Rare presentation of endometrial carcinoma with singular bone metastasis.

The major symptom at diagnosis of endometrial cancer is post-menopausal bleeding; it is present in around 90% of cases. Singular bone metastasis is described as an uncommon site for endometrial cancer at diagnosis, showing in just 5-6% of cases. In this report we describe a rare presentation of a singular bone metastasis because of endometrial cancer of a woman with previous diagnosis of early breast cancer. A review of literature uncovered some cases of bone metastasis at presentation of endometrial cancer and that it can occur as first symptom of cancer before vaginal bleeding. This rare presentation of uterine cancer needs to be studied and described because it may be seen and needs a homogeneous treatment to improve survival.

The Veneto Region's Barrett's Oesophagus Registry: aims, methods, preliminary results.

BACKGROUND: The natural history of Barrett's Oeosphagus is not completely clarified and Barrett's Oeosphagus Registries are considered useful tools to expand our knowledge on this disease. A Barrett's Oeosphagus Registry has been therefore established in the Veneto Region and neighbouring provinces. AIMS: The aims of the Registry are to assess the demographical, endoscopical and histological characteristics of Barrett's Oeosphagus patients; the prevalence of non-invasive neoplasia and Barrett's Adenocarcinoma and the timing and incidence of Barrett's Oeosphagus progression to malignancy. METHODS: An interdisciplinary committee of endoscopists, pathologists and information technology experts was established in 2004 to design a website-based Barrett's Oesophagus Registry for the Veneto Region and neighbouring north-eastern Italian provinces. Protocols for endoscopies and biopsies and standard reports were carefully defined. RESULTS: In the first 18 months, 397 patients with endoscopically visible and histologically proven Barrett's Oeosphagus were enrolled in the Registry; the median age of these patients was 66 years (male:female=3:1). Most patients (75%) had a Short Segment of Barrett's Oesophagus (3 cm). Long Segment of Barrett's Oesophagus patients were 5 years older than the Short Segment of Barrett's Oesophagus patients (p<0.05), suggesting a progression from Short Segment of Barrett's Oesophagus to Long Segment of Barrett's Oesophagus. Though no data are available on the incidence of non-invasive neoplasia or Barrett's Adenocarcinoma (i.e., progression to cancer at least 12 months after enrolment), the prevalence of neoplastic lesions (found within 12 months of enrolment) was 5% for Short Segment of Barrett's Oesophagus and 19% for Long Segment of Barrett's Oesophagus, indicating that a careful multiple-biopsy endoscopic protocol is needed, especially when Long Segment of Barrett's Oesophagus are suspected at endoscopy. The prevalence of Barrett's Adenocarcinoma among patients with non-invasive neoplasia was 1/17 cases of low-grade non-invasive neoplasia and 2/3 cases of high-grade non-invasive neoplasia, indicating that these patients require strict endoscopic and bioptic follow-up. CONCLUSION: A regional Barrett's Oeosphagus Registry is feasible at a relatively low cost and enables significant data to be collected in a relatively short time. The use of a standardised endoscopic nomenclature and report form, a strict biopsy protocol, a standard report for pathologists improves the quality of endoscopic and histological diagnoses.

Microsatellite instability and gastric non-invasive neoplasia in a high risk population in Cesena, Italy.

BACKGROUND/AIMS: In the natural history of gastric cancer, non-invasive neoplasia (NiN) precedes invasive carcinoma. A histological classification of gastric NiN has recently been proposed by a World Health Organisation international panel of experts. Genetic instability is known to be among the molecular pathways involved in gastric oncogenesis. In this retrospective cross sectional study, microsatellite instability (MSI) was analysed in a consecutive series of NiN and NiN related histological alterations from a northern Italian region at high risk for gastric cancer. PATIENTS/METHODS: Fifty five consecutive cases (indefinite for NiN, 29 cases; low grade NiN, 17 cases; high grade NiN, nine cases) were analysed by radioactive polymerase chain reaction and electrophoresis for microsatellite alterations at six loci (BAT25, BAT26, D2S123, D5S346, D17S250, and D3S1317). MSI was defined according to the Bethesda criteria distinguishing: (1) no instability in the analysed loci; (2) low frequency MSI (MSI-L); and (3) high frequency MSI (MSI-H). Immunohistochemical expression of MLH1 and MSH2 proteins was also analysed in all cases. RESULTS: Overall, MSI was found in 11 of 55 cases (indefinite for NiN, five of 29 (MSI-L, four; MSI-H, one); low grade NiN, three of 17 (MSI-L, one; MSI-H, two); high grade NiN, three of nine (MSI-L, one; MSI-H, two). CONCLUSIONS: In an Italian high risk area for gastric cancer, MSI is part of the spectrum of genetic alterations in gastric non-invasive neoplasia. In European populations at high risk of gastric cancer, DNA repair system alterations are thought to be among the early molecular events in gastric carcinogenesis.

The long term outcome of gastric non-invasive neoplasia.

BACKGROUND: The cancer risk associated with gastric non-invasive neoplasia (formerly dysplasia) is debated. This prospective long term follow up study investigates the clinicopathological behaviour of non-invasive gastric neoplasia (and related lesions), focusing on the cancer risk associated with each different histological phenotype. PATIENTS AND METHODS: A total of 118 consecutive cases (nine indefinite for non- invasive neoplasia; 90 low grade non-invasive neoplasia; 16 high grade non- invasive neoplasia; and three suspicious for invasive adenocarcinoma) with a histological follow up of more than 12 months (average 52 months; range 12-206) were prospectively followed up with a standardised protocol. Patients in whom gastric cancer was detected within 12 months from the initial diagnosis of non-invasive neoplasia were excluded, assuming that invasive carcinoma had been missed at the initial endoscopy procedure. RESULTS: Non-invasive neoplasia was no longer detectable in 57/118 cases (48%), was unchanged in 32 (30%), and evolved into gastric cancer in 20 patients (17%). Evolution to invasive adenocarcinoma was documented in both low and high grade non-invasive neoplastic lesions (8/90 low grade; 11/16 high grade) and correlated with histological severity (low versus high grade) at baseline (p<0.001). Seventy five per cent of cancers occurring during the long term follow up were stage I. CONCLUSIONS: The risk of invasive gastric cancer increases with the histological grade of the non-invasive neoplasia. Following up non-invasive gastric neoplasia increases the likelihood of gastric cancer being detected in its early stages.

Colonic metaplasia in the long-term follow-up of the ileal neobladder.

OBJECTIVE: To look for the presence of colonic metaplasia (CM), the shifting from sialomucins (SIs) to sulfomucins (SUs), considered as a probably premalignant lesion in the stomach in the mucosa of the ileal neobladder (IN). METHODS: 19 patients with IN were subjected to endoscopic biopsy; the samples were analyzed by means of histochemistry with high iron diamine, a test indicated to identify SIs and SUs. RESULTS: CM was never observed earlier than 1 year after the operation, was absent in 9/19 patients (mean follow-up 14 months) and present in 10/19 (mean follow-up 59 months). CONCLUSION: Time-dependent phenotypic changes, already described in the stomach as being premalignant, take place after constant contact with urine in the mucosa of the IN. It is at present unclear whether they may be defíned as only metaplastic or frankly preneoplastic; anyway, a careful follow-up remains indicated in all patients with íntestinal urinary diversions.

The p53 gene in patients under the age of 40 with gastric cancer: mutation rates are low but are associated with a cardiac location.

BACKGROUND: Determining both the frequency and the spectrum of p53 gene mutation in young patients with gastric cancer might provide clues to the host related genetic mechanism(s) in gastric carcinogenesis. PATIENTS AND METHODS: p53 mutations were assessed (by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), followed by DNA sequencing) in a cohort of 105 consecutive Italian patients in whom gastric cancer was ascertained before the age of 41. RESULTS: A low prevalence of p53 mutations (eight of 105) was observed, with no significant difference between intestinal (three of 31; 10%) and diffuse (five of 74; 7%) phenotypes. A significantly higher prevalence of p53 mutations was associated with the cardiac location (odds ratio, 7.09; confidence interval, 1.56 to 32.11). In all but one case, p53 mutations were associated with a stage higher than I. All eight mutations were located at CpG sites, where G : C to A : T transitions have been associated with frequent methylation at the C5 position of cytosine. CONCLUSIONS: These findings show that, unlike what has been consistently demonstrated in the general population, p53 mutations are uncommon in gastric cancer occurring in young patients, and in such patients, p53 alterations are significantly associated with the cardiac location.

Topographic patterns of intestinal metaplasia and gastric cancer.

OBJECTIVE: The role of intestinal metaplasia in gastric oncogenesis has been demonstrated by both cross-sectional and longitudinal studies. This study was designed to determine whether, in a population at high risk for gastric cancer, different topographical patterns and phenotypes of intestinal metaplasia were associated with different degrees of cancer risk. METHODS: A total of 68 Colombian patients with gastric cancer and 67 controls with nonulcer dyspepsia were studied by an extensive biopsy protocol. Intestinal metaplasia was assessed semiquantitatively by histology and was characterized histochemically. In both patients and controls, the Spearman's correlation test was applied to the test if the gastric distribution of metaplastic lesions resulted in specific topographical patterns associated with different risks for cancer. RESULTS: Four topographical patterns of intestinalization emerged: 1) "Focal," in 14 cancer patients and 16 controls; 2) "Antrum-predominant," in seven cancer patients and six controls; 3) "Magenstrasse" (involving the lesser curvature from cardia to pylorus) in 25 cancer patients and four controls. This pattern was associated with higher cancer risk (OR = 5.7; 95% CI: 1.3-26) than were the two less extensive patterns; and 4) "Diffuse," involving essentially the entire gastric mucosa with the exception of the fundus, was unique to 13 cancer patients. The OR for cancer was 12.2; 95% CI: 2.0-72.9. Incomplete-type metaplasia significantly correlated with the extent of total metaplasia and was also associated with greater cancer risk. CONCLUSIONS: In a population with high risk for gastric cancer, the extension of intestinal metaplasia correlates with the extent of its "incomplete" phenotype and is significantly associated with increased cancer risk. Both the extent and location of intestinal metaplasia along the lesser curvature (from the cardia to the prepyloric zones) identify patients with the highest cancer risk.

The dark side of the gastric biopsy.

Based on the assumption that both sides of a gastric biopsy sample have a similar appearance, the choice of which side of a specimen is to be sectioned is usually random. We tested the hypothesis that the diagnosis reached by examining the two sides of a gastric biopsy may differ. Eighty-one antral biopsy specimens from patients with neither focal lesions nor previous gastric surgery were evaluated. After preparing 8-10 sections from each of the two opposite faces of each biopsy, sections were scored for Helicobacter pylori, activity, atrophy, intestinal metaplasia, lymphoid follicles. The presence of other lesions was also noted. Intrabiopsy agreement (the consistency in the identification of histological lesions on the opposite sides of the same sample) was calculated by using kappa statistics. A kappa value lower than 0.5 was considered "poor"; between 0.51 and 1.00 "moderate to excellent." The intrabiopsy agreement kappa values were: activity = 0.83, atrophy = 0.54, intestinal metaplasia = 0.51 and lymphoid follicles = 0.19. A mean of 42 serial sections (ranging from a mean of 22 for lymphoid follicles to a mean of 81 for xanthogranulomata) was needed to achieve an excellent (ie, kappa > or = 0.75) intrabiopsy agreement between the features showed at the opposite sides of a biopsy specimen. Intrabiopsy variability may represent a hitherto unrecognized source of error, and it should be minimized or avoided. In a research context information about the number of sections examined from a biopsy would provide a crucial element necessary to evaluate the accuracy of the histological data.

Microsatellite instability and/or loss of heterozygosity in young gastric cancer patients in Italy.

Gastric cancers are rarely diagnosed before the age of 40 years and the incidence reaches a peak during the 7th decade in the general population. A molecular mechanism of early tumor onset may be determined by comparing microsatellite instability (MSI), indicative of error-prone mismatch repair, and loss of heterozygosity (LOH) between gastric cancers in patients < or = 40 years of age and those of older ages. Three to 5 chromosomal loci, where MSI and/or LOH are commonly found in gastric cancers in the general population, were examined in formalin-fixed, paraffin-embedded samples from 102 patients < or = 40 years of age using a polymerase chain reaction-based non-radioactive screening method. MSI and/or LOH at a minimum of 1 locus were detected in 11/102 patients. The frequency of MSI and/or LOH at the D11S904 locus was significantly higher than that at the D2S119, D2S123, D5S409 and IFNA regions. No preferential genetic changes at the D11S904 locus were observed in elderly patients. Among several clinicopathological variables, a statistically significant association with MSI and/or LOH was observed only for tumors located at the cardia, compared with tumors at the antrum and the corpus. Our findings suggest that a unique mechanism may be involved in increasing the susceptibility of the D11S904 locus for either MSI or LOH, especially for cardia tumors in young patients. Early onset of gastric cancers in patients < or = 40 years of age is associated with genetic changes at preferential chromosomal loci, including D11S904.

Patients younger than 40 years with gastric carcinoma: Helicobacter pylori genotype and associated gastritis phenotype.

BACKGROUND: In the general population, Helicobacter pylori (H. pylori), particularly the cagA positive strain, has been associated with intestinal-type gastric carcinoma. Gastric carcinomas are rarely observed in patients age < or = 40 years. Host-related factors have been thought to be more important than environmental agents in these early-onset cancers. The aim of this study was to ascertain the possible role of H. pylori infection and that of cagA positive strains in the development of gastric carcinoma in these young patients. METHODS: In this case-control study, 105 gastric carcinoma patients (male-to-female ratio = 1.1; mean age, 34.4 years; range, 16-40 years) and an equal number of controls (matched for gender and age) were retrospectively selected from the same geographic area. The phenotypes of gastritis and H. pylori were histologically assessed, and the presence of the ureC gene, which is indicative of H. pylori infection, and the cagA genotype were determined by polymerase chain reaction. Gastric carcinoma risk was calculated by both univariate and multivariate statistical methods, taking into account the cancer phenotype, the gastritis phenotype detected in both patients and controls, and the H. pylori genotype. RESULTS: For 74 diffuse and 31 intestinal gastric carcinomas, multivariate logistic regression analysis produced results consistent with those of univariate statistical tests, showing a significant association between gastric carcinoma and both H. pylori infection (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.52-5.11) and cagA positive status (OR = 2.94; 95% CI = 1.56-5.52). CONCLUSIONS: In young Italian patients with gastric carcinoma, the significant association with cagA positive H. pylori infection suggests that the bacterium has an etiologic role in both diffuse-type and intestinal-type gastric carcinoma.

[Phenotypic changes in mucin-secreting cells in the ileal neobladder mucosa: a metaplastic or precancerous lesion?]. / Modificazioni fenotipiche delle cellule mucino-secernenti nella mucosa delle neovesciche ileali: lesione metaplastica o precancerosa?

Colonic metaplasia with shifting from sialo-to sulfomucins was observed in 10/18 patients with ileal orthotopic neobladder; their median follow-up was 59 months. There is a significant statistical relationship (p = 0.002) between Colonic Metaplasia and a follow-up longer than 14 months. Diversion Cancer is nowadays a practical problem and probably urologists will be confronted with it in the future more than at present. A modification of established attitudes as regards urinary diversion in standard situations (i.e., 60 over years old patients with invasive bladder cancer) don't seems, at present, justified, although our study confirms the suspicion that ileal neobladder could be considered theoretically at risk for cancer onset.

Prevalence of upper gastrointestinal lesions and Helicobacter pylori infection in Crohn's disease.

Crohn's disease can affect the upper gut with reported variable frequency, although concurrent Helicobacter pylori infection has been reported to be low. We prospectively investigated the prevalence of esophageal, gastric, and duodenal lesions and Helicobacter pylori infection in 67 Crohn's disease, 41 ulcerative colitis patients, and 43 controls. Symptoms, esophagogastroduodenoscopy, and multiple biopsies were performed on all patients consecutively. Endoscopic lesions were found in 63% of Crohn's disease patients, with a Helicobacter pylori prevalence of 28%. Granulomas were found in three patients. Twenty-two percent of the ulcerative colitis patients had lesions, with a 29% prevalence of Helicobacter pylori infection. Half of the controls had pathological endoscopy, and Helicobacter pylori was positive in 40% of the cases. Subjective symptoms did not predict the presence of endoscopic lesions or Helicobacter pylori infection in inflammatory bowel disease patients. Chronic gastritis and duodenitis are common in Crohn's disease patients, and the majority are not associated with Helicobacter pylori infection.

Low dose of clarithromycin in triple therapy for the eradication of Helicobacter pylori: one or two weeks?

The aims of this pilot study were: (i) to compare the efficacy of low-dose clarithromycin (250 mg twice daily) for 1 or 2 weeks; and (ii) to evaluate possible therapeutic advantages in associating the low-dose clarithromycin with an anti-secretory agent or tripotassium dicitrate bismuthate (De Nol; Yamanouchi Pharm, Corugate Milano, Italy). A prospective, randomized, open trial was carried out on consecutive outpatients with dyspeptic symptoms and Helicobacter pylori infection. We enrolled 129 patients in one of the following schedules: (A) De Nol 120 mg q.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; (B) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; or (C) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 1 week. Results were evaluated by Per Protocol (PP) and Intention-To-Treat analysis (ITT). Eradication rate was 100% after treatment A, 92.6% after treatment B and 86.5% after treatment C by PP and 83.3, 75.7, and 68.1%, respectively by ITT. Side effects were reported by 16 subjects: 26.6% in group A; 9.1% in group B; and 7.5% in group C; in two cases side effects led to the withdrawal of the treatment. In conclusion, 500 mg clarithromycin per day in association with omeprazole and metronidazole, for 1 week gave comparable results to the same schedule for a 2 week period. The use of clarithromycin with bismuth and metronidazole produced a therapeutic gain compared with both of the anti-secretory schedules, although this was not statistically significant.