Specialized columnar epithelium of the esophagogastric junction: prevalence and associations. The Central Finland Endoscopy Study Group

OBJECTIVES: In Barrett's esophagus (BE) normal squamous esophageal epithelium is replaced by specialized columnar epithelium (SCE). BE is related to gastroesophageal reflux disease (GERD) and is a risk factor for esophageal adenocarcinoma. SCE is detected also at normal-appearing esophagogastric junction without BE (junctional SCE). The relationships between junctional SCE, GERD, and cardia adenocarcinoma are obscure and controversial. The aims of the present study were to investigate the prevalence and demographics of junctional SCE and to compare these figures with those reported for BE, and esophageal and cardia adenocarcinoma. A further aim was to examine the association between junctional SCE and GERD, Helicobacter pylori infection, and gastritis. METHODS: One thousand one hundred-nineteen consecutive dyspeptic patients underwent gastroscopy and were enrolled into the study. RESULTS: Junctional SCE was detected in 110 patients (10%). The age-specific prevalence of junctional SCE increased with age. The male:female ratio was 1:1.1. In multivariate analysis, junctional SCE was independently and positively related to endoscopic erosive esophagitis (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-3.1), cardia inflammation (carditis) (OR, 3.1; 95% CI, 1.4-6.8), and age (OR, 1.4 per decade; 95% CI, 1.2-1.6), but not to corpus H. pylori infection (OR, 1.4; 95% CI, 0.7-2.8), antral (OR, 1.0; 95% CI, 0.5-2.1) or corpus (OR, 0.8; 95% CI, 0.4-1.8) gastritis, or intestinal metaplasia of the antral mucosa in stomach (OR, 1.2; 95% CI, 0.7-2.1). In univariate analysis, junctional SCE was, however, significantly more common in patients with antral-predominant atrophic gastritis (20%), compared with those with normal gastric histology (8%, p < 0.001). CONCLUSIONS: Junctional SCE is age related and may therefore be an acquired lesion. It is associated with cardia inflammation and endoscopic erosive esophagitis, but not with H. pylori infection or gastric intestinal metaplasia. Unlike BE and cardia cancer, junctional SCE occurs with similar frequency in men and women.     

No support for endoscopic surveillance for gastric cancer in hereditary non-polyposis colorectal cancer

BACKGROUND: The DNA mismatch repair gene mutations underlying hereditary non-polyposis colorectal cancer syndrome (HNPCC) also predispose, besides colorectal and endometrial cancer, to gastric cancer. usually of the intestinal type. The carcinogenetic pathway behind the elevated gastric cancer risk is largely unknown. METHODS: The aim of this study was to determine whether there are any premalignant lesions to search for in gastric surveillance in HNPCC by comparing gastric histopathology between mutation-positive and mutation-negative family members. We searched for differences in occurrence of Helicobacter pylori, inflammation, atrophy, intestinal metaplasia and dysplastic changes. Upper gastrointestinal endoscopy was performed for 73 mutation-positive and 32 mutation-negative family members. RESULTS: One case of duodenal cancer was detected in the mutation-positive group, but no gastric neoplastic lesions were seen in either group. There were no differences in the occurrence of polyps, H. pylori, inflammation, activity, atrophy nor intestinal metaplasia tested with binaric, logistic, regression analysis. CONCLUSIONS: We conclude that surveillance gastroscopy may not be beneficial in HNPCC, since neither cases of early cancer nor premalignant lesions could be detected in our series of 73 mutation-positive subjects.     

Frequency of hereditary nonpolyposis colorectal cancer

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome characterized by early onset of colorectal carcinomas (CRC). Recently, two HNPCC genes have been mapped and cloned, one in the short arm of chromosome 2 and another in the short arm of chromosome 3. There has been a major controversy about the frequency of HNPCC. The few estimates available have been based on series selected by age or series representing local area. The purpose of the present study was to design a nonselected, prospective, multicenter study, taking into account the family background and other risk factors of CRC. METHODS: The proportion of HNPCC of all (N=406) CRC cases was evaluated in a prospective multicenter study. Family history and other risk factors were investigated over a 12-month period for all new CRC patients in ten hospitals. These cases constituted 23 percent of all CRCs diagnosed in Finland during the study period. RESULTS: Three (0.7 percent) cases of verified and seven (1.7 percent) cases of suspected HNPCC were identified, following the evaluation of all families with features indicative of susceptibility to cancer. The proportion of identifiable risk factors of CRC was 5.8–7.5 percent (HNPCC, 0.7-2.4 percent; previous CRC, 3.4 percent; ulcerative colitis, 1.0 percent; familial adenomatous polyposis coli, 0.7 percent). CONCLUSION. This prospective multicenter study revealed that the frequency of hereditary colorectal cancer is lower than in some previous studies, when diagnosis is based on extensive pedigree analysis. This result with recent findings of common ancestral founding mutation in Finnish HNPCC families indicates that there may be geographic differences in the occurrence of HNPCC. However, this does not change the fact that identification of HNPCC—perhaps one of the most common inherited diseases identified in humans—has become a question of vital importance now when diagnosis of the syndrome and largescale screening of gene carriers using specific tests are on the horizon.Supported by grants from the Finnish Cancer Society, the Finnish Foundation for Gastroenterological Research, the Sigrid Juselius Foundation, and the Academy of Finland, Helsinki, Finland.     

Histopathology of colorectal carcinomas and adenomas in cancer family syndrome

Seventy-five colorectal carcinoma patients (100 separate cancers) with verified cancer family syndrome were re-examined for the evaluation of histologic characteristics in carcinomas and adenomatous polyps in this inherited syndrome in a comparison with control patients with colorectal carcinoma but no hereditary background. In the cancer family syndrome group there were significantly more mucinous carcinomas (35 to 39 percent vs. 20 percent;P<0.05–0.01), and also more poorly differentiated tumors (24 vs. 12 percent) than in the control group. The differences could not be explained by the site or stage of the tumors or by the age or sex of the patients. Additional adenomas occurred quite often both in cancer family syndrome patients (19 percent) and in the controls (16 percent). In the cancer family syndrome group, however, there were more adenomas with moderate or severe dysplasia (P<0.01) and more adenomas with villous features (P<0.05) than in the control group. Mucinous histologic features in colorectal carcinoma, although not fully specific, might be characteristic of cancer family syndrome, and thus serve as one sign in the indentification of the syndrome. The presence of the adenoma-carcinoma sequence in cancer family syndrome also was supported, and the histologic aggressivity of the associated adenomas might signify an accelerated advancement of this phenomenon in cancer family syndrome. Supported by the Finnish Cancer Foundation.     

Direct contact in inviting high-risk members of hereditary colon cancer families to genetic counselling and DNA testing

Background

Identification of hereditary predisposition to cancer has limited significance if not followed by efficient cancer prevention in the family. Probands are traditionally left to inform their relatives about the increased risk, but distant relatives may remain uninformed. An approach to contacting directly at‐risk persons assumed to be unaware of their increased cancer risk was taken. With cancer prevention as the ultimate goal, the study was aimed at investigating attitudes towards and psychosocial consequences of this novel strategy.

Methods

In families with hereditary non‐polyposis colorectal cancer (Lynch syndrome), 286 healthy adult relatives with a 50% risk of a predisposing mutation were contacted by letter. Of these, 112 participated in counselling and predictive testing. Baseline information and information obtained 1 month after the test for 73 respondents were compared with 299 corresponding subjects, approached via the proband (family‐mediated approach in our previous study) in these families.

Results

After the contact letter, 51% consented to the study. Of these, 92% approved of the direct contact and 33% had tried to seek information. In 34% of the mutation carriers, neoplasia was identified in the first post‐test colonoscopy. Although post‐test fear of cancer increased among the mutation carriers and decreased among noncarriers, almost all participants were satisfied with their decision to participate, independently of their test results, parallel to the family‐mediated approach.

Conclusion

In this large‐scale study, relatives in cancer families were actively contacted to inform them of the condition and genetic counselling. Their attitudes were encouraging, and the psychosocial consequences were similar to the family‐mediated approach. Our results suggest the appropriateness of direct contact as an alternative method of contact in cases of life‐threatening treatable disease.     

A hierarchical cluster analysis to determine whether injured runners exhibit similar kinematic gait patterns

Previous studies have suggested that runners can be subgrouped based on homogeneous gait patterns; however, no previous study has assessed the presence of such subgroups in a population of individuals across a wide variety of injuries. Therefore, the purpose of this study was to assess whether distinct subgroups with homogeneous running patterns can be identified among a large group of injured and healthy runners and whether identified subgroups are associated with specific injury location. Three-dimensional kinematic data from 291 injured and healthy runners, representing both sexes and a wide range of ages (10-66 years), were clustered using hierarchical cluster analysis. Cluster analysis revealed five distinct subgroups from the data. Kinematic differences between the subgroups were compared using one-way analysis of variance (ANOVA). Against our hypothesis, runners with the same injury types did not cluster together, but the distribution of different injuries within subgroups was similar across the entire sample. These results suggest that homogeneous gait patterns exist independent of injury location and that it is important to consider these underlying patterns when planning injury prevention or rehabilitation strategies.     

Potential mechanism for Calvados-related oesophageal cancer

The old Normandian habit of consumption of hot Calvados is associated with an increased risk of oesophageal cancer compared to other alcoholic beverages. The role of alcohol consumption in the risk of oesophageal cancer is well established. The first metabolite of alcohol, acetaldehyde is a potential local carcinogen in humans. Accordingly, different acetaldehyde concentrations in different beverages could account for some of the variations in cancer risk with regard to the type of alcoholic beverage. Eighteen samples of farm-made Calvados were collected in Normandy. Samples of commercially available beverages were purchased, including factory-made Calvados, other spirits, wines, beer and cider. The samples were analysed gas-chromatically for acetaldehyde and ethanol concentrations. All results are expressed as mean ± SD. The mean acetaldehyde concentration of all Calvados samples (1781 ± 861 μM, n = 25) differed highly significantly (p < 0.001) from that of all wine samples (275 ± 236 μM), from all other spirits samples (1251 ± 1155 μM, p < 0.05), and from all beer and cider samples (233 ± 281 μM, p < 0.001). Farm-made Calvados and farm-made cognac had the highest mean acetaldehyde concentration of the measured beverages. The high concentration of acetaldehyde combined with possible effects of the high temperature at which Calvados is consumed could account for the increased risk of Calvados-related oesophageal cancer.