Recent Publications by CFE Educators

Leukemia is one of the cancers most susceptible to induction by ionizing radiation, but the effects of lower doses delivered over time have not been quantified adequately. After the Chornobyl (Chernobyl) accident in Ukraine in April 1986, several hundred thousand workers who were involved in cleaning up the site and its surroundings received fractionated exposure, primarily from external gamma radiation. To increase our understanding of the role of protracted low-dose radiation exposure in the etiology of leukemia, we conducted a nested case-control study of leukemia in a cohort of cleanup workers identified from the Chornobyl State Registry of Ukraine. The analysis is based on 71 cases of histologically confirmed leukemia diagnosed in 1986-2000 and 501 age- and residence-matched controls selected from the same cohort. Study subjects or their proxies were interviewed about their cleanup activities and other relevant factors. Individual bone marrow radiation doses were estimated by the RADRUE dose reconstruction method (mean dose = 76.4 mGy, SD = 213.4). We used conditional logistic regression to estimate leukemia risks. The excess relative risk (ERR) of total leukemia was 3.44 per Gy [95% confidence interval (CI) 0.47-9.78, P 0.01]. The dose response was linear and did not differ significantly by calendar period of first work in the 30-km Chornobyl zone, duration or type of work. We found a similar dose-response relationship for chronic and non-chronic lymphocytic leukemia [ERR = 4.09 per Gy (95% CI 0-14.41) and 2.73 per Gy (95% CI 0-13.50), respectively]. To further clarify these issues, we are extending the case-control study to ascertain cases for another 6 years (2001-2006).

After the accident that took place on 26 April 1986 at the Chornobyl nuclear power plant, hundreds of thousands of cleanup workers were involved in emergency measures and decontamination activities. In the framework of an epidemiological study of leukemia and other related blood diseases among Ukrainian cleanup workers, individual bone marrow doses have been estimated for 572 cases and controls. Because dose records were available for only about half of the study subjects, a time-and-motion method of dose reconstruction that would be applicable to all study subjects, whether dead or alive, was developed. The doses were calculated in a stochastic mode, thus providing estimates of uncertainties. The arithmetic mean individual bone marrow doses were found to range from 0.00004 to 3,300 mGy, with an average value of 87 mGy over the 572 study subjects. The uncertainties, characterized by the geometric standard deviation of the probability distribution of the individual dose, varied from subject to subject and had a median value of about 2. These results should be treated as preliminary; it is likely that the dose calculations and particularly the uncertainty estimates will be improved in the follow-up of this effort.

There are relatively few data on the risk of leukemia among those exposed to external radiation during cleanup operations after the Chornobyl nuclear accident, and results have not been consistent. To investigate this further, we assembled a cohort of 110,645 male cleanup workers from Ukraine and identified cases of leukemia occurring during the period 1986 to 2000. Detailed interviews were conducted and individual bone marrow doses estimated using a new time-and-motion method known as RADRUE described in companion paper II. For the initial analyses we used a nested case-control approach with a minimum of five controls per case, matched for year of birth, oblast (region) of registration, and residence. All identified cases were reviewed by an international panel of experts; 87 of 111 were confirmed. The dose-response analysis and results are given in companion paper III. As background, we describe herein the design, procedures, outcome of case finding and confirmation, control selection, dose estimation and interviewing of subjects.

OBJECTIVE

Over time, the histology of papillary thyroid cancers detected in a repeatedly screened population exposed to radiation at Chornobyl (Chernobyl) has shifted from a more aggressive subtype toward less aggressive subtypes. This change may reflect biologic behavior but could also be influenced by the detectability of different subtypes. The study objective was to identify whether there is any relationship between the conspicuity of sonographically detected papillary cancers and histologic subtype.

MATERIALS AND METHODS

Sonographic images of 84 papillary cancers occurring in young people exposed to radiation at Chornobyl were each given a conspicuity score using a subjective 1-5 scale by four independent expert readers blinded to histologic subtype. The effects of tumor subtype, tumor encapsulation, reader, machine type, and nodule size on sonographic conspicuity were determined using analysis of variance and Spearman correlations.

RESULTS

Cancer subtype was related to sonographic conspicuity (p 0.01). The relatively aggressive solid subtype of papillary carcinoma was more conspicuous than the papillary, follicular, and mixed subtypes (p 0.05). The other subtypes did not differ significantly from each other in conspicuity. Conspicuity was not significantly related to nodule size, degree of encapsulation, age and sex of the subject, or machine type. Although the mean conspicuity score for each reader differed significantly, reliability of conspicuity judgments across readers was fair.

CONCLUSION

In subjects exposed to radiation from the Chornobyl accident, the solid subtype of papillary carcinoma appears to be more conspicuous on sonography than the other subtypes. Therefore, the change in subtype observed over time in this repeatedly screened population may be influenced by differences in nodule conspicuity.

BACKGROUND

High surgeon volume is associated with improved outcomes in adult endocrine surgery. This is the first population-based outcomes study for thyroidectomy/parathyroidectomy in children.

METHODS

Cross-sectional analyses were performed using 1999 to 2005 Healthcare Cost and Utilization Project Nationwide Inpatient Sample data. Outcomes included complications, length of stay (LOS), and costs. High-volume surgeons performed >30 cervical endocrine procedures per year in adults and children; pediatric surgeons restricted >90% of their practices to patients

RESULTS

We included 607 patients, representing 20% of the pediatric endocrine operations done between 1999 and 2005 in the United States. Seventy-six percent of patients were female. Among the procedures performed, 92% were thyroidectomies and 8% were parathyroidectomies. Surgeons were classified as follows: 18% High-volume, 21% Pediatric, and 61% Other. High-volume surgeons had the lowest LOS (1.5 days vs 2.3 Pediatric, 2.0 Other; P = .01), costs ($12,474 vs $19,594 Pediatric, $13,614 Other; P .01), and complications (6% vs 11% Pediatric, 10% Other; P = NS). In multivariate analyses, case volume of the endocrine surgeons was an independent predictor of LOS and costs.

CONCLUSION

High-volume surgeons have better outcomes after thyroidectomy/parathyroidectomy in children compared with Pediatric and Other surgeons. Surgeon experience was an independent predictor of LOS and costs. High-volume endocrine and pediatric surgeons could combine expertise to improve outcomes in children.

BACKGROUND

Despite burgeoning scientific knowledge about Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma (KS), little is known about awareness of this virus in the general community. This is particularly the case for men who have sex with men (MSM), the group at greatest risk for infection.

METHODS

The California Health Interview Survey was a random digit- dial survey of over 50,000 households. Men aged 18 to 64 years who self-identified as gay or bisexual were subsequently recontacted for a follow-up study of HIV-related knowledge and behavior in which they were asked if they had heard of KS and to describe the cause of KS.

RESULTS

Of 398 MSM interviewed, 73.0% (95% CI 65.0-79.7) had heard of KS. However, only 6.4% (95% CI 4.4-9.2) of participants correctly identified that KS is caused by KSHV or a virus other than HIV. Postgraduate education, urban residence, and concurrent HIV infection were all independently associated with greater awareness of the viral origin of KS.

CONCLUSION

Awareness of KSHV is very low, overall, among MSM and only somewhat higher, but still unacceptably low, among HIV-infected MSM. Significant efforts are needed to increase awareness of KSHV as a sexually transmitted infection in this population.

BACKGROUND

Most current animal models of hindlimb ischemia use acute arterial occlusion that does not accurately reflect the pathogenesis of gradual arterial occlusion in humans. We, therefore, developed the first mouse model of gradual arterial occlusion and tested the hypothesis that the mechanisms regulating blood flow recovery are critically dependent on the rate of arterial occlusion.

METHODS

Gradual arterial occlusion was induced by placing ameroid constrictors on the proximal and distal left femoral artery, and ligating the femoral arterial branches (n = 36). Acute arterial occlusion was accomplished by excising the left femoral artery (n = 36). The blood flow recovery was studied by laser Doppler imaging. Differential gene expression between these two models was assessed by quantitative real-time polymerase chain reactions (PCR). Inflammatory and progenitor cells recruitment were determined by immunohistochemistry.

RESULTS

We found that hypoxia-related genes increased significantly in the calf, but not in the thigh, after gradual and acute femoral arterial occlusion (P .05). Shear-stress dependent genes and inflammatory genes were upregulated immediately in the thigh only after acute femoral arterial occlusion (P .05). These differences in gene expression were consistent with increased SDF-1alpha expression, recruitment of macrophages and hemangiocytes, and higher blood flow recovery after acute arterial occlusion than after gradual arterial occlusion (P .05).

CONCLUSION

This is the first study to show the mechanisms that regulate blood flow recovery are critically dependent on the rate of arterial occlusion. This novel model of gradual arterial occlusion may more closely resemble the human diseases, and may provide more accurate mechanistic insights for creating novel molecular therapies.