Risk and Benefit Estimates: Risk estimates for mediastinoscopy and benefits of earlier diagnosis of AD were derived from a literature survey.
Cost Estimates: Comprehensive charges for mediastinoscopy and transbronehial biopsy, inclusive of sample processing, were provided by the fee schedule department, Kaiser Permanente, Northwest Region, which are market rates based on 50 to 80% of the community standard, and from the Utilization Management Department, Blue Cross, Blue Shield of Oregon.
Statistical Analysis
We computed the 95% confidence interval (Cl) for the proportion of patients, P, in the population of HD with BHL by a variant of the binomial likelihood function: the probability of not observing this event in N patients = (1-P)N; setting this equation=0.05 and solving for P gives the 95% boundary. The incidence estimates of other ADs wrere based on complex derivations and assumptions not susceptible to computation of a CI. We estimated the number of mediastinoscopies required to identify each AD by computing the likelihood ratio, Isis^abhl-ad’ where I is the estimated incidence and the subscript identifies the disorder.
General Assumptions
For clarity and simplicity of exposition and quantitative analysis, we assumed the following: 100% sensitivity and specificity of mediastinoscopy for each diagnosis; all patients with ABHL not due to TB, HD, or NHL have SIS; ethnicity and symptoms characteristic of sarcoidosis did not affect the prior probability of SIS; all patients with SIS were either asymptomatic or had symptoms characteristic of SIS; and the mean duration of SIS and ABHL-AD were equal. These assumptions are discussed in the text and appendix. Among ADs, we did not include coccidioidomycosis, which is endemic to the southwest United States and rarely enters into the differential diagnosis of BHL elsewhere: it is generally symptomatic when treatment is required, and is serologically verifiable. Similar considerations apply to histoplasmosis. Patients with AIDS may present with mediastinal adenopathy due to TB or neoplasm. Testing for HIV, when clinically indicated, will guide further investigation. Patients with metastatic neoplasia rarely present with BHL; they are almost invariably symptomatic; nearly all exhibit abnormalities on examination or routine laboratory testing, which will guide the direction of further investigation;2 the course is not substantially improved by early diagnosis; and where benefit tends to zero, risk/benefit and cost/benefit ratios tend to infinity.