Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

BACKGROUND: Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. METHODS: Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. KEY RESULTS: Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. CONCLUSIONS & INFERENCES: Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration.

Asymptomatic isolated coccygeal metastasis in low rectal carcinoma.

As well as being relatively rare, osseous metastases from colorectal cancer are frequently asymptomatic and represent a late manifestation of disease. We report a case of an unidentified, asymptomatic coccygeal metastasis discovered on histological processing of the resection specimen from a patient with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by radical abdomino-perineal resection with coccygectomy. The anatomical explanation for this finding may involve passage of tumour cells via the vertebral venous plexus.

Epithelial cell turnover, p53 and bcl-2 protein expression during oncogenesis of early and advanced gastric cancer in a Western population.

OBJECTIVES: To investigate epithelial cell turnover alterations, and p53, bcl-2 protein expression during development of early and advanced gastric cancer in a Western population. METHODS: We investigated cell apoptosis and proliferation rates, p53 and bcl-2 protein expression in 17 early and 34 advanced gastric carcinomas and in the adjacent non-dysplastic mucosa. Cell proliferation, p53 and bcl-2 expression were detected immunohistochemically using MIB-1, anti-p53 and anti-bcl-2 monoclonal antibodies. Apoptosis was measured by TUNEL. The rate of the positive stained cells (labelling index) was count using image analysis technique. RESULTS: No difference was observed of either apoptotic (10 vs. 11) or proliferation (35 vs. 25) index between early and advanced cancers. However, the apoptotic index was significantly higher in intestinal type advanced tumors. While both apoptotic and proliferation indices were significantly higher in tumors than in the adjacent mucosa, no difference was observed of either apoptotic (2 vs. 2) or proliferation (8 vs. 13) index between the tissues adjacent to early and advanced tumors. p53 protein expression was significantly higher in advanced cancers (7 vs. 5, p=0.001) and in the non-dysplastic tissue adjacent to advanced tumors (3.5 vs. 2, p=0.001). bcl-2 labelling index was significantly higher in the mucosa adjacent to advanced carcinomas (15 vs. 5, p=0.016) but this difference did not reach significance in the tumors (20 vs. 15, p=0.37). CONCLUSIONS: Our data indicate similar cell turnover during tumorigenesis of early and advanced cancer. p53 and bcl-2 protein accumulation is more intense in gastric mucosa adjacent to advanced tumors and p53 immunoreactivity peaks in advanced carcinomas.

Prospective evaluation of a whole-blood antibody test (FlexPack HP) for in-office diagnosis of Helicobacter pylori infection in untreated patients.

OBJECTIVES: Rapid, reliable in-office tests are needed for applying the adopted screen-and-treat strategy in Helicobacter pylori-positive young dyspeptic patients. DESIGN: We have evaluated the performance characteristics of a whole-blood antibody (WBA) test for the detection of H. pylori infection under in-office conditions. METHODS: In a prospective double-blind study, 183 untreated patients referred to a tertiary centre for endoscopy because of dyspepsia were studied. Patients were defined as H. pylori-positive if two out of three tests (histology, rapid urease test, Gram staining of biopsy smears) were positive, and H. pylori-negative if all three tests were negative. An in-office test detecting IgG antibodies to H. pylori (FlexPack HP, Abbott Diagnostics) was used with capillary blood and compared with an ELISA detecting IgG (quantitative) and IgA (qualitative) H. pylori serum antibodies. RESULTS: Of the 183 patients, 139 were defined as H. pylori-positive. The in-office test had 79% sensitivity, 95% specificity, 98% positive and 59% negative predictive value. The respective values for IgG serum antibodies were 94, 70, 91 and 79% and those for IgA antibodies were 86, 82, 94 and 64%. About 50% of the false-negative in-office tests had a serum IgG antibody titre > 100 units. Co-evaluation of our data with published reports suggested that both the median sensitivity and negative predictive value of the kit are significantly inferior when performed with whole-blood (five studies) compared with serum (nine studies) (82 versus 92% and 82 versus 93% respectively, P < 0.035). CONCLUSIONS: Improvement of the performance characteristics of FlexPack HP in-office test is needed. However, the test may be a useful tool for identifying H. pylori-positive patients in younger age groups who could be managed without upper gastrointestinal endoscopy.

Predictive factors and prevalence of follicular gastritis in adults with peptic ulcer and nonulcer dyspepsia.

Follicular gastritis is an important histological entity, because it may progress to overt gastric MALT lymphoma. However, there is no universal agreement on whether there is any correlation of follicular gastritis with histological features of the antral mucosa or on the prevalence of follicular gastritis. To shed further light on these issues, we studied antral biopsies obtained from 735 adult patients, who had participated in six consecutive clinical trials. They included 348 patients with duodenal ulcer, 82 with gastric ulcer, and 305 with nonulcer dyspepsia. The Sydney classification system of gastritis was used, using a score of 0-3 to grade degree and activity of inflammation, gland atrophy, intestinal metaplasia, and H. pylori colonization density. Follicular gastritis was defined as prominent lymphoid follicles with no lymphoepithelial lesion. None of the H. pylori-negative patients (N = 159) had follicular gastritis. Among H. pylori-positive patients, 80/340 (23.5%) with duodenal ulcer, 5/77 (6.5%) with gastric ulcer, and 20/159 (12.6%) with nonulcer dyspepsia had follicular gastritis (P < 0.001). Multivariate discriminant analysis selected the following four significant predictor variables for follicular gastritis (Wilks lambda = 0.91, chi2 = 70.6, df = 4, P < 0.001): gastritis sum score, atrophic gastritis, age of the patient, and disease. The prevalence of follicular gastritis was linearly correlated (gamma = 24.55 - 0.98chi, r = -0.62, F1,11 = 6.12, P = 0.03) with the age groups of the 576 H. pylori-positive patients studied. In conclusion, follicular gastritis is highly correlated with H. pylori-caused severe, active gastritis. It is mostly prevalent in the young H. pylori-infected patients with duodenal ulcer.

Prevalence of Sjögren's-like syndrome in a cohort of HIV-1-positive patients: descriptive pathology and immunopathology.

The aims of the study were (a) to investigate the prevalence of Sjögren's-like syndrome (SLS) in an unselected population of HIV-1-positive patients and (b) to describe the pathology and immunopathology of the labial minor salivary gland biopsy. Seventy-seven HIV-1-positive patients were asked to answer the validated questionnaire of the European preliminary criteria for the classification of Sjögren's syndrome on oral and ocular sicca symptoms. Twenty-six patients gave one positive answer to both ocular and oral symptoms, and of these 14 (hepatitis C virus negative) consented to participate in the study (patients group). Ten age- and sex-matched HIV-1-positive patients with a negative questionnaire constituted the control group. Patients and controls had: (a) Schirmer's test and slit-lamp examination after Rose Bengal staining; (b) parotid gland scanning with technetium; (c) detection of autoantibodies in sera to Ro/SSA and La/SSB; (d) labial salivary gland biopsy (patients group only). The control group gave negative parotid gland scanning and only one gave a positive Rose Bengal staining test. In the patients group, parotid gland enlargement was manifested by three patients and only one gave positive Rose Bengal staining test. Six out of the 14 patients had biopsies identical with Sjögren's syndrome and five of these gave positive parotid gland scanning. In the biopsies of four other patients, mucoid degeneration of the stroma was found. Immunopathology revealed that the predominant cells were T cells with the CD8 phenotype. None of the patient and control sera had autoantibodies to Ro/SSA and La/SSB, whereas all patients had hypergammaglobulinaemia. The overall prevalence of possible SLS in a mixed population of HIV(+) patients (88.3% men and 11.7% women) was 7.79% which is >2.5 times higher than that observed in normal Greek adult females.