Controlled study using wireless capsule endoscopy for the evaluation of the small intestine in chronic refractory pouchitis.

BACKGROUND: Pouchitis is a common long-term complication after ileal pouch anal anastomosis for ulcerative colitis. Chronic refractory pouchitis is a treatment-resistant condition that affects 5-15% of patients. AIM: To test the hypothesis of a small bowel involvement using wireless capsule endoscopy. MATERIAL AND METHODS: This is a single-blind, prospective, cohort study. Twenty-four patients: 16 were patients with chronic refractory pouchitis and eight, with a macroscopically and histologically normal ileal pouch, were considered as control subjects. Diagnosis of pouchitis was confirmed using the pouchitis disease activity index. All subjects were submitted to wireless capsule endoscopy procedure. Within 2 weeks before wireless capsule endoscopy, patients underwent a pouch endoscopy and a small bowel follow-through. Re-examination of the colonic surgical and histological specimens was also performed. RESULTS: One patient with chronic pouchitis was excluded because of incomplete bowel cleaning. At small bowel follow-through of 16 patients, two subjects (13%) showed only a focal ectasia of the middle ileum and a substenosis of the pouch. At wireless capsule endoscopy all the 15 evaluable patients with chronic pouchitis (100%) showed diffuse lesions from duodenum to ileum consisting of aphthae, erosions, erythema, atrophy, cobblestone, deep/fissural ulcers. CONCLUSIONS: This enteropathy needs further research, and wireless capsule endoscopy could be useful to show involvement of small bowel in patients with chronic pouchitis.

Endoscopic appearance of GERD: putative role of cell proliferation.

BACKGROUND: Erosive esophagitis is a frequent endoscopic feature in patients with gastro-oesophageal reflux disease. However, most of patients with heartburn/regurgitation have a non-erosive reflux disease. The reason for this heterogeneous impact of gastro-oesophageal reflux disease on oesophageal mucosa is unknown to date. AIM: To evaluate the cell proliferation status of oesophageal epithelium in both healthy normal subjects and patients with gastro-oesophageal reflux disease with or without erosions. MATERIALS AND METHODS: All the subjects underwent endoscopy and biopsies were taken at 5 cm from the squamo-columnar junction. Specimens were analysed both at histology and at transmission electron microscopy. Cell proliferation was evaluated by MIB1 immunostaining. Of the 85 subjects were studied, 10 were healthy controls with normal pH-testing and macroscopical, histological and ultrastructural patterns; 37 were patients with erosive esophagitis, and 38 patients with non-erosive reflux disease. RESULTS: At histology, of the 37 patients affected by erosive esophagitis, 30 had normal mucosa and 7 showed mild oesophagitis. One patient with non-erosive reflux disease showed signs of oesophagitis at histology. At TEM, all patients with gastro-oesophageal reflux disease had ultrastructural patterns of damage i.e. dilations of intercellular spaces (DIS), and all controls had a normal ultrastructural pattern. The mean (+/-SD) MIB1-LI values of normal subjects and non-erosive reflux disease and erosive oesophagitis patients were 62.2% (+/-9.1), 29.7% (+/-7.2) and 16.2% (+/-5.2), respectively; there were significant differences among the three groups (p<0.001). CONCLUSIONS: Oesophageal mucosa of patients with reflux symptoms presents a decrease in MIB1 immunostaining of 50% and 25% in non-erosive reflux disease and erosive esophagitis patients with respect to normal subjects.

Ex vivo HR-MAS Magnetic Resonance Spectroscopy of human gastric adenocarcinomas: a comparison with healthy gastric mucosa.

The present study reports the characteristics of the biochemical profile of human gastric adenocarcinoma in comparison with that of healthy gastric mucosa, using ex vivo HR-MAS Magnetic Resonance Spectroscopy. Healthy human mucosa is mainly characterized by the presence of small metabolites (more than 50 identified) and macromolecules, whereas the adenocarcinoma spectra are dominated by the presence of signals due to triglycerides, whose content on the contrary is very low in healthy gastric mucosa. The use of spin-echo experiments enable us to detect some metabolites in the unhealthy tissues and to determine their variation with respect to the healthy ones. We have observed that the Cho:ChoCC ratio changes from 20:80 in the healthy tissues to 80:20 in the neoplastic gastric mucosa.

Rectal cell proliferation and colon cancer risk in ulcerative colitis.

Cell proliferation kinetics of 30 patients affected by extensive ulcerative colitis in remission have been studied with autoradiography of rectal biopsies incubated with tritiated thymidine. The results have been compared with those of 20 control subjects without evidence of colonic diseases, and of 16 patients with multiple nonfamilial colonic adenomas. The labeling index was similar in the three groups (P = NS). On the contrary, the labeling frequency (SEM) in the upper 40% of the crypt (phi h value) was 0.04 +/- 0.01 in controls, 0.16 +/- 0.02 in ulcerative colitis, and 0.10 +/- 0.01 in adenoma patients (P less than 0.001 ulcerative colitis versus controls, P less than 0.01 adenomas versus controls, P = NS ulcerative colitis versus adenomas). The distribution of phi h values in ulcerative colitis showed a bimodal trend with 22 patients having mean phi h values similar to adenoma patients (0.10 +/- 0.01) and 8 with higher values (0.30 +/- 0.02). No relationship was found between phi h values and duration of colitis, age of patients, or age at onset of symptoms. These data show that cell kinetics studies can detect patients at particularly high risk of colon cancer, and that additional factors should determine colon cancer risk level in ulcerative colitis.

Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis.

It has been suggested that colon cancer risk in ulcerative colitis (UC) is correlated to a reduced bioavailability of folate. We studied the effects of folate supplementation on the pattern of rectal cell proliferation in patients affected by long-standing UC. In the rectal mucosa of these patients, an expansion of proliferating cells to the crypt surface is found frequently. This abnormality is considered an intermediate biomarker in chemoprevention trials. Twenty-four patients (13 males; age, 26-70 years; UC duration, 7-34 years) with UC in remission for 1 month at least were assigned randomly to one of the following treatments: (a) folinic acid (15 mg/day) or (b) placebo. Cell proliferation was analyzed through immunohistochemistry on sections of rectal biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine. Fragments were taken at admission to the study and after 3 months of treatment. As compared to the baseline values, after 3 months of therapy in patients treated with folinic acid, a significant reduction of the frequency of occurrence of labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836 +/- 0.0278 versus 0.1023 +/- 0.0255; P < 0.01). On the contrary, no significant proliferative changes were observed in the placebo group. These results suggest that folate supplementation contributes to regulating rectal cell proliferation in patients with long-standing UC. These findings may be significant for chemoprevention of colon cancer in these patients.

Circadian variations of rectal cell proliferation in patients affected by advanced colorectal cancer.

The circadian rhythm of the rectal cell proliferation was studied in five patients affected by advanced colon cancer. Biopsies were taken from apparently normal mucosa at 10 cm from the anal verge, every 6 h in a 24-h period. Fragments were incubated for 1 h in a culture medium containing bromodeoxyuridine (BrdUrd). As compared with the mean 24 h values, the percentage of BrdUrd-labelled cells in the crypts (Labelling Index, LI) was lower in the specimens collected at 10.00 PM (P = 0.02) The LI in such biopsies was also lower than the LI observed at the baseline time, 10.00 AM (P = 0.001) The results suggest that the rectal cell proliferation in patients with advanced colon cancer fluctuates during the day. The study of the rhythmicity of the intestinal cells may be useful to modulate the infusion of antiproliferative agents to prevent damage of the normal colorectal mucosa.

Pantoprazole, azithromycin and tinidazole: short duration triple therapy for eradication of Helicobacter pylori infection.

BACKGROUND: Azithromycin is an acid-stable macrolide that achieves remarkably high concentrations in gastric tissue, persisting above the MIC90 for Helicobacter pylori over a period of 5-days, after a single 500 mg oral dose. AIM: To evaluate and compare the efficacy, safety, and tolerability of two eradicating regimens of pantoprazole, azithromycin and tinidazole. METHODS: A total of 100 consecutive symptomatic H. pylori-positive patients received pantoprazole 40 mg b.d. for 1 week, and were randomly assigned to either azithromycin 500 mg o.m. and tinidazole 500 mg b.d. during the first 3 days (early group, n=50) or during the last 3 days of therapy with pantoprazole (late group, n=50). H. pylori status was assessed by histology and rapid urease test at entry and by histology and 13C-urea breath test 1 month after the end of the therapy. RESULTS: Ninety-nine patients completed the study. H. pylori was eradicated in 86% of patients in the early group (intention-to-treat 86%) and in 88% of patients in the late group (intention-to-treat 88%). CONCLUSIONS: This short triple therapy is effective for H. pylori eradication. The compliance was excellent and side-effects negligible. Moreover, the pantoprazole pre-treatment did not modify the efficacy of the therapy.

Dilated intercellular spaces as a marker of oesophageal damage: comparative results in gastro-oesophageal reflux disease with or without bile reflux.

BACKGROUND: The dilation of oesophageal intercellular spaces, clearly apparent in transmission electron microscopy images, is a marker of cellular damage induced by acid. AIM: To analyse the presence of dilated intercellular spaces and to quantify the scores in controls and in patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux accompanied by erosive or non-erosive reflux disease. METHODS: Thirty-eight symptomatic patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux and 12 asymptomatic controls, classified on the basis of pH-metry and bilimetry, underwent endoscopy. Six tissue biopsies were taken from the normal mucosa for light microscopy and transmission electron microscopy evaluation. Dilated intercellular spaces were measured on photomicrographs of the specimens (at least 100 transects were measured for each patient). RESULTS: Twenty-two patients with gastro-oesophageal reflux disease had normal macroscopic mucosa but, at histology, five patients with erosive gastro-oesophageal reflux disease had mild oesophagitis and one had moderate oesophagitis. Seven patients with duodenal gastro-oesophageal reflux had normal mucosa, whilst three with erosive duodenal gastro-oesophageal reflux had mild oesophagitis at histology. At transmission electron microscopy, all controls had dilated intercellular spaces of less than 1.69 microm. Each symptomatic patient had a mean dilated intercellular space value and a mean value of the maximum dilated intercellular space at least three or more times greater than that in controls (P < 0.001). No statistical differences were observed between erosive and non-erosive oesophagitis. CONCLUSIONS: The dilated intercellular space is an extremely sensitive marker of damage in gastro-oesophageal reflux disease, duodenal gastro-oesophageal reflux and non-erosive reflux disease, and serves as the most appropriate marker of damage evaluation in non-erosive reflux disease reported to date. A mean dilated intercellular space of 0.74 micro m provides a cut-off score for damage. No quantitative or qualitative differences in dilated intercellular space scores were found between pure and mixed acid reflux.

Cell proliferation and ultrastructural changes of the duodenal mucosa of patients affected by familial adenomatous polyposis.

Patients affected by familial adenomatous polyposis (FAP) are at risk of developing duodenal neoplasia. Our objective was to detect early abnormalities of the epithelial cell proliferation and ultrastructure of apparently normal duodenal mucosa of FAP patients. Biopsy specimens were taken from the duodenal mucosa. Cell proliferation was studied by immunohistochemistry with proliferating cell nuclear antigen (PCNA), and ultrastructure, by transmission electron microscopy. We found that the PCNA labeling index for duodenal mucosa of patients with FAP was higher in comparison to the case of hospital controls without cancer risk (P = 0.019). Moreover, ultrastructural changes related to an impairment of cell adhesion function were found in all biopsies of FAP patients but not in the duodenal mucosa of the controls. We conclude that alterations of cell proliferation kinetics and epithelial adherens junction structures were phenotypic characteristics of histologically normal duodenal mucosa of FAP patients. These abnormalities may be considered as intermediate biomarkers of neoplasia and potential surrogate endpoints in chemoprevention studies.

Serum pepsinogen I and II concentrations and IgG antibody to Helicobacter pylori in dyspeptic patients.

AIMS: To investigate the association between histologically confirmed gastritis, carriage of Helicobacter pylori and pepsinogen (PG) I and PG II concentrations. METHODS: Prospective study of 81 dyspeptic patients undergoing upper gastrointestinal endoscopy was made. The extent of gastric mucosal inflammation and the presence of H pylori was determined, and serology to evaluate PG I and II concentrations and IgG titres to H pylori was carried out. RESULTS: The presence of H pylori was strongly correlated with high IgG antibody titres to H pylori and gastritis. Patients who were H pylori positive had significantly higher PG I and PG II concentrations and a significantly lower PG I:PG II ratio than patients who were negative for H pylori. In 13 patients with duodenal ulcer and H pylori positive gastritis serum PG I concentrations were significantly higher than in H pylori positive patients without duodenal ulcer. Significant correlations were found between the age of patients and serum PG II, the PG I:PG II ratio, IgG antibodies to H pylori, the severity of body gastritis and H pylori infection, and between the degree of gastritis in the body of the stomach and the PG II concentration. CONCLUSIONS: Serum PG I and II concentrations, together with a fall in the PG I:PG II ratio, could be used as predictors of H pylori infection as well as serum IgG antibody response to H pylori.

HCV infection and chronic active hepatitis in alcoholics.

Histological signs of chronic active hepatitis were found in 11/41 (27%) patients with chronic alcoholic liver disease. All these 11 patients tested positive for antibodies to HCV and no other causes of chronic hepatitis were found.

Molecular characterization of human gastric mucosa by HR-MAS magnetic resonance spectroscopy.

The present study was aimed at identifying the molecular profile characteristic of the healthy human gastric mucosa. Ex vivo HR-MAS magnetic resonance spectroscopy performed at 9.4 Tesla (400.13 MHz for (1)H) on gastric specimens collected during endoscopy, permits the identification of more than forty species giving a detailed picture of the biochemical pattern of the gastric tissues. These preliminary data will be used for a comparison with gastric preneoplastic and neoplastic situations. Moreover, the full knowledge of the biochemical pattern of the healthy gastric tissues is the necessary presupposition for the application of magnetic resonance spectroscopy directly in vivo.

Cancer surveillance in ulcerative colitis: critical analysis of long-term prospective programme.

BACKGROUND: Patients with longstanding ulcerative colitis are at increased risk of colorectal cancer. In the literature, no agreement has yet been reached regarding prevention strategies. Our report sums up a prospective study started in 1980. METHODS: A total of 65 patients affected by ulcerative colitis for more than seven years were admitted to a regular colonoscopic and biopsy follow-up programme. RESULTS: Some 20 years after the beginning of the study, 23 (35.3%) patients have been operated upon, 2 patients have died but not from cancer 29 (44.66%) patients have abandoned the programme. Only 11 (16.9%) patients have remained under colonoscopic surveillance. CONCLUSION: These results cast some doubts on the significance of such a programme and on its long-term feasibility.

Morphologic and cytoproliferative patterns of duodenal mucosa in two patients after long-term total parenteral nutrition: changes with oral refeeding and relation to intestinal resection.

The morphologic and cytoproliferative patterns of the duodenal mucosa of two adult patients, one of whom had a short bowel, were evaluated after more than 2 months of postoperative total parenteral nutrition and 2 and 12 months after the resumption of oral alimentation. Morphometric analysis was performed on routinely processed duodenal biopsies. Cell proliferation was evaluated by means of in vitro bromodeoxyuridine uptake. The results were compared with those obtained in five healthy controls. After parenteral nutrition, patients showed significantly lower villus height and crypt depth than those of controls and a normal bromodeoxyuridine labeling index. After 2 months of refeeding, villus and crypt returned to normal, and the labeling index was increased. After 12 months of oral refeeding, labeling index, villus height, and crypt depth were similar to those of controls. The patient with the short bowel showed a number of cells per unit length of villus and crypt significantly greater than those of the controls and of the patient who underwent shorter intestinal resection. In human duodenal mucosa, (1) hypoplasia develops after long-term total parenteral nutrition; (2) mucosal recovery occurs through an increased cell proliferation after oral refeeding; and (3) extensive small bowel resection determines the development of relative hyperplasia.

Quantitative analysis of intrahepatic bile duct component in normal adult human liver and in primary biliary cirrhosis.

The volume density of bile ducts in adult normal liver has been analyzed in order to provide stereometric parameters to which refer on performing quantitative evaluations of bile duct loss in acquired liver diseases. Five livers were studied by applying a semi-automatic image analysis system (ASM 68K Leitz) to histological sections. No significant differences (P > 0.10) were found for all measures and the following values were derived from the pooled data: (1) mean % volume of bile ducts in liver = 0.318 +/- 0.171; (2) mean % volume of portal tracts in liver = 4.351 +/- 2.860; (3) mean % volume of bile ducts in portal tracts = 6.567 +/- 3.813. The parallelism of bile duct to arterial components of portal tracts was also investigated and expressed as the ratio of their respective volume fractions (mean ratio = 1.72). The validity of the obtained parameters was tested by comparing them with values determined in five cases of primary biliary cirrhosis (PBC). All PBC cases showed a marked decrease in both bile duct % volume in liver (ranging between 0.028 and 0.057) and bile duct % volume in portal tracts (ranging between 0.673 and 0.914), as well as inversion of the bile duct to artery volume ratio in portal tracts (ranging between 0.246 and 0.437).

[2 cases of Apud cell tumors of the rectum and colon]. / Due casi di tumori a cellule Apud del retto-colon.

Two cases of Apud cell tumour of the rectosigmoid are presented. The question of gross diagnosis and the therapeutic efficacy of polypectomy are discussed. Lastly, an account is given of the morphological, functional and embryogenetic features of these tumours.

[The aberrant pancreas in gastro-duodenal disease. A clinical, endoscopic-bioptic study]. / Il pancreas aberrante nella patologia gastro-duodenale. Studio clinico ed endoscopico-bioptico.

30 instances of aberrant pancreas were noted in 13,620 routine gastroduodenoscopies (0.22%), usually in the antrum or duodenum (antrum 83.5%, cap 6.6%, D2 6.6%). Symptoms, where present, took many forms and were aspecific, since they were related to size and site. The difficulties surrounding conventional methods of diagnosis are explained. Radiology reveals local alteration in 80% of cases, though its offers formally useful data in only 10%. Endoscopy and oriented biopsy partly make up for this inadequancy, because an aberrant pancreas may present as an atypical, nonumbelicated form that cannot be endoscopically distinguished from other benign growths. In addition, biopsy of the pancreas may be difficult in a submucosal site. Given the relative inefficacy of even the most recent techniques, perendoscopic polypectomy is proposed as a means of combining optimum diagnosis and radical treatment.

[Our experience with the effectiveness and tolerance of ibuproxam in rheumatology]. / Nostra esperienza sull'efficacia e tollerabilità dell'ibuproxam in reumatologia.

The tolerance and effectiveness of Ibuproxam were investigated in 54 patients with arthrosis, R.A., ankylosing spondylitis, and fibrositis. Statistically significant reduction of pain at the end of the treatment was accompanied by decreased limitation of joint movement and morning stiffness. Simultaneous investigation of clinical and biological tolerance showed that the drug is infrequently responsible for side-effects that are always of negligible importance. Oesophagogastroduodenoscopy in subjects with a prior history and/or signs of active pathology of the upper digestive tract did not reveal exacerbation or recrudescence of lesions, nor the appearance of acute lesions.

[Diagnosis of chronic reflux esophagitis. Role of endoscopic and histological examination]. / Diagnosi dell'esofagite cronica da reflusso. Ruolo dell'esame endoscopico ed istologico.

Fibroendoscopic and histobioptic study of the distal oesophageal mucosa has been carried out in a series of patients suffering from gastro-oesophageal regurgitation. The regurgitation condition was verified and its extent established by means of anamnestic, spot-fluorographic and manometric-pHmetric investigations. On the basis of the analysis of relations between the extent of the oesophagitis assessed on the basis of endoscopy and that arising out of microscopic examination of the biopsy, it is concluded that there is no complete correspondence between the two techniques insofar as endoscopy can give false positive or false negative results. On the basis of these results and of those of functional investigations, histology is considered desirable even when the oesophageal mucosa is normal, if there are clinical and/or laboratory signs of gastro-oesophageal regurgitation.

[Acute inflammation of ileal reservoir after restorative ileoanal anastomosis]. / Infiammazione acuta del reservoir ileale dopo intervento di ileo-ano anastomosi.

Ileo-anal anastomosis (IAA) is a suitable surgical treatment for selected patients with ulcerative colitis or familial adenomatous polyposis. Acute inflammation of the ileal reservoir (pouchitis) is the most frequent late complication and is characterized by endoscopic and histological changes of acute inflammation similar to ulcerative colitis with abdominal and sometimes systemic symptoms. Between May 1984 and April 1993, 160 patients (103 male and 57 female) aged between 7 and 64 years (mean age 32.6) underwent IAA; twenty of these for familial adenomatous polyposis, 138 for ulcerative colitis and 2 for indeterminate colitis. After a mean follow-up of 41.8 months (range 1-108), 138 patients (86.3%) were symptoms free and twenty-two (16 male and 6 female-13.7%) who underwent IAA for ulcerative colitis, had pouchitis. Clinical, biochemical, endoscopic and histologic findings suggest pouchitis as a chronic recurrent disease similar to inflammatory bowel disease. In conclusion, the etiopathology of this new entity is unknown. Bacterial overgrowth is one of the most popular hypothesis, but the onset of the acute inflammation observed by us only in patients with previous ulcerative colitis and in some cases during the period of protective ileostomy suggests a multifactorial pathogenesis.