PURPOSE:To examine the controversial association of gallstones, cholecystectomy and colorectal cancer. Methodologic explanations for the association include ascertainment bias, unequal diagnostic testing, and necropsy selection bias. Necropsy screening, which eliminates unequal diagnostic testing and ascertainment bias and reduces necropsy selection bias, was used to study this controversy.METHODS:Adult necropsies at the University of Kansas Medical Center from 1950 to 1984 were reviewed. Patients with colorectal cancer, gallstones, or who had cholecystectomy during life were excluded. The remaining patients were those in whom neither colorectal cancer nor gallstones were suspected during life (reducing selection bias). The occurrence of gallstones and colorectal cancer among these individuals was then determined (reducing ascertainment bias and unequal diagnostic testing).RESULTS:Of 7485 persons receiving necropsy, 239 had colorectal cancer diagnosed during life and an additional 604 had gallstones or cholecystectomy, leaving 6642 patients available for study. Overall, no association between colorectal cancer and gallstones was found. In women, gallstones were associated with colorectal cancer; 6/447 (1.3%) with gallstones had colorectal cancer compared with 11/2259 (0.4%) without gallstones who had colorectal cancer, p = 0.048, odds ratio 2.78 (95% CI 0.84-8.25). A stronger association was found between right-sided colorectal cancer and gallstones (odds ratio 6.79, 95% CI 1.14-46.46).CONCLUSIONS:These data suggest an association between gallstones and colorectal cancer among women. Gallstones may indicate patients at higher risk for colorectal cancer. Studies associating cholecystectomy with colorectal cancer may be explained--not by ascertainment bias--but, rather, by susceptibility bias. The reason for the cholecystectomy (gallstones) may be the correct association and not the cholecystectomy itself.

Recent reports have suggested a minimal difference in demographics between hospital deaths undergoing necropsy and those that do not. In order to assess whether the clinical diagnosis at death influenced the decision to request necropsy in deaths occurring in the hospital, a 10% sample of all adult necropsies at the University of Kansas Medical Center (Kansas City) from 1962 through 1981 was obtained. These patients (cases) were matched by age, race, sex, and date of death to hospital deaths not undergoing necropsy (controls). The charts were reviewed, and the primary diagnosis at death was ascertained and categorized into one of the 14 categories of the International Classification of Diseases. There were 412 case-control pairs, with 237 men and 175 women in each group. Most patients were classified under the headings Circulatory (142 cases vs 140 controls) and Neoplasm (143 cases vs 148 controls), followed by Respiratory (21 cases vs 33 controls) and Digestive (44 cases vs 28 controls). Overall, no statistically significant differences were observed between cases and controls. There were no gender-specific differences in all but two of the categories. In men, the controls had more patients classified under the heading injury (19 vs seven). In women, the control group had more patients classified under the heading Respiratory (14 vs four). Because of multiple comparisons, these findings could have occurred by chance. These data suggest that the primary diagnosis at death is not a source of bias in the selection for necropsy. Consequently, necropsy-selection bias, if it exists, may be due to other factors, such as the complexity of the patient's clinical course.

In previous research, we have demonstrated the value of using necropsy "surprise" lung cancer cases, in those in whom lung cancer was not suspected during life, to estimate the size and composition of the "reservoir" of undetected lung cancer in the general population. The current research was done to determine the characteristics and consequences of secular changes over time in the composition of the lung cancer "reservoir." The results suggest that further advances in diagnostic technology will enhance detection during life of the large "reservoir" of resectable lung cancer, particularly in women. With the increased detection of these reservoir cases during life, the statistical occurrence rates for lung cancer will seem to increase, but survival rates will seem to improve because more of the detected cases will be resectable.

When rising rates of occurrence are reported for a particular disease, clinicians often cannot determine whether the disease has increased in actual occurrence or in the improved detection provided by better diagnostic technology and expanded access to medical care. The epidemiologic use of necropsy data, which might help answer these questions, has been inhibited by fears of bias in demographic and clinical selection of patients for necropsy. The demographic problem can be managed by suitable adjustment and standardization of the disease rates found at necropsy, and the clinical problem can be reduced or avoided by studying the rates with which the disease is found unexpectedly in necropsies performed for other, unrelated clinical reasons. The results, obtained in population groups "screened" via necropsy, can suggest the magnitude of the "undetected reservoir" that coexists and supplements the rates of reported occurrence for a disease. In a study of necropsies at Yale-New Haven (Conn) Hospital from 1972 to 1981, the necropsy detection rates for lung cancer were slightly higher for women than for men, and were substantially higher for both genders than the customarily reported rates in the general population. The results suggest that the reported rates may continue to rise in both genders until they become essentially equal at a size approximating that of the currently undetected reservoir. The "epidemiologic necropsy" offers a potentially valuable method to help distinguish the true occurrence rates of disease from the changes attributable to improved diagnostic detection with modern technology.

The epidemiologic use of necropsy data has been inhibited by the belief that the information is demographically biased. This study was undertaken to investigate whether patients who have died and who have undergone a necropsy are representative of hospital deaths. In a review of all hospital and necropsied deaths from 1962 to 1981 in adult patients at the University of Kansas Medical Center, Kansas City, it was found that 7393 hospital patients died and 4122 underwent necropsy (56%), with similar proportions in both men and women. The mean age of those undergoing necropsy was slightly younger: 60 years vs 62 years in men and 57 years vs 59 years in women. The proportion of necropsies performed was relatively similar for whites (57%) and nonwhites (51%). Although the large sample size made all these differences "statistically significant," there were no clinically relevant differences with regard to gender, age, or race. These findings confirm a previous study at another institution and suggest that a demographic bias does not distort necropsy population data compared with data of the population of hospital deaths.