Combination of gastric atrophy, reflux symptoms and histological subtype indicates two distinct aetiologies of gatric cardia cancer.

<b>INTRODUCTION</b> Atrophic gastritis is a risk factor for non-cardia gastric cancer, and gastro-oesophageal reflux disease (GORD) for oesophageal adenocarcinoma. The role of atrophic gastritis and GORD in the aetiology of adenocarcinoma of the cardia remains unclear. We have investigated the association between adenocarcinoma of the different regions of the upper gastrointestinal tract and atrophic gastritis and GORD symptoms. <b>METHODS</b> 138 patients with upper GI adenocarcinoma and age and sex matched controls were studied. Serum pepsinogen I/II was used as a marker of atrophic gastritis and categorised to five quintiles. History of GORD symptoms, smoking and H.pylori infection was incorporated in logistic regression analysis. Lauren classification of gastric cancer was used to subtype gastric and oesophageal adenocarcinoma. <b>RESULTS</b> Non-cardia cancer was associated with atrophic gastritis but not with GORD symptoms; 55% of these cancers were intestinal subtype. Oesophageal adenocarcinoma was associated with GORD symptoms, but not with atrophic gastritis; 84% were intestinal subtype. Cardia cancer was positively associated with both severe gastric atrophy [OR, 95% CI: 3.92 (1.77 – 8.67)] and with frequent GORD symptoms [OR, 95% CI: 10.08 (2.29 – 44.36)] though the latter was only apparent in the nonatrophic subgroup and in the intestinal subtype. The association of cardia cancer with atrophy was stronger for the diffuse versus intestinal subtype and this was the converse of the association observed with non-cardia cancer. <b>CONCLUSION</b> These findings indicate two distinct aetiologies of cardia cancer, one arising from severe atrophic gastritis and being of intestinal or diffuse subtype similar to non-cardia cancer, and one related to GORD and intestinal in subtype, similar to oesophageal adenocarcinoma. Gastric atrophy, GORD symptoms and histological subtype may distinguish between gastric versus oesophageal origin of cardia cancer

Oesophageal cancer among the Turkomans of northeast Iran

A Caspian Littoral Cancer Registry survey in the early 1970s established northern Iran as one of the highest oesophageal cancer incidence regions of the world. To verify this, an oesophageal cancer survey was carried out between 1995 and 1997 in the Turkoman Plain at the southeastern corner of the Caspian Sea. Oesophageal balloon cytology screening was carried out on 4192 asymptomatic adults above age 30 years in one town and three adjoining villages with a total population of 20 392 people at risk. Oesophagoscopy was performed on 183 patients with abnormal cytological findings. The discovery of two asymptomatic small squamous cell cancers and one ‘carcinoma- suspect’ implied a prevalence ranging from 47.7 per 100 000 to 71.5 per 100 000. During a 1-year active surveillance, 14 patients were found with clinically advanced oesophageal squamous cell cancer, yielding age-standardized incidence rates of 144.09 per 100 000 for men and 48.82 per 100 000 for women. The very high frequency of oesophageal cancer reported for northern Iran 25 years ago stands confirmed. Differences in incidence rates, then and now, can be attributed to survey methods used and diagnostic criteria applied, but not to socioeconomic factors, which have remained relatively stable. Oesophageal balloon cytology is a practical method of mass screening for oesophageal cancer in Iran. © 2000 Cancer Research Campaig

Epidemiology of upper gastrointestinal cancers in Iran: A sub site analysis of 761 cases

Aim: To define the sub site distribution of upper gastrointestinal cancers in three provinces of Iran. Methods: The study was carried out in three provinces in Iran: Ardabil, Golestan, and Tehran. In Arbabil and Golestan, the data was collected from the sole referral center for gastrointestinal cancers and the local cancer registry. For Tehran province, data from two major private hospitals were used. All gastric and esophageal cancer patients diagnosed during the period from September 2000 and April 2002 were included in the study. Results: A total of 761 patients with upper gastrointestinal cancers were identified, 314 from Ardabil, 261 from Golestan, and 186 from Tehran. In Tehran, the relative rate of cancer increased from the upper esophagus to the distal stomach. In Golestan, the reverse pattern was observed. In Ardabil, the mid portion (distal esophagus and proximal stomach) was involved most frequently. Conclusion: There were considerable variations in the sub site of upper gastrointestinal cancers in the three provinces studied. We cannot provide any explanation for this variation. Further research aimed at explaining the discrepancies in sub site distribution of upper gastrointestinal cancers may help identify important risk factors. © 2007 WJG. All rights reserved

Qualitative analysis of Adenomatous Polyposis Coli promoter: Hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker

<p>Abstract</p> <p>Background</p> <p>Squamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (<it>APC</it>) promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of <it>APC </it>promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and <it>APC </it>promoter methylation.</p> <p>Methods</p> <p>For evaluating the status of <it>APC </it>promoter hypermethylation and its association with SCCE, a qualitative methylation specific PCR (MSP) was used. DNA was extracted and digested with an appropriate restriction enzyme, treated with sodium bisulfite in agarose beads and amplified in two-step PCR reaction by applying either methylated or unmethylated promoter specific primers. Universally methylated DNA and methylase treated blood DNA of healthy donors were used as positive controls as well. Survival of patients was followed up for two years after treatment and survival rate of patients with methylated <it>APC </it>promoter was compared with that of unmethylated patients.</p> <p>Results</p> <p>Assessment of <it>APC </it>promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4%) tumor tissues were hypermethylated either in one or both alleles of <it>APC</it>. Among the tissues in which methylation was detected, seven were hypermethylated in both alleles while the other thirteen were hypermethylated in one of the two alleles of <it>APC</it>. Analyzing two-year survival rate of patients with respect to promoter hypermethylation showed a lower rate of survival for patients with methylated <it>APC </it>promoter following their treatment. Further investigation into the association between promoter hypermethylation and tumor differentiation status indicated that patients with well differentiated tumors were more likely to develop promoter hypermethylation.</p> <p>Conclusion</p> <p>Observing similar level of <it>APC </it>promoter hypermethylation in patients with SCCE in this high risk region and comparing it with other parts of the world could support the hypothesis that a common molecular mechanism might be involved in tumorigenesis of SCCE. In addition, the higher rate of two-year survival for patients with unmethylated <it>APC </it>promoter as well as its relationship with tumor differentiation would suggest that this tumor suppressor could be an appropriate candidate molecular marker for evaluating tumor malignancy and predicting survival of patients subsequent to treatment.</p

Necrotizing Fasciitis of vulva: A report of two cases

Vulvar necrotizing fascitis is an uncommon infectious disorder. Since the first reported cases almost 100 years, ago, necrotizing fasciitis continues to present a diagnostic and therapeutic challenge. What usually begins as a subtle infection can become life-threatening. We report two cases of vulvar necrotizing fasciitis, one after posterior colporrhaphy in a woman with four risk factors and the other in a young woman without any risk factor

Telomerase Activity In Iranian Patients With Esophageal Squamous Cell Carcinoma

Telomerase activation is one of the main pathways to immortalize cancer cells. In many kinds of cancer cells, this special reverse transcriptase stabilizes and elongates telomeres and prevents telomere erosion that naturally occurs in every cell division. Esophageal cancer is the fifth most frequent cause of cancer death worldwide, and is highly associated with alcohol, smoking, cultural habits, and environmental factors. Telomerase has been suggested as a tumor marker and a molecular target for drug design in several kinds of cancers. In this work telomerase activation was inspected among Iranian patients with Esophageal Squamous Cell Carcinoma (ESCC), and detected in 90% of samples of different stages. This may be an indication that telomerase activation happens in an initial step in the development of ESCC. Although there is no correlation between telomerase activity and the progress of ESCC, it could be considered as a good tumor marker in ESCC. Telomerase activity te! sts are suggested for screening purposes in high risk areas for ESCC, which can be easily done on a small amount of scrapped samples of esophageal mucosa. It is also possible that ESCC results from incomplete differentiation or a failure in telomerase gene switching off that normally occurs during the differentiation of esophageal epithelial cells

Topography Of Helicobacter Pylori Gastritis In Different Biopsy Sites Of Gastric Mucosa Of Residents Of A High Risk Area For Gastric Adenocarcinoma

Background: Many recent studies have examined potential risk factors of H. pylori gastritis to improve our understanding of the early events in gastric carcinogenesis. We evaluated the extent and topography of chronic gastritis in a high risk area for gastric cardia cancer and investigated the critical role of H.pylori, risk index and age in its pathogenesis. Materials and Methods: During a national population-based endoscopic survey, we enrolled 508 participants aged &amp;#8805;40 from urban and rural areas of Meshkin-Shahr, Ardebil province of Iran. After informed consent, all underwent complete upper GI endoscopy. At least one mucosal biopsy was obtained from 6 standard sites: three of antrum (sites 1, 2, 3), two of corpus (sites 4, 5) and one of cardia (site 6). Severity, activity and combined inflammatory scores (CIS) of chronic gastritis and H.pylori infection status were assessed according to modified Sydney Classification of Gastritis. Statistical effects of H.pylori, age, gender, and residency place on mean gastritis severity, activity and CIS were separately calculated in each site. Results: Total of 508 participants with mean age (±SD) of 54.6(±SD) were enrolled. 234(46.1%) were male and 274(53.9%) were female. Histologically 80.5% of cases were H.pylori positive. Mean activity scores of all sites except for site 5 are significantly (P&lt;0.01) higher in H.pylori + cases. Mean CIS of all sites was significantly (P&lt;0.01) higher in H.pylori + patients. In 44% of infected subjects, CIS of the corpus was at least equally as severe as that in antrum. Also in 54% of H.pylori + cases, cardia’s CIS was &amp;#8805; than antral CIS. Age had a significant (P&lt;0.01) negative relationship with CIS of antral site, but this relationship in cardia was positive and more potent. Conclusion: H.pylori is the main cause of gastritis activity in all sites of stomach; this causality is more potent in antrum and cardia. Continuous cardia inflammation in advanced age may contribute to high incidence of gastric cardia cancer in this region

High incidence of adenocarcinoma arising from the right side of the gastric cardia in NW Iran

Background: In the West, the subsite incidence of gastric cancer has changed in recent decades, with cancer of the cardia increasing in incidence and that of the more distal stomach decreasing. NW Iran has a very high incidence of upper gastrointestinal cancer and we have examined the anatomical site specific incidence in this geographical region. Method and materials: Of 33 718 patients who visited our clinic from March 2000 to Jan 2003, 3119 (9.3%) with persistent upper gastrointestinal symptoms underwent upper gastrointestinal fibreoptic endoscopy. Exact tumour site, subsite, and axial view were determined. Demographic data including age, sex, and place of residence were assessed. Using matched data from the cancer registry and endoscopic survey, age standardised rates (ASR) for all subsites were calculated. Results: Upper gastrointestinal cancer was diagnosed histologically in 499 patients (16.0%). The most frequent site was the gastric cardia (126 (25.3%)) followed by the oesophageal body (90 (18.0%)), antrum (82 (16.4%)), corpus (74 (14.8%)), distal oesophagus (57 (11.4%)), gastro-oesophageal junction (47 (9.4%)), and proximal oesophagus (22 (4.4%)). From axial views of the cardia, 51.4% and 6.8% of tumours were found to originate from the lesser and greater curve, respectively. ASR for gastric cancer were 51.2 in males and 15.4 in females. Cardia cancer with ASR of 26.4 in males and 8.6 in females was the major component of gastric cancer. Conclusion: NW Iran is a geographical region with a very high incidence of cardia cancer and with the great majority originating from the right side of the cardia. This suggests a locally acting luminal carcinogen. Studying the aetiology of this cancer in NW Iran is likely to increase our understanding of the rising incidence of this cancer throughout the Western world

Differential gene expression between squamous cell carcinoma of esophageus and its normal epithelium; altered pattern of mal, akr1c2, and rab11a expression

AIM: To identify the altered gene expression patterns in squamous cell carcinoma of esophagus (ESCC) in relation to adjacent normal esophageal epithelium. METHODS: Total RNA was extracted using SV total RNA isolation kit from snap frozen tissues of ESCC samples and normal esophageal epithelium far from the tumor. Radio-labeled cDNA were synthesized from equal quantities of total RNAs of tumor and normal tissues using combinations of 24 arbitrary 13-mer primers and three different anchoring oligo-dT primers and separated on sequencing gels. cDNA with considerable different amounts of signals in tumor and normal tissue were reamplified and cloned. Using southern blot, the clones of each band were controlled for false positive results caused by probable heterogeneity of cDNA population with the same size. Clones that confirmed differential expression by slot blot selected for sequencing and northern analysis. Corresponding full-length gene sequences was predicted using human genome project data, related transcripts were translated and used for various protein/motif searches to speculate their probable functions. RESULTS: The 97 genes showed different levels of cDNA in tumor and normal tissues of esophagus. The expression of mal gene was remarkably down regulated in all 10 surveyed tumor tissues. Akr1c2, a member of the aldo-keto reductase 1C family, which is involved in metabolism of sex hormones and xenobiotics, was up-regulated in 8 out of 10 inspected ESCC samples. Rab11a, RPL7, and RPL28 showed moderate levels of differential expression. Many other cDNAs remained to further studies. CONCLUSION: The mal gene which is switched-off in all ESCC samples can be considered as a tumor suppressor gene that more studies in its regulation may lead to valuable explanations in ESCC development. Akr1c2 which is up-regulated in ESCC probably plays an important role in tumor development of esophagus and may be proposed as a potential molecular target in ESCC treatments. Differential display technique in spite of many disadvantages is still a valuable technique in gene function exploration studies to find new candidates for improved ones like gene chips