COX-2, CDX2, and CDC2 immunohistochemical assessment for dysplasia-carcinoma progression in Barrett's esophagus.

BACKGROUND: Immunohistochemical changes associated with development of cancer in Barrett's esophagus offer potential areas of intervention to prevent and manage esophageal cancer. AIMS: To assess the role of cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2/cyclin-dependent kinase 1 in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. PATIENTS AND METHODS: Specimens from 46 patients with Barrett's esophagus (39% without dysplasia, 33% with dysplasia and 28% with adenocarcinoma) were stained for cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2. RESULTS: Cyclooxygenase 2: No expression differences between groups were found, except for adenocarcinomas (p=0.04). Caudal-type homeobox transcription factor 2: Nuclear positivity decreased from Barrett's esophagus without dysplasia (71.6%), to Barrett's esophagus with low grade dysplasia (35.3%), to Barrett's esophagus with high grade dysplasia (17.14%); in adenocarcinoma these percentages were intermediate between high and low grade dysplasia (30.5%). Cell division cycle 2: Expression on deeper glandular structures was 40% in Barrett's esophagus without dysplasia, 55.47% in Barrett's esophagus with dysplasia, and 63.84% in adenocarcinoma, with no statistical differences between groups. Concerning cells of the superficial layer, Barrett's esophagus with low grade dysplasia expressed focal positivity (p=0.0001 vs. no dysplasia); Barrett's esophagus with high grade dysplasia displayed diffuse positivity (p=0.0001 vs. no dysplasia and low grade dysplasia). A diffuse positivity was found in Barrett's esophagus with adenocarcinoma (p=0.0001 vs. no dysplasia and low grade dysplasia). CONCLUSIONS: Further evaluation of cyclooxygenase 2, cell division cycle 2 and caudal-type homeobox transcription factor 2, in association with morphology, might help to improve the accuracy of diagnosis and be useful for the clinical-pathological assessment of patients with Barrett's esophagus.

Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease.

BACKGROUND: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis. AIMS: To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis. PATIENTS: Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls. METHODS: Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively. RESULTS: Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p = 0.103 and p = 0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p = 0.0003) reduced compared with controls, as were glial cells (p = 0.0041). CONCLUSIONS: Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.

Immunological markers anti-saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: a helpful diagnostic tool.

AIM: Nowadays the diagnosis of inflammatory bowel disease (IBD) and the differentiation between Crohn disease (CD) and ulcerative colitis (UC) is still based on morphological changes identified at endoscopy, radiology, and histopathology. In 5-15% of cases this differentiation is not possible (diagnosed with indeterminate colitis). METHODS: We evaluated if recently developed commercial kits for the determination of anti-Saccharomyces Cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) are useful in differentiating cases of UC from CD diseases with a consequent reduced number of undefined colitis and improved clinical management. Sera from 56 consecutive patients with a clinical diagnoses of IBD were evaluated in a blinded fashion for the presence of ASCA IgA and IgG and ANCA IgG with 2 different diagnostic methods: indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). RESULTS: In our cases we observed good agreement between histopathological examination and laboratory results and the combined use of ASCA and ANCA yielded a correct diagnosis in 93% of patients with CD and in 97% of the UC patients. CONCLUSIONS: We confirm the value of the test for the diagnosis of CD and UC and the differentiation from other forms of colitis.

Gastric metaplasia and small bowel ulcerogenesis in a case of ulcerative jejunitis not related to celiac disease.

The possible relationship between gastric metaplasia and ulcerative lesions in an unusual case of ulcerative jejunitis not related to celiac disease and with extensive gastric metaplasia is discussed. Previous studies have described gastric metaplasia in duodenal ulcers on the basis of endoscopic data, and some authors maintain that acid secretion in metaplastic mucosa could represent a pathogenetic factor of ulcerogenesis, with a self-amplifying mechanism. In the absence of functional evidence, we could provide data, in a case of ulcerative jejunitis, about morphologic signs of acid secretion in gastric metaplastic epithelium using an antibody against HMFG-1, a good marker of acid-secreting fundic cells. Metaplastic areas demonstrated a focal positivity for HMFG-1, and these finding are suggestive of local acid secretion.

Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease?

BACKGROUND: The counting of intraepithelial lymphocytes (IELs) in the villous tips of architecturally normal small bowel biopsy specimens was proposed as a method to measure mucosal infiltration in gluten sensitive patients. AIMS: To apply this straightforward method in duodenal biopsy specimens from patients affected by potential coeliac disease (PCD) to verify whether it can discriminate these patients from controls. METHODS: Paraffin wax embedded duodenal sections from 11 patients affected by PCD were stained with an antihuman CD3 antibody. Sections from 19 patients affected by treated coeliac disease (TCD) and 17 patients in whom coeliac disease was excluded were stained with the same antibody to serve as controls. The slides were examined blindly. IELs/20 enterocytes in five randomly chosen villous tips were counted. Patients affected by PCD were all on a gluten containing diet. They had an architecturally normal duodenal mucosa and were positive for endomysial antibody. Both TCD and non-coeliac controls were negative for endomysial antibody. RESULTS: The mean villous tip IEL scores were 4.6 (SD, 1.5; range, 1.4-7.8) in non-coeliac controls, 7.9 (SD, 4.0; range, 2.0-18.6) in TCD, and 9.2 (SD, 4.7; range, 5.8-21.8) in patients with PCD. The difference between PCD and non-coeliac controls was significant. CONCLUSIONS: This is a very simple and sufficiently reliable method to count IELs. In patients with an architecturally normal duodenal mucosa, the IEL count in villous tips helps to distinguish between patients with PCD and non-coeliac controls.

[The hyperplasia-adenoma sequence: a case supporting this hypothesis]. / La sequenza iperplasia-adenoma: un caso a sostegno di questa ipotesi.

We described the morphological, histochemical and immunohistochemical findings of a polyp detected in the left colon (splenic flexure) in which the diagnosis was atypical hyperplastic polyp. The description is focused on the capability of a hyperplastic polyp to evolve into adenomatous tissue through different modalities.

[Ultrasonography and computerized tomography in the diagnosis of gallbladder carcinoma]. / Ecografia e tomografia computerizzata nella diagnosi del carcinoma della colecisti.

The US and CT images of 40 surgical patients with histologically proved gallbladder carcinoma were retrospectively reviewed. The radiologic diagnosis was correct in 22 patients (55%). Gallbladder carcinoma patterns were: an intraluminal mass (type I) (7 patients, 17.5%), focal or diffuse wall thickening (type II) (5 patients, 12.5%) a mass replacing the gallbladder (type III) (10 patients, 25%). In 5 patients with type I or II gallbladder carcinoma, US and CT diagnosis was made easier by the presence of associated findings--i.e., liver infiltration and/or metastases, lymphadenopathy, dilated intrahepatic ducts, ascites. In 7 patients a gallbladder carcinoma was suspected in the presence of a small intraluminal mass (6 cases) or of focal wall thickening (1 case), with no stones and with dilated intrahepatic biliary ducts. In the extant 18 patients (45%) the radiologic diagnosis was: polyps (6 cases), stones with cholecystitis (11 cases) and empyema (1 case). US is the examination of choice in the diagnosis of gallbladder and biliary ducts conditions, but several diagnostic problems may arise in the differentiation from polyps and acute inflammatory disease. CT better demonstrates gastrointestinal tract invasion and lymphadenopathy, which can be a valuable finding for treatment planning.

[Calcification of the basal nuclei in hypoparathyroidism. The computed and magnetic resonance tomographic aspects]. / Calcificazione dei nuclei della base nell'ipoparatiroidismo. Aspetti con tomografia computerizzata e con risonanza magnetica.

Six female patients with hypoparathyroidism (2 idiopathic and 4 postoperative cases following total thyroidectomy) were examined with brain CT scans; 4 of them underwent MR exams too. Two patients presented with no symptoms, 4 exhibited extrapyramidal syndrome, tetany, fainting seizures or ischemic attacks and only 2 presented with abnormal calcium-phosphorus balance. CT showed calcifications of the basal nuclei in 5 patients. The caudate nucleus was always affected (100%). The calcifications were in the putamen, globus pallidus and thalamus in 4 cases (80%), in the dentate nuclei, centrum semiovale and cerebral cortex in 2 cases (40%) and in the mesencephalic gray matter in 1 case (20%). In one case only CT failed to detect the abnormalities, which were nevertheless depicted by MRI. In the other 3 patients who underwent MRI, CT findings were confirmed as low-signal areas on SE T1- and T2-weighted MR scans where the calcifications were present, but areas of increased signal intensity were also evident on SE T2-weighted images; in one patient, low-signal areas were surrounded by a ring of increased signal intensity on SE T1-weighted scans. Low-signal areas reflect an early stage of calcium deposition; on the other hand, high-signal areas are probably caused by proteins and mucopolysaccharides or by liquid pools secondary to endothelial membrane incompetence. CT better defined the site and extent of the calcifications which may be found in both idiopathic and postoperative hypoparathyroidism, in symptomatic or asymptomatic patients. On the other hand, MRI seems to be capable of depicting the various stages of calcium deposition on the basis of the presence of reduced or increased SE T2 signal intensity.

[Role of computerized tomography in the densitometric assessment of lithiasis of the gallbladder]. / Ruolo della tomografia computerizzata nella valutazione densitometrica della litiasi della colecisti.

Radiolucent gallstones frequently contain significant calcium deposits. Their detection is important to select the patients to submit to medical gallstone dissolution. Since CT facilitates the identification of calcifications undetected at conventional radiologic procedures, 60 patients were studied with CT. All of them had US confirmation of cholelithiasis and in the whole of cases an X-ray examination of the right upper abdominal quadrant was performed (for the identification of radiopaque stones), together with oral cholecystography (to evaluate gallbladder function). CT attenuation values of the stones were measured and the patients subsequently divided into 2 groups; the threshold value was 50 HU: below it, the stones were considered hypo- or isodense (group I); above it, they were considered hyperdense (group II). Later on, 28 patients (14 from group I and 14 from group II) were selected for chemical dissolution with ursodeoxycholic acid over a 1-year period. US examinations were performed at 6 and 12 months. Seventy per cent of the patients in group I responded to treatment (50% with complete stone dissolution and 20% with partial dissolution), whereas no patient in group II had complete dissolution and only 30% had partial response.

Computed tomography in predicting gall stone solubility: a prospective trial.

This prospective study was undertaken to evaluate the correlation between densitometric values of gall stones assessed by computed tomography and the success rate of litholytic therapy in 28 patients eligible for oral treatment. A densitometric study of the stones was performed in all patients before treatment. A cut off point of 60 Hounsfield units (HU) was chosen to divide the subjects into two groups--group 1, 14 patients with low density stones (less than 60 HU) and group 2, 14 patients with high density stones (greater than 60 HU). All patients were treated with ursodeoxycholic acid (8-10 mg/kg/day) for 12 months and followed up by ultrasound. In group 1, dissolution was complete in 50% of the patients and partial in a further 20%. In group 2 patients, complete dissolution was not observed but 33% showed partial dissolution. The number of patients with total dissolution at 12 months was significantly higher in group 1 compared with group 2 (p less than 0.02). These results suggest that computed tomography can be used to select patients with a better likelihood of successful stone dissolution after bile acid therapy.

Association between habitual coffee consumption and blood pressure levels.

The relationship between habitual coffee consumption and blood pressure was investigated in 9601 subjects (7506 men and 2095 women) who were office managers and employees, aged 18-65 years. Those who drank coffee had lower blood pressure levels than those who did not and the mean blood pressure levels decreased with increasing coffee consumption. In the men, blood pressure (systolic/diastolic) was highest in the non-coffee drinkers (130.0/83.0 mmHg) and lowest in those drinking greater than 5 cups/day (126.0/81.3 mmHg). Mean differences (+/- s.e.m.) corrected by analysis of covariance for age and body mass index (kg/m2) were: systolic -4.0 +/- 0.7 mmHg, P less than 0.0001; diastolic -1.7 +/- 0.5 mmHg, P less than 0.001. In the women, blood pressure ranged from 121.1/77.4 mmHg in the non-coffee drinkers to 117.7/76.2 mmHg in those drinking greater than 5 cups/day (mean +/- s.e.m. systolic difference -3.4 +/- 1.4 mmHg, P less than 0.05; diastolic -1.2 +/- 0.9 mmHg, P greater than 0.05). These observations were confirmed after correction for physical activity, and cigarette and alcohol consumption (for age and body mass index). In the men, blood pressure ranged from 130.8/83.1 mmHg in non-coffee drinkers to 127.5/81.9 mmHg in those drinking greater than 5 cups/day, with the effect of classification by coffee consumption being very important (analysis of covariance: systolic F = 12.17, 3 degrees of freedom at numerator, P less than 0.0001; diastolic F = 3.56, 3 degrees of freedom at numerator, P = 0.0135).(ABSTRACT TRUNCATED AT 250 WORDS)