Quality of life in operated cases was almost good except 1 recurrent case. Even if operated case is recurred, patients are easily managed and leading in satisfactory life.

Crohn Disease↗

Value of counting colonic mucosal Ig-containing cells in the differential diagnosis of chronic inflammatory bowel disease.

AIMS: To investigate whether counting cells containing immunoglobulin (Ig) subclass in colonic biopsy specimens of patients with chronic inflammatory bowel disease, in addition to conventional histological evaluation, can improve the differentiation of patients with Crohn's disease from those with ulcerative colitis. METHODS: The colonic and rectal biopsy specimens of 40 patients with chronic inflammatory bowel disease, comprising 20 patients with Crohn's disease and 20 with ulcerative colitis, were used and sections were stained specifically for IgA, IgM, and IgG heavy chains using an indirect immune peroxidase method. The immunoglobulin subclass containing cells were counted using an ocular grid counting method in a light microscope. A linear stepwise discriminant analysis was performed on Ig subclass containing cell counts in combination with 16 reproducible histological features. The results of this discriminant analysis were compared with the results of the discriminant analyses in which only the histological features were used. RESULTS: Applying stepwise discriminant analysis, two histological features (an excess of histiocytes in the lamina propria and the villous or irregular aspect of the mucosal surface) in combination with IgMax were selected as the most discriminatory parameters that distinguish Crohn's disease from ulcerative colitis. IgMmax was defined as the maximum value of the mean percentage of IgM containing cells over all the biopsy locations. The use of this combination resulted in a better classification in 20% of the patients with Crohn's disease and in 9% of the patients with ulcerative colitis compared with the use of histological features alone. CONCLUSIONS: Morphometric enumeration of Ig subclass containing cells in colonic mucosal biopsy specimens has diagnostic value as a means of differentiating individual patients with Crohn's disease from those with ulcerative colitis.

Adolescent↗

Morphological and biochemical alterations in the jejunum following iodoacetamide-induced colitis in rats.

This study aims to describe the morphological alterations in the small and large intestines as well as the expression of some enterocyte enzymes and carriers in a rat model of iodoacetamide-induced colitis. Biopsies from the large and small intestines were taken at 1, 2, 4, 8, and 16 days postinduction and studied by light microscopy. The expressions of lactase, sucrase, aminopeptidase, and Glut-5 in the jejunum were studied by immunohistochemistry. Gene expressions of enterocyte lactase and sucrase were determined by RT-PCR using specific oligonucleotides. Microscopic examination of the large intestines revealed manifestations concordant with inflammation. Such alterations peaked at 2 days, were maintained to a lesser extent for 4 days, regressed by 8 days, and healed by 16 days. In the jejunum, the expression of lactase, sucrase, and aminopeptidase decreased 2 days after colitis induction, and recovered 2 days later. Similarly, Glut-5 expression decreased transiently with partial recovery by day 8. Compared with sham, gene expression of jejunal brush border enzymes sucrase and lactase showed a 4-fold increase in lactase and a 9-fold increase in sucrase after 4 days. We conclude that colitis can induce significant functional abnormalities in distant noninflamed small bowel regions.

Aminopeptidases↗

Dysplasia-associated polypoid mucosal lesion in a pelvic pouch after restorative proctocolectomy for ulcerative colitis.

A 32-year-old man with ulcerative colitis had a colectomy for toxic colitis. Later, a rectal mucosectomy was performed along with the creation of a pelvic pouch. In 1998, approximately 10 years after this staged restorative proctocolectomy was completed, endoscopic examination of the pelvic pouch detected a small mucosal polypoid mass lesion. Although the lesion had the macroscopic appearance of an inflammatory polyp, microscopic sections of the resected lesion revealed dysplastic changes. Endoscopic polypectomy was performed to remove the lesion, and further histological surveillance examinations of the pelvic pouch have not detected additional dysplastic mucosal changes.

Adult↗

Activation of eosinophils in the pathophysiology of ulcerative colitis.

We studied the role of eosinophils as effector cells in the pathophysiology of ulcerative colitis. In the active stage of this disease, the colonic mucosa exhibited infiltration of numerous eosinophils positive to the EG2 antibody, which reacts specifically with the secretory form of eosinophil cationic protein. Electron microscopic studies demonstrated that the eosinophils had specific granules in various stages of degranulation. Hence, it is strongly suggested that the eosinophils infiltrating the inflamed mucosa are activated and may induce tissue damage during the degranulation and release of this cationic protein. Changes in the levels of serum eosinophil cationic protein in 14 patients who remained for in long-term remission were studied. Four of these patients showed persistently high concentrations of eosinophil cationic protein (equal to or greater than 30 micrograms/l) and persistently high percentage (mean, 30.2%) of hypodense eosinophils (specific gravity < 1.082) in the peripheral blood. Such findings were associated with mild active disease at colonoscopy. These features suggest that the activation of eosinophils is one of the factors that contribute to the chronic inflammation in ulcerative colitis.

Biopsy↗

Juvenile polyposis coli: a facultative precancerosis with some similarities to ulcerative colitis?

We investigated the case of a 13-year-old male with juvenile polyposis (JP) to determine the extent of intraepithelial neoplasia and associated genetic changes, as well as cellular proliferation, within these polyps using immunohistochemistry with antibodies against p53, bcl-2, and Ki-67. Examination of the total proctocolectomy specimen revealed 70 polyps. The 18 largest polyps were investigated microscopically and disclosed the typical hamartomas with frequent erosions of the surface epithelium and reparative changes. Only one polyp showed focal low-grade intraepithelial neoplasia. The immunohistochemical studies revealed an expression of p53 and an abnormal Ki-67 pattern of the surface epithelium only within the neoplastic area. These findings may hint at a possible pathogenetic mechanism for the evolution of colorectal cancer in JP. As in ulcerative colitis, carcinomas in JP may develop along a dysplasia-carcinoma sequence resulting from permanent mechanical insults, inflammation, and repair rather than from an adenoma-carcinoma sequence as in familial adenomatous polyposis (FAP).

Adenomatous Polyposis Coli↗

Is biopsy necessary if colonoscopy is normal?

Multiple endoscopic biopsies were taken from 100 consecutive patients who had a macroscopically normal colon at colonoscopy. Of these, 78 were regarded as histologically normal; 13 cases of melanosis coli, 7 cases of intestinal spirochetosis, and 2 cases of collagenous colitis were identified. In no cases was there histologic evidence of inflammatory bowel disease. Histologic abnormality could not be predicted by retrospective analysis of various clinical, hematologic and biochemical data. In individual subjects the microscopic abnormality was present to a varying degree in all biopsies, except in intestinal spirochetosis where patchy distribution occurred in some subjects. It is therefore concluded that significant pathology may be missed without biopsy of the apparently normal colon, but in order to reduce the workload of pathology departments and shorten the duration of the examination two biopsies from the hepatic flexure and sigmoid colon may be adequate.

Adolescent↗