Incidence Rates Of Esophageal Adenocarcinoma Research Articles

Fiberoptic Confocal Raman Spectroscopy for Real-Time In Vivo Diagnosis of Dysplasia in Barrett's Esophagus

Barrett’s esophagus (BE) is a metaplastic precursor of esophageal adenocarcinoma (EAC). Since the late 1970s, despite extensive efforts for prevention (eg, periodic surveillance of high-risk BE patients), EAC still has had a substantial rise in incidence rates (>350%), and is growing more rapidly than other cancers in the developed countries. Given the poor therapeutic response of symptomatic EAC, early identification of high-risk lesions (ie, dysplasia) together with therapeutic interventions is the most critical measures to improving survival rates of BE patients. However, dysplastic lesions or grossly inconspicuous cancers are endoscopically indistinguishable from the surrounding benign tissue. This is because conventional endoscopy heavily relies on visual assessment of structural and morphologic changes of the tissue surface, resulting in poor diagnostic accuracy. Existing diagnostic guidelines recommend extensive biopsy samplings (typically 4-quadrant samplings) at every 1to 2-cm interval along suspicious Barrett’s segments during endoscopic inspections of BE patients. This approach produces a vast number of negative biopsies and is clinically labor intensive and a burden to the patients. Because only a minute amount of the mucosa is sampled (as little as 5%), tissue biopsies may not accurately characterize BE segments. Foci of dysplasia in a background of intestinal metaplasia are frequently overlooked, even when the biopsies are diligently performed by the experienced endoscopists using extensive 4-quadrant biopsy protocols. Taken into account the enormous rise in incidence rates of EAC and the existing clinical challenges, the need for new advanced endoscopic modalities has never been greater. The objective targeting of high-risk tissue areas (eg, high-grade dysplasia [HGD]) with a noninvasive or minimally invasive technique could greatly reduce random biopsy sampling errors as well as health care expenses on the patients. Recent attention has thus been directed toward molecular diagnosis using optical spectroscopy and imaging. Raman spectroscopy represents a unique optical vibrational technique based on the fundamental premise of inelastic light scattering for tissue diagnosis and characterization. When an incident laser light induces a polarization change of molecules, a small proportion of incident light photons (w1 in 10) is inelastically scattered with the frequency shifts corresponding to the specific Raman active vibrational modes of the molecules in the sample. Taking advantage of the Raman spectroscopic ability of harvesting a wealth of fingerprint information from interand/or intracellular components (eg, proteins, lipids, and DNA) in cells and tissue, Raman technique has shown great promise for histopathologic assessments (ie, optical biopsy) at the biomolecular level. In the last 2 decades, there has been accumulating evidence on the accurate diagnostic capability of Raman spectroscopy through comprehensive in vitro studies. In vivo Raman endoscopic applications, however, have been limited not only by the difficulty in capturing inherently very weak tissue Raman signals, but also by the slow speed of spectral measurements (>5 s). The miniaturization of flexible fiberoptic Raman probes with depth-resolving capability that can pass down the instrument channel of medical endoscopes for effective tissue Raman light collections presents another technical challenge in endoscopic applications of Raman spectroscopy. To tackle these challenges, we have developed a novel beveled fiberoptic confocal Raman probe coupled with a ball lens capable of enhancing in vivo epithelial tissue Raman measurements at endoscopy. We present this work on in vivo clinical applications of the fiberoptic confocal Raman spectroscopy for real-time objective diagnosis of dysplasia in BE at endoscopy. The direct assessment of the biomolecular contents of epithelial cells and tissue in vivo enables the gastroenterologists to perform noninvasive or minimally invasive optical biopsies in real-time during clinical endoscopy.

Abstract 4802: Gender disparity in esophageal cancer incidence.

Abstract Introduction: Over the past thirty years, esophageal cancer (EC) incidence has been increasing more rapidly than any other solid neoplasm in the Western world. Globally, there is a large male predominance in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). The reasons for this gender difference and the possible role of estrogen remains unclear. We conducted an analytical epidemiological study to determine if estrogen exposure explains the male predominance in observed esophageal cancer incidence. Materials/Methods: We evaluated the Surveillance Epidemiology and End Results (SEER) cancer incidence trends from 1975 to 2008 using SEER Stat to calculate the annual percentage change (APC) in each five year age group and in EAC and ESCC by gender. Results: Male predominance in incidence rates of EC was most evident in the younger population and those with EAC histology as previously demonstrated. EAC and ESCC incidence rates both increases with aging, consistent with cancer being an age-related disease, but the male: female incidence ratio of EAC significantly decreased with aging. The rate of increase for EAC incidence in post menopausal females is greater than in any other demographic category. This increasing incidence rate in the post menopausal female was also observed in the ESCC, but to a lesser extent. The APC was negative (-1.5) between 1975-2008 only in the 50-64 age female cohort. Interestingly, the APC doubled in the last two age groupings of older females (age 65-74 = + 0.3 and age 75 and greater = + 0.7). APC rates for the males increased gradually in all their age groups (age 50-64 = +1.2, age 65-74 = +1.4, age 75+ = +1.9). Conclusions: The males’ incidence of EAC increases at a steep rate with aging and females’ incidence rates are not as steep except after age 60-64 where their incidence rate of change steeply increases. The steeper change in EAC incidence rates in the post menopausal female may explain why the male: female EAC incidence ratio decreases with age as seen nationally (SEER). The negative APC in the female 50-64 years age group may be explained by their peri-menopausal state and by the increased use of post-menopausal hormonal therapy since 1975 for this age group. Using age as a proxy for estrogen exposure, our findings suggest a hormonal component for the observed age-related, declining male to female EAC incidence rate ratios. It also confirms gender differences in incidence long observed in EC and suggests that the pre-menopausal estrogen milieu in females may serve as a protective factor against EAC. Moreover, this protective state dissipates with time in the post menopausal females where the effect of estrogen exposure dissipates. Implications: Our initial epidemiological observation of gender-age differences warrants translation into a molecular epidemiology study with the use of sophisticated biomarkers to establish the seemingly protective role of estrogen exposure in esophageal adenocarcinoma. Citation Format: Luckson N. Mathieu, Norma Kanarek, Craig Hooker, Malcolm Brock. Gender disparity in esophageal cancer incidence. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4802. doi:10.1158/1538-7445.AM2013-4802

Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study

BackgroundReported incidence rates of oesophageal adenocarcinoma (OAC) in Barrett's oesophagus (BO) vary widely. As the effectiveness of BO surveillance is crucially dependent on this rate, its clarification is essential.MethodsTo estimate...

Abstract 4565: Tissue protein biomarkers of neoplastic progression in Barrett's esophagus

Abstract The incidence rate of esophageal adenocarcinoma (EAC) has risen by 350% since 1970, outpacing all other cancers (www.nci.gov). There are approximately 15,000 new cases of esophageal cancer per year in the United States, half of which are EAC. The incidence of EAC is 4 cases per 100,000 person years. This cancer is associated with a dismal prognosis, with an overall five-year survival of less than 15%. Although the survival rate depends on the stage of disease, more than 50% of patients present with dysphagia (difficulty swallowing) secondary to obstruction from the tumor and with incurable disease. Upon review of the Surveillance Epidemiology and End Results database for the last 27 years, it is ominous that the incidence rate for esophageal cancer is mirrored precisely by the age-adjusted mortality for a given year. Currently, risk for esophageal cancer is determined solely by the histologic appearance of Barrett's esophagus (BE), however there is a large degree of intra- and inter-observer variability among pathologists. The ability to identify and validate protein biomarkers of disease progression from Barrett's metaplasia to esophageal adenocarcinoma, when treatment outcome is still favorable, would result in a reduction in mortality by aiding in the identification of new diagnostic and treatment options for this disease. We hypothesized that signature protein biomarkers predictive of BE progression could be identified in tissue biopsies that correlate with the metaplasia-dysplasia-carcinoma pathway, which may provide a more reliable set of diagnostic tools, prognostic markers, and therapeutic targets for EAC. Cells from formalin-fixed paraffin embedded (FFPE) tissue sections from defined histological regions of metaplasia (n=9), dysplasia (n=10) and adenocarcinoma (n=12) of the esophagus were procured by laser capture microdissection. A mass spectrometry (MS)-friendly heat-induced/enzyme-mediated antigen retrieval method developed in our laboratory was utilized to produce global tryptic digests from the LCM-procured cells. The digests were randomized and analyzed by high-resolution liquid chromatography-tandem mass spectrometry with an Orbitrap MS, resulting in the identification of an average of 2015 peptides and 652 proteins per sample, with an average relative standard deviation of 15%. Spectral counting and hierarchical cluster analysis enabled the identification of over 80 proteins whose abundances significantly change as a function of neoplastic progression of BE. Several of these putative BE progression biomarkers were validated by quantitative multiple reaction monitoring MS and/or immunohistochemistry, including mucin 5 A/C and 2, cytokeratin 20 and galectin 3. This study is the largest and most comprehensive discovery-driven proteomic analysis of Barrett's esophagus tissue where multiple candidates of progression have been validated by orthogonal techniques. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4565.

Response: Re: Incidence of Adenocarcinoma of the Esophagus Among White Americans by Sex, Stage, and Age

In their correspondence, Chien et al. shared data on the incidence of adenocarcinoma of the esophagus from Taiwan and presented comparisons with other data from the Far East. It appears that the rates are not rising in Hong Kong or Taiwan, in contrast to some increases suggested in Japan. Given the historically low prevalence in the Far East of risk factors such as obesity, gastroesophageal reflux disease, Barrett's esophagus, and cigarette smoking compared with Western countries, it may not be surprising that esophageal adenocarcinoma rates have been quite low and generally not rising in the Far East. We noted with interest that Chien et al. showed in their table 1 that rates did rise in Japan, on the basis of rates that were back-calculated by use of the estimated annual percent changes presented by Shibata et al. (1). Although the incidence rates in Japan were quite low, the estimated annual percent changes during the time period 1993–2001 of 4.73 (95% confidence interval [CI] = 0.74 to 8.88) among men and 6.03 (95% CI = 2.37 to 9.82) among women were statistically significantly different from zero (null hypothesis of no change in rates over time) as shown in table 2 of Shibata et al. the authors interpreted the increase as not “dramatic.” These rates of change are in fact remarkably similar to the estimated annual percent changes among the US white population of 6.52 (95% CI = 5.83 to 7.22) among men and 5.95 (95% CI = 5.11 to 6.81) among women during the period 1973–2005 in the Surveillance, Epidemiology, and End Results nine registries (2,3). Not included in the correspondence by Chien et al. was a publication from Singapore by Fernandes et al. (4) that suggested rising incidence rates of esophageal adenocarcinoma among both men and women during the time period 1968–2002, although the trends did not reach statistical significance. We note, however, that the number of patients classified as having “other type” declined substantially in Singapore over time and may have contributed to the apparent increases in adenocarcinoma. The number of patients classified as having “other and unspecified type” did not decline in Japan and were not presented by Chien for Taiwan; changes in histological type specificity need to be considered when describing type-specific temporal trends.

Time Trends and Racial Disparities in the Stage of Diagnosis of Esophageal Adenocarcinoma (EAC) in the United States

Background: The incidence of EAC continues to increase in US at an alarming rate. Overall 5-year survival rate for EAC is ∼15% and is dependent on its stage of diagnosis. Aims: a)Study the trends in the stage of diagnosis of EACb)Assess racial disparities in the stage of diagnosis of EAC. Methods: The Surveillance Epidemiology and End Results (SEER) database of NCI was searched to identify all pts diagnosed with invasive EAC between January 1, 1976 and December 31, 2005. Data from 9 population-based registries were used to calculate incidence rates of EAC. Age-adjusted incidence rates, using the 2000 US standard, and 95% confidence intervals (CI) were calculated by gender and race (whites, blacks, and others) using SAS. These were calculated in six discrete 5-year time periods (1976-1980 through 2001-2005). Tumor stage was defined as SEER Historic Stage (local - confined to the esophagus; regional - invaded adjacent tissues or spread to regional lymph nodes; distant - metastasized or with distant lymph node involvement; unstaged). To assess for an overall change in the stage of diagnosis, χ2 test of equal proportions across time was performed. To assess for a change in the individual stage of diagnosis, Cochran-Armitage test for trend were performed. Results: Between 1976 and 2005, 10,596 cases of EAC were diagnosed. Incidence of EAC/100,000 person-yrs increased from 0.51 in 1976-80 (95% CI 0.47-0.57) to 2.54 2001-05 (95% CI 2.45-2.63), an increase of 400%. In 2001-2005 (compared to 1976-1980) significantly higher number of local and regional EACs were diagnosed [33% increase in local tumors,32% increase in regional]; p for trend for both <0.0001 whereas lower number of distant cancers were diagnosed;p for trend =0.0002. Significantly less tumors were unstaged in 2001-05 compared with 1976-80 (decline of 57%, p for trend <0.001). Incidence of EAC among whites increased 4-fold with significantly more tumors diagnosed at a local and regional stage; (39% increase in local tumors, 32% increase in regional, p for trend for both <0.0001; 6% decrease in distant, p<0.0005). The incidence of EAC among blacks also increased 2-fold but no significant change in the stage of diagnosis was noted. Conclusions: Updated results (up to 2005) of this population-based study suggest that the incidence rates of EAC continue to rise in whites and blacks. Currently, significantly more EAC are diagnosed at the local and regional stage along with a significant decrease in the distant and unstaged cancers in whites; however, a similar trend was not seen among blacks. Determination of factors driving these racial disparities in EAC stage diagnosis need to be explored.

Epidemiological trends in oesophageal cancer in the Nordic countries

Objective. The incidence rates of oesophageal cancer vary more than those of any other cancer, world-wide. The aim of this study was to examine the epidemiological features of oesophageal cancer in the Nordic countries. Material and methods. Epidemiological data from the Nordic Cancer Registry (NORDCAN Database, http://www.ancr.nu/nordcan.asp) were used for the study analysis. Results. From 1971 to 2000 in the Nordic countries, 18,034 oesophageal cancers were detected in males and 8216 in females. In males, the incidence rates (world age standardized incidence per 100,000) of oesophageal cancer in 1971–75 and 1996–2000 were 2.7 and 6.0 in Denmark, 4.2 and 3.2 in Finland, 3.4 and 5.6 in Iceland, 2.6 and 3.3 in Norway, and 2.9 and 3.3 in Sweden, respectively. In females, the corresponding figures were: Denmark 1.1 and 1.8, Finland 3.1 and 1.3, Iceland 2.5 and 1.3, Norway 0.7 and 0.9, and Sweden 1.1 and 1.0. Each Nordic country showed a significant geographical variation in the incidence of oesophageal cancer. In both males and females the incidence curves began rising after 40 years of age, but significantly more steeply in males than in females. Over the study period, oesophageal cancer mortality increased from 2.97 to 3.68 per 100,000 in males but decreased from 1.30 to 1.08 in females. The incidence rates of oesophageal adenocarcinoma increased in males in all Nordic countries, and the increase was most marked in Denmark. The incidence of oesophageal adenocarcinoma also increased among Danish females, but compared with males, the incidence rate remained significantly lower. Conclusions. The time trends in incidence of oesophageal cancer differ between the Nordic countries, and there has also been geographical variation within them. On a global comparison, the incidence rates of oesophageal cancer are low in the Nordic region. Oesophageal cancer is a male-predominant disease in all Nordic countries, and the incidence rates of oesophageal adenocarcinoma have increased in males and Danish females.

Descriptive epidemiology of esophageal carcinoma in the Ohio Cancer Registry

Background: Etiologic factors and demographics in esophageal cancer have not been fully characterized at a population-level. This study aimed to compare incidence rates of esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) by race. Other aims were to evaluate the impact of race, age, gender, and histology on presenting stage, and to describe tobacco use history in EAC as documented in a cancer registry. Methods: Invasive esophageal cancer cases reported to Ohio's Cancer Registry 1998–2002 were identified. Incident staged EAC and ESCC cases were analyzed for factors associated with metastatic disease. Results: 930 ESCC and 1801 EAC cases were identified. African-Americans had higher ESCC incidence than whites (5.0 versus 1.3 cases/100,000/year). However, whites had higher EAC incidence (3.3 versus 0.8 cases/100,000/year). 77% of EAC cases with available tobacco history were reported in tobacco users. In univariate analyses, race, age, gender, and histology differed significantly by stage. 31% of patients aged ≥65 presented with distant stage, versus 26% of those <65 ( p < 0.001). 32% of African-Americans had distant stage, versus 34% of whites ( p = 0.048). In logistic regression modeling, male gender [OR 1.76, CI (1.15, 2.67)] and age <75 [OR 1.95, CI (1.21, 3.15)], but not race, predicted distant stage ESCC. Distant stage EAC was associated with age <56 [OR 1.82, CI (1.39, 2.38)] but not significantly associated with African-American race ( p = 0.062) for the sample size available. Conclusions: Whites had higher EAC rates, and African-Americans had higher ESCC rates. African-Americans were not more likely than whites to present with metastatic ESCC.

The Effect of Antireflux Surgery on Esophageal Carcinogenesis in Patients With Barrett Esophagus

To determine whether patients with Barrett esophagus who undergo antireflux surgery differ from medically treated patients in incidence of esophageal adenocarcinoma and probability of disease regression/progression. Barrett esophagus is a risk factor for the development of esophageal adenocarcinoma. A question exists as to whether antireflux surgery reduces this risk. Query of PubMed (1966 through October 2005) using predetermined search terms revealed 2011 abstracts, of which 100 full-text articles were reviewed. Twenty-five articles met selection criteria. A review of article references and consultation with experts revealed additional articles for inclusion. Studies that enrolled adults with biopsy-proven Barrett esophagus, specified treatment-type rendered, followed up patients with endoscopic biopsies no less than12 months of instituting therapy, and provided adequate extractable data. The incidence of adenocarcinoma and the proportion of patients developing progression or regression of Barrett esophagus and/or dysplasia were extracted. In surgical and medical groups, 700 and 996 patients were followed for a total of 2939 and 3711 patient-years, respectively. The incidence rate of esophageal adenocarcinoma was 2.8 (95% confidence interval, 1.2-5.3) per 1000 patient-years among surgically treated patients and 6.3 (3.6-10.1) among medically treated patients (P = 0.034). Heterogeneity in incidence rates in surgically treated patients was observed between controlled studies and case series (P = 0.014). Among controlled studies, incidence rates were 4.8 (1.7-11.1) and 6.5 (2.6-13.8) per 1000 patient-years in surgical and medical patients, respectively (P = 0.320). Probability of progression was 2.9% (1.2-5.5) in surgical patients and 6.8% (2.6-12.1) in medical patients (P = 0.054). Probability of regression was 15.4% (6.1-31.4) in surgical patients and 1.9% (0.4-7.3) in medical patients (P = 0.004). Antireflux surgery is associated with regression of Barrett esophagus and/or dysplasia. However, evidence suggesting that surgery reduces the incidence of adenocarcinoma is largely driven by uncontrolled studies.

Incidence of esophageal and gastric cancers among Hispanics, non-Hispanic whites and non-Hispanic blacks in the United States: subsite and histology differences

We examined subsite- and histology-specific esophageal and gastric cancer incidence patterns among Hispanics/Latinos and compared them with non-Hispanic whites and non-Hispanic blacks. Data on newly diagnosed esophageal and gastric cancers for 1998-2002 were obtained from 37 population-based central cancer registries, representing 66% of the Hispanic population in the United States. Age-adjusted incidence rates (2000 US) were computed by race/ethnicity, sex, anatomic subsite, and histology. The differences in incidence rates between Hispanics and non-Hispanics were examined using the two-tailed z-statistic. Squamous cell carcinoma accounted for 50% and 57% of esophageal cancers among Hispanic men and women, respectively, while adenocarcinoma accounted for 43% among Hispanic men and 35% among Hispanic women. The incidence rate of squamous cell carcinoma was 48% higher among Hispanic men (2.94 per 100,000) than non-Hispanic white men (1.99 per 100,000) but about 70% lower among Hispanics than non-Hispanic blacks, for both men and women. In contrast, the incidence rates of esophageal adenocarcinoma were lower among Hispanics than non-Hispanic whites (58% lower for men and 33% for women) but higher than non-Hispanic blacks (70% higher for men and 64% for women). Cardia adenocarcinoma accounted for 10-15% of gastric cancers among Hispanics, and the incidence rate among Hispanic men (2.42 per 100,000) was 33% lower than the rate of non-Hispanic white men (3.62 per 100,000) but 37% higher than that of non-Hispanic black men. The rate among Hispanic women (0.86 per 100,000), however, was 20% higher than that of non-Hispanic white women (0.72 per 100,000) and 51% higher than for non-Hispanic black women. Gastric non-cardia cancer accounted for approximately 50% of gastric cancers among Hispanics (8.32 per 100,000 for men and 4.90 per 100,000 for women), and the rates were almost two times higher than for non-Hispanic whites (2.95 per 100,000 for men and 1.72 per 100,000 for women) but about the same as the non-Hispanic blacks. Subsite- and histology-specific incidence rates of esophageal and gastric cancers among Hispanics/Latinos differ from non-Hispanics. The incidence rates of gastric non-cardia cancer are almost two times higher among Hispanics than non-Hispanic whites, both men and women. The rates of gastric cardia cancer are lower among Hispanics than non-Hispanic whites for men but higher for women. The rates of esophageal and gastric cardia adenocarcinomas are higher among Hispanics than non-Hispanic blacks.

Obesity and lifestyle risk factors for gastroesophageal reflux disease, Barrett esophagus and esophageal adenocarcinoma

The aim of this study was to examine the association of obesity with esophageal adenocarcinoma, and with the precursor lesions Barrett esophagus and gastroesophageal reflux disease (GERD). This case-control study included cases with GERD (n = 142), Barrett esophagus (n = 130), and esophageal adenocarcinoma (n = 57). Controls comprised 102 asymptomatic individuals. Using logistic regression methods, we compared obesity rates between cases and controls adjusting for differences in age, gender, and lifestyle risk factors. Relative to normal weight, obese individuals were at increased risk for esophageal adenocarcinoma (Odds Ratio [OR] 4.67, 95% Confidence Interval [CI] 1.27-17.9). Diets high in vitamin C were associated with a lower risk for GERD (OR 0.40, 95% CI 0.19-0.87), Barrett esophagus (OR 0.44, 95% CI 0.20-0.98), and esophageal adenocarcinoma (OR 0.21, 95% CI 0.06-0.77). For the more established risk factors, we confirmed that smoking was a significant risk factor for esophageal adenocarcinoma, and that increased liquor consumption was associated with GERD and Barrett esophagus. In light of the current obesity epidemic, esophageal adenocarcinoma incidence rates are expected to continue to increase. Successful promotion of healthy body weight and diets high in vitamin C may substantially reduce the incidence of this disease.

Disparities in the Classification of Esophageal and Cardia Adenocarcinomas and Their Influence on Reported Incidence Rates

To evaluate the diagnostic accuracy of esophageal and cardia adenocarcinoma in the Swedish Cancer Register. Based on cancer registers, a rising incidence of esophageal and cardia adenocarcinoma has been reported in several populations, but possible influence of differences in tumor classification has not been evaluated. In a nationwide study in 1995 through 1997, all Swedish patients, born in Sweden and younger than 80 years with esophageal or cardia adenocarcinoma and half of all patients with esophageal squamous cell carcinoma, were prospectively, uniformly, and thoroughly classified. This study classification was compared with the tumor classification in the Swedish Cancer Register, which is based on routine clinical practice. The overall completeness of the Cancer Register was high (98.3%), whereas the site-specific completeness of the Register was 63% for esophageal adenocarcinoma, 74% for cardia adenocarcinoma, and 91% for esophageal squamous cell carcinoma. The incidence of esophageal adenocarcinomas was 16% higher in the study classification compared with that of the Register during the study period, whereas the incidence of cardia adenocarcinoma was 2% lower in the study classification. There is a diagnostic mismatch between esophageal and cardia adenocarcinoma in the clinical setting and, therefore, also in Cancer Registers. In etiologic and therapeutic research, this problem needs consideration, since these tumors have distinct risk factor profiles and could be subjected to different treatment strategies. The increasing incidence rate of esophageal adenocarcinoma in Sweden is unlikely to be explained by such differences in tumor classification, however.

Barrett's Esophagus-Is It Bad for Your Health?

Barrett's esophagus is a clearly recognized risk factor for the development of esophageal adenocarcinoma. Despite the rapidly increasing incidence rate of esophageal adenocarcinoma, the vast majority of patients with Barrett's esophagus will never go on to develop this cancer. Furthermore, esophageal adenocarcinoma is a rare cause of death in Barrett's esophagus patients, and most of these patients die from other causes. While some studies demonstrate that the overall survival of patients with Barrett's esophagus is no different than that of the general population, others have suggested that Barrett's esophagus may be associated with increased mortality. Work by Solaymani-Dodran et al., in the current issue of the American Journal of Gastroenterology, found that all cause mortality was increased by 37% and mortality from causes other than esophageal cancer was increased by 23% compared to the general population, differences that were eliminated when adjusted for ischemic heart disease. Findings such as these point out the need for large, well-done epidemiologic studies of Barrett's esophagus cohorts in order to develop a better understanding of the natural history of this disease.

Etiologic Clues from the Similarity of Histology-specific Trends in Esophageal and Lung Cancers

We tested whether descriptive evidence exists for differing roles of specific tobacco constituents on different histologic subtypes of esophageal cancer. Esophageal adenocarcinoma incidence rates are increasing while squamous cell esophageal cancer rates are declining in Westernized countries as are the histology-specific lung counterparts. Squamous cell lung cancers, while caused by smoking, are believed to be caused by different constituents of tobacco smoke than lung adenocarcinomas. Smoking is also a risk factor for esophageal cancers. We compared patterns of incidence of squamous cell cancers of the lung with those of squamous cell esophageal cancers, and incidence trends in lung adenocarcinomas with those of esophageal adenocarcinomas during the time period from 1976 to 2000 using data from the population-based Los Angeles Cancer Surveillance Program. Rates of squamous cell esophageal cancer declined in a similar fashion to those of squamous cell lung cancer, while esophageal adenocarcinoma incidence increased at a rate similar to that of lung adenocarcinoma, in both men and women, and blacks and whites. Histology-specific socio-economic gradients in lung and esophageal cancers were also strikingly similar. Increases in esophageal adenocarcinoma were confined to the lower third of the esophagus. While increases in obesity over time might explain these trends, they are also consistent with a specific effect of some constituent of tobacco smoke working through reflux disease to cause esophageal adenocarcinoma.

Obesity in ireland is fuelling incidence rates of oesophageal adenocarcinoma

Obesity in ireland is fuelling incidence rates of oesophageal adenocarcinoma

Marked multi-ethnic variation of esophageal and gastric cardia carcinomas within the United States.

No prior studies have contrasted esophageal and gastric cardia carcinoma incidence rates among multiple ethnicities. We evaluated whether these adjacent cancers differ; such detailed demographic analyses would inform risk factor, screening, and intervention studies. We contrasted incidence rates and temporal trends from the Surveillance, Epidemiology, and End Results (SEER) cancer registry data between 1992 and 1998 for five groups: non-Hispanic whites (Caucasians), white Hispanics (Hispanics), blacks, Asians/Pacific Islanders (Asians/PI), and Native Americans (NA). Caucasian males' esophageal adenocarcinoma rate (4.2 per 100,000 population/yr) was double that of Hispanics and four-fold higher than those of blacks, Asians/PI, and NA (p < 0.01). Female rates were much lower than male rates for all ethnicities. Similar to esophageal adenocarcinoma, cardia adenocarcinoma rates were highest in Caucasian males (3.4 per 100,000 population/yr); however, the ethnic differences were much less and female rates were comparable for all almost all ethnicities (range 0.6-0.7 per 100,000 population/yr) except NA. Esophageal adenocarcinoma incidence rates increased significantly only in Caucasians (males 5.6%/yr, females 9%/yr; p < 0.05) and cardia cancer rates did not increase for any ethnicity during this period. In contrast, esophageal squamous cell carcinoma incidence rates were highest in blacks (8.8 per 100,000 population/yr) and Asians/PI (3.9 per 100,000 population/yr) and rates were stable or declined for all ethnicities between 1992 and 1998. Esophageal and cardia carcinoma incidence rates vary much more markedly by ethnicity and gender than previously reported and the two sites differ from each other. Current putative risk factors do not adequately explain these large differences. These data have implications for risk factor, screening, and intervention studies.

Epidemiological differences between adenocarcinoma of the oesophagus and adenocarcinoma of the gastric cardia in the USA.

It has been suggested that gastric cardia adenocarcinoma (GCA) is a distinct entity from oesophageal adenocarcinoma (OA). We examined several epidemiological features of GCA and OA in the USA to elucidate differences/similarities between these malignancies. Using the database of Surveillance, Epidemiology, and End Results (SEER) program, we examined incidence rates for temporal changes, and ethnic and age distributions, and performed birth cohort analyses for cases with morphologically and histologically confirmed OA or GCA. The age adjusted incidence rates of OA rose progressively, reaching 1.8 per 100 000 (95% confidence interval 1.7-1.9) during 1987-1991 and 2.5 per 100 000 (2.3-2.6) during 1992-1996. In 1992-1996, Whites were affected five times more than Blacks, and men eight times more than women. A significant increase in incidence occurred among younger persons aged 45-65 years. Irrespective of age, OA was characterised by higher incidence rates among more recent birth cohorts: a 40% increase in incidence for each five year increase in the date of birth--a "birth cohort effect". On the other hand, the incidence rates of GCA reached their highest level of 3.3 per 100 000 (3.2-3.4) in 1987-1991 and subsequently declined during 1992-1996 to 3.1 per 100 000 (3.0-3.3). Whites were affected twice more than blacks and men five times more than women. Most patients with GCA were older than 60 years with no increase among younger persons and no birth cohort effect (p=0.99). Several significant epidemiological differences exist between OA and GCA. These differences suggest that these two malignancies are separate entities with different risk factors.

Esophageal adenocarcinoma: a review and perspectives on the mechanism of carcinogenesis and chemoprevention.

The incidence rate of esophageal adenocarcinoma (EAC) has increased sharply in the past 30 years. Many risk factors have been identified and gastroesophageal reflux disease (GERD) is the most important one. Columnar-lined esophagus, resulting from GERD, is recognized as a key precursor lesion of EAC. In this article, we review the studies on EAC in humans and animal models. We propose that the pathogenesis of EAC is mainly driven by inflammation and oxidative stress, which are augmented by iron overload. The overproduction of prostaglandin E2 and leukotriene B4 and overexpression of their receptors are believed to be major factors in exacerbating inflammation and oxidative stress. Based on this mechanistic understanding, antioxidants, inhibitors of arachidonic acid metabolism enzymes and receptor antagonists of certain eicosanoids are proposed as potential chemopreventive agents for EAC in future studies.

Adenocarcinoma of the esophagus and Barrett's esophagus: a population-based study.

We described incidence rates of esophageal adenocarcinoma in Denmark in a 20-yr period and determined the proportion of patients diagnosed with esophageal adenocarcinoma who had a previous diagnosis of Barrett's esophagus, making them potential candidates for endoscopic surveillance. Rates of esophageal and gastric cancers were collected from the Danish Cancer registry for the period 1970-1991. The registry was used to identify all cases of esophageal adenocarcinoma in the period 1987-1992. Medical records were retrieved and details concerning previous diagnosis of reflux disease and Barrett's esophagus were recorded. The age- and gender-adjusted incidence of esophageal adenocarcinoma increased eightfold, from 0.3/10(5)/yr in 1970 to 2.3/10(5)/yr in 1990. This increase could not be explained by changes in classification or diagnostic routines. Medical data were retrieved for 524 of the 578 cases of esophageal adenocarcinoma reported during the period 1987-1992. A history of reflux symptoms or a diagnosis compatible with reflux was reported in 113 of 524 patients. A total of 119 patients (23%) had previously been investigated for dyspepsia or reflux symptoms, most often by endoscopy. A previous diagnosis of Barrett's esophagus was found in only 1.3% of the cancer patients. The rate of esophageal adenocarcinoma in Denmark has increased eightfold over a 20-yr period, and this increase is not explained by changes in classification or diagnostic routines. More than 98% of esophageal adenocarcinomas were found in patients who could not have entered endoscopic surveillance, as Barrett's esophagus had not been diagnosed before the cancer diagnosis. Endoscopic surveillance to detect dysplasia may be an option for the individual patient with Barrett's esophagus, but these screening programs are not likely to reduce the death rate from esophageal adenocarcinomas in the general population.

Adenocarcinoma of the esophagus and Barrett’s esophagus: a population-based study

Objective: We described incidence rates of esophageal adenocarcinoma in Denmark in a 20-yr period and determined the proportion of patients diagnosed with esophageal adenocarcinoma who had a previous diagnosis of Barrett’s esophagus, making them potential candidates for endoscopic surveillance. Methods: Rates of esophageal and gastric cancers were collected from the Danish Cancer registry for the period 1970–1991. The registry was used to identify all cases of esophageal adenocarcinoma in the period 1987–1992. Medical records were retrieved and details concerning previous diagnosis of reflux disease and Barrett’s esophagus were recorded. Results: The age- and gender-adjusted incidence of esophageal adenocarcinoma increased eightfold, from 0.3/10 5/yr in 1970 to 2.3/10 5/yr in 1990. This increase could not be explained by changes in classification or diagnostic routines. Medical data were retrieved for 524 of the 578 cases of esophageal adenocarcinoma reported during the period 1987–1992. A history of reflux symptoms or a diagnosis compatible with reflux was reported in 113 of 524 patients. A total of 119 patients (23%) had previously been investigated for dyspepsia or reflux symptoms, most often by endoscopy. A previous diagnosis of Barrett’s esophagus was found in only 1.3% of the cancer patients. Conclusions: The rate of esophageal adenocarcinoma in Denmark has increased eightfold over a 20-yr period, and this increase is not explained by changes in classification or diagnostic routines. More than 98% of esophageal adenocarcinomas were found in patients who could not have entered endoscopic surveillance, as Barrett’s esophagus had not been diagnosed before the cancer diagnosis. Endoscopic surveillance to detect dysplasia may be an option for the individual patient with Barrett’s esophagus, but these screening programs are not likely to reduce the death rate from esophageal adenocarcinomas in the general population.