Manifestations of acute appendicitis: a prospective study on acute abdominal pain.

BACKGROUND/AIMS: The aim of this prospective study was to identify the clinical symptoms and signs most important for the prediction of appendicitis among patients with acute abdominal pain. METHODS: Clinical findings in 2,478 patients admitted to the emergency department of Mora Hospital from February 1997 to June 2000, with acute abdominal pain of up to 7 days' duration, were registered in a database. The medical records were reviewed after 1 year. RESULTS: A total of 432 patients were suspected of having appendicitis and in 221 this diagnosis was confirmed. Some 53 patients, with another preliminary diagnosis, were eventually found to suffer from appendicitis, making a total of 274 patients with appendicitis. Appendectomy was performed in 316 patients and was negative in 14%. Clinical diagnosis of appendicitis had a sensitivity of 0.81, a specificity of 0.90, a positive predictive value of 0.51, a positive likelihood ratio of 8.1, and a diagnostic accuracy of 0.89. The highest odds ratios were found for isolated tenderness in the right iliac fossa (3.29), rebound tenderness (3.00), right-sided rectal tenderness (2.53), migration of pain to the right iliac fossa (2.18), and local guarding (2.11). CONCLUSION: Clinical findings indicating localised inflammation in the right iliac fossa were reliable in predicting acute appendicitis. The patients' history of pain combined with a careful clinical examination still plays an important role in detecting appendicitis among patients with acute abdominal pain.

Impact of time in the development of acute appendicitis.

BACKGROUND: The aim of this study was to elucidate the natural history of appendicitis. METHODS: Data was collected prospectively from consecutive patients admitted to hospital for acute abdominal pain. The degree of appendiceal inflammation in relation to preoperative duration of pain was analysed. RESULTS: The study comprised 253 patients operated on for acute appendicitis that could recall the onset of abdominal pain. There was a longer duration of pre-hospital pain in patients, irrespective of age, with perforated appendicitis compared to patients with phlegmonous or gangrenous appendicitis (p < 0.001). In the multivariate analysis, patient age and preoperative duration of pain were independent risk factors for perforation. CONCLUSION: Patient delay in presentation is the predominant factor determining the incidence of complicated appendicitis, and this delay is not influenced by age or gender.

Why do surgeons miss malignancies in patients with acute abdominal pain?

BACKGROUND: The aim of this study was to characterize patients seeking medical advice for acute abdominal pain who were later diagnosed with an intra-abdominal malignancy. PATIENTS AND METHODS: Patients with acute abdominal pain were registered between 1997 and 2000, employing a detailed schedule comprising 111 parameters. The diagnoses (n=2395 patients) were re-evaluated one year later. RESULTS: A total of 66 patients (2.8%) were found to have an intra-abdominal malignancy at follow-up, of whom 37 cases had been undetected at discharge. Malignancy of the liver, biliary tract and pancreas constituted 30% and colorectal cancer 32% of the tumours undetected at discharge. Constipation, intestinal obstruction and non-specific abdominal pain (NSAP) were the most common preliminary diagnoses in patients among whom abdominal malignancy was later detected. CONCLUSION: Except for age and pain duration, the history and clinical investigation provide few clues to suggest an abdominal malignancy in patients with acute abdominal pain. NSAP, of unknown or known etiology, including constipation, should be suspected as a possible sign of abdominal malignancy in all patients over 50 years of age.

Evaluating gastric cancer misclassification: a potential explanation for the rise in cardia cancer incidence.

BACKGROUND: Reports of dramatic increases in gastric cardia cancer incidence warrant concern. However, the recent introduction of a separate diagnostic code, the lack of a consensus definition of the cardia area, and the accelerating interest in cardia cancer may affect classification practices. Little is known about the magnitude of cardia cancer misclassification in large cancer registries. METHODS: In a well-defined Swedish population (1.3 million), we uniformly classified all patients with newly diagnosed gastric adenocarcinoma (from 1989 through 1994) with respect to gastric subsite, and we used this patient group as our gold standard. We then evaluated the completeness of the Swedish Cancer Registry in registering gastric adenocarcinomas against this gold standard and, further, assessed the completeness of cardia cancer registration and the rate of falsely included cases to estimate the potential impact on observed incidence trends. RESULTS: Our gold standard contained 1337 case subjects with gastric adenocarcinoma. Overall, the Swedish Cancer Registry was 98% complete with regard to gastric adenocarcinomas and had a 4% rate of falsely included cases. The completeness of coding cardia cancer was only 69%, and the positive predictive value for cardia cancer was 82%, with no improvement over time. CONCLUSIONS: Although overall completeness of gastric cancer registration by the Swedish Cancer Registry was excellent, accuracy in registering cardia tumors was surprisingly low. Our estimates suggest that true cardia cancer incidence could be up to 45% higher or 15% lower than that reported in the Cancer Registry. This margin of error could accommodate the observed increase in cardia cancer in Sweden. Therefore, secular trends in cardia cancer incidence should be interpreted cautiously.

Occupational exposures and risk of gastric cancer in a population-based case-control study.

Gastric cancer trends seem to follow improvements in the environment of blue-collar workers, but the etiological role of occupational exposures in gastric carcinogenesis is scantily investigated. The risk of gastric adenocarcinoma in 10 common occupational industries, and particularly the long-term effects of asbestos, organic solvents, impregnating agents, insecticides, and herbicides, were evaluated in a population-based case-control study, including data on most established risk factors. The study base included all individuals of ages 40-79, born in Sweden and living in either of two areas (total population, 1.3 million) with differing gastric cancer incidences, from February 1989 through January 1995. We interviewed 567 cases classified to site (cardia/noncardia) and histological type, and 1,165 population-based controls, frequency-matched for age and sex. Metal workers had a 46% excess gastric cancer risk [adjusted odds ratio (OR), 1.46; 95% confidence interval (CI), 1.10-1.94], increasing to 1.65 (95% CI, 1.17-2.32) for >10 years in the industry. The elevated risk after exposure to herbicides (OR, 1.56; 95% CI, 1.13-2.15) was attributable to phenoxyacetic acids (adjusted OR, 1.70; 95% CI, 1.16-2.48), similarly across tumor subtypes, and not modified by smoking, body mass index, or Helicobacter pylori. The absence of interaction was demonstrated by the pure multiplicative effect found among those exposed to both H. pylori and phenoxyacetic acids (OR, 3.42; 95% CI, 1.41-8.26). Organic solvents, insecticides, impregnating agents, and asbestos were not associated with gastric cancer risk. Employment in the metal industry and exposure to phenoxyacetic acids were both positively and independently associated with gastric cancer risk. The fractions of all gastric cancers attributable to these job-related exposures were small but not negligible (7 and 5%, respectively) in the Swedish population.

Gastric cancer and human leukocyte antigen: distinct DQ and DR alleles are associated with development of gastric cancer and infection by Helicobacter pylori.

DNA and sera from 130 cases of gastric cancer and 263 population-based controls were analyzed to study the association of HLA class II DR-DQ alleles with Helicobacter pylori (Hp) infection and the risk for gastric cancer. Presence of the DQA1*0102 allele was inversely and significantly associated with Hp seropositivity (P = 2 x 10(-5)), which is an independent replication of previous findings. However, this inverse relationship with Hp did not correspond with a reduced risk of gastric cancer. At the DRB1 locus, the *1601 allele was significantly associated with an increased gastric cancer risk with an odds ratio (95% confidence interval) of 8.7 (range, 2.7-28.0). The effect of *1601 was more pronounced among Hp-negative subjects, and the association was stronger with the diffuse, rather than with the intestinal, histological type of gastric cancer. Because none of the HLA alleles were associated with both Hp infection and gastric cancer, the HLA DR-DQ alleles are linked with gastric cancer risk through other mechanisms than an increased susceptibility to Hp infection.

Acute diverticulitis--clinical presentation and differential diagnostics.

OBJECTIVE: To describe the clinical presentation of acute diverticulitis in an emergency department and to characterize the natural history of diverticulitis in the short perspective. Comparisons are made with an important differential diagnosis, nonspecific abdominal pain (NSAP). METHOD: Patients admitted to our hospital with abdominal pain of up to 7 days' duration were registered prospectively using a detailed schedule for history, symptoms and signs, from 1 February 1997 to 1 June 2000. Of 3349 patients initially included, 3073 (92%) were eligible for follow up after 1-3 years. RESULTS: Acute diverticulitis was the final diagnosis in 145 patients and NSAP in 1142 patients. The incidence of hospitalized patients with diverticulitis was 47 per year and 100 000 population, with a mean hospital stay of 3.3 days. Patients with diverticulitis, more frequently than NSAP, had a longer history and laboratory signs of inflammatory activity. Isolated left abdominal tenderness was more common in diverticulitis, whereas isolated right abdominal tenderness was more common in NSAP. Duration of symptoms on arrival was independent of age and was not correlated to C-reactive protein, leucocytes or body temperature. Sensitivity of diverticulitis as primary diagnosis was 64% and specificity 97%. Corresponding figures for NSAP were 43% and 90% respectively. Age and gender did not influence diagnostic accuracy or risk of surgery. CONCLUSION: Diverticulitis differs significantly from NSAP in clinical presentation and laboratory parameters. Sensitivity of primary diagnosis for diverticulitis and NSAP was low.

Acute abdominal pain among elderly patients.

BACKGROUND: Diagnosis of acute abdominal pain in older persons is a challenge, with the age-related increase in concurrent diseases. In most western countries the number of elderly people is constantly rising, which means that an increasing proportion of patients admitted for abdominal pain at the emergency department are elderly. OBJECTIVE: To characterize differences in clinical presentation and diagnostic accuracy between younger and more elderly patients with acute abdominal pain. METHODS: Patients admitted to Mora Hospital with abdominal pain of up to seven days' duration were registered according to a detailed schedule. From 1st February 1997 to 1st June 2000, 557 patients aged 65-79 years and 274 patients aged > or = 80 years were registered. Patients aged 20-64 years (n = 1,458) served as a control group. RESULTS: A specific diagnosis, i.e. other than 'nonspecific abdominal pain', was established in 76 and 78% of the patients aged 65-79 and > or = 80 years respectively, and in 64% of those aged 20-64 (p < 0.001). Pain duration before admission increased with age (p < 0.003), as did frequency and duration of hospitalization (p < 0.0001). Hospital stay increased from 170 days per 100 emergency admissions in the control group to 320 and 458 days in the younger and older study groups, respectively. At the emergency department, older patients were more often misdiagnosed than control patients (52 vs. 45%; p = 0.002). At discharge the diagnosis was more accurate in the control group (86 vs. 77%; p < 0.0001). Hospital mortality was higher among older patients (23/831 vs. 2/1,458; p < 0.001). The admission-to-surgery interval was increased (1.8 vs. 0.9 days, p < 0.0001) in patients > or = 65 years. Rebound tenderness (p < 0.0001), local rigidity (p = 0.003) and rectal tenderness (p = 0.004) were less common in the older than in the control patients with peritonitis. In patients > or = 65 years, C-reactive protein did not differ between patients operated on and those not, contrary to the finding in patients < 65 years (p < 0.0001). CONCLUSION: Both the preliminary diagnosis at the emergency department and the discharge diagnosis were less reliable in elderly than in younger patients. Elderly patients more often had specific organic disease and arrived at the emergency department after a longer history of abdominal pain compared to younger patients.

Risk of stomach cancer in patients with peptic ulcer disease.

The relation between peptic ulcer and stomach cancer has long been disputed, but there is accumulating evidence that gastric ulcer disease is positively associated and duodenal ulcerations negatively associated with the risk of developing stomach cancer. As Helicobacter pylori infection is associated with both types of ulceration and stomach cancer, the varying outcomes of the infection indicate that factors other than the infection must be of importance. At present, there is no convincing evidence that pharmacologic inhibition of acid secretion for treatment of peptic ulcer increases the risk of stomach cancer. However, some recent studies indicate that prolonged treatment with proton pump inhibitors may accelerate the development of atrophic gastritis, a risk factor for stomach cancer, in individuals infected with H. pylori. It has repeatedly been shown that there is an at least twofold increased risk of stomach cancer 15 years after gastric resection for peptic ulcer disease, and that the risk increases with the passage of time. Whether vagotomy has the same risk-increasing effect is still unclear.

Increasing incidence of both major histological types of esophageal carcinomas among men in Sweden.

Although a rare tumor form, there is evidence that the incidence of esophageal adenocarcinomas is increasing in Western Europe and the US. The aim of this nationwide population-based study was to describe the secular trends in the incidence rates of adenocarcinoma and squamous-cell carcinoma of the esophagus over a 28-year period from 1960 to 1987. The Swedish Cancer Registry, complete to more than 95%, was used to identify the cases. The percentage verified by histology rose from 89% to 98%. The age-standardized incidence rate of adenocarcinoma increased in males from 0.5 per 10(5) in 1960-63 to 1.1 per 10(5) in 1984-87, corresponding to an average annual increase of 1.5%. In females the incidence remained stable around 0.2 per 10(5). The age-standardized incidence rate of squamous-cell carcinoma in males increased from 2.9 to 4.0 per 10(5), corresponding to an average annual increase of 1.0%. In females the rate decreased from 1.4 to 1.2 per 10(5), corresponding to an annual average decrease of 0.5%. The male/female ratio was 4.6 for adenocarcinoma and 2.7 for squamous-cell carcinoma of the esophagus. Since the incidence rates of squamous-cell carcinoma of the esophagus and of adenocarcinoma seem to be rising, there is a great need for well-planned analytical epidemiological studies of these tumor locations, taking the histological type into consideration.

Increasing incidence of carcinoma of the gastric cardia in Sweden from 1970 to 1985.

Several American, Japanese and European centres have reported an increase in carcinoma of the gastric cardia, contrary to the general trend in the incidence of gastric cancer. The aim of this nationwide population-based study was to describe trends in the incidence of tumours of the gastric cardia in Sweden over the 16-year period from 1970 to 1985. The Swedish cancer register, which is more than 95 per cent complete, was used to identify cases. There were 1514 men and 481 women with cancer of the gastric cardia. The age-standardized rates increased in men from 1.9 per 10(5) population in 1970-1973 to 3.0 per 10(5) in 1982-1985, corresponding to a mean annual increase of 2.5 per cent (95 per cent confidence interval (c.i.) 1.6-3.4 per cent). In women, the age-standardized rates increased from 0.5 per 10(5) in 1970-1973 to 0.8 per 10(5) in 1982-1985, the mean annual increase being 0.9 per cent (95 per cent c.i. 0.0-1.8 per cent). The highest incidences were found in southern Sweden, contrary to the geographical distribution of gastric cancer in general, which shows a south-to-north gradient. The disparate epidemiological features of cancer of the cardia and gastric cancer at other sites suggest that the aetiologies may also be different. Since little is known about the aetiology of cancer of the cardia, and the incidence seems to be rising rapidly, analytical studies are urgently needed.

Can endoscopic biopsy specimens be used for reliable Laurén classification of gastric cancer?

BACKGROUND: The aim of this study was to ascertain whether routine endoscopic biopsy specimens are of sufficient quality and representative enough to enable reliable classification of histologic type, grade of differentiation, and frequency of signet ring cells. METHODS: As part of a population-based etiologic study of gastric cancer in Sweden, the histologic slides of 687 incident cases were independently reviewed by one pathologist. In 305 cases both biopsy and surgical specimens were available for assessment of sensitivity and specificity of diagnoses on the basis of biopsy specimens, with the classification based on surgical specimens as the gold standard. RESULTS: The sensitivity and specificity of the diagnoses on the basis of biopsy specimens was 86% and 82%, respectively, for detecting the intestinal type, and 87% and 90%, respectively, for the diffuse type of gastric cancer. The percentage agreement between biopsy and surgical specimens with regard to grade of differentiation was 71%. CONCLUSIONS: This study shows that misclassification of Laurén type due to random intraobserver variation needs to be taken into account in epidemiologic studies. The degree of misclassification appears to be of similar magnitude regardless of the source material.

Reliability of retrospective information on diet 20 years ago and consistency of independent measurements of remote adolescent diet.

Although dietary exposures in the distant past are considered important in the etiology of several diseases, few studies have addressed methodological aspects of long-term (> or = 20 yrs) recall. We evaluated the reliability of retrospective self-reports about diet 20 years before the interview and consistency (between siblings) of self-reports about diet during adolescence in a population-based case-control study of stomach cancer in Sweden. Short-term reliability (a questionnaire self-administered 9-12 mos after the personal interview) of reports on diet 20 years ago by 374 control subjects showed mean correlation coefficients for 42 foods/beverages of 0.41 (Pearson) and 0.46 (Spearman) and a mean weighted kappa statistic of 0.42; for 15 nutrients/food constituents the corresponding mean values were 0.46, 0.47, and 0.42, respectively. Consistency of independent reports by siblings about their own diet during adolescence studied in 201 control-sibling pairs was modest. The mean Pearson correlation coefficient for 33 foods/beverages was 0.29, and the mean weighted kappa statistic was 0.30; at the nutrient level the means were 0.26 and 0.24, respectively. A comparison of intersibling differences between controls and stomach cancer cases revealed correlations of a similar magnitude (mean Pearson correlation for 33 foods = 0.29 for control-sibling and 0.27 for case-sibling pairs), thus contradicting differential recall. Our results imply that although reliability of self-reports about the diet in the distant past is generally lower than for the actual diet, we can use these measurements when remote time periods are of special interest in etiological epidemiologic studies.

Survival in stomach cancer is improving: results of a nationwide population-based Swedish study.

OBJECTIVE: To monitor for secular trends in survival among patients with stomach cancer. SUMMARY BACKGROUND DATA: The overall survival among patients with stomach cancer has remained stable at a low level for several decades. METHODS: Relative survival was estimated for all 53,862 living patients reported from 1960 to 1989 to the Swedish Cancer Registry, which is nationwide and virtually complete, with compulsory reporting of new cases of stomach cancer. Follow-up was from cancer diagnosis until death, emigration, or December 31, 1991. RESULTS: During the 1980s, statistically significant improvements were seen in the 2-month, 5-year, and 10-year relative survival of patients with stomach cancer, and in the subgroup with noncardiac cancer. The 5-year relative survival rate increased from 13.3% (95% confidence interval [CI] 12.4 to 14.1) among patients diagnosed with noncardiac stomach cancer in 1970-1974 to 19.4% (95% CI 18.1-20.7) among those given this diagnosis in 1985-1986; the overall mean life expectancy increased from 2.2 to 3.3 years. In patients with cancer of the gastric cardia, the 5-year relative survival rate increased from 4.7% (95% CI 2.3-7.1) to 10.4% (95% CI 7.7-13.1), but the 10-year relative survival rate did not improve. The overall mean life expectancy in this group increased from 1.4 to 2.2 years. Age at diagnosis was strongly and inversely related to relative survival. Patients diagnosed at university hospitals had a moderate survival advantage. CONCLUSION: The survival of patients with a stomach cancer diagnosis appears to be increasing. The reasons for this are probably multifactorial and are likely to include improvements in surgical and anesthesiologic management. However, the long-term prognosis of cancer of the gastric cardia remains dismal.

Stomach leiomyosarcoma: secular trends in incidence and survival in Sweden, 1960-1989.

BACKGROUND: This population-based study was undertaken to investigate the epidemiology of stomach leiomyosarcoma (GIS tumors) and to study the prognosis in affected patients. METHODS: The Swedish Cancer Registry was used to identify all incident cases of stomach leiomyosarcoma from 1960 to 1989, and the Death Registry and the Registry of Population Changes were used for follow-up. RESULTS: The age-standardized incidence in men increased from 1.0 per 10(6 ) per year in 1960-69 to 1.8 per 10(6) per year in 1980-89. The corresponding rates in women were 0.6 per 10(6) and 1.2 per 10(6), respectively. The relative 5-year survival was 39.4% in men and 62.4% in women (P = 0.03). There was no statistically significant improvement in 5-year relative survival during the study period. CONCLUSION: The observed incidence of stomach leiomyosarcoma increased during the study period, most likely due to improved diagnostic accuracy. The survival of patients with this malignant tumor remained unchanged.

Surgery for stomach cancer in a defined Swedish population: current practices and operative results. Swedish Gastric Cancer Study Group.

OBJECTIVE: To study routine surgical in-hospital care, and to relate postoperative morbidity and mortality to age, sex, tumour stage, operation done, and surgical workload of the hospital. DESIGN: Prospective population-based study. SETTING: All hospitals that diagnosed new cases of stomach cancer in five counties in central and northern Sweden, 1 February 1989-31 January 1995. PATIENTS: All 1024 patients diagnosed as having a new adenocarcinoma of the stomach. RESULTS: The stomach cancer was in such an advanced stage at diagnosis that only half of the patients could be offered a potentially curative operation. The tumour was resectable in 632 patients (62%). Distal gastric resection was done for 359 (57%) and total gastrectomy in 259 (41%) of all the resected cases. Postoperative complications occurred in 250 patients (31%). In multivariate analyses the relative risk (RR) for postoperative complications increased to 2.3 (95% confidence interval [CI] = 1.3 to 4.3) in patients over 79 years of age compared with those under 60. The corresponding RR for postoperative death was 5.1 (95% CI = 2.0 to 12.7) in patients over 79 years. Total gastrectomy combined with splenectomy and distal pancreatectomy carried the highest postoperative morbidity (RR = 3.3) and mortality (RR = 3.7) compared with distal gastrectomy. CONCLUSION: There was no difference in postoperative morbidity or mortality among different types of hospital categories. Surgical treatment of stomach cancer still carries a substantial morbidity and mortality in an unselected series of patients, particularly among elderly patients.

Tobacco, alcohol and the risk of gastric cancer. A population-based case-control study in Sweden.

Previous studies have provided conflicting information on the role of tobacco and alcohol in gastric carcinogenesis. A population-based case-control study with 338 histologically confirmed gastric-cancer cases and 679 control subjects was conducted. Information relating to life-time tobacco consumption, alcohol intake and diet during adolescence and 20 years before interview, and to socio-economic conditions was obtained through face-to-face interviews. Current cigarette smokers were found to have a greater risk than non-users of tobacco. The duration of cigarette or pipe smoking was positively associated with gastric-cancer risk. There was significant interaction between tobacco use and fruit consumption. High fruit intake was more protective among users of tobacco than among non-users, and the risk estimates associated with cigarette smoking were higher among those with low fruit consumption than among frequent fruit-eaters. Likewise, though to a lesser extent, vegetable intake interacted with tobacco use. Snuff dipping and alcohol intake was not associated with gastric-cancer risk. However, high alcohol intake tended to increase the risk associated with tobacco use. This study adds further support to the role of tobacco smoking in gastric carcinogenesis, and demonstrates that high intake of fruits and vegetables may be particularly beneficial in smokers.

The risk of gastrointestinal and other primary malignant diseases following gastric cancer.

The risk of developing a second primary cancer was studied among 34,506 gastric cancer patients identified through the Swedish Cancer Registry. A second cancer was reported in 962 patients compared to an expected number of 826 (relative risk = 1.16, 95% confidence limits = 1.09-1.24). The slightly but significantly elevated risk was largely confined to the first year after the gastric cancer diagnosis, and to patients under 70 years old at the time of diagnosis. The risk was significantly increased for cancer in the small intestine, colon, rectum, kidney, breast and prostate. A closer look at the data, however, revealed that a substantial proportion of the second cancers were diagnosed within one month after the gastric cancer diagnosis, or at autopsy. We recalculated the relative risk estimates under the assumption that only 75% of the cancers incidentally detected in connection with diagnosis/treatment of the gastric cancer would have become clinically manifest during the relatively short observation time. and that 20% of the cancers revealed at autopsy in the gastric cancer patients would have been detected if the death and autopsy rates in this group had been equal to those in the general population (matched for age and gender). Under those assumptions the risk of having a second primary cancer among gastric cancer patients was close to what would be expected. The increased risk reported in some previous studies could be the result of closer patient surveillance.

The decline in the incidence of stomach cancer in Sweden 1960-1984: a birth cohort phenomenon.

Trends in the incidence of stomach cancer among 52,604 patients notified to the National Swedish Cancer Registry in 1960 through 1984 were analysed. Age-standardized incidence rates declined throughout the period, from 47.1 to 24.6 per 10(5) in males and from 23.8 to 12.7 per 10(5) in females. Among males the decline in incidence was more pronounced in younger age strata, 35-54 years, while in females it reached a maximum at ages 70-74 years. In a multivariate analysis the age-cohort model adequately represented the data and there was no reason to separate the effects of the full age-period-cohort model. Compared with the cohort born in 1876-1884, the relative risk of developing stomach cancer was 0.46 (95% CI:0.44-0.48) in males and 0.39 (95% CI:0.37-0.42) in females born in 1906-1914. This supports the view that the declining incidence is due to a change in the exposure of the population to aetiological factors of stomach cancer and not to refinement of the diagnosis and classification of abdominal tumours. The results also imply that exposure to aetiological factors early in life together with a long induction period is of importance in the development of stomach cancer.

Dietary antioxidant intake and the risk of cardia cancer and noncardia cancer of the intestinal and diffuse types: a population-based case-control study in Sweden.

In spite of diverging incidence trends, subsite, and subtype-specific gastric cancer data on the association with dietary antioxidants are sparse. We aimed to test whether the apparent protective effect of antioxidants is mainly confined to noncardia (distal) cancer of the intestinal subtype, to which most of the incidence decline in gastric cancer has been ascribed. In a Swedish study base (total population 1.3 million), we interviewed 567 cases uniformly classified to subsite (cardia vs. noncardia) and subtype (intestinal vs. diffuse), and 1165 population-based controls, frequency matched for age and sex. Serologic data on H. pylori status was available for a subset of 542 individuals. Ascorbic acid (vitamin C) was inversely associated with all subsites and subtypes of gastric cancer in a significant dose-response manner (all p<0.05), with risk reductions between 40% and 60%. beta-carotene was also strongly and negatively associated with risk, particularly with the intestinal type. The associations with alpha-tocopherol (vitamin E) were less clear. The highest parallel intake of all three antioxidants (quartiles 4), compared to those with the lowest parallel intakes (quartiles 1), was associated with a 70% lower risk of developing noncardia cancer (OR 0.3, 95% CI 0.1-0.9). Our results suggest that antioxidants might be especially beneficial among subjects at increased risk for gastric cancer such as smokers and those infected by H. pylori. We conclude that a high intake of antioxidants, as a consequence of high consumption of fruit and vegetables, may lower the risk not only for gastric cancer of the intestinal type, but also for diffuse type adenocarcinoma and cardia cancer.