Risk Of Esophageal Carcinoma Research Articles

Esophageal carcinoma after sleeve gastrectomy

The severely obese have an increased risk of esophageal carcinoma. Esophageal carcinoma can be difficult to detect after bariatric surgery. Furthermore, operative interventions can be limited because of the altered anatomy after surgery. A case of esophageal carcinoma discovered after laparoscopic sleeve gastrectomy is presented to increase awareness of this possibility.

Chromosomal imbalances are uncommon in chagasic megaesophagus.

BackgroundChagas' disease is a human tropical parasitic illness and a subset of the chronic patients develop megaesophagus or megacolon. The esophagus dilation is known as chagasic megaesophagus (CM) and one of the severe late consequences of CM is the increased risk for esophageal carcinoma (ESCC). Based on the association between CM and ESCC, we investigated whether genes frequently showing unbalanced copy numbers in ESCC were altered in CM by fluorescence in situ (FISH) technology.MethodsA total of 50 formalin-fixed, paraffin-embedded esophageal mucosa specimens (40 from Chagas megaesophagus-CM, and 10 normal esophageal mucosa-NM) were analyzed. DNA FISH probes were tested for FHIT, TP63, PIK3CA, EGFR, FGFR1, MYC, CDKN2A, YES1 and NCOA3 genes, and centromeric sequences from chromosomes 3, 7 and 9.ResultsNo differences between superficial and basal layers of the epithelial mucosa were found, except for loss of copy number of EGFR in the esophageal basal layer of CM group. Mean copy number of CDKN2A and CEP9 and frequency of nuclei with loss of PIK3CA were significantly different in the CM group compared with normal mucosa and marginal levels of deletions in TP63, FHIT, PIK3CA, EGFR, CDKN2A, YES and gains at PIK3CA, TP63, FGFR1, MYC, CDNK2A and NCOA3 were detected in few CM cases, mainly with dilation grades III and IV. All changes occurred at very low levels.ConclusionsGenomic imbalances common in esophageal carcinomas are not present in chagasic megaesophagus suggesting that these features will not be effective markers for risk assessment of ESCC in patients with chagasic megaesophagus.

Polymorphisms of HLA-A and HLA-B genes in genetic susceptibility to esophageal carcinoma in Chaoshan Han Chinese

Esophageal carcinoma (EC) occurs at high rate in Chaoshan region of southern China. Human leukocyte antigen (HLA) polymorphism has been implicated in risk for various cancers. To investigate the impact of HLA-A and HLA-B polymorphisms on susceptibility to EC, a case-control study was conducted among 206 patients with esophageal squamous cell carcinoma and 524 controls from Chaoshan Han population. HLA-A and HLA-B polymorphisms were genotyped by polymerase chain reaction-sequence-specific primers. Genotypic association tests for dominant, recessive, and additive models, and haplotypic association were calculated using unconditional logistic regression. A*11 was identified in a recessive model as an only allele strongly associated with EC risk (odds ratios [OR]=2.10, 95% confidence interval [CI]=1.33-3.31) even after correction for multiple test. The haplotypes A*02-B*46 (OR=1.53, 95% CI=1.04-2.24) and A*11-B*51 (OR=2.29, 95% CI=1.20-4.40) showed association with increased risk for EC, whereas A*11-B*58 (OR=0.00, 95% CI=0.00-0.82) was associated with decreased risk, though the significance of these haplotypes was lost after correction. This is a first association study at genetic level identifying HLA-A and HLA-B-related variations in genetic susceptibility to EC among Chaoshan population. The variation pattern is likely to be EC-specific because it is different from that observed for nasopharyngeal carcinoma in the same study population and might, at least in part, explain the high rate of EC in this ethnic group.

Association of ECRG2 TCA short tandem repeat polymorphism with the risk of oesophageal cancer in a North Indian population

Oesophageal cancer-related gene (ECRG2) is a tumour suppressor gene and it has been suggested that a triplet TCA short tandem repeat (STR) in the noncoding region of exon 4 plays a role in genetic susceptibility to oesophageal cancer. In the present study, ECRG2 STR polymorphism was studied in 134 patients with oesophageal cancer and 194 controls, using PCR and polyacrylamide gel electrophoresis. The results showed a higher frequency of the ECRG2 TCA (3)/TCA (4) genotype in cancer patients than in controls (odds ratio 2.6, 95% CI 1.0-6.4, p = 0.03). The association of the ECRG2 TCA (3)/TCA (4) genotype with clinical characteristics showed an increased risk for squamous cell histology (2.8, 95% CI 1.1-7.1, p = 0.03), while no association with tumor location or lymph node involvement was observed. Interaction of tobacco, alcohol and occupational exposure with the ECRG2 genotypes did not show modulation of risk. In conclusion, the ECRG2 TCA (3)/TCA (4) genotype is associated with the risk of oesophageal carcinoma in a North Indian population.

Exploratory Factor Analysis of Squamous Cell Carcinoma of the Esophagus in Uruguay

In the period 1996–2004, a hospital-based, case-control study on diet and risk of squamous cell carcinoma of the esophagus was conducted in Montevideo, Uruguay. The study included 234 cases and 468 controls, frequency matched on age, sex, and residence. Factor analysis (principal components) was used to identify the major food patterns associated with esophageal cancer. The analysis of food groups led to the identification of four patterns, arbitrarily labeled as traditional, healthy, high-fat, and drinker. The traditional pattern was not associated with risk of esophageal carcinoma, whereas the healthy pattern displayed a strong inverse association with this malignancy [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.17–0.48, P value for trend < 0.0001]. Unexpectedly, the high-fat foods diet was also marginally protective (OR 0.60, 95% CI 0.36–1.01, P value for trend = 0.07). On the other hand, the drinker pattern displayed a twofold increase in risk of esophageal carcinoma (OR 2.03, 95% CI 1.17–3.51, P value for trend = 0.01). The present study suggests that factor analysis might contribute to the elucidation of the contribution of diet on human cancer. Because diet represents a complex set of highly correlated exposures, dietary patterns could be more explicative of the etiology of squamous cell carcinoma of the esophagus than the traditional reductionist approach.

PTENpolymorphisms and the risk of esophageal carcinoma and gastric cardiac carcinoma in a high incidence region of China

PTEN, as a tumor suppressor gene, plays an important role in regulating cell growth, proliferation, and apoptosis. Two common polymorphisms, -9C/G and IVS4 (-/+), may alter susceptibility to the disease. To test the hypothesis that the genetic variations of PTEN play a role in the etiology of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), a population-based case-control study was conducted in 350 ESCC patients, 257 GCA patients, and 634 healthy controls from a high-incidence region of Hebei province, China. The PTEN polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The results showed that the family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age, gender and smoking status adjusted OR = 1.73 and 1.67; 95% CI = 1.29-2.32 and 1.28-2.19, respectively). The overall distribution of the PTEN -9C/G genotype was not significantly different between cancer patients and controls. Compared with the PTEN IVS4-/- genotype, the IVS4+/+ genotype significantly decreased the risk of ESCC and GCA development, the adjusted OR was 0.64 (95% CI = 0.44-0.94) and 0.63 (95% CI = 0.41-0.98), respectively. Stratification analysis by gender, age, smoking status and family history of UGIC showed that the PTEN IVS4-/+ genotype only reduced the risk of ESCC (adjusted OR = 0.55, 95%CI = 0.34-0.90) among subjects with family history of UGIC. While the IVS4+/+ genotype decreased the susceptibility to both ESCC and GCA (adjusted OR = 0.61 and 0.57, 95% CI = 0.37-0.98 and 0.34-0.98, respectively) among male subjects, the IVS4+/+ genotype only decreased the risk of ESCC development among subjects younger than 55 years (adjusted OR = 0.43, 95% CI = 0.21-0.85). In addition, the haplotype analysis found that the -9C/IVS4- haplotype increased the risk of developing ESCC and GCA (OR = 1.31 and 1.24, 95% CI = 1.08-1.58 and 1.001-1.53). Our results suggested that the PTEN IVS4+/+ homozygote may play a protective role in the development of ESCC and GCA, while the haplotype -9C/IVS4- might be the risk factor of the development of ESCC and GCA in the high incidence region population of Hebei province, China.

Dietary habits, ethanol and tobacco consumption as predictive factors in the development of esophageal carcinoma in patients with head and neck neoplasms

Patients with primary head and neck cancers have a higher risk of developing esophageal cancer. The aim of this study was to investigate esophageal cancer prevalence, its risk factors (ethanol and tobacco consumption) and dietary habits in patients with head and neck cancer. Three hundred and twenty-six adults with primary head and neck cancer were followed by a retrospective observational study in a general university hospital in Sao Paulo, Brazil. Flexible videoendoscopy with lugol chromoscopy was the method used to investigate esophageal cancer prevalence. All subjects were interviewed face-to-face, revealing detailed information about their tobacco and alcohol use, as well as their dietary habits. Thirty-six patients with esophageal cancer were diagnosed and the overall prevalence rate was 11.04%. Patients who developed second esophageal tumors had the following characteristics: earlier age of initial ethanol consumption (P < 0.05), longer duration period of ethanol consumption (P < 0.05) and higher weekly consumption rate (P < 0.05). There was an increased risk of esophageal carcinoma in those patients who both smoked and drank (P < 0.05). There was no association between carcinoma of the esophagus and dietary habits in patients who developed esophageal neoplasms, compared with those who did not. Prevalence rate of esophageal neoplasms was 11.04% in patients with head and neck carcinoma, whose ethanol consumption was associated with esophageal cancer. There was an increased risk between ethanol and tobacco consumption and esophageal carcinoma development. On the other hand, there was no association regarding dietary habits between patients who developed esophageal cancer and those who did not.

Helicobacter pylori, chronic atrophic gastritis, inactive aldehyde dehydrogenase‐2, macrocytosis and multiple upper aerodigestive tract cancers and the risk for gastric cancer in alcoholic Japanese men

Gastric carcinoma occurs at a high rate in alcoholic Japanese men. Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/2*2) and macrocytosis (mean corpuscular volume [MCV] > or = 106 fl) enhance the risk for esophageal carcinoma, which frequently occurs with gastric carcinoma in this population. Whether alcoholism affects Helicobacter pylori-induced chronic atrophic gastritis (CAG) is unknown. This study of Japanese alcoholic men with (n = 45) and without (n = 281) gastric carcinoma included assessment of H. pylori IgG antibody, serum pepsinogen-confirmed CAG, MCV, and ALDH2 genotype. The gastric carcinoma cases had a significantly higher age-adjusted prevalence of H. pylori-positivity (78%vs 57%), CAG (78%vs 42%), ALDH2*1/2*2 (36%vs 14%), MCV > or =106 fl (38%vs 20%), and concurrent esophageal/oropharyngolaryngeal carcinoma (18%vs 5%) than controls. Among gastric cancer-free controls, the prevalence of CAG was higher than generally reported in Japan, regardless of H. pylori status (H. pylori-positive, 56%vs 35-36% for Japanese general population; H. pylori-negative, 8%vs 1-3%). Alcoholism may accelerate the progression of CAG. Each of these factors increased the risk of gastric carcinoma (OR(s) = 3.7 for H. pylori-positive, 2.7 for non-severe CAG, 8.7 for severe CAG, 3.5 for ALDH2*1/2*2, 2.5 for MCV > or =106 fl, and 3.7 for concurrent carcinoma). A multivariate analysis showed that CAG and ALDH2*1/2*2 were independently related to the risk of gastric carcinoma. Combinations of CAG and ALDH2*1/2*2 showed greater risks of gastric carcinoma (OR(s) = 4.0 for non-severe CAG alone, 17.6 for severe CAG alone, 9.7 for ALDH2*1/2*2 alone, 17.1 for non-severe CAG plus ALDH2*1/2*2, and 39.2 for severe CAG plus ALDH2*1/2*2). Combining blood tests for H. pylori, CAG, MCV and ALDH2 genotype could offer a new means of predicting risk of gastric carcinoma in Japanese alcoholic men.

LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China

Esophageal carcinoma is characterized by a widely ranged incidence variation among the different geographic regions. Anyang is a county in Henan Province of North China with the highest prevalence of esophageal carcinoma. Human papillomavirus (HPV) infection has been linked to the etiology of esophageal cancer in this area. In this study, we investigated correlations of the polymorphisms at low molecular weight polypeptide (LMP) and transporters with antigen processing (TAP) genes, with the risk of esophageal carcinoma. DNA extracted from either tumor specimens or esophageal epithelial cells was used to test HPV infection. Peripheral blood lymphocyte DNA was used for LMP/TAP genotyping. Polymerase chain reaction was performed to analyze HPV infection and LMP/TAP gene polymorphisms. The combined effect of LMP/TAP gene polymorphisms and HPV infection on esophageal carcinoma was analyzed by using unconditional logistic regression models. The TAP2 codons 379 isoleucine carriers and LMP7 codons 145 lysine carriers were found to be more susceptible to esophageal carcinoma (OR = 2.74, 95% CI = 1.15-6.49, P = 0.023 for TAP2; OR = 2.19, 95% CI = 1.09-4.37, P = 0.027 for LMP7). Patients carrying homozygous LMP7/TAP2 haplotype C, which contained the glutamine at LMP7 codons 145 and the isoleucine at TAP2 codons 379, were more prone to develop esophageal carcinoma (OR = 2.96, 95% CI = 1.13-7.81, P = 0.027). An additive effect on the risk of esophageal carcinoma development was found among individuals carrying LMP7/TAP2 haplotype C and infected by HPV (OR = 4.33, 95% CI = 2.53-7.42, P < 0.0001). LMP7/TAP2 haplotype C may act as the risk factor in esophageal carcinoma development and it may influence the tumorigenesis in HPV infected individuals.

Diagnosis and Management of Barret's Esophagus

Incidence of esophageal adenocarcinoma is increasing in western countries and has poor prognosis due to late diagnosis. Barrett’s esophagus is considered as premalignant lesion in which some of squamous epithelium in distal esophagus has been replaced by metaplastic columnar ephithelium. It occurs as complication of longstanding gastroesophageal reflux. Endoscopic examination is very important for early detection especially in patients with chronic symptoms of gastroesophageal reflux disease (GERD) for more than 5 years. Aggressive antireflux treatment may reduce the risk of esophageal carcinoma. However, no single therapeutic modality had been proven superior compare to others, but until now surgery remains the most popular treatment of choice in the management of Barrett’s esophagus. Keywords: Barrett’s esophagus,GERD, premalignant lesion, management

Barrett′s oesophagus: Is there a need for laparoscopic anti-reflux surgery?

Barrett′s oesophagus: Is there a need for laparoscopic anti-reflux surgery?

NSAIDs and Esophageal Cancer: A Systematic Review and Meta-Analysis

Use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) has been linked with reduced risk for esophageal carcinoma. However, the data to

Cholecystectomy, peptic ulcer disease and the risk of adenocarcinoma of the oesophagus and gastric cardia.

Gastro-oesophageal reflux is a strong risk factor for oesophageal adenocarcinoma. Bile and pancreatic enzymes may be particularly carcinogenic. Cholecystectomy causes an increased gastric level of these constituents. A decreased risk of oesophageal adenocarcinoma has been observed in persons infected with cagA-positive Helicobacter pylori. There is a strong correlation between ulcer disease and Helicobacter pylori infection. The aim of this study was to determine whether previous cholecystectomy or peptic ulcer disease affects the risk of oesophageal carcinoma. Data were collected as a nationwide population-based case-control study in Sweden between 1995 and 1997. Multivariate adjusted odds ratios (ORs) were calculated with logistic regression. There was no statistically significant association between cholecystectomy and the risk of oesophageal carcinoma. Among persons with previous peptic ulcer, the adjusted OR for oesophageal adenocarcinoma was below unity (OR = 0.6, 95 per cent confidence interval 0.3-1.1). The relative risk estimates for cardia adenocarcinoma and oesophageal squamous cell carcinoma were close to unity. Cholecystectomy, despite its effect on the composition of gastric juice, does not appear to increase the risk of adenocarcinoma of the oesophagus or gastric cardia. While the data do not contradict a protective effect of H. pylori, the results are also consistent with absence of such an effect.

Radiation therapy for breast cancer and increased risk for esophageal carcinoma.

Several case reports have suggested an association between radiation therapy for breast cancer and the subsequent occurrence of esophageal carcinomas. To examine the association between radiation therapy for breast cancer and subsequent esophageal squamous-cell carcinomas and adenocarcinomas. Population-based retrospective cohort study. Population-based U.S. cancer registries. 220,806 women in whom breast cancer was diagnosed between 1 January 1973 and 31 December 1993; 1,216,853 person-years of follow-up. Age- and period-adjusted standardized incidence ratio as a measure of relative risk for the second primary cancer. In women who had received radiation therapy for breast cancer, the relative risk for esophageal squamous-cell carcinoma increased to 5.42 (95% CI, 2.33 to 10.68) and the relative risk for esophageal adenocarcinoma increased to 4.22 (CI, 0.47 to 15.25) 10 or more years after radiation therapy. No increased risk was seen for either type of carcinoma among patients with breast cancer who did not receive radiation therapy. The risk for esophageal carcinoma is increased in women who receive radiation therapy for breast cancer.

Risk factors for the development of oesophageal cancer as a second primary tumour

Exposure to irradiation or chemotherapy as well as prolonged exposure to risk factors, such as alcohol and tobacco, may induce a second primary carcinoma of the oesophagus. To estimate the potential risk of previous treatment regimens, we performed a case-control study. In the Tumour Registry of The Netherlands Cancer Institute, from 1955, 27 cases of squamous cell carcinoma of the oesophagus were identified following treatment for malignant lymphoma (n = 11), breast cancer (n = 8) and lung cancer (n = 8). The median interval was 6.6 years (range 1-16). Preferably 3 controls from the same tumour registry were matched to each case on the basis of sex, age, primary tumour, location of primary treatment (academic or general hospital), calendar year at diagnosis of primary tumour and duration of follow-up. Clinical data and details of treatment were obtained from the medical records. In patients who had smoked for more than 5 years, there was a 3.2-fold increased risk of oesophageal carcinoma (P = 0.04); for those with a regular alcohol intake the relative risk was 3.3 (P = 0.01). There was no significant relationship between irradiation of the mediastinum and subsequent risk for oesophageal cancer. The number of chemotherapy-treated patients was too small to calculate the relative risk associated with cytostatic drugs. In conclusion, oesophageal cancer as second primary cancer is extremely rare. Risk factors include the well known abuse of alcohol and tobacco. No significant relationship with previous mediastinal irradiation could be demonstrated.

Aspirin and reduced risk of esophageal carcinoma

Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) have been shown experimentally to inhibit chemically induced esophageal cancers. An epidemiologic study of more than 600,000 adults in the United States followed for 6 years found that aspirin use was associated with a reduced risk of death from esophageal cancer. The relation of aspirin use and esophageal cancer was examined using data from the National Health and Nutrition Examination Survey (NHANES I) and the National Epidemiologic Follow-up Studies (NEFS). Of the 14,407 United States residents followed for 12-16 years, esophageal cancer developed in 15. Persons were classified as nonusers, occasional users, or regular users of aspirin based on their response to two questions at the baseline examination: whether they had taken aspirin in the past 30 days and whether they had used pain medications regularly during the prior 6 months. Occasional use was associated with a 90% decreased risk (95% confidence interval, 0.01-0.76) of developing esophageal cancer, and no person classified as a regular user developed the disease. Adjusting for cigarette smoking (ever vs. never) and alcohol intake (at least monthly vs. not) did not explain the finding. Aspirin use was associated with a 90% decreased risk of developing esophageal carcinoma. Further studies to determine whether aspirin is protective against both squamous cell esophageal carcinoma and adenocarcinoma of the esophagus are indicated.

Carcinoma of the esophagus and tylosis. A lethal genetic combination

Hyperkeratosis of the palms and soles (tylosis) is an uncommon genetic disorder. A small number of English families, however, have been described in which it is associated with carcinoma of the esophagus. The current report is of the first American family described with this condition. Members of those families affected with tylosis have at least a 90% risk of esophageal carcinoma by age 65 years. The paired conditions have an autosomal dominant mode of transmission and probably are controlled at a single genetic locus. The actual pathologic state might be mediated through an increase in epidermal growth factor receptors in the abnormal tissues.

Precursor lesions of esophageal cancer in high-risk populations in Henan Province, China.

This report discusses precancerous changes in the esophageal mucosa from three points of view: the histopathologic features of the esophageal mucosa in persons known to be at high risk for esophageal carcinoma (EC); the histopathologic features of the esophageal mucosa of asymptomatic persons randomly selected from areas at high and low risk for EC; and a prospective follow-up of a randomly examined group to determine the impact of esophagitis and dysplasia upon subsequent development of EC. Esophagitis was commonly found at endoscopic examination, but there was no difference in frequency of esophagitis in the randomly selected subjects from high-risk and low-risk areas. Although one third of patients with dysplasia developed cancer over a follow-up period of 30 to 78 months, only 4% of those with esophagitis alone developed EC. The authors conclude that dysplasia, diagnosed by cytologic or histologic examination, is a precancerous state, and that esophagitis is a nonspecific pathologic condition of the esophagus, but moderate and severe types of chronic esophagitis might create an environment favorable for the development of esophageal carcinoma.

Toluidine Blue Staining of the Esophagus: A Useful Adjunct in the Panendoscopic Evaluation of Patients With Squamous Cell Carcinoma of the Head and Neck

Carcinoma of the esophagus has a much higher incidence among patients with squamous cell carcinoma of the head and neck than among the population at large. Esophageal cancer has a low cure rate, and the possibility for increased survival can be enhanced primarily through early detection. Toluidine blue has proved to be effective in demonstrating early malignant lesions that would not be detectable otherwise. A technique has been developed for toluidine blue staining of the esophagus during panendoscopy. In this initial series of 18 patients with squamous cell carcinoma of the upper aerodigestive tract, we found a 17% incidence of early carcinoma of the esophagus. We believe this technique to be an important adjunct to the evaluation of these patients at high risk for esophageal carcinoma.

Histopathology of Methylbenzylnitrosamine-Induced Esophageal Carcinoma in the Rat: Comparison With Cytomorphology&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

The incidence of human carcinoma of the esophagus is increased in association with environmental nitrosamines and dietary zinc deficiency. For examination of the role of zinc deficiency in esophageal carcinogenesis, methylbenzylnitrosamine [(MBN) CAS: 937-40-6] was used to induce esophageal carcinoma in rats fed either a zinc-deficient or control diet. Histologic examination of the MBN-treated Sprague-Dawley rat esophagi revealed a significantly higher incidence of esophageal carcinoma in the zinc-deficient rats vs. controls (62 vs. 33%). In addition, three distinct cytologic and histologic patterns were observed in the animals with esophageal carcinoma: pattern I--basal cell hyperplasia, atypical basal cells, few dyskeratotic cells; pattern II--basal cell hyperplasia, atypical basal cells, many dyskeratotic cells; and pattern III--many dyskeratotic cells without basal cell hyperplasia. These three patterns did not occur simultaneously in the same esophagi, and zinc deficiency did not alter the appearance of these patterns. A strong correlation between the appearance of moderate or severe dysplasia cytologically and microinvasive carcinoma histologically was demonstrated. In those animals with histologically evident microinvasive carcinoma, there was no cytologic evidence of carcinoma in situ or invasive carcinoma. Cytology of these esophageal carcinomas revealed only moderate or severe dysplasia. To the extent that the rat model represents the evolution of esophageal carcinoma in humans, the results presented here suggest that the cytologic appearance of moderate or severe dysplasia indicates the need for further evaluation of patients at risk for esophageal carcinoma.