Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis.

Background: Periodontal disease (PD), now our commonest infectious disorder leads to tooth loss, and has been linked to various systemic diseases, including various types of cancer. The aim of this study is to provide a systematic review and a meta-analysis of the relationship between PD, edentulism, and pancreatic cancer (PC). Patients and methods: From an initial review of 327 references we selected eight studies concerning periodontitis or edentulism with sufficient quantitative information to allow us to examine the risk of PC. We used relative risks (RRs), hazard ratios, or odds ratios to measure the association between periodontitis, edentulism, and PC. We employed random effects models to obtain summary risks, and we also provide measures of study differences and possible biases. Results: The summary RR for periodontitis and PC was 1.74 [95% confidence interval (CI) 1.41-2.15] and 1.54 for edentulism (95% CI 1.16-2.05). There was no evidence of heterogeneity for either variable, and no evidence of publication bias. The studies included reports from three continents, suggesting that the association is generalizable. Most of the studies were adjusted for variables thought to be associated with PC, such as gender, smoking, BMI, diabetes, and alcohol. Conclusions: Using meta-analysis, both periodontitis and edentulism appear to be associated with PC, even after adjusting for common risk factors. As yet, the mechanisms linking oral disease and PC are uncertain, but could be related to changes in the oral microbiome-an area of current research.

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

Effect of neomycin on azoxymethane-induced colon carcinogenesis in F344 rats.

The effect of oral administration of neomycin (100 and 200 micrograms/ml in drinking water) on colon tumors induced by azoxymethane [(AOM); CAS: 25843-45-2] was studied in female F344 rats. Five-week-old rats were fed NIH-07 diet and given daily in drinking water 0, 100, and 200 micrograms neomycin/ml (0, 100, and 200 ppm). At 7 weeks of age, all animals except vehicle-treated groups received weekly sc injections of 8 mg AOM/kg body weight for 8 weeks. The AOM- or vehicle-treated groups were necropsied 30 weeks after the last injection of AOM. The combined incidence of adenomas and adenocarcinomas of the colon did not differ significantly among the 3 groups. The animals in the groups given 100 and 200 micrograms neomycin had a higher incidence of colon adenocarcinomas than did those in the control group. Colonic and cecal bacterial beta-glucuronidase activity was significantly lower in the group given 200 micrograms neomycin than it was in the control group. The excretion of fecal cholesterol, total bile acids, and deoxycholic acid was increased significantly in animals given 100 and 200 micrograms neomycin as compared to animals given no neomycin. These results suggest that long-term oral administration of neomycin increases the incidence of colon adenocarcinomas.

Gallstones and risk of gallbladder cancer.

The relationship between gallstones and gallbladder cancer was investigated in a case-control study in 131 subjects with gallbladder cancer and 2,399 subjects without gallbladder cancer. Included in the study were male and female subjects from 3 racial groups: white, black, and Southwestern American Indian. For the non-Indian group there was a significant relationship between gallstones and gallbladder cancer, with an overall estimated relative risk (RR) of 4.4 (95% confidence interval, 2.6-7.3). For the Indian population the overall estimated RR was much higher: RR = 20.9; 95% confidence interval = 8.1-54. By the combination of the RR, the prevalence of gallstones, and the overall incidence of gallbladder cancer, the risk of gallbladder cancer was calculated in each population for subjects with untreated gallstones. In older subjects with gallstones the estimated 20-year cumulative risk for gallbladder cancer ranged from 0.13% in black males to 1.5% in Indian females. It was concluded that the risk of gallbladder cancer in untreated subjects with gallstones is heterogeneous, depending on race and sex as well as the period of exposure to gallstones.

Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group.

BACKGROUND: Hereditary pancreatitis is an autosomal-dominant disease, with a variable expression and an estimated penetrance of 80%. The gene for this disease has recently been mapped to chromosome 7q35, and the defect is believed to be caused by a mutation in the cationic trypsinogen gene. Acute attacks of abdominal pain begin early in life and the disease often progresses to chronic pancreatitis. Although the risk of pancreatic cancer is thought to be increased in more common types of chronic pancreatitis, the frequency of pancreatic cancer in the inherited type of pancreatitis is uncertain. PURPOSE: The aim of this study was to assess the frequency of pancreatic cancer and other tumors in patients with hereditary form of pancreatitis. METHODS: To determine the natural history of hereditary pancreatitis, we invited all members of the American Pancreatic Association and the International Association of Pancreatology to participate in a longitudinal study of this rare form of pancreatitis. The initial criteria for patient eligibility were as follows: early age (< or = 30 years) at onset of symptoms, positive family history, and absence of other causes. From April 1995 through February 1996, 37 physicians from 10 countries contributed medical records of 246 (125 males and 121 females) patients thought to have hereditary pancreatitis as the most likely diagnosis. This group included 218 patients where the diagnosis appeared to be highly probable and 28 additional patients where the diagnosis of hereditary pancreatitis was less certain: 25 patients who had relatively late onset of disease and a positive family history and three patients with onset of disease before age 30 years but with an uncertain family history. We reviewed all causes of death and compared the observed to the expected frequency of cancer in this historical cohort of patients with hereditary pancreatitis. The strength of the association between pancreatitis and pancreatic cancer was estimated by the standardized incidence ratio (SIR), which is the ratio of observed pancreatic cancer cases in the cohort to the expected pancreatic cancers in the background population, adjusted for age, sex, and country. RESULTS: The mean age (+/- standard deviation [SD]) at onset of symptoms of pancreatitis was 13.9 +/- 12.2 years. Compared with an expected number of 0.150, eight pancreatic adenocarcinomas developed (mean age +/- SD at diagnosis of pancreatic cancer: 56.9 +/- 11.2 years) during 8531 person-years of follow-up, yielding an SIR of 53 (95% confidence interval [CI] = 23-105). The frequency of other tumors was not increased: SIR = 0.7 (95% CI = 0.3-1.6). Eight of 20 reported deaths in the cohort were from pancreatic cancer. Thirty members of the cohort have already been tested for the defective hereditary pancreatitis gene: all 30 carry a mutated copy of the trypsinogen gene. The transmission pattern of hereditary pancreatitis was known for 168 of 238 patients without pancreatic cancer and six of eight with pancreatic cancer. Ninety-nine of the 238 patients without pancreatic cancer and six of the patients with pancreatic cancer inherited the disease through the paternal side of the family. The estimated cumulative risk of pancreatic cancer to age 70 years in patients with hereditary pancreatitis approaches 40%. For patients with a paternal inheritance pattern, the cumulative risk of pancreatic cancer is approximately 75%. CONCLUSIONS: Patients with hereditary pancreatitis have a high risk of pancreatic cancer several decades after the initial onset of pancreatitis. A paternal inheritance pattern increases the probability of developing pancreatic cancer.

Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer.

BACKGROUND: There are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor. PURPOSE: Our purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease. METHODS: A large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel. RESULTS: After adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease. CONCLUSIONS: These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.

Effect of voluntary exercise on azoxymethane-induced colon carcinogenesis in male F344 rats.

The effect of voluntary exercise on azoxymethane (AOM; CAS: 25843-45-2)-induced colon carcinogenesis was investigated in male F344 rats. Beginning at 5 wk of age, all animals were divided into two groups (sedentary and exercise) and fed AIN-76A semipurified diet ad libitum. At 7 wk of age, animals were given AOM s.c. at a dose level of 15 mg/kg of body weight, once weekly for 2 wk. Four days after the second dose of AOM, all animals in the exercise group were housed in individual wheel-cage units, and the animals in the sedentary group were housed in plastic cages. The experiment was terminated at 38 wk post-AOM treatment. Body weights of animals in the exercise and sedentary groups were comparable. The incidence (percentage of animals with tumors) and multiplicity (tumors/animal) of colon adenocarcinomas were significantly inhibited in the exercise group, but the incidence and multiplicity of colon adenomas were unaffected by the exercise. The incidence of small intestinal adenocarcinomas and liver foci was also inhibited in the exercise group.

Reduced frequency of percutaneous injuries in surgeons: 1993 versus 1988.

OBJECTIVE: To compare the frequency of occupational injuries reported by surgeons in 1993 with similar data obtained in 1988. DESIGN AND SETTING: Two point-prevalence studies of percutaneous injuries of surgeons practicing in tertiary and non-tertiary-care hospitals in the New York metropolitan area. PARTICIPANTS: A total of 202 surgeons and surgical residents surveyed in 1988 and 347 surveyed in 1993 (67 and 65% of the eligible groups, respectively), including 85 surgeons in 1993 (71% of the eligible group) who had participated in the 1988 survey. OUTCOME MEASURES: Yearly frequency of percutaneous injuries, and injury frequency per 1000 operative hours. RESULTS: There was a significant decrease in the frequency of reported percutaneous injuries over the 5-year period. For all surgeons, the mean number of yearly injuries decreased from 5.5 +/- 14.4 SD to 2.1 +/- 6.0 SD (P < or = 0.001). Paired analysis of the subgroup of 85 surgeons who participated in both surveys showed a nearly identical decrease (P = 0.001). Significant decreases were observed in general surgeons, specialists and residents. CONCLUSIONS: During the 5 years studied, surgeons practicing in the greater New York metropolitan area reported a significant reduction in the frequency of occupationally associated percutaneous injuries. The reduced risk of percutaneous injuries should substantially lower the rate of acquired infections from blood-borne pathogens.

Distribution of small bowel tumors.

We have studied the anatomic distribution of 784 small bowel carcinomas and have analyzed available epidemiologic data to determine the relation of these rare cancers to other gastrointestinal tumors and to diet. The anatomic distribution of small bowel cancer in unusual: most tumors occur in the duodenum or proximal jejunum, relatively few tumors occur in the central bowel, and only in the lower ileum do the expected number of tumors appear. Review of available epidemiologic data shows a correlation between small bowel cancer and lower, but not upper gastrointestinal cancer. The incidence of small bowel cancer is positively correlated with protein and fat consumption.

Effect of voluntary exercise on azoxymethane-induced hepatocarcinogenesis in male F344 rats.

The effect of voluntary exercise on azoxymethane-induced hepatocarcinogenesis was investigated in male F344 rats. Beginning at 5 weeks of age, all animals were divided into two groups (sedentary and exercise) and fed AIN-76A semipurified diet ad libitum. At 7 weeks of age, animals were given azoxymethane (AOM) s.c. at a dose level of 15 mg/kg of body weight, once weekly for 2 weeks. Four days after the second dose of AOM, all animals in the exercise group were housed in individual wheel-cage units and the animals in the sedentary group were housed in plastic cages. The experiment was terminated at 38 weeks post-AOM treatment. Body weights of animals in the exercise and sedentary groups were comparable. Immunohistochemical staining of glutathione S-transferase placental form (GST-P) was performed in the liver and measured GST-P positive foci. Density (number of GST-P positive foci/cm2 area of liver section), average area of foci and unit area of foci were significantly inhibited in the exercise group, although the incidence of neoplastic nodules and GST-P positive foci were unaffected by the exercise. Thus, energy expenditure due to exercise may reduce hepatocarcinogenesis in a laboratory animal model.

Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study.

This report notes the differences in the classification of the primary renal disease (PRD) used in different renal dialysis and transplant registries worldwide. The heterogeneity of coding systems complicates the comparative analysis of end-stage renal disease from different regions. Using data collected over two decades in the United States, Europe, and Australia/New Zealand, we present a method for reorganization of the classes of PRD that allows a straightforward comparison of retrospective data from these registries.

One less for the road. International trends in alcohol consumption and vehicular fatalities.

We used data for the years 1965 to 1987 from 19 countries to study the relationship between per capita alcohol consumption and vehicular fatalities. Cross-sectional data for the most recent years show a strong relationship between per capita alcohol consumption and vehicular deaths (r = .83, P < .001). When we examined time trends, we noted an increase in per capita alcohol consumption and vehicular deaths for the years 1965 to 1973, a dissociation of the two variables in response to the oil crisis during the 1970s, and a recent gratifying reduction in both variables for the period 1980 to 1987. On average, for the years 1980 to 1987, a 1% reduction in per capital alcohol consumption was associated with a 1% reduction in vehicular deaths (95% confidence interval, .9 to 1.1). For many countries alcohol consumption has already peaked and these findings provide quantitative support for the beneficial effects of continued efforts to control overall per capita consumption of alcohol.

Gallstone growth, size, and risk of gallbladder cancer: an interracial study.

To investigate gallstone size, growth, and the relation between stone size and gallbladder cancer we have used cholecystectomy reports from 1676 female subjects (169 Whites, 531 Blacks, and 976 Native American Indians). Although the prevalence of gallstones differs markedly in these groups it appears that the estimated growth rate of gallstones in younger subjects, 2.0 mm per year (95% confidence interval: 1.7-2.3 mm) is homogeneous for all three groups. In both Indian and non-Indian populations the proportion of small stones diminished and the proportion of large stones increased over time. We found a strong relationship between gallstone size and gallbladder cancer. Large stones (greater than or equal to 3 cm) were found in 40% of patients with gallbladder cancer but in only 12% of all subjects of similar age. The relative risk for gallbladder cancer in subjects with stones greater than or equal to 3 cm was 9.2 compared with subjects with stones less than 1 cm. (95% confidence interval: 2.3-37). We estimate that one-third of all gallbladder cancers in subjects with calculi will be associated with large (greater than or equal to 3 cm) stones. We believe that stone size might be used to determine the risk of gallbladder cancer in patients with gallstones.

Seroprevalence of human immunodeficiency virus-1, hepatitis B virus, and hepatitis C virus in patients having major surgery.

OBJECTIVE: To determine the proportion of major surgical procedures that involve patients having serologic evidence of infection with human immunodeficiency virus-1 (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) in a single center in Westchester County, New York. METHODS: Blood samples sent for transfusion screening or cross-match were tested blindly for HIV antibody (anti-HIV), HBV core antibody, HBV surface antigen (HBsAg), and HCV antibody (anti-HCV). Demographic characteristics and operation category were correlated with serologic results by univariate and regression analyses. RESULTS: Of 1,062 operations evaluated, 71 (6.7%, 95% confidence interval [CI95], 5.2% to 8.4%) were performed on patients with either anti-HIV, HBsAg, or anti-HCV. In 17 (1.6%, CI95, .93% to 2.5%) of these operations, the patient evidenced anti-HIV; in 15 (1.4%; CI95, .79% to 2.3%), HBsAg; and in 55 (5.2%, CI95, 3.9% to 6.7%), anti-HCV. Anti-HCV was detected significantly more often than anti-HIV (5.2% versus 1.6%, P < .001) or HBsAg (5.2% versus 1.4%, P < .001). Operations involving women aged 25 to 44 years had the highest proportion with serologic evidence of at least one of the three viruses (17.2%); of anti-HCV (15.3%); and of anti-HIV (6.7%). Logistic regression analysis found that being in the 25- to 44-year age group was associated significantly with infection with any virus (P < .001) and with anti-HCV (P < .001). The strongest logistic predictors of anti-HIV seropositivity were having anti-HCV seropositivity (P < .001), being age 25 to 44 years (P < .001), and having a general surgery operation (P = .002). CONCLUSION: The prevalences of serologic evidence of at least one of the three viruses (16.7%), of anti-HCV (14.5%), and of anti-HIV (5.6%) are high in patients aged 25 to 44 years undergoing major surgery at a tertiary-care medical center located in Westchester County, New York. Anti-HCV is more prevalent than anti-HIV or HBsAg and is predictive of anti-HIV seropositivity. Testing for anti-HIV alone would have detected only 24% of patients infected with a bloodborne pathogen. These data strongly underscore the importance of universal precautions.

Pancreatic cancer: development of a unifying etiologic concept.

Our knowledge of the etiology of all forms of cancer including pancreatic cancer has improved dramatically in the second half of this century. The current model describes a gradual change from a normal pancreatic cell to a fully malignant cell requiring several stages with gradual and progressive alterations appearing at the genetic and the tissue level. Although there are many germ line diseases that are associated with pancreatic cancer it is probable that inherited diseases account for only about 10% of the total burden of pancreatic cancer. Avoidance of smoking and dietary modification are the current best strategies for reducing the risk of this tumor. In addition, newer molecular techniques and imaging procedures should provide clinicians with the ability to detect pancreatic cancer at an early, potentially curable stage.

Frequency of puncture injuries in surgeons and estimated risk of HIV infection.

To evaluate the occupational risk of human immunodeficiency virus (HIV) infection, we surveyed 202 surgeons working in the New York City metropolitan area. One hundred seventy-three (86%) surgeons reported at least one puncture injury in the preceding year (median number, 2 per year; interquartile range, 1 to 4 per year). Seventy-six percent of the injuries occurred during surgery, and the median injury rate was 4.2 per 1000 operating room hours. Twenty-five percent of the surgeons sustained yearly injury rates of 9 or more per 1000 operating room hours, and these high rates were independent of sex, age, type of practice, operative work load, or hospital location. Fifty-three percent of all injuries involved the index finger of the nondominant hand. If the prevalence of HIV infection in surgical patients is 5%, then the estimated 30-year risk of HIV seroconversion is less than 1% for 50% of the group, 1% to 2% for 25% of the group, 2% to 6% for 15% of the surgeons, and greater than 6% for 10% of the surgeons.